Soluble Suppression of Tumorigenicity-2 Predicts Mortality and Right Heart Failure in Patients With a Left Ventricular Assist Device.

BACKGROUND: Soluble suppression of tumorigenicity-2 (sST2) predicts mortality in patients with heart failure. The predictive value of sST2 in patients with a left ventricular assist device remains unknown. Therefore, we studied the relationship between sST2 and outcome after left ventricular assist device implantation. METHODS AND RESULTS: sST2 levels of patients with a left ventricular assist device implanted between January 2015 and December 2022 were included in this observational study. The median follow-up was 25 months, during which 1573 postoperative sST2 levels were measured in 199 patients, with a median of 29 ng/mL. Survival of patients with normal and elevated preoperative levels was compared using Kaplan-Meier analysis, which did not differ significantly (P=0.22) between both groups. The relationship between postoperative sST2, survival, and right heart failure was evaluated using a joint model, which showed a significant relationship between the absolute sST2 level and mortality, with a hazard ratio (HR) of 1.20 (95% CI, 1.10-1.130; P<0.01) and an HR of 1.22 (95% CI, 1.07-1.39; P=0.01) for right heart failure, both per 10-unit sST2 increase. The sST2 instantaneous change was not predictive for survival or right heart failure (P=0.99 and P=0.94, respectively). Multivariate joint model analysis showed a significant relationship between sST2 with mortality adjusted for NT-proBNP (N-terminal pro-B-type natriuretic peptide), with an HR of 1.19 (95% CI, 1.00-1.42; P=0.05), whereas the HR of right heart failure was not significant (1.22 [95% CI, 0.94-1.59]; P=0.14), both per 10-unit sST2 increase. CONCLUSIONS: Time-dependent postoperative sST2 predicts all-cause mortality after left ventricular assist device implantation after adjustment for NT-proBNP. Future research is warranted into possible target interventions and the optimal monitoring frequency.

Identifying patients at risk: multi-centre comparison of HeartMate 3 and HeartWare left ventricular assist devices.

AIMS: Since the withdrawal of HeartWare (HVAD) from the global market, there is an ongoing discussion if and which patients require prophylactically exchange for a HeartMate 3 (HM3). Therefore, it is important to study outcome differences between HVAD and HM3 patients. Because centres differ in patient selection and standard of care, we performed a propensity score (PS)-based study including centres that implanted both devices and aimed to identify which HVAD patients are at highest risk. METHODS AND RESULTS: We performed an international multi-centre study (n = 1021) including centres that implanted HVAD and HM3. PS-matching was performed using clinical variables and the implanting centre. Survival and complications were compared. As a sensitivity analysis, PS-adjusted Cox regression was performed. Landmark analysis with conditional survival >2 years was conducted to evaluate long-term survival differences. To identify which HVAD patients may benefit from a HM3 upgrade, Cox regression using pre-operative variables and their interaction with device type was performed. Survival was significantly better for HM3 patients (P < 0.01) in 458 matched patients, with a median follow-up of 23 months. Within the matched cohort, HM3 patients had a median age of 58 years, and 83% were male, 80% of the HVAD patients were male, with a median age of 59 years. PS-adjusted Cox regression confirmed a significantly better survival for HM3 patients when compared with HVAD, with a HR of 1.46 (95% confidence interval 1.14-1.85, P < 0.01). Pump thrombosis (P < 0.01) and ischaemic stroke (P < 0.01) occurred less in HM3 patients. No difference was found for haemorrhagic stroke, right heart failure, driveline infection, and major bleeding. Landmark-analysis confirmed a significant difference in conditional survival >2 years after implantation (P = 0.03). None of the pre-operative variable interactions in the Cox regression were significant. CONCLUSIONS: HM3 patients have a significantly better survival and a lower incidence of ischaemic strokes and pump thrombosis than HVAD patients. This survival difference persisted after 2 years of implantation. Additional research using post-operative variables is warranted to identify which HVAD patients need an upgrade to HM3 or expedited transplantation.

Validity and success rate of noninvasive mean arterial blood pressure measurements in cf-LVAD patients: A technical review.

BACKGROUND: The life expectancy of patients with a continuous flow left ventricular assist device (cf-LVAD) is increasing. Adequate determination and regulation of mean arterial pressure (MAP) is important to prevent adverse events. Given the low pulsatility characteristics in these patients, standard blood pressure equipment is inadequate to monitor MAP and not recommended. We provide an overview of currently available noninvasive techniques, using an extensive search strategy in three online databases (Pubmed, Scopus and Google Scholar) to find validation studies using invasive intra-arterial blood pressure measurement as a reference. Mean differences with the reference values smaller than 5 ± 8 mm Hg were considered acceptable. OBSERVATIONS: After deduplication, screening, and exclusion of incorrect sources, eleven studies remained with 3139 successful MAP measurements in 386 patients. Four noninvasive techniques, using Doppler, pulse oximetry, finger cuff volume clamp, or slow upper arm cuff deflation, were identified and evaluated for validity and success rate in cf-LVAD patients. Here, a comprehensive technical background of the blood pressure measurement methods is provided in combination with a clinical use comparison. Of the reported noninvasive techniques, slow cuff devices performed most optimally (mean difference 1.3 ± 5.2 mm Hg). CONCLUSIONS: Our results are encouraging and indicate that noninvasive blood pressure monitoring options with acceptable validity and success rate are available. Further technical development and validation is warranted for the growing population of patients on long-term cf-LVAD support.

Hyperpolypharmacy is a predictor of mortality after left ventricular assist device (LVAD) implantation.

Background: The prevalence of (hyper)polypharmacy in patients on left ventricular assist device (LVAD) support and its effect on clinical outcomeis unknown. Therefore, we aimed to determine the prevalence of (hyper)polypharmacy in LVAD patients and evaluate its association with mortality and complications. Materials and methods: 210 patients aged ≥40 years who received a primary LVAD implantation between 2011 and 2019 were included for analysis. Polypharmacy and hyperpolypharmacy were defined as the concomitant use of 5-9 and ≥10 medications at discharge after LVAD implantation, respectively. Cause specific cox regression was used to assess the association of ≥10 medications with mortality, cardiac arrhythmia, driveline infection and major bleeding. Results: The median age of the patients was 57.5 years, and 35.7 % were female. The average number of discharge medications was 8.8 ± 2.3 per patient. The prevalence of patients with 5-9 medications and ≥10 medications was 62.9 % and 34.8 %, respectively. The median follow-up duration was 948 days (interquartile range 874 days). The prescription of ≥10 medications was significantly associated with a higher risk of mortality (HR 2.03; 95 % CI 1.15-3.6, p-value 0.02) adjusted for sex, age, comorbidity and stratified for device type. The prescription of ≥10 medications was not associated with a higher risk of major bleeding, cardiac arrhythmia or driveline infection. Conclusions: (Hyper)polypharmacy is highly prevalent in LVAD patients and is independently associated with a higher risk of mortality. Future research is needed to assess the efficacy of individual risk-benefit profiling of (cardiovascular) medication to ensure appropriate polypharmacy and to decrease negative health outcomes.

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

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.