Presentation, medical history and initial treatment
The patient was a 36-year-old male with a demanding job, which he was balancing with master’s degree studies and responsibilities of being a new father. He had a history of gout and occasional, subtle shortness of breath (SoB).
In early September 2024, he presented with bilateral ankle oedema and ankle pain, initially suspected to be a gout flare. His uric acid level was elevated, but examination led to hospitalization for cardiac investigation, including echocardiography and cardiac MRI.
Results showed an N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of 217 pg/mL. Blood pressure (BP) was consistently low (115–112/57–66 mm Hg), while creatinine was stable at 95 μmol/L. The patient’s body weight was 74.9 kg and body mass index was 26.35 kg/m2.
Based on a low left ventricular ejection fraction (LVEF) of 30–31 percent, dilated left atrium and left ventricle, and mild mitral regurgitation (MR), he was diagnosed with dilated cardiomyopathy and chronic heart failure (HF), classified as New York Heart Association (NYHA) functional class II. During hospitalization, guideline-directed medical therapy (GDMT) was initiated, including a sodium-glucose cotransporter-2 inhibitor (SGLT2i) at 10 mg QD, an angiotensin receptor– neprilysin inhibitor (ARNi) at 100 mg BID, and a beta blocker (BB) at 2.5 mg QD. (Table) The possibility of implantable cardioverter–defibrillator (ICD) was discussed, which the patient required more time to consider. He was subsequently discharged.
Addition of vericiguat and outcome
By mid-October 2024, the patient’s symptoms improved, and he was able to jog for 7 km. However, mild MR persisted, and eplerenone 25 mg QD (the fourth pillar of GDMT) was added. In early November 2024, during a follow-up visit, he reported being able to walk up three flights of stairs without SoB, yet mild MR remained. Given his persistently low BP, vericiguat 2.5 mg QD was added, instead of uptitrating existing GDMT.
By late November 2024, his symptoms improved and he was able to climb roughly four flights of stairs, but mild MR persisted. Vericiguat was increased to 5 mg QD. On 30 December 2024, his NT-proBNP decreased to 100.9 pg/mL, and the dose of BB was increased to 5 mg QD. By late February 2025, his exercise tolerance was no longer limited, his energy increased, and vericiguat was uptitrated to 10 mg QD. (Table)
The patient tolerated vericiguat well, and LVEF and BP improved. As he became asymptomatic, ARNi was subsequently uptitrated in April and May 2025, with the expectation of further benefits. At the latest follow-up visit on 18 August 2025, LVEF improved to 55 percent, BP was 122/71 mm Hg, HR was 89 bpm, and he was classified as NYHA functional class I. (Table) He reported being able to hike for 5 hours without symptoms and graduated from his master’s programme. An ICD is no longer indicated at present.
Discussion
HF with reduced ejection fraction (HFrEF) is characterized by repeated hospitalizations and progressive worsening. While GDMT has proven effective, recent evidence indicates that younger patients with HF, such as this patient, face a prognosis comparable to that of older patients, with high rehospitalization rates within 2 years. This highlights the need to reduce the residual risk of cardiovascular (CV) events and hospitalizations.1,2
European Society of Cardiology (ESC) guidelines recommend pharmacotherapy before device therapy for chronic HF. The four pillars of GDMT – SGLT2i, BB, ARNi and mineralocorticoid receptor antagonists (MRA) – should be uptitrated to maximally tolerated doses, unless contraindicated. The guidelines further recommend vericiguat, in addition to the four pillars, to reduce CV mortality or hospitalization for HF (HHF).3 Reinforcing this, the 2023 ESC consensus statement on worsening HF (WHF) recommends initiating vericiguat, alongside the four pillars, for symptomatic patients with LVEF <45 percent following a WHF event.4
Vericiguat is an oral soluble guanylate cyclase (sGC) stimulator targeting the nitric oxide (NO)–sGC–cyclic guanosine monophosphate (cGMP) pathway through a distinct mechanism complementing existing HF treatments. It directly binds to and stimulates sGC through a binding site independent of NO, increasing cGMP production. This increase in cGMP has beneficial effects in HF, including vasodilation, improved endothelial function, reduced fibrosis and remodelling of the heart.1,5,6 Real-world studies conducted in Slovenia and Japan indicated that vericiguat, with or without GDMT, may induce myocardial functional and structural reverse ventricular remodelling in patients with chronic HFrEF and recent HF worsening.7,8
In the phase III VICTORIA trial involving 5,050 patients with chronic HF and LVEF <45 percent receiving GDMT, vericiguat demonstrated a 10 percent risk reduction in the primary composite outcome of CV death or HHF (hazard ratio [HR], 0.90; 95 percent confidence interval [CI], 0.83–0.98; p=0.02) vs placebo after a median follow-up of 10.8 months.5 Importantly, no statistically significant differences in symptomatic hypotension were observed between the two groups (9.1 vs 7.9 percent; p=0.12).5
Given its established efficacy, vericiguat was prescribed to our patient just 2 months after diagnosis, before full optimization of GDMT, as further uptitration was limited by his persistent hypotension. Although our young patient’s initial HF symptoms were relatively mild, his exercise capacity increased following vericiguat initiation. This improvement in physical performance aligns with findings from the real-world, observational VERITA study of 103 patients with HFrEF, which demonstrated a significant improvement in NYHA functional class, with the proportion of patients in classes III, II and I shifting from 61.2 percent, 38.8 percent and 0 percent at baseline to 26.2 percent, 63.1 percent and 9.7 percent at study end (p<0.001).9
Our patient’s elevated baseline NT-proBNP (217 pg/mL) provided further rationale for adding vericiguat to his GDMT regimen to reduce mortality and rehospitalization risk. A study (n=5,050) found that vericiguat, compared with placebo, reduced CV death and HHF in HFrEF patients with NT-proBNP levels <8,000 pg/mL at baseline. (Figure) Notably, those with NT-proBNP <4,000 pg/mL had a 23 percent reduction in the primary composite endpoint of CV death or HHF (HR, 0.77; 95 percent CI, 0.68–0.88), a 25 percent reduction in CV death (HR, 0.75; 95 percent CI, 0.60–0.94) and a 22 percent reduction in HHF (HR, 0.78; 95 percent CI, 0.67–0.90).10
The established dose-dependent relationship between vericiguat and treatment outcomes supported its uptitration to the maximum dose in our patient, in order to optimize potential benefit. Consistent with findings from the SOCRATES-REDUCED study, our patient’s HF symptoms, exercise tolerance and LVEF continued to improve as the dose of vericiguat was increased.11 Ultimately, the improvement in LVEF after increasing vericiguat to 10 mg QD meant ICD was no longer indicated.
Vericiguat exhibits a favourable safety profile, with no impact on sodium and potassium, making electrolyte monitoring unnecessary.1,12 Furthermore, its risks for symptomatic hypotension, renal and urinary disorders, and acute kidney injury are similar to placebo.13 This, coupled with its distinct mechanism of action, allows vericiguat to facilitate GDMT intensification and optimization as suggested in VERITA and a German real-world study.14,15
Final thoughts
Diagnosing HF in young, active individuals, such as our patient, can be challenging due to subtle and nonspecific symptoms. Constant tiredness, lack of energy, cough, and difficulty concentrating are easily dismissed as stress, potentially delaying accurate diagnosis. Therefore, detailed history taking and careful questioning about symptoms are essential in identifying underlying HF. In our patient’s case, timely diagnosis and early introduction of vericiguat alongside GDMT, and vericiguat’s role in facilitating GDMT optimization despite initial hypotension, enabled him to regain fitness and well-being, perform at his demanding job, and fulfil his family and study commitments.
This case highlights the significant impact of timely and appropriate intervention in improving the life of a young HF patient and underscores the importance of overcoming therapeutic inertia to proactively uptitrate GDMT and initiate vericiguat early.
