HIV-associated cardiomyopathy

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HIV-associated cardiomyopathy
Specialty Cardiology

Heart problems are more common in people with HIV/AIDS. Those with left ventricular dysfunction have a median survival of 101 days as compared to 472 days in people with AIDS with healthy hearts. [1] HIV is a major cause of cardiomyopathy (problems with the heart muscle that reduce the efficiency with which the heart pumps blood). The most common type of HIV induced cardiomyopathy is dilated cardiomyopathy also known as eccentric ventricular hypertrophy which leads to impaired contraction of the ventricles due to volume overload. The annual incidence of HIV associated dilated cardiomyopathy was 15.9/1000 before the introduction of highly active antiretroviral therapy (HAART). [2] However, in 2014, a study found that 17.6% of HIV patients have dilated cardiomyopathy (176/1000) meaning the incidence has greatly increased. [3]

Contents

Presentation

Signs and symptoms such as malabsorption and diarrhea respectively, may occur with HIV infection causing many HIV patients to have nutritional deficiencies and altered levels of vitamin B12, carnitine, and growth and thyroid hormones - all have been associated with left ventricular dysfunction. [4] A lowered BMI in HIV patients is also associated with cardiomyopathy. [5]

Cause

Dilated cardiomyopathy can be due to pericardial effusion or infective endocarditis, especially in intravenous drug users which are common in the HIV population. [6] [7] However, the most researched cause of cardiomyopathy is myocarditis (myocardial inflammation and infection) caused by HIV-1, which the main subtype of HIV (the other being HIV-2), with greater likelihood of transmission and shorter period between infection and illness. HIV-1 virions infect cardiomyocytes in patches but there is no direct correlation between viral infection and dysfunction of cardiomyocytes. HIV-related cardiomyopathy is often not associated with any specific opportunistic infection, and approximately 40% of patients have not experienced any opportunistic infection before the onset of cardiac symptoms. [8] [9]

Myocarditis

Myocarditis has been documented at autopsy in 40–52% of patients who died of AIDS before the introduction of HAART. [10] Toxoplasma gondii is the most common opportunistic infectious agent associated with myocarditis in AIDS occurring in 12% of deaths from AIDS 1987-1991 in one autopsy series. [11] Myocardial toxoplasmosis causes an increase in the myocardial fraction of creatine kinase (CK-MB). In situ hybridization or polymerase chain reaction studies illustrate a high frequency of cytomegalovirus and HIV-1 in AIDS patients with lymphocytic myocarditis and severe left ventricular dysfunction. [12] [13] Thus, it supports the hypothesis that HIV-1 has a pathogenetic action and influences dilated cardiomyopathy. Coinfection with viruses (usually, coxsackievirus B3 and cytomegalovirus) seems to have an important effect as the GISCA autopsy records show that 83% of patients with myocarditis and 50% with dilated cardiomyopathy were coinfected with viruses. [14]

Myocardial cytokine expression

HIV-1 invades the myocardium through endothelial cells by micropinocytosis infecting perivascular macrophages which produce additional virus and cytokines such as tumour necrosis factor-α (TNF-α). This induces cardiomyocyte apoptosis either by signalling through CCR3, CCR5 or CXCR4, by entry into cardiomyocytes (after binding to ganglioside GM1), or through TNF-α. [15] [16] In addition, HIV-1-associated protein gp 120 may induce apoptosis through a mitochondrion-controlled pathway after activating inflammatory cytokines. [17] TNF-α is produced by infected macrophages and the interaction between dendritic cells presenting the antigen to CD8 (T Killer cells). [18] [19] It causes a negative inotropic effect by interfering with the intracellular calcium ion concentrations perhaps by inducing the synthesis of nitric oxide (NO), also decreasing contractility. [20] [21] The intensity of the stains for TNF-α and inducible nitric oxide synthase (iNOS) of the myocardium was greater in patients with HIV associated cardiomyopathy (as opposed to idiopathic cardiomyopathy), myocardial viral infection and was inversely correlated with CD4 count with antiretroviral therapy having no effect.[ citation needed ]

Autoimmune cardiomyopathy

Cardiac autoimmunity affects the pathogenesis of HIV-related heart disease as HIV-infected patients with dilated cardiomyopathy are more likely to have cardiac-specific autoantibodies (anti-α-myosin autoantibodies) than HIV-infected patients with healthy hearts and HIV-negative controls. [22] In addition, patients with echocardiographic evidence of left ventricular dysfunction had a higher chance of having cardiac autoantibodies. Furthermore, impaired myocardial growth and left ventricular dysfunction may be immunologically mediated as monthly intravenous immunoglobulins (IVIG) in HIV-infected children reduces left ventricular dysfunction, increases left ventricular wall thickness, and reduces peak left ventricular wall stress. Perhaps this is because immunoglobulins inhibit the cardiac autoantibodies by competing for Fc receptors. Alternatively, the immunoglobulins can reduce the effects or secretions of cytokines and cellular growth factors. [23]

Encephalopathy

HIV-infected patients with encephalopathy are more likely to die of congestive heart failure than are those without encephalopathy; the hazard ratio is 3.4. [24] [25] Cardiomyopathy and encephalopathy are hypothesised to be linked by the HIV reservoir cells which are in the myocardium and cerebral cortex and keep HIV-1 on their surfaces for long periods of time even after receiving HAART. They also secrete TNF-α, interleukin-6 (IL-6) and endothelin-1 which are cytotoxic cytokines causing tissue damage.[ citation needed ]

Drug cardiotoxicity

Zidovudine is an example of a nucleoside analogue and has been shown to cause: myocarditis and dilated cardiomyopathy as well as an increase in total cholesterol, triglycerides, LDL, HDL and insulin resistance. [26] [27] Protease inhibitors are another group of drugs (e.g. ritonavir) and some of them can cause a range of problems such as: lipodystrophy, atherosclerosis, increase total cholesterol, triglyceride, HDL, LDL, and insulin resistance. Amphotericin B can cause dilated cardiomyopathy, hypertension and bradycardia whereas, Ganciclovir can cause ventricular tachycardia. Interferon-alpha can cause arrhythmia and myocardial infarction/ischemia. [28] [29]

Treatment

Mortality in HIV-infected patients with cardiomyopathy is increased independently of CD4 count, age, sex, and HIV risk group. [30] [31] The therapy is similar to therapy for non-ischemic cardiomyopathy: after medical therapy is begun, serial echocardiographic studies should be performed at 4-months intervals. If function continues to worsen or the clinical course deteriorates, a biopsy should be considered. [32] [33] HAART has reduced the incidence of myocarditis thus reducing the prevalence of HIV-associated cardiomyopathy by about 30% in developed countries. [34] [35] However, the prevalence in developing countries is 32% and increasing as HAART is scarce – not to mention the effects of other risk factors such as high cholesterol and lipid diet. [36] IVIGs can also help patients with HIV-associated myocarditis as mentioned earlier.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Cardiomyopathy</span> Disease of the heart muscle

Cardiomyopathy is a group of primary diseases of the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. An irregular heart beat and fainting may occur. Those affected are at an increased risk of sudden cardiac death.

<span class="mw-page-title-main">Premature ventricular contraction</span> Skipped beat with ventricular origin

A premature ventricular contraction (PVC) is a common event where the heartbeat is initiated by Purkinje fibers in the ventricles rather than by the sinoatrial node. PVCs may cause no symptoms or may be perceived as a "skipped beat" or felt as palpitations in the chest. PVCs do not usually pose any danger.

<span class="mw-page-title-main">Cardiac muscle</span> Muscular tissue of heart in vertebrates

Cardiac muscle is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of the heart. The cardiac muscle (myocardium) forms a thick middle layer between the outer layer of the heart wall and the inner layer, with blood supplied via the coronary circulation. It is composed of individual cardiac muscle cells joined by intercalated discs, and encased by collagen fibers and other substances that form the extracellular matrix.

<span class="mw-page-title-main">Myocarditis</span> Inflammation of the heart muscle

Myocarditis is defined as inflammation of the myocardium. Myocarditis can progress to inflammatory cardiomyopathy when there are associated ventricular remodeling and cardiac dysfunction due to chronic inflammation. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. The duration of problems can vary from hours to months. Complications may include heart failure due to dilated cardiomyopathy or cardiac arrest.

<span class="mw-page-title-main">Arrhythmogenic cardiomyopathy</span> Medical condition

Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease.

<span class="mw-page-title-main">Dilated cardiomyopathy</span> Condition involving an enlarged, ineffective heart

Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Complications can include heart failure, heart valve disease, or an irregular heartbeat.

<span class="mw-page-title-main">Peripartum cardiomyopathy</span> Medical condition

Peripartum cardiomyopathy (PPCM) is a form of dilated cardiomyopathy that is defined as a deterioration in cardiac function presenting typically between the last month of pregnancy and up to six months postpartum. As with other forms of dilated cardiomyopathy, PPCM involves systolic dysfunction of the heart with a decrease of the left ventricular ejection fraction (EF) with associated congestive heart failure and an increased risk of atrial and ventricular arrhythmias, thromboembolism (blockage of a blood vessel by a blood clot), and even sudden cardiac death. In essence, the heart muscle cannot contract forcefully enough to pump adequate amounts of blood for the needs of the body's vital organs.

HIV-associated neurocognitive disorders (HAND) are neurological disorders associated with HIV infection and AIDS. It is a syndrome of progressive deterioration of memory, cognition, behavior, and motor function in HIV-infected individuals during the late stages of the disease, when immunodeficiency is severe. HAND may include neurological disorders of various severity. HIV-associated neurocognitive disorders are associated with a metabolic encephalopathy induced by HIV infection and fueled by immune activation of macrophages and microglia. These cells are actively infected with HIV and secrete neurotoxins of both host and viral origin. The essential features of HIV-associated dementia (HAD) are disabling cognitive impairment accompanied by motor dysfunction, speech problems and behavioral change. Cognitive impairment is characterised by mental slowness, trouble with memory and poor concentration. Motor symptoms include a loss of fine motor control leading to clumsiness, poor balance and tremors. Behavioral changes may include apathy, lethargy and diminished emotional responses and spontaneity. Histopathologically, it is identified by the infiltration of monocytes and macrophages into the central nervous system (CNS), gliosis, pallor of myelin sheaths, abnormalities of dendritic processes and neuronal loss.

HIV-associated nephropathy (HIVAN) refers to kidney disease developing in association with infection by human immunodeficiency virus, the virus that causes AIDS. The most common, or "classical", type of HIV-associated nephropathy is a collapsing focal segmental glomerulosclerosis (FSGS), though other forms of kidney disease may also occur. Regardless of the underlying histology, kidney disease in HIV-positive patients is associated with an increased risk of death.

Loeffler endocarditis is a form of heart disease characterized by a stiffened, poorly-functioning heart caused by infiltration of the heart by white blood cells known as eosinophils. Restrictive cardiomyopathy is a disease of the heart muscle which results in impaired diastolic filling of the heart ventricles, i.e. the large heart chambers which pump blood into the pulmonary or systemic circulation. Diastole is the part of the cardiac contraction-relaxation cycle in which the heart fills with venous blood after the emptying done during its previous systole.

Endocardial fibroelastosis (EFE) is a rare heart disorder usually occurring in children two years old and younger. It may also be considered a reaction to stress, not necessarily a specific disease.

<span class="mw-page-title-main">Takotsubo cardiomyopathy</span> Sudden temporary weakening of the heart muscle

Takotsubo cardiomyopathy or takotsubo syndrome (TTS), also known as stress cardiomyopathy, is a type of non-ischemic cardiomyopathy in which there is a sudden temporary weakening of the muscular portion of the heart. It usually appears after a significant stressor, either physical or emotional; when caused by the latter, the condition is sometimes called broken heart syndrome.

The following outline is provided as an overview of and topical guide to cardiology, the branch of medicine dealing with disorders of the human heart. The field includes medical diagnosis and treatment of congenital heart defects, coronary artery disease, heart failure, valvular heart disease and electrophysiology. Physicians who specialize in cardiology are called cardiologists.

<span class="mw-page-title-main">Coxsackievirus and adenovirus receptor</span> Protein found in humans

Coxsackievirus and adenovirus receptor (CAR) is a protein that in humans is encoded by the CXADR gene. The protein encoded by this gene is a type I membrane receptor for group B coxsackie viruses and subgroup C adenoviruses. CAR protein is expressed in several tissues, including heart, brain, and, more generally, epithelial and endothelial cells. In cardiac muscle, CAR is localized to intercalated disc structures, which electrically and mechanically couple adjacent cardiomyocytes. CAR plays an important role in the pathogenesis of myocarditis, dilated cardiomyopathy, and in arrhythmia susceptibility following myocardial infarction or myocardial ischemia. In addition, an isoform of CAR (CAR-SIV) has been recently identified in the cytoplasm of pancreatic beta cells. It's been suggested that CAR-SIV resides in the insulin secreting granules and might be involved in the virus infection of these cells.

<span class="mw-page-title-main">Diabetic cardiomyopathy</span> Medical condition

Diabetic cardiomyopathy is a disorder of the heart muscle in people with diabetes. It can lead to inability of the heart to circulate blood through the body effectively, a state known as heart failure(HF), with accumulation of fluid in the lungs or legs. Most heart failure in people with diabetes results from coronary artery disease, and diabetic cardiomyopathy is only said to exist if there is no coronary artery disease to explain the heart muscle disorder.

sCAR-Fc is an experimental prophylactic treatment against coxsackievirus B3 (CVB) infections. Coxsackievirus B3 can cause cardiac damage, eventually resulting in a weakened and enlarged heart that is termed dilated cardiomyopathy. While many other treatments inhibit viral proliferation in myocytes, sCAR-Fc prevents the virus entering the cell by competitively binding to coxsackie virus and adenovirus receptors (CAR) on the membrane of myocytes.

Coxsackieviruses-induced cardiomyopathy are positive-stranded RNA viruses in picornavirus family and the genus enterovirus, acute enterovirus infections such as Coxsackievirus B3 have been identified as the cause of virally induced acute myocarditis, resulting in dilated cardiomyopathy. Dilated cardiomyopathy in humans can be caused by multiple factors including hereditary defects in the cytoskeletal protein dystrophin in Duchenne muscular dystrophy (DMD) patients). A heart that undergoes dilated cardiomyopathy shows unique enlargement of ventricles, and thinning of the ventricular wall that may lead to heart failure. In addition to the genetic defects in dystrophin or other cytoskeletal proteins, a subset of dilated cardiomyopathy is linked to enteroviral infection in the heart, especially coxsackievirus B. Enterovirus infections are responsible for about 30% of the cases of acquired dilated cardiomyopathy in humans.

Viral cardiomyopathy occurs when viral infections cause myocarditis with a resulting thickening of the myocardium and dilation of the ventricles. These viruses include Coxsackie B and adenovirus, echoviruses, influenza H1N1, Epstein–Barr virus, rubella, varicella, mumps, measles, parvoviruses, yellow fever, dengue fever, polio, rabies and the viruses that cause hepatitis A and C, as well as COVID-19, which has been seen to cause this in persons otherwise thought to have a "low risk" of the virus's effects.

<span class="mw-page-title-main">Ischemic cardiomyopathy</span> Medical condition

Ischemic cardiomyopathy is a type of cardiomyopathy caused by a narrowing of the coronary arteries which supply blood to the heart. Typically, patients with ischemic cardiomyopathy have a history of acute myocardial infarction, however, it may occur in patients with coronary artery disease, but without a past history of acute myocardial infarction. This cardiomyopathy is one of the leading causes of sudden cardiac death. The adjective ischemic means characteristic of, or accompanied by, ischemia — local anemia due to mechanical obstruction of the blood supply.

Eosinophilic myocarditis is inflammation in the heart muscle that is caused by the infiltration and destructive activity of a type of white blood cell, the eosinophil. Typically, the disorder is associated with hypereosinophilia, i.e. an eosinophil blood cell count greater than 1,500 per microliter. It is distinguished from non-eosinophilic myocarditis, which is heart inflammation caused by other types of white blood cells, i.e. lymphocytes and monocytes, as well as the respective descendants of these cells, NK cells and macrophages. This distinction is important because the eosinophil-based disorder is due to a particular set of underlying diseases and its preferred treatments differ from those for non-eosinophilic myocarditis.

References

  1. ↑ Barbarini G, Barbaro G. Incidence of the involvement of the cardiovascular system in HIV infection. AIDS 2003;17:Suppl 1:S46–50.
  2. ↑ Barbarini G, Barbaro G. Incidence of the involvement of the cardiovascular system in HIV infection. AIDS 2003;17:Suppl 1:S46–50.
  3. ↑ Jain N, Reddy DH, Verma SP, Khanna R, Vaish AK, Usman K, Tripathi AK, Singh A, Mehrotra S, Gupta A. Cardiac Abnormalities in HIV-Positive Patients: Results from an Observational Study in India. J Int Assoc Provid AIDS Care. 2014 Jan-Feb;13(1):40-6.
  4. ↑ Miller TL, Orav EJ, Colan SD, et al. Nutritional status and cardiac mass and function in children infected with the human immunodeficiency virus. Am J Clin Nutr 1997;66:660–4.
  5. ↑ Lemmer CE, Badri M, Visser M, Mayosi BM. A lower body mass index is associated with cardiomyopathy in people with HIV infection: evidence from a case comparison study. S Afr Med J. 2011 Feb;101(2):119-21.
  6. ↑ Barbaro G, Di Lorenzo G, Grisorio B, et al., and the Gruppo Italiano per lo Studio Cardiologico dei pazienti affetti da AIDS Investigators. Cardiac involvement in the acquired immunodeficiency syndrome: a multicentre clinical-pathological study. AIDS Res Hum Retroviruses 1998;14:1071–7.
  7. ↑ Klatt EC. Cardiovascular pathology in AIDS. Adv Cardiol 2003;40:23–48.
  8. ↑ Barbaro et.al., Incidence of Dilated Cardiomyopathy and Detection of HIV in Myocardial Cells of HIV-positive patients, NEJM 2002;347(2):140.
  9. ↑ Braunwald’s, Heart Disease A Textbook of Cardiovascular Medicine, Volume II, 1793-1805.
  10. ↑ Klatt EC, Nichols L, Noguchi TT. Emerging patterns of heart disease in human immunodeficiency virus infection. Hum Pathol 1994;118:884–90.
  11. ↑ Klatt EC, Nichols L, Noguchi TT. Emerging patterns of heart disease in human immunodeficiency virus infection. Hum Pathol 1994;118:884–90.
  12. ↑ Barbaro G, Di Lorenzo G, Grisorio B, et al., and the Gruppo Italiano per lo Studio Cardiologico dei pazienti affetti da AIDS Investigators. Cardiac involvement in the acquired immunodeficiency syndrome: a multicentre clinical-pathological study. AIDS Res Hum Retroviruses 1998;14:1071–7.
  13. ↑ Herskowitz A, Tzyy-Choou W, Willoughby SB, et al. Myocarditis and cardiotropic viral infection associated with severe left ventricular dysfunction in late-stage infection with human immunodeficiency virus. J Am Coll Cardiol 1994;24:1025–32.
  14. ↑ Barbaro G, Di Lorenzo G, Grisorio B, et al., and the Gruppo Italiano per lo Studio Cardiologico dei pazienti affetti da AIDS Investigators. Cardiac involvement in the acquired immunodeficiency syndrome: a multicentre clinical-pathological study. AIDS Res Hum Retroviruses 1998;14:1071–7.
  15. ↑ Fiala M, Popik W, Qiao J-H, et al. HIV-1 induces cardiomyopathy by cardiomyocyte invasion and gp120,Tat, and cytokine apoptotic signaling. Cardiovasc Toxicol 2004;4:97–107.
  16. ↑ Twu C, Liu QN, Popik W, et al. Cardiomyocytes undergo apoptosis in human immunodeficiency virus cardiomyopathy through mitochondrion and death receptor- controlled pathways. Proc Natl Acad Sci USA 2002;99:14386–91.
  17. ↑ Twu C, Liu QN, Popik W, et al. Cardiomyocytes undergo apoptosis in human immunodeficiency virus cardiomyopathy through mitochondrion and death receptor- controlled pathways. Proc Natl Acad Sci USA 2002;99:14386–91.
  18. ↑ Liu QN, Reddy S, Sayre JW, et al. Essential role of HIV-1 infected and cyclooxygenase 2 activated macrophages and T cells in HIV type 1 myocarditis. AIDS Res Hum Retroviruses 2001;17:1423–33.
  19. ↑ Matsumori A. Cytokines in myocarditis and cardiomyopathy. Curr Opin Cardiol 1996;11:302–9.
  20. ↑ Finkel MS, Oddis CV, Jacob TD, et al. Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 1992;257:387–9.
  21. ↑ Yokohama T, Vaca L, Rossen RD, et al. Cellular basis for the negative inotropic effect of tumor necrosis factor alpha in the adult mammalian heart. J Clin Invest 1993;92:2303–12.
  22. ↑ Currie PF, Goldman JH, Caforio AL, et al. Cardiac autoimmunity in HIV related heart muscle disease. Heart 1998;79:599–604.
  23. ↑ Lipshultz SE, Easley KA, Orav EJ, et al. Cardiac dysfunction and mortality in HIV-infected children. The Prospective P2C2 HIV Multicenter Study. Circulation 2000;102:1542–8.
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  25. ↑ Lipshultz SE, Easley KA, Orav EJ, et al. Left ventricular structure and function in children infected with human immunodeficiency virus. The prospective P2C2 HIV multicenter study. Circulation 1998;97:1246–56.
  26. ↑ Lewis W, Grupp IL, Grupp G, et al. Cardiac dysfunction in the HIV-1 transgenic mouse treated with zidovudine. Lab Invest 2000;80:187–97.
  27. ↑ Lewis W, Simpson JF, Meyer RR. Cardiac mitochondrial DNA polymerase gamma is inhibited competitively and noncompetitively by phosphorylated zidovudine. Circ Res 1994;74:344–8.
  28. ↑ Barbaro et.al., Incidence of Dilated Cardiomyopathy and Detection of HIV in Myocardial Cells of HIV-positive patients, NEJM 2002;347(2):140
  29. ↑ Braunwald’s, Heart Disease A Textbook of Cardiovascular Medicine, Volume II, 1793-1805
  30. ↑ Barbaro et.al., Incidence of Dilated Cardiomyopathy and Detection of HIV in Myocardial Cells of HIV-positive patients, NEJM 2002;347(2):140.
  31. ↑ Braunwald’s, Heart Disease A Textbook of Cardiovascular Medicine, Volume II, 1793-1805.
  32. ↑ Barbaro et.al., Incidence of Dilated Cardiomyopathy and Detection of HIV in Myocardial Cells of HIV-positive patients, NEJM 2002;347(2):140.
  33. ↑ Braunwald’s, Heart Disease A Textbook of Cardiovascular Medicine, Volume II, 1793-1805.
  34. ↑ Bijl M, Dieleman JP, Simoons M, et al. Low prevalence of cardiac abnormalities in an HIV-seropositive population on antiretroviral combination therapy. J Acquir Immune Defic Syndr 2001;27:318–20.
  35. ↑ Pugliese A, Isnardi D, Saini A, et al. Impact of highly active antiretroviral therapy in HIV-positive patients with cardiac involvement. J Infect 2000;40:282–4.
  36. ↑ Nzuobontane D, Blackett KN, Kuaban C. Cardiac involvement in HIV-infected people in Yaounde, Cameroon. Postgrad Med J 2002;78:678–81.
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