Cardiac Manifestations of HIV Patients

NON INVASIVE CARDIAC WORK UP OF HIV POSITIVE PATIENTS

Ponangi Udaya Prashant Consultant, GLOBAL Hospitals, Hyderabad Email: [email protected]

J.J GROUP OF HOSPITALS DISSERTATION SUBITTED FOR THE DEGREE OF D.M. CARDIOLOGY EXAMINATION (BRANCH II), UNIVERSITY OF MUMBAI May 2008,

INTRODUCTION HIV aptly called plague of modern era has spread throughout the world in matter of few decades and is now a global pandemic, with cases reported from virtually every country. According to the Centres for Disease Control and Prevention (CDC), the case definition of AIDS is (1) HIV-infected individuals who have 500.

Stage 2

= CD4 count 200-499.

Stage 3

= CD4 count 500/µL

A1

B1

C1

200-499/µL

A2

B2

C2

< 200/µL

A3

B3

C3

Chest X ray in PA view and standard 12 lead electrocardiograms were obtained for all the patients. Chest roentgenogram was interpreted as normal, cardiac abnormality, pulmonary abnormality or both. Cardiothoracic ratio of more than 50% was taken as criteria for diagnosing cardiomegaly on X ray. ECG was studied for abnormalities in rate, rhythm, P wave, QRS complex, T

wave and U wave. PR interval, QT & RR interval abnormalities and ST segment deviations were looked for. ECHOCARDIOGRAPHY: We used SEIMENS ACCUSON Sequoia C 520 Ehocardiography machine with 3.5 and 5.0 MHz transducers. Transthoracic echocardiography done with subjects in left lateral decubitus position. Detailed echocardiography was done as per convention using standard 2D imaging, M mode, Colour, Pulse and Continuous Doppler. The patients were evaluated for left and right ventricular systolic function in the form of fractional shortening and ejection fraction. Left and right ventricular dimensions recorded and compared with normal values for age and sex21. Other abnormalities like diastolic dysfunction, valvular abnormalities, PAH, vegetations, effusions are specifically looked for

ECHOCARDIOGRAPHIC CRITERIA21 Following Echocardiographic Criteria were used for diagnosis of respective cardiac conditions •

Dilated cardiomyopathy

Global LV hypokinesia with LV end systolic diameter >55mm and fractional shortening 12 gm. 12 patients had minor auscultable physical findings and majority were normal clinically.

.

TABLE 9: DISTRIBUTION OF PATIENTS IN DIFFERENT BMI GROUPS: N=96 BMI

No of Patients

Percentage %

30

2

2

Most of patients (70%) were in normal BMI range group between 18-25, 24% were underweight i.e. BMI < 18, 3% belonged to overweight and 2% obese group.

TABLE 10: ABNORMAL X RAY FINDINGS N=96 X RAY ABNORMALITY

NO. OF PATIENTS

PERCENTAGE

NORMAL X RAY

78

82

CARDIOMEGALY

4

4

OTHER CARDIAC FINDINGS

3

4

PULMONARY PATHOLOGY

9

9

BOTH CARDIOPULMONARY PATHOLGY

2

2

64 (66%) patients had normal ECG findings and rest had minor ECG changes. 8 patients had right axis deviation and non specific T inversions, 2 had VPC`S, 4 had bundle branch blocks and 5 had early repolarisation abnormalities. 82% had normal x-ray findings and 4 patients had cardiomegaly out of which 2 patients were found to have dilated cardiomyopathy ( Table 10:, Figure: 7)

ECHOCARDIOGRAPHY TABLE 11: ECHOCARDIOGRAPHY FINDINGS OF HIV PATIENTS AND INFLUENCE OF HAART N=45 CARDIAC DISEASE

TOTAL patients

No patients on HAART

p value

DILATED CARDIOMYPATHY

4 (6%)

2

0.634

PERICARDIAL DISEASE

14 (21%)

8

0.748

LV SYSTOLIC DYSFUNCTION

15 (23%)

9

0.66

LV DIASTOLIC DYSFUNCTION

16 (24%)

10

0.9252

PULMONARY HYPERTENSION

9 (14%)

4

0.303

RV DYSFUNCTION

8 (12%)

5

0.747

Out of 96 patients examined 45 (46.8%) patients had positive ECHO findings. The commonest echocardiography finding in our study was diastolic dysfunction, which was present in 16 (24%) patients. Next common abnormality was LV systolic dysfunction not associated with much dilatation or regional wall motion abnormality. Some of them had increased myocardial thickness with poor contractility. Only one patient had very poor left ventricular function (20%) and others had mild to moderate impaired LV function Pericardial effusion was detected in 14 (21%) patients. 3 patients had moderate effusion and rest had mild pericardial effusion. Frank dilated cardiomyopathy occurred in only 4 (6%) patients, which was less common than idiopathic pulmonary hypertension 9 (14%) patients, or isolated RV dysfunction 8 (12%) patients.

The pulmonary hypertension and RV

dysfunction could not be attributed to pulmonary or left heart abnormality. One patient had severe mitral stenosis due rheumatic heart disease. 57% of patients with positive ECHO findings were on HAART regimes and others were not. There was no statistical difference between those patients on HAART and those who were not with respect to any of the echocardiography findings. Table 12: Influence of Duration of HIV illness and ECHO findings N=96 CARDIAC DISEASE

< 1 year n = 24

DILATED CARDIOMYPATHY

2

1-5 years n =59 1

>5y ears n=12 1

Total

P value

4

0.35

PERICARDIAL DISEASE

3

8

3

14

0.727

LV SYSTOLIC DYSFUNCTION

7

6

3

16

0.102

LV DIASTOLIC DYSFUNCTION

6

8

2

16

0.484

PULMONARY HYPERTENSION

6

4

0

9

0.02

RV DYSFUNCTION

4

4

0

8

0.18

Patients were categorised into 3 groups depending upon known HIV illness duration. The incidence of abnormal cardiac findings were more frequently detected in those with symptom duration < 1 year (n=30) than when compared to other groups, second group with symptom duration between 1 – 5 years (n=53) and last one with illness duration >5 years (n=13). However the numbers did not achieve statistical significance. Only PAH was significantly association with duration of illness (p = 0.02) occurs more commonly in those with lesser duration of illness.

TABLE 13: RELATIONSHIP OFECHOCARDIOGRAPHY FINDINGS AND CD4 COUNTS N=45 CARDIAC DISEASE

Category 1 CD4

Category N= 42

Category 3 N =28

Total

P value

0

0

4

4

0.006

PERICARDIAL DISEASE

4

5

5

14

0.8

LV SYSTOLIC

1

10

5

16

0.08

2

9

5

16

0.31

1

4

4

9

0.424

1

2

5

8

0.09

DILATED CARDIOMYPATHY

DYSFUNCTION LV DIASTOLIC DYSFUNCTION PULMONARY HYPERTENSION RV DYSFUNCTION RHD MS

1

On subgroup analysis of various echocardiography findings with CD4 count, only dilated cardiomyopathy was associated with low CD4 count (p = 0.006) whereas other ECHO findings did not achieve statistical significance.

TABLE 14: STRESS TEST RESULTS N=96 STRESS TEST RESULT

No of Pateints

Percentage %

Negative

68

71

Not done

14

15

Positive

8

8

Terminated early

6

6

Eight patients had positive stress test among, 15 patients not done and 6 patients terminated early because of poor effort tolerance. 67 patients had negative test. The positive yield of the stress test was approximately 10%. Average METS achieved by HIV patients was 10.13 (SD 2.32). Average work duration of exercise of HIV patients was 10.57(SD 2.23) minutes. The average heart rate of the subjects was 153 bpm. 92 % of patients achieved target heart rate. Average BP recorded of the subjects during stress test was 140/88 mm Hg. Out of 8 patients 3 had history of angina and 5 patients had no symptoms of angina. There were no significant differences between stress test positive and those with negative groups, with respect to age group, BMI, duration of illness, CD4 count or lipid profile status.

TABLE 15: LIPID LEVELS IN HIV PATIENTS N=85 Type of cholestrol

Mean value of

Mean value of not

patients on

on HAART

p value

HAART Total cholestrol

170

184

0.146

Total triglycerides

147

142

0.824

LDL cholestrol

102

120

0.018

HDL cholestrol

40

39

0.958

VLDL cholestrol

27

25

0.61

85 HIV patients had complete lipid profile. 52 patients were found to have dyslipidemia i.e. 61% of our HIV patients were found to be dyslipidemic. 57% of the dyslipidemic patients were receiving HAART, whereas rest were not on any antiretroviral drugs. None pf the patients were found to have lipodystrophy. The mean values of various lipids in two groups, those who were on ART drugs and those who were not, are similar except LDL cholesterol which was lower in HAART group (mean 102 vs 120; p = 0.018)

TABLE 16: INCIDENCE OF DYSLIPIDEMIA IN HIV PATIENTS N=85 Cholesterol Levels

Total no of

No on

p value

patients

HAART

Hypercholestremia

6 (8%)

2

0.13

Low HDL

45 (62%)

27

0.419

High LDL

7 (10%)

2

.06

Hypertriglyceridemia

9 (12%)

6

.417

High VLDL

6 (8%)

4

0.7

. The commonest lipid abnormality found was low HDL (62%) followed by hypertriglceridemia (12%), high LDL cholesterol (10%), high VLDL cholesterol (8%) and hypercholestremia (8%). There were no statistically significant differences in numbers between those who were on HAART and those who were not on antiretroviral drugs.

DISCUSSION The heart is an organ frequently affected in patients with AIDS. Researchers have demonstrated cardiac involvement in as many as 28%– 73% of patients infected with HIV3,8,9,11 Cardiac involvement generally occurs in the latter stages of the disease but can occur at any point. Although it can be clinically silent or masked by other comorbid diseases and demonstrated only by echocardiography or at autopsy, cardiac involvement can result in significant

cardiac

morbidity

and

mortality.

In

1996,

the

estimated

prevalence’s of a significant cardiac morbidity or cardiac mortality among HIVpositive patients were 6%–7% and 1%–5%, respectively34. During the period of one year total of 96 clinically stable patients attending JJ ART Centre OPD were randomly selected and enrolled into the study. The total no of male patients were 70 (73%) and females were 26 (27%). Patients belonged to age group between 18 years to 60 years with average age of being 36.5 years. The mean duration of illness is 2 years and majority belonged to Category 2 with CD4 count in range of 200- 499. 60% of patients were on HAART and the commonest regime is SLN. 47% of our study patients had positive ECHO findings. Himelman33 and colleagues showed echocardiographic abnormality in 64% of admitted HIV patients. De Casto8 et al in 1992 studied 72 AIDS patients and found that 47 (65.2%) presented with cardiac involvement. However some studies showed a lower prevalence of heart disease. Steffen43 and colleagues reported 21% prevalence of heart disease in HIV infected patients. Among

those patients with positive ECHO findings, many of them had non specific complaints of minor degree and even ECG, Chest X-ray were not suggestive of significant cardiac disease in these cases Electrocardiographic changes were of little clinical relevance. In one multicenter trial, 57 percent of asymptomatic HIV infected individuals had baseline abnormalities on ECG including supraventricular and ventricular ectopic beats. The chest radiogram has low sensitivity and specificity for congestive heart failure72. Our study showed 44% of patients had minor ECG changes and 6 percent had cardiac findings on chest X-ray. So we conclude that Echocardiography was very useful in detecting cardiac abnormalities in HIV patients even when clinical pointers for cardiac disease are not very significant

STUDY

PE

SYSTOLIC DSFUNCTION ECHO

DE Casto8

18%

5.5%

Himelman33

10%

Cuire36 et al Barbaro73 et al

PAH

12%

1%

15%

16%

21%

DCM

RVD

11% 7%

Cardoso75 JS Present study

DD

4%

8% 16.4%

64%

23%

24%

2% 6%

9%

8%

The incidence of pericardial effusion in patients with asymptomatic AIDS (defined as patients with CD4 count 5 year duration of illness, but none of our patients were on protease inhibitors. Therefore these patients are likely to have abnormal cardiovascular risk status. Results from D:A:D Study indicate that incidence of MI increases 26% per year of exposure to HAART10 but none of our patients had history, ECG or ECHO evidence of myocardial infarction.

Out of 85 patients who had complete lipid profile and 61% had dyslipedemia which is similar to several other several studies55-59 indicating that incidence of dyslipidemia is very common in HIV patients (44%-66%). The commonest lipid abnormality observed was low HDL cholesterol (62%) followed by hypertriglceridemia (12%). Carr et al reported elevated total cholesterol levels, defined as greater than 5.5 mmol/L, in 58% of patients receiving protease inhibitors vs 11% of those not receiving them; elevated triglycerides, defined as greater than 2.0 mmol/L, were seen in 50% of patients receiving these drugs vs 22% of those not receiving them55. Segerer et al, in another study, reported a 15% increase in total cholesterol and a 25% increase in triglycerides after 3 to 6 months of protease inhibitor therapy64 . Our study showed (Table 15; Fig 11) that mean total cholesterol level is lower in HAART group than non drug group (170 vs 184). Mean triglycerides and LDL cholesterol were also low in HAART group whereas mean HDL and VLDL levels are higher. Only LDL cholesterol was significantly lower in HAART group than non drug group (p = 0.018) Dyslipidemia has been seen in patients with HIV infection, even prior to use of protease inhibitors and has been linked both to HIV infection and to ART. In untreated HIV infected patients, lower CD4 counts are associated with lower total blood cholesterol, lower HDL cholesterol, and higher triglyceride levels67. Total and LDL cholesterol decreased after the onset of HIV disease, but rose to preinfection levels or higher with ART, while HDL cholesterol levels decreased markedly after the onset of HIV and did not recover. Furthermore, an early placebo-controlled study of zidovudine monotherapy reported declines in both IFN-α and triglycerides in patients

taking zidovudine56. This may be the likely reason why no significant elevation of lipids is seen in HAART group. Dyslipidemia is an important risk factor for atherosclerotic coronary heart disease and the high prevalence of dyslipidemia (61% in our study) and improved survival of AIDS patients, indicates these patients must be investigated more often and treated early to prevent adverse cardiovascular events in future.

LIMITATIONS This is an observational study and there are no matched controls of normal population to compare.

There is no follow up to determine the long term effects on mortality and morbidity in HIV patients of the cardiac abnormalities detected.

Sample size is relatively small especially for the individual cardiac abnormalities detected.

ART regimes used in JJ Hospital do not contain protease inhibitors and therefore

SUMMARY Total of 96 clinically stable HIV patients not known to have any prior cardiac illness were studied, which included 70 male patients and 26 female patients. The average age of patients was 36.7±8 years.

37 % of patients had insignificant cardiac complaints often nonspecific involving other systems also.

60 % of patients were on some HAART regime, the commonest being SLN regime. Routine 12 lead ECG and chest X ray were not very sensitive in detecting cardiac abnormalities in HIV patients.

47% had some cardiac abnormality detected echocardiographically, commonest being diastolic dysfunction followed by impaired LV function, pericardial effusion, PAH, isolated RV dysfunction and least dilated cardiomyopathy. The

positive

echocardiographic

findings

were

not

significantly

influenced by duration of illness or CD4 counts except for dilated cardiomyopathy, which was strongly associated with CD4, count < 200.

HAART regimes used in JJ hospital had no influence on any of the echocardiographic abnormalities detected.

Exercise testing was positive in 10 % of HIV patients tested, which is higher than general population prevalence constituting high risk group for coronary artery disease. Dyslipidemia is widely prevalent in HIV patients (61%) even when patients are not on any protease inhibitors.

The commonest lipid abnormality detected was low HDL cholesterol (62%) followed by hypertrigliceredemia (12%).

HAART regimes used in JJ Hospital did not significantly influence the lipid levels in except for LDL cholesterol.

CONCLUSIONS Cardiovascular complications are very common in HIV patients, especially after introduction of HAART. ECHO, exercise testing and lipid profiles are useful to detect cardiac complications early and should be performed routinely when indicated.

FIGURE 1:

SEX RATIO

FEMALE 27% MALE

MALE 73%

FEMALE

AGE SEX DISTRIBUTION 40 35 35

NO OF PATIENTS

30 25 MALE

19

20

FEMALE

15 11 10

8

8 6

5

5 2

0 20- 29

30 39 30-

40- 49 AGE GROUPS

50- 60

FIGURE 2:

FIGURE 3:

DURATION OF HIV ILLNESS

18

in years

>5

53

1–5

Total No Patients

24

500) Category 2 (CD4 = 499499 200) Category 3 (CD4 5 y ears n=13

LV SYSTOLIC DYSFUNCTION

1-5 years

PERICARDIAL DISEASE

< 1 year

DILATED CARDIOMYPATHY

0

0

FIGURE 10:

INCIDENCE OF CARDIAC DISEASES BASED ON CD4 COUNT 10 10

9

9 8 7 6

5 5

No fo patients 5

4

5

5

5

4

4 4

4 3

2

2 1

2

1

1

CD4 COUNT >500

1

0 0 RV DYSFUNCTION

PULMONARY HYPERTENSION

LV DIASTOLIC DYSFUNCTION

LV SYSTOLIC DYSFUNCTION

PERICARDIAL DISEASE

DILATED CARDIOMYPATHY

0

Cardiac disease

FIGURE 11: MEAN LIPID LEVELS IN HIV PATIENTS

200 180

184 170 147 142

160

120

140 102

120 100 80 60

40 39

40

27 25

20 0 Total cholestrol

Total triglycerides

LDL cholestrol

HDL cholestrol

VLDL cholestrol

CD4 COUNT 500-200 CD4 COUNT