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ABSTRACT: Cardiac Resynchronization Therapy and QRS Axis. Background: Mildly symptomatic heart failure (HF) patients derive substantial clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D) as shown in MADIT-CRT. The presence of QRS axis deviation may influence response to CRT-D. The objective of this study was to determine whether QRS axis deviation will be associated with differential benefit from CRT-D. Methods : Baseline electrocardiograms of 1,820 patients from MADIT-CRT were evaluated for left axis deviation (LAD: quantitative QRS axis -30 to -90) or right axis deviation (RAD: QRS axis 90-180) in left bundle branch block (LBBB), right bundle branch block (RBBB), and nonspecific interventricular conduction delay QRS morphologies. The primary endpoints were the first occurrence of a HF event or death and the separate occurrence of all-cause mortality as in MADIT-CRT. Results: Among LBBB patients, those with LAD had a higher risk of primary events at 2 years than non-LAD patients (20% vs 16%; P = 0.024). The same was observed among RBBB patients (20% vs 10%; P = 0.05) but not in IVCD patients (22% vs 23%; P = NS). RAD did not convey any increased risk of the primary combined endpoint in any QRS morphology subgroup. When analyzing the benefit of CRT-D in the non-LBBB subgroups, there was no significant difference in hazard ratios for CRT-D versus ICD for either LAD or RAD. However, LBBB patients without LAD showed a trend toward greater benefit from CRT therapy than LBBB patients with LAD (HR for no LAD: 0.37, 95% CI: 0.26-0.53 and with LAD: 0.54, 95% CI: 0.36-0.79; P value for interaction = 0.18). Conclusions: LAD in non-LBBB patients (RBBB or IVCD) is not associated with an increased benefit from CRT. In LBBB patients, those without LAD seem to benefit more from CRT-D than those with LAD. (J Cardiovasc Electrophysiol, Vol. pp. 1-7).
Journal of Cardiovascular Electrophysiology 11/2012; · 3.06 Impact Factor
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ABSTRACT: QRS Fragmentation and the Risk of Sudden Cardiac Death in MADIT II. Background: QRS fragmentation (fQRS) has been reported as a useful ECG parameter in predicting mortality in high-risk postinfarction patients. Its prognostic value for sudden cardiac death (SCD) and ventricular arrhythmias in ischemic cardiomyopathy (ICM) remains unknown. Methods: MADIT II enrollment 12-lead ECGs were analyzed for fQRS defined as RSR' patterns (≥1 R' or notching of S or R wave) in patients with a normal QRS duration and >2 notches on the R or S wave in patients with abnormal QRS duration, present in 2 contiguous leads. Exclusion criteria included a paced rhythm and an uninterpretable or incomplete ECG. Study endpoints included SCD, SCD or appropriate implantable cardioverter defibrillator (ICD) shock, and total mortality (TM). Results: Of the 1,232 ECGs reviewed, 1,040 were of suitable quality for fQRS analysis. QRS fragmentation was found in 33% of patients in any leads, in 10% of patients in anterior leads, in 8% of patients in lateral leads and in 21% of patients in inferior leads. Anterior and lateral location of QRS fragmentation was not associated with follow-up events. Inferior location of fQRS was found to be predictive of SCD/ICD shock (hazard ratio [HR] 1.46, P = 0.032), SCD (HR 2.05, P = 0.007), and TM (HR 1.44, P = 0.036). This association was driven primarily by the increase in events found in LBBB patients: SCD/ICD shock (HR 2.05, P = 0.046), SCD (HR 4.24, P = 0.002), and TM (HR 2.82, P = 0.001). Conclusions: Fragmented QRS, especially identified in inferior leads, is predictive of SCD, SCD or appropriate ICD shock, and all-cause mortality in patients with ICM. Identifying inferior fQRS in patients with LBBB is of particular prognostic significance and should reinforce the use of ICD therapy in this high-risk group. (J Cardiovasc Electrophysiol, Vol. pp. 1-6).
Journal of Cardiovascular Electrophysiology 06/2012; · 3.06 Impact Factor
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ABSTRACT: The right ventricular (RV) apex has been the standard pacing site since the development of implantable pacemaker technology. Although RV pacing was initially only utilized for the treatment of severe bradyarrhythmias usually due to complete heart block, today the indications for and implantation of RV pacing devices is dramatically larger. Recently, the adverse effects of chronic RV apical pacing have been described including an increased risk of heart failure and death. This review details the detrimental effects of RV apical pacing and their shared hemodynamic pathophysiology. In particular, the role of RV apical pacing induced ventricular dyssynchrony is highlighted with a specific focus on differential outcome based upon QRS morphology at implant.
Indian pacing and electrophysiology journal 05/2012; 12(3):102-13.
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ABSTRACT: Mildly symptomatic heart failure (HF) patients were shown to derive substantial clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D) in Multicenter Automatic Defibrillator Implantation Trial in Cardiac Resynchronization Therapy. However, the relationship between functional capacity (FC) and CRT-D benefit in the trial was not assessed.
To evaluate the association between FC and response to CRT-D in Multicenter Automatic Defibrillator Implantation Trial in Cardiac Resynchronization Therapy.
We evaluated the association between preimplantation FC and the benefit of CRT-D in reducing the risk of HF or death in Multicenter Automatic Defibrillator Implantation Trial in Cardiac Resynchronization Therapy. Functional status was assessed by a 6-minute walk test (6MWT), dichotomized at the median value as poor (<350 m) or good (≥350 m).
Implantable cardioverter-defibrillator-only patients with a poor FC had an adjusted 73% increased risk for HF or death (P <.001) and a 2.4-fold (P = .001) increased risk for all-cause mortality. CRT-D therapy was associated with 63% (P <.001) and 44% (P <.001) reductions in the risk of HF or death among left bundle branch block patients with a poor FC and a good FC, respectively (P for interaction = .10). Among left bundle branch block patients with a poor FC, CRT-D was also associated with a significant reduction in the risk of all-cause mortality (hazard ratio 0.52; P = .015) whereas the survival benefit of CRT-D was not observed among those who had a higher FC at enrollment (hazard ratio 1.01; P = .98; P for interaction = .10).
Poor FC is a strong independent predictor for mortality and HF events in patients with mildly symptomatic HF. Left bundle branch block patients with poor baseline FC derive a pronounced benefit from CRT-D, manifest by a significant reduction in mortality.
Heart rhythm: the official journal of the Heart Rhythm Society 04/2012; 9(9):1454-9. · 4.56 Impact Factor
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ABSTRACT: Men and women with heart failure display important differences in clinical characteristics that might affect their responses to pharmacological and nonpharmacological therapies. In women, heart failure is associated with a higher frequency of hypertension, nonischemic cardiomyopathy and left bundle branch block than in men. Subgroup analyses of data from randomized clinical trials suggest that these differences result in a differential response to heart failure therapies, including a somewhat better response to β-blockers, a worse prognosis with digoxin therapy, and a lower survival benefit with implantable cardioverter-defibrillators in women. Importantly, female patients with heart failure also derive significantly greater improvements in cardiac volumes from cardiac resynchronization therapy than do male patients, and this treatment is associated with reduced risks of all-cause mortality and heart failure events among women with mild symptoms. These data suggest that sex-related differences might exist in response to both medical and device therapies for patients with heart failure.
Nature Reviews Cardiology 02/2012; 9(4):234-42. · 8.83 Impact Factor
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Andrew Brenyo,
Mohan Rao,
Sushma Koneru,
William Hallinan,
Samit Shah,
H T Massey,
Leway Chen,
Bronislava Polonsky,
Scott McNitt,
David T Huang,
Ilan Goldenberg,
Mehmet Aktas
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ABSTRACT: There are limited data regarding the incidence and prognostic significance of ventricular arrhythmias (VA) in ambulatory continuous flow left ventricular assist device (LVAD) patients.
Sixty-one consecutive patients from November 1, 2006 through December 31, 2010 with an LVAD and implantable cardioverter defibrillator that survived to discharge from the LVAD implantation admission were studied. Follow-up began from date of discharge with both devices in situ and ended with death, transplant, on June 1, 2011. Pre-LVAD VA history was related to the primary endpoints of post-LVAD VA, mortality, and the combined endpoint of post-LVAD VA/mortality.
During a mean follow-up of 622 days 19 patients (31%) experienced VA (14 episodes of VT, 5 episodes of VF). Pre-LVAD VA was predictive of post-LVAD VA (hazard ratio [HR] 2.91, P = 0.026) and the combined post-LVAD VA/mortality endpoint (HR 2.70, P = 0.021) but only displayed a nonsignificant association with mortality (HR 2.30, P = 0.11). In multivariate analysis, pre-LVAD VA remained a significant predictor of post-LVAD VA (HR 2.84, P = 0.03) and the combined post-LVAD VA/mortality endpoint (HR 2.65, P = 0.025). Post-LVAD VA was the strongest univariate predictor of mortality (HR 13.92, P < 0.001) and remained so after multivariate adjustment (HR 9.69, P = 0.001). Post-LVAD VA occurred at a mean of 1 year from mortality events with 45% within 1 month.
Pre-LVAD VA is a significant predictor of post-LVAD VA but not of mortality. VA in the continuous flow LVAD population carries a significant risk of mortality often within the first month.
Journal of Cardiovascular Electrophysiology 11/2011; 23(5):515-20. · 3.06 Impact Factor
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Andrew Brenyo,
Mark S Link,
Alon Barsheshet,
Arthur J Moss,
Wojciech Zareba,
Paul J Wang,
Scott McNitt,
David Huang,
Elyse Foster,
Mark Estes,
Scott D Solomon,
Ilan Goldenberg
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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).
Journal of the American College of Cardiology 10/2011; 58(16):1682-9. · 14.16 Impact Factor
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Mohan Rao,
Ilan Goldenberg,
Arthur J Moss,
Helmut Klein,
David T Huang,
Nicole R Bianco,
Steven J Szymkiewicz,
Wojciech Zareba, Andrew Brenyo,
Jonathan Buber,
Alon Barsheshet
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ABSTRACT: Patients with congenital structural heart disease (CSHD) and inherited arrhythmias (IAs) are at high risk of ventricular tachyarrhythmias and sudden cardiac death. The present study was designed to evaluate the short- and long-term outcomes of patients with CSHD and IA who received a wearable cardioverter-defibrillator (WCD) for the prevention of sudden cardiac death. The study population included 162 patients with CSHD (n = 43) and IA (n = 119) who were prospectively followed up in a nationwide registry from 2005 to 2010. The mortality rates were compared using Kaplan-Meier survival analysis. The mean age of the study patients was 38 ± 27 years. The patients with CSHD had a greater frequency of left ventricular dysfunction (ejection fraction <30%) than did the patients with IA (37% vs 5%, respectively; p = 0.002). The predominant indication for WCD was pending genetic testing in the IA group and transplant listing in the CSHD group. Compliance with the WCD was similar in the 2 groups (91%). WCD shocks successfully terminated 3 ventricular tachyarrhythmias in the patients with IA during a median follow-up of 29 days of therapy (corresponding to 23 appropriate WCD shocks per 100 patient-years). No arrhythmias occurred in the patients with CSHD during a median follow-up of 27 days. No patients died while actively wearing the WCD. At 1 year of follow-up, the survival rates were significantly lower among the patients with CSHD (87%) than among the patients with IA (97%, p = 0.02). In conclusion, our data suggest that the WCD can be safely used in high-risk adult patients with IA and CSHD. Patients with IA showed a greater rate of ventricular tachyarrhythmias during therapy but significantly lower long-term mortality rates.
The American journal of cardiology 09/2011; 108(11):1632-8. · 3.58 Impact Factor
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Resuscitation 08/2011; 82(12):e19. · 3.60 Impact Factor
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ABSTRACT: Advances in genetic testing technology have led to a proliferation of new genetic tests and accelerated developments in the field of cardiovascular genetic medicine. These advances enhance presymptomatic diagnosis and can establish a definitive molecular diagnosis for symptomatic patients at risk for sudden cardiac death. Most importantly, genotype-phenotype correlations can add important information for predicting outcome and selecting treatment for patients with inherited arrhythmic disorders. This paper reviews the current data regarding genotype-phenotype correlations and the role of clinical genetic testing in diagnosis, prognosis, and management of inheritable disorders leading to sudden cardiac death.
Current Cardiology Reports 07/2011; 13(5):364-76.
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ABSTRACT: QRS duration and morphology, evaluated via a standard 12-lead electrocardiogram (ECG), represent an opportunity to derive useful prognostic information regarding the risk of subsequent cardiac events or therapeutic outcomes. Prolonged QRS duration, and the presence of intraventricular conduction abnormalities, usually indicate the presence of changes in the myocardium due to underlying heart disease. Prolonged QRS duration is often associated with depressed ejection fraction or enlarged left ventricular volumes, but several studies have demonstrated that this simple ECG measure provides independent prognostic value, after adjusting for relevant clinical covariates. Post-infarction patients with prolonged QRS duration have a significantly increased risk of mortality, although data associating QRS prolongation specifically with sudden death is less supportive. In non-ischemic cardiomyopathy, there is no evidence that QRS duration has prognostic significance in predicting mortality or sudden death. Prolonged QRS duration, and especially presence of left bundle branch block, seems to predict a benefit from cardiac resynchronization therapy in both ischemic and non-ischemic cardiomyopathy patients. Therefore, QRS duration and morphology should not only be considered a predictor of death or sudden death in patients after myocardial infarction, and in those suspected of coronary artery disease, but also as a predictor of benefit from cardiac resynchronization therapy in patients with heart failure, whether of an ischemic or non-ischemic origin.
Cardiology journal 01/2011; 18(1):8-17. · 1.31 Impact Factor
