Characterizing HIV-related Diastolic Dysfunction (HFN_HIV)

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

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure; HIV; Diastolic Dysfunction

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.

• Study Type: Observational
• Enrollment (Actual): 195

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital-Washington University Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospital Cleveland Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Health System
    • Philadelphia, Pennsylvania, United States, 19104
      • Thomas Jefferson University
  • Vermont
    • Burlington, Vermont, United States, 05401
      • The University of Vermont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects who are receiving care at a site participating in the Heart Failure Clinical Research Network program, are HIV positive, have been on HAART for >6 months and are virally suppressed will be screened for participation.

Description

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.)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
HIV+/DD+; Subjects are HIV positive and have diastolic dysfunction
HIV+/DD-; Subjects are HIV positive and do not have diastolic dysfunction
HIV-/DD+; Subjects do not have HIV and have diastolic dysfunction

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Kevin Anstrom, PhD, Duke University Health Services

Publications and helpful links

General Publications

• Colaco NA, Wang TS, Ma Y, Scherzer R, Ilkayeva OR, Desvigne-Nickens P, Braunwald E, Hernandez AF, Butler J, Shah SH, Shah SJ, Hsue PY. Transmethylamine-N-Oxide Is Associated With Diffuse Cardiac Fibrosis in People Living With HIV. J Am Heart Assoc. 2021 Aug 17;10(16):e020499. doi: 10.1161/JAHA.120.020499. Epub 2021 Aug 7.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2016
• Primary Completion (Actual): February 9, 2018
• Study Completion (Actual): February 9, 2018

Study Registration Dates

• First Submitted: July 28, 2016
• First Submitted That Met QC Criteria: August 5, 2016
• First Posted (Estimate): August 9, 2016

Study Record Updates

• Last Update Posted (Actual): March 4, 2019
• Last Update Submitted That Met QC Criteria: February 28, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: Pro00074493

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO