HIV associated Dilated CardiomyopathyLeonard Sowah, MBChB, MPHAssistant Professor of MedicineUniversity of Maryland School of Medicine

Educational Objectives Relative Magnitude of Dilated Cardiomyopathy in HIV patients Discuss the Pathophysiological Mechanisms involved in this condition Discuss clinical Manifestations Evaluation of patients with suspected Cardiomyopathy Therapeutic Options for HIV associated Dilated Cardiomyopathy Areas of Future Research

Disease Epidemiology Incidence of HIV associated Dilated Cardiomyopathy was 15.9/1,0000 person yrs in the pre HAART era1 HAART therapy has reduced incidence by close to 30% in developed countries2, 3 The adjusted hazard ratio of mortality comparing HIV DCM to Idiopathic DCM is 5.861 Prevalence in Developing countries is about 32%4 1. AIDS 2003; 17: Suppl 1, S46 S50 2. J Infect Dis 2000; 40: 282 -4 3. J. Acquir Immune DeficSyndr 2001; 27: 318 20 4. Postgrad Med J 2002: 78: 678 - 81

Epidemiology Continued 40 52% of patients who died of AIDS in the Pre HAART era had evidence of Myocarditis at autopsy1 In data from the Pre to Early HAART Era median survival in HIV positive children with LV dysfunction was 101 days compared with 472 days in patients with normal hearts2 In a Cohort of Perinatally infected HIV patients the cumulative 5 yr survival was lower in patients with baseline depressed LV fractional shortening3 1. Klatt EC. 2003; Adv Cardiol; 40: 23 - 48 2. N Engl J Med 1998, 339: 1153 1155 3. J Peadiatric 2002, 141: 327 - 334

Etiology Likely related to infection of Cardiac Myocytes by opportunistic organisms DNA Hybridization of cardiac tissue from autopsies of HIV associated DCM reveal Toxoplasmagondi 12 % Coxsackie B3 32% EBV 8% CMV 4% HIV 82% Klatt EC. 2003; Adv Cardiol; 40: 23 - 48

Etiology HIV cardiac muscle auto-immunity, HIV positive patients are 4x more likely to have cardiac auto-antibodies In one study 43% of had cardiac specific auto-antibodies AIDS 2003, 17: S21 S28 Heart 1998, 79: 599 - 604

Nutritional Factors Malabsorption and diarrhea in HIV may lead to micro-nutrient deficiency Selenium replacement may restore LV function in HIV and reverse DCM in selenium deficient patients HIV may be associated with vitamin B12, carnitine, growth hormone and thyroid hormone deficiencies all of which may be associated with LV dysfunction J ClinNutr 1997; 66: 660 - 4

Association with HIV Encephalopathy HIV Encephalopathy is associated with severe LV dysfunction HIV virus persists in myocardial and cerebral viral reservoir even after starting HAART These cells may cause progressive tissue damage by the release of cytotoxic cytokines Fischer SD, Lipschultz SE, Ann NY AcadSci 2001; 946:13 - 22

Clinical Presentation May present as acute myocarditis if seen early Fever with flu-like symptoms Palpitations Atypical chest pain Shortness of breath Am J Emergen Med 2001; 19: 566 - 74

Physical Signs Physical exam may be normal Signs of heart failure may be present Bilateral basal crackles Bi-pedal edema Pericardial friction rub Am J Emergen Med 2001; 19: 566 - 74

Lab Investigations New changes from baseline EKG Usually conduction abnormalities, LBBB, First degree AV block Chest X-ray Cardiomegaly mainly LV Dilatation with rounding of the apex Elevated Cardiac Troponins Occurs in early stages with myocarditis may be confused with a new Myocardial Infarction Increase in CK-MB Am J Emergen Med 2001; 19: 566 - 74

CONDUCTION SYSTEM ABNORMALITIES First degree AV Block Bundle branch Block In one autopsy series 5/12 patients who died of HIV associated DCM had intracardiac conduction abnormalities Histopathology shows myocarditis with fibromatous degeneration of the conduction system AIDS Res Human Retroviruses 1998; 14: 1071 - 77

ECHOCARDIOGRAPHY Echocardiography is the mainstay diagnosis There is Concentric Left Ventricular hypertrophy There is ventricular dilatation Left Ventricular Ejection Fraction is reduced with global hypokinesia Usually no regional wall motion abnormalities AIDS Res Human Retroviruses 1998; 14: 1071 77 Indian Heart J. 2010 Jul-Aug;62(4):330-4

Coronary Angiograms Not required in all cases however in patients with significant CAD risk factors may be helpful. Coronary blood vessels are usually free of significant occlusive atheroscleroctic disease Am J Emergen Med 2001;19: 566 - 74

HISTOPATHOLOGY HIV associated Cardiomyopathy is associated with intense staining for TNF and iNOS (inducible Nitric Oxide Synthase) compared with Idiopathic DCM Other histological features did not differ significantly from idiopathic DCM 1. AIDS Res Human Retroviruses 1998; 14: 1071 - 77

NYHA CLASSIFICATION OF HEART FAILURE American Heart Association

Clinical Management In one Pediatric series patients treated with monthly IV Immunoglobulin infusions were shown to revert back to normal LV wall thickness1 Therapy for LV systolic dysfunction is otherwise the mainstay of management2 1. Circulation 1995,; 92: 2220 25 2. Am J Emergen Med 2001; 19: 566 - 74

Management Patients with systolic dysfunction are treated like standard CHF patients Loop Diuretics Aldosterone Receptor Blockers Ace-Inhibotors B-blockers can be started once patient is euvolemic Digoxin may be added to improve contractility 1. Am J Emergen Med 2001; 19: 566 - 74

Adjunctive Management AICD (Automatic Implantable Cardiac Defibrillators) Can be used in patients with severely depressed LV dysfunction This has not been validated to reduce incidence of sudden cardiac death in the HIV positive population N Engl J Med 2005; 352:225237

USE OF AICD IN HEART FAILURE N Engl J Med 2005; 352:225237

Areas of Future Research Validation of standard CHF therapy in HIV associated DCM ? Data on the efficacy of AICD in HIV associated DCM Use of IV immunoglobulin in early identified adult disease at the early myocarditis stage