Search Results (29)

Angina or objective myocardial ischaemia in the absence of obstructive coronary artery disease, referred to as ANOCA/INOCA, represents a prevalent and clinically significant condition associated with persistent symptoms, impaired quality of life, and increased healthcare utilisation. Contemporary evidence has reframed these syndromes as manifestations of coronary vascular dysfunction, encompassing structural and functional coronary microvascular dysfunction, epicardial vasospasm, microvascular spasm, and mixed phenotypes. In this context, multimodality imaging should not be conceptualised as sequential test accumulation, but rather as a structured, mechanism-based diagnostic strategy aimed at defining the underlying coronary endotype. The 2024 ESC Guidelines for chronic coronary syndromes endorse dedicated diagnostic pathways beyond a stenosis-centred paradigm and support the use of invasive coronary function testing (ICFT) in selected patients with persistent symptoms or inconclusive non-invasive findings. An integrated approach combining anatomical assessment (coronary computed tomography angiography or invasive angiography ± pressure-based indices), quantitative perfusion imaging (positron emission tomography or stress cardiovascular magnetic resonance), and ICFT (including coronary flow reserve, microvascular resistance indices, and acetylcholine provocation testing) enables comprehensive characterisation of coronary physiology and vasomotor function. This review proposes a pragmatic framework linking diagnostic findings to targeted therapy through a test-to-endotype-to-therapy paradigm. We summarise the strengths and limitations of each modality, discuss implementation challenges, and highlight the clinical relevance of endotype-driven management. By shifting from a stenosis-centred to a physiology- and mechanism-based approach, this strategy has the potential to close the longstanding gap between diagnosis and treatment in patients with ischaemia beyond obstructive coronary disease. Full article

Coronary artery spasm (CAS) is a common endotype in patients with angina with non-obstructive coronary arteries. Pathophysiologically, the presence of CAS among arteries is not normal, as evidenced by several interacting mechanisms involving CAS development, including the endothelium, vascular smooth muscle cells, adventitia, autonomic nervous system, local inflammation, and systemic inflammation. Clinically, CAS is a dynamic process with a threshold effect on presentation; it can present as silent ischemia, atypical chest pain, resting angina, chronic coronary syndrome, acute coronary syndrome, variant angina, and even sudden cardiac arrest. Incomplete intracoronary provocation testing to exclude CAS as the etiology of chronic or acute coronary syndrome leads to an incorrect diagnosis and, subsequently, inappropriate treatment. Identification of the correct endotypes of chronic and acute coronary syndromes is critical for the selection of appropriate therapy, which thus affects disease outcome. Therefore, it is essential to complete intracoronary provocation testing for both the right and left coronary arteries to reach a correct diagnosis regarding CAS, including epicardial vasospasm and microvascular spasm. If CAS is found not to be the cause of myocardial ischemia, then a microvascular functional assessment is the next step to identify the etiology of the ischemic event. A comprehensive assessment of CAS is essential before appropriate treatments can be started. Full article

Cardiovascular disease and diabetes mellitus have now reached pandemic proportions, and their association has become very common. Some patients with coronary artery disease and diabetes remain symptomatic, with chest pain present despite the implementation of evidence-based medical treatment and maximal therapy. A hypothesis increasingly confirmed in clinical practice is that epicardial or microvascular spasm, or both, are frequently responsible for the lack of symptom control or for the occurrence of major adverse cardiovascular events. Our review provides the most up-to-date and in-depth analysis of the available literature to provide solid knowledge about coronary spasm in diabetes patients. We have deepened the substrate of coronary spasm in relation to the multiple and complex structural and functional abnormalities produced by chronic hyperglycemia, with the ultimate goal of allowing optimization of treatment and improving patient outcomes. Full article

Background: Pharmacologic therapy guided by invasive coronary function tests (CFTs) may improve symptomatic outcomes in patients with angina and non-obstructive coronary artery disease (ANOCA). In this study, we specifically aimed to investigate whether the induction of coronary microvascular spasm (CMVS) by the acetylcholine (Ach) test predicts a better therapeutic effect of calcium-channel blocker therapy compared to beta-blocker therapy. Methods: We enrolled 31 ANOCA patients, who were divided into two groups according to the result of Ach testing: 16 patients with CMVS (CMVS group) and 15 patients with a negative test (NEG group). Patients with Ach-induced epicardial spasm were excluded. In an open-label crossover trial, patients were randomly assigned to each receive, for a period of 4 weeks, either metoprolol (50 mg twice daily) or diltiazem (120 mg twice daily). At the end of each 4-week period, patients underwent an ECG–exercise stress test (EST) and were invited to fill out the Seattle Angina Questionnaire (SAQ). Results: No significant differences were found between metoprolol and diltiazem in terms of SAQ scores, and ECG-EST results were also largely comparable with the two drug treatments, both in the CMVS group and the NEG group. In particular, the SAQ summary score was 63.1 ± 24 and 66.0 ± 25 (p = 0.59) for metoprolol and diltiazem, respectively, in the CMVS group, and 70.9 ± 17 and 74.3 ± 16 (p = 0.37) with the two drugs, respectively, in the NEG group. Conclusions: Our small open-label study shows that patients with ANOCA with negative Ach test or Ach-induced CMVS show largely comparable short-term symptomatic outcomes and ECG-EST results when treated with either metoprolol or diltiazem. Full article

Coronary microvascular obstruction and dysfunction (CMVO) frequently arise following primary percutaneous coronary intervention (PCI), particularly in individuals with myocardial infarction. Despite the restoration of epicardial blood flow, microvascular perfusion might still be compromised, resulting in negative clinical outcomes. CMVO is a complex condition resulting from a combination of ischemia, distal thrombotic embolization, reperfusion injury, and individual susceptibilities such as inflammation and endothelial dysfunction. The pathophysiological features of this condition include microvascular spasm, endothelial swelling, capillary plugging by leukocytes and platelets, and oxidative stress. Traditional angiographic assessments, such as Thrombolysis in Myocardial Infarction (TIMI) flow grade and myocardial blush grade, have limited sensitivity. Cardiac magnetic resonance imaging (CMR) stands as the gold standard for identifying CMVO, while the index of microvascular resistance (IMR) is a promising invasive option. Treatment approaches involve powerful antiplatelet drugs, anticoagulants, and supersaturated oxygen, yet no treatment has been definitively shown to reverse established CMVO. CMVO remains a significant therapeutic challenge in coronary artery disease management. Enhancing the comprehension of its core mechanisms is vital for the development of more effective and personalized treatment strategies. Full article

Despite significant advances in understanding and management, cardiovascular diseases remain the leading cause of mortality worldwide. Historically, diagnostic and therapeutic strategies have typically targeted obstructive coronary arteries. However, growing evidence supports the pivotal role of non-obstructive mechanisms in myocardial ischemia, prompting a new classification that distinguishes Acute Myocardial Ischemic Syndromes from Non-Acute Myocardial Ischemic Syndromes. In this evolving context, Optical Coherence Tomography (OCT) plays an important diagnostic role in the assessment of both obstructive and non-obstructive ischemic mechanisms. In Acute Myocardial Ischemic Syndromes, OCT enables the identification of major plaque destabilization mechanisms and contributes to the diagnosis of Myocardial Infarction with Non-Obstructive Coronary Arteries, helping to differentiate between atherosclerotic and non-atherosclerotic causes. In Non-Acute Myocardial Ischemic Syndromes, OCT assists in evaluating stenosis severity, plaque morphology, vulnerability, and healing, and may contribute to the diagnosis of Ischemia with Non-Obstructive Coronary Arteries, identifying myocardial bridge and epicardial spasm alongside conventional functional assessment of intermediate stenoses. This narrative review outlines the expanding clinical applications of OCT across the full spectrum of ischemic syndromes, emphasizing its role in bridging obstructive and non-obstructive pathophysiology and supporting a more comprehensive diagnostic approach to ischemic heart disease. Full article

Coronary artery spasm (CAS) is a reversible vasoconstriction of normal or atherosclerotic epicardial coronary arteries with a subsequent reduction in myocardial blood flow, leading to myocardial ischemia, myocardial infarction, severe arrhythmias, or even sudden death. It is an entity that should be recognized based on a particular clinical presentation. Numerous differences exist between CAS and obstructive coronary disease in terms of mechanisms, risk factors, and therapeutic solutions. The gold standard for CAS diagnosis is represented by transitory and reversible occlusion of the coronary arteries at spasm provocation test, which consists of an intracoronary administration of Ach, ergonovine, or methylergonovine during angiography. The pathophysiology of CAS is not fully understood. However, the core of CAS is represented by vascular smooth muscle cell contraction, with a circadian pattern. The initiating event of this contraction may be represented by endothelial dysfunction, inflammation, or autonomic nervous system unbalance. Our study explores the intricate balance of these factors and their clinical relevance in the management of CAS. Full article

(1) Background: Prevalence of patent foramen ovale (PFO) in the general population is estimated at around 24%. We hypothesized that right-to-left shunting (RLS) resulting from PFO might contribute to angina symptoms in patients with coronary artery spasm (CAS), potentially triggered by vasoactive metabolites. Therefore, the aim of this study was to investigate the prevalence of PFO-related RLS in patients with documented CAS. (2) Methods: This single-center prospective cohort study included patients with documented CAS undergoing transthoracic echocardiography (TTE), including a contrast bubble study between 2021 and 2023. The Seattle Angina Questionnaire (SAQ) and Migraine Disability Assessment (MIDAS) were used to survey patients. (3) Results: RLS (PFO group) was observed in 11 of the 48 patients included (23%). In the PFO group, 64% had epicardial spasm and 36% microvascular spasm. Furthermore, RLS was more prevalent in patients with CAS and concomitant migraine (29%). Remarkably, the density plot of the SAQ summary score showed a worse score for patients with RLS (median of 38 [Q1–Q3: 31–49]) than patients without RLS (median of 49 [Q1–Q3: 41–55]) (p = 0.0282). (4) Conclusions: The prevalence of RLS due to PFO in patients with CAS was in line with the PFO prevalence in the general population, and patients with RLS are more symptomatic according to the SAQ summary score. Whether PFO closure could be beneficial to patients with CAS and concomitant migraine requires further investigation. Full article

Background/Objectives: The diagnosis of coronary artery spasm (CAS) frequently requires invasive provocation testing, typically utilising acetylcholine (ACh). Although the left coronary artery (LCA) is routinely assessed as a part of the testing protocol, assessment of the right coronary artery (RCA) is often avoided since it requires the insertion of a temporary pacing wire. We sought to compare the prevalence of inducible CAS in the LCA and RCA, among patients with CAS undergoing multivessel spasm provocation testing with ACh. Methods: A local multi-institutional ANOCA (angina and non-obstructive coronary arteries) database was analysed, which included 316 patients with angina and suspected CAS who underwent provocation testing (single vessel n = 266, multivessel n = 50) with incremental bolus doses of intracoronary ACh (25, 50, 100 μg in the LCA; 25, 50 μg in the RCA). CAS was defined as >90% constriction of the epicardial coronary artery as assessed visually on coronary angiography. Results: In the 50 patients (55 ± 10 years, 77% female) who underwent multivessel spasm provocation testing, CAS was induced in 20 patients (40%), with ACh provoking CAS only in the LCA system in 45%, only in the RCA system in 35%, and both LCA/RCA in 20%. Conclusions: These findings demonstrate that assessing only the LCA may miss up to one-third of CAS cases. Therefore, it is essential to routinely evaluate the RCA, particularly when no inducible spasm is detected in the LCA. Full article

Coronary artery disease is one of the leading public health problems in the world in terms of mortality and economic burden from the disease. Traditionally, the focus of research and clinical pathways leading to the diagnosis and treatment of coronary artery disease was on the more common variant of the disease resulting from atherosclerosis in the epicardial coronary arteries. However, coronary microvasculature, representing the vast majority of the total heart circulation, has the greatest influence on overall coronary resistance and, therefore, blood flow. Coronary microvascular dysfunction (CMD), characterized by structural or functional abnormalities in the microvasculature, significantly impacts myocardial perfusion. Endothelial dysfunction results in inadequate coronary dilation during exercise or spontaneous spasm in the microvasculature or epicardial arteries. A significant proportion of people presenting for coronary angiography in the context of angina have unobstructed epicardial coronary arteries yet are falsely reassured about the benign nature of their condition. Meanwhile, increasing evidence indicates that patients diagnosed with CMD as well as vasospastic angina (VSA) face an increased risk of Major Adverse Cardiovascular Events (MACEs), including death. The aim of this review is to outline the current practice with regard to invasive and non-invasive methods of CMD and VSA diagnosis and assess the evidence supporting the existing treatment strategies. These include endotype-specific pharmacological therapies, a holistic approach to lifestyle modifications and risk factor management and novel non-pharmacological therapies. Furthermore, the review highlights critical gaps in research and suggests potential areas for future investigation, to improve understanding and management of these conditions. Full article

Gender medicine has increasingly underscored the necessity of addressing sex-based differences in disease prevalence and management, particularly within cardiovascular conditions and drug intolerance. Women often present cardiovascular diseases distinctively from men, with a higher prevalence of non-obstructive coronary artery disease and varied ischemic manifestations, such as coronary microvascular dysfunction and epicardial or microvascular coronary spasm. This disparity is further exacerbated by elevated drug intolerance rates among women, influenced by hormonal, genetic, and psychosocial factors. The 2024 ESC guidelines for managing chronic coronary syndromes stress the need for personalized approaches to treat angina and ischemia with non-obstructive coronary artery disease (ANOCA/INOCA), recommending a combination of antianginal medications. Despite standard treatments, up to 40% of ANOCA/INOCA patients experience refractory angina, necessitating a multifaceted approach that often involves multiple antianginal drugs, which can increase the likelihood of drug intolerances. Future research should focus on including women in drug studies and addressing sex-specific differences, while healthcare providers must be equipped to manage gender-specific drug intolerances. Enhanced awareness, individualized treatment strategies, and gender-sensitive healthcare policies are crucial for improving outcomes and bridging the gender gap in cardiovascular medicine. Full article

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a clinical entity characterized by the absence of significant coronary artery obstruction in epicardial arteries (<50%) on coronary angiography in the setting of acute myocardial infarction (AMI). This article aims to provide a narrative review of the pathophysiological mechanisms, diagnostic challenges, and prognosis associated with MINOCA based on pathophysiology regarding the atherosclerotic and non-atherosclerotic causes. Etiological factors, including thromboembolism, coronary artery spasm, spontaneous coronary artery dissection, coronary microvascular disease, and supply–demand mismatch, are addressed. Imaging modalities such as echocardiography, advances in coronary angiography like intravascular ultrasound (IVUS) and optical coherence tomography (OCT), cardiac magnetic resonance (CMR), and coronary computed tomography angiography (CCTA) are also analyzed. MINOCA patients have a better short-term prognosis compared to those with obstructive coronary artery disease but face significant long-term risks, underscoring the need for precise diagnosis and management strategies. Elevated inflammatory markers and specific genetic predispositions are also associated with adverse outcomes in MINOCA. This review focused on MINOCA from a pathophysiological perspective on the diverse underlying mechanisms, the challenges in achieving accurate diagnosis, the importance of a tailored therapeutic approach and the necessity for further investigation of clinical outcomes. Full article

Transient left ventricular dysfunction (TLVD), a temporary condition marked by reversible impairment of ventricular function, remains an underdiagnosed yet significant contributor to morbidity and mortality in clinical practice. Unlike the well-explored atherosclerotic disease of the epicardial coronary arteries, the diverse etiologies of TLVD require greater attention for proper diagnosis and management. The spectrum of disorders associated with TLVD includes stress-induced cardiomyopathy, central nervous system injuries, histaminergic syndromes, various inflammatory diseases, pregnancy-related conditions, and genetically determined syndromes. Furthermore, myocardial infarction with non-obstructive coronary arteries (MINOCA) origins such as coronary artery spasm, coronary thromboembolism, and spontaneous coronary artery dissection (SCAD) may also manifest as TLVD, eventually showing recovery. This review highlights the range of ischemic and non-ischemic clinical situations that lead to TLVD, gathering conditions like Tako-Tsubo Syndrome (TTS), Kounis syndrome (KS), Myocarditis, Peripartum Cardiomyopathy (PPCM), and Tachycardia-induced cardiomyopathy (TIC). Differentiation amongst these causes is crucial, as they involve distinct clinical, instrumental, and genetic predictors that bode different outcomes and recovery potential for left ventricular function. The purpose of this review is to improve everyday clinical approaches to treating these diseases by providing an extensive survey of conditions linked with TLVD and the elements impacting prognosis and outcomes. Full article

Background: Intracoronary acetylcholine testing may induce epicardial coronary artery spasm (CAS) or coronary microvascular spasm (CMVS) in patients with angina syndromes but non-obstructive coronary artery disease, but their causal role in individual patients is not always clear. In this prospective, observational single-center study, we aimed to assess whether (1) the induction of myocardial ischemia/angina by electrocardiogram (ECG) exercise stress test (EST) differs between patients showing different results in response to acetylcholine testing (i.e., CAS, CMVS, or no spasm); (2) the preventive administration of short-acting nitrates has any different effects on the EST of those patients who showed a positive basal EST. We expected that if exercise-induced angina and/or ischemic ECG changes are related to CAS, they should improve after nitrates administration, whereas they should not significantly improve if they are caused by CMVS. Methods: We enrolled 81 patients with angina syndromes and non-obstructive coronary artery disease, who were divided into three groups according to acetylcholine testing: 40 patients with CAS (CAS-group), 14 with CMVS (CMVS-groups), and 27 with a negative test (NEG-group). All patients underwent a basal EST (B-EST). Patients with a positive B-EST repeated the test 24–48 h later, 5 min after the administration of short-acting nitrates (N-EST). Results: There were no significant differences among the groups in terms of the B-EST results. B-EST was positive in eight (20%) patients in the CAS-group, seven (50%) in the CMVS-group, and six (22%) in the NEG-group (p = 0.076). N-EST, performed in eight, six, and five of these patients, also showed similar results in the three groups. Furthermore, the N-EST results also did not significantly differ compared to B-EST in any group, remaining positive in seven (87.5%), four (66.7%), and four (80%) patients in the CAS-group, CMVS-group, and NEG-group, respectively (p = 0.78). Conclusions: Our data show that patients with angina and non-obstructive coronary artery disease show largely comparable results of the ECG exercise stress test and similar poor effects of short-acting nitrates on abnormal ECG exercise stress test results. On the whole, our findings suggest caution in attributing to the results of Ach testing a definite causal role for the clinical syndrome in individual patients. Full article

Takotsubo syndrome (TTS) is a clinical condition characterized by temporary regional wall motion anomalies and dysfunction that extend beyond a single epicardial vascular distribution. Various pathophysiological mechanisms, including inflammation, microvascular dysfunction, direct catecholamine toxicity, metabolic changes, sympathetic overdrive-mediated multi-vessel epicardial spasms, and transitory ischemia may cause the observed reversible myocardial stunning. Despite the fact that TTS usually has an acute coronary syndrome-like pattern of presentation, the absence of culprit atherosclerotic coronary artery disease is often reported at coronary angiography. However, the idea that coronary artery disease (CAD) and TTS conditions are mutually exclusive has been cast into doubt by numerous recent studies suggesting that CAD may coexist in many TTS patients, with significant clinical and prognostic repercussions. Whether the relationship between CAD and TTS is a mere coincidence or a bidirectional cause-and-effect is still up for debate, and misdiagnosis of the two disorders could lead to improper patient treatment with unfavourable outcomes. Therefore, this review seeks to provide a profound understanding of the relationship between CAD and TTS by analyzing potential common underlying pathways, addressing challenges in differential diagnosis, and discussing medical and procedural techniques to treat these conditions appropriately. Full article