Journal of

Clinical Medicine

Article
Combined Use of MITRACLIP and Ventricular ASSIST Devices
in Cardiogenic Shock: MITRA-ASSIST Registry
Borja Rivero-Santana 1,2, *,† , Alfonso Jurado-Roman 1,2, *,† , Isaac Pascual 3 , Chi Hion Li 4 , Pilar Jimenez 5 ,
Rodrigo Estevez-Loureiro 6 , Pedro Cepas-Guillén 7 , Tomás Benito-González 8 , Ana Serrador 9 , Jose Maria De La
Torre-Hernandez 10 , Pablo Avanzas 3 , Estefania Fernandez-Peregrina 4 , Luis Nombela 5 ,
Berenice Caneiro-Queija 6 , Xavier Freixas 7 , Felipe Fernandez-Vazquez 8 , Ignacio Amat-Santos 9 , Dae-Hyun Lee 10 ,
Victor Leon 3 , Dabit Arzamendi 4 , Raul Moreno 1,2 and Guillermo Galeote 1,2

1 Cardiology Department, La Paz University Hospital, 28046 Madrid, Spain

2 Hospital La Paz Institute for Health Research, IdiPAZ, 28029 Madrid, Spain
3 Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
4 Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain
5 Hospital Clínico San Carlos, 28040 Madrid, Spain
6 Complexo Hospitalario Universitario de Vigo, 36312 Vigo, Spain
7 Hospital Clinic, 08036 Barcelona, Spain
8 Hospital Universitario de León, 24008 León, Spain
9 Hospital clínico de Valladolid, 47003 Valladolid, Spain
10 Hospital Universitario Marqués de Valdecilla, 39008 Santander, Spain
* Correspondence: borja.riversa@gmail.com (B.R.-S.); alfonsojuradoroman@gmail.com (A.J.-R.)
† These authors contributed equally to this work.

Abstract: Background: Patients with cardiogenic shock (CS) and mitral regurgitation (MI) have a
prohibitive risk that contraindicates surgical treatment. Although the feasibility of transcatheter
edge-to-edge therapy (TEER) has been demonstrated in this setting, the benefit of the combined
use of TEER with mechanical circulatory support devices (MCS) has not been studied. The aim
Citation: Rivero-Santana, B.; Jurado-
of this study was to evaluate the clinical outcomes of TEER in patients with MCS. Methods: The
Roman, A.; Pascual, I.; Li, C.H.;
MITRA-ASSIST study is a retrospective multicentre Spanish registry that included patients with
Jimenez, P.; Estevez-Loureiro, R.;
Cepas-Guillén, P.; Benito-González, T.;
MR and CS who underwent TEER in combination with MCS. The primary endpoint was death
Serrador, A.; De La Torre-Hernandez, from any cause at 12 months. The secondary endpoint was a composite of death from any cause
J.M.; et al. Combined Use of or hospitalisation for heart failure at 12 months. Results: A total of twenty-four patients in nine
MITRACLIP and Ventricular ASSIST high-volume Spanish centres (66.2 (51–82) years, 70.8% female, EuroSCORE II 20.4 ± 17.8) were
Devices in Cardiogenic Shock: included. Acute ST-elevation myocardial infarction was the main CS aetiology (56%), and the most
MITRA-ASSIST Registry. J. Clin. Med. implanted MCS was the intra-aortic balloon pump (82.6%), followed by ECMO (8.7%), IMPELLACP®
2024, 13, 4408. https://doi.org/ (4.3%), or a combination of both (4.3%). Procedural success was 95.8%, with 87.5% in-hospital survival.
10.3390/jcm13154408
At 12-month follow-up, 25.0% of patients died, and 33.3% had a composite event of death from any
Academic Editor: Daniele Masarone cause or hospitalisation for heart failure. Conclusions: TEER in patients with concomitant CS and
MR who require MCS appears to be a promising therapeutic alternative with a high device procedural
Received: 16 June 2024
success rate and acceptable mortality and heart failure readmission rates at follow-up.
Revised: 21 July 2024
Accepted: 24 July 2024
Keywords: cardiogenic shock; mitral regurgitation; transcatheter edge-to-edge repair; mechanical
Published: 28 July 2024
circulatory support; heart failure

Copyright: © 2024 by the authors.

Licensee MDPI, Basel, Switzerland. 1. Introduction
This article is an open access article Cardiogenic shock (CS) continues to have an unfavourable prognosis despite the use
distributed under the terms and
of all currently available treatment options. Even when patients are adequately treated, the
conditions of the Creative Commons
30-day mortality rate may often exceed 50% [1,2]. In addition, CS with concurrent valvular
Attribution (CC BY) license (https://
heart disease is common and aggravates the prognosis of these patients. Several studies
creativecommons.org/licenses/by/
have shown that moderate-to-severe mitral regurgitation (MR) is present in approximately
4.0/).

J. Clin. Med. 2024, 13, 4408. https://doi.org/10.3390/jcm13154408 https://www.mdpi.com/journal/jcm

J. Clin. Med. 2024, 13, 4408 2 of 12

10–20% of patients with CS [3,4] and significantly increases the risk of death by up to three
times [5,6].
Surgical intervention for mitral valve disease may have benefits in the setting of CS.
However, it is generally not a viable option due to the prohibitive risk associated with
most cases of CS and MR [7]. Consequently, transcatheter edge-to-edge repair (TEER)
has emerged as a potential therapeutic alternative [8–10]. To date, many studies have
shown that TEER is a feasible procedure for CS and can reduce mortality and heart failure
readmissions.
However, despite the promising results, more than 20% of patients with CS require
mechanical ventricular support (MCS) for hemodynamic support, and the feasibility and
benefit of TEER in this setting have not been established [11,12]. To date, the combined use
of MCS and TEER in patients with CS and MR is marginal because the evidence is limited
to case series [13,14]. The MITRA-ASSIST Registry is the first study specifically designed to
evaluate the use of TEER in CS and MR patients requiring MCS.

2. Materials and Methods

2.1. Study Population
The MITRA-ASSIST Registry is a multicentre retrospective registry that included
patients with grade 3+ (moderate to severe) or 4+ (severe) MR and CS who underwent
TEER in combination with MCS between June 2016 and December 2022 at nine Spanish
high-volume centres. Only patients with Society for Cardiovascular Angiography and
Interventions (SCAI) stage C to E cardiogenic shock were selected. Both functional mitral
regurgitation and degenerative mitral regurgitation were included, and there were no
specific anatomic requirements except the technical feasibility of grasping the mitral leaflets.
All patients were found to be eligible for TEER by the Heart Team at each centre after being
deemed unsuitable for other therapies, such as mitral valve surgery, heart transplantation,
or implantation of a permanent left ventricular assist device (LVAD). The study was
approved by the ethics committees of the participating hospitals.

2.2. Definitions
Cardiogenic shock (CS) was defined as hypotension (SBP < 90 mmHg) despite ade-
quate filling status with signs of hypoperfusion according to the diagnostic criteria used in
the European Guidelines for the diagnosis and treatment of acute and chronic heart fail-
ure [15]. The following signs of hypoperfusion were considered: cold extremities, oliguria,
altered mental status (AMS), narrow pulse pressure, metabolic acidosis, elevated serum
lactate (≥2.5 mmol/L), and elevated serum creatinine.
Functional mitral regurgitation (FMR) was defined as regurgitation produced through
the mitral valve in the absence of organic involvement of the elements that integrate the
valvular and subvalvular apparatus. Degenerative mitral regurgitation (DMR) was defined
as mitral regurgitation resulting from primary anatomical alterations of the mitral valve
apparatus.

2.3. Procedure
The procedure was performed in the catheterization room under general anaesthesia,
using a 24F guiding catheter from the femoral vein and guided by fluoroscopy and transoe-
sophageal echocardiography (TEE). In all cases, TEER was performed with the third (NTR
and XTR) and fourth (NT, NTW, XT, and XTW) generation devices of the MitraClip® system
(Abbott Vascular, Santa Clara, CA, USA). Acute success of the procedure was defined as
MR reduction of ≥1 grade and a final MR to grade ≤ 2+ after placement of at least one clip
with a transmitral gradient (TPMG) < 5 mm Hg. In all cases, the hemodynamic support
of the ventricular assist devices had to be reduced to the minimum allowed according
to the clinical situation of the patient to adequately assess the TPMG and the degree of
residual MR, both after the first clip and to assess the result. Furthermore, in those patients
who were hemodynamically supported by the IMPELLA® device (Abiomed, Danvers, MA,
 MitraClip® system (Abbott Vascular, Santa Clara, CA, USA). Acute success of the proce-
dure was defined as MR reduction of ≥1 grade and a final MR to grade ≤ 2+ after placement
of at least one clip with a transmitral gradient (TPMG) < 5 mm Hg. In all cases, the hemo-
dynamic support of the ventricular assist devices had to be reduced to the minimum al-
J. Clin. Med. 2024, 13, 4408
lowed according to the clinical situation of the patient to adequately assess the TPMG3 of 12
and
the degree of residual MR, both after the first clip and to assess the result. Furthermore,
in those patients who were hemodynamically supported by the IMPELLA® device (Abio-
USA), TEE wasMA,usedUSA),
to monitor the possibility of punctual interference of the MitraClip ®
med, Danvers, TEE was used to monitor the possibility of punctual interfer-
release ®
ence ofcatheter with the
the MitraClip IMPELLA
® release catheter
catheter withwhen crossing the
the IMPELLA mitral valve
® catheter whentocrossing
capture the
the
leaflets (Figure 1).
mitral valve to capture the leaflets (Figure 1).

Figure 1. Multimodal imaging of a MitraClip implantation in a patient with IMPELLA CP® device
Figure 1. Multimodal imaging of a MitraClip implantation in a patient with IMPELLA CP® device
support. Angiography shows acute myocardial infarction due to occlusion of the proximal circum-
support. Angiography shows acute myocardial infarction due to occlusion of the proximal circumflex
flex artery (A) with severe functional ischemic mitral regurgitation. On transoesophageal echocar-
artery (A) with
diography (TEE)severe functional
(B) and ischemic mitral
3D reconstruction (C), aregurgitation.
mid-level jet On
wastransoesophageal echocardiog-
observed, predominantly be-
raphy
tween (TEE)
P2-A2.(B) and
(D). 3D reconstruction
Angiography confirms(C),the
a mid-level jet was observed,
correct placement predominantly
of IMPELLA CP® devicebetween
and the
P2-A2.
optimal(D). Angiography
results confirmsimplanted
of the previously the correctstents.
placementThe of IMPELLA
valve CP® device
was repaired and the optimal
by implantation of a
results of the
MitraClip NTWpreviously
device atimplanted
A3-P3 andstents. TheNT
a second valveclipwas repaired
at A2-P2, by excellent
with implantation of aasMitraClip
results assessed
by TEEdevice
NTW (E) and
at 3D reconstruction
A3-P3 and a second(F).NT
ADA:
clipanterior
at A2-P2, descendent artery;
with excellent CX: circumflex;
results as assessedOM: obtuse
by TEE (E)
marginal.
and 3D reconstruction (F). ADA: anterior descendent artery; CX: circumflex; OM: obtuse marginal.

2.4. Echocardiographic Evaluation

2.4. Echocardiographic Evaluation
Echocardiographic measurementswere
Echocardiographic measurements wereconducted
conducted prior
prior to, to, during,
during, andand
afterafter the
the pro-
procedure and before discharge. The severity of mitral regurgitation was graded
cedure and before discharge. The severity of mitral regurgitation was graded according according
to
to the
the criteria
criteria recommended
recommended in in the
the European
European guidelines
guidelines for
for the
the management
management of of valvular
valvular
heart
heart disease
disease[15].
[15].Additional
Additionalechocardiographic
echocardiographicparameters
parameters such
such as as
leftleft
ventricular ejection
ventricular ejec-
fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), tricuspid
tion fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), tricuspid annular annular plane
systolic excursion
plane systolic (TAPSE),
excursion effective
(TAPSE), regurgitant
effective orifice
regurgitant area area
orifice (EROA),(EROA),TMPG,
TMPG,and and
the
presence of a ruptured mitral chord or prolapse were collected.
the presence of a ruptured mitral chord or prolapse were collected.
2.5. Outcomes
2.5. Outcomes
The primary endpoint was death from any cause at 12 months. The secondary end-
The primary endpoint was death from any cause at 12 months. The secondary end-
point was a composite event of death from any cause or hospitalisation for HF at 12 months.
point was a composite event of death from any cause or hospitalisation for HF at 12
In addition, in-hospital complications such as minor and major bleeding, acute kidney
months. In addition, in-hospital complications such as minor and major bleeding, acute
injury (AKI), myocardial infarction (MI), and acute stroke were collected. Bleeding events
kidney injury (AKI), myocardial infarction (MI), and acute stroke were collected. Bleeding
and vascular complications that were procedure-related were defined using Bleeding Aca-
demic Research Consortium (BARC) definitions. AKI was defined according to Kidney
Disease: Improving Global Outcomes (KDIGO) criteria as any of the following: increase in
serum creatine (SCr) by 0.3 mg/dL or more within 48 h; increase in SCr baseline to 1.5 times
or more, which is known or presumed to have occurred within the prior 7 days; or urine
volume < 0.5 mL/kg/h for 6 h [16]. MI was defined as the development of recurrent angina
symptoms accompanied by changes in the 12-lead electrocardiogram or increased levels of
J. Clin. Med. 2024, 13, 4408 4 of 12

cardiac-specific biomarkers. A stroke was defined as an acute episode of focal neurological

dysfunction that persists for more than 24 h.

2.6. Statistical Analysis

Variables were expressed as mean and standard deviation (SD) or as median and
interquartile range (IQR), where appropriate. The normality of the distribution of con-
tinuous variables was explored using the Shapiro–Wilk tests. Categorical variables were
presented as counts and percentages and were compared. Differences between all groups
were studied with ANOVA analysis for continuous variables and using the chi-square or
Fisher exact test for categorical data. The survival rate free from clinical endpoints was
estimated by the Kaplan–Meier method and compared by a log-rank test. An overall alpha
level of 0.05 was used as the cut-off point for statistical significance, and all statistical tests
were two-tailed. All data was analysed with R Project 4.2.1 (R Foundation for Statistical
Computing, Vienna, Austria).

3. Results
3.1. Patient Characteristics
A total of 24 patients were included. Baseline characteristics of the study population
are given in Table 1. The mean age of the patients was 65.7 ± 8.7 years; 70.8% were female;
50% had a previous infarction; and 20.8% had previous MR. The mean EuroSCORE II risk
score was 20.4 ± 17.8, and the STS risk score was 12.4 ± 10.1.

Table 1. Baseline characteristics. Values are mean ± SD, n (%), or median (interquartile range).
Abbreviations: ADA: anterior descending artery; AMI: acute myocardial infarction; CABG: coronary
artery bypass grafting; CRRT: continuous renal replacement therapy; CX: circumflex artery; DCM:
dilated cardiomyopathy; LM: left main artery; MCS: mechanical circulatory support; MV: mitral
valve; NYHA: New York Heart Association; PCI: percutaneous coronary intervention; RCA: right
coronary artery; STEMI: ST-elevation myocardial infarction; NSTEMI: non-ST-elevation myocardial
infarction; STS: Society of Thoracic Surgeons.

TOTAL (n = 24)
Age, years 65.7 ± 8.7
Female 17 (70.8)
Diabetes 12 (50)
Hypertension 13 (54.2)
Dyslipidemia 17 (70.8)
History of AMI 12 (50)
Prior PCI 10 (41.7)
Prior CABG 4 (16.7)
Any prior stroke 2 (8.3)
Peripheral vascular disease 7 (29.2)
STS risk score for MV repair 12.4 ± 10.1
EuroSCORE II risk score for MV repair 20.4 ± 17.8
Shock etiology
STEMI 13 (54.2)
NSTEMI 5 (20.8)
Ischemic DCM 5 (20.8)
Non-ischemic DCM 1 (4.2%)
J. Clin. Med. 2024, 13, 4408 5 of 12

Table 1. Cont.

TOTAL (n = 24)
Culprit vessel
LM 1 (4.2)
ADA 1 (4.2)
CX 10 (41.6)
RCA 6 (26)
SCAI stage
C 13 (54.2)
D 11 (45.8)
INTERMACS profile
1 6 (25.0)
2 7 (29.2)
3 11 (45.8)
Multiple organ failure at admission 16 (66.7)
Cardiac arrest (within 24 h) 1 (4.2)
Acute pulmonary edema 20 (83.3)
Intubated 11 (45.8)
CRRT 4 (16.7)
Admission to MCS (days) 5.9 ± 4.2

3.2. Shock Characteristics

Shock characteristics are presented in Tables 1 and 2. The most frequent cause of CS
was acute ST-elevation myocardial infarction (54.2%), with the circumflex coronary artery
being the culprit vessel in most cases (circumflex coronary artery 41.6%, right coronary
artery 26%, other vessels 8.4%). At the time of admission, most patients were classified as
INTERMACS class 2 or 3 (75%), and SCAI C (54.2%), with 66.7% experiencing multiple
organ failure. Prior to TEER therapy, 45.8% of patients required invasive mechanical
ventilation, 16.7% required continuous renal replacement therapy (CRRT), and 4.2% had
suffered a cardiac arrest. The mean time from the onset of shock to MCS implantation
was 5.9 ± 4.2 days. Inotropic support was used in 15 patients (62.5%) and vasopressor
treatment in 18 patients (75%). The mean arterial blood pressure was 52.5 ± 8.2 mm Hg,
and the mean pulmonary capillary wedge pressure was 22.5 ± 5.3 mm Hg. The additional
hemodynamics and laboratory characteristics prior to TEER therapy are detailed in Table 2.

Table 2. Hemodynamics and laboratory data prior to the TEER procedure. Values are mean ± SD, n
(%), or median (interquartile range). Abbreviations: eGFR: estimated glomerular filtration rate.

TOTAL (n = 24)
Hemoglobin (g/dL) 10.4 (1.8)
eGFR (mL/min) 45.0 ± 19.4
Lactate, mmol/L 3.8 ± 2.6
Vasopressors support 18 (75)
Norepinephrine 16 (66.7)
Epinephrine 12 (50)
Inotropic support 15 (62.5)
Dobutamine 11 (45.8)
J. Clin. Med. 2024, 13, 4408 6 of 12

Table 2. Cont.

TOTAL (n = 24)
Levosimendan 4 (16.7)
Systolic blood pressure, mm Hg 97.5 ± 18.9
Diastolic blood pressure, mm Hg 63.5 ± 7.7
Mean arterial blood pressure, mm Hg 52.5 ± 8.2
Pulmonary capillary wedge pressure, mm Hg 22.5 ± 5.3
Pulmonary artery systolic pressure, mm Hg 57.4 ± 7.3

3.3. Echocardiographic Characteristics

Baseline echocardiographic measurements are given in Table 3. The mean LVEF was
33.4 ± 9.6%, the left ventricular end-diastolic diameter (LVEDD) was 5.5 ± 0.9 cm, and the
TAPSE was 17.4 ± 2.9 cm. Regarding mitral regurgitation, 83.3% of patients had FMR, while
16.7% had DMR. MR was graded as 4+ and 3 in 95.8% and 4.2% of patients, respectively.
The mean EROA was 0.7 (±0.5) cm2 by PISA evaluation. In three patients (15%), there was
a rupture of the mitral chord. LVEF, LVEDD, EROA, TAPSE, and colour Doppler MR were
obtained in all the cases.

Table 3. Echocardiographic characteristics. Values are mean ± SD, n (%), or median (interquartile
range). Abbreviations: ADA: anterior descendent artery; CX: circumflex artery; DCM: dilated
cardiomyopathy; ECMO: extracorporeal membrane oxygenation; IABP: intra-aortic balloon pump;
LM: left main artery; MCS: mechanical circulatory support; MR: mitral regurgitation; NSTEMI:
non-acute ST-elevation myocardial infarction; RCA: right coronary artery; STEMI: acute ST-elevation
myocardial infarction.

TOTAL (n = 24)
LVEF (%) 33.4 ± 9.6
LVEDD (mm) 5.5 ± 0.9
TAPSE (mm) 17.4 ± 2.9
EROA (cm2 ) 0.7 ± 0.5
Mitral regurgitation: severity
3+ 1 (4.2)
4+ 23 (95.8)
Mitral regurgitation: etiology
Functional 20 (83.3)
Degenerative 4 (16.7)
De novo MR 19 (79.2)
Acute papillary muscle rupture 3 (12.5)

3.4. Procedural Features and In-Hospital Outcomes

Procedural characteristics are depicted in Table 4. The mean time from the onset of
shock to clip implantation was 8.8 ± 19.6 days. In the STEMI subgroup, the mean time was
7 ± 7.9 days. Procedural success was achieved in 95.8% of cases, and the mean number of
clips implanted was 1.6 ± 0.8. The mean procedure time was 95.6 (61–126) min, and the
post-procedural MV mean gradient was 3.1 ± 1.2 mmHg.
Data regarding clinical evolution after the procedure are shown in Table 4. MCS
could be removed in 83.4% of patients in 1.7 ± 1.8 days after the TEER procedure. The
duration of ICU and hospital stays was 15 (5–20) and 34 (17–36) days, respectively. Severe
procedure-related major bleeding (BARC > 2) occurred in 12.5% of cases, and 29.2% of
patients met AKI criteria. No MI or stroke was reported during the hospital outcome.
J. Clin. Med. 2024, 13, 4408 7 of 12

Table 4. Procedural features and in-hospital outcome. Values are mean ± SD, n (%), or median
(interquartile range). Abbreviations: AKI: acute kidney injury; BARC: Bleeding Academic Research
Consortium; ICU: intensive unit care; MCS: mechanical circulatory support; MV: mitral valve;
MI: myocardial infarction.

TOTAL (n = 24)
Admission to TEER (days) 8.8 ± 9.6
Procedural success 23 (95.8)
Procedural time (min) 95.6 (61–126)
No. of clips implanted 1.6 ± 0.8
Implanted clip size
XT 6 (25)
NTW 5 (20.8)
NT 9 (37.5)
Post-procedural MV mean gradient (mmHg) 3.1 ± 1.2
MCS withdrawal 20 (83.3%)
Days until MCS withdrawal 1.7 ± 1.8
Bleeding
BARC 3 2 (8.3)
BARC 4 1 (4.2)
AKI 7 (29.2)
MI N/A
Stroke N/A
ICU stay (days) 15 (5–20)
Intrahospital stay (days) 30 (17–36)
MR ≤ 2+ at discharge 21 (87.5)
Post-procedural intrahospital death 3 (12.5)

In-hospital mortality was 12.5%. A total of three patients died, although the TEER
procedure was successful for all of them. The reported causes of death were cardiovascular
in two patients and infectious diseases in one patient. At discharge, the severity of residual
MR persisted at ≤2 in all cases. Of the patients who were discharged home, all were able
to be discharged without the need for additional circulatory support therapies, with the
exception of one patient who required LVAD implantation.

3.5. Mechanical Circulatory Support

All patients were supported by MCS prior to the TEER procedure. The intra-aortic
balloon pump was the most frequently implanted MCS (79.2%), followed by ECMO (8.3%),
IMPELLA CP® (8.3%), or the combination IMPELLA CP® and ECMO (4.2%). TEER was
carried out successfully independently of the type of MCS. There were also no differences
in the rate of complications, days of admission to the ICU, days of hospitalisation, or death
during hospitalisation according to the type of ventricular assist device implanted (Table 5).

Table 5. Mechanical circulatory support features. Values are mean ± SD, n (%), or median (interquar-
tile range). Abbreviations: ICU: intensive unit care; MCS: mechanical circulatory support; MR: mitral
regurgitation; TEER: transcatheter edge-to-edge repair.

ECMO/IMPELLA
IABP (n = 19) IMPELLA (n = 2) ECMO (n = 2) p Value
(n = 1)
Successful TEER procedure 18 (94.7) 2 (100.0) 2 (100.0) 1 (100.0) 0.96
Procedural time (min) 93.9 (30.0–180.0) 115.0 (90.0–140.0) 62 (45–115) 121.0 (N/A) 0.25
MCS withdrawal 16 (84.2) 2 (100) 2 (100) N/A 0.09
ICU stay (days) 19.3 (23.0) 11.0 (8.5) 20.0 (22.6) 21.0 (N/A) 0.17
Intrahospital stay (days) 33.8 (29.8) 22.5 (14.8) 49.0 (38.2) NA 0.85
Post-procedural MR ≤ 2+ 19 (100) 2 (100) 2 (100) 1 (100) 0.83
Post-procedural
3.0 (15.8) N/A N/A N/A 0.69
intrahospital death
 J. Clin. Med. 2024, 13, x FOR PEER REVIEW 8 of 13

J. Clin. Med. 2024, 13, 4408 8 of 12

3.6. Outcomes
The median follow-up was 414 days (IQR 343–1236). At 12-month follow-up, six pa-
tients died (25.0%), and the reported causes of death were cardiovascular in four patients,
3.6. Outcomes
infectious disease in one patient, and cancer in one patient (Table 5 and Figure 2A). At 12-
The median
month follow-up,follow-up was had
eight patients 414adays (IQRevent
composite 343–1236).
of deathAt 12-month
from any causefollow-up,
or hospi- six
patients diedfor
talisation (25.0%), and5the
HF (Table andreported causes
Figure 2B). MCSofcould
death were
not cardiovascular
be removed after clipinimplanta-
four patients,
tion in three
infectious patients.
disease in oneHowever,
patient,inandone case, thein
cancer patient could be(Table
one patient discharged
5 and from the hos-
Figure 2A). At
pital after
12-month upgradingeight
follow-up, to long-term
patientsventricular support. Heart
had a composite eventtransplantation
of death from wasanynot per-
cause or
formed in anyfor
hospitalisation case.
HFMCS(Tableremoval
5 andwasFigure
associated
2B).with
MCS lower death
could notrates from any cause
be removed after clip
at 12 months, according to a univariate analysis of the Cox regression
implantation in three patients. However, in one case, the patient could be discharged model. Kaplan– from
Meier survival curves showed that patients who could not be weaned from MCS had a
the hospital after upgrading to long-term ventricular support. Heart transplantation was
higher mortality rate (Figure 3).
not performed in any case. MCS removal was associated with lower death rates from
A comparative analysis was performed of the characteristics of those patients who
anydied
cause at 12 months,
compared to thoseaccording
who survivedto a univariate
(Appendix A analysis of the
Table A1). Cox regression
Differences were onlymodel.
Kaplan–Meier
found in age. The patients who died were significantly older than those who survived MCS
survival curves showed that patients who could not be weaned from
had(73.6
a higher mortality
± 5.7 vs. rate
62.5 ± 7.7; p <(Figure
0.002). 3).

Figure
Figure 2. The
2. The 12-month
12-month Kaplan–Meier
Kaplan–Meier survivalcurves
survival curvesfor
fordeath
deathfrom
from any
any cause
cause (A)
(A) and
and the
the com-
composite
J. Clin. Med. 2024, 13, x FOR PEER REVIEW posite of death from any cause or hospitalisation for heart failure at 12 months (B). Vertical
9 of 13 dashes
of death from any cause or hospitalisation for heart failure at 12 months (B). Vertical dashes indicate
indicate censored data. HF: heart failure.
censored data. HF: heart failure.

Figure
Figure3. The
3. 12-month Kaplan–Meier
The 12-month survival curves
Kaplan–Meier for all-cause
survival curves formortality according
all-cause to theaccording
mortality pos- to the
sibility of MCS removal. MCS: mechanical circulatory support.
possibility of MCS removal. MCS: mechanical circulatory support.
4. Discussion
The Mitra-ASSIST registry is the first study to specifically explore TEER treatment in
CS patients requiring MCS. The main findings of this study are that the success rate of the
intervention is greater than 95%, allowing MCS removal in most patients with a low com-
plication rate and an acceptable rate of mortality and readmissions for HF at short and 12-
J. Clin. Med. 2024, 13, 4408 9 of 12

A comparative analysis was performed of the characteristics of those patients who

died compared to those who survived (Appendix A Table A1). Differences were only found
in age. The patients who died were significantly older than those who survived (73.6 ± 5.7
vs. 62.5 ± 7.7; p < 0.002).

4. Discussion
The Mitra-ASSIST registry is the first study to specifically explore TEER treatment
in CS patients requiring MCS. The main findings of this study are that the success rate of
the intervention is greater than 95%, allowing MCS removal in most patients with a low
complication rate and an acceptable rate of mortality and readmissions for HF at short and
12-month follow-up.
Mortality in cardiogenic shock remains very high despite all therapeutic advances [4,17,18].
In addition, it should be noted that CS with concomitant valvular disease is present in up
to 20% of cases [8,19]. These patients are underrepresented in clinical studies, constituting
a management challenge. Although surgery could be an option, due to the prohibitive
surgical risk of these patients, surgical treatment is often not feasible [17]. For this reason,
TEER has been used in recent years as a potential therapeutic alternative. Although the
evidence is limited and is confined to several case series and multicentre registries, the
results are promising [8,9,20]. In a recent observational study involving 3797 patients with
CS undergoing TEER, the procedural success was 85.6%, with a 48% reduction in 1-year
mortality and a 46% reduction in HF readmission at 1 year in those patients who achieved
an MR ≤ 2+ grade [21].
Despite these promising results, the use of TEER therapy in patients with CS requiring
MCS for hemodynamic support is poorly studied. MCS in the setting of CS with MR may
provide benefits by reducing preload, increasing cardiac output, and, depending on the
implanted support, improving coronary percussion. However, it is not known whether
the combination of TEER therapy in patients with CS and MCS may be useful. To date,
the only study performed specifically in this setting is a case series involving six patients
who underwent a combined MITRACLIP® and IMPELLA® implantation procedure [13].
The procedure was successfully performed in all cases and was associated with a hospital
survival rate of 83%. However, this study has not proven benefits beyond the first 6 months,
nor did it include other types of MCS different from IMPELLA® .
It is important to note that the use of any type of CSM was allowed for the analysis.
Most patients received IABP (79.2%), followed by ECMO (8.3%), IMPELLA (8.3%), or a
combination of both (4.3%). A favourable conclusion of our study is that the procedure had
high effectiveness without differences in in-hospital mortality or in the rate of complications
independently of the implanted MCS. In addition, in the MITRA-ASSIST registry, the
procedural success was very high (95.6%), the procedure time was shorter than expected
compared to previous series (95.6 (61–126) min), and the MR at discharge was less than
two in all cases. These are good results compared to contemporary studies in which the
success rate was similar but the implantation time and complication rate were higher even
in patients who did not require MCS [18,19,21,22].
In terms of events, the results are promising. A total of 87.5% of patients were able
to be discharged. Moreover, at 12-month follow-up, only 25.0% died, and 33% had a
composite event of death from any cause or hospitalisation for HF. The MITRA-ASSIST
study population possibly presented a priori a worse vital prognosis than in other published
studies because all patients required MCS for adequate hemodynamic support. Even so,
compared with other contemporary studies, the results are better than expected for a
population that has not been studied to date.
The role of MCS in patients with CS depends on the time of onset of MR and the
severity of shock [23]. When MR is present before the implant of MCS, ECMO is not recom-
mended because it increases afterload and worsens pulmonary edema. IABP or IMPELLA,
which provides ventricular unloading, are preferable in these cases [24]. However, MR is
often diagnosed or develops at a late stage when an MCS has been implanted. Furthermore,
J. Clin. Med. 2024, 13, 4408 10 of 12

even with an early diagnosis of MR, ECMO may be the only effective hemodynamic sup-
port option for patients with right ventricular dysfunction [25]. However, it is important
to note that TEER under ECMO is safe and feasible, although it is advisable to confirm
the severity of MR prior to the procedure. Although it is true that MR may improve after
correction of the cause of shock, especially those secondary to coronary syndrome, up to
50% of cases do not recover [26]. Therefore, due to the high mortality of patients with CS, it
seems appropriate to intervene early in MI after evaluation by a multidisciplinary team
with expertise in mitral valve disease.

5. Limitations
Even though this is a promising study, it should be emphasised that this is a retrospec-
tive study with a small sample size. For this reason, this registry is subject to selection bias,
and the results should be considered with caution. First, regarding mortality, the outcomes
are promising, and the mortality rates are lower than anticipated for this patient cohort.
However, it is crucial to acknowledge the potential presence of indication bias. It is probable
that only those patients deemed to be in a relatively healthier state were selected for the
TEER procedure. Second, although it is true that the measurements were performed in all
the centres following the recommendations of the current European guidelines for manage-
ment of valvular heart disease, the analysis was not performed in a central laboratory, and
there may be biases in the MR assessment. Therefore, the implantation success rate may
differ between centres because it depends on the MR assessment. Third, the limited number
of patients who received ECMO or IMPELLA precludes drawing definitive conclusions for
this subgroup of patients. Fourth, although Kaplan–Meier survival curves showed positive
outcomes in this study, the limited number of cases may lead to uncertain differences in the
compared results. Therefore, these data should be interpreted with caution. For this reason,
this study can only generate hypotheses. New prospective studies, such as the CAPITAL
MINOS trial [27], will be necessary to evaluate the importance of TEER in CS, especially in
those patients who require MCS.

6. Conclusions
The Mitra-ASSIST Registry describes the safety and feasibility of TEER therapies in
patients with concomitant CS and MR requiring MCS. TEER in patients with concomitant
CS and MR who require MCS would seem to be a promising therapeutic alternative with a
high device procedural success rate and an acceptable mortality and HF admission rate at
12-month follow-up.

Author Contributions: B.R.-S. and A.J.-R. contributed equally to this manuscript and are co-first
authors. Conceptualization, B.R.-S. and A.J.-R.; methodology, B.R.-S. and A.J.-R.; software, B.R.-S.
and A.J.-R.; validation, B.R.-S. and A.J.-R.; investigation, B.R.-S., A.J.-R., I.P., C.H.L., P.J., R.E.-L.,
P.C.-G., T.B.-G., A.S., J.M.D.L.T.-H., P.A., E.F.-P., L.N., B.C.-Q., X.F., F.F.-V., I.A.-S., D.-H.L., V.L., D.A.,
R.M. and G.G.; resources, B.R.-S., A.J.-R., I.P., C.H.L., P.J., R.E.-L., P.C.-G., T.B.-G., A.S., J.M.D.L.T.-H.,
P.A., E.F.-P., L.N., B.C.-Q., X.F., F.F.-V., I.A.-S., D.-H.L., V.L., D.A., R.M. and G.G.; data curation,
B.R.-S., A.J.-R. and R.M.; writing—original draft preparation, B.R.-S. and A.J.-R.; writing—review
and editing, B.R.-S., A.J.-R. and R.M.; visualization, B.R.-S., A.J.-R., I.P., C.H.L., P.J., R.E.-L., P.C.-G.,
T.B.-G., A.S., J.M.D.L.T.-H., P.A., E.F.-P., L.N., B.C.-Q., X.F., F.F.-V., I.A.-S., D.-H.L., V.L., D.A., R.M. and
G.G.; supervision, B.R.-S. and A.J.-R.; project administration: B.R.-S. and A.J.-R. All authors have read
and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable. Our study did not receive a traditional
approval code as it involved the retrospective analysis of anonymized data. We engaged with the
Institutional Review Board at Hospital Universitario La Paz for a consultative review. The Board has
comprehensively assessed the research protocol and has granted us the necessary ethical endorsement
to proceed.
Informed Consent Statement: Not applicable.
J. Clin. Med. 2024, 13, 4408 11 of 12

Data Availability Statement: The data presented in this study are available on request from the
corresponding author.
Conflicts of Interest: The authors declare no conflicts of interest.

Appendix A

Table A1. Comparative analysis of mortality.

ALIVE (n = 17) DEATH (n = 7) TOTAL (n = 24) p Value

Age, years 62.5 ± 7.7 73.6 ± 5.7 65.7 ± 8.7 0.002
Female 12 (70.6) 5 (71.4) 17 (70.8)
Diabetes 8 (47.1) 4 (57.1) 12 (50.0) 0.653
Prior PCI 7 (41.2) 3 (42.9) 10 (41.7) 0.939
INTERMACS profile 0.575
1 5 (29.4) 1 (14.3) 6 (25.0)
2 4 (23.5) 3 (42.9) 7 (29.2)
3 8 (47.1) 3 (42.9) 11 (45.8)
SCAI stage 0.380
C 14 (82.4) 4 (57.1) 18 (75)
D 3 (17.6) 3 (42.9) 6 (25.0)
STEMI 10 (58.8) 3 (42.9) 13 (54.2) 0.476
Mitral regurgitation:
0.512
severity
3+ 1 (5.9) 0 1 (4.2)
4+ 16 (94.1) 7 (100.0) 23 (95.8)
Mitral regurgitation:
etiology
Functional 15 (88.2) 5 (71.4) 20 (83.3)
Degenerative 2 (11.8) 2 (28.6) 4 (16.7)
Acute papillary muscle
2 (11.8) 1 (14.3) 3 (12.5) 0.865
rupture
LVEF (%) 33.0 ± 9.3 34.4 ± 10.9 33.4 ± 9.6 0.742
Admission to TEER (days) 8.6 ± 9.0 9.1 ± 11.7 8.8 ± 9.6 0.901

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