1Klinikum rechts der Isar der Technischen Universität München Klinik und Poliklinik für Innere Medizin I München, Deutschland; 2Institut für Biostatistik und Epidemiologie Klinkum rechts der Isar der Technische Universität München München, Deutschland; 3Universitätsklinikum Schleswig-Holstein Innere Medizin III mit den Schwerpunkten Kardiologie, Angiologie und internistische Intensivmedizin Kiel, Deutschland; 4Medizinisch Genetisches Zentrum München, Deutschland; 5Deutsches Herzzentrum München Klinik für Herz- und Kreislauferkrankungen München, Deutschland
Objectives
Aortic valve stenosis is a common valvular disease in the aging population. Transcatheter aortic valve replacement (TAVR) has revolutionized treatment options, especially for multimorbid elderly patients. Despite promising TAVR results compared to surgical aortic valve replacement, some patients do not benefit.
Aortic stenosis causes chronic pressure overload on the left ventricle (LV), resulting in different forms of reactive hypertrophic cardiac remodeling. In this study different pre-TAVI echocardiographic LV hypertrophy patterns were compared to assess a possible impact on postprocedural outcome after TAVR.
Scores for measuring the polygenic inheritance of dilated (DCM) and hypertrophic cardiomyopathy (HCM) have already been established (polygenic risk scores, PRS). The genetic impact on LV hypertrophy was evaluated using these established PRS. Our aim is to provide a comprehensive analysis on both genetical and clinical determinants of LV hypertrophy.
Patients and methods
The clinical study comprised 1483 patients with severe aortic stenosis who underwent TAVR between 01/2014 and 08/2022 in 2 major centers for TAVR in Munich and Kiel. Patients were categorized into four groups based on LV mass index and relative wall thickness: normal (N; n=57), concentric remodeling (CR; n=276), concentric hypertrophy (CH; n=981) and eccentric hypertrophy (EH; n=169).
Polygenic risk score analysis for DCM and HCM risk alleles was conducted on a subgroup of 540 patients, including 332 patients from the clinical study as well as 208 additional patients from a third TAVR-center in Munich (CR: n=164, CH: n=237, EH: n=139). Kaplan-Meier survival analysis, particularly comparing CH and EH subgroups, was performed. Multivariate regression was used to analyze the genetic impact on the CH and EH phenotype.
Results
Regarding postprocedural outcomes, mortality at 1 and 5 years was highest in the EH group, whereas survival was significantly higher in the CH group (p Log-Rank< 0.001). Figure 1 illustrates mid-term survival up to 5 years, comparing all four groups.Figure 1. Mid-term survival after TAVR; Kaplan-Meier estimates of the survival after TAVR in the 4 groups determined by hypertrophy (Log rank <0.001).
The percentile values of the PRS showed significant differences in group comparisons. A notable link was found between the HCM-PRS and the presence of EH (p=0.046). An elevated HCM-PRS correlated with a reduced likelihood of EH. However, no correlation was observed between the CH phenotype and the examined PRS or the EH phenotype and the DCM-PRS.
|
PRS-HCM |
PRS-DCM | ||
CH |
EH |
CH |
EH | |
Percentile value (mean ± SD) |
52,5±28,6 |
54,9±27,3 |
49,5±30,1 |
40,3±29,3 |
p=0,038 |
p=0,011 | |||
Regression coefficient (Exp(β)) |
-0,0009 (0,913) |
-0,011 (0,348) |
0,005 (1,646) |
0,005 (1,580) |
p-value |
0,863 |
0,046 |
0,333 |
0,381 |
Table 1. Polygenic risk score analysis of the subgroups CH and EH. Genetic impact on the echocardiographic phenotyp analyzed using regression analysis. Exp(β) estimates for a 10 percentil point difference.
Conclusion
The pre-TAVR patient cohort predominantly exhibited a concentric hypertrophy pattern. Among the groups, the EH group displayed the poorest clinical outcome, followed by the CH group. A genetic association was observed between HCM risk alleles and the presence of the EH phenotype. These findings suggest that the high-risk EH group may benefit from more precise peri-interventional monitoring and further studies to incorporate genetic screening.