Cause Of Angina Research Articles

Obscure Rare Cause of Recurrent Angina in Post CABG Patient: Coronary-Subclavian Steal Syndrome

Coronary subclavian steal syndrome (CSSS) is a rare and unrecognized complication of coronary bypass grafting surgery when a left internal mammary artery (LIMA) graft is utilized for left anterior descending (LAD) artery revascularization without knowing left subclavian artery status. We describe a case of a 67-year-old male, with a known history of triple vessel coronary artery disease (CAD) managed with CABGx3 in March 2003. The patient presented after 16 years with complaints of recurrent angina for the past 15 years which aggravates on exertion, especially of left hand. Recurrent hospitalizations and repeated Coronary angiograms (CAG) as well as CT Coronary angiography failed to diagnose the cause of angina. Subclavian angiography and subsequent methodical clinical examination during the present admission revealed left subclavian origin stenosis which was successfully revascularized by deployment of a stent resulting in convincing relief in the patient’s angina.

Coronary Sinus Reducer Improves Angina, Quality of Life, and CoronaryFlow Reserve in MicrovascularDysfunction.

Coronary microvascular dysfunction (CMD) is a common cause of angina with no obstructive coronary artery disease (ANOCA), and effective treatment options are limited. This study aims to assess the safety and efficacy of the coronary sinus (CS) Reducer (Neovasc, Inc/Shockwave Medical) for treatment of angina in patients with CMD. This Phase II trial enrolled 30 patients with ANOCA, invasively diagnosed CMD, and Canadian Cardiovascular Society (CCS) class 3 to 4 angina despite medical therapy. CMD was defined by coronary flow reserve (CFR)≤2.5 and/or≤50% increase in coronary blood flow (CBF) in response to intracoronary infusion of acetylcholine. Invasive coronary microvascular function testing was performed before and at 120days postimplantation. The primary endpoint was change in microvascular function at 120days. Secondary endpoints were changes in CCS angina class and Seattle Angina Questionnaire (SAQ) scores. Mean age was 54.8 ± 11.0 years; 67% (20/30) were women. In patients with low baseline CFR (endothelium-independent CMD), CFR increased significantly from 2.1 (1.95-2.30) to 2.7 (2.45-2.95) (n=19; P=0.0011). Patients with abnormal CBF response to acetylcholine at baseline (endothelium-dependent CMD) had an increase in CBF response to acetylcholine:-11.0% (-20.15% to 5.85%) to 11.5% (-4.82% to 39.29%) (n=11; P=0.042). There was a significant improvement in CCS angina class from 4.0 (3.25-4.0) to 2.0 (2.0-3.0) (P< 0.001) and increase in each domain of the SAQ questionnaire (P< 0.006 for all). This study demonstrates that the CS Reducer is associated with significant improvement in angina, quality of life, and coronary microvascular function in patients with CMD and may emerge as a novel therapy for patients with ANOCA.

Evaluation of coronary microvascular dysfunction and vasospasm in patients with angina and non-obstructive coronary artery disease

Abstract Background Angina in the absence of obstructive coronary artery disease (CAD) is a growing cause of morbidity and mortality, exceeding the economic burden of CAD. Roughly 50-70% of patients undergoing invasive angiography for anginal symptoms have non-obstructive CAD. Within this category, there are distinct sub-populations including patients with angina without evidence of ischemia on prior stress testing (ANOCA), evidence of ischemia on stress testing (INOCA), or history of obstructive CAD with prior revascularization (ANOCA-HxCAD). Coronary microvascular dysfunction (CMD) and/or epicardial vasospasm are common causes of angina in the absence of epicardial CAD despite optimal medical therapy. Differences between these groups, in terms of risk factors and diagnoses remain relatively unknown. Purpose To compare clinical characteristics, symptoms, and diagnoses between patients with ANOCA, INOCA, and ANOCA-HxCAD. Methods In a prospective registry-based cohort study of 306 patients without obstructive CAD (&amp;lt;50% stenosis in epicardial artery) undergoing coronary functional angiography (CFA), we assessed differences in clinical characteristics, symptoms, and CFA diagnoses: (1) endothelial-independent CMD (coronary flow reserve [CFR] &amp;lt;2.5) to adenosine testing, (2) endothelial-dependent CMD (coronary blood flow [CBF]&amp;lt;50% or no change in vessel diameter to 54 mcg intracoronary acetylcholine [ACH]), (3) epicardial vasospasm to 108 mcg intracoronary ACH in 3 groups of patients (ANOCA, INOCA, and ANOCA-HxCAD). Results Among the 306 patients undergoing CFA, 89% were female with a median age of 58 years (49, 67). Patients with ANOCA-HxCAD had a significantly higher prevalence of hypertension, diabetes, heart failure with preserved ejection fraction, and experienced worse dyspnea on exertion as measured by University of San Diego Shortness of Breath (UCSD SOB) in comparison to ANOCA or INOCA patients. However, there were no differences between the groups in terms of anginal severity, functional capacity, or quality of life. In terms of CFA diagnoses, vasospasm was more prevalent in ANOCA-HxCAD (p&amp;lt;0.001) and CMD was more prevalent in ANOCA and INOCA patients (p=0.034) (Table 1). Conclusions Despite differences in clinical characteristics, patients without obstructive CAD have similar anginal severity, functional capacity, and quality of life regardless of evidence of ischemia on prior stress imaging or history of revascularization. There are differences in CFA diagnoses with higher prevalence of CMD in ANOCA and INOCA patients and higher prevalence of vasospasm in ANOCA-HxCAD patients. Determining the underlying diagnoses changes clinical management; therefore, CFA should be considered in all patients without obstructive CAD.

Relationship between peripheral and intracoronary blood flow in patients with angina and nonobstructive coronary arteries.

Coronary vasomotor dysfunction, an important underlying cause of angina and nonobstructive coronary arteries (ANOCA), encompassing coronary vasospasm, coronary endothelial dysfunction, and/or coronary microvascular dysfunction, is clinically assessed by invasive coronary function testing (ICFT). As ICFT imposes a high burden on patients and carries risks, developing noninvasive alternatives is important. We evaluated whether coronary vasomotor dysfunction is a component of systemic microvascular endothelial and smooth muscle dysfunction and can be detected using laser speckle contrast analysis (LASCA). Forty-three consecutive patients with ANOCA underwent ICFT, with intracoronary acetylcholine, adenosine, and flow measurements, to assess coronary vasomotor dysfunction. Cutaneous microvascular function was assessed using LASCA in the forearm, combined with vasodilators acetylcholine, sodium nitroprusside, and insulin and using EndoPAT, by measuring the reactive hyperemia index (RHI). Of the 43 included patients with ANOCA (79% women, 59 ± 9 yr old), 38 patients had coronary vasomotor dysfunction, including 28 with coronary vasospasm, 26 with coronary endothelial dysfunction, and 18 with coronary microvascular dysfunction, with overlapping endotypes. Patients with and without coronary vasomotor dysfunction had similar peripheral flow responses to acetylcholine, insulin, and RHI. In contrast, coronary vasomotor dysfunction was associated with lower peripheral flow responses to sodium nitroprusside (P < 0.001). An absolute flow response to sodium nitroprusside of 83.95 APU resulted in 86.1% sensitivity and 80.0% specificity for coronary vasomotor dysfunction (area under the ROC curve, 0.883; P = 0.006). In conclusion, this study provides evidence of systemic vascular smooth muscle dysfunction in patients with ANOCA with coronary vasomotor dysfunction and the diagnostic value of peripheral microvascular function testing as a noninvasive tool for detecting coronary vasomotor dysfunction.NEW & NOTEWORTHY This study provides proof of concept that assessment of the peripheral vasculature, particularly vascular smooth muscle cells measured using the LASCA technology holds potential as a noninvasive tool for detecting coronary vasomotor dysfunction. This finding highlights the potential of the LASCA technology in, for example, medication studies for coronary vasomotor dysfunction, especially when investigating whether medication improves vascular function, as repeated peripheral measurements are less invasive than invasive coronary function testing, the current gold standard.

Myocardial ischaemic syndromes: a new nomenclature to harmonize evolving international clinical practice guidelines.

Since the 1960s, cardiologists have adopted several binary classification systems for acute myocardial infarction (MI) that facilitated improved patient management. Conversely, for chronic stable manifestations of myocardial ischaemia, various classifications have emerged over time, often with conflicting terminology-e.g. 'stable coronary artery disease' (CAD), 'stable ischaemic heart disease', and 'chronic coronary syndromes' (CCS). While the 2019 European guidelines introduced CCS to impart symmetry with 'acute coronary syndromes' (ACS), the 2023 American guidelines endorsed the alternative term 'chronic coronary disease'. An unintended consequence of these competing classifications is perpetuation of the restrictive terms 'coronary' and 'disease', often connoting only a singular obstructive CAD mechanism. It is now important to advance a more broadly inclusive terminology for both obstructive and non-obstructive causes of angina and myocardial ischaemia that fosters conceptual clarity and unifies dyssynchronous nomenclatures across guidelines. We, therefore, propose a new binary classification of 'acute myocardial ischaemic syndromes' and 'non-acute myocardial ischaemic syndromes', which comprises both obstructive epicardial and non-obstructive pathogenetic mechanisms, including microvascular dysfunction, vasospastic disorders, and non-coronary causes. We herein retain accepted categories of ACS, ST-segment elevation MI, and non-ST-segment elevation MI, as important subsets for which revascularization is of proven clinical benefit, as well as new terms like ischaemia and MI with non-obstructive coronary arteries. Overall, such a more encompassing nomenclature better aligns, unifies, and harmonizes different pathophysiologic causes of myocardial ischaemia and should result in more refined diagnostic and therapeutic approaches targeted to the multiple pathobiological precipitants of angina pectoris, ischaemia and infarction.

Myocardial Ischemic Syndromes: A New Nomenclature to Harmonize Evolving International Clinical Practice Guidelines.

Since the 1960s, cardiologists have adopted several binary classification systems for acute myocardial infarction (MI) that facilitated improved patient management. Conversely, for chronic stable manifestations of myocardial ischemia, various classifications have emerged over time, often with conflicting terminology-eg, "stable coronary artery disease" (CAD), "stable ischemic heart disease," and "chronic coronary syndromes" (CCS). While the 2019 European guidelines introduced CCS to impart symmetry with "acute coronary syndromes" (ACS), the 2023 American guidelines endorsed the alternative term "chronic coronary disease." An unintended consequence of these competing classifications is perpetuation of the restrictive terms "coronary" and 'disease', often connoting only a singular obstructive CAD mechanism. It is now important to advance a more broadly inclusive terminology for both obstructive and non-obstructive causes of angina and myocardial ischemia that fosters conceptual clarity and unifies dyssynchronous nomenclatures across guidelines. We, therefore, propose a new binary classification of "acute myocardial ischemic syndromes" and "non-acute myocardial ischemic syndromes," which comprises both obstructive epicardial and non-obstructive pathogenetic mechanisms, including microvascular dysfunction, vasospastic disorders, and non-coronary causes. We herein retain accepted categories of ACS, ST-segment elevation MI, and non-ST segment elevation MI, as important subsets for which revascularization is of proven clinical benefit, as well as new terms like ischemia and MI with non-obstructive coronary arteries. Overall, such a more encompassing nomenclature better aligns, unifies, and harmonizes different pathophysiologic causes of myocardial ischemia and should result in more refined diagnostic and therapeutic approaches targeted to the multiple pathobiological precipitants of angina pectoris, ischemia, and infarction.

Female mice with menopause exhibit coronary microvascular disease

Menopause is a natural process as women age, and women with menopause are at higher risk of having cardiovascular diseases than men at the same age. Coronary microvascular disease (CMD) is one of the causes of angina, and the prevalence of CMD is higher in women than in men, and more postmenopausal women have CMD than premenopausal women. However, the causes of CMD in postmenopausal women are not clear. In this study, we investigate whether and how menopause leads to coronary microvascular disease in female mice. Menopausal mice were generated by administering a 20-day injection of 4-Vinylcyclohexene diepoxide (VCD, 160 mg/kg/day in sesame oil, i.p.). VCD gradually destroys primordial and primary follicles in ovaries and leads to ovary failure while keeping the ovary tissues intact; this model is close to the natural progression of human menopause. The vehicle, sesame oil, was administered in control mice. Coronary flow velocity reserve (CFVR) was measured to assess coronary microvascular function. Isometric tension was conducted in third-order coronary arteries (CAs). Capillary density was measured and compared in the left ventricle. Experiments were performed at 6 weeks (perimenopause period) and 8 weeks (post-menopause period) after the injection of VCD or vehicle in female mice. There was no significant difference in CFVR between VCD-injected mice and vehicle-injected mice 6 weeks after the injection. However, at 8 weeks after the injection, VCD-injected mice exhibited a significant decline in CFVR compared to the control mice. Coronary microvascular dysfunction can be driven by attenuated vascular relaxation in small coronary arteries and/or capillary rarefaction. We first conducted isometric tension and found that endothelium-dependent relaxation was significantly attenuated in VCD-injected mice at 8 weeks after the injection, but not at 6 weeks, compared to the controls. There was no significant difference in EC-independent relaxation between the two groups at any age. Interestingly, there was no significant difference in capillary density between VCD-injected mice and vehicle-injected mice at 6 weeks and 8 weeks after the injection. Postmenopausal mice, but not perimenopausal mice, develop CMD due to attenuated endothelium-dependent relaxation. This suggests that improving endothelium-dependent relaxation is the potential mechanism to treat CMD in postmenopausal women. Supported by NIH R01HL142214 and DOD W81XWH2110472. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Left ventricular hypertrophy: hypertensive or hypertrophic cardiomyopathy? What a dilemma! A case report.

In the presence of the left ventricle hypertrophy (LVH), the differential diagnosis with hypertrophic cardiomyopathy (HCM) or some phenocopy must be always considered, which can be easily suspected when the hypertrophy is markedly asymmetric. However, when the hypertrophy is homogeneous, especially if the patient has concomitant hypertension, it may be a challenge to distinguish between hypertensive and HCM, although some clinical features may help us to suspect it. In addition, patients with HCM may present with exertional angina due to microcirculation involvement in the setting of the hypertrophy itself or dynamic obstruction in the left ventricular outflow tract, but in some cases, the presence of concomitant coronary artery disease must be suspected as the cause of angina, especially if the patient has an intermediate or high-risk probability of having ischemic heart disease. We present the case of a 46-year-old Afro-American man with poorly controlled hypertension who was found to have severe LVH, and who presented with symptoms of exertional angina during follow-up. We will review the clinical features that can help us in the differential diagnosis in this context.

Comparison of the Diagnostic Yield of Intracoronary Acetylcholine Infusion and Acetylcholine Bolus Injection Protocols During Invasive Coronary Function Testing

Coronary endothelial dysfunction (CED) and coronary artery spasm (CAS) are causes of angina in patients with no obstructive coronary arteries (ANOCA). Both can be diagnosed by invasive coronary function testing (ICFT) using Acetylcholine (ACh). This study aimed to evaluate the diagnostic yield of a 3-minute ACh infusion as compared to a 1-minute ACh bolus injection protocol in testing CED and CAS. In total 220 consecutive ANOCA patients underwent ICFT using continuous Doppler flow measurements. Per protocol, 110 patients were tested using 3-minute infusion and thereafter 110 patients using 1-minute bolus injections, due to a protocol change. CED was defined as a <50% increase in coronary blood flow or any epicardial vasoconstriction in reaction to low dose ACh and CAS according to the COVADIS criteria, both with and without T-wave abnormalities, in reaction to high dose ACh. The prevalence of CED was equal in both protocols (78% vs 79%; p=0.869). Regarding the endotypes of CAS according to COVADIS, the equivocal endotype was diagnosed less often in the 3-minutes vs 1-minute protocol (24% vs 44%; p=0.004). Including T-wave abnormalities to the COVADIS criteria resulted in a similar diagnostic yield of both protocols. Hemodynamic changes from baseline to the low or high ACh doses were comparable between the protocols for each endotype. In conclusion, ICFT using 3-minute infusion or 1-minute bolus injections of ACh showed a similar diagnostic yield of CED. When using the COVADIS criteria, a difference in the equivocal diagnosis was observed. Including T-wave abnormalities as diagnostic criterion reclassified equivocal test results into CAS and decreased this difference. For clinical practice, we recommend the inclusion of T-wave abnormalities as diagnostic criterion for CAS and the 1-minute bolus protocol for practicality.

Inhibition of valve mesenchymal stromal cell calcium deposition by bFGF through alternative polyadenylation regulation of the CAT gene

ObjectiveCalcific aortic valve disease (CAVD) is the leading cause of angina, heart failure, and death from aortic stenosis. However, the molecular mechanisms of its progression, especially the complex disease-related transcriptional regulatory mechanisms, remain to be further elucidated.MethodsThis study used porcine valvular interstitial cells (PVIC) as a model. We used osteogenic induced medium (OIM) to induce calcium deposition in PVICs to calcify them, followed by basic fibroblast growth factor (bFGF) treatment to inhibit calcium deposition. Transcriptome sequencing was used to study the mRNA expression profile of PVICs and its related transcriptional regulation. We used DaPars to further examine alternative polyadenylation (APA) between different treatment groups.ResultsWe successfully induced calcium deposition of PVICs through OIM. Subsequently, mRNA-seq was used to identify differentially expressed mRNAs for three different treatments: control, OIM-induced and OIM-induced bFGF treatment. Global APA events were identified in the OIM and bFGF treatment groups by bioinformatics analysis. Finally, it was discovered and proven that catalase (CAT) is one of the potential targets of bFGF-induced APA regulation.ConclusionWe described a global APA change in a calcium deposition model related to CAVD. We revealed that transcriptional regulation of the CAT gene may contribute to bFGF-induced calcium deposition inhibition.

Fistulous communication between the left main coronary artery and the pulmonary artery as a cause of angina.

Fistulous communication between the left main coronary artery and the pulmonary artery as a cause of angina.

Invasive coronary function testing in patients with INOCA - a single center experience

Abstract Background Coronary vasomotion disorders (CVDs) represent a frequent cause of angina in patients with ischemia with non-obstructed coronary arteries (INOCA). Invasive coronary angiography (ICA) often fails to identify patients with vasospastic angina and/or microvascular dysfunction. Purpose Our aim was to describe and characterize CVDs in INOCA patients, using a multi-parametric, invasive, coronary function testing protocol. Methods Patients with INOCA that underwent our protocol for coronary function testing (CFT), between July 2021 and October 2022 were included in this single-center prospective study. The protocol consisted of an invasive assessment of coronary circulation vasorelaxation at rest and during hyperemia, as well as the propensity for coronary vasospasm using increasing doses of intra-coronary acetylcholine. Fractional flow reserve, coronary flow reserve (CFR), and index of microvascular resistance (IMR) were recorded. CVDs were diagnosed based on the criteria proposed by the Coronary Vasomotor Disorders International Study Group. Results A total of 56 patients were included, mean age was 64±12 years and 57.1% were female. At baseline, all patients had either typical angina (82.1%, n=46) or a positive ischemia test (67.9%, n=38). Twenty patients (35.7%) had a history of a previous ICA or computed tomography due to anginal symptoms, while only 8.9% of patients had known structural ischemic heart disease and were subjected to percutaneous coronary intervention. Our CFT protocol was completed in all patients without any serious complications. Isolated epicardial vasospasm was found in 16 (28.6%) patients, isolated coronary microvascular dysfunction (CMD) in 9 (16.1%), and a combination of CMD and coronary vasospasm in 9 (16.1%). Only 1 patient (1.8%) had isolated microvascular spasm. We were able to further identify two distinct endotypes of CMD, using a combined assessment of CFR and IMR, termed structural and functional CMD: Functional CMD - 7 patients (12.5%) had CFR &amp;lt; 2.0 and IMR &amp;lt; 25; Structural CMD - 6 patients (10.7%) had CFR &amp;lt; 2.0 and IMR &amp;gt; 25. Conclusion Coronary vasomotion disorders are a common cause of INOCA. A CFT protocol is safe, can be used in clinical practice, and can provide a definite diagnosis for the underlying cause of angina.

Abstract 15772: From Agony to Relief: Overcoming Angina Through Endovascular Coiling of the Left Internal Mammary Artery (LIMA) to Pulmonary Artery (PA) Fistulae- A Case Report

Introduction: LIMA to PA fistulae are a rare complication after coronary artery bypass graft (CABG) surgery. We present a patient with angina secondary to a steal syndrome from LIMA-PA fistulae, treated with endovascular coiling. Case: The patient is a 49-year-old active male with coronary artery disease, status post CABG at age 46 with a LIMA graft to the left anterior descending artery, radial artery graft to the first obtuse marginal artery, and saphenous venous graft (SVG) to the posterior descending artery. At age 48, he developed angina and underwent stent placement to the distal right coronary artery after the SVG was found to be occluded. Several months later, he reported dyspnea and chest pain on exertion. An exercise nuclear stress test showed abnormal myocardial perfusion in the anteroseptal region, and he was referred for left heart catheterization (LHC). LHC revealed unchanged native coronary disease, patent LIMA, and a network of collateral vessels from the LIMA feeding into the pulmonary vasculature (Figure 1). The collaterals were not seen on LHC 9 months prior. CT coronary angiography confirmed multiple fistulae originating from the superior aspect of the LIMA graft communicating with the PA (Figure 1). After a multidisciplinary, patient-centered, heart team discussion, he underwent successful endovascular coiling of the collateral branches (Figure 2). Discussion: LIMA-PA fistulae is a rare cause of angina and there is a paucity of literature on management. To our knowledge, coil embolization has been described in roughly 10 cases. Here, we present a successful case of endovascular coiling of collateral vessels leading to symptomatic improvement.

Identification of Genetic Variants Associated with Severe Myocardial Bridging through Whole-Exome Sequencing.

Myocardial bridging (MB) is a congenital coronary artery anomaly and an important cause of angina. The genetic basis of MB is currently unknown. This study used a whole-exome sequencing technique and analyzed genotypic differences. Eight coronary angiography-confirmed cases of severe MB and eight age- and sex-matched control patients were investigated. In total, 139 rare variants that are potentially pathogenic for severe MB were identified in 132 genes. Genes with multiple rare variants or co-predicted by ClinVar and CADD/REVEL for severe MB were collected, from which heart-specific genes were selected under the guidance of tissue expression levels. Functional annotation indicated significant genetic associations with abnormal skeletal muscle mass, cardiomyopathies, and transmembrane ion channels. Candidate genes were reviewed regarding the functions and locations of each individual gene product. Among the gene candidates for severe MB, rare variants in DMD, SGCA, and TTN were determined to be the most crucial. The results suggest that altered anchoring proteins on the cell membrane and intracellular sarcomere unit of cardiomyocytes play a role in the development of the missed trajectory of coronary vessels. Additional studies are required to support the diagnostic application of cardiac sarcoglycan and dystroglycan complexes in patients with severe MB.

Meta-analysis and systematic review of coronary vasospasm in ANOCA patients: Prevalence, clinical features and prognosis.

Coronary artery spasm (CAS), encompassing epicardial and microvascular spasm, is increasingly recognized as cause of angina in patients with non-obstructive coronary artery disease (ANOCA). However, various spasm provocation testing protocols and diagnostic criteria are used, making diagnosis and characterization of these patients difficult and interpretation of study results cumbersome. This review provides a structured overview of the prevalence, characterization and prognosis of CAS worldwide in men and women. A systematic review identifying studies describing ANOCA patients with CAS was performed. Multiple outcomes (prevalence, clinical features, and prognosis) were assessed. Data, except for prognosis were pooled and analysed using random effects meta-analysis models. Twenty-five publications (N = 14.554) were included (58.2 years; 44.2% women). Percentages of epicardial constriction to define epicardial spasm ranged from >50% to >90%. Epicardial spasm was prevalent in 43% (range 16-73%), with a higher prevalence in Asian vs. Western World population (52% vs. 33%, p = 0.014). Microvascular spasm was prevalent in 25% (range 7-39%). Men were more likely to have epicardial spasm (61%), women were more likely to have microvascular spasm (64%). Recurrent angina is frequently reported during follow-up ranging from 10 to 53%. CAS is highly prevalent in ANOCA patients, where men more often have epicardial spasm, women more often have microvascular spasm. A higher prevalence of epicardial spasm is demonstrated in the Asian population compared to the Western World. The prevalence of CAS is high, emphasizing the use of unambiguous study protocols and diagnostic criteria and highlights the importance of routine evaluation of CAS in men and women with ANOCA. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=272100.

Ischemia with Nonobstructive Coronary Artery Disease and Atrial Cardiomyopathy-Two Sides of the Same Story?

Ischemia with nonobstructive coronary artery disease (INOCA) is increasingly recognized as a significant cause of angina, myocardial remodeling, and eventually heart failure (HF). Coronary microvascular dysfunction (CMD) is a major endotype of INOCA, and it is caused by structural and functional alterations of the coronary microcirculation. At the same time, atrial cardiomyopathy (ACM) defined by structural, functional, and electrical atrial remodeling has a major clinical impact due to its manifestations: atrial fibrillation (AF), atrial thrombosis, stroke, and HF symptoms. Both these pathologies share similar risk factors and have a high comorbidity burden. CMD causing INOCA and ACM frequently coexist. Thus, questions arise whether there is a potential link between these pathologies. Does CMD promote AF or the reverse? Which are the mechanisms that ultimately lead to CMD and ACM? Are both part of a systemic disease characterized by endothelial dysfunction? Lastly, which are the therapeutic strategies that can target endothelial dysfunction and improve the prognosis of patients with CMD and ACM? This review aims to address these questions by analyzing the existing body of evidence, offering further insight into the mechanisms of CMD and ACM, and discussing potential therapeutic strategies.

How to deal with myocardial bridge and angina.

Coronary microvascular dysfunction is a highly prevalent cause of angina in the 'ischemia with nonobstructed coronary artery' (INOCA) patients. The presence of myocardial bridge could represent the direct cause of angina in this patient subset. In this case, full physiological assessment allowed complete evaluation of an INOCA patient with myocardial bridge, unmasking its un-obstructive physiology, the presence of microvascular dysfunction, and the presence of epicardial spasm. Full physiological evaluation will be of paramount importance in the future in INOCA patients in order to establish tailored medical treatment.

MULTIVESSEL CORONARY VASOSPASM WITH ABORTED SUDDEN DEATH AND REFRACTORY ANGINA: EFFICACY OF ALPHA-BLOCKERS AND INDICATION OF IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR

Vasospasm of the coronary arteries is an uncommon and underdiagnosed cause of angina pectoris. There is a myriad of clinical presentations with variable prognoses. The typical presentation in the scenario of chronic coronary syndrome includes angina at rest or with variable threshold, from late evening to early morning, including transient ischemia responsive to nitrates, detectable by 12-lead electrocardiogram or Holter. Concurrent multivessel vasospasm is rare and with worse prognosis, given the potential for acute ST-elevation myocardial infarction, ventricular arrhythmias and subsequent sudden cardiac death. The presence of refractory angina is a sign of persistent vasospasm, indicating severe manifestations. The complex physiopathology, including hypercontractility of the vascular smooth muscle, endothelial dysfunction and adrenergic receptor activation has not been fully elucidated, which makes it difficult to define a targeted therapy. We present a case of refractory angina after multivessel vasospasm with aborted sudden death, which responded to alpha-blocker and had implantable cardioverter-defibrillator implantation postponed.

The risk of acute coronary events in microvascular disease.

The microvascular disease represents a widespread clinical entity in the general population, especially among women. The dysfunction of the microcirculation is often responsible for myocardial ischaemia and angina in the absence of significant stenosis of the epicardial district, while in other cases it can represent a contributing cause of angina even in the presence of coronary artery disease, cardiomyopathies or heart failure. The cardiovascular risk factors of people with microvascular disease are similar to those who develop epicardial atherosclerotic disease. However, the prognostic significance of microvascular disease remains a matter of debate. An element to be clarified, in fact, is whether subjects with dysfunction of the microcirculation and coronary tree without significant stenoses present an increased risk of myocardial infarction and sudden death. In recent years, several studies seem to confirm an association between microvascular disease and progression of coronary epicardial atherosclerosis. The prognosis of microvascular disease would therefore not be benign as was previously believed, but associated with an increased risk of cardiovascular events including revascularization, heart attack, and cardiac death.

Myocardial bridge evaluation towards personalized medicine: study design and preliminary results of the RIALTO registry.

Myocardial bridge (MB) is the most frequent inborn coronary artery variant in which a portion of the myocardium overlies an epicardial coronary artery segment. Although MB has long been considered a benign entity, a growing body of evidence has suggested its association with angina and adverse cardiac events. However, to date, no data on long-term prognosis are available, nor on therapies improving cardiovascular outcomes. We are currently conducting an ambispective, observational, multicentre, study in which we enrol patients with a clinical indication to undergo coronary angiography (CA) and evidence of MB, aiming to describe the incidence of symptoms and cardiovascular events at baseline and at long-term follow-up (FUP). The role of invasive full-physiology assessment in modifying the discharge therapy and eventually the perceived quality of life and the incidence of major cardiovascular events will be analysed. Basal clinical-instrumental data of eligible and consenting patients have been acquired after CA; FUP was performed 6, 12, and 24 months after the angiographic diagnosis of MB. The primary endpoint of the study is the incidence of major adverse cardiovascular events (MACE), defined as the composite of cardiac death, myocardial infarction, cardiac hospitalization, and target vessel revascularization; the secondary endpoints are the rate of patients with Seattle Angina Questionnaire (SAQ) summary score <70 and the incidence of MACE in patients undergoing invasive intracoronary assessment. Among patients undergone FUP visits, we recorded 31 MACE at 6 months (11.6%), 16 MACE at 12 months (6.5%), and 26 MACE at 24 months (13.5%). The rate of patients with SAQ <70 is 18.8% at 6 months, 20.6% at 12 months, and 21.8% at 24 months. To evaluate the prognostic role of invasive intracoronary assessment, we compared MB patients who underwent only angiographic evaluation (Angio group) to those who underwent acetylcholine (ACH) provocative test with indication to calcium-channel blockers (CCBs) at discharge (Angio + ACH + CCBs group) and those who underwent functional assessment with fractional flow reserve (FFR) with indication to beta-blockers (BBs) at discharge (Angio + FFR + BBs group). After 2 years of FUP, the rate of MACE was significantly reduced in both Angio + ACH + CCBs group (6 vs. 25%, P = 0.029) and Angio + FFR + BBs group (3 vs. 25%, P = 0.005) compared with Angio group. The preliminary results of our study showed that MB may be a cause of angina and adverse cardiac events in patients referred to CA for suspected coronary artery disease (CAD). Full-physiology assessment unmasking MB-related ischaemia mechanisms, allowed to guide the treatment, personalizing the clinical management, improving the quality of life, and cardiovascular outcomes in patients with MB.