b.TRICVALVE

The TRICVALVE (P&F Products & Features, Vienna, Austria) is a device specifically designed for its implantation in VC. It consists of two self-expanding bovine pericardium valves on a nitinol stent, one for each VC. Lauten et al. published first in-human experience in 2011 in a patient that showed clinical functional improvement after 8 weeks [63]. The TRICUS feasibility study is currently ongoing and will include 10 patients in order to evaluate of clinical and adverse events using this device [NCT03723239].

## c.TRICENTO

The Tricento (NVT, Muri, Switzerland) is a coated bicaval covered stent with a bicuspid valve positioned laterally that that allows inflow into the right atrium. Since the first experience reported in 2018 [64], isolated cases have been published, with good periprocedural results [65, 66].

#### **3.3 Outcomes after transcatheter tricuspid valve therapies**

#### *3.3.1 Clinical benefits*

Most feasibility studies and observational registries have shown a significant clinical improvement in terms of NYHA functional class, quality of life or 6-minute walk test in patients undergoing PTVR or TTVI. These changes were observed even after conservative reductions of TR of 1 or 2 grades after PTVR. Nevertheless, no data are available from randomized controlled trials comparing percutaneous approach with medical management, and current reported follow-up does not exceed 1 or 2 years after the invasive procedure.

With regard to cardiovascular events, Orban et al. evaluated rates of admissions due to HF in 119 patients undergoing isolated PTVR (MitraClip 97%) comparing the year before and after the procedure [67]. PTVR was associated with a significant reduction in the grade of TR to moderate or less in 72% of the cases and with a significant lesser incidence of HF admissions (p = 0.02).

Recently, results from the TriValve registry that included 312 patients mostly treated with MitraClip device, reported that 30-day mortality was significantly lower among those with procedural success (1.9% vs. 6.9%, p = 0.04) [68]. Furthermore, more recently, Taramasso et al. published a retrospective propensity matched case–control study that included 268 patients from the same registry who underwent PTVR and observed significant lower 1-year mortality (23 ± 3% vs. 36 ± 3%, p = 0.001) and rehospitalization (26 ± 3% vs. 47 ± 3%, p < 0.0001) rates when compared to controls managed conservatively [69]. In addition, those patients treated with PTVR had higher survival after adjusted for sex, NYHA functional class, right ventricular dysfunction and AF. Although these results are encouraging, potential survival benefit of transcatheter tricuspid valve interventions over stand-alone medical therapy needs to be tested in clinical trials. Currently, diverse ongoing randomized trials will assess this issue in patients receiving TriClip, Pascal, Cardioband, and other PTVR devices.

#### *3.3.2 Predictors of outcomes*

One of the major limitations of TV surgery is reported high periprocedural mortality. Despite transcatheter approaches seem to significantly reduce this risk, patient selection remains key to achieve optimal procedural and clinical results. In this regard, some important determinants of outcomes have ben already suggested:

a.PH and RV function: Lurz et al. evaluated invasive pulmonary artery pressures and echocardiographic parameters in 243 patients who underwent PTVR [70]. The presence of invasive PH, defined as pulmonary artery systolic pressure > 50 mmHg), together with discordant absence of PH by echocardiographic estimation, was associated with the combined primary endpoint of all-cause mortality, need for repeat hospitalization for HF and reintervention during follow-up. This could be explained because in advanced stages of TR associated with adverse RV remodeling with severe dilation of the TV annulus, pulmonary hypertension may be severely underestimated by echocardiography. Moreover, Stocker et al. observed in a multicenter study including 236 patients that invasive mean pulmonary artery pressure, transpulmonary gradient, pulmonary vascular resistance and RV stroke work were significant predictors of 1-year mortality, and that patients with pre-capillary PH had the worse prognosis [71]. Similarly, the ratio between TAPSE/invasive PH <0.29 mm/mmHg has also shown adverse prognosis impact [72]. This finding points out the close relationship between the RV function and PH. So-called RV-PA coupling refers to the fact that RV contractility should "match" the RV afterload.

b.Nutritional status: from a clinical perspective, a recent study reported that an impaired nutritional status is also associated with an increased risk of death and rehospitalization for heart failure after PTVR [73]. This finding is important since to date most patients were referred to invasive management at an advance stage of RV failure in which nutritional status might be already impaired and this can impact outcomes.
