Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
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Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
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Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




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Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




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Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2023 | Month : June | Volume : 17 | Issue : 6 | Page : SC10 - SC14 Full Version

Cardiovascular Complications in Patients with Kawasaki Disease in a Tertiary Care Hospital in West Bengal, Eastern India- A Prospective Clinical Study


Published: June 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/63525.18013
Sayani Pan, Uttam Kumar Roy, Nilanjan Ghosh, Tarak Nath Ghosh

1. Senior Resident, Department of Paediatrics, Burdwan Medical College and Hospital, Burdwan, West Bengal, India. 2. Associate Professor, Department of Pharmacology, Burdwan Medical College and Hospital, Burdwan, West Bengal, India. 3. Assistant Professor, Department of Paediatrics, Burdwan Medical College and Hospital, Burdwan, West Bengal, India. 4. Professor, Department of Paediatrics, Burdwan Medical College and Hospital, Burdwan, West Bengal, India.

Correspondence Address :
Dr. Sayani Pan,
Indraprastha, Baburbag, Burdwan-713101, West Bengal, India.
E-mail: sayanipan92@gmail.com

Abstract

Introduction: Kawasaki Disease (KD) is an acute self-limiting systemic vasculitis involving medium and small sized arteries. It may soon replace rheumatic fever to become the most common cause of acquired heart disease in Indian children. Coronary Artery Aneurysm (CAA) which can develop in 15-25% of untreated children remains the most dreaded complication of KD. Predicting the risk of CAA and taking timely measures can help in reducing the fatality of the condition.

Aim: To study the spectrum of cardiovascular complications in patients with KD and also to assess associated risk factors for developing CAA in the patients under study.

Materials and Methods: The prospective clinical study was carried out in the Paediatric Medicine Ward, Burdwan Medical College and Hospital, West Bengal, Eastern India, from 1st January, 2020 to 31st May, 2021. A total of 52 children diagnosed with KD, aged between one month to 12 years, were included and followed-up for six months. Data regarding demographic variables, duration of fever, Intravenous Immunoglobulin (IVIG) resistance, hepatomegaly, neutrophilia, thrombocytopaenia, haematocrit, Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), hepatic transaminases (alanine transaminase, aspartate amino-transferase), hyponatraemia, hypoalbuminaemia, and N-terminal-brain natriuretic peptide (NT-proBNP) were collected. Univariate and multivariate regression analyses were done using these variables for assessment of risk factors.

Results: In the present study, out of 52 children, 28 (53.85%) were males and 24 (46.15%) were females with mean age of 3.74±2.55 years. Cardiovascular complications were observed in 27 (51.92%) patients, of whom 19 (35.54%) had CAA. Duration of fever ≥10 days, IVIG resistance, thrombocytopaenia, low haematocrit, Alanine Transaminase (ALT) ≥100 U/L, hypoalbuminaemia, and raised NT-proBNP were proven to be significant risk factors for development of CAA on univariate analysis. Thrombocytopaenia and raised NT-proBNP came across as significant on binary logistic regression analysis.

Conclusion: In this study, one or more types of cardiovascular abnormalities were present in 51.92% cases. Seven risk factors were identified to be significant in development of CAA on univariate analysis and among them two were proven significant in binary logistic regression.

Keywords

Aneurysm, Coronary arteries, Echocardiography, Risk factors, Vasculitis

Kawasaki disease, an acute self-limiting systemic vasculitis involving medium and small-sized arteries, is the leading cause of acquired heart disease in children in most of the developed countries (1). In India there has been a steady increase in the number of cases of KD since the mid-1990s (2). There is anecdotal evidence that KD may soon replace rheumatic fever to become the most common cause of acquired heart disease in Indian children (3).

The primary concern in KD is coronary artery abnormalities, which can develop in 15-25% of untreated children (1). Untreated CAA can lead to Myocardial Infarction (MI), ischaemic heart disease or even sudden death (4).

Several risk stratification models have been constructed to determine which patients with KD are at highest risk for CAA. Out of these, the Kobayashi Score is the most widely used and has high sensitivity and specificity (5). Duration of fever has been consistently proven to be a powerful risk factor (6). Younger age, particularly age less than one-year, male, delayed diagnosis and treatment have also been associated with development of CAA (1). Laboratory detected conditions, including neutrophilia, thrombocytopaenia, elevated hepatic transaminases, elevated CRP, and lower serum albumin, are also prominent risk factors (7).

There is a possible difference in clinical presentation of KD in India (8). Whether these differences are the reason that none of the published risk scores can accurately identify all the at-risk children in the Indian population is open to question. Although, there are a multitude of Indian studies on the epidemiology, clinicolaboratory features, and cardiovascular sequelae of KD (9),(10),(11),(12), authors could not find any study particularly pertaining to the risk factors of developing CAA in KD in India.

Hence, the present study was undertaken to study the spectrum of cardiovascular complications in patients with KD and also to assess the risk factors for developing CAA in the Indian scenario.

Material and Methods

The present prospective clinical study was carried out in the Paediatric Medicine Ward, Burdwan Medical College and Hospital, West Bengal, India, from 1st January, 2020 to 31st May, 2021. Approval for the study was taken from the Institutional Ethics Committee (Memo no: BMC/Ethics/030). Informed consents were taken from the parents for use of anonymised data.

Inclusion criteria: Children aged between one month to 12 years, with KD (meeting the criteria for complete or incomplete KD) were included in the study. Complete KD was defined as persistent fever for atleast five days along with presence of atleast for out of the five principal features namely: (i) bilateral non exudative conjunctival injection with limbal sparing; (ii) erythema of the oral and pharyngeal mucosa with strawberry tongue and red, cracked lips; (iii) oedema (induration) and erythema of the hands and feet; (iv) rash of various forms (maculopapular, erythema multiforme, scarlatiniform or less often psoriatic-like, urticarial or micro-pustular); and (v) nonsuppurative cervical lymphadenopathy, usually unilateral, with node size >1.5 cm. Atypical KD included patients who had persistent fever, fulfilled <4 of the five principal criteria but echocardiographic and laboratory finding were suggestive of KD (1).

Exclusion criteria: Patients who had pre-exiting heart disease, and whose guardians refused to provide consent were excluded from the study.

A total of 52 patients, who presented to the Department of Paediatric Medicine Ward, within the study duration, following the inclusion criteria, were enrolled in the study by convenient sampling.

Study Procedure

Once the diagnosis was confirmed, two-dimensional (2D) echocardiography was performed at diagnosis and on second week of the disease. The diameters of the Right Main Coronary Artery (RMCA), Left Main Coronary Artery (LMCA), the Left Anterior Descending coronary artery (LAD) and the Left Circumflex (LCX) coronary artery were measured with the help of 2D echocardiography.

All the patients were followed-up for six months after admission. If the initial results were normal, a repeat echocardiography was performed six weeks after onset of illness. Echocardiography study was repeated in these patients after three months and at the end of six months. If results of either of the initial studies were abnormal or the patient had recurrent fever or other symptoms of KD, then echocardiography was done monthly or tailored to the patient’s coronary status.

As Body Surface Area (BSA) adjusted coronary artery dimensions (z-scores) on baseline echocardiography in the first 10 days of illness appear to be good predictors of involvement during follow-up and the American Heart Association (AHA) uses Z-score classification system for CAA in KD, serial Z-score assessment was done (with every echocardiographic study as mentioned previously) throughout the follow-up period (13). The AHA z-score classification system is as follows:

i. No involvement: always <2
ii. Dilation only: 2 to <2.5; or if initially <2, a decrease in Z-score during follow-up ≥1
iii. Small aneurysm: ≥2.5 to <5
iv. Medium aneurysm: ≥5 to <10, and absolute dimension <8 mm
v. Large or giant aneurysm: ≥10, or absolute dimension ≥8 mm (1)

For assessment of risk factors for developing CAA, 17 independent variables (considering importance as per literature search) namely age, sex, religion, socioeconomic status, duration of fever, IVIG resistance (persistent or recrudescent fever 36 hours after completion of the initial IVIG infusion of 2 g/kg), hepatomegaly, neutrophilia (absolute neutrophil count/ANC >7,700/mm3), thrombocytopaenia (Platelet count <1,50,000/mm3), haematocrit, ESR, CRP, hepatic transaminases (alanine transaminase, aspartate aminotransferase, hyponatraemia (serum sodium <135 mEq/L), hypoalbuminaemia (serum albumin <3.5 g/dL), and N-terminal-brain natriuretic peptide (NT-proBNP) [14-19]. All these necessary investigations were sent to the Pathology, Biochemistry, and Radiology Department of the study institution on the first week upon diagnosis of the illness.

Statistical Analysis

The collected data was entered in Microsoft Excel worksheet (Microsoft, Redwoods, WA, USA) and double-checked. International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS), software version 26.0 for Windows software package (IBM SPSS Inc., Chicago, IL, USA) and statistical software, STATA (version 14.2) were used for recording the data and analysing the results. Means were compared by Chi-square test. The p-value of <0.05 was considered as statistically significant.

Results

Out of the 52 KD patients, 28 (53.85%) were males, rest were females with a mean age of 3.74±2.55 years. In the present study, 32(61.54%) patients aged below four years and only 2 (3.85%) patients were more than eight years of age (Table/Fig 1).

The most frequently encountered cardiac abnormality was myocarditis, found in 24 (46.15 %) patients, followed by CAA, were present in 19 (35.54%) patients. In the present study, 27 (51.92%) patients had developed more than one cardiac abnormality (Table/Fig 2). Of total, 19 (36.54%) patients had myocarditis in the acute phase of the disease and developed CAA in the follow-up period. A total of 5 (9.62%) other patients developed pericarditis with myocarditis, pericarditis/pericardial effusion (15.38%) mitral regurgitation like valvular disease (3.85%) and mild aortic root dilatation (1.92%). Nine (17.31%) patients who had both CAA and myocarditis, suffered from cardiogenic shock in the acute phase of the disease. Three (5.77%) patients who had developed valvular disease and aortic root dilatation, also had associated CAA. Case fatality rate was zero.

All the patients were followed-up with utmost care and sincerity for six months after admission. In the present study, 14 (26.92%) patients had small aneurysms, 4 (7.69%) had moderate aneurysms and only 1 (1.92%) patient had a large aneurysm (Table/Fig 3).

On follow-up, 17 out of the 19 patients with CAA showed regression in Z-scores. In four patients Z-score reduced by >2, in six patients between ≥1 to 2 and in seven patients Z-score had decreased only slightly (<1). Two patients had no regression in Z-score and developed thrombi in coronary arteries (LMCA in both cases).

Risk Factor Assessment for Development of Coronary Artery Aneurysm (CAA)

Seventeen independent variables were considered while assessing risk factors for development of CAA. Among them, seven variables i.e., duration of fever ≥10 days, IVIG resistance, thrombocytopaenia, haematocrit <35%, ALT ≥100U/L, hypoalbuminaemia, and NT-proBNP ≥1000 pg/mL, were found to have significant association with development of CAA (Table/Fig 4)a,b

On multivariate analysis using binary logistic regression, two variables: Thrombocytopaenia (p-value=0.02, OR=9.00), and NT-proBNP (p-value=0.02, OR=1.003) had p-value of <0.05. The model can collectively explain 60.1%-82.2% variability of development of CAA (Table/Fig 5)..

Discussion

The study aimed to diagnose various cardiovascular manifestations of KD and identify the risk factors for development of CAA. Majority of the children (61.54%) were aged below four years and only two children were more than eight years of age. One or more type of cardiovascular abnormalities was present in 51.92% cases. The major cardiovascular manifestations observed were myocarditis (46.15%), CAA (36.54%), cardiogenic shock (17.31%), pericarditis/pericardial effusion (15.38%), mitral regurgitation like valvular disease (3.85%) and mild aortic root dilatation (1.92%). On univariate analysis, we found that duration of fever ≥10 days, IVIG resistance, thrombocytopaenia, haematocrit <35%, ALT ≥100 U/L, hypoalbuminaemia, and NT-proBNP ≥1000 pg/mL were significantly associated with development of CAA. Thrombocytopaenia (p-value=0.02, OR=9.00), and NT-proBNP (p-value=0.02, OR=1.003) were proven to be significant in binary logistic regression model.

One study by Kato H et al., demonstrated CAA in 7 (35%) out of 20 KD patients (20). This finding is similar to the present study where there was development of CAA in 36% patients. Various studies by Newburger JW et al., Rowley AH and Shulman ST, and Burns JC have estimated the incidence to be between 15-25% [21-23]. Anderson MS et al., found the incidence of CAA to be 24% when diagnosis of KD was delayed (24). The higher incidence of CAA in the present study might indicate their rising incidence in KD, or it may be owed to delayed presentation by the patient at the hospital, delay in diagnosis or due to the mysterious link between Multisystem inflammatory Syndrome in Children (MIS-C) and KD. All the present cases, however tested negative for both Coronavirus Disease-2019 (COVID-19) Real-Time Reverse Transcription Polymerase Chain (RT-PCR) and antibody.

Authors did serial echocardiography to diagnose as well as document the progression of CAAs. On follow-up, 17 out of the 19 patients with CAA showed regression in Z-scores. In four patients Z-score had reduced by >2, in six patients between ≥1 to 2 and in seven patients Z-score had decreased only slightly (<1).

Two patients on the other hand, had no regression in Z-score and developed thrombi in coronary arteries (LMCA in both cases). Hörl M et al., studied 94 patients with KD between 2002 and 2018 and concluded that a significant progression of patients’ coronary artery Z-scores in serial echocardiographic measurements may be helpful to ensure diagnosis of CAA early even if Z-scores are within the normal range (25).

Gowin E et al., did a retrospective analysis in 2008-2014 with 30 KD patients (26). Cardiac involvement was detected in 18 (60%) patients, including CAA in 10 (33.3%). During 12 months of follow-up, coronary artery dilatation resolved in five children, and one patient developed aneurysm. They concluded that KD should be considered in the differential diagnosis of children with prolonged fever. During the acute stage of the disease, children with KD require regular cardiac evaluation, and long-term care is needed when cardiovascular complications occur and the present study had similar results.

Pilania RK et al., concluded in their study that while CAAs are the most well-recognised complications of this condition, other affectations like myocarditis, KD shock syndrome, valvular abnormalities, and endothelial dysfunction are also being increasingly recognised (27). Studies by Kao CH et al., and Rinder CS et al., have documented myocardial inflammation in 50% to 70% of patients using 67Ga citrate scans (planar or single photon emission CT) and 99mTc-labeled white blood cell scans [28,29]. However, the severity of myocarditis does not appear to be associated with the risk of CAA (30). In the current study, myocarditis was found in 46.15% and 21.15% had both myocarditis and CAA. These findings corroborated with findings of the studies mentioned above.

Over the years, a handful of scoring systems have been developed to identify children at highest risk for coronary artery abnormalities mostly from Japan and the United States (US). In some centres in Japan, a risk scoring system developed by Harada K is used to determine whether IVIG treatment will be used (17). IVIG is given to children who fulfil four of the following criteria, assessed within nine days of onset of illness: 1) white blood cell count >12000/mm3;

2) platelet count <350000/mm3; 3) CRP >3+; 4) haematocrit <35%; 5) albumin <3.5 g/dL; 6) age ≤12 months; and 7) male sex. Bai L et al., conducted a decade-long study from the year 1998 to 2008 in north-west and central China in order to provide early intervention for coronary artery lesions caused by KD and observed that the KD patients with CRP higher than 30 mg/L, ESR higher than 40 mm/h, hepatomegaly and IVIG ineffectiveness, had higher incidence of CAA development (19). Son MBF et al., designed a practical risk score assigning points to each variable like baseline Z score of LAD or RMCA ≥2.0, age less than six months, Asian race, and CRP ≥13 mg/dL and created low, moderate, and high-risk groups. The odds of CAA were 16-fold greater in the high versus the low-risk groups in the development cohort (31). Various other studies by Kaneko K et al., Honkanen VE et al., and Nakamura Y et al., concluded prolonged duration of fever, thrombocytopaenia, raised ESR, hypoalbuminaemia, and age less than one year to be associated with higher chance of development of CAA [32-34]. Dionne A and Dahdah N concluded that patients with resistance to IVIG treatment and CAA had higher levels of NT-proBNP, suggesting a prognostic role (35). The present study also mirrored these results.

In the present study, authors found seven independent risk factors for occurrence of CAA in KD. Giving special attention to patients with any of these features and subsequently following them up with serial echocardiography will help in early diagnosis of CAA and prevent grave consequences.

Although several Japanese risk scoring systems (Kobayashi, Egami, Sano, and Harada K risk scores) are available for prediction of CAA in KD, unfortunately, none of them are properly applicable on Indian population (13). In one of the first initiatives in this country, authors have tried to identify the risk factors of development of CAA in KD and have able to delineate quite a few of them. The present study is a small step towards devising an Indian risk scoring system for CAA, but there is a need for more studies from other parts of the country to formulate that.

Limitation(s)

This is a single-centre hospital-based study conducted on a predominantly homogenous ethnic population that limits its generalisation. Though, authors could find several statistically significant risk factors of CAA in this population, to formulate a risk score, large-scale multi-center studies conducted over a larger geographical area with diverse ethnic composition. Also, following up the patients beyond six months was not done.

Conclusion

In this study, one or more type of cardiovascular abnormalities was present in 51.92% cases. Seven risk factors were identified to be significant in development of CAA on univariate analysis and among them two were proven significant in binary logistic regression. In one of the first initiatives in this country, authors have tried to identify the risk factors of development of CAA in KD and have able to delineate quite a few of them. Further studies on these parameters with larger number of patients might be helpful in devising an Indian risk scoring system for CAA, so that it becomes possible to assess the probability of CAA early in the course of the disease and take necessary measures to minimise the fatality of this condition.

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DOI and Others

DOI: 10.7860/JCDR/2023/63525.18013

Date of Submission: Feb 25, 2023
Date of Peer Review: Mar 20, 2023
Date of Acceptance: May 13, 2023
Date of Publishing: Jun 01, 2023

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Mar 02, 2023
• Manual Googling: Apr 05, 2023
• iThenticate Software: May 10, 2023 (12%)

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