Prognostic impact of maximum vasodilation therapy in heart failure

Introduction Heart failure (HF) is a severe and progressive clinical syndrome, with therapeutic management based on optimizing quadruple therapy. Among the vasodilators with mortality-reducing effects, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), the combination of hydralazine + nitrate, and sacubitril/valsartan are particularly noteworthy. While vasodilator therapy optimization is often considered when the maximum dose of a single agent is reached, evidence suggests that achieving maximum vasodilation—guided by the highest tolerated dose, including hydralazine + nitrate—may provide additional benefits for patients with HF. Objective To evaluate the effects of maximum vasodilation therapy in the management of Heart Failure with Reduced Ejection Fraction (HFrEF) by assessing the reduction in the risk of progression to Worsening Heart Failure (WHF) and improvement in patients' functional class. Methods A prospective, observational, randomized, open-label, single-center study including 685 patients with HFrEF. Patients were divided into two groups: HF therapy guided by maximum vasodilation versus HF therapy not guided by maximum vasodilation. The follow-up period was two years. Maximum vasodilation was defined as the highest tolerated dose of life-modifying vasodilators in HFrEF, including ACEI/ARB, sacubitril/valsartan, and the hydralazine + nitrate combination. Results Among the 685 patients included and randomized, 192 (28%) received HF therapy not guided by maximum vasodilation, while 493 patients underwent therapy guided by maximum vasodilation. In the non-maximum vasodilation group, 25% of patients experienced worsening heart failure (WHF). In the maximum vasodilation group, 16 patients (3.2%) developed WHF, corresponding to a 24% reduction in the risk of HF worsening with the maximum vasodilation strategy (HR: 0.76; 95% CI: 0.40-0.82; p<0.0001). For the secondary outcome, the maximum vasodilation strategy led to a 15% reduction in the risk of worsening HF functional class (HR: 0.85; 95% CI: 0.50-0.92; p<0.0001). Conclusions Maximum vasodilation in HFrEF significantly reduced the risk of WHF and functional class deterioration. This pilot study highlights the necessity of targeting maximum vasodilation to improve prognostic outcomes in a high-morbidity and high-mortality disease such as heart failure.