Cardiomyopathies (CMPs) represent a diverse group of heart muscle diseases, grouped into specific morphological and functional phenotypes. CMPs are associated with mutations in sarcomeric and non-sarcomeric genes, with several suspected epigenetic and environmental mechanisms involved in determining penetrance and expressivity. The understanding of the underlying molecular mechanisms of myocardial diseases is fundamental to achieving a proper management and treatment of these disorders. Among these, inflammation seems to play an important role in the pathogenesis of CMPs. The aim of the present study is to review the current knowledge on the role of inflammation and the immune system activation in the pathogenesis of CMPs and to identify potential molecular targets for a tailored anti-inflammatory treatment.

Background: The advanced lung cancer inflammation index (ALI) is an independent prognostic biomarker used to assess inflammation and nutritional status in various cancers, heart failure, and acute coronary syndromes. This study investigates the prognostic significance of ALI in patients experiencing ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI), comparing its predictive abilities with the established Neutrophil-Lymphocyte Ratio (NLR). Methods: We conducted a retrospective analysis of 1171 patients from the Matrix Registry, encompassing demographic and clinical data for STEMI cases treated with pPCI, and ALI was determined using the formula [serum albumin (g/dL) × body mass index (kg/m²)]/NLR at the time of hospital admission. The primary outcome was all-cause mortality. Results: Of the 1171 patients, 86 died during the follow-up period. Univariate analysis identified age, female gender, smoking, hypertension, diabetes, prior myocardial infarction (PMI), lower left ventricular ejection fraction (LVEF), and reduced ALI as factors associated with mortality. Multivariate analysis confirmed age (HR: 1.1, 95% CI: 1.05–1.11, p < 0.001) and PMI (HR: 2.4, 95% CI: 1.4–4.3, p = 0.001) as prominent independent predictors, alongside ALI (HR: 0.95, 95% CI: 0.92–0.97, p < 0.001) and LVEF (HR: 0.98, 95% CI: 0.97–0.99, p = 0.04). An ALI cut-off of ≤10 indicated a higher mortality risk (HR: 2.3, 95% CI: 1.5–3.7, p < 0.001). The area under the curve for ALI (0.732) surpassed that for NLR (0.685), demonstrating ALI’s superior predictive capability. Conclusions: ALI is an independent prognostic factor for all-cause mortality in STEMI patients undergoing pPCI, showing greater discriminatory power than NLR, particularly in patients with ALI values ≤ 10, who face a 2.3-fold higher mortality risk.

Coronavirus disease 2019 (COVID-19) has quickly become a worldwide health crisis. Although respiratory disease remains the main cause of morbidity and mortality in COVID patients, myocardial damage is a common finding. Many possible biological pathways may explain the relationship between COVID-19 and acute myocardial infarction (AMI). Increased immune and inflammatory responses, and procoagulant profile have characterized COVID patients. All these responses may induce endothelial dysfunction, myocardial injury, plaque instability, and AMI. Disease severity and mortality are increased by cardiovascular comorbidities. Moreover, COVID-19 has been associated with air pollution, which may also represent an AMI risk factor. Nonetheless, a significant reduction in patient admissions following containment initiatives has been observed, including for AMI. The reasons for this phenomenon are largely unknown, although a real decrease in the incidence of cardiac events seems highly improbable. Instead, patients likely may present delayed time from symptoms onset and subsequent referral to emergency departments because of fear of possible in-hospital infection, and as such, may present more complications. Here, we aim to discuss available evidence about all these factors in the complex relationship between COVID-19 and AMI, with particular focus on psychological distress and the need to increase awareness of ischemic symptoms.

In this report, an atypical case of Noonan syndrome (NS) associated with sarcomeric hypertrophic cardiomyopathy (HCM) in a 33-year-old patient was described. Genetic testing revealed two different disease-causing mutations: a mutation in the PTPN11 gene, explaining NS, and a mutation in the MYBPC3 gene, known to be associated with HCM. This case exemplifies the challenge in achieving a definite etiological diagnosis in patients with HCM and the need to exclude other diseases mimicking this condition (genocopies or phenocopies). Compound heterozygous mutations are rare but possible in HCM patients. In conclusion, this study highlights the important role of genetic testing as a necessary diagnostic tool for performing a definitive etiological diagnosis of HCM.

Frailty degree plays a critical role in the decision-making and outcomes of elderly patients with severe aortic stenosis (AS). Acute heart failure (AHF) results in a severely worse clinical hemodynamic status in this population. This study aimed to evaluate the impact of AHF on frailty degree and outcomes in older patients referred for tailored interventional treatment due to AS. A total of 109 patients (68% female; mean age 83.3 ± 5.4), evaluated by a multidisciplinary path for “frailty-based management” of valve disease, were divided into two groups, one with (AHF+) and one without AHF (AHF-) and preserved ejection fraction (mean value EF: 57.4 ± 8.6). AHF occurred a mean value of 55 days before geriatric, clinical, and surgical assessment. A follow-up for all-cause mortality and readmission was conducted at 20 months. AHF+ patients showed a higher frequency of advanced frailty (53.3% vs. 46.7%, respectively), rehospitalization (35.5% vs. 12.8; p = 0.007), and death (41.9% vs. 12.8%; p < 0.001). In stepwise logistic regression analysis, AHF emerged as an independent risk factor for advanced frailty (OR: 3.8 CI 1.3–10.7; p = 0.01) and hospital readmission (OR: 3.6 CI 1.1–11.6; p = 0.03). In addition, preceding AHF was an independent determinant associated with a higher risk of mortality (HR 2.65; CI 95% 1.04–6.74; p-value 0.04). AHF is independently associated with advanced frailty and poor outcomes in elderly patients with severe AS. So, this population needs careful clinical and geriatric monitoring and the implementation of interventional therapy for AS in the early stages of frailty to avoid the occurrence of AHF and poor outcomes.

Calcific aortic stenosis (CAS) is a newly emerging pandemic in elderly individuals due to the aging of the population in the world. Surgical Aortic Valve Replacement (SAVR) and Transcatheter Aortic Valve Replacement (TAVR) are the cornerstone of the management of severe aortic stenosis accompanied by one or more symptoms. Moreover, an appropriate interventional treatment of CAS, in elderly patients, is a very complex decision for heart teams, to avoid bad outcomes such as operative mortality, cardiovascular and all-cause death, hospitalization for heart failure, worsening of quality of life. In fact, CAS in the elderly is not only a focal valve disease, but a very complex clinical picture with different risk factors and etiologies, differing underlying pathophysiology, large phenotypic heterogeneity in a context of subjective biological, phenotypic and functional aging until frailty and disability. In this review, we analyzed separately and in a more integrated manner, the natural and prognostic histories of the progression of aortic stenosis, the phenotypes of myocardial damage and heart failure, within the metrics and aging trajectory. The aim is to suggest, during the clinical timing of valve disease, the best interval time for an appropriate and effective interventional treatment in each older patient, beyond subjective symptoms by integration of clinical, geriatric, chemical, and advanced imaging biomarkers.