Patients with HIV were more likely to have cardiac dysfunction, according to a systematic review and meta-analysis published in JACC: Heart Failure.
“Together, these data suggest that early detection of cardiac dysfunction in [people living with HIV] could provide a window of opportunity in which it may be possible to institute intervention to reverse the course, as has been proposed for individuals in the general population with asymptomatic cardiac dysfunction,” Sebhat Erqou, MD, PhD, assistant professor of medicine at Brown University Alpert Medical School in Providence, Rhode Island, and staff cardiologist at VA Providence Medical Center and Lifespan Cardiovascular Institute in Providence, and colleagues wrote.
Patients with HIV, cardiac dysfunctions
Researchers analyzed data from 63 reports from 54 studies with up to 125,382 patients with HIV and 12,655 cases of various cardiac dysfunctions, including HF, left ventricular systolic dysfunction, dilated cardiomyopathy, diastolic dysfunction, pulmonary hypertension or right ventricular dysfunction.
Of the patients included in the meta-analysis, the pooled prevalence for LV systolic dysfunction was 12.3% and 12% for dilated cardiomyopathy. The pooled prevalence for grades I to III diastolic dysfunction was 29.3% and 11.7% for diastolic dysfunction grades II to III. Clinical HF had a pooled incidence of 0.9 per 100 person-years and a prevalence of 6.5%. The combined prevalence of right ventricular dysfunction was 8% and 11.5% for pulmonary hypertension.
The outcomes analyzed in all of the studies had significant heterogeneity (I2 > 70%; P < .01), which may be partially explained by the available study level characteristics.
Prevalence of LV systolic dysfunction
There was a lower prevalence of LV systolic dysfunction in the studies that reported high use of antiretroviral therapy or fewer patients with AIDS, the researchers wrote. In addition, there was a higher prevalence of LV systolic dysfunction in the African region. The prevalence of LV systolic dysfunction was lower in studies that were published more recently after taking into account the regional variation effect.
“The substantial risk of various types of cardiac dysfunction in [people living with HIV] helps create awareness within the medical community caring for these patients to watch for complications and implement early intervention when indicated,” Erqou and colleagues wrote. “In addition to subclinical cardiac dysfunction identified using imaging modalities, [people living with HIV] have materially increased risk of clinical HF, indicating that asymptomatic cardiac dysfunction identified on imaging can be progressive in a subset of participants.”
In a related editorial, Christopher R. deFilippi, MD, member of the Inova Heart and Vascular Institute in Falls Church, Virginia, and Steven K. Grinspoon, MD, director of Massachusetts General Hospital Program in Nutritional Metabolism and of the Nutrition Obesity Research Center at Harvard Medical School, wrote: “Similar to the prevention of atherosclerotic disease in [people living with HIV], development of prevention strategies for HF is an imperative for those infected with HIV to continue to enjoy hard-won victories to improve duration and quality of life.”
By Darlene Dobkowski
Disclosures: The authors report no relevant financial disclosures. DeFilippi reports he received grants through his institution from Roche Diagnostics, consults for Abbott Diagnostics, FujiRebio, Metabolomics, OrthoDiagnostics, Roche Diagnostics and Siemens Healthcare, received honoraria from WebMD and received royalties from UpToDate. Grinspoon reports he is a consultant for Theratechnologies and received research funding from Gilead, KOWA, Navidea and Theratechnologies.
The main takeaway is that HIV is a field that has clearly changed over the last 2 decades or so. This is because of the profound effectiveness of antiretroviral therapy so that patients today have a chance to have their HIV treated early before they have advanced immunosuppression. There is a general sense among specialists, including both cardiologists and infectious disease doctors who take care of these patients, that the cardiomyopathy that we used to see a lot of in the 1990s is much less prevalent today.
What was interesting in this meta-analysis is that they tried to really look at not only systolic dysfunction as represented by LV systolic function, but also parameters of diastolic function. We know from studies at the VA that are very well done from the Veterans Aging Cohort Study (Freiberg MS, et al. JAMA Cardiol. 2017;doi:10.1001/jamacardio.2017.0264.) that both HF with reduced ejection fraction and HF with preserved ejection fraction appear to be elevated among people living with HIV compared to those without HIV infection.
In this systematic review and meta-analysis, researchers look at diastolic parameters as well as systolic function parameters. Clearly, there is a high prevalence of diastolic dysfunction as well in these HIV cohort studies that have been done over the years.
There is clearly a lot of heterogeneity in the studies that were included in this systematic review and meta-analysis. That makes it difficult sometimes to synthesize the data, but when they do the meta-regression and look over time, it does seem that over time, adjusting for geographic location of the studies, mainly studies that were done in Africa vs. studies in the U.S. and Europe, that the prevalence of both diastolic dysfunction abnormalities and systolic dysfunction abnormalities seems to be going down in more recent years. As greater percentages of the patients are on antiretroviral therapy and as the average CD4 count in participants is higher, the prevalence of these abnormalities is lower.
The take-home message is that more studies need to be done to understand in a contemporary way what is the incidence of HF and subclinical cardiac dysfunction and what is the natural history of those clinical problems in today’s modern treatment era.
The implications of these sorts of studies is really to help clinicians be aware of problems in a specific population that they might not otherwise be looking for. To the extent that a publication like this can help raise awareness in the cardiology community in particular, that cardiac dysfunction and HF in people living with HIV is not a problem of the past. We still see it even in people who are well-controlled on antiretroviral therapy. There may be problems, but it does appear to be getting better.
There are a few unanswered questions. One of them is that it is very common for patients to present with cardiomyopathy when they have advanced AIDS before they have started on antiretroviral therapy, and then to have them recover their ejection fraction and to not have any clinical HF going forward once they are on effective antiretroviral therapy. We see this in clinical practice, but because it is relatively uncommon at any one center, longitudinal cohort studies studying the natural history are relatively few. We need to understand the natural history of AIDS cardiomyopathy in the current treatment era a little bit better. That could be done with prospective studies, but also looking at large retrospective studies and large data sets of electronic medical records data, for example, could help to answer that question.
Christopher Longenecker, MD
Director, Research and Innovation Center
University Hospitals Harrington Heart and Vascular Institute
Director, HIV Cardiometabolic Risk Clinic
University Hospitals John T. Carey Special Immunology Unit
Assistant Professor of Medicine
Case Western Reserve University School of Medicine, Cleveland
Cardiology Today Next Gen Innovator