**3. Percutaneous therapies for tricuspid regurgitation in heart failure**

#### **3.1. Functional tricuspid regurgitation**

Functional tricuspid regurgitation (TR) represents over 90% of cases of TR and it is typically due to tricuspid annular dilatation (mainly in anteroposterior diameter) and right ventricular (RV) enlargement (leading to leaflet tethering) secondary to progressive left heart disease (LHD) [86]. The tricuspid valve (TV) has been considered for years the "forgotten" valve. This issue may be explained by the fact that TR was believed to be well tolerated and reduced after treating LHD. On the contrary, patients with significant TR and HF tend to be highly symptomatic due to decrease in CO and abdominal and peripheral congestion [87]. Furthermore, the presence of moderate or severe TR is independently associated with an increased mortality (over 25% at 1 year) regardless of biventricular function or pulmonary pressures [88, 89].

Despite surgical treatment of LHD, significant TR can be found in over two-thirds of patients in long-term follow-up, suggesting that a lower threshold for TV repair should be considered when MV surgery is carried out [87, 90–92]. Current data support that TV repair at the time of MV surgery is safe, whereas reoperation for persistent TR is related to high morbidity and mortality rates [93–95]. Notwithstanding, few patients undergo TR surgery and the vast majority are managed medically. Data from the STS database suggest that moderate to severe TR is present in almost 2 million of patients in the United States, but not even 10,000 undergo TV surgery each year. Progressive RV dysfunction may lead to an irreversible RV damage, which is thought to be the reason for the poor outcomes of late surgery in this scenario. Therefore, there is a large unmet clinical need for patients with significant TR who are not referred for conventional surgery, mainly due to expected high-surgical risk. Percutaneous therapies for functional TR are emerging as an alternative to surgery in this scenario. Patients with symptomatic severe TR and prior open-heart surgery and those with significant TR and progressive RV dysfunction and failure despite OMT may benefit from transcatheter TV interventions. Initial experiences include the off-label use MV devices and first-in-human cases of dedicated new technologies [96] (**Table 4**). Among different therapies that have been tested in preclinical setting, transcatheter TV annuloplasty, resembling different successful surgical techniques, might be one of the most promising approaches [97, 98].

#### **3.2. Transcatheter tricuspid valve interventions**

#### *3.2.1. Percutaneous tricuspid valve repair with mitral valve dedicated devices*

The acquired experience in catheter-based therapies for MV with satisfactory results has emerged the appealing concept of using some of these devices in tricuspid position. Recently, Braun et al. have reported first series of edge-to-edge TV repair in 18 patients with moderate to severe functional TR and right-sided heart failure [99]. Six patients were treated for isolated severe TR, whereas 12 patients were treated concomitantly to PMVR. A reduction of at least one TR grade was achieved in all patients and no in-hospital major events were reported. A significant improvement in TR was observed (TR ≥ 3+ 94% vs. 33%, *p* < 0.001) and sixteen patients (89%) referred an improvement in NYHA functional class at 30-day follow-up. In 2015, the first-in-human transcatheter TV repair with Mitralign® system was published, reproducing Kay posterior annuloplasty [100]. Recently, acute results of Trialign® early human use were reported. A single pair of pledgets was successfully implanted in 14 of the 16 patients (87.5%), with an average postprocedural reduction of 37% in TA and 59% in TV regurgitant orifice area. No procedural mortality occurred. Potential advantage of additional pledgets will be assessed. Cardioband® has been also successfully implanted in TA in humans [101] and European CE mark study (TRI-REPAIR) is currently initiated.

#### Percutaneous Treatment of Mitral and Tricuspid Regurgitation in Heart Failure http://dx.doi.org/10.5772/intechopen.68493 129


**Table 4.** Catheter-based therapies for TR that have been already tested in humans.

issue may be explained by the fact that TR was believed to be well tolerated and reduced after treating LHD. On the contrary, patients with significant TR and HF tend to be highly symptomatic due to decrease in CO and abdominal and peripheral congestion [87]. Furthermore, the presence of moderate or severe TR is independently associated with an increased mortality (over 25% at 1 year) regardless of biventricular function or pulmonary pressures [88, 89]. Despite surgical treatment of LHD, significant TR can be found in over two-thirds of patients in long-term follow-up, suggesting that a lower threshold for TV repair should be considered when MV surgery is carried out [87, 90–92]. Current data support that TV repair at the time of MV surgery is safe, whereas reoperation for persistent TR is related to high morbidity and mortality rates [93–95]. Notwithstanding, few patients undergo TR surgery and the vast majority are managed medically. Data from the STS database suggest that moderate to severe TR is present in almost 2 million of patients in the United States, but not even 10,000 undergo TV surgery each year. Progressive RV dysfunction may lead to an irreversible RV damage, which is thought to be the reason for the poor outcomes of late surgery in this scenario. Therefore, there is a large unmet clinical need for patients with significant TR who are not referred for conventional surgery, mainly due to expected high-surgical risk. Percutaneous therapies for functional TR are emerging as an alternative to surgery in this scenario. Patients with symptomatic severe TR and prior open-heart surgery and those with significant TR and progressive RV dysfunction and failure despite OMT may benefit from transcatheter TV interventions. Initial experiences include the off-label use MV devices and first-in-human cases of dedicated new technologies [96] (**Table 4**). Among different therapies that have been tested in preclinical setting, transcatheter TV annuloplasty, resembling different successful surgical

techniques, might be one of the most promising approaches [97, 98].

*3.2.1. Percutaneous tricuspid valve repair with mitral valve dedicated devices*

and European CE mark study (TRI-REPAIR) is currently initiated.

The acquired experience in catheter-based therapies for MV with satisfactory results has emerged the appealing concept of using some of these devices in tricuspid position. Recently, Braun et al. have reported first series of edge-to-edge TV repair in 18 patients with moderate to severe functional TR and right-sided heart failure [99]. Six patients were treated for isolated severe TR, whereas 12 patients were treated concomitantly to PMVR. A reduction of at least one TR grade was achieved in all patients and no in-hospital major events were reported. A significant improvement in TR was observed (TR ≥ 3+ 94% vs. 33%, *p* < 0.001) and sixteen patients (89%) referred an improvement in NYHA functional class at 30-day follow-up. In 2015, the first-in-human transcatheter TV repair with Mitralign® system was published, reproducing Kay posterior annuloplasty [100]. Recently, acute results of Trialign® early human use were reported. A single pair of pledgets was successfully implanted in 14 of the 16 patients (87.5%), with an average postprocedural reduction of 37% in TA and 59% in TV regurgitant orifice area. No procedural mortality occurred. Potential advantage of additional pledgets will be assessed. Cardioband® has been also successfully implanted in TA in humans [101]

**3.2. Transcatheter tricuspid valve interventions**

128 Interventional Cardiology

#### *3.2.2. Transcatheter tricuspid valve repair therapies*

TriCinch® (4Tech Cardio, Galway, Ireland) consists of a steerable catheter with a corkscrew at the tip. Under echocardiographic and fluoroscopic guidance, supraannular fixation of the device is carried out in the mid part of the anterior TA. Afterwards, the catheter is tensioned in order to produce TA cinching, therefore reducing the anteroseptal dimension of the TA and improving leaflet coaptation. Finally, a self-expandable nitinol stent is positioned at the inferior vena cava in order to secure the system and maintain the tension applied. TriCinch® implantation preserves the native anatomy, allowing potential future treatment options. First in-human cases [102, 103] and early results from the PREVENT CE trial have been reported. The system was successfully implanted in 13 of 18 patients (72%). Two patients developed periprocedural hemopericardium and device TA detachment was observed in two patients. No mortality events occurred during up to 29 months follow-up. A significant improvement in 6-minute walk test and quality of life were documented, although only 37.5% remain in NYHA class I–II during this period.

#### *3.2.3. Other percutaneous approaches for tricuspid regurgitation*

The FORMA® Repair System (Edwards Lifescience, Irvine, USA) is a valve spacer created to increase coaptation surface by occupying space in the regurgitant orifice of the TV. The device is usually delivered through a transsubclavian venous route and anchored to the RV apex distally and proximally fixed within a small surgically prepared pocket. Preliminary results in seven high-risk patients with severe TR and advanced NYHA functional class III–IV were recently available [104]. The device was successfully implanted in all patients without major complications, obtaining at least one grade acute reduction in TR. 30-day results showed clinical improvements (100% NYHA class II) and stable TR reduction (100% moderate TR) without significant tricuspid stenosis.
