Myocardial infarction with non-obstructive coronary artery disease occurs in 6% to 15% of all presentation of myocardial infarctions. The pathophysiologic mechanisms of MINOCA include epicardial vasospasm, coronary microvascular disorder, spontaneous coronary artery dissection, and coronary thrombus/embolism. The diagnosis is challenging, supported by intracoronary imaging with intravascular ultrasound (IVUS) and optical coherent tomography (OCT), coronary physiology testing, and cardiac magnetic resonance imaging (CMR). OCT is able to identify atherosclerotic causes of MINOCA (plaque erosion, plaque rupture, and calcified nodule) and nonatherosclerotic causes (spontaneous artery dissection, and spasm). In this review, we summarize the performance of the two intracoronary imaging modalities (IVUS and OCT) in MINOCA and discuss the importance of supplementing these modalities with CMR in order to drive target therapy.

Background: Genetic testing in hypertrophic cardiomyopathy (HCM) yields variable positivity rates. Identifying clinical predictors of positive genetic tests could improve pre-test counseling and refine expectations about diagnostic yield. Methods: We analyzed consecutive genotyped HCM probands from a contemporary multicenter cohort across four Italian tertiary centers. Genotype positivity was defined as the presence of ≥1 pathogenic or likely pathogenic variant (ACMG classes 4–5). Multivariable logistic regression identified predictors of genotype positivity. Sensitivity analyses assessed the incremental value of left atrial volume index (LAVI) ≥ 34 mL/m² and the mode of first clinical presentation. Results: Among 274 genotyped probands (median age at diagnosis 54 years; 62% male), 86 (31%) were genotype-positive (38% MYBPC3, 29% MYH7). Age at diagnosis 20 mm and gender were not predictive of genotype positivity. Inclusion of LAVI modestly improved the model performance (AUC 0.769, p = 0.016, ΔAUC +0.024; DeLong p = 0.016) but without leading to meaningful patient reclassification. Conclusions: Genotype positivity in HCM links to earlier onset and family history; traditional severity markers and initial presentation may not independently suggest genetic causality. These findings may help shape a personalized approach to genetic counseling in HCM.

Non-dilated left ventricular cardiomyopathy (NDLVC) presents a unique clinical paradox: patients with nearly identical phenotypes can face radically different clinical outcomes. NDLVC has been recently recognized as a distinct dynamic phenotype within the spectrum of non-ischemic cardiomyopathies, linked by a high risk of life-threatening arrhythmias. Recent advances in genetics have overcome clinical phenotyping in prognostic accuracy. Specifically, gene-specific scores have been introduced to guide primary prevention ICD in high-risk gene carriers. On the other hand, while gene-elusive cases present a more favourable arrhythmic profile, their long-term clinical outcome is more challenging to predict. Despite advancements in therapeutic strategies, the heterogeneity of the disease represents an ongoing dilemma for risk stratification and long-term surveillance. This review offers a comprehensive analysis of NDLVC management in clinical practice, highlighting the profound prognostic divergence between genetic (both in actionable and VUS carriers) and gene elusive cohorts. By synthesizing current evidence, we aim to clarify how genotype-phenotype correlations influence clinical outcomes and to provide a framework for more personalized approaches in the follow-up and treatment of these distinct patient populations. Furthermore, we address the current lack of standardized guidelines specifically tailored to gene-elusive phenotypes.

Non-dilated left ventricular cardiomyopathy (NDLVC) presents a unique clinical paradox: patients with nearly identical phenotypes can face radically different clinical outcomes. NDLVC has been recently recognized as a distinct dynamic phenotype within the spectrum of non-ischemic cardiomyopathies, linked by a high risk of life-threatening arrhythmias. Recent advances in genetics have overcome clinical phenotyping in prognostic accuracy. Specifically, gene-specific scores have been introduced to guide primary prevention ICD in high-risk gene carriers. On the other hand, while gene-elusive cases present a more favourable arrhythmic profile, their long-term clinical outcome is more challenging to predict. Despite advancements in therapeutic strategies, the heterogeneity of the disease represents an ongoing dilemma for risk stratification and long-term surveillance. This review offers a comprehensive analysis of NDLVC management in clinical practice, highlighting the profound prognostic divergence between genetic (both in actionable and VUS carriers) and gene-elusive cohorts. By synthesizing current evidence, we aim to clarify how genotype–phenotype correlations influence clinical outcomes and to provide a framework for more personalized approaches in the follow-up and treatment of these distinct patient populations. Furthermore, we address the current lack of standardized guidelines specifically tailored to gene-elusive phenotypes. In conclusion, NDLVC management requires a paradigm shift towards a multi-parametric, genotype-directed framework, where cardiac magnetic resonance tissue characterisation and personalized risk scores are essential to optimize sudden cardiac death prevention. Future research must leverage artificial intelligence and polygenic risk scores (PRSs) to integrate multi-parametric clinical-imaging data and refine risk stratification beyond traditional binary models. Concurrently, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) will be pivotal as a translational platform to clarify VUS pathogenicity, unravel gene-specific arrhythmic mechanisms, and accelerate targeted therapeutic interventions.