Continuous-flow Left Ventricular Assist Devices Patients Research Articles

Machine Learning Assisted Stroke Prediction in Mechanical Circulatory Support: Predictive Role of Systemic Mitochondrial Dysfunction.

Stroke continues to be a major adverse event in advanced congestive heart failure (CHF) patients after continuous-flow left ventricular assist device (CF-LVAD) implantation. Abnormalities in mitochondrial oxidative phosphorylation (OxPhos) have been critically implicated in the pathogenesis of neurodegenerative diseases and cerebral ischemia. We hypothesize that prior stroke may be associated with systemic mitochondrial OxPhos abnormalities, and impaired more in post-CF-LVAD patients with risk of developing new stroke. We studied 50 CF-LVAD patients (25 with prior stroke, 25 without); OxPhos complex proteins (complex I [C.I]-complex V [C.V]) were measured in blood leukocytes. Both at baseline (pre-CF-LVAD) and postoperatively (post-CF-LVAD), the prior-stroke group had significantly lower C.I, complex II (C.II), complex IV (C.IV), and C.V proteins when compared to the no-prior-stroke group. Oxidative phosphorylation proteins were significantly decreased in prior-stroke group at post-CF-LVAD compared to pre-CF-LVAD. Machine learning Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest modeling identified six prognostic factors that predicted postoperative stroke with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.93. Oxidative phosphorylation protein reduction appeared to be associated with the new stroke after implantation. Our study found for the first time the existence of mitochondrial dysfunction at the peripheral level in CHF patients with prior ischemic stroke even before CF-LVAD implantation. The changes in OxPhos protein expression could serve as biomarkers in predicting new post-CF-LVAD strokes.

Impact of statins on incidence of gastrointestinal bleeding events among patients with continuous-flow left ventricular assist devices.

Patients with continuous flow left ventricular assist devices (CF-LVADs) are at increased risk of gastrointestinal bleeding (GIB). Statins are commonly prescribed in LVAD patients for cardiovascular disease prevention. However, their impact on GIB events is controversial. Importantly, literature regarding statins impact on GIB in CF-LVAD patients is lacking. A single-center, retrospective review of adult patients who underwent CF-LVAD implantation between May 2016 and January 2020 was performed. Patients were categorized based on statin use throughout the study period. The primary outcome was the composite of arteriovenous malformation confirmed GIB and major GIB events for up to 1-year post-LVAD implantation. Of 123 patients included in the final analysis, 66 (54%) received statin therapy during the study period. No difference was observed in the primary outcome between the statin and control groups (RR: 1.73; 95% CI: 0.75-3.98; p=0.20). Multivariable Cox regression revealed that older age and higher baseline creatinine were associated with an increased risk of GIB within 1-year of CF-LVAD implantation. Among patients with CF-LVADs, there was no significant difference in the incidence of major GIB events associated with the use of statin therapy. Further studies are needed to assess whether a true association exists.

Managing ventricular arrhythmias and implantable cardiac defibrillator shocks after left ventricular assist device implantation.

Continuous flow left ventricular assist devices (CF-LVADs) have been shown to reduce mortality and morbidity in patients with advanced heart failure with reduced ejection fraction. However, ventricular arrhythmias (VA) are common, are mostly secondary to underlying myocardial scar, and have a higher incidence in patients with pre-LVAD VA. Sustained VA is well tolerated in the LVAD patient but can result in implantable defibrillator (ICD) shocks, right ventricular failure, hospitalizations, and reduced quality of life. There is limited data regarding best practices for the medical management of VA as well as the role for procedural interventions in patients with uncontrolled VA and/or ICD shocks. Vast majority of CF-LVAD patients have a preexisting cardiovascular implantable electronic device (CIED) and ICD and/or cardiac resynchronization therapies are continued in many. Several questions, however, remain regarding the efficacy of ICD and CRT following CF-LVAD. Moreover, optimal CIED programming after CF-LVAD implantation. Therefore, the primary objective of this review article is to provide the most up-to-date evidence and to provide guidance on the clinical significance, pathogenesis, predictors, and management strategies for VA and ICD therapies in the CF-LVAD population. We also discuss knowledge gaps as well as areas for future research.

Bridging therapy and risk of major bleeding and thrombosis in continuous-flow left ventricular assist device patients: a quasi-experimental study

Abstract Background Bridging with low molecular weight heparin (LMWH) on top of vitamin K antagonist treatment is recommended in continuous-flow left ventricular assist device (CF-LVAD) patients during subtherapeutic anticoagulation. However, the consequence of bridging on the risk of bleeding and thrombosis are unknown. Aim To assess the risk of major bleeding and thrombosis associated with bridging in CF-LVAD patients, through a regression discontinuity (RD) design, a quasi-experimental design. Methods We included CF-LVAD patients implanted at our university medical center between 2010-2021. Outcomes were major bleeding (INTERMACS type 3, 4, 5) and thromboembolic events (pump thrombosis, arterial non-central nervous system and venous thromboembolism). We estimated incidence rates and hazard ratios (HR) with 95% confidence intervals (95%CI) by time-dependent Cox regression. Using an RD design, a quasi-experimental design, we compared patients using LMWH due to a subtherapeutic international normalized ratio (INR) to patients with no LMWH and an INR just in target range. As LMWH treatment is initiated based on an INR threshold (i.e., when INR is below the lower target range) and INR is subject to random variability, patients just below and in the INR target range are comparable, mimicking a randomized trial. Analyses were performed five times including INRs±0.1, ±0.2, ±0.3, ±0.4 and ±0.5 around the INR threshold. Results 77 patients were included, with a median age at implantation of 69 years, 60 (78%) were male, 45 (58%) had ischemic heart failure and 35 (45%) had INTERMACS classification 3. We included 35,466 INRs during 91 patient-years of follow-up. Bridging was associated with increased major bleeding rates compared to no-bridging in all analyses (Figure 1). In particular, the risk of major bleeding was 6.9-fold increased (95%CI 1.2-38.9) during bridging compared to no-bridging considering INR+0.1, and 3.4-fold (95%CI 1.4-8.2) considering INR±0.5 (Figure 2A). While thrombotic events were infrequent, the risk of thrombosis was around unity during bridging compared to no-bridging considering INR±0.5 (HR 1.1, 95%CI 0.1-9.9, Figure 2B). Conclusions During bridging with LMWH, CF-LVAD patients had a 6.9-fold increased risk of major bleeding, while the risk of thrombosis was around unity compared to no-bridging.Incidence ratesHazard ratios

An Institutional Overview of Gastrointestinal Bleeding Among 563 Continuous-Flow Left Ventricular Assist Device Recipients

Background and AimsGastrointestinal bleeding (GIB) is a common morbidity among continuous-flow left ventricular assist device (CF-LVAD) recipients. The study objectives were to investigate the incidence, recurrence, risk factors, and medical and endoscopic management of GIB among CF-LVAD patients. MethodsThis is a single-center retrospective study analyzing 563 CF-LVAD recipients implanted at a large tertiary referral center from 2007 to 2018 with 619 bleeding events characterized. Patients with device exchanges or history of right ventricular assist devices were excluded. Chart review data pertaining to demographics, LVAD characteristics, endoscopic reports, and medications were collected. ResultsThe incidence of GIB was 44%, with a median time to first bleed of 133 days and a recurrence rate of 53%. Approximately 13% of patients had ≥5 GIB events. There is an association of reduced GIB among patients taking angiotensin-converting enzyme inhibitors (ACEis). There was no association with GIB and acid-reducing medications, antiplatelet medications, and history of GIB before device implantation. Arteriovenous malformations were the most common bleeding etiology. CF-LVAD patients that bled more frequently were older, had their CF-LVAD longer, and bled earlier after LVAD implantation. ConclusionThis is the largest comprehensive single-center GIB study among CF-LVAD recipients. The incidence and recurrence of GIB among CF-LVAD recipients is underreported. Push enteroscopy improves diagnostic yield for upper GIB. Special attention should be given to CF-LVAD patients that bleed within the first 18 days of implantation. There is an associative, dose-dependent benefit of ACEi medications among CF-LVAD recipients. Further studies on this effect are warranted.

Continuous-flow left ventricular assist devices associated survival awaiting heart and heart-kidney transplant.

Improvement in continuous-flow left ventricular assist device (CF-LVAD) technology has translated to better outcomes for patients on CF-LVAD support as a bridge-to-transplant. However, data are lacking regarding the subset of CF-LVAD patients with renal failure awaiting simultaneous heart-kidney transplant (HKTx). We sought to better understand the characteristics and outcomes of patients in this group. The United Network for Organ Sharing (UNOS) database was used to identify adult patients listed for heart transplant (HTx) or HKTx from January 1, 2009 to March 31, 2017. Patients were followed from time on waitlist to either removal from waitlist or transplantation. Demographic and clinical data for HTx and HKTx patients were assessed. Kaplan-Meier analysis assessed waitlist and post-transplant survival. For waitlisted patients, both death and removal from the waitlist due to deteriorating medical condition were considered events. Overall, 26 638 patients registered for transplant were analyzed. 25 111 (94%) were listed for HTx, and 1527 (6%) for HKTx. 7683 (29%) patients listed for HTx had CF-LVAD support. For those listed for HKTx, 441 (28%) underwent dialysis alone, 256 (17%) had CF-LVAD support alone, and 85 (6%) were treated with both CF-LVAD and dialysis. 15 567 (58%) underwent HTx, and 621 (2%) underwent HKTx. In these groups, post-transplant survival was similar (p=0.06). Patients listed for HKTx treated with both dialysis and CF-LVAD had significantly worse waitlist survival compared to HKTx recipients (p < 0.001). Post-transplant survival is comparable between HTx and HKTx, and early survival is similar between HTx patients and those listed for HTx with CF-LVAD support. However, outcomes on the waitlist for HKTx in CF-LVAD patients on dialysis is significantly worse compared to HKTx recipients. This highlights the need to better account for this patient population when allocating organs.

Sex-related differences in left ventricular assist device utilization and outcomes: results from the PCHF-VAD registry.

Data on sex and left ventricular assist device (LVAD) utilization and outcomes have been conflicting and mostly confined to US studies incorporating older devices. This study aimed to investigate sex-related differences in LVAD utilization and outcomes in a contemporary European LVAD cohort. This analysis is part of the multicentre PCHF-VAD registry studying continuous-flow LVAD patients. The primary outcome was all-cause mortality. Secondary outcomes included ventricular arrhythmias, right ventricular failure, bleeding, thromboembolism, and the haemocompatibility score. Multivariable Cox regression models were used to assess associations between sex and outcomes. Overall, 457 men (81%) and 105 women (19%) were analysed. At LVAD implant, women were more often in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 or 2 (55% vs. 41%, P=0.009) and more often required temporary mechanical circulatory support (39% vs. 23%, P=0.001). Mean age was comparable (52.1 vs. 53.4years, P=0.33), and median follow-up duration was 344 [range 147-823] days for women and 435 [range 190-816] days for men (P=0.40). No significant sex-related differences were found in all-cause mortality (hazard ratio [HR] 0.79 for female vs. male sex, 95% confidence interval [CI] [0.50-1.27]). Female LVAD patients had a lower risk of ventricular arrhythmias (HR 0.56, 95% CI [0.33-0.95]) but more often experienced right ventricular failure. No significant sex-related differences were found in other outcomes. In this contemporary European cohort of LVAD patients, far fewer women than men underwent LVAD implantation despite similar clinical outcomes. This is important as the proportion of female LVAD patients (19%) was lower than the proportion of females with advanced HF as reported in previous studies, suggesting underutilization. Also, female patients were remarkably more often in INTERMACS profile 1 or 2, suggesting later referral for LVAD therapy. Additional research in female patients is warranted.

Pulsatile Pressure Delivery of Continuous-Flow Left Ventricular Assist Devices Is Markedly Reduced Relative to Heart Failure Patients.

Although continuous-flow left ventricular assist devices (CF-LVADs) provide an augmentation in systemic perfusion, there is a scarcity of in vivo data regarding systemic pulsatility on support. Patients supported on CF-LVAD therapy (n = 71) who underwent combined left/right catheterization ramp study were included. Aortic pulsatility was defined by the pulsatile power index (PPI), which was also calculated in a cohort of high-output heart failure (HOHF, n = 66) and standard HF cohort (n = 44). PPI was drastically lower in CF-LVAD-supported patients with median PPI of 0.006 (interquartile range [IQR], 0.002-0.012) compared with PPI in the HF population at 0.09 (IQR, 0.06-0.17) or HOHF population at 0.25 (IQR, 0.13-0.37; p < 0.0001 among groups). With speed augmentation during ramp, PPI values fell quickly in patients with higher PPI at baseline. PPI correlated poorly with left ventricular ejection fraction (LVEF) in all groups. In CF-LVAD patients, there was a stronger correlation with LV dP/dt (r = 0.41; p = 0.001) than LVEF (r = 0.21; p = 0.08; pint < 0.001). CF-LVAD support is associated with a dramatic reduction in arterial pulsatility as measured by PPI relative to HOHF and HF cohorts and decreases with speed. Further work is needed to determine the applicability to the next generation of device therapy.

Tissue plasminogen activator in left ventricular assist device-related intravascular hemolysis after failed augmented anticoagulation.

We sought to examine the efficacy and safety of adding fibrinogen-guided low-dose multi-day Alteplase™ tissue plasminogen activator (tPA) in the management of intravascular hemolysis (IVH) in patients with the HeartMate II (HM-II) continuous flow (CF) left ventricular assist device (LVAD) who failed to achieve IVH resolution with conventional augmented anticoagulation (AAC). IVH in patients with LVAD is often treated with AAC, failing which pump exchange is considered. We hypothesized that a trial of low-dose tPA after failed AAC therapy could resolve IVH and prevent pump exchange in some patients. We performed a retrospective study of 31 HM-II CF LVAD patients admitted to our center from January 2015 to January 2020 for IVH management who received tPA following failed AAC. Primary 6-month outcomes included successful IVH resolution, unsuccessful IVH resolution requiring pump exchange, gastrointestinal bleeding, ischemic and hemorrhagic cerebrovascular accident (CVA), and death. Thirty-one patients with IVH were treated with tPA following failed AAC. Successful resolution of IVH occurred in 22/31 (71%) patients. Pump exchange occurred in 9/31 (29%) patients. Gastrointestinal bleeding occurred in 7/31 (22.6%) patients. Ischemic CVA occurred in 6/31 (19.4%) patients. Management of IVH with administration of low-dose tPA after failed AAC is feasible and may prevent pump exchange in some patients.

Self-Measured Doppler Blood Pressure Readings in Continuous-Flow LVAD Patients are Reliable

Self-Measured Doppler Blood Pressure Readings in Continuous-Flow LVAD Patients are Reliable

Pulsatile Pressure Delivery of Continuous Flow LVAD is Speed Dependent and Markedly Reduced Relative to Heart Failure Patients

<h3>Purpose</h3> Although continuous flow left ventricular assist devices (CF-LVADs) provide an augmentation in systemic perfusion, there is a scarcity of in-vivo data regarding systemic pulsatility on support. <h3>Methods</h3> A retrospective cohort study was performed in patients supported on CF-LVAD therapy (n=67) who underwent a combined left and right heart catheterization ramp protocol. Aortic pulsatility was defined by the pulsatile power index (PPI), a quantity derived from the amplitudes of the harmonics of the pressure waveform. PPI was calculated in a cohort of high-output heart failure (HOHF, n=66) and standard HF cohort (n=44) and invasive hemodynamics and pulsatility were compared. <h3>Results</h3> Systemic, pulmonary artery, and pulmonary capillary wedge pressures were lower in the LVAD cohort (<i>P</i>≤.04 for each) compared with HOHF or HF. PPI was drastically lower in CF-LVAD supported patients with median PPI .006 (IQR .002-.012) vs PPI .09 (IQR .06-.17) in HF and PPI .25 (IQR .13-.37) in HOHF (<i>P</i><.0001 among groups). PPI more significantly differed between groups than aortic pulse width. With speed augmentation during ramp, PPI values fell more quickly in centrifugal flow pumps than axial flow (slopes -3.3 × 10⁻⁵ and -1.1 × 10⁻⁵ vs -6.9 × 10⁻⁶ for HW, HM3, and HMII respectively). PPI correlated poorly with LV ejection fraction (LVEF) in CF-LVAD patients and HOHF (<i>P</i>>.05) and modestly (r=.38, <i>P</i>=.01) in HF but in CF-LVAD patients, there was a stronger correlation with LV dP/dt (r=.41, <i>P</i>=.002) than LVEF (r=.21, <i>P</i>=.09, <i>P_int</i> <.001). <h3>Conclusion</h3> CF-LVAD support is associated with a dramatic reduction in arterial pulsatility as measured by PPI relative to HOHF and HF cohorts and decreases with increasing speed. Further work is needed to determine the applicability to the next generation of device therapy.

Impact of Concomitant Cardiac Valvular Surgery During Implantation of Continuous-Flow Left Ventricular Assist Devices: A European Registry for Patients with Mechanical Circulatory Support (EUROMACS) Analysis

<h3>Purpose</h3> We investigated the clinical outcomes after cardiac valvular surgery procedures concomitant (CCPs) with left ventricular assist device (LVAD) implantation compared to propensity score (PS) matched controls using the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) data. <h3>Methods</h3> Between 2006 and 2018, 2760 continuous-flow LVAD patients were identified. Of these, 533 underwent a CCP during the LVAD implant. <h3>Results</h3> Cardiopulmonary bypass time (p < 0.001) and time for implant (p < 0.001) were both significantly longer in the LVAD+CCP group. Hospital mortality was comparable between the two groups from the unmatched population (15.7% vs. 14.1%, p = 0.073). Similarly, short-to-mid-term survival was similar in both groups, with 1-year, 3-year, and 5-year survival rates of 67.9%, 48.2%, and 27.7% versus 66.4%, 46.1%, and 26%, respectively (log-rank, p = 0.25). The results were similar in the PS-matched population. Hospital mortality was comparable between the two groups (18.9% vs. 17.4%, p = 0.074<b>)</b>. The short-to-mid-term Kaplan-Meier survival analysis was similar for both groups, with 1-year, 3-year, and 5-year survival rates of 63.4%, 49.2%, and 24.7% versus 66.5%, 46%, and 25.1%, respectively (log-rank, p = 0.81). In the unmatched population, LVAD+CCP patients had longer intensive care unit (ICU) stays (p < 0.0001), longer mechanical ventilation time (p = 0.001), a higher rate of temporary right ventricular assist device (RVAD) support (p = 0.033), and a higher rate of renal replacement therapy (n = 35, 6.6% vs. n = 89, 4.0%, p = 0.014). In the PS-matched population, the LVAD+CCP patients had longer ICU stays (p = 0.019), and longer mechanical ventilation time (p = 0.002). <h3>Conclusion</h3> The effect of additive valvular procedures (CCPs) does not seem to affect short-term survival, significantly, based on our registry data analysis. However, the decision to perform CCPs should be balanced with projected type of surgery and preoperative characteristics. LVAD+CCP patients remain a delicate population and adverse device-related events should be strictly monitored and managed.

Multicenter Italian Study on Radial Mechanically Assisted Circulatory Support (MIRAMACS): Ongoing Analyses

<h3>Purpose</h3> The Multicenter Italian study on Radial Mechanically Assisted Circulatory Support (MIRAMACS) represents the first national observational registry, gathering continuous-flow (CF) left ventricular (LVAD) and biventricular assist device (BiVAD) implantation performed in adult patients. <h3>Methods</h3> Eight participating Italian hospitals contributed pre-, peri- and long-term postoperative data on LVAD implants to the registry. Data for all implants in adult patients (>18 years of age) performed between January 2000 to December 2020 were analysed. BiVADs were excluded in this preliminary analysis. This initial report focuses on patient demographics, survival, device types, adverse events and competing outcomes. <h3>Results</h3> A total of 515 patients received a CF LVAD. The mean age of LVAD recipients was 60.2 +/- 10.5 years. The majority of patients were male (89.3%). The adopted systems were: HeartWare HVAD (n=213), HeartMate III (n=140), HeartMate II (n=89), Jarvik 2000 (n=50), Berlin Heart Incor (n=19) and other brands (n=4). In 6.6% of patients the LVAD implantation was performed by usage of less invasive surgical approaches. Mortality at 30- and 90-days was 6.1% and 11.1%, respectively. A temporary right ventricular assist device (RVAD) support was necessary in 5.1% of patients. Mean follow-up time was 54.2 +/- 17.1 months. Heart transplantation was performed in 99 patients (19.2%). Survival at 1-year, 3-years, and 5-years of bridge to transplantation (BTT) cohort was 82.1%, 60.4% and 41.8%, respectively. Survival at 1-year, 3-years, and 5-years of destination therapy (DT) cohort was 69.8%, 45.6% and 30.1%, respectively. Major infection, neurological events, major bleeding and device malfunction were reported in 143 (27.7%), 97 (18.8%), 40 (7.7%) and 36 (6.9%) patients, respectively. Full Maglev technology showed competitive results. <h3>Conclusion</h3> This first MIRAMACS report reveals frequencies and results comparable with other registries. Overall success rate of CF LVAD patients is satisfactory. Detailed prospective data collection, additional participating centres and further analyses may provide robust scientific contributions.

Adverse Events in HVAD vs. HM3 Patients under Outpatient Bridging with Low-Molecular Weight Heparin for Subtherapeutic Anticoagulation

<h3>Purpose</h3> The standard of care in patients with durable left-ventricular assist devices combines antiplatelet with anticoagulation therapy. Current guidelines recommend use of intravenous (IV) unfractionated heparin as bridge to therapeutic INR-values in the postoperative period. However, management of subtherapeutic INR in the ambulatory setting is not yet clearly defined by guidelines. The protocol at our center proposes the use of unfractionated heparin perioperatively and low-molecular weight heparin in outpatients. Therefore, we aimed to analyse outcomes in patients with continuous-flow LVAD (CF-LVAD). <h3>Methods</h3> In this single-center retrospective trial all patients after CF-LVAD implantation at our center were included between 1/2015 and 12/2020 (n=110 patients; HVAD n=80, HM3 n=30). Patients were followed up from initial discharge after LVAD implantation until death, heart transplantation or end of the observation period (9/2021). Bridging for subtherapeutic INR (≤ 0.4 below target INR) were provided with enoxaparin in a therapeutic dose adapted to weight and renal function. Only patients with an INR > 0.4 below target INR were admitted to hospital for bridging with IV unfractionated heparin. Bleeding events leading to hospital admission, cerebrovascular events and pump thromboses were evaluated and provided in percent of study population and/or events per patient year (eppy). <h3>Results</h3> Follow-up covers a total of 214.2 patient years. Overall mortality was 18.2 %. Bleeding events occurred in 42.7 %, of which GI bleeding constituted the largest group with 21.8 % (HVAD: 0.25 eppy; HM3: 0.05 eppy). Stroke/TIA/PRIND occurred in 5.5 % of the patients (HVAD: 0.07 eppy; HM3: 0.01 eppy; in total: 0.03 eppy). Intracerebral hemorrhage (overall 0.04 eppy) occurred 6.3 times more often in HVAD patients. Pump thrombosis occurred in 8.2 % of all CF-LVAD patients and was limited to HVAD (0.13 eppy). <h3>Conclusion</h3> Current studies tend to promote the use of low molecular weight heparins, especially enoxaparin for outpatient anticoagulation bridging in case of subtherapeutic INRs. However, in most cases old generation CF-LVADs were studied. Our study includes a relevant number of HM3 devices. Overall, the adverse event rates presented herein suggest feasibility of low-molecular weight heparin bridging in patients with HM3 devices.

Outcomes With Phosphodiesterase-5 Inhibitor Use After Left Ventricular Assist Device: An STS-INTERMACS Analysis.

Elevated right ventricular afterload following continuous-flow left ventricular assist device (CF-LVAD) may contribute to late right heart failure (LRHF). PDE5i (phosphodiesterase-5 inhibitors) are used to treat pulmonary hypertension and right heart dysfunction after CF-LVAD, but their impact on outcomes is uncertain. We queried Interagency Registry for Mechanically Assisted Circulatory Support from 2012 to 2017 for adults receiving a primary CF-LVAD and surviving ≥30 days from index discharge. Patients receiving early PDE5i (ePDE5i) at 1 month were propensity-matched 1:1 with controls. The primary outcome was the cumulative incidence of LRHF, defined using prevailing Interagency Registry for Mechanically Assisted Circulatory Support criteria; secondary outcomes included all-cause mortality and major bleeding. Among 9627 CF-LVAD recipients analyzed, 2463 (25.6%) received ePDE5i and 1600 were propensity-matched 1:1 with controls. Before implant, ePDE5i patients had more severe RV dysfunction (13.1% versus 9.6%) and higher pulmonary vascular resistance (2.8±2.7 versus 2.2±2.4 WU), both P<0.001, but clinical factors were well-balanced after propensity-matching. In the unmatched cohort, ePDE5i patients had a higher 3-year cumulative incidence of LRHF, mortality, and major bleeding, but these differences were attenuated in the propensity-matched cohort: LRHF 40.8% versus 35.7% (hazard ratio, 1.14 [95% CI, 0.99-1.32]; P=0.07); mortality 38.6% versus 35.8% (hazard ratio, 0.99 [95% CI, 0.86-1.15]; P=0.93); major bleeding 51.2% versus 46.0% (hazard ratio, 1.12 [95% CI, 0.99-1.27]; P=0.06). Compared with propensity-matched controls, adult CF-LVAD patients receiving ePDE5i had similar rates of LRHF, mortality, and major bleeding. While intrinsic patient risk factors likely account for more adverse outcomes with ePDE5i in the unmatched cohort, there is no obvious benefit of ePDE5i in the LVAD population.

The Interaction of Amiodarone and Continuous-flow Left Ventricular Assist Device Use in Risk of Severe Primary Graft Dysfunction Following Heart Transplantation.

Primary graft dysfunction (PGD) increases morbidity and mortality after heart transplant. Here we investigated (1) the association of continuous-flow left ventricular assist device (CF-LVAD), amiodarone, and severe PGD and (2) the safety of amiodarone discontinuation in CF-LVAD patients. Retrospective, single-center study of heart transplant recipients was conducted to investigate the association of risk factors and severe PGD. Patients were grouped into 4 groups based on the presence (denoted +) or absence (denoted -) of amiodarone and CF-LVAD. Prospective amiodarone discontinuation was undertaken to investigate its safety in a cohort of CF-LVAD patients. Study endpoints were severe PGD and recurrence of arrhythmia. Severe PGD was strongly associated with CF-LVAD and amiodarone use, and its prevalence is highest if both risk factors were present (CF-LVAD-/amiodarone - 1.5%, CF-LVAD -/amiodarone+ 4.5%, CF-LVAD+/amiodarone - 7.1%, CF-LVAD+/amiodarone+ 21.8%; P < 0.01). The product of every 1-y additional CF-LVAD support by every 100 mg amiodarone was associated with severe PGD (adjusted odds ratio, 1.43; 95% confidence interval, 1.15-1.78; P < 0.01). Amiodarone was prospectively discontinued in 28 CF-LVAD patients. Of them, 6 patients had recurrence of arrhythmia requiring treatment or heart failure admission. There were no deaths. Nine patients in whom amiodarone had been discontinued had heart transplants with no severe PGD. Amiodarone and CF-LVAD were independently associated with severe PGD. The combination of both risk factors was associated with a higher prevalence of severe PGD. Amiodarone discontinuation was associated with recurrence of arrhythmia in 6 CF-LVAD patients. There was no mortality associated with amiodarone discontinuation.

An external validation study of the Utah Bleeding Risk Score.

Gastrointestinal bleeding in patients with continuous-flow left ventricular assist devices (CF-LVAD) impairs quality of life and increases hospitalization rate. The Utah Bleeding Risk Score (UBRS) has been created to predict gastrointestinal bleeding (GIB) in patients on left ventricular assist device. We here aimed to externally validate UBRS on our cohort of CF-LVAD patients. Utah Bleeding Risk Score was calculated, GIB events summarized on follow-up and patients stratified into 3 risk groups. Predictive ability of UBRS was examined at 3 years and during whole support time and person time incidence rates correlated to UBRS. In a sub-analysis, single effects of UBRS variables on freedom from GIB were assessed. A total of 111 CF-LVAD patients were included. The median UBRS was 2 (3-1). Receiver operating characteristic curve analysis showed an area under the curve of 0.519 (P = 0.758, 95% confidence interval = 0.422-0.615) at 3 years and an area under the curve of 0.515 (P = 0.797, 95% confidence interval = 0.418-0.611) during whole support time. No significant difference was observed in UBRS between bleeders and non-bleeders (P = 0.80). No significant difference in freedom from GIB was observed (P3 years = 0.7; Psupport-time = 0.816) and no independent significance regarding the freedom from bleeding at 3 years for any variable was observed. Coronary artery disease was associated with higher risk of GIB beyond the 3rd year (P = 0.048). UBRS was not able to predict GIB and therefore not applicable in our cohort of patients. Coronary artery disease could lead to a higher risk for GIB during support time. An additional validation in a larger cohort is advisable.

Impact of concomitant cardiac valvular surgery during implantation of continuous-flow left ventricular assist devices: A European registry for patients with mechanical circulatory support (EUROMACS) analysis.

We investigated the clinical outcomes after cardiac valvular surgery procedures concomitant (CCPs) with left ventricular assist device (LVAD) implantation compared to propensity score (PS) matched controls using the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) data. Between 2006 and 2018, 2760 continuous-flow LVAD patients were identified. Of these, 533 underwent a CCP during the LVAD implant. Cardiopulmonary bypass time (p<0.001) and time for implant (p<0.001) were both significantly longer in the LVAD+CCP group. Hospital mortality was comparable between the two groups from the unmatched population (15.7% vs. 14.1%, p=0.073). Similarly, short-to-mid-term survival was similar in both groups, with 1-year, 3-year, and 5-year survival rates of 67.9%, 48.2%, and 27.7% versus 66.4%, 46.1%, and 26%, respectively (log-rank, p=0.25). The results were similar in the PS-matched population. Hospital mortality was comparable between the two groups (18.9% vs. 17.4%, p=0.074). The short-to-mid-term Kaplan-Meier survival analysis was similar for both groups, with 1-year, 3-year, and 5-year survival rates of 63.4%, 49.2%, and 24.7% versus 66.5%, 46%, and 25.1%, respectively (log-rank, p=0.81). In the unmatched population, LVAD+CCP patients had longer intensive care unit (ICU) stays (p<0.0001), longer mechanical ventilation time (p=0.001), a higher rate of temporary right ventricular assist device (RVAD) support (p=0.033), and a higher rate of renal replacement therapy (n=35, 6.6% vs. n=89, 4.0%, p=0.014). In the PS-matched population, the LVAD+CCP patients had longer ICU stays (p=0.019) and longer mechanical ventilation time (p=0.002). The effect of additive valvular procedures (CCPs) does not seem to affect short-term survival, significantly, based on our registry data analysis. However, the decision to perform CCPs should be balanced with the projected type of surgery and preoperative characteristics. LVAD+CCP patients remain a delicate population and adverse device-related events should be strictly monitored and managed.

B-PO03-145 POST LVAD ATRIAL ARRHYTHMIAS IN PATIENTS WITH NO PRIOR HISTORY OF ATRIAL ARRHYTHMIAS

Data on incidence of post LVAD atrial arrhythmias (AA) in patients with no prior history of AA remain sparse. We sought to assess the incidence and predictors of de novo AA in continuous flow LVAD patients. A multi-center LVAD arrhythmia registry was queried for patients with no history of AA before LVAD implant. AA was defined as atrial tachycardia, flutter, or fibrillation lasting >6 hours or >1% burden. Univariate demographic and pre-operative risk factors were evaluated for association with post-LVAD AA. A multivariate regression model was used to identify independent factors associated with incidence of post-LVAD AA. A total of 298 patients (56±14 years, 73% male) with no history of AA underwent LVAD implantation. Patients with post LVAD AA (31%, n=92) were older (61 vs 58 years). There was no statistically significant difference between post LVAD AA and No AA groups in terms of gender (female 44% v 39%, p=.5), COPD (42 v 41%, p=.8), sleep apnea (43 v 40%, p=.6) or diabetes (42 v 51%, p=.2). Patients with higher INTERMACS profiles had a higher incidence of post LVAD AA (for class 1, 2, 3, 4+ respectively 33%, 28%, 35%, 56%, p=.04) whereas those with pulmonary hypertension (PHTN) were less likely to have post LVAD AA (33% v 50%, p=.01). The regression model identified higher INTERMACS class as an independent predictor of the post LVAD AA (OR=1.36, p=.02), Table 1. Patients with no history of AA were more likely to have de novo AA post LVAD with increasing INTERMACS profile and age whereas presence of PHTN was associated with lesser incidence of post LVAD AA. Gender, BMI, presence of COPD or sleep apnea were not significant predictors of post LVAD AA.

Implantable cardioverter defibrillators in left ventricular assist device patients: Α systematic review and meta-analysis

Implantable cardioverter-defibrillators (ICDs) remain the standard of care in advanced heart failure with reduced ejection fraction patients for the prevention of sudden cardiac death. However, current guidelines remain conflicting with respect to the use of ICDs in patients supported with a continuous flow left ventricular assist device (CF-LVAD). The current review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies comparing the use of ICD in patients with CF-LVADs were included. The 2 primary outcomes studied were all-cause mortality, and a successful bridge to heart transplantation. We calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs). We also compared baseline characteristics between US and European studies, for CF-LVAD patients with an ICD. Among all studies, the use of an ICD was not associated with all-cause mortality in patients with CF-LVADs (OR: 0.85, 95% CIs: 0.64-1.12, p=0.24). The presence of an ICD was associated with a trend towards increased likelihood of successful bridge to heart transplantation (OR: 1.12, 95% CI: 1.0-1.3, p=0.06). A subgroup analysis of studies published by European centers revealed a significant decrease in pooled mortality (OR: 0.58, 95% CI: 0.4-0.83, p=0.003) with the use of ICD, contrary to an increase in pooled mortality among studies published by US centers (OR: 1.2, 95% CI 1.02-1.33, p=0.025). Moreover, we identified significant differences in baseline characteristics such as bridge to transplantation rate, Interagency Registry for Mechanically Assisted Circulatory Support profiles, and use of an intra-aortic balloon pump or extracorporeal membrane oxygenation preoperatively, between the US and European populations. While this meta-analysis did not show an overall survival benefit with the use of an ICD in CF-LVAD patients, it revealed significant differences in the derived benefit, in distinct patient populations. This might reflect differences in baseline patient characteristics and warrants further investigation.