Cardiac and vascular disease in patients with HIV

INTRODUCTION — Cardiac abnormalities were appreciated early in the epidemic of acquired immunodeficiency syndrome (AIDS), even before the etiologic agent, human immunodeficiency virus (HIV), was isolated and characterized. Decades later, the etiology and pathogenesis of myocarditis and cardiomyopathy associated with HIV infection remain a subject of intense speculation [1,2]. In the era of potent antiretroviral therapy (ART), patients are living longer, and the disease has become a chronic infection, even in low- and middle-income countries [3]. Nevertheless, HIV infection is associated with increased mortality [4], and a growing body of evidence implicates chronic inflammation that persists despite effective ART in the development of vascular dysfunction and accelerated atherosclerosis [5]. There is also evidence that HIV and possibly ART produce myocardial dysfunction by inflammatory cytokine release that results in myocardial fibrosis, apoptosis, and cardiac steatosis [6]. Atherosclerotic vascular disease, especially coronary artery disease, has become the most important cardiovascular complication of HIV infection and has had the most attention directed to its pathogenesis, prevention, and therapy [7,8]. In some resource-limited settings where medical treatment is sparse, limited, or absent, HIV disease and its complications are similar to the disease in the pre-ART era [9].

This topic is devoted to the spectrum of cardiac and vascular diseases seen in patients with HIV. Discussions related specifically to coronary artery disease and its management in patients with HIV are found elsewhere. (See "Epidemiology of cardiovascular disease and risk factors in patients with HIV" and "Pathogenesis and biomarkers of cardiovascular disease in patients with HIV" and "Management of cardiovascular risk (including dyslipidemia) in patients with HIV".)

TYPES OF CARDIAC DISEASE — Patients with HIV infection can have a variety of cardiac and vascular manifestations. However, certain cardiac disorders have been reported with greater frequency among patients with HIV compared with the general population; the specific type of cardiac disease varies by setting.

●Cardiovascular/coronary artery disease – In resource-rich countries, with the widespread availability of potent antiretroviral therapy (ART), patients are living longer, and other comorbidities have surfaced, such as hypertension, metabolic abnormalities (hyperglycemia, hyperlipidemia, lipodystrophy), and accelerated atherosclerosis, including coronary artery disease [7,9-13]. Thus, cardiovascular disease has emerged as a major cause of morbidity and mortality in patients with HIV. As an example, in a study from the United States of death certificates that listed HIV infection, the proportion of deaths attributed to heart disease increased from 5 to 10 percent from 1996 to 2006 [14]. Although cardiovascular disease is accounting for a larger percentage of all those who died, the number of patients dying from cardiovascular disease has actually decreased. In a study of almost 50,000 patients with HIV, all-cause deaths decreased by 48 percent from 17.5 deaths per 1000 person-years in 1999 to 2000 to 9.1 deaths per 1000 person-years in 2009 to 2011; cardiovascular deaths also decreased by 50 percent over this time period from 1.8 to 0.9 deaths per 1000 person-years [15]. Of all mortality related to HIV infection, only 6.5 percent is attributable to cardiovascular disease [16]. The decrease in cardiovascular death could be explained by improved use of non-HIV-specific cardiovascular disease preventive measures. (See "Epidemiology of cardiovascular disease and risk factors in patients with HIV", section on 'Epidemiology'.)

●Heart failure – HIV infection has been associated with an increased risk of heart failure in the ART era [17,18]. In the Veterans Aging Cohort Study, which followed 98,015 patients without baseline cardiovascular disease for a median of 7.1 years, veterans with HIV had an increased risk of heart failure with reduced ejection fraction (HFrEF; hazard ratio [HR] 1.61, 95% CI 1.40-1.86) and heart failure with preserved (HFpEF; HR 1.37, 95% CI 1.09-1.72) compared with matched seronegative veterans [17]. The risk of HFrEF was associated with high HIV viral loads (>500 copies/mL) and low CD4 cell counts (<200/microL), and it was pronounced in veterans younger than 40 years at baseline (HR 3.59, 95% CI 1.95-6.58).

●Pericardial and myocardial disease – By contrast, pericardial effusion and myocardial disease, such as myocarditis and cardiomyopathy, which were frequently reported among patients with HIV before the widespread use of ART, particularly in the setting of significant immunosuppression, are increasingly uncommon. However, in resource-limited settings, where some patients have limited access to ART, these syndromes remain common manifestations of HIV-associated cardiac disease [19,20]. In a study of 5328 patients presenting with a first diagnosis of heart disease to a large cardiology center in South Africa, 518 (10 percent) had HIV, among whom cardiomyopathy was diagnosed in 38 percent and pericarditis in 13 percent [20]. Only 14 patients with HIV (2.7 percent) had a diagnosis of coronary artery disease. This pattern may change as the use of ART worldwide has been increasing. (See "Global epidemiology of HIV infection", section on 'ART coverage'.)

●Pulmonary hypertension – Pulmonary arterial hypertension is a relatively uncommon vascular complication associated with HIV infection. It can occur at all stages of infection, does not seem to be related to the degree of immunodeficiency, and carries a poor prognosis. (See "Pulmonary arterial hypertension associated with human immunodeficiency virus".)

Other cardiac and vascular processes that have been associated with HIV infection include venous thromboembolic disease, peripheral artery disease (PAD), infective endocarditis (mainly in people who inject drugs), cardiac rhythm disturbances, and very rarely, cardiac tumors.

CARDIOVASCULAR DISEASE AND RISK FACTORS — In resource-rich settings, where there is widespread availability of potent antiretroviral therapy (ART), cardiovascular disease has emerged as an important cause of death in patients with HIV relative to the decreasing incidence of opportunistic disease. Several lines of evidence, from modeling of calculated cardiovascular risk to clinical studies evaluating such hard endpoints as stroke, myocardial infarctions, and sudden cardiac death, have cumulatively supported this finding. The epidemiology, pathogenesis, and management of cardiovascular disease and risk factors in patients with HIV are discussed in detail elsewhere. (See "Epidemiology of cardiovascular disease and risk factors in patients with HIV" and "Pathogenesis and biomarkers of cardiovascular disease in patients with HIV" and "Management of cardiovascular risk (including dyslipidemia) in patients with HIV".)

MYOCARDIAL DISEASE

Clinical findings and prevalence — Although the prevalence of HIV-associated myocardial disease has dropped significantly in resource-rich areas since the widespread use of antiretroviral therapy (ART), subtle abnormalities in myocardial structure and function on echocardiography and imaging are still observed among treated individuals with HIV. Cardiomyopathy associated with HIV infection remains a major issue in resource-limited settings.

The spectrum of myocardial disease in patients with HIV infection ranges from incidental asymptomatic findings to symptomatic heart failure:

●Focal myocarditis, usually seen incidentally at autopsy

●Evidence of abnormal myocardial structure or function on cardiovascular imaging

●Clinical cardiomyopathy

Focal myocarditis — In autopsy studies performed before the widespread availability and use of ART, myocarditis was detected among 9 to 52 percent of patients with HIV (average 33 percent) [21-23]. Nearly all had focal collections of mononuclear cells with or without evidence of myocardial necrosis, and ventricular dilatation was occasionally seen [22]. Most of these patients had had no cardiovascular signs or symptoms [24].

There are minimal data on the prevalence of histopathological myocarditis among individuals with HIV in the ART era; however, advanced imaging studies suggest that subtle findings potentially reflective of prior myocarditis are still evident in patients with HIV on ART. In a study from the United Kingdom of 90 patients with HIV taking ART with a mean CD4 cell count of 546 cells/microL and without a known history of cardiac disease or associated symptoms, 76 percent had evidence by cardiac magnetic resonance imaging (MRI) of patchy myocardial fibrosis, possibly suggestive of prior myocarditis, compared with 13 percent among 39 age- and ethnicity-matched controls without HIV [25]. Despite the increased frequency in myocardial fibrosis among patients with HIV overall, the actual volume of focal fibrosis in each individual remained low in both groups. The overall burden of left ventricular patchy fibrosis was small: 4 percent in the cohort with HIV and 2 percent in the control subjects. An endomyocardial biopsy study from South Africa conducted in the ART era found histologic evidence of myocarditis in 44 percent of 14 patients with HIV-associated cardiomyopathy compared with 25 percent of patients with idiopathic cardiomyopathy [26]. Infection with a cardiotropic virus (eg, Epstein-Barr virus, herpes simplex virus, etc) was present in 100 percent of HIV-associated cardiomyopathy and in 90 percent of idiopathic dilated cardiomyopathy patients. Patients with HIV-associated cardiomyopathy had a mean of 2.5 cardiotropic viruses identified.

Abnormalities on cardiovascular imaging

Echocardiographic abnormalities — Several asymptomatic echocardiographic abnormalities have been reported among patients with HIV at various disease stages. In particular, left ventricular diastolic dysfunction appears to be the most common finding; with the more widespread use of ART, the presentation of HIV cardiomyopathy has evolved from clinically severe cardiac systolic dysfunction to a pattern of subclinical cardiac dysfunction manifest by abnormal diastolic function and strain [27]. Nevertheless, systolic dysfunction is also observed with moderate frequency, particularly among untreated patients with HIV.

Among patients with HIV who have access to ART, subclinical structural and functional cardiac abnormalities are found more frequently compared with the general population and appear to be associated with cardiovascular and metabolic risk factors [28-33]. As an example, in a study of 196 adults with HIV in the United States, 97 (49 percent) had echocardiographic evidence of diastolic dysfunction compared with 15 (29 percent) of 52 age- and gender-matched controls [30]. Among patients with HIV, the presence of diastolic dysfunction was not independently associated with CD4 cell count, HIV ribonucleic acid (RNA) level, or duration of ART after adjustment for age and hypertension. Only 4 percent of patients with HIV and no controls had systolic dysfunction (ejection fraction <50 percent). In a meta-analysis of 11 studies from the ART era including over 2000 patients with HIV, the prevalence of diastolic and systolic dysfunction by echocardiography was 43.4 and 8.3 percent, respectively [33]. Hypertension and older age were independently associated with diastolic dysfunction, and a history of myocardial infarction, an elevated C-reactive protein level, and current tobacco smoking were independently associated with systolic dysfunction.

By contrast, in resource-limited settings, echocardiographic abnormalities associated with HIV, in particular left ventricular systolic dysfunction, are generally associated with immunosuppression [34,35]. As an example, in a study from Rwanda that included 416 untreated patients with HIV and without known cardiac disease, left ventricular dilatation and dysfunction (ejection fraction <45 percent) was found in 71 (18 percent) [34]. On multivariate analysis, low socioeconomic status, longer duration of HIV infection, higher HIV viral load, more advanced HIV stage, and low selenium plasma level were factors significantly associated with the presence of systolic dysfunction.

Magnetic resonance abnormalities — Cardiac MRI can also identify more subtle and subclinical myocardial abnormalities. Several studies have suggested that individuals with HIV have a higher rate of MRI findings suggestive of myocardial inflammation and fibrosis [25,36,37].

As an example, a cross-sectional study of 90 individuals with HIV reported a 47 percent greater myocardial lipid content on proton magnetic resonance spectroscopy compared with matched controls [25]. In this study, subjects with HIV had lower median high-density lipoprotein cholesterol, higher total cholesterol/high-density lipoprotein ratio, and higher plasma triglycerides than subjects without HIV.

Other MRI findings are generally consistent with those of echocardiographic findings associated with HIV infection [25,37] (see 'Echocardiographic abnormalities' above). In a study of 103 patients with HIV without known cardiovascular disease on ART, MRI demonstrated lower left ventricle ejection fraction, higher left ventricle mass, and lower peak diastolic strain rates compared with 92 uninfected controls [37]. Small pericardial effusions and myocardial fibrosis were three and four times more common in the patients with HIV infection. Chronic systemic inflammation affecting the pericardium and myocardium may explain these findings.

Symptomatic cardiomyopathy — Clinically symptomatic cardiomyopathy is less common than histopathologic and cardiovascular imaging abnormalities, even in the era prior to the availability of potent ART, when it was reported in approximately 1 to 3 percent of patients with AIDS and the incidence of new cases was 1 to 2 percent [38-41]. Nevertheless, it remains a significant manifestation of cardiac disease among individuals with HIV in resource-limited settings.

In a study from South Africa of patients presenting with newly diagnosed heart disease, among the 518 patients with HIV included, cardiomyopathy (left ventricular dysfunction or dilatation) was the most common primary diagnosis, made in 38 percent, and the majority (86 percent) of these patients reported some level of symptoms and functional limitation [20]. By contrast, among the total cohort of 5328 patients, cardiomyopathy was only documented in 3.7 percent.

The clinical presentation of cardiomyopathy is similar in patients with HIV as in those who are not infected. The initial symptoms are nonspecific: as an example, dyspnea may be due to pulmonary involvement or cardiac disease. More specific signs of cardiac involvement are an S3 gallop or pulmonary edema or a pathologic murmur. The clinical presentation of heart failure is discussed in detail elsewhere. (See "Heart failure: Clinical manifestations and diagnosis in adults".)

Etiology — The pathophysiology of HIV cardiomyopathy is unclear but is probably multifactorial. Some patients with asymptomatic or overt left ventricular dysfunction have a known or clear etiology such as coronary artery disease, cocaine use, alcoholic heart disease, drug toxicity, or myocarditis due to an opportunistic infection such as toxoplasmosis or cryptococcosis [1,2,42]. The endothelium is a reservoir for HIV and produces cytokines such as tumor necrosis factor, interleukin-6, and free radicals in response to inflammation that in turn causes myocardial dysfunction. Direct infection of myocardial cells by HIV, while possible, is controversial, since cardiac myocytes lack HIV receptors [43]. Other possible causes of myocardial dysfunction include mitochondrial damage from certain antiretroviral agents, such as nucleoside reverse transcriptase inhibitors (NRTIs) [43]. These possible etiologies are discussed in detail below.

However, in a number of cases, the etiology and pathogenesis is unknown or unidentified.

The etiology of heart failure and myocarditis in general is discussed elsewhere. (See "Causes of dilated cardiomyopathy" and "Myocarditis: Causes and pathogenesis".)

Cardiac ischemia — With the increasing prevalence of cardiovascular disease among individuals with HIV in resource-rich settings, cardiac ischemia has emerged as an important cause of clinical or subclinical cardiomyopathy in this population [43-45]. The etiology of vascular disease in patients with HIV is multifactorial and includes an increased prevalence of traditional coronary disease risk factors, dyslipidemia with certain antiretrovirals, insulin resistance, and endothelial dysfunction. The role of chronic inflammation and immune activation may be central to the increased risk of coronary artery disease [44]. (See "Epidemiology of cardiovascular disease and risk factors in patients with HIV".)

In a study of 608 patients with HIV hospitalized for an acute myocardial infarction in France, the prevalence of ischemic cardiomyopathy was higher compared with 1216 uninfected controls matched for age and gender (7.6 versus 4.2 percent) [46]. Although in-hospital and one-year mortality rates were similar in both groups, patients with HIV were more likely to be rehospitalized for heart failure during that year than the controls (3.3 versus 1.4 percent).

Myocarditis — Although an alternative causative pathogen can be identified in some cases of myocarditis in patients with HIV, the etiology of 80 to 85 percent of cases remain uncertain. Direct invasion by HIV itself may be responsible, but this is controversial. Although HIV has been identified in myocardial biopsies from patients with HIV cardiomyopathy [47], the virus may have been in blood or endothelial cells rather than in myocardial cells. Other cardiotropic viruses that are not directly identified, such as cytomegalovirus, coxsackievirus, or Epstein-Barr virus, also may be important [7,26,42]. Additionally, a dysregulated inflammatory process induced by HIV or other cardiotropic viruses may also contribute.

Coinfections — Among patients with myocarditis, opportunistic bacterial, fungal, and protozoan pathogens can be identified in approximately 10 to 15 percent of cases [7,26,42]. Other cardiotropic viruses may also contribute to cardiomyopathy in patients with HIV.

In a South African study in which 14 patients with HIV-associated cardiomyopathy underwent endomyocardial biopsy, myocarditis was identified in 44 percent, and a cardiotropic virus was identified in all [26]. The most common were Epstein-Barr virus, herpes simplex virus, and HIV.

Other infectious etiologies that have been implicated in dilated cardiomyopathy associated with HIV infection include coxsackievirus [23,41,48], cytomegalovirus [23,41,49], and Cryptococcus neoformans [50].

One autopsy series published in 1993 found 12 percent of 182 patients with HIV had cardiac toxoplasmosis [51]. However, symptomatic disease appears to be rare. A French survey estimated the prevalence of clinical extracerebral toxoplasmosis among individuals with HIV presenting to care at 1.5 to 2 percent; only 3 percent of these patients had cardiac disease [52].

Role of direct HIV infection — Whether direct infection of the heart by HIV contributes to development of myocarditis in patients with end-stage HIV disease is unclear, but some studies suggest that it is possible. Since the myocardial cell lacks CD4 receptors, HIV is denied the usual mode of entrance into the cell. However, the organism could enter the cell if the cell was injured by another virus. In in vitro studies, for example, Epstein-Barr virus permitted the entrance and replication of HIV into CD4 receptor-negative myocardial cells [53]. In addition, HIV has been localized in or near the myocardial cell by immunocytochemical techniques [54-56] and in situ deoxyribonucleic acid (DNA) hybridization [23,57,58]. In one study, HIV was seen in 25 percent of samples by in situ hybridization, albeit in low signal level [57]. However, HIV sequences also can be identified in patients with HIV and without apparent cardiac disease.

HIV may also cause indirect damage through inflammation, production of free radicals, and increased susceptibility to infections, toxins, and ischemia [43]. Endothelial cells can act as a reservoir for HIV as well as produce cytokines, such as tumor necrosis factor (TNF) and interleukin (IL)-6.

Evidence from studies of simian immunodeficiency virus (SIV)-infected primates supports retroviral infection of cells other than myocytes, mainly monocytes, as being the major cell type in inflammatory heart disease in the simian model [59].

Altered immune response — The dysregulated immune function observed in the setting of HIV infection has been hypothesized to contribute to myocardial dysfunction. Cytokines, such as TNF-alpha, IL-1, IL-2, endothelin (ET)-1, and alpha interferon [60-62] are proteins or large peptides released by HIV-infected macrophages. These cytokines increase the production of inducible nitric oxide synthase (iNOS) and nitric oxide, which are cytotoxic to myocardial cells; furthermore, TNF and reactive oxygen species may signal the onset of myocyte apoptosis leading to progressive loss of ventricular function [56,63-65]. Enhanced expression of iNOS is seen particularly in patients with low CD4 cell counts [66]. (See "Myocarditis: Causes and pathogenesis" and "Pathophysiology of heart failure: Neurohumoral adaptations", section on 'Nitric oxide'.)

The immune reconstitution inflammatory syndrome (IRIS), a pathologic inflammatory response associated with the rapid recovery of the immune system, has also been implicated in the development of acute myocarditis [67]. Similarly, autoimmune disease, which can surface when immune competence is restored with introduction of ART, may contribute to myocardial dysfunction [68,69]. Cardiotropic viruses have the potential to alter cell surface antigens, leading to an autoimmune reaction to endogenous epitopes; cardiac-specific autoantibodies are more commonly found among patients with HIV infection than patients without [43]. HIV-associated polyclonal B-cell stimulation could also be related to the formation of autoantibodies.

Cardiotoxic agents

●Alcohol and other substances – Alcohol, cocaine, and methamphetamine have all been associated with the development of cardiomyopathy. These issues are discussed in detail elsewhere. (See "Alcohol-induced cardiomyopathy" and "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine abuse", section on 'Cardiomyopathy' and "Methamphetamine use disorder: Epidemiology, clinical features, and diagnosis", section on 'Cardiovascular disease'.)

Concomitant methamphetamine use and HIV infection enhances immunosuppression and increases the risk of cardiac complications [70]. Methamphetamines have been shown to significantly increase HIV reverse transcriptase activity in human monocyte-derived macrophages by upregulating the expression of the HIV entry coreceptor CCR5 on macrophages. In this way, methamphetamines function as a cofactor in the immunopathogenesis of HIV infection [71].

●Therapeutic agents – Cardiotoxicity from therapeutic drugs such as pentamidine [72] and possibly zidovudine [73] may contribute to the development of cardiomyopathy in patients with HIV. Zidovudine produces cardiomyopathy in mice with pathologic changes in the mitochondria [1,74]. Patients with HIV and cardiomyopathy have been reported on myocardial biopsy to have similar ultrastructural changes in their mitochondria. In one case, reversal of the cardiac dysfunction was seen on discontinuation of the zidovudine therapy [75]. However, zidovudine is rarely used given the availability of less toxic antiretroviral agents.

Nutritional factors — Some studies have suggested that nutritional issues such as general cachexia or selenium deficiency may play a role in HIV-associated cardiomyopathy [34,41,76,77], although there is no convincing direct evidence of this. In one report of eight patients with HIV-associated cardiomyopathy, six had a deficiency of selenium [77]. Of the three patients who received selenium supplementation, two had clinical and electrocardiographic improvement after selenium levels normalized; the third had no improvement.

Diagnosis and evaluation — The diagnosis of cardiomyopathy in patients with HIV, as in the general population, is made through the finding of characteristic abnormalities on electrocardiography, chest radiograph, and echocardiography in the setting of symptoms and signs suggestive of heart failure. (See "Heart failure: Clinical manifestations and diagnosis in adults".)

Routine echocardiography in asymptomatic patients with HIV is not indicated, as there appears to be no advantage to finding subclinical disease, except for possibly motivating more rigorous control of vascular risk factors, which may be warranted even in the absence of asymptomatic cardiomyopathy. Although echocardiography can detect diastolic dysfunction in an asymptomatic patient with HIV, apart from treating diseases that can precipitate or worsen the ventricular dysfunction, such as hypertension or coronary artery disease, there is no evidence that there is any therapy that can improve diastolic dysfunction.

Further evaluation of patients with HIV and symptomatic cardiomyopathy is similar to that for the general population, which includes an assessment for cardiovascular risk factors, underlying coronary artery disease, and use of potentially cardiotoxic agents (alcohol, illicit substances, or therapeutic drugs). Additionally, because of the potential of certain opportunistic infections to cause myocarditis, patients with significant immunosuppression (ie, CD4 cell count <200 cells/microL) should also be tested for Toxoplasma serology and Cryptococcus neoformans serum antigen. (See "Determining the etiology and severity of heart failure or cardiomyopathy".)

Certain biomarkers may be useful in predicting myocardial dysfunction and outcomes in patients with HIV, but evidence supporting them is limited and most are not clinically available. In a study of 332 patients with HIV and 50 age- and sex-matched controls, the stress-related biomarkers ST2 and growth differentiation factor-15 were associated with cardiovascular dysfunction and all-cause mortality in ambulatory patients with HIV [78]. However, the rate of systolic dysfunction in this study was low, with a left ventricular ejection fraction <50 percent in only 5 percent. There were 38 deaths in the patients with HIV in a median of 6.1 years.

The utility of myocardial biopsy is controversial, as the identification of a treatable etiology of myocarditis is rare. The indications for myocardial biopsy in general are discussed elsewhere. (See "Endomyocardial biopsy", section on 'Indications'.)

Management — The treatment of the patient with HIV and symptomatic cardiomyopathy is similar to that in the general population, which is discussed in detail elsewhere. There are limited data on the efficacy of these interventions in the setting of HIV infection, so the efficacy is extrapolated from evidence in the general population. (See "Treatment and prognosis of heart failure with preserved ejection fraction" and "Overview of the management of heart failure with reduced ejection fraction in adults".)

Correction of any identified underlying cause of the cardiomyopathy is warranted. As an example, drugs that have been implicated in cardiomyopathy should be discontinued. Additionally, with increasing evidence that patients with HIV, especially those on ART regimens, have an increased risk of atherosclerotic disease, including coronary artery disease, special attention to eliminating conventional cardiovascular risk factors such as smoking, controlling hypertension and diabetes, statin use, and reducing weight in overweight patients is important. (See "Epidemiology of cardiovascular disease and risk factors in patients with HIV" and "Management of cardiovascular risk (including dyslipidemia) in patients with HIV".)

In light of the overall improved prognosis with the advent of potent ART, procedures such as coronary bypass or valve replacement should be done for the same indications as in uninfected subjects, unless the patient has advanced immunosuppression and high risk of mortality from AIDS-related complications [79]. Circulatory assist devices and cardiac transplantation have been increasingly and successfully used in patients with HIV infection [43,44,80]. (See "Heart transplantation in adults: Indications and contraindications", section on 'Chronic viral infection'.)

There is no definite direct evidence that ART leads to an improvement in cardiomyopathy, although the decline in the prevalence of HIV-associated cardiomyopathy following the introduction of potent ART suggest a benefit. Additionally, a study of five children with HIV and dilated cardiomyopathy reported reversal of left ventricular dilatation and decreased contractility after the initiation of combination ART [81]. In another study of perinatally infected children, ART appeared cardioprotective, with better measures of left ventricular contractility among treated compared with untreated children [82]. Initiation of ART is associated with a reduction in overall morbidity and mortality as well as public health benefits and is recommended for all patients with HIV. This is discussed in detail elsewhere. (See "When to initiate antiretroviral therapy in persons with HIV".)

PERICARDIAL DISEASE

Epidemiology — Prior to the introduction of potent antiretroviral therapy (ART), pericarditis was the most frequent clinical manifestation of cardiac disease in patients with HIV infection and, specifically, AIDS. However, in countries with widespread access to ART, the incidence of symptomatic pericardial disease in patients with HIV has decreased dramatically.

In a study of 802 outpatients with HIV in Germany recruited between 2004 and 2006, 85 percent were receiving ART, 12 percent had a CD4 cell count <200 cells/microL, and only two patients were found to have a pericardial effusion on transthoracic echocardiography [83]. This is in contrast to pre-ART studies, in which the prevalence of pericardial effusions ranged from 10 to 40 percent; effusions were mainly observed in patients with AIDS [84-88].

In resource-limited settings, the prevalence of pericardial disease in patients with HIV is similar to that reported from pre-ART studies [50,89]. In sub-Saharan Africa, it is the most common manifestation of cardiovascular disease in HIV infection [90]. In a study of 518 patients with HIV who presented to a cardiology center in South Africa between 2006 and 2008 with a first manifestation of heart disease, pericardial disease was diagnosed in 128 patients (25 percent) [20].

Clinical features — HIV-associated pericardial disease generally manifests as a pericardial effusion. Most patients are asymptomatic, identified incidentally through an increase in the cardiac silhouette on chest radiograph. Among those with symptomatic pericardial effusion, however, approximately one-third present with or develop cardiac tamponade [91,92]. (See "Cardiac tamponade".)

Otherwise, clinical features of symptomatic HIV-associated pericardial disease are similar to those caused by other etiologies and include dyspnea, fever, pleuritic chest pain, and, in some cases, a pericardial friction rub. With cardiac tamponade, tachycardia, decrease in blood pressure, and elevated jugular venous pressure occur. (See "Acute pericarditis: Clinical presentation and diagnosis" and "Cardiac tamponade".)

In cases of tuberculous pericarditis, myocarditis is also commonly present. In a study of 81 patients, 58 of whom had HIV, myocarditis (defined by echocardiographic left ventricular dysfunction immediately after pericardiocentesis, troponin T level >0.03 ng/mL, or elevated creatine kinase-MB) was found in 53 percent [93]. (See "Tuberculous pericarditis", section on 'Myopericarditis'.)

Constrictive pericarditis can also uncommonly occur with HIV-associated pericardial disease. Among 121 patients requiring pericardiectomy in a South Africa study, 14 (11.6 percent) of cases were HIV associated [94].

Etiology — In the majority of asymptomatic patients, the etiology of pericardial effusion is not known or identified [88]. Among symptomatic patients, approximately two-thirds are caused by infection or neoplasm.

The differential of infectious and neoplastic etiologies of pericardial effusions in patients with HIV is broad [11,21,91,92,95,96]. Mycobacteria are often the most common infectious pathogens involved [42,92,97-99]. As an example, in a review of 185 cases of HIV-associated pericardial tamponade, mycobacterial infection including Mycobacterium tuberculosis, M. avium-intracellulare, and M. kansasii accounted for 42 percent [99]. Other etiologies included Staphylococcus aureus (11 percent), neoplasms such as lymphoma and Kaposi sarcoma (15 percent), and isolated cases of Cryptococcus, Nocardia, and Aspergillus species. In 26 percent, no etiology was identified.

Geography impacts the likelihood of specific mycobacterial infection. In sub-Saharan Africa, tuberculosis is the major cause of pericarditis among patients with HIV infection [100], accounting for 70 to 90 percent of pericardial effusions in patients with HIV in some studies [90,101]. By contrast, in resource-rich settings, only approximately 5 percent of patients with HIV and pericarditis have tuberculosis [102].

Other infectious etiologies that have been associated with pericardial effusions in patients with HIV include Streptococcus pneumoniae, Listeria monocytogenes, Rhodococcus equi, and Chlamydia trachomatis.

Primary effusion lymphoma is a rare high-grade B-cell non-Hodgkin lymphoma associated with Kaposi sarcoma-associated herpesvirus/human herpes virus 8 infection, mostly seen with patients with HIV with low CD4 cell counts, and can be associated with pericardial effusion [103].

Diagnosis and evaluation — The diagnosis and evaluation of a pericardial effusion in an individual with HIV are the same as those in the general population. (See "Pericardial effusion: Approach to diagnosis".)

Although most patients with HIV and pericardial effusions are incidentally identified, there is no indication to screen asymptomatic patients for an effusion with chest radiograph or echocardiography.

For symptomatic patients, an attempt at establishing the etiology should be made. This generally includes pericardiocentesis or biopsy to obtain fluid and/or tissue for microbiological and cytological or pathological analysis. (See "Pericardial effusion: Approach to diagnosis".)

Tuberculous pericarditis remains an important disease in areas where tuberculosis is endemic, although it may be difficult to diagnose in patients with HIV [90]. Cutaneous anergy to the tuberculin skin test is common in the setting of AIDS (61 percent in one series) [104]; as a result, a negative tuberculin skin test does not exclude the diagnosis. Pericardial biopsy is more sensitive than smears and culture of pericardial fluid but may not be positive for caseating granulomata. The diagnosis of tuberculous pericarditis is discussed in detail elsewhere. (See "Tuberculous pericarditis", section on 'Diagnosis'.)

Management — The management of pericardial effusion in patients with HIV varies by the severity and etiology of the disease. (See "Pericardial effusion: Approach to diagnosis".)

The majority of patients with a pericardial effusion have small effusions causing no symptoms. An asymptomatic, small pericardial effusion without tamponade often requires no further testing except for follow-up [86,105].

By contrast, for patients who are symptomatic with a large effusion, even without tamponade, pericardiocentesis is indicated to evaluate for the etiology, as above. If tamponade occurs, immediate drainage is indicated. Management of cardiac tamponade is discussed in detail elsewhere. (See "Cardiac tamponade".)

Additional management is warranted depending on the identified or suspected etiology.

As an example, antituberculous therapy is indicated in patients with pericardial disease due to M. tuberculosis [106-108]. Additionally, it is generally recommended that patients with a large pericardial effusion in whom no etiology is established be treated empirically for tuberculosis. Details on the management of suspected or confirmed tuberculous pericarditis, including the role of corticosteroids for constrictive tuberculous pericarditis, are found elsewhere. (See "Tuberculous pericarditis", section on 'Treatment'.)

Other causes of pericarditis in patients with HIV should also be treated when identified. Bacterial or fungal infection should be treated with appropriate antimicrobial agents. Management of primary effusion lymphoma, which can cause pericardial effusion in patients with HIV, is discussed elsewhere. (See "Primary effusion lymphoma", section on 'Management'.)

If the patient is not already taking ART, this therapy should be started. Initiation of ART is associated with a reduction in overall morbidity and mortality as well as public health benefits and is discussed in detail elsewhere. (See "When to initiate antiretroviral therapy in persons with HIV".)

Prognosis — The development of pericardial effusion in a patient with HIV is a poor prognostic sign, even if asymptomatic [87,99,105]. In a series of 195 patients with HIV from the pre-ART era, mortality in the patients with pericardial effusion was significantly higher than in the patients with AIDS who did not have an effusion (64 versus 7 percent at six months) [87]. The shortened survival remained significant (relative risk [RR] 2.2) after adjustment for lead time bias and risk factors. The pericardial effusions rarely directly contribute to mortality but rather serve as a marker of advanced HIV infection. Nevertheless, certain etiologies of pericardial disease carry especially poor prognoses. As an example, the median survival of patients with effusion related to primary effusion lymphoma is less than six months [103].

PULMONARY HYPERTENSION — Elevation of pulmonary artery pressures has been reported in a large minority of patients with HIV [109], but clinically significant pulmonary arterial hypertension is a relatively uncommon complication of HIV infection. It can occur at all stages of infection, does not seem to be related to the degree of immunodeficiency, and carries a poor prognosis [110]. In a prospective French study done in the antiretroviral therapy (ART) era that involved over 7000 patients with HIV, the estimated prevalence of pulmonary hypertension was very low (0.46 percent), approximately the same as it was in the 1990s [111,112]. The histopathologic picture is similar to that seen in idiopathic pulmonary hypertension, with obstruction of the pulmonary vasculature by endothelial proliferation, medial hypertrophy, and plexiform lesions [113]. This condition is discussed in detail elsewhere. (See "Pulmonary arterial hypertension associated with human immunodeficiency virus".)

OTHER CARDIAC AND VASCULAR DISEASES

Venous thromboembolic disease — Patients with HIV appear to have an increased risk of venous thromboembolic disease [114-118]. Some studies have estimated that the risk is 2 to 10-fold higher than that in the general population, although the majority of thromboembolic events associated with patients with HIV were noted among those with CD4 cell counts <200 cells/microL or an AIDS-defining illness [119-121].

As an example, in a retrospective assessment of data from the National Hospital Discharge Survey from 1996 to 2004, the odds ratio of developing a pulmonary embolism was 43 percent greater among patients with HIV compared with age-matched controls [122]. Patients with HIV also had a 10 percent greater risk of developing deep vein thrombosis.

Factors that have been implicated in the development of thrombotic complications in patients with HIV, in addition to opportunistic infections, malignancy, and an indwelling central venous catheter, include [121,123-127]:

●Lower CD4 counts.

●Elevated HIV RNA levels.

●Elevated levels of factor VIII and homocysteine.

●Elevated lipid levels.

●Elevated D-dimer and other markers of dysregulated coagulation and fibrinolysis [128-131].

●Presence of antiphospholipid antibodies (anticardiolipin antibodies [aCL] or lupus anticoagulants [LA]) or autoimmune hemolytic anemia. (See "Pathogenesis of antiphospholipid syndrome" and "Clinical manifestations of antiphospholipid syndrome".)

•Elevated levels of aCL are often encountered in patients with chronic infections and have been described in as many as 64 percent of patients with HIV [132,133].

●Acquired deficiencies of proteins S and C and antithrombin [124,134-136].

The clinical manifestations, diagnosis, and management of venous thromboembolic disease in patients with HIV are the same as for the general population and are discussed in detail elsewhere. (See "Epidemiology and pathogenesis of acute pulmonary embolism in adults" and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

Peripheral artery disease — In the general population, peripheral artery disease (PAD) is associated with traditional cardiovascular risk factors, such as smoking, diabetes, hypertension, and hypercholesterolemia. Many of these risk factors are more prevalent among individuals with HIV compared with the general population, and HIV infection itself appears to be an independent risk factor for PAD [137,138]. (See "Epidemiology of cardiovascular disease and risk factors in patients with HIV".)

Most [139-142], but not all [143], suggest a relatively high burden of PAD among this population. In a study of over 90,000 participants in the Veterans Aging Cohort Study, the rate of PAD was higher among those with HIV than without (11.9 versus 9.9 events per 1000 person-years), although the excess risk was confined to individuals with CD4 cell counts <200 cells/microL and HIV viral levels >500 copies/mL [142].

In one study of 92 adults with HIV (mean age 50 years), the prevalence of PAD was evaluated through a claudication questionnaire and measurement of the systolic ankle-brachial index (ABI) at rest and after exercise [140]. Patients with PAD by ABI were further evaluated with duplex scanning of the lower-limb arteries (see "Noninvasive diagnosis of upper and lower extremity arterial disease", section on 'Ankle-brachial index'). The following findings were noted:

●Claudication was reported by 15 percent of patients through the questionnaire.

●Twenty-one percent of patients with HIV had peripheral vascular disease compared with the expected prevalence in the general population of 3 percent at age 60.

●Among the 16 patients who had an abnormal ABI, all had evidence of atherosclerotic occlusions/stenoses of the iliac or femoral arteries on duplex scanning. Age, diabetes, smoking, and low CD4 cell counts were identified as independent predictors of disease.

Potential mechanisms that predispose to the development of vascular disease include the recognized vascular risk factors, the negative impact of certain antiretroviral therapy (ART) medications on lipid metabolism, and the direct effect of HIV on the arterial wall. In a study of 54 patients with HIV and without a history of cardiovascular disease and 54 controls closely matched for age, gender, body mass index (BMI), and vascular risk factors, HIV infection was associated with decreased arterial compliance, while all other arterial stiffness parameters were similar in both groups and correlated with age [144]. Decreased arterial compliance may contribute to the development of atherosclerosis and PAD. (See "Pathogenesis and biomarkers of cardiovascular disease in patients with HIV".)

The clinical manifestations, diagnosis, and management of PAD in patients with HIV are the same as for the general population and are discussed in detail elsewhere. (See "Clinical features and diagnosis of lower extremity peripheral artery disease" and "Management of claudication due to peripheral artery disease".)

Additionally, the incidence of ischemic stroke among patients with HIV has been increasing, likely reflecting the prevalence of disease of the carotid arteries [145,146]. In one study of 209 patients with HIV infection but without known vascular disease, the rate of carotid plaques and noncalcified high-risk plaques identified by computed tomography was higher than in uninfected controls; at three years, any plaques were associated with a fourfold increase in the risk of strokes [147]. In a meta-analysis of five studies including nearly 90,000 adults with HIV (approximately 46 to 50 years old) on ART, 1.8 percent had ischemic strokes after a median follow-up of four years [148]. Traditional risk factors such as age, smoking, hypertension, hyperlipidemia, atrial fibrillation, and diabetes were independent predictors of stroke. In one of the included studies, high HIV viral load and CD4 cell count <200 cells/microL were associated with stroke; ART had a neutral effects [148].

Valvular disease — In general, valvular diseases among patients with HIV are similar to those among the general population. In a prospective multicenter study of 803 adults with HIV, 77.2 percent had mild valvular regurgitation on transthoracic echocardiography, but only 4.7 percent had clinically relevant regurgitation and 0.4 percent had clinically significant stenosis [149]. There was no association between CD4 cell count or viral load and the presence of valvular disease.

Overall, the risk and incidence of infective endocarditis among patients with HIV is similar to HIV-uninfected populations who share similar risk behaviors, particularly injection drug use [85,150-153]. In a study of 105 patients with HIV and infective endocarditis, the mean age was 30.1 years and 94 percent had a history of injection drug use [150]. A very low CD4 cell count (<50 cells/microL) and high HIV RNA levels (>100,000 copies/mL) have been associated with an increased risk of infective endocarditis, and the incidence has appeared to decline since the introduction of ART in resource-rich settings [151]. As with infective endocarditis in injection drug users without HIV, the most common valve involved is the tricuspid valve and the most common organism S. aureus [150,151]. Clinicians should consider the possibility of methicillin-resistant S. aureus (MRSA) in patients with HIV and endocarditis, as the pathogen is relatively common among this population [151,154].

The treatment approach to infective endocarditis, including the indications for valve surgery, is the same for patients with and without HIV. Overall, response to antibiotic therapy is similar among injection drug users with and without HIV [153,155]. One study reported a higher mortality rate in the setting of endocarditis among injection drug users with HIV compared with those without HIV, but all deaths were among patients with a CD4 cell count <200 cells/microL [156]. (See "Right-sided native valve infective endocarditis" and "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis" and "Antimicrobial therapy of left-sided native valve endocarditis".)

In the United States, between 2000 and 2010, the proportion of patients with HIV undergoing surgery for endocarditis decreased from 32 to 8 percent and operative mortality among patients with HIV decreased from 5.6 to 0.9 percent [157].

Nonbacterial thrombotic (marantic) endocarditis, which consists of sterile vegetations and can occur on any of the valves, was found on autopsy in up to 10 percent of AIDS patients at the outset of the HIV epidemic in the United States. There have been no cases reported in patients with HIV since 1989 [11].

Cardiac rhythm disturbances

Long QT syndrome — QT prolongation and torsade de pointes (TdP) have been described in patients with HIV, even in the absence of therapy with agents associated with these features. In a study of 135 consecutive patients with HIV seen at an outpatient clinic, 17 to 29 percent had a prolonged QT interval [158]. In a study of 351 patients with HIV, 26 (7.4 percent) had a prolonged corrected QT interval [159]. Similarly, in a study of hospitalized patients with HIV, 29 percent had QT prolongation [160]. Postulated mechanisms include myocarditis, a subclinical cardiomyopathy, and autonomic neuropathy [161]. There is evidence an HIV protein (tat) inhibits KCNH2 (formerly hERG) protein expression and thus inhibits KCNH2 potassium currents, which could be a potential mechanism for HIV-associated long QT findings [162]. A low CD4 cell count and high viral load have been associated with prolonged QT interval [94,159]. Among ART-treated patients with viral suppression, prolonged QT interval has been associated with hyperlipidemia and diastolic dysfunction, whereas atazanavir use was associated with a lower rate of QT prolongation [163].

In addition, certain therapeutic agents used in HIV infection may contribute to the development of QT prolongation. Pentamidine may promote TdP both directly and by causing hypomagnesemia [164,165], and certain HIV protease inhibitors, such as atazanavir with ritonavir, and lopinavir with ritonavir, block the KCNH2 channel and could thus directly cause the long QT syndrome [165,166]. However, in a large study that randomly assigned HIV-infected patients to receive either intermittent ART or continuous ART, different protease inhibitor-based regimens were not independently associated with prolongation in the QT interval compared with regimens that did not contain a protease inhibitor [167,168]. However, all protease inhibitor-based regimens were associated with prolongation of the PR interval. Nevertheless, protease inhibitors may also inhibit the CYP p450 metabolism of drugs known to prolong the QTc interval (eg, methadone, moxifloxacin), thereby increasing the risk of QTc prolongation. (See "Overview of antiretroviral agents used to treat HIV", section on 'Protease inhibitors (PIs)'.)

Precautions for patients using drugs associated with QT prolongation and management of patients with QT syndrome are discussed in detail elsewhere. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".)

The main concern with prolonged QT is the development of life-threatening arrhythmias and sudden cardiac death. In a study of almost 3000 patients with HIV, there were 2.6 sudden cardiac deaths per 1000 person-years, 4.5 times the rate in the general population [169]. Compared with death from AIDS and natural causes, sudden cardiac death was associated with a history of prior myocardial infarction, cardiomyopathy, heart failure, and arrhythmias. Postulated mechanisms included inflammation, ART interruption, and concomitant medications.

Atrial fibrillation — The overall incidence of atrial fibrillation among individuals with HIV is low. In a study of 30,533 United States veterans with HIV, 2.6 percent developed atrial fibrillation over a median follow-up of 6.8 years [170]. CD4 cell count <200 cells/microL and viral load >100,000 copies/mL were associated with atrial fibrillation.

In the general population, the CHA2S2-VASc score is often used to determine the risk of embolic stroke with atrial fibrillation and thus to guide decisions on anticoagulation. Given that HIV infection is associated with a baseline risk of stroke that is not accounted for in traditional risk score calculators, anticoagulation may thus be warranted for patients with HIV despite a low CHA2S2-VASc score [171]. In a study of 914 veterans with HIV and atrial fibrillation, the CHA2DS2-VASc scores were only weakly associated with thromboembolic risk [172]. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation".)

When selecting anticoagulation for patients with HIV, consideration of drug interactions with antiretroviral agents is essential. For specific drug interactions, refer to the Lexicomp drug interactions program included with UpToDate.

Autonomic dysfunction — Autonomic nervous system dysfunction appears relatively common among patients with HIV [173]. A meta-analysis of studies on heart rate variation in patients with HIV found a general reduction in autonomic function with a shift toward sympathetic dominance that may predispose patients with HIV to the risk of arrhythmias, cardiac events, and accelerated HIV disease progression [174].

Some evidence suggests that the lower heart rate variability with HIV is indicative of autonomic nervous system inflammatory-immune dysfunction [175]. Another study suggested that the decreased parasympathetic function compared with HIV-uninfected patients was evident among both viremic and aviremic patients with HIV [176]. ART did not appear to affect autonomic function [177]. The proposed mechanism for the autonomic dysfunction is unknown but may be related to the HIV-induced changes in the brain responsible for autonomic nervous system function. It has also been associated with distal symmetric polyneuropathy [173].

Despite the prevalence of autonomic dysfunction among patients with HIV, it is rarely recognized by clinicians, and symptoms often remain unexplained or attributed to medication side effects [178]. Nevertheless, it carries significant morbidity and can lead to QTc prolongation and malignant ventricular arrhythmias.

Sudden cardiac death — Sudden death is an important cardiovascular complication among patients with HIV, who appear to be at higher risk compared with the general population [179,180]. In the Veterans Aging Cohort Study, which followed over 144,000 veterans for a median of nine years, HIV was associated with an increased risk of sudden cardiac death (hazard ratio 1.14, 95% CI 1.04-1.25) [180]. The increased risk was predominantly seen in veterans with HIV and with CD4 counts <200 cells/microL and viral load >500 copies/mL. Risk of sudden cardiac death in veterans with HIV and with CD4 counts >500 cells/microL or viral load <500 copies/mL were comparable to veterans who did not have HIV [180]. In a postmortem study of individuals with HIV who had out-of-hospital cardiac arrest, the rate of sudden cardiac death was estimated at 53.3 per 100,000 person-years compared with 23.7 per 100,000 person-years among individuals without known HIV [179]. Among the 47 individuals with HIV and sudden cardiac death who underwent autopsy, the cause was arrhythmia for 47 percent and noncardiac for 51 percent. The most common underlying case was occult drug overdose (in one-third of cases).

Sudden cardiac deaths appear to account for a majority of cardiac deaths in patients with HIV. In a study of 230 deaths over a median of 3.7 years among patients with HIV infection, 30 of the 35 cardiac deaths (86 percent) were sudden deaths [169].

Cardiac tumors — Certain malignancies associated with HIV infection, namely Kaposi sarcoma and non-Hodgkin lymphoma, may present with cardiac involvement. However, following the introduction of combination ART, the incidence of cardiac tumor involvement in patients with HIV in resource-rich countries has dropped substantially, possibly as a result of less immunologic depression and a marked decrease in opportunistic infections such as Epstein-Barr virus and human herpes virus 8 that are known to be etiologically related to these neoplasms [181].

Prior to the widespread use of ART in resource-rich settings, Kaposi sarcoma was observed to involve the myocardium or the pericardium and cause pericardial effusion and, in some cases, tamponade among patients with AIDS [92,182]. In autopsy reports from that era, the prevalence of Kaposi sarcoma in patients with AIDS was 12 to 28 percent [23]. (See "AIDS-related Kaposi sarcoma: Clinical manifestations and diagnosis".)

Similarly, there are reports of primary cardiac lymphoma among patients with AIDS [183-186]. Lymphomas are the second most common cardiac tumors in AIDS, and despite effective ART, the incidence of non-Hodgkin lymphoma among individuals with HIV remains higher than among the noninfected population. When lymphoma involves the heart, it is usually diffusely infiltrative but can form nodules and even intracavitary masses [21,187,188]. Cardiac lymphoma can cause heart failure, superior vena caval syndrome, atrial and ventricular arrhythmias, and heart block. With intracavitary growth, the masses can cause mechanical obstruction to the blood flow across the valves. In such cases, surgical resection may be indicated. Since the introduction of ART and more advanced chemotherapy, the prognosis in patients with non-Hodgkin lymphoma has improved [189,190]. (See "HIV-related lymphomas: Clinical manifestations and diagnosis" and "HIV-related lymphomas: Treatment of systemic lymphoma".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Primary care of adults with HIV".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here is the patient education article that is relevant to this topic. We encourage you to print or e-mail this topic to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Coronary artery disease (The Basics)" and "Patient education: Heart failure with preserved ejection fraction (The Basics)")

●Beyond the Basics topics (see "Patient education: Pericarditis (Beyond the Basics)" and "Patient education: Heart failure (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●In resource-rich countries, coronary artery disease has emerged as the major cause of cardiac-related morbidity and mortality in HIV-infected patients. (See "Epidemiology of cardiovascular disease and risk factors in patients with HIV" and "Management of cardiovascular risk (including dyslipidemia) in patients with HIV".)

●Pericardial and myocardial disease had historically been the most frequent clinical manifestations of heart disease in patients with HIV, but their prevalence has decreased dramatically with the widespread use of antiretroviral therapy (ART). Nevertheless, they remain common in settings where access to diagnosis and treatment of HIV infection is limited. (See 'Types of cardiac disease' above.)

●Although the prevalence of HIV-associated myocardial disease has dropped significantly since the widespread use of ART, subtle abnormalities in myocardial structure and function on echocardiography and imaging are still observed among treated individuals with HIV. Nevertheless, routine echocardiography in asymptomatic patients with HIV is not indicated, as there appears to be no advantage to finding subclinical disease. (See 'Myocardial disease' above.)

●Cardiac ischemia may emerge as an important cause of clinical cardiomyopathy in treated patients with HIV. The clinical presentation, diagnosis and evaluation, and management of heart failure in patients with HIV are generally the same as in the general population. However, the potential involvement of opportunistic infections should be considered among patients with HIV and CD4 cell counts <200 cells/microL. (See 'Myocardial disease' above and "Heart failure: Clinical manifestations and diagnosis in adults" and "Determining the etiology and severity of heart failure or cardiomyopathy" and "Overview of the management of heart failure with reduced ejection fraction in adults".)

●Pericardial disease among patients with HIV generally manifests as a pericardial effusion in patients with significant immunosuppression, often found incidentally. The majority of symptomatic pericardial effusions are due to infection (particularly tuberculosis) or malignancy. The diagnosis and evaluation of a pericardial effusion in an individual with HIV are the same as those in the general population. The management of pericardial effusion in patients with HIV varies by the severity and etiology of the disease. (See 'Pericardial disease' above and "Pericardial effusion: Approach to diagnosis" and "Tuberculous pericarditis".)

●Pulmonary arterial hypertension is a relatively uncommon complication of HIV infection that can occur at all stages of infection, does not seem to be related to the degree of immunodeficiency, and carries a poor prognosis. (See "Pulmonary arterial hypertension associated with human immunodeficiency virus".)

●Other cardiac and vascular processes that have been associated with HIV infection include venous thromboembolic disease, peripheral artery disease (PAD), infective endocarditis (almost exclusively in injection drug users), cardiac rhythm disturbances, and, very rarely, cardiac tumors. (See 'Other cardiac and vascular diseases' above.)