HIV associated Dilated Cardiomyopathy

Leonard Sowah, MBChB, MPHAssistant Professor of MedicineUniversity of Maryland School of Medicine

Educational ObjectivesRelative Magnitude of Dilated Cardiomyopathy in

HIV patientsDiscuss the Pathophysiological Mechanisms

involved in this conditionDiscuss clinical Manifestations Evaluation of patients with suspected

Cardiomyopathy Therapeutic Options for HIV associated Dilated

CardiomyopathyAreas of Future Research

Disease EpidemiologyIncidence 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 – S502. J Infect Dis 2000; 40: 282 -4 3. J. Acquir Immune Defic Syndr 2001; 27: 318 – 204. Postgrad Med J 2002: 78: 678 - 81

Epidemiology Continued40 – 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 - 482. N Engl J Med 1998, 339: 1153 – 11553. J Peadiatric 2002, 141: 327 - 334

EtiologyLikely related to infection of Cardiac

Myocytes by opportunistic organismsDNA Hybridization of cardiac tissue

from autopsies of HIV associated DCM reveal

• Toxoplasma gondi – 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 – S28Heart 1998, 79: 599 - 604

Nutritional FactorsMalabsorption 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 Clin Nutr 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 Acad Sci 2001; 946:13 - 22

Clinical PresentationMay present as acute myocarditis if

seen earlyFever with flu-like symptomsPalpitationsAtypical chest painShortness of breath

Am J Emergen Med 2001; 19: 566 - 74

Physical SignsPhysical exam may be normalSigns of heart failure may be presentBilateral basal cracklesBi-pedal edemaPericardial friction rub

Am J Emergen Med 2001; 19: 566 - 74

Lab InvestigationsNew changes from baseline EKG

Usually conduction abnormalities, LBBB, First degree AV block

Chest X-rayCardiomegaly mainly LV Dilatation with

rounding of the apexElevated Cardiac Troponins

Occurs in early stages with myocarditis may be confused with a new Myocardial Infarction

Increase in CK-MBAm J Emergen Med 2001; 19: 566 - 74

CONDUCTION SYSTEM ABNORMALITIES

First degree AV BlockBundle branch BlockIn 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 systemAIDS Res Human Retroviruses 1998; 14: 1071 - 77

ECHOCARDIOGRAPHYEchocardiography is the mainstay

diagnosisThere is Concentric Left Ventricular

hypertrophyThere is ventricular dilatationLeft Ventricular Ejection Fraction is

reduced with global hypokinesiaUsually 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

HISTOPATHOLOGYHIV associated Cardiomyopathy is

associated with intense staining for TNF α 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 ManagementIn 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 – 252. Am J Emergen Med 2001; 19: 566 - 74

ManagementPatients with systolic dysfunction

are treated like standard CHF patients

Loop DiureticsAldosterone Receptor BlockersAce-InhibotorsB-blockers can be started once

patient is euvolemicDigoxin may be added to improve

contractility1. 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; 352:225–237

USE OF AICD IN HEART FAILURE

N Engl J Med 2005; 352:225–237

Areas of Future ResearchValidation of standard CHF

therapy in HIV associated DCM ?Data on the efficacy of AICD in

HIV associated DCMUse of IV immunoglobulin in early

identified adult disease at the early myocarditis stage