Combined Tricuspid and Mitral Versus Isolated Mitral Valve Repair for Severe Mitral and Tricuspid Regurgitation

JACC: CARDIOVASCULAR INTERVENTIONS

VOL.

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ª 2020 PUBLISHED BY ELSEVIER ON BEHALF OF THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

Combined Tricuspid and Mitral Versus Isolated Mitral Valve Repair for Severe Mitral and Tricuspid Regurgitation An Analysis From the TriValve and TRAMI Registries Michael Mehr,a,b Nicole Karam,a,c Maurizio Taramasso,d Taoufik Ouarrak,e Steffen Schneider,e Philipp Lurz,f Ralph Stephan von Bardeleben,g Neil Fam,h Alberto Pozzoli,d Edith Lubos,i Peter Boekstegers,j Wolfgang Schillinger,k Björn Plicht,l Holger Eggebrecht,m Stephan Baldus,n Jochen Senges,e Francesco Maisano,d Jörg Hausleitera,b for the TriValve and TRAMI Investigators

ABSTRACT OBJECTIVES The aim of this study was to retrospectively compare the characteristics, procedural courses, and outcomes of patients presenting with concomitant mitral regurgitation (MR) and tricuspid regurgitation (TR) in the TriValve (Transcatheter Tricuspid Valve Therapies) and TRAMI (Transcatheter Mitral Valve Interventions) registries. BACKGROUND Transcatheter mitral edge-to-edge valve repair (TMVR) has been shown to be successful in patients with severe MR. Lately, edge-to-edge repair has also emerged as a possible treatment for severe TR in patients at high risk for cardiac surgery. In patients with both severe MR and TR, the yield of concomitant transcatheter mitral and tricuspid valve repair (TMTVR) for patients at high surgical risk is unknown. METHODS The characteristics, procedural data, and 1-year outcomes of all patients in the international multicenter TriValve registry and the German multicenter TRAMI registry, who presented with both severe MR and TR, were retrospectively compared. Patients in TRAMI (n ¼ 106) underwent isolated TMVR, while those in TriValve (n ¼ 122) additionally underwent concurrent TMTVR in compassionate and/or off-label use. RESULTS All 228 patients (mean age 77  8 years, 44.3% women) presented with significant dyspnea at baseline (New York Heart Association functional class III or IV in 93.9%), without any differences in the rates of pulmonary hypertension and chronic pulmonary disease. The proportion of patients with left ventricular ejection fraction <30% was higher in the TMVR group (34.9% vs. 18.0%; p < 0.001), while patients in the TMTVR group had lower glomerular filtration rates. At discharge, MR was comparably reduced in both groups. At 1 year, overall all-cause mortality was 34.0% in the TMVR group and 16.4% in the TMTVR group (p ¼ 0.035, Cox regression). On multivariate analysis, TMTVR was associated with a 2-fold lower mortality rate (hazard ratio: 0.52; p ¼ 0.02). The rate of patients in New York Heart Association functional class #II at 1 year did not differ (69.4% vs. 67.0%; p ¼ 0.54). CONCLUSIONS Concurrent TMTVR was associated with a higher 1-year survival rate compared with isolated TMVR in patients with both MR and TR. Further randomized trials are needed to confirm these results. (J Am Coll Cardiol Intv 2020;-:-–-) © 2020 Published by Elsevier on behalf of the American College of Cardiology Foundation.

From aMedizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; bGerman Centre for Cardiovascular Research, Partner Site Munich Heart Alliance, Munich, Germany; cEuropean Hospital Georges Pompidou (Cardiology Department) and Paris Cardiovascular Research Center (INSERMU970), Paris, France; dDepartment of Cardiovascular Surgery, University Hospital of Zurich, University of Zurich, Zurich, Switzerland; eStiftung für Herzinfarktforschung, Ludwigshafen, Germany; fLeipzig Heart Center, University of Leipzig, Leipzig, Germany; gHeart Valve Center Mainz, Center of Cardiology University Medical Center, Mainz, Germany; hDivision of Cardiology, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada; iUniversity Heart Center Hamburg, University of Hamburg, Hamburg, Germany; jKlinikum Siegburg, Siegburg, Germany; kHelios Albert-Schweitzer-Klinik, Northeim, Germany; lKlinikum Westfalen, Dortmund, Germany; m

Cardioangiologisches Centrum Bethanien, Frankfurt am Main, Germany; nCologne University Hospital, Cologne, Germany. The

ISSN 1936-8798/$36.00

https://doi.org/10.1016/j.jcin.2019.10.023

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S

ABBREVIATIONS AND ACRONYMS EuroSCORE = European System for Cardiac Operative

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Combined vs. Isolated Mitral Valve Repair for Severe MR and TR

evere tricuspid regurgitation (TR) is

METHODS

associated with an increased risk for mortality and morbidity (1–4). Current

STUDY DESIGN. We retrospectively analyzed all pa-

therapeutic options include medical therapy,

tients from the international multicenter TriValve

Risk Evaluation

mainly diuretic agents, and surgical cure.

(NCT03416166) registry and from the German multi-

LVEF = left ventricular ejection

However, the yield of cardiac surgery for iso-

center TRAMI registry, who presented with both se-

fraction

lated TR is uncertain, as it carries significant

vere MR and TR. Patients from the TRAMI registry

MR = mitral regurgitation

mortality and morbidity risk (5–7).

(n ¼ 106) underwent isolated TMVR using a MitraClip

Transcatheter edge-to-edge mitral valve

device (Abbott Structural Heart, Santa Clara, Califor-

Association

repair (TMVR) has been shown to be an

nia). Among patients from the TriValve registry

TMTVR = transcatheter mitral

effective and safe therapeutic option in pa-

(n ¼ 122), those with simultaneous MR and TR un-

tients with mitral regurgitation (MR) at high

derwent combined TMTVR in compassionate and/or

surgical risk (8–11). Recently, the percuta-

off-label use of the same MitraClip device.

NYHA = New York Heart

and tricuspid valve repair

TMVR = transcatheter edge-toedge mitral valve repair

neous edge-to-edge repair technique has

The design of both registries has been described

been used successfully as an interventional

previously (20,21). For TriValve, a total of 12 centers

option for symptomatic TR in selected patients with

from Europe and North America treated patients with

high surgical risk, with encouraging results so far

tricuspid

(12–17).

and/or off-label use from June 2015 to June 2018. Data

TR = tricuspid regurgitation

edge-to-edge

repair

in

compassionate

MR and TR often coexist. Although concomitant

acquisition was performed using a pre-specified

treatment of both valves is indicated during mitral

dataset and supplemental communication with the

surgery, it is unclear whether both valves should be

centers. Clinical, laboratory, and echocardiographic

treated

data were collected at baseline, time of procedure,

simultaneously

using

a

percutaneous

approach. More than half of the patients in the in-

discharge, and follow-up.

ternational TriValve (Transcatheter Tricuspid Valve

The TRAMI registry was open to all German centers

Therapies) registry on transcatheter tricuspid valve

performing TMVR, and patients were included be-

repair underwent concurrent transcatheter mitral and

tween August 2010 and July 2013. Central prospective

tricuspid valve repair (TMTVR), with similar out-

follow-up was conducted by Stiftung Institut für

comes compared with patients undergoing isolated

Herzinfarktforschung (Foundation IHF, Ludigshafen)

tricuspid repair. A subset of patients undergoing

at 30 days and at 1, 3, and 5 years. Yet because of the

TMVR in the German multicenter TRAMI (Trans-

historical patient cohort, no follow-up data for TR

catheter Mitral Valve Interventions) registry also had

were available for the TRAMI patients.

high-grade TR (18), which was associated with both

Echocardiographic grading of TR and MR was per-

increased mortality and adverse events (19). Yet un-

formed by each participating site according to Amer-

like in TriValve, TRAMI patients had not been treated

ican and European guidelines for quantification of

in the tricuspid position, raising the question of

native valvular regurgitation (22,23). The trans-

whether concurrent TMTVR would have prevented

catheter edge-to-edge repair system was introduced

this excess mortality.

via the femoral vein under general anesthesia in most

To address this issue, we retrospectively compared

cases. The intervention was guided by 2-dimensional

the characteristics, procedural courses, and outcomes

and 3-dimensional transthoracic and transesophageal

of patients presenting with concomitant MR and TR

echocardiography,

in the TriValve and TRAMI registries.

described previously (13,14,16).

as

well

as

fluoroscopy,

statistical analysis for this manuscript was supported by an unrestricted grant from Abbott Medical. The TRAMI registry received support from Abbott Vascular. The TriValve registry was not supported by external funding. Dr. Karam has received consulting fees from Abbott Vascular. Dr. Taramasso is a consultant for Abbott Vascular, Boston Scientific, 4tech, and CoreMedic; and has received speaking honoraria from Edwards Lifesciences. Dr. Lurz has received speaking fees from Abbott Vascular. Dr. von Bardeleben has received speaking fees from Abbott Vascular and Edwards Lifesciences. Dr. Lubos has received research support and speaking honoraria from Abbott Vascular. Dr. Schillinger has received consulting and lecture fees and travel expenses from Abbott Vascular. Dr. Maisano has served as a consultant for Abbott Vascular, Edwards Lifesciences, Cardiovalve, Valtech, and Medtronic; and is a cofounder of 4tech. Dr. Hausleiter has received research support and speaking honoraria from Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received June 28, 2019; revised manuscript received September 19, 2019, accepted October 8, 2019.

as

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PATIENT

3

Combined vs. Isolated Mitral Valve Repair for Severe MR and TR

COHORT. All

patients

included

were

symptomatic with signs of global heart failure such as

T A B L E 1 Baseline Characteristics

dyspnea, peripheral edema, ascites, or pleural effusion despite optimal medical treatment. The majority of patients were in New York Heart Association (NYHA) functional class III or IV and were deemed at high or prohibitive risk for surgery. Treatment was

Female Age, yrs Body mass index, kg/m2

Combined TMTVR (n ¼ 122)

Isolated TMVR (n ¼ 106)

63 (51.6)

38 (35.8)

p Value

0.017

77.8  8.6

76.4  8.1

0.11

24.8 (22.5, 27.7)

24.3 (22.7, 28.0)

0.58

NA

26.2  18.9

NA

indicated according to international guidelines for

Logistic EuroSCORE

MR and TR (24,25) and local heart team consensus in

EuroSCORE II

12.1  13.1

NA

NA

all patients.

History of myocardial infarction

30 (24.8)

28 (26.4)

0.78

Left ventricular ejection fraction <30% 30%–50% >50%

22 (18.0) 44 (36.1) 56 (45.9)

37 (34.9) 38 (35.8) 31 (29.2)

54 (47, 60)

59 (51, 67)

0.007

NA

69 (68.3)

NA

Mitral regurgitation 0, none 1þ, mild 2þ, moderate 3þ, severe

0 2 (1.6) 20 (16.4) 100 (82)

0 0 7 (6.7) 97 (93.3)

Functional tricuspid regurgitation

112 (91.8)

NA

Tricuspid regurgitation 0, none 1þ, mild 2þ, moderate 3þ. severe 4þ, massive

0 0 0 69 (56.6) 53 (43.4)

0 0 0 106 (100) NA

performed in line with local ethical regulations and

Tricuspid annular plane systolic excursion, mm

15.7  4

NA

adhered to international rules for scientific studies as

Tricuspid annular diameter, mm

47  8

NA

well as the principles of the World Medical Associa-

NT-proBNP, pg/ml

STUDY ENDPOINTS AND DEFINITIONS. Procedural suc-

cess was defined as a successful implantation of at least 1 clip with a reduction to MR #1þ and TR #2þ, respectively. In TRAMI and TriValve, patients’ surgical risk was evaluated using logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) and EuroSCORE II, respectively. The primary outcome was all-cause mortality at 12 months after the procedure. The secondary clinical outcome was NYHA functional class at last follow-up. Patients were deemed eligible for the evaluation of NYHA class, if the patients survived at least 6 months after edge-to-edge treatment. ETHICAL CONSIDERATIONS. Collection of data was

tion Declaration of Helsinki. Patients needed to be of

Left ventricular end-diastolic diameter, mm

< 0.001

Functional mitral regurgitation

3,865 (2,099–7,044)

4,343 (2,038–8,071)

NA

NA

0.92

Atrial fibrillation

85 (68.7)

59 (55.7)

Pacemaker or ICD

46 (37.7)

38 (36.2)

0.81

40 (30–53)

46 (34–58)

0.021

Diabetes

44 (36.1)

39 (36.8)

0.91

Peripheral artery disease

29 (23.8)

18 (17.1)

0.22

STATISTICAL ANALYSIS. Continuous variables are

Chronic obstructive pulmonary disease

26 (21.3)

28 (26.4)

0.37

expressed as mean  SD or as median (interquartile

Pulmonary hypertension (sPAP >40 mmHg)

72 (59.5)

62 (58.5)

0.88

range) as appropriate. Categorical variables are

NYHA functional class III or IV

119 (97.4)

95 (89.6)

0.013

legal age and able to consent. The inclusion of patients in both registries was approved as required by

the

local

Institutional

Review

Board

and

ethics committee.

eGFR, ml/min

0.029

expressed as number (proportion). Comparisons between TRAMI and TriValve patients were performed using Wilcoxon rank sum and chi-square tests. Cumulative survival was visualized as a Kaplan-Meier

Values are n (%), mean  SD, or median (interquartile range). eGFR ¼ estimated glomerular filtration rate; EuroSCORE ¼ European System for Cardiac Operative Risk Evaluation; ICD ¼ implantable cardioverter-defibrillator; NA ¼ not available; NT-proBNP ¼ N-terminal pro–brain natriuretic peptide; NYHA ¼ New York Heart Association; sPAP ¼ systolic pulmonary artery pressure; TMTVR ¼ transcatheter mitral and tricuspid valve repair; TMVR ¼ transcatheter mitral edge-to-edge valve repair.

curve, compared between groups using the log-rank test and analyzed using a Cox regression model. All statistical calculations were performed using SAS version 9.4 (SAS Institute, Cary, North Carolina). A p

who underwent isolated TMVR from the TRAMI reg-

value of <0.05 was considered to indicate statisti-

istry). Their baseline characteristics are presented in

cal significance.

Table 1. There were no differences between the 2 groups in terms of age (76.4 years in the TriValve

RESULTS

cohort vs. 77.8 years in the TRAMI cohort; p ¼ 0.11) and body mass index (24.8 kg/m2 vs. 24.3 kg/m 2,

BASELINE CHARACTERISTICS. Overall, 228 patients

respectively; p ¼ 0.11), whereas women were more

were included in the analysis (122 who underwent

frequent in the TriValve cohort (51.6% vs. 35.8%;

combined TMTVR from the TriValve registry and 106

p ¼ 0.017). The TriValve cohort included fewer

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p < 0.001). Procedural outcomes are summarized in

T A B L E 2 Procedural and Late Outcomes

Table 2. Concerning safety, there was no difference in Combined TMTVR (n ¼ 122)

Number of clips (1, 2, >2)

Isolated TMVR (n ¼ 106)

34%, 46%, 20% 46%, 49%, 5%

Duration of intervention, min Tricuspid regurgitation post-intervention 0, none 1þ, mild 2þ, moderate 3þ. severe 4þ, massive Mitral regurgitation post-intervention 0, none 1þ, mild 2þ, moderate 3þ, severe

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Combined vs. Isolated Mitral Valve Repair for Severe MR and TR

140 (104–179)

90 (58–130)

1 (0.8) 48 (39.2) 48 (39.2) 19 (15.6) 6 (4.9)

NA NA NA NA NA

in-hospital major adverse cardiac and cerebrovascup Value

lar events between the 2 groups, even though there

0.022

was a nonsignificant trend toward a shorter hospital

< 0.001 NA

stay among patients undergoing combined TMTVR (5 days vs. 7 days; p ¼ 0.051). MORTALITY AND IMPROVEMENT IN NYHA FUNCTIONAL CLASS. One-year mortality was 16% with TMTVR in

TriValve patients and 34% with TMVR in TRAMI patients. Kaplan-Meier analysis estimated 1-year mor0.67

tality of 19.8% for TriValve (95% confidence interval:

3 (2.6) 85 (73.3) 26 (22.4) 2 (1.7)

5 (4.7) 77 (72.6) 20 (18.9) 4 (3.8)

In-hospital MACCE (death, myocardial infarction, stroke)

6 (4.9)

6 (5.6)

0.86

In-hospital death

5 (4.1)

6 (5.6)

0.60

val: 1.04 to 3.17; p ¼ 0.035), indicating a higher sur-

In-hospital myocardial infarction

0 (0)

0 (0)

NA

vival rate in TriValve. After adjustment for patients

In-hospital stroke

2 (1.6)

1 (0.9)

0.48

In-hospital length of stay, days

5 (4–7)

7 (4–10)

0.051

All-cause mortality at 30 days

13.2% to 29.2%) and 33.1% for TRAMI (95% confidence interval: 24.8% to 43.3%) (Central Illustration) (log-

5 (4.1)

8 (7.9)

0.23

All-cause mortality at 1 yr Cardiovascular Noncardiovascular Unknown

20 (16.4) 13 (65) 4 (20) 3 (15)

33 (34) NA NA NA

0.002

NYHA functional class III or IV* at last follow-up

27 (30.7)

15 (30.6)

0.99

Improvement of at least 1 NYHA functional class*

69 (78.4)

34 (69.4)

0.24

rank p ¼ 0.032). An unadjusted Cox regression model showed a hazard ratio of 1.82 (95% confidence inter-

with severely reduced LVEFs (<30%), the hazard ratio remained 1.76 (95% confidence interval: 1.00 to 3.10; p ¼ 0.049). Differences in mortality stratified for LVEF are noted in the Online Appendix. In multivariate analysis, after adjustment for age, sex, left ventricular function, and estimated glomerular filtration rate (see Table 3), absence of TMTVR remained inde-

Values are median (interquartile range) or n (%). *In patients surviving at least 6 months. MACCE ¼ major adverse cardiac and cerebrovascular event; other abbreviations as in Table 1.

pendently associated with increased mortality, with a hazard ratio of 0.52 for the TMTVR group (p ¼ 0.02). With respect to clinical symptoms, patients in both groups improved significantly at follow-up as indicated by NYHA functional class (NYHA functional class #II in 67% of patients in TriValve and 69% of

patients with severely reduced left ventricular ejection fraction (LVEF; 18.0% vs. 34.9%; p < 0.001), and their median left ventricular end-diastolic diameter was smaller (54 mm vs. 59 mm; p ¼ 0.007). They more frequently presented with atrial fibrillation (68.7% vs. 55.7%; p ¼ 0.029) and were more frequently in NYHA functional class IV (32.8% vs. 18.9%; p ¼ 0.013). Age, LV function and comorbidities resulted in an elevated surgical risk for mortality as indicated by logistic EuroSCORE in TRAMI (26.2%) and EuroSCORE II in TriValve (12.1%). In the TriValve cohort, tricuspid annular diameter was dilated (47  8 mm; the measurement was not available in TRAMI).

patients in TRAMI) (Figure 1). Median follow-up duration was 333 days (interquartile range: 181 to 398 days) in TriValve, including survival status and follow-up dates for all patients. This includes 16 of 122 patients (13%) with follow-up duration of <180 days who were alive at last followup. Median follow-up duration was 369 days (interquartile range: 169 to 390 days) for all patients in TRAMI, including survival status and follow-up dates for all patients.

DISCUSSION Among patients presenting with both severe MR and

PROCEDURAL OUTCOMES. Mitral procedural success

TR, concurrent edge-to-edge TMTVR was safe and

was achieved in 76% of patients in the TriValve reg-

did not result in a higher adverse events rate

istry and 77% in the TRAMI registry (p ¼ 0.79).

compared with isolated TMVR. TMTVR was associ-

Tricuspid procedural success was achieved in 81% of

ated with a nonsignificant trend toward a shorter

patients in the TriValve registry. Because of the

hospital stay after the procedure and a 2-fold lower

additional tricuspid valve repair, procedure duration

1-year mortality rate, even after adjustment for dif-

was longer in patients undergoing combined TMTVR

ferences in left ventricular function and in multi-

in the TriValve registry (140 min vs. 90 min;

variate analysis.

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Combined vs. Isolated Mitral Valve Repair for Severe MR and TR

C ENTR AL I LL U STRA T I O N Kaplan-Meier Analysis of All-Cause-Mortality at 1 Year

50

Mortality (%)

40

30

Log-Rank test p = 0.032

20

10

0 0

60

120

No. at risk 105 122

88 105

82 100

180 240 Days After Procedure 78 90

73 76

TRAMI

300

360

70 66

63 52

TRIVALVE

Mehr, M. et al. J Am Coll Cardiol Intv. 2020;-(-):-–-.

Kaplan-Meier analysis of all-cause mortality, stratified for treatment groups. Estimated mortality at 1 year was 19.8% for TriValve (Transcatheter Tricuspid Valve Therapies) (95% confidence interval: 13.2% to 29.2%) and 33.1% for TRAMI (Transcatheter Mitral Valve Interventions) (95% confidence interval: 24.8% to 43.3%).

A high proportion of patients undergoing left-sided

Patients in both registries had both severe TR and

valvular surgery have moderate or severe TR (24), and

dilated annuli and would therefore have undergone

a substantial proportion of patients develop TR late

tricuspid repair if they underwent mitral surgery ac-

after previous left-sided heart valve surgery (26).

cording to current guidelines. However, contrary to

When both TR and MR are severe at diagnosis,

surgery, after a previous percutaneous mitral inter-

simultaneous treatment of both is indicated during

vention, redo percutaneous procedure to treat TR

left-sided valvular surgery. Considering the risk for

does not carry an increased risk for complications;

progressive TR and right ventricular failure in the

notably, the pericardial adherences that complicate

presence of tricuspid annular dilatation, and the high

redo cardiac surgery are not encountered with

surgical risk associated with redo procedure for TR,

percutaneous procedures. Accordingly, avoiding a

European Society of Cardiology and American College of Cardiology/American Heart Association guidelines recommend prophylactic concomitant tricuspid valve

T A B L E 3 Multivariate Analysis of 1-Year Mortality*

repair in patients with dilated annuli ($40 mm

Hazard Ratio

95% CI

p Value

or $21 mm/m 2) undergoing left-sided valve surgery,

TMTVR

0.51

0.28–0.91

0.02

even when TR is moderate or even mild (24–26).

Age

1.03

0.99–1.08

0.10

Furthermore, data from retrospective analyses and a

Female

1.09

0.60–1.97

0.78

1.37

0.71–2.66

0.35

concomitant tricuspid valve repair at the time of

Left ventricular ejection fraction <30%

mitral valve surgery improves echocardiographic and

eGFR

0.98

0.97–0.99

0.04

small randomized controlled trial suggested that

functional outcomes (26). In the era of percutaneous repair, the chronological and staged order of valve repair can be reconsidered.

*Based on a Cox proportional hazard model, using the PHREG procedure in SAS. CI ¼ confidence interval; other abbreviations as in Table 1.

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Combined vs. Isolated Mitral Valve Repair for Severe MR and TR

evolution of TR after TMVR in 67 patients, TR

F I G U R E 1 NYHA Functional Class

improved in 22 patients (33%) and was unchanged or worse in 45 patients (67%) (27). Of note, among the 20 patients who presented with severe TR at baseline, only 3 (15%) presented with mild TR at last follow-up. This is in line with another study, by Yzeiraj et al. (28), in which only 31 of 77 (40%) patients with highgrade TR at baseline presented with no or mild TR at 30-day follow-up after TMVR. Conversely, another study reported an improvement of moderate or severe TR to no or mild TR in 18 of 31 patients (58%) at 1 year (29). Regarding symptom alleviation, baseline NYHA functional class was higher in the TriValve registry, with almost 98% being in NYHA functional class III or

Stacked diagram indicating the development of New York Heart

IV, compared with 89.6% in the TRAMI registry. After

Association (NYHA) functional class at baseline and at last

combined TMTVR in the TriValve registry and iso-

follow-up in both treatment groups, with a significant clinical

lated TMVR in TRAMI, there was no difference in

benefit in both the TRAMI (Transcatheter Mitral Valve Interventions) and TriValve (Transcatheter Tricuspid Valve

NYHA functional class at follow-up, suggesting a better improvement in NYHA functional class with

Therapies) registries.

combined TMTVR compared with TMVR, even though the difference did not reach statistical significance. prolongation of the initial mitral procedure, a staged

STUDY LIMITATIONS. Despite being the first study to

procedure might be considered, which might avoid

compare combined TMTVR and isolated TMVR in

unnecessary tricuspid procedures in cases in which

patients with both severe MR and TR, using 2 large

spontaneous TR reduction occurs after MR treatment.

nonrandomized, noncontrolled registries, several

However, previous studies of TMVR have shown

limitations must be acknowledged. First, the TRAMI

that concomitant TR at the time of intervention

cohort was treated from 2010 to 2013, and advances in

carries an increased risk for adverse outcome and

medical and device therapy for patients with heart

mortality (in-hospital and at 30 days) when left un-

failure might have had an impact on the outcomes in

treated. Besides, despite the relative simplicity of

TriValve, a more recent registry.

rescheduling a second percutaneous procedure for TR

Second, this was a retrospective cohort study

hospital

without central event adjudication or an echocardi-

admission, with anesthesia and intubation in an

ography core laboratory. Detailed echocardiographic

elderly and often frail population, leading to an

information such as etiology of regurgitation, effec-

additional risk for the patient and to additional costs

tive regurgitant orifice area, vena contracta, and

to society, which could be avoided by combining

coaptation gap size were not available for TR in

mitral and tricuspid repair. According to our study,

TRAMI and for MR in TriValve. In addition, there was

combining mitral and tricuspid repair, despite leading

no information on right ventricular function in

to a longer procedural duration of only 50 min, was

TRAMI.

treatment,

this

requires

an

additional

rather associated with a trend toward a reduced

Third, causes of death were not available in

hospital stay after the procedure, even though im-

TRAMI. Fourth, none of the patients in TRAMI un-

provements in patients’ post-operative management

derwent subsequent tricuspid repair in the following

in the second study period could have accounted for

year. Whether a staged procedure with tricuspid

the shortening of hospital stay. Besides, there was a

repair could have prevented the excess 1-year mor-

clear benefit in terms of mortality at 1 year, with a

tality remains unknown. However, a staged proced-

2-fold lower mortality rate with TMTVR compared

ure would have led to the previously described extra

with isolated TMVR. Of note, the mortality curves

costs, which are avoided with a combined procedure.

diverged soon after the procedure, implying a potential hazard from postponing the TR intervention,

CONCLUSIONS

to ascertain that it does not resolve after TMVR, even if combined TMTVR might lead to overtreatment in

Concurrent TMTVR appears safe and associated

some cases. In a previous study assessing the

with a 2-fold higher 1-year survival rate compared

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Combined vs. Isolated Mitral Valve Repair for Severe MR and TR

with isolated TMVR in patients with simultaneous MR

and

TR.

Further

needed

to

TMTVR

compared

assess

the with

randomized yield isolated

trials

of

are

combined

TMVR

with

subsequent tricuspid repair in case of persistent TR.

PERSPECTIVES WHAT IS KNOWN? TR leads to heart failure and increased morbidity and mortality, and MR often coexists. WHAT IS NEW? In patients with high-grade MR and TR, TMTVR was associated with lower mortality compared with mitral valve

ADDRESS FOR CORRESPONDENCE: Prof. Dr. med.

Jörg Hausleiter, Medizinische Klinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität Munich, Marchioninistrasse 15, 81377 Munich, Germany.

repair alone. WHAT IS NEXT? Designated trials are needed to investigate a potential benefit on survival as indicated by these data.

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KEY WORDS edge-to-edge repair, heart failure, structural heart disease, TR, tricuspid valve interventional repair

22. Lancellotti P, Tribouilloy C, Hagendorff A, et al. Recommendations for the echocardiographic assessment of native valvular regurgitation: an

A PP END IX For supplemental results and a list of investigators and their disclosures, please see the online version of this paper.

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