Coronary flow reserve is reduced in sarcoidosis

doi:10.1016/j.atherosclerosis.2017.05.005

Atherosclerosis

Volume 264, September 2017, Pages 115-121

https://doi.org/10.1016/j.atherosclerosis.2017.05.005 Get rights and content

Highlights

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Coronary flow velocity reserve is reduced in sarcoidosis.
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Sarcoidosis was an independent predictor for low coronary flow velocity reserve, along with age and systolic blood pressure.
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Reduced response to vasodilators suggests possible structural alterations of the myocardial microvasculature in sarcoidosis.

Abstract

Background and aims

Sarcoidosis is a multisystem disease with frequent cardiac involvement, albeit manifest cardiac disease is rare. Though epicardial coronary arteries are not frequently involved, microvascular disease is rather common in both symptomatic and asymptomatic patients. The mechanism of microvascular involvement has not been elaborated yet. The aim of this study is to investigate coronary flow velocity reserve (CFVR) using transthoracic echocardiography in patients with sarcoidosis but without known atherosclerotic coronary artery disease or risk factors for atherosclerosis.

Methods

A total of 40 patients with sarcoidosis and 42 healthy volunteers without any known medical conditions were enrolled prospectively. Diastolic peak coronary flow velocities were measured during rest and maximal hyperemia induced with adenosine.

Results

Patients within the sarcoidosis group had significantly higher diastolic peak velocity at rest (29.5 ± 5.8 vs. 22.8 ± 3.2, p < 0.01) but both the diastolic peak velocity during hyperemia (60.5 ± 18.2 vs. 68.9 ± 15.7, p = 0.03) and CFVR (2.08 ± 0.57 vs. 3.03 ± 0.60, p < 0.01) were lower compared to controls. Sarcoidosis was an independent predictor for low (≤2.0) CFVR (OR: 56.8, 95%CI: 6.1–531.7, p < 0.001), along with age and systolic blood pressure. For patients with sarcoidosis, age and systolic blood pressure were independent predictors for a low CFVR.

Conclusions

Despite a lack of known risk factors for atherosclerosis, patients with sarcoidosis had lower CFVR compared to healthy controls, thus suggesting a dysfunction in the coronary microvasculature. A reduced response to vasodilators suggests possible structural alterations of the myocardial microvasculature, rather than being secondary to microvascular spasm as suggested previously.

Introduction

Sarcoidosis is a chronic inflammatory disorder characterized by formation of noncaseating granulomas within the involved tissue. Histopathologic examinations of biopsies or necropsy specimens have demonstrated that up to 25% of patients with sarcoidosis have myocardial involvement, although only 5% of patients show clinical manifestations of cardiac disease [1]. When manifest, cardiac involvement could cause systolic myocardial dysfunction, restrictive cardiomyopathy, ventricular arrhythmias or various degrees of atrioventricular block [2]. Angina is a frequent complaint in patients with sarcoidosis, while only a small fraction of patients have obstructive coronary artery disease (CAD) secondary to atherosclerosis or direct involvement [3].

Even in the absence of significant epicardial coronary stenosis, patients with cardiac sarcoidosis can present with angina and ischemic findings on myocardial perfusion imaging. This phenomenon, which was attributed to microvascular dysfunction, was initially described 40 years ago by Bulkey et al. and the presence of perfusion defects was demonstrated in both symptomatic and asymptomatic patients [4]. More recently, a contemporary study that utilized hybrid positron emission tomography/cardiac tomography (PET/CT) technology found abnormal myocardial blood flow during hyperemia, as well as reduced flow reserve, in patients with cardiac sarcoidosis [5]. Still, the understanding of coronary flow dynamics in patients in sarcoidosis is incomplete, owing to the low number of studies focused on this topic.

Measurement of coronary flow velocity reserve (CFVR) using transthoracic echocardiography (TTE) is both accurate and feasible if adequate expertise is available [6], [7]. In the present study, we aimed to study CFVR in patients with sarcoidosis, but without risk factors for CAD, to clarify whether “sole” sarcoidosis could cause disturbances in myocardial blood flow during hyperemia. As a secondary aim, we investigated the relationship of CFVR with surrogate markers of disease activity in patients with sarcoidosis to understand the extent of the relationship between disease activity and disturbances in myocardial blood flow.

Section snippets

Patient selection

Patients with a diagnosis of sarcoidosis that were 18 years or older, and admitted to the study institution between May and September 2016, were enrolled consecutively in the study in the absence of exclusion criteria. The diagnosis was confirmed histopathologically using the consensus criteria proposed by the American Thoracic Society (ATS)/European Respiratory Society (ERS) prior to enrolment [8]. While systemic sarcoidosis without pulmonary involvement was not an exclusion criteria per se,

Results

Demographic, clinical, laboratory and echocardiographic findings, as well as coronary blood flow measurements are given in Table 1. A significantly low number of subjects were male in the sarcoidosis group (32%) compared to controls (67%, p < 0.01). Besides that, demographic and clinical characteristics were similar between groups. Erythrocyte sedimentation rate was significantly higher in the sarcoidosis group, as well as a trend towards higher hsCRP (p = 0.14) and lower hemoglobin (p = 0.11)

Discussion

The present study had some novel findings regarding the coronary blood flow in patients with sarcoidosis, but without risk factors for CAD, which could be summarized as follows: (i) more than half of the patients with sarcoidosis have an inadequate flow during adenosine-induced hyperemia despite the lack of any coronary risk factors, (ii) besides sarcoidosis, age and systolic blood pressure were determinants of a low CFVR, (iii) while sarcoidosis appears as a risk factor for an abnormal CFVR,

Conflict of interest

The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript.

References (23)

J.S. Kim et al.
Cardiac sarcoidosis
Am. Heart J.
(2009)
B.H. Bulkley et al.
The use of 201-thallium for myocardial perfusion imaging in sarcoid heart disease
Chest
(1977)
S.F. Nagueh et al.
Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures
J. Am. Coll. Cardiol.
(1997)
D.A. Kass
Assessment of diastolic dysfunction: invasive modalities
Cardiol. Clin.
(2000)
H. Lambertz et al.
Noninvasive assessment of coronary flow reserve with transthoracic signal-enhanced Doppler echocardiography
J. Am. Soc. Echocardiogr.
(1999)
C.E. Korcarz et al.
Noninvasive assessment of coronary flow reserve by echocardiography: technical considerations
J. Am. Soc. Echocardiogr.
(2004)
J. Butany et al.
The intricacies of cardiac sarcoidosis: a case report involving the coronary arteries and a review of the literature
Cardiovasc Pathol.
(2006)
E.L. Kinney et al.
Thallium-scan myocardial defects and echocardiographic abnormalities in patients with sarcoidosis without clinical cardiac dysfunction. An analysis of 44 patients
Am. J. Med.
(1980)
P.P. Mehrotra et al.
Myocardial perfusion defect on thallium-201 imaging in patients with chronic obstructive pulmonary disease
J. Am. Coll. Cardiol.
(1983)
K. Okayama et al.
Diagnostic and prognostic value of myocardial scintigraphy with thallium-201 and gallium-67 in cardiac sarcoidosis
Chest
(1995)

M. Bulut et al.

Is the presence of AA amyloidosis associated with impaired coronary flow reserve?

Atherosclerosis

(2016)

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Citation Excerpt :
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Coronary flow reserve is reduced in sarcoidosis

Highlights

Abstract

Background and aims

Methods

Results

Conclusions

Introduction

Section snippets

Patient selection

Results

Discussion

Conflict of interest

Am. Heart J.

Chest

J. Am. Coll. Cardiol.

Cardiol. Clin.

J. Am. Soc. Echocardiogr.

J. Am. Soc. Echocardiogr.

Cardiovasc Pathol.

Am. J. Med.

J. Am. Coll. Cardiol.

Chest

Atherosclerosis