Arthur J Moss

University Center Rochester, Рочестер, Minnesota, United States

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Publications (621)4867.45 Total impact

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    ABSTRACT: It has been proposed that competitive sport increases the risk of ventricular tachyarrhythmias (VTA) and death in patients with arrhythmogenic right-ventricular cardiomyopathy (ARVC). However, it is unknown whether this only applies to competitive sport or if recreational sports activity also increases the risk of VTA/death. Probands diagnosed with ARVC according to the 2010 task force criteria for ARVC (n = 108) were included in the current analysis. At the time of enrolment, study participants were questioned about exercise level prior to and after ARVC diagnosis, within three categories of sports participation: competitive (n = 41), recreational (n = 48), and inactive (n = 19). Competitive sport was associated with a significantly higher risk of VTA/death when compared with both recreational sport [HR = 1.99 (1.21-3.28), P = 0.007] and inactive patients [HR = 2.05 (1.07-3.91), P = 0.030]. No increased risk of VTA/death was associated with recreational sport when compared with patients who were inactive [HR = 1.03 (0.54-1.97), P = 0.930]. Symptoms developed at an earlier age in patients who participated in competitive sport (30 ± 12 years), when compared with patients who participated in recreational sport (38 ± 17 years) (P = 0.015) and inactive patients (41 ± 11 years) (P = 0.002). No difference in age at first symptom was seen between patients who participated in recreational sport and inactive patients (P = 0.651). Competitive sport was associated with a two-fold increased risk of VTA/death, and earlier presentation of symptoms, when compared with inactive patients, and to patients who participated in recreational sport. When compared with inactive patients, recreational sport was not associated with earlier onset of symptoms or increased risk of VTA/death. NCT00024505. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
    European Heart Journal 04/2015; DOI:10.1093/eurheartj/ehv110 · 14.72 Impact Factor
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    ABSTRACT: To date, most risk stratification studies in long-QT syndrome (LQTS) have focused on identification of high-risk subjects. Current data on the long-term clinical course of low-risk adult LQTS patients are limited. Patients in this study were from the Rochester-based LQTS Registry. We hypothesized that long-term survival of LQT1-2 patients with QTc <500ms and no cardiac symptoms before age 20 (n = 523) would be similar to that of their unaffected genotype-negative family members (n = 1134). Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression models were used to evaluate the incidence and risk of all-cause mortality in the study population. The low-risk LQTS study group comprised 27% (523/1919) of genetically confirmed LQTS Registry patients alive at age 20. The cumulative probability of all-cause mortality between age 20 and 65 was similar in the low-risk LQTS group and the genotype-negative control group (4.3% and 4.4%, respectively at age 65; p = 0.49 for overall difference). Multivariate analysis showed no significant difference in the risk of all-cause mortality between the two groups (HR = 0.89; 95% CI 0.33-2.43, p = 0.82). Consistent results were revealed in subgroup analyses in female and male LQTS patients and in patients with genetically identified LQT1 and LQT2 mutations. We identified a sizeable proportion of low-risk, adult LQTS patients with no cardiac symptoms before age 20 and QTc<500ms who had 45-year survival similar to unaffected family members. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Cardiovascular Electrophysiology 04/2015; DOI:10.1111/jce.12686 · 2.88 Impact Factor
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    ABSTRACT: The Selvester QRS scoring system uses quantitative criteria from the standard 12-lead electrocardiogram (ECG) to estimate the myocardial scar size of patients, including those with left bundle branch block (LBBB). Automation of the scoring system could facilitate the clinical use of this technique which requires a set of multiple QRS patterns to be identified and measured. We developed a series of algorithms to automatically detect and measure the QRS parameters required for Selvester scoring. The 'QUantitative and Automatic REport of Selvester Score' was designed specifically for the analysis of ECGs from patients meeting new strict criteria for complete LBBB. The algorithms were designed using a training (n = 36) and a validation (n = 180) set of ECGs, consisting of signal-averaged 12-lead ECGs (1000 Hz sampling) recorded from 216 LBBB patients from the MADIT-CRT. We assessed the performance of the methods using expert manually adjudicated ECGs. The average of absolute differences between automatic and adjudicated Selvester scoring was 1.2 ± 1.5 points. The range of average differences for continuous measurements of wave locations and interval durations varied between 0 and 6 ms. Erroneous detection of Q, R, S, R', and S' waves (oversensed or missed) were 3, 1, 1, 16, and 6%, respectively. Seven percent of notches detected in the first 40 ms were misdetected. We propose an efficient computerized method for the automatic measurement of the Selvester score in patients with the strict LBBB. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
    Europace 03/2015; DOI:10.1093/europace/euv040 · 3.05 Impact Factor
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    ABSTRACT: This study sought to assess the association between medication utilization, outcome, and the efficacy of resynchronization therapy in the MADIT-CRT study. Medication usage of patients in the MADIT-CRT study was analyzed. Time-dependent Cox proportional hazard regression analyses were performed to assess differences in hospitalization for heart failure (HF) or death. The greater the efficacy of cardiac resynchronization therapy (CRT) as measured by reduction in left ventricular end-systolic volume (LVESV) and increase in left ventricular ejection fraction (LVEF) between baseline and 1-year of follow-up, the greater the likelihood that patients remained on an angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) and avoided use of or reduced treatment with diuretics. Treatment with diuretics was associated with a significantly increased risk of HF hospitalization or death (hazard ratio [HR]: 1.87, [95% confidence interval (CI):1.45 to 2.41], p<0.001). In contrast, treatment with an ACE-I/ARB was associated with a significantly decreased risk of HF hospitalization or death (HR: 0.58 [95% CI: 0.42-0.80], p=0.001). In HF patients in New York Heart Association functional class I and II and with wide QRS complexes, efficacy of CRT as measured by improvement in LVESV and LVEF was associated with an increased likelihood of remaining on an ACE-I/ARB and discontinuing diuretic therapy. Discontinuation of diuretics was reflective of improved hemodynamic response to cardiac resynchronization therapy. Copyright © 2015 Elsevier Inc. All rights reserved.
    Journal of cardiac failure 03/2015; DOI:10.1016/j.cardfail.2015.03.006 · 3.07 Impact Factor
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    ABSTRACT: Data on the time-dependent benefit of cardiac resynchronization therapy with defibrillator (CRT-D) compared with a dual-chamber implantable cardioverter-defibrillator (ICD) to reduce death or ventricular tachycardia (VT) or ventricular fibrillation (VF) are limited. We aimed to evaluate the time-related risk of death or sustained VT or VF in patients receiving CRT-D vs. ICD in the MADIT-RIT trial. Kaplan-Meier survival analyses and multivariate Cox regression models were utilized to compare the incidence and the risk of death or sustained VT/VF in the CRT-D and ICD subgroups by the elapsed time after device implantation (6 months). Of the ICD (n = 742) and CRT-D (n = 757) patients enrolled, the risk of death was lower in CRT-D vs. in ICD early after device implantation [hazard ratio (HR) = 0.42, 95% confidence interval (CI): 0.17-1.03, P = 0.058] and beyond 6 months of follow-up (HR = 0.39, 95% CI: 0.21-0.73, P = 0.004), with the 6-month interaction P = 0.899. The overall risk of sustained VT/VF was reduced in CRT-D vs. ICD patients (HR = 0.73, 95% CI: 0.52-1.03, P = 0.07). However, the risk was similar in the first 6 months (HR = 1.00, 95% CI: 0.62-1.62, P = 0.988), and a lower risk emerged 6 months after CRT-D implantation (HR = 0.58, 95% CI: 0.38-0.88, P = 0.011), with the 6-month interaction P = 0.059. The reduced mortality risk of CRT-D compared with an ICD alone began early after device implantation and was sustained during long-term follow-up; the reduced risk for ventricular tachyarrhythmias did not emerge until 6 months after device implantation. http://clinicaltrials.gov/ct2/show/NCT00947310. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
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    ABSTRACT: We investigated the risk for recurrent coronary events associated with insulin resistance in post infarction patients from the Thrombogenic Factors and Recurrent Coronary Events (THROMBO) study. The association between insulin resistance expressed by Homeostatic Model Assessment 2 for Insulin Resistance (HOMA2-IR) and the risk for recurrent coronary events was investigated in a cohort of 1,032 patients evaluated 2 months after myocardial infarction with a follow-up of 26 months. The end point for the study was recurrent coronary event defined as cardiac death, nonfatal myocardial infarction, or unstable angina, whichever occurred first. We used time dependent survival analysis and Cox proportional hazards regression method to determine the association between HOMA2 categorized as high >75th percentile and endpoints after adjustment for relevant clinical covariates and series of thrombogenic and dyslipogenic factors. High HOMA2-IR defined as in fourth quartile (>=2.4) was associated with increased risk for recurrent coronary events ([HR] 1.44; [CI] 1.03-2.01; P=0.03) after adjustment for the clinical covariates: age, gender, diabetes, prior MI, pulmonary congestion, CABG and PTCA. The highest risk of cardiac events was observed in non-obese patients (BMI<=30kg/m2) with high HOMA2-IR ([HR] 1.5; [CI] 1.02-2.22; P=0.038). The plasma level of plasminogen activator inhibitor-1 (PAI-1) was associated with higher risk for recurrent coronary events in patients with insulin resistance ([HR] 1.79; [CI] 1.05-3.03; P=0.03, interaction P=0.018). insulin resistance predicts recurrence of coronary events in post-infarction population. HOMA2-IR is better than BMI to stratify risk of recurrent coronary events.
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    ABSTRACT: Cardiac-related clinical practice guidelines have become an integral part of the practice of cardiology. Unfortunately, these guidelines are often long, complex, and difficult for practicing cardiologists to utilize. Guidelines should be condensed and their format upgraded so that the key messages are easier to comprehend and can be applied more readily by those involved in patient care. After presenting the historical background and describing the guideline structure, we make several recommendations to make clinical practice guidelines more user-friendly for clinical cardiologists. Our most important recommendations are that the clinical cardiology guidelines should focus exclusively on: 1) Class I recommendations with established benefits that are supported by randomized clinical trials; and 2) Class III recommendations for diagnostic or therapeutic approaches in which quality studies show no benefit or possible harm. Class II recommendations are not evidence-based, but reflect expert opinions related to published clinical studies, with potential for personal bias by members of the guideline committee. Class II recommendations should be published separately as “Expert Consensus Statements” or “Task Force Committee Opinions” so that both majority and minority expert opinions can be presented in a less dogmatic form than the way these recommendations currently appear in clinical practice guidelines.
    The American Journal of Cardiology 03/2015; DOI:10.1016/j.amjcard.2015.03.026 · 3.43 Impact Factor
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    ABSTRACT: The temporal effect of heart failure (HF) hospitalization occurring at different time periods before implantation has not yet been studied in detail. The aim of the present study was to investigate the potential association between time from last HF hospitalization to device implantation and effects on subsequent outcomes and benefit from cardiac resynchronization therapy with a defibrillator (CRT-D). Multivariate Cox models were used to determine the temporal influence of previous HF hospitalization on the end point of HF or death within all left bundle branch block implantable cardioverter-defibrillator (ICD) and CRT-D patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) trial (n = 1,250) and to evaluate the clinical benefit of CRT-D implantation, comparing CRT-D patients with ICD patients within each previous HF hospitalization group. The patients with previous HF hospitalization ≤12 months before device implantation had the greatest incidence of HF or death during 4-year follow-up (31%), while those with previous HF hospitalization >12 months and those with no previous HF hospitalization had similar lower rates of HF or death (22% and 24%, respectively). All patients treated with CRT-D derived significant clinical benefit compared with their ICD counterparts, regardless of time of previous hospitalization (hazard ratios 0.38 [no previous hospitalization], 0.49 (≤12 months), and 0.45 (>12 months); p for interaction = 0.67). In conclusion, in the present study of patients with mild HF with prolonged QRS intervals and LBBB, a previous HF hospitalization ≤12 months was associated with increased risk for HF or death compared with >12 months and no previous HF hospitalizations. The clinical benefit of CRT-D was evident in all patients regardless of time from last HF hospitalization to implantation compared with ICD only. Copyright © 2015 Elsevier Inc. All rights reserved.
    The American Journal of Cardiology 02/2015; DOI:10.1016/j.amjcard.2015.02.029 · 3.43 Impact Factor
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    ABSTRACT: Premature ventricular contractions (PVCs) frequently occur in patients with left ventricular dysfunction. However, there are limited data regarding the burden and morphologic characteristics of PVCs in patients receiving cardiac resynchronization therapy. Patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) with >5000 PVCs on a predevice implant 12-lead, 24-hour Holter were identified. The putative PVC site of origin for the most dominant PVC was characterized and their effects on clinical outcomes were evaluated. A total of 146 patients were identified to have >5000 PVCs on Holter of which 75 (51%) had PVCs originating from a non-outflow tract site. Other sites included the left ventricular outflow tract (LVOT), right ventricular outflow tract (RVOT), and the sinus of Valsalva. In multivariate analysis, the risk for HF/Deatd was similar in patients with Outflow tract PVCs when compared to patients with Non-outflow tract PVCs (HR 1.4, 95% CI 0.7-2.8, P = 0.3). The degree of echocardiographic reverse remodeling was similar in patients with outflow tract versus Non-outflow tract PVCs. One-third of patients with nonischemic cardiomyopathy were found to have PVCs originating from the RVOT. In patients with mild symptoms of heart failure, there is no difference in the risk of HF or death in patients with outflow versus non-outflow tract PVCs. One-third of patients with NICM have frequent PVCs originating from the RVOT. © 2015 Wiley Periodicals, Inc.
    Annals of Noninvasive Electrocardiology 02/2015; DOI:10.1111/anec.12268 · 1.08 Impact Factor
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    ABSTRACT: The impact of patient age on the risks of death or rehospitalization after primary prevention implantable cardioverter-defibrillator (ICD) placement is uncertain. Data from 5 major ICD trials were merged: the Multicenter Automatic Defibrillator Implantation Trial I (MADIT-I), the Multicenter UnSustained Tachycardia Trial (MUSTT), the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II), the Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation Trial (DEFINITE), and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Median age at enrollment was 62 (interquartile range 53-70) years. Compared with their younger counterparts, older patients had a greater burden of comorbid illness. In unadjusted exploratory analyses, ICD recipients were less likely to die than nonrecipients in all age groups: among patients aged <55 years: hazard ratio 0.48, 95% posterior credible interval 0.33 to 0.69; among patients aged 55 to 64 years: hazard ratio 0.69, 95% posterior credible interval 0.53 to 0.90; among patients aged 65 to 74 years: hazard ratio 0.67, 95% posterior credible interval, 0.53 to 0.85; and among patients aged ≥75 years: hazard ratio 0.54, 95% posterior credible interval 0.37 to 0.78. Sample sizes were limited among patients aged ≥75 years. In adjusted Bayesian-Weibull modeling, point estimates indicate ICD efficacy persists but is attenuated with increasing age. There was evidence of an interaction between age and ICD treatment on survival (two-sided posterior tail probability of no interaction <0.01). Using an adjusted Bayesian logistic regression model, there was no evidence of an interaction between age and ICD treatment on rehospitalization (two-sided posterior tail probability of no interaction 0.44). In this analysis, the survival benefit of the ICD exists but is attenuated with increasing age. The latter finding may be because of the higher burden of comorbid illness, competing causes of death, or limited sample size of older patients. There was no evidence that age modifies the association between ICD treatment and rehospitalization. © 2015 American Heart Association, Inc.
    Circulation Cardiovascular Quality and Outcomes 02/2015; 8(2). DOI:10.1161/CIRCOUTCOMES.114.001306 · 5.66 Impact Factor
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    ABSTRACT: The MADIT-RIT trial demonstrated reduction of inappropriate and appropriate ICD therapies and mortality by high-rate cut-off and 60-second-delayed VT therapy ICD programming in patients with a primary prophylactic ICD indication. The aim of this analysis was to study effects of MADIT-RIT ICD programming in patients with ischemic and non-ischemic cardiomyopathy. First and total occurrences of both inappropriate and appropriate ICD therapies were analyzed by multivariate Cox models in 791 (53%) patients with ischemic and 707 (47%) patients with non-ischemic cardiomyopathy. Patients with ischemic and non-ischemic cardiomyopathy had similar incidence of first inappropriate (9% and 11%, P = 0.21) and first appropriate ICD therapy (11.6% and 14.1%, P = 0.15). Patients with ischemic cardiomyopathy had higher mortality rate (6.1% vs. 3.3%, P = 0.01). MADIT-RIT high-rate cut-off (arm B) and delayed VT therapy ICD programming (arm C) compared with conventional (arm A) ICD programming were associated with a significant risk reduction of first inappropriate and appropriate ICD therapy in patients with ischemic and non-ischemic cardiomyopathy (HR range 0.11-0.34, P < 0.001 for all comparisons). Occurrence of total inappropriate and appropriate ICD therapies was significantly reduced by high-rate cut-off ICD programming and delayed VT therapy ICD programming in both ischemic and non-ischemic cardiomyopathy patients. High-rate cut-off and delayed VT therapy ICD programming are associated with significant reduction in first and total inappropriate and appropriate ICD therapy in patients with ischemic and non-ischemic cardiomyopathy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Cardiovascular Electrophysiology 12/2014; DOI:10.1111/jce.12605 · 2.88 Impact Factor
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    ABSTRACT: The most common inherited cardiac arrhythmia, LQT1, is due to IKs potassium channel mutations and is linked to high risk of adrenergic-triggered cardiac events. We recently showed that although exercise triggered events are very well treated by ß-blockers for these patients, acute arousal triggered event rate were not significantly reduced after beta-blocker treatment, suggesting that the mechanisms underlying arousal-triggered arrhythmias may be different from those during exercise. IKs is strongly regulated by β-adrenergic receptor (β-AR) signaling, but little is known about the role of α1-AR-mediated regulation. Here we show, using a combination of cellular electrophysiology and computational modeling, that IKs phosphorylation and α1-AR regulation via activation of calcium-dependent PKC isoforms (cPKC) may be a key mechanism to control channel voltage-dependent activation and consequently action potential duration (APD) in response to adrenergic-stimulus. We show that simulated mutation-specific combined adrenergic effects (β+α) on APD were strongly correlated to acute stress-triggered cardiac event rate for patients while β-AR effects alone were not. We were able to show that calcium dependent PKC signaling is key to normal QT shortening during acute arousal and when impaired, correlates with increased rate of sudden arousal triggered cardiac events. Our study suggests that acute α1-AR-cPKC regulation of IKs is important for QT shortening in "fight-or-flight" response and is linked to decreased risk of sudden emotion/arousal triggered cardiac events in LQT1 patients. Copyright © 2014. Published by Elsevier Ltd.
    Journal of Molecular and Cellular Cardiology 12/2014; 79. DOI:10.1016/j.yjmcc.2014.11.020 · 5.22 Impact Factor
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    ABSTRACT: Background-In Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT), patients with non-left bundle branch block (LBBB; including right bundle branch block, intraventricular conduction delay) did not have clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D). We hypothesized that baseline PR interval modulates clinical response to CRT-D therapy in patients with non-LBBB. Methods and Results-Non-LBBB patients (n=537; 30%) were divided into 2 groups based on their baseline PR interval as normal (including minimally prolonged) PR (PR <230 ms) and prolonged PR (PR >= 230 ms). The primary end point was heart failure or death. Separate secondary end points included heart failure events and all-cause mortality. Cox proportional hazards regression models were used to compare risk of end point events by CRT-D to implantable cardioverter defibrillator therapy in the PR subgroups. There were 96 patients (22%) with a prolonged PR and 438 patients (78%) with a normal PR interval. In non-LBBB patients with a prolonged PR interval, CRT-D treatment was associated with a 73% reduction in the risk of heart failure/death (hazard ratio, 0.27; 95% confidence interval, 0.13-0.57; P<0.001) and 81% decrease in the risk of all-cause mortality (hazard ratio, 0.19; 95% confidence interval, 0.13-0.57; P<0.001) compared with implantable cardioverter defibrillator therapy. In non-LBBB patients with normal PR, CRT-D therapy was associated with a trend toward an increased risk of heart failure/death (hazard ratio, 1.45; 95% confidence interval, 0.96-2.19; P=0.078; interaction P<0.001) and a more than 2-fold higher mortality (hazard ratio, 2.14; 95% confidence interval, 1.12-4.09; P=0.022; interaction P<0.001) compared with implantable cardioverter defibrillator therapy. Conclusions-The data support the use of CRT-D in MADIT-CRT non-LBBB patients with a prolonged PR interval. In non-LBBB patients with a normal PR interval, implantation of a CRT-D may be deleterious.
    Circulation Arrhythmia and Electrophysiology 12/2014; 7(6):1280. DOI:10.1161/CIRCEP.114.002303 · 5.42 Impact Factor
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    ABSTRACT: It is unknown whether circadian variation of ventricular tachyarrhythmias (VTA) affects clinical outcome in heart failure patients. A total of 1790 patients (males 75%) with heart failure, NYHA class I and II and implantable cardioverter defibrillators (ICD) or cardiac resynchronization (CRT-D) enrolled in the MADIT-CRT study were included. Time of first and all VTAs as detected and treated by the device with appropriate ICD therapy (ATP or shock) was evaluated by hours of the day and weekdays and related to all-cause mortality using Cox regression analyses. During a mean follow-up period of 40 months, a total of 3300 VTA episodes were registered. Of all VTAs recorded, most of them (n = 2977, 90%) occurred in males. Recurrent as well as first VTA episodes were more common in the morning and evening with bimodal peaks from 7:00-10:59 (21%) and 18:00-21:59 (23%). VTAs that occurred during morning hours were associated with higher mortality when compared to VTA episodes occurring at other hours (HR = 2.07, CI: 1.135-3.77, p = 0.018) with a significant gender interaction placing females at significantly higher risk of death (HR 6.78, CI 1.55-29.860 p = 0.011) than males (HR 1.79, CI 0.92-3.46, p = 0.086) (interaction p = 0.041) despite an overall lower probability for morning VTA among females (HR 0.32, CI 0.16-0.68 p = 0.003) CONCLUSIONS: The occurrence of VTAs in heart failure patients shows a circadian variation with highest incidence during morning hours that translates into a significant higher risk of all-cause mortality, with significantly higher risk among females than males. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Cardiovascular Electrophysiology 11/2014; 26(3). DOI:10.1111/jce.12592 · 2.88 Impact Factor
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    ABSTRACT: Long QT syndrome type 3 (LQT3) is caused by mutations in the SCN5A-encoded Nav1.5 channel. LQT3 patients exhibit time of day associated abnormal increases in their heart rate corrected QT (QTc) intervals and risk for life-threatening episodes. This study determines the effects of uncoupling environmental time cues that entrain circadian rhythms (time of light and time of feeding) on heart rate and ventricular repolarization in wild type (WT) or transgenic LQT3 mice (Scn5a(+/ΔKPQ)). We used an established light-phase restricted feeding paradigm that disrupts the alignment among the circadian rhythms in the central pacemaker of the suprachiasmatic nucleus and peripheral tissues including heart. Circadian analysis of the RR and QT intervals showed the Scn5a(+/ΔKPQ) mice had QT rhythms with larger amplitudes and 24-hr midline means and a more pronounced slowing of the heart rate. For both WT and Scn5a(+/ΔKPQ) mice, light-phase restricted feeding shifted the RR and QT rhythms ~12 hrs, increased their amplitudes >2-fold, and raised the 24-hr midline mean by ~10%. In contrast to WT mice, the corrected QT (QTc) interval in Scn5a(+/ΔKPQ) mice exhibited time-of-day prolongation that was flipped after light-phase restricted feeding. The time-of-day changes in the QTc intervals of Scn5a(+/ΔKPQ) mice were secondary to a steeper power relation between their QT and RR intervals. We conclude that uncoupling time of feeding from normal light cues can dramatically slow heart rate to unmask genotype-specific differences in the QT intervals and aggravate the LQT3-related phenotype.
    AJP Heart and Circulatory Physiology 10/2014; DOI:10.1152/ajpheart.00341.2014 · 4.01 Impact Factor
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    ABSTRACT: -Appropriate guideline criteria for use of ICDs do not take into account potential recovery of left ventricular ejection fraction (LVEF) in patients treated with CRT-D.
    Circulation 10/2014; DOI:10.1161/CIRCULATIONAHA.114.011283 · 14.95 Impact Factor
  • Circulation 10/2014; 130(15):e133. DOI:10.1161/CIRCULATIONAHA.114.010926 · 14.95 Impact Factor
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    ABSTRACT: Low pulse pressure (PP) is associated with poor outcome among hospitalized patients with systolic heart failure (HF). However, the relation between PP and response to cardiac resynchronization therapy with defibrillator (CRT-D) is unknown. We aimed to evaluate the relation between pre-implantation PP and echocardiographic response to CRT-D and subsequent clinical outcome after 1-year. The relationship between pre-implantation PP and echocardiographic response to CRT-D (defined as >15% reduction in left ventricular end systolic volume [LVESV] at 1 year) was evaluated among 754 CRT-D patients with left bundle branch block (LBBB) enrolled in MADIT-CRT (Multicenter Automatic Defibrillator Cardioverter Defibrillator Implantation Trial-Cardiac Resynchronization Therapy). The association between PP at 1 year and the risk for subsequent heart failure (HF) or death was evaluated using multivariate Cox model. Patients with high vs. low PP (>40 vs. ≤ 40 mmHG [lower quartile]) had a significantly greater reduction in LVESV, LV end diastolic volume, and LV dyssynchrony (p<0.01 for all comparisons). In multivariate analysis, the presence of high PP was associated with a 3.5-fold (p<0.001) increase in the likelihood of a positive echocardiographic response to CRT-D. Patients with high PP (>40 mmHG, >lower quartile) one year after CRT-D implantation experienced a 50% reduction in the risk of subsequent HF or death (p=0.001) and 63% reduction in death only (p=0.001), compared to patients with low PP. In conclusion, high baseline PP is an independent predictor of echocardiographic response to CRT-D and high PP following device implantation is associated with improved subsequent clinical outcome.
    The American Journal of Cardiology 10/2014; 114(7). DOI:10.1016/j.amjcard.2014.07.014 · 3.43 Impact Factor
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    ABSTRACT: Background In LQTS, β-blocker therapy is effective in reducing the risk of cardiac events (syncope, aborted cardiac arrest, sudden cardiac death). Limited studies have compared the efficacy of different β-blockers. Objectives The goal of this study was to compare the efficacy of different β-blockers in long QT syndrome (LQTS) and in genotype-positive patients with LQT1 and LQT2. Methods The study included 1,530 patients from the Rochester, New York–based LQTS Registry who were prescribed common β-blockers (atenolol, metoprolol, propranolol, or nadolol). Time-dependent Cox regression analyses were used to compare the efficacy of different β-blockers with the risk of cardiac events in LQTS. Results Relative to being off β-blockers, the hazard ratios and 95% confidence intervals (CIs) for first cardiac events for atenolol, metoprolol, propranolol, and nadolol were 0.71 (0.50 to 1.01), 0.70 (0.43 to 1.15) 0.65 (0.46 to 0.90), and 0.51 (0.35 to 0.74), respectively. In LQT1, the risk reduction for first cardiac events was similar among the 4 β-blockers, but in LQT2, nadolol provided the only significant risk reduction (hazard ratio: 0.40 [0.16 to 0.98]). Among patients who had a prior cardiac event while taking β-blockers, efficacy for recurrent events differed by drug (p = 0.004), and propranolol was the least effective compared with the other β-blockers. Conclusions Although the 4 β-blockers are equally effective in reducing the risk of a first cardiac event in LQTS, their efficacy differed by genotype; nadolol was the only β-blocker associated with a significant risk reduction in patients with LQT2. Patients experiencing cardiac events during β-blocker therapy are at high risk for subsequent cardiac events, and propranolol is the least effective drug in this high-risk group.
    Journal of the American College of Cardiology 09/2014; 64(13):1352–1358. DOI:10.1016/j.jacc.2014.05.068 · 15.34 Impact Factor
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    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. Copyright © 2014 Elsevier Inc. All rights reserved.
    The American Journal of Cardiology 09/2014; 114(12):1855-1860. DOI:10.1016/j.amjcard.2014.09.026 · 3.43 Impact Factor

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4,867.45 Total Impact Points

Institutions

  • 1983–2015
    • University Center Rochester
      • • Department of Medicine
      • • Cardiology Division
      Рочестер, Minnesota, United States
  • 1988–2014
    • University of Rochester
      • • Department of Medicine
      • • Division of Hospital Medicine
      • • Department of Electrical and Computer Engineering
      Rochester, New York, United States
  • 2013
    • Southcoast Health System
      New Bedford, Massachusetts, United States
  • 2012
    • Duke University Medical Center
      • Division of Cardiology
      Durham, North Carolina, United States
    • Lund University
      • Department of Cardiology
      Lund, Skåne, Sweden
  • 2011
    • Sheba Medical Center
      • Department of Pathology
      Gan, Tel Aviv, Israel
    • King Saud University
      Ar Riyāḑ, Ar Riyāḑ, Saudi Arabia
    • University of Florence
      Florens, Tuscany, Italy
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2002–2011
    • The University of Arizona
      • • Department of Psychiatry
      • • Department of Medicine
      Tucson, AZ, United States
  • 2010
    • Azienda Ospedaliera Niguarda Ca' Granda
      Milano, Lombardy, Italy
  • 2008
    • Oregon Health and Science University
      • Division of Cardiovascular Medicine
      Portland, Oregon, United States
  • 2006
    • Highland Hospital
      Oakland, California, United States
  • 1992–2005
    • New York University College of Dentistry
      New York City, New York, United States
    • Cornell University
      • Department of Psychiatry
      Итак, New York, United States
  • 2004
    • Southwest Foundation For Biomedical Research
      San Antonio, Texas, United States
  • 2000
    • University of Florida
      Gainesville, Florida, United States
  • 1993–2000
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
    • University of Dallas
      Irving, Texas, United States
  • 1999
    • Hebrew University of Jerusalem
      Yerushalayim, Jerusalem, Israel
    • Middlebury College
      Middlebury, Indiana, United States
  • 1997–1999
    • Shiga University of Medical Science
      • First Department of Internal Medicine
      Ōtu, Shiga, Japan
  • 1998
    • University of Ottawa
      Ottawa, Ontario, Canada
  • 1996
    • Uniformed Services University of the Health Sciences
      • Department of Medicine
      Bethesda, MD, United States
    • American Heart Association
      Dallas, Texas, United States
  • 1994
    • Washington Hospital Center
      Washington, Washington, D.C., United States
    • Tufts University
      • Division of Cardiology
      Georgia, United States
  • 1991
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States