RESUMO
Hypertension and metabolic syndrome frequently coexist to increase the risk for adverse cardiometabolic outcomes. To date, no drug has been proven to be effective in treating hypertension with metabolic syndrome. M-atrial natriuretic peptide is a novel atrial natriuretic peptide analog that activates the particulate guanylyl cyclase A receptor. This study conducted a double-blind, placebo-controlled trial in 22 patients and demonstrated that a single subcutaneous injection of M-atrial natriuretic peptide was safe, well-tolerated, and exerted pleiotropic properties including blood pressure-lowering, lipolytic, and insulin resistance-improving effects. (MANP in Hypertension and Metabolic Syndrome [MANP-HTN-MS]; NCT03781739).
RESUMO
BACKGROUND: It is unknown whether cardiac resynchronization therapy (CRT) would improve or halt the progression of heart failure (HF) in patients with mild to moderately reduced ejection fraction (HFmmrEF) and left bundle branch block (LBBB). OBJECTIVE: This study aimed to investigate the outcomes of CRT in patients with HFmmrEF and left ventricular conduction delay. METHODS: A prospective, randomized clinical trial sponsored by the National Heart, Lung, and Blood Institute included 76 patients who met the study inclusion criteria (left ventricular ejection fraction [LVEF] of 36%-50% and LBBB). Patients received CRT-pacemaker and were randomized to CRT-OFF (right ventricular pacing 40 beats/min) or CRT-ON (biventricular pacing 60-150 beats/min). At a 6-month follow-up, pacing programming was changed to the opposite settings. New York Heart Association class, N-terminal pro-brain natriuretic peptide levels, and echocardiographic variables were collected at baseline, 6 months, and 12 months. The primary study end point was the left ventricular end-systolic volume (LVESV) change from baseline, and the primary randomized comparison was the comparison of 6-month to 12-month changes between randomized groups. RESULTS: The mean age of the patients was 68.4 ± 9.8 years (male, 71%). Baseline characteristics were similar between the 2 randomized groups (all P > .05). In patients randomized to CRT-OFF first, then CRT-ON, LVESV was reduced from baseline only after CRT-ON (baseline, 116.1 ± 36.5 mL; CRT-ON, 87.6 ± 26.0 mL; P < .0001). The randomized analysis of LVEF showed a significantly better change from 6 to 12 months in the OFF-ON group (P = .003). LVEF was improved by CRT (baseline, 41.3% ±.7%; CRT-ON, 46.0% ± 8.0%; P = .002). In patients randomized to CRT-ON first, then CRT-OFF, LVESV was reduced after both CRT-ON and CRT-OFF (baseline, 109.8 ± 23.5 mL; CRT-ON, 91.7 ± 30.5 mL [P < .0001]; CRT-OFF, 99.3 ± 28.9 mL [P = .012]). However, the LVESV reduction effect became smaller between CRT-ON and CRT-OFF (P = .027). LVEF improved after both CRT-ON and CRT-OFF (baseline, 42.7% ± 4.3%; CRT-ON, 48.5% ± 8.6% [P < .001]; CRT-OFF, 45.9% ± 7.7% [P = .025]). CONCLUSION: CRT for patients with HFmmrEF significantly improves LVEF and ventricular remodeling after 6 months of CRT. The study provides novel evidence that early CRT benefits patients with HFmmrEF with LBBB.