Background: Ischemic and hemorrhagic cerebrovascular accidents remain common among patients with centrifugal-flow left ventricular assist devices, despite improvements in survival and device longev...

Cerebrovascular Events in Patients With Centrifugal-Flow Left Ventricular Assist Devices: Propensity Score-Matched Analysis From the Intermacs Registry.

OBJECTIVES The HeartWare HVAD (HW) and the HeartMate3 (HM3) are presently the most commonly used continuous-flow left ventricular assist devices worldwide. We compared the outcomes of patients supported with either of these 2 devices based on data from the EUROMACS (European Registry for Patients with Mechanical Circulatory Support). METHODS A retrospective analysis of the survival and complications profile in propensity score-matched adult patients enrolled in the EUROMACS between 01 January 2016 and 01 September 2020 and supported with either an HW or HM3. Matching included demographic parameters, severity of cardiogenic shock and risk-modifying end-organ parameters that impact long-term survival. Survival on device and major postoperative adverse events were analysed. RESULTS Following 1:1 propensity score matching, each group consisted of 361 patients. Patients were well balanced (<0.1 standardized mean difference). The median follow-up was similar in both groups [396 (interquartile range (IQR) 112-771) days for HW and 376 (IQR 100-816) days for HM3]. The 2-year survival was similar in both groups [HW: 61% 95% confidence interval (CI) (56-67%) vs HM3: 68% 95% CI (63-73%) (stratified hazard ratio for mortality: 1.13 95% CI (0.83-1.54), P = 0.435].The cumulative incidence for combined major adverse events and unexpected readmissions was similar in both groups [subdistribution hazard ratio (SHR) 1.0 (0.84-1.21), P = 0.96]. Patients in the HW group demonstrated a higher risk of device malfunction [SHR 2.44 (1.45-3.71), P < 0.001], neurological dysfunction [SHR 1.29 (1.02-1.61), P = 0.032] and intracranial bleeding [SHR 1.76 (1.13-2.70), P = 0.012]. CONCLUSIONS Mid-term survival in both groups was similar in a propensity-matched analysis. The risk of device malfunction, neurological dysfunction and intracranial bleeding was significantly higher in HW patients.

Propensity score-based analysis of long-term follow-up in patients supported with durable centrifugal left ventricular assist devices: the EUROMACS analysis.

Redictors of repetitive left-ventricular assist device (LVAD)-thrombosis have not been studied yet. We identified predictors of recurrent LVAD thrombosis in HeartWare (HVAD) patients in a long-term study from 2010 until 2020. We included all patients with two or more thrombolysis treatments for repetitive HVAD thrombosis and effectiveness of thrombolytic therapy was defined as freedom from stroke, death, another HVAD thrombosis, or surgical device exchange within 30 days after the event. Study endpoints also include all-cause mortality and heart transplantation. A total of 534 HVAD implantations have been screened, and 73 patients (13.7%) developed first HVAD thrombosis after a median of 10 months (IQR; 6–21 months). 46 of these patients had effective thrombolysis in 71.7% (n = 33/46). After a median of 14 months (IQR 4–32 months) follow-up, 17 patients (51.5%) had developed a second HVAD thrombosis and all were treated with t-PA therapy again, resulting in effectiveness in 76.5% (n = 13/17). The four patients with ineffective t-PA therapy underwent subsequent surgical HVAD exchange. Multiple Cox regression model analysis revealed time interval between HVAD implantation and first thrombosis as an independent risk factor of recurrent thrombosis (HR, 0.93, 95% CI 0.87–0.99, p = 0.031). Kaplan–Meier analysis at 3 year follow-up showed no significant difference in overall survival for recurrent vs non-recurrent thrombosis groups (log-rank test, p = 0.959). Recurrent HVAD thrombosis mostly appears within 12 months after first thrombosis. Systemic t-PA therapy for recurrent pump thrombosis seems safe, achieving comparable effectiveness rates to initial t-PA therapy. Survival does not differ between patients with or without recurrent HVAD thrombosis.

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Identification of characteristics, risk factors, and predictors of recurrent LVAD thrombosis: conditions in HeartWare devices

Aims Left ventricular assist device therapy has become the cornerstone in the treatment of end-stage heart failure and is increasingly used as destination therapy next to bridge to transplant or recovery. HeartMate 3 (HM3) and HeartWare (HVAD) are centrifugal continuous flow devices implanted intrapericardially and most commonly used worldwide. No randomized controlled trials have been performed yet. Analysis based on large registries may be considered as the best alternative but has the disadvantage of different standard of care between centres and missing data. Bias is introduced, because the decision which device to use was not random, even more so because many centres use only one type of left ventricular assist device. Therefore, we performed a propensity score (PS)-based analysis of long-term clinical outcome of patients that received HM3 or HVAD in a single centre. Methods and results Between December 2010 and December 2019, 100 patients received HVAD and 81 patients HM3 as primary implantation at the University Medical Centre Utrecht. We performed PS matching with an extensive set of covariates, resulting in 112 matched patients with a median follow-up of 28 months. After PS matching, survival was not significantly different (P = 0.21) but was better for HM3. The cumulative incidences for haemorrhagic stroke (P = 0.01) and pump thrombosis (P = 0.02) were significantly higher for HVAD patients. The cumulative incidences for major bleeding, ischaemic stroke, right heart failure, and driveline infection were not different between the groups. We found no interaction between the surgeon who performed the implantation and survival (P = 0.59, P = 0.78, and P = 0.89). Sensitivity analysis was performed, by PS matching without patients on preoperative temporary support resulting in 74 matched patients. This also resulted in a non-significant difference in survival (P = 0.07). The PS-adjusted Cox regression showed a worse but non-significant (P = 0.10) survival for HVAD patients with hazard ratio 1.71 (95% confidence interval 0.91-3.24). Conclusions Survival was not significantly different between both groups after PS matching, but was better for HM3, with a significantly lower incidence of haemorrhagic stroke and pump thrombosis for HM3. These results need to be interpreted carefully, because matching may have introduced greater imbalance on unmeasured covariates. A multicentre approach of carefully selected centres is recommended to enlarge the number of matched patients.

Propensity score-based analysis of long-term outcome of patients on HeartWare and HeartMate 3 left ventricular assist device support.

Despite improved outcomes of modern continuous-flow left ventricular assist devices (CF-LVADs), device exchange is still needed for various indications. While the majority of CF-LVADs are exchanged to the same model, exchange to a different pump model is occasionally warranted. In this meta-analysis, we sought to consolidate the existing evidence to better elucidate the indications and outcomes in these cases. A comprehensive systematic search of adult patient cohorts who underwent CF-LVAD exchange to a different CF-LVAD model was performed. Study-level data from 10 studies comprising 98 patients were extracted and pooled for analysis. Mean patient age was 58 (95% CI: 48-65) and 81% were male. Indication for initial CF-LVAD was ischemic cardiomyopathy in 45% (34-57). Initial device was HeartMate II LVAD (HMII) in 93 (94.9%) and HeartWare HVAD (HW) in 5 (5.1%) patients. After mean CF-LVAD support time of 18.8 (15.2-22.4) months, exchange indications included thrombosis in 71% (43-89), infection in 21% (8-47) and device malfunction in 12% (7-21). HMII to HW exchange occurred in 53 (54.1%) patients, HMII to HeartMate III (HM3) in 32 (32.7%), and HM II to either HW or HM3 in 13 (13.2%) patients. Postoperatively, right ventricular assist device was required in 16% (8-32). Overall, 20% (8-40) of patients experienced a stroke, while HW patients had a significantly higher stroke incidence than HM3 patients (HW: 21% (8-47) vs. HM3: 5% (1-24), P < .01). Overall 30-day mortality was 10% (6-17), while HW had a significantly worse 30-day mortality than HM3 (HW: 13% (7-24) vs. HM3: 5% (1-24), P = .03). Following device exchange from a different CF-LVAD model, HM3 is associated with lower stroke and higher survival when compared to HW.

Continuous-flow LVAD exchange to a different pump model: Systematic review and meta-analysis of the outcomes.

Aims Centrifugal continuous flow pumps are currently the state of the art in left ventricular assist device therapy. This study was conducted to compare the results after implantation of the HVAD® and the HeartMate 3®. Methods and results We retrospectively analysed preoperative and post-operative patient data of all 106 patients, who received a HeartMate 3 (HM3) at our centre between 2014 and 2018. A total of 392 patients receiving a sintered HVAD® served as controls. Patient matching was performed for age, sex, Interagency Registry for Mechanically Assisted Circulatory Support level at the time of implant, perioperative right heart failure, and implantation strategy, that is, bridge to transplant or destination therapy, as well as preoperative renal function, that is, as indicated by serum creatinine levels. A total of 79 matched pairs could be identified. During a median follow-up of 15.3 months (range: 0-30 months), 23 (29.1%) and 19 (24.1%) patients died in the HVAD and HM3 groups, respectively, with a hazard ratio for mortality of 0.84 [95% confidence interval (CI): 0.46-1.54; P = 0.568]. Freedom from cerebrovascular events did not differ significantly between study groups, with a hazard ratio of 0.57 (95% CI: 0.23-1.45; P = 0.241). The risk of driveline infection was significantly lower in the HM3 (n = 33) than in the HVAD (n = 55) group (hazard ratio = 0.54; 95% CI: 0.35-0.84; P = 0.006). Eight HVAD, but no HM3, patients developed a pump thrombosis during follow-up (P = 0.148). Conclusions Performance of both currently used centrifugal left ventricular assist device systems is comparable in terms of short-term patient survival and freedom from cerebrovascular events. In our single-centre experience, HM3 patients less frequently develop driveline infections and no pump thrombosis, which requires further evaluation.

Ellen von Roessing

Papers

Comparing short-term outcome after implantation of the HeartWare® HVAD® and the Abbott® HeartMate 3®.