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Original Research (Original Article) 


Hussain Jafer Alsowaiket et al, 2019;3(11):909–912.

International Journal of Medicine in Developing Countries

Cardiac manifestations of children with sickle cell disease in Qatif area

Hussain Jafer Alsowaiket1, Ibrahim Abdulla AlDabbous2, Anwar Hassan Darwich1, Mohammed Ali Alsultan3, Ali Hussain Ali AlKhalifa4*

Correspondence to: Ali Hussain Ali AlKhalifa

*Pediatric Senior Registrar, Qatif Central Hospital, Al Qatif, Saudi Arabia.

Email: dr.alkhalifa1 [at] gmail.com

Full list of author information is available at the end of the article.

Received: 18 July 2019 | Accepted: 29 August 2019


ABSTRACT

Background:

Limited information is available in literature about cardiac manifestations of children with Arab-Indian haplotype sickle cell disease (SCD). The aim of the current study was cardiovascular assessment of children with SCD.


Methodology:

It is a Prospective observational and cross-sectional study which was conducted at Qatif Central Hospital, Qatif, Saudi Arabia between December 2012 and June 2015. Asymptomatic children with SCD attending general pediatric and pediatric cardiology clinics were enrolled in this study. Eighty-seven patients were included in the study with mean age 7.8 (2–12) years, mean weight 23.7 (13–67) kg and 55 (63%) were male.


Results:

On cardiac examination, it was revealed that all the patients had normal BP, normal oxygen saturation, and normal auscultation of first and second heart sounds, wherein 6% patients had tachycardia, 20 (23%) had wide pulse pressure, 32 (37%) had soft ejection systolic murmur, 10 (11%) had ECG evidence of left ventricular (LV) hypertrophy, and 2 (2%) had PR prolongation. Echocardiography showed that all the patients had normal chambers inflow, outflow, wall thickness, and function. No evidence of pulmonary hypertension and no right atrial or ventricular enlargement was found. Among the participants, 6 (7%) patients had left atrial enlargement, 18 (21%) had LV enlargement, and 6 (7%) had simple congenital heart disease.


Conclusion:

Children with SCD originally from Qatif area have variable cardiac abnormalities. However, the prevalence of these was less frequent than that mentioned in literature with no distinct sickle cell cardiomyopathy. Although this is reassuring information to families, routine cardiac follow up is valuable.


Keywords:

Cardiac manifestations, children, sickle cell disease, Qatif area.


Introduction

Sickle cell disease (SCD) is an autosomal recessive hemoglobin disorder. It is characterized by recurrent episodes of hemolytic and vaso-occlusive crisis due to the production of abnormal hemoglobin resulting in entrapment of red blood corpuscles in the microvasculature, which leads to ischemia-reperfusion injury and infarction in multiple organs. Mechanisms causing organ and cardiac damage include chronic hemolysis, recurrent episodes of organ infarction, hyperdynamic circulation, and sickle cell vasculopathy leading to endothelial dysfunction and increase vascular resistance [1].

In Saudi Arabia, the major sickle haplotype is called “Arab-Indian” haplotype. This is relatively a benign type of SCD as compared to the other four major African sickle haplotypes [2,3]. Milder disease phenotype in Eastern province is also associated with the presence of alpha-thalassemia and high levels of fetal hemoglobin [35]. The prevalence of SCD in the Eastern province of Saudi Arabia is 2.6% [6,7].


Methodology

Children (1–12 years old) with SCD (confirmed by hemoglobin electrophoresis) originally from Qatif, who were following up in the pediatric clinic at Qatif Central Hospital, were enrolled in a cross-sectional hospitalbased study. Visits of 87 children with SCD, who were asymptomatic during OPD, were collected between December 2012 and June 2015. Consent was taken from parents, and the hospital scientific and ethical committee approved the study.

Through clinical examination, data were obtained, including gender, age, weight, height, body surface area, heart rate, blood pressure, pulse pressure, and oxygen saturation. The collected hematological data include the type of SCD (sickle cell anemia, sickle cell B-thalassemia, or others), hemoglobin level, mean corpuscular volume (MCV), fetal hemoglobin level (HbF), glucose six phosphate dehydrogenase (G6PD) status, complications of SCD, and presence of other comorbid medical conditions.

From a cardiac point of view, each patient underwent cardiac auscultation, 12- lead ECG, and standard echocardiography. M-mode dimensions were analyzed using Z-scores method (http://parameterz.blogspot.com/) [8].

Z-score = (observed dimension – mean normal dimension) ÷ Standard dimension around mean normal dimension

Features of pulmonary hypertension were screened and included; right atrial or right ventricular hypertrophy, abnormal septal shift, the maximum velocity of tricuspid valve ≥2.5 m/s [9].


Results

Between December 2012 and June 2015, 87 children originally from Qatif area with SCD attended both general pediatric clinic and pediatric cardiology clinics and enrolled in a cross-sectional hospital-based study. Mean age of the participants was 7.8 years (2–12 years), mean weight was 23.7 kg (13–67 kg) corresponding to weight for age percentile 45% (5%–97%). The participants included 55 males (63%) and 32 females (37%). All of them were asymptomatic during OPD visits.

Hematological parameters revealed (Table 1); mean Hb 9.6 (7.2-12.8) g/dl, mean MCV 70 (54–90) fl, mean HbF 23 (5.4–77.4)%. Among the participants, 79 (91%) patients had HbSS disease, 28 (32%) had G6PD deficiency, and 32 (37%) had some complications of SCD (including splenic sequestration, hepatic crisis, massive spleen, frequent painful crisis, gallstones, central nervous system crisis, avascular necrosis of femoral hip, acute chest syndrome). No patient has other chronic medical diseases.

Clinical cardiac examination (Table 2) revealed that all the patients had normal BP, normal oxygen saturation, and normal auscultation of first and second heart sounds. Among the participants, 5 (6%) patients had tachycardia (defined as HR>99% for age) [10]. All patients had normal BP, but 9 (10%) patients had wide pulse pressure (defined as the difference between systolic and diastolic BP >40 mmHg or > half systolic BP) [11,12]. Thirty-two (37%) patients had soft systolic ejection murmurs at the left sternal border and widely radiated.

There was no ECG evidence of ischemic changes, no pre-excitation, and standard QTc intervals. Among the participants, 10 (11%) patients had ECG evidence of LV hypertrophy (LVH) (Table 2), while 2 (2%) had mild PR prolongation (0.17 second) [9].

Echocardiography (Table 3) revealed that all the patients had normal LV function (defined as EF > 50% or FS > 28%), competent valves, no evidence of pulmonary hypertension, no ventricular hypertrophy and normal right atrium and right ventricle size. Moreover, six (7%) patients had simple congenital heart disease; five patients had small Secundum atrial septal defect, and one patient had post device closure of patent ductus arteriosus. Among the participants, 18 (21%) patients had LV dilation (defined as LV end-systolic or end-diastolic Z-score dimensions more than or equal to 2), and 6 (7%) patients had left atrial enlargement.

Table 1. Hematological data of sickle cell patients.

Variables
Type of SCD: number (%)
Sickle cell anemia 79 (91%)
Sickle cell B-thalassemia 8 (9%)
Hemoglobin (gm/dl) (mean and range) 9.6 (7.212.8)
MCV (fl) (mean and range) 70 (54-90)
HbF % (mean and range) 23 (5.477.4)
G6PD deficiency 28 (32 %)
The complication of SCD* 32 (37%)

*Complications of CSD include acute chest syndrome, splenic or hepatic sequestration crisis, avascular necrosis of femoral head, CNS crisis, gallstones, osteoporosis, and frequent painful vaso-occlusive crisis.

Table 2. Data on cardiac examination and abnormal ECG findings.

Variables
HR 94 (60140) bpm
Systolic BP 100 (79169) mmHg
Diastolic BP 64 (4796) mmHg
Pulse pressure 36 (1373) mmHg
Heart murmur 32 (37%)
ECG evidence of LVH 10 (11%)
PR interval from ECG 0.14 (0.100.17) seconds

Table 3. Echocardiographic M-mode findings of sickle cell patients.

Variables Mean (range) Z-score: mean (range)
LVED (mm) 39 (2948) 1 (-1.6 to 3.4)
LVES (mm) 25(1833) 0.7 (-1.9 to 3.4)
EF (%) 68 (5585)
FS (%) 38 (2953)
IVS (mm) 5.6 (3.58) 0.3 (-1.8 to 1.9)
LVPW (mm) 5 (3.59) -0.6 (-1.9 to 1.8)
LA (mm) 24 (1834) 0.6 (-1.3 to 3.1)
Ao root (mm) 17 (1.623) -0.7 (-1.9 to 1.5)

LVED: left ventricular end-diastolic dimension, LVES: left ventricular end-systolic dimension, EF: ejection fraction, FS: fractional shortening, IVS: interventricular septal thickness, LVPW: LV posterior wall thickness, LA: left atrium diameter, AO root: aortic root diameter.


Discussion

In this (limited prospective) cross-sectional and hospitalbased study, the vast majority of pediatric patients (91%) had sickle cell anemia (HbSS) with mean steady-state Hb 9.6 (7.2–12.8) g/dl, mean HbF 23 (5.4–77.4)% and approximately one-third had G6PD deficiency with complications of SCD.

During the steady-state evaluation of these patients, it was revealed that 6% of participants had tachycardia, 10% had wide pulse pressure, and 37% had a heart murmur. Other studies detected tachycardia in 28% and heart murmur in 61% of patients [13,14]. Batra et al. [15] found loud heart murmur (grade ≥ 2) among nonblood transfused (84%) and chronically blood-transfused children with sickle cell anemia (40%). Moreover, no systemic hypertension had been detected in our study.

We found ECG evidence of LVH in 11% and mild PR prolongation in 2% of the participants. In a study of Sudanese children with SCD, the researchers found LV hypertrophy in 24% of the participants, prolong PR interval in 8%, and right ventricular hypertrophy in 1% of the participants [13]. In the current study, QTc was within the normal range, while some studies showed an increasing prevalence of borderline or moderately prolonged QTc intervals among pediatric and adolescent patients with SCD (8.5%–38%) [16,17]. In the current and other studies, there were no pathological evidence of ST-segment changes, T wave changes, or arrhythmias [15].

Many studies revealed several significant echocardiographic abnormalities in children with SCD as compared to controls. These abnormalities include left or right ventricular dilation, left atrial dilation, septal and posterior wall hypertrophy, and aortic root dilation [1321]. Some of these studies detected the following findings in these patients; LV dilation in 51%–66% of the patients, left atrial dilation in 16%, right ventricular dilation in 22%–60%, and right atrial dilation in 6% of the patients. All these studies agreed of normal systolic ventricular function with no evidence of pulmonary hypertension. However, many studies showed a high prevalence of diastolic dysfunction in children with SCD [2224]. In the current study, we found two echocardiographic abnormalities; LV dilation in 21% and left atrial dilation in 7% of the patients. Right ventricular and atrial size, septal and posterior wall thickness, aortic root, and ventricular systolic function all were normal in our patients. None of the patients had evidence of pulmonary hypertension.

We detected 6% of patients with SCD had potential shunting lesions through Secundum atrial septal defect and patent ductus arteriosus (already closed). Hypercoagulable states and increased right heart pressure, which both occur in SCD, predispose to paradoxical embolization. Dowling et al. [25,26] found one-quarter of children with SCD and stroke had potential intracardiac shunts.


Conclusion

Children with SCD originally from Qatif area (Eastern Province, Saudi Arabia) had variable cardiac abnormalities, but the prevalence of these was less frequent than that mentioned in the literature. The most worrisome of these cardiac abnormalities was LV dilation, which was detected in one-fifth of patients, but there was no distinct sickle cell cardiomyopathy. Although this information is a critical reassuring factor for the families, careful cardiac follow up is valuable as these cardiac abnormalities could contribute to adulthood morbidity and mortality.

This is an observational cross-sectional study and not a case-control study, with a relatively small sample population, and a duration of over 2.5 years. Cardiac diastolic dysfunction was not studied during busy cardiac clinics. We recommend further cohort and case-control studies with a more significant sample number.


Acknowledgments

The authors want to express our sincerest appreciation to our nursing staff at both general pediatric clinic and pediatric cardiology clinic for their usual remarkable effort for patient care.


List of abbreviations

LV Left ventricular
LVH Left ventricular hypertrophy
MCV Mean corpuscular volume
SCD Sickle cell disease

Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this article.


Funding

None.


Ethical approval

Ethics committee at Qateef Central Hospital approved the study via leeter number 41/34/11937 dated, September 27, 2011.


Author details

Hussain Jafer Alsowaiket1, Ibrahim Abdulla AlDabbous2, Anwar Hassan Darwich1, Mohammed Ali Alsultan3, Ali Hussain Ali AlKhalifa4

  1. Pediatric Cardiology Consultant, Qatif Central Hospital, Al Qatif, Saudi Arabia
  2. Formerly Consultant Pediatrician, Qatif Central Hospital, Al Qatif, Saudi Arabia
  3. Pediatric Resident, Qatif Central Hospital, Al Qatif, Saudi Arabia
  4. Pediatric Senior Registrar, Qatif Central Hospital, Al Qatif, Saudi Arabia

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How to Cite this Article
Pubmed Style

Alsowaiket HJ, Dabbous IAA, Darwich AH, Alsultan MA, AlKhalifa AHA. Cardiac manifestations of children with sickle cell disease in Qatif area. IJMDC. 2019; 3(11): 909-912. doi:10.24911/IJMDC.51-1563490778


Web Style

Alsowaiket HJ, Dabbous IAA, Darwich AH, Alsultan MA, AlKhalifa AHA. Cardiac manifestations of children with sickle cell disease in Qatif area. https://www.ijmdc.com/?mno=57613 [Access: October 15, 2021]. doi:10.24911/IJMDC.51-1563490778


AMA (American Medical Association) Style

Alsowaiket HJ, Dabbous IAA, Darwich AH, Alsultan MA, AlKhalifa AHA. Cardiac manifestations of children with sickle cell disease in Qatif area. IJMDC. 2019; 3(11): 909-912. doi:10.24911/IJMDC.51-1563490778



Vancouver/ICMJE Style

Alsowaiket HJ, Dabbous IAA, Darwich AH, Alsultan MA, AlKhalifa AHA. Cardiac manifestations of children with sickle cell disease in Qatif area. IJMDC. (2019), [cited October 15, 2021]; 3(11): 909-912. doi:10.24911/IJMDC.51-1563490778



Harvard Style

Alsowaiket, H. J., Dabbous, . I. A. A., Darwich, . A. H., Alsultan, . M. A. & AlKhalifa, . A. H. A. (2019) Cardiac manifestations of children with sickle cell disease in Qatif area. IJMDC, 3 (11), 909-912. doi:10.24911/IJMDC.51-1563490778



Turabian Style

Alsowaiket, Hussain Jafer, Ibrahim Abdulla Al Dabbous, Anwar Hassan Darwich, Mohammed Ali Alsultan, and Ali Hussain Ali AlKhalifa. 2019. Cardiac manifestations of children with sickle cell disease in Qatif area. International Journal of Medicine in Developing Countries, 3 (11), 909-912. doi:10.24911/IJMDC.51-1563490778



Chicago Style

Alsowaiket, Hussain Jafer, Ibrahim Abdulla Al Dabbous, Anwar Hassan Darwich, Mohammed Ali Alsultan, and Ali Hussain Ali AlKhalifa. "Cardiac manifestations of children with sickle cell disease in Qatif area." International Journal of Medicine in Developing Countries 3 (2019), 909-912. doi:10.24911/IJMDC.51-1563490778



MLA (The Modern Language Association) Style

Alsowaiket, Hussain Jafer, Ibrahim Abdulla Al Dabbous, Anwar Hassan Darwich, Mohammed Ali Alsultan, and Ali Hussain Ali AlKhalifa. "Cardiac manifestations of children with sickle cell disease in Qatif area." International Journal of Medicine in Developing Countries 3.11 (2019), 909-912. Print. doi:10.24911/IJMDC.51-1563490778



APA (American Psychological Association) Style

Alsowaiket, H. J., Dabbous, . I. A. A., Darwich, . A. H., Alsultan, . M. A. & AlKhalifa, . A. H. A. (2019) Cardiac manifestations of children with sickle cell disease in Qatif area. International Journal of Medicine in Developing Countries, 3 (11), 909-912. doi:10.24911/IJMDC.51-1563490778