Author + information
- Michael D. Nelson, PhD,
- Lidia S. Szczepaniak, PhD,
- Troy M. LaBounty, MD,
- Edward Szczepaniak, PhD,
- Debiao Li, PhD,
- Mourad Tighiouart, PhD,
- Quanlin Li, MS,
- Rohan Dharmakumar, PhD,
- Gregg Sannes, RN,
- Zhaoyang Fan, PhD,
- Roya Yumul, PhD, MD,
- W. David Hardy, MD and
- Antonio Hernandez Conte, MD, MBA∗ ()
- ↵∗Cedars-Sinai Medical Center, Department of Anesthesiology, 8700 Beverly Blvd., Suite 8211, Los Angeles, California 90048
Heart disease is a major contributor to morbidity and mortality in persons infected with human immunodeficiency virus (HIV), and both HIV and highly active antiretroviral therapy (HAART) may be associated with abnormalities in cardiac function and metabolism (1). Ectopic fat deposition in cardiomyocytes constitutes one possible mechanism, especially considering the influence of HIV itself and HAART on the human metabolic milieu. To test this hypothesis, we studied 27 HIV-seropositive (+) cases on stable HAART (≥3 years) and 22 HIV-negative control subjects; neither group had history of personal or family history of cardiovascular disease.
Myocardial triglyceride content was measured by magnetic resonance spectroscopy (3T MAGNETOM Verio, Siemens, Germany) (2) and revealed a 3-fold elevation in cases compared with control subjects (Figure 1A). To assess left ventricular (LV) function, magnetic resonance tissue tagging was performed on a mid-ventricular short-axis image (3). Both peak circumferential strain and the peak rate of circumferential strain in diastole were impaired in cases compared with control subjects (Figures 1B and 1C, respectively). Clinical evidence of lipodystrophy was also assessed by physical exam of the dorsal back, neck, extremities, and abdomen.
Myocardial triglyceride content was significantly associated with circumferential strain (r = 0.41, p = 0.009) and diastolic strain rate (r = –0.47, p = 0.004). Moreover, HAART exposure was also significantly associated with myocardial triglyceride content (r = 0.42, p = 0.043) and diastolic strain rate (r = –0.43, p = 0.029), both of which were significantly higher with clinical presence of lipodystrophy (p = 0.02 and 0.001, respectively).
The data herein support the hypothesis that ectopic fat deposition in the myocardium may contribute to cardiac disease in patients with HIV infection treated with HAART. In this study, clinically visible lipodystrophy predicted myocardial triglyceride content and LV dysfunction in HIV(+) patients; this may provide an important mechanistic insight into the pathogenesis of heart disease in patients treated for HIV infection. Lipodystrophy can indeed lead to ectopic spillover of triglyceride into nonadipose tissues—including the myocardium—and has previously been associated with adverse LV remodeling (2). Furthermore, that HAART exposure also predicted myocardial triglyceride content and LV dysfunction provides further insight into the pathogenesis of heart disease in HIV(+) patients. For example, HAART has been associated with lipodystrophy, hyperlipidemia, and hyperglycemia (4) and may be directly cardiotoxic (5). Thus, whereas HAART has significantly reduced HIV-related morbidity and mortality, we speculate that HAART may also contribute to the cardiovascular decline in HIV(+) patients. Future studies are warranted to further investigate these findings.
Please note: This study was supported in part by a grant (#UL1TR000124) from the National Center for Advancing Translational Sciences and by a seed grant from the Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California. Dr. Nelson is supported by research fellowships from the Heart and Stroke Foundation of Canada and the Canadian Institutes for Health Research. Dr. D. Li receives research support from Siemens Healthcare. Dr. Hardy consults for Gilead Sciences, Janssen, ViiV Healthcare, and Boehringer Ingelheim; and performs clinical research for Bionor, Gilead Sciences, Pfizer, Vertex, and ViiV Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation