Ischemic heart disease (IHD) is commonly recognized as the consequence of coronary atherosclerosis and obstructive coronary artery disease (CAD). However, a significant number of patients may present ...angina or myocardial infarction even in the absence of any significant coronary artery stenosis and impairment of the coronary microcirculation has been increasingly implicated as a relevant cause of IHD. The term “coronary microvascular dysfunction” (CMD) encompasses several pathogenic mechanisms resulting in functional and/or structural changes in the coronary microcirculation and determining angina and myocardial ischemia in patients with angina without obstructive CAD (“primary” microvascular angina), as well as in several other conditions, including obstructive CAD, cardiomyopathies, Takotsubo syndrome and heart failure, especially the phenotype with preserved ejection fraction. The pathogenesis of CMD is complex and involves the combination of functional and structural alterations leading to impaired coronary blood flow and resulting in myocardial ischemia. In the absence of therapies specifically targeting CMD, attention has been focused on the role of modifiable risk factors. Here, we provide updated evidence regarding the pathophysiological mechanisms underlying CMD, with a particular focus on the role of cardiovascular risk factors and comorbidities. Moreover, we discuss the specific pathogenic mechanisms of CMD across the different cardiovascular diseases, aiming to pave the way for further research and the development of novel strategies for a precision medicine approach.
Coronary microvascular dysfunction (CMD) encompasses several pathogenetic mechanisms involving coronary microcirculation and plays a major role in determining myocardial ischemia in patients with ...angina without obstructive coronary artery disease, as well as in several other conditions, including obstructive coronary artery disease, nonischemic cardiomyopathies, takotsubo syndrome, and heart failure, especially the phenotype associated with preserved ejection fraction. Unfortunately, despite the identified pathophysiological and prognostic role of CMD in several conditions, to date, there is no specific treatment for CMD. Due to the emerging role of CMD as common denominator in different clinical phenotypes, additional research in this area is warranted to provide personalized treatments in this "garden variety" of patients. The purpose of this review is to describe the pathophysiological mechanisms of CMD and its mechanistic and prognostic role across different cardiovascular diseases. We will also discuss diagnostic modalities and the potential therapeutic strategies resulting from recent clinical studies.
Inflammation is an important player both for the initiation and progression of coronary artery disease and for coronary plaque instability. Moreover, inflammation contributes to stent thrombosis and ...in-stent restenosis after percutaneous coronary intervention. In the past several decades, most studies evaluated the involvement of cellular effectors of classic inflammatory responses, such as monocytes/macrophages, neutrophils, and T cells. Yet, besides classic inflammation, mounting evidence derived from both experimental and clinical studies suggests an important, often unrecognized, role for effector cells of allergic inflammation in both the pathogenesis of coronary artery disease and adverse events following stent implantation. In this review, we discuss the role of effector cells of allergic inflammation in the setting of coronary artery disease progression and instability, and in the occurrence of adverse events following stent implantation, as well. Moreover, we discuss possible therapeutic approaches targeting different specific pathways of allergic inflammatory activation.
Abstract
Aims
Functional alterations of epicardial coronary arteries or coronary microcirculation represent a frequent cause of myocardial infarction and non-obstructive coronary arteries (MINOCA). ...We aimed at assessing the prognostic value of intracoronary provocative tests in patients presenting with MINOCA and in which other causes of MINOCA have been excluded.
Methods and results
We prospectively evaluated patients with a diagnosis of MINOCA, excluding patients with aetiologies other than suspected coronary vasomotor abnormalities. Immediately after coronary angiography, an invasive provocative test using acetylcholine or ergonovine was performed. The incidence of death from any cause, cardiac death, and recurrence of acute coronary syndrome (ACS) was assessed at follow-up. We also assessed angina status using Seattle Angina Questionnaires (SAQ). We enrolled 80 consecutive patients mean age 63.0 ± 10.7 years, 40 (50%) male. Provocative test was positive in 37 (46.2%) patients without any complication. Among patients with a positive test, epicardial spasm was detected in 24 (64.9%) patients and microvascular spasm in 13 (35.1%) patients. After a median follow-up of 36.0 (range 12.0–60.0) months, patients with a positive test had a significantly higher occurrence of death from any cause 12 (32.4%) vs. 2 (4.7%); P = 0.002, cardiac death 7 (18.9%) vs. 0 (0.0%); P = 0.005, and readmission for ACS 10 (27.0%) vs. 3 (7.0%); P = 0.015 as well as a worse angina status as assessed by SAQ Seattle score: 88.0 (33.0–100.0) vs. 100.0 (44.0–100.0); P = 0.001 when compared with patients with a negative test.
Conclusions
We demonstrate that in patients presenting with MINOCA and suspected coronary vasomotor abnormalities, a positive provocative test for spasm is safe and identifies a high-risk subset of patients.
The term "coronary microvascular dysfunction" (CMD) encompasses several pathogenetic mechanisms resulting in functional and/or structural changes in the coronary microcirculation. CMD often ...determines angina and myocardial ischemia in a broad spectrum of cardiovascular diseases, including patients with ischemia with non-obstructive coronary arteries or ischemia with obstructive coronary artery disease, infarction with non-obstructive coronary arteries, cardiomyopathies, the Takotsubo syndrome and heart failure, especially heart failure with preserved ejection fraction. In this article, we provide updated evidence regarding the pathophysiological mechanisms underlying CMD across the different cardiovascular diseases, aiming to pave the way for further research and the development of novel strategies for a precision medicine approach.
Heart failure with preserved ejection fraction (HFpEF) is an increasingly studied entity accounting for 50% of all diagnosed heart failure and that has claimed its own dignity being markedly ...different from heart failure with reduced EF in terms of etiology and natural history (
Graziani et al., 2018
). Recently, a growing body of evidence points the finger toward microvascular dysfunction as the major determinant of the pathological cascade that justifies clinical manifestations (
Crea et al., 2017
). The high burden of comorbidities such as metabolic syndrome, hypertension, atrial fibrillation, chronic kidney disease, obstructive sleep apnea, and similar, could lead to a systemic inflammatory state that impacts the physiology of the endothelium and the perivascular environment, engaging complex molecular pathways that ultimately converge to myocardial fibrosis, stiffening, and dysfunction (
Paulus and Tschope, 2013
). These changes could even self-perpetrate with a positive feedback where hypoxia and locally released inflammatory cytokines trigger interstitial fibrosis and hypertrophy (
Ohanyan et al., 2018
). Identifying microvascular dysfunction both as the cause and the maintenance mechanism of this condition has opened the field to explore specific pharmacological targets like nitric oxide (NO) pathway, sarcomeric titin, transforming growth factor beta (TGF-β) pathway, immunomodulators or adenosine receptors, trying to tackle the endothelial impairment that lies in the background of this syndrome (
Graziani et al., 2018
;
Lam et al., 2018
). Yet, many questions remain, and the new data collected still lack a translation to improved treatment strategies. To further elaborate on this tangled and exponentially growing topic, we will review the evidence favoring a microvasculature-driven etiology of this condition, its clinical correlations, the proposed diagnostic workup, and the available/hypothesized therapeutic options to address microvascular dysfunction in the failing heart.
The paradigm for the management of patients presenting with angina and/or myocardial ischemia has been historically centered on the detection and treatment of obstructive coronary artery disease ...(CAD). However, in a considerable proportion (30–50%) of patients undergoing coronary angiography, obstructive CAD is excluded. Thus, functional mechanisms may be involved in determining myocardial ischemia and should be investigated. In particular, coronary vasomotor disorders both at epicardial and at microvascular level may play a crucial role, but a definitive diagnosis of these disorders can at times be difficult, given the transience of symptoms, and often requires the use of coronary provocative tests. Of importance, these tests may provide relevant information on the pathogenic mechanism of myocardial ischemia, allowing physicians to tailor the therapies of their patients. Furthermore, several studies underscored the important prognostic information deriving from the use of coronary provocative tests. Nevertheless, their use in clinical practice is currently limited and mainly restricted to specialized centers, with only a minority of patients receiving a benefit from this diagnostic approach.
In this review, we explain the pathophysiological bases for the use of provocative tests, along with their clinical, prognostic and therapeutic implications.
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•Coronary vasomotor disorders may play a relevant role in the pathogenesis of ischemic syndromes.•The use of coronary provocative tests enables to unmask vasomotor disorders.•Provocative tests allow to tailor therapy targeted to the underlying mechanism of disease.•Provocative tests can provide relevant prognostic information.
Primary percutaneous coronary intervention is nowadays the preferred reperfusion strategy for patients with acute ST-segment–elevation myocardial infarction, aiming at restoring epicardial ...infarct-related artery patency and achieving microvascular reperfusion as early as possible, thus limiting the extent of irreversibly injured myocardium. Yet, in a sizeable proportion of patients, primary percutaneous coronary intervention does not achieve effective myocardial reperfusion due to the occurrence of coronary microvascular obstruction (MVO). The amount of infarcted myocardium, the so-called infarct size, has long been known to be an independent predictor for major adverse cardiovascular events and adverse left ventricular remodeling after myocardial infarction. Previous cardioprotection studies were mainly aimed at protecting cardiomyocytes and reducing infarct size. However, several clinical and preclinical studies have reported that the presence and extent of MVO represent another important independent predictor of adverse left ventricular remodeling, and recent evidences support the notion that MVO may be more predictive of major adverse cardiovascular events than infarct size itself. Although timely and complete reperfusion is the most effective way of limiting myocardial injury and subsequent ventricular remodeling, the translation of effective therapeutic strategies into improved clinical outcomes has been largely disappointing. Of importance, despite the presence of a large number of studies focused on infarct size, only few cardioprotection studies addressed MVO as a therapeutic target. In this review, we provide a detailed summary of MVO including underlying causes, diagnostic techniques, and current therapeutic approaches. Furthermore, we discuss the hypothesis that simultaneously addressing infarct size and MVO may help to translate cardioprotective strategies into improved clinical outcome following ST-segment–elevation myocardial infarction.
Approximately 50% of patients with ST-segment elevation myocardial infarction (STEMI) have multivessel coronary artery disease, a condition associated with an increased incidence of recurrent ...ischaemic events and higher mortality. Based on recent evidences, a strategy of staged percutaneous coronary intervention (PCI) of obstructive non-culprit lesions should be considered the gold standard for the management of these patients. However, several issues remain still unresolved. Indeed, what is the optimal timing of staged PCI is not completely defined. Moreover, assessment of intermediate non-culprit lesions represent still a clinical conundrum, as pressure-wire indexes do not seem able to correctly identify those patients in whom deferral is safe. Intracoronary imaging may help to identify untreated non-culprit lesions containing vulnerable plaques that may portend a higher risk of future cardiovascular events. However, there are hitherto no studies demonstrating that preventive PCI of vulnerable plaques or more intensive pharmacological treatment is associated with an improved clinical outcome. In this review, we discuss the recent evolving concepts about management of non-culprit plaques in STEMI patients, proposing a diagnostic and therapeutic algorithm to guide physicians in clinical practice. We also underscore the several knowledge gaps to address in future studies.