Clinical Research Directory

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.

Abnormal Vascular, Metabolic, and Neural Function During Exercise in Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of the heart failure population in the United States. The primary chronic symptom in patients with HFpEF is severe exercise intolerance quantified as reduced peak oxygen uptake during whole body exercise (peak V̇O2). To date, studies have focused almost exclusively on central cardiac limitations of peak V̇O2 in HFpEF. However, in stark contrast to heart failure with reduced ejection fraction (HFrEF), drug therapies targeting central limitations have invariably failed to improve peak V̇O2, quality of life, or survival in HFpEF. Emerging evidence from our lab suggests reduced skeletal muscle oxidative capacity may contribute to exercise intolerance in HFpEF patients. However, the mechanisms responsible for peripheral metabolic inefficiency remain unclear. Reduced blood flow (oxygen delivery), and slowed oxygen uptake kinetics (O2 utilization) may both contribute to reduced peripheral oxidative capacity. Importantly, reduced oxidative capacity may result in increased production of metabolites known to activate muscle afferent nerves and stimulate reflex increases in muscle sympathetic (vasoconstrictor) nervous system activity (MSNA). However, to date there have been no studies specifically investigating the contribution of peripheral metabolic and neural impairments to reduced exercise capacity in HFpEF. The overall aim of this proposal will be 1) to identify impairments in peripheral vascular, metabolic, and sympathetic neural function and 2) to assess the ability of small muscle mass (knee extensor, KE) training, specifically targeting these peripheral skeletal muscle deficiencies, to improve aerobic capacity and exercise tolerance in HFpEF. GLOBAL HYPOTHESIS 1: HFpEF patients will demonstrate reduced skeletal muscle oxygen delivery, slowed oxygen uptake kinetics, and elevated resting and metaboreflex mediated MSNA. Hypothesis 1.1: The vasodilatory response to knee extensor exercise will be impaired in HFpEF patients. Specific Aim 1.1: To measure the immediate rapid onset vasodilatory response to muscle contraction, as well as the dynamic onset, and steady state vasodilatory responses to dynamic KE exercise. Hypothesis 1.2: Skeletal muscle oxygen uptake kinetics will be slowed in HFpEF. Specific Aim 1.2: To measure pulmonary oxygen uptake kinetics during isolated KE exercise in order to isolate peripheral impairments in metabolic function independent of any central impairment. Hypothesis 1.3: HFpEF patients will demonstrate elevated MSNA at rest, and exaggerated metaboreflex sensitivity during exercise. Specific Aim 1.3: To test this hypothesis the investigators will measure MSNA from the peroneal nerve at rest, and during post exercise ischemia to directly assess metaboreflex sensitivity in HFpEF. GLOBAL HYPOTHESIS 2: Isolating peripheral adaptations to exercise training using single KE exercise training will improve peripheral vascular, metabolic, and neural function and result in greater functional capacity in HFpEF. Hypothesis 2.1: Isolated KE exercise training will improve the vasodilatory response to exercise, speed oxygen uptake kinetics, and reduce MSNA at rest HFpEF. Specific Aim 2.1: The assessments of vascular, metabolic, and neural function proposed in hypothesis 1 will be repeated after completing 8 weeks of single KE exercise training. Hypothesis 2.2: Single KE exercise training will improve whole body exercise tolerance, peak V̇O2, and functional capacity in HFpEF. Specific Aim 2.2: To test this hypothesis the investigators will measure maximal single KE work rate, V̇O2 kinetics and peak V̇O2 during cycle exercise, as well as distance covered in the six minute walk test.

Open-Label Rollover Study of Levosimendan in PH-HFpEF Patients

PH-HFpEF patients will receive open-label doses of levosimendan and be periodically evaluated for safety in extended use.

Exercise Intolerance in Heart Failure

The investigators are studying whether metabolic abnormalities in cardiac and skeletal muscle in patients with heart failure with preserved ejection fraction (HFpEF) are associated with debilitating exercise intolerance.

Imaging Histone Deacetylase in the Heart

The overall goal of this PET-MR imaging trial is to evaluate 11C-Martinostat, a histone deacetylase targeted radioligand, in patients with aortic stenosis, individuals with diabetes, and healthy volunteers.

Circulating RNAs in Acute Congestive Heart Failure

The purpose of this American Heart Association-funded and NIH-funded study is to examine circulating RNAs in the acute CHF setting, how they change with decongestive therapy, and their function in vitro and in vivo. The investigators are testing the hypothesis that ex-RNA levels change significantly during decongestion therapy and can be used as a marker of those individuals who respond to CHF therapy (in terms of cardiac structure or outcome). Additionally, the translational research design allows the investigators to assay the effects of these RNAs on tissue phenotypes in vitro.

Chronic Exogenous Ketosis in HFpEF

The goal of this clinical research study is to test what effects a ketone drink will have in people with heart failure with preserved ejection fraction (HFpEF), including on exercise and heart function. Patients with HFpEF often have difficulty exercising, and our goal is to understand whether a ketone drink changes much patients can exercise. The study has three visits, including a baseline visit to assess for study eligibility, and two visits (one after 8 weeks of a ketone drink or a placebo drink, and another one after 8 weeks of whichever drink the participant did not receive the first time).

New Orleans Pulmonary Hypertension Biobank

Pulmonary hypertension (PH) is a serious condition characterized by a mean pulmonary artery pressure \>=25mmHg on right heart catheterization (RHC). Despite advances in PH care, outcomes are still sub-optimal and further research is required into the pathobiology of the disease and development of biomarkers that can guide clinical care. The investigators are establishing a biobank to collect samples (blood, urine, stool) from patients with pulmonary hypertension, patients at high risk for pulmonary hypertension, healthy controls, and patients undergoing right heart catheterization. Specimens will be stored for future investigations.