Authors

• Nina Jakuš — ORCID: 0000-0001-7304-1127
• Jasper J. Brugts — ORCID: 0000-0002-5522-9318
• Philippe Timmermans
• Anne-Catherine Pouleur — ORCID: 0000-0002-2395-1787
• Pawel Rubis — ORCID: 0000-0002-6979-3411
• Emeline Van Craenenbroeck — ORCID: 0000-0001-7686-2668
• Edvinas Gaizauskas
• Sebastian Grundmann — ORCID: 0000-0002-6416-6873
• Stephania Paolillo — ORCID: 0000-0003-4683-0993
• Eduardo Barge-Caballero
• Domenico D’Amario
• Aggeliki Gkouziouta
• Ivo Planinc — ORCID: 0000-0003-0561-6704
• Jesse F. Veenis — ORCID: 0000-0001-7234-8266
• Laura Houard — ORCID: 0000-0001-7292-7751
• Katarzyna Holcman — ORCID: 0000-0002-6895-4076
• Arno Gigase
• Bojan Biočina — ORCID: 0000-0003-3362-9596
• Hrvoje Gašparović — ORCID: 0000-0002-2492-3702
• Lars H. Lund — ORCID: 0000-0003-1411-4482
• Andreas Flammer — ORCID: 0000-0002-1373-0630
• Frank Ruschitzka — ORCID: 0000-0001-5972-0596
• Davor Miličić — ORCID: 0000-0001-9101-1570
• Maja Čikeš — ORCID: 0000-0002-4772-5549

Abstract

**Background:** LVAD (left ventricular assist device) candidates are typically stratified according to three most typical treatment strategies – BTT (bridge to transplantation), BTD (bridge to decision) or DT (destination therapy), reflecting the acute vs. chronic state of disease, age, comorbidities and overall condition of the patient. (1, 2) Approximately half of the European LVAD carriers are concomitantly treated with CIED-D (cardiovascular implantable electronic devices with a defibrillator component), in which we have shown substantial survival benefit from concomitant therapy. We aimed to investigate in more detail whether specific LVAD treatment strategies portended a difference in benefit from CIED-D therapy. **Methods:** 429 patients with continuous flow LVADs have been included in a multicentre registry formed by 12 European centres (median age 56 (IQR 46-62), 82% male), 53% also had CIED-D. Patients were analyzed according to VAD intention (**Table 1**). Median follow-up time was 1.1 years (IQR 0.5-2.0) from the time of LVAD implant. ### TABLE 1: Baseline characteristics of the studied left ventricular assist device population according to implant strategy. | | **BTT (N=305)** | **BTD (N=68)** | **DT (N=56)** | **P value** | | --- | --- | --- | --- | --- | | Female gender, n (%) | 53 (17.4%) | 19 (27.9%) | 4 (7.1%) | 0.01 | | Age | 50.28 ±12.68 | 51.54 ± 13.36 | 64.85 ± 7.30 | <0.001 | | Etiology of disease | | | | 0.18 | | Dilated cardiomyopathy, n (%) | 140 (45.9%) | 23 (33.8%) | 18 (32.1%) | | | Ischemic cardiomyopathy, n (%) | 132 (43.3%) | 35 (51.5%) | 31 (55.4%) | | | Other cause of heart failure, n (%) | 33 (10.8%) | 10 (14.7%) | 7 (12.5%) | | | Arterial hypertension, n (%) | 61 (20.0%) | 15 (22.1%) | 23 (41.1%) | 0.003 | | Diabetes mellitus, n (%) | 49 (16.1%) | 13 (19.1%) | 26 (46.4%) | <0.001 | | Chronic kidney disease, n (%) | 63 (20.7%) | 14 (20.6%) | 24 (42.9%) | 0.001 | | Coronary artery disease, n (%) | 65 (21.3%) | 17 (25.0%) | 22 (39.3%) | 0.015 | | Chronic obstructive pulmonary disease, n (%) | 21 (6.9%) | 6 (8.8%) | 15 (26.8%) | <0.001 | | Atrial fibrillation/flutter, n (%) | 86 (28.2%) | 11 (16.2%) | 29 (51.8%) | <0.001 | | Ventricular arrhythmias, n (%) | 71 (23.3%) | 15 (22.1%) | 16 (28.6%) | 0.65 | | Cerebrovascular accidents, n (%) | 21 (6.9%) | 8 (11.8%) | 4 (7.1%) | 0.39 | | No prior cardiac surgery, n (%) | 265 (86.9%) | 59 (86.8%) | 52 (92.9%) | 0.45 | | INTERMACS class, n (%) | | | | <0.001 | | Class 1 | 49 (16.3%) | 17 (26.2%) | 3 (5.6%) | | | Class 2 | 94 (31.3%) | 18 (27.7%) | 5 (9.3%) | | | Class 3 | 89 (29.7%) | 13 (20.0%) | 28 (51.9%) | | | Class 4-7 | 68 (22.7%) | 17 (26.2%) | 18 (33.3%) | | | Device type, n (%) | | | | <0.001 | | Heart Mate II | 193 (63.3%) | 26 (38.2%) | 15 (26.8%) | | | Heart Ware | 56 (18.4%) | 20 (29.4%) | 16 (28.6%) | | | Heart Mate 3 | 49 (16.1%) | 22 (32.4%) | 14 (25.0%) | | | Other device | 7 (2.3%) | 0 (0.0%) | 11 (19.6%) | | | Prior life support, n (%) | | | | <0.001 | | None | 214 (73.0%) | 42 (61.8%) | 52 (92.9%) | | | Extracorporeal membrane oxygenation | 24 (8.2%) | 8 (11.8%) | 1 (1.8%) | | | Temporary LVAD | 2 (0.7%) | 2 (2.9%) | 0 (0.0%) | | | Temporary BiVAD | 0 (0.0%) | 1 (1.5%) | 0 (0.0%) | | | Intraaortic balloon pump | 42 (14.3%) | 7 (10.3%) | 3 (5.4%) | | | Other life support | 11 (3.8%) | 8 (11.8%) | 0 (0.0%) | | | CIED-D therapy during VAD support, n (%) | 137 (44.9%) | 23 (33.8%) | 42 (75.0%) | 0.001 | [†] BTT = bridge to transplantation; BTD = bridge to decision; DT = destination therapy; INTERMACS = Interagency Registry for Mechanically Assisted Circulatory Support; LVAD = left ventricular assist device; BiVAD = biventricular assist device; CIED-D = cardiovascular implantable electronic devices with a defibrillator component; VAD = ventricular assist device. **Results:****Table 1** presents the baseline characteristics of patients according to LVAD treatment strategy. Crude event rates for the primary outcome (all-cause mortality) were equally distributed among the three groups (event rates per 100 person-years): BTT: 22.4 [18.2-27.5], BTD: 23.5 [15.2-36.4], DT: 21.7 [13.7-34.5]), with similar hazard ratios for all-cause death compared to BTT group in unadjusted analysis: HR (95% CI) for BTD and DT was 1.06 (0.65-1.73), p=0.809 and 1.00 (0.60-1.65), p=0.987, respectively. CIED-D use contiguously with an LVAD significantly altered survival in the BTT and DT groups: for BTT patients, CIED-D use carried a 40% mortality reduction (p=0.017) and 65% for DT group (p=0.032). However, LVAD treatment strategy at implantation did not modify the association between CIED-D therapy and mortality reduction (interaction p=0.055). **Conclusion:** In this analysis, concomitant CIED-D therapy during LVAD support was associated with a reduction in mortality in patients receiving an LVAD as BTT and DT. However, neither BTT or BTD strategy modified the treatment effect of CIED-D on survival. This finding confirms the relevance of continuation of CIED-D therapy throughout the duration of LVAD support.

Keywords

heart assist devices, implantable defibrillators, heart failure

DOI

Literature

1. Clerkin KJ, Topkara VK, Demmer RT, Dizon JM, Yuzefpolskaya M, Fried JA, et al. Implantable Cardioverter-Defibrillators in Patients With a Continuous-Flow Left Ventricular Assist Device: An Analysis of the INTERMACS Registry. JACC Heart Fail. 2017 Dec;5(12):916–26. https://doi.org/10.1016/j.jchf.2017.08.014
2. Berg DD, Vaduganathan M, Upadhyay GA, Singh JP, Mehra MR, Stewart GC. Cardiac Implantable Electronic Devices in Patients With Left Ventricular Assist Systems. J Am Coll Cardiol. 2018 Apr 3;71(13):1483–93. https://doi.org/10.1016/j.jacc.2018.01.061