This single-center retrospective pilot cohort study was conducted at a tertiary care hospital between November 1, 2023 and September 30, 2025. To ensure complete follow-up for all included patients, enrollment was censored on September 30, 2025, allowing a minimum of 3 months of follow-up through December 31, 2025.

The study protocol was reviewed and approved by the Institutional Ethics Committee. Given the retrospective nature of the study, the Ethics Committee approved the collection of clinical data from hospital records. Surviving patients were contacted during follow-up and consent was obtained for use of their clinical information whenever feasible. Consent status did not influence inclusion in the retrospective analysis.

We screened 145 patients admitted with de novo ADHF following an AMI. ADHF was diagnosed via clinical evaluation using the Framingham criteria and confirmed by elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) standardized for age, alongside echocardiographic evidence of an LVEF < 50%. AMI was defined according to the Fourth Universal Definition of Myocardial Infarction [5].

Patients were excluded if they had a previous diagnosis of heart failure, primary valvular heart disease requiring intervention, significant uncorrected valvular disease, secondary cardiomyopathies (rheumatic, alcoholic, or dilated), autoimmune diseases, advanced tumors, severe sepsis, primary functional disorders of vital organs (brain, liver, lungs), abnormal thyroid function, mental disorders impeding communication, or were on ventilatory support.

Of 145 patients screened with de novo acute decompensated heart failure following acute myocardial infarction, 39 were excluded. Reasons for exclusion included prior history of heart failure (n = 12), significant valvular heart disease (n = 6), secondary cardiomyopathy (n = 5), severe sepsis or advanced systemic illness (n = 7), requirement for prolonged mechanical ventilatory support (n = 4), and incomplete clinical records or loss to follow-up before discharge (n = 5). The remaining 106 consecutive eligible patients received vericiguat and comprised the study cohort.

Among the eligible cohort, 106 consecutive patients were treated with oral vericiguat initiated within 48 hours of hospital admission. All patients were managed with guideline-directed medical therapy (GDMT) for heart failure—including angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), beta-blockers, mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter-2 (SGLT2) inhibitors—as tolerated based on blood pressure, renal function, and electrolyte status. Acute management included intravenous diuretics, and, tailored to hemodynamic status, intravenous inotropes or vasodilators. Revascularization via percutaneous coronary intervention (PCI) and secondary prevention with dual antiplatelet therapy and statins were provided per ACC/AHA guidelines.

Vericiguat was initiated within 48 hours of admission at a dose of 2.5 mg once daily. Dose escalation followed standard prescribing recommendations as tolerated, with uptitration to 5 mg and subsequently 10 mg once daily at approximately 2-week intervals based on blood pressure, renal function, and clinical stability. Drug tolerability was assessed during follow-up visits through review of symptoms, blood pressure measurements, renal function, and treatment continuation.

The primary endpoint was change in NYHA functional class from baseline to 3 months.

Secondary endpoints included changes in left ventricular ejection fraction, estimated glomerular filtration rate and vericiguat discontinuation due to adverse effects.

Repeated measurements across baseline, 7 days, and 3 months were analyzed using repeated-measures analysis of variance (ANOVA) for continuous variables and Cochran’s Q test for categorical variables, followed by pairwise comparisons where appropriate.

Patients were systematically evaluated during the index admission, at 7 days post-discharge, and at 3 months post-discharge. Assessments included NYHA functional classification, blood pressure, renal function, serum electrolytes, and LVEF estimation via echocardiography.

Statistical analysis was performed using SPSS version 22.0. Categorical data were reported as counts and percentages, and comparisons were made using chi-square tests. Continuous variables were presented as mean ± standard deviation (SD). For normally distributed data exhibiting homogeneity of variance, paired sample t-tests were utilized for within-patient comparisons across timepoints. A two-sided P-value < 0.05 was considered statistically significant. Because 5 patients died prior to the 3-month follow-up, they were excluded from the longitudinal paired comparative analysis, leaving a final analytic cohort of 101 survivors.

Of the 106 patients enrolled and treated with vericiguat, 5 patients died during the index admission or follow-up period and were excluded from the 3-month comparative outcomes analysis. The final baseline characteristics for the remaining 101 patients are detailed in Table 1. The cohort was predominantly male (85%) with a mean age of 56 ± 10 years. Comorbidities were common, including chronic kidney disease (CKD stage III-V) in 78%, diabetes in 67%, and hypertension in 45%. All 101 patients (100%) in the analytic cohort underwent PCI. The severity of decompensation was high: all patients presented with NYHA class III (69%) or IV (31%) symptoms, 80% experienced cardiogenic shock requiring inotropic support, and 100% required intravenous diuretics. Echocardiography indicated HFrEF in 85% and mildly reduced EF (HFmrEF) in 15%. All 101 patients (100%) in the analytic cohort underwent PCI. The severity of decompensation was high: all patients presented with NYHA class III (69%) or IV (31%) symptoms, 80% experienced cardiogenic shock requiring inotropic support, and 100% required intravenous diuretics. Echocardiography indicated HFrEF in 85% and mildly reduced EF (HFmrEF) in 15%.

145 patients screened De novo ADHF following AMI 106 consecutive patients Enrolled & treated with vericiguat 5 patients died (Excluded from comparison) 101 survivors Included in 3-month follow-up.

Table 1. Baseline characteristics.

Table 2 summarizes the clinical and laboratory trajectories of the 101 survivors. Vericiguat therapy was well-tolerated over the follow-up period, with no reported adverse effects necessitating drug withdrawal. In the total enrolled cohort of 106 patients, there were 4 deaths (4%) observed by 7 days post-discharge and 1 additional death by 3 months.

Figure 1.Study flow diagram. Depicting the selection, treatment, and final analytic inclusion of patients presenting with de novo acute decompensated heart failure (ADHF) after acute myocardial infarction (AMI).

Table 2. Effect of vericiguat on post AMI de novo ADHF.

*P values denote comparisons between baseline and 3 months. NS = not significant. Dashes indicate data not reported at that time point. Deaths (n = 5) were reported among the initial 106 treated patients but excluded from these paired comparisons.

Among the survivors, significant improvement was observed in functional capacity; baseline NYHA classes were exclusively III and IV, transitioning to predominantly class II (90%) by both 7 days and 3 months (P < 0.01). The incidence of clinical hypotension diminished markedly from 80% at admission to 35% at 7 days, and 10% by 3 months (P < 0.01).

Echocardiographic and laboratory assessments also demonstrated improvement. Mean LVEF improved from 30.5% ± 8.5% at baseline to 36.6% ± 6.4% at 3 months (P < 0.05), and renal function, assessed by estimated glomerular filtration rate (eGFR), increased from 45 ± 14 to 66 ± 18 (P < 0.05). Serum sodium and potassium levels remained broadly stable without statistically significant changes. Correspondingly, reliance on diuretics diminished substantially, with active diuretic prescriptions dropping from 100% at baseline to 22% at 3 months (P < 0.01), while ACEI/ARNI use increased from 20% to 90% (P < 0.01). These temporal trends are illustrated in Figure 2 and the additional laboratory and treatment visualizations in Figure 3.

Figure 2.Clinical and Hemodynamic Changes over Time. Shown are trends across baseline, 7 days post-discharge, and 3 months post-discharge in the analytic survivor cohort (n = 101) receiving vericiguat and standard GDMT.