AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2692-9759/020
1Specialist in Pediatric and Cardiology. Professor and Researcher, Pediatric Cardiocenter William Soler, Havana Cuba.
2Specialist in Pediatric. Professor, Pediatric Cardiocenter William Soler, Havana Cuba.
*Corresponding Author: Mariela Céspedes Almira, Institute of Clinical Medicine. Tbilisi. Georgia.
Citation: Mariela C Almira, Adel E G Morejón, Giselle S Ricardo, Tania R G Rodríguez, Judith E Bermúdez. (2021) Algorithm for diagnosis and typing of ALCAPA syndrome. Cardiology Research and Reports. 3(2): Doi: 10.31579/2692-9759/020
Copyright: © 2021 Mariela Céspedes Almira. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 05 April 2021 | Accepted: 16 April 2021 | Published: 21 April 2021
Keywords: ALCAPA syndrome; anomalous coronary artery; diagnosis; echocardiography
ALCAPA syndrome was characterized by anomalous origin of left coronary artery from pulmonary artery. Its clinical presentation is varied and although it is an anomaly of congenital origin, it is not exclusive to pediatric ages. Its epidemiological documentation is difficult. We aimed to make the non-invasive diagnosis of the ALCAPA syndrome and its variants.
An observational, prospective and cross-sectional study was conducted with 31 patients with a positive echocardiographic diagnosis of ALCAPA syndrome at Pediatric Cardio Center “William Soler” from 2005 to 2018.
The variables with significance for diagnosis were the echocardiographic visualization of the anomalous connection and the reversed flow in the left coronary artery. The variables with significance for typing were age at diagnosis, ischemia in the electrocardiogram, echocardiographic visualization of left ventricle papillary muscles fibrosis, presence of severe mitral regurgitation, left ventricle spheroidal remodeling, left ventricle ejection fraction, left ventricular end-diastolic volume index, and left ventricular end-diastolic diameter index. An algorithm integrated by various diagnostic modalities associated with echocardiography as a tool for the detection of ALCAPA was developed.
The documentation of the diagnostic and classificatory aspects of the syndrome is possible by detecting echocardiographic elements in conjunction with electrocardiographic and radiological aspects.
This was an observational, prospective and cross-sectional study at a single tertiary care center. We included 31 patients of both sexes with a positive echocardiographic diagnosis of ALCAPA monitoring in the Pediatric Cardio Center “William Soler”, in the period comprised from 2005 to 2018.
The hospital where the research was developed is a national reference center for the diagnosis, treatment and monitoring of patients with congenital heart disease, which justifi es the possibility of studying all subjects.
The research was based on the analysis of various clinical, electrical, radiological and echocardiographic variables that have been conceptually defined [21-22]. As dependent or response variables were included the diagnosis and typification of the ALCAPA syndrome. As independent or explanatory variables were included for diagnosis the echocardiographic visualization of the anomalous connection, reversed flow in the anomalous coronary artery, location of the anomalous left coronary artery, coronary artery dilatation and increased coronary collateral vascularization. Were included for typing: ischemia in the electrocardiogram, cardiothoracic index, left ventricle spheroidal remodeling, left ventricle papillary muscles fibrosis, the presence of severe mitral regurgitation, left ventricular end-diastolic diameter index (LVEDD index), left ventricular end-diastolic volume index (LVEDV index) and left ventricular ejection fraction (LVEF). Age and gender as control variables.
The information was obtained from the anamnesis, physical examination and echocardiographic investigation, collected and recorded in two models, a census model for the population of sick individuals and a survey for supposedly healthy subjects, with a structure a database capable of being used by the free statistical platform R Project 3.0.1.
As a single experienced cardiologist performed echocardiographic examinations of all patients, a third-party blinded study was performed to avoid bias.
The statistical analysis was based on the application of a logistic regression model with which it was intended to evaluate the relationship and independent influence of each variable on the possibility of making the diagnosis and typing by echocardiography of the ALCAPA syndrome. The independent variables were made up of those that, according to the research findings, were considered as prone to diagnosis and typification of the disease under study. The quantitative variables were coded for their introduction in the model analysis process; This considered identifying, as elements that generate influences on the predetermined dependent variables, those aspects for which the Wald statistician showed probability less than 5 % (p < 0.05) when the exponential of the model coefficients was analyzed (Exp ß) as an estimator of the ratio of cross products or Odds ratio (OR).
The goodness of fit corresponding to the proposed model was determined using the Hosmer and Lemeshow test, which allowed evaluating the value of the deviation between it was observed and it was expected, integrated by the evaluation by Chi-squared (X2) and by the coefficients of determination R2 of Cox and Snell and Nagelkerke's R2, which indicate the variance of the dependent variable explained by the model.
The present study was carried out in accordance with the precepts and strict compliance with the Declaration of Helsinki [23].
Table 1 showed the logistic regression that identifies the facilitating variables of the echocardiographic diagnosis in the ALCAPA syndrome. The echocardiographic visualization of the anomalous connection and the detection of reversed flow in the anomalous coronary artery were the only variables that presented absolute statistical significance as useful elements for the effective diagnosis of the disease (p < 0.001).
Table 2 demonstrated the result that emanates from the multivariate analysis at the starting point of the logistic regression carried out to identify the aspects that influence or determine the echocardiographic typification of the ALCAPA syndrome used, the latter, as the dependent variable in the present model. Documentation of differences regarding age at diagnosis (Exp β - 2,699; Wald - 4,812; p 0.043), the presence of (Exp β - 36,108; Wald - 7,415; p 0,005), the existence left ventricle papillary muscles fibrosis (Exp β - 21.457; Wald - 5.986; p 0.01), the detection of severe mitral regurgitation (Exp β - 15.106; Wald -5.710; p 0.019) and the identification of the left ventricle spheroidal remodeling (Exp β - 21.465; Wald - 5.992; p 0.013) are part of the set of independent variables that define the afore mentioned typing. Also included ischemia in the electrocardiogram in this group are the perception of quantitative differences corresponding to the ejection fraction (Exp β - 1,998; Wald - 4,361; p 0.031), the end-diastolic volume index (Exp β - 21,300; Wald - 5,872; p 0,015) and the end-diastolic diameter index (Exp β - 15.714; Wald - 5.971; p 0.014) in the left ventricle.
The goodness of fit corresponding to the proposed model because of the logistic regression carried out was determined using the Hosmer and Lemeshow test. Table 3 showed that the analysis of the test statistician in the studied population did not present statistical significance (p 0.81) or differences between predicted and observed, so the proposed model was valid.
The application of the Hosmer and Lemeshow test to the model built based on multivariate analysis incorporated the coefficient of determination (R2) of Cox and Snell, as well as its corrected version of Nagelkerke in order to document the proportion of variance corresponding to the dependent variable according to its independent counterparts. The findings, which are shown in Table 4, denoted that the mentioned model was able to predict the exact typing in 88.2 % of the patients with the infantile-type and 78.5 % of the subjects afflicted by the adult-type of the disease. The general quantification of success, in percentage terms, to 83.3 %. The resulting figures from the Cox and Snell coefficient of determination (0.317) and its corrected version (0.424) support the clinical application of the model obtained.
In order to establish useful strategies for the population research focused on the diagnosis in conjunction with the typification of the ALCAPA syndrome, an algorithm integrated by various diagnostic modalities associated with echocardiography as an initial, precise and fundamental tool was developed. The algorithm can be seen in Figure 1.
The medical literature that addresses the general aspects inherent to the ALCAPA syndrome establishes some non-invasive diagnostic criteria of the condition that was based on the ambiguous observation of indirect echocardiographic signs and identifies two variants of the disease that are well defined from the conceptual point of view, although does not establish the methodology for differentiation through the applicability of non-invasive modalities [24-27].
Other imaging techniques such as computerized axial tomography, magnetic resonance imaging and cardiac catheterization can demonstrate the coronary abnormality; however, these diagnostic modalities are not very accessible, exhibit high cost and require optimization during the inherent process of image acquisition [28-33].
Logistic regression is the direct probability model that integrates the set of so-called dependency techniques that have explanatory or predictive capacity of a phenomenon defined by a variable that acts as a dependent depending on some factors that are related to it and that interact as independent variables (explanatory or predictive) [34-36]. The logistic regression model identifies the group of probable risk factors for the occurrence of the dependent variable studied.
In the present investigation, the statistical processing determined that the visualization of the anomalous connection belonging to the left coronary artery and the detection of reversed blood flow inside the mentioned vessel have absolute value for the echocardiographic diagnosis of the ALCAPA syndrome.
Ya - Li Yang et al. agree with the postulates emanating from the present investigation by relating the direct visualization of the anomalous connection corresponding to the left coronary artery and the detection of reversed blood flow inside the mentioned vessel with the echocardiographic diagnosis of ALCAPA syndrome [37].
The conjugation of the clinical state documented in each patient with the electrocardiographic and radiological findings can facilitate, in a limited way, the establishment of the differential analysis between types of the disease under study [17, 38-40]. Age as an absolute element of judgment for the typification of the ALCAPA syndrome lacks value since both classificatory variants can be expressed in pediatric patients [41-43].
There are several useful studies as cognitive elements of the symptoms found in groups of patients of different ages who are afflicted by the ALCAPA syndrome. Yau et al. report in a descriptive way, a set of patients detected in adulthood; of these, 12 % had a silent course during life and were classified as necropsy findings, 66 % had symptoms of angina, dyspnea, palpitations or fatigue, and 17 % suffered from ventricular arrhythmia, syncope states or episodes of sudden death [11].
Congenital heart disease in adulthood is associated with heart failure, arrhythmias, vascular complications, and sudden death [11, 14]. Many of these diagnoses are made, in this age group, incidentally, due to concomitant heart disease and sometimes, due to the presence of symptoms that lead to the finding of the lesion. When performing an echocardiographic study in an adult patient with signs and symptoms of heart failure, consider congenital heart disease [12, 13, 44].
According to the hypothesis raised by the present investigation, echocardiography stands as the ideal diagnostic modality in the capacity to integrate and enrich the concepts exposed in the face of the afore mentioned diagnostic ambiguities generated by the condition.
The identified results are compatible with the stated postulates.
The group of patients classified as belonging to infantile-type was made up of younger subjects when the condition was detected by echocardiography; these patients presented a predominance of the typical ischemic electrocardiographic pattern and were clinically expressed as individuals suffering from suspected dilated cardiomyopathy or severe isolated mitral regurgitation. Echocardiographic investigation of the left ventricle detected final diastolic dilation, spheroidal remodeling, left ventricle papillary muscles fibrosis, and global contractile dysfunction; these findings were accompanied by the cardiomegaly documented in the radiographic studies performed.
The patients with the adult-type of the syndrome were older at the time of echocardiographic diagnosis, which, at the same time, revealed the extensive existing collateral coronary vascular network. In these subjects, it was not possible to document processes tending to ventricular remodeling, the presence left ventricle papillary muscles fibrosis, global contractility disorders, or left ventricle final diastolic dilation. The radiographic study performed did not show cardiomegaly.
The logistic regression and its model, built from the independent variables identified as presumed classificatory elements, constituted the tools applicable to the multivariate analysis aimed at the typification of the ALCAPA syndrome adopted, the latter, as a dichotomous dependent variable. The figures set for the quantitative variables that were integrated into the model were adopted according to the values recorded by the standard deviations or the interquartile range used as measures of dispersion according to the examination corresponding to the intrinsic distribution of each variable in question. Afore mentioned statistical process allowed the finding of notable differences between both types related to age at diagnosis of the anomaly, presence of ischemia in the electrocardiogram, existence of left ventricle papillary muscles fibrosis, detection of insufficiency mitral injury, presence of elements tending to left ventricle spheroidal remodeling, left ventricular ejection fraction, left ventricular end-diastolic volume index, and left ventricular end-diastolic diameter index.
The information provided by the goodness-of-fit analysis corroborates the accuracy of the model in terms of echocardiographic typing of the ALCAPA syndrome.
In patients with cardiac symptoms of any age group, it is important to exclude the presence of ALCAPA. The conjugation of the clinical manifestations (unexplained crying spells in young infants, cardiomegaly, murmur of mitral regurgitation, dilated cardiomyopathy, myocardial ischemia, sudden death, arrhythmias, chest pain, myocarditis, coronary fistulas), with the electrocardiographic, radiological and echocardiographic findings can facilitate the diagnosis of this anomaly.
Echocardiographic visualization of the anomalous origin of the left coronary artery from pulmonary artery and the detection of local intracoronary reverse flow are the factors to be consider for the effective diagnosis of the disease. Non-invasive characterization of each variant of the ALCAPA syndrome is possible by detection of well-defined echocardiographic elements in conjunction with some electrocardiographic and radiological aspects.
Conflict of interests
The authors declare that they have no conflict of interest in conducting the study.
Mariela Céspedes Almira: conception, design of the study and preparation of the draft of the article.
Adel Eladio González Morejón: analysis and interpretation of data, critical review of the article, approval of the final version.
Giselle Serrano Ricardo: critical review of the article, contributions to its intellectual content.
Tania Rosa González Rodríguez: contributions to its intellectual content.
Judith Escobar Bermúdez: contributions to its intellectual content.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
