74 (49.3%) patients experienced postoperative infections. Of these infections 54 (73%) were non-device related. Pulmonary (n=23; 43%) and urinary infections (n=15; 28%) were most frequently observed non-LVAD infections.
Device related infections were observed in 20 (13.3%) patients, 18 patients developed a driveline infection (DL) and two patients had a pump pocket infection. Patients were treated by local wound care, targeted antibiotic therapy and eventually surgical debridement, vacuum assisted closure therapy and in cases of DL infection also re-position of the driveline exit site.
Neurological dysfunction was observed in 16 (10.6%) patients. 5 patients suffered from a transient ischemic attack (TIA), 11 (7.3%) patients experienced hemorrhagic (n=5; 3.3%) or ischemic (n=6; 4%) stroke.
Pump thrombosis occurred in 3 (2%) patients. In 2 patients the cause of the thrombosis was an embolus, which was present during inspection of the device. 4 (2.6%) patients underwent surgery due to outflow graft twist, which was de-rotated via lateral thoracotomy.
The most prevalent cause of death in presented patient population after LVAD implantation was multiorgan failure or RHF (n=16; 10.6%), sepsis (n=8; 5.3%) or cerebro-vascular accident (n=4; 2.6%). Overview of causes of death is provided in tab. 4.
Table 4. Primary causes of death
Discussion
In this retrospective study we present an analysis of 4-year single-center experience with centrifugal magnetically levitated left ventricular assist device, the HeartMate 3 LVAS, for treatment of advanced heart failure. The key features of the device include with wide blood flow pathways, friction free movement of magnetically levitated rotor and intrinsic pulsatility to reduce shear stress and blood stasis [6]. As previously demonstrated, Heart-Mate 3 does not degrade high-molecular weight multimers od Von Willebrand factor to the extent observed with other devices [16], which further supports the enhanced hemocompatibility of the device, and along with low lactate dehydrogenase levels reported in recent trials, suggesting lower occurrence of hemolysis [6]. In a largest comparative LVAD trial, the MOMENTUM 3 the HeartMate 3 showed lower rates of hemocompatibility-related adverse event and superior survival free of disabling stroke or reoperation to replace or remove a malfunctioning device in comparison to its predecessor, the HeartMate II [6].
In contrast to HeartMate II the small size of HeartMate 3 allows for intrathoracic placement and also for less invasive implantations. Minimally invasive procedures could carry some positive effects such as reduction of trauma, blood loss and infection rates, or decrease of in-hospital stay and accelerated recovery. Observations in ELEVATE registry found that bleeding (requiring surgery), infection and arrhythmias were lower in the group implanted via the less-invasive surgical approach than those who underwent open heart surgery. Additionally, using less invasive technique may have a positive effect on the incidence of postoperative right heart failure as the pericardium remains intact and right ventricular dilation during onset of the LVAD is prevented [17]. In our series 20 (13.3%) patients were implanted using less-invasive technique, via left anterolateral mini-thoracotomy and upper J mini-sternotomy, utilizing CPB or ECMO. Several groups reported use of bilateral mini-thoracotomy and off-pump less invasive implantations [18, 19].
In this study a 4-year experience with HM 3 are presented. Postoperative survival in our patient population was 77.6 and 74.6% at 12 and 24 months respectively. These results are comparable with results reported in annual reports of Imacs (81.1 and 72.4% respectively) and INTERMACS (82 and 72% respectively). The 2 year results of overall survival are comparable not only with the 2-year follow-up in the ELEVATE registry, but also with two-year survival in MOMENTUM 3 trial (74.5 and 79% respectively) [5, 6]. However, the one-year survival rate for HM 3 patients reported in MOMENTUM 3 trial was slightly higher (86.6%). This observation may be at least partially contributed to two main reasons. First, almost one third of our patients underwent previous cardiac surgery, and second, 22% of the patients required preoperative mechanical circulatory support (ECMO, Impella or combination). These factors could have negatively influenced the risk of perioperative complications and patient outcomes. The long-term survival in our cohort of patients at 36 and 48 months was 74.6 and 69.9% respectively. However, despite the observation of favorable patient survival, the burden of adverse event remained significant.
Right heart failure (RHF) after LVAD implantation is associated with increased morbidity and mortality and thus remains a serious concern [13]. The incidence of early RHF varies according to definitions used. According to data from EUROMACS registry it occurs in 21.7% cases, the report of 2-year results of ELEVATE registry showed the incidence of RHF up to 15% [5]. Furthermore, recent meta-analysis estimated the incidence of RV failure to approximately 35% [20]. On top of frequent occurrence of RHF, the reliability of prediction scores is questionable and the RHF consequences are fateful. In our series the incidence of use mechanical RV support was 31%, in contrast to HM 3 CE Mark Study, ELEVATE Registry or MOMENTUM 3, where the incidence of temporary RVAD use varies between 4 and 7% [4-6]. As the addition of temporary RVAD may lead to improvement of RV recovery and improved patient outcomes, we tend to be liberal in use of temporary RVAD. The implant technique with inflow cannula inserted percutaneously through femoral vein and outflow cannula inserted via Dacron graft anastomosed to pulmonary artery is simple and allows for mini-invasive explantation, which in our opinion does not create serious additional burden to the patient.
In past years one the most discussed complications was the LVAD thrombosis [21]. In our patient population, a suspected or confirmed pump thrombosis occurred in 3 (2%) patients. In 2 patients an embolus was present during the pump inspection at explant. In 1 patient the episode of pump thrombosis was preceded by an ischemic stroke, and related to a new onset of atrial fibrillation. We believe, that this finding further supports our strategy to address possible pre-pump factors of thrombotic adverse events, such as closure of left atrial appendage in patients with atrial fibrillation, extraction of ventricular thrombi and closure of patient foramen ovale at the time of device implantation. Furthermore, with the HeartMate 3 a new advanced diagnostics in the log files is possible, which could be instrumental in cases of pump thrombosis as reported recently [22]. Overall, in MOMENTUM 3 trial and primary cohort of the ELEVATE registry, the rate of suspected or confirmed pump thrombosis was reported at 1.4 and 1.5% respectively, which is comparable to our observation. These very encouraging results are very probably attributed to the novel design features of Heart-Mate 3 (magnetically levitated rotor, wide blood flow paths, and artificial pulse). The overall hemocompatibility of HeartMate 3 had been proved to be superior to HeartMate II in a recent sub-analysis of MOMENTUM 3 trial [23].
Nevertheless, bleeding remains a frequent complication after HeartMate 3 implantation [4-6].
Compared to previously reported results, the rates of bleeding events were lower in our study (25.8%). On contrary, we have observed similar rates of gastrointestinal bleeding as reported in ELEVATE registry results (9.7% at 2 years). The rather favorable bleeding rates in our study might have been influenced by our ongoing studies focused on low intensity anticoagulation protocols in HearMate 3 patients [14, 15]. In one of this studies we have shown, that targeted low-intensity anticoagulation is achievable and safe with HeartMate 3 [14]. Recently, several groups reported cessation of warfarin in patients who have suffered from bleeding complications with rather disputable outcomes [24, 25]. Further studies will have to evaluate also the ASA use in HeartMate 3 patients, as the recent analysis of MOMENTUM 3 showed that the dose of the ASA did not affect bleeding and thrombotic events rates [26]. The prospective, randomized, double-blind, placebo-controlled, international ARIES HM3 (Anti-platelet Removal and Hemocompatibility Events with the HM3 Pump) will provide a definitive answer to question whether ASA therapy provides any meaningful therapeutic effect in HM 3 patients.
Postoperative strokes were reported in MOMENTUM 3 and ELEVATE Registry in 9.9 and 9.7% respectively at 2-years after implantation. In our study cohort we have observed slightly favorable stroke rate of 7.3%. Occurrence of hemorrhagic stroke in almost half of the stroke events may advocate for reduced anticoagulation trials and protocols, to further decrease the stroke rates with HeartMate 3.
Infection was a frequent complication after device implantation. Almost half of the patients suffered from any infection (49.3%), similarly to other reported patient cohorts [5, 6, 27, 28]. Interestingly, device related infections were observed in 13.3% patients, which is significantly superior to rates reported in MOMENTUM 3 or ELEVATE Registry at 2 years. Driveline infection was observed in 12% of patients. At our institution great attention is dedicated to driveline exit site management and staff and patient training. Our institutional protocol comprises meticulous driveline fixation, aseptic dressing exchanges in early postoperative period or, in latter phase, regular ambulatory visits to assess the exit site status. Also frequent patient re-trainings ensure strict adherence of the patients to the dressing protocol. Nevertheless, occurrence of the driveline infections emphasizes the need for fully-implantable device.
Limitations
Retrospective design of the study is a subject to limitations associated with retrospective studies. Also, reproducibility may be limited and affected by institutional experience and institutional specific characteristics, as all the patients were implanted at a single center. Moreover, this study is focused on a single device only and is not comparing outcomes of other available devices.
Conclusion
We have observed survival rates comparable with international registries using the HeartMate 3 LVAS for long-term circulatory support. The results of the study confirm high reliability of the system, enhanced hemocompatibility and have showed adverse event rates comparable or superior to previously published studies. Still, complications such as infections, bleeding or strokes remain a concern.
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