Prognostic significance of beta-blocker up-titration in conjunction with cardiac resynchronization therapy in heart failure management.

Clinical practice guidelines emphasize that optimal pharmacotherapy, including beta-blockers (BB), is a prerequisite before receiving cardiac resynchronization therapy (CRT) in eligible patients with heart failure (HF). However, the optimal dose of BB before CRT implantation cannot be tolerated in a number of patients. Sixty-three consecutive patients who underwent CRT in 2006-2013 were retrospectively investigated. Before receiving CRT, BB could not be introduced in 20 patients (32 %); the daily carvedilol-equivalent dose in other 43 patients was 5.6 ± 7.0 mg because of significant HF and bradycardia. After receiving CRT, BB could be introduced in almost all patients (n = 61, 97 %), and the daily BB dose increased from 5.6 ± 7.0 to 13.2 ± 7.8 mg (P < 0.001). Multivariate analysis indicated that the change of BB dose after CRT was independently associated with improved left ventricular end-systolic volume (LVESV) [ß = -0.36; 95 % confidence interval (CI) -2.13 to -0.45; P < 0.01] after 6-months follow-up. Furthermore, Cox proportional hazard analysis also showed that the change in the BB dose (hazard ratio, 0.92; 95 % CI, 0.87-0.98; P < 0.01) as well as the New York Heart Association functional classification was an independent predictor of cardiac events. After initiating CRT, BB therapy can be introduced and up-titrated in intolerant HF patients. The up-titrated dose of BB after CRT was an independent predictor for the improvement of LVESV and HF prognosis.

Time course of left ventricular reverse remodeling in response to pharmacotherapy: clinical implication for heart failure prognosis in patients with idiopathic dilated cardiomyopathy.

The present study aimed to identify the clinical significance of differences in detection timings of left ventricular reverse remodeling (LVRR) on heart failure (HF) prognosis in patients with idiopathic dilated cardiomyopathy (IDCM). We investigated 207 patients with IDCM who underwent pharmacotherapeutic treatment. LVRR was defined as improvements in both LV ejection fraction ≥10 % and indexed LV end-diastolic dimension (LVEDDi) ≥10 %. Patients were stratified into 3 groups by LVRR timing: patients with LVRR <24 months (Early LVRR), those with LVRR ≥24 months (Delayed LVRR), and those without LVRR during the entire follow-up period (No LVRR). The major endpoint was first detection of composite event including readmission for decompensated HF, major ventricular arrhythmias, or all-cause mortality. LVRR was recognized in 108 patients (52 %): Early LVRR in 83 (40 %), Delayed LVRR in 25 (12 %), and No LVRR in 99 (48 %). The survival rate for the major endpoint was significantly higher for Delayed LVRR than for No LVRR (P = 0.001); there was no significant difference between Early and Delayed LVRR. Among patients without LVRR <24 months (Delayed + No LVRR), receiver operating characteristic curve analysis showed that the area under the curve for improvement in LVEDDi during the first 6 months for predicting subsequent LVRR (Delayed LVRR) [0.822 (95 % confidence interval, 0.740-0.916; P = 0.038)] was greater than that for improvement in LVEF. In conclusion, LVRR was a favorable prognostic indicator in patients with IDCM irrespective of its detection timing. Reduced LVEDDi during the first 6 months was predictive for subsequent LVRR in the later phase.