Multimodal characterization of dilated cardiomyopathy: Geno- And Phenotyping of PrImary Cardiomyopathy (GrAPHIC).

AIMS: Cardiomyopathies (CMPs) are a heterogeneous group of diseases that are defined by structural and functional abnormalities of the cardiac muscle. Dilated cardiomyopathy (DCM), the most common CMP, is defined by left ventricular dilation and impaired contractility and represents a common cause of heart failure. Different phenotypes result from various underlying genetic and acquired causes with variable effects on disease development and progression, prognosis, and response to medical treatment. Current treatment algorithms do not consider these different aetiologies, due to lack of insights into treatable drivers of cardiac failure in patients with DCM. Our study aims to precisely phenotype and genotype the various subtypes of DCM and hereby lay the foundation for individualized therapy. METHODS AND RESULTS: The Geno- And Phenotyping of PrImary Cardiomyopathy (GrAPHIC) is a currently ongoing prospective observational monocentric cohort study that recruits patients with DCM after exclusion of other causes such as coronary artery disease, valvular dysfunction, myocarditis, exposure to toxins, and peripartum CMP. Patients are enrolled at our heart failure outpatient clinic or during hospitalization at the University Hospital Hamburg. Clinical parameters, multimodal imaging and functional assessment, cardiac biopsies, and blood samples are obtained to enable an integrated genomic, functional, and biomarker analysis. CONCLUSIONS: The GrAPHIC will contribute to a better understanding of the heterogeneous nature of primary CMPs focusing on DCM and provide improved prognostic approaches and more individualized therapies.

Association of atrial myopathy in mitral valve disease on safety outcomes in left atrial appendage closure.

BACKGROUND: Patients undergoing left atrial appendage (LAA) occlusion (LAAO) are multi-morbid, including mitral valve disease (MVD) which is associated with anatomic changes of the left atrium (LA). This study aims to identify how atrial myopathy in MVD influences outcomes in LAAO. METHODS: Atrial myopathy in MVD was defined as LA diameter > 45 mm (♀) and > 48 mm (♂) and existing MVD or history of surgical/interventional treatment. Patients were compared with controls from the prospective, multicentre LAArge registry of LAAO. RESULTS: A total of 528 patients (52 MVD, 476 no-MVD) were included. The MVD group was significantly more likely to be older (78.2 years vs 75.9 years, p = 0.036) and female (59.6% vs 37.8%, p = 0.002). Altered LA anatomy was observed in MVD with significantly larger LA diameter (53 mm vs. 48 mm, p < 0.001) and LAA Ostia [at 135° 23.0 mm (20.5, 26.0) vs 20.0 mm (18.0, 23.0), p = 0.002]. Implant success was high with 96.2% and 97.9%, respectively, without differences in severe complications (7.7% vs 4.6%, p = 0.31). One-year mortality (17.8% vs 11.5%, p = 0.19) and a combined outcome of death, stroke, and systemic embolism (20.3% vs 12.4%, p = 0.13) were not different. Independent predictors of the combined outcome were peripheral artery disease (HR 2.41, 95% CI 1.46-3.98, p < 0.001) and chronic kidney disease (HR 3.46, 95% CI 2.02-5.93, p < 0.001) but not MVD and atrial myopathy. CONCLUSION: Patients with MVD present with altered LA anatomy with increased LA and LAA diameter. However, procedural success and safety in LAAO are not compromised. One-year mortality is numerically higher in patients with MVD but driven by comorbidities.

Prosthesis-patient mismatch after transcatheter aortic valve implantation: prevalence and prognostic impact with respect to baseline left ventricular function.

AIMS: We aimed to assess the prevalence and features of prosthesis-patient mismatch (PPM) following transcatheter aortic valve implantation (TAVI) and its prognostic impact considering baseline left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Data from 1,309 patients undergoing TAVI for severe aortic stenosis were derived from a single-centre dedicated TAVI registry. PPM was assessed according to echocardiography at discharge and was defined in accordance with VARC-2. Median follow-up time was 2.03 years. Moderate and severe PPM was detected in 22.9% and 12.9%, respectively. Patients with severe PPM had smaller annuli and more often received transcatheter heart valve (THV) sizes ≤23 mm. Supra-annular THV design showed the lowest rate of PPM. In patients with LVEF <40%, but not in those with LVEF ≥40%, severe PPM was associated with an increased three-year mortality rate (no vs. severe PPM for LVEF ≥40%: 34.6% vs. 29.5%, p=0.96; LVEF <40%: 45.1% vs. 68.0%, p=0.041) and was independently predictive of all-cause mortality according to multivariate analysis in these patients (HR 2.97; 95% CI: 1.58-5.59, p<0.001). CONCLUSIONS: The presence of severe PPM depends on annular dimensions and THV size and design and is an independent predictor of mortality in patients with reduced LVEF. Hence, the risk of PPM should be considered within the process of THV selection.