From June 2010 to December 2022, the Multicenter Italian Study on Radial Mechanically Assisted Circulatory Support (MIRAMACS) Registry [7] enrolled all-comer adult patients (>18 years of age) requiring LVAD support for end-stage heart failure at seven experienced Cardiac Surgery Centres. Only patients receiving HM3 (Abbott, Chicago, IL, United States) or HVAD (Medtronic, Minneapolis, MN, United States) devices were included in the analysis. All patients with biventricular VADs, isolated right ventricular assist device (RVAD), or axial -flow pumps were excluded. Pre-, intra- and post-operative data were collected. Five-years follow-up was prospectively conducted for all participants, through outpatient visits or direct phone contact to the patient or the referring cardiologist. All data were collected in a dedicated datasheet with predefined variables shared among the Participating Centres. All patient’s data were anonymized with a code of serial numbers. Each Centres had a Principal Investigator and a Collaborator who checked and granted for the anonymization and for the completeness of data. The datasheets from each Centre were then merged in a single database.

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the “Area Vasta Emilia Centro della Regione Emilia-Romagna” Ethical Committee, “Azienda Ospedaliero—Universitaria di Bologna, Policlinico S. Orsola-Malpighi” (n° 990/2020/Oss/AOUBo; date of approval: 19/11/2020).

Five-year survival in patients supported by HM3 and HVAD was the primary endpoint of the study. Predictors of survival and 5 years freedom from major adverse events (ischaemic and haemorrhagic stroke, thrombosis, right ventricular failure, gastrointestinal bleeding, and driveline infection) were secondary endpoints. Perioperative outcomes were also assessed. A sub analysis between the first 50 patients implanted with HVAD and the first 50 patients implanted with HM3 was performed in order to investigate a potential learning curve effect. Finally, two sub-analyses were also conducted in patients requiring LVAD as a Destination Therapy (DT) or as a Bridge-To-Transplant (BTT).

Early and late adverse events were defined according to the latest ISHLT definition of adverse events for trials and registries of mechanical circulatory support [8].

The STROBE checklist was used for reporting observational studies [9]. Descriptive statistics were used to analyse data. Continuous variables are reported as mean ± standard deviation or median (interquartile range), and categorical variables are reported as counts and percentages. Differences between groups were assessed using one-way ANOVA for continuous variables. Categorical data were compared between groups using Pearson’s χ² tests or Fisher’s exact tests, as appropriate. Time-to-event analysis was performed. Kaplan–Meier curves were estimated for mortality and each late adverse event. Differences between groups were assessed by the Log-Rank test. A Cox-regression analysis adjusted for major confounders was used to derive the hazard ratios (HR) and 95% confidence intervals (CI). A multivariate Cox-logistic regression was performed to assess predictors of survival among preoperative and post-operative factors in both HVAD and HM3 population. To account for imbalances between the two cohorts, a propensity score was calculated by logistic regression considering the statistically significant differences among preoperative variables. The Propensity-Score Matching (PSM) was conducted using greedy nearest neighbour matching with a 0.01 caliper and a 1:1 match ratio. The Standardized Mean Differences (SMD) were calculated to assess balance after PSM. The statistical analysis was performed using SPSS Version 27.0 (Armonk, NY, IBM Corp.). A p-value of <0.05 was considered statistically significant.

Between June 2010 and December 2022, a total of 447 patients were implanted with CF-LVADs at seven Italian Cardiac Surgery Centres: 214 patients (47.9%) received the HM3 and 233 patients (52.1%) received the HVAD (See Figure 1). The two populations differed in several preoperative characteristics. Patients receiving HVAD were younger, with a smaller body surface area and greater preoperative hepatic injury, when compared with HM3 recipients. On the other hand, HM3 patients presented a higher systolic pulmonary arterial pressure, and a more advanced renal impairment than HVAD patients (Supplementary Table S1). Fifty per cent of both populations was in INTERMACS 3, while 10% in INTERMACS 1. Ischemic heart disease and idiopathic cardiomyopathy represented the main indications in both groups, while hypertrophic cardiomyopathy was more observed in HM3 patients (Supplementary Table S1). Periprocedural mortality (14% vs. 9% for HM3 vs. HW; p = 0.1) was comparable between the two populations. Detailed hospital outcomes data were reported in Supplementary Table S2.

The mean follow-up time was 65.7 ± 3.1 months. The overall survival at 5 years was higher in HM3 patients (64.1% vs. 42.6%, p = 0.004) (Figure 2A). In HVAD cohort, age (HR 1.03 [1.003–1.057]; p = 0.028), post-operatively dialysis (HR 2.7 [1.53–4.79]; p < 0.001) and ischaemic stroke (HR 2.87 [1.16–7.1]; p = 0.023) resulted risk factors for mortality at follow-up (Table 1). In HM3 cohort, preoperative creatinine level (HR 1.46 [1.03–1.2.07]; p = 0.032), post-operatively dialysis (HR 1.99 [1.077–3.67]; p < 0.03), ischaemic stroke (HR 7.24 [3.4–15.6]; p < 0.001) and right ventricular failure (HR 2.96 [1.62–5.43]: p < 0.001) resulted risk factors for mortality at follow-up (Table 2).

HVAD patients reported a significantly lower freedom from both haemorrhagic (88.6% vs. 69.8%; p < 0.001) and ischaemic stroke (91.7% vs. 75.1%; p = 0.054), and from pump thrombosis (99.1% vs. 76.8%; p < 0.001) (Supplementary Figures S1, S2). No statistical differences in 5 years freedom from right ventricular failure and from driveline infection were reported between groups (Supplementary Figure S2). The Cox-regression analysis adjusted for major confounders showed that HVAD patients had a significantly increased risk for mortality (HR 1.5 [1.2–1.9]; p = 0.031), for pump thrombosis (HR 25.7 [3.4–188.9]; p < 0.001), and for both haemorrhagic stroke (HR 2.6 [1.3–4.9]; p = 0.005) and ischemic stroke (HR 2.08 [1.06–4.08]; p = 0.033) (Table 1). Five-year freedom from gastrointestinal bleeding was significantly higher in HM3 patients (90.5% vs. 80.2%; p = 0.008) (Supplementary Figure S2), though this difference was lost after adjusting for major confounders at Cox-regression analysis (Table 3).

A total of 65 HVAD (57 BTT and 8 BTC) and 20 HM3 (19 BTT and 1 BTC) patients underwent to heart transplant. Among HVAD patients, 22 (33.8%) underwent to heart transplant because of LVAD complications (14 because of pump thrombosis, 4 because of LVAD infection), eight of whom in urgency tier. Only four patients (one in urgency) in HM3 cohort were transplanted because of LVAD infection. Only two patients underwent to HVAD explant for recovery, while one patient underwent HVAD exchange for pump thrombosis, but died postoperatively. All other patients who experienced thrombosis were pharmacologically treated and 14 of them transplanted.

The sub analysis on the first 50 cases of implantation of HVAD and HM3 confirmed a worse outcome in HVAD patients. Perioperative mortality was higher in HVAD patients compared to HM3, though not statistically significant (10% vs. 4%; p = 0.43). Long-term outcome analysis confirmed worse 5 years survival (24.8% vs. 68.1%; p < 0.001), lower freedom from haemorrhagic (54.5% vs. 80.8%; p = 0.04) and ischaemic stroke (71.2% vs. 95.8; p = 0.007) and from pump thrombosis (62.6% vs. 100%; p < 0.001). Five-year freedom from gastrointestinal bleeding (79.4% vs. 90.2%; p = 0.12), from right ventricular failure (66.4% vs. 77.9%; p = 0.29) and from drive-line infection (54.6% vs. 63.4%; p = 0.83) were similar between the two cohorts.

After PSM-analysis, 130 pairs of patients with similar preoperative profiles receiving HM or HVAD were selected. Preoperative characteristics are reported in Table 4. Post-operative complications remained similar between the groups, with the exception for prolonged ventilation and sepsis which were more frequent in HM3 patients (Table 5). HVAD patients confirmed a significantly lower 5 years survival (64.1% vs. 41.7%; p 0.02) (Figure 2B), freedom from haemorrhagic stroke (90.5% vs. 70.1%; p < 0.001) and from pump thrombosis (98.5% vs. 74.7%; p < 0.001) (Figure 3). Freedom from ischaemic stroke remained lower in HVAD compared to HM3, but non-statistically significant (Figure 4). Freedom from gastrointestinal bleeding, driveline infection and right heart failure were comparable between HM3 and HVAD (Figure 4).

Out of 103 DT patients, 49 received HM3 and 54 received HVAD. More than 80% were male in both groups, with a mean age of 66.2 ± 5.6 in HM3 vs. 67.5 ± 5.02 in HVAD (p = 0.18) (Table 6). Post-operative mortality was comparable (8.2% vs. 5.6% in HM3 and HVAD respectively; p = 0.7), as well as all post-operative complications, except for right ventricular failure that was more common in HM3 patients (Table 7). The HVAD cohort had lower 5 years cumulative survival (59.9% vs. 37% p = 0.03) (Supplementary Figure S3A) and freedom from haemorrhagic stroke (76.7% vs. 65.4%; p = 0.01) (Supplementary Figure S3B). In this sub-population, freedom from thrombosis resulted lower in HVAD, though not statistically significant (Supplementary Figure S4). No statistical differences were reported for the other adverse events (Supplementary Figure S5).

Out of 116 BTT patients, 59 were supported by HM3 and 53 by HVAD. Time to transplant was shorter in HVAD (36.7 vs. 49.9 months; p = 0.019) (Supplementary Figure S6B). The cumulative 5 years survival was comparable between the two cohorts (Supplementary Figure S6A), as well as the freedom from adverse events (Supplementary Figures S7, S8), except freedom from pump thrombosis which was lower in HVAD patients (Supplementary Figure S7B). Preoperative and post-operative data of BTT are displayed in Supplementary Tables S3, S4.

The main limitation of the study stems for its non-randomized nature. However, the strength of the study is that confirms over 5 years of follow up findings already reported over shorter time frames. MIRAMACS is the first Italian nation-level observational multicentre registry, gathering all-comer adult patients undergoing third generation CF-LVAD. Therefore, it reports “real-world” data from a wide interinstitutional experience. Though it confirms the worse-life expectation of HVAD patients, it also highlights the good 5 years outcome of HM3 device outside from MOMENTUM-3 data [3].

Another limitation relates to the difference in mean follow-up time between HVAD and HM3, though this unavoidable bias stems from the different marketing time of the two devices. However, Cox regression analysis and PSM analysis were performed to account for possible confounders.

Finally, this study reports a national trend in LVAD policy and management, and unaddressed bias might limit its reproducibility in countries with other allocation systems and policies.