In patients with nonischemic CCM, the study with the largest number of weaned patients and the longest post-weaning follow-up revealed probabilities of 67.1 ± 7.6% and 47.3 ± 9.2% for 5-year and 10-year freedom from HF recurrence after VAD explantation, respectively, without differences between patients weaned from pulsatile and non-pulsatile VADs [9]. These good results were possible although before explantation, only 8,7% of the weaned patients had an LV ejection fraction (LVEF) >50% [9]. Thus VAD explantation can be successful even after incomplete cardiac recovery. In another study, the post-explant rate of freedom from death or HTx reached 69% at both 5 and 7 years [26]. A recent evaluation of 53 weaned patients with nonischemic CCM as the underlying cause for VAD implantation revealed 5- and 10-year post-explant survival probabilities (including post-HTx survival for those with HF recurrence) of 72.8 ± 6.6% and 67.0 ± 7.2%, respectively [9]. Assessment of post-weaning survival only from HF recurrence or weaning-related complications revealed higher probabilities for 5- and 10-year survival (87.8 ± 5.3% and 82.6 ± 7.3%, respectively) [9]. In a study which compared long-term outcomes of patients bridged to recovery versus patients bridged to HTx, the actuarial survival rate at 5 years after LVAD explantation was 73.9%, whereas in the group bridged to HTx where all patients were finally transplanted, the actuarial post-HTx survival rate at 5 years was 78.3% [26]. Thus, patients weaned from VADs were not at a higher risk for death in comparison to those who underwent HTx, even if the recovery was incomplete and the underlying cause for VAD implantation was a chronic cardiomyopathy. For patients with nonischemic CCM as the underlying cause for MCS, the 5-year survival probability of VAD-explanted patients was also higher than that of patients who could not be weaned from their VAD (73% versus 52%, p < 0.01) [7]. The good long-term survival data of weaned patients with IDCM as the underlying cause for MCS, a disease that long time was considered to be almost irreversible, also suggest that VAD explantation should be considered in all VAD recipients with relevant cardiac improvement, not only in those with potentially more reversible cardiac diseases [3].

Assessment of recovery, either at rest or during exercise, necessitates temporary interruptions of mechanical unloading (“off-pump trials”). Short off-pump trials allow evaluations of the heart under the same circumstances which will exist after VAD removal. However, whereas pulsatile VADs allow optimal cardiac assessment during complete pump stops, complete stops of axial-flow pumps lead to retrograde flow into the LV followed by reduction of the diastolic arterial pressure which, reducing the LV afterload, can generate overestimations of LV systolic function. The misleading retrograde blood flow into the LV during off-pump trials can impede correct weaning decisions. Therefore, for such pumps, rotor speed reduction to values which result in close to zero flow in one cardiac cycle (3000–6000 rpm) is better than complete pump stop [3]. Before off-pump trials heparin must be given (60–100 IU/kg according to the prothrombin time) to prevent thrombus formation inside the pump [8, 22]. Patients with heparin-induced thrombocytopenia should receive argatroban (synthetic thrombin inhibitor) infusions (2 μg/kg/min started 1 h before off-pump trials) [22]. Duration of individual off-pump periods can vary between 3 and 15 min [8, 22]. In patients with a BVAD, it is appropriate to stop both pumps (RV pump 30 s earlier than the LV pump) [22]. In patients with insufficient recovery, as already shown during the first 3 min, the off-pump trial should be stopped [9]. With appropriate caution, the risk of off-pump trials is low [9, 22]. In patients with cardiac recovery, it appeared useful to conduct such trials weekly or every 2 weeks and to make the final decision for elective LVAD explantation only after cardiac improvement has reached its maximum (no further improvement in at least two consecutive off-pump trials) [9]. During recovery it appears useful to change the working mode of the pumps in order to intensify the unloading if the ventricle size needs further reduction or to exert moderate load on the ventricular muscle after maximum improvement [1, 2, 8].

The main diagnostic methods to assess cardiac recovery are echocardiography, heart catheterization, and cardiopulmonary exercise testing.

Whereas renin, angiotensin II (Ang-II), and aldosterone plasma levels usually decrease after LVAD implantation, in the unloaded myocardium, both norepinephrine (NE) and Ang-II tissue levels are elevated and promote cardiac interstitial fibrosis with increase in myocardial stiffness [32]. Angiotensin-converting enzyme (ACE) inhibitors, being able to reduce myocardial Ang-II and also the Ang-II-induced myocardial sympathetic activation, can prevent the progression of extracellular matrix remodeling, and in combination with MCS, ACE inhibitors might be able to reverse, at least partially, that remodeling [32]. Additionally, also Ang-II receptor antagonists, aldosterone antagonists, and β-blockers are recommended to promote recovery during VAD support [8, 25]. Medication doses should be individually adapted with the goal of reducing HR toward 55–60 bpm and blood pressure to the lowest optimally tolerated value, as well as to maintain optimal renal function [9].

More recently, clenbuterol (selective β₂-adrenergic receptor agonist) appeared able to promote myocardial recovery during VAD support [21, 25]. With clenbuterol as additional therapy, the weaning rate from VADs increased beyond 60% (Harefield study) [21, 25]. To confirm these results, a multicenter trial using the Harefield protocol was initiated in the USA (Harp trial) [25]. Unfortunately, only one of the 17 patients enrolled in the HARP study finally underwent explantation.

A potential tool for facilitation of unloading-promoted myocardial recovery might in the future be the development of automatic control strategies for the LV afterload impedance allowing optimization of unloading and a controlled “myocardial training” [7].

After VAD implantation, TTE parameters of “off-pump” cardiac function, ventricular size and geometry, their stability between and during off-pump trials after maximum improvement, and HF duration before VAD implantation allow detection of patients with the potential to remain stable for >5 post-weaning years [8, 9, 22]. Final off-pump LVEF of ≥45% at rest showed a predictive value of 74% for post-explant cardiac stability of ≥5 years, but together with either HF history length of ≤5 years, or final off-pump LV end-diastolic diameter (LVEDD) ≤55 mm, or LV end-diastolic relative wall thickness (RWT_ED) ≥0.38, or LV systolic peak wall motion velocity (Sm) ≥8 cm/sec that predictive value can increase to 86% [8, 22]. Taking into consideration also the pre-explant stability of LVEF, LV size and LV geometry during the time between maximum improvement and VAD explantation, as well as during the final off-pump trial before VAD removal, the predictive value of TTE for post-explant cardiac stability of ≥5 years increases beyond 93% [9]. In patients with stable off-pump LVEF ≥45% at rest plus normal and stable LV size (LVEDD ≤55 mm) and/or geometry (RWT_ED ≥0.38), even the predictive value for post-explant cardiac stability of ≥10 years can reach 90% [9]. Exercise testing also appeared predictive for recovery. Stable or increased MAP and pulse pressure, as well as LVEF ≥53% after the 6 MW, appeared to be strong predictors of recovery [25].