Background and Aims: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is associated with a significant risk of mortality, rehospitalization, and angina burden. Despite its clinical impact, no randomized clinical trials have hitherto evaluated optimal management strategy for MINOCA. The PROMISE trial was designed to assess whether a stratified treatment improves clinical outcomes in patients with MINOCA as compared to standard care. Methods: PROMISE is a multicentre randomized trial. Patients with MINOCA were randomized 1:1 to either a stratified treatment based on a comprehensive diagnostic workup aimed at identifying the underlying aetiology, or to standard care. The primary endpoint was the between-group difference in the change in angina status at 12 months, assessed by the Seattle Angina Questionnaire summary score (SAQSS). The secondary endpoint was the incidence of major adverse cardiovascular events (MACE), defined as the composite of all-cause mortality, myocardial infarction, stroke, heart failure hospitalization and repeated coronary angiography. The trial was terminated early upon recommendation by the Data and Safety Monitoring Board due to clear benefits observed in the intervention group and potential harm in the control group. Results: Of 101 randomized patients, 92 were confirmed as MINOCA and included in the final analysis (mean age 62 ± 13 years, 48% women; stratified treatment n = 45; standard care n = 47). At 12-month follow-up, SAQSS was significantly higher in the stratified treatment than in standard care group, with a mean between-group difference of +9.38 in favour of the stratified treatment (95% confidence interval 6.81 to 11.95; P < .001). MACE occurred in 1 patient (2.2%) in the stratified treatment and in 4 patients (8.5%) in the standard care group, though the difference was not statistically significant (P = .18). Conclusions: In this first randomized trial of treatment strategies in MINOCA, a stratified treatment, based on comprehensive diagnostic assessment and aetiology-guided therapy, led to a significant improvement in angina-related health status. While the study findings provide the first evidence supporting individualized management in this heterogeneous and often under-recognized patient population, these results require confirmation in a larger prospective study with longer follow-up.

Background: Cardiovascular sequelae after COVID-19 are frequent. However, the predictors for their occurrence are still unknown. In this study, we aimed to assess whether myocardial injury during COVID-19 hospitalization is associated to CV sequelae and death after hospital discharge. Methods: In this prospective observational study, consecutive patients who were admitted for COVID-19 in a metropolitan COVID-19 hub in Italy, between March 2021 and January 2022, with a ≥ 1 assessment of high sensitivity cardiac troponin I (hs-cTnI) were included in the study, if they were alive at hospital discharge. Myocardial injury was defined as elevation hs-cTnI > 99th percentile of the upper reference limit. The incidence of all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE, including cardiovascular death, admission for acute or chronic coronary syndrome, hospitalization for heart failure, and stroke/transient ischemic attack) at follow-up were the primary outcomes. Arrhythmias, inflammatory heart diseases, and/or thrombotic disorders were analyzed as well. Results: Among the 701 COVID-19 survivors (mean age 66.4 ± 14.4 years, 40.2% female), myocardial injury occurred in 75 (10.7%) patients. At a median follow-up of 270 days (IQR 165, 380), all-cause mortality (21.3% vs. 6.1%, p < 0.001), MACCE (25.3% vs. 4.5%, p < 0.001), arrhythmias (9.3% vs. 5.0%, p = 0.034), and inflammatory heart disease (8.0% vs. 1.1%, p < 0.001) were more frequent in patients with myocardial injury compared to those without. At multivariate analysis, myocardial injury (HR 1.95 [95% CI:1.05–3.61]), age (HR 1.09 [95% CI:1.06–1.12]), and chronic kidney disease (HR 2.63 [95% CI:1.33–5.21]) were independent predictors of death. Myocardial injury (HR 3.92 [95% CI:2.07–7.42]), age (HR 1.05 [95% CI:1.02–1.08]), and diabetes (HR 2.35 [95% CI:1.25–4.43]) were independent predictors of MACCE. Conclusion: In COVID-19 survivors, myocardial injury during the hospital stay portends a higher risk of mortality and cardiovascular sequelae and could be considered for the risk stratification of COVID-19 sequelae in patients who are successfully discharged.

Coronary microvascular dysfunction (CMD) plays a crucial role across the spectrum of heart failure (HF) pathology, contributing to disease development, progression, and outcomes. The pathophysiological mechanisms linking CMD to HF are complex and still not completely understood and include chronic inflammation, oxidative stress, and neurohormonal activation. Despite the diagnostic and prognostic relevance in patients with HF, there is no specific therapeutic strategy targeting CMD to date. Moreover, the diagnosis of this clinical condition is challenging. In this review article, we aim to discuss the different clinical pathogenetic mechanisms linking CMD to HF across the different spectra of these diseases, their prognostic relevance, and the possible therapeutic targets along with the remaining knowledge gaps in the field.

Air pollution is emerging as an important risk factor for acute coronary syndrome (ACS). In this study, we investigated the association between short-term air pollution exposure and mechanisms of coronary plaque instability evaluated by optical coherence tomography (OCT) imaging in ACS patients. Patients with ACS undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT. Based on each case's home address, the mean daily exposures to several pollutants, including particulate matter 2.5 (PM_2.5), on the same day of ACS and in the immediate days (up to 6 days) prior to the index ACS, were collected. 139 ACS patients were included [69 (49.6%) had PR and 70 (50.4%) IFC]. Patients with PR, compared to those with IFC, had higher PM_2.5 exposure levels on the same day of ACS, without differences in the immediate 6 days before index ACS. At multivariate analysis, PM_2.5 exposure on the same day of ACS was the only independent predictor of PR [OR = 1.912 per SD (8.6 μg/m³), CI95 % (1.087-3.364), p = 0.025]. Patients with PR presented a steady increase in PM_2.5 daily exposure levels in the days preceding the occurrence of ACS, with a peak the day of ACS (p for trend = 0.042) CONCLUSIONS: This study demonstrates for the first time that a higher short-term PM2.5 exposure, on the same day of ACS, is associated with an increased risk of PR as a pathobiological mechanism of coronary plaque instability.

Nowadays, current guidelines on acute coronary syndrome (ACS) provide recommendations mainly based on the clinical presentation. However, greater attention is being directed to the specific pathophysiology underlying ACS, considering that plaque destabilization and rupture leading to luminal thrombotic obstruction is not the only pathway involved, albeit the most recognized. In this review, we discuss how intracoronary imaging and biomarkers allow the identification of specific ACS endotypes, leading to the recognition of different prognostic implications, tailored management strategies, and new potential therapeutic targets. Furthermore, different strategies can be applied on a personalized basis regarding antithrombotic therapy, non-culprit lesion revascularization, and microvascular obstruction (MVO). With respect to myocardial infarction with non-obstructive coronary arteries (MINOCA), we will present a precision medicine approach, suggested by current guidelines as the mainstay of the diagnostic process and with relevant therapeutic implications. Moreover, we aim at illustrating the clinical implications of targeted strategies for ACS secondary prevention, which may lower residual risk in selected patients.