Paul J. Wang, MD

All Publications

• Regional Longitudinal Deformation Improves Prediction of Ventricular Tachyarrhythmias in Patients With Heart Failure With Reduced Ejection Fraction: A MADIT-CRT Substudy (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy) CIRCULATION-CARDIOVASCULAR IMAGING Biering-Sorensen, T., Knappe, D., Pouleur, A., Claggett, B., Wang, P. J., Moss, A. J., Solomon, S. D., Kutyifa, V. 2017; 10 (1)

  Abstract

  Left ventricular dysfunction is a known predictor of ventricular arrhythmias. We hypothesized that measures of regional longitudinal deformation by speckle-tracking echocardiography predict ventricular tachyarrhythmias and provide incremental prognostic information over clinical and conventional echocardiographic characteristics.We studied 1064 patients enrolled in the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy) with speckle-tracking data available. Peak longitudinal strain was obtained for the septal, lateral, anterior, and inferior myocardial walls at baseline. The end point was the first event of ventricular tachycardia (VT) or fibrillation (VF). During the median follow-up of 2.9 years, 254 (24%) patients developed VT/VF. Patients with VT/VF had significantly lower left ventricular ejection fraction (28.3% versus 29.5%; P<0.001) and longitudinal strain in all myocardial walls compared with patients without VT/VF (anterior-strain, -7.7% versus -8.8%; P<0.001; lateral-strain, -7.3% versus -7.9%; P=0.022; inferior-strain, -8.3% versus -9.9%; P<0.001; septal-strain, -9.1% versus -10.0%; P<0.001). After multivariate adjustment, only anterior and inferior longitudinal strain remained independent predictors of VT/VF (anterior: hazard ratio, 1.08 [1.03-1.13]; P=0.001; inferior: hazard ratio, 1.08 [1.04-1.12]; P<0.001; per 1% absolute decrease for both). When including B-type natriuretic peptide in the model, only a decreasing myocardial function in the inferior myocardial wall predicted VT/VF (hazard ratio, 1.05 [1.00-1.11]; P=0.039). Only strain obtained from the inferior myocardial wall provided incremental prognostic information for VT/VF over clinical and echocardiographic parameters (C statistic 0.71 versus 0.69; P=0.005).Assessment of regional longitudinal myocardial deformation in the inferior region provided incremental prognostic information over clinical and echocardiographic risk factors in predicting ventricular tachyarrhythmias.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

  View details for DOI 10.1161/CIRCIMAGING.116.005096

  View details for Web of Science ID 000394390100004

  View details for PubMedID 28003221

• Effectiveness and Safety of an Independently Run Nurse Practitioner Outpatient Cardioversion Program (2009 to 2014) AMERICAN JOURNAL OF CARDIOLOGY Norton, L., Tsiperfal, A., Cook, K., Bagdasarian, A., Varady, J., Shah, M., Wang, P. 2016; 118 (12): 1842-1846

  Abstract

  Sustained growth in the arrhythmia population at Stanford Health Care led to an independent nurse practitioner-run outpatient direct current cardioversion (DCCV) program in 2012. DCCVs performed by a medical doctor, a nurse practitioner under supervision, or nurse practitioners from 2009 to 2014 were compared for safety and efficacy. A retrospective review of the electronic medical records system (Epic) was performed on biodemographic data, cardiovascular risk factors, medication history, procedural data, and DCCV outcomes. A total of 869 DCCVs were performed on 557 outpatients. Subjects were largely men with an average age of 65 years; 1/3 were obese; most had atrial fibrillation; and majority of subjects were on warfarin. The success rate of the DCCVs was 93.4% (812 of 869) with no differences among the groups. There were no short-term complications: stroke, myocardial infarction, or death. The length of stay was shortest in the NP group compared to the other groups (p <0.001). In conclusion, the success rate of DCCV in all groups was extremely high, and there were no complications in any of the DCCV groups.

  View details for DOI 10.1016/j.amjcard.2016.08.074

  View details for Web of Science ID 000389868400011

  View details for PubMedID 27771002

• Bipolar left ventricular pacing is associated with significant reduction in heart failure or death in CRT-D patients with LBBB HEART RHYTHM Jame, S., Kutyifa, V., Aktas, M. K., McNitt, S., Polonsky, B., Al-Ahmad, A., Zareba, W., Moss, A., Wang, P. J. 2016; 13 (7): 1468-1474

  Abstract

  There are limited data on the significance of left ventricular (LV) lead pacing polarity to predict clinical outcomes.We aimed to determine the association between the LV lead pacing polarity for heart failure (HF) or death and ventricular tachyarrhythmias (VTA) in patients enrolled in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy), receiving a cardiac resynchronization therapy device with implanted cardioverter-defibrillator (CRT-D).We retrospectively analyzed LV pacing polarity. Patients with LV bipolar leads paced between LV ring and LV tip were identified as True Bipolar, while those with LV bipolar leads paced between LV tip or LV ring and right ventricular coil or unipolar leads were identified as Unipolar/Extended Bipolar. Kaplan-Meier survival analyses and multivariate Cox proportional hazards regression models were used.Of the 969 patients, 421 had True Bipolar pacing while the remainder (n = 548) had Unipolar/Extended Bipolar pacing. Among patients with left bundle branch block (LBBB), True Bipolar pacing was associated with lower cumulative incidence of death (P = .022) and HF/death (P = .046) compared to those with Unipolar/Extended Bipolar LV pacing. After adjustment for clinical covariates, bipolar LV pacing in LBBB patients was associated with 54% lower risk for death (HR: 0.46; 95% CI: 0.24-0.88; P = .020) and 32% lower risk for HF/death (HR: 0.68; 95% CI: 0.46-1.00; P = .048) compared to Unipolar/Extended Bipolar LV pacing, but not in those with non-LBBB. No association was seen with risk of ventricular tachyarrhythmia.True Bipolar LV pacing configuration is associated with a significantly lower risk of HF/death and all-cause mortality in CRT-D patients with LBBB.

  View details for DOI 10.1016/j.hrthm.2016.03.009

  View details for Web of Science ID 000378090000014

  View details for PubMedID 26961303

• Cost-Effectiveness of Percutaneous Closure of the Left Atrial Appendage in Atrial Fibrillation Based on Results From PROTECT AF Versus PREVAIL CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Freeman, J. V., Hutton, D. W., Barnes, G. D., Zhu, R. P., Owens, D. K., Garber, A. M., Go, A. S., Hlatky, M. A., Heidenreich, P. A., Wang, P. J., Al-Ahmad, A., Turakhia, M. P. 2016; 9 (6)

  Abstract

  Randomized trials of left atrial appendage (LAA) closure with the Watchman device have shown varying results, and its cost effectiveness compared with anticoagulation has not been evaluated using all available contemporary trial data.We used a Markov decision model to estimate lifetime quality-adjusted survival, costs, and cost effectiveness of LAA closure with Watchman, compared directly with warfarin and indirectly with dabigatran, using data from the long-term (mean 3.8 year) follow-up of Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation (PROTECT AF) and Prospective Randomized Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation (PREVAIL) randomized trials. Using data from PROTECT AF, the incremental cost-effectiveness ratios compared with warfarin and dabigatran were $20 486 and $23 422 per quality-adjusted life year, respectively. Using data from PREVAIL, LAA closure was dominated by warfarin and dabigatran, meaning that it was less effective (8.44, 8.54, and 8.59 quality-adjusted life years, respectively) and more costly. At a willingness-to-pay threshold of $50 000 per quality-adjusted life year, LAA closure was cost effective 90% and 9% of the time under PROTECT AF and PREVAIL assumptions, respectively. These results were sensitive to the rates of ischemic stroke and intracranial hemorrhage for LAA closure and medical anticoagulation.Using data from the PROTECT AF trial, LAA closure with the Watchman device was cost effective; using PREVAIL trial data, Watchman was more costly and less effective than warfarin and dabigatran. PROTECT AF enrolled more patients and has substantially longer follow-up time, allowing greater statistical certainty with the cost-effectiveness results. However, longer-term trial results and postmarketing surveillance of major adverse events will be vital to determining the value of the Watchman in clinical practice.

  View details for DOI 10.1161/CIRCEP.115.003407

  View details for Web of Science ID 000378143300006

  View details for PubMedID 27307517

  View details for PubMedCentralID PMC4911813

• Brain natriuretic peptide and the risk of ventricular tachyarrhythmias in mildly symptomatic heart failure patients enrolled in MADIT-CRT HEART RHYTHM Medina, A., Moss, A. J., McNitt, S., Zareba, W., Wang, P. J., Goldenberg, I. 2016; 13 (4): 852-859

  View details for DOI 10.1016/j.hrthm.2015.12.024

  View details for Web of Science ID 000372369100013

• The precise timing of tachycardia entrainment is determined by the postpacing interval, the tachycardia cycle length, and the pacing rate: Theoretical insights and practical applications HEART RHYTHM Kaiser, D. W., Hsia, H. H., Dubin, A. M., Liem, L. B., Viswanathan, M. N., Zei, P. C., Wang, P. J., Narayan, S. M., Turakhia, M. P. 2016; 13 (3): 695-703

  View details for DOI 10.1016/j.hrthm.2015.11.032

  View details for Web of Science ID 000372367800012

• Sex Differences in Device Therapies for Ventricular Arrhythmias or Death in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) Trial JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Tompkins, C. M., Kutyifa, V., Arshad, A., McNitt, S., Polonsky, B., Wang, P. J., Moss, A. J., Zareba, W. 2015; 26 (8): 862-871

  Abstract

  Studies suggest that women with ischemic heart disease are less likely to experience appropriate ICD therapies for ventricular arrhythmias (VT/VF). We evaluated the influence of sex on arrhythmic events or death in subjects enrolled in MADIT-CRT.Arrhythmic event rates, defined as VT/VF treated with defibrillator therapy or all-cause death, were determined among 1,790 subjects enrolled in MADIT-CRT with documented 3-year follow-up. Predictors of VT/VF/death were identified using multivariate analysis. Ninety-one (21%) women and 466 (35%) men experienced VT/VF/death over the follow-up period. The overall probability of VT/VF/death was significantly lower in women versus men (HR 0.62; P < 0.001). The probability of VT/VF/death was the lowest in women with ischemic heart disease (HR 0.51; P = 0.003). In ICD subjects, the 3-year risk of VT/VF was lower in ischemic women versus men (P = 0.021), and in nonischemic women versus men (P = 0.049). The probability of VT/VF/death was significantly lower in women (HR 0.52; P = 0.007) and men (HR 0.74; P = 0.018) with LBBB who received CRT-D. Appropriate shock therapy strongly correlated with increased risk of death during postshock follow-up in women (HR 5.18; P = 0.001) and men (HR 1.63; P = 0.033); interaction P value of 0.034.In this substudy of MADIT-CRT, sex, etiology of heart disease and type of device implanted significantly influenced subsequent risk for VT/VF or death. Women with ischemic heart disease and women with LBBB who received CRT-D had the lowest incidence of VT/VF or death when compared to men. Appropriate shock therapy was a strong predictor of death, particularly in women.

  View details for DOI 10.1111/jce.12701

  View details for Web of Science ID 000358686300008

  View details for PubMedID 25929699

• Feasibility of Extended Ambulatory Electrocardiogram Monitoring to Identify Silent Atrial Fibrillation in High-risk Patients: The Screening Study for Undiagnosed Atrial Fibrillation (STUDY-AF) CLINICAL CARDIOLOGY Turakhia, M. P., Ullal, A. J., Hoang, D. D., Than, C. T., Miller, J. D., Friday, K. J., Perez, M. V., Freeman, J. V., Wang, P. J., Heidenreich, P. A. 2015; 38 (5): 285-292

  Abstract

  Identification of silent atrial fibrillation (AF) could prevent stroke and other sequelae.Screening for AF using continuous ambulatory electrocardiographic (ECG) monitoring can detect silent AF in asymptomatic in patients with known risk factors.We performed a single-center prospective screening study using a wearable patch-based device that provides up to 2 weeks of continuous ambulatory ECG monitoring (iRhythm Technologies, Inc.). Inclusion criteria were age ≥55 years and ≥2 of the following risk factors: coronary disease, heart failure, hypertension, diabetes, sleep apnea. We excluded patients with prior AF, stroke, transient ischemic attack, implantable pacemaker or defibrillator, or with palpitations or syncope in the prior year.Out of 75 subjects (all male, age 69 ± 8.0 years; ejection fraction 57% ± 8.7%), AF was detected in 4 subjects (5.3%; AF burden 28% ± 48%). Atrial tachycardia (AT) was present in 67% (≥4 beats), 44% (≥8 beats), and 6.7% (≥60 seconds) of subjects. The combined diagnostic yield of sustained AT/AF was 11%. In subjects without sustained AT/AF, 11 (16%) had ≥30 supraventricular ectopic complexes per hour.Outpatient extended ECG screening for asymptomatic AF is feasible, with AF identified in 1 in 20 subjects and sustained AT/AF identified in 1 in 9 subjects, respectively. We also found a high prevalence of asymptomatic AT and frequent supraventricular ectopic complexes, which may be relevant to development of AF or stroke. If confirmed in a larger study, primary screening for AF could have a significant impact on public health.

  View details for DOI 10.1002/clc.22387

  View details for Web of Science ID 000354748000005

  View details for PubMedID 25873476

  View details for PubMedCentralID PMC4654330

• The association between biventricular pacing and cardiac resynchronization therapy-defibrillator efficacy when compared with implantable cardioverter defibrillator on outcomes and reverse remodelling EUROPEAN HEART JOURNAL Ruwald, A., Kutyifa, V., Ruwald, M. H., Solomon, S., Daubert, J. P., Jons, C., Brenyo, A., McNitt, S., Duc Do, D., Tanabe, K., Al-Ahmad, A., Wang, P., Moss, A. J., Zareba, W. 2015; 36 (7): 440-448

  Abstract

  Previous studies on biventricular (BIV) pacing and cardiac resynchronization therapy-defibrillator (CRT-D) efficacy have used arbitrarily chosen BIV pacing percentages, and no study has employed implantable cardioverter defibrillator (ICD) patients as a control group.Using Kaplan-Meier plots, we estimated the threshold of BIV pacing percentage needed for CRT-D to be superior to ICD on the end-point of heart failure (HF) or death in 1219 left bundle branch block (LBBB) patients in the MADIT-CRT trial. Patients were censored at the time of crossover. In multivariable Cox analyses, no difference was seen in the risk of HF/death between ICD and CRT-D patients with BIV pacing ≤90% [HR = 0.78 (0.47-1.30), P = 0.344], and with increasing BIV pacing the risk of HF/death was decreased [CRT-D BIV 91-96% vs. ICD: HR = 0.63 (0.42-0.94), P = 0.024 and CRT-D BIV ≥97% vs. ICD: HR = 0.32 (0.23-0.44), P < 0.001]. The risk of death alone was reduced by 52% in CRT-D patients with BIV ≥97% (HR = 0.48, P < 0.016), when compared with ICD patients. Within the CRT-D group, for every 1 percentage point increase in BIV pacing, the risk of HF/death and death alone significantly decreased by 6 and 10%, respectively. Increasing BIV pacing percentage was associated with significant reductions in left ventricular volume.In patients with LBBB, who were in sinus rhythm at enrolment, BIV pacing exceeding 90% was associated with a benefit of CRT-D in HF/death when compared with ICD patients. Furthermore, BIV pacing ≥97% was associated with an even further reduction in HF/death, a significant 52% reduction in death alone, and increased reverse remodelling. Clinical trials.gov identifier: NCT00180271.

  View details for DOI 10.1093/eurheartj/ehu294

  View details for Web of Science ID 000351589000016

• Comparison of Age (<75 Years Versus >= 75 Years) to Risk of Ventricular Tachyarrhythmias and Implantable Cardioverter Defibrillator Shocks (from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) AMERICAN JOURNAL OF CARDIOLOGY Aktas, M. K., Goldenberg, I., Moss, A. J., Huang, D. T., Kutyifa, V., Wang, P. J., Brenyo, A., McNitt, S., Zareba, W., Barsheshet, A. 2014; 114 (12): 1855-1860

  Abstract

  There are limited data regarding the effect of age on the risk of ventricular tachyarrhythmias (VTAs). The present study was designed to compare the risk for VTAs in young and older patients with left bundle branch block (LBBB) and mildly symptomatic heart failure who receive device therapy. The risk of the first ventricular tachycardia (VT) or ventricular fibrillation (VF) event and the risk of first appropriate implantable cardioverter defibrillator (ICD) shock was compared between young (<75 years, n = 1,037) and older (≥75 years, n = 227) patients with LBBB enrolled in Multicenter Automatic Implantation Trial with Cardiac Resynchronization Therapy. The cumulative incidence of a first VTA through 2 years of follow-up was significantly lower in older patients than in younger patients. Multivariate analysis showed that older patients experienced a significantly lower risk of VT/VF (hazard ratio 0.38, 95% confidence interval 0.22 to 0.64, p <0.001) and a significantly lower risk of appropriate ICD shocks (hazard ratio 0.37, 95% confidence interval 0.17 to 0.82, p = 0.014) compared with younger patients. Each increasing decade of life was associated with a 19% (p = 0.002) and 22% (p = 0.018) reduction in the risk of VT/VF and appropriate ICD shocks, respectively. The lower risk of VT/VF and appropriate ICD shocks in older patients was evident in patients implanted with an ICD only and in those implanted with a cardiac resynchronization therapy with defibrillator. In conclusion, in patients with LBBB and mild symptoms of heart failure, aging is associated with a significant decrease in the incidence of VT/VF and ICD shocks.

  View details for DOI 10.1016/j.amjcard.2014.09.026

  View details for Web of Science ID 000346887300012

  View details for PubMedID 25438913

• Association Between Frequency of Atrial and Ventricular Ectopic Beats and Biventricular Pacing Percentage and Outcomes in Patients With Cardiac Resynchronization Therapy JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Ruwald, M. H., Mittal, S., Ruwald, A., Aktas, M. K., Daubert, J. P., McNitt, S., Al-Ahmad, A., Jons, C., Kutyifa, V., Steinberg, J. S., Wang, P., Moss, A. J., Zareba, W. 2014; 64 (10): 971-981

  Abstract

  A high percentage of biventricular pacing is required for optimal outcome in patients treated with cardiac resynchronization therapy (CRT), but the influence of ectopic beats on the success of biventricular pacing has not been well established.This study sought to determine if increased ectopic beats reduce the chance of high biventricular pacing percentage and are associated with subsequent adverse outcomes.From the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy), 801 patients with an implanted CRT-defibrillator device with data available on biventricular pacing percentage and pre-implantation 24-h Holter recordings were included. Using logistic regression, we estimated the influence of ectopic beats on the percentage of biventricular pacing. Reverse remodeling was measured as reductions in atrial and left ventricular end-systolic volumes (LVESV) at 1 year. Cox models were used to assess the influence of ectopic beats on the outcomes of heart failure (HF) or death, ventricular tachyarrhythmias (VTAs), and death.In the pre-implantation Holter recording, ectopic beats accounted for a mean 3.2 ± 5.5% of all beats. The probability of subsequent low biventricular pacing percentage (<97%) was increased 3-fold (odds ratio: 3.37; 95% confidence interval: 1.74 to 6.50; p < 0.001) in patients with 0.1% to 1.5% ectopic beats and 13-fold (odds ratio: 13.42; 95% confidence interval: 7.02 to 25.66; p < 0.001) in patients with >1.5% ectopic beats compared with those with <0.1% ectopic beats. Patients with ≥0.1% ectopic beats had significantly less reverse remodeling (percent reduction in LVESV 31 ± 15%) than patients with <0.1% ectopic beats (percent reduction in LVESV 39 ± 14%; p < 0.001). The risk of HF/death and VTA was increased significantly in those with 0.1% to 1.5% ectopic beats (hazard ratio: 3.13 and 1.84, respectively) and for >1.5% ectopic beats (hazard ratio: 2.38 and 2.74, respectively).Relatively low frequencies of ectopic beats (≥0.1%) dramatically increase the probability of low biventricular pacing (<97%), with reduced CRT efficacy by less reverse remodeling and higher risk of HF/death and VTA. This supports pre-implantation Holter monitoring of patients selected for CRT for optimal outcome. (MADIT-CRT: Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy; NCT00180271).

  View details for DOI 10.1016/j.jacc.2014.06.1177

  View details for Web of Science ID 000341085900003

  View details for PubMedID 25190230

• Association Between Success Rate and Citation Count of Studies of Radiofrequency Catheter Ablation for Atrial Fibrillation Possible Evidence of Citation Bias CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Perino, A. C., Hoang, D. D., Holmes, T. H., Santangeli, P., Heidenreich, P. A., Perez, M. V., Wang, P. J., Turakhia, M. P. 2014; 7 (5): 687-692

  View details for DOI 10.1161/CIRCOUTCOMES.114.000912

  View details for Web of Science ID 000342365200011

• Cardiac resynchronization therapy is associated with reductions in left atrial volume and inappropriate implantable cardioverter-defibrillator therapy in MADIT-CRT HEART RHYTHM Slyngstad, T., Ruwald, A. H., Kutyifa, V., McNitt, S., Polonsky, B., Solomon, S. D., Foster, E., Goldenberg, I., Wang, P. J., Klein, H., Zareba, W., Moss, A. J. 2014; 11 (6): 1001-1007

  Abstract

  There are no prior studies assessing the relationship between left atrial volume (LAV) and inappropriate implantable cardioverter-defibrillator (ICD) therapy following treatment with cardiac resynchronization therapy.The purpose of this study was to investigate the hypothesis that patients randomized to cardiac resynchronization therapy with defibrillator (CRT-D) in the Multicenter Automatic Defibrillator Trial-Cardiac Resynchronization Therapy (MADIT-CRT) who had significant LAV reductions would have reduced risks of inappropriate ICD therapy.Cardiac resynchronization remodeling was assessed by measuring LAV change between baseline and 12-month echocardiograms in 751 CRT-D treated patients. Patients were stratified into quartiles based on percent reduction of LAV change. High LAV responders were those in the highest 3 quartiles of LAV reduction (LAV reduction ≥21%). Low LAV responders were those in the lowest quartile of LAV reduction (LAV reduction <21%). Clinical factors associated with ≥21% reduction in LAV were evaluated by linear regression analysis.In Cox proportional hazards regression analyses, high LAV responders had a 39% reduction in the risk of inappropriate therapy (hazard ratio 0.61, P = .04) and left bundle branch block patients exhibited an even greater risk reduction in inappropriate therapy (hazard ratio 0.51, P = .02) compared to low LAV responders during follow-up extending up to 3 years after the 12-month echocardiogram. High LAV responders also had a significantly lower risk of heart failure or death during follow-up than did low LAV responders.A ≥21% reduction in LAV with cardiac resynchronization therapy is associated with significant reductions in inappropriate ICD therapy and in heart failure or death during a 3-year follow-up.

  View details for DOI 10.1016/j.hrthm.2014.01.033

  View details for Web of Science ID 000336395600014

  View details for PubMedID 24502968

• A histological and mechanical analysis of the cardiac lead-tissue interface: implications for lead extraction. Acta biomaterialia Rennert, R. C., Rustad, K., Levi, K., Harwood, M., Sorkin, M., Wong, V. W., Al-Ahmad, A., Zei, P., Hsia, H., Beygui, R. E., Norton, L., Wang, P., Gurtner, G. C. 2014; 10 (5): 2200-2208

  Abstract

  The major risks of pacemaker and implantable cardioverter defibrillator extraction are attributable to the fibrotic tissue that encases them in situ, yet little is known about the cellular and functional properties of this response. In the present research, we performed a histological and mechanical analysis of human tissue collected from the lead-tissue interface to better understand this process and provide insights for the improvement of lead design and extraction. The lead-tissue interface consisted of a thin cellular layer underlying a smooth, acellular surface, followed by a circumferentially organized collagen-rich matrix. 51.8±4.9% of cells were myofibroblasts via immunohistochemistry, with these cells displaying a similar circumferential organization. Upon mechanical testing, samples exhibited a triphasic force-displacement response consisting of a toe region during initial tensioning, a linear elastic region and a yield and failure region. Mean fracture load was 5.6±2.1N, and mean circumferential stress at failure was 9.5±4.1MPa. While the low cellularity and fibrotic composition of tissue observed herein is consistent with a foreign body reaction to an implanted material, the significant myofibroblast response provides a mechanical explanation for the contractile forces complicating extractions. Moreover, the tensile properties of this tissue suggest the feasibility of circumferential mechanical tissue disruption, similar to balloon angioplasty devices, as a novel approach to assist with lead extraction.

  View details for DOI 10.1016/j.actbio.2014.01.008

  View details for PubMedID 24434537

• Shock-induced ventricular tachycardia: what is the mechanism? Pacing and clinical electrophysiology : PACE Santangeli, P., Hsia, H. H., Wang, P. J., Al-Ahmad, A. 2014; 37 (4): 516-519

  View details for DOI 10.1111/pace.12244

  View details for PubMedID 23980924

• The Effect of Intermittent Atrial Tachyarrhythmia on Heart Failure or Death in Cardiac Resynchronization Therapy With Defibrillator Versus Implantable Cardioverter-Defibrillator Patients A MADIT-CRT Substudy (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Ruwald, A., Pietrasik, G., Goldenberg, I., Kutyifa, V., Daubert, J. P., Ruwald, M. H., Jons, C., McNitt, S., Wang, P., Zareba, W., Moss, A. J. 2014; 63 (12): 1190-1197

  Abstract

  This study aimed to investigate the effect of both history of intermittent atrial tachyarrhythmias (IAT) and in-trial IAT on the risk of heart failure (HF) or death comparing cardiac resynchronization therapy with defibrillator (CRT-D) to implantable cardioverter-defibrillator (ICD) treatment in mildly symptomatic HF patients with left bundle branch block (LBBB).Limited data exist regarding the benefit of CRT-D in patients with IAT.The benefit of CRT-D in reducing the risk of HF/death was evaluated using multivariate Cox models incorporating the presence of, respectively, a history of IAT at baseline and time-dependent development of in-trial IAT during follow-up in 1,264 patients with LBBB enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) study.The overall beneficial effect of CRT-D versus ICD on the risk of HF/death was not significantly different between LBBB patients with or without history of IAT (HR: 0.50, p = 0.028, and HR: 0.46, p < 0.001, respectively; p for interaction = 0.79). Among patients who had in-trial IAT, CRT-D was associated with a significant 57% reduction in the risk of HF/death compared with ICD-only therapy (HR: 0.43, p = 0.047), similar to the effect of the device among patients who did not have IAT (HR: 0.47, p < 0.001; p for interaction = 0.85). The percentage of patients with biventricular pacing ≥92% was similar in both groups (p = 0.43). Consistent results were shown for the benefit of CRT-D among patients who had in-trial atrial fibrillation/flutter (HR: 0.30, p = 0.027; p for interaction = 0.41).In the MADIT-CRT study, the clinical benefit of CRT-D in LBBB patients was not attenuated by prior history of IAT or by the development of in-trial atrial tachyarrhythmias. (MADIT-CRT: Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy; NCT00180271).

  View details for DOI 10.1016/j.jacc.2013.10.074

  View details for Web of Science ID 000333256100012

  View details for PubMedID 24333490

• Exercise capacity and paroxysmal atrial fibrillation in patients with hypertrophic cardiomyopathy. Heart Azarbal, F., Singh, M., Finocchiaro, G., Le, V., Schnittger, I., Wang, P., Myers, J., Ashley, E., Perez, M. 2014; 100 (8): 624-630

  Abstract

  Atrial fibrillation (AF) is the most common arrhythmia among patients with hypertrophic cardiomyopathy (HCM). The relationship between paroxysmal AF and exercise capacity in this population is incompletely understood.Patients with HCM underwent symptom-limited cardiopulmonary testing with expired gas analysis at Stanford Hospital between October 2006 and October 2012. Baseline demographics, medical histories and resting echocardiograms were obtained for all subjects. Diagnosis of AF was established by review of medical records and baseline ECG. Those with paroxysmal AF were in sinus rhythm at the time of cardiopulmonary testing with expired gas analysis. Exercise intolerance was defined as peak VO2<20 mL/kg/min. We used multivariate logistic regression to evaluate the association between exercise intolerance and paroxysmal AF.Among the 265 patients recruited, 55 had AF (28 paroxysmal and 27 permanent). Compared with those without AF, subjects with paroxysmal AF were older, more likely to use antiarrhythmic and anticoagulant medications, and had larger left atria. Patients with paroxysmal AF achieved lower peak VO2 (21.9±9.2 mL/kg/min vs 26.9±10.8 mL/kg/min, p=0.02) and were more likely to have exercise intolerance (61% vs 28%, p<0.001) compared with those without AF. After adjustment for age, sex and body mass index (BMI) exercise intolerance remained significantly associated with paroxysmal AF (OR 4.65, 95% CI 1.83 to 11.83, p=0.001).Patients with HCM and paroxysmal AF demonstrate exercise intolerance despite being in sinus rhythm at the time of exercise testing.

  View details for DOI 10.1136/heartjnl-2013-304908

  View details for PubMedID 24326897

• Accuracy Assessment of Catheter Guidance Technology in Electrophysiology Procedures: A Comparison of a New 3D-Based Fluoroscopy Navigation System to Current Electroanatomic Mapping Systems JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Bourier, F., Fahrig, R., Wang, P., Santangeli, P., Kurzidim, K., Strobel, N., Moore, T., Hinkel, C., Al-Ahmad, A. 2014; 25 (1): 74-83

  Abstract

  With increasing complexity in electrophysiology (EP) procedures, the use of electroanatomic mapping systems (EAMS) as a supplement to fluoroscopy has become common practice. This is the first study that evaluates spatial and point localization accuracy for 2 current EAMS, CARTO3(®) (Biosense Webster, Diamond Bar, CA, USA) and EnSite Velocity(®) (St. Jude Medical Inc., St. Paul, MN, USA), and for a novel overlay guidance (OG) software (Siemens AG, Forchheim, Germany) in a phantom experiment.A C-arm CT scan was performed on an acrylic phantom containing holes and location markers. Spatial accuracy was assessed for each system using distance measurements involving known markers inside the phantom and properly placed catheters. Anatomical maps of the phantom were acquired by each EAMS, whereas the 3D-based OG software superimposed an overlay image of the phantom, segmented from the C-arm CT data set, onto biplane fluoroscopy. Registration processes and landmark measurements quantitatively assessed the spatial accuracy of each technology with respect to the ground truth phantom. Point localization performance was 0.49 ± 0.25 mm in OG, 0.46 ± 0.17 mm in CARTO3(®) and 0.79 ± 0.83 mm in EnSite(®) . The registration offset between virtual visualization and reality was 1.10 ± 0.52 mm in OG, 1.62 ± 0.77 mm in CARTO3(®) and 2.02 ± 1.21 mm in EnSite(®) . The offset to phantom C-arm CT landmark measurements was 0.30 ± 0.26 mm in OG, 0.24 ± 0.21 mm in CARTO3(®) and 1.32 ± 0.98 mm in EnSite(®) .Each of the evaluated EP guidance systems showed a high level of accuracy; the observed offsets between the virtual 3D visualization and the real phantom were below a clinically relevant threshold of 3 mm.

  View details for Web of Science ID 000334516800019

  View details for PubMedID 24102965

• Decisional Balance among Potential Implantable Cardioverter Defibrillator Recipients: Development of the ICD-Decision Analysis Scale (ICD-DAS) PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Hazelton, A. G., Sears, S. F., Ford, J., Cahill, J., Nekkanti, R., DeAntonio, H., Ottoboni, L., Norton, L., Wang, P. 2014; 37 (1): 63-72

  Abstract

  Sudden cardiac death is a well-documented public health problem and the implantable cardioverter defibrillator (ICD) has demonstrated benefit in reducing mortality. Prospective patients must identify and evaluate the ICD's pros and cons and produce a personal decision. The purpose of this study was to create and evaluate a measure of patient-evaluated pros and cons of the ICD, and its relationship to patient decision regarding ICD implantation.The ICD-decision analysis scale (ICD-DAS) was created and tested in prospective ICD recipients (N = 104). Factor analysis was performed to evaluate interitem relationships, and subsequently, identified subscales; additional psychosocial measures were used to predict the ICD decision. A two-factor measure for ICD decision making was established with two subscales: ICD Pros and ICD Cons. The subscales have high internal consistency and were strong predictors of intent to choose an ICD. Other psychosocial measures were not significantly predictive of ICD Choice, yet simultaneous entry of ICD Pros and Cons subscales resulted in a significant increase in R(2) , F(2, 59) = 19.36, P < 0.001. The full model was significantly greater than zero, F(11, 70) = 5.017, P < 0.001, R(2)  = 0.48.The ICD-DAS provides the first empirically tested and clinically useful approach to understanding the specific pros and cons for prospective ICD patients. The measure can assist clinicians with patient-centered discussions regarding sudden cardiac arrest treatments. The ICD-DAS will allow for the provision of tailored education or counseling and may be used to predict postdecision outcomes.

  View details for DOI 10.1111/pace.12253

  View details for Web of Science ID 000329258600008

  View details for PubMedID 24219117

• Palpitations in a patient with a dual-chamber pacemaker: what is the mechanism? Heart rhythm Santangeli, P., Tsiperfal, A., Wang, P. J., Al-Ahmad, A. 2013; 10 (12): 1824-1825

  View details for DOI 10.1016/j.hrthm.2013.07.036

  View details for PubMedID 23891958

• PHLEBITIS IN AMIODARONE ADMINISTRATION: INCIDENCE, CONTRIBUTING FACTORS, AND CLINICAL IMPLICATIONS AMERICAN JOURNAL OF CRITICAL CARE Norton, L., Ottoboni, L. K., Varady, A., Yang-Lu, C., Becker, N., Cotter, T., Pummer, E., Haynes, A., Forsey, L., Matsuda, K., Wang, P. 2013; 22 (6): 498-505

  Abstract

  Intravenous amiodarone is an important treatment for arrhythmias, but peripheral infusion is associated with direct irritation of vessel walls and phlebitis rates of 8% to 55%. Objectives To determine the incidence and factors contributing to the development of amiodarone-induced phlebitis in the coronary care unit in an academic medical center and to refine the current practice protocol.Medical records from all adult patients during an 18-month period who received intravenous amiodarone while in the critical care unit were reviewed retrospectively. Route of administration, location, concentration, and duration of amiodarone therapy and factors associated with occurrence of phlebitis were examined. Descriptive statistics and regression methods were used to identify incidence and phlebitis factors.In the final sample of 105 patients, incidence of phlebitis was 40%, with a 50% recurrence rate. All cases of phlebitis occurred in patients given a total dose of 3 g via a peripheral catheter, and one-quarter of these cases (n = 10) developed at dosages less than 1 g. Pain, redness, and warmth were the most common indications of phlebitis. Total dosage given via a peripheral catheter, duration of infusion, and number of catheters were significantly associated with phlebitis.Amiodarone-induced phlebitis occurred in 40% of this sample at higher drug dosages. A new practice protocol resulted from this study. An outcome study is in progress.

  View details for DOI 10.4037/ajcc2013460

  View details for Web of Science ID 000328167700012

  View details for PubMedID 24186821

• Outcomes from a Postgraduate Biomedical Technology Innovation Training Program: The First 12 Years of Stanford Biodesign ANNALS OF BIOMEDICAL ENGINEERING Brinton, T. J., Kurihara, C. Q., Camarillo, D. B., Pietzsch, J. B., Gorodsky, J., Zenios, S. A., Doshi, R., Shen, C., Kumar, U. N., Mairal, A., Watkins, J., Popp, R. L., Wang, P. J., Makower, J., Krummel, T. M., Yock, P. G. 2013; 41 (9): 1803-1810

  Abstract

  The Stanford Biodesign Program began in 2001 with a mission of helping to train leaders in biomedical technology innovation. A key feature of the program is a full-time postgraduate fellowship where multidisciplinary teams undergo a process of sourcing clinical needs, inventing solutions and planning for implementation of a business strategy. The program places a priority on needs identification, a formal process of selecting, researching and characterizing needs before beginning the process of inventing. Fellows and students from the program have gone on to careers that emphasize technology innovation across industry and academia. Biodesign trainees have started 26 companies within the program that have raised over $200 million and led to the creation of over 500 new jobs. More importantly, although most of these technologies are still at a very early stage, several projects have received regulatory approval and so far more than 150,000 patients have been treated by technologies invented by our trainees. This paper reviews the initial outcomes of the program and discusses lessons learned and future directions in terms of training priorities.

  View details for DOI 10.1007/s10439-013-0761-2

  View details for Web of Science ID 000323736800002

  View details for PubMedID 23404074

• Risk factors for atrial fibrillation and their population burden in postmenopausal women: the Women's Health Initiative Observational Study. Heart Perez, M. V., Wang, P. J., Larson, J. C., Soliman, E. Z., Limacher, M., Rodriguez, B., Klein, L., Manson, J. E., Martin, L. W., Prineas, R., Connelly, S., Hlatky, M., Wassertheil-Smoller, S., Stefanick, M. L. 2013; 99 (16): 1173-1178

  Abstract

  OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia in women. Large studies evaluating key AF risk factors in older women are lacking. We aimed to identify risk factors for AF in postmenopausal women and measure population burden of modifiable risk factors. DESIGN: Prospective observational study. SETTING: The Women's Health Initiative (WHI) Observational Study. PATIENTS: 93 676 postmenopausal women were followed for an average of 9.8 years for cardiovascular outcomes. After exclusion of women with prevalent AF or incomplete data, 8252 of the remaining 81 892 women developed incident AF. MAIN OUTCOME MEASURES: Incident AF was identified by WHI-ascertained hospitalisation records and diagnosis codes from Medicare claims. Multivariate Cox hazard regression analysis identified independent risk factors for incident AF. RESULTS: Age, hypertension, obesity, diabetes, myocardial infarction and heart failure were independently associated with incident AF. Hypertension and overweight status accounted for 28.3% and 12.1%, respectively, of the population attributable risk. Hispanic and African-American participants had lower rates of incident AF (HR 0.58, 95% CI 0.47 to 0.70 and HR 0.59, 95% CI 0.53 to 0.65, respectively) than Caucasians. CONCLUSIONS: Caucasian ethnicity, traditional cardiovascular risk factors and peripheral arterial disease were independently associated with higher rates of incident AF in postmenopausal women. Hypertension and overweight status accounted for a large proportion of population attributable risk. Measuring burden of modifiable AF risk factors in older women may help target interventions.

  View details for DOI 10.1136/heartjnl-2013-303798

  View details for PubMedID 23756655

• ATP during charging: A failure of therapy? Heart rhythm Santangeli, P., Tsiperfal, A., Wang, P. J., Al-Ahmad, A. 2013; 10 (7): 1091-1093

  View details for DOI 10.1016/j.hrthm.2013.03.010

  View details for PubMedID 23499622

• Clinical significance of ventricular tachyarrhythmias in patients treated with CRT-D HEART RHYTHM Kutyifa, V., Klein, H. U., Wang, P. J., McNitt, S., Polonsky, B., Zima, E., Merkely, B., Moss, A. J., Zareba, W. 2013; 10 (7): 943-950

  Abstract

  Data on the outcome of cardiac resynchronization therapy with defibrillator (CRT-D) in patients developing ventricular arrhythmias are limited.To evaluate the prognostic value of ventricular tachycardia (VT) or ventricular fibrillation (VF) episodes by heart rate in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy trial.Slow VT was defined as VTs with heart rate < 200 beats/min. Fast VT with a heart rate ≥200 beats/min and VF (>250 beats/min) were considered as a combined category. Primary end point was heart failure (HF) or death. Secondary end point included all-cause mortality.There were 228 (12.7%) patients with slow VT and 198 (11.1%) with fast VT/VF. In time-dependent analysis, slow VT was associated with an increased risk of HF/death in CRT-D patients with left branch bundle block (LBBB; hazard ratio [HR] 3.19; 95% confidence interval [CI] 1.83-5.55; P < .001), but not in patients with implantable cardioverter-defibrillator (ICD) (HR 1.03; 95% CI 0.52-2.19; P = .867; interaction P value = .017). CRT-D patients with LBBB and fast VT/VF doubled their risk of HF/death compared to ICD patients (interaction P value = .06). Slow VT events were also predictive of death in CRT-D patients with LBBB (HR 3.48; 95% CI 1.66-7.28; P < .001), but not in ICD patients (interaction P value = .06). Slow VTs were highly predictive of subsequent fast VT/VF (HR 4.33; 95% CI 3.01-6.24; P < .001).Slow VT episodes are predictive of subsequent fast VT/VF. Slow VT and fast VT/VF episodes in CRT-D patients are associated with an increased risk of subsequent HF/death. CRT-D-treated LBBB patients with slow VTs have a significantly higher risk of mortality.

  View details for DOI 10.1016/j.hrthm.2013.04.006

  View details for Web of Science ID 000321497500001

  View details for PubMedID 23639624

• Frequency of Inappropriate Therapy in Patients Implanted with Dual- Versus Single-Chamber ICD Devices in the ICD Arm of MADIT-CRT JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Ruwald, A. H., Sood, N., Ruwald, M. H., Jons, C., Clyne, C. A., McNitt, S., Wang, P., Zareba, W., Moss, A. J. 2013; 24 (6): 672-679

  Abstract

  The majority of implantable cardioverter defibrillators (ICDs) are dual-chamber devices, but studies on the frequency of inappropriate therapy in dual- versus single-chamber devices have shown conflicting results. The aim of this study is to determine whether implantation of dual-chamber ICD devices decrease the incidence of inappropriate therapy without an unacceptable increase in complications.In the ICD arm of the MADIT-CRT study (N = 704), comparisons of single- versus dual-chamber ICD devices were investigated on the endpoints of inappropriate therapy (antitachycardia pacing [ATP] and shocks) and device- and procedure-related complications by use of multivariate Cox proportional hazard regression analysis (hazard ratio dual:single chamber) adjusting for relevant covariates.The frequency of inappropriate therapies in single- and dual-chamber recipients was 41/294 (14%) and 50/410 (12%), respectively. There was no significant difference in overall inappropriate therapy (hazard ratio [HR] = 0.95 [CI: 0.63-1.45], P = 0.95) or inappropriate ATP (HR = 0.98 [CI: 0.61-1.58], P = 0.94), between single- and dual-chamber devices, using single-chamber as a reference (Dual:Single). However, there was a trend toward a decrease in inappropriate shocks (HR = 0.60 [CI: 0.34-1.08], P = 0.09) in the dual-chamber group. The same was evident when only analyzing inappropriate therapy for atrial tachyarrhythmias (HR = 0.88 [CI: 0.56-1.38], P = 0.58). There was no significant difference between the groups in device- or procedure-related complications (HR = 1.54 [CI: 0.82-2.90], P = 0.18).No significant difference was found in inappropriate therapy or complications in patients treated with single- versus dual-chamber ICD devices.

  View details for DOI 10.1111/jce.12099

  View details for Web of Science ID 000319898500011

  View details for PubMedID 23445493

• Drug screening using a library of human induced pluripotent stem cell-derived cardiomyocytes reveals disease-specific patterns of cardiotoxicity. Circulation Liang, P., Lan, F., Lee, A. S., Gong, T., Sanchez-Freire, V., Wang, Y., Diecke, S., Sallam, K., Knowles, J. W., Wang, P. J., Nguyen, P. K., Bers, D. M., Robbins, R. C., Wu, J. C. 2013; 127 (16): 1677-1691

  Abstract

  Cardiotoxicity is a leading cause for drug attrition during pharmaceutical development and has resulted in numerous preventable patient deaths. Incidents of adverse cardiac drug reactions are more common in patients with preexisting heart disease than the general population. Here we generated a library of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from patients with various hereditary cardiac disorders to model differences in cardiac drug toxicity susceptibility for patients of different genetic backgrounds.Action potential duration and drug-induced arrhythmia were measured at the single cell level in hiPSC-CMs derived from healthy subjects and patients with hereditary long QT syndrome, familial hypertrophic cardiomyopathy, and familial dilated cardiomyopathy. Disease phenotypes were verified in long QT syndrome, hypertrophic cardiomyopathy, and dilated cardiomyopathy hiPSC-CMs by immunostaining and single cell patch clamp. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and the human ether-a-go-go-related gene expressing human embryonic kidney cells were used as controls. Single cell PCR confirmed expression of all cardiac ion channels in patient-specific hiPSC-CMs as well as hESC-CMs, but not in human embryonic kidney cells. Disease-specific hiPSC-CMs demonstrated increased susceptibility to known cardiotoxic drugs as measured by action potential duration and quantification of drug-induced arrhythmias such as early afterdepolarizations and delayed afterdepolarizations.We have recapitulated drug-induced cardiotoxicity profiles for healthy subjects, long QT syndrome, hypertrophic cardiomyopathy, and dilated cardiomyopathy patients at the single cell level for the first time. Our data indicate that healthy and diseased individuals exhibit different susceptibilities to cardiotoxic drugs and that use of disease-specific hiPSC-CMs may predict adverse drug responses more accurately than the standard human ether-a-go-go-related gene test or healthy control hiPSC-CM/hESC-CM screening assays.

  View details for DOI 10.1161/CIRCULATIONAHA.113.001883

  View details for PubMedID 23519760

  View details for PubMedCentralID PMC3870148

• Drug screening using a library of human induced pluripotent stem cell-derived cardiomyocytes reveals disease-specific patterns of cardiotoxicity. Circulation Liang, P., Lan, F., Lee, A. S., Gong, T., Sanchez-Freire, V., Wang, Y., Diecke, S., Sallam, K., Knowles, J. W., Wang, P. J., Nguyen, P. K., Bers, D. M., Robbins, R. C., Wu, J. C. 2013; 127 (16): 1677-1691

  View details for DOI 10.1161/CIRCULATIONAHA.113.001883

  View details for PubMedID 23519760

• Dyssynchrony and the Risk of Ventricular Arrhythmias JACC-CARDIOVASCULAR IMAGING Kutyifa, V., Pouleur, A., Knappe, D., Al-Ahmad, A., Gibinski, M., Wang, P. J., McNitt, S., Merkely, B., Goldenberg, I., Solomon, S. D., Moss, A. J., Zareba, W. 2013; 6 (4): 432-444

  Abstract

  The aim of our study was to evaluate the relationship between left ventricular (LV) dyssynchrony and the risk of ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy) trial.Intraventricular mechanical dyssynchrony might be an important factor in ventricular arrhythmogenesis by enhancing electrical heterogeneity in heart failure patients. The effects of dyssynchrony have not yet been evaluated in a large cohort of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy with defibrillator (CRT-D) patients.LV dyssynchrony was measured at baseline and at 12-months by speckle-tracking echocardiography, defined as the standard deviation of time to peak systolic strain in 12 LV myocardial segments. The endpoint was the first VT/VF/death or VT/VF. LV dyssynchrony was evaluated in 764 left bundle branch block (LBBB) patients and in 312 non-LBBB patients.Baseline LV dyssynchrony was not predictive of VT/VF/death or VT/VF in LBBB or non-LBBB patients in either treatment arm. In CRT-D patients with LBBB, improvement in LV dyssynchrony over a year was associated with significantly lower incidence of VT/VF/death (p < 0.001) and VT/VF (p < 0.001) compared to ICD patients and to CRT-D patients with unchanged or worsening dyssynchrony. Among LBBB patients, 15% decrease in LV dyssynchrony was associated with lower risk of VT/VF/death (hazard ratio: 0.49, 95% confidence interval: 0.24 to 0.99, p = 0.049) and VT/VF (hazard ratio: 0.30, 95% confidence interval: 0.12 to 0.77, p = 0.009) as compared to ICD patients. Patients without LBBB receiving CRT-D did not show reduction in VT/VF/death or in VT/VF in relation to improving dyssynchrony when evaluating cumulative event rates or risk of events.Baseline LV dyssynchrony did not predict VT/VF/death or VT/VF in mild heart failure patients with or without LBBB. CRT-induced improvement of LV dyssynchrony was associated with significant reduction of ventricular arrhythmias in patients with LBBB.

  View details for DOI 10.1016/j.jcmg.2012.12.008

  View details for Web of Science ID 000317842300003

  View details for PubMedID 23579010

• PAROXYSMAL ATRIAL FIBRILLATION IS ASSOCIATED WITH EXERCISE INTOLERANCE AMONG INDIVIDUALS WITH HYPERTROPHIC CARDIOMYOPATHY 62nd Annual Scientific Session of the American-College-of-Cardiology Azarbal, F., Singh, M., Finocchiaro, G., Le, V., Schnittger, I., Wang, P., Myers, J., Perez, M., Ashley, E. ELSEVIER SCIENCE INC. 2013: E1617–E1617

  View details for Web of Science ID 000316555201722

• DECLINE IN DEVICE-DERIVED ACTIVITY LEVEL IS A SHORT-TERM PROGNOSTIC PREDICTOR OF DEATH 62nd Annual Scientific Session of the American-College-of-Cardiology Jame, S., Polonsky, B., McNitt, S., Al-Ahmad, A., Moss, A., Zareba, W., Wang, P. ELSEVIER SCIENCE INC. 2013: E658–E658

  View details for Web of Science ID 000316555200658

• Effects of cardiac resynchronization therapy on left ventricular mass and wall thickness in mild heart failure patients in MADIT-CRT HEART RHYTHM Kutyifa, V., Solomon, S. D., Bourgoun, M., Shah, A. M., Pouleur, A., Knappe, D., McNitt, S., Wang, P. J., Merkely, B., Pfeffer, M., Moss, A. J., Zareba, W. 2013; 10 (3): 354-360

  Abstract

  The effect of cardiac resynchronization therapy (CRT) on left ventricular wall thickness and left ventricular mass (LVM) is unknown.To evaluate the effects of CRT on septal and posterior wall thickness (SWT and PWT) and LVM in patients with left bundle branch block (LBBB) and non-LBBB vs implantable cardioverter-defibrillator patients and to assess the relationship between CRT-induced changes and cardiac events.We investigated 843 patients with LBBB and 366 patients with non-LBBB enrolled in the Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy (MADIT-CRT) trial to analyze changes in SWT, PWT, and LVM at 12 months and subsequent outcome. The primary end point was heart failure or death; secondary end points included ventricular tachycardia, ventricular fibrillation, or death.In LBBB patients, reduction in SWT, PWT, and LVM was more pronounced in CRT defibrillator (CRT-D) than in implantable cardioverter-defibrillator (SWT:-6.7% ± 4.4% vs-1.0% ± 1.9%; PWT:-6.4% ± 4.3% vs-0.8% ± 1.9%; LVM:-23.6% ± 9.9% vs-5.1% ± 5.1%; P<.001 for all). In CRT-D patients with non-LBBB, LVM reduction was less pronounced; however, changes in SWT and PWT were comparable. Changes in LVM correlated with changes in left ventricular end-diastolic volume. In CRT-D patients with LBBB, reduction in SWT and LVM was associated with reduction in heart failure/death (SWT: hazard ratio 0.94; 95% confidence interval 0.89-0.99 per percent change; P = .03) and ventricular tachycardia/ventricular fibrillation/death (SWT: hazard ratio 0.95; 95% confidence interval 0.91-1.00; P = .04). CRT-D patients with non-LBBB did not show favorable reduction in clinical or arrhythmic end points related to changes in SWT, PWT, or LVM.CRT-D was associated with significant reduction in SWT, PWT, and LVM in patients with LBBB along with left ventricular volume changes and associated favorable clinical and arrhythmia outcomes.

  View details for DOI 10.1016/j.hrthm.2012.11.007

  View details for Web of Science ID 000315773000009

  View details for PubMedID 23174486

• Differences and trends in stroke prevention anticoagulation in primary care vs cardiology specialty management of new atrial fibrillation: The Retrospective Evaluation and Assessment of Therapies in AF (TREAT-AF) study. American heart journal Turakhia, M. P., Hoang, D. D., Xu, X., Frayne, S., Schmitt, S., Yang, F., Phibbs, C. S., Than, C. T., Wang, P. J., Heidenreich, P. A. 2013; 165 (1): 93-101 e1

  Abstract

  Atrial fibrillation and flutter (AF, collectively) cause stroke. We evaluated whether treating specialty influences warfarin prescription in patients with newly diagnosed AF.In the TREAT-AF study, we used Veterans Health Administration health record and claims data to identify patients with newly diagnosed AF between October 2004 and November 2008 and at least 1 internal medicine/primary care or cardiology outpatient encounter within 90 days after diagnosis. The primary outcome was prescription of warfarin.In 141,642 patients meeting the inclusion criteria, the mean age was 72.3 ± 10.2 years, 1.48% were women, and 25.8% had cardiology outpatient care. Cardiology-treated patients had more comorbidities and higher mean CHADS2 scores (1.8 vs 1.6, P < .0001). Warfarin use was higher in cardiology-treated vs primary care only-treated patients (68.6% vs 48.9%, P < .0001). After covariate and site-level adjustment, cardiology care was significantly associated with warfarin use (odds ratio [OR] 2.05, 95% CI 1.99-2.11). These findings were consistent across a series of adjusted models (OR 2.05-2.20), propensity matching (OR 1.98), and subgroup analyses (OR 1.58-2.11). Warfarin use in primary-care-only patients declined from 2004 to 2008 (51.6%-44.0%, P < .0001), whereas the adjusted odds of warfarin receipt with cardiology care (vs primary care) increased from 2004 to 2008 (1.88-2.24, P < .0001).In patients with newly diagnosed AF, we found large differences in anticoagulation use by treating specialty. A divergent 5-year trend of risk-adjusted warfarin use was observed. Treating specialty influences stroke prevention care and may impact clinical outcomes.

  View details for DOI 10.1016/j.ahj.2012.10.010

  View details for PubMedID 23237139

• Differences and trends in stroke prevention anticoagulation in primary care vs cardiology specialty management of new atrial fibrillation: The Retrospective Evaluation and Assessment of Therapies in AF (TREAT-AF) study AMERICAN HEART JOURNAL Turakhia, M. P., Hoang, D. D., Xu, X., Frayne, S., Schmitt, S., Yang, F., Phibbs, C. S., Than, C. T., Wang, P. J., Heidenreich, P. A. 2013; 165 (1): 93-?

  View details for DOI 10.1016/j.ahj.2012.10.010

  View details for Web of Science ID 000312272900017

  View details for PubMedID 23237139

• Left ventricular lead location and the risk of ventricular arrhythmias in the MADIT-CRT trial EUROPEAN HEART JOURNAL Kutyifa, V., Zareba, W., McNitt, S., Singh, J., Hall, W. J., Polonsky, S., Goldenberg, I., Huang, D. T., Merkely, B., Wang, P. J., Moss, A. J., Klein, H. 2013; 34 (3): 184-190

  Abstract

  We aimed to evaluate the influence of left ventricular (LV) lead position on the risk of ventricular tachyarrhythmias in cardiac resynchronization therapy (CRT) patients.Left ventricular (LV) lead position was evaluated by biplane coronary venograms and anterior/posterior, lateral chest X-rays in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy (MADIT-CRT). The LV lead location could be defined in 797 of 1089 patients (73%). The LV lead was placed at the LV apex in 110 (14%) patients, in the anterior position in 146 (18%), in the lateral position in 448 (56%), and in the posterior position in 93 (12%) patients. After adjustment for clinical covariates, lateral or posterior lead location was associated with significantly lower risk of ventricular tachycardia (VT)/ventricular fibrillation (VF) [hazard ratio (HR) = 0.57, 95% confidence interval (CI): 0.38-0.85; P = 0.006] when compared with an anterior lead location. Patients with anterior lead position had similar risk of VT/VF as patients with implantable cardioverter defibrillator (ICD)-only (HR = 1.04, 95% CI: 0.72-1.81; P = 0.837). There was no difference in the risk of mortality between posterior or lateral and anterior LV lead locations.Cardiac resynchronization therapy with posterior or lateral LV lead position is associated with decreased risk of arrhythmic events in comparison with anterior lead location and ICD-only patients. There is no evidence for increased risk of VT/VF episodes associated with CRT.

  View details for DOI 10.1093/eurheartj/ehs334

  View details for Web of Science ID 000313831000009

  View details for PubMedID 23053173

• Effects of Postmenopausal Hormone Therapy on Incident Atrial Fibrillation The Women's Health Initiative Randomized Controlled Trials CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Perez, M. V., Wang, P. J., Larson, J. C., Virnig, B. A., Cochrane, B., Curb, J. D., Klein, L., Manson, J. E., Martin, L. W., Robinson, J., Wassertheil-Smoller, S., Stefanick, M. L. 2012; 5 (6): 1108-1116

  Abstract

  Atrial fibrillation (AF) is less prevalent in women versus men, but associated with higher risks of stroke and death in women. The role hormone therapy plays in AF is not well understood.The Women's Health Initiative randomized postmenopausal women to placebo or conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) if they had a uterus (N=16 608) or to conjugated equine estrogens only if they had prior hysterectomy (N=10 739). Incident AF was identified by ECG and diagnosis codes from Medicare claims or hospitalization records. Hazard ratios for incident AF were estimated using Cox proportional hazards regression. After excluding participants with baseline AF, there were 611 incident AF cases over a mean of 5.6 years among 16 128 estrogen plus progestin participants, and 683 cases over a mean of 7.1 years among 10 251 conjugated equine estrogens alone participants. Incident AF was more frequent in the active groups of both trials, reaching statistical significance in the trial of conjugated equine estrogens alone in women with prior hysterectomy (hazard ratio, 1.17; CI, 1.00-1.36; P=0.045) and in the pooled analysis (hazard ratio, 1.12; CI, 1.00-1.24; P=0.05), but not in the estrogen plus progestin trial (hazard ratio, 1.07; CI, 0.91-1.25; P=0.44). These results were only minimally affected by adjustment for incident stroke, coronary heart disease, and heart failure.Incident AF was modestly elevated in hysterectomized women randomized to postmenopausal E-alone, and in the pooled group randomized to E-alone or estrogen plus progestin. The trend in women with intact uterus receiving estrogen plus progestin, considered separately, was not statistically significant.ClinicalTrials.gov; Identifier: NCT00000611.

  View details for DOI 10.1161/CIRCEP.112.972224

  View details for Web of Science ID 000313586900018

  View details for PubMedID 23169946

• Reduction in Life-Threatening Ventricular Tachyarrhythmias in Statin-Treated Patients With Nonischemic Cardiomyopathy Enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Buber, J., Goldenberg, I., Moss, A. J., Wang, P. J., McNitt, S., Hall, W. J., Eldar, M., Barsheshet, A., Shechter, M. 2012; 60 (8): 749-755

  Abstract

  This study hypothesized that time-dependent statin therapy will reduce the risk of life-threatening ventricular tachyarrhythmias among patients with nonischemic cardiomyopathy (NICM) enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy).Prior studies suggested that statin therapy exerts antiarrhythmic properties among patients with coronary artery disease. However, data regarding the effect of statins on arrhythmic risk among patients with NICM are limited.Multivariate Cox proportional hazards regression modeling was used to assess the effect of statin therapy, evaluated as a time-dependent covariate, on the risk of appropriate defibrillator therapy for fast ventricular tachycardia (VT) (defined as a rate faster than 180 beats/min)/ventricular fibrillation (VF) or death (primary endpoint) and appropriate defibrillator shocks (secondary endpoint) among 821 patients with NICM enrolled in the MADIT-CRT trial.Statin users (n = 499) were older and had a higher prevalence of diabetes and hypertension yet were less frequently smokers. Multivariate analysis showed that time-dependent statin therapy was independently associated with a significant 77% reduction in the risk of fast VT/VF or death (p < 0.001) and with a significant 46% reduction in the risk of appropriate implantable cardioverter defibrillator shocks (p = 0.01). Consistent with these findings, the cumulative probability of fast VT/VF or death at 4 years of follow-up was significantly lower among patients who were treated with statins (11%) as compared with study patients who were not treated with statins (19%; p = 0.006 for the overall difference during follow-up).Statin use was associated with a significant reduction in the risk of life-threatening ventricular tachyarrhythmias among patients with NICM.

  View details for DOI 10.1016/j.jacc.2012.03.041

  View details for Web of Science ID 000307463800008

  View details for PubMedID 22703927

• Abrupt bradycardia and grouped beating during treadmill testing: A mimic of upper rate behavior HEART RHYTHM Woods, C. E., Friday, K., Wang, P., Turakhia, M. P. 2012; 9 (7): 1165-1167

  View details for DOI 10.1016/j.hrthm.2011.12.020

  View details for Web of Science ID 000305616900031

  View details for PubMedID 22209946

• Incidence and clinical predictors of low defibrillation safety margin at time of implantable defibrillator implantation JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY Cheng, Z., Turakhia, M., Lo, R., Gupta, A., Zei, P. C., Hsia, H. H., Al-Ahmad, A., Wang, P. J. 2012; 34 (1): 93-100

  Abstract

  Determination of the defibrillation safety margin (DSM) is the most common method of testing device effectiveness at the time of implantation of implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRTD). Low DSM remains a problem in clinical practice.The purpose of this study is to ascertain the incidence and clinical predictors of low DSM and the treatment strategies for low DSM in ICD or CRTD recipients.Selected ICD or CRTD recipients from January 2006 to May 2008 who underwent DSM test at the time of implantation were included. Low DSM patients were defined as patients who had a DSM within 10 J of the maximum delivered energy of the device. These patients were compared to patients who had DSM > 10 J.This study included 243 patients. Of these, 13 (5.3%) patients had low DSM, and 230 patients had adequate DSM. Patients with low DSM had a high prevalence of amiodarone use (69% vs 13%, p < 0.01), secondary prevention indications (69% vs 30%, p < 0.01), and a trend toward younger age (51 ± 18 vs 58 ± 15 years, p = 0.08). After adjustment for age and sex, amiodarone use was significantly associated with low DSM. All low DSM patients except one obtained adequate DSM after taking additional steps, including discontinuing amiodarone and starting sotalol, RV lead repositioning, adding a subcutaneous array or shock coil, changing single-coil to dual-coil lead, and upgrading to a high output device.The incidence of low DSM patients is low with high-energy devices. Amiodarone use is associated with low DSM, and its discontinuation or substitution with sotalol is one of a variety of available options for low DSM patients.

  View details for DOI 10.1007/s10840-011-9648-z

  View details for Web of Science ID 000303541200013

  View details for PubMedID 22391960

• EFFECTS OF POSTMENOPAUSAL HORMONE THERAPY ON INCIDENT ATRIAL FIBRILLATION: THE WOMEN'S HEALTH INITIATIVE RANDOMIZED CONTROLLED TRIALS 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC)/Conference on ACC-i2 with TCT Perez, M. V., Wang, P., Larson, J., Virnig, B. A., Cochrane, B., Curb, D., Klein, L., Manson, J., Martin, L., Robinson, J., Wassertheil-Smoller, S., Stefanick, M. ELSEVIER SCIENCE INC. 2012: E661–E661

  View details for Web of Science ID 000302326700663

• Ability of microvolt T-wave alternans to modify risk assessment of ventricular tachyarrhythmic events: A meta-analysis AMERICAN HEART JOURNAL Gupta, A., Hoang, D. D., Karliner, L., Tice, J. A., Heidenreich, P., Wang, P. J., Turakhia, M. P. 2012; 163 (3): 354-364

  Abstract

  Prior studies have indicated that the magnitude of risk association of microvolt T-wave alternans (MTWA) testing appears to vary with the population studied. We performed a meta-analysis to determine the ability of MTWA to modify risk assessment of ventricular tachyarrhythmic events (VTEs) and sudden cardiac death (SCD) across a series of patient risk profiles using likelihood ratio (LR) testing, a measure of test performance independent of disease prevalence.We identified original research articles published from January 1990 to January 2011 that investigate spectrally derived MTWA. Ventricular tachyarrhythmic event was defined as the total and arrhythmic mortality and nonfatal sustained or implantable cardioverter-defibrillator-treated ventricular tachyarrhythmias. Summary estimates were created for positive and nonnegative MTWA results using a random-effects model and were expressed as positive (LR+) and negative (LR-) LRs.Of 1,534 articles, 20 prospective cohort studies met our inclusion criteria, consisting of 5,945 subjects predominantly with prior myocardial infarction or left ventricular dysfunction. Although there was a modest association between positive MTWA and VTE (relative risk 2.45, 1.58-3.79) and nonnegative MTWA and VTE (3.68, 2.23-6.07), test performance was poor (positive MTWA: LR+ 1.78, LR- 0.43; nonnegative MTWA: LR+ 1.38, LR- 0.56). Subgroup analyses of subjects classified as prior VTE, post-myocardial infarction, SCD-HeFT type, and MADIT-II type had a similar poor test performance. A negative MTWA result would decrease the annualized risk of VTE from 8.85% to 6.37% in MADIT-II-type patients and from 5.91% to 2.60% in SCD-HeFT-type patients.Despite a modest association, results of spectrally derived MTWA testing do not sufficiently modify the risk of VTE to change clinical decisions.

  View details for DOI 10.1016/j.ahj.2011.11.021

  View details for Web of Science ID 000301597200010

  View details for PubMedID 22424005

• Catheter ablation of atrial fibrillation: state-of-the-art techniques and future perspectives JOURNAL OF CARDIOVASCULAR MEDICINE Santangeli, P., Di Biase, L., Burkhardt, D. J., Horton, R., Sanchez, J., Bai, R., Pump, A., Perez, M., Wang, P. J., Natale, A., Al-Ahmad, A. 2012; 13 (2): 108-124

  Abstract

  The impact of atrial fibrillation on the healthcare systems of Western countries is overwhelming, due to its independent association with death, systemic thromboembolism, impaired quality of life and hospitalizations. Catheter ablation is the only treatment thus far demonstrated capable of achieving cure in a substantial proportion of patients. Pulmonary vein antrum isolation (PVAI) is the cornerstone of current atrial fibrillation ablation techniques, with the greatest efficacy as a stand-alone procedure in patients with paroxysmal atrial fibrillation. Use of general anesthesia, open-irrigated ablation catheters and maintenance of periprocedural therapeutic warfarin has been demonstrated to increase the safety and effectiveness of PVAI. In patients with paroxysmal atrial fibrillation, the systematic addition of superior vena cava isolation increases the long-term freedom from atrial fibrillation recurrence. A more extensive ablation approach extending to the entire left atrial posterior wall and to complex fractionated electrograms (CFAEs) is warranted in nonparoxysmal atrial fibrillation patients, in whom nonpulmonary vein trigger sites are frequently identified. Up to one-third of these patients experiencing atrial fibrillation recurrence after ablation have evidence of triggers from the left atrial appendage. Isolation of this structure is the best treatment strategy to improve the long-term success rate. In recent years, in addition to the development of ablation techniques to increase the success rate, outcomes of atrial fibrillation treatment trials have been reconsidered. In particular, reduction of hospitalization, stroke and mortality, as well as economic factors, have all been considered relevant to evaluate the effectiveness of atrial fibrillation treatment. Large ongoing trials are specifically evaluating the impact of atrial fibrillation ablation on these outcomes. This article will summarize the state-of-the art techniques for atrial fibrillation ablation, and will discuss the contribution of ongoing studies to the future of atrial fibrillation ablation.

  View details for DOI 10.2459/JCM.0b013e32834f2371

  View details for Web of Science ID 000299652200004

  View details for PubMedID 22193837

• Procedural Complications, Rehospitalizations, and Repeat Procedures After Catheter Ablation for Atrial Fibrillation JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Shah, R. U., Freeman, J. V., Shilane, D., Wang, P. J., Go, A. S., Hlatky, M. A. 2012; 59 (2): 143-149

  Abstract

  The purpose of this study was to estimate rates and identify predictors of inpatient complications and 30-day readmissions, as well as repeat hospitalization rates for arrhythmia recurrence following atrial fibrillation (AF) ablation.AF is the most common clinically significant arrhythmia and is associated with increased morbidity and mortality. Radiofrequency or cryotherapy ablation of AF is a relatively new treatment option, and data on post-procedural outcomes in large general populations are limited.Using data from the California State Inpatient Database, we identified all adult patients who underwent their first AF ablation from 2005 to 2008. We used multivariable logistic regression to identify predictors of complications and/or 30-day readmissions and Kaplan-Meier analyses to estimate rates of all-cause and arrhythmia readmissions.Among 4,156 patients who underwent an initial AF ablation, 5% had periprocedural complications, most commonly vascular, and 9% were readmitted within 30 days. Older age, female, prior AF hospitalizations, and less hospital experience with AF ablation were associated with higher adjusted risk of complications and/or 30-day readmissions. The rate of all-cause hospitalization was 38.5% by 1 year. The rate of readmission for recurrent AF, atrial flutter, and/or repeat ablation was 21.7% by 1 year and 29.6% by 2 years.Periprocedural complications occurred in 1 of 20 patients undergoing AF ablation, and all-cause and arrhythmia-related rehospitalizations were common. Older age, female sex, prior AF hospitalizations, and recent hospital procedure experience were associated with a higher risk of complications and/or 30-day readmission after AF ablation.

  View details for DOI 10.1016/j.jacc.2011.08.068

  View details for Web of Science ID 000298796600009

  View details for PubMedID 22222078

• Cardiac Resynchronization Therapy Reduces Left Atrial Volume and the Risk of Atrial Tachyarrhythmias in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Brenyo, A., Link, M. S., Barsheshet, A., Moss, A. J., Zareba, W., Wang, P. J., McNitt, S., Huang, D., Foster, E., Estes, M., Solomon, S. D., Goldenberg, I. 2011; 58 (16): 1682-1689

  Abstract

  We hypothesized that reductions in left atrial volume (LAV) with a cardiac resynchronization therapy-defibrillator (CRT-D) would translate into a subsequent reduction in the risk of atrial tachyarrhythmias (AT).There is limited information regarding the effect of CRT-D on the risk of AT.Percent reduction in LAV at 1 year following CRT-D implantation (pre-specified as low [lowest quartile: <20% reduction in LAV] and high [≥20% reduction in LAV] response to CRT-D) were related to the risk of subsequent AT (comprising atrial fibrillation, atrial flutter, atrial tachycardia, and supraventricular tachyarrhythmias) among patients enrolled in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy).The cumulative probability of AT 2.5 years after assessment of echocardiographic response was lowest among high LAV responders to CRT-D (3%) and significantly higher among both low LAV responders to CRT-D (9%) and implantable cardioverter-defibrillator-only patients (7%; p = 0.03 for the difference among the 3 groups). Consistently, multivariate analysis showed that high LAV responders to CRT-D experienced a significant 53% (p = 0.01) reduction in the risk of subsequent AT as compared with implantable cardioverter-defibrillator-only patients, whereas low LAV responders did not derive a significant risk reduction with CRT-D therapy (hazard ratio [HR]: 1.05 [95% confidence interval (CI): 0.54 to 2.00]; p = 0.89). Patients who developed in-trial AT experienced significant increases in the risk for both the combined endpoint of heart failure or death (HR: 2.28 [95% CI: 1.45 to 3.59]; p < 0.001) and the separate occurrence of all-cause mortality (HR: 1.89 [95% CI: 1.08 to 3.62]; p = 0.01).In the MADIT-CRT study, favorable reverse remodeling of the left atrium with CRT-D therapy was associated with a significant reduction in risk of subsequent AT. (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271).

  View details for DOI 10.1016/j.jacc.2011.07.020

  View details for Web of Science ID 000295882800008

  View details for PubMedID 21982313

• 3D INTRACARDIAC ECHOCARDIOGRAPHY IN LEFT ATRIAL ABLATION Venice Arrhythmias Conference Al Ahmad, A., Chia, K., Evans, J., Schoenhard, J., Harwood, M., Perez, M., Zei, P., Hsia, H., Wang, P. WILEY-BLACKWELL. 2011: S43–S43

  View details for Web of Science ID 000296255000115

• Intraprocedure Visualization of the Esophagus Using Interventional C-arm CT as Guidance for Left Atrial Radiofrequency Ablation ACADEMIC RADIOLOGY Tognolini, A., Al-Ahmad, A., Wang, P. J., Hsia, H. H., Herfkens, R. J., Girard, E., Moore, T., Fahrig, R. 2011; 18 (7): 850-857

  Abstract

  During radiofrequency catheter ablation for atrial fibrillation, the esophagus is at risk for thermal injury. In this study, C-arm computed tomography (CT) was compared to clinical CT, without the administration of oral contrast, to visualize the esophagus and its relationship to the left atrium and the ostia of the pulmonary veins (PVs) during the radiofrequency ablation procedure.Sixteen subjects underwent both cardiac clinical CT and C-arm CT. Computed tomographic scans were performed on a multidetector scanner using a standard electrocardiographically gated protocol. C-arm computed tomographic scans were obtained using either a multisweep protocol with retrospective electrocardiographic gating or a non-gated single-sweep protocol. C-arm and clinical computed tomographic scans were analyzed in a random order and then compared for the following criteria: (1) visualization of the esophagus (yes or no), (2) relationship of esophageal position to the four PVs, and (3) direct contact or absence of a fat pad between the esophagus and the PV antrum.The esophagus was identified in all C-arm and clinical computed tomographic scans. In four cases, orthogonal planes were needed on C-arm CT (inferior PV level). In six patients, the esophageal location on C-arm CT was different from that on CT. Direct contact was reported in 19 of 64 of the segments (30%) examined on CT and in 26 of 64 (41%) on C-arm CT. In five of 64 segments (8%), C-arm CT overestimated a direct contact of the esophagus to the left atrium.C-arm computed tomographic image quality without the administration of oral contrast agents was shown to be sufficient for visualization of the esophagus location during a radiofrequency catheter ablation procedure for atrial fibrillation.

  View details for DOI 10.1016/j.acra.2011.01.023

  View details for Web of Science ID 000292066200010

  View details for PubMedID 21440465

• Reverse Remodeling and the Risk of Ventricular Tachyarrhythmias in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy) JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Barsheshet, A., Wang, P. J., Moss, A. J., Solomon, S. D., Al-Ahmad, A., McNitt, S., Foster, E., Huang, D. T., Klein, H. U., Zareba, W., Eldar, M., Goldenberg, I. 2011; 57 (24): 2416-2423

  Abstract

  We aimed to evaluate the relationship between echocardiographic response to cardiac resynchronization therapy (CRT) and the risk of subsequent ventricular tachyarrhythmias (VTAs).Current data regarding the effect of CRT on the risk of VTA are limited and conflicting.The risk of a first appropriate implantable cardioverter-defibrillator (ICD) therapy for VTA (including ventricular tachycardia, ventricular fibrillation, and ventricular flutter) was compared between high- and low-echocardiographic responders to CRT defibrillator (CRT-D) therapy (defined as ≥ 25% and <25% reductions, respectively, in left ventricular end-systolic volume [LVESV] at 1 year compared with baseline) and ICD-only patients enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy).The cumulative probability of a first VTA at 2 years after assessment of echocardiographic response was highest among low responders to CRT-D (28%), intermediate among ICD-only patients (21%), and lowest among high responders to CRT-D (12%), with p < 0.001 for the overall difference during follow-up. Multivariate analysis showed that high responders to CRT-D experienced a significant 55% reduction in the risk of VTA compared with ICD-only patients (p < 0.001), whereas the risk of VTA was not significantly different between low responders and ICD-only patients (hazard ratio [HR]: 1.26; p = 0.21). Consistently, assessment of response to CRT-D as a continuous measure showed that incremental 10% reductions in left ventricular end-systolic volume were associated with corresponding reductions in the risk of subsequent VTA (HR: 0.80; p < 0.001), VTA/death (HR: 0.79; p < 0.001), ventricular tachycardia (HR: 0.80; p < 0.001), and ventricular fibrillation/ventricular flutter (HR: 0.75; p = 0.044).In patients with left ventricular dysfunction enrolled in the MADIT-CRT trial, reverse remodeling was associated with a significant reduction in the risk of subsequent life-threatening VTAs. (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271).

  View details for DOI 10.1016/j.jacc.2010.12.041

  View details for Web of Science ID 000291424100007

  View details for PubMedID 21658562

• Subcutaneous Implantable Cardioverter-Defibrillator Technology HEART FAILURE CLINICS Gupta, A., Al-Ahmad, A., Wang, P. J. 2011; 7 (2): 287-?

  Abstract

  The advent of subcutaneous implantable cardioverter-defibrillator (ICD) systems represents a paradigm shift for the detection and therapy of ventricular tachyarrhythmias. Despite advances in transvenous lead technology, problems remain that notably include requirement for technical expertise; periprocedural complications during implantation and explantation; and long-term lead failure. Although subcutaneous ICD systems may mitigate some of these risks, they provide new shortcomings, such as inability to provide pacing therapy for bradyarrhythmias, ventricular tachyarrhythmias, and cardiac resynchronization. Ongoing clinical evaluation and development are required before the role of subcutaneous ICDs as an adjunctive or primary therapy can be defined. This article examines studies investigating the subcutaneous ICD and discusses its possible advantages and disadvantages as compared with current transvenous ICD systems.

  View details for DOI 10.1016/j.hfc.2011.01.005

  View details for Web of Science ID 000307488700016

  View details for PubMedID 21439506

• Effectiveness of Cardiac Resynchronization Therapy by QRS Morphology in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) CIRCULATION Zareba, W., Klein, H., Cygankiewicz, I., Hall, W. J., McNitt, S., Brown, M., Cannom, D., Daubert, J. P., Eldar, M., Gold, M. R., Goldberger, J. J., Goldenberg, I., Lichstein, E., Pitschner, H., Rashtian, M., Solomon, S., Viskin, S., Wang, P., Moss, A. J. 2011; 123 (10): 1061-1072

  Abstract

  This study aimed to determine whether QRS morphology identifies patients who benefit from cardiac resynchronization therapy with a defibrillator (CRT-D) and whether it influences the risk of primary and secondary end points in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) trial.Baseline 12-lead ECGs were evaluated with regard to QRS morphology. Heart failure event or death was the primary end point of the trial. Death, heart failure event, ventricular tachycardia, and ventricular fibrillation were secondary end points. Among 1817 patients with available sinus rhythm ECGs at baseline, there were 1281 (70%) with left bundle-branch block (LBBB), 228 (13%) with right bundle-branch block, and 308 (17%) with nonspecific intraventricular conduction disturbances. The latter 2 groups were defined as non-LBBB groups. Hazard ratios for the primary end point for comparisons of CRT-D patients versus patients who only received an implantable cardioverter defibrillator (ICD) were significantly (P < 0.001) lower in LBBB patients (0.47; P < 0.001) than in non-LBBB patients (1.24; P = 0.257). The risk of ventricular tachycardia, ventricular fibrillation, or death was decreased significantly in CRT-D patients with LBBB but not in non-LBBB patients. Echocardiographic parameters showed significantly (P < 0.001) greater reduction in left ventricular volumes and increase in ejection fraction with CRT-D in LBBB than in non-LBBB patients.Heart failure patients with New York Heart Association class I or II and ejection fraction ≤ 30% and LBBB derive substantial clinical benefit from CRT-D: a reduction in heart failure progression and a reduction in the risk of ventricular tachyarrhythmias. No clinical benefit was observed in patients with a non-LBBB QRS pattern (right bundle-branch block or intraventricular conduction disturbances).URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

  View details for DOI 10.1161/CIRCULATIONAHA.110.960898

  View details for Web of Science ID 000288369900011

  View details for PubMedID 21357819

• Cost-Effectiveness of Dabigatran Compared With Warfarin for Stroke Prevention in Atrial Fibrillation ANNALS OF INTERNAL MEDICINE Freeman, J. V., Zhu, R. P., Owens, D. K., Garber, A. M., Hutton, D. W., Go, A. S., Wang, P. J., Turakhia, M. P. 2011; 154 (1): 1-U129

  Abstract

  Warfarin reduces the risk for ischemic stroke in patients with atrial fibrillation (AF) but increases the risk for hemorrhage. Dabigatran is a fixed-dose, oral direct thrombin inhibitor with similar or reduced rates of ischemic stroke and intracranial hemorrhage in patients with AF compared with those of warfarin.To estimate the quality-adjusted survival, costs, and cost-effectiveness of dabigatran compared with adjusted-dose warfarin for preventing ischemic stroke in patients 65 years or older with nonvalvular AF.Markov decision model.The RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial and other published studies of anticoagulation. The cost of dabigatran was estimated on the basis of pricing in the United Kingdom.Patients aged 65 years or older with nonvalvular AF and risk factors for stroke (CHADS₂ score ≥1 or equivalent) and no contraindications to anticoagulation.Lifetime.Societal.Warfarin anticoagulation (target international normalized ratio, 2.0 to 3.0); dabigatran, 110 mg twice daily (low dose); and dabigatran, 150 mg twice daily (high dose).Quality-adjusted life-years (QALYs), costs (in 2008 U.S. dollars), and incremental cost-effectiveness ratios.The quality-adjusted life expectancy was 10.28 QALYs with warfarin, 10.70 QALYs with low-dose dabigatran, and 10.84 QALYs with high-dose dabigatran. Total costs were $143 193 for warfarin, $164 576 for low-dose dabigatran, and $168 398 for high-dose dabigatran. The incremental cost-effectiveness ratios compared with warfarin were $51 229 per QALY for low-dose dabigatran and $45 372 per QALY for high-dose dabigatran.The model was sensitive to the cost of dabigatran but was relatively insensitive to other model inputs. The incremental cost-effectiveness ratio increased to $50 000 per QALY at a cost of $13.70 per day for high-dose dabigatran but remained less than $85 000 per QALY over the full range of model inputs evaluated. The cost-effectiveness of high-dose dabigatran improved with increasing risk for stroke and intracranial hemorrhage.Event rates were largely derived from a single randomized clinical trial and extrapolated to a 35-year time frame from clinical trials with approximately 2-year follow-up.In patients aged 65 years or older with nonvalvular AF at increased risk for stroke (CHADS₂ score ≥1 or equivalent), dabigatran may be a cost-effective alternative to warfarin depending on pricing in the United States.American Heart Association and Veterans Affairs Health Services Research & Development Service.

  View details for Web of Science ID 000285830900001

  View details for PubMedID 21041570

• Cost-Effectiveness of Genetic Testing in Family Members of Patients With Long-QT Syndrome CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Perez, M. V., Kumarasamy, N. A., Owens, D. K., Wang, P. J., Hlatky, M. A. 2011; 4 (1): 76-84

  Abstract

  Family members of patients with established long-QT syndrome (LQTS) often lack definitive clinical findings, yet may have inherited an LQTS mutation and be at risk of sudden death. Genetic testing can identify mutations in 75% of patients with LQTS, but genetic testing of family members remains controversial.We used a Markov model to assess the cost-effectiveness of 3 strategies for treating an asymptomatic 10-year-old, first-degree relative of a patient with clinically evident LQTS. In the genetic testing strategy, relatives undergo genetic testing only for the mutation identified in the index patient, and relatives who test positive for the mutation are treated with β-blockers. This strategy was compared with (1) empirical treatment of relatives with β-blockers and (2) watchful waiting, with treatment only after development of symptoms. The genetic testing strategy resulted in better survival and quality-adjusted life years at higher cost, with a cost-effectiveness ratio of $67 400 per quality-adjusted life year gained compared with watchful waiting. The cost-effectiveness of the genetic testing strategy improved to less than $50 000 per quality-adjusted life year gained when applied selectively either to (1) relatives with higher clinical suspicion of LQTS (pretest probability 65% to 81%), or to (2) families with a higher than average risk of sudden death, or to (3) larger families (2 or more first-degree relatives tested).Genetic testing of young first-degree relatives of patients with definite LQTS is moderately expensive, but can reach acceptable thresholds of cost-effectiveness when applied to selected patients.

  View details for DOI 10.1161/CIRCOUTCOMES.110.957365

  View details for Web of Science ID 000286311700014

  View details for PubMedID 21139095

• A Novel Method for Patient-Specific QTc-Modeling QT-RR Hysteresis ANNALS OF NONINVASIVE ELECTROCARDIOLOGY Hadley, D. M., Froelicher, V. F., Wang, P. J. 2011; 16 (1): 3-12

  Abstract

  Cardiac repolarization adaptation to cycle length change is patient dependent and results in complex QT-RR hysteresis. We hypothesize that accurate patient-specific QT-RR curves and rate corrected QT values (QTc) can be derived through patient-specific modeling of hysteresis.Model development was supported by QT-RR observations from 1959 treadmill tests, allowing extensive exploration of the influences of autonomic function on QT adaptation to rate changes. The methodology quantifies and then removes patient-specific repolarization adaptation rates. The estimated average 95% QT confidence limit was approximately 1 msec for the studied population. The model was validated by comparing QT-RR curves derived from a submaximal exercise protocol with rapid exercise and recovery phases, characterized by high hysteresis, with QT-RR values derived from an incremental stepped protocol that held heart rate constant for 5 minutes at each stage of exercise and recovery.The underlying physiologic changes affecting QT dynamics during the transitions from rest to exercise to recovery are quite complex. Nevertheless, a simple patient-specific model, comprising only three parameters and based solely on the preceding history of RR intervals and trend, is sufficient to accurately model QT hysteresis over an entire exercise test for a diverse population. A brief recording of a resting ECG, combined with a short period of submaximal exercise and recovery, provides sufficient information to derive an accurate patient-specific QT-RR curve, eliminating QTc bias inherent in population-based correction formulas.

  View details for DOI 10.1111/j.1542-474X.2010.00401.x

  View details for Web of Science ID 000286428400002

  View details for PubMedID 21251128

• Inappropriate Pacing in a Patient with Managed Ventricular Pacing: What Is the Cause? HEART RHYTHM Perez, M. V., Al-Ahmad, A. A., Wang, P. J., Turakhia, M. P. 2010; 7 (12)

  View details for Web of Science ID 000284875500003

• Optical Control of Cardiomyocyte Depolarization and Inhibition Utilizing Channelrhodopsin-2 (ChR2) and a Third Generation Halorhodopsin (eNpHR3.0) Park, S., Vijaykumar, R., Yock, P. G., Wang, P. J., Deisseroth, K. LIPPINCOTT WILLIAMS & WILKINS. 2010

  View details for Web of Science ID 000208231601701

• Time dependence of life-threatening ventricular tachyarrhythmias after coronary revascularization in MADIT-CRT HEART RHYTHM Barsheshet, A., Goldenberg, I., Narins, C. R., Moss, A. J., McNitt, S., Wang, P. J., Huang, D. T., Hall, W. J., Zareba, W., Eldar, M., Guetta, V. 2010; 7 (10): 1421-1427

  Abstract

  Coronary revascularization (CR) may confer electrical stability in patients with ischemic cardiomyopathy. However, data regarding the effect of CR on the development of ventricular tachyarrhythmias in this population are limited.The purpose of this study was to evaluate the association between CR and arrhythmic risk in postmyocardial infarction (post-MI) patients with left ventricular dysfunction.The risk for life-threatening ventricular tachyarrhythmias (defined as a first appropriate defibrillator therapy for ventricular tachycardia [VT]/ventricular fibrillation [VF] or death) was compared between post-MI patients with and those without prior CR (n = 612 and 147, respectively) enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT).The 3-year cumulative rate of VT/VF or death was significantly higher among patients without prior CR (42%) than in patients who underwent prior CR (32%, P = .02). Multivariate analysis demonstrated that patients without prior CR had 48% increased risk (P = .01) for VT/VF or death. Risk reduction associated with CR was related to elapsed time from CR, assessed both as a categorical variable (tertiles for time from CR: ≥7 years, hazard ratio [HR] = 1.93, P = .001; 1.5-7 years, HR = 1.70, P = .01 vs <1.5 years) and as a continuous measure (4%, P = .002, increased risk for VT/VF or death per 1-year increment of elapsed time from CR). The effect of CR on arrhythmic risk was similar in patients treated with a defibrillator alone or when combined with cardiac resynchronization therapy.Post-MI patients with left ventricular dysfunction who undergo CR experience a time-dependent reduction in the risk for subsequent life-threatening ventricular tachyarrhythmias.

  View details for DOI 10.1016/j.hrthm.2010.07.005

  View details for Web of Science ID 000282187300014

  View details for PubMedID 20620231

• Inappropriate pacing in a patient with managed ventricular pacing: What is the cause? HEART RHYTHM Perez, M. V., Al-Ahmad, A. A., Wang, P. J., Turakhia, M. P. 2010; 7 (9): 1336-1337

  Abstract

  A case of inappropriate atrial pacing in a patient with a pacemaker programmed with Managed Ventricular Pacing (MVP) mode, a proprietary algorithm in Medtronic devices, is presented. The patient was an 84-year-old woman who presented in sinus rhythm with complete atrioventricular block. A dual-chamber pacemaker was implanted and programmed to an MVP pacing mode. After the implant, the patient developed a relatively slow atrial tachyarrhythmia with 2:1 atrioventricular block and inappropriate atrial pacing, followed by a delay in tracking of the atrial tachyarrhythmia. The mechanisms for these behaviors are described.

  View details for DOI 10.1016/j.hrthm.2010.04.028

  View details for Web of Science ID 000281444100033

  View details for PubMedID 20435165

• Left Atrial Appendage An Underrecognized Trigger Site of Atrial Fibrillation CIRCULATION Di Biase, L., Burkhardt, J. D., Mohanty, P., Sanchez, J., Mohanty, S., Horton, R., Gallinghouse, G. J., Bailey, S. M., Zagrodzky, J. D., Santangeli, P., Hao, S., Hongo, R., Beheiry, S., Themistoclakis, S., Bonso, A., Rossillo, A., Corrado, A., Raviele, A., Al-Ahmad, A., Wang, P., Cummings, J. E., Schweikert, R. A., Pelargonio, G., Dello Russo, A., Casella, M., Santarelli, P., Lewis, W. R., Natale, A. 2010; 122 (2): 109-U26

  Abstract

  Together with pulmonary veins, many extrapulmonary vein areas may be the source of initiation and maintenance of atrial fibrillation. The left atrial appendage (LAA) is an underestimated site of initiation of atrial fibrillation. Here, we report the prevalence of triggers from the LAA and the best strategy for successful ablation.Nine hundred eighty-seven consecutive patients (29% paroxysmal, 71% nonparoxysmal) undergoing redo catheter ablation for atrial fibrillation were enrolled. Two hundred sixty-six patients (27%) showed firing from the LAA and became the study population. In 86 of 987 patients (8.7%; 5 paroxysmal, 81 nonparoxysmal), the LAA was found to be the only source of arrhythmia with no pulmonary veins or other extrapulmonary vein site reconnection. Ablation was performed either with focal lesion (n=56; group 2) or to achieve LAA isolation by placement of the circular catheter at the ostium of the LAA guided by intracardiac echocardiography (167 patients; group 3). In the remaining patients, LAA firing was not ablated (n=43; group 1). At the 12+/-3-month follow-up, 32 patients (74%) in group 1 had recurrence compared with 38 (68%) in group 2 and 25 (15%) in group 3 (P<0.001).The LAA appears to be responsible for arrhythmias in 27% of patients presenting for repeat procedures. Isolation of the LAA could achieve freedom from atrial fibrillation in patients presenting for a repeat procedure when arrhythmias initiating from this structure are demonstrated.

  View details for DOI 10.1161/CIRCULATIONAHA.109.928903

  View details for Web of Science ID 000279801700003

  View details for PubMedID 20606120

• Periprocedural Stroke and Management of Major Bleeding Complications in Patients Undergoing Catheter Ablation of Atrial Fibrillation CIRCULATION Di Biase, L., Burkhardt, J. D., Mohanty, P., Sanchez, J., Horton, R., Gallinghouse, G. J., Lakkireddy, D., Verma, A., Khaykin, Y., Hongo, R., Hao, S., Beheiry, S., Pelargonio, G., Dello Russo, A., Casella, M., Santarelli, P., Santangeli, P., Wang, P., Al-Ahmad, A., Patel, D., Themistoclakis, S., Bonso, A., Rossillo, A., Corrado, A., Raviele, A., Cummings, J. E., Schweikert, R. A., Lewis, W. R., Natale, A. 2010; 121 (23): 2550-2556

  Abstract

  Catheter ablation of atrial fibrillation is associated with the potential risk of periprocedural stroke, which can range between 1% and 5%. We developed a prospective database to evaluate the prevalence of stroke over time and to assess whether the periprocedural anticoagulation strategy and use of open irrigation ablation catheter have resulted in a reduction of this complication.We collected data from 9 centers performing the same ablation procedure with the same anticoagulation protocol. We divided the patients into 3 groups: ablation with an 8-mm catheter off warfarin (group 1), ablation with an open irrigated catheter off warfarin (group 2), and ablation with an open irrigated catheter on warfarin (group 3). Outcome data on stroke/transient ischemic attack and bleeding complications during and early after the procedures were collected. Of 6454 consecutive patients in the study, 2488 were in group 1, 1348 were in group 2, and 2618 were in group 3. Periprocedural stroke/transient ischemic attack occurred in 27 patients (1.1%) in group 1 and 12 patients (0.9%) in group 2. Despite a higher prevalence of nonparoxysmal atrial fibrillation and more patients with CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score >2, no stroke/transient ischemic attack was reported in group 3. Complications among groups 1, 2, and 3, including major bleeding (10 [0.4%], 11 [0.8%], and 10 [0.4%], respectively; P>0.05) and pericardial effusion (11 [0.4%], 11 [0.8%], and 12 [0.5%]; P>0.05), were equally distributed.The combination of an open irrigation ablation catheter and periprocedural therapeutic anticoagulation with warfarin may reduce the risk of periprocedural stroke without increasing the risk of pericardial effusion or other bleeding complications.

  View details for DOI 10.1161/CIRCULATIONAHA.109.921320

  View details for Web of Science ID 000278754900002

  View details for PubMedID 20516376

• Finite element modeling of subcutaneous implantable defibrillator electrodes in an adult torso HEART RHYTHM Jolley, M., Stinstra, J., Tate, J., Pieper, S., MacLeod, R., Chu, L., Wang, P., Triedman, J. K. 2010; 7 (5): 692-698

  Abstract

  Total subcutaneous implantable subcutaneous defibrillators are in development, but optimal electrode configurations are not known.We used image-based finite element models (FEM) to predict the myocardial electric field generated during defibrillation shocks (pseudo-DFT) in a wide variety of reported and innovative subcutaneous electrode positions to determine factors affecting optimal lead positions for subcutaneous implantable cardioverter-defibrillators (S-ICD).An image-based FEM of an adult man was used to predict pseudo-DFTs across a wide range of technically feasible S-ICD electrode placements. Generator location, lead location, length, geometry and orientation, and spatial relation of electrodes to ventricular mass were systematically varied. Best electrode configurations were determined, and spatial factors contributing to low pseudo-DFTs were identified using regression and general linear models.A total of 122 single-electrode/array configurations and 28 dual-electrode configurations were simulated. Pseudo-DFTs for single-electrode orientations ranged from 0.60 to 16.0 (mean 2.65 +/- 2.48) times that predicted for the base case, an anterior-posterior configuration recently tested clinically. A total of 32 of 150 tested configurations (21%) had pseudo-DFT ratios

  View details for DOI 10.1016/j.hrthm.2010.01.030

  View details for Web of Science ID 000277354400024

  View details for PubMedID 20230927

• Measurement Precision in the Optimization of Cardiac Resynchronization Therapy CIRCULATION-HEART FAILURE Turcott, R. G., Witteles, R. M., Wang, P. J., Vagelos, R. H., Fowler, M. B., Ashley, E. A. 2010; 3 (3): 395-404

  Abstract

  Cardiac resynchronization therapy improves morbidity and mortality in appropriately selected patients. Whether atrioventricular (AV) and interventricular (VV) pacing interval optimization confers further clinical improvement remains unclear. A variety of techniques are used to estimate optimum AV/VV intervals; however, the precision of their estimates and the ramifications of an imprecise estimate have not been characterized previously.An objective methodology for quantifying the precision of estimated optimum AV/VV intervals was developed, allowing physiologic effects to be distinguished from measurement variability. Optimization using multiple conventional techniques was conducted in individual sessions with 20 patients. Measures of stroke volume and dyssynchrony were obtained using impedance cardiography and echocardiographic methods, specifically, aortic velocity-time integral, mitral velocity-time integral, A-wave truncation, and septal-posterior wall motion delay. Echocardiographic methods yielded statistically insignificant data in the majority of patients (62%-82%). In contrast, impedance cardiography yielded statistically significant results in 84% and 75% of patients for AV and VV interval optimization, respectively. Individual cases demonstrated that accepting a plausible but statistically insignificant estimated optimum AV or VV interval can result in worse cardiac function than default values.Consideration of statistical significance is critical for validating clinical optimization data in individual patients and for comparing competing optimization techniques. Accepting an estimated optimum without knowledge of its precision can result in worse cardiac function than default settings and a misinterpretation of observed changes over time. In this study, only impedance cardiography yielded statistically significant AV and VV interval optimization data in the majority of patients.

  View details for DOI 10.1161/CIRCHEARTFAILURE.109.900076

  View details for Web of Science ID 000277825800009

  View details for PubMedID 20176716

• The impact of statins and renin-angiotensin-aldosterone system blockers on pulmonary vein antrum isolation outcomes in post-menopausal females EUROPACE Patel, D., Mohanty, P., Di Biase, L., Wang, Y., Shaheen, M. H., Sanchez, J. E., Horton, R. P., Gallinghouse, G. J., Zagrodzky, J. D., Bailey, S. M., Burkhardt, J. D., Lewis, W. R., Diaz, A., Beheiry, S., Hongo, R., Al-Ahmad, A., Wang, P., Schweikert, R., Natale, A. 2010; 12 (3): 322-330

  Abstract

  To assess whether treatment with statins or renin-angiotensin-aldosterone system (RAAS) inhibitors as potential procedural 'augmenting agents' improved atrial fibrillation (AF) catheter ablation recurrence rates in post-menopausal females (PMFS).Five hundred and eighteen consecutive female patients had undergone AF catheter ablation from January 2005 to May 2008. Post-menopausal females were selected and procedure outcomes were compared between cohorts of PMFS treated with statins or RAAS inhibitors to untreated PMFS. Out of 408 PMFS, 36 (8.8%) were treated with a combination of RAAS inhibitors and statins, thus were excluded leaving a total of 372 (91.2%) patients in the study. Out of 372 patients, 111 (29.8%) were on statins (Group 1), 59 (15.9%) on RAAS inhibitors (Group 2), and 202 (54.3%) without RAAS inhibitors or statins [(Group 3) control population]. Over a mean follow-up time of 24 +/- 8.3 (median 25) months, 78 (70.6%) in Group 1, 38 (65.4%) in Group 2, and 139 (68.8%) in Group 3 had procedural success. Statin or RAAS inhibitor use did not predict lower recurrence rates [hazard ratio (HR): 1.26, P = 0.282 and HR: 1.14, P = 0.728, respectively]. When compared with controls, no difference in the cumulative incidence of recurrence was found with statin or RAAS inhibitors use (P = 0.385 and P = 0.761, respectively).Treatment with statins or RAAS inhibitors did not improve catheter ablation success rates among PMFS. Thereby, from a clinical standpoint, PMFS should not be started on these treatments as a procedural 'augmenting agent' at this time.

  View details for DOI 10.1093/europace/eup387

  View details for Web of Science ID 000276050200010

  View details for PubMedID 20064822

• Outcomes and complications of catheter ablation for atrial fibrillation in females HEART RHYTHM Patel, D., Mohanty, P., Di Biase, L., Sanchez, J. E., Shaheen, M. H., Burkhardt, J. D., Bassouni, M., Cummings, J., Wang, Y., Lewis, W. R., Diaz, A., Horton, R. P., Beheiry, S., Hongo, R., Gallinghouse, G. J., Zagrodzky, J. D., Bailey, S. M., Al-Ahmad, A., Wang, P., Schweikert, R. A., Natale, A. 2010; 7 (2): 167-172

  Abstract

  Most atrial fibrillation (AF) ablation studies have consisted predominantly of males; accordingly, there is a paucity of information on the safety and efficacy of catheter ablation in a large cohort of female AF patients.The purpose of this study was to evaluate catheter ablation for AF in female patients.From January 2005 to May 2008, 3265 females underwent pulmonary vein antrum isolation. Success rates, patient profiles, and complications were collected.Approximately 16% of our population was female (P <.001). Females were older (59 +/- 13 vs. 56 +/- 19 years; P <.01) and had a lower prevalence of paroxysmal atrial fibrillation (PAF; 46% vs. 55%; P <.001). Females failed more antiarrhythmics (4 +/- 1 vs. 2 +/- 3; P = .04) and were referred later for catheter ablation (6.51 +/- 7 vs. 4.85 +/- 6.5 years; P = .02) than males. More females failed ablation (31.5% vs. 22.5%; P = .001) and had nonantral sites of firing than males (P <.001). Female patients had 11 (2.1%) hematomas versus 27 (0.9%) in males.Five times as many males underwent catheter ablation than females. Females failed more ablations possibly because of a higher prevalence of nonantral firing, non-PAF, and longer history of AF. Females had more bleeding complications than males.

  View details for DOI 10.1016/j.hrthm.2009.10.025

  View details for Web of Science ID 000276189400005

  View details for PubMedID 20022814

• Dyssynchrony Assessment with Tissue Doppler Imaging and Regional Volumetric Analysis by 3D Echocardiography Do Not Predict Long-Term Response to Cardiac Resynchronization Therapy. Cardiology research and practice Kuppahally, S. S., Fowler, M. B., Vagelos, R., Wang, P., Al-Ahmad, A., Hsia, H., Liang, D. 2010; 2011: 568918-?

  Abstract

  Background. Currently there are no reliable predictors of response to cardiac resynchronization therapy (CRT) before implantation. We compared pre-CRT left ventricular (LV) dyssynchrony by tissue Doppler imaging (TDI) and regional volumetric analysis by 3-dimensional transthoracic echocardiography (3DTTE) in predicting response to CRT. Methods. Thirty-eight patients (79% nonischemic cardiomyopathy) with symptomatic heart failure who underwent CRT were enrolled. Clinical and echocardiographic responses were defined as improvement in one NYHA class and reduction in LV end-systolic volume by ≥15% respectively. Functional status was assessed by Minnesota Living with Heart Failure questionnaire and 6-minute walk distance. Results. In 33 patients, after CRT for 7.86 ± 2.27 months, there were 24 (73%) clinical and 19 (58%) echocardiographic responders. Functional parameters, LV dimensions, volumes and synchrony by TDI and 3DTTE improved significantly in responders. There was no difference in the number of responders and nonresponders when cut-off values for dyssynchrony by different measurements validated in other trials were applied. Area under receiver-operating-characteristic curve ranged from 0.4 to 0.6. Conclusion. CRT improves clinical and echocardiographic parameters in patients with systolic heart failure. The dyssynchrony measurements by TDI and 3DTTE are not comparable and are unable to predict response to CRT.

  View details for DOI 10.4061/2011/568918

  View details for PubMedID 21234100

• Left Atrial Appendage: An Undercognized Trigger Site of Atrial Fibrillation 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Di Biase, L., Burkhardt, J. D., Horton, R., Sanchez, J., Bailey, S., Mohanty, P., Patel, D., Hao, S., Hongo, R., Behelry, S., Al-Ahamad, A., Wang, P., Casella, M., Santarelli, P., Pelargonio, G., Dello Russo, A., Natale, A. LIPPINCOTT WILLIAMS & WILKINS. 2009: S690–S691

  View details for Web of Science ID 000271831501793

• Management of Pericardial Effusion During and After Ablation for Atrial Fibrillation in Patients Undergoing the Procedure With Therapeutic INR 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Di Biase, L., Burkhardt, J. D., Horton, R., Sanchez, J., Gallinghouse, G. J., Bailey, S., Mohanty, P., Patel, D., Schweikert, R. A., Cummings, J. E., Lakkireddy, D., Verma, A., Hao, S., Hongo, R., Beheiry, S., Al-Ahamad, A., Wang, P., Dello Russo, A., Pelargonio, G., Casella, M., Lewis, W. R., Bonso, A., Themistoclakis, S., Raviele, A., Natale, A. LIPPINCOTT WILLIAMS & WILKINS. 2009: S658–S658

  View details for Web of Science ID 000271831501662

• Effects of Postmenopausal Hormone Therapy on Atrial Fibrillation: The Women's Health Initiative Randomized Controlled Trials 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Perez, M., Wang, P. J., Cochrane, B., Curb, J. D., Klein, L., Larson, J., Manson, J., Martin, L. W., Robinson, J., Wassertheil-Smoller, S., Stefanick, M. LIPPINCOTT WILLIAMS & WILKINS. 2009: S519–S519

  View details for Web of Science ID 000271831501090

• Independent Clinical Correlates of Atrial Fibrillation in Postmenopausal Women: The Women's Health Initiative Observational Study 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Perez, M., Wang, P. J., Klein, L., Connelly, S., Larson, J., Limacher, M., Manson, J., Martin, L. W., Prineas, R., Rodriguez, B. L., Smoller, S., Soliman, E., Stefanick, M. L. LIPPINCOTT WILLIAMS & WILKINS. 2009: S520–S520

  View details for Web of Science ID 000271831501093

• Atrial Mechanical Function Using Left Atrial Pressure Waveform Analysis in Persistent and Paroxysmal Atrial Fibrillation Patients 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Cheng, Z., Lo, R., Gupta, A., Perez, M., Zei, P., Hsia, H. H., Turakhia, M., Al-Ahmad, A., Wang, P. J. LIPPINCOTT WILLIAMS & WILKINS. 2009: S628–S628

  View details for Web of Science ID 000271831501532

• Electrocardiographic predictors of atrial fibrillation AMERICAN HEART JOURNAL Perez, M. V., Dewey, F. E., Marcus, R., Ashley, E. A., Al-Ahmad, A. A., Wang, P. J., Froelicher, V. F. 2009; 158 (4): 622-628

  Abstract

  Atrial fibrillation (AF) is the most prevalent arrhythmia in the United States and accounts for more than 750,000 strokes per year. Noninvasive predictors of AF may help identify patients at risk of developing AF. Our objective was to identify the electrocardiographic characteristics associated with onset of AF.This was a retrospective cohort analysis of 42,751 patients with electrocardiograms (ECGs) ordered by physician's discretion and analyzed using a computerized system. The population was followed for detection of AF on subsequent ECGs. Cox proportional hazard regression analysis was performed to test the association between these ECG characteristics and development of AF.For a mean follow-up of 5.3 years, 1,050 (2.4%) patients were found to have AF on subsequent ECG recordings. Several ECG characteristics, such as P-wave dispersion (the difference between the widest and narrowest P waves), premature atrial contractions, and an abnormal P axis, were predictive of AF with hazard ratio of approximately 2 after correcting for age and sex. P-wave index, the SD of P-wave duration across all leads, was one of the strongest predictors of AF with a concordance index of 0.62 and a hazard ratio of 2.7 (95% CI 2.1-3.3) for a P-wave index >35. These were among the several independently predictive markers identified on multivariate analysis.Several ECG markers are independently predictive of future onset of AF. The P index, a measurement of disorganized atrial depolarization, is one of the strongest predictors of AF. The ECG contains valuable prognostic information that can identify patients at risk of AF.

  View details for DOI 10.1016/j.ahj.2009.08.002

  View details for Web of Science ID 000270706100020

  View details for PubMedID 19781423

• Visualizing ablation gaps in vitro using a deflectable fiber optic endocardial visualization catheter JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY Irani, A. R., Lin, B., Eversull, C., Hsia, H. H., Zei, P. C., Wang, P. J., Al-Ahmad, A. 2009; 25 (2): 107-110

  Abstract

  The efficacy of pulmonary vein isolation for the treatment of atrial fibrillation may be limited by the ability to make continuous and transmural lesions utilizing an ablation catheter. Gaps often persist between ablation lesions leading to failed electrical isolation and thus failed ablation. Recently, a deflectable fiberoptic endocardial visualization catheter has been introduced for use in imaging the coronary sinus using light in the visible spectrum. We utilize this catheter to visualize the endocardial surface and examine radiofrequency ablation lesions in porcine endocardium to determine the presence of gaps between radiofrequency lesions.Videos were taken of the lesions and shown to two readers who were asked to identify the gaps ranging from less than 0.1 mm-9.8 mm.Ninety-four lesion gaps were reviewed. The readers demonstrated a combined accuracy of 98.4% at identifying gaps.Gaps between ablation lesions can be accurately identified down to less than 1 mm distances in vitro using a direct visualization catheter. Further studies are warranted to confirm these finding in vivo.

  View details for DOI 10.1007/s10840-008-9338-7

  View details for Web of Science ID 000267683500004

  View details for PubMedID 19148727

• Worsening of Left Ventricular End-Systolic Volume and Mitral Regurgitation without Increase in Left Ventricular Dyssynchrony on Acute Interruption of Cardiac Resynchronization Therapy ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES Kuppahally, S. S., Fowler, M. B., Vagelos, R., Wang, P., Al-Ahmad, A., Paloma, A., Liang, D. 2009; 26 (7): 759-765

  Abstract

  Responders to cardiac resynchronization therapy (CRT) have greater left ventricular (LV) dyssynchrony than nonresponders prior to CRT.We conducted this study to see whether the long term responders have more worsening of LV dyssynchrony and LV function on acute interruption of CRT.We identified 22 responders and 13 nonresponders who received CRT as per standard criteria for 23.73 +/- 7.9 months (median 24.5 months). We assessed the acute change in LV function, mitral regurgitation (MR) and compared LV dyssynchrony in CRT on and off modes.On turning off CRT, there was no significant worsening of LV dyssynchrony in both responders and nonresponders. The dyssynchrony measurements by SPWMD, TDI and 3D echocardiography did not correlate significantly. LVESV increased (p = 0.02) and MR (p = 0.01) worsened in CRT-off mode in responders only without significant change in LVEF or LV dimensions. Discussion andIn long-term responders to CRT, there is alteration in the function of remodeled LV with acute interruption of CRT, without significant worsening of LV dyssynchrony. The role of different echocardiographic parameters in the assessment of LV dyssynchrony remains controversial. Even after long-term CRT reversely remodels the LV, the therapy needs to be continued uninterrupted for sustained benefits.

  View details for DOI 10.1111/j.1540-8175.2008.00887.x

  View details for Web of Science ID 000268457100002

  View details for PubMedID 19558521

• Prevention of phrenic nerve injury during epicardial ablation: Comparison of methods for separating the phrenic nerve from the epicardial surface HEART RHYTHM Di Biase, L., Burkhardt, J. D., Pelargonio, G., Dello Russo, A., Casella, M., Santarelli, P., Horton, R., Sanchez, J., Gallinghouse, J. G., Al-Ahmad, A., Wang, P., Cummings, J. E., Schweikert, R. A., Natale, A. 2009; 6 (7): 957-961

  Abstract

  The proximity of the phrenic nerve (PN) to cardiac tissue relevant to arrhythmias may increase the risk of PN injury. Strategies for preventing PN injury in the pericardial space are limited.The purpose of this study was to compare methods for separating the PN from the epicardial surface in order to prevent PN injury.Eight patients referred for epicardial ablation of arrhythmias were enrolled in the study. All patients required ablation near the PN. Endocardial and epicardial access was obtained in all patients. A three-dimensional mapping system was used to guide mapping and ablation. All patients underwent epicardial catheter ablation. Pacing via the ablation catheter identified the location of the PN. In order to prevent PN injury, four new strategies were tested in each patient. We sought to increase the distance between the epicardium and the PN by (1) placing a large-diameter balloon between the nerve and the myocardium, (2) introducing saline in steps of 20 ml until PN capture was lost or blood pressure dropped below 60 mmHg, (3) introducing air until PN capture was lost or blood pressure dropped below 60 mmHg, or (4) introducing a combination of saline and air until PN capture was lost or blood pressure dropped below 60 mmHg.At each step, epicardial pacing was performed to assess for PN stimulation. The combination of air and saline resulted in the greatest decrease of PN stimulation. Saline only failed in all cases. Air only and balloon placement were infrequently successful.Controlled and progressive inflation of air and saline together with careful monitoring of hemodynamic parameters appears to be the best strategy for preventing PN injury during epicardial ablation. Placement of a large balloon in the appropriate location can be difficult.

  View details for DOI 10.1016/j.hrthm.2009.03.022

  View details for Web of Science ID 000267791900005

  View details for PubMedID 19560084

• Direct Visualization of Cardiac Radiofrequency Ablation Lesions JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH Eversull, C. S., Lin, B., Irani, A. R., Quigley, M. L., Mourlas, N. J., Hsia, H. H., Zei, P. C., Al-Ahmad, A., Wang, P. J. 2009; 2 (2): 198-201

  Abstract

  Effective ablation of atrial fibrillation and other cardiac arrhythmias requires precise catheter navigation and controlled delivery of energy to cardiac tissue. In this study, we summarize our initial experience using a fiber optic direct visualization catheter to evaluate and guide placement of endocardial radiofrequency (RF) ablation lesions. RF lesions were created in cadaveric porcine hearts and examined in a blood-filled field using a direct visualization catheter. Direct visualization of RF lesions was repeated in vivo using an ovine model. Lesions and interlesion gaps were clearly identifiable using the direct visualization catheter. It was possible to place lesions in proximity to anatomical landmarks and in relation to one another. Catheter-generated images correlated well with lesion appearance on gross examination. Direct catheter-based visualization is a feasible technique for guiding RF lesion placement, estimating lesion size, and identifying interlesion gaps. Future work is needed to correlate surface appearance with transmurality and electrical isolation.

  View details for DOI 10.1007/s12265-009-9094-9

  View details for Web of Science ID 000284690100010

  View details for PubMedID 20559988

• The Efficacy of Implantable Cardioverter-Defibrillators in Heart Transplant Recipients Results From a Multicenter Registry CIRCULATION-HEART FAILURE Tsai, V. W., Cooper, J., Garan, H., Natale, A., Ptaszek, L. M., Ellinor, P. T., Hickey, K., Downey, R., Zei, P., Hsia, H., Wang, P., Hunt, S., Haddad, F., Al-Ahmad, A. 2009; 2 (3): 197-201

  Abstract

  Sudden cardiac death among orthotopic heart transplant recipients is an important mechanism of death after cardiac transplantation. The role for implantable cardioverter-defibrillators (ICDs) in this population is not well established. This study sought to determine whether ICDs are effective in preventing sudden cardiac death in high-risk heart transplant recipients.We retrospectively analyzed the records of all orthotopic heart transplant patients who had ICD implantation between January 1995 and December 2005 at 5 heart transplant centers. Thirty-six patients were considered high risk for sudden cardiac death. The mean age at orthotopic heart transplant was 44+/-14 years, the majority being male (n=29). The mean age at ICD implantation was 52+/-14 years, whereas the average time from orthotopic heart transplant to ICD implant was 8 years +/-6 years. The main indications for ICD implantation were severe allograft vasculopathy (n=12), unexplained syncope (n=9), history of cardiac arrest (n=8), and severe left ventricular dysfunction (n=7). Twenty-two shocks were delivered to 10 patients (28%), of whom 8 (80%) received 12 appropriate shocks for either rapid ventricular tachycardia or ventricular fibrillation. The shocks were effective in terminating the ventricular arrhythmias in all cases. Three (8%) patients received 10 inappropriate shocks. Underlying allograft vasculopathy was present in 100% (8 of 8) of patients who received appropriate ICD therapy.Use of ICDs after heart transplantation may be appropriate in selected high-risk patients. Further studies are needed to establish an appropriate prevention strategy in this population.

  View details for DOI 10.1161/CIRCHEARTFAILURE.108.814525

  View details for Web of Science ID 000269161600007

  View details for PubMedID 19808340

• Atrial Fibrillation Ablation Strategies for Paroxysmal Patients Randomized Comparison Between Different Techniques CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Di Biase, L., Elayi, C. S., Fahmy, T. S., Martin, D. O., Ching, C. K., Barrett, C., Bai, R., Patel, D., Khaykin, Y., Hongo, R., Hao, S., Beheiry, S., Pelargonio, G., Dello Russo, A., Casella, M., Santarelli, P., Potenza, D., Fanelli, R., Massaro, R., Wang, P., Al-Ahmad, A., Arruda, M., Themistoclakis, S., Bonso, A., Rossillo, A., Raviele, A., Schweikert, R. A., Burkhardt, D. J., Natale, A. 2009; 2 (2): 113-119

  Abstract

  Whether different ablation strategies affect paroxysmal atrial fibrillation (AF) long-term freedom from AF/atrial tachyarrhythmia is unclear. We sought to compare the effect of 3 different ablation approaches on the long-term success in patients with paroxysmal AF.One hundred three consecutive patients with paroxysmal AF scheduled for ablation and presenting in the electrophysiology laboratory in AF were selected for this study. Patients were randomized to pulmonary vein antrum isolation (PVAI; n=35) versus biatrial ablation of the complex fractionated atrial electrograms (CFAEs; n=34) versus PVAI followed by CFAEs (n=34). Patients were given event recorders and followed up at 3, 6, 9, 12, and 15 months postablation. There was no statistical significant difference between the groups in term of sex, age, AF duration, left atrial size, and ejection fraction. At 1 year follow-up, freedom from AF/atrial tachyarrhythmia was documented in 89% of patients in the PVAI group, 91% in the PVAI plus CFAEs group, and 23% in the CFAEs group (P<0.001) after a single procedure and with antiarrhythmic drugs.No difference in terms of success rate was seen between PVAI alone and PVAI associated with defragmentation. CFAEs ablation alone had the smallest impact on AF recurrences at 1-year follow-up. These results suggest that antral isolation is sufficient to treat most patients with paroxysmal AF.

  View details for DOI 10.1161/CIRCEP.108.798447

  View details for Web of Science ID 000266127400005

  View details for PubMedID 19808455

• Statin Use and Ventricular Arrhythmias During Clinical Treadmill Testing JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Dewey, F. E., Perez, M., Hadley, D., Freeman, J. V., Wang, P., Ashley, E. A., Myers, J., Froelicher, V. F. 2009; 20 (2): 193-199

  Abstract

  Premature ventricular complexes (PVCs) during exercise are associated with adverse prognosis, particularly in patients with intermediate treadmill test findings. Statin use reduces the incidence of resting ventricular arrhythmias in patients with coronary artery disease; however, the relationship between statin use and exercise-induced ventricular arrhythmias has not been investigated.We evaluated the association between statin use and PVCs in 1,847 heart-failure-free patients (mean age 58, 95% male) undergoing clinical exercise treadmill testing between 1997 and 2004 in the VA Palo Alto Health Care System. PVCs were quantified in beats per minute and frequent PVCs were defined as PVC rates greater than the median value (0.43 and 0.60 PVCs per minute for exercise and recovery, respectively). Propensity-adjusted logistic regression was used to evaluate the odds of developing PVCs during exercise and recovery periods associated with statin use. There were 431 subjects who developed frequent PVCs during exercise and 284 subjects had frequent recovery PVCs. After propensity score adjustment, subjects treated with statins (n = 145) had 42% lower odds of developing frequent PVCs during exercise (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.37-0.93) and 44% lower odds of developing frequent PVCs during recovery (OR 0.56, 95% CI 0.30-0.94). These effects were not modified by age, prior coronary disease, hypercholesterolemia, exercise-induced angina, or exercise capacity.Statin use was associated with reduced odds of frequent PVCs during and after clinical exercise testing in a manner independent of associations with coronary disease or ischemia in our study population.

  View details for DOI 10.1111/j.1540-8167.2008.01284.x

  View details for Web of Science ID 000262889000012

  View details for PubMedID 18775041

• A New Approach for ICD Rhythm Classification based on Support Vector Machines Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society Kamousi, B., Tewfik, A., Lin, B., Al-Ahmad, A., Hsia, H., Zei, P., Wang, P. IEEE. 2009: 2478–2481

  Abstract

  Inappropriate shocks due to misclassification of supraventricular and ventricular arrhythmias remain a major problem in the care of patients with Implantable Cardioverter Defibrillators (ICDs). The purpose of this study was to investigate the ability of a new covariance-based support vector machine classifier, to distinguish ventricular tachycardia from other rhythms such as supraventricular tachycardia. The proposed algorithm is applicable on both single and dual chamber ICDs and has a low computational demand. The results demonstrate that suggested algorithm has considerable promise and merits further investigation.

  View details for Web of Science ID 000280543601357

  View details for PubMedID 19964965

• Pulmonary-vein isolation for atrial fibrillation in patients with heart failure NEW ENGLAND JOURNAL OF MEDICINE Khan, M. N., Jais, P., Cummings, J., Di Biase, L., Sanders, P., Martin, D. O., Kautzner, J., Hao, S., Themistoclakis, S., Fanelli, R., Potenza, D., Massaro, R., Wazni, O., Schweikert, R., Saliba, W., Wang, P., Al-Ahmad, A., Beheiry, S., Santarelli, P., Starling, R. C., Dello Russo, A., Pelargonio, G., Brachmann, J., Schibgilla, V., Bonso, A., Casella, M., Raviele, A., Haissaguerre, M., Natale, A. 2008; 359 (17): 1778-1785

  Abstract

  Pulmonary-vein isolation is increasingly being used to treat atrial fibrillation in patients with heart failure.In this prospective, multicenter clinical trial, we randomly assigned patients with symptomatic, drug-resistant atrial fibrillation, an ejection fraction of 40% or less, and New York Heart Association class II or III heart failure to undergo either pulmonary-vein isolation or atrioventricular-node ablation with biventricular pacing. All patients completed the Minnesota Living with Heart Failure questionnaire (scores range from 0 to 105, with a higher score indicating a worse quality of life) and underwent echocardiography and a 6-minute walk test (the composite primary end point). Over a 6-month period, patients were monitored for both symptomatic and asymptomatic episodes of atrial fibrillation.In all, 41 patients underwent pulmonary-vein isolation, and 40 underwent atrioventricular-node ablation with biventricular pacing; none were lost to follow-up at 6 months. The composite primary end point favored the group that underwent pulmonary-vein isolation, with an improved questionnaire score at 6 months (60, vs. 82 in the group that underwent atrioventricular-node ablation with biventricular pacing; P<0.001), a longer 6-minute-walk distance (340 m vs. 297 m, P<0.001), and a higher ejection fraction (35% vs. 28%, P<0.001). In the group that underwent pulmonary-vein isolation, 88% of patients receiving antiarrhythmic drugs and 71% of those not receiving such drugs were free of atrial fibrillation at 6 months. In the group that underwent pulmonary-vein isolation, pulmonary-vein stenosis developed in two patients, pericardial effusion in one, and pulmonary edema in another; in the group that underwent atrioventricular-node ablation with biventricular pacing, lead dislodgment was found in one patient and pneumothorax in another.Pulmonary-vein isolation was superior to atrioventricular-node ablation with biventricular pacing in patients with heart failure who had drug-refractory atrial fibrillation. (ClinicalTrials.gov number, NCT00599976.)

  View details for Web of Science ID 000260245800005

  View details for PubMedID 18946063

• Optimal Programming of ICDs for Prevention of Appropriate and Inappropriate Shocks. Current treatment options in cardiovascular medicine Lo, R., Al-Ahmad, A., Hsia, H., Zei, P. C., Wang, P. J. 2008; 10 (5): 408-416

  Abstract

  Expansion of indications for implantable cardioverter-defibrillators (ICDs) has led to a significant increase in the number of patients receiving ICDs and the number of lives saved because of ICD therapy. However, appropriate or inappropriate shocks are frequent and may result in a significant decrease in quality of life in patients with ICDs. Atrial fibrillation with rapid ventricular response, sinus tachycardia, atrial tachycardia or atrial flutter with rapid conduction, and other supraventricular tachycardias are the most common arrhythmias causing inappropriate therapy. Other causes include oversensing of diaphragmatic potentials or myopotentials, T-wave oversensing, double or triple counting of intracardiac signals, lead fractures or header connection problems, lead chatter or noise, and electromagnetic interference. Strategies to reduce inappropriate therapy using device programming rely on the ability to distinguish supraventricular and atrial arrhythmias from ventricular tachycardia. Avoiding therapy for nonsustained ventricular arrhythmias and increasing the role of antitachycardia pacing to terminate ventricular tachycardia are key approaches to reducing shocks for ventricular arrhythmias. Optimal programming holds great promise for decreasing the overall incidence of shock therapy and increasing ICD acceptance.

  View details for PubMedID 18814830

• Pacemaker alternans terminated by telemetry wand: What is the mechanism? HEART RHYTHM Chun, H. J., Cook, K., Wang, P. J., Al-Ahmad, A. 2008; 5 (7): 1080-1082

  View details for DOI 10.1016/j.hrthm.2008.03.007

  View details for Web of Science ID 000257502900024

  View details for PubMedID 18598969

• Genetics of Arrhythmia: Disease Pathways Beyond Ion Channels JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH Perez, M. V., Wheeler, M., Ho, M., Pavlovic, A., Wang, P., Ashley, E. A. 2008; 1 (2): 155-165

  Abstract

  Diseases of the electrical conduction system that lead to irregularities in cardiac rhythm can have morbid and often lethal clinical outcomes. Linkage analysis has been the principal tool used to discover the genetic mutations responsible for Mendelian arrhythmic disease. Although the majority of arrhythmias can be accounted for by mutations in genes encoding ion channels, linkage analysis has also uncovered the role of other gene families such as those encoding members of the desmosome. With a list of candidates in mind, mutational analysis has helped confirm the suspicion that proteins found in caveolae or gap junctions also play a role in arrhythmogenesis. Atrial fibrillation and sudden cardiac death are relatively common arrhythmias that may be caused by multiple factors including common genetic variants. Genome-wide association studies are already revealing the important and poorly understood role of intergenic regions in atrial fibrillation. Despite the great advancements that have been made in our understanding of the genetics of these diseases, we are still far from able to routinely use genomic data to make clinical management decisions. There remain several hurdles in the study of genetics of arrhythmia, including the costs of genotyping, the need to find large affected families for linkage analysis, or to recruit large numbers of patients for genome-wide studies. Novel techniques that incorporate epigenetic information, such as known gene-gene interactions, biologic pathways, and experimental gene expression, will need to be developed to better interpret the large amount of genetic data that can now be generated. The study of arrhythmia genetics will continue to elucidate the pathophysiology of disease, help identify novel therapies, and ultimately allow us to deliver the individualized medical therapy that has long been anticipated.

  View details for DOI 10.1007/s12265-008-9030-4

  View details for Web of Science ID 000207734800012

  View details for PubMedID 20559910

• Time-resolved three-dimensional imaging of the left atrium and pulmonary veins in the interventional suite - A comparison between muttisweep gated rotational three-dimensional reconstructed fluoroscopy and multislice computed tomography HEART RHYTHM Al-Ahmad, A., Wigstroem, L., Sandner-Porkristl, D., Wang, P. J., Zei, P. C., Boese, J., Lauritsch, G., Moore, T., Chan, F., Fahrig, R. 2008; 5 (4): 513-519

  Abstract

  Cardiac computed tomography (CT) is commonly used to visualize left atrial (LA) anatomy for ablation of atrial fibrillation. We have developed a new imaging technique that allows acquisition and visualization of three-dimensional (3D) cardiac images in the catheter lab.We sought to compare LA and pulmonary vein (PV) dimensions acquired using gated multisweep rotational fluoroscopy (C-arm CT) system and multislice computed tomography (MSCT) in an in vivo porcine model.A Siemens AXIOM Artis dTA C-arm system (Siemens AG, Medical Solutions) was modified to allow acquisition of four bidirectional sweeps during synchronized acquisition of the electrocardiogram signal to allow retrospective gating. C-arm CT image volumes were then reconstructed. Gated MSCT (SOMATOM Sensation 16 and 64, Siemens AG, Medical Solutions) and C-arm CT images were acquired in six animals. The two main PV diameters were measured in orthogonal axes. LA volumes were calculated. C-arm CT measurements were compared with the MSCT measurements.The average PV diameters using the C-arm CT were 2.24 x 1.35 cm, versus 2.27 x 1.38 cm for CT. The average difference was 0.034 cm (1.9%) between the C-arm CT and standard CT. The average LA volume using MSCT was 49.1 +/- 12.7 cm(3), as compared with 51.0 +/- 8.7 cm(3) obtained by the C-arm CT. The average difference between the C-arm CT and the MSCT was 1.9 cm(3) (3.7%). There were no significant differences in either the PV or LA measurements.Visualization of 3D cardiac anatomy during ablation procedures is possible and highly accurate. The 3D cardiac reconstructions acquired during ablation procedures will be valuable for procedural planning and guidance.

  View details for DOI 10.1016/j.hrthm.2007.12.027

  View details for Web of Science ID 000254596600003

  View details for PubMedID 18362018

• A Covariance-Based Algorithm: A Novel Technique for Rhythm Discrimination in ICDs 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society Kamousi, B., Lin, B., Al-Ahmad, A., Hsia, H., Zei, P., Natale, A., Moss, A., Daubert, J., Zareba, W., Wang, P. IEEE. 2008: 5478–5481

  Abstract

  Inappropriate shocks due to misclassification of supraventricular and ventricular arrhythmias remain a major problem in the care of patients with Implantable Cardioverter defibrillators (ICDs). In this study we have investigated the ability of a new covariance-based algorithm, to distinguish Ventricular Tachycardia from other rhythms such as Supraventricular Tachycardia. The proposed algorithm has a low computational demand and with a small adjustment is applicable on both single-chamber and dual-chamber ICDs. The results are promising and suggest that the new covariance-based algorithm may be an effective method for ICD rhythm classification and may decrease inappropriate shocks.

  View details for Web of Science ID 000262404503170

  View details for PubMedID 19163957

• Characterization of human coronary sinus valves by direct visualization during biventricular pacemaker implantation PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Anh, D. J., Eversull, C. S., Chen, H. A., Mofrad, P., Mourlas, N. J., Mead, R. H., Zel, P. C., Hsia, H. H., Wang, P. J., Al-Ahmad, A. 2008; 31 (1): 78-82

  Abstract

  The precise reasons for failure to cannulate the coronary sinus during biventricular device implantation are unknown. Visualization of the coronary sinus ostium during electrophysiology procedures may enhance understanding of how unusual anatomy can affect successful cannulation of the coronary sinus.The aim of this study was to describe the morphology of valves at the coronary sinus ostium (CSO) visualized directly with an illuminated fiberoptic endoscope during implantation of biventricular devices.The coronary sinus anatomy of one hundred consecutive patients undergoing implantation of biventricular devices was investigated using a fiberoptic endocardial visualization catheter (EVC).The CSO was clearly visualized in 98 patients using the EVC. A Thebesian valve was seen in 54% of these. Almost all Thebesian valves were positioned at the inferior (61%) or posterior (33%) aspect of the CSO. Only six patients had Thebesian valves that covered more than 70% of the CSO, but all were successfully implanted with a transvenous left ventricular pacing lead after cannulating the coronary sinus under direct visualization.Over half of patients undergoing biventricular device implantation have identifiable Thebesian valves. Even valves covering the majority of the ostial area may be traversed using direct visualization and modern catheterization techniques.

  View details for Web of Science ID 000253373400015

  View details for PubMedID 18181913

• Driving and implantable cardioverter-defibrillator shocks for ventricular arrhythmias JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Albert, C. M., Rosenthal, L., Calkins, H., Steinberg, J. S., Ruskin, J. N., Wang, P., Muller, J. E., Mittleman, M. A. 2007; 50 (23): 2233-2240

  Abstract

  This study examined the risk of implantable cardioverter-defibrillator (ICD) shocks for ventricular tachycardia (VT) or ventricular fibrillation (VF) associated with driving.Concerns regarding VT/VF occurring during driving are the basis for driving restrictions in ICD patients; however, limited data are available to inform recommendations.This study used a prospective nested case-crossover design to compare the risk of ICD shock for VT/VF both during and up to 60 min after an episode of driving as compared with that during other activities among 1,188 ICD patients enrolled in the TOVA (Triggers of Ventricular Arrhythmia) study.Over a median follow-up of 562 days, there were 193 ICD shocks for VT/VF with data on exposure to driving before ICD shock. The absolute risk of ICD shock for VT/VF within 1 h of driving was estimated to be 1 episode per 25,116 person-hours spent driving. The ICD shocks for VT/VF were twice as likely to occur within 1 h of driving a car as compared with other times (relative risk [RR] 2.24, 95% confidence interval [CI] 1.57 to 3.18). This risk was specific for shocks for VT/VF and occurred primarily during the 30-min period after driving (RR 4.46, 95% CI 2.92 to 6.82) rather than during the driving episode itself (RR 1.05, 95% CI 0.48 to 2.30).Although the risk of ICD shock for VT/VF was transiently increased in the 30-min period after driving, the risk was not elevated during driving and the absolute risk was low. These data provide reassurance that driving by ICD patients should not translate into an important rate of personal or public injury.

  View details for DOI 10.1016/j.jacc.2007.06.059

  View details for Web of Science ID 000251330800007

  View details for PubMedID 18061071

• Cardiac device infections complicated by erosion JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY Tsai, V., Chen, H., Hsia, H., Zei, P., Wang, P., Al-Ahmad, A. 2007; 19 (2): 133-137

  Abstract

  Implantation of pacemakers and implantable cardioverter-defibrillators (ICDs) can be complicated by infection and device erosion. It is unclear if the clinical features of patients who have device erosion differ from those without erosion.We retrospectively examined the records of all patients referred for explantation of a pacemaker or defibrillator from January 2000 to May 2005. We examined demographic variables including age, gender, and body mass index (BMI) as well as clinical variables related to erosion and procedural variables.Seventy-two patients with infected pacemakers or ICDs were identified. Of these cases, 30 (42%) developed infection complicated by erosion, of which 8/28 (29%) were related to ICDs, and 22/44 (50%) were related to pacemakers.Device erosion was significantly associated with the presence of a non-systemic infection as opposed to cases without erosion. This finding may have implications in the timing of device re-implantation.

  View details for DOI 10.1007/s10840-007-9143-8

  View details for Web of Science ID 000249009800008

  View details for PubMedID 17668305

• VF and fatal cardiac arrest following ICD therapy delivery: What is the cause? PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Mofrad, P. S., Ottoboni, L., Zei, P. C., Hsia, H. H., Wang, P. J., Amin-Al-Ahmad 2007; 30 (4): 551-553

  View details for Web of Science ID 000245642600018

  View details for PubMedID 17437582

• The effect of gender on mortality or appropriate shock in patients with nonischemic cardiomyopathy who have implantable cardioverter-defibrillators PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Chen, H. A., Hsia, H. H., Vagelos, R., Fowler, M., Wang, P., Al-Ahmad, A. 2007; 30 (3): 390-394

  Abstract

  As heart disease is increasingly recognized in women and as important studies have elucidated the benefit of implantable cardioverter defibrillators (ICDs) in patients with nonischemic cardiomyopathy (NICM), little is known regarding the effect of gender difference on arrhythmic risk in this population. We sought to determine if there are gender differences in arrhythmic risk and potential defibrillator benefit in patients with NICM.The records of 767 consecutive patients who underwent ICD implant at the Stanford Medical Center from 1984 to 2002 were reviewed. Only patients with NICM were considered (n = 201, 26.2%). Of these, 140 patients had clinical follow-up information available. Baseline variables were examined, including age, baseline heart rate, ejection fraction, and medications. We evaluated the time to first shock as well as all-cause mortality in this patient population. Kaplan-Meier survival curves were plotted, a log-rank test was used to evaluate significance, and Cox-proportional hazards test was used for multivariate analysis.There were 88 (62.9%) men and 52 (37.1%) women. Between male and female patients, there were no significant differences in baseline mean age (54.8 +/- 1.9 years vs 53.1 +/- 2.3 years, respectively), ejection fraction (35.2 +/- 2.0% vs 33.3 +/- 2.3%, respectively), and mean left ventricular end-diastolic dimension (6.4 +/- 0.3 cm vs 5.9 +/- 0.2 cm, respectively). Mean follow-up time was 30.8 months. Thirty-two male patients (36.4 +/- 0.05%) received appropriate shocks compared with 20 female patients (38.5 +/- 0.07%). Mean time to the first appropriate shock was 11.9 +/- 3.9 months for male patients and 21.3 +/- 5.8 months for female patients (P = 0.2). Nineteen male patients (21.6 +/- 0.05%) died or received heart transplant during the follow-up period compared with 6 female patients (11.5 +/- 0.04%) (P = 0.11).Male and female patients with NICM who received ICDs had similar rate of appropriate shock and mortality. In this population gender does not appear to be an important risk factor for mortality or arrhythmic events.

  View details for Web of Science ID 000244886500013

  View details for PubMedID 17367359

• Inappropriate shock: A failure of SVT discriminators in a dual chamber ICD? PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Al-Ahmad, A., Tsiperfal, A., Hsia, H. H., Wang, P. J. 2006; 29 (12): 1413-1415

  Abstract

  Inappropriate shock remains a major issue in patients with implantable cardioverter defibrillators. We examine an inappropriate shock delivered in a patient with atrial tachycardia that conducted 1:1. We reconstruct the device algorithms that led to therapy delivery and discuss programming changes that could be considered.

  View details for Web of Science ID 000243530800015

  View details for PubMedID 17201851

• Isolated giant cell myocarditis in the atrium: An incidental finding? PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Ahmad, I., Miller, D. C., Berry, G. J., Hsia, H. H., Wang, P. J., Al-Ahmad, A. 2006; 29 (10): 1179-1180

  Abstract

  Giant cell myocarditis (GCM) is an uncommon disorder that affects ventricular myocardium causing severe left ventricular dysfunction and ventricular arrhythmias. We report a case of GCM that only affected the atrium sparing the ventricle.

  View details for Web of Science ID 000241995100019

  View details for PubMedID 17038151

• Early human experience with use of a deflectable fiberoptic endocardial visualization catheter to facilitate coronary sinus cannulation HEART RHYTHM Anh, D. J., Chen, H. A., Eversull, C. S., Mourlas, N. J., Mead, R. H., Liem, L. B., Hsia, H. H., Wang, P. J., Al-Ahmad, A. 2006; 3 (8): 875-878

  Abstract

  Despite improvements in cardiac resynchronization therapy (CRT) implantation techniques, a significant minority of CRT attempts are unsuccessful. Inability to cannulate the coronary sinus (CS) because of difficult anatomy is a major reason for unsuccessful CRT implantation. Direct visualization of intracardiac structures during the implant may facilitate access into the CS. The present study describes CRT implantation with the aid of an endocardial visualization catheter (EVC).Fifty-eight consecutive patients (mean age 72 +/- 12 years; ejection fraction 26.2% +/- 7.0%; New York Heart Association [NYHA] class 2.9) underwent CRT implantation using a steerable fiberoptic EVC (Acumen Medical, Inc., Sunnyvale, CA).The EVC was able to visualize the CS ostium in all cases. The CS was successfully cannulated in 57 (98.3%) of 58 patients. The time from vascular access to CS visualization was 6 +/- 5 minutes, and the total time to CS access was 8 +/- 6 minutes. Successful left ventricle (LV) lead implantation was accomplished in 55 (94.8%) of 58 patients. Three patients who had a previous history of failed LV lead implantation were successfully implanted using the EVC.Fiberoptic imaging of intracardiac structures during CRT implantation may be performed rapidly in a wide range of patients with an EVC. The ability to visualize right atrial anatomy may aid CS access and LV lead implantation.

  View details for DOI 10.1016/j.hrthm.2006.04.029

  View details for Web of Science ID 000239746400001

  View details for PubMedID 16876731

• Left ventricular dyssynchrony does not deteriorate acutely on cessation of cardiac resynchronization therapy in long term responders 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America Kuppahally, S., Fowler, M., Wang, P., Vagelos, R., Al-Ahmad, A., Paloma, A., Liang, D. CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2006: S76–S76

  View details for Web of Science ID 000240205000246

• Improvement in quality of life after radiofrequency ablation PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Hlatky, M. A., Wang, P. 2006; 29 (4): 341-342

  View details for Web of Science ID 000237453300001

  View details for PubMedID 16650259

• Supraventricular tachycardia vs ventricular tachycardia: What is the rhythm HEART RHYTHM Al-Ahmad, A., Tsiperfal, A., Hsia, H. H., Wang, P. J. 2006; 3 (4): 490-491

  View details for DOI 10.1016/j.hrthm.2005.11.031

  View details for Web of Science ID 000236743400023

  View details for PubMedID 16567303

• Premature ventricular contractions causing pacemaker-mediated tachycardia: A failure of postventricular atrial refractory period after premature ventricular contraction extension? HEART RHYTHM Witteles, R., Engel, G., Wang, P. J., Al-Ahmad, A. 2005; 2 (12): 1389-1390

  View details for DOI 10.1016/j.hrthm.2005.08.023

  View details for Web of Science ID 000234241200023

  View details for PubMedID 16360099

• Delivery of antitachycardia pacing after a full-energy shock during the same ventricular tachycardia episode: Appropriate device function? HEART RHYTHM Sirulnick, E., Tsiperfal, A., Wang, P. J., Al-Ahmad, A. 2005; 2 (11): 1266-1267

  View details for Web of Science ID 000233102900018

  View details for PubMedID 16253921

• Use of the implantable cardioverter-defibrillator in long-term survivors of orthotopic heart transplantation HEART RHYTHM Ptaszek, L. M., Wang, P. J., Hunt, S. A., Valantine, H., Perlroth, M., Al-Ahmad, A. 2005; 2 (9): 931-933

  Abstract

  Orthotopic heart transplantation is considered an effective treatment for patients with refractory heart failure. The long-term survival of orthotopic heart transplantation recipients has increased over the last several decades, but many long-term survivors of orthotopic heart transplantation develop graft atherosclerosis and associated left ventricular dysfunction. The risk of sudden cardiac death in long-term survivors of orthotopic heart transplantation with these complications is believed to be high. There are no data on the usefulness of implantable cardioverter-defibrillators (ICDs) in this population; therefore, we report our early experience with ICD placement in such patients.The purpose of this study was to examine the use of ICDs in adults who are long-term survivors of heart transplantation.We retrospectively reviewed all adult patients who underwent orthotopic heart transplantation at Stanford University Hospital (Stanford, CA, USA) from 1980 to 2004. All patients who received an ICD after transplant were included in this study. We reviewed demographic data, medical history, ejection fraction, presence of graft atherosclerosis, indication for ICD placement, and any device therapy delivered.Of the 925 patients who had orthotopic heart transplantation during this time period, 493 patients were alive at the beginning of the year 2000. Of these patients, 10 ( approximately 2%) had subsequent placement of an ICD. All 10 patients were male. The average age at orthotopic heart transplantation was 37.8 years. The average age at ICD placement was 50.5 years. The average time from orthotopic heart transplantation to ICD placement was 14.6 years. The average ejection fraction at the time of implant was 46.5%. Five of the 10 patients had a low ejection fraction (within this subgroup, the average ejection fraction was 31%, range 15%-45%) and graft atherosclerosis. ICDs were placed because of symptomatic episodes of ventricular tachycardia (3 patients), low ejection fraction and severe graft atherosclerosis without symptoms (3 patients), and after thorough evaluation for otherwise unexplained syncope (4 patients). The average follow-up after device implantation was 13 months. Complications related to ICD placement were an infected ICD system requiring explant in one patient and a lead fracture in another patient. Three patients had subsequent appropriate shocks for ventricular arrhythmias, and one patient underwent a second orthotopic heart transplantation. One patient died of malignancy.Use of the ICD in long-term survivors of orthotopic heart transplantation should be considered in appropriately selected patients. Further data are needed regarding ICD use in this population.

  View details for DOI 10.1016/j.hrthm.2005.06.018

  View details for Web of Science ID 000231986200008

  View details for PubMedID 16171746

• T-wave abnormalities are a better predictor of cardiovascular mortality than ST depression on the resting electrocardiogram ANNALS OF NONINVASIVE ELECTROCARDIOLOGY Beckerman, J., Yamazaki, T., Myers, J., Boyle, C., Chun, S., Wang, P., Froelicher, V. 2005; 10 (2): 146-151

  Abstract

  ST depression and T-wave amplitude abnormalities are known to be independent predictors of cardiovascular (CV) death, but a direct comparison between them has not been described.Analyses were performed on the first electrocardiogram (ECG) digitally recorded on 46,950 consecutive patients at the Palo Alto Veterans Affairs Medical Center since 1987. Females and patients with electrocardiograms exhibiting bundle branch block, left ventricular hypertrophy, electronic pacing, diagnostic Q waves, or Wolff-Parkinson-White syndrome were excluded, leaving 31,074 male patients for analysis (mean age 55 +/- 14). There were 1878 (6.0%) cardiovascular deaths (mean follow-up of 6 +/- 4 years). Electrocardiograms were classified using Minnesota code according to the degree of ST depression and T-wave abnormality, and the nine possible combinations of ST segment and T-wave abnormalities were recoded for analysis.The combination of major abnormalities in ST segments and T-waves carried the greatest hazard [3.2 (CI 2.7-3.8)]. Minor ST depression combined with more severe T-wave abnormalities carried a hazard of 3.1 (CI 2.5-3.7), whereas minor T-wave abnormalities combined with more severe ST depression carried a hazard of only 1.9 (CI 1.6-2.3).While both ST segment depression and abnormal T-wave amplitude are clinically important, T-wave abnormalities appear to be greater predictors of cardiovascular mortality.

  View details for Web of Science ID 000228826100005

  View details for PubMedID 15842426

• Early experience with a computerized robotically controlled catheter system JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY Al-Ahmad, A., Grossman, J. D., Wang, P. J. 2005; 12 (3): 199-202

  Abstract

  Recently, the use of robotic assisted surgery has been utilized in cardiac surgical procedures. The use of robotics may offer benefits in precision, stability and control of instruments remotely. We report early experience with a novel remote robotic catheter control system (CCS).We used a computerized robotically controlled catheter system that enables the user to remotely manipulate the tip of a catheter precisely in three dimensions. We tested the robotic catheter control systems ability to navigate within the heart and to make precise, rapid and repeatable movements. We compared the CCS with the ability of a standard quadripolar steerable ablation catheter placed in a deflectable sheath to navigate and make precision movements. Twelve ex-vivo porcine hearts were utilized to permit accurate measurements of navigation and precision. Eight targets were selected for navigation and precision testing. Time was measured for the catheter to reach the predefined target from a specific starting point to test navigation. In addition, time was measured to contact a discrete 0.8 mm target in order to test precision.The use of the CCS reduced the time needed for both navigation (8.5 +/- 13.9 sec vs. 22.7 +/- 26.7 sec, p = 0.002) and significantly decreased the time for precision targeting (10.1 +/- 6.9 sec vs. 29.6 +/- 26.4 sec, p < 0.001) in the specific RA and LA sites in the ex-vivo hearts.The use of a computerized robotically assisted catheter control system is feasible and shows promise in rapid precision movement of the catheter. Further study is needed to elucidate the role of such a system in-vivo and in patient specific catheter ablation and mapping.

  View details for DOI 10.1007/s10840-005-0325-y

  View details for Web of Science ID 000228972600004

  View details for PubMedID 15875110

• Atrial pacing above the sensor rate: What is the cause? HEART RHYTHM Al-Ahmad, A., Tsiperfal, A., Wang, P. J. 2005; 2 (2): 210-211

  View details for DOI 10.1016/j.hrthm.2004.10.005

  View details for Web of Science ID 000226953200022

  View details for PubMedID 15851301

• Spatial QRS-T angle predicts cardiac death in a clinical population HEART RHYTHM Yamazaki, T., Froelicher, V. F., Myers, J., Chun, S., Wang, P. 2005; 2 (1): 73-78

  Abstract

  The purpose of this study was to validate the prognostic value of computer-derived measurements of the spatial alignment of ventricular depolarization and repolarization from the standard 12-lead ECG in a general medical population.Analyses were performed on the first ECG digitally recorded from 46,573 consecutive patients since 1987. QRS and T vector were synthesized by deriving XYZ leads from the 12 leads using the inverse Dower weighting matrix. Subset analyses were considered in patients with and those without standard ECG diagnoses (i.e., atrial fibrillation, Q waves, left ventricular hypertrophy, prolonged QRS duration). The main outcome measure was cardiovascular mortality.During a mean follow-up of 6 years, 4,127 cardiovascular deaths occurred. After adjusting for age, heart rate, and gender in a Cox regression analysis, spatial QRS-T angle was the most significant predictor of cardiovascular mortality, outperforming all other ECG measurements and diagnostic statements. In the subset with ECGs free of any standard diagnoses, annual cardiovascular mortality was 0.8% for normal (0-50 degrees ), 2.3% for borderline (50-100 degrees ), and 5.1% for abnormal (100-180 degrees ) QRS-T angle groups. The borderline and abnormal angle groups had 1.5- and 1.9-fold higher risk, respectively, relative to the normal QRS-T angle group after adjustment for age, gender, and heart rate. Similar results were found when patients with standard ECG diagnosis were included or compared.Spatial QRS-T angle is a significant and independent predictor of cardiovascular mortality that provides greater prognostic discrimination than any of the commonly utilized ECG diagnostic classifications.

  View details for DOI 10.1016/j.hrthm.2004.10.040

  View details for Web of Science ID 000226446500014

  View details for PubMedID 15851268

• Loss of biventricular pacing: What is the cause? HEART RHYTHM Richardson, K., Cook, K., Wang, P. J., Al-Ahmad, A. 2005; 2 (1): 110-111

  View details for DOI 10.1016/j.hrthm.2004.09.015

  View details for Web of Science ID 000226446500023

  View details for PubMedID 15851277

• Electrocardiographic arrhythmia risk testing CURRENT PROBLEMS IN CARDIOLOGY Engel, G., Beckerman, J. G., Froelicher, V. F., Yamazaki, T., Chen, H. A., Richardson, K., McAuley, R. J., Ashley, E. A., Chun, S., Wang, P. J. 2004; 29 (7): 365-432

  Abstract

  Among the most compelling challenges facing cardiologists today is identification of which patients are at highest risk for sudden death. Automatic implantable cardioverter-defibrillators are now indicated in many of these patients, yet the role of noninvasive risk stratification in classifying patients at high risk is not well defined. The purpose of this review is to evaluate the various electrocardiographic (ECG) techniques that appear to have potential in assessment of risk for arrhythmia. The resting ECG (premature ventricular contractions, QRS duration, damage scores, QT dispersion, and ST segment and T wave abnormalities), T wave alternans, late potentials identified on signal-averaged ECGs, and heart rate variability are explored. Unequivocal evidence to support the widespread use of any single noninvasive technique is lacking; further research in this area is needed. It is likely that a combination of risk evaluation techniques will have the greatest predictive power in enabling identification of patients most likely to benefit from device therapy.

  View details for DOI 10.1016/j.cpcardiol.2004.02.007

  View details for Web of Science ID 000222170600002

  View details for PubMedID 15192691

• Cardiovascular screening of athletes CLINICAL JOURNAL OF SPORT MEDICINE Beckerman, J., Wang, P., Hlatky, M. 2004; 14 (3): 127-133

  Abstract

  Cardiovascular screening of athletes is a challenging aspect of the preparticipation evaluation. While sudden cardiac death in young athletes is uncommon, preparticipation screening may identify some predisposing conditions that place individuals at increased risk. The most common pre-existing cardiac abnormalities in athletes causing sudden death in the United States are hypertrophic cardiomyopathy, congenital coronary anomalies, and Marfan syndrome. Preparticipation cardiovascular screening should pursue any history of cardiac symptoms or family history of premature cardiac disease, as well as abnormal cardiovascular physical findings. Positive findings should be investigated; an electrocardiogram, echocardiogram, or consultation with a specialist should be considered. Recommendations are then available to guide athletic participation according to the cardiovascular diagnosis.

  View details for Web of Science ID 000230327200004

  View details for PubMedID 15166900

• Frequent ICD shocks due to double sensing in patients with bi-ventricular implantable cardioverter defibrillators JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY Al-Ahmad, A., Wang, P. J., Homoud, M. K., Estes, N. A., Link, M. S. 2003; 9 (3): 377-381

  Abstract

  Biventricular pacing has emerged as a modality for treatment of patients with heart failure. Combined biventricular pacers and implantable cardioverter defibrillators offer treatment of heart failure as well as protection from sudden cardiac death. However, inappropriate ICD shocks as a result of double sensing due to widely spaced ventricular bipoles may pose a significant problem in these patients. We examined the ICD records of twenty-three patients with biventricular ICDs, and evaluated all episodes of double sensing that resulted in aborted or delivered therapy. In follow-up of 3.7 +/- 2.6 months, thirty-three shocks in fifteen episodes occurred in five patients (21.7%) due to double sensing. Four patients (17.4%) had aborted shocks due to double sensing. All episodes resulting in shock occurred because of sinus tachycardia or supraventricular tachycardia above the upper programmed pacing rate of the device with resultant AV conduction and double sensing of the nonpaced ventricular depolarization. In conclusion, double sensing of the R-wave is a common and clinically important cause of inappropriate ICD detection and shock in patients with biventricular ICDs. Appropriate programming of the ICD can prevent episodes of inappropriate shocks.

  View details for Web of Science ID 000186420900011

  View details for PubMedID 14618060

• Cardiac arrhythmias in the athlete: the evolving role of electrophysiology. Current sports medicine reports Link, M. S., Homoud, M. K., Wang, P. J., Estes, N. A. 2002; 1 (2): 75-85

  Abstract

  Arrhythmia management has undergone a revolution in the past decade. The diagnosis and treatment of arrhythmias in the athlete can be complicated by the need to compete and exercise. Some arrhythmias may be benign and asymptomatic, but others may be life threatening. Sinus bradyarrhythmias are common and even expected in athletes; these are rarely a cause for concern. Heart block is unusual and merits a thorough work-up. Atrial fibrillation may be more common in the athlete, and supraventricular tachycardias other than atrial fibrillation warrant consideration of radiofrequency ablation for cure. Ventricular arrhythmias in the athlete generally occur in the setting of structural heart disease that is genetically determined (hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, anomalous coronary arteries), or acquired (coronary artery disease, myocarditis, idiopathic dilated cardiomyopathies). In these conditions the arrhythmia is life threatening. Ventricular arrhythmias that occur in the athlete without structural heart disease are not thought to be life threatening. Athletes with structural heart disease and those with exertional syncope merit a complete evaluation.

  View details for PubMedID 12831715

• Advances in implantable cardioverter defibrillators CURRENT OPINION IN CARDIOLOGY Swygman, C., Wang, P. J., Link, M. S., Homoud, M. K., Estes, N. A. 2002; 17 (1): 24-28

  Abstract

  Implantable cardioverter defibrillators (ICDs) have become an important therapeutic modality for patients who have had a cardiac arrest or are at risk for life-threatening ventricular arrhythmias. Clinical trials have confirmed the role of the ICD for patients with sustained ventricular arrhythmias and have expanded the indications to include patients with coronary artery disease, left ventricular dysfunction, nonsustained ventricular tachycardia, and inducible ventricular tachycardia. Numerous technologic advances in ICDs have resulted in decreased size, greater ease of placement, and increased functionality. Important advancements have been made in the effectiveness of arrhythmia classification and electrogram storage. Dual-chamber ICDs have become increasingly sophisticated with rate-adaptive sensors. Biventricular pacing is being combined with ICD function in patients with heart failure, systolic dysfunction, and QRS widening. Future advances in devices will likely lead to improved arrhythmia classification, more advanced automated features, and additional features including more sophisticated sensors and biventricular pacing systems.

  View details for Web of Science ID 000173100500004

  View details for PubMedID 11790930

• ECG findings in active patients - Differentiating the benign from the serious PHYSICIAN AND SPORTSMEDICINE Estes, N. A., Link, M. S., Homoud, M., Wang, P. J. 2001; 29 (3): 67-74

  Abstract

  ECGs and cardiac rhythms of normal athletes can vary widely. The heightened vagal tone from athletic conditioning can result in variant ECG findings that may mimic serious disorders. ECG patterns of long-QT syndrome, arrhythmogenic right ventricular dysplasia, Wolff-Parkinson-White syndrome, and hypertrophic cardiomyopathy signal the need for further evaluation, therapy, and possible participation restriction. Radiofrequency ablation may be appropriate when symptomatic supraventricular arrhythmias or Wolff-Parkinson-White syndrome is present. Further research is needed to effectively distinguish normal ECG changes in the athlete from changes that underlie cardiac disease. Improvements in identifying athletes at risk of serious or life-threatening arrhythmias are also needed.

  View details for Web of Science ID 000167312200013

  View details for PubMedID 20086567

• Cardiac arrhythmias in the athlete. Cardiology in review Link, M. S., Homoud, M. K., Wang, P. J., Estes, N. A. 2001; 9 (1): 21-30

  Abstract

  Cardiac arrhythmias in the athlete are a frequent cause for concern. Some arrhythmias may be benign and asymptomatic, but others may be life threatening and a sign that serious cardiovascular disease is present. Physicians often are consulted with regard to arrhythmias, or symptoms consistent with arrhythmias, in athletes. Sinus bradyarrhythmias are common and even expected in athletes. These bradyarrhythmias are rarely a cause for concern. Heart block is unusual and merits a thorough workup. Atrial fibrillation may be more common in the athlete. Supraventricular tachycardias other than atrial fibrillation generally warrant consideration of radiofrequency ablation for cure of the tachyarrhythmia. Ventricular arrhythmias in the athlete generally occur in the setting of structural heart disease that is genetically determined (hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, anomalous coronary arteries) or acquired (coronary artery disease, myocarditis, idiopathic dilated cardiomyopathies). In these conditions, the arrhythmia generally is life threatening. Ventricular arrhythmias that occur in the athlete without structural heart disease are not thought to be life threatening. Athletes with structural heart disease and syncope and those with exertional syncope merit a complete evaluation.

  View details for PubMedID 11174912

• ANTITACHYCARDIA PACING AND LOW-ENERGY CARDIOVERSION FAR VENTRICULAR-TACHYCARDIA TERMINATION - A CLINICAL PERSPECTIVE Symposium on Electrical Device Therapy for Cardiac Arrhythmias: New Concepts, Problems, and Alternatives Estes, N. A., Haugh, C. J., Wang, P. J., Manolis, A. S. MOSBY-YEAR BOOK INC. 1994: 1038–46

  Abstract

  When incorporated into tiered therapy implantable cardioverter defibrillators (ICDs), antitachycardia pacing (ATP) techniques have proved useful for termination of sustained monomorphic ventricular tachycardias (VT) and have the advantages of rapid delivery, absence of patient discomfort, and minimal battery drain. The efficacy of low-energy cardioversion (LEC) is similar to that of pacing techniques for VT termination, but LEC has the disadvantages of patient discomfort, atrial proarrhythmia, and greater battery drain compared with ATP. Acceleration of VT occurs with similar frequency with each technique. Neither technique should be used without back-up defibrillation capability in an ICD. VT termination algorithms are currently empiric and require repetitive arrhythmia induction and trials of ATP or LEC. Future studies of the risk and benefits of each technique are likely to define optimal programming strategies in tiered therapy ICDs.

  View details for Web of Science ID A1994NF85500011

  View details for PubMedID 8160578