Search

Heartmate II risk score (HMRS) and MELD-Xi score are validated mortality risk predictors in Heartmate II left ventricular assist device (LVAD) patients. Prognostic utility of these risk scores remains unknown in patients considered for Heartmate 3 (HM3) LVAD therapy. HMRS were calculated for 175 consecutive patients who underwent HM3 LVAD implantation at a single academic institution. Receiver operating characteristic (ROC) curve and logistic- and cox-regression models were developed to assess the impact of HMRS and MELD-Xi scores on short- and long-term outcomes in HM3 patients. Mean HMRS and MELD-Xi scores in HM3 population was 1.38±0.57 and 14.4±0.28, respectively. Pre-implant HMRS was not predictive of RVAD use (OR 1.25, p=0.392), CVVHD (OR 1.16, p=0.722), in-hospital mortality (OR 1.52, p=0.409), or 90-day mortality (OR 1.44, p=0.457). Pre-implant MELD-Xi score showed trend towards increased RVAD use (OR 1.09, p=0.056) and need for CVVH (OR 1.14, p=0.064), however was not predictive of in-hospital mortality (OR 1.02, p=0.836), or 90-day post-LVAD mortality (OR 0.958, p=0.636). Area under curve (AUC) for in-hospital mortality was 0.531 for HMRS and 0.525 for MELD-Xi score (Figure). There was no difference in post-implant survival (88.6% vs. 85.7%, log-rank p=0.569), freedom from GI bleeding (73.5% vs. 65.1%, log-rank p =0.257) or freedom from stroke (93.3% vs. 90.8% log-rank p = 0.478) at 2-year follow-up in patients with below average vs. above average HMRS. Similarly, There was no difference in post-implant survival (91.3% vs. 82.3%, log-rank p=0.121), freedom from gastrointestinal bleeding (72.2% vs. 65.2%, log-rank p =0.257) or freedom from stroke (92.0% vs. 92.4% log-rank p = 0.820) at 2-year follow-up in patients with below average vs. above average MELD-Xi score. HMRS and MELD-Xi scores do not predict mortality in patients undergoing HM3 implantation. New prediction models are required to optimize patient selection and outcomes in HM3 patients. [ABSTRACT FROM AUTHOR]

Gastrointestinal bleeding (GIB) remains a common and vexing complication of left ventricular assist device (LVAD) support. Recent single-center analyses suggest that ACE inhibitors (ACEi)/angiotensin receptor blockers (ARB) and digoxin may prevent GIB in LVAD patients. Here we evaluate the effect of heart failure (HF) drug therapies on rates of GIB through analysis of the INTERMACS registry database. 13,732 patients who received a continuous-flow LVAD and were on antiplatelet therapy coupled with warfarin anticoagulation at 3 months of pump support were included in the analysis. GIB events beyond 3 months following implant were assessed receipt of ACEi/ARB, beta-blockers (BB), aldosterone antagonists (AA), amiodarone (Amio), digoxin, loop diuretics, and phosphiesterase inhibitors (PDE5) at 3 months of support. Backwards stepwise cox regression was used to control for confounding of each drug class on each other, as well as for clinical variables like age, gender, renal function, HF etiology, and device strategy. Medication use in LVAD patients were BB (65.0%), ACEi/ARB (51.7%), Amio (43.7%), AA (37.9%), and loop diuretics (70.1%) at 3 months of pump support. In patients with available data, PDE and digoxin use were 18.2% and 16.9% respectively. The overall incidence of GIB was 23.7% at 2 years of support. After adjustment for other clinical variables, loop diuretics (HR 1.274, p<0.001) and PDE5 (HR 1.241, p<0.001) use were associated with increased risk GIB, while use of BB (HR 0.871, p=0.006) was associated with lower risk of GIB. ACEi/ARB (HR 1.002, p=0.971), Amio (HR 1.083, p=0.106), AA (HR 0.967, p=0.522) or digoxin (HR 1.087, p=0.169) did not affect GIB rates on LVAD support (Figure). Despite recent reports, ACEi/ARB, AA, Amio, and digoxin use have minimal association with GIB on LVAD support. The heightened risk seen in those on loop diuretics may reflect venous congestion in these patients, while antiplatelet effects of PDE5 could drive the higher risk of GIB. [ABSTRACT FROM AUTHOR]

Whether C-reactive protein (CRP) levels prior to left ventricular assist device implantation (LVAD) are predictive of post-implantation outcomes is not well established. Current data are limited to small, single-center studies. 5,183 adult recipients of continuous-flow left ventricular assist devices with pre-implant CRP measurement were identified from INTERMACS. Patients were divided into three groups based on pre-implant CRP levels: CRP of 0 to 10 mg/L (low), 11 to 30 mg/L (intermediate), and >30 mg/L (high). Outcomes of interest were mortality, gastrointestinal bleeding, device thrombosis, infection, stroke, and right heart failure. Analyses included Kaplan-Meier survival estimates and Cox proportional hazards models. Patients with higher pre-implant CRP were younger (55.3 vs 56.5 vs 57.8 yrs), had sicker INTERMACS profiles (Class I: 33.7% vs 22.6% vs 9.5%); higher use of IABP (34.1% vs 26.0% vs 14.5%) and ECMO (12.0% vs 6.9% vs 2.1%) compared to patients with intermediate and low CRP levels (all p <0.001). High CRP group had higher WBC count (10.4 vs 9.3 vs 8.0 × 10/uL), total bilirubin (1.6 vs 1.4 vs 1.2 mg/dL), and serum BNP levels (958 vs 887 vs 726 pg/mL) compared to lower CRP groups (all p<0.001). After adjustment for baseline characteristics, compared to the low CRP group, higher CRP was associated with greater risk of mortality (HR 1.14 for intermediate CRP, HR 1.29 for high CRP, p=0.006) and right heart failure (HR 0.91 for intermediate CRP, HR 1.41 for high CRP, p=0.004). Rates of device thrombosis, device-related infection, stroke, and gastrointestinal bleeding were similar across groups. Higher CRP levels indicate comorbidity prior to LVAD implantation and predict higher risk of post-implant right heart failure and mortality. These findings suggest that baseline CRP may be a useful predictor of clinical outcome after LVAD implantation. [ABSTRACT FROM AUTHOR]

Post-operative vasoplegia is a leading cause of mortality after cardiac surgery. The purpose of this study is to investigate the incidence and predictors of vasoplegia after heart transplantation (HT). Data was collected from a consortium of 10 participating sites in the United States, Canada, and Europe. Adult HT recipients between 2010 and 2020 were included. Vasoplegia was defined as reduced systemic vascular resistance (SVR) <1000 dyn-s-cm-5 with normal cardiac index (CI) >2.5 L/min/m2 or use of methylene blue within the first 24 hours after HT. Multivariate logistic regression was performed to identify predictors of vasoplegia. Data from 1244 HT recipients (median age 57 years, IQR: [48-63], 66.7% male) were analyzed: 471 (37.9%) patients had vasoplegia including 46 (3.7%) patients with severe vasoplegia defined as SVR <600 dyn-s-cm-5 or use of methylene blue. There was no significant difference in 1-year mortality between patients with and without vasoplegia: 8.7% vs. 9.0%, p=0.82. However, severe vasoplegia was associated with increased 1-year mortality (Figure): 22.0% vs. 2.5%, p<0.001. Patients with vasoplegia had lower SVR (828, IQR [731-921] vs. 1302, IQR [1146-1527] dyn-s-cm-5, p<0.001) and higher CI (3.0, IQR [2.5-3.5] vs. 2.1, IQR [1.8-2.5] L/min/m2, p<0.001). There was no significant difference in the incidence of severe primary graft dysfunction in patients with and without vasoplegia (3.2% vs. 3.2%, p=1.0). Multivariable analysis showed pre-HT short-term mechanical circulatory support (MCS, OR: 2.03, 95% CI: [1.25-3.29], p=0.004), pre-HT dialysis (OR: 1.91, 95% CI: [1.03-3.52], p=0.04), younger age (OR: 1.01 per year, 95% CI: [1.01-1.02], p=0.004), and higher body mass index (BMI, OR: 1.06, 95% CI: [1.04-1.09], p<0.001) were associated with vasoplegia. Vasoplegia is a common phenomenon post-HT. Pre-HT short-term MCS, dialysis, younger age and higher BMI were identified as risk factors of vasoplegia. [ABSTRACT FROM AUTHOR]

MOMENTUM 3 trial excluded patients with planned biventricular support prior to enrollment and 4.2% right ventricular failure requiring RVAD in Heartmate 3 (HM 3) patients. The aim of this study was to assess the use of RVAD in the real-world post-approval era. HM3 implantation at a major academic center were categorized into two era: HM 3 implanted 1) before FDA approval (8/23/2017) [N=67] and 2) after FDA approval [N=107]. Baseline patient characteristics, RVAD utilization patterns, and LVAD complications and mortality were analyzed in the pre- vs. post-approval era. In the post-approval era, HM3 patients were younger (57.5±14.1 vs 61.7±11.2 yrs, p=0.031), more likely to have ischemic etiology of heart failure (55.6% vs 34.3%, p=0.006), to be INTERMACS Class I (21.3% vs. 1.5%, p=0.002), and to have VA-ECMO or paracorporeal VAD support (12.0% vs 0.0%, p=0.012) prior to HM3 implant. 8 (11.9%) patients out of 67 required RVAD in the pre-approval era as opposed to 47 patients out of 108 (43.5%) in the post-approval era (p<0.001). All patients in the pre-approval era received unplanned RVAD (8, 100%) compared to 16 patients (34.0%) in the post-approval era (p<0.001). Despite increased utilization of RVADs, the risk of CVVHD (6.0% vs 10.2%, p=0.413), post-LVAD length of stay (34.3±32.9 vs 41.7±40.0 days), and in-hospital mortality (4.5% vs 6.9%, p=0.741) were comparable in pre- vs. post-approval era. There was no difference in post-implant survival (89.7% vs. 84.7%, log-rank p=0.357), freedom from gastrointestinal bleeding (70.0% vs. 70.4%, log-rank p =0.831) or freedom from stroke (93.2% vs. 92.2% log-rank p = 0.547) at 2-year follow-up in the pre- vs. post- approval period. Level of sickness at the time of device implantation as well as need for RVAD utilization increased substantially in HM3 patients following the FDA approval. However, the change in practice did not adversely affect post-LVAD morbidity or mortality. [ABSTRACT FROM AUTHOR]

Pulmonary artery pulsatility index (PAPi) recently emerged as a predictor of right ventricular failure after Heartmate II LVAD Implantation. Clinical utility of this marker in Heartmate 3 patients is unknown. We hypothesized that PAPi is a stronger predictor of RV failure compared to central venous pressure to pulmonary artery capillary wedge pressure ratio (CVP/PCWP) or RV stroke work index (RVSWI) in Heartmate 3 population. 175 patients who received a Heartmate 3 LVAD at a single academic center between 2014 - 2019 were included in the study. Primary outcome was right ventricular assist device (RVAD) use following HM3 implant. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis determined predictors of RVAD use in HM3 patients. 55 patients (31.4%) required RVAD following HM3 implantation including 19 percutaneous, 24 paracorporeal, and 2 durable RVADs. Age, gender, and implant strategy were comparable between RVAD and no RVAD groups. Patients requiring RVAD were more likely to be INTERMACS Class I or II (78.2% vs. 56.6%), have a higher WBC count (9.2±3.4 vs. 8.1±2.8) and C-reactive protein (57.7±59.2 vs. 38.4±34.7) prior to device implant (all p <0.05). RVAD group had significantly lower PAPi (3.4±2.0 vs. 6.0±6.8, p=0.001), higher CVP/PCWP ratio (0.50±0.27 vs. 0.42±0.25, p=0.036) and comparable RVSWI (0.534±0.285 vs. 0.572±0.240, p=0.368) before device implant. ROC curve analysis provided higher AUC for PAPi compared to CVP/PCWP ratio or RVSWI (Figure). After adjusting for age, etiology of HF, creatinine, bilirubin, WBC count, INTERMACS Class, RVSWI, and CVP/PCWP ratio, PAPi was the only significant predictor of RVAD use in multivariable model (OR 0.913 [95%CI: 0.835 - 0.999], p=0.049). PAPi is an independent predictor of RV failure in Heartmate 3 patients. Incorporating PAPi in clinical decision-making may improve patient selection and perioperative outcomes in this population. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) emerged as a biomarker of inflammation in heart failure patients and associated with increased morbidity and mortality. We hypothesized that higher serum CRP level prior to Heartmate 3 LVAD implantation is associated with increased risk of post-implant adverse events and mortality. 123 patients who underwent Heartmate 3 LVAD implantation at a tertiary care center and had a CRP level measured prior to device implant were included in the analysis. Optimal CRP cut-off was determined used ROC curve and patients were categorized into high vs. low CRP groups accordingly. Study end-points included RVAD use, need for CVVH, in-hospital mortality, and 2-year survival. Mean and median pre-implant CRP levels in HM3 patients were 35.5±43.6 mg/L and 15.0 mg/L respectively. Patients with an elevated pre-implant CRP (≥12 mg/L) were more likely to be in INTERMACS Class I or II (78.4% vs. 46.6%), to have temporary MCS (49.2% vs. 27.5%), and elevated WBC count (9.1 vs. 7.5) compared to those with a pre-implant CRP less than 12 mg/L (all p <0.05). High CRP group had significantly higher RVAD use (32.3% vs. 15.5%, p=0.030), need for CVVHD (13.8% vs. 3.4%), and in-hospital mortality (14.0% vs. 1.8%, p=0.028). Patients with elevated pre-implant CRP had significantly lower survival compared to those with lower pre-implant CRP (74.2% vs. %96.1, log-rank p =0.020) and a trend-towards lower freedom from post-implant stroke (%89.2 vs. %98.3, log-rank p =0.072) at 2-year follow-up (Figure). After adjustment for age, ischemic etiology, creatinine, bilirubin, albumin, and INTERMACS Class, high CRP (≥ 12 mg/L) remained as an independent predictor of survival on LVAD support (HR 3.81 [1.35 - 10.75], p=0.011). Pre-implant CRP is a strong predictor of morbidity and mortality in patients undergoing HM3 implantation. Routine assessment of CRP prior to implant may improve patient selection and outcomes in this population. [ABSTRACT FROM AUTHOR]

MOMENTUM 3 trial demonstrated superiority of Heartmate 3 (HM 3) compared to Heartmate II (HM 2) with regards to hemocompatibility, however, their differential effects on de-novo HLA allosensitization, which may create a challenge for future transplantation, remains unknown. Patients who underwent HM2 or HM3 implantation and had no prior HLA antibodies by solid-phase assay (Luminex) testing at a major academic center were included for the study. Complement dependent cytotoxicity (CDC) panel reactive antibody (PRA) levels as well as Luminex antibody profiles were followed until cardiac transplantation, device explantation, or death. 34 HM3 and 34 HM2 patients with no HLA antibodies by Luminex testing prior to LVAD implant were identified with a mean follow-up duration of 1.71 ± 1.1 years on device support. HM3 and HM2 groups had similar age at implant (56.1±8.6 vs 54.7±12.0, p=0.575), female gender (11.8% vs. 14.7%, p=0.720), ischemic HF etiology (38.2% vs 35.3%, p=0.801), and bridge strategy at implant (44.1% vs 58.8%, p=0.225). Over the follow-up period, 41.2% of HM3 and 47.1% of HM2 patients had detectable HLA antibodies by Luminex testing (p=0.625). Development of high level (MFI>10, 000) Class I HLA antibodies were significantly lower in HM3 patients (2.9% vs 17.9%, p=0.046) compared to high-level Class II HLA antibodies which were similar in two device groups (2.9% vs 5.9%, p=0.555). CDC PRA testing showed lower proportion of HM3 patients with a positive result (PRA >0%) for T cell (32.4% vs. 55.9%, p=0.050) compared to positive B cell panel which was comparable in two groups (32.4% vs 47.1%, p=0.215). Peak PRA levels in patients who turned positive was comparable for T cell (5.8% vs 6.5%, p=0.775) and B cell (10.2% vs. 12.4%, p=0.568) in HM3 vs. HM2 patients. Our findings suggest that HM3 is associated with a lower likelihood of de-novo HLA sensitization than HM2 specifically against Class I antigens. [ABSTRACT FROM AUTHOR]

In addition to goal-directed therapies, advanced therapies for heart failure including left ventricular assist devices (LVADs) remain underutilized in women. Sex-specific data in the area of mechanical circulatory support remains sparse and women are often underrepresented in heart failure trials. Even less is known about sex differences in outcomes with the HeartMate 3 LVAD, an FDA approved centrifugal-flow device. Consecutive patients who received HeartMate 3 LVAD as bridge-to-transplant or destination therapy at a single institution were included in the study. Demographics, co-morbidities, device-related factors, and outcomes were comparatively examined between women and men. 175 patients (28 women, 16.0%) were identified. Women were significantly younger than men (53.9 vs. 60.1 years, p=0.023) with smaller body surface area (1.83 vs 2.08, p <0.001). Women were less likely to have hypertension (42.9% vs 64.6%, p=0.030), to use tobacco (35.7% vs 57.5%, p=0.034), and to have an ischemic etiology of HF (21.4% vs 52.4%, p=0.003). There were no differences in the use of temporary mechanical circulatory support and INTERMACS profiles. There were similar rates of RVAD use (35.7% vs. 30.6%, p=0.594) and continuous veno-venous hemofiltration (10.7% vs 8.2%, p=0.659) in women and men. There were no differences in in-hospital mortality (3.7% vs 6.3%, p=0.595) or 90-day mortality (8.7% vs 6.9%, p=0.762) between women and men. There was no difference in post-implant survival (82.8% vs 87.7%, log-rank p=0.944) [Figure], freedom from gastrointestinal bleeding (70.5% vs 69.1%, log-rank p =0.278) or freedom from stroke (96.4% vs 91.4%, log-rank p = 0.471) at 2-year follow-up between women and men. In our single-center experience with HeartMate 3 LVADs, there were no significant differences in early morbidity and mortality between women and men. [ABSTRACT FROM AUTHOR]