Pattern of electrocardiographic abnormalities in pediatric HIV/AIDS clients at Federal Medical Center, Abeokuta

Musa Kayode Yusuf; Adebiyi O Olowu; Chinyere C Uzodimma; Florence IO Dedeke

doi:10.4103/njc.njc_13_20

ORIGINAL ARTICLE

Year : 2021 | Volume : 18 | Issue : 1 | Page : 6-13

Pattern of electrocardiographic abnormalities in pediatric HIV/AIDS clients at Federal Medical Center, Abeokuta

Musa Kayode Yusuf¹, Adebiyi O Olowu², Chinyere C Uzodimma¹, Florence IO Dedeke¹
¹ Department of Paediatrics, Federal Medical Centre, Abeokuta, Ogun State, Nigeria
² Department of Paediatrics, Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State, Nigeria

Date of Submission	21-Apr-2020
Date of Decision	06-Jun-2020
Date of Acceptance	02-Nov-2021
Date of Web Publication	11-Aug-2022

Correspondence Address:
Dr. Musa Kayode Yusuf
Department of Paediatrics, Federal Medical Centre, Abeokuta, Ogun State
Nigeria

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/njc.njc_13_20

Abstract

Background: Sub-Saharan Africa presently contributes about 70% of global HIV/AIDS population with little or no emphasis on the contribution of cardiovascular abnormalities to the associated morbidity and mortality in the region.
Objectives: The objective is to determine the prevalence of electrocardiographic (ECG) abnormalities and association of such abnormalities with HIV/AIDS severity in terms of clinical manifestations and level of CD4 depletion.
Design: A hospital-based cross-sectional case-control study.
Methodology: One hundred and five (105) HIV-infected children attending HIV clinic and equivalent age- and sex-matched HIV un-infected controls attending pediatrics General Outpatient Clinics at FMCA were consecutively recruited over 8 months. They were evaluated clinically and had CD4 count, hematocrit, plasma calcium and potassium, and standard 12-lead ECG done.
Results: Thirty-five (33.3%) of the subjects had ECG abnormalities compared with four (3.8%) in the controls (χ² = 28.34, P < 0.05). The left ventricular hypertrophy was the commonest (13.3%) among other detected abnormalities such as Q-wave abnormalities, right ventricular hypertrophy, and ventricular repolarization abnormalities. The detected abnormalities were not significantly associated with advanced clinical or immunological stage of HIV/AIDS (χ² < 4.0, P > 0.05).
Conclusion: There was a high prevalence of ECG abnormalities in children with HIV/AIDS. These abnormalities occurred irrespective of the extent of the disease advancement. There is therefore a need for at least an ECG to identify from among HIV infected children those who may subsequently require echocardiography since the cost of echocardiography is presently too high and precludes its routine use in the Sub-Saharan Africa.

Keywords: Electrocardiography, HIV/AIDS, pediatrics

How to cite this article:
Yusuf MK, Olowu AO, Uzodimma CC, Dedeke FI. Pattern of electrocardiographic abnormalities in pediatric HIV/AIDS clients at Federal Medical Center, Abeokuta. Nig J Cardiol 2021;18:6-13

How to cite this URL:
Yusuf MK, Olowu AO, Uzodimma CC, Dedeke FI. Pattern of electrocardiographic abnormalities in pediatric HIV/AIDS clients at Federal Medical Center, Abeokuta. Nig J Cardiol [serial online] 2021 [cited 2023 May 29];18:6-13. Available from: https://www.nigjcardiol.org/text.asp?2021/18/1/6/353681

Introduction

HIV/AIDS since discovery in 1983 has remained a major cause of morbidity and mortality worldwide.^[1] The advent of highly active antiretroviral therapy (HAART) has converted it into a chronic treatable illness with effects on every organ system of the body. The associated cardiovascular abnormalities have been shown to be persistent, progressive, and often subclinical.^[2],[3],[4] Both congenital and acquired cardiovascular abnormalities have been described in both symptomatic and asymptomatic HIV infection using various investigative tools.^{[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23]}

The current guidelines for the care of HIV/AIDS clients have placed no emphasis on the need for the treatment of associated cardiovascular co-morbidities despite evidence that showed an improved overall prognosis if these co-morbidities are detected early and treated in addition to the use of HAART.^[8],[23]

In spite of the fact that Nigeria has the highest incidence of AIDS-related deaths and Sub-Sahara African countries account for about 71% of the world population of HIV infected people,^[1] little or no attention is given to the cardiovascular assessment in children with HIV infection in this part of the world. Consequently, the specific interventions directed at reversing or improving such cardiovascular compromise is not being considered.^[24]

We undertook this cross-sectional study to characterize electrocardiographic (ECG) abnormalities in HIV/AIDS children and establish the burden of such abnormalities on them, thereby drawing attention to their need for further cardiovascular evaluation since routine echocardiography on all HIV infected children in this region of the world may be too costly for the international donor agencies that are majorly providing the HAART.^[1],[9]

Objectives

To determine the prevalence of ECG abnormalities among HIV/AIDS children and compare same with age and sex matched HIV un-infected controls
To describe the ECG abnormalities in children that are symptomatic for HIV infection and those that are not
To determine the association, if any, of such ECG abnormalities with the CD4 level and clinical stage of the HIV infection.

Methodology

The study was a hospital-based cross-sectional case–control study that employed a non-probability sampling method. The population of children ≤15 years with HIV infection attending clinic at FMCA was 160 per annum. With available estimate of 26.5%,^[5] 95% confidence, and 5% precision; the study size was estimated to be 105.^[25] One hundred and five HIV/AIDS clients aged 15 years and below who presented at the HIV clinic and 105 age and sex matched HIV un-infected controls that presented at the General Paediatric Outpatient Clinic of FMCA between September 2014 and May 2015, and consented were consecutively recruited.

The subjects have been confirmed HIV infected either by polymerase chain reaction (age <18 months at diagnosis) or two positive rapid antibody tests ''Determine and Unigold Kits'' (age ≥18 months at diagnosis).^[24] The controls had provider-initiated counseling and testing and confirmed HIV un-infected before recruitment. They all had detailed clinical history and physical examination. Subjects with confirmed structural heart disease before HIV infection and those whose parents/guardians refused consent were excluded from the study. Un-infected children with confirmed or suspected cardiac disease, febrile illness with axillary temperature ≥38°C, gastroenteritis and electrolyte derangements, and other childhood illnesses with likely cardiovascular dysfunction were considered ineligible in addition to refusal of consent.

EDAN SE-3 ECG machine (China) with pediatric electrodes was used for both subjects and controls ECG recording. Plasma calcium and potassium of both groups were assayed at the Institute of Human Virology of Nigeria laboratory attached to the HIV clinic at FMCA using VITROS DT 60II/DTE II (Orthoclinical Diagnostic) while the subjects CD4 count was done using Cyflow Counter (2013 model). Hematocrit was done using approved standard for micro-hematocrit method.^[26]

Interpretation format for ECG included rhythm, heart rate, morphology and amplitude of waves (P, QRS, T), intervals (PR, QT/Corrected QT [QTc]), electrical axes (P, QRS, T), and ST segment. Each ECG parameter was compared with established normal for age to detect any abnormality.^[27],[28] Lead 11 was set as the rhythm lead. P wave of 0.03–0.09 s in ≤3 years and0.05-–0.10 s in >3 years old was taken as normal P duration respectively while P amplitude of ≤2.5 mm was taken as normal for all age groups. P-duration and P-amplitude above these values were taken as left atrial-and right atrial-hypertrophy, respectively.^[27],[28] Heart rate was calculated from the formula HR = 1500/RR (mm) with values above the upper limit and below the normal limits taken as tachycardia and bradycardia, respectively.^[27],[28]

QRS axis of 0 to +90° was taken as normal since none of the subjects was ≤6 months at sampling time.^[27],[28] Normal P and T axes were taken as 0 to +90 degrees irrespective of age.^[28] QTc was calculated from the recorded QT and RR interval using the Bazzet's formula; QTc = QT/√RR (sec) with upper limit of normal taken as 0.44 sec (no subject was ≤6 months of age).^[27]

Anemia was graded as mild, moderate, and severe using the World Health Organization (WHO) classification.^[29] The severity of the CD4 depletion was graded according to the WHO immune staging as; Not significant, Mild, Advanced, and Severe.^[30] Normal plasma calcium was taken as 8.4–10.5 mg/dL with values below lower limit taken as hypocalcemia and values above upper limit as hypercalcemia.^[31],[32] Potassium values from 3.4 to 5.5 mmol/L were taken as normal while hypokalemia and hyperkalemia were values below lower and above upper limits, respectively.^[31],[32]

Data analysis

Data analysis was done using the Statistical Package for Social Sciences (SPSS) for windows software version 20.0. International Business Machines Cooperation (IBM); 1 New Orchard Road, Armonk, New York 10504-1722, United States; 2011. The means and standard deviations (SD) were calculated for continuous variables while ratios and proportions were calculated for discrete variables. Paired samples t-test was used to compare the continuous variables between subjects and controls.

The ECG abnormalities as they relate to some selected subject characteristics (considered confounders) and to controls were analyzed using logistic regression and cross-tabulations, respectively. Proportions and ratios were compared using the Pearson's Chi-square test with Yate correction applied to values <5. Values of “P” < 0.05 were accepted as statistically significant.

Ethical consideration

An ethical clearance was obtained from the Hospital Research Ethics Committee of FMCA. Written informed consent was obtained from parent(s)/guardian(s) of each subject and control. Consent of matured minors (≥13 years)^[33] among the subjects and controls was also obtained in addition to assent from those aged 7–13 years.

Results

One hundred and five HIV/AIDS subjects and equivalent number of age and sex matched controls ≤15 years were analyzed. Fifty-seven (54.3%) were male, given a male-to-female ratio of 1.19:1. [Table 1] shows the paired sample t-test on some selected variables of subjects and controls.

Table 1: Comparison of physical, haematocrit, and biochemistry parameters of subjects and controls

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The mean age of the subjects was 7.27 ± 2.88 (SD) years with a range of 1.58–15.00 years. Seventy-one (67.6%) of the subjects were diagnosed on presenting with symptom complexes suggestive of intercurrent illnesses seen in HIV infection (i.e., symptomatic). Seventy-seven (73.3%) of the subjects were on one form of HAART combination or another. Sixty-one (79.2%) of these 77 were on AZT/3TC/NVP while others were on either AZT/3TC/EFV or AZT/3TC/LPV/r combinations. The mean duration of HAART use was 2.97 ± 2.08 years with a range of 0.04–10 years.

Ten (9.5%) and 13 (12.4%) of the subjects were severely malnourished and severely stunted respectively using WHO criteria.^[34] Hepatomegaly was the most prevalent physical abnormality seen in 25 (23.8%) of the subjects. Two subjects had digital clubbing, pedal edema, dyspnea, tachypnea, tender hepatomegaly, and loud P2 suggesting a right heart failure, probably secondary to Pulmonary Arterial Hypertension (PAH).

Using the WHO clinical staging; 46 (43.8%) subjects had stage III disease while stage I, stage II, and stage IV accounted for 34.3%, 18.1%, and 3.8% respectively. Concerning CD4 count, 53 (50.5%) subjects had no significant immune suppression while 20 (19.0%), 19 (18.1%), and 13 (12.4%) subjects had mild, advanced, and severe immune suppression respectively.

Seventy (66.7%) of the subjects had normal hematocrit, while mild, moderate, and severe anemia were accounted for by 15.2%, 15.2%, and 2.9% respectively. Hyperkalemia was detected in only three (2.9%) subjects.

The most common diagnosis among the controls was uncomplicated malaria with low grade fever and anorexia; and upper respiratory tract infections that accounted for 31 and 23 controls respectively. Others that presented in various frequencies to make up the 105 include pre-school entrance medical test, uncomplicated hernia, acute tonsillitis, uncomplicated pneumonia, minor trauma, impetigo, vernal conjunctivitis, functional abdominal pain, allergic rhinitis, dyspepsia, foreign body in the nose, and tinea capitis.

Electrocardiographic abnormalities

Thirty-five (33.3%) of the subjects had one or more forms of ECG abnormality compared with four (3.8%) in the control group. Fourteen (13.3%) and four (3.8%) of the subjects had Left Ventricular Hypertrophy (LVH) and right ventricular hypertrophy (RVH), respectively. Nine of these ventricular hypertrophies were diagnosed based on voltage criteria alone; vis-à-vis abnormally tall R waves, abnormally deep S waves, and abnormal R/S ratios in the corresponding leads. Three of those with ventricular hypertrophies had malnutrition. These three, however, had in addition to voltage criteria associated abnormally deep Q– waves that strengthened real ventricular hypertrophy in them more than just expected high ventricular voltages seen in wasted or thin subjects. None of the subjects with LVH had associated left axis deviation (LAD). Right axis deviation (RAD) was associated with one of the RVH. Other cases of LVH had voltage criteria supported by associated abnormally deep Q– waves and repolarization abnormality as diagnostic criteria. One (1.0%) each of the subjects had sinus tachycardia, electrical alternans, and Wolff-Parkinson-White Syndrome (WPWS). Three (2.9%) subjects had hyperkalemia but with no associated ECG abnormality.

The detected ECG abnormalities in the controls included LAD in two (1.9%) and one each of Incomplete Right Bundle Branch Block (IRBBB) and WPWS. The two cases of LAD presented at the clinic for school entrance medical fitness test and uncomplicated umbilical hernia respectively, while the IRBBB and WPWS recorded were diagnosed foreign body in the nose and tinea capitis respectively. None of these controls had any symptoms or sign referable to cardiovascular disease.

The prevalence of ECG abnormalities in the subjects (33.3%) was significantly higher when compared with the 3.8% recorded in the controls (χ² = 28.340; P = 0.000 [yate corrected]). The Chi– square test also showed a strong evidence of a difference in the distribution of ECG abnormalities between the subjects and controls. This was particularly statistically significant in the distribution of LVH, RVH, IRBBB, Q – wave abnormality, and ST – T wave abnormality (P < 0.05). LAD, RAD, sinus tachycardia, and electrical alternans also occurred at higher frequencies in subjects but these were not statistically significant. This is shown in [Table 2].

Table 2: Distribution and comparison of electrocardiographic abnormalitybetween subjects and controls

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The analysis of some selected subject features that were referable to cardiovascular system among other systems is shown in [Table 3]. There was a higher odd of having abnormal ECG in children with digital clubbing. This was however not statistically significant.

Table 3: Logistic regression on association between selected subjects characteristics and risk of electrocardiographic abnormality

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The presence of low CD4 count was not strongly associated with increased risk of abnormal ECG in the subjects as shown in [Table 4]. The ECG abnormality also occurred irrespective of the clinical stage of the HIV disease in the subjects [Table 5]. The ECG abnormalities were commoner in subjects that were symptomatic for HIV infection although not statistically significant as shown in [Table 6].

Table 4: Association between electrocardiographic abnormality and CD4 count

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Table 5: Association between electrocardiographic abnormality and clinical stage of HIV disease

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Table 6: Association between electrocardiographic abnormality and HIV associated intercurrent illnesses

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Discussion

The prevalence of ECG abnormalities in the current study (33.3%) fell within the range (26.5%–93.0%) previously reported by earlier studies.^{[3],[5],[6],[7],[19],[23]} The Lipshultz et al.^[3] study that reported 93.0% prevalence was in the pre– HAART era and also, used 24 h Holter monitoring in addition to the standard 12– lead recording. Pongprot et al.^[6] reported ECG abnormality as high as 52% in subjects that already had radiographic evidence of cardiomegaly in addition to respiratory distress. Diógenes et al.^[7] also recorded a 48.8% ECG abnormality in a cohort of perinatally infected children; of which 65% already had clinical cardiac changes at study time. These studies however had no subject on HAART treatment. The lower prevalence recorded in the current study when compared with the above studies could therefore have resulted from probable miss of episodic ECG abnormalities that might have been picked by 24 h Holter, protective effect of HAART on cardiovascular morbidities in our studied subjects, and absence of clinical cardiac changes in most of our subjects.

LVH was documented in 13.3% of the subjects in the present study. Ige et al. documented LVH prevalence comparable to the finding in this study using echocardiography (14.0%).^[22] The current study recorded a much higher prevalence of ECG evidence of LVH when compared with studies by Lubega et al.(1.3%) in Kenya^[5] and Pongprot et al.(0.04%) in Thailand.^[6] This disparity may be due to the larger sample size (105 vs. 22^[6]) in the current study which increased the power. Only one of the 14 cases of LVH had associated respiratory distress, and pedal edema. Three were associated with malnutrition. No cardiac examination findings suggestive of left ventricular dysfunction were detected in any of the LVH cases. Pongprot et al.^[6] recruited children with symptoms suggestive of underlying cardiac dysfunction but also recorded a low prevalence of LVH on ECG (4.3%). This emphasizes that clinical features may not reliably predict underlying LVH in children with HIV infection. Gopal et al.^[9] and Lipshultz et al.^[13] also made similar observations.

RVH was noted to be much less common than LVH among the subjects. The prevalence of RVH in this study was 3.8% which is comparable to 2.6% observed by Lubega et al.^[5] and 2.4% observed by Diógenes et al.^[7] While all cases of RVH in the Lubega et al. study were associated with easy fatigability, digital clubbing, and loud P_2, only two of the RVH cases in the present study had these features. The presence of RVH has been shown to be strongly suggestive of PAH in HIV infected patients.^{[6],[11],[12]} None of the controls had ECG evidence of ventricular hypertrophy; this may suggest HIV infection as an important precursor to ventricular hypertrophy.

Q-wave abnormality in the form of abnormally deep Q– waves was observed in 6.7% of the subjects in this study. This has not been substantially reported in the literature. Of these seven, three were associated with LVH, two with RVH, while the remaining occurred in isolation. While the association of Q-wave abnormality with ventricular hypertrophy suggested “volume overload,” isolated Q-wave abnormality in HIV/AIDS children would suggest underlying dilated cardiomyopathy.^[27],[28] The lack of Q–wave abnormality among the controls supports HIV infection as a likely cause of the detected Q–wave abnormality.

The prevalence of IRBBB in this study (6.7%) was higher than 2.6% but comparable to 5.9% reported in Uganda^[5] and Brazil^[7] respectively. The IRBBB in the current study was more in clinically advanced stages of HIV disease. Although Diógenes et al.^[7] observed that IRBBB was the earliest ECG abnormality in their study, our study being cross-sectional cannot examine this longitudinal relationship.

The explanation for IRBBB may not be far-fetched. IRBBB has been associated with the stretching of the right peripheral specialized conduction fibers from distension or selective hypertrophy of the right ventricular outflow tract.^[27] Therefore, the usual chronic and recurrent respiratory disorders seen in HIV infection could result in PAH with consequent RVH and stretching of right specialized conduction fibres.

ST-T wave abnormality was detected in 5.7% of the subjects. This was much lower than 26.8% found by Diógenes et al. in Brazil. Badal et al.^[19] in a comparable cross-sectional study observed a ST-T wave abnormality of 16.8% prevalence. Although the sample size was comparable (119), the higher prevalence recorded might have been a result of higher age cut-off (18 years) compared with 15 years in the present study since HIV associated cardiac abnormality is often progressive; especially without HAART which was characteristic of this Badal et al.'s study. This also lent credence to the 39% repolarization abnormality documented by Pongprot et al.^[6] among children that presented for cardiac evaluation on account of respiratory distress and established cardiomegaly on chest radiograph. Four of these ST– T wave abnormalities in the present study were associated with ventricular hypertrophy suggesting “strain” in the subjects.^[28]

LAD was documented in three (2.9%) of the subjects. One of these was a mild LAD associated with the only case of WPWS detected in the present study. The remaining two were cases of asymptomatic HIV infections with isolated LAD. Previous studies have been silent on the occurrence of LAD in HIV infected children. It is however not impossible that the various pathologic processes involved in myocardial dysfunction seen in HIV infection also damages the peripheral conducting fibers of the left ventricle especially the left anterior radiations resulting in LAD.^[27] This is supported by the higher prevalence of LAD in the subjects when compared with the controls in the current study.

RAD was observed in one (1.0%) of the subjects, and associated with a case of RVH. This is comparable to 2.4% incidence rate observed in a longitudinal study by Diógenes et al.^[7] Pongprot et al.^[6] while investigating a group of children that were symptomatic (radiographic cardiomegaly and dyspnea) for cardiorespiratory dysfunction recorded a 52% evidence of RAD and RVH. The single case of RAD recorded in the current study was associated with respiratory distress, supporting the reports by Pongprot et al.,^[6] Diógenes et al.,^[7] Cicalini et al.,^[11] Speich et al.,^[12] and Dubé et al.^[23] The inclusion of both asymptomatic and symptomatic HIV infection in the present study subjects might have contributed to the much lower prevalence of RAD recorded. RAD, being a pathologic ECG feature, was not recorded in any of the controls supporting HIV infection as a probable causal factor in the subjects.

The prevalence of sinus tachycardia in this study was very low; approximately 1% when compared with previous studies that recorded as high as 29% prevalence.^[5],[19] This low prevalence may be in support of the current belief that HAART may be protective on autonomic abnormalities seen in HIV infection because the present study recorded a mean duration of HAART use of 2.97 years. A cross-sectional study by Rajeshwari et al. on HIV-infected children who were on similar combinations of anti-retroviral drugs like in the present study, observed a 10% prevalence of tachycardia.^[21] This also was probably in support of the protective effect when compared with 20.9% by Lubega et al.^[5] and 29% by Badal et al.^[19] where only two of the 230 and none of the 119 subjects respectively were on anti-retroviral drugs at the study time. Rajeshwari et al. however did not state the duration of anti-retroviral drug use in the subjects studied. The single case of sinus tachycardia in the present study had normal hematocrit for age and sex and was not associated with fever. This none association of tachycardia with anemia in these subjects will also suggest probable chronic characteristics to HIV-associated anemia.

Cardiac arrhythmias like prolonged QTc and ventricular tachycardia were not observed in the present study. The explanation may not be far-fetched. The presence of these arrhythmias had been linked with drug-drug interactions in HIV care.^[13] No subject was on drug combinations (except co-trimoxazole) that predispose to these arrhythmias. This was however different from the findings by Sani and Okeahialam^[18] whose adult AIDS cohorts had 45% prevalence of prolonged QTc. The clinically advanced subjects and adult age might have contributed to the difference.

This study did not find any cardiac abnormality that is attributable to HAART use. This is consistent with the findings by Lipshultz et al.,^[15],[16] Wilkinson et al.,^[14] and Cerato et al.;^[17] especially in relation to the AZT. None of the studied subjects was on Abacavir and/or Stavudine that are presently considered cardiotoxic.^[14],[24] Thus, the risk of anti-retroviral drug-associated cardiovascular toxicity is minimal at FMCA.

Majority of the subjects with ECG abnormalities had CD4 count/CD4 percent in the normal range. This agreed with other studies that observed no association between low CD4 and the presence of underlying cardiovascular abnormalities in HIV-infected children.^{[4],[6],[17],[19],[28]} Also, majority of the subjects with ECG abnormalities were symptomatic for intercurrent illnesses in HIV infection. Likewise, the prevalence of specific ECG abnormalities (except LAD) was higher in those with symptomatic HIV infection when compared with asymptomatic cases. These differences were however not significant, consistent with the previous findings by Lubega et al.,^[5] Pongprot et al.,^[6] Diógenes et al.,^[7] Miller et al.,^[20] and Ige et al.^[22] that symptom complexes of HIV disease did not predict underlying cardiovascular disease. This is probably because most of these symptom complexes are more specific for other organ system of the body.

We conclude that ECG abnormalities are common in children with HIV/AIDS; that these abnormalities occurred in both symptomatic and asymptomatic HIV clients; and that the abnormalities occurred with low or normal CD4 count and irrespective of the clinical stage of the HIV infection.

Finally, the findings in this study should therefore alert the HIV care providers to give early consideration to cardiovascular abnormalities while taking care of HIV-infected children. Policymakers in charge of HIV patients' care in sub-Saharan Africa should consider the incorporation of ECG screening to the care of HIV-infected children with the intention of maximizing their care at cheaper cost for donor agencies.

Limitations

Our study been a cross-sectional study might have missed some episodic ECG abnormalities in addition to inability to assess any time bound changes in the detected abnormalities. It is also a single hospital and relatively small population-based study. Inability to do echocardiography to confirm some detected abnormalities due to financial constraint could not be left unmentioned.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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