**5. Impact of LVAD implantation on sarcopenia**

As mentioned earlier, many investigators have shown that sarcopenia was associated with increased comorbidity and mortality after implantation of LVAD. On the other hand, only limited studies concerning the impact of LVAD implantation on sarcopenia have been available. Several investigators reported improvement of HGS after implantation of CF-LVAD [21, 22]. Although it has been reported that frailty prior to BTT LVAD implantation is associated with an increased post-LVAD morbidity and mortality, it has also been reported that frailty is reversible in most patients who survive the perioperative period [45, 46]. Maurer et al. [47] assessed reversal of frailty in 29 elderly frail LVAD recipients with a mean age of 71 years. Although frailty improved overall, 53% of the patients remained frail 6 months after LVAD implantation. These data suggested that frailty may be less reversible in aged patients supported with LVAD.

Multiple studies have shown that implantation of LVAD not only provides adequate hemodynamic support but also improves renal and liver function and psychical capacity especially after receiving physical rehabilitation. However, there are multifactorial limitations to exercise in patients supported with LVAD [38]. Although LVAD implantation improves hemodynamics in end-stage HF patients at rest, the device is unable to provide full circulatory support during exercise,

especially in patients with CF-LVAD. Thus, significant limitations in exercise capacity persist soon and long after CF-LVAD implantation. Maximizing LV unloading and improving native myocardial function in association with an automated increase in LVAD speed could provide an increase in maximal exercise capacity in patients with the old-type pulsatile implantable LVAD. However, CF-LVAD can provide only partial improvement in maximal exercise capacity. Further studies are needed regarding the role of RV function, recovery of native cardiac function, the role of rehabilitation and nutrition intervention, changes in skeletal muscle function after CF-LVAD, and their contribution to endurance exercise [38].

## **6. Impact of HTx on sarcopenia**

Fernandes et al. [48] investigated the impact of HTx on the recovery of peripheral and respiratory muscle mass and strength in patients with congestive HF. They showed significant decreases in a cross-sectional area of the bilateral psoas major muscle (CSAbPm), a bilateral HGS, and the maximum inspiratory and expiratory pressure (MIP and MEP) in patients on the waiting list compared with the healthy controls with normal cardiac function. They also found significant increases during waiting for HTx to 6- and 18-month post-HTx in the CSAbPm (1305.4 vs. 1458.1 vs. 1431.3 mm2 , respectively), bilateral HGS (27.3 vs. 30.2 vs. 34.7 kg/f, respectively), MIP (59.5 vs. 85.5 vs. 90.9 cmH2O, respectively), and MEP (79.5 vs. 93.2 vs. 101.8 cmH2O, respectively). These results revealed that patients recovered peripheral and respiratory muscle mass and strength early after HTx. However, Schaufelberger et al. [49] demonstrated that intrinsic abnormalities in skeletal muscle found before HTx remained 6–9 months after HTx and might contribute to a reduced exercise capacity and muscle strength in these patients, in contrast to the former paper's findings.

## **7. Management of sarcopenia after LVAD implantation**

As mentioned earlier, sarcopenia is a strong negative predictor on outcome after LVAD implantation and HTx. Therefore, sarcopenia is one of the main therapeutic targets in patients with end-stage HF referred to LVAD implantation and HTx to avoid related comorbidity and to improve prognosis post-LVAD implantation and post-HTx. Although moderate or severe sarcopenia as well as frailty is a contraindication for HTx, patients who can reverse frail after LVAD implantation would be considered eligible for HTx. Therefore, to further improve outcomes after LVAD implantation or HTx, therapeutic management for sarcopenia should be established in patients supported with LVAD as well as those prior to LVAD implantation. As the management of sarcopenia in patients prior to LVAD implantation might be the same in medically treated patients with end-stage HF and has been previously well discussed in many previous literatures, those for patients supported with CF-LVAD will be discussed in this review.

According to the pathophysiological factors involved in the pathogenesis of sarcopenia, therapeutic approaches for sarcopenia are summarized in **Figure 2**. Although Khawaja et al. [22] reported that CF-LVAD implantation corrects GH/IGF-1 signaling and improves muscle structure and function, only limited data were available regarding anti-inflammation strategies and hormonal therapies, such as GF/IGF-1 and ghrelin administration for sarcopenia in patients supported with LVAD. Therefore, exercise training and nutrition supplementation in patients supported with LVAD are reviewed in this review.

*Sarcopenia in Patients with End-Stage Cardiac Failure Requiring Ventricular Assist Device or… DOI: http://dx.doi.org/10.5772/intechopen.100612*

**Figure 2.** *Sarcopenia pathogenesis and therapeutic approaches: GH growth hormone, IGF-1 insulin-like growth factor-1.*

#### **7.1 Exercise training (rehabilitation) in LVAD patients**

Generally, HTx or LVAD recipients attend a cardiac rehabilitation program to promote recovery after surgery. Such rehabilitation programs consist of standardized sessions of physical exercise training, with the same intensity and duration regardless of HTx or LVAD implantation. However, surgical indication and method, individual medical and surgical therapies, and possible adverse events after surgery might affect the efficacy of cardiac rehabilitation differently in HTx and LVAD patients. If this occurs, rehabilitation programs better tailored to LVAD patients should be designed.

Yanase et al. [44] reported that short term, such as 3-month rehabilitation program, could significantly increase post-HTx exercise capacity irrespective of age, gender, type of LVAD, and underlying disease. But, even in those patients, better several nutrition factors at exercise program admission were significantly associated with peak VO2 at the end of the exercise program. Therefore, nutrition supplementation during LVAD support might be also essential to improve exercise capacity post-HTx as well as exercise training. However, there are no guidelines regarding the best way to cardiac exercise prescription, especially for CF-LVAD patients. As a result, LVAD patients currently undergo rehabilitation protocols designed for other types of cardiovascular diseases or cardiac surgeries.

As patients receiving LVAD are deeply deconditioned due to advanced HF, it is recommended that patients with sarcopenia as well as frailty are admitted to an in-patient rehabilitation program soon after implanting LVAD. Alsara et al. [50] reviewed the literatures regarding cardiac rehabilitation in patients supported with LVAD and concluded that exercise training is safe and recommended early mobilization between 7 and 10 days post-LVAD and treadmill exercise training beginning at 21 days post-LVAD. However, there is very few information regarding the improvements derived from exercise training in LVAD patients.

Currently, pulsatile-flow LVADs (PF-LVADs) are seldom used as durable support in patients with end-stage HF, but they have a pneumatically/electrically driven ventricle operating in the complete fill/ and empty mode. Therefore, cardiac output during exercise will increase by an automatic increase in pump rate responding to an increase in left ventricular (LV) preload. PF-LVADs work independently from LV afterload and produce a maximal cardiac output of 10 liters/min with a pump rate

of 120 beats/min [51]. On the other hand, the CF-LVAD has no inflow or outflow valves, unloads the ventricle in both systole and diastole, and operates at a fixed pump speed. The two types of CF-LVADs are axial and centrifugal. Pump flow changes according to the differential pressure between the inflow and outflow cannulas. The sensitivity of axial and centrifugal pumps to changes in preload is similar, whereas centrifugal pumps are more sensitive to afterload [52]. During exercise, pump flow increases in the CF-LVAD according to changes in LV preload and afterload. For example, RV failure decreases LV preload and high systemic pressure decreases LV afterload, resulting in reduced pump flow. Therefore, CF-LVAD cannot fully increase pump flow with exercise, whereas PF-LVAD can do so.

Haft et al. [53] reported the differences in the exercise hemodynamic responses between PF-LVAD and CF-LVAD. Peak VO2 as well as resting central venous pressure, mean arterial pressure, and pulmonary capillary wedge pressure were similar and pump flow increased peak VO2 in both groups. However, the increase in pump flow was approximately 20% greater in the PF-LVAD than in the CF-LVAD. Moreover, the significance of this finding is unclear because the pump flow through for the CF-LVAD is not directly measured but only estimated. Martina et al. [54] reported that patients supported with CF-LVAD showed a mean peak VO2 of 18 mL/kg/min (55% of predicted) and a mean total maximum cardiac output of 8.5 liters/min. From these studies, patients supported with CF-LVAD may have a similar peak VO2 independently of the type of CF-LVAD. Although maximum cardiac output increases with exercise in patients supported with CF-LVAD, it does not reach levels found in healthy individuals with normal cardiac function.

Many factors, such as underlying heart disease, native heart function, especially right ventricular function, both ventricular morphology, co-existing arrhythmia, type of LVAD, rehabilitation protocol, and nutrition intervention may influence the effect of cardiac rehabilitation on improvement in exercise capacity and recovery from sarcopenia. Therefore, individualized exercise prescriptions leading to optimal improvements in exercise capacity in patients supported with CF-LVAD are not well known and should be established in the field of LVAD therapy [47].

#### **7.2 Nutrition**

There is no doubt that malnutrition is involved in the pathogenesis of sarcopenia, and that it contributes to the poor muscle function observed in patients with end-stage HF, particularly in frail elderly patients. In general, the proposition of nutritional interventions should be based on the delivery of an adequate energy supply and on the supplementation of specific nutrients as an effective treatment in preventing and/or reversing sarcopenia in patients with advanced HF. However, there are very few literatures regarding the recovery from sarcopenia by nutrition interventions particularly in patients supported by LVAD.

### **8. Conclusion**

Sarcopenia as well as frailty is a strong negative predictor on outcome after LVAD implantation and HTx. Assessment of skeletal muscle function such as HGS and gait speed, and measurement of skeletal muscle mass and CER index prior to surgery are useful tools to predict patient's outcome after LVAD implantation and HTx. Therefore, therapeutic strategies to reverse sarcopenia prior to surgery and after LVAD implantation are important to improve their outcomes. However, many factors, such as the indication, surgical method, postoperative therapies, and possible adverse events, might affect the efficacy of cardiac rehabilitation and nutrition *Sarcopenia in Patients with End-Stage Cardiac Failure Requiring Ventricular Assist Device or… DOI: http://dx.doi.org/10.5772/intechopen.100612*

supplementation on quality of life as well as survival differently in HTx and LVAD patients. Therefore, individualized exercise prescriptions and nutrition interventions leading to the reversal of sarcopenia as well as frailty in patients undergoing and supported with CF-LVAD should be established in the near future.
