Among the most common causes of death worldwide, ischemic heart disease (IHD) is recognized to rank first. Even if atherosclerotic disease of the epicardial arteries is known as the leading cause of IHD, the presence of myocardial infarction with non-obstructive coronary artery disease (MINOCA) is increasingly recognized. Notwithstanding the increasing interest, MINOCA remains a puzzling clinical entity that can be classified by distinguishing different underlying mechanisms, which can be divided into atherosclerotic and non-atherosclerotic. In particular, coronary microvascular dysfunction (CMD), classifiable in non-atherosclerotic mechanisms, is a leading factor for the pathophysiology and prognosis of patients with MINOCA. Genetic susceptibility may have a role in primum movens in CMD. However, few results have been obtained for understanding the genetic mechanisms underlying CMD. Future studies are essential in order to find a deeper understanding of the role of multiple genetic variants in the genesis of microcirculation dysfunction. Progress in research would allow early identification of high-risk patients and the development of pharmacological, patient-tailored strategies. The aim of this review is to revise the pathophysiology and underlying mechanisms of MINOCA, focusing on CMD and actual knowledge about genetic predisposition to it.

Spontaneous coronary artery dissection (SCAD) is a cause of myocardial infarction without obstructive coronary artery disease (MINOCA). It is determined by a coronary artery wall layers separation, which occurs regardless of traumatic or iatrogenic injuries. Even if it is often a missed diagnosis, its incidence is growing along with the improvement of intracoronary imaging techniques that allow for better detection. The main angiographical classification distinguishes three different forms, with slightly different prognoses at long-term follow up. SCAD is a recurrent condition, severely hampering the life quality of affected patients. The predominantly young age of patients with SCAD and the high prevalence of females among them have made the topic increasingly important, especially regarding therapeutic strategies. According to the data, the most recommended treatment is conservative, based on the use of antiplatelet agents and supportive anti-ischemic therapy. However, there are conflicting opinions concerning the need for dual antiplatelet therapy and its duration. In the case of invasive treatment, the choice between percutaneous coronary intervention and coronary artery bypass graft depends on the patient’s clinical stability and the interested vessel. The purpose of the current review is to revise the pathophysiological mechanisms underlying SCAD and the current knowledge of its treatment.

Background: Ischemic heart disease (IHD) represents the main cause of heart failure (HF). A prognostic stratification of HF patients with ischemic etiology, particularly those with acute coronary syndrome (ACS), may be challenging due the variability in clinical and hemodynamic status. The aim of this study is to assess the prognostic power of the HLM score in a population of patients with ischemic HF and in a subgroup who developed HF following ACS. Methods: This is an observational, prospective, single-center study, enrolling consecutive patients with a diagnosis of ischemic HF. Patients were stratified according to the four different HLM stages of severity, and the occurrence of CV death, HFH, and worsening HF events were evaluated at 6-month follow-up. A sub-analysis was performed on patients who developed HF following ACS at admission. Results: The study included 146 patients. HLM stage predicts the occurrence of CV death (p = 0.01) and CV death/HFH (p = 0.003). Cox regression analysis confirmed HLM stage as an independent predictor of CV death (OR: 3.07; 95% IC: 1.54–6.12; p = 0.001) and CV death/HFH (OR: 2.45; 95% IC: 1.43–4.21; p = 0.001) in the total population of patients with HF due to IHD. HLM stage potentially predicts the occurrence of CV death (p < 0.001) and CV death/HFH (p < 0.001) in patients with HF following ACS at admission. Conclusions: Pathophysiological-based prognostic assessment through HLM score is a potentially promising tool for the prediction of the occurrence of CV death and CV death/HFH in ischemic HF patients and in subgroups of patients with HF following ACS at admission.

Purpose: SGLT2i role in the treatment of heart failure (HF) regardless of clinical presentation and left ventricular ejection fraction (LVEF) has been widely proven and real-world data regarding patients with HF and ischemic heart disease (IHD) and, in particular with recent acute coronary syndrome (ACS) and de novo HF, are lacking. We aim to evaluate the occurrence of the composite of cardiovascular death (CV)/ HF hospitalization (HFH), all-cause death, CV death and HFH at 6 months follow up, in patients with HF due to IHD as well as in recent ACS who introduced SGLT2i during the index hospitalization. Methods: The present is an observational, prospective, single center study, enrolling patients with a diagnosis of HF due to IHD as primary etiology. According to SGLT2i introduction timing, two groups were created: pre-discharge (G1) or post-discharge (G2) introduction. A sub-analysis in patients admitted due to ACS has been performed. Results: A total of 222 consecutive patients have been enrolled from April 2022 to April 2024 and were followed-up for a period of 6 months. At multivariate Cox regression analysis, statistically significant differences have been observed between the two groups in terms of the composite CV death/HFH (HR = 0.24; 95%CI [0.101–0.564]; p = 0.001), all-cause death (HR = 0.27; 95% CI [0.100–0.725]; p = 0.009), CV death (HR = 0.32; 95%CI [0.101–0.999] p = 0.045) and HFH (HR = 0.31; 95%CI [0.098–0.963]; p = 0.043). Patients with ACS treated with SGLT2i before discharge showed a reduced rate of CV death/HFH (log-rank p = 0.008), CV death (log-rank p = 0.015) and all-cause death (log-rank p = 0.005) compared to patients who were not treated with SGLT2i before discharge. In this subpopulation, no differences have been observed in terms of HFH (log-rank p = 0.155). Significant differences in term of CV death/HFH (log-rank p = 0.039) have been observed in de novo HF patients, but not in terms of the other study endpoints. Conclusions: The early in-hospital introduction of SGLT2i reduced the occurrence of the composite CV death/HFH, all-cause death, CV death and HFH in patients with ischemic cardiomyopathy. In the subgroup analysis of patients admitted due to ACS, the introduction of SGLT2i during the index hospitalization resulted in a significant reduction of the composite CV death/HFH, CV death and all-cause death, but not in HFH. The same therapeutic strategy resulted in reduced rate of CV death/HFH in the de novo HF subpopulation.