Predictors of left ventricular function deterioration in patients with left bundle branch block and ejection fraction >50%.

Resynchronization therapy has become standard of care in patients with left bundle branch block (LBBB), congestive heart failure (CHF), and low ejection fraction (EF). In order to characterize the left ventricular (LV) function evolution in patients with LBBB and baseline preserved LVEF, records of all patients who visited an academic echocardiography laboratory during a period of 4 years were retrospectively investigated. Patients were included if they had a baseline EF >50%, LBBB on surface electrocardiography, and at least one follow-up echocardiogram no earlier than 3 months after the baseline study. The endpoint was the occurrence of EF deterioration to values ≤40%. Clinical variables associated with this outcome were identified. Forty-nine patients satisfied the entry criteria. Over a mean 13±8.5 months of follow-up (range 3 to 36), 8 patients (16%) experienced EF deterioration ≤40%. History of CHF prior to baseline echocardiogram and LV mass >300 g were associated with this phenomenon (P=.004 and P=.015, respectively), with a negative predictive value of 100% and 92%, respectively. Our data profiles a risk-stratification methodology in patients with LBBB and baseline EF >50% and possibly a triage strategy toward resynchronization therapy in this population.

Accelerated junctional rhythm and nonalternans repolarization lability precede ventricular tachycardia in Casq2-/- mice.

BACKGROUND: Calsequestrin-2 (CASQ2) is a Ca(2+) buffering protein of myocardial sarcoplasmic reticulum. CASQ2 mutations underlie a form of catecholaminergic polymorphic ventricular tachycardia (CPVT). The CPVT phenotype is recapitulated in Casq2 -/- mice. Repolarization lability (RL)-beat-to-beat variability in the T wave morphology-has been reported in long-QT syndrome, but has not been evaluated in CPVT. METHODS AND RESULTS: ECG from Casq2 -/- mice was evaluated with respect to heart rate (HR) and RL changes prior to onset of ventricular tachycardia (VT) to gain insight into arrhythmogenesis in CPVT. Telemetry from unrestrained mice (3-month-old males, 5 animals of each genotype) and ECG before and after isoproterenol administration in anesthetized mice was analyzed. Average HR in sinus rhythm (SR), occurrence of nonsinus rhythm and RL were quantified. HR was slower in Casq2 -/- animals. Accelerated junctional rhythm (JR) occurred more frequently in Casq2 -/- mice and often preceded VT. In Casq2 -/- mice, HR increased prior to VT onset, prior to onset of JR and on transition from JR to VT. RL increased during progression from SR to VT and after isoproterenol administration in Casq2 -/-, but not in Casq2+/+ animals. Isoproterenol did not increase repolarization alternans in either genotype. CONCLUSIONS: Accelerated JR, likely caused by triggered activity in His/Purkinje system, occurs frequently in Casq2 -/- mice. The absence of CASQ2 results in increased RL. The increase in HR and in RL precede onset of arrhythmias in this CPVT model. Nonalternans RL precedes ventricular arrhythmia in wider range of conditions than previously appreciated.