Key result
Vericiguat linked to ~166% higher CRT response in previous non-responders with endothelial dysfunction.
Why the study?
Endothelial dysfunction negatively affects HF patients treated with CRT, and vericiguat may improve endothelial function and CRT response by reducing inflammatory and oxidative stress.
Does vericiguat improve endothelial function and restore CRT response in heart failure patients who are prior 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.
May warrant vericiguat in CRT non-responders with endothelial dysfunction; hypothesis-generating and requires randomized confirmation.
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.
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Sardu et al. (2026) conducted an 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.
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