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.

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 energy balance and metabolism as causes of myocardial ischemia.

The current approach to myocardial ischemia has been influenced by the misconception of a close link between ischemia and coronary atherosclerotic obstructions. Recent guidelines have, however, acknowledged the multifactorial nature of this condition, with an identifiable cause present in less than half of angina patients, and a large fraction with angina of unknown origin. Because of this background, focusing on cardiac energy metabolim offers new opportunities to manage myocardial ischemia even when its cause is unknown.

Sex Differences in Quality of Life in Patients with Ischemia with No Obstructive Coronary Artery Disease (INOCA): A Patient Self-Report Retrospective Survey from INOCA International.

Women with obstructive coronary artery disease (CAD) have a relatively lower quality of life (QoL) compared to men, but our understanding of sex differences in QoL in ischemia with no obstructive coronary artery disease (INOCA) is limited. We conducted a survey of patient members of INOCA International with an assessment of self-reported health measures. Functional capacity was retrospectively estimated using the Duke Activity Status Index (DASI), assessing levels of activities performed before and after INOCA symptom onset. Of the 1579 patient members, the overall survey completion rate was 21%. Women represented 91% of the respondents. Estimated functional capacity, expressed as metabolic equivalents (METs), was higher before compared to after INOCA diagnosis comparably for both women and men. For every one MET decline in functional capacity, there was a significantly greater decline in QoL for men compared with women in physical health (4.0 ± 1.1 vs. 2.9 ± 0.3 days/month, p < 0.001), mental health (2.4 ± 1.2 vs. 1.8 ± 0.3 days/month, p = 0.001), and social health/recreational activities (4.1 ± 1.0 vs. 2.9 ± 0.3 days/month, p = 0.0001), respectively. In an international survey of patients living with INOCA, despite similar diagnoses, clinical comorbidities, and symptoms, INOCA-related functional capacity declines are associated with a greater adverse impact on QoL in men compared to women.

HIV-Related Atherosclerosis: State-of-the-Art-Review.

The infection caused by the Human Immunodeficiency Virus (HIV) has spread rapidly across the globe, assuming the characteristics of an epidemic in some regions. Thanks to the introduction of antiretroviral therapy into routine clinical practice, there was a considerable breakthrough in the treatment of HIV, that is now HIV is potentially well-controlled even in low-income countries. To date, HIV infection has moved from the group of life-threatening conditions to the group of chronic and well controlled ones and the quality of life and life expectancy of HIV+ people, with an undetectable viral load is closer to that of an HIV- people. However, unsolved issues still persist. For example: people living with HIV are more prone to the age-related diseases, especially atherosclerosis. For this reason, a better understanding of the mechanisms of HIV-associated destabilization of vascular homeostasis seems to be an urgent duty, that may lead to the development of new protocols, bringing the possibilities of pathogenetic therapies to a new level. The purpose of the article was to evaluate the pathological aspects of HIV-induced atherosclerosis.

Evolving Management Paradigm for Stable Ischemic Heart Disease Patients: JACC Review Topic of the Week.

Management of stable coronary artery disease (CAD) has been based on the assumption that flow-limiting atherosclerotic obstructions are the proximate cause of angina and myocardial ischemia in most patients and represent an important target for revascularization. However, the role of revascularization in reducing long-term cardiac events in these patients has been limited mainly to those with left main disease, 3-vessel disease with diabetes, or decreased ejection fraction. Mounting evidence indicates that nonepicardial coronary causes of angina and ischemia, including coronary microvascular dysfunction, vasospastic disorders, and derangements of myocardial metabolism, are more prevalent than flow-limiting stenoses, raising concerns that many important causes other than epicardial CAD are neither considered nor probed diagnostically. There is a need for a more inclusive management paradigm that uncouples the singular association between epicardial CAD and revascularization and better aligns diagnostic approaches that tailor treatment to the underlying mechanisms and precipitants of angina and ischemia in contemporary clinical practice.

Ischemia with no obstructive coronary artery disease (INOCA): A patient self-report quality of life survey from INOCA international.

BACKGROUND: There is limited information available regarding evidence of ischemia with no obstructive coronary arteries (INOCA) and quality of life. PURPOSE: To determine associations between INOCA and self-reported physical, social, and mental health. METHODS: We conducted a survey of all members (n = 1579) of the INOCA International patient support group. Current self-reported diagnosis and health measures were collected. Functional capacity was retrospectively estimated using the Duke Activity Status Index (DASI), assessing levels of activities performed prior and after symptom onset. RESULTS: A total of 297 (20.8% response rate, 91% women) reported symptoms of chest pain, pressure, or discomfort in 92.9%. Overall, 34.4% were living with symptoms for ≥3 years before an INOCA diagnosis, and 77.8% were told their symptoms were not cardiac. Estimated functional capacity was higher prior to compared to after symptom onset (8.6 ± 1.8 METs vs 5.6 ± 1.8 METs; P < 0.0001). Most respondents reported an adverse impact of symptoms on their home life (80.5%), social life (80.1%), mental health (70.4%), outlook on life (69.7%), sex life (55.9%), and their partner/spouse relationship (53.9%), while approximately three-quarters reduced their work hours or stopped work completely, 47.5% retired early, and 38.4% applied for disability. CONCLUSIONS: INOCA symptoms are associated with adverse physical, mental and social health quality of life. Increased patient awareness, physician recognition and diagnosis, and clinical trials are needed to develop evidence-based guidelines for this increasingly recognized cardiovascular disorder.

Perspectives in noninvasive imaging for chronic coronary syndromes.

Both the latest European guidelines on chronic coronary syndromes and the American guidelines on chest pain have underlined the importance of noninvasive imaging to select patients to be referred to invasive angiography. Nevertheless, although coronary stenosis has long been considered the main determinant of inducible ischemia and symptoms, growing evidence has demonstrated the importance of other underlying mechanisms (e.g., vasospasm, microvascular disease, energetic inefficiency). The search for a pathophysiology-driven treatment of these patients has therefore emerged as an important objective of multimodality imaging, integrating "anatomical" and "functional" information. We here provide an up-to-date guide for the choice and the interpretation of the currently available noninvasive anatomical and/or functional tests, focusing on emerging techniques (e.g., coronary flow velocity reserve, stress-cardiac magnetic resonance, hybrid imaging, functional-coronary computed tomography angiography, etc.), which could provide deeper pathophysiological insights to refine diagnostic and therapeutic pathways in the next future.

Clinical outcomes of newly diagnosed, stable angina patients managed according to current guidelines. The ARCA (Arca Registry for Chronic Angina) Registry: A prospective, observational, nationwide study.

BACKGROUND: Clinical outcomes of stable angina patients treated according to guidelines recommendations (medical therapy first, selective revascularization in high risk or unresponsive patients) are not fully known. METHODS AND RESULTS: Eight hundred thirty-three patients with newly diagnosed, stable angina were enrolled in a prospective, observational, nationwide registry and followed for 1 year. Symptoms and quality of life were evaluated with the CCS angina grading, with a self-assessment scale and with the SAQ-7. A composite end-point of MACEs (all-cause death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for unstable angina) at 1 year was considered. Upon enrollment, all patients were prescribed guidelines directed medical therapy. After one month of therapy, angina relieved or improved in 47% of the overall population. Patients in CCS class I significantly increased from 28.4% at enrollment to 67.1% at 12 months, and the SAQ-7 score from 58.4 ± 20 to 85.9 ± 14. The rate of MACEs was low (2.9%) in the overall population. After one month of medical therapy, 40.6% of patients were referred for coronary angiography and revascularization for resistant symptoms (invasive strategy). Among these, 38.2% had normal coronary arteries and 47% actually underwent revascularization. No difference between invasive and medical groups was found at 12 months in symptoms, quality of life and MACEs, except for a greater improvement in self-assessed symptoms in the invasive group. Combined medical and invasive strategies left 28.5% of patients still symptomatic at the end of the study. CONCLUSIONS: The study confirms the efficacy and safety of a tailored approach to stable angina, as recommended by guidelines, with medical therapy first followed by selective revascularization when needed.

What Is the Role of Assessing Ischemia to Optimize Therapy and Outcomes for Patients with Stable Angina and Non-obstructed Coronary Arteries?

Ischemic heart disease (IHD) is a leading global cause of ill-health and premature death. Clinical research into IHD is providing new insights into the pathophysiology, epidemiology and treatment of this condition. The major endotypes of IHD include coronary heart disease (CHD) and vasomotor disorders, including microvascular angina and vasospastic angina. Considering unselected patients presenting with stable chest pain, the pre-test probability of CHD is higher in men whereas the pre-test probability of a vasomotor disorder is higher in women. The diagnostic accuracy of diagnostic tests designed to assess coronary anatomy and disease and/or coronary vascular function (functional tests) differ for coronary endotypes. Clinical management should therefore be personalized and take account of sex-related factors. In this review, we consider the definitions of angina and myocardial ischemia. We then appraise the mechanistic links between myocardial ischemia and anginal symptoms and the relative merits of non-invasive and invasive diagnostic tests and related clinical management. Finally, we describe the rationale and importance of stratified medicine of IHD.

Why the Term MINOCA Does Not Provide Conceptual Clarity for Actionable Decision-Making in Patients with Myocardial Infarction with No Obstructive Coronary Artery Disease.

When acute myocardial injury is found in a clinical setting suggestive of myocardial ischemia, the event is labeled as acute myocardial infarction (MI), and the absence of ≥50% coronary stenosis at angiography or greater leads to the working diagnosis of myocardial infarction with non-obstructed coronary arteries (MINOCA). Determining the mechanism of MINOCA and excluding other possible causes for cardiac troponin elevation has notable implications for tailoring secondary prevention measures aimed at improving the overall prognosis of acute MI. The aim of this review is to increase the awareness that establishing the underlying cause of a MINOCA is possible in the vast majority of cases, and that the proper classification of any MI should be pursued. The initial diagnosis of MINOCA can be confirmed or ruled out based on the results of subsequent investigations. Indeed, a comprehensive clinical evaluation at the time of presentation, followed by a dedicated diagnostic work-up, might lead to the identification of the pathophysiologic abnormality leading to MI in almost all cases initially labeled as MINOCA. When a specific cause of acute MI is identified, cardiologists are urged to transition from the "all-inclusive" term "MINOCA" to the proper classification of any MI, as evidence now exists that MINOCA does not provide conceptual clarity for actionable decision-making in MI with angiographically normal coronary arteries.

Salivary lactate and 8-isoprostaglandin F2α as potential non-invasive biomarkers for monitoring heart failure: a pilot study.

Heart failure (HF) is a cardiovascular disease affecting about 26 million people worldwide costing about $100 billons per year. HF activates several compensatory mechanisms and neurohormonal systems, so we hypothesized that the concomitant monitoring of a panel of potential biomarkers related to such conditions might help predicting HF evolution. Saliva analysis by point-of-care devices is expected to become an innovative and powerful monitoring approach since the chemical composition of saliva mirrors that of blood. The aims of this study were (i) to develop an innovative procedure combining MEPS with UHPLC-MS/MS for the simultaneous determination of 8-isoprostaglandin F2α and cortisol in saliva and (ii) to monitor lactate, uric acid, TNF-α, cortisol, α-amylase and 8-isoprostaglandin F2α concentrations in stimulated saliva samples collected from 44 HF patients during their hospitalisation due to acute HF. Limit of detection of 10 pg/mL, satisfactory recovery (95-110%), and good intra- and inter-day precisions (RSD ≤ 10%) were obtained for 8-isoprostaglandin F2α and cortisol. Salivary lactate and 8-isoprostaglandin F2α were strongly correlated with NT-proBNP. Most patients (about 70%) showed a significant decrease (a factor of 3 at least) of both lactate and 8-isoprostaglandin F2α levels at discharge, suggesting a relationship between salivary levels and improved clinical conditions during hospitalization.

Myocardial ischemia: From disease to syndrome.

Although current guidelines on the management of stable coronary artery disease acknowledge that multiple mechanisms may precipitate myocardial ischemia, recommended diagnostic, prognostic and therapeutic algorithms are still focused on obstructive epicardial atherosclerotic lesions, and little progress has been made in identifying management strategies for non-atherosclerotic causes of myocardial ischemia. The purpose of this consensus paper is three-fold: 1) to marshal scientific evidence that obstructive atherosclerosis can co-exist with other mechanisms of ischemic heart disease (IHD); 2) to explore how the awareness of multiple precipitating mechanisms could impact on pre-test probability, provocative test results and treatment strategies; and 3) to stimulate a more comprehensive approach to chronic myocardial ischemic syndromes, consistent with the new understanding of this condition.

Trimetazidine in cardiovascular medicine.

Abnormalities of myocardial energy metabolism appear as a common background of the two major cardiac disorders: ischemic heart disease (IHD) and heart failure (HF). Myocardial ischemia has been recently conceived as a multifaceted syndrome that can be precipitated by a number of mechanisms including metabolic abnormalities. HF is a progressive disorder characterised by a complex interaction of haemodynamic, neurohormonal and metabolic disturbances. HF may further promote metabolic changes, generating a vicious cycle. Thus, targeting cardiac metabolism in IHD patients may prevent the deterioration of left ventricular function, stopping the progression to HF. For these reasons, several studies have explored the potential benefits of trimetazidine (TMZ), an inhibitor of free fatty acids oxidation that shifts cardiac and muscle metabolism to glucose utilization. Because of its mechanism of action, TMZ has been found to provide a cardioprotective effect in patients with angina, diabetes mellitus, and left ventricular (LV) dysfunction, and those undergoing revascularization procedures, without relevant side effects. In addition, the lack of interference with heart rate, arterial pressure, and most of frequent comorbidities, makes TMZ an attractive option for patients and clinicians as well. The impact of TMZ on long term mortality and morbidity in ischemic syndromes and in heart failure need to be conclusively confirmed in properly designed RCT.