Scholarlink

Background <p>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.</p> Study hypothesis <p>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.</p> Methods <p>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&#xa0;months. The primary endpoints were normalization of endothelial function (FMD &gt; 7.1%) and CRT response at 1&#xa0;year. Secondary endpoints included changes in inflammatory/oxidative stress markers, ET-1 levels, and clinical outcomes (HF hospitalizations, cardiac, and all-cause mortality).</p> Results <p>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 (<i>p</i> &lt; 0.05). Vericiguat users vs. non-users showed a significant reduction in inflammatory/oxidative stress biomarkers, B-type natriuretic peptide, and ET-1 (<i>p</i> &lt; 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 (<i>p</i> &lt; 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%), <i>p</i> &lt; 0.05) and restored CRT responders (28 (34.6%) vs. 27 (13%), <i>p</i> &lt; 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]).</p> Conclusions <p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Vericiguat for endothelial dysfunction and CRT response in non-responders: the VERCET prospective observational study

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月3日

查看全文
  • Celestino Sardu,
  • Ludovica Vittoria Marfella,
  • Luca Rinaldi,
  • Ferdinando Carlo Sasso,
  • Domenico Cozzolino,
  • Francesco Nappo,
  • Ausilia Sellitto,
  • Ciro Romano,
  • Caterina Carusone,
  • Nunzia D’Onofrio,
  • Maria Consiglia Trotta,
  • Joshua Riccio,
  • Domenico Cioffi,
  • Mario Volpicelli,
  • Carmine La Marca,
  • Natale Marrazzo,
  • Valerio Giordano,
  • Carlo Fumagalli,
  • Alessandro Landolfi,
  • Marianna Abitabile,
  • Lorenza Marfella,
  • Maria Luisa Balestrieri,
  • Raffaele Marfella

摘要

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.