**3. Ventricular assist devices as bridge to transplant**

MCS has largely evolved over the last years and nowadays it constitutes a real option for patients in AHF situation, especially in those who are in INTERMACS 1 to 4 profiles. As a matter of fact, in 2000, the International Society of Heart and Lung Transplantation (ISHLT) reported that 19.1% of HTxs were mechanically supported, and by the year 2012 this number had increased to 41% [33]. Lately, the clinical outcomes of a Spanish registry of 291 patients supported by STVAD as a BTT strategy have been published, showing an overall survival rate from listing to hospital discharge of 61%, and 1-year survival after listing of 58% [34]. Although there was a significant mortality rate, it is important to mention that the majority of patients were in an emergency situation (INTERMACS 1-2) and were supported by a very heterogeneous group of STVADs. Accordingly, it seems reasonable to use LTVADs as a BTT strategy at an early stage of the disease (INTERMACS 3-4) to improve HTx outcomes.

Irrespective of the design, LTVAD unloads the heart by pumping blood from the left ventricle to the aorta. Technology of LTVADs has been continuously evolving since the creation of the first generation devices, which had a diaphragm and unidirectional valves to replicate the pulsatile cardiac cycle. The HeartMate XVE was approved by the FDA; first as BTT in 1998 and in 2002 as a DT, after the publication of the REMATCH trial. Later advances in technology have been directed to minimize the size of the pump and to increase its durability. Nowadays, continuous flow LTVADs have substituted pulsatile devices; these utilize a permanent magnetic field designed to rapidly spin a single impeller supported by mechanical, hydrodynamic or magnetic bearings. In second-generation continuous flow LTVAD the impeller outflow is directed parallel to the axis of rotation (e.g., Heartmate II, Thoratec and Incor, Berlin Heart) while in the third generation devices the impeller outflow is directed perpendicular to the axis of rotation (e.g., HVAD, Medtronic and HeartMate 3, Abbot). Third generation pumps have lower risk of suction events, more pulsatile waveform, and more precise flow estimation than second-generation pumps, but pump flow has a higher dependency on loading conditions [35].

The best candidates for a BTT strategy are patients in INTERMACS 3-4 profile; especially if a long waiting time for HTx is expected, as it avoids further deterioration, allows clinical optimization, and provides a better quality of life. In this regard, some factors that may increase the difficulty in finding a appropriate donor should be taken into consideration, as for example previous allosensitization or large body size.

BTC LTVAD strategy is the preferred option for those patients with relative contraindications to HTx that could be potentially reversible with hemodynamic support. For instance, most patients with initially irreversible PHT reach reversibility or even normal pulmonary pressure after some months with LTVAD [24]. In a similar fashion, renal dysfunction due to cardiorenal syndrome can improve enough to consider HTx. In this group, we can also include patients with recently diagnosed cancer or obesity (BMI > 35 kg/m2 ), in which the implantation of a LTVAD could give them time to re-evaluate candidacy.

thromboembolism. If there is no responsible pulmonary disease, there are several studies that have shown that the chronic use of bosentan or sildenafil might reduce PHT and acheive reversibility of PHT after 3–4 months of this therapy [31]. If despite an appropriate vasodilator treatment there is no reversibility of the PHT, LTVAD therapy should be considered,

MCS has largely evolved over the last years and nowadays it constitutes a real option for patients in AHF situation, especially in those who are in INTERMACS 1 to 4 profiles. As a matter of fact, in 2000, the International Society of Heart and Lung Transplantation (ISHLT) reported that 19.1% of HTxs were mechanically supported, and by the year 2012 this number had increased to 41% [33]. Lately, the clinical outcomes of a Spanish registry of 291 patients supported by STVAD as a BTT strategy have been published, showing an overall survival rate from listing to hospital discharge of 61%, and 1-year survival after listing of 58% [34]. Although there was a significant mortality rate, it is important to mention that the majority of patients were in an emergency situation (INTERMACS 1-2) and were supported by a very heterogeneous group of STVADs. Accordingly, it seems reasonable to use LTVADs as a BTT

strategy at an early stage of the disease (INTERMACS 3-4) to improve HTx outcomes.

Irrespective of the design, LTVAD unloads the heart by pumping blood from the left ventricle to the aorta. Technology of LTVADs has been continuously evolving since the creation of the first generation devices, which had a diaphragm and unidirectional valves to replicate the pulsatile cardiac cycle. The HeartMate XVE was approved by the FDA; first as BTT in 1998 and in 2002 as a DT, after the publication of the REMATCH trial. Later advances in technology have been directed to minimize the size of the pump and to increase its durability. Nowadays, continuous flow LTVADs have substituted pulsatile devices; these utilize a permanent magnetic field designed to rapidly spin a single impeller supported by mechanical, hydrodynamic or magnetic bearings. In second-generation continuous flow LTVAD the impeller outflow is directed parallel to the axis of rotation (e.g., Heartmate II, Thoratec and Incor, Berlin Heart) while in the third generation devices the impeller outflow is directed perpendicular to the axis of rotation (e.g., HVAD, Medtronic and HeartMate 3, Abbot). Third generation pumps have lower risk of suction events, more pulsatile waveform, and more precise flow estimation than second-generation pumps, but pump flow has a higher dependency on loading conditions [35].

The best candidates for a BTT strategy are patients in INTERMACS 3-4 profile; especially if a long waiting time for HTx is expected, as it avoids further deterioration, allows clinical optimization, and provides a better quality of life. In this regard, some factors that may increase the difficulty in finding a appropriate donor should be taken into consideration, as

BTC LTVAD strategy is the preferred option for those patients with relative contraindications to HTx that could be potentially reversible with hemodynamic support. For instance, most patients with initially irreversible PHT reach reversibility or even normal pulmonary

for example previous allosensitization or large body size.

together with selective vasodilator treatment (usually sildenafil) [32].

**3. Ventricular assist devices as bridge to transplant**

18 Heart Transplantation

Regarding LTVAD as DT, one of the limitations of this strategy is the increase in adverse events associated with long-term use of LTVAD. The ROADMAP study took a sample of 200 patients in INTERMACS 4–7 and divided them into two groups: optimal medical management (OMM) or OMM plus LTVAD. The final result showed an improvement in functional capacity in the second group but with a significant increase in adverse events, especially hemorrhagic complications [36]. Although current indications for DT consider a more advanced profile of patients (criteria derived from the REMATCH and HeartMate II DT trials [37]), the results of the ROADMAP study give us and idea of the advantages and disadvantages of the use of LTVAD as DT, further supporting the fact that HTx remains the ideal therapy in this population.

Regardless of the selected strategy, the most important fact is to ensure a correct selection of candidates for LTVAD implantation. One of the tools used to predict outcomes of these patients using mechanical support is the HeartMate II Risk Score, which is derived from an analysis of the HeartMate II registry. Briefly, it is based on five variables (age, serum albumin, creatinine, INR, and center volume of LVAD) used to create an equation that predicts mortality at 90 days [38]. Moreover, because LTVADs only support the left ventricle, one of the critical points to take into consideration is the potential right ventricular failure (RVF) after MCS is initiated. Nowadays, there are no comprehensively evaluated tools to predict RVF, but some hemodynamic and echocardiographic parameters might be useful. Concerning hemodynamic evaluation, a right ventricular stroke work index less than 250 mmHg·mLm2 [39], right atrial pressure > 15 mmHg and central venous pressure/PCWP >0.63 are considered important risk factors of RVF [40]. Echocardiographic parameters include tricuspid annular motion (TAPSE) < 7.5 mm [41], right ventricular to left ventricular end diastolic diameter ratio > 0.72 [42], severe tricuspid regurgitation, right ventricular short/long axis ratio > 0.6 [43] and right ventricular free wall strain [44]. A biventricular approach using continuous blood flow pumps has recently been reported with limited success considering the significant number of adverse events during follow-up [45].

Finally, it is very important to ensure optimal patient's self-care training by specialized nurses, and appropriate follow-up is indispensable for the success of a LTVAD program. Daily care of the device, especially considering the correct management of the driveline wound is of paramount importance to avoid infection. Moreover, the correct management of concomitant cardiovascular risk factors such as hypertension or diabetes, and other comorbidities is also a relevant issue in these patients that should be pursued.
