Clinical Research Directory

Metabolic Changes in Heart Failure Patients Treated With Vericiguat

Heart failure is a condition in which the heart cannot pump blood as effectively as it should. It can cause symptoms such as shortness of breath, tiredness, and fluid retention. Vericiguat is a medication used in certain patients with heart failure whose symptoms have recently worsened. The aim of this study is to better understand how vericiguat treatment is associated with changes in metabolism, heart function, and blood vessel health in patients with heart failure. This is a prospective, observational study conducted at a single hospital in Italy. Researchers will collect clinical information and analyze biological samples to investigate changes in molecules involved in energy production, inflammation, and cardiovascular function. Heart imaging and assessments of blood vessel function will also be used to better understand the patients' cardiovascular health. The study will explore whether these biological and cardiovascular measurements are associated with treatment with vericiguat and whether they could help identify patients who may benefit most from this therapy. The results may improve our understanding of heart failure and support more personalized treatment strategies in the future.

Empagliflozin in Heart Failure With Reduced Ejection Fraction and End Stage Renal Disease

In patients with ESRD, up to 20% of patients suffer from HFrEF, leading to significant CV morbidity and mortality. Several drug classes that provide survival benefits for patients with HFrEF, including SGLT2i, lack data regarding their efficacy and safety in patients under chronic hemodialysis. As the primary target of SGLT2i is expressed mostly in the kidneys, the efficacy of SGLT2i in patients with ESRD may be limited. On the other hand, patients with ESRD are at higher risks of experiencing cardiovascular events and may still benefit from treatment. Several mechanistic studies have demonstrated direct actions of SGLT2i on the myocardium, thus it is possible that the benefits of SGLT2i on heart failure are independent of their glycosuric actions and may still be present in anuric subjects. Furthermore, pharmacokinetics and pharmacodynamics studies on empagliflozin demonstrated that peak plasma levels of empagliflozin in subjects with renal failure/ESRD were similar to those in subjects with normal renal function. The use of empagliflozin in patients with ESRD seemed safe in terms of pharmacokinetics and pharmacodynamics, yet its efficacy remains to be explored.

Vsling™ I: Clinical Evaluation of the Vsling™ Device for Ventricular Repair in Patients With Heart Failure

Prospective, multi-center, open-label clinical study of the feasibility and initial safety and performance of the Vsling™ in patients with heart failure (HF) with evidence of reduced left ventricular ejection fraction, associated with ventricular dilation.

Synchronized Diaphragmatic Stimulation in Symptomatic Heart Failure

RECOVER HF is a clinical study designed to evaluate the safety and efficacy of Synchronized Diaphragmatic Stimulation delivered using the VisONE System in the treatment of patients with heart failure.

HFrEF Polypill in Sri Lanka RCT

The aim of this study is to evaluate, in adults with HFrEF in Sri Lanka, the effects of an HFrEF polypill implementation strategy on the composite rate of cardiovascular disease mortality and recurrent heart failure hospitalizations, compared with usual care over a minimum of 12-months of follow-up. Primary outcome of the study: 1\) Composite rate of cardiovascular disease mortality and recurrent heart failure hospitalizations over study duration Secondary outcomes of the study: 1. Rate of cardiovascular disease mortality over study duration 2. Rate of recurrent heart failure hospitalizations over the study duration 3. Rate of all-cause mortality over the study duration 4. Change in left ventricular ejection fraction at 12-months and end of study assessed by transthoracic echocardiogram 5. Change in BNP levels at 12 months and end of study 6. Change in overall and domain specific health-related quality of life at 12-months and end of study assessed by a translated validated version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) 7. Change in physician-reported New York Heart Association class at 12-months and end of study 8. Adherence to guideline-directed medical therapy assessed by pill count and MARS-5 questionnaire at baseline, 1-, 6-, 12-months, and end of study. Persistence assessed as continuation of assigned therapy at each follow-up visit. Dose optimization assessed as proportion achieving target doses (Strength 3 of the polypill, or comparable individual GDMT doses in the comparator arm) at 6-, 12-months, and end of study. Safety outcomes: 1. Proportion of participants with serious adverse events according to Good Clinical Practice guidelines over study duration 2. Proportion of participants with adverse events of special interest over study duration 3. Proportion of participants with adverse events leading to HF drug discontinuation over study duration 4. Mean change from baseline to 12-months and end of study in serum potassium (mEq/L) 5. Mean change from baseline to 12-months and end of study in serum creatinine (mg/dL) Participants will be randomly assigned 1:1 stratified by sex and site to one of two groups, intervention (experimental arm) or usual care (control arm). The intervention group will be given four guideline-recommended medications for heart failure with reduced ejection fraction, combined in one over-encapsulated pill, with three dose strength options. Both groups will be observed over a minimum of 12-months of follow-up to assess key outcomes.

Assessment of Biomarkers in Patients With Decompensated Heart Failure and Underlying Coronary Artery Disease

Assessment of Biomarkers in Patients with Decompensated Heart Failure and Underlying Coronary Artery Disease

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.

Mechanistic Clinical Trial Comparing the Pharmacokinetics/Pharmacodynamics of Metoprolol in Heart Failure With Reduced Ejection Fraction Patients With Low vs. High Polygenic Score

The purpose of this trial is to better understand how the beta-blocker metoprolol works in people with Heart Failure with Reduced Ejection Fraction (HFrEF) according to participants genetics. Participants will have the beta-blocker (BB) polygenic score calculated from genotype data. The score will be used to stratify the patients in the low and high polygenic score groups in the study. The hypotheses for this trial are: * HFrEF patients with high polygenic score will have weaker cardiovascular responses to metoprolol succinate than HFrEF patients with low polygenic score. * HFrEF patients with high polygenic score have lower steady-state plasma concentrations of metoprolol succinate than HFrEF patients with low polygenic score. * HFrEF patients with high polygenic score require higher metoprolol succinate plasma concentrations to achieve similar cardiovascular effects as those with low polygenic score.

Optimal PharmacoTherapy and Invasive Management of Atrial Fibrillation in Patients With Heart Failure

Atrial Fibrillation (AF) and Heart Failure (HF) are colliding global cardiovascular epidemics, individually impairing quality of life and cardiac performance, as well as increasing the risk of hospitalisation and mortality. When AF and HF co-exist, disease progression accelerates and the adverse outcomes are magnified, leading to incrementally higher morbidity, mortality, and healthcare expenditure. The management of AF is dichotomised into the restoration and maintenance of sinus rhythm ("Rhythm control") or acceptance of AF with control of the ventricular response ("Rate control"). Previous studies suggested that pharmacologic rhythm control and pharmacologic rate control confer similar survival and morbidity outcomes in patients with significant left ventricular dysfunction. Recognising the limitations of pharmacotherapy, more recent studies have examined the utility of catheter ablation procedures designed to restore and maintain sinus rhythm (e.g., catheter-based pulmonary vein isolation). Studies have suggested that catheter ablation procedures may provide sustained improvements in quality of life, decreased hospitalisation and, potentially, improved survival for patients with co-existing AF and HF, when compared to pharmacotherapy. However, significant limitations in these small trials have limited their impact on clinical practice. We propose a randomised controlled trial to definitively answer the question regarding the optimal treatment of AF in patients with heart failure with reduced ejection fraction (HFrEF), specifically aiming to determine if catheter ablation can reduce death, stroke, and heart failure events.

Study With Omecamtiv Mecarbil (CK-1827452) to Treat Chronic Heart Failure With Severely Reduced Ejection Fraction

The purpose of this study is to find out if the investigational drug called omecamtiv mecarbil can reduce the risk of the effects of heart failure, like hospitalization, transplantation, or death in patients with heart failure and severely reduced ejection fraction.

[11C]PS13 PET Imaging of Neuroinflammation in Heart Failure With Reduced Ejection Fraction

Heart failure reduces the amount of blood the heart pumps, which can lead to memory and thinking problems in many patients. One possible reason is that heart failure triggers brain inflammation, a process in which certain brain immune cells (called microglia) become overactive. A heart failure medication called sacubitril-valsartan has been shown to reduce the risk of developing dementia, but it is not known whether this is because it reduces brain inflammation. This study uses a new experimental brain scan drug called \[11C\]PS13 (PS13) to measure brain inflammation directly and non-invasively, using a technique called positron emission tomography (PET). PS13 sticks to a molecule called COX-1, which is found mainly in brain immune cells (microglia). By measuring how much PS13 accumulates in the brain, researchers can estimate how much brain inflammation is present. In this pilot study, 18 patients with heart failure and mild memory or thinking problems who are being started on sacubitril-valsartan by their cardiologist (as standard clinical care) will undergo two brain PET scans: one before starting sacubitril-valsartan, and one approximately 12 weeks after. The study will also assess memory, thinking, daily function, mood, and social well-being using standard questionnaires. The study will test whether sacubitril-valsartan is associated with measurable changes in brain inflammation, and whether this type of imaging is feasible in heart failure patients. The study is funded by the American Heart Association and the National Institute on Aging, and an independent Data and Safety Monitoring Board oversees participant safety. The results will be used to design a larger study.

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.

A Safety and Tolerability Study of HJB647 in Heart Failure Participants With Reduced Ejection Fraction

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of HJB647 at two different doses in participants with chronic stable heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF).

Intermediate Outcomes of HFrEF Patients on Guideline-Directed Medical Therapy

This prospective observational study aims to evaluate intermediate clinical, renal, and functional outcomes in patients with heart failure with reduced ejection fraction treated with contemporary guideline-directed medical therapy over a 6 to 12 month follow-up period.

Utilization of Guided Point of Care Ultrasound in Heart Failure Diagnosis Pilot Trial

The purpose of the study is to implement point of care ultrasound (POCUS) to generate preliminary, or pilot, data to support a full future POCUS study across multiple Corewell Health outpatient rural facilities. The study aims to demonstrate feasibility of the procedure utilizing input from the patient, provider, and the clinic staff. Preliminary data will also be used to estimate the magnitude of effect in estimating sample size and power in participants who receive the POCUS procedure versus those who continue with standard of care. Up to 100 participants will be enrolled.

Yoga Based Cardiac Rehabilitation in Heart Failure Failure

The clinical study compares the benefits of yoga based rehabilitation programme versus an educational package during recovery of patients with heart failure. Cardiac rehabilitation programmes help patients with cardiac illness to return as quickly as possible to full and productive life and to reduce the chances of further cardiac illness or death. We want to know whether our package of yoga classes can provide effective cardiac rehabilitation and how that compares with a package of educational classes. Both packages are especially designed by us to improve heart health

Midodrine in Heart Failure With Reduced Ejection Fraction With Hypotension

The evidence-based pharmacologic treatments available for patients with heart failure with reduced ejection fraction (HFrEF) has been established over the last few decades of cardiovascular research. These treatments, termed Foundational Guideline-Directed-Medical Therapies (GDMT), prolong patient life, improve patient-reported symptoms, and reduce hospitalizations for heart failure. A direct effect of most medication classes encompassed within GDMT is the reduction in blood pressure due to their mechanisms of action. In addition, as patients with HFrEF become more advanced in their disease, a significant proportion develop hypotension related to pump failure and autonomic dysfunction, amongst other possible mechanisms. As a result, a significant proportion of HFrEF patients are not optimized on GDMT with hypotension as their limiting barrier that would otherwise have served to improve their heart function, heart failure symptoms, and mortality. Currently, there does not exist any evidence-based strategies to address the problem of hypotension in HFrEF patients who are not optimized on GDMT. Midodrine is an alpha-adrenergic agonist (α1-AR) that exerts its effects on peripheral venous and arteriolar vasculature to increase blood pressure. This medication has been used off-label by some clinicians in the hypotensive HFrEF population to increase blood pressure and has been reported to have beneficial effects in improving GDMT utilization as well as increasing left ventricular ejection fraction (LVEF) in published case reports/case series. There does not exist any randomized prospective data on the use of midodrine in the hypotensive HFrEF population. The investigators' objective is to complete the first open-label, randomized control trial of midodrine in the hypotensive HFrEF population to demonstrate feasibility in performing a trial in this patient population and to show efficacy in increasing blood pressure without associated harm. The results of this trial will be used as the foundation and rationale for future studies assessing the impact of midodrine use on GDMT utilization as well as hard cardiovascular outcomes in the hypotensive HFrEF population, including hospitalizations for heart failure and mortality.

Ketones in Heart Failure With Reduced Ejection Fraction

The purpose of this study is to understand the effects of a ketone drink on exercise capacity and other cardiovascular parameters in patients with heart failure. In heart failure, patients are limited in their ability to do all the things they want to do, and exercise as much as they would like, due to becoming tired and short of breath early. There may be several reasons why these symptoms occur. This study is assessing whether the ketone drink can improve these symptoms. This drink has been given status by Food and Drug Administration as "generally regarded as safe". The use of DeltaG in this study is experimental. DeltaG has not been approved by the Food and Drug Administration (FDA) for the use being evaluated in this study.

STEPwise De-escalation and Optimizing Withdrawal of ARNI and SGLT2i in Normalized Heart Failure

This is a multicenter, randomized, open-label pilot study to evaluate whether stepwise withdrawal of two heart failure medications-angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose cotransporter-2 inhibitor (SGLT2i)-is safe in patients with Heart Failure with improved Ejection Fraction (HFimpEF) whose underlying structural cause (valvular heart disease or ischemic cardiomyopathy) has been completely corrected by surgery or intervention. Eighty adult patients (40 per arm) whose left ventricular ejection fraction (LVEF) has recovered to 50% or higher and whose NT-proBNP is ≤ 250 ng/L will be randomized 1:1 to either (1) stepwise withdrawal of ARNI followed by SGLT2i over one month under close echocardiographic monitoring, or (2) continuation of their current guideline-directed medical therapy. The primary outcome is the change in LVEF at 12 months, with non-inferiority of the withdrawal strategy declared if the LVEF decline is within 5 percentage points of the continuation arm. Secondary outcomes include cardiovascular death, heart failure hospitalization, NT-proBNP, quality of life (KCCQ-12), 6-minute walk distance, and adverse events. Results from this pilot will inform the design and sample size of a subsequent definitive non-inferiority trial and may provide initial evidence to guide deprescribing decisions in clinical practice.

A Study to Assess Safety & Effectiveness of Tovinontrine in Chronic Heart Failure With Reduced Ejection Fraction (Cycle-1-REF)

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 reduced ejection fraction.

Circulating RNA Markers of Ventricular Arrhythmias in Remotely Monitored Patients With Post-Infarction Heart Failure and Implanted Cardioverter-Defibrillators

This prospective observational study evaluates whether circulating small non-coding RNAs, particularly microRNAs, are associated with ventricular arrhythmias in patients with post-myocardial infarction heart failure who have an implanted cardioverter-defibrillator and are followed by remote monitoring. Blood samples were collected from 57 participants. Small RNA profiles are analyzed in relation to ventricular tachycardia or ventricular fibrillation episodes recorded by the implanted device. Participants are not assigned to any treatment or intervention as part of this study. The initial analysis includes six months of follow-up, with longer-term observational follow-up planned.

Biomechanical Precision Medicine Registry for Patients With and Without Heart Failure

In this single-center, longitudinal observational study, we will comprehensively examine clinical characteristics, proteomic, metabolomic, genomic and imaging data to better understand how different heart failure types may develop and progress over time. We will evaluate distinct sub-groups of heart failure (also known as heart failure phenotypes) and cardiomyopathies including amyloidosis with an ultimate goal of bringing the right medications and therapy to the right patients to optimize benefit and minimized side effects, an effort to improve precision medicine in heart failure.

A Study Investigating the Impact of IMT With CR On Exercise Responses In HF

The purpose of this study is to compare the impact of inspiratory muscle training (IMT) combined with cardiac rehabilitation (CR) on cardiovascular function in patients with heart failure.

Respiratory Sinus Arrhythmia (RSA) Pacing Post-CABG Surgery in Patients With HFrEF

The goal of this clinical trial is to test a new type of pacemaker in heart failure patients following a heart bypass operation. The new pacemaker restores respiratory sinus arrhythmia which is a natural pattern where the heart rate increases when the participants breathe in and slows down when participants breathe out. The main questions the trial aims to answer are: * Is the new type of pacemaker safe? * Does the new type of pacemaker improve how patients' hearts work (also known as cardiac output)? Participants will have a range of tests before their operation and during their recovery in hospital while participants have the new type of pacemaker in place, and will be monitored very closely. Participants will also receive a phone call 1 month after their surgery. Researchers will compare the new type of heart pacing against standard treatment to see if it is as safe, and if it is any better for patients.