Table 2.

Ongoing clinical trials evaluating the therapeutic modalities against endothelial dysfunction in heart failure.

Clinical Trial Identifier/Official Title	Study Design/Estimated Enrollment/Inclusion Criteria	Primary Outcome Measures	Secondary Outcome Measures
NCT04539093 “Assessment of Endothelial Function in Patients with Advanced Heart Failure Requiring Mechanical Circulatory Support”	Prospective cohort; n = 20 patients with end-stage HF scheduled for LVAD implantation	Evaluation of endothelial function (blood NO levels, FMD) Evaluation of microvascular function (contrast-enhanced ultrasound of the peripheral skeletal muscle of lower extremities)	Functional outcomes: Quality of Life (KCCQ); Mobility (6 MWT); Handgrip; Lower extremity strength; Ventilation and gas exchange (CPET)
NCT05230732 “Neuromodulation of Inflammation and Endothelial Function to Treat Elderly Patients With Systolic Heart Failure”	Prospective, randomized, double-blind study; n = 158 patients with systolic HF and EF < 40%; use of Low-level Tragus stimulation- vs. sham treatment for 1 h daily/12 weeks	6 MWT	Quality of life (Minnesota living with heart failure questionnaire) FMD HRV Inflammatory cytokines
NCT02997462 “Monocyte Phenotypic Changes in Heart Failure”	Prospective cohort; n = 60 patients with HF admitted to the ICU or HF service vs. healthy, age-matched controls	Change in IL-6 levels between hospital admission and discharge	Evaluation of cell surface markers, cytokines, monocyte-gene expression, microRNA, monocyte/macrophage morphology, markers of oxidative stress and inflammation at admission, discharge, and at first post-discharge appointment
NCT04323371 “Cardiogenic Shock Integrated PHenotyping for Event Reduction”	Prospective observational study; n = 26 patients with acute decompensated HF complicated by cardiogenic shock	Markers of inflammation, endothelial permeability, endothelial glycocalyx perturbation, and metabolomics profile
NCT05498584 “Targeting LOXL2 and Cardiac Fibrosis for Post-acute Heart Failure Treatment- A Prospective Study”	Prospective cohort study; n = 126 patients with HF (EF ≤ 40%) admitted for worsening HF in 3 years; administration of a cardiac rehabilitation program according to cardiopulmonary exercise test	All-cause mortality	HF readmission FMD (change from baseline to 6 months) KCCQ (change from baseline to 6 and 12 months)

6 MWT: six-minute walk test; CPET: Cardiopulmonary Exercise Test; EF: Ejection fraction; HF: Heart failure; HGS: Handgrip strength; HRV: Heart rate variability; FMD: Flow mediated dilatation; ICU: Intensive care unit; KCCQ: Kansas City Cardiomyopathy Questionnaire; LVAD: left ventricular assist devices; NO: Nitric oxide.