The co-ordinated interaction between atria and ventricles, termed atrioventricular (AV) coupling, is essential for maintaining efficient cardiac performance. The left/right atrium (LA/RA) modulates left/right ventricular (LV/RV) filling through its reservoir, conduit, and booster pump functions, while the LV/RV in turn determines atrial pressures and compliance. Disruption of this finely balanced interplay leads to impaired filling dynamics, abnormal pressure–volume relationships, and progressive remodelling. Mechanisms of uncoupling include mechanical dysfunction from atrial dilatation and fibrosis, ventricular diastolic stiffness, and loss of atrial contractile reserve, as well as electromechanical desynchrony due to conduction abnormalities such as AV block or prolonged PR interval. The concept of quantifying AV coupling has been formalized through the left/right AV coupling index (LACI/RACI), defined as the ratio of LA/RA end-diastolic volume to LV/RV end-diastolic volume. LACI/RACI can be non-invasively derived across imaging modalities—including echocardiography, computed tomography, and cardiovascular magnetic resonance—without requiring specific acquisition protocols. First described in large population cohorts, LACI has demonstrated independent and incremental prognostic value for heart failure, atrial fibrillation and mortality, outperforming isolated atrial or ventricular parameters. Moreover, its ability to capture dynamic remodelling makes it a promising biomarker for risk stratification across a broad spectrum of cardiovascular diseases. This review synthesizes current knowledge on left and right AV coupling, outlines the physiological and pathophysiological mechanisms of uncoupling, and highlights the role of LACI/RACI as both a diagnostic and prognostic tool. Standardization of assessment strategies and reference values will be essential to facilitate clinical translation and precision cardiology.

Dilated cardiomyopathy (DCM) represents a group of disorders affecting the structure and function of the heart muscle, leading to a high risk of heart failure and sudden cardiac death (SCD). DCM frequently involves an underlying genetic etiology. Genetic testing is valuable for risk stratification, treatment decisions, and family screening. Romanian population data on the genetic etiology of DCM are lacking. We aimed to investigate the genetic causes for DCM among Romanian adult patients at tertiary referral centers across the country. Clinical and genetic investigations were performed on adult patients presenting to tertiary hospitals in Romania. The genetic investigations used next-generation sequencing panels of disease-associated DCM genes. A total of 122 patients with DCM underwent genetic testing. The mean age at DCM diagnosis was 41.6 ± 12.4 years. The genetic investigations identified pathogenic or likely pathogenic variants in 50.8% of participants, while 25.4% had variants of unknown significance. Disease-causing variants in 15 genes were identified in people with DCM, with 31 previously unreported variants. Variants in TTN, LMNA, and DSP explained 75% of genetic causes for DCM. In total, 52.4% of patients had a family history of DCM/SCD. Left ventricular ejection fraction of <35% was observed in 41.9% of patients with disease-causing variants and 55% with negative or uncertain findings. Further genotype-phenotype correlations were explored in this study population. The substantial percentage (50.8%) of disease-causing variants identified in patients with DCM acknowledges the importance of genetic investigations. This study highlights the genetic landscape in genes associated with DCM in the Romanian population.

Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic disorder, most often caused by sarcomeric gene mutations, with a small proportion due to variants in non-sarcomeric loci. Phospholamban (PLN) is a phosphoprotein associated with the cardiac sarcoplasmic reticulum, a major determinant of cardiac contractility and relaxation. We conducted a retrospective study to determine the prevalence, phenotypical spectrum and clinical course of patients carrying the PLN p.Leu39* variant. A cohort including 11 PLN patients was identified among all patients with HCM (9/189, 4.8%) and DCM (2/62, 3.2%) who underwent genetic testing from two tertiary centers and five more were detected through cascade screening. Complete phenotyping was performed. PLN p.Leu39* variant-driven cardiomyopathy presented mostly as hypertrophic, with frequent progression to end-stage dilated HCM. We proceeded to compare these results to a similar analysis of a control cohort consisting of age-matched individuals that inherited pathogenic or likely pathogenic variants in common sarcomeric genes (MYBPC3/MYH7). Overall, the clinical characteristics and examination findings of patients carrying PLN p.Leu39* were not different from patients with cardiomyopathy related to sarcomeric mutations except for the presence of pathological Q waves and the incidence of non-sustained ventricular arrhythmias, which were higher in PLN patients than in those with MYBPC3/MYH7-related diseases.

BACKGROUND: Stress perfusion cardiovascular magnetic resonance (CMR) is widely used to detect myocardial ischemia, mostly through visual assessment. Recent studies suggest that strain imaging at rest and during stress can also help in prognostic stratification. However, the additional prognostic value of combining both rest and stress strain imaging has not been fully established. This study examined the incremental benefit of combining these strain measures with traditional risk prognosticators and CMR findings to predict major adverse clinical events (MACE) in a cohort of consecutive patients referred for stress CMR. METHODS: This retrospective, single-center observational study included all consecutive patients with known or suspected coronary artery disease referred for stress CMR between 2016 and 2018. Fully automated machine learning was used to obtain global longitudinal strain at rest (rest-GLS) and global circumferential strain at stress (stress-GCS). The primary outcome was MACE, including cardiovascular death or hospitalization for heart failure. Cox models were used to assess the incremental prognostic value of combining these strain features with traditional prognosticators. RESULTS: Of 2778 patients (age 65±12 years, 68% men), 96% had feasible, fully automated rest-GLS and stress-GCS measurements. After a median follow-up of 5.2 (4.8–5.5) years, 316 (11.1%) patients experienced MACE. After adjustment for traditional prognosticators, both rest-GLS (hazard ratio, 1.09 [95% CI, 1.05–1.13]; P <0.001) and stress-GCS (hazard ratio, 1.08 [95% CI, 1.03–1.12]; P –10% for rest-GLS and stress-GCS, with a C-index improvement of 0.02, continuous net reclassification improvement of 15.6%, and integrative discrimination index of 2.2% (all P –10% provided an incremental prognostic value over and above traditional prognosticators, including CMR parameters, for predicting MACE in patients undergoing stress CMR.

Multiple and mixed valvular heart disease (MMVD) is defined as the combination of stenotic or regurgitant lesions occurring on ≥2 cardiac valves (ie, multiple valvular heart disease [VHD]) or the combination of stenotic and regurgitant lesions on the same valve (ie, mixed VHD). This condition is frequent in clinical routine, with a notable shift in epidemiology over recent years, marked by a decline in rheumatic heart disease and an increase in degenerative causes. Even if echocardiography stands as the cornerstone for diagnosing VHD, practicians need to remain cautious because some echocardiographic parameters might be invalid in the context of MMVD. Considering echocardiography's pitfalls, MMVD needs to be assessed using multiparametric perspective, including cardiovascular magnetic resonance, cardiac computed tomography, biomarkers, and the assessment of comorbidities. Multimodality imaging seems to be a promising approach to assess patient's prognosis, by providing a precise analysis of cardiac remodeling and an accurate evaluation of MMVD severity. Due to the heterogeneity of this clinical scenario, studies are typically conducted in single centers with a limited number of patients. Therefore, there is a lack of dedicated guidelines regarding the severity assessment and the clinical decision-making for these MMVD patients. The aim of this review is to provide a state-of-the-art using the available evidence on the management of MMVD considering the interactions between different valve lesions, the diagnostic pitfalls, and the strategies that should be considered including the role of multimodality imaging in the presence of MMVD.

Background: Hypertrophic cardiomyopathy (HCM) is a genetic disorder marked by myocardial hypertrophy, leading to diastolic and systolic dysfunction and heart failure. Traditionally, the burn-out stage is defined by systolic dysfunction, but we propose expanding its definition to include advanced diastolic dysfunction. Methods: We retrospectively analyzed HCM patients (2004–2023) with either systolic dysfunction (left ventricular ejection fraction [LVEF] < 50%) or advanced diastolic dysfunction (preserved LVEF with left atrial enlargement and elevated filling pressures: E/A ≥ 2 or E/e′ ≥ 14). Both subgroups were included under the term “end-stage HCM” and compared to HCM controls with preserved LVEF and impaired relaxation. Results: Of 696 HCM patients, 94 had end-stage HCM (23 with systolic dysfunction, 71 with advanced diastolic dysfunction). Median age was 56.5 years, and 55.3% were male. End-stage HCM patients were more symptomatic at follow-up than controls (91.5% vs. 75.0%, p-value = 0.006), with higher rates of dyspnea and advanced heart failure (38.3% vs. 6.3%, p-value < 0.001). Advanced diastolic dysfunction was associated with a more symptomatic profile (p-value = 0.013) and a high annual mortality rate (2.34%, p = 0.014). Male sex, older age, lower LVEF, and higher E/A predicted systolic dysfunction. Conclusions: Advanced diastolic dysfunction represents an alternative progression pathway in burn-out HCM, requiring distinct management strategies alongside systolic dysfunction.