Lower left ventricular ejection fraction and higher serum angiotensin-converting enzyme activity are associated with histopathological diagnosis by endomyocardial biopsy in patients with cardiac sarcoidosis
Introduction
Sarcoidosis is a systemic disorder of unknown etiology, characterized by the formation of epithelioid granulomas in multiple organs, such as the lungs, eyes, lymph nodes, skin and heart [1]. Among these, cardiac involvement, which leads to atrioventricular or bundle branch block, ventricular tachycardia or fibrillation, congestive heart failure, and sudden cardiac death, is a key determinant of worse clinical outcomes in patients with sarcoidosis [2,3]. Thus, earlier diagnosis of cardiac involvement would be important to improve clinical outcomes with effective treatment in patients with sarcoidosis. Notably, corticosteroid therapy would reduce cardiovascular-related adverse events such as sudden cardiac death, heart failure admission, fatal ventricular arrhythmias and progression of impaired left ventricular (LV) systolic function in patients with cardiac sarcoidosis (CS) [4,5]. Unfortunately, it is difficult to make a histopathological diagnosis of CS because the sampling error of endomyocardial biopsy (EMB) is associated with low sensitivity in the detection of epithelioid granulomas in myocardial tissue [6]. Moreover, EMB procedures have not yet gained widespread acceptance because of its specific serious complications [7]. Thus, identifying the determinants of positive EMB would be worthwhile to enable physicians to make the decision to perform EMB in patients with suspected CS. Lower left ventricular ejection fraction (LVEF) is a common parameter of the extent of myocardial damage in CS patients [8]. A previous study revealed that a histopathological diagnosis of CS by EMB was more frequently obtained in patients who exhibited a dilated cardiomyopathy-like clinical phenotype than in those with normal LVEF [9]. In addition, epithelioid granulomas produce angiotensin-converting enzyme (ACE), and its level would indicate the spread of disease activity in patients with CS [10,11]. However, the clinical implication of these factors as relations to histopathological diagnosis by EMB in patients with CS has not been well investigated. Accordingly, the aim of this study was to determine whether LVEF and serum ACE activity were related to positive findings of histopathological diagnosis by EMB in patients with CS.
Section snippets
Study design
This was an observational, retrospective study that included consecutive patients who were clinically diagnosed with CS. CS was defined as meeting the diagnostic criteria specified in the guidelines of the Japanese Ministry of Health and Welfare (JMHW) and the Japan Society of Sarcoidosis and Other Granulomatous Disorders (JSSOG) in 2015 (JMHW/JSSOG 2015) (https://www.jssog.com/journal). Briefly, according to the guidelines, a definite diagnosis of CS was made on the basis of histopathological
Baseline characteristics
The baseline characteristics of the total 94 studied patients are shown in Table 1. Patients with positive EMB were younger and had lower LVEF and higher plasma brain natriuretic peptide level than those with negative EMB. There were no significant differences in gender, body mass index, prevalence of hypertension, dyslipidemia, diabetes mellitus, coronary artery disease, and congestive heart failure, and LVDD, LVDS, LAD, IVS wall thinning, electrocardiogram findings, hemoglobin, serum ACE,
Discussion
The major finding of the present study was that both lower LVEF and higher serum ACE activity were independently associated with positive EMB in patients with CS. Furthermore, CS patients categorized as having both lower LVEF and higher serum ACE activity had a markedly higher frequency of positive EMB, suggesting that the extent of myocardial damage and the spread of systemic disease activity could associate with a higher likelihood of obtaining a histopathological diagnosis by EMB in CS
Funding
This work was supported by a Grant-in-Aid for Young Scientists from the Japan Society for the Promotion of Science (T.N., 15K19402) and a Grant from the Japan Heart Foundation (T.N.). The funding sources had no involvement in any research process.
Declaration of Competing Interest
The authors have no conflicts of interest to disclose.
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Drs Hirokazu Komoriyama and Kazunori Omote contributed equally to this work.