Critical predictors of heart transplant necessity in children with advanced DCM

Abstract

Background

Dilated Cardiomyopathy (DCM) frequently culminates in Heart Failure (HF), positioning it as the primary instigator of cardiac transplantation among pediatric patients. Nevertheless, the issue of cardiac transplantation in children demands a comprehensive and judicious strategy. The aim of this research was to ascertain the clinical attributes at the point of diagnosis that could potentially signal the requirement for transplantation in pediatric patients diagnosed with Dilated Cardiomyopathy (DCM).

Methods

In our study, we recognized 99 instances of pediatric cardiomyopathy accompanied by advanced heart failure (EF < 30%). The patients were categorized into two cohorts, namely, the transplantation group and the non-transplantation group, based on whether they underwent cardiac transplantation. Each patient in both groups was administered conventional medication. Patients within the non-transplantation group demonstrated improved cardiac function following a minimum of six months of medication therapy. The identification of factors associated with heart transplantation in pediatric DCM was facilitated through the utilization of competing risks and multivariable modeling.

Result

Out of a total of 99 children, 35 were recipients of transplants, henceforth referred to as the transplantation group, while the remaining 64, diagnosed with Dilated Cardiomyopathy (DCM), did not undergo transplantation, forming the non-transplantation group. A comparative analysis revealed no significant differences in age, gender, and weight between the two groups. However, the transplantation group demonstrated a significantly higher New York Heart Association (NYHA) class 4, incidence of galloping rhythm, hepatomegaly, morphological changes, ascites, and orthopnea in comparison to the non-transplantation group (all p < 0.05).In the meantime, there was a significantly higher incidence of abnormal left ventricular end-diastolic diameter, aortic and pulmonary valve regurgitation rates, and incomplete myocardial compaction in the left ventricle within the transplant group as compared to the non-transplant group (p < 0.05).Nonetheless, the analysis revealed no significant disparities in biochemical markers, which include BNP, CK-MB, CTnI, GOT, BUN, sCr, and GPT, between the two groups (all p > 0.05). A univariate logistic regression analysis demonstrated that NYHA score [aOR (95%CI) = 2.78 (1.06–7.27), p = 0.037], Ascites [aOR (95%CI) = 12.93 (2.45–68.22), p = 0.003], and Left ventricular noncompaction [aOR (95%CI) = 3.73 (1.01–13.86), p = 0.048] were all significantly correlated with the Transplantation group.

Conclusions

Pediatric dilated cardiomyopathy (DCM) presenting with indicators of progressive heart failure, including an elevated New York Heart Association (NYHA) classification, ascites, and left ventricular non-compaction, necessitates increased vigilance. It is advised that these cases be closely monitored, and early consideration should be given to heart transplantation as a potential therapeutic intervention.

Introduction

Dilated cardiomyopathy (DCM) represents the most prevalent form of cardiomyopathy in pediatric patients, characterized by a dilated left ventricular and systolic dysfunction. The etiology of DCM in children is often linked to genetic factors, however, approximately 22% of pediatric DCM cases are idiopathic, presenting without any identifiable cause [1]. The clinical manifestations of pediatric DCM are diverse and largely dependent on the etiology. Heart failure (HF) is the most frequently observed clinical presentation, exhibiting a high incidence rate among pediatric patients diagnosed with DCM. The prognostic outcomes of Dilated Cardiomyopathy (DCM) in pediatric patients exhibit significant variability, ranging from complete recuperation to necessitating heart transplantation, or in extreme cases, resulting in mortality. Given the infrequency of myocardial fibrosis in pediatric populations, the incidence of sudden death is comparatively lower than in adult DCM cases [2]. Notwithstanding the ongoing debate, it is an incontrovertible fact that the same pharmacological regimens employed for managing heart failure in adults are also utilized in the clinical treatment of children [3].Angiotensin-converting enzyme (ACEI) inhibitors, angiotensin receptor blockers, β-blockers, mineralocorticoid receptor antagonists, angiotensin receptor/neprilysin inhibitors, ivabradine, and the most recent addition, sodium-glucose cotransporter 2 inhibitors, are all utilized in the treatment of heart failure [4]. Furthermore, long-term mechanical circulatory support is employed either as a bridge to heart transplantation or as destination therapy in advanced cases of pediatric dilated cardiomyopathy (DCM) [5]. It is important to note that DCM remains the most prevalent indication for heart transplantation in both adult and pediatric populations of advanced heart failure patients [6]. In recent years, there has been a noted increase in the ratio of patients receiving transplants for Dilated Cardiomyopathy (DCM) in comparison to other Heart Failure (HF) etiologies. Generally, patients diagnosed with DCM exhibit a favorable prognosis in both the short and long term, with a median survival rate of 12.2 years post-transplantation [7]. Despite these statistics, the necessity of heart transplantation remains a clinically contentious issue. While the medication regimen for DCM can potentially result in sudden death, parents of pediatric DCM patients often prefer a more permanent treatment approach using medication until it is no longer effective, at which point they consider heart transplantation. Consequently, there exists a clinical necessity for enhanced evaluation of the temporal progression towards heart transplantation.

In the current study, we assembled a cohort of 99 pediatric patients suffering from severe heart failure, who were on the waiting list for heart transplantation. Simultaneously, these patients were on a regular regimen of cardiotonic, diuretic, and vasodilator drugs. The medication’s effectiveness was evaluated for a period of six months prior to reassessing the necessity for continued wait for a heart transplant. It was observed that some patients exhibited significant improvement due to the heart failure treatment, thus moving them from the transplant waiting group. The primary objective of conducting a comparative analysis between the medication group and the heart transplantation group was to identify potential risk factors associated with transplantation.

Materials and methods

Study design

This study is a single-center, retrospective, observational analysis conducted at the Department of Pediatric and Cardiac Surgery, Tongji Medical College Affiliated Union Hospital, Huazhong University of Science and Technology. It involves a total of 99 pediatric cardiomyopathy cases with advanced heart failure (Ejection fraction EF < 30%) that were collected between January 1, 2018, and December 30, 2023. The study cohort comprised 38 males and 61 females, with ages ranging from 6.7 to 120 months. All cases were diagnosed by specialists based on distinctive clinical symptoms and imaging examinations, adhering to the diagnostic criteria for Cardiomyopathy [8]. The exclusion criteria are as follows: (1) End-stage viral myocarditis; (2) Restrictive cardiomyopathy with a definitive diagnosis; (3) Rheumatic heart disease; (4) Pulmonary heart disease; (5) congenital heart disease in children;6) Massive pericardial effusion; 7) Keshan disease. All patients received regular medication for six months to improve left ventricular ejection function by at least 10%. Patients who achieve this improvement will be removed from the transplantation group. Prior to reassessing the necessity of continuing the heart transplantation waiting list, some patients demonstrating significant improvement in heart failure are transitioned to the non-transplantation group. According to whether the pediatric patients eventually underwent heart transplantation, the patients were divided into the heart transplantation group (n = 35) and the non-heart transplantation group (n = 64). Our study was approved by the ethics committee at Tongji Medical College Affiliated Union Hospital, Huazhong University of Science and Technology.

Data collection

This investigation utilized a retrospective research approach to gather foundational data concerning pediatric patients from the electronic medical record system. The data collected included the age at initial diagnosis, gender, clinical manifestations, heart function classification, past medical history, family history, and levels of creatine kinase and its MB isoenzyme (CK-MB), cardiac troponin I (cTnI), and B-type natriuretic peptide (BNP). Additionally, results from electrocardiograms, cardiac echocardiography [including left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and mitral valve regurgitation],24-hour dynamic electrocardiogram and cardiac magnetic resonance imaging were also collected and analyzed. The modified ROSS scoring system was used to classify HF in pediatric patients aged 0 to 14 years: scores of 0–2 as functional class I, 3–6 as functional class II, 7–9 as functional class III, and 10–12 as functional class IV; while patients over 14 years old were classified using the NYHA functional classification standard. In addition to the primary data, we gathered supplementary laboratory parameters at the point of admission. These included alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamic oxaloacetic transaminase (GOT), urea nitrogen (BUN), serum creatinine (sCr), glutamic pyruvic transaminase (GPT), and various other indicators related to blood coagulation.

Statistical analysis

SPSS 22.0 (IBM Co., Armonk, NY, USA) was used for statistical analysis. Continuous and integral variables were presented as the mean value and standard deviation (SD) for normally distributed variables, and the median and quartile for abnormal distributed variables. Categorical variables were expressed as their counts and proportions. Childrens with and without heart transplantation were compared by two-sided independent, Student’s t-test for normally distributed variables, Mann–Whitney U test for variables obeyed abnormal distribution, and chi-square test or Fisher’s exact test for categorical data. The risk factors for heart transplantation were determined by logistic regression analysis. After analyzing the difference between the heart transplantation group and the non- heart transplantation group, we chose to incorporate those significant indicators into the logistic regression analysis model. The diagnostic value of the risk factors for DCM patients with Transplantation was evaluated by calculating the area under receiver’s operator characteristic (ROC) curve (AUC). In the two-tailed test, P < 0.05 was considered statistically significant.

Results

Demographic and clinical characteristics of DCM patients with or without transplantation

This study incorporated a total of 99 pediatric cases of dilated cardiomyopathy (DCM). The cohort was bifurcated into two distinct groups predicated on the requirement for a cardiac transplant: the transplant group (n = 35) and the non-transplant group (n = 64). A comprehensive summary of the demographic and clinical attributes of all participants is presented in Table 1. Comparative analysis revealed no statistically significant disparities in age, weight, gender, shock, abdominal discomfort, and embolization between the two groups. Nonetheless, the group that underwent transplantation demonstrated a significantly higher prevalence of NYHA 4, galloping rhythm, hepatomegaly, morphological changes, ascites, and orthopnea in comparison to the group that did not undergo transplantation (all p < 0.05).

Table 1.

Comparison of demographic and clinical characteristics among non-transplantation and transplantation

	Transplantation n = 35	Non-transplantation n = 64	P value
Age, months	50.0 [19.0-120.0]	42.0 [6.7-113.5]	0.337
Body weight, kg	20.5 [14.9–31.3]	15.5 [6.5–34.3]	0.116
Male, n	16 (45.7)	22 (34.4)	0.267
NYHA, score NYHA 1	0 (0)	2 (3.1)
NYHA 2	2 (5.7)	14 (21.9)
NYHA 3	7 (20.0)	24 (37.5)
NYHA 4	26 (74.3)	21 (32.8)	< 0.001
Shock, n	6 (17.1)	4 (6.3)	0.160
Galloping rate, n	4 (11.4)	0 (0)	0.014
Abdominal pain, n	3 (8.6)	7 (10.9)	0.709
Hepatomegaly, n	29 (82.9)	18 (28.1)	< 0.001
Ascites, n	20 (57.1)	3 (4.7)	< 0.001
Orthopnea, n	14 (40.0)	10 (15.6)	0.007
Embolization, n	4 (11.4)	3 (4.7)	0.240

Values are median [interquartile range]. Numbers in parentheses denote percentages

Comparison of cardiac imaging and electrocardiographic indicators between children in the transplantation group and the non-transplantation group

As evidenced in Table 2, there was a significant increase in the heart-to-thorax ratio and the abnormality rate of dynamic electrocardiogram in the transplant group as compared to the non-transplant group (p < 0.05). Furthermore, a higher incidence rate of abnormal left ventricular end-diastolic diameter, regurgitation rate of aortic and pulmonary valves, and incomplete myocardial compaction in the left ventricle was observed in the transplant group relative to the non-transplant group (p < 0.05). Considering the clinical characteristics and conditions of both cohorts, we assert that these findings provide a precise reflection of the health statuses of the patients within each group.

Table 2.

Comparison of clinical characteristics among non-transplantation and transplantation

	Transplantation n = 35	Non-transplantation n = 64	P value
Cardiothoracic ratio, n	27 (77.1)	26 (40.6)	< 0.001
Electrocardiographic abnormity, n	23 (65.7)	48 (75.0)	0.357
Holter abnormity, n	12 (34.3)	8 (12.7)	0.011
Abnormity of LVDd, n	23 (65.7)	27 (42.2)	0.025
LVEF, %	23.0 [19.2–26.0]	25.0 [21.0-28.7]	0.079
Valvular regurgitation, n	34 (97.1)	63 (98.4)	1.000
Mitral valve	36 (97.1)	60 (95.2)	0.357
Aortic valve	0 (0)	11 (17.5)	0.013
Tricuspid valve	28 (77.8)	47 (74.6)	0.853
Pulmonary valve	3 (8.8)	19 (30.2)	0.038
Pericardial effusion, n	10 (28.6)	16 (25.0)	0.699
Left ventricular noncompaction, n	23 (65.7)	26 (40.6)	0.017
Ratio of ventricular noncompacted to compacted layers	2.0 [0-3.3]	0 [0–3]	0.093

Values are median [interquartile range]. Numbers in parentheses denote percentages

Comparison of characteristics of myocardial injury-related indicators between children in the transplantation group and children in the non-transplantation group

Furthermore, our examination of Table 3 revealed no statistically significant disparities in biochemical markers, including B-type natriuretic peptide (BNP), creatine kinase-MB (CK-MB), cardiac troponin I (CTnI), glutamic oxaloacetic transaminase (GOT), blood urea nitrogen (BUN), serum creatinine (sCr), and glutamic pyruvic transaminase (GPT), between the two groups under study (all p > 0.05).

Table 3.

Comparison of myocardial injury-related indicators among non-transplantation and transplantation

	Transplantation n = 35	Non-transplantation n = 64	P value
BNP abnormity, n	31 (88.6)	54 (84.4)	0.561
CK-MB abnormity, n	2 (5.7)	9 (14.1)	0.319
CTnI abnormity, n	15 (42.9)	17 (26.6)	0.097
BUN abnormity, n	11 (31.4)	18 (28.6)	0.767
sCr abnormity, n	9 (25.7)	27 (42.9)	0.092
GOT abnormity, n	14 (40.0)	32 (50.8)	0.305
GPT abnormity, n	22 (62.9)	27 (42.9)	0.058

Values are median [interquartile range]. Numbers in parentheses denote percentages

Logistic regression analysis of the risk factors for DCM patients with transplantation

A univariate logistic regression analysis was initially conducted to preliminarily investigate the independent factors contributing to an elevated risk of Dilated Cardiomyopathy (DCM) in patients who have undergone transplantation. Subsequently, a multivariate logistic regression was utilized to delve deeper into the risk factors associated with DCM in post-transplant patients. All variables listed in Table 4 were incorporated into the univariate logistic regression model. Based on the data from Table 4; Fig. 1, the results indicated that the New York Heart Association (NYHA) score [odds ratio (OR) 95% confidence interval (CI) = 3.50 (1.74–7.03), p < 0.001], Hepatomegaly [OR (95%CI) = 12.35 (4.39–34.75), p < 0.001], and Ascites [OR (95%CI) = 27.00 (insert confidence interval and p-value here)] were significant risk factors. The multivariate logistic regression analysis revealed significant associations between the Transplantation group and several variables: the NYHA score [adjusted odds ratio (aOR) 95% confidence interval (CI) = 2.78 (1.06–7.27), p = 0.037], Ascites [aOR (95%CI) = 12.93 (2.45–68.22), p = 0.003], and Left ventricular noncompaction [aOR (95%CI) = 3.73 (1.01–13.86), p = 0.048].

Table 4.

Association of clinical variables with transplantation

	Univariate logistic regression		Multivariate logistic regression
	OR (95%CI)	P value	AORa (95%CI)	P value
NYHA score	3.50 (1.74–7.03)	< 0.001	2.78 (1.06–7.27)	0.037
Shock, n	3.05 (0.80-11.67)	0.103	NA
Hepatomegaly, n	12.35 (4.39–34.75)	< 0.001	NA
Ascites, n	27.11 (7.11-103.39)	< 0.001	12.93 (2.45–68.22)	0.003
Orthopnea, n	3.60 (1.39–9.36)	0.009	0.82 (0.15–4.41)	0.820
Cardiothoracic ratio, n	4.93 (1.94–12.55)	< 0.001	1.92 (0.44–8.44)	0.391
Morphological abnormity of heart, n	1.50 (0.88–2.57)	0.135	NA
Morphological changes of lung, n	9.36 (3.21–27.33)	< 0.001	4.82 (0.88–26.40)	0.070
Holter abnormity, n	3.59 (1.30–9.93)	0.014	2.24 (0.48–10.44)	0.315
Abnormity of LVDd, n	2.63 (1.12–6.18)	0.027	NA
LVEF, %	0.95 (0.88–1.02)	0.18	NA
Left ventricular noncompaction, n	2.80 (1.19–6.61)	0.019	3.73 (1.01–13.86)	0.048
CTnI abnormity, n	2.07 (0.87–4.95)	0.100	NA
sCr abnormity, n	0.46 (0.19–1.14)	0.095	0.43 (0.10–1.77)	0.425
GPT abnormity, n	2.26 (0.97–5.27)	0.060	1.58 (0.40–6.23)	0.512

Varibles in Table 1 with P value < 0.1 were further analyzed in univariate logistic regression in Table 2

^aVaribles of Table 2 were further analyzed in multivariate logistic regression after evaluation of the multicollinearity of variables

Fig. 1.

Forest plot of the correlation between clinical variables and transplantation in multivariate logistic regression models as described in Methods

Discussion

In the present research, a comparative analysis was conducted on the clinical manifestations of the transplant and non-transplant cohorts, with the aim of identifying any interrelations. Despite the lack of variations in age, body mass, or gender among the two cohorts, the transplant cohort demonstrated more marked indications of galloping rate, hepatomegaly, ascites, and orthopnea compared to the non-transplant cohort. Additionally, it is noteworthy that the group receiving transplants exhibited an elevated cardiothoracic ratio and prevalence of Holter irregularities, coupled with a pronounced incidence of heart failure characterized by a superior-grade NYHA classification. Despite the absence of any disparity in LVEF between the two groups, a greater percentage of patients within the transplant group were diagnosed with left ventricular non-compaction. Unexpectedly, we observed no significant differences in the levels of cardiac enzymes, and liver and kidney function between the two groups under investigation. Further scrutiny of the collected data unveiled associations between the NYHA score, ascites, and left ventricular non-compaction with transplantation. This evidence underscores the necessity for enhanced focus on the evaluation of heart transplants in pediatric patients exhibiting severe heart failure symptoms and left ventricular non-compaction.

DCM has been observed across all pediatric age groups, yet it predominantly manifests during infancy and early childhood. Scholarly resources suggest that DCM typically presents with a slow onset during its initial stages, thereby complicating its early detection [9]. Nevertheless, as the disease advances, certain symptomatic indicators of heart failure, including hepatomegaly, dyspnea, and ascites, may become apparent in some children. Our retrospective study revealed that pediatric patients with DCM who necessitated heart transplantation commonly exhibited symptoms aligning with NYHA functional class IV or above, including hepatomegaly, ascites, and orthopnea, corroborating previous studies (Table 1). This emphasizes the critical need for early surveillance for heart failure markers such as hepatomegaly, dyspnea, and ascites in pediatric DCM patients. The manifestation of DCM can range from an asymptomatic presentation to the exhibition of heart failure symptoms or sudden cardiac death, even in individuals with prior asymptomatic conditions [10]. The clinical manifestations in pediatric populations are markedly diverse. Furthermore, the symptoms may present atypically, encompassing coughing, fatigue, oedema, abdominal distension, and abdominal discomfort [11]. Consequently, numerous parents of children afflicted with DCM postpone pursuing medical intervention due to the clinical symptoms resembling those of upper respiratory tract infections or dyspepsia. As such, only a limited number of children are diagnosed sufficiently early to benefit from timely intervention.

In pediatric cases of DCM, the predominant cause necessitating treatment is heart failure. The standard screening procedure for these cases typically involves the use of cardiac ultrasound [12]. It is common for pediatric DCM patients to exhibit a LVEF below 40% during clinical examinations. Our research findings indicated that most patients in both the transplanted and non-transplanted groups had an LVEF below 30%. The lowest recorded LVEF was 19% in the transplanted group and 21% in the non-transplanted group. Hence, it is crucial to acknowledge that a low ejection fraction in isolation does not qualify for heart transplantation. The progression of HF in DCM can be delineated into three unique pathways: (i) structural and functional recuperation following the onset of HF; (ii) a remission of HF symptoms coupled with improvement or stabilization of LV systolic function; and (iii) progression towards advanced HF, potentially leading to heart transplantation or death [13]. The initial stage does not characterize our current scenario. It is hypothesized that children diagnosed with DCM predominantly fall into the second stage. In pediatric patients, symptoms of heart failure are alleviated and there is an enhancement in LV systolic function, particularly when guideline-directed medical therapy is employed. Nonetheless, accurately identifying and intervening with patients in stage iii from those in stage ii continues to pose a significant challenge.

DCM is discerned through the echocardiographic attributes of LV dilation and LV systolic dysfunction. Despite identical echocardiographic presentations, prognostic disparities may emerge due to diverse underlying etiologies [14]. The likelihood of mortality or necessitating cardiac transplantation is correlated with the severity of LV dilation and LV systolic dysfunction at the time of diagnosis. Our research findings corroborate previous studies, indicating that the LVDd is significantly larger in patients who have undergone transplant procedures. LVNC, a form of cardiomyopathy characterized by excessive trabeculations of the left ventricle and a greater than two-fold thickening of the endocardial noncompacted layer relative to the epicardial compacted layer of the myocardium (NC/C > 2), has been increasingly recognized due to advancements in cardiac imaging techniques that enable more precise visualization [15]. Consistent with this perspective, our data revealed a higher incidence of patients exhibiting LVNC and transplantation. Further exploration is necessitated to elucidate the pathogenic mechanisms implicated. The etiology of another manifestation, namely valvular regurgitation, remains obscure. The cohort not subjected to transplantation exhibited a heightened incidence of valvular regurgitation in both the aortic and pulmonary valves. Additional empirical evidence and scholarly inquiry may be requisite to explicate this occurrence.

In pediatric patients with DCM, early detection and the immediate commencement of routine, standardized treatment are crucial for enhancing cardiac function, improving quality of life, and postponing the requirement for heart transplantation [11]. Nonetheless, certain clinical situations may necessitate transplantation due to insufficient responsiveness to medical intervention. Consequently, it is of paramount importance to identify and maintain vigilance for such instances at an early stage. In this research, clinical data was gathered from pediatric patients who had undergone heart transplantation. The dataset incorporated a range of parameters including NYHA functional classification, hepatomegaly, dyspnea, ascites, cardiothoracic ratio, left ventricular end-diastolic and end-systolic dimensions, left ventricular myocardial non-compaction, left ventricular ejection fraction, 24-hour dynamic electrocardiogram abnormalities, and cardiac enzyme profiles. Based on the outcomes of the regression analysis, it can be inferred that specific factors such as NYHA functional classification, ascites, and left ventricular non-compaction could potentially heighten the risk of heart transplantation in pediatric patients diagnosed with DCM. Significantly, it has been observed that patients necessitating transplantation consistently present with a NYHA functional class IV or above. The literature underscores the importance of the NYHA functional class as a predictive marker for transplantation requirement. Furthermore, it posits that the occurrence of ascites could signal right heart failure or biventricular failure, conditions that may be resistant to medical management and could ultimately necessitate transplantation. These observations align with the findings from our study [16]. Left ventricular non-compaction, a condition frequently seen in pediatric patients, may be associated with compromised contractility and relaxation of the left ventricle [16].This particular pathological condition has the potential to precipitate progressive cardiac failure, thereby establishing itself as a significant risk factor for pediatric DCM [17]. Regression analyses have substantiated the assertion that LVNC significantly elevates the risk of heart transplantation among DCM patients. Consequently, it is advisable for medical practitioners to maintain vigilant surveillance of pediatric patients exhibiting cardiac imaging evidence of LVNC. This is due to the likelihood of such patients developing cardiac failure and subsequently necessitating transplantation, in conjunction with the consideration of other clinical parameters.

DCM is responsible for approximately half of all pediatric cardiomyopathy cases, frequently resulting in pediatric heart failure and sudden cardiac death [18]. It is also a leading cause of heart transplantation in pediatric patients. Our analysis suggests that a greater number of pediatric patients with DCM within the same state could initially be managed with pharmacological interventions as opposed to heart transplantation. However, careful consideration should be given to children presenting with a high NYHA class and significant densification insufficiency, as they may necessitate heart transplantation.

Conclusions

For children with dilated cardiomyopathy who present with end-stage heart failure, combined with ascites, elevated NYHA function grading, and left ventricular insufficiency, we need to be vigilant. We suggest strengthening monitoring and early consideration of heart transplantation as a therapeutic intervention.

Abbreviations

DCM

Dilated Cardiomyopathy

HF

Heart Failure

NYHA

New York Heart Association

ACEI

Angiotensin-converting enzyme inhibitors

EF

Ejection fraction

CK-MB

Creatine kinase and its MB isoenzyme

cTnI

Cardiac troponin I

BNP

B-type natriuretic peptide

LV

Left ventricular

LVEF

Left ventricular ejection fraction

LVFS

Left ventricular fractional shortening

LVDd

Left ventricular end diastolic diameter

LVNC

Left ventricular non-compaction cardiomyopathy

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

ALP

Alkaline phosphatase

GOT

Glutamic oxaloacetic transaminase

BUN

Blood urea nitrogen

sCr

Serum creatinine

GPT

Glutamic pyruvic transaminase

ROC

Receiver’s operator characteristic

aOR

Adjusted odds ratio

CI

Confidence interval

Author contributions

Authors ZW and JS designed the study and drafted the manuscript. Authors JZ and WL collected and organized the data. Authors HH, JL, and QG performed the statistical analysis. Authors ND, LW, and HP revised the manuscript. All authors read and approved the final manuscript.

Funding

This study received support from multiple sources, including the National Key Research and Development Program of China (2023YFC2706200, 2023YFC2706201, and 2023YFC2706202), the Key Research and Development Program of Hubei Province, China (2022BCA043), the Natural Science Foundation of Hubei Province, China (2022CFB181), the Free Innovation Pre-research Fund of Union Hospital of Tongji Medical College, Huazhong University of Science and Technology (Grant No.2021xhyn059) and the Wuhan Knowledge Innovation Special Project (2023020201010160).

Data availability

The data underlying this article are available in the article.

Declarations

Ethics approval and consent to participate

Our study was approved by the ethics committee at Tongji Medical College Affiliated Union Hospital, Huazhong University of Science and Technology and was conducted in accordance with HIPAA regulations and with the tenets of the Declaration of Helsinki.

Consent for publication

Consent for publication were obtained from the institution and the patient’ parents.

Competing interests

All authors have declared no conflicts of interest.