|
 
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| ORIGINAL RESEARCH |
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| Year : 2022 | Volume
: 6
| Issue : 1 | Page : 1-7 |
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A Study on the Cardiac Manifestations and Their Short-Term Outcome in Patients with Kawasaki Disease in an Indian Population
Gopalan Nair Rajesh1, S Prasanth2, Haridasan Vellani1, Jomy Vadasseril Jose1
1 Department of Cardiology, Government Medical College, Kozhikode, Kerala, India
2 Department of Cardiology, KMCT Medical College, Kozhikode, Kerala, India
| Date of Submission | 25-Mar-2021 |
| Date of Acceptance | 28-Mar-2021 |
| Date of Web Publication | 17-Jun-2021 |
Correspondence Address:
Dr. Jomy Vadasseril Jose
Department of Cardiology, Government Medical College, Kozhikode - 673 008, Kerala
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jiae.jiae_75_20
Objectives: This study aimed to assess the prevalence of cardiac manifestations and their short-term outcome in patients with Kawasaki disease (KD) in an Indian population. Methods: This single-center prospective study enrolled a total of 56 consecutive patients with classic and incomplete KD. Six months and 1-year clinical outcomes were analyzed. Results: Fifty-six consecutive patients were enrolled in the study and followed up for 1 year. About 87% completed 6 months follow-up. A diagnosis of complete KD was made in 41 (73%) patients and incomplete KD in 15 (27%). Cardiac manifestations were present in 25% of patients with KD. Coronary involvement was observed in 11 (20%) patients by either Japanese Ministry of Health Criteria or a z score of ≥2.5. Nonpurulent conjunctivitis was significantly higher among children with cardiac involvement (79% vs. 43% P = 0.04). The mean value of erythrocyte sedimentation rate (ESR) was significantly higher among patients with cardiac involvement (101.92 ± 22 vs. 74.26 ± 28.6; P = 0.002). An ESR value of >100 mm/hr was predictive of cardiac involvement (P = 0.03). The mean serum glutamic-pyruvic transaminase value was higher among those with cardiac involvement (P = 0.008). Coronary dilatation got resolved in 3 months in 73% of patients. Valvular regurgitations, aortic root involvement, and depressed left ventricular myocardial function were not observed in the population studied. Conclusions: Cardiac manifestations were present in 25% of patients with KD, 20% of children had coronary involvement in the form of an aneurysm, or ectasia. About 73% of patients with coronary dilatation got resolved in 3 months. Significant valvular heart diseases, aortic root involvement, and myocardial contractile dysfunction were not seen in the studied population with KD. Keywords: Coronary aneurysm, Kawasaki disease, Indian population
How to cite this article:
Rajesh GN, Prasanth S, Vellani H, Jose JV. A Study on the Cardiac Manifestations and Their Short-Term Outcome in Patients with Kawasaki Disease in an Indian Population. J Indian Acad Echocardiogr Cardiovasc Imaging 2022;6:1-7 |
How to cite this URL:
Rajesh GN, Prasanth S, Vellani H, Jose JV. A Study on the Cardiac Manifestations and Their Short-Term Outcome in Patients with Kawasaki Disease in an Indian Population. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2022 [cited 2023 Sep 27];6:1-7. Available from: https://jiaecho.org/text.asp?2022/6/1/1/318748 |
| Introduction | |  |
Kawasaki disease (KD) affecting predominantly infants and young children is an acute, self-limited vasculitis of unknown etiology that involves small- and medium-sized arteries with a predilection for coronaries. The disease was first described in Japan in l967, by Tomisaku Kawasaki.[1] There are clinical and laboratory findings that are associated with an increased risk of coronary artery aneurysm in KD.[2] The clinical features include male gender, extremes of age, prolonged fever, delay in diagnosis and persistent fever after treatment. The laboratory parameters include low hemoglobin, increased white blood cell count, high absolute band count, very increased or persistently increased erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), low platelet count, and low albumin.
Although coronary artery sequelae are responsible for the major morbidity and mortality of KD, it is often accompanied by noncoronary cardiac abnormalities, including left ventricular (LV) dysfunction, valvar regurgitation, myocarditis, pericardial effusion, and aortic root dilation. Prior studies have confirmed a relationship between inflammatory changes in acute KD and the risk of coronary artery dilation.[3],[4],[5],[6] Up to 20% of untreated children with KD may progress to develop coronary artery aneurysms, usually after the 1st week of illness.[7] Anecdotal experience suggests that there is significant delay in the diagnosis of KD in India, especially in areas and regions where this condition is still not being diagnosed frequently.[8] KD has a much higher mortality in India than in developed countries. In the Chandigarh cohort, the mortality rate over the last 20 years was reported as 0.8%, as compared to 0.01%–0.08% in children in developed countries.[9]
Currently, we do not have any prospective data regarding incidence and prevalence of cardiac involvement in KD in Indians, compared with rest of the world. This study aimed to know the prevalence of cardiac manifestations and their short-term outcome in KD in an Indian population.
| Methods | | |
Study population
This was a prospective cohort study of all consecutive patients with suspected KD admitted from January 2014 to December 2015 in a tertiary care teaching hospital in Kerala [Figure 1]. After getting informed consent, patient's demographic data were obtained including height, weight, and body surface area (BSA) calculated by DuBois formula. Patient's clinical characteristics, history of the duration of fever, treatment with intravenous immunoglobulin (IVIG), and aspirin were noted. Treatment decision was made entirely by the pediatrician in charge of the patient. | Figure 1: Study design flow chart. JRA: Juvenile rheumatoid arthritis, KD: Kawasaki disease, UTI: Urinary tract infection
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Study end points and definitions
Laboratory investigations included complete blood count, ESR, CRP, serum albumin, serum glutamic-pyruvic transaminase (SGPT), urine for pus cells, troponin I, electrocardiogram, and chest X-ray. Necessary investigations were repeated at 1 month follow-up. Troponin I elevation of ≥0.05 ng/mL was considered as evidence of myocardial involvement. Leukocytosis was defined as a total count of >15000/mm3 and thrombocytosis as the platelet count of >4.5 L/mm3. ESR and CRP were considered elevated if >40 mm/hr and >3 mg/dL, respectively. Abnormal SGPT was defined as as >45 units (U)/L. Sterile pyuria was defined as urine pus cells >10/high power field (HPF) with sterile urine culture.[10]
Echocardiography
Two-dimensional echocardiography was performed using PHILIPS HD7 XE echocardiography machine with a 5 MHz transducer. All the patients were subjected for initial echocardiography on the day of enrollment itself. All the studies were performed by a single investigator. The child was sedated with Triclofos (30–50 mg/kg) syrup. After taking LV measurements and assessing regional wall motion abnormalities (RWMA) in parasternal long-axis view, coronary measurements were taken in parasternal short-axis view. Multiple imaging planes and transducer positions were required for optimal visualization of all major coronary segments.
Coronary measurements were made from inner edge to inner edge and excluded branching points. Left main coronary artery was measured at the midway between ostium and bifurcation. Left anterior descending (LAD) and left circumflex (LCX) were measured 2–3 mm after the bifurcation point. Proximal right coronary artery (RCA) was measured 5 mm after the ostium. Z-Score was calculated for each measurement, based on Montreal study population.[11] Coronary involvement was considered present if the absolute measurements met Japanese Ministry of Health criteria or a Z-score of ≥2.5 in any of the coronary segment.
The presence of wall motion abnormalities, valvular regurgitations, and pericardial effusion were also documented. The severity of valvar regurgitation was qualitatively assessed by color Doppler imaging, with notation made if there was at least mild MR or aortic regurgitation. Pericardial effusion was considered present if its maximal dimension was at least 1 mm in any imaging plane.[12]
Statistical analysis
Data were analyzed using SPSS for Windows, version 16.0. (Chicago, SPSS Inc.). Results are presented as mean ± standard deviation for quantitative variables and number (percentage) for qualitative variables. The difference in mean was assessed using sample t-test. A P < 0.05 are considered statistically significant.
| Results | | |
Baseline characteristics
Out of 56 patients enrolled, 37 (66%) were males with a male-to-female ratio of 2:1. More number of cases, i.e., 24 cases (43%) were admitted during winter, and maximum admissions were in January - 9 (16%). Mean age was 5.3 ± 2.8 years. The distribution of age among study population is given in [Table 1]. Thirty (54%) patients were among 1–5-year age group. Less than 5 years old children were 59% and children >5 years were 41%. A diagnosis of complete KD was made in 41 (73%) patients and incomplete KD in 15 (27%). The average duration of fever among the population was 8.77 ± 3.5 days. IVIG was given in 34 (62.5%) cases. The decision to give IVIG was entirely at the discretion of the treating pediatrician. The mean duration of fever onset to IVIG treatment was 10.41 ± 3.4 days. Eighteen (53%) patients received IVIG after 10 days of fever onset. Fifty four (97%) patients received aspirin, which was continued for an average duration of 8 weeks. Baseline characteristics among study population are given in [Table 2].
Clinical characteristics
Among the classic clinical features described, most common were strawberry tongue which was present in 53 (95%) patients and least common were conjunctivitis (52%) and oral mucosal changes (42%). The details of clinical characteristics are given in [Table 3].
Laboratory parameters
Mean hemoglobin value among the study population was 10.88 ± 1.21 g/dL, and total white cell count was 15071 ± 4860/mm3. Twenty five (45%) patients had ESR >40 mm/hr and 89% had CRP >3 mg/dL. SGPT value among the study population was 33.5 ± 34 U/L, and 23% had an elevated SGPT of >45 U/L. Sterile pyuria was present in 29% of the patients.
Cardiac manifestations
Coronary involvement was observed in 11 (20%) patients by either Japanese Ministry of Health Criteria or a z score of ≥2.5. Nine (16%) patients were found to have coronary involvement when Japanese Ministry of Health Criteria were applied. When the American Heart Association (AHA) criteria (Z score of ≥2.5) were applied, 10 (18%) patients had coronary involvement. Among patients with coronary involvement, Japanese Ministry of Health Criteria when applied resulted in under detection of the number of coronary segments involved in comparison with Z score criterion. Ten out of 11 (91%) patients were detected to have coronary involvement in the initial echocardiogram, and one patient manifested coronary dilatation at 4 weeks follow-up. Ten (91%) patients had left main coronary involvement, followed by LAD in 8 (73%) patients, RCA lesion in 5 (45%), and LCX in 1 (9%) patient [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Video 1] and [Video 2]]. | Figure 2: Left anterior descending artery taneurysm in a child with Kawasaki disease
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 | Figure 6: Right coronary artery aneurysm. AO: Aorta, RCA: Right coronary artery
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[Additional file 1]
Video 1: Parasternal short axis view on transthoracic echocardiogram showing an aneurysm of the left anterior descending artery in a patient with Kawasaki disease.
[Additional file 2]
Video 2: Parasternal short axis view on transthoracic echocardiogram showing an aneurysm of the left main coronary artery in a patient with Kawasaki disease.
Other cardiac manifestations observed were elevated troponin I and pericardial effusion. Troponin I estimation was done for 36 patients and was elevated in four (7%) patients. One of these patients had coronary artery involvement. Mild pericardial effusion was observed among two patients in the initial echocardiogram which got resolved at 4 weeks follow-up. One of them had coronary involvement and the other had elevated troponin I. Hence, the cardiac involvement was present in 14 patients (25%). Three patients had trivial mitral regurgitation, and two had trivial aortic regurgitation. None of the patients had mild or more degrees of valvular regurgitation. LV dysfunction or RWMA were not observed in any of the cases. There was no mortality or myocardial infarction during the entire period of the study.
Comparison of patients with and without cardiac involvement
Distribution of baseline characteristics and laboratory parameters among patients with or without cardiac involvement are given in [Table 4] and [Table 5]. Among clinical features, the presence of conjunctivitis was significantly higher among patients with cardiac involvement (P = 0.04). Among laboratory parameters, mean hemoglobin and packed cell volume (PCV) were lower among children with cardiac involvement (10.66 ± 1.13 g/dL vs. 10.95 ± 1.23 g/dL and 30.95 ± 2.8 % vs. 31.66 ± 3.0 %, respectively). Mean total white cell count was higher among patients with cardiac involvement. Mean platelet count among those with cardiac involvement was 6.26 ± 2.5 lac/mm3 against 5.01 ± 1.46 lac/mm3 among patients without cardiac involvement which was statistically significant (P = 0.03). Mean value of ESR was significantly higher among patients with cardiac involvement (101.92 ± 22 mm/hr vs. 74.26 ± 28.6 mm/hr; P 0.002). An ESR value of >100 mm/hr predicted cardiac involvement (P = 0.03). The mean SGPT value was higher among those with cardiac involvement (54 ± 55.5 U/L vs. 26.64 ± 20.5 U/L) which was statistically significant (P = 0.008). | Table 4: Correlation of cardiac involvement with clinical characteristics*
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| Discussion | | |
KD is reported to be a disease of young children with 75%–80% of cases being below 5 years.[1],[2] A survey from Japan found that <1% of cases occurred in children aged 9 years or older.[13] In our study, 59% of children were under 5 years of age. Mean age in the present study (5.3 ± 2.8) was higher concerning the reported data. A study conducted in Post Graduate Institute, Chandigarh[14] showed that significant number of children were more than 5 years of age. These data and the present study suggest that a greater number of older children present with KD in India compared to other countries. It could represent skewed data because of possible under-diagnosis of KD in infants and young children in our country.[15] Younger children with KD in India are probably being misdiagnosed as having viral exanthemata (especially measles) and other febrile illnesses.[9],[16]
More number of cases were reported during winter season (43%) with a maximum incidence in January (16%) during the study period. This finding is similar to other reports showing higher incidence of the disease during winters.[2],[17],[18] KD is common in males with a reported male: female ratio 1.5–2:1.[2],[19] In our study, male: female ratio was 2:1. A diagnosis of complete KD was made in 41 (73%) patients and incomplete KD in 15 (27%). The mean duration of fever was 8.7 ± 3.5 days. IVIG was given in 62.5% of cases and 53% of children received IVIG 10 days after onset of fever. The decision on IVIG treatment was the discretion of treating pediatrician. Most of the patients did not receive IVIG due to financial constraints. Majority of the patients with cardiac involvement (80%) had received IVIG after the initial positive echocardiogram. Aspirin was given to almost all patients (97%) for a minimum of 6 weeks.
In this study, strawberry tongue was the most frequent (91%) manifestation among clinical features. Oral mucosal changes (42%) and nonpurulent conjunctivitis (52%) were the least common clinical features. According to previously published data, the least common manifestation is cervical lymphadenopathy[2],[17],[20] which in the present study was reported to be 86%. Thus, there is significant geographic variation in clinical presentation of KD.
Polymorphonuclear leukocytosis, normocytic anemia, lymphocytosis, elevated acute-phase reactants, elevated aminotransferase enzyme, and sterile pyuria are classically seen among patients with KD.[2],[13],[17],[21] In the present study, mean hemoglobin and PCV were lower for the age. Mean total white cell count and platelet count were more than the maximum reference range (15071 ± 4860/mm3 and 5.32 ± 1.85 lac/mm3, respectively). The mean value for ESR and CRP were also significantly higher among the study population (81.17 ± 29.5 mm/hr and 28.87 ± 30 mg/L, respectively). Sterile pyuria was observed in 29% of children with KD. However, mean SGPT value was within the normal reference range (33.51 ± 34 U/L), and only 23% of patients had a higher value >45 U/L.
Cardiac involvement has been variably reported in up to 25% of the cases.[2],[10],[17],[21],[22] A retrospective study from Pakistan[20] reported an incidence of 41%. In our study, incidence of overall cardiac involvement was 25%. Eleven (20%) patients had coronary involvement, four had troponin elevation, and 2 had mild pericardial effusion. No patient had significant valvular regurgitation, LV dysfunction or RWMA. No death or myocardial infarction was reported during the entire duration of the study. A similar incidence of coronary involvement has been reported from different parts of India.[7],[9],[16],[21],[23],[24]
Coronary involvement was detected by applying both Japanese Ministry of Health criteria[25] and AHA criteria[2],[26] (Z score ≥ 2.5). On applying Japanese Ministry of Health criteria, nine patients (16%) were detected to have coronary involvement. Ten cases (18%) were detected by applying Z score. Among patients with coronary involvement, Japanese Ministry of Health Criteria when applied resulted in significant under-detection of the number of coronary segments involved in comparison with Z score criterion (25% vs. 33.3%), as also observed by de Zorzi et al.[27] and Newburger et al.[2] Coronary segments involved in the order of frequency were left main >LAD >RCA >LCX. Majority of reported data shows LCA more commonly involved than RCA.[2],[17],[20]
On follow-up of 11 children with coronary involvement, all except three had resolution within 3 months. Coronary aneurysm persisted for 1 year in two children and for at least 6 months in one child who was lost to follow-up after 6 months. One child had giant coronary aneurysm of LAD and later developed thrombus in the aneurysm. He was started on warfarin along with low dose aspirin, and the aneurysm persisted even after 1 year and 6 months.
On comparing patients with or without cardiac involvement according to baseline characteristics, there was no statistically significant difference among variables such as age, male:female ratio, type of KD, fever duration, and duration of fever onset to IVIG treatment. Mean duration of fever onset to IVIG treatment was similar between patients with or without cardiac involvement (10.47 ± 3.7 days and 10.21 ± 3.5 days, respectively). Mean delay in treatment was >10 days in both the groups. All the patients with cardiac involvement received IVIG, whereas only 50% of children without cardiac involvement received the treatment. However, most of the studies have shown that IVIG treatment results in significant reduction in the occurrence of cardiac manifestations among children affected with KD.[2],[17],[22],[27],[28],[29] In the present study, most of the children with cardiac involvement (80%) had received IVIG only after initial echocardiography. The higher occurrence of cardiac involvement among patients who received IVIG must be due to treatment bias. Two patients among those with cardiac involvement received the second dose of IVIG due to treatment failure.
Clinical characteristics were similar in the two groups except nonpurulent conjunctivitis which was significantly higher among children with cardiac involvement (79% vs. 43% P = 0.04).
Among laboratory parameters, mean hemoglobin and PCV were lower among children with cardiac involvement while mean total white cell count was higher. However, none of these were statistically significant. Similarly, no statistically significant differences were observed between the patients with or without cardiac involvement in the values of CRP, serum albumin and in the prevalence of sterile pyuria. However, the patients with cardiac involvement had significantly higher values of mean platelet count, ESR and SGPT. An ESR value >100 mm/hr predicted cardiac involvement with statistical significance.
Study limitations
Although 87% of our patients completed 6 months follow-up, 1 year follow-up was completed only by 57% of study the population. Although echocardiography for coronary measurements was performed by a single operator, inter- and intra-observer variability in coronary artery measurements were not assessed in the study. Coronary measurements based on BSA were compared with western population (Montreal study[11]) to obtain Z score, due to the lack of enough Indian data for normal coronary measurements based on BSA.
| Conclusions | | |
Cardiac manifestations were present in 25% of patients with KD; 20% of the children had coronary involvement in the form of aneurysm or ectasia. In nearly three-forth of patients, coronary dilatation got resolved in 3 months. Nonpurulent conjunctivitis, mean platelet count and mean SGPT were significantly higher among patients with cardiac manifestations. ESR value of >100 mm/hr was significantly higher among patients with coronary dilatation. Significant valvular heart diseases, aortic root involvement, RWMA, and myocardial contractile dysfunction were not seen in this Indian population with KD.
What is already known?
Cardiovascular sequel is the most serious manifestation of KD and associated with significant morbidity and mortality. Coronary artery involvement is the most important lesion and can cause myocardial ischemia, infarction, or sudden cardiac death. Cardiac involvement in KD is however not limit to coronary arteries alone and may include myocarditis, pericarditis, endocarditis, valvular dysfunction, and arrhythmias.
What this study adds?
This study provides prospective data regarding incidence and prevalence of cardiac involvement in KD in an Indian population. The study showed that significant valvular heart diseases, aortic root involvement, RWMA, and myocardial contractile dysfunction were not seen in this Indian population with KD.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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