- Academic Editors
Pharmacological treatment is the cornerstone therapy of heart failure with reduced ejection fraction (HFrEF). In addition, several percutaneous techniques have been developed to treat symptomatic patients, with specific heart failure (HF) phenotypes (e.g., valvular heart disease) that require non-pharmacological treatment. Given their prognostic relevance, it is imperative to deliver high-level patient care. This review provides a clinical overview on the available data regarding transcatheter devices in the armamentarium of contemporary interventional cardiologists, focusing on the clinical and anatomical selection criteria.
Heart failure (HF) is present in about 1–2% of the adult population in
developed countries, with approximately a half being affected from HF with
reduced ejection fraction (HFrEF), defined by the presence of symptoms and/or
signs of HF and a left ventricular ejection fraction (LVEF)
The armamentarium of transcatheter option for HFrEF treatment. CCM, cardiac contractility modulation; CRT, cardiac resynchronisation therapy; TAVI, transcatheter aortic valve implantation.
Device | Indication | Class of recommendation | Level of evidence | |
Aortic stenosis° | ||||
TAVI | I | A | ||
Secondary mitral regurgitation° | ||||
TEER | symptomatic patients, not eligible for surgery and fulfilling criteria suggesting an increased chance of responding to the treatment | IIa | B | |
transcatheter annuloplasty | n.a. | |||
transcatheter replacement systems | n.a. | |||
Concomitant aortic stenosi and secondary mitral regurgitation° | ||||
TAVI + TEER | TAVI followed by MV TEER (in case of persisting severe SMR) in symptomatic patients, judged not appropriate for surgery by the Heart Team | IIa | C | |
Tricuspid regurgitation° | ||||
TEER | inoperable symptomatic patients, at a Heart Valve Centre with expertise in the treatment of tricuspid valve disease | IIb | C | |
transcatheter annuloplasty | ||||
transcatheter replacement systems | ||||
heterotopic caval valve | ||||
Interatrial shunt devices* | ||||
V-wave Shunt | n.a. | |||
Atrial Flow Regulator | n.a. | |||
Transcatheter Atrial Shunt System | n.a. | |||
Left ventricular remodeling devices | ||||
Parachute device | n.a. | |||
AccuCinch | n.a. | |||
EuroSCORE, European System for Cardiac Operative
Risk Evaluation; HFrEF, heart failure with reduced ejection fraction; MV, mitral valve;
SMR, secondary mitral regurgitation; TAVI, transcatheter aortic valve implantation; STS-PROM,
Society of Thoracic Surgeons predicted risk of mortality; TEER, transcatheter edge-to-edge repair;
n.a., not applicable.
°2021 ESC/EACTS Guidelines for the management of valvular heart disease: Developed by the Task Force for the management of valvular heart disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) [4]. *2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure [1]. |
Device and NCT | Trial full title | Trial acronym | Trial type | Estimated enrollement (n) | Anticipated completion date | LVEF inclusion criteria | Study arms | Primary endpoint |
Aortic stenosis | ||||||||
TAVI | ||||||||
NCT02661451 | Transcatheter Aortic Valve Replacement to UNload the Left Ventricle in Patients With ADvanced Heart Failure: A Randomized Trial | TAVR UNLOAD | RCT | 300 | Mar-24 | LVEF |
Device: TAVR (with SAPIEN 3) and GDMT; Control: GDMT alone | 1-year all-cause death, disabling stroke, hospitalizations related to HF, symptomatic aortic valve disease or non-disabling stroke - or - clinically significant worsening of HF, change in Kansas City Cardiomyopathy Questionnaire (KCCQ) relative to baseline |
Secondary mitral regurgitation | ||||||||
MitraClip | ||||||||
NCT02444338 | A RandomizEd Study of tHe MitrACliP DEvice in Heart Failure Patients With Clinically Significant Functional Mitral Regurgitation | Reshape-HF2 | RCT | 650 | Jun-24 | LVEF of |
Device: MitraClip device plus GDMT; Control: GDMT alone | 2-year composite rate of recurrent HF hospitalizations and cardiovascular death |
NCT05292716 | Mitral Regurgitation Treatment in Advanced Heart Failure | MITRADVANCE | RCT | 172 | Apr-25 | LVEF |
Experimental: MitraClip device plus GDMT; No Intervention: GDMT alone | 3-month Absolute change in overall KCCQ summary score |
Pascal | ||||||||
NCT03706833 | Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial (CLASP IID/IIF): A Prospective, Multicenter, Randomized, Controlled Pivotal Trial to Evaluate the Safety and Effectiveness of Transcatheter Mitral Valve Repair With the Edwards PASCAL Transcatheter Valve Repair System Compared to Abbott MitraClip in Patients With Mitral Regurgitation | CLASP IIF | RCT | 1275* | Jan-28 | n.a. | Experimental: PASCAL System; Active Comparator: Mitraclip System | Pascal non-inferiority to MitraClip with respect to MACEs at 30-day and time to first HF hospitalization or death at 5-year |
Cardioband | ||||||||
NCT03016975 | Annular ReduCtion for Transcatheter Treatment of Insufficient Mitral ValvE (ACTIVE): A Prospective, Multicenter, Randomized, Controlled Pivotal Trial to Assess Transcatheter Mitral Valve Repair With Edwards Cardioband System and GDMT vs GDMT Alone in Patients With FMR and Heart Failure | ACTIVE | RCT | 12 | Sep-24 | n.a. | Experimental: ©Edwards Cardioband System plus GDMT; Active Comparator: GDMT alone | Hierarchical comparison of MR |
Carillon Mitral Contour System | ||||||||
NCT03142152 | Assessment of the Carillon Mitral Contour System in Treating Heart Failure With at Least Mild Functional Mitral Regurgitation | EMPOWER | RCT | 300 | Dec-28 | LVEF |
Intervention: Carillon Mitral Contour System and GDMT; Control: GDMT alone | Intervention group is superior to the control group on the hierarchical composite endpoint of death, transplant or left ventricular assist device, percutaneous or surgical MV intervention, HF hospitalization, improvement in KCCQ, and improvement in 6MWT at 1-year |
Tendyne | ||||||||
NCT03433274 | Clinical Trial to Evaluate the Safety and Effectiveness of Using the Tendyne Transcatheter Mitral Valve System for the Treatment of Symptomatic Mitral Regurgitation | SUMMIT | RCT | 958 | Jun-27 | LVEF |
Treatment: Tendyne Transcatheter Mitral Valve System; Control: MitraClip system | 1-year survival free of HF hospitalization |
Intrepid | ||||||||
NCT03242642 | Transcatheter Mitral Valve Replacement With the Medtronic Intrepid TMVR System in Patients With Severe Symptomatic Mitral Regurgitation | APOLLO | prospective, non-randomized, interventional, pre-market trial | 1350 | Oct-28 | LVEF |
Device: Intrepid Transcatheter Mitral Valve Replacement System | 1-month all-cause mortality or HF hospitalization days or KCCQ improvement |
Tricuspid regurgitation | ||||||||
TriClip | ||||||||
NCT03904147 | Clinical Trial to Evaluate Cardiovascular Outcomes In Patients Treated With the Tricuspid Valve Repair System Pivotal | TRILUMINATE Pivotal trial | RCT | 700 | Dec-28 | LVEF |
Device: TriClip plus GDMT; Control: GDMT alone | 1-year hierarchical composite of number of participants with all-cause mortality or number of participants with tricuspid valve surgery, rate of HF hospitalizations, and assessment of quality of life improvement using the KCCQ |
Pascal | ||||||||
NCT04097145 | A Prospective, Multicenter, Randomized, Controlled Pivotal Trial to Evaluate the Safety and Effectiveness of Transcatheter Tricuspid Valve Repair With the Edwards PASCAL Transcatheter Valve Repair System and Optimal Medical Therapy (OMT) Compared to OMT Alone in Patients With Tricuspid Regurgitation | CLASP II TR | RCT | 825 | Mar-29 | n.a. | Experimental: PASCAL System & GDMT; Active Comparator: GDMT alone | 2-year composite of all-cause mortality, right ventricular assist device implantation or heart transplant, TV intervention, HF hospitalizations, and quality of Life improvement (measured by KCCQ score) |
Inteatrial shunt device | ||||||||
V-wave shunt | ||||||||
NCT03499236 | REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure | RELIEVE-HF | RCT | 605 | Oct-27 | n.a. | Treatment: V-Wave Shunt implantation plus GDMT; Control: GDMT alone | 1- to 2-year Hierarchical composite of death, heart transplant or LVAD implantation, HF hospitalizations, worsening HF events treated as an outpatient, and change in KCCQ |
Left ventricular remodeling device | ||||||||
AccuCinch | ||||||||
NCT04331769 | Randomized Clinical Evaluation of the AccuCinch® Ventricular Restoration System in Patients Who Present With Symptomatic Heart Failure With Reduced Ejection Fraction (HFrEF) | CORCINCH-HF | RCT | 400 | Dec-30 | LVEF |
Device: AccuCinch Ventricular Restoration System plus GDMT; Control: GDMT alone | 1-year hierarchical composite endpoint of all-cause deaths, LVAD implants or heart transplants, HF hospitalizations, and changes from baseline in KCCQ Overall Score |
* refers to both CLASP IID/IIF trials.
CLASP IIF, Edwards PASCAL TrAnScatheter Mitral Valve RePair System Pivotal Clinical Trial; FMR, functional mitral regurgitation; GDMT, guideline-directed medical therapy; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; KCCQ, Kansas City Cardiomyopathy questionnaire; LVAD, left ventricular assist device; LVEF, left ventricular ejection fraction; MACE, major adverse cardiovascular event; MITRADVANCE, Mitral Regurgitation Treatment in Advanced Heart Failure; MR, mitral regurgitation; NCT: national clinical trial; NYHA, New York Heart Association; RCT, randomized controlled trial; TAVI, transcatheter aortic valve implantation; TAVR-UNLOAD, Transcatheter Aortic Valve Replacement to UNload the Left Ventricle in Patients With ADvanced Heart Failure; n.a., not applicable. |
The hemodynamic consequences of aortic stenosis (AS) consist in an increased LV afterload, reduced myocardial compliance due to fibrosis, and increased myocardial workload resulting into a progressive pressure-related LV remodeling [5, 6]. These changes in LV function and workload are believed to evolve into a progressive systolic and diastolic dysfunction resulting in a complex interaction between transvalvular flow, mean gradient, and LVEF.
Symptomatic severe AS has a dismal prognosis and timely intervention is strongly
recommended [7]. Since the first-in-human procedure performed by Alain Cribier in
2002, transcatheter aortic valve implantation (TAVI) has shown impressive
progress in terms of procedural standardization and clinical use, with its
indications having been extended [8]. According to current European Society of
Cardiology (ESC) guidelines, TAVI is recommended (Class of Recommendation I,
Level of Evidence A) in patients aged
In the context of HFrEF, two different phenotypes of AS can be identified: high gradient AS (HG-AS) and low-flow low-gradient AS (LFLG-AS). Commonly, HG-AS with low LVEF is associated with an afterload-mismatch, in which the increased afterload causes a reduction of the stroke volume and a decline in ejection fraction despite a preserved contractile reserve. In such cases, the resolution of the AS might lead to an improvement in LV systolic function and a regression in LV mass hypertrophy. In a single-center 5-year analysis of cardiovascular mortality, major adverse cardiovascular and all-cause mortality, events did not differ significantly between HG-AS patients dichotomized according to baseline LVEF (preserved vs. reduced), thus demonstrating that TAVI in HG-AS patients with HFrEF had clinical outcomes similar to patients with preserved LVEF [15].
Conversely, LFLG-AS is usually associated to irreversible myocardial damage due
to extensive myocardial fibrosis and/or concomitant coronary artery disease.
Other conditions, such as atrial fibrillation (AF) and associated mitral and/or
tricuspid regurgitation, may contribute to a low-flow state. In these settings,
the magnitude of benefit achieved by valve replacement should be carefully
evaluated case-by-case. Indeed, in the presence of a low transvalvular gradient
at baseline or concomitant valvular disease, aortic valve replacement might be
considered ineffective from an haemodynamic and prognostic standpoint [16]. On
the other hand, conservative management of these patients has been associated
with mortality rates
Recently, Jean et al. [22] evaluated prognostic contribution of
moderate aortic stenosis (aortic valve area 1.0 to 1.5 cm
As procedural safety of TAVI has improved, we should re-evaluate the established indications for aortic valve replacement, as we should also consider implementing its use to treat patients with moderate AS and low (¡50%) LVEF. The potential benefit of TAVI in this setting will be evaluated in the ongoing Transcatheter Aortic Valve Replacement to UNload the Left Ventricle in Patients With ADvanced Heart Failure (TAVR-UNLOAD) trial (NCT02661451) which is recruiting patients with HF, LVEF between 20% and 50%, and moderate AS to receive either TAVI on top of guideline-directed medical therapy (GDMT) or appropriate HF therapy alone.
Chronic setting—Secondary (or functional) mitral regurgitation (SMR) is a common finding in patients with HFrEF [23], resulting from spherical remodeling and enlargement of the LV leading to geometrical distortion of the subvalvular apparatus. With disease progression and worsening SMR, increased leaflets tethering and decreased closing forces perpetuate the vicious cycle involved in “valvular HFrEF” until the final phase of “advanced HFrEF” characterized by recurrent acute HF episodes. Any kind of intervention at this point may be effective only in alleviating symptoms while percutaneous mitral valve (MV) interventions may reduce the burden of volume overload, thus reversing LV dilation and dysfunction and ultimately improving symptoms and even survival [24], if performed at an earlier stage.
Transcatheter edge-to-edge repair (TEER) devices have been developed as percutaneous counterparts of the surgical Alfieri stitch [25], in order to treat symptomatic patients with severe mitral regurgitation (MR) considered by the Heart Team at high risk for surgery or inoperable [24].
The MitraClip system (©Abbott Vascular, Santa Clara, CA, USA) is currently the only device whose efficacy on outcome has been evaluated in RCTs. Although it was originally conceived for the treatment of primary MR (especially considering the results of the pivotal Endovascular Valve Edge-to-Edge REpair Study (EVEREST) trial), the indication was then extended for SMR treatment too, with favorable early and mid-term results in multi-center experiences [26, 27, 28]. In reference to these studies, although limited to their intrinsic observational nature, several predictors of cardiovascular outcomes have been proposed. Among them, LVEF has expectedly shown to be a strong predictor of outcome, with lower values being associated with poorer results [29]. In addition, the etiology of MR itself and acute post-procedural results have also been shown to be associated with poorer outcome [30, 31]. In this regard, newer generations of the device, such as the MitraClip G4, allowed more satisfactory results, in terms of residual MR, even in the most complex anatomies, including extreme tethering in SMR [32]. Moreover, in patients with advanced HFrEF, intra-procedural challenges related to ventricular dysfunction, hypoperfusion, or risk of mismatch should be considered. The use of inotropic support during the procedure, as well as mechanical assist devices, can be useful in selected cases or in hemodynamic unstable patients [33].
Recent evidence from the latest RCTs has therefore highlighted the importance
of an adequate patient selection and a correct intervention timing, prior to LVEF
deterioration. The Cardiovascular Outcomes Assessment of the MitraClip
Percutaneous Therapy for Heart Failure Patients with Functional Mitral
Regurgitation (COAPT) trial showed that in patients with HF and severe SMR, TEER
with MitraClip improved survival compared with GDMT alone (HR: 0.62; 95% CI:
0.47–0.82; p
All of the following criteria should be fulfilled | ||
Absence of left ventricular impairment | Absence of right ventricular impairment | Absence of hemodynamic instability |
COAPT, Cardiovascular Outcomes Assessment of the Mitral Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation; GDMT, guideline-directed medical therapy; HF, heart failure; LV, left ventricle; LVEF, left ventricular ejection fraction; MV, mitral valve; TEER, transcatheter edge-to-edge repair; TR, tricuspid regurgitation. |
Based on these trials, the definitions of proportionate and disproportionate MR were then suggested, in order to define the balance between LV dysfunction and MR degree [36]. However, sub-analysis from Mitra-FR and COAPT trials showed that the benefit of TEER with the MitraClip system is not fully supported by the proportionate-disproportionate hypothesis [37, 38]. In addition, while the baseline medical therapy in the COAPT trial had to be optimized in order to make the patient eligible, the baseline medical therapy in the MITRA-FR trial was not optimized in all patients and multiple adjustments occurred during follow-up, possibly masking the effect of TEER on outcomes. Finally, the more sustained efficacy of the MitraClip procedure found in the COAPT trial may be a consequence of a more aggressive strategy for MR correction [39].
Further insight will come from the results of the A RandomizEd Study of tHe MitrACliP DEvice in Heart Failure Patients With Clinically Significant Functional Mitral Regurgitation (Reshape-HF2) trial (NCT02444338), which has the same inclusion criteria as the COAPT trial in terms of MR severity and intermediate criteria between COAPT and MITRA-FR in terms of LV dysfunction severity, and the Mitral Regurgitation Treatment in Advanced Heart Failure (MITRADVANCE) trial (NCT05292716), which has the objective to evaluate the absolute changes in overall quality of life in patients with advanced HFrEF randomized between MitraClip therapy added to GDMT or GDMT alone.
The more recent Pascal device (©Edwards Lifesciences,
Irvine, CA, USA) received CE mark approval for the treatment of SMR in February
2019 [40, 41]. Analysis from compassionate use experience (52% SMR patients) and
early feasibility study (55% SMR patients) demonstrated Pascal to be safe and
effective in the treatment of this subset of patients [42, 43]. Those results were
confirmed by the expanded 1- and 2-year Edwards PASCAL Transcatheter Mitral Valve
Repair System Study (CLASP) experience [44, 45]. The only available comparison
between MitraClip and Pascal devices is a 2:1 propensity-matched retrospective
analysis, which revealed no significant differences in terms of Mitral Valve
Academy Research Consortium technical, device, and procedural success and
clinical improvement at 1-year follow-up, except for higher rates of patients
with MR
Transcatheter annuloplasty implants, such as Cardioband
(©Edwards Lifesciences, Irvine, CA, USA) and Carillon
Mitral Contour System (©Cardiac Dimensions, Kirkland, Washington
DC, USA), were designed to reduce MV annulus to minimize regurgitation. The
Cardioband Mitral System is a transcatheter, transseptal, adjustable, direct
mitral annuloplasty device. In a multicentre study, the Cardioband mitral system
demonstrated safety and reasonable performance (MR
Lastly, transcatheter replacement systems such as Tendyne (©Abbott Vascular, Santa Clara, CA, USA) and Intrepid (©Medtronic, Minneapolis, MN, USA) are emerging therapies that address the clinical need of MR treatment in the context of unfavorable anatomies for TEER or annuloplasty, including short, calcified, or severely tethered leaflets, severe annular calcification, multiple jets of regurgitation, and elevated transvalvular gradient [50].
The Tendyne is a 36-F transapical MV replacement device. In the Expanded
Clinical Study of the Tendyne Mitral Valve System, its impact on MR severity and
symptomatic improvement was evaluated for a 2-year follow-up period in a cohort
of 100 patients (89% SMR) undergoing Tendyne implantation. The overall mortality
rate was 39%, the highest in the first 3 months after procedure together with
re-hospitalization for HF rate. Among survivors, a statistically significant
reduction of LVEF was noticed, despite the presence of hemodynamic improvement in
terms of pulmonary pressure reduction [51]. However, potential complications
associated with transapical delivery, such as myocardial injury, bleeding,
thoracotomy incisional pain, ventricular arrhythmias and prolonged
hospitalization, remain an important aspect to consider, especially in frail
elderly patients with reduced LVEF [52]. The Clinical Trial to Evaluate the
Safety and Effectiveness of Using the Tendyne Transcatheter Mitral Valve System
for the Treatment of Symptomatic Mitral Regurgitation (SUMMIT) trial
(NCT03433274) will provide the opportunity to evaluate the safety and clinical
benefits of Tendyne compared to the MitraClip System in patients with LVEF
The Intrepid is a 35-F transfemoral, transseptal MV replacement device whose
safety and efficacy at 30-day follow-up have been evaluated in a series of 15
patients (33% SMR), revealing excellent valve function and no mortality or
stroke [53]. Transseptal MV replacement remains a challenging approach for
numerous reasons, including excessive access-site bleeding (related to sheath
size and need for anticoagulation to minimize the risk for valve thrombosis),
safety of transseptal access, ability to align with the mitral annulus, and the
need to obtain adequate height above the MV in order to minimize the risk for LV
outflow tract obstruction while achieving optimal valve position [54]. The
Transcatheter Mitral Valve Replacement with the Medtronic
Intrepid™ TMVR System in Patients with Severe Symptomatic Mitral
Regurgitation (APOLLO) trial (NCT03242642) will evaluate this valve in a larger
cohort in a longer follow-up and assess LV remodeling related to elimination of
MR, in patients with LVEF
Acute setting—Ischemic SMR may emerge as a consequence of papillary muscle rupture or apical and inferior displacement of the papillary muscles due to rapid remodeling of the infarcted area. Acute SMR can lead to acute pulmonary edema and hemodynamic instability, affecting short-term prognosis. The efficacy of TEER using the MitraClip system in patients with acute SMR has been retrospectively evaluated and compared to conservative and surgical treatment [55]. Of note, patients with papillary muscle rupture were excluded from analysis. Patients undergoing conservative strategy had the worst prognosis whereas survival was higher in TEER-treatment group when compared to surgery, mainly due to lower in-hospital mortality rate. Hence, authors have suggested that TEER may be considered a rescue therapy for patients that are deemed high risk for surgical intervention. However, it should be taken into account that neither randomized clinical trials nor other analyses comparing percutaneous treatment of MR with other clinical strategies in this acute and complex setting are currently available.
In the context of HFrEF, increased left atrial pressure (LAP) may lead to (a) increasing post-capillary pulmonary pressure, resulting in pulmonary hypertension (PH), right ventricle (RV)-to-pulmonary artery (PA) uncoupling and, finally, RV dilation and dysfunction and (b) LA negative remodeling and enlargement with subsequent atrial AF onset, volume overload, and progressive right atrium (RA) enlargement. All these mechanisms may elicit tricuspid annulus (TA) dilation leading to leaflet malcoaptation and, ultimately, tricuspid regurgitation (TR). Furthermore, lead-induced TR has to be considered [56, 57]. In the last few years, percutaneous transcatheter tricuspid repair/replacement systems emerged as a new tool to treat symptomatic high surgical risk patients with severe TR. Transcatheter devices can be grouped into leaflet devices for TEER, annuloplasty devices, transcatheter TV replacement and heterotopic caval valve implantation. Global RV dysfunction is a predictor of outcomes among patients undergoing percutaneous procedures [58].
Leaflet devices, whose target is to improve leaflet coaptation, are the
most commonly applied for interventional TR treatment, as they combine the
possibility to repair rather than replace with the experience acquired on MV
treatment through a transcatheter approach [59]. The Trial to Evaluate Treatment
With Abbott Transcatheter Clip Repair System in Patients With Moderate or Greater
Tricuspid Regurgitation (TRILUMINATE) enrolled 85 patients with moderate or
greater TR undergoing TriClip (©Abbott Vascular, Santa
Clara, CA, USA) implantation in a prospective, multicenter, single-arm study.
After 1 year of follow-up, a durable reduction to moderate or less TR in 71% of
patients, a significant clinical benefit in terms of NYHA functional class, and a
reduction of the rate of rehospitalization by 40% compared to the period before
the procedure was reported [60]. Non-anteroseptal location of the TR and a
coaptation gap
In the TriBAND study, the Cardioband direct annuloplasty system (©Edwards Lifesciences, Irvine, CA, USA) showed to be effective in reducing significantly the septo-lateral diameter, leading to an improvement of TR severity to moderate or less in 69% of patients at 30 days follow-up [63]. One of the main complications related to device implantation is right coronary artery perforation or occlusion, which occurred in 15% of the cases.
The Evoque bioprosthesis (©Edwards Lifesciences, Irvine, CA, USA) is delivered by a 28-F transfemoral system. The prospective, single-arm, multi-centre Edwards EVOQUE Tricuspid Valve Replacement: Investigation of Safety and Clinical Efficacy after Replacement of Tricuspid Valve with Transcatheter Device (TRISCEND) study demonstrated technical feasibility, acceptable safety (with severe bleeding as the most frequent complication), significant TR reduction, and symptomatic improvement at 30 days [64].
Lastly, heterotopic caval valve implantation can relieve TR-related symptoms, improving venous congestion, without directly treating tricuspid valve. The TricValve (©P+F Products+Features GmbH, Wessling, Germany) consists of two valves implanted separately in the superior and inferior vena cava, able to treat patients with diameters of the inferior vena cava up to 40–43 mm, in the presence of a distance from the right atrium junction to the hepatic veins of at least 10 mm [61]. Six-month outcomes analysis from the Safety and Efficacy of the TricValve Transcatheter Bicaval Valves System in the Superior and Inferior Vena Cava in Patients With Severe Tricuspid Regurgitation (TRICUS EURO) study revealed high procedural success rate and significant improvements in both quality of life and functional classification. Compared to other transcatheter tricuspid repair or replacement techniques, both volume overload of the right ventricle and N-terminal pro–brain natriuretic peptide concentration increased during follow-up after TricValve implantation [65]. Heterotopic caval valve implantation might therefore represent a simplistic approach to the complex issue of tricuspid valve, and, unless longer follow-up becomes available, the procedure should be limited to patients unsuitable for tricuspid valve repair or replacement (i.e., large coaptation gap, lead-related severe TR, failed previous transcatheter valve repair, severe RV dysfunction, and too large annular size).
MR frequently coexists in patients with severe AS. Despite patients with both valvular heart diseases being more compromised when compared to those without, whether concomitant MR independently affects outcomes in patients undergoing TAVI remains a matter of debate [66]. In the presence of simultaneous severe AS and secondary MR in patients suffering from HFrEF undergoing TAVI, different strategies may be adopted: (1) TAVI only, (2) combined bivalvular transcatheter therapy or (3) isolated TAVI and reassessment for possible staged MV procedure. According to current ESC guidelines, although bivalvular transcatheter procedures have been demonstrated to be technically feasible and safe, TAVI followed possibly by MV TEER (in case of persisting severe SMR) should be considered only symptomatic patients judged as unsuitable for surgery by the Heart Team [4, 67].
Moderate or severe TR is present in about one third of the patients undergoing surgical or transcatheter MV interventions, and has been proven to negatively impact prognosis and quality of life [68, 69]. Since TR does not regress after successful treatment of the MV in a majority of the patients, either concomitant or staged combined procedures should be considered based on patient anatomic and hemodynamic characteristics [70].
Increase in LAP is the key determinant of pulmonary congestion, with consequent dyspnea and exercise limitation, in patients with HFrEF [71]. Moreover, it is the precipitating mechanism of acute decompensation in chronic HF [72]. An implantable device for real-time indirect monitoring of LAP (CardioMEMS HF System, ©Abbott Vascular, Santa Clara, CA, USA) has been shown to decrease re-hospitalization for HF by guiding dose titration of decongestion therapies [73, 74]. Similarly, devices able to reduce LAP through an interatrial communication that determines a left-right shunt have been developed. Shunt flow is based on the interatrial pressure gradient, leading to an on-demand, auto-regulating reduction in LAP [75].
While the InterAtrial Shunt Device (©Corvia Medical, Tewksbury, MA, USA) has been evaluated in patients with HF with preserved or at least mildly reduced LVEF, V-wave Shunt device (©V-Wave Ltd, Caesarea, Israel) was the first interatrial shunt technology implanted in a patient with HFrEF [76, 77]. It is a self-expanding, hourglass-shaped, percutaneously implanted device containing a one-way bioprosthetic valve implanted through the femoral vein and subsequent interatrial septal puncture. A single-arm open-label study of 38 HF patients (~79% HFrEF) with NYHA functional class III or IV on optimal medical therapy was performed at 6 centers, with the shunt device having been successfully implanted in all cases. At 1-year follow-up, significant clinical improvement was observed despite attenuation of shunt patency in 50% of patients, perhaps due to intra-shunt valve deterioration. Patients with full patent shunts exhibited significant improvements in hemodynamic parameters and had the tendency to maintain clinical benefit for a longer follow-up period [78]. The 2nd generation device, eliminating the one-way valve component, is under evaluation in patients with advanced HF, regardless of LVEF, in the ongoing Reducing Lung Congestion Symptoms using the V-Wave Shunt in Advanced Heart Failure (RELIEVE-HF) trial (NCT03499236).
The Atrial Flow Regulator (©Occlutech, Istanbul, Turkey)
is a double disc device designed to allow interatrial bidirectional flow. The
Prospective, Non-randomized, Pilot Study to Assess Safety and Efficacy of a Novel
Atrial Flow Regulator (AFR) in Heart Failure Patients With Reduced Ejection
Fraction or in Heart Failure Patients With Preserved Ejection Fraction (PRELIEVE)
was a prospective, non-randomized, open-label, multicentre study in symptomatic
HF patients (~45% HFrEF) with increased pulmonary capillary
wedge pressure (PCWP;
It should be considered that patients undergoing shunting procedures may suffer from right heart volume overload related to (a) increasing right atrial pressure and consequent persistent right-to-left shunt leading to hypoxemia and systemic embolization and (b) right ventricular function worsening. In addition, preservation of the interatrial septum is essential to allow any further transseptal transcatheter interventions. Therefore, a novel percutaneous atriotomy technique, the Transcatheter Atrial Shunt System (©Edwards Lifesciences, Irvine, CA, USA), has been developed in order to create a LA-to-CS shunt potentially able to reduce LAP without interacting with the interatrial septum. Using the right internal jugular vein as access point, CS cannulation is followed by CS-to-LA puncture and balloon dilation of the LA in order to deploy the device and create the shunt. In the first in-human application, the procedure was demonstrated to be feasible and resulted in clinical and hemodynamic improvement [80].
Cardiac resynchronisation therapy (CRT), either with a defibrillator (CRT-D) or
without (CRT-P), represents the only percutaneous treatment of HFrEF, proposed by
current guidelines, with a Class of Recommendation I Level of Evidence A [1]. In
appropriately selected patients, CRT reduces mortality and improves cardiac
function [81]. However, it should be considered that its benefits do not extend
to patients with normal or marginally increased (120-130 ms) QRS complex duration
(~80% of HFrEF patients) [82] and that almost one-third of CRT
recipients are noticed to be non-responders [83]. In this perspective, QRS width
(
Cardiac contractility modulation (CCM) is a percutaneous device-based therapy for HF, involving the application of non-excitatory electrical impulses to the RV septal wall during the absolute myocardial refractory period in order to influence the biology of failing myocardium in terms of LV contractility improvement and positive reverse remodelling [85]. Implantation is similar to a traditional transvenous pacemaker system, but with the use of two RV leads. A meta-analysis of 3 clinical trials involving 641 patients with HF undergoing CCM in addition to optimal medical therapy compared to GDMT alone has shown a significant, albeit somewhat modest, improvement in peak oxygen consumption, 6-minute walking test, and quality of life [86]. Nevertheless, no prospective trials evaluated effects of CCM on mortality as the primary outcome. A meta-analysis of data from randomized trials suggested that CCM did not significantly improve either overall mortality or all-cause re-hospitalizations [81]. Guidelines consider current evidence insufficient to support specific recommendations for CCM [1]. However, recommendations on its use in the treatment of HF compared to CRT have been suggested. CCM could be combined with an implanted cardiac defibrillator in patients with severe LV disfunction (LVEF 25–35%), while it could be offered as the only device-based therapeutic option for patients with a moderate LV dysfunction (LVEF 35%–45%) [87].
Despite continuous improvements in percutaneous reperfusion therapy over recent decades, myocardial injury following myocardial infarction and the subsequent LV adverse remodeling leading to HF remains a major health concern [88]. Based on previous surgical experiences aimed to reverse ventricular remodeling by excluding the infarcted akinetic region, devices have been developed to attempt LV shape restoration and to potentially improve prognosis, in combination with pharmacological therapy [89, 90].
The Parachute device (©Cardiokinetix, Redwood City, CA, USA) is a transaortic, umbrella-like system designed to partition off the akinetic or aneurysmatic portion of the LV while restoring the elliptical shape of the LV cavity. Decreased global wall stress and improved diastolic compliance might be the mechanisms by which the implant improves cardiac performance. Importantly, LV anatomy should be carefully evaluated through pre-procedural computed tomography since prominent trabeculation or an LV moderator band is unsuitable for device implantation [91]. In the PARACHUTE First-In-Human trial, 39 patients with NYHA functional class II–IV, dilated akinetic or dyskinetic anterior-apical wall that did not necessitate revascularization and LVEF between 15% and 40% were enrolled in a nonrandomized, prospective, multicenter study. At 3-year follow-up, there was a stable and significant reduction in LV end-diastolic volume, whereas stroke volume and LVEF were also significantly lower compared to baseline [92]. The PARACHUTE IV trial (NCT 01614652) represented the first randomized controlled trial comparing device implantation plus HF medical therapy to GDMT alone, but was terminated in June 2017 after enrolling 331 patients, due to device-related safety concerns, and it is unclear whether investigation will be continued.
The AccuCinch (©Ancora Heart, Santa Clara, CA, USA) is
the first and only percutaneous ventricular restoration system designed to treat
both HF and SMR. It is an endocardial implant deployed 1–2 cm below the mitral
annulus. Through 12–16 anchors implanted over a 220° arc in the
subannular space and cinched together with a cable, it may reduce the
basal-to-mid LV free wall circumference, improving mitral leaflet apposition and
reducing LV wall tension [93]. In the early feasibility study, 21 patients with
HFrEF and SMR were scheduled to receive AccuCinch procedure. Device implantation
success was 90%, with an average procedure time of 150 minutes and no
device-related adverse events. At 6-month follow-up, significant reductions in
MR degree and LV volumes with concomitant improvements in LVEF and clinical
status were observed [93]. As suggested in a case report, since the beneficial
effects are progressive over a short-term follow-up, its effectiveness, which
initially depends on a mechanism that involves physically altering the size or
shape of the ventricle, may be secondarily enhanced by inducing biological
responses that result in progressive reverse modeling [94]. The AccuCinch System
is currently under evaluation in the Randomized Clinical Evaluation of the
AccuCinch Ventricular Restoration System in Patients Who Present With Symptomatic
Heart Failure With Reduced Ejection Fraction (CORCINCH-HF) (NCT04331769) pivotal
trial, which is a prospective, randomized, open-label, multicenter,
international, clinical safety and efficacy investigation designed to enroll 400
symptomatic patients with LVEF 20–40% and LV end-diastolic diameter
The newer and existing techniques in the armamentarium of contemporary interventional cardiologists may allow various treatment strategies in order to achieve different targets specifically tailored for the several HFrEF phenotypes. However, despite the aforementioned studies, it should be underlined that only a few procedures and devices (i.e., TAVR, mitral edge-to-edge-repair, CRT) have been proven to significantly reduce major cardiovascular events in HF patients.
Hence, device-based therapies for HF should be considered complementary to pharmacological treatment and should thus be aimed at improving prognosis when pharmacotherapy is deemed to be insufficient. Appropriate patient selection and timely indication are essential for their proper implementation and success in clinical practice and patient care.
AS, aortic stenosis; CCM, cardiac contractility modulation; CRT, cardiac resynchronisation therapy; GDMT, guideline-directed medical therapy; EuroSCORE, European System for Cardiac Operative Risk Evaluation. HF, heart failure; HFrEF, heart failure with reduced ejection fraction; LVEF, left ventricular ejection fraction; MV: mitral valve; NYHA, New York Heart Association; RCT, randomized control trials; SMR, secondary mitral regurgitation; TAVI, transcatheter aortic valve implantation; TEER, transcatheter edge-to-edge repair; STS-PROM, Society of Thoracic Surgeons predicted risk of mortality; TR, tricuspid regurgitation.
AS—Conceptualization; Writing - Original Draft; Visualization; MC—Conceptualization; Writing - Review & Editing; Visualization; APR—Conceptualization; Writing - Review & Editing; Visualization; AB—Conceptualization; Writing - Review & Editing; Supervision; FB—Conceptualization; Writing - Review & Editing; Supervision; EB—Conceptualization; Writing - Review & Editing; Supervision. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.
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This research received no external funding.
The authors declare no conflict of interest.
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