Diastolic Dysfunction, Heart Failure, HIV
Conditions
Brief summary
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
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.
Interventions
None listed
Sponsors
Duke University
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>40 years 2. Willingness and ability to provide informed consent 3. HIV antibody positive 4. On HAART for \>6 months (HIV positive cohort only) 5. History of adequate viral suppression as defined by HIV RNA level \<200 copies/mL in the past 6 months 6. LVEF \>50% -
Exclusion criteria
1. Past EF \<50% 2. Moderate or severe valve stenosis or regurgitation, or past repair or replacement 3. Percutaneous or surgical revascularization or active angina 4. Persistent atrial fibrillation 5. BP\>160mmHg SBP or \>100mmHg DBP 6. Comorbid inflammatory disease (e.g. RA or SLE) 7. Active cancer or cancer chemotherapy treatment in the prior year (except skin cancer that did not require chemotherapy or radiation) 8. Chronic use of steroids or anti-inflammatory therapy 9. GFR \<30 mL/min 10. Active in a clinical trial with investigational product 11. Pregnant or lactating females 12. Contraindication to cMR or gadolinium injection (such as severe claustrophobia, metal implants, etc.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| persistent inflammation between HIV+/DD- and HIV+/DD+ subjects | baseline visit | Compare inflammation between HIV+/DD- and HIV+/DD+ subjects. |
| immune activation between HIV+/DD- and HIV+/DD+ subjects | baseline visit | Compare immune activation between HIV+/DD- and HIV+/DD+ subjects. |
| inflammation between HIV+/DD- and HIV+/DD+ subjects | baseline visit | To compare inflammation between HIV+/DD- and HIV+/DD+ |
| 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+ | baseline visit | To compare myocardial fibrosis by magnetic resonance imaging between HIV+/DD- and HIV+/DD+ |
| serum levels of biomarkers | baseline visit | To identify systemic determinants (biomarkers) of DD in HIV+ persons |
| novel mechanisms underlying DD in HIV+ subjects as measured by proteomic and metabolomics panels | baseline visit | To study the proteomic and metabolomics panels to enable identification of novel mechanisms underlying DD in HIV+ subjects |
| the effect of DD on mechanics of the left atrium in HIV | baseline visit | To study the effect of DD on mechanics using left atrial strain during passive leg raise |
| sub-clinical necrosis in HIV+/DD+ subjects | baseline visit | To study the sub-clinical necrosis using Troponin levels in HIV+/DD+ subjects |
| myocardial stress in HIV+/DD+ subjects | baseline visit | To study myocardial stress using NTProBNP levels in HIV+/DD+ subjects |
| Perform phenomics of aggregate clinical data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects | baseline visit | Clinical data |
| Perform phenomics of aggregate biomarker data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects | baseline visit | Biomarker data |
| Perform phenomics of aggregate electrocardiogram data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects | baseline visit | electrocardiogram data |
| Perform phenomics of aggregate imaging data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects | baseline visit | imaging data |
Countries
United States
Outcome results
None listed