Clinical Research Directory

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.

Cardiomyopathies and Heart Muscle Diseases: Cardiac Imaging in the Evaluation of Myocardial Fibrosis Transition

Heart scarring, also known as fibrosis, plays a major role in a lot of heart muscle abnormalities. These abnormalities of the heart muscle can lead to major issues such as symptoms of heart failure, dangerous heart rhythm disturbances and even death. However, a lot of these conditions are still not fully understood and treatment options are limited. We here aim to use a new radioactive dye called 68Ga-FAPI to identify patterns and the activity of heart muscle scarring. This radioactive dye is being used in humans particularly in identifying and monitoring cancers and has shown promise in identifying scarring in the heart as well. This will help us not only understand the underlying disease process and risk stratify these patients but also potentially help us develop new targeted therapies that can affect heart muscle scarring. Participants will undergo a baseline MRI scan using this new dye and a plain MRI scan will repeated 12-18 months after to see if there are any changes in the process.

Incretin Therapies in Obesity-related HFpEF

The central hypothesis to be tested is that patients with obesity and heart failure with preserved ejection fraction (HFpEF) prescribed tirzepatide will demonstrate reductions in measured plasma volume. In conjunction with state-of-the-art body composition analysis and measures of adipokines, this will establish an important mechanism of clinical benefit and inform disease pathophysiology. To accomplish this, this study will perform a 15-month prospective cohort study in 50 patients with obesity and HFpEF who clinically qualify for treatment with tirzepatide. The investigators will serially measure plasma volume and body composition with quantitative magnetic resonance to determine changes over time with tirzepatide treatment.

A Preliminary Study for INFORMED

Investigators will determine whether N-of-1 trials, as a pragmatic, participant-centered approach to medication optimization that can overcome key barriers of deprescribing, can lead to increased participant confidence regarding their preference to continue or discontinue beta-blockers in older adults with Heart Failure with Preserved Ejection Fraction (HFpEF).

Exercise Cardiovascular Magnetic Resonance In Heart Failure With Preserved Ejection Fraction

The purpose of this study is to internally validate low-field Ex-CMR as a noninvasive tool for diagnosing, phenotyping, and risk stratifying HFpEF in patients with exertional dyspnea.

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.

HS235 Study in Obese Participants With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction (HFpEF)

Study of HS235 in Obese Participants with Pulmonary Hypertension and Heart Failure with Preserved Ejection Fraction

WeighT LOSS Surgery and Comprehensive Cardiometabolic Responses to to EXercise

The goal of this study is to define how treatment of obesity impacts cardiometabolic performance during exercise in patients with established HFpEF or at risk for HFpEF. Multi-dimensional physical activity, including 6 minute walk distance, resting metabolic rate, the metabolic cost of initiating exercise, and low-level, intermediate, peak exercise, and recovery oxygen utilization patterns will be examined in relation to weight loss in people having bariatric surgery. The investigators also aim to learn more about the relationship between obesity, exercise intolerance, and heart failure with preserved ejection fraction (HFpEF). The investigators are interested in the extent to which HFpEF\'s manifestations are preventable or reversible with weight-loss interventions. The main questions it aims to answer are: 1. How does weight loss surgery affect comprehensive measures of physical activity? 2. What are the biochemical signatures of obesity and their reversibility in patients with HFpEF and obesity?

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%.

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.

Effect of Dapagliflozin on Metabolomics and Cardiac Mechanics in Chronic Kidney Disease

The goal of this study is to better understand the effects of a sodium-glucose transport protein 2 inhibitor, dapagliflozin, added on to standard of care on heart and lung function and circulating metabolites (substances created when our bodies break down food, drugs, or its own tissues) in patients with chronic kidney disease.

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.

A Randomised, Controlled Trial of a Low-energy Diet for Improving Functional Status in Heart Failure With PRESERVED Ejection Fraction Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is a common and serious complication of obesity and type 2 diabetes (T2D). HFpEF occurs when the heart muscle unable to relax efficiently to pump the blood around the body. This leads to fluid build-up, breathlessness and inability to tolerate physical exertion. People who develop HFpEF do less well because treatment options are limited. Pilot data in patients with obesity and diabetes and a small number of patients with HFpEF have shown improvements in exercise capacity and reversal of changes in the heart and blood vessels. This study will assess if this is achievable in a multi-ethnic cohort of patients with established HFpEF. A total of 63 adults will be invited and allocate by chance into two groups: 1) 12-weeks of a low calorie diet or 2) Standard care and health advice on how to lose weight followed by the option to have the low calorie diet after 12-weeks. The study will determine if weight loss over 12 weeks can improve heart function, symptoms and ability to exercise. Additionally, participants' views on changing their diet and how this has impacted their symptoms will be sought during the study in an optional interview. This will help guide treatments planning in the future to get maximum benefits, and to individualize support to patients from different cultural backgrounds.

A Trial to Evaluate the Safety and Efficacy of Pulmonary Artery Denervation for the Treatment of Pulmonary Hypertension Associated With Left Heart Failure

It's a phase III, prospective, multicenter, randomized controlled trial to evaluate the safety and efficacy of the pulmonary artery denervation (PADN) for heart failure (HF) patients diagnosed with pulmonary hypertension associate with left heart disease (PH-LHD) by right heart catheterization.

Novel Respiratory Training as Part of Palliative Care for Older Adults With Heart Failure

In a randomized controlled trial, to study the utility of inspiratory muscle training (IMT) to improve functional outcomes in adults aged ≥70 years with heart failure (HF) who have been referred to palliative care for end-stage HF management. * The study team hypothesize that older HF patients will be able to use IMT safely, reliably, and effectively in a 12-week home-based training regimen. * The study team hypothesize that physical function (sit to stand, gait speed, grip strength), respiratory/pulmonary function, self-efficacy, fatigue and quality of life will increase among older HF patients randomized IMT versus those randomized to usual care.

Physical Activity, Cardiac and Skeletal Muscle Energetics in Healthy Subjects and HFpEF Patients

This research is being done to better understand the relationship between information collected by wearable devices and clinical measurements in people with heart failure with preserved ejection fraction (HFpEF) and others without HFpEF. This is an observational study with no study intervention or randomization. Participants will undergo baseline history and physical, 12-lead EKG, laboratory studies of blood/serum/urine, echocardiography, activity questionnaire, 6 minute walk test, and placement of wearable devices to be worn for up to 14 days (activity monitors, EKG monitor and continuous glucose monitor). Participants will return after \~14 days of wearing the devices and repeat of physical examination, 12-lead EKG, 6 minute walk test, activity questionnaire. Additionally, participants will undergo magnetic resonance imaging (MRI) of their leg with exercise, cardiopulmonary exercise testing (CPET) and, for those who qualify, magnetic resonance imaging (MRI) of their heart with exercise.

EXercise and Activin Inhibition to Modulate InflammatioN Effects on Heart Failure and Cognition (EXAMINE-HFC)

The goal of this clinical trial is to learn if therapy with activin ligand-trap biological therapy (an investigational drug) combined with exercise training can improve exercise capacity and cognitive function in heart failure with preserved ejection fraction (HFpEF). The main questions it aims to answer are: * Does activin-ligand trap biological therapy improve exercise capacity as measured by change in peak oxygen uptake (peak VO2) from baseline to week 12? * Does activin-ligand trap biological therapy improve cognitive function as assessed by the NIH-Toolbox Cognition Battery (NIHTB-CB) composite score and Rey Auditory Verbal Learning Test (RAVLT) from baseline to week 12? Researchers will compare activin-ligand trap biological therapy to a placebo (a look-alike substance that contains no drug) to see if activin-ligand trap therapy works to improve exercise capacity and cognitive function in patients with HFpEF.

Emulation of the EMPEROR-Preserved Trial Using Healthcare Claims Data

Investigators are building an empirical evidence base for real world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.

A Study of 68Ga-Fibroblast Activation Protein Inhibitor (FAPI) Positron Emission Tomography in Heart Failure

The purpose of this study is to assess the performance of 68Ga- FAPI PET in heart failure with preserved ejection fraction (HFpEF)

A Study of TX000045 in Patients With Pulmonary Hypertension Secondary to Heart Failure With Preserved Ejection Fraction (the APEX Study)

TX000045-003 is a double-blind, randomized, parallel group, placebo-controlled, proof- of-concept (POC) study, evaluating 2 dose regimens of TX000045 over the course of a 24-week treatment period (the APEX study).

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.