Elsevier

International Journal of Cardiology

Volume 321, 15 December 2020, Pages 113-117
International Journal of Cardiology

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

https://doi.org/10.1016/j.ijcard.2020.07.034Get rights and content

Highlights

  • Lower LVEF and higher serum ACE activity were independently associated with positive EMB in CS patients.

  • The combination of lower LVEF and higher serum ACE activity was related to a higher rate of positive EMB.

  • It would be meaningful to perform EMB in suspected CS patients, especially those with low LVEF and high serum ACE activity.

Abstract

Background

The histopathological diagnosis of cardiac sarcoidosis (CS) is challenging because of sampling error in endomyocardial biopsy (EMB) and the determinants of positive EMB are unclear. Reduced left ventricular ejection fraction (LVEF) is a simple parameter of the extent of myocardial damage, and higher serum angiotensin-converting enzyme (ACE) activity would indicate the spread of disease activity in CS patients. Thus, we sought to examine whether these parameters are related to the histopathological diagnosis of CS by EMB.

Methods

A total of 94 consecutive clinically diagnosed CS patients between August 1986 and March 2019 who were admitted to two academic hospitals were examined. We determined EMB as positive if non-caseating epithelioid granulomas were confirmed in the myocardial tissue. Patients were divided into two groups according to positive (n = 37) and negative (n = 57) EMB. We assessed the relationship between LVEF, serum ACE activity and positive EMB.

Results

Multivariable analysis revealed that both LVEF and serum ACE were independently associated with positive EMB (OR 0.83, 95% CI 0.70–0.99; OR 1.39, 95% CI 1.02–1.90, respectively). Moreover, patients with both lower LVEF (<37%, median) and higher ACE activity (≥13.5 IU/L, median) had the highest frequency of positive EMB (p = .003). The combination of lower LVEF and higher serum ACE showed better specificity (91.2%) and positive predictive value (73.7%) than either LVEF or serum ACE alone for positive EMB.

Conclusions

Lower LVEF and higher serum ACE activity were associated with positive EMB, suggesting that these parameters might be useful for predicting positive EMB in CS patients.

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.

References (31)

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1

Drs Hirokazu Komoriyama and Kazunori Omote contributed equally to this work.

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