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. 2023 Aug 8;1(3):381-392.
doi: 10.1016/j.mcpdig.2023.07.002. eCollection 2023 Sep.

Topological Data Analysis Identified Prognostically-Distinct Phenotypes in Transcatheter Edge-to-Edge Repair Patients

Chieh-Ju Chao  1   2 , Timothy Barry  1 , Amith Seri  1 , Ahmed El Shaer  2 , Nadia Chavez Ponce  2 , Soham Chakraborty  3 , Sean Smith  1 , Mohamad Alkhouli  2 , Jeremy Thaden  2 , David Fortuin  1 , John P Sweeney  1 , Mackram Eleid  2 , Charanjit S Rihal  2 , David R Holmes  2 , Peter M Pollak  4 , Abdallah El Sabbagh  4 , Steven J Lester  1 , Jae K Oh  2 , Win-Kuang Shen  1 , Imon Banerjee  1 , Reza Arsanjani  1
Affiliations

Topological Data Analysis Identified Prognostically-Distinct Phenotypes in Transcatheter Edge-to-Edge Repair Patients

Chieh-Ju Chao et al. Mayo Clin Proc Digit Health. .

Abstract

Objective: To identify prognostically distinct phenotype clusters in transcatheter edge-to-edge repair (TEER) patients based on topological data analysis (TDA), which was never used to assess the heterogeneous TEER population.

Patients and methods: Patients who underwent TEER (June 2014-September 2020) at Mayo Clinic sites were identified from the institutional database. Thirteen variables were used for TDA. The topological network graph was created using the Python Scikit-TDA Kepler-Mapper package (v. 2.0.1), and clustering was performed at the graph level with Louvain's modularity method. Kaplan-Meier survival analysis was used to assess the all-cause mortality of each cluster.

Result: A total of 389 consecutive patients were included in the final analysis, and 2 major clusters were identified. The mean age was 80.3 ± 8.7 years; 256 (65.8%) were male. Fifty-five (14.5%) patients died during the mean follow-up duration (185 days). Kaplan-Meier analysis showed significant survival differences among the 2 clusters (hazard ratio, 2.70; 95% CI, 1.50-4.87; P=.0005). Cluster 1 (n=227) had moderate or increased residual mitral regurgitation (cluster 0 vs cluster 1: 19.4% vs 41.9%; P<.001) and worse survival performance. Cluster 1 was characterized by worse tricuspid regurgitation severity, higher proportions of patients with atrial fibrillation or flutter, anterior or bileaflet leaflet prolapse, anterior leaflet flail, and mitral annular or leaflet calcification.

Conclusion: TDA can identify prognostically distinct clusters in TEER patients based on mitral valve morphology and clinical risk factors. This simple model can facilitate risk stratification for TEER patients regarding procedural success and survival performance.

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Conflict of interest statement

The authors report no competing interests.

Figures

Figure 1
Figure 1
The topological graph representing the TEER dataset. (A) The distribution of the 2 clusters; cluster 0 on the left (green-colored) and cluster 1 (red-colored) on the right. There were transitional nodes that contained patients of both clusters (orange or light-orange colored). (B) The distribution of the STS MV Replace risk score. Nodes with high-risk patients (red-colored) were distributed in both clusters. (C) The distribution of mortality rate. Nodes with higher-mortality rate patients (orange-red colored) were mainly located in the area of cluster 1 (right side). The color of each node represents the average value of the interested parameter of all the patients included in the node. Please refer to the Supplemental Method for detailed interpretation of the topological graphs.
Figure 2
Figure 2
SHAP analysis plots for model interpretation. (A) Histogram of feature importance at the global level showed the input features in the order of relative importance: TR, MV prolapse, MV tethering, AFib or Aflutter, MV leaflet calcification, mitral annulus calcification, MV flail, prior MI, functional MR, degenerative MR and other etiologies. The clusters were color-coded (cluster 0: blue and cluster 1: red). Higher absolute mean SHAP value indicates more importance of the variable in contributing to the model output. (B) cluster 0 was characterized with higher proportion patients of none or mild TR, posterior MV prolapse, no MV tethering, no Afib or flutter, no leaflet calcification, no annulus calcification, posterior MV flail, and no previous MI. Cluster 1 had the opposite characters as found in (C)
Figure 3
Figure 3
Kaplan-Meier survival analysis of the 2 clusters. (A) Cluster 0 (blue line) had significantly better survival performance compared to cluster 1 (red line) in the development cohort (log-rank P<.001). (B) Similar survival difference was observed in the prospective validation cohort (log-rank P=.04).
Figure 4
Figure 4
The topological graph represents the MV morphology variables. The low-risk cluster (cluster 0) nodes were on the left side and the high-risk cluster nodes were on the right side, as shown in Figure 1. (A) Cluster 1 had higher proportions of anterior leaflet or bileaflet prolapse. (B) Cluster 1 had more patients with MV tethering, and cases with anterior (orange colored) or bileaflet tethering (red-colored) were mostly belong to cluster 1. (C) Cluster 0 predominantly had posterior leaflet flail cases (light green to white colored) compared to cluster 1. (D and E) Cluster 1 had higher proportions of patients with mitral annular and leaflet calcifications.
Supplemental Figure S1
Supplemental Figure S1
Supplemental Figure S2
Supplemental Figure S2
Supplemental Figure S3
Supplemental Figure S3
Supplemental Figure S4
Supplemental Figure S4
See this image and copyright information in PMC

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