BMC medicine · 2026
Vericiguat for endothelial dysfunction and CRT response in non-responders: the VERCET prospective observational study.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Sardu Celestino, Marfella Ludovica Vittoria, Rinaldi Luca, Sasso Ferdinando Carlo, Cozzolino Domenico, Nappo Francesco, Sellitto Ausilia, Romano Ciro, Carusone Caterina, D'Onofrio Nunzia, Trotta Maria Consiglia, Riccio Joshua, Cioffi Domenico, Volpicelli Mario, La Marca Carmine, Marrazzo Natale, Giordano Valerio, Fumagalli Carlo, Landolfi Alessandro, Abitabile Marianna, Marfella Lorenza, Balestrieri Maria Luisa, Marfella Raffaele
Аннотация
BACKGROUND: 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.
STUDY HYPOTHESIS: 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.
METHODS: 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).
RESULTS: 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]).
CONCLUSIONS: 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.
STUDY HYPOTHESIS: 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.
METHODS: 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).
RESULTS: 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]).
CONCLUSIONS: 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.