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Ischemic heart disease (IHD) is common in women, and cardiovascular disease is a leading cause of morbidity and mortality. While obstructive coronary artery disease is the most common form of IHD, millions of women suffer from angina with nonobstructive coronary arteries (ANOCA), an umbrella term encompassing multiple nonatherosclerotic disorders of the coronary tree. The underlying pathology leading to ischemia in these syndromes may be challenging to diagnose, leaving many women without a diagnosis despite persistent symptoms that impact quality of life and adversely affect long-term cardiovascular prognosis. In the last decade, there have been significant advances in the recognition and diagnostic evaluation of ANOCA. Despite these advances, the standard approach to evaluating suspected IHD in women continues to focus predominantly on the assessment of atherosclerotic coronary artery disease, leading to missed opportunities to accurately diagnose and treat underlying coronary vasomotor disorders. The goal of this review is to describe advances in diagnostic testing that can be used to evaluate angina in women and present a pragmatic diagnostic algorithm to guide evaluation of ANOCA in symptomatic patients. The proposed approach for the assessment of ANOCA is consistent with prior expert consensus documents and guidelines but is predicated on the medical interview and pretest probability of disease to inform a personalized diagnostic strategy.
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Background: Approximately 30% to 50% of patients who are referred for diagnostic coronary angiography are found to have no obstructive coronary artery disease (CAD). Ischemia and nonobstructive coronary arteries (INOCA) is increasingly recognized and encompasses coronary microvascular dysfunction, vasospastic angina, symptomatic myocardial bridging, and other vasomotor disorders. However, the prevalence of these disorders and whether underlying atherosclerotic plaque burden and morphology affect the long-term outcomes of each physiologic phenotype is unknown. Methods: The DISCOVER INOCA registry is ongoing at 8 centers in the United States and plans to enroll 500 patients with ischemic heart disease referred for angiography undergoing coronary function testing (CFT). All participants will complete patient-reported outcome measures and undergo protocol-guided angiography, acetylcholine provocation, coronary thermodilution, and intravascular imaging. Follow-up assessments occur at 30 days, 6 months, 1 year, and annually for 5 years. The primary short-term end point is the prevalence of INOCA phenotypes based on physiology and the degree of atherosclerosis based on intravascular ultrasound or optical coherence tomography (intravascular imaging). The primary long-term end point is the incidence of major adverse cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, hospitalization for cardiovascular causes, or coronary revascularization at a follow-up of 5 years. At the time of this publication, 100 participants have been enrolled. Conclusions: DISCOVER INOCA is the first prospective study of INOCA patients to integrate anatomic and physiologic measures of disease and correlate them with long-term outcomes. DISCOVER INOCA will report on the prevalence of INOCA phenotypes, the safety of comprehensive invasive CFT, and the impact of testing on diagnoses and medical therapy. Symptoms and cardiovascular adverse events at long-term follow-up will be determined in patients with no obstructive CAD undergoing angiography.
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Angiografia Coronária , Humanos , Resultado do Tratamento , Valor Preditivo dos Testes , Tomada de Decisão Clínica , Intervenção Coronária Percutânea , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Infarto do Miocárdio/cirurgia , Seleção de Pacientes , Reserva Fracionada de Fluxo MiocárdicoRESUMO
The practice patterns and outcomes of protected left main (PLM) and unprotected left main (ULM) percutaneous coronary intervention (PCI) are not well defined in contemporary US clinical practice. Data were collected from all Veteran Affairs catheterization laboratories participating in the Clinical Assessment Reporting and Tracking Program between 2009 and 2019. The analysis included 4,351 patients who underwent left main PCI, of whom 1,306 pairs of PLM and ULM PCI were included in a propensity-matched cohort. Selected temporal trends were also assessed. The primary outcome was major adverse cardiovascular event (MACE) outcomes at 1 year, which was defined as a composite of all-cause mortality, rehospitalization for myocardial infarction (MI), rehospitalization for stroke, or urgent revascularization. Patients who underwent ULM PCI compared with patients who underwent PLM PCI were older (age 71.5 vs 69.2 years, p <0.001), more clinically complex, and more likely to present with acute coronary syndrome. In the propensity-matched cohort, radial access was used more often for ULM PCI (21% [273] vs 14% [185], p <0.001) and ULM PCI was more likely to involve the left main bifurcation (22% vs 14%, p = 0.003) and require mechanical circulatory support (10% [134] vs 1% [17], p <0.001). The 1-year MACEs occurred more frequently with ULM PCI than PLM PCI (22% [289] vs 16% [215], p ≤0.001) and all-cause mortality was also higher (16% [213] vs 10% [125], p ≤0.001). In the matched cohort, there was a low incidence of rehospitalization for MI (4% [48] ULM vs 4% [48] PLM, p = 1.000) or revascularization (7% [94] ULM vs 6% [84] PLM, p = 0.485). In this real-world experience, patients who underwent PLM PCI had better 1-year outcomes than those who underwent ULM PCI; however, in both groups, there was a high rate of mortality and MACEs at 1 year despite a relatively low rate of MI or revascularization.
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Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/métodos , Masculino , Idoso , Feminino , Estados Unidos/epidemiologia , Doença da Artéria Coronariana/cirurgia , United States Department of Veterans Affairs , Pontuação de Propensão , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento , Infarto do Miocárdio/epidemiologiaRESUMO
Background: Practice patterns and outcomes of protected left main (PLM) and unprotected left main (ULM) percutaneous coronary intervention (PCI), as well as the differences between these types of PCI, are not well defined in real-world clinical practice. Methods: Data collected from all Veteran Affairs (VA) catheterization laboratories participating in the Clinical Assessment Reporting and Tracking Program between 2009 and 2019. The analysis included 4,351 patients undergoing left main PCI, of which 1,306 pairs of PLM and ULM PCI were included in a propensity matched cohort. Patients and procedural characteristics were compared between PLM and ULM PCI. Temporal trends were also assessed. Peri-procedural and one-year major adverse cardiovascular events (MACE) were compared using cumulative incidence plots. The primary outcome was MACE outcomes at 1-year, which was defined as a composite of all-cause mortality, rehospitalization for myocardial infarction (MI), rehospitalization for stroke or urgent revascularization. Results: ULM PCI patients in comparison to PLM PCI were older (71.5 vs 69.2; P < 0.001), more clinically complex and more likely to present with ACS. In the propensity matched cohort, radial access was used more often for ULM PCI (21% [273] vs. 14% [185], P < 0.001), and ULM PCI was more likely to involve the LM bifurcation (22% vs 14%; P = 0.003) and require mechanical circulatory support (10% [134] vs 1% [17]; P <0.001). One-year MACE occurred more frequently with ULM PCI compared to PLM PCI (22% [289] vs. 16% [215]; P = < 0.001) and all-cause mortality was also higher (16% [213] vs. 10% [125]; P = < 0.001). In the matched cohort there was a low incidence of rehospitalization for MI (4% [48] ULM vs. 4% [48] PLM; P = 1.000) or revascularization (7% [94] ULM vs. 6% [84] PLM; P = 0.485). Conclusions: Veterans undergoing PLM PCI had better one-year outcomes than those undergoing ULM PCI, but in both groups there was a high rate of mortality and MACE at one-year despite a relatively low rate of MI or revascularization.
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Angina with nonobstructive coronary arteries (ANOCA) is increasingly recognized and may affect nearly one-half of patients undergoing invasive coronary angiography for suspected ischemic heart disease. This working diagnosis encompasses coronary microvascular dysfunction, microvascular and epicardial spasm, myocardial bridging, and other occult coronary abnormalities. Patients with ANOCA often face a high burden of symptoms and may experience repeated presentations to multiple medical providers before receiving a diagnosis. Given the challenges of establishing a diagnosis, patients with ANOCA frequently experience invalidation and recidivism, possibly leading to anxiety and depression. Advances in scientific knowledge and diagnostic testing now allow for routine evaluation of ANOCA noninvasively and in the cardiac catheterization laboratory with coronary function testing (CFT). CFT includes diagnostic coronary angiography, assessment of coronary flow reserve and microcirculatory resistance, provocative testing for endothelial dysfunction and coronary vasospasm, and intravascular imaging for identification of myocardial bridging, with hemodynamic assessment as needed.
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Ponte Miocárdica , Isquemia Miocárdica , Humanos , Microcirculação , Angina Pectoris , Angiografia CoronáriaRESUMO
Centers specializing in coronary function testing are critical to ensure a systematic approach to the diagnosis and treatment of angina with nonobstructive coronary arteries (ANOCA). Management leveraging lifestyle, pharmacology, and device-based therapeutic options for ANOCA can improve angina burden and quality of life in affected patients. Multidisciplinary care teams that can tailor and titrate therapies based on individual patient needs are critical to the success of comprehensive programs. As coronary function testing for ANOCA is more widely adopted, collaborative research initiatives will be fundamental to improve ANOCA care. These efforts will require standardized symptom assessments and data collection, which will propel future large-scale clinical trials.
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Angina Pectoris , Qualidade de Vida , Humanos , Desenvolvimento de Programas , Vasos Coronários , Estilo de VidaRESUMO
BACKGROUND: Ischemia and no obstructive coronary artery disease (INOCA) disproportionately impacts women, yet the underlying pathologies are often not distinguished, contributing to adverse health care experiences and poor quality of life. Coronary function testing at the time of invasive coronary angiography allows for improved diagnostic accuracy. Despite increased recognition of INOCA and expanding access to testing, data lack on first-person perspectives and the impact of receiving a diagnosis in women with INOCA. METHODS: From 2020 to 2021, we conducted structured telephone interviews with 2 groups of women with INOCA who underwent invasive coronary angiography (n=29) at Yale New Haven Hospital, New Haven, CT: 1 group underwent coronary function testing (n=20, of whom 18 received a mechanism-based diagnosis) and the other group who did not undergo coronary function testing (n=9). The interviews were analyzed using the constant comparison method by a multidisciplinary team. RESULTS: The mean age was 59.7 years, and 79% and 3% were non-Hispanic White and non-Hispanic Black, respectively. Through iterative coding, 4 themes emerged and were further separated into subthemes that highlight disease experience aspects to be addressed in patient care: (1) distress from symptoms of uncertain cause: symptom constellation, struggle for sensemaking, emotional toll, threat to personal and professional identity; (2) a long journey to reach a definitive diagnosis: self-advocacy and fortitude, healthcare interactions brought about further uncertainty and trauma, therapeutic alliance, sources of information; (3) establishing a diagnosis enabled a path forward: relief and validation, empowerment; and (4) commitment to promoting awareness and supporting other women: recognition of sex and racial/ethnic disparities, support for other women. CONCLUSIONS: Insights about how women experience the symptoms of INOCA and their interactions with clinicians and the healthcare system hold powerful lessons for more patient-centered care. A coronary function testing-informed diagnosis greatly influences the healthcare experiences, quality of life, and emotional states of women with INOCA.
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Doença da Artéria Coronariana , Isquemia Miocárdica , Humanos , Feminino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Qualidade de Vida/psicologia , Isquemia Miocárdica/diagnóstico , Isquemia , PercepçãoRESUMO
Endothelial cell damage related to coronavirus disease 2019 (COVID-19) has been described in multiple vascular beds, and many survivors of COVID-19 report chest pain. This case series describes two previously healthy middle-aged individuals who survived COVID-19 and were subsequently found to have symptomatic coronary endothelial dysfunction months after initial infection.
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PURPOSE OF REVIEW: This review describes the effects of psychological stress on the physiology of the entire vascular system, from individual cellular components to macrovascular and microvascular responses, and highlights the importance of the vascular system in the context of current limitations in cardiac imaging for evaluation of the cardiovascular response to mental stress. RECENT FINDINGS: The physiological responses that mediate vascular changes are based on evolutionary needs, but there is increasing evidence that the long-term consequences of psychological stress can precipitate the development and progression of cardiovascular disease (CVD). While there is an extensive body of literature describing localized physiological responses or overt cardiovascular manifestations, often framed within the organ-specific scope of cardiovascular imaging, there has not been a comprehensive description of the global vascular effects of psychological stress. Given the global nature of these processes, targeted cardiovascular imaging modalities may be insufficient. Here we approach the vascular response to mental stress systematically, describing the effects on the endothelium, vascular smooth muscle, and adventitia. We then address the mental stress effects on large vessels and the microvascular compartment, with a discussion of the role of microvascular resistance in the pathophysiology of mental stress-induced myocardial ischemia. Vascular responses to psychological stress involve complex physiological processes that are not fully characterized by routine cardiovascular imaging assessments. Future research incorporating standardized psychological assessments targeted toward vascular mechanisms of stress responses is required to guide the development of behavioral and therapeutic interventions.
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Doenças Cardiovasculares , Sistema Cardiovascular , Doença da Artéria Coronariana , Isquemia Miocárdica , Doenças Cardiovasculares/diagnóstico por imagem , Humanos , Estresse PsicológicoRESUMO
BACKGROUND: Drug-coated balloon (DCB) angioplasty has emerged as a mainstay of therapy for the treatment of peripheral arterial disease (PAD) involving the superficial femoral and popliteal arteries. We performed a meta-analysis including all available randomized controlled trials (RCTs) to date which compare DCB to plain balloon angioplasty (POBA) in femoropopliteal disease (FPD). METHODS: Five databases were analyzed including EMBASE, PubMed, Cochrane, Scopus, and Web-of-Science from January 2000 to September 2018 for RCTs comparing DCB to POBA in patients with FPD. Heterogeneity was determined using Cochrane's Q-statistics. Random effects model was used. RESULTS: Twenty-two RCTs, including five trials of in-stent restenosis (ISR) intervention, with 3,217 patients were included in the analysis. Mean follow-up was approximately 21.6 ± 14.4 months. Overall, DCB use was associated with a 51% reduction in target vessel revascularization (TLR) when compared to POBA at follow-up (relative risk [RR]: 0.49, 95% confidence interval [CI]: 0.40-0.61, P < 0.0001). Rates of TLR were 45% lower in the DCB group when compared to POBA in patients with ISR (RR: 0.55, 95% CI: 0.37-0.81, P = 0.002). DCB was associated with lower rates of binary stenosis, late lumen loss and higher primary safety endpoints. Major amputation and mortality were not different between DCB and POBA. CONCLUSIONS: Use of DCBs is associated with improved vessel patency and a lower risk of TLR when compared to POBA in patients with FPD, especially in the setting of ISR. There was no difference in mortality between DCB and POBA in our meta-analysis. Extended follow-up of the available RCT data will be essential to analyze long-term device-related mortality.
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Angioplastia com Balão/instrumentação , Fármacos Cardiovasculares/administração & dosagem , Materiais Revestidos Biocompatíveis , Artéria Femoral , Doença Arterial Periférica/terapia , Artéria Poplítea , Dispositivos de Acesso Vascular , Idoso , Amputação Cirúrgica , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/mortalidade , Desenho de Equipamento , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Humanos , Salvamento de Membro , Masculino , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
Coronary angiography has been the principle modality for assessing the severity of atherosclerotic coronary artery disease for several decades. However, there is a complex relationship between angiographic coronary stenosis and the presence or absence of myocardial ischemia. Recent technological advances now allow for the assessment of coronary physiology in the catheterization laboratory at the time of diagnostic coronary angiography. Early studies focused on coronary flow reserve (CFR) but more recent work has demonstrated the physiologic accuracy and prognostic value of the fractional flow reserve (FFR) and instantaneous wave free ratio (iFR) for the assessment of coronary artery disease. These measurements have been validated in large multi-center clinical trials and have become indispensable tools for guiding revascularization in the cardiac catheterization laboratory. The physiological assessment of chest pain in the absence of epicardial coronary artery disease involves coronary thermodilution to obtain the index of microcirculatory resistance (IMR) or Doppler velocity measurement to determine the coronary flow velocity reserve (CFVR). Physiology-based coronary artery assessment brings "personalized medicine" to the catheterization laboratory and allows cardiologists and referring providers to make decisions based on objective findings and evidence-based treatment algorithms. The purpose of this review is to describe the theory, technical aspects, and relevant clinical trials related to coronary physiology assessment for an intended audience of general medical practitioners.
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Serotonin type 3 (5-HT(3)) receptors have been shown to participate in the negative-feedback control of food intake. We previously reported that cholecystokinin (CCK)-induced suppression of food intake is partly mediated through 5-HT(3) receptors when rats were tested on a preferred liquid diet, but whether such an effect occurs when they are tested on a solid maintenance diet is unknown. In the present study, we examined the effects of ondansetron, a selective 5-HT(3) antagonist, on CCK-induced suppression of solid chow intake. Intraperitoneal administration of ondansetron significantly attenuated 30- and 60-min CCK-induced reduction of food intake, with suppression being completely reversed by 120 min. It is not known whether 5-HT(3) receptors directly mediate CCK-induced satiation or whether their participation depends on CCK acting as part of a feedback cascade to inhibit ongoing intake. Because CCK-induced inhibition of sham feeding does not depend on additive gastric/postgastric-feedback signals, we examined the ability of ondansetron to reverse CCK-induced satiation in sham-feeding rats. Ondansetron did not attenuate reduction of sham feeding by CCK, suggesting that ondansetron does not directly antagonize CCK-satiation signals. CCK suppresses real feeding through a delay in gastric emptying. Ondansetron could attenuate CCK-induced reduction of food intake by reversing CCK-induced inhibition of gastric emptying. We found that blockade of 5-HT(3) receptors attenuates CCK-induced inhibition of gastric emptying of a solid meal, as well as saline and glucose loads. We conclude that 5-HT(3) receptors mediate CCK-induced satiation through indirect mechanisms as part of a feedback cascade involving inhibition of gastric emptying.