Centro Cardiologico Monzino

Hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, represents a paradigmatic condition for precision cardiovascular medicine. Once regarded as a monogenic autosomal dominant disorder driven by rare sarcomeric variants, HCM is now recognized as a genetically complex disease characterized by incomplete penetrance, variable expressivity, and heterogeneous clinical trajectories. This review summarizes current evidence on the evolving genetic architecture of HCM, emphasizing the predominant role of definitively validated sarcomeric genes, particularly MYBPC3 and MYH7, and the clinical value of gene panel expansion. Phenotypic variability reflects interactions among variant classes, gene-specific mechanisms, and modifying factors. Differences between missense and truncating variants, haploinsufficiency and poison-peptide effects, allelic imbalance, and age-dependent penetrance contribute to diverse disease expression. Emerging data further support oligogenic inheritance and polygenic modulation, with genome-wide association studies and polygenic risk scores elucidating their contribution to disease susceptibility and variability, especially in genotype-negative patients and carriers of rare variants. We also address genes with emerging evidence and underrecognized pathogenic mechanisms, including deep intronic and splice-altering variants that may explain part of the missing heritability. The importance of distinguishing phenocopies is highlighted, advocating for phenotype-anchored diagnostic pathways integrating clinical assessment, multimodality imaging, and targeted genetic testing. Overall, contemporary data support a targeted, gene-validity-driven approach to genetic testing, where molecular findings primarily inform diagnosis and cascade screening, while risk stratification remains phenotype-led and longitudinal. Future progress will depend on integrative models combining rare variants, polygenic background, imaging, and biomarkers to translate genetic complexity into actionable precision care.

In hypertrophic cardiomyopathy (HCM), cardiopulmonary exercise testing (CPET) is considered the gold standard for assessing exercise tolerance, with O2-pulse commonly used as a surrogate for stroke volume (SV). However, because SV reduction can be masked by increased oxygen extraction, direct non-invasive measurement of SV is valuable. This study involved 102 HCM patients (mean age 53 ± 16 years, 78% male), predominantly with a non-obstructive phenotype (74%), who underwent CPET with SV measurement using Physioflow (PF). Abnormal O2-pulse kinetics were observed in 12 patients, all confirmed by abnormal SV trends with PF. Additionally, PF identified another 28 patients with altered SV kinetics. Abnormal SV trends were associated with higher peak VE/VO2 ratios (42.6 [37.4–47.5] vs. 38.0 [33.6–41.3]) and lower end-tidal CO2 values (31.8 ± 4.9 vs. 34.3 ± 5.6 mmHg, p < 0.05). Patients with greater SV growth during the final 25% of exercise showed improved anaerobic threshold VO2 (49.8 ± 12.3% vs. 43.9 ± 15.2% predicted peak VO2), VO2/work slope (10.2 ± 2.0 vs. 9.3 ± 1.3 mL/min/Watt), and peak PetCO2 (34.5 ± 5.6 vs. 32.3 ± 5.2 mmHg), alongside a lower VE/VCO2 slope (28.7 [24.9–31.0] vs. 31.3 [27.3–34.2], p < 0.05). Integrating PF and CPET may enhance the detection of abnormal SV kinetics, which are associated with reduced functional capacity in HCM patients.

treatment of obstructive coronary artery disease (CAD) requires accurate planning to ensure effective revascularization and full restoration of myocardial perfusion. In this study, we introduce Virtual PCI, a novel computational tool designed to support pre-operative planning of Percutaneous Coronary Intervention (PCI) by predicting the hemodynamic consequences of selected revascularization treatments. the tool leverages a fully personalized 3D multiscale perfusion model, calibrated using pre-intervention stress CT perfusion (CTP) imaging, to simulate the hemodynamic impact of different revascularization strategies in terms of post-intervention stress myocardial blood flow (MBF) and FFR. The computational framework is also capable of computing the FFR index. We conduct a validation study on patients treated with elective PCI and compare model predictions with dynamic stress CTP at follow-up. the validation study demonstrates high accuracy in predicting post-PCI myocardial perfusion, including potential residual ischemia and cardiac mass at ischemic risk. Through an integrated analysis with FFR, the tool shows potential for its prospective use, identifying in two patients optimal treatment strategies and, in one case, outperforming the executed revascularization in reduction of ischemic burden. Virtual PCI enables the prediction of post-PCI myocardial blood flow (MBF) and FFR, offering a comprehensive assessment of treatment outcomes to identify the best revascularization option from the hemodynamic standpoint. since it relies solely on non-invasive imaging (cCTA, stress-CTP), Virtual PCI can be integrated early in the diagnostic workflow, providing cardiologists with a powerful, patient-specific tool to optimize PCI planning.

The present study aimed to report the early and late clinical outcomes of patients who underwent surgical repair for acute type A aortic dissection requiring concomitant coronary artery bypass grafting (CABG), and to explore potential risk factors associated with the need for this additional procedure. Data were retrieved from the multicenter European Registry of Type A Aortic Dissection (ERTAAD). Bootstrapped least absolute shrinkage and selection operator logistic regression and multilevel multivariate logistic regression were performed for variable selection to identify predictors of hospital death, and logistic regression was used for the prediction of CABG. A total of 292 (8.04%) of 3633 patients required additional CABG. The in-hospital mortality rate was 33% for patients undergoing CABG vs 16% of non-CABG recipients (P < .001; odds ratio [OR], 2.52; 95% CI, 1.93-3.35). Dissection of the aortic root involving the right coronary cusp (P < .001; OR, 7.83; 95% CI, 5.55-11.0), a tear in the aortic root (P = .002; OR, 2.08; 95% CI, 1.29-3.32), mitral valve insufficiency (P = .034; OR, 1.33; 95% CI, 1.01-1.71), and a genetic syndrome (P < .001; OR, 3.23; 95% CI, 1.66-5.99) independently predicted the need for CABG. The need for additional CABG is not a rare occurrence during repair of type A aortic dissection and is associated with an increased mortality risk. Intimal tear localization and right coronary sinus dissection should be carefully examined in the preoperative image evaluation to stratify the risk of revascularization and plan the most appropriate approach.

Despite advancements in surgical techniques and perioperative care, postoperative bleeding and neurological complications remain significant concerns after bioprosthetic surgical aortic valve replacement (SAVR). The present study assessed the incidence of short-term and long-term major bleeding and strokes and their association with antithrombotic treatment after isolated bioprosthetic SAVR. The CAREAVR study included 721 patients who underwent isolated bioprosthetic SAVR at four Finnish university hospitals between 2002 and 2014. The day-to-day information on short-term antithrombotic treatment was available from a subgroup including 227 patients. The median follow-up time was 4.9 (interquartile range 3.0-7.0) years. During the 30-day postoperative period, in the subgroup of 227 patients, 31 (13.7%) patients experienced a major bleeding event, and 13 (5.7%) patients a major stroke. A vast majority of the bleedings (80.6%) occurred within two days after the surgery, and the tail effect of preoperative aspirin was present in 54.8% of episodes, indicating unintentional antithrombotic effect. During the long-term follow-up (>30days after the index surgery), major bleeding episodes occurred in 40 (5.5%) patients, and 47 (6.5%) patients experienced a major stroke. Overall, 23 (57.5%) of the patients with major bleeding and 13 (27.7%) of the patients experiencing major stroke were on OAC during the event. The incidence of perioperative major bleeding was over two-fold compared to major stroke, the majority occurring during the tail effect of preoperatively used aspirin. During the long-term follow-up, the rates of stroke and major bleeds were similar, and most bleeding episodes occurred while on OAC.