Coronary microvascular dysfunction due to Chagas disease: where are we now?

ABSTRACT

Introduction

Myocardial ischemia is common in patients with chronic Chagas cardiomyopathy (CCC), but only recently clinical and experimental studies highlighted the involvement of this abnormality as contributing to the progression of myocardial damage.

Areas covered

Despite the absence of obstructive epicardial coronary artery disease at angiography, and limited evidence of abnormal flow regulation at the macrovascular level, remarkable functional and structural microvascular abnormalities are consistently reported by independent investigations of CCC. These derangements occur early and contribute to myocardial dysfunction. Recent research focused on reversing microvascular dysfunction as a target to positively impact the course of CCC. We conducted an extensive review of the scientific literature, aiming to summarize the role of coronary dysfunction causing myocardial ischemia in CCC, with a focus on implications for clinical management of individuals affected by this disease.

Expert Opinion

Preclinical studies showed a clear correlation between perfusion defects and inflammation in viable but impaired dysfunctional myocardium. These findings provided further insight into the CCC complex pathophysiology and support the role of very few recent therapeutic interventions aiming to relieve myocardial ischemia. Further research is warranted to assess the efficacy of new interventions addressing reversal of microvascular ischemia and inflammation modulation and halting ventricular dysfunction progression in CCC.

KEYWORDS:

• Chagas heart disease
• coronary microvascular dysfunction
• Chagas disease
• ventricular dysfunction
• chest pain

Article highlights

• The occurrence of myocardial perfusion disturbances resulting from coronary microvascular dysfunction has been extensively documented and characterized IN CCC

• The potential involvement and significance of such abnormalities as mechanisms responsible for the progression of myocardial damage have been highlighted in independent clinical and experimental studies.

• A topographical correlation between perfusion defects and myocardial inflammation was found in viable but contractile impaired myocardial regions, thus indicating a mechanism similar to myocardial hibernation.

• In preclinical studies, pharmacological interventions acting at the microvascular level were associated with significant improvement of myocardial perfusion and provide some potential to reverse myocardial damage in CCC.

• Only one clinical trial has been reported in the context of therapeutic approaches to address myocardial microvascular ischemia in patients with CCC. The combination of verapamil plus aspirin showed promising results in terms of improving quality of life and objectively reducing perfusion defects in patients with anginal symptoms associated with microvascular dysfunction.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by research grants from Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP – Process numbers: 2016/25403-9, 2017/16450-6, and Process: 2019/21250-1).