Abstract
Background
Multiple valvular heart disease correlates with poor outcomes following transcatheter aortic valve replacement. Previous studies have focused on mitral regurgitation (MR) or tricuspid regurgitation (TR) individually, without comparing their long‐term effects. The impact of staged transcatheter edge‐to‐edge repair (TEER) remains unclear. We aimed to assess the prevalence and effects of severe multiple valvular heart disease (sMVHD) and evaluate the impact of staged TEER on outcomes.
Methods
Patients were recruited from 4 transcatheter aortic valve replacement centers. The primary cohort included 2823 patients to evaluate the prevalence of sMVHD. All patients were screened for additional valvular interventions; those undergoing TEER for severe MR (n=147) or TR (n=59) were included.
Results
Concomitant sMVHD was observed in 369 patients, with 208 having severe MR and 161 having severe TR. The 1‐year mortality rate was higher in patients with sMVHD compared with the overall cohort (9.0 versus 5.2 per 100 person‐years; P<0.01). Severe TR was associated with the highest 1‐year mortality rate, followed by severe MR and no or mild multiple valvular heart disease (13.3 versus 6.4 versus 3.9 per 100 person‐years; P<0.01). This difference persisted over 5 years (P<0.01). Patients undergoing staged TEER showed a reduced 1‐year mortality rate compared with conservative management (4.1 versus 12.1 per 100 person‐years; P<0.001). This trend continued over 5 years (P<0.001). Severe TR was independently associated with an increased mortality rate (hazard ratio, 1.79 [95% CI, 1.17–2.74]; P<0.01).
Conclusions
Persistent sMVHD was associated with an increased mortality rate following transcatheter aortic valve replacement, with severe TR posing a higher risk than severe MR. Staged TEER was associated with improved outcomes and warrants consideration in sMVHD.
Keywords: mitral regurgitation, multiple valvular heart disease, TAVR, TEER, transcatheter edge‐to‐edge repair, tricuspid regurgitation
Subject Categories: Valvular Heart Disease, Aortic Valve Replacement/Transcather Aortic Valve Implantation
Nonstandard Abbreviations and Acronyms
- AS
aortic stenosis
- MR
mitral regurgitation
- M‐TEER
mitral transcatheter edge‐to‐edge repair
- MVHD
multiple valvular heart disease
- PY
person‐years
- sMVHD
Severe multiple valvular heart disease
- TAVR
transcatheter aortic valve replacement
- TEER
transcatheter edge‐to‐edge repair
- TR
Tricuspid regurgitation
- T‐TEER
tricuspid transcatheter edge‐to‐edge repair
CLINICAL PERSPECTIVE.
What Is New?
This multicenter study highlights the high prevalence of concomitant multiple valvular heart disease among contemporary patients undergoing transcatheter aortic valve replacement, ranging from 5.7% for severe tricuspid regurgitation to 7.4% for severe mitral regurgitation.
Persistent severe multiple valvular heart disease was associated with increased short‐ and long‐term mortality rates following transcatheter aortic valve replacement, with severe tricuspid regurgitation posing a higher risk than severe mitral regurgitation.
Staged transcatheter edge‐to‐edge repair for severe mitral regurgitation or tricuspid regurgitation following transcatheter aortic valve replacement significantly reduced mortality rates, demonstrating potential to improve outcomes.
What Are the Clinical Implications?
A comprehensive diagnostic and therapeutic approach to concomitant severe mitral regurgitation and tricuspid regurgitation is crucial for improving outcomes in patients undergoing transcatheter aortic valve replacement.
Integrating staged transcatheter edge‐to‐edge repair into the treatment algorithm for selected patients may be warranted to address multiple valvular heart disease in the context of lifetime management.
Multiple valvular heart disease (MVHD), characterized by dysfunction in ≥2 different heart valves, is a prevalent condition among patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). 1 Concomitant mitral regurgitation (MR) and tricuspid regurgitation (TR) are observed in a significant proportion of these patients, with reported prevalence ranging from 11% to 37% for MR and 11% to 27% for TR. 2 , 3 , 4 , 5 Previous investigations have demonstrated increased short‐term mortality rates in patients undergoing TAVR with concomitant moderate to severe MR or TR compared with those with isolated AS. 5 , 6 , 7 , 8 However, the comprehensive, long‐term impact of MVHD on outcomes in these individuals remains unclear. Additionally, existing research predominantly focuses on the individual effects of concomitant MR or TR, without providing a comparative analysis of the impact of different entities of MVHD on outcome. Furthermore, the majority of studies in this field fail to differentiate between moderately impaired valve function and clinically significant severe valve dysfunction that may require interventional treatment. 5 , 9
In recent years, transcatheter valvular interventions for both severe MR and TR have significantly evolved, resulting in substantial improvements in functional status, quality of life, and survival of affected patients. 10 , 11 Specifically, transcatheter edge‐to‐edge repair (TEER) has demonstrated promising results in selected patient cohorts. 12 , 13 , 14 However, the efficacy of staged valvular interventions for concomitant MVHD in improving outcomes for patients with AS undergoing TAVR remains uncertain. Consequently, the current American and European guidelines for the management of valvular heart disease do not provide specific evidence‐based recommendations for clinical decision making in these cases. 15 , 16
To address these evidence gaps, we conducted a multicenter study to evaluate the prevalence of severe MVHD (sMVHD) within a contemporary, real‐world TAVR cohort. Our primary objective was to assess and compare the impact of concomitant severe MR and TR on outcomes at both 1 and 5 years after TAVR. Additionally, we aimed to examine the potential impact of staged TEER for managing persistent sMVHD in patients treated with TAVR.
Methods
Patient Population
Patients were recruited from 4 high‐volume TAVR centers in Germany. The primary study cohort consisted of 2823 consecutive patients undergoing TAVR with next‐generation transcatheter heart valves between January 2015 and December 2022. This representative cohort was used to evaluate the prevalence of sMVHD in a contemporary TAVR population and to assess and compare the clinical characteristics as well as the impact of severe MR and TR on outcomes following TAVR. Additionally, all patients were screened for staged valvular intervention. Patients who underwent additional staged TEER for severe MR (n=147) or TR (n=59) were included in this study.
Before the valvular intervention, all patients underwent a detailed preoperative evaluation and were discussed by the local interdisciplinary heart team. The study complied with Good Clinical Practice guidelines and received approval from the local ethics committee of the individual centers. All patients provided written informed consent. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Echocardiographic Assessment, Study End Point and Follow‐Up
Transthoracic and transesophageal echocardiography were performed in all patients before the TAVR procedure. Before discharge and at 30 to 90 days after TAVR, transthoracic echocardiography was used to evaluate transcatheter heart valve function and to determine whether significant MR or TR persisted despite the altered hemodynamics following TAVR. The severity of MR and TR was determined using a multiparametric approach, including qualitative, semiquantitative, and quantitative echocardiographic assessments, following European and American guidelines. 17 , 18 Concomitant persistent MR and TR were classified in accordance with current recommendations as no/trace, mild, moderate, and severe. 19 In cases of combined mitral and tricuspid valve dysfunction, the leading pathogenesis was prioritized in classification. Patients considered for additional staged TEER underwent comprehensive preinterventional transthoracic and transesophageal echocardiographic assessments to determine the severity and pathogenesis of valve dysfunction and to assess anatomic feasibility before the procedure.
The primary end points included 1‐ and 5‐year all‐cause death following TAVR. Key secondary end points included 30‐day all‐cause death, stroke, myocardial infarction, major bleeding complications, and acute kidney injury at 30 days according to the Valve Academic Research Consortium 3 definition criteria. 20 Follow‐up data were collected during routine outpatient visits and via standardized telephone interviews with the referring cardiologists or general practitioners.
Statistical Analysis
Continuous variables are presented as means±SD if normally distributed, or as the median and interquartile range (IQR) if not normally distributed. Normality of data distribution was assessed using the Kolmogorov–Smirnov test. Continuous variables were analyzed using either Student's t test or the Mann–Whitney U test, depending on their distribution. For analyses involving >2 groups, either simple linear models or the Kruskal–Wallis test were used. Categorical variables are presented as absolute numbers and percentages. Fisher's exact test was used to evaluate differences in categorical variables.
The primary and secondary outcomes, stratified by the presence of concomitant sMVHD, were estimated using the Kaplan–Meier method, with follow‐up time beginning after the TAVR procedure. The log‐rank test was applied to determine statistical significance. The impact of a staged TEER on the outcomes was assessed using a landmark analysis, with the follow‐up period starting after the additional valvular intervention. To identify statistically significant predictors of cumulative death, parameters were first examined in a univariable analysis. Significant variables with a P value ≤0.05 were then included in a multivariable Cox proportional hazards model. A sensitivity analysis including treatment center as a fixed‐effect covariate was performed to account for potential site‐level variability. The inclusion of center did not materially alter effect estimates or significance levels. Model comparison using the likelihood ratio test (P=0.89) confirmed that center adjustment did not improve model fit, supporting the robustness of the simplified multivariable model.
The statistical analyses were conducted using SPSS version 29 (IBM Corporation, Somers, NY) and Stata version 14.2 (StataCorp LLC, College Station, TX). A 2‐tailed probability value of ≤0.05 was considered statistically significant.
Results
The baseline characteristics of the patients are summarized in Table 1. The overall cohort consisted of 2823 patients with AS undergoing TAVR, among whom 1645 (58.3%) had no concomitant or only mild additional MVHD. Persistent concomitant sMVHD was observed in 369 (13.1%) patients, with 208 (7.4%) having severe MR, and 161 (5.7%) having severe TR. The overall study population had a mean age of 80.9±6.2 years with an average EuroSCORE II of 3.7% (IQR, 2.2–6.3) and a Society of Thoracic Surgeons Predicted Risk of Mortality of 3.3% (IQR, 2.2–4.9), indicating a low to intermediate surgical risk. Common comorbidities included coronary artery disease (61.0%), atrial fibrillation (45.6%), and chronic obstructive pulmonary disease (15.7%). Cardiovascular risk factors, such as hypertension, dyslipidemia, and diabetes were prevalent, affecting 85.8%, 65.0%, and 30.4% of the cohort, respectively. The overall mean left ventricular ejection fraction was 55.1±11.5%, as detailed in Table 2. Moderate MR was observed in 739 (26.2%) patients, while moderate TR was present in 505 (17.9%) patients. The mean TR pressure gradient was 35.4±14.7 mm Hg, and the tricuspid annular plane systolic excursion measured 21.0±7.5 mm.
Table 1.
Baseline Characteristics: Comparison Between Severe MR and Severe TR
| Overall cohort (n=2823) | No/mild MVHD (n=1645) | Concomitant severe MR (n=208) | Concomitant severe TR (n=161) | P value | |
|---|---|---|---|---|---|
| Age, y | 80.9±6.2 | 80.3±6.3 | 81.3±6.1 | 83.0±5.6 | <0.01 |
| Body mass index, kg/m2 | 26.3±4.5 | 26.5±4.3 | 25.3±4.1 | 24.8±4.1 | 0.28 |
| Female sex, n (%) | 1286 (45.6) | 667 (40.5) | 95 (45.7) | 95 (59.0) | 0.01 |
| EuroSCORE II, % | 3.7 (2.2–6.3) | 3.0 (2.0–5.3) | 4.9 (3.1–8.1) | 5.7 (4.1–9.4) | <0.01 |
| STS‐PROM, % | 3.3 (2.2–4.9) | 2.8 (2.0–4.2) | 4.0 (2.7–5.5) | 5.0 (3.8–6.8) | <0.01 |
| COPD, n (%) | 444 (15.7) | 269 (16.4) | 37 (17.8) | 27 (16.8) | 0.89 |
| Coronary artery disease, n (%) | 1721 (61.0) | 1005 (61.1) | 118 (56.7) | 100 (62.1) | 0.52 |
| Myocardial infarction, n (%) | 329 (11.7) | 182 (11.1) | 33 (15.9) | 20 (12.4) | 0.37 |
| Previous PCI, n (%) | 1139 (40.3) | 694 (42.2) | 85 (40.9) | 63 (39.1) | 0.59 |
| Previous CABG, n (%) | 347 (12.3) | 183 (11.1) | 33 (15.9) | 32 (19.8) | 0.41 |
| Atrial fibrillation, n (%) | 1286 (45.6) | 586 (35.6) | 131 (63.0) | 137 (85.1) | <0.01 |
| Previous stroke/TIA, n (%) | 290 (10.3) | 158 (9.6) | 23 (11.1) | 29 (18.0) | 0.07 |
| Hypertension, n (%) | 2422 (85.8) | 1403 (85.3) | 171 (82.2) | 141 (87.5) | 0.19 |
| Diabetes, n (%) | 858 (30.4) | 525 (31.9) | 44 (21.2) | 46 (28.6) | 0.11 |
| Dyslipidemia, n (%) | 1836 (65.0) | 1075 (65.3) | 114 (54.8) | 91 (56.5) | 0.75 |
| Peripheral artery disease, n (%) | 1175 (41.6) | 670 (40.7) | 92 (44.2) | 74 (46.0) | 0.75 |
| Carotid artery disease, n (%) | 1114 (39.5) | 660 (40.1) | 86 (41.3) | 70 (43.5) | 0.75 |
| Permanent pacemaker, n (%) | 351 (12.4) | 171 (10.4) | 37 (17.8) | 38 (23.6) | 0.24 |
| Creatinine, mg/dL | 1.1 (0.9–1.4) | 1.1 (0.9–1.4) | 1.2 (1.0–1.5) | 1.4 (1.0–1.8) | 0.10 |
| Hemoglobin, g/dL | 11.7±1.8 | 11.9±1.7 | 11.4±2.0 | 11.1±1.9 | 0.16 |
| Leukocytes, g/L | 7.5±2.2 | 7.4±2.1 | 7.5±2.0 | 7.3±2.3 | 0.28 |
| Troponin, pg/mL |
24.8 (16.8–40.6) |
23.1 (15.6–37.7) |
30.9 (19.8–52.6) |
34.6 (22.2–51.9) |
0.69 |
| NT‐proBNP, pg/mL | 1690 (664–3943) | 1126 (489–2797) | 3422 (1704–7471) | 3571 (1669–7573) | 0.99 |
| CKD stage ≥4, n (%) | 240 (8.5) | 110 (6.7) | 24 (11.5) | 33 (20.5) | 0.02 |
| Dialysis, n (%) | 58 (2.1) | 27 (1.6) | 10 (4.8) | 3 (1.9) | 0.16 |
P values are derived from comparisons between patients with severe MR and those with severe TR. CABG indicates coronary artery bypass grafting; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; MR, mitral regurgitation; MVHD; multiple valvular heart disease; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; PCI, percutaneous coronary intervention; STS‐PROM, Society of Thoracic Surgeons Predicted Risk of Mortality; TIA, transient ischemic attack; and TR, tricuspid regurgitation.
Table 2.
Baseline Echocardiographic Parameters: Comparison Between Severe MR and Severe TR
| Overall cohort (n=2823) | No/mild MVHD (n=1645) | Concomitant severe MR (n=208) | Concomitant severe TR (n=161) | P value | |
|---|---|---|---|---|---|
| Left ventricular ejection fraction, % | 55.1±11.5 | 56.2±10.9 | 51.9±12.9 | 53.2±11.5 | 0.33 |
| Aortic valve area, cm2 | 0.75±0.18 | 0.78±0.17 | 0.72±0.18 | 0.71±0.19 | 0.61 |
| Mean PG in aortic valve, mm Hg | 40.2±14.5 | 41.0±14.2 | 37.1±10.6 | 31.1±12.1 | <0.01 |
| Maximum PG in aortic valve, mm Hg | 69.4±22.9 | 70.6±21.6 | 66.6±20.7 | 51.4±15.1 | <0.01 |
| Moderate MR, n (%) | 739 (26.2) | 0 (0) | 0 (0) | 78 (48.4) | <0.01 |
| Moderate TR, n (%) | 505 (17.9) | 0 (0) | 102 (49.0) | 0 (0) | <0.01 |
| TR pressure gradient, mm Hg | 35.4±14.7 | 30.9±12.3 | 42.9±14.2 | 46.5±16.8 | 0.04 |
| Stroke volume, mL | 72.6±24.0 | 76.5±23.5 | 67.1±25.3 | 61.2±21.9 | 0.14 |
| Vena contracta width, cm | 0.74±0.11 | 0.91±0.21 | <0.01 | ||
| PISA radius, cm | 0.79±0.12 | 0.89±0.18 | <0.01 | ||
| EROA, cm2 | 0.38±0.07 | 0.51±0.19 | <0.01 | ||
| Regurgitant volume, mL/beat | 48.54±11.79 | 52.83±13.49 | 0.12 | ||
| TAPSE, mm | 21.0±7.5 | 21.5±5.5 | 20.6±5.4 | 18.0±5.7 | 0.01 |
| Left atrial volume, mL | 50.0 (35.0–75.2) | 35.0 (26.5–47.0) | 83.7 (58.4–110.0) | 91.0 (69.4–119.2) | 0.34 |
| Right atrial area, cm2 | 18.0 (15.0–21.7) | 17.0 (15.0–18.0) | 18.7 (13.5–22.1) | 25.5 (20.0–31.0) | <0.01 |
| Inferior vena cava, mm | 1.4±0.6 | 1.3±0.5 | 1.7±0.5 | 1.9±0.6 | 0.04 |
P values are derived from comparisons between patients with severe MR and those with severe TR. EROA indicates effective regurgitant orifice area; MR, mitral regurgitation; MVHD; multiple valvular heart disease; PG, pressure gradient; PISA, proximal isovelocity surface area; TAPSE, tricuspid annular plane systolic excursion; and TR, tricuspid regurgitation.
Comparison Between Patients With Severe MR and TR
Patients with severe MR were slightly younger than those with severe TR (81.3±6.1 years versus 83.0±5.6 years; P<0.01). The prevalence of female patients was significantly lower in the severe MR group (45.7% versus 59.0%; P=0.01). Additionally, the median EuroSCORE II and the Society of Thoracic Surgeons Predicted Risk of Mortality scores were significantly lower in patients with severe MR compared with those with severe TR (P<0.01), indicating a lower surgical risk. Patients with severe TR had higher rates of atrial fibrillation (85.1% versus 61.1%; P<0.01) and chronic kidney disease stage ≥4 (20.5% versus 11.5%; P=0.02). However, no significant differences were observed in the body mass index (P=0.28) or the prevalence of other comorbidities, including coronary artery disease (P=0.52), chronic obstructive pulmonary disease (P=0.89), or diabetes (P=0.11). Moreover, there were no significant differences in the baseline levels of hemoglobin, leukocytes, troponin, or NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) between the 2 groups (P≥0.16).
The multiparametric echocardiographic analysis confirmed the severity of MR and TR in both groups. For MR, the vena contracta width, proximal isovelocity surface area radius, effective regurgitant orifice area, and regurgitant volume were 0.74±0.11 cm, 0.79±0.12 cm, 0.38±0.07 cm2, and 48.54±11.79 mL/beat, respectively. For TR, the corresponding values were 0.91±0.21 cm, 0.89±0.18 cm, 0.51±0.19 cm2, and 52.83±13.49 mL/beat, respectively. Moreover, echocardiographic assessments at baseline revealed a comparable left ventricular ejection fraction between patients with severe MR and TR (51.9±12.9% versus 53.2±11.5%; P=0.33). However, the TR pressure gradient was higher in patients with TR (46.5±16.8 mm Hg versus 42.9±14.2 mm Hg; P=0.04), whereas tricuspid annular plane systolic excursion was higher in patients with MR (20.6±5.4 mm versus 18.0±5.7 mm; P=0.01). Additionally, patients with TR had larger right atrial areas (25.5 cm2 versus 18.7 cm2; P<0.01) and a slightly larger inferior vena cava diameter (1.9±0.6 mm versus 1.7±0.5 mm; P=0.04).
Comparison Between Patients With sMVHD and Staged TEER
The baseline clinical characteristics of patients undergoing TAVR with concomitant severe MR or TR compared with those who underwent staged TEER of the mitral and tricuspid valve (M‐TEER, T‐TEER), as assessed before TAVR, are shown in Table 3. For patients with severe MR (n=150) compared with those undergoing staged M‐TEER (n=147), no significant differences were observed in age (81.4±6.4 years versus 81.1±5.4 years; P=0.64) or average surgical risk score (P=0.09). Similarly, there were no significant differences in the body mass index (P=0.18) or the prevalence of comorbidities such as chronic obstructive pulmonary disease, coronary artery disease, or atrial fibrillation between the 2 groups (P>0.05). However, patients who underwent staged M‐TEER had significantly lower postprocedural levels of troponin (26.0 [IQR, 17.0–37.0] pg/mL versus 32.2 [IQR, 20.9–51.5] pg/mL; P=0.03) and NT‐proBNP (2066 [IQR, 1234–4872] pg/mL versus 3707 [IQR, 1957–8152] pg/mL; P<0.01), measured after the TEER procedure, compared with those with persistent severe MR.
Table 3.
Baseline Characteristics: Comparison Between sMVHD and Staged TEER
| Concomitant severe MR (n=150) | Staged M‐TEER (n=147) | P value | Concomitant severe TR (n=124) | Staged T‐TEER (n=59) | P value | |
|---|---|---|---|---|---|---|
| Age, y | 81.4±6.4 | 81.1±5.4 | 0.64 | 83.7±5.6 | 80.7±4.8 | <0.01 |
| Body mass index, kg/m2 | 25.1±4.2 | 25.7±3.8 | 0.18 | 24.9±4.4 | 25.3±4.2 | 0.56 |
| Female sex, n (%) | 75 (50) | 70 (47.6) | 0.73 | 75 (60.5) | 31 (52.5) | 0.34 |
| EuroSCORE II, n (%) | 4.9 (3.2–7.7) | 6.4 (3.0–10.6) | 0.09 | 5.9 (4.0–8.9) | 5.2 (3.6–9.0) | 0.66 |
| STS‐PROM, n (%) | 4.1 (2.8–5.6) | 4.4 (2.9–8.0) | 0.09 | 5.2 (4.0–6.8) | 4.8 (3.2–5.9) | 0.10 |
| COPD, n (%) | 29 (19.3) | 24 (16.3) | 0.55 | 22 (17.7) | 7 (11.9) | 0.39 |
| Coronary artery disease, n (%) | 84 (56.0) | 87 (59.2) | 0.34 | 78 (62.9) | 36 (61.0) | 0.87 |
| Myocardial infarction, n (%) | 23 (15.3) | 30 (20.4) | 0.23 | 14 (11.3) | 9 (15.3) | 0.48 |
| Previous PCI, n (%) | 59 (39.3) | 59 (40.1) | 0.59 | 49 (39.5) | 24 (40.7) | 1.0 |
| Previous CABG, n (%) | 19 (12.7) | 30 (20.4) | 0.06 | 23 (18.5) | 10 (16.9) | 0.84 |
| Atrial fibrillation, n (%) | 92 (61.3) | 105 (71.4) | 0.09 | 105 (84.7) | 50 (84.7) | 1.0 |
| Previous stroke/TIA, n (%) | 15 (10.0) | 15 (10.2) | 1.0 | 21 (16.9) | 9 (15.3) | 0.83 |
| Arterial hypertension, n (%) | 121 (80.7) | 127 (86.4) | 0.21 | 108 (87.1) | 54 (91.5) | 0.46 |
| Diabetes, n (%) | 31 (20.7) | 43 (29.3) | 0.11 | 33 (26.6) | 20 (33.9) | 0.38 |
| Dyslipidemia, n (%) | 80 (53.3) | 66 (44.9) | 0.38 | 69 (55.6) | 38 (64.4) | 0.34 |
| Peripheral artery disease, n (%) | 69 (46.0) | 55 (37.4) | 0.16 | 56 (45.2) | 21 (35.6) | 0.26 |
| Carotid artery disease, n (%) | 67 (44.7) | 51 (34.7) | 0.10 | 52 (41.9) | 22 (37.3) | 0.63 |
| Permanent Pacemaker, n (%) | 27 (18.0) | 34 (23.1) | 0.25 | 32 (25.8) | 9 (15.3) | 0.13 |
| Creatinine, mg/dL | 1.2 (0.9–1.6) | 1.1 (0.9–1.4) | 0.20 | 1.4 (1.0–1.8) | 1.2 (0.8–1.7) | 0.16 |
| Hemoglobin, g/dL | 11.5±2.1 | 11.1±2.2 | 0.16 | 11.1±1.9 | 10.8±2.2 | 0.42 |
| Leukocytes, g/L | 7.4±2.0 | 7.7±2.1 | 0.13 | 7.5±2.4 | 7.0±2.6 | 0.17 |
| Troponin, pg/mL | 32.2 (20.9–51.5) | 26.0 (17.0–37.0) | 0.03 | 34.6 (22.7–53.9) | 27.0 (13.2–48.8) | 0.05 |
| NT‐proBNP, pg/mL | 3707 (1957–8152) | 2066 (1234–4872) | <0.01 | 3785 (1695–8347) | 2128 (1353–4321) | 0.04 |
| CKD stage ≥4, n (%) | 15 (10.0) | 15 (10.2) | 1.0 | 26 (21.0) | 11 (18.6) | 0.84 |
| Dialysis, n (%) | 7 (4.7) | 3 (2.0) | 0.34 | 3 (2.4) | 1 (1.7) | 1.0 |
CABG indicates coronary artery bypass grafting; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; M‐TEER, mitral transcatheter mitral valve repair; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; PCI, percutaneous coronary intervention; sMVHD, severe multiple valvular heart disease; STS‐PROM, Society of Thoracic Surgeons Predicted Risk of Mortality; TEER, transcatheter edge‐to‐edge repair; TIA, transient ischemic attack; and T‐TEER, tricuspid transcatheter tricuspid valve repair.
In contrast, when comparing patients with concomitant severe TR (n=124) with those who underwent staged T‐TEER (n=59), a significant difference was observed in average age, with patients undergoing T‐TEER being younger (80.7±4.8 years versus 83.7±5.6 years; P<0.01). However, there were no significant differences in body mass index, sex distribution, or prevalence of comorbidities between the 2 groups (P>0.05). Notably, patients who underwent staged T‐TEER showed significantly lower postprocedural levels of troponin (27.0 [IQR, 13.2–48.8] pg/mL versus 34.6 [IQR, 22.7–53.9] pg/mL; P=0.05) and NT‐proBNP (2128 [IQR, 1353–4321] pg/mL versus 3785 [IQR, 1695–8347] pg/mL; P=0.04), measured after the TEER procedure, compared with those with persistent severe TR.
Echocardiographic evaluation before the TEER procedure showed no significant differences in left and right ventricular function or left and right atrial dimensions among patients with sMVHD who underwent staged TEER and those who did not. Moreover, the TR pressure gradient was comparable between the groups, as patients with significant precapillary pulmonary hypertension identified through right heart catheterization were excluded from undergoing TEER (Table 4). However, significant differences were observed in the prevalence of moderate valve dysfunction between the groups, with 56.0% of severe MR patients having moderate TR compared with 29.9% in the staged M‐TEER group (P<0.01). Similarly, among patients with severe TR, 51.6% had moderate MR compared with 35.6% in the staged T‐TEER group (P=0.04).
Table 4.
Echocardiographic Parameters: Comparison Between sMVHD and Staged TEER
| Concomitant severe MR (n=150) | Staged M‐TEER (n=147) | P value | Concomitant severe TR (n=124) | Staged T‐TEER (n=59) | P value | |
|---|---|---|---|---|---|---|
| Left ventricular ejection fraction, % | 51.5±13.3 | 53.9±13.2 | 0.15 | 53.3±11.1 | 54.9±11.2 | 0.37 |
| Moderate MR, n (%) | 0 (0) | 0 (0) | 1.0 | 64 (51.6) | 21 (35.6) | 0.04 |
| Moderate TR, n (%) | 84 (56.0) | 44 (29.9) | <0.01 | 0 (0) | 0 (0) | 1.0 |
| TR pressure gradient, mm Hg | 43.0±14.2 | 43.2±15.3 | 0.47 | 46.4±16.8 | 41.6±17.0 | 0.12 |
| Stroke volume, mL | 65.0±24.0 | 72.2±28.1 | 0.25 | 58.8±22.4 | 67.5±18.7 | 0.13 |
| TAPSE, mm | 20.2±5.0 | 21.9±6.5 | 0.29 | 18.4±5.8 | 17.1±5.4 | 0.40 |
| Left atrial volume, mL | 79.1 (57.6–105.4) | 104.6 (81.3–112.0) | 0.15 | 94.4 (70.6–118.2) | 84.8 (60.0–120.0) | 0.56 |
| Right atrial area, cm2 | 17.5 (13.5–21.5) | 21.4 (14.1–28.1) | 0.32 | 24.0 (20.2–31.0) | 26.0 (18.5–32.0) | 0.68 |
| Inferior vena cava, mm | 1.8±0.6 | 1.6±0.4 | 0.17 | 1.9±0.7 | 2.0±0.6 | 0.62 |
MR indicates mitral regurgitation; M‐TEER, mitral transcatheter mitral valve repair; PG, pressure gradient; sMVHD, severe multiple valvular heart disease; TAPSE, tricuspid annular plane systolic excursion; TEER, transcatheter edge‐to‐edge repair; TR, tricuspid regurgitation; and T‐TEER, tricuspid transcatheter tricuspid valve repair.
Staged TEER procedures demonstrated high success rates, with no periprocedural deaths or conversions to surgery, as presented in Table S1. In both the staged M‐TEER and T‐TEER groups, all patients experienced successful device deployment and regurgitation reduction by at least 1 grade. Postprocedural mean gradients were low in both groups, with slightly higher residual regurgitation grades in the T‐TEER group.
Clinical Outcomes
In the overall cohort, the 1‐ and 5‐year all‐cause mortality rates were 5.2 and 13.2 per 100 person‐years (PY), respectively (Table 5). The 1‐year mortality rate was significantly higher in patients with sMVHD (9.0 per 100 PY) compared with the overall cohort (5.2 per 100 PY; P<0.01). Notably, the highest 1‐year mortality rate was observed in patients with severe TR (13.3 per 100 PY) followed by patients with severe MR (6.4 per 100 PY) and those with no concomitant or mild MVHD (3.9 per 100 PY; P<0.01).
Table 5.
Clinical End Points
| Overall cohort (n=2823) | No/mild MVHD (n=1645) | Concomitant severe MR (n=208) | Concomitant severe TR (n=161) | P value | |
|---|---|---|---|---|---|
| Primary end point, n (IR/100 PY) | |||||
| 1‐y all‐cause death | 263 (5.2) | 107 (3.9) | 27 (6.4) | 34 (13.3) | <0.01 |
| 5‐y all‐cause death | 671 (13.2) | 293 (10.6) | 70 (16.7) | 71 (27.8) | <0.01 |
| Key secondary end points at 30 days, n (IR/100 PY) | |||||
| Major bleeding complication | 96 (1.9) | 64 (2.3) | 8 (1.9) | 6 (2.3) | 1.0 |
| Major vascular complication | 40 (0.8) | 19 (0.7) | 3 (0.7) | 4 (1.6) | 0.47 |
| Minor vascular complication | 451 (8.9) | 276 (10.0) | 25 (6.0) | 22 (8.6) | 0.64 |
| Stroke | 40 (0.8) | 22 (0.8) | 4 (1.0) | 2 (0.8) | 1.0 |
| Myocardial infarction | 6 (0.1) | 4 (0.1) | 0 | 0 | 1.0 |
| Acute kidney injury | 270 (5.3) | 142 (5.1) | 22 (5.2) | 23 (9.0) | 0.26 |
| New permanent pacemaker | 282 (5.5) | 160 (5.8) | 21 (5.0) | 15 (5.9) | 1.0 |
| Paravalvular leakage ≥ II | 26 (0.5) | 8 (0.9) | 4 (1.0) | 2 (0.8) | 0.68 |
| 30‐d all‐cause death | 74 (1.5) | 41 (1.5) | 6 (1.4) | 8 (3.1) | 0.41 |
IR indicates incidence rate; MR, mitral regurgitation; MVHD; multiple valvular heart disease; PY, person‐years; and TR, tricuspid regurgitation.
According to Kaplan–Meier analysis, the estimated probability of all‐cause death at 1 year was 29.3% in patients with severe TR, 17.0% in those with severe MR, and 10.1% in those with no or mild MVHD (P<0.01), as shown in Figure 1A. This difference was persistent over a follow‐up period of 5 years following TAVR, with mortality rates of 27.8, 16.7, and 10.6 per 100 PY in patients with severe TR, severe MR, and no or mild MVHD, respectively (P<0.01). Consistently, the Kaplan–Meier estimated probability of all‐cause death at 5 years was 77.2% for patients with severe TR, 59.2% for those with severe MR, and 42.2% for those with no or mild MVHD (P<0.01), as illustrated in Figure 1B.
Figure 1. One‐ and five‐year mortality according to multiple valvular heart disease.
A, One‐year mortality rate according to MVHD. One‐year mortality rate among patients undergoing TAVR with concomitant severe TR compared with those with severe MR, and patients with no concomitant or mild MVHD. B, Five‐year mortality rate according to MVHD. Five‐year mortality rate among patients undergoing TAVR with concomitant severe TR compared with those with severe MR, and patients with no concomitant or mild MVHD. MR indicates mitral regurgitation; MVHD, multiple valvular heart disease; TAVR, transcatheter aortic valve replacement; and TR, tricuspid regurgitation.
Regarding key secondary end points, no significant differences were observed between patients with concomitant sMVHD and those with no concomitant or mild MVHD. Incidence rates were comparable across groups for 30‐day all‐cause death (P=0.41), major bleeding complication (P=1.0), major vascular complication (P=0.47), stroke (P=1.0), and acute kidney injury (P=0.26).
Impact of Staged TEER on Outcomes
The multicenter landmark analyses on clinical outcomes among patients undergoing TAVR who underwent additional staged TEER, compared with those with persistent sMVHD on guideline‐directed medical therapy, revealed notable differences in survival rates between the groups: The 1‐year all‐cause mortality rate was significantly lower in the staged TEER group (4.1 per 100 PY) compared with patients with concomitant sMVHD (12.1 per 100 PY; P<0.001). This trend continued at the 5‐year follow‐up, with a mortality rate of 11.6 per 100 PY in the staged TEER group versus 25.8 per 100 PY in the sMVHD group (P<0.001).
Specifically, patients who underwent staged M‐TEER had notably lower 1‐year mortality rates (3.6 per 100 PY) compared with those with concomitant severe MR (8.9 per 100 PY, P=0.004). At the 5‐year mark, the mortality rate for patients who underwent staged M‐TEER was 11.7 per 100 PY, significantly lower than the rate of 20.8 per 100 PY observed in the severe MR group (P=0.006). The Kaplan–Meier estimated probability of the 5‐year mortality rate was 45.5% in patients undergoing M‐TEER, compared with 69.5% in those with severe MR (P<0.01), as illustrated in Figure 2A.
Figure 2. Five‐year mortality according to staged transcatheter edge‐to‐edge repair.
A, Five‐year mortality rate among patients undergoing TAVR who underwent staged M‐TEER compared with those with persistent severe MR. B, Five‐year mortality rate according to staged T‐TEER. Five‐year mortality rate among patients undergoing TAVR who underwent staged T‐TEER compared with those with persistent severe TR. MR indicates mitral regurgitation; M‐TEER, mitral transcatheter edge‐to‐edge repair; TAVR, transcatheter aortic valve replacement; TR, tricuspid regurgitation; and T‐TEER, tricuspid transcatheter edge‐to‐edge repair.
Similarly, the 1‐year mortality rate was markedly lower in the staged T‐TEER group (5.8 per 100 PY) compared with patients with concomitant severe TR (16.8 per 100 PY; P=0.003). This difference continued over the 5‐year follow‐up period, with a mortality rate of 11.5 per 100 PY in the T‐TEER group versus 33.0 per 100 PY in the severe TR group (P<0.001). According to Kaplan–Meier analysis, the estimated 5‐year mortality rate probability was 48.5% in patients who underwent T‐TEER, compared with 82.2% in those with persistent severe TR (P<0.01), as presented in Figure 2B.
Predictors of Clinical Outcomes
Univariable and multivariable analyses revealed that only hemoglobin (hazard ratio [HR], 0.90 [95% CI, 0.85–0.95]; P<0.01), acute kidney injury (HR, 1.77 [95% CI, 1.26–2.47]; P<0.01), and concomitant severe TR (HR, 1.79 [95% CI, 1.17–2.74]; P<0.01) were statistically significantly associated with the 1‐year mortality rate, as shown in Table 6.
Table 6.
Predictors of 1‐Year Death
| Univariable analysis | Multivariable analysis | |||||
|---|---|---|---|---|---|---|
| P value | HR | 95% CI | P value | HR | 95% CI | |
| Age | 0.07 | 1.02 | 0.99–1.04 | |||
| Sex | 0.05 | 1.28 | 1.00–1.65 | 0.21 | 1.19 | 0.91–1.55 |
| Left ventricular ejection fraction | 0.01 | 0.99 | 0.98–1.0 | 0.75 | 1.00 | 1.0–1.01 |
| CKD stage ≥4 | <0.01 | 2.01 | 1.55–2.63 | 0.14 | 1.41 | 0.88–2.25 |
| Dialysis | 0.04 | 1.92 | 1.05–3.50 | 0.18 | 0.54 | 0.22–1.34 |
| Acute kidney injury | <0.01 | 2.34 | 1.69–3.23 | <0.01 | 1.77 | 1.26–2.47 |
| COPD | <0.01 | 1.51 | 1.11–2.04 | 0.08 | 1.32 | 0.97–1.79 |
| Coronary artery disease | 0.10 | 1.24 | 0.96–1.60 | |||
| Myocardial infarction | 0.01 | 1.71 | 1.23–2.37 | 0.07 | 1.39 | 0.99–1.96 |
| Previous CABG | 0.06 | 1.37 | 0.99–1.89 | |||
| Atrial fibrillation | <0.01 | 1.25 | 1.13–1.39 | 0.22 | 1.08 | 0.96–1.21 |
| Creatinine | <0.01 | 1.30 | 1.18–1.44 | 0.41 | 1.10 | 0.88–1.37 |
| Hemoglobin | <0.01 | 0.88 | 0.83–0.92 | <0.01 | 0.90 | 0.85–0.95 |
| Troponin | 0.01 | 1.00 | 1.00–1.01 | 0.09 | 1.00 | 0.99–1.00 |
| NT‐proBNP | 0.01 | 1.00 | 1.00–1.01 | 0.17 | 1.00 | 0.99–1.00 |
| Mean PG in aortic valve | <0.01 | 0.98 | 0.97–0.99 | 0.07 | 0.99 | 0.97–1.00 |
| Maximum PG in aortic valve | <0.01 | 0.99 | 0.98–1.00 | 0.76 | 1.0 | 0.99–1.01 |
| TR pressure gradient | <0.01 | 1.02 | 1.00–1.02 | 0.25 | 1.0 | 1.0–1.02 |
| TAPSE | 0.18 | 0.96 | 0.90–1.02 | |||
| Right atrial area | 0.77 | 1.00 | 0.98–1.03 | |||
| Left atrial volume | 0.13 | 1.01 | 1.00–1.01 | |||
| Inferior vena cava | <0.01 | 1.72 | 1.29–2.30 | 0.17 | 1.23 | 0.90–1.64 |
| Severe mitral regurgitation | <0.01 | 1.25 | 1.10–1.42 | 0.65 | 0.96 | 0.82–1.14 |
| Severe tricuspid regurgitation | <0.01 | 2.55 | 1.80–3.61 | <0.01 | 1.79 | 1.17–2.74 |
CABG indicates coronary artery bypass grafting; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; HR, hazard ratio; PG, pressure gradient; STS‐PROM, Society of Thoracic Surgeons Predicted Risk of Mortality; TAPSE, tricuspid annular plane systolic excursion; and TR, tricuspid regurgitation.
While significant in the univariable analysis, concomitant severe MR (HR, 1.25 [95% CI, 1.10–1.42]; P<0.01), chronic kidney disease stage ≥4 (HR, 2.01 [95% CI, 1.55–2.63]; P<0.01) and atrial fibrillation (HR, 1.25 [95% CI, 1.13–1.39]; P<0.01) showed no significant association with the outcome in multivariable analyses.
Discussion
The principal findings of the present study, which undertook a comprehensive assessment of the prevalence and management of MVHD among patients undergoing TAVR, are as follows:
There is a notable prevalence of concomitant sMVHD among contemporary patients undergoing TAVR, ranging from 5.7% for severe TR to 7.4% for severe MR.
Persistent sMVHD correlates with increased short‐ and long‐term mortality rates in patients with AS undergoing TAVR. Notably, concomitant severe TR was associated with higher mortality rates compared with severe MR.
Staged TEER for concomitant sMVHD demonstrated potential benefits in improving patient outcomes.
The insights gained from this contemporary cohort of 2823 patients undergoing TAVR significantly enhance our understanding of the epidemiology and clinical implications of sMVHD in this population. The differentiated assessment of the prevalence of MVHD, considering the severity grades of valve dysfunction, and the comparative analysis of their effects on outcomes, provides novel insights into clinical characteristics and complexity of the disease.
The present study revealed a high prevalence of concomitant moderate to severe MR and TR among patients with AS undergoing TAVR, with rates of 33.5% and 23.6%, respectively. Notably, the rate of clinically significant, severe valve dysfunction was 7.4% for the mitral valve and 5.7% for the tricuspid valve. These findings align with and expand upon existing research in this domain. For instance, Witberg et al 8 reported moderate to severe MR in 27.2% of 7303 patients, while Mavromatis et al4 found moderate MR in 31.3% and severe MR in 5.5% of 11 104 patients. The Society of Thoracic Surgeons–American College of Cardiology Transcatheter Valve Therapy Registry identified a prevalence of moderate and severe TR at 19.3% and 5.0%, respectively. 21 Another study involving 2008 patients reported a prevalence of 12.1% for moderate TR and 5.3% for severe TR. 22 While these studies have contributed valuable insights, they have primarily focused on evaluating either the mitral or tricuspid valve, mainly assessing their prognostic impact. In contrast, our study adopts a holistic approach, starting with a multiparametric assessment of concomitant MVHD and evaluating temporary changes of the valvular dysfunction severity due to altered hemodynamics following TAVR. Additionally, it provides insights into the clinical, laboratory, and echocardiographic characteristics of these patients. Our study reveals that patients with severe TR were, on average, 2 years older and more frequently women compared with those with severe MR (P≤0.01). This aligns with existing evidence demonstrating an increasing prevalence of TR with age and identifying female sex as an independent predictor of severity. 23 Additionally, patients with severe TR had significantly higher surgical risk scores (P<0.01), as reflected in a 22% higher rate of atrial fibrillation (P<0.01). These observations are consistent with previous research indicating that atrial fibrillation and right ventricular enlargement can lead to tricuspid annular dilation, thereby worsening TR severity. 6 The subsequent pulmonary hypertension results in progressive right ventricular dysfunction and right atrial enlargement. 24 , 25 Consistently, echocardiographic assessment of our study cohort revealed an 8.4% increase of the TR pressure gradient and a 12% decrease of tricuspid annular plane systolic excursion in patients with TR compared with patients with MR (P≤0.04). Moreover, severe TR was associated with a significant enlargement of the right atrial area and the inferior vena cava diameter by 36.4% and 11.8%, respectively (P≤0.04).
Regarding clinical outcomes, the findings of this study underline the significant implication of concurrent native valvular dysfunction in individuals undergoing TAVR. Patients with persistent sMVHD experienced a 1.7‐fold higher mortality rate at 1 year compared with the overall cohort, and a 2.3‐fold increase compared with those with no or mild MVHD (P<0.01). Importantly, the highest 1‐year mortality rate was observed in patients with concomitant severe TR followed by patients with severe MR (P<0.01). Compared with patients with no concomitant or mild MVHD, the mortality rates were 3.4 times and 1.6 times higher for those with severe TR and severe MR, respectively (P<0.01). This trend not only persisted but also widened over a follow‐up period of 5 years, with patients with severe TR facing a mortality rate of 27.8 per 100 PY, significantly exceeding those with severe MR at 16.7 per 100 PY, and markedly higher than in the group with no or mild MVHD at 10.6 per 100 PY (P<0.01). These observations align with existing literature. 8 , 21 However, existing studies have primarily focused on short‐term follow‐up periods, limiting our understanding of the prolonged consequences of multivalvular dysfunction. 6 , 9 Our findings on the impact of sMVHD on mortality rate over 5 years contribute to the existing body of evidence. Moreover, our study provides insights into the differential impacts of severe TR versus MR on outcomes, suggesting a more pronounced risk associated with TR. In fact, multivariable analysis revealed that only concomitant severe TR was independently associated with 1‐year all‐cause death (P<0.01), despite both MR and TR showing significance in univariable analysis. This distinction may reflect underlying pathophysiological differences, with severe TR indicating an advanced stage of heart failure characterized by chronically elevated right ventricular afterload secondary to pulmonary hypertension. 26 Despite the relief of left‐sided obstruction achieved by TAVR, persisting right‐sided filling pressures in patients with TR perpetuate right ventricular dysfunction that can lead to progressive end‐organ damage, culminating in congestive hepatopathy and renal failure. 27 , 28
In light of the detrimental effects of sMVHD on outcomes following TAVR, our multicenter analysis on the impact of staged TEER underscores the importance of addressing concomitant sMVHD to enhance patient prognosis. The landmark analysis revealed significant differences in survival rates between groups, with 1‐year mortality rates being 59% and 65% lower in patients who underwent staged M‐TEER and T‐TEER, respectively, compared with those with persistent severe MR or TR on guideline‐directed medical therapy (P≤0.004). This difference persisted over the 5‐year follow‐up period (P≤0.006), with interventionally treated patients showing comparable mortality rates to those without concomitant sMVHD. Of note, the baseline characteristics were well balanced between the patients, except for T‐TEER patients being younger compared with those with severe TR. The biochemical assessment revealed significantly lower postprocedural levels of troponin (P=0.05) and NT‐proBNP (P=0.04) in patients who underwent staged TEER. This might be indicative of the relieving effects of TEER on the heart, as evidenced by multimodality measurements of cardiac dimensions. 29 Moreover, effective reduction of MR and TR has been shown to induce positive heart remodeling, potentially improving patient outcomes. 30 While the feasibility and efficacy of TEER in MR and TR have been reported, our study extends these findings by demonstrating improved long‐term survival with staged interventions in a real‐world TAVR cohort. 12 , 13 , 14 However, it is important to note that selection for TEER was based on interdisciplinary heart team discussions, which included assessments of valve morphology, lesion pathogenesis, and suitability for interventional therapy. Consequently, patients selected for staged M‐TEER were predominantly those with functional MR (74%), a subgroup generally more responsive to transcatheter interventions compared with those with degenerative MR. 13 In contrast, patients managed conservatively may have presented with more complex lesion pathogeneses, potentially limiting the feasibility and procedural success of transcatheter therapy. Furthermore, the apparent survival benefit in patients undergoing T‐TEER may have been influenced by the fact that these individuals were, on average, 3 years younger at the time of intervention and may have had less advanced right ventricular dysfunction or secondary organ damage due to structured post‐TAVR follow‐up. 26 Additionally, unmeasured clinical confounders such as frailty, functional status, and malnutrition may have influenced both the decision‐making process and the outcomes. 31 Consequently, a causal relationship between improved overall survival and TEER cannot be unequivocally determined on the basis of our exploratory findings.
Our findings have substantial clinical implications, suggesting that a comprehensive diagnostic and therapeutic approach to concomitant severe MR and TR in patients undergoing TAVR may be warranted. The current guidelines provide limited guidance on managing these additional valvular lesions, often leaving clinicians to rely on consensus and expert opinion. Our study supports the integration of staged TEER into the treatment algorithm for selected patients and reflects the benefits of addressing sMVHD in the context of lifetime management considerations, especially for younger patients undergoing TAVR. However, prospective, randomized trials are warranted to further assess the impact of staged TEER on outcomes.
Limitations
This study has several limitations that warrant consideration. Due to the nonrandomized, observational design in a real‐world setting, a causal relationship between the observed effects and MVHD or additional valvular intervention cannot be unequivocally assumed. Despite rigorous statistical adjustments, potential confounders inherent to observational research may influence the results. Moreover, the decision to proceed with TEER was based on discussions by an interdisciplinary heart team, reflecting clinical judgment and patient preferences. This approach may have introduced selection bias by favoring individuals with lesion characteristics more suitable for a TEER approach. Additionally, patients managed conservatively with guideline‐directed medical therapy may have had anatomic or pathogenetic complexities, such as significant annular calcification or degenerative leaflet disease, which were not captured in this study and could have influenced outcomes. Thus, randomized controlled trials are essential to definitively determine the impact of staged TEER on death and other clinical outcomes.
Conclusions
A concomitant clinically significant MVHD was prevalent among patients with AS undergoing TAVR. The persistence of sMVHD was associated with increased 1‐ and 5‐year mortality rates following TAVR. Specifically, severe TR was associated with higher mortality rates compared with severe MR. The potential benefit of an additional staged edge‐to‐edge valvular repair for concomitant sMVHD should be carefully considered, as it shows promise in improving outcomes for patients with persistent sMVHD.
Sources of Funding
Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Grant Number 397484323‐TRR259.
Disclosures
Drs Zimmer and Nickenig have received speaker honoraria and research grants from Abbott, Abiomed, Medtronic, Boston Scientific, and Edwards Lifesciences. Dr Veulemans has received grant support or personal fees from Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Kelm has received institutional grant support and/or personal fees from Philips, Abbott, Medtronik, Boston Scientific, Mars, Boehringer Ingelheim, Daiichi‐Sanyko GmbH, Amgen, Ancora Heart, and B. Braun. Dr Baldus has received speaker honoraria from JenaValve and Edwards Lifesciences. Dr Wienemann has received travel grants from JenaValve. Dr Adam has received personal fees from Abbott, JenaValve, Edwards Lifesciences, Medtronic and Meril. The other authors report no conflicts of interest.
Supporting information
Table S1
This manuscript was sent to Amgad Mentias, MD, Associate Editor, for review by expert referees, editorial decision, and final disposition.
Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.124.040150
For Sources of Funding, see page 11.
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Supplementary Materials
Table S1