Initial single-center experience of a standardized protocol for invasive assessment of ischemia and non-obstructive coronary artery disease.

INTRODUCTION: Coronary vasomotion disorders (CVDs), including microvascular angina (MVA) and vasospastic angina (VSA), account for significant morbidity among patients with non-obstructive coronary artery disease (NOCAD). However, protocols for CVD assessment in clinical practice are seldom standardized and may be difficult to implement. PURPOSE: To assess the safety and feasibility of a comprehensive coronary function test (CFT) protocol for assessment of CVD and the prevalence of different phenotypes of CVD in patients with angina and NOCAD (ANOCA). METHODS: Patients with persistent angina referred for invasive coronary angiogram and found to have NOCAD were prospectively recruited and underwent a CFT. Functional parameters (fractional flow reserve, coronary flow reserve and index of myocardial resistance) and coronary vasoreactivity were assessed in all patients. RESULTS: Of the 20 patients included, the mean age was 63±13 years and 50% were females. Most patients had persistent typical angina and evidence of ischemia in noninvasive tests (75%). The CFT was successfully performed in all subjects without serious complications. Isolated MVA was found in 25%, isolated VSA in 40%, both MVA and VSA in 10% and noncardiac chest pain in 25% of patients. Antianginal therapy was modified after the results of CFT in 70% of patients. CONCLUSION: A coronary function test was feasible and safe in a cohort of patients with ANOCA. CVD were prevalent in this selected group of patients, and some presented mixed CVD phenotypes. CFT may provide a definitive diagnosis in patients with persistent angina and prompt the stratification of pharmacological therapy.

Exertional chest pain is sometimes more than just coronary atherosclerosis.

CLINICAL CASE: A 64-year-old male, with cardiovascular risk factors and previous history of bilateral carpal tunnel syndrome, presented with exertional retrosternal pain. The resting echocardiogram was unremarkable. A stress echocardiogram with dobutamine revealed hypokinesis of the inferior wall, associated with angina, followed by ventricular tachycardia. The coronary angiography revealed slow flow, a dominant right coronary artery with non-obstructive atherosclerosis and a left anterior descending artery with intermediate lesions in mid and distal segments. The invasive functional evaluation, including fractional flow reserve, thermodilution coronary flow reserve and index of microvascular resistance, led to the diagnosis of microvascular angina, treated with calcium channel blockers and transdermal nitrate, giving symptom relief. EVOLUTION: Three years later he developed complete atrioventricular block and a dual chamber pacemaker was implanted. Shortly after, the patient developed progressive symmetrical tetraparesis, associated with marked muscle atrophy, hand numbness, orthostatic hypotension and dysphagia. The neurology workup led to the diagnosis of familial amyloidotic polyneuropathy, with the Val30Met mutation in the transthyretin gene. The following year he developed congestive heart failure. The echocardiogram showed moderate concentric left ventricular hypertrophy with preserved ejection fraction. A 99mTc-DPD Scintigraphy showed significant myocardial tracer uptake, leading to a diagnosis of TTR amyloid infiltration. DISCUSSION: Patients with exertional angina and microvascular disease should be kept under close surveillance, as they may have systemic disease with cardiac involvement. Carpal tunnel syndrome, in the context of undiagnosed cardiac disease, should trigger suspicion of cardiac amyloidosis.

Medição do Fluxo Sanguíneo Coronário em Angiogramas Coronários Convencionais por um Novo Método Baseado na Detecção da Densidade de Contraste. Uma Visão Fisiológica / Coronary Blood Flow Measurement in Conventional Coronary Angiograms by a New Method Based on Contrast Density Detection. A Physiological Insight

Resumo Fundamento O grau de fluxo TIMI e a contagem quadro a quadro TIMI corrigida (CTFC) são métodos amplamente utilizados para avaliar o fluxo sanguíneo coronariano angiográfico. A medição do fluxo sanguíneo coronariano (FSC) na coronariografia (CAG) padrão despertou grande interesse recentemente, tentando combinar o conceito de CTFC com novos métodos para pós-angioplastia e avaliação da síndrome cardíaca X. Além disso, o fluxo coronariano lento é considerado um critério importante para a angina microvascular. Objetivo Explorar uma nova abordagem de medição angiográfica quantitativa do FSC com base na detecção densitométrica de contraste na CAG offline, usando um software acessível para obter uma avaliação mais precisa e confiável do FSC. Métodos Trinta pacientes foram estudados e divididos em 2 grupos: fluxo sanguíneo coronariano normal (FN) e fluxo sanguíneo coronariano lento (FL), de acordo com a definição da CTFC. O MD foi aplicado à amostra do estudo para diferenciar entre FN e FL. A estatística não paramétrica foi usada para avaliar diferenças entre os grupos com p<0,05. Resultados O valor de referência normal do MD obtido para o fluxo sanguíneo coronariano foi de 9 [5-10] quadros. Os grupos FN vs. FL foi comparado e expresso como mediana [intervalo interquartil], para a artéria descendente anterior esquerda: 10 [7-11] vs. 21 [8-33]; p=0,016; artéria circunflexa: 9 [4-13] vs. 14 [11-30]; p=0,012 e artéria coronária direita: 5 [3-11] vs. 13 [8-26]; p=0,009. Conclusão O MD mostrou a viabilidade de medir o fluxo sanguíneo coronariano com precisão, consistência e reprodutibilidade em um angiograma coronariano padrão, mostrando a capacidade adicional de diferenciar FN de FL em pacientes com dor precordial e artérias coronárias normais. (Arq Bras Cardiol. 2020; 115(3):503-512)

Abstract Background TIMI flow grade and corrected TIMI frame count (CTFC) are widely used methods to evaluate angiographic coronary blood flow. Measurement of coronary blood flow (CBF) on standard coronary angiography (CAG) has aroused great interest recently, trying to combine the CTFC concept with new methods for post-angioplasty and for cardiac syndrome X assessment. Additionally, coronary slow flow it is now considered a major criterion for microvascular angina. Objective Explore a new approach of quantitative angiographic measurement of CBF based on densitometric contrast detection in CAG off-line, using an accessible software to obtain a more precise and reliable CBF assessment. Methods Thirty patients were studied and divided in 2 groups, normal coronary blood flow (NF) and slow coronary blood flow (SF), according to CTFC definition. The DM was applied to the study sample to differentiate between NF and SF. Non-parametric statistics was used to assess differences between groups at p<0.05. Results The DM normal reference value obtained for coronary blood flow was 9 [5-10] frames. NF vs SF group were compared and expressed as median [interquartile range], for the left anterior descending: 10 [7-11] vs 21 [8-33];p= 0.016; circumflex: 9 [4-13] vs 14 [11-30]; p= 0.012 and right coronary artery: 5 [3-11] vs 13 [8-26]; p=0.009. Conclusion The DM showed the feasibility of measuring coronary blood flow with precision, consistency and reproducible in a standard coronary angiogram, showing the additional capability to differentiate between NF and SF in chest pain patients with normal coronary arteries. (Arq Bras Cardiol. 2020; 115(3):503-512)

Whole blood viscosity in microvascular angina and coronary artery disease: Significance and utility.

INTRODUCTION AND OBJECTIVES: Whole blood viscosity (WBV) is the intrinsic resistance of blood flow in vessels, and when elevated induces endothelial shear stress and endothelial inflammation and can accelerate the atherosclerotic process. This study aims to compare WBV levels in patients with microvascular angina (MVA), patients with coronary artery disease (CAD), and normal controls, and to identify the relationship between WBV and high-sensitivity C-reactive protein as a marker of inflammation in MVA and CAD. METHODS: A total of 573 patients were studied. The MVA group consisted of 189 subjects, the CAD group consisted of 203 subjects, and the control group consisted of 181 age- and gender-matched individuals. WBV was calculated from hematocrit and plasma protein concentration at a low shear rate (0.5 s-1) and high shear rate (208 s-1) by a validated equation. RESULTS: Patients with CAD and MVA had significantly higher WBV at both low and high shear rates compared to the control group. Correlation analysis revealed a significant relationship between high-sensitivity C-reactive protein and WBV at low (r=0.556; p<0.001) and high shear rates (r=0.562) in the CAD group and at low (r=0.475) and high shear rates (r=0.493) in the MVA group. CONCLUSIONS: Overall, this study demonstrated a significant and independent association between blood viscosity and the existence of endothelial inflammation and the atherosclerotic process.

Prevalencia de angina microvascular en pacientes del Centro de Investigaciones Médico Quirúrgicas / Prevalence of microvascular angina in patients from the Center for Medical Surgical Research

Introducción: un considerable número de pacientes que son sometidos a coronariografía, no tienen lesiones ateroscleróticas en su árbol coronario. El subgrupo con dolor anginoso y prueba ergométrica positiva se engloba en el diagnóstico de angina microvascular. Objetivo: determinar la prevalencia de angina microvascular en pacientes sometidos a coronariografía. Métodos: investigación trasversal descriptiva, en pacientes estudiados en el Laboratorio de Hemodinámica del Centro de Investigaciones Médico Quirúrgicas, en los años 2010 y 2011, que presentaban como diagnóstico inicial, angina de esfuerzo y prueba ergométrica positiva. El universo estuvo constituido por los 1 452 pacientes sometidos a coronariografía en este período. La muestra se conformó por los 452 en los que no se demostraron lesiones de aterosclerosis coronaria. Resultados: el 31,1 por ciento de los pacientes sometidos a coronariografía presentaron angina microvascular con mayor predominio del sexo femenino. La hipertensión arterial fue el factor de riesgo que más prevaleció en los dos años de evaluación. Conclusiones: la angina microvascular es una entidad frecuente en Cuba que se relaciona con la presencia de factores de riesgo cardiovascular(AU)

Introduction: a considerable number of patients undergoing coronary arteriography do not present any atherosclerotic lesions in their coronary tree. The subgroup with chest pain and a positive ergometric test was included in the diagnosis of microvascular angina. Objective: determine the prevalence of microvascular angina in patients undergoing coronary arteriography. Methods: descriptive cross-sectional study of patients examined at the Hemodynamic Laboratory of the Center for Medical Surgical Research from 2010 to 2011, initially diagnosed with effort angina and with a positive ergometric test. The study universe was 1 452 patients undergoing coronary arteriography in the period. The sample consisted of the 452 patients who did not show any coronary atherosclerotic lesions. Results: 31.1 percent of the patients undergoing coronary arteriography had microvascular angina, with a predominance of the female sex. Arterial hypertension was the main risk factor throughout the two years' evaluation. Conclusions: microvascular angina, a common condition in Cuba, is related to the presence of cardiovascular risk factors(AU)

Prevalencia de angina microvascular en pacientes del Centro de Investigaciones Médico Quirúrgicas / Prevalence of microvascular angina in patients from the Center for Medical Surgical Research

Introducción: un considerable número de pacientes que son sometidos a coronariografía, no tienen lesiones ateroscleróticas en su árbol coronario. El subgrupo con dolor anginoso y prueba ergométrica positiva se engloba en el diagnóstico de angina microvascular. Objetivo: determinar la prevalencia de angina microvascular en pacientes sometidos a coronariografía. Métodos: investigación trasversal descriptiva, en pacientes estudiados en el Laboratorio de Hemodinámica del Centro de Investigaciones Médico Quirúrgicas, en los años 2010 y 2011, que presentaban como diagnóstico inicial, angina de esfuerzo y prueba ergométrica positiva. El universo estuvo constituido por los 1 452 pacientes sometidos a coronariografía en este período. La muestra se conformó por los 452 en los que no se demostraron lesiones de aterosclerosis coronaria. Resultados: el 31,1 % de los pacientes sometidos a coronariografía presentaron angina microvascular con mayor predominio del sexo femenino. La hipertensión arterial fue el factor de riesgo que más prevaleció en los dos años de evaluación. Conclusiones: la angina microvascular es una entidad frecuente en Cuba que se relaciona con la presencia de factores de riesgo cardiovascular.

Introduction: a considerable number of patients undergoing coronary arteriography do not present any atherosclerotic lesions in their coronary tree. The subgroup with chest pain and a positive ergometric test was included in the diagnosis of microvascular angina. Objective: determine the prevalence of microvascular angina in patients undergoing coronary arteriography. Methods: descriptive cross-sectional study of patients examined at the Hemodynamic Laboratory of the Center for Medical Surgical Research from 2010 to 2011, initially diagnosed with effort angina and with a positive ergometric test. The study universe was 1 452 patients undergoing coronary arteriography in the period. The sample consisted of the 452 patients who did not show any coronary atherosclerotic lesions. Results: 31.1 % of the patients undergoing coronary arteriography had microvascular angina, with a predominance of the female sex. Arterial hypertension was the main risk factor throughout the two years' evaluation. Conclusions: microvascular angina, a common condition in Cuba, is related to the presence of cardiovascular risk factors.

Base racional e plano de estudo prospectivo para avaliar o efeito de terapêutica antiplaquetária e vasodilatadora microcirculatória em pacientes com cardiopatia chagásica crônica e distúrbios microvasculares coronários / Rationale and design of a prospective study to assess the effect of microcirculatory antiplatelet and vasodilation therapy in patients with chronic chagas heart disease and coronary microvascular disease

Introdução: Há evidência, embasada por estudos em modelos experimentais de infecção pelo Trypanosoma cruzi, e também por investigações histopatológicas em humanos com a doença de Chagas, de que distúrbios de natureza isquêmica participem da patogênese de lesões miocárdicas na fase crônica da moléstia. Esses distúrbios isquêmicos derivam de desregulação microcirculatória. Dor precordial atípica é sintoma comum em pacientes na fase crônica da doença de Chagas. Em substancial proporção desses pacientes, apesar da inexistência de obstruções coronárias angiograficamente detectáveis, documenta-se com cintilografia miocárdica a ocorrência de distúrbios perfusionais durante o estresse, que são reversíveis após repouso. Métodos: Estudo unicêntrico, prospectivo, de coorte única, com intervenção terapêutica seguida de reavaliação quantitativa, após 90 dias, da área ventricular apresentando alterações perfusionais isquêmicas inicialmente detectadas em pacientes cardiopatas chagásicos com coronárias angiograficamente normais. A cintilografia miocárdica de perfusão será executada com o método SPECT,antes e após 90 dias da intervenção terapêutica, tendo os estamibi-Tc99m como radiotraçador e o esforço físico ou o estímulo vasodilatador com dipiridamol como estressores. A intervenção terapêutica consistirá de ácido acetilsalicílico (dose de 100 mg diária) associado a verapamil (dose diária de160 mg, em duas tomadas de 80 mg). O desfecho primário do estudo será redução > 50% da área ventricular de isquemia miocárdica reversível calculada pelo mapa polar da cintilografia miocárdica de perfusão. Conclusões: Este é o primeiro estudo de intervenção terapêutica para atenuar ou reverter alterações miocárdicas isquêmicas de origem microvascular em pacientes com cardiopatia chagásica crônica.

Hemorheology and microvascular disorders.

The present review presents basic concepts of blood rheology related to vascular diseases. Blood flow in large arteries is dominated by inertial forces exhibited at high flow velocities, while viscous forces (i.e., blood rheology) play an almost negligible role. When high flow velocity is compromised by sudden deceleration as at a bifurcation, endothelial cell dysfunction can occur along the outer wall of the bifurcation, initiating inflammatory gene expression and, through mechanotransduction, the cascade of events associated with atherosclerosis. In sharp contrast, the flow of blood in microvessels is dominated by viscous shear forces since the inertial forces are negligible due to low flow velocities. Shear stress is a critical parameter in microvascular flow, and a force-balance approach is proposed for determining microvascular shear stress, accounting for the low Reynolds numbers and the dominance of viscous forces over inertial forces. Accordingly, when the attractive forces between erythrocytes (represented by the yield stress of blood) are greater than the shear force produced by microvascular flow, tissue perfusion itself cannot be sustained, leading to capillary loss. The yield stress parameter is presented as a diagnostic candidate for future clinical research, specifically, as a fluid dynamic biomarker for microvascular disorders. The relation between the yield stress and diastolic blood viscosity (DBV) is described using the Casson model for viscosity, from which one may be able determine thresholds of DBV where the risk of microvascular disorders is high.

Hemorheology and Microvascular Disorders

The present review presents basic concepts of blood rheology related to vascular diseases. Blood flow in large arteries is dominated by inertial forces exhibited at high flow velocities, while viscous forces (i.e., blood rheology) play an almost negligible role. When high flow velocity is compromised by sudden deceleration as at a bifurcation, endothelial cell dysfunction can occur along the outer wall of the bifurcation, initiating inflammatory gene expression and, through mechanotransduction, the cascade of events associated with atherosclerosis. In sharp contrast, the flow of blood in microvessels is dominated by viscous shear forces since the inertial forces are negligible due to low flow velocities. Shear stress is a critical parameter in microvascular flow, and a force-balance approach is proposed for determining microvascular shear stress, accounting for the low Reynolds numbers and the dominance of viscous forces over inertial forces. Accordingly, when the attractive forces between erythrocytes (represented by the yield stress of blood) are greater than the shear force produced by microvascular flow, tissue perfusion itself cannot be sustained, leading to capillary loss. The yield stress parameter is presented as a diagnostic candidate for future clinical research, specifically, as a fluid dynamic biomarker for microvascular disorders. The relation between the yield stress and diastolic blood viscosity (DBV) is described using the Casson model for viscosity, from which one may be able determine thresholds of DBV where the risk of microvascular disorders is high.

Algunos apuntes sobre el diagnóstico de la angina micro-vascular y Síndrome / Some notes on the diagnosis of the micro vascular angina and X syndrome

El término síndrome X se emplea habitualmente para definir a un grupo de pacientes que presentan dolor torácico característico, depresión del segmento ST durante el esfuerzo y arterias coronarias angiográficamente normales. Clínicamente cursa con dolor anginoso típico no siempre relacionado con el esfuerzo y con frecuencia prolongado lo que dificulta su diagnóstico. Existe actualmente una gran diversidad de complementarios, unos dirigidos a las causas conocidas y otros de muy diversa índole dirigidos al diagnóstico de la entidad, destacándose dentro de ellos los estudios de imágenes y los de Medicina Nuclear.

The term X syndrome is habitually used to define a group of patients presenting characteristic thoracic pain, depression of the ST segment during the effort and coronary arteries angiographically normal. Clinically it presents with a typical angina's pain not always related with the effort and frequently prolonged, making it difficult the diagnosis. There is a great diversity of complementary analysis and tests, some directed to the already known causes, and other directed to the diagnosis of the entity, being the imagine study and the studies of nuclear medicine the most outstanding.

Algunos apuntes sobre el diagnóstico de la angina micro-vascular y Síndrome / Some notes on the diagnosis of the micro vascular angina and X syndrome

El término síndrome X se emplea habitualmente para definir a un grupo de pacientes que presentan dolor torácico característico, depresión del segmento ST durante el esfuerzo y arterias coronarias angiográficamente normales. Clínicamente cursa con dolor anginoso típico no siempre relacionado con el esfuerzo y con frecuencia prolongado lo que dificulta su diagnóstico. Existe actualmente una gran diversidad de complementarios, unos dirigidos a las causas conocidas y otros de muy diversa índole dirigidos al diagnóstico de la entidad, destacándose dentro de ellos los estudios de imágenes y los de Medicina Nuclear(AU)

The term X syndrome is habitually used to define a group of patients presenting characteristic thoracic pain, depression of the ST segment during the effort and coronary arteries angiographically normal. Clinically it presents with a typical angina's pain not always related with the effort and frequently prolonged, making it difficult the diagnosis. There is a great diversity of complementary analysis and tests, some directed to the already known causes, and other directed to the diagnosis of the entity, being the imagine study and the studies of nuclear medicine the most outstanding(AU)

Relation between Peripheral Vascular Endothelial Function and Coronary Flow Reserve in Patients with Chest Pain and Normal Coronary Angiogram

BACKGROUND AND OBJECTIVES: Previous studies suggest the endothelium dependent coronary vasodilation is impaired in many patients with microvascular angina. However, the relationship between the peripheral vascular endothelial function and coronary flow reserve (CFR) in these patients remains elusive. The relationship between the peripheral vascular endothelial function and CFR was sought in patients with chest pain and a normal coronary angiogram. SUBJECTS AND METHODS: In 32 subjects (mean age 58+/-9 yrs, M:F=9:23) with chest pain and a normal coronary angiogram, the flow mediated dilation (FMD) was assessed in the brachial artery by measuring the change in brachial artery diameter in response to hyperemic flow. In all subjects, the intimamedia thickness (IMT) of the carotid artery was also measured using a 15 MHz linear array transducer. Subjects were divided into 2 groups according to their CFR:> or =2.1 or or =2.1 (p or =2.1 (p=NS), respectively. The percentage FMD was not related to the IMT (p=NS). CONCLUSION: Microvascular dysfunction is primarily related to endothelial dysfunction, rather than advanced atherosclerosis, and this endothelial dysfunction is a generalized process that involves whole arteries in patients with chest pain and a normal coronary angiogram.