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      Aspirin plus verapamil relieves angina and perfusion abnormalities in patients with coronary microvascular dysfunction and Chagas disease: a pilot non-randomized study

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          Abstract

          INTRODUCTION:

          Most patients with chronic cardiomyopathy of Chagas disease (CCCD) harbor a secondary cause of coronary microvascular dysfunction (CMD), for which there is no evidence-based therapy. We evaluated the impact of verapamil plus aspirin on symptoms and perfusion abnormalities in patients with CCCD and CMD.

          METHODS:

          Consecutive patients with angina pectoris, who had neither coronary artery obstructions nor moderate-severe left ventricular dysfunction (left ventricular ejection fraction > 40%) despite showing wall motion abnormalities on ventriculography, were referred for invasive angiography and tested for Chagas disease. Thirty-two patients with confirmed CCCD and ischemia on stress-rest SPECT myocardial perfusion scintigraphy (MPS) were included. Clinical evaluation, quality of life (EQ-5D/ Seattle Angina Questionnaire), and MPS were assessed before and after 3 months of treatment with oral verapamil plus aspirin (n=26) or placebo (n=6).

          RESULTS:

          The mean patient age was 64 years, and 18 (56%) were female. The ischemic index summed difference score (SDS) in MPS was significantly reduced by 55.6% after aspirin+verapamil treatment. A decrease in SDS was observed in 20 (77%) participants, and in 10 participants, no more ischemia could be detected. Enhancements in quality of life were also detected. No change in symptoms or MPS was observed in the placebo group.

          CONCLUSIONS:

          This low-cost 3-month treatment for patients diagnosed with CCCD and CMD was safe and resulted in a 55.6% reduction in ischemic burden, symptomatic improvement, and better quality of life.

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          Most cited references65

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          Chagas disease

          The Lancet, 375(9723), 1388-1402
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            International standardization of diagnostic criteria for microvascular angina.

            Standardization of diagnostic criteria for ischemic symptoms due to coronary microvascular dysfunction (CMD) is needed for further investigation of patients presenting with anginal chest pain consistent with "microvascular angina" (MVA). At the annual Coronary Vasomotion Disorders International Study Group (COVADIS) Summits held in August 2014 and 2015, the following criteria were agreed upon for the investigative diagnosis of microvascular angina: (1) presence of symptoms suggestive of myocardial ischemia; (2) objective documentation of myocardial ischemia, as assessed by currently available techniques; (3) absence of obstructive CAD ( 0.80) (4) confirmation of a reduced coronary blood flow reserve and/or inducible microvascular spasm. These standardized criteria provide an investigative structure for mechanistic, diagnostic, prognostic and clinical trial studies aimed at developing an evidence base needed for guidelines in this growing patient population. Standardized criteria will facilitate microvascular angina registries and recruitment of suitable patients into clinical trials. Mechanistic research will also benefit from the implementation of standardized diagnostic criteria for MVA.
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              Pathogenesis of chronic Chagas heart disease.

              Chagas disease remains a significant public health issue and a major cause of morbidity and mortality in Latin America. Despite nearly 1 century of research, the pathogenesis of chronic Chagas cardiomyopathy is incompletely understood, the most intriguing challenge of which is the complex host-parasite interaction. A systematic review of the literature found in MEDLINE, EMBASE, BIREME, LILACS, and SCIELO was performed to search for relevant references on pathogenesis and pathophysiology of Chagas disease. Evidence from studies in animal models and in anima nobile points to 4 main pathogenetic mechanisms to explain the development of chronic Chagas heart disease: autonomic nervous system derangements, microvascular disturbances, parasite-dependent myocardial aggression, and immune-mediated myocardial injury. Despite its prominent peculiarities, the role of autonomic derangements and microcirculatory disturbances is probably ancillary among causes of chronic myocardial damage. The pathogenesis of chronic Chagas heart disease is dependent on a low-grade but incessant systemic infection with documented immune-adverse reaction. Parasite persistence and immunological mechanisms are inextricably related in the myocardial aggression in the chronic phase of Chagas heart disease. Most clinical studies have been performed in very small number of patients. Future research should explore the clinical potential implications and therapeutic opportunities of these 2 fundamental underlying pathogenetic mechanisms.
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                Author and article information

                Journal
                Rev Soc Bras Med Trop
                Rev Soc Bras Med Trop
                rsbmt
                Revista da Sociedade Brasileira de Medicina Tropical
                Sociedade Brasileira de Medicina Tropical - SBMT
                0037-8682
                1678-9849
                12 November 2021
                2021
                : 54
                : e0181-2021
                Affiliations
                [1 ]Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Divisão de Cardiologia, Ribeirão Preto, SP, Brasil.
                Author notes
                Corresponding author: Prof. J. Antonio Marin-Neto MD, PhD, FACC e-mail: marin_neto@ 123456yahoo.com

                Authors' contribution: RBP, JAMN, AS: Conception and design of the study. RBP, AOP, JLH, AVB, MOLF, IML, JRAC: Acquisition of data. RBP, JAMN: Analysis and interpretation of data. RBP, AVB, JAMN: Final approval of the version to be submitted.

                Conflict of Interest: The authors declare that there is no conflict of interest.

                Author information
                http://orcid.org/0000-0001-6162-0965
                http://orcid.org/0000-0002-4543-4684
                http://orcid.org/0000-0002-1244-6590
                http://orcid.org/0000-0003-0929-6111
                http://orcid.org/0000-0002-7863-7912
                http://orcid.org/0000-0001-5073-8407
                http://orcid.org/0000-0003-3684-7767
                http://orcid.org/0000-0002-5822-3632
                http://orcid.org/0000-0002-1090-8165
                http://orcid.org/0000-0002-8651-8833
                Article
                00338
                10.1590/0037-8682-0181-2021
                8582967
                34787258
                0d7bf1ae-f021-4ed1-8e88-8e431874583e

                This is an open-access article distributed under the terms of the Creative Commons Attribution License

                History
                : 26 March 2021
                : 20 August 2021
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 54
                Categories
                Major Article

                chagas disease,coronary microvascular dysfunction,cardiomyopathy,myocardial perfusion scintigraphy,aspirin,verapamil

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