Characterizing HIV-related Diastolic Dysfunction

Study Overview
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Brief Summary
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This is a multicenter clinical trial of a cross section of HIV+ patients with and without diastolic dysfunction. Approximately 200 HAART-treated virally suppressed HIV+ subjects (100 HIV+/DD+ & 100 HIV+/DD-) will be enrolled. This study will evaluate biomarkers, phenomapping, metabolomics, cMRI, echocardiography to determine characteristics unique to this patient population.

Detailed Description
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With the advent of highly active antiretroviral therapy (HAART), human immuno¬deficiency virus (HIV) type 1 infection has become a chronic disease. The proportion of patients expected to survive 5, 10, and 15 years after conversion in the HAART era are 99%, 93% and 89% respectively. With increased life expectancy and decreased morbidity from opportunistic infections, the importance of chronic complications associated with HIV-1 infection, including HF is becoming more evident. The advent of HAART has altered the epidemiology of HIV associated cardiomyopathy evolving from a primarily left ventricular systolic dysfunction to the growing recognition of left ventricular DD. DD is associated with the development of atrial fibrillation and heart failure (HF), and portends higher risk for all-cause mortality. Thus there is a widespread prevalence of cardiac abnormalities in HIV infected individuals that are associated with HF development and may represent a sub-clinical abnormality that may be potentially intervened upon to reduce the risk of subsequent HF. There are little data to understand the natural history and pathogenesis of cardiac abnormalities, specifically DD in HIV+ individuals, which may adversely affect the longevity and quality of life of these individuals.

Official Title
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Characterizing HIV-related Diastolic Dysfunction: A Cross Sectional Study Leveraging the NHLBI Heart Failure Clinical Research Network

Conditions
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Heart Failure, HIV, Diastolic Dysfunction

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >40 years Willingness and ability to provide informed consent HIV antibody positive On HAART for >6 months (HIV positive cohort only) History of adequate viral suppression as defined by HIV RNA level <200 copies/mL in the past 6 months LVEF >50% - Exclusion Criteria: Past EF <50% Moderate or severe valve stenosis or regurgitation, or past repair or replacement Percutaneous or surgical revascularization or active angina Persistent atrial fibrillation BP>160mmHg SBP or >100mmHg DBP Comorbid inflammatory disease (e.g. RA or SLE) Active cancer or cancer chemotherapy treatment in the prior year (except skin cancer that did not require chemotherapy or radiation) Chronic use of steroids or anti-inflammatory therapy GFR <30 mL/min Active in a clinical trial with investigational product Pregnant or lactating females Contraindication to cMR or gadolinium injection (such as severe claustrophobia, metal implants, etc.)

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HIV+/DD+<br>Subjects are HIV positive and have diastolic dysfunction | |
| HIV+/DD-<br>Subjects are HIV positive and do not have diastolic dysfunction | |
| HIV-/DD+<br>Subjects do not have HIV and have diastolic dysfunction | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| persistent inflammation between HIV+/DD- and HIV+/DD+ subjects | Compare inflammation between HIV+/DD- and HIV+/DD+ subjects. | baseline visit | 
| immune activation between HIV+/DD- and HIV+/DD+ subjects | Compare immune activation between HIV+/DD- and HIV+/DD+ subjects. | baseline visit | 
| inflammation between HIV+/DD- and HIV+/DD+ subjects | To compare inflammation between HIV+/DD- and HIV+/DD+ | baseline visit | 
| Perform phenomics of aggregate demographic data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects |  | baseline visit | 
| myocardial fibrosis by magnetic resonance imaging between HIV+/DD- and HIV+/DD+ | To compare myocardial fibrosis by magnetic resonance imaging between HIV+/DD- and HIV+/DD+ | baseline visit | 
| serum levels of biomarkers | To identify systemic determinants (biomarkers) of DD in HIV+ persons | baseline visit | 
| novel mechanisms underlying DD in HIV+ subjects as measured by proteomic and metabolomics panels | To study the proteomic and metabolomics panels to enable identification of novel mechanisms underlying DD in HIV+ subjects | baseline visit | 
| the effect of DD on mechanics of the left atrium in HIV | To study the effect of DD on mechanics using left atrial strain during passive leg raise | baseline visit | 
| sub-clinical necrosis in HIV+/DD+ subjects | To study the sub-clinical necrosis using Troponin levels in HIV+/DD+ subjects | baseline visit | 
| myocardial stress in HIV+/DD+ subjects | To study myocardial stress using NTProBNP levels in HIV+/DD+ subjects | baseline visit | 
| Perform phenomics of aggregate clinical data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects | Clinical data | baseline visit | 
| Perform phenomics of aggregate biomarker data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects | Biomarker data | baseline visit | 
| Perform phenomics of aggregate electrocardiogram data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects | electrocardiogram data | baseline visit | 
| Perform phenomics of aggregate imaging data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects | imaging data | baseline visit |