Metaanalysis on effects of cardiac resynchronization therapy in heart failure patients with narrow QRS complex

Background: To systematically review the benefits of cardiac resynchronization therapy (CRT) in heart failure patients with narrow QRS (< 120 ms) who have baseline mechanical asynchrony. Methods: We searched the MEDLINE, Cochrane Central Register of Controlled Trials, and reference lists of retrieved articles for relevant trials through October 2007. Studies were included if they were clinical trials in heart failure patients with narrow QRS complex, had at least 3 months of duration and measured baseline mechanical dyssynchrony. Weighted mean difference (WMD) for changes in left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) class and 6 minute walk distance (6MWD) at the end of follow up period were estimated using fixed effects meta-analysis. Results: Three relevant clinical trials (enrolling 98 patients) out of 80 identified studies were included in the final analysis. When compared to baseline, CRT in heart failure patients with narrow QRS complex significantly improved mean LVEF (WMD 7.98%, 95% CI 5.94, 10.03) and 6MWD (WMD 67 m, 95% CI 39.12, 94.98) at the end of follow up period with no significant heterogeneity between the included studies (I2 < 50%). Similarly, there was a significant reduction in NYHA at the end of follow-up (WMD &#8211;0.87, 95% CI &#8211;1.01, &#8211;0.74) but there was significant heterogeneity between the included studies. Conclusions: In patients with narrow QRS complex and baseline mechanical asynchrony, who underwent CRT after optimal medical management, there was a significant reduction in NYHA class, improvement in LVEF and increase in 6MWD during follow up. Further data from large randomized trials are warranted to explore the role of CRT in heart failure patients with narrow QRS complex. (Cardiol J 2008; 15: 230-236

Comparison of the effects of cardiac resynchronization therapy in patients with class II versus class III and IV heart failure (from the InSync/InSync ICD Italian Registry)

Cardiac resynchronization therapy (CRT) is recommended for patients with New York Heart Association (NYHA) class III or IV heart failure and wide QRS complexes. The aim of this study was to compare the effects of CRT in patients in NYHA class II with those in NYHA class III or IV. Nine hundred fifty-two patients (188 in NYHA class II) consecutively implanted with biventricular devices and enrolled in a national observational registry were studied. Clinical outcomes were estimated after 12 months of CRT, and long-term survival was assessed. At a median follow-up of 16 months, significantly fewer major cardiovascular events were reported in patients in NYHA class II compared with NYHA class III or IV (rate 13 vs 23 per 100 patient-years of follow-up, p&lt;0.001). The percentage of patients who improved in NYHA class status after 12 months of CRT was lower in those in class II than in those in class III or IV (34% vs 69%, p&lt;0.001), whereas the absolute increase in the ejection fraction was similar (8+/-9% vs 9+/-11%, p=NS), as well as the reductions in end-diastolic diameter (-3+/-8 vs -3+/-8 mm, p=NS) and end-systolic diameter (-4+/-10 vs -6+/-10 mm, p=NS). The NYHA class II group experienced lower all-cause mortality (log-rank test p=0.018). In the 2 groups, patients with major cardiovascular events during follow-up exhibited less or no reverse remodeling compared with those with better long-term clinical outcomes. In conclusion, the results of this study indicate that CRT induced similar improvements in ventricular function in the 2 groups, whereas the improvement in functional status was significantly lower for patients in NYHA class II than for those in class III or IV. A positive effect of CRT on cardiac dimensions was associated with a long-term beneficial effect on disease progression in patients in NYHA class II

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)