Vericiguat increased normalization of endothelial function from 10.1% to 37% and CRT response rate from 13% to 34.6% at 1 year in CRT non-responders with endothelial dysfunction.
Observational (n=289)
Yes
Does vericiguat improve endothelial function and restore CRT response in heart failure patients who are prior CRT non-responders with endothelial dysfunction?
Vericiguat therapy in CRT non-responders with endothelial dysfunction significantly improves endothelial function, reduces inflammatory markers, and restores CRT response.
Absolute Event Rate: 37% vs 10.1%
p-value: p=<0.05
Endothelial dysfunction (ED) is a negative prognostic factor for patients with heart failure (HF) who are treated with cardiac resynchronization therapy (CRT). ED could lead to CRT non-responders by increasing endothelin-1 (ET-1) expression and inflammatory/oxidative stress markers. Vericiguat is an anti-HF medication that may reduce inflammatory/oxidative stress, ET-1 expression, and improve endothelial function in ED-CRT non-responders, leading to better outcomes. We conducted a prospective observational study enrolling ED-CRT non-responders treated with vericiguat (vericiguat users) versus those who did not receive vericiguat (non-vericiguat users). ED was diagnosed by flow-mediated vasodilation (FMD ≤ 7.1%) of the brachial artery. Clinical, echocardiographic, and biochemical assessments (inflammatory markers and ET-1) were performed at baseline and at 12 months. The primary endpoints were normalization of endothelial function (FMD > 7.1%) and CRT response at 1 year. Secondary endpoints included changes in inflammatory/oxidative stress markers, ET-1 levels, and clinical outcomes (HF hospitalizations, cardiac, and all-cause mortality). A total of 289 ED-CRT non-responders were included, of whom 81 received vericiguat (vericiguat users) and 208 did not receive vericiguat (nonusers). At 1-year follow-up, vericiguat users vs. non-users demonstrated significant improvement in New York Heart Association class, 6-min walking test, and left ventricular remodeling (p < 0.05). Vericiguat users vs. non-users showed a significant reduction in inflammatory/oxidative stress biomarkers, B-type natriuretic peptide, and ET-1 (p < 0.05). At the end of follow-up, a lower rate of vericiguat users versus nonusers was under treatment with loop diuretics, aldosterone blockers, and sodium-glucose-transporter 2 inhibitors (p < 0.05). At follow-up end, a higher rate of vericiguat users vs. nonusers showed normalization of endothelial function (30 (37%) vs. 21 (10.1%), p < 0.05) and restored CRT responders (28 (34.6%) vs. 27 (13%), p < 0.05). At 1-year follow-up, the normalization of endothelial function was predicted by left-ventricle ejection fraction (0.42, CI 95% 0.02–0.72) and vericiguat (4.35, CI 95% 2.45–7.70). The CRT responders’ outcome was predicted by vericiguat therapy (2.85, 95% CI 1.67–4.89). Our findings demonstrate that vericiguat reduces ED and enhances the response to CRT in prior non-responders by significantly lowering inflammatory/oxidative stress markers and ET-1.
Sardu et al. (Tue,) conducted a observational in Adults with stable chronic heart failure (NYHA class II-IV), left bundle branch block, severe left ventricular ejection fraction reduction (<35%), stable sinus rhythm, and classified as cardiac resynchronization therapy (CRT) non-responders with endothelial dysfunction (FMD ≤ 7.1%) (n=289). vericiguat vs. no vericiguat (non-users) was evaluated on Normalization of endothelial function defined as FMD >7.1% and CRT response at 1 year defined by ≥10% reduction in LVESV, improvement in 6MWT, and Minnesota Living with Heart Failure Questionnaire score >8 (p=<0.05). Vericiguat increased normalization of endothelial function from 10.1% to 37% and CRT response rate from 13% to 34.6% at 1 year in CRT non-responders with endothelial dysfunction.