Author + information
- Matthew J. Feinstein, MD∗ (, )
- Sumeet S. Mitter, MD,
- Ajay Yadlapati, MD,
- Chad J. Achenbach, MD, MPH,
- Frank J. Palella Jr., MD,
- Pedro E. Gonzalez, MD,
- Sheridan Meyers, MD,
- Jeremy D. Collins, MD,
- Sanjiv J. Shah, MD and
- Donald M. Lloyd-Jones, MD ScM
- ↵∗Division of Cardiology, Department of Medicine, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 North Lake Shore Drive, Suite 1400, Chicago, Illinois 60611
Human immunodeficiency virus-infected (HIV+) persons have significantly greater risks for myocardial infarction (MI), heart failure, and sudden death than the general population (1–3). HIV-related inflammation and immune dysfunction have been implicated in atherogenesis and MI, but the extent to which these processes potentiate myocardial ischemic scarring in HIV is unknown. Emerging data suggest that CD4+ T regulatory (Treg) cells—which are often depleted and dysfunctional in HIV—reduce infarct size and attenuate adverse remodeling following MI (4). Accordingly, it is plausible that HIV-related inflammation and immune dysregulation make the myocardium particularly vulnerable to ischemic injury.
The purpose of this study was to evaluate whether HIV+ persons have more extensive myocardial scar associated with MI and coronary artery disease (CAD) than uninfected persons.
We created an electronic cohort (HIVE-4CVD) of HIV+ patients and uninfected control patients (matched 1:2 on demographics and cardiovascular disease [CVD] test modality) who underwent CVD testing at our institution between 2000 and 2015. For this nested study within the larger HIVE-4CVD cohort, patients were eligible if they had moderate or greater CAD (≥50% diameter stenosis of ≥1 major coronary artery or branch >2 mm in diameter) on coronary angiography and thereafter underwent cardiac magnetic resonance (CMR) imaging with contrast. Patients were excluded from analyses if they had nonischemic etiologies of cardiomyopathy. Additionally, we excluded patients with myocardial scar sparing the endocardium (determined by expert readers blinded to HIV serostatus). The purpose of these exclusions was to optimize the likelihood that myocardial scar observed was vascular in nature, with the understanding that a substantial portion of patients without documented MI, but with significant CAD and subendocardial-based scar likely did have “silent” or undocumented MI. We also performed parallel analyses including only patients with documented, adjudicated MI.
Our coprimary analyses compared % myocardium with scar and % myocardium with scar/number of coronary arteries with ≥50% diameter stenosis for HIV+ patients versus uninfected control patients. Two expert readers blinded to HIV serostatus estimated myocardial scar burden based on extent of late gadolinium enhancement on CMR using the point system recommended by 2013 Society of Cardiovascular Magnetic Resonance guidelines (0 to 4 for each segment corresponding to late gadolinium enhancement affecting 0% to 25%, 26% to 50%, 51% to 75%, or >75% of each myocardial segment, respectively). For CAD assessments, 2 experts blinded to HIV serostatus determined the maximal percent stenosis of each coronary artery based on coronary angiography.
Patient characteristics prior to CMR were comparable for HIV+ (n = 12; 83% male, 58% white, 33% diabetic, 42% hypertensive, 58% with adjudicated MI) and uninfected patients (n = 22; 88% male, 50% white, 27% diabetic, 54% hypertensive, 59% with adjudicated MI). The 2 comparison groups had nearly identical CAD burden (2.25 coronary arteries with ≥50% stenosis for HIV+, 2.27 for uninfected patients), CAD distribution, and indications for angiography and CMR.
Despite these similarities, HIV+ patients had twice the extent of myocardial scar compared with uninfected control patients (22.8% vs. 11.3%; p = 0.01) (Figure 1). After accounting for CAD extent by dividing total myocardial scar burden by number of arteries with ≥50% stenosis, this difference between HIV+ patients and uninfected control patients remained highly significant (10.7% vs. 5.0%; p < 0.001). Parallel analyses of only patients with EHR-documented, adjudicated MI yielded similar results; HIV+ control patients with adjudicated MI (n = 7), compared with uninfected controls patients with adjudicated MI (n = 13), had roughly double the mean scar burden (26.5% vs. 14.5%; p = 0.07) and scar per coronary arteries with ≥50% stenosis (12.3% vs. 6.3%; p = 0.01). Location and severity of scar corresponded closely for all patients, suggesting that myocardial scar analyzed tended to be vascular in nature; the mean % of scar in myocardial segments corresponding to coronary arteries with versus without severe CAD (≥70% stenosis) was 33.9% versus 12.5% (p = 0.03).
Our finding that HIV+ persons have more extensive myocardial scar than uninfected persons in the setting of CAD and MI warrants further study. Despite the small size of this study, the effect size of our findings and degree of statistical significance generate novel hypotheses regarding HIV and vascular scar burden that merit examination in larger cohorts. If our findings are confirmed and HIV+ persons have larger areas of necrosis and scar following MI, this may ultimately help inform HIV-related mechanisms implicated in heart failure and sudden cardiac death.
Please note: Dr. Palella Jr. is on the speakers bureau and is a consultant for Janssen Pharmaceuticals, Merck & Co, and Bristol-Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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