HIV and the heart –

latest developments

Mahmoud U. Sani Bayero University Kano & Aminu Kano Teaching

Hospital, Kano state, Nigeria.

Inflammation

Endothelial &

Immune Dysfunction

Coagulation& Platelet Reactivity

HIV

Conventional RF

Dyslipidemia, DM

HTN, Smoking

Obesity

Cardiometabolic Adverse

Effects of ART

CVD

HIV-Related CV Disease

Figure 1. As the frequency of use of antiretroviral therapy, including PIs,

increased in HIV-infected patients, their mortality during this same time period

decreased.

Hsue P Y , Waters D D Circulation 2005;112:3947-3957

Inflammation and Immune Activation

Gut

microbiome

Hypercoagulability Aging

HIV Infection

Hsue, P et al. The Journal of Infectious Disease. 2012; 13: S375-82.

HIV-related CVD – Significant Mortality

• 1,876 deaths among 39,727 patients

• Non-AIDS related deaths accounted for 50.5%

• ~16% were due to CVD

13 HIV Cohorts

1996-2006

CVD

15.7%

Non-AIDS

infection

16.3%

Non-AIDS

Malignancy

23.5%

Violence,

Substance

abuse

15.4%

Liver-related

14.1%

Other

9.0% Respiratory

3.1%

Renal

3%

Antiretroviral Therapy Cohort Collaboration. Clin Infect Dis. 2010;50:1387-1396

Slide courtesy JS Currier

Pericardial disease

HIV Cardiomyopathy/HF

Pulmonary hypertension

Arrhythmias and sudden cardiac death

Hypertension/vascular disease

Coronary artery disease

Malignancies

• Pericardial disease may be the initial manifestation in

the early stage of the illness

• Aetiology of cardiac disease tends to reflect the

prevalent infectious disease like TB

• Association with aneurysm of large vessels

• Constraints in resources makes diagnosis and

management of heart disease difficult 7

1. More than 90% in SSA is from M. Tb ( 50 -70% in HIV –ve, 5% in the developed world)

2. HIV infection causes a higher prevalence & more severe myopericardial disease with a higher mortality,

3. HIV infection lead to lower rate of progression to constriction, due to altered pericardial immunology .

4. Mortality is higher compared to uninfected patients

5. Role of adjunctive steroids :

– The IMPI Trial was a definitive study that answered this question

HIV and Pericardial disease

Complete hospital discharge form and arrange visits at weeks 2, 4 and 6, and months 3, 6 and

thereafter 6 monthly for 2 years and then annually for 4 years to assess mortality,

recurrent tamponade, constriction

Placebo X 5 Doses

PATIENTS WITH DIFINITE OR PROBABLE TUBERCULOUS PERICARDIAL EFFUSION

RANDOMIZATION

PREDNISOLONE

X 6 weeks

PLACEBO

X 6 weeks

Mycobacterium w X 5 Doses

Placebo X 5 Doses

Mycobacterium w X 5 Doses

IMPI Trial: Study Design

0.5 2Prednisolone

BetterPlacebo Better

Primary efficacy outcome

Death

Tamponade

Constriction

Hospitalization

Opportunistic infection

Malignancy

AE, Not Hospitalized

Injection side effect

Prednisolone Placebo Hazard Ratio (95% CI) P

N(%) N(%)

168 (23.8) 170 (24.5 ) 0.95 (0.77 - 1.18 ) 0.66

133 (18.8) 115 (16.6 ) 1.15 (0.90 - 1.48 ) 0.26

22 ( 3.1 ) 28 ( 4.0 ) 0.77 (0.44 - 1.35 ) 0.37

31 ( 4.4 ) 54 ( 7.8 ) 0.56 (0.36 - 0.87 ) 0.01

146 (20.7) 175 (25.2 ) 0.79 (0.63 - 0.99 ) 0.04

78 (11.0) 68 ( 9.8 ) 1.16 (0.84 - 1.61 ) 0.36

13 ( 1.8 ) 4 ( 0.6 ) 3.27 (1.07 - 10.03 ) 0.03

171 (24.2) 149 (21.5 ) 1.15 (0.93 - 1.44 ) 0.20

140 (19.8) 137 (19.7 ) 0.98 (0.77 - 1.24 ) 0.84

Effect of Prednisolone on Outcomes

IMPI: Time To Malignancy

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HIV Associated Cardiomyopathy

• HAART caused a 50% in HIV- CMP in

developed countries

• By contrast, 32% in HIV- CMP in

developing countries

• Low rates of HIV-CMP in series with high

uptake of HAART

• HAART improves deterioration in patients

with established HIV-CMP but does not

reverse cardiac function

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HIV Associated Cardiomyopathy

• Malnutrition has been postulated to be a

contributory factor In Africa

• Role of genetic factors largely unknown

• HIV is an unlikely risk factor for PPCM in

the era of widespread HAART use

• HIV infected women had similar 2 year

prognosis with uninfected PPCM patients

• Dobutamine stress echo was found to be

incremental to NYHA class in risk

stratifying patients for cardiac death. 15

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HIV Associated HF

• HIV infected patients usually have HF diagnosed in

the third decade

• HF in HIV usually often women.

• Systolic and diastolic dysfunction are both more

common (30% prevalence) in HIV than in controls

• Rarely, diastolic dysfunction is more prevalent

• Ventricular dimensions and volumes are large in

HIV patients with HF in SSA

• Early detection of subclinical myocardial dysfunction,

can be made by 2-dimensional strain and strain rate

using speckle tracking

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HIV and Diastolic Dysfunction

• LVSD is currently less common among HIV infected

patients with HF in high-income countries

• Diastolic dysfunction is present in up to 64% of

asymptomatic HIV patients on HAART in high-income

countries

• Diastolic dysfunction appears to be independent of

traditional risk factors including age and hypertension

• DD is often the only echo abnormality found in

asymptomatic HIV infected patients

• Mechanisms poorly understood - but may involve

direct myocardial effects of HIV, occult CAD, cardiac

fibrosis

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10% of 5328 patients with de novo heart disease were HIV

+ve

38% had HIV assoc CMP (LVEF 46%),25% had pericarditis/

pericardialeffusion, 8% had HIV related PAH

2.4% had CAD ( mean age of 41 years) 21

Primary diagnosis of all human immunodeficiency virus-positive

cases (n = 518).

Sliwa K et al. Eur Heart J 2012;33:866-874

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author

2011. For permissions please email: journals.permissions@oup.com

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HIV Associated HF

• In THESUS HF Compared with patients with

emerging causes of HF, those with endemic

causes of HF (including HIV):-

• were younger by 10 to 15 years

• were less often smokers, hypertensive, or diabetic,

• had larger LV systolic and diastolic dimensions

• Had slightly longer lengths of hospital stay (9.8 vs.

8.7 days), higher in-hospital mortality (28% vs. 14%),

60-day mortality (13% vs. 9.0%), and 180-day

mortality (21% vs. 16%)

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HIV related PAH

• Prevalence is 0.5% (vs. 0.02% in general population)

• Reported in 30% of cases of isolated PAH and 8.1 %

of de novo presentations of HIV-associated CVD

• No apparent association with CD4 cells or viral load

• Pulmonary vessel endothelial cell proliferation

triggered by cytokines – endothelin 1 IL-6, TNF alpha.

• Certain ARVs may paly a role by causing endothelial

dysfunction through endothelial NO synthase down

regulation and superoxide anion production

• More rapidly progressive than IPAH; poorer prognosis

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This is probably the first histologically confirmed case of PAH associated

with HIV and pregnancy in Africa. The authors raised the following issues:

1. The question of antenatal screening for HIV +ve pregnant patients for PAH

with echo or BNP

2. The consideration of diagnosis of PAH in all pregnant HIV +ve patients

with dyspnoea, signs of right heart failure and clinically normal lung

3. The need for research to establish the clinical epidemiology and

appropriate management of PAH in HIV +ve pregnant patients

HIV Infection, pulmonary arterial hypertension and

pregnancy: a fatal triad

Nyo MTL, Schoeman L, Sookhayi R, Mayosi BM

(CVJA 2012; Vol 23, No 7)

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• HIV infection and ART treatment are both associated

with differences in cardio-metabolic traits compared

with HIV-uninfected or ART-naive patients in SSA.

• Further research aimed towards the development of

specific guidelines for assessment and management

of cardiometabolic risk in HIV-infected individuals in

the region.

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Acute Coronary Syndromes in Treatment-

Naïve Black South Africans with Human

Immunodeficiency Virus Infection

Becker AC et al J Interv Cardiology 2010

• Younger ( 43yrs Vs 54yrs)

• Smokers (73% Vs 33%)

• Less HTN (23% Vs 77%)

• Less DM ( 3% Vs 23%)

• Lower LDLc ( 2.2 Vs 3.0)

• Lower HDL Cholesterol (0.8 Vs 1.1)

• Less atherosclerotic burden with more normal infarct

related vessel (47% Vs 13%)

• Higher large thrombus burden (43% Vs 17%)

• More target lesion revascularization

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HIV and Coronary Artery disease

• Picture in SSA different from the developed

world

• Clinical profile of HIV patients with acute MI

was not influence by HAART

• More studies needed to explain lack in

increase in CAD following increased use of

HAART in SSA

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(J Natl Med Assos 2005; 97:1657 – 1661)

QT Prolongation and Sudden Death

• HIV infection was associated with a 4.5-fold higher

than expected rate of SCD

• Conduction abnormalities in HIV is being increasingly

recognized.

• HIV infection is independently associated with QT

prolongation, more marked in those with hepatitis C

coinfection

• PIs and Other medications e.g. macrolides antifungals

pentamidine may play a role.

• 20 percent of individuals with HIV in developed

countries may have prolonged QT, more in women,

those with CAD risk factors. 36

• Better understanding of HIV related CVD in SSA

• TB pericarditis carries a high mortality despite therapy.

• Few feasible options for management of HRPH

• Few targeted therapies available for HIV-CMP &

vasculopathy

• CAD from ART still not common on the continent

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Summary

• HIV increases risk of CVD 1.5-2X

• Metabolic changes associated with HIV and HAART

have not shown increase in CAD in Africa

• As the population with HIV ages with HAART, and

lifestyle-associated coronary risk factors increase, this

may change

• Early detect and treat other co-morbidities that

increase CVD risk in all patients

• Minimized modifiable CVD risk factors i.e. smoking

• Integrate CVD and HIV care; add CV outcomes to

HIV trials, increase enrollment of HIV patients in CV

trials

Thank you for your attention

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