Comment
The primary endpoint of this study was 6-month survival in postapproval (post-trial) patients who received the HM3 as a primary device in the United States. Our single-center 6-month survival for post-trial patients is 93.3%, which mirrors the 6-month survival in the trial group from our center (93.8%). Our postapproval patients were not selected based on strict inclusion criteria as set for the trial patients. As a result, younger acutely and critically ill patients underwent implantation of the HM3 who otherwise would not have qualified for the HM3 device during the trial phase. This population reflects real-world experience. Although our trial and postapproval patients were not statistically different based on overall baseline INTERMACS profile(p=0.17) , the postapproval group included more patients with INTERMACS profile 1 (p=0.04 ) than the trial group, and these patients required a higher degree of hemodynamic support with Impella 5.0, Tandem, or ECMO devices (p=0.01 ). At our center, we have historically seen higher percentages of INTERMACS 1 and 2 profile patients than reported in the MOMENTUM 3 and European postapproval ELEVATE registry (73.9% vs 32.3% vs 31%, respectively).10,12 This difference in patient profiles can be attributed to differences in patient populations, referral patterns, and differences in access to health care facilities, insurance coverage for advanced therapies, and late transfers from outside institutions (our center is the only heart transplant and LVAD center for the state of Louisiana). Another explanation for this difference can be related to the fact that because the trial findings showed a significant improvement in the device hemocompatibility profile when compared with the previous generation devices, surgeons at our center had more confidence in implanting the HM3 in sicker patients vs other devices.
Our postapproval group patients were younger than the trial group patients because the HM 3 device was used in all comers, including patients who were upgraded from IABP to higher support devices (Tandem, Impella, and ECMO) due to ongoing cardiogenic shock while on IABP support ( which was an exclusion for the trial patients). Due to postapproval group consisting of more young patients, a higher percentage of these patients were BTT candidates as compared to the trial group (p=0.05). Also, the postapproval group had a statistically elevated pre-operative INR (a decreased synthetic function of the liver) compared to the trial group, reflecting a higher degree of illness (p=0.04).
Six deaths occurred in the postapproval group and five deaths in the trial group. Two patients in the trial group and four in the postapproval group were transplanted within the first 6 months of their LVAD implant. Six-month postapproval survival data are comparable with the results from the MOMENTUM 3 trial and the primary implants cohort of the ELEVATE registry (93.3% vs 88% vs 92%, respectively).10,12 The observed long-term benefit of the HM3 vs the previous generation of CF-LVADS is a marked reduction in stroke rates.13 Stroke rates 6 months after an implant at our center were comparable between the trial and postapproval groups (7.3% vs 4.4%; p =0.52). However, the stroke rate at our center is comparable to the 6-month MOMENTUM 3 and postapproval ELEVATE registry (4.4% vs 7.9% vs 5.4%, respectively).7,10The lower rate of stroke seen at our center could be attributed to our adherence to robust blood pressure and anticoagulation management protocols.14,15
A significant reduction in re-exploration rates was observed in the postapproval group. This observation can be explained by a series of changes made during the perioperative phase of the implant: modification in surgical technique (placing 16 vs 12 pledgetted stitches around the sewing ring), preoperative administration of vitamin K (2 doses 24 hours prior to implantation), and use of thromboelastogram analysis for correction of coagulopathy prior to leaving the operating room. Lessons learned during the trial phase showed that the majority of patients who underwent re-exploration for bleeding had a bleeding site at the apical sewing ring. Increasing the number of pledgetted stitches from 12 to 16 eliminated bleeding from the sewing ring site. We have determined that administration of 2 doses of vitamin K 24 hours prior to LVAD implantation reduces bleeding complications. Vitamin K administration has become a part of our routine and was used during the postapproval phase of device implantation.16
Pump thrombosis was comparable between the two groups, and all cases of pump thrombosis were related to outflow graft twist identified by computed tomography scan. All patients presented with acute onset low-flow alarms. At the time of pump exchange, thrombus was present in the outflow graft extending into the HM 3 device. All of these patients underwent successful pump exchange with full recovery. The incidence of outflow graft twist has now been completely eradicated with the changes in the spline cover of the HM3 pump.
The MCS-ARC definition of acute severe RVF was used for analysis.11 A reduction in the incidence of severe RVF requiring inotropes >14 days was observed in the postapproval group (34.8% vs 41.5%; p =0.36) compared to the trial group patients. This finding can be explained by our incremental improvement in understanding the HM3 device, improved perioperative management, and a significant reduction in the incidence of postoperative bleeding requiring re-exploration (a well-established risk factor for the development of RVF).17-23 Also, the incidence of right ventricular assist device (RVAD) use for severe RVF was similar between the two groups.