Dyssynchrony and the risk of ventricular arrhythmias

OBJECTIVES: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271)

LMNA Mutation in a Family with a Strong History of Sudden Cardiac Death

We report a family with heterozygous deletion of exons 3&ndash;6 of the LMNA gene. The main presentation of affected family members was characterized by ventricular and supraventricular arrhythmias, atrioventricular (AV) block and sudden cardiac death (SCD) but also by severe dilative cardiomyopathy (DCM). We report on two siblings, a 36-year-old female and her 40-year-old brother, who suffer from heart failure with mildly reduced ejection fraction, AV conduction delays and premature ventricular complexes. Their 65-year-old mother underwent heart transplantation at the age of 55 due to advanced heart failure. Originally, the LMNA mutation was detected in one of the uncles. This index patient and three of his brothers died of SCD as well as their father and aunt. The two siblings were treated with implanted defibrillators in our specialized tertiary heart failure center. This case report places this specific genetic variant in the context of LMNA-associated familial DCM

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)

BACKGROUND: 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. METHODS AND RESULTS: 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). CONCLUSIONS: Assessment of regional longitudinal myocardial deformation in the inferior region provided incremental prognostic information over clinical and echocardiographic risk factors in predicting ventricular tachyarrhythmias. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271

Combining diastolic dysfunction and natriuretic peptides to risk stratify patients with heart failure with reduced ejection fraction

Background: Diastolic dysfunction (DD) might help to risk stratify patients with heart failure (HF) with reduced ejection fraction (HFrEF). Nonetheless, HF guidelines/risk scores don't consider DD. We aimed to show the independent prognostic value of DD for nonfatal HF/death in patients with HFrEF on top of natriuretic peptides (NP). Methods: We analyzed 1155 baseline echocardiograms of the MADIT-CRT study (LVEF≤30%, QRS ≥ 130 ms, NYHA class I/II), classifying DD according to 2016 ASE/EACVI classification. Results: Patients were 64 ± 11 years-old, 24% females, LVEF was 24 ± 5%, 58% had abnormal BNP (≥100 pg/ml). While 45% had impaired relaxation, 33% had pseudonormal filling, 12% restrictive pattern, 6% indeterminate diastolic function, 4% were not classifiable due to missing data. During a follow-up of 2.1 ± 1.0 years, there were 233 HF/death. Compared to patients without pseudonormal/restrictive filling and with normal NP (23%), patients with pseudonormal/restrictive filling, alone (15%) or combined to elevated NP (30%), were at higher risk of events (respectively padj = 0.025 and padj < 0.001), as opposed to those with abnormal NP alone (22%; padj = 0.55). Adding DD to conventional markers of risk and NP improved prediction (C-statistic 0.733 versus 0.708, p = 0.024). DD was the first parameter to be considered to risk stratify MADIT-CRT population, according to Classification-And-Regression-Tree analysis. Conclusions: Among HFrEF patients with mild symptoms, pseudonormal/restrictive filling, either alone or combined with elevated NP, was associated with high risk of events, as opposed to isolated elevation of NP. DD provided incremental risk prediction for death/HF beyond commonly used markers. These data might suggest to integrate DD into HF guidelines/risk score