Clinical Research Directory

HS235 Study in Overweight and Obese Participants With Combined Pre and Post-Capillary Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction

Study of HS235 in Overweight and Obese Participants with Combined Pre and Post-Capillary Pulmonary Hypertension due to Heart Failure with Preserved Ejection Fraction

Maridebart Cafraglutide in Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity

This trial will examine if maridebart cafraglutide as an adjunct to standard of care will lead to a reduction in heart failure (HF) events such as HF hospitalizations and urgent HF visits, cardiovascular (CV) deaths and improvement in HF symptoms in participants with HF with preserved ejection fraction (HFpEF) and HF with mildly reduced ejection fraction (HFmrEF) who are obese. This is a phase 3, global, multicenter, 2-part trial with a double-blind period and an open-label extension (OLE). The trial is event-driven, and Part 1 will conclude when approximately 850 primary endpoint events have occurred.

Leg Heat Therapy in Heart Failure With Preserved Ejection Fraction

The objective of this pilot study is to establish evidence to support the validity of HT in improving skeletal muscle function and physical capacity of patients with HFpEF. Our central hypothesis is that HT treatment will lead to improvements in skeletal muscle and microvascular function compared to a control intervention. As a result, we anticipate that patients treated with HT will demonstrate improved skeletal muscle microvascular blood flow and oxygenation resulting in enhanced exercise tolerance. To explore this hypothesis, we propose the following specific aim: Explore the effects of home-based HT on exercise tolerance in patients with HFpEF.

Fast Induced Remodeling in Heart Failure With Preserved Ejection Fraction

FIRE-HFpEF is a multi-center, prospective, randomized, single-blinded, clinical feasibility study. This study will enroll up to 105 subjects with heart failure with preserved ejection fraction in the United States. Data will be collected to evaluate whether pacing therapies can lead to improvements in exercise capacity and health status of subjects.

Assessment of CCM in HF With Higher Ejection Fraction

The AIM HIGHer Clinical Trial will evaluate the safety and efficacy of Cardiac Contractility Modulation (CCM) therapy in patients with heart failure with LVEF ≥40% and ≤70%.

A Randomized Placebo-procedure Controlled Trial of the Enhancor System (PULmonary Artery Denervation) to Evaluate Safety and Efficacy in Patients With Combined Pre- and Post-capillary Pulmonary Hypertension Associated With Left Heart Disease

The goal of this clinical study is to evaluate the safety and efficacy of percutaneous pulmonary artery denervation with the Multi-Pole Pulmonary Artery Radiofrequency Ablation Enhancor System in patients with combined pre- and post-capillary pulmonary hypertension (CpcPH) associated with left heart disease (LHD). This randomized control trial will compare the investigational device (The Enhancor System) to control (medical therapy.) Participants who will consist of patients with chronic heart failure (HF) who are receiving maximally tolerated guideline-directed medical therapy (GDMT) for left heart failure, are clinically stable, and who have been diagnosed with CpcPH by right heart catheterization (RHC), will be treated with PADN and followed for 3 years.

Ketogenic Diet vs Mixed Diet in Patients With Heart Failure

This study is being done to evaluate the effects of a low carbohydrate ketogenic diet (KD) versus a low-fat diet (MD) on exercise tolerance in participants with heart failure with normal pumping function and diabetes or pre-diabetes, or metabolic syndrome, or obesity.

IV Iron Therapy for Older Adults With Heart Failure With Preserved Ejection Fraction and Iron Deficiency

This randomized, double-blind, placebo-controlled clinical trial evaluates intravenous ferric derisomaltose in older adults with HFpEF and iron deficiency.

A Study of EDG-15400 in Adults With Heart Failure With Preserved Ejection Fraction (EQUINOX-HFpEF)

This is a Phase 2 placebo-controlled study to evaluate the safety and tolerability of different doses of EDG-15400 in adults with heart failure with preserved ejection fraction (HFpEF).

The ENCHANTMENT HIV Study

Persons with HIV, even those well-treated, are at increased risk for heart disease when compared to the general population. Two hormones called aldosterone and brain natriuretic peptide (BNP), which have been shown to be abnormal in HIV, may be associated with inflammation as well as early changes in structure and function of the heart. This study is being conducted to evaluate whether therapies to block aldosterone and increase BNP levels may reduce the burden and progression of heart failure to improve cardiovascular health.

Multiple-biomarker Approach for Individualized Treatment of Heart Failure With Preserved Ejection Fraction

The primary objective is to investigate the association between temporal evolutions of blood biomarkers and clinical adverse events, in order to produce a dynamic, individual, and accurate prediction model for patients with HFpEF. Moreover several secondary objectives will be investigated.

Cardiac Rehab Effects in HFpEF

This research in Veterans with heart failure with preserved ejection fraction (HFpEF) will provide new information on the mechanisms determining the patients' exercise intolerance and the efficacy of regular physical activity to improve this shortcoming by alleviating the patients' neurocirculatory abnormalities. Specifically, the investigators will focus on the role of nerves originating in working limb muscles in determining the patients' exercise intolerance and compromised fatigue resistance before and after a chronic exercise intervention. By focusing on a specific mechanism, this project will evaluate the validity of exercise as an alternative treatment strategy with the overall purpose of improving the quality of life of Veterans with HFpEF.

Home-Based Cardiac Rehabilitation for Patients With Heart Failure

The vast majority of individuals with heart failure do not participate in center based cardiac rehabilitation (CBCR). While steps to increase utilization of CBCR are important, many individuals will still not participate for a variety of reasons. This pilot randomized controlled trial is evaluating a home-based cardiac rehabilitation (HBCR) intervention delivered using a custom app and digital tools in patients with heart failure. After a brief roll-in period, participants are randomized to one of two groups: (1) control or (2) HBCR mobile health intervention. The intervention targets key health behaviors and includes traditional cardiac rehabilitation components. The study will assess the effect of the intervention on physical activity, quality of life, clinical events, and other outcomes.

CASTLE-HFpEF (Catheter Ablation for Atrial Fibrillation Patients With Heart Failure With Mildly Reduced and Preserved Ejection Fraction)

The clinical equipoise in the treatment of Atrial Fibrillation (AF) in patients with Heart Failure with mildly reduced Ejection Fraction/Heart Failure with Preserved Ejection Fraction (HFmrEF/HFpEF) reflects the scarcity of randomized trials on different treatment modalities. By generating high-quality, evidence-based, randomized data on the impact of treatment on hard outcomes, Catheter Ablation Versus Standard Conventional Treatment in Atrial Fibrillation Patients with Heart Failure with Preserved Ejection Fraction (CASTLE-HFpEF) will provide clinical decision-making guidance and help physicians in the management of patients with HFmrEF/HFpEF and AF. The main hypothesis is that Catheter Ablation (CA) for AF is associated with improved clinical outcomes in patients with HFmrEF/HFpEF and AF compared to medical AF treatment strategies on top of optimal medical HF treatment. CASTLE-HFpEF aims to study these hard clinical outcomes in a randomized cohort of patients with AF and HFmrEF/HFpEF.

Myocardial Mechanisms in Heart Failure With Preserved Ejection Fraction

The purpose of this study is to identify changes in heart tissue structure and biological function in patients with heart failure by performing an endomyocardial biopsy (EMB or heart biopsy) during a right heart catheterization (RHC). The ultimate goal is to use this information to develop new treatments for heart failure.

HeartShare: Combining Omics, Deep Phenotyping, and Electronic Health Records for Heart Failure Subtypes and Treatment Targets

HeartShare is a comprehensive study of heart failure, a common and serious medical condition which occurs when the heart is unable to keep up with the demands of the body, resulting in shortness of breath, fluid retention, and fatigue. HeartShare aims to better classify heart failure into subtypes to help develop more personalized treatments for patients, with the hope that this will improve the lives of heart failure patients. To do this, HeartShare is bringing together a large amount of data (including images, such as heart ultrasounds and MRIs and molecular data from the blood, such as genetics) from previously conducted studies and electronic health records, and is gathering new data through participants enrolled in the HeartShare Deep Phenotyping Study.

Pioglitazone on Heart Failure in Type-2 Diabetes Mellitus Participants

Our goal of the study is to learn the effects of the diabetes medication named Pioglitazone, in type-2 diabetic obese participants with Heart failure. The main question it aims to answer are: 1. To demonstrate that impaired mitochondrial function leading to reduced ATP generation plays a key pathophysiologic role in the development of heart failure with preserved ejection fraction (HFpEF) in obese type 2 diabetic (T2D) individuals. 2. To demonstrate that pioglitazone, improves diastolic (as well as systolic) function by improving myocardial insulin sensitivity and by reducing both myocardial and epicardial fat content.

Finerenone and Cardiac Remodeling in HFpEF

This prospective randomized study aims to evaluate the efficacy of Finerenone as add-on therapy to standard of care compared to standard of care alone in preventing heart failure worsening and preserving cardiac function assessed by left ventricular strain in patients with heart failure with preserved ejection fraction.

Transitions of Care Clinic (TOCC)

The transition period from hospital to home is a time of heightened risk for patients to experience adverse events, medication errors, and readmission to the hospital. Patients at the highest risk include older adults and patients with low health literacy, socioeconomic disadvantages, and/or multiple comorbidities. This project proposes to expand the existing Transitions of Care Clinic (TOCC) which was recently introduced in our institution in 2024, to bridge the gap in care between hospital discharge to home and connect discharged patients to their outpatient providers with a focus on patients with heart failure (HF). The existing TOCC, a multidisciplinary team composed of a pharmacist and a nurse practitioner, seeks to improve the services that are currently being provided to patients and enhance the transitions of care process by providing patients with education, tools, and resources to help manage their chronic disease. With this study, we propose to expand TOCC by offering extensive education to patients via iPad videos and providing them with HF tool kits prior to their discharge. We will also assist with scheduling follow appointments with their outpatient providers and follow up with patients after the appointment takes place to re-evaluate their needs and reinforce self management of heart failure. By targeting patients being treated for acute exacerbation of heart failure with preserved ejection fraction (HFpEF), this study aims to facilitate the transition of care, reduce hospital readmissions and improve patients' quality of life and satisfaction. Patients with HFpEF represent a majority of the HF patients that are readmitted at OUMC. HFpEF patients have fewer guideline recommended treatments and represent a vulnerable patient population. The HF tool kits will provide these patients with the essential tools, resources, and log sheets for self-management such as monitoring daily weights, monitoring blood pressure and heart rate. Patients provided with a kit will receive an initial phone call from TOCC within 1 to 3 days of discharge and a second phone call within 21-24-days post discharge.

Longitudinal Multimarker Risk Models for Very Elderly Patients With Heart Failure and Preserved Ejection Fraction

The goal of this observational study is to develop longitudinal multimarker risk models for decision support during the clinical follow-up of very elderly patients with heart failure and preserved ejection fraction (HFpEF). The main questions it aims to answer are: * Can advanced risk prediction models accurately estimate the prognosis of very elderly patients with HFpEF over a 1-year follow-up after a hospitalization for acute heart failure? * Do novel biomarkers, in addition to routine clinical variables and elderly-specific predictors, contribute to improved risk prediction for these patients? To this end, very elderly patients (aged 80 or older) who have HFpEF and were admitted for acute heart failure will be included. Clinical and biological data will be collected during their hospitalization and also during follow-up visits 30 and 90 days after discharge. There is no comparison group in this observational study.

Atrioventricular Node Ablation and Conduction System Pacing in Patients With Well Controlled Permanent Atrial Fibrillation (AF), Heart Failure and Preserved Ejection Fraction: Heart Rate Regularization Versus Medical Rate Control

The goal of this clinical trial is to assess the clinical efficacy of physiological pacing combined with atrioventricular node ablation, in patients with Heart Failure with preserved Ejection Fraction (HFpEF) and well controlled permanent atrial fibrillation.The main question it aims to answer is that heart rate regularization added to physiological pacing - preventing the deleterious effect of right ventricular apical pacing - would reduce mortality and heart failure hospitalizations. Researchers will compare physiological pacing combined with atrioventricular node ablation (intervention arm) versus optimal pharmacological therapy (control arm) to see if physiological pacing combined with atrioventricular node ablation reduce time to the composite of all-cause mortality or hospitalization due to heart failure or intravenous diuretics (time frame 24 months). Participants will : * Be randomized in intervention arm or control arm. * Visit the clinic 3 months, 12 months and 24 months after the randomization for checkups and tests.

Impact of Intravenous Iron Repletion On Mechanisms of Exercise InTolerance in HFpEF (IRONMET-HFpEF)

The primary objective of this study is to determine if the correction of functional iron deficiency by administering a single dose of intravenous iron (ferric derimaltose or Monoferric®) in participants with heart failure with preserved ejection fraction (HFpEF) will improve exercise capacity as measured by the change in peak oxygen uptake (peak VO2) from baseline to 12 weeks.

Neprilysin Inhibition to Reduce Myocardial Fibrosis in Heart Failure With Preserved Ejection Fraction

Cardiac magnetic resonance imaging (MRI) measures of myocardial interstitial fibrosis (MIF) are elevated in heart failure with preserved ejection fraction (HFpEF) patients and associated with poor prognosis. Extracellular volume (ECV) is the most reproducible and best validated cardiac MRI measure of MIF. Sacubitril/valsartan reduces histological MIF in mice and levels of some extracellular matrix regulatory proteins in humans with HFpEF. However, the effect of sacubitril/valsartan on robust measures of MIF in humans is unknown. Demonstrating reductions in ECV with sacubitril/valsartan would clarify the mechanism of this approved medication. Given the borderline reduction in heart failure hospitalizations with sacubitril/valsartan and the heterogeneity of HFpEF pathophysiology, this result would suggest that neprilysin inhibition may particularly benefit HFpEF patients with greater MIF. The investigators propose a proof-of-concept clinical trial to evaluate the effect of neprilysin inhibition (sacubitril/valsartan vs valsartan alone) on cardiac MRI measures of fibrosis (principally ECV) and circulating protein levels.

GLP-1/GIP Receptor Agonists in Obesity-Related HFpEF: The GLIDE-HF Registry

GLIDE-HF is a prospective, single-center, non-interventional observational cohort registry conducted within routine outpatient heart failure care at a cardiology clinic in Poland. It enrolls patients with obesity-related heart failure with preserved ejection fraction (HFpEF), defined by chronic heart failure symptoms or exertional dyspnea, body mass index at least 30 kg/m2, left ventricular ejection fraction at least 50%, and objective evidence of HFpEF using contemporary diagnostic scores (H2FPEF and HFA-PEFF), without a dominant alternative cause of dyspnea. The registry's guiding principle is that all eligible obesity-related HFpEF patients are enrolled regardless of their treatment. Therapy with a glucagon-like peptide-1 (GLP-1) receptor agonist or a dual GLP-1/GIP receptor agonist (for example semaglutide, tirzepatide, liraglutide, dulaglutide, or others) is an observed exposure, not an assigned intervention. All decisions about initiating, selecting, dosing, or modifying such therapy are made solely by the treating physician according to clinical, regulatory, and reimbursement indications, as part of standard care and independently of the registry. The protocol does not propose, allocate, or modify any pharmacological treatment, does not randomize, and does not create a protocol-defined control group. Patients not receiving such therapy serve as a naturally occurring observational comparator. The scientific value of GLIDE-HF lies in deep mechanistic phenotyping rarely available in large-scale registries. The core assessment tool is serial exercise (stress) echocardiography, which allows direct evaluation of diastolic reserve during exercise, an abnormality that may be absent at rest and revealed only under load. This is complemented by lung ultrasound for pulmonary congestion (B-lines), left atrial and right ventricular strain analysis, a full iron and hepcidin panel, right ventricular-pulmonary artery coupling assessment, cardiac and congestion biomarkers (NT-proBNP, CA-125), quality of life (Kansas City Cardiomyopathy Questionnaire), and functional capacity (6-minute walk test). The identical assessment panel is applied to all enrolled patients regardless of treatment status, ensuring comparability between treated and untreated patients. Observation is embedded in the routine outpatient visit schedule, with assessment points at baseline and at 12, 24, and 52 weeks, and the possibility of continued follow-up. The registry characterizes trajectories of exercise diastolic reserve and accompanying mechanistic and clinical parameters over time in treated patients (primary axis), and explores comparisons between treated and untreated patients (secondary axis), with a methodological aim of assessing the feasibility of reliable serial exercise echocardiography and lung ultrasound in an unselected, real-world obesity-related HFpEF population, in whom obesity substantially complicates imaging. The registry is descriptive and hypothesis-generating. Because of its observational design, all analyses relating to treatment effect are descriptive only and cannot be interpreted as evidence of a causal drug effect, given the absence of randomization, possible regression to the mean, and confounding by indication. Target enrollment is at least 150 patients, recruited continuously from January 2027. GLIDE-HF is a non-commercial study conducted under bioethics committee opinion and applicable data protection law.