Abstract and Introduction
Background: With the number of people living with human immunodeficiency virus (HIV) steadily increasing, cardiovascular disease has emerged as a leading cause of non-HIV related mortality. People living with HIV (PLWH) appear to be at increased risk of coronary artery disease and heart failure (HF), while the underlying mechanism appears to be multifactorial. In the general population, ectopic cardiac adiposity has been highlighted as an important modulator of accelerated coronary artery atherosclerosis, arrhythmogenesis and HF with preserved ejection fraction (HFpEF). Cardiac adiposity is also strongly linked with obesity, especially with visceral adipose tissue accumulation.
Aims: This review aims to summarize the possible role of cardiac fat depositions, assessed by imaging modalities, as potential contributors to the increased cardiac morbidity and mortality seen in PLWH, as well as therapeutic targets in the current ART era.
Materials & Methods: Review of contemporary literature on this topic.
Discussion: Despite antiretroviral therapy (ART), PLWH have evidence of persistent, HIV-related systemic inflammation and body fat alterations. Cardiac adiposity can play an additional role in the pathogenesis of cardiovascular disease in the HIV setting. Imaging modalities such as echocardiography, cardiac multidetector computed tomography and cardiac magnetic resonance have demonstrated increased adipose tissue. Studies show that high cardiac fat depots play an additive role in promoting coronary artery atherosclerosis and HFpEF in PLWH. Systemic inflammation due to HIV infection, metabolic adverse effects of ART, adipose alterations in the ageing HIV population, inflammation and immune activation are likely important mechanisms for adipose dysfunction and disproportionately occurrence of ectopic fat depots in the heart among PLWH.
Conclusions: High cardiac adiposity seems to plays an additive role in promoting coronary artery atherosclerosis and HFpEF in PLWH. The underlying mechanisms are multiple and warrant further investigation. Improved understanding of the regulating mechanisms that increase cardiovascular risk in HIV infection may give rise to more tailored therapeutic strategies targeting cardiac fat depots.
With the number of people living with HIV (PLWH) steadily increasing, cardiovascular (CV) disease has emerged as a leading cause of non-HIV-related mortality and is responsible for 2.6 million disability-adjusted life-years per annum.[1,2] People living with HIV appear to be at increased risk of coronary artery disease and heart failure (HF), the phenotype of which has significantly shifted from HF with reduced ejection to HF with preserved ejection fraction (HFpEF) in the last two decades.[3–6] The underlying mechanism appears to be multifactorial with HIV-associated immune activation and inflammation, specific antiretroviral therapy (ART) exposure, micronutrient deficiency and excess of the traditional CV factors playing interrelating roles.
Histological and imaging studies have highlighted ectopic cardiac adiposity as an important modulator of accelerated coronary artery atherosclerosis, arrhythmogenesis and HFpEF, due to structural changes in the general population.[7,8] The high-energy demands of the heart are covered by the oxidation of circulating plasma free fatty acids. Although cardiac adipose tissue has a cardioprotective role by regulating adipogenesis, excessive free fatty acid and triglyceride delivery may result in myocardial lipid overstorage when alterations in cardiac fatty acid metabolism occur, such as in obesity and diabetes. The main ectopic fat depots are: (1) epicardial adipose tissue (EAT) which is located between the myocardium and the visceral pericardium, with no fascia separating the tissues; (2) pericardial adipose tissue (PAT) that is not anatomically adjacent to the myocardium and includes the combination of fat between the visceral and parietal pericardial layers and fat located on the external surface of the parietal pericardium; and (3) intramyocardial fat infiltrations, termed cardiac steatosis (Figure 1). Increased cardiac fat depositions are associated with metabolic dysregulation, glucose intolerance and inflammation, mediated by various types of adipokines, such as adiponectin and leptin, reactive oxidative species and micro-RNAs, which in turn may diffuse to the underlying myocardium in the absence of a separating fascia, via paracrine and vasocrine pathways, mediating endothelial dysfunction, atherosclerosis and myocardial dysfunction.
The three different types of ectopic cardiac fat depots. Modified from Villasante Fricke AC and Iacobellis  under Creative Commons license 4.0
Ectopic fat depots can be visualized by noninvasive screening modalities such as echocardiography, cardiac multidetector computed tomography (CT) and cardiac magnetic resonance (CMR) and have been associated with increased CV risk in the general population.[8,11–13] Although, EAT and PAT are used to identify different adipose tissues, these terms are often not discriminated on imaging studies. With echocardiography, EAT/PAT thickness can be measured in front of the free right ventricle wall, at end-systole, in either the parasternal long or short axis views. Nevertheless, this modality does not enable the assessment of the whole EAT volume. On the other hand, CT and CMR are able to provide a three-dimensional volumetric quantification of cardiac adipose tissue. Furthermore, CT can provide information about inflammation of EAT tissue by quantification of fat attenuation, with higher EAT attenuation reflecting a state of inflammation. Cardiac magnetic resonance is regarded as the gold standard for pericardium visualization and has the advantage over CT that it lacks radiation exposure. In addition, magnetic resonance spectroscopy (MRS) is considered the reference standard for the diagnosis of cardiac steatosis; moreover, newer CMR techniques such as multi-echo Dixon methods, are also useful tools in quantifying myocardial triglyceride content.[14,15] The EAT/PAT thickness and volume have been associated with presence of coronary artery disease, atrial fibrillation, HFpEF and adverse outcomes in the general population.[8,16–18] In addition, CT-derived peri-coronary fat attenuation carries prognostic value in both primary and secondary prevention and offers a significant improvement in CV risk stratification beyond traditional risk factors.[19,20] The advantages and disadvantages of the screening modalities in imaging cardiac adiposity are summarized in Table 1.
Cardiac adiposity is strongly linked with obesity, especially with visceral adipose tissue (VAT) accumulation. Obesity leads to excessive ectopic lipid accumulation in non-adipose tissues such as the heart, liver and muscles, and in the visceral adipose depots, contributing to a low-grade inflammatory state, therefore fostering the progression of obesity-associated metabolic abnormalities, including coronary artery disease and stroke.
Despite ART, PLWH show evidence of persistent, HIV-related systemic inflammation and body fat alterations. Cardiac adiposity can play an additional role in the pathogenesis of cardiovascular disease in the HIV setting. This review summarizes the role of cardiac fat depositions, assessed by imaging modalities, as potential contributors to the increased cardiac morbidity and mortality seen in PLWH, as well as therapeutic targets in the current ART era.