|Year : 2019 | Volume
| Issue : 4 | Page : 156-160
A study of cardiac dysfunction in human immunodeficiency virus-infected patients and its correlation with cd4 count
Vinay Tuteja Junior Resident 1, CL Nawal Senior Professor 1, CB Meena Senior Professor 2, Aradhana Singh Associate Professor 1, RS Chejara Associate Professor 1, Rajbeer Singh Junior Resident 1, Pradeep Kumar Bansal Junior Resident 1
1 Department of Internal Medicine, SMS Medical College, Jaipur, Rajasthan, India
2 Cardiology, SMS Medical College, Jaipur, Rajasthan, India
|Date of Web Publication||6-Jan-2020|
Dr. Pradeep Kumar Bansal
Room No. F.38, Resident Doctor Hostel, SMS Medical College, JLN Marg, Jaipur . 302 004, Rajasthan
Source of Support: None, Conflict of Interest: None
Introduction: Human immunodeficiency virus (HIV) is an infectious disease, leading to rapid failure of the immune system. Since the introduction of combination antiretroviral therapy (ART), it has led to a substantial decrease in the incidence of AIDS-related conditions and all-cause mortality over time. However, clinical chronic nonAIDS conditions including cardiovascular disease are on a rise with the prolonged life expectancy of HIV-infected patients. Study Design: The study design involves hospital-based observational comparative analysis.Materials and Methods: A total of 200 individuals, including 100 infected with HIV and 100 controls, were taken after ruling out the various exclusion factors. Cases were further scrutinized on the basis of CD4 count and duration of highly active ART. Every patient underwent a battery of tests, and also various echocardiography parameters were recorded and analyzed carefully. Results: Male:female ratio in cases and controls was 3.3:1. Cases were divided according to CD4 count, as patients having CD4 <200/200–350/>350. The mean CD4 count was 108.47 ± 36.51/277.85 ± 46.73/576.63 ± 195, respectively. Forty-one percent of individuals had abnormal electrocardiography findings, pulmonary hypertension (PH) was found in 10% of patients, and also three patients (30%) had a moderate grade of PH. Twenty-seven percent had minimal pericardial effusion. Among cases, the mean ejection fraction observed was 54.68% ± 6.82% which was significantly lower than controls (60.72% ± 1.47%). Left ventricular diastolic dysfunction was seen in 46% of cases as compared to 3% controls. Conclusions: This study indicates that cardiovascular abnormalities are more common in HIV-infected patients than the normal population. Even asymptomatic patients had abnormal echocardiographic findings. Echocardiography is a useful noninvasive technique for the early recognition of cardiac dysfunction in such patients.
Keywords: Highly active antiretroviral therapy, human immunodeficiency virus, left ventricular diastolic dysfunction, pericardial effusion, pulmonary hypertension
|How to cite this article:|
Tuteja V, Nawal C L, Meena C B, Singh A, Chejara R S, Singh R, Bansal PK. A study of cardiac dysfunction in human immunodeficiency virus-infected patients and its correlation with cd4 count. J Clin Prev Cardiol 2019;8:156-60
|How to cite this URL:|
Tuteja V, Nawal C L, Meena C B, Singh A, Chejara R S, Singh R, Bansal PK. A study of cardiac dysfunction in human immunodeficiency virus-infected patients and its correlation with cd4 count. J Clin Prev Cardiol [serial online] 2019 [cited 2020 Feb 22];8:156-60. Available from: http://www.jcpconline.org/text.asp?2019/8/4/156/275162
| Introduction|| |
<Human immunodeficiency virus (HIV) is an infectious disease, which causes rapid fall in the body's immune system, thus making way for life-threatening opportunistic infections and cancers into the body. About 36.9 million people are living with HIV around the world; there were about 1.8 million new cases of HIV in 2017. An estimated 35 million people have lost their lives from AIDS-related illnesses so far. Situation in India is no different than the rest of the world; during 2017, new HIV infections reported were 88,000, and HIV incidence/1000 population was 0.1.
Recognized in 1981, since then much has been discovered about the pathophysiology, transmission of virus, and treatment of HIV. With many new modalities of treatment, the life expectancy of people living with HIV/AIDS has improved dramatically.,,, While many noninfective diseases have unfolded in these individuals; cardiovascular disease is found to be on the top (28%–73%). The benefits of highly active antiretroviral therapy (HAART) have thus been indisputable in high-resource settings, as HIV has gone from being a disease with a fatal discourse to primarily a chronic condition. NonAIDS cancers and liver-related diseases are among other most prevalent noninfective causes of death in HIV patients.,
The cardiac involvement in HIV-infected patients can occur due to a variety of causes; HIV infection itself, opportunistic infections such as viruses, fungi, and protozoa or side effects of antiretroviral drugs, and a combination of these factors. Various cardiac abnormalities reported in HIV-infected patients are dilated cardiomyopathy, pericarditis, pericardial effusion (PE), pulmonary hypertension (PH), vascular diseases, and various fatal arrhythmia.
In developing countries as India, the data about cardiovascular involvement in HIV are very limited, and not much literature about the pattern of disease is available. Hence, we conducted a study to look for the various cardiac diseases in HIV-infected patients in comparison to healthy individuals, and also to study the relation between the CD4 count and frequency of the cardiac involvement.
| Materials and Methods|| |
One hundred HIV-infected patients of age years were included in this study. Clinical assessment, electrocardiography (ECG), chest radiography, and Doppler echocardiographic examination were done. Hemoglobin measurement, CD4 count, erythrocyte sedimentation rate, and routine serum biochemistry analysis were also done. Patients with hypertension, Type 2 diabetes mellitus, ischemic heart disease, rheumatic heart disease, and congenital heart disease were excluded from the study.
One hundred HIV-negative individuals served as controls. They were recruited after voluntary screening in the HIV clinic side laboratory to confirm their negative status. They were recruited to match the age and gender of HIV cases.
Two-dimensional (2D), M-mode, pulse-wave, continuous-wave, and color Doppler echocardiography assessment were done with the patient in the left lateral decubitus position. The 2D images were obtained in the parasternal long- and short-axis views, apical, and subcostal views.
Ejection fraction (EF) (%), left atrium diameter (mm), left ventricular end-diastolic dimension (mm), right ventricular outflow tract, left ventricular end-systolic diameter, and left ventricular end-diastolic diameter were obtained from 2D directed, M-mode recordings from the parasternal long axis. The mean of three measurements was recorded.
Doppler studies included pulmonary velocity, aortic velocity, transmitral flow, right ventricular systolic pressure, and deceleration time (DT) measurements. Pulse-wave Doppler was used for measuring isovolumetric relaxation time.
EF <60% was considered as abnormal, diastolic dysfunction grading done on the basis of E/A ratio and DT; diastolic dysfunction was categorized into three grades, namely Grade 1 defined as E/A ratio <0.75, Grade 2 defined as E/A ratio >1, DT <140 ms, and Grade 3 defined as E/A ratio >2, DT <140 ms. The mean pulmonary artery pressure (mPAP) was calculated from the initial peak velocity of the pulmonary regurgitation (PR) spectrum and adding the right atrial pressure (RAP) to it (mPAP = 4 [PR peak velocity]2 + RAP). PH was categorized into three severity grades, namely mild defined as mPAP between 25 and 34 mmHg, moderate defined as mPAP between 35 and 44 mmHg, and severe defined as mPAP mmHg.
Echocardiographic abnormalities, for example, PE, thickening, separation, valvular lesions such as stenosis, and regurgitations and regional wall-motion abnormalities were also looked for. Data were analyzed statistically on the SPSS 17 (IBM, Armonk, New York, USA); paired t-test, the Chi-square test, and ANOVA test were used. P < 0.05 was considered statistically significant.
| Results|| |
One hundred patients with HIV infection, hospitalized and attending the ART center were included in the study. One hundred healthy controls were recruited for the study. Male: female ratio was 3.3:1. Youngest individual among cases and controls were 18-year-old, while the oldest was 50-year-old, with a mean age of 36.84 (±8.03) years among cases, and 38.04 (±7.08) years among controls, respectively (P = 0.264).
The CD4 count ranged from 29 to 1112/μl with a mean of 247.04 ± 211.4/μl. Fifty-seven percent of patients had CD4 count <200/μl, 21% of cases had CD4 count between 200 and 350/μl, and 22% had CD4 count >350/μl. Among cases, the mean creatine phosphokinase-muscle/brain (CPK-MB) observed was 24.95 ± 14.15 (U/L), and among controls, the mean CPK-MB observed was 17.2 ± 6.035 (U/L) (P < 0.001).
Forty-one cases had abnormal ECG findings in comparison to controls, and among these, eight had only minor arrhythmias.
The echocardiographic abnormalities are summarized in [Table 1]. Of the 100 cases studied, 28% had PE (P = 0.001), 10% had pulmonary artery hypertension (P = 0.002), and 48% had reduced epicardial fat thickness (P = 0.001) compared with 4% of controls. Forty-six percent of cases had left ventricular diastolic dysfunction (LVDD) compared with 3% among controls (P < 0.001).
As shown in [Table 2], HIV-positive patients had significantly increased DT (<0.001), E velocity (<0.001), e' (<0.001), and left atrial diameter 0.004 (S) as compared with the controls. Furthermore, LVDD (mm) 0.415 (not significant [NS]), Isovolumetric Relaxation Time (IVRT) (ms) 0.130 (NS), and late diastolic flow velocity (cm/sec) 0.143 (NS) increased in cases but not reached to significant level.
As shown in [Table 3], various abnormalities in echocardiographic findings were seen in patients with CD4 count <200. Out of the total of 27 patients with PE, 23 patients had CD4 count <200. All 46 patients with LVDD had CD4 count <200. Furthermore, mean EF in patients with CD4 count <200/200–350 was 50.50% ± 6.17%/59.90 ± 2.76 (P < 0.001) that is significantly lower than the other two groups.
|Table 3: Association of echocardiographic findings with CD4 count in cases|
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| Discussion|| |
One hundred patients with HIV infection presented to indoor and registered in the ART center and 100 controls were included in this study. Majority of the patients (77 patients) were male and 23 patients were female. We further scrutinized cases according to the CD4 count, and thus observed that mean CD4 among the three groups, that is, with CD4 count <200/200–350/>350 was 108.47 ± 36.51/277.85 ± 46.73/576.63 ± 195.45, and among patients with CD4 count <200, 84.21% were male and 15.78% were female. This division is similar to the study by Rupal et al. which had similar groups according to the CD4 counts.
Cases were also divided according to the duration of HAART among patients, who are newly diagnosed, on HAART therapy for <5 years and >5 years, to see any relation between the duration of HAART and cardiac abnormalities on echocardiography. As in this study, duration of HAART had no positive correlation with various cardiac abnormalities, similar finding was also observed in the study done by Bozzette SA et al.
In this study, 41% of individuals among cases group had abnormal ECG findings in comparison to controls, whereas only 8% of patients among these showed only minor arrhythmias. Of total patients with abnormal ECG findings, 34% of patients had a CD4 count <200. The average CD4 count of patients with abnormal ECGs was 140.6, and average CD4 count of patients with normal ECG was 321. There was highly significant correlation between ECG abnormalities and low CD4 count with a P < 0.001. A study done by Okoye and Anyabolu had similar observations, where an abnormal ECG was present in 70% of the HIV-positive patients. The HIV-positive patients had more ECG abnormalities than the HIV-negative patients (P = 0.001).
Ten patients among cases had evidence of PH, which was statistically significant with P = 0.002, also among these, three patients had moderate grade PH. In controls, no patient had PH. However, there was no correlation between PH and CD4 count and duration of HAART as well. Similar observations were seen in a study done by Maurya SK et al., in which 16 (14%) patients had PH (P = 0.030) compared with controls.
In our study, among HIV-infected patients, 27% had minimal PE, whereas 1% patient had moderate effusion as compared to no effusion among controls (P < 0.001); also among cases with effusion maximum patients had CD4 count <200/mm3 (P = 0.007), similar observations were obtained in the study by Bhattacharya et al., where PE was seen among 13% of cases compared to none of the control population. Low CD4 count was significantly associated with PE (P = 0.048).
Furthermore, the mean CPK-MB value observed was 24.95 ± 14.15 (U/L) in cases, and among controls, the mean CPK-MB observed was 17.2 ± 6.035 (U/L). Thus, a significantly higher mean CPK-MB value was seen among cases as compared to controls (P < 0.001). This was similar to the study by Ngala and Fianko.
Among cases, the mean EF observed was 54.68% ± 6.82%, and in controls, the mean EF observed was 60.72% ± 1.47%. Thus, a significantly higher left ventricular systolic dysfunction was seen among cases as compared to controls (P < 0.001). The mean EF in patients with CD4 count <200/200–350/>350 was 50.50% ±6.17%/59.90 ± 2.76/60.50 ± 0.85, respectively, which showed a statistically significant decrease in EF among patients with CD4 count < 200 than in patients with CD4 >200(P < 0.001). A highly significant positive correlation was observed between the CD4 count and EF% among cases (r = +0.566, P < 0.001 h) using Pearson's correlation coefficient [Figure 1]. The significant relationship found between the CD4 count and EF% is similar to the result of study done by Oslusegun-joseph et al, where systolic dysfunction was observed in (30% vs. 8%; P = 0.024) and study done by Twagirumukiza et al, 17%had low left ventricular EF%.
|Figure 1: Showing significant positive correlation between CD4 count and ejection fraction|
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In this study, among cases, LVDD was seen in 46% of individuals. While in controls, 3% of individuals had LVDD. Thus, a significantly higher number of individuals with LVDD was observed in cases as compared to controls (P < 0.001). Of total 46 patients, 32 patients with CD4 count <200 had Grade 1 LVDD and 12 and 2 patients had Grade 2nd and 3rd LVDD grade, respectively, and patients with CD4 between 200 and 350 or >350 had no LVDD (P < 0.001). According to a study by Reinsch et al., the prevalence of LVDD in HIV-infected patients was 48%. In another study by Chang et al., the LVDD was positively correlated with decreased CD4 count.
Previous studies have shown that HIV-related cardiac manifestations are often seen in a state of severe immunosuppression with low CD4 count (CD4 <200/μl).,,
Various studies agree that the most important factor in the development of cardiac abnormalities is the level of immunosuppression, and there is a tight correlation between CD4 count and echocardiographic abnormalities, which is also demonstrated in the present study.,, Our study also represents a direct correlation between various cardiac abnormalities and CD4 count, however it failed to show any relation to the duration of HAART.
The present study showed a significant prevalence of cardiac involvement in HIV-infected patients, However a number of other risk factors Namely; Smoking, Alcohol Abuse and various familial risk factors which commonly affects cardiovascular system in a similar manner cannot be ruled out.
| Conclusions|| |
This study indicated that cardiovascular abnormalities are more common in HIV-infected patients than the normal population. Even asymptomatic patients had positive echocardiographic findings. The prevalence of echocardiographic abnormalities increases as the CD4 count falls, and the tendency to develop these manifestations increases when CD4 falls <200. Hence, these parameters can also be used as predictors of disease progression. Echocardiography is a useful noninvasive technique for the early recognition of cardiac dysfunction in such patients. Early diagnosis and the management of these complications are associated with increased survival rates and clinical outcomes in HIV patients.
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Conflicts of interest
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[Table 1], [Table 2], [Table 3]