Clinical Research Directory

Exercise, Mediterranean Diet and Inflammation in Heart Failure

This randomized clinical trial will test whether a multimodal anti-inflammatory program added to standard treatment improves the prognosis of patients with heart failure who have recently been hospitalized or visited the emergency department for worsening heart failure. The program combines two parts: a structured physical exercise plan and a Mediterranean diet plan, adapted to each patient. A total of 214 adults with heart failure and mildly reduced or preserved ejection fraction (LVEF 40% or higher), recent worsening of heart failure, and elevated inflammatory markers (C-reactive protein) will take part. Patients with frailty or malnutrition are excluded from the study. Patients will be recruited from heart failure clinics of participating Spanish hospitals. After agreeing to participate, patients will be randomly assigned to one of two groups: one group will continue their usual heart failure treatment, and the other will follow the same treatment plus the exercise and nutrition program delivered remotely by trained professionals for 12 months. The main question is whether the multimodal program reduces the combined occurrence of cardiovascular death, repeated heart failure hospitalizations, worsening exercise capacity (6-minute walk test), or worsening quality of life (Kansas City Cardiomyopathy Questionnaire) at 12 months. The study will also check whether the program lowers blood inflammatory and heart failure biomarkers (NT-proBNP, CA125), improves heart function on echocardiography, and whether patients' adherence to the program affects the results. All participants will continue to receive standard heart failure care; no medication is being tested, and the intervention consists of lifestyle coaching delivered by telephone or video calls.

Allopurinol Improves Heart Function in African Americans With Resistant Hypertension

African American adults in the United States have the highest prevalence rate of high blood pressure (hypertension) and heart failure in the world. African Americans with treatment resistant hypertension have higher levels of the enzyme - xanthine oxidase compared to Caucasians. This trial will test if administration of the xanthine oxidase inhibitor - Allopurinol (commonly used in the treatment of gout), given over a period of 8 weeks, will improve heart function, exercise ability and quality of life in African American Veterans with resistant hypertension.

Safety & Effectiveness of Tovinontrine in Chronic Heart Failure With Preserved Ejection Fraction (Cycle-2-PEF)

The purpose of this study is to evaluate the safety and effectiveness of tovinontrine compared to placebo to lower NT-proBNP in patients with chronic heart failure with preserved ejection fraction

Epicardial Adipose Tissue Composition and Heart Failure With Preserved Ejection Fraction

This study seeks to develop improved cardiac MRI (CMR) methods to quantify epicardial adipose tissue (EAT) composition and to demonstrate the advantages of EAT composition imaging (a) in advancing the understanding of the relationship between EAT and heart failure with preserved ejection fraction (HFpEF) and (b) for understanding mechanisms of and guiding medical therapy in HFpEF. The investigators recently developed the first method for quantifying EAT FAC in human subjects, utilizing a rate-6 accelerated radial 2D multi-echo gradient-echo breathhold acquisition with a local low rank reconstruction. In this project the first specific aim is to develop a rapid free-breathing 3D EAT FAC MRI method that reduces motion-related artifacts, increases coverage, and facilitates higher spatial resolution and improved FAC reproducibility. The second specific aim is to show that EAT FAC is more strongly associated than EAT volume with cardiometabolic HFpEF. In this context, individuals with known or suspected HFpEF will undergo CMR, echocardiography, and other testing to (a) diagnose cardiometabolic HFpEF; (b) characterize features associated with the severity of HFpEF; and (c) assess EAT volume and FAC. The investigators will determine if EAT FAC is more strongly associated than EAT volume with HFpEF and with features associated with the severity of HFpEF. The third specific aim is to show, in the context of cardiometabolic HFpEF and pre-HFpEF, (a) that GLP-1 receptor agonism with semaglutide (SEMA) shifts the EAT FAC to a less proinflammatory profile and (b) that baseline EAT FAC is a stronger predictor than EAT volume of improved cardiovascular function due to SEMA. Cardiometabolic HFpEF and pre-HFpEF subjects will undergo echocardiography and CMR with EAT FAC at baseline and after 3 months to serve as a self-control. Subjects will then undergo repeat imaging 6 months after the initiation of SEMA. The change in FAC after treatment with SEMA will be compared to the change in FAC prior to SEMA. Data will be analyzed to show that SEMA changes EAT FAC, and that baseline EAT FAC is a stronger predictor than EAT volume of improvements in severity of HFpEF.

Coronary Sinus Reducer For The Management Of Symptomatic Heart Failure

The purpose of this study is to evaluate the efficacy of CS Reducer implantation in patients with HFpEF and CMD on left ventricular filling pressures, specifically invasive measurement of PAWP during standardized exercise.

Exercise Testing After Preeclampsia

Though cardiovascular disease (CVD) is the leading cause of mortality in women, traditional epidemiology in this area has focused on later life, when cardiometabolic risk has already exacted a cumulative toll on the vascular system. Recent data from the investigators and others has highlighted pregnancy as a unique, early moment of cardiovascular stress in young women that may "unmask" CVD propensity. It is unclear if PreE simply represents a "failed stress test" or directly contributes to the pathophysiology of future CVD. While mechanistic studies have largely been the purview of model-based studies, endothelial dysfunction has emerged as central to the pathogenesis of both PreE and peripartum cardiac dysfunction. Indeed, biomarkers of endothelial dysfunction and angiogenic imbalance during pregnancy have been shown to remain elevated at least 6 months post-partum. Moreover, peri-partum endothelial dysfunction can persist for years post-delivery and remains a significant risk factor for CVD (even after adjustment for other traditional risk factors). While these findings suggest that PreE-associated endothelial dysfunction and inflammation may contribute to early myocardial dysfunction that presages HF risk decades before its onset, the modifiable epidemiology of PreE-associated LVDD, including potential mechanisms of risk, remains unclear, limited by lack of precision molecular phenotypes accessible in a large number of American women across race. Ultimately, understanding the epidemiology and pathobiology of PreE-associated myocardial dysfunction affords a unique opportunity to identify women at risk with a longer lead-time for risk factor modification to interrupt CVD. The investigators hypothesize that persistent structural-functional myocardial alterations after PreE are linked to pre- and post-gravid cardiometabolic risk factors (SA1), functional and hemodynamic impairment (SA2) and select pathways of vascular and inflammatory stress relevant to HF risk (SA3). Despite extensive study on the role of inflammation/ischemia in PreE, there have been no large studies connecting these phenotypes with early PP functional response and biochemical alterations, a key barrier to designing studies for improving CVD/HF in women. SA1: To identify pregnancy-specific clinical factors related to postpartum HFpEF phenotypes Clinical Implication: Improve identification of women at highest risk for developing post-PreE LV diastolic dysfunction (a harbinger of HFpEF). SA2: To define functional and hemodynamic signatures of early HFpEF due to preeclampsia Clinical Implication: Identify women at highest risk for developing early HFpEF. SA3: To identify shared pathophysiologic mechanistic pathways for PreE-associated HFpEF Clinical Implication: Identify targetable pathways for post-PreE cardiac dysfunction that may prevent/ delay HFpEF development.

Cardiovascular and Renal Endpoints With Flozins - an Observational Prospective Study in CKD HFpEF Patients

The main aim of this study is to holistically assess the cardiovascular and renal outcomes in HFpEF CKD patients with and without SGLT2 inhibition, with focus on the endothelial disfunction, MACE and mortality using clinical evaluation, flow mediated dilatation, carotid-femoral pulse wave velocity, intima-media thickness, echocardiographic parameters, NMR metabolomics and a series of novel biomarkers.

Mechanistic Insights From Temporary Pacing in HFpEF

Heart failure with preserved ejection fraction (HFpEF) is characterised by impaired diastolic function. A recent clinical trial has demonstrated multiple beneficial outcomes in HFpEF patients receiving personalised accelerated pacing from indwelling permanent pacemakers, including symptomatic improvement, objective reductions in NT-proBNP level and AF-burden. The investigators aim to determine the underlying mechanisms behind these documented effects, to investigate the acute intracardiac haemodynamic response to temporary multisite pacing in HFpEF participants and to gain further mechanistic insight with additional haemodynamic, electrical and echocardiographic data collection during temporary pacing in this cohort. This will all provide valuable information towards new potential targets of therapy.