Continuous-flow Left Ventricular Assist Device Recipients Research Articles

Abstract 12859: Clinical Correlates and Prognostic Value of B-type Natriuretic Peptide in Left Ventricular Assist Device Recipients With Cardiogenic Shock: Insights From INTERMACS

Introduction: B-type natriuretic peptide (BNP) is a robust predictor of outcomes across the heart failure (HF) spectrum. However, data characterizing BNP levels in end-stage HF with cardiogenic shock (CS) is lacking. Furthermore, the prognostic value of BNP in left ventricular assist device (LVAD) receiving Stage D HF patients with CS has not been assessed previously. Methods: Continuous flow LVAD recipients with CS enrolled in INTERMACS between 2005 to 2017 were included. CS was defined as INTERMACS profile 1-3. The primary outcome of the study was long-term mortality. Long-term mortality was assessed in patients alive at 1-month post-surgery. Secondary outcomes included peri-operative mortality (<30 days of surgery), cardiovascular mortality, arrhythmia, and right HF. The cohort was stratified by quartiles of BNP levels. Multivariable Cox proportional hazard models, adjusted for age, sex, body mass index, INTERMACS profile, center volume, implantation year, device strategy, estimated glomerular filtration rate, employment status, and education level, were used to assess the association between BNP levels and outcomes. Results: Among 7,290 LVAD recipients with CS, the median pre-implantation BNP value was 859 (427, 1,614) pg/mL. Males [851(429, 1,557) pg/mL, P =0.07], non-Hispanic Blacks [777 (362, 1,514) pg/mL, P =<0.001], and obese [642 (311, 1,170) pg/mL, P =<0.001] patients had lower BNP values. Over a median follow-up of 14.7 (6.9, 28.7) months, the risk of long-term mortality was similar in the second [HR adj :1.06 (0.94-1.20)], third [HR adj :0.97 (0.85-1.10)], and fourth [HR adj :1.04 (0.91-1.18)] quartiles of BNP compared with the first quartile of BNP. Similarly, the risk of peri-operative mortality, cardiovascular mortality, arrhythmia, and right HF did not vary by the quartiles of BNP. Conclusions: BNP has poor prognostic value in LVAD recipients with CS and the value of routine measurement of BNP in this population needs further investigation.

Clinical Predictors and Outcomes After Left Ventricular Assist Device Implantation and Tracheostomy.

Postoperative respiratory failure is a major complication that affects up to 10% of patients who undergo cardiac surgery and has a high in-hospital mortality rate. Few studies have investigated whether patients who require tracheostomy for postoperative respiratory failure after continuous-flow left ventricular assist device (CF-LVAD) implantation have worse survival outcomes than patients who do not. To identify risk factors for respiratory failure necessitating tracheostomy in CF-LVAD recipients and to compare survival outcomes between those who did and did not require tracheostomy. Consecutive patients who underwent primary CF-LVAD placement at a single institution between August 1, 2002, and December 31, 2019, were retrospectively reviewed. Propensity score matching accounted for baseline differences between the tracheostomy and nontracheostomy groups. Multivariate logistic regression was used to identify tracheostomy risk factors and 90-day survival; Kaplan-Meier analysis was used to assess midterm survival. During the study period, 664 patients received a CF-LVAD; 106 (16.0%) underwent tracheostomy for respiratory failure. Propensity score matching produced 103 matched tracheostomy-nontracheostomy pairs. Patients who underwent tracheostomy were older (mean [SD] age, 57.9 [12.3] vs 54.6 [13.9] years; P = .02) and more likely to need preoperative mechanical circulatory support (61.3% vs 47.8%; P = .01) and preoperative intubation (27.4% vs 8.8%; P < .001); serum creatinine was higher in the tracheostomy group (mean [SD], 1.7 [1.0] vs 1.4 [0.6] mg/dL; P < .001), correlating with tracheostomy need (odds ratio, 1.76; 95% CI, 1.21-2.56; P = .003). Both before and after propensity matching, 30-day, 60-day, 90-day, and 1-year survival were worse in patients who underwent tracheostomy. Median follow-up was 0.8 years (range, 0.0-11.2 years). Three-year Kaplan-Meier survival was significantly worse for the tracheostomy group before (22.0% vs 61.0%; P < .001) and after (22.4% vs 48.3%; P < .001) matching. Given the substantially increased probability of death in patients who develop respiratory failure and need tracheostomy, those at high risk for respiratory failure should be carefully considered for CF-LVAD implantation. Comprehensive management to decrease respiratory failure before and after surgery is critical.

Gastrointestinal bleeding and pro-angiogenic shift in the angiopoietin axis with continuous flow left ventricular assist device implantation

BackgroundGastrointestinal bleeding (GIB) affects up to 40% of continuous-flow left ventricular assist device (CF-LVAD) recipients. A higher risk of GIB is seen in CF-LVAD recipients with lower device pulsatility without a known mechanism. One hypothesis is that the novel hemodynamics in CF-LVAD recipients affect angiogenesis signaling. We aimed to (1) measure serum levels of angiopoietin (Ang)-1, Ang-2, and VEGF-A in CF-LVAD recipients with and without GIB and in healthy controls and (2) evaluate correlations of those levels with hemodynamics. MethodsWe recruited 12 patients with CF-LVADs (six who developed GIB after device implantation) along with 12 age-matched controls without heart failure or GIB and measured Ang-1, Ang-2, and VEGF-A levels in serum samples from each patient. ResultsCF-LVAD recipients had significantly higher Ang-2 and lower Ang-1 levels compared to controls with no difference in VEGF-A levels. CF-LVAD recipients with GIB had lower Ang-1 levels than those without GIB. There were trends for pulse pressure to be positively correlated with Ang-1 levels and negatively correlated with Ang-2 levels in CF-LVAD recipients with no correlation observed in healthy controls. ConclusionCF-LVAD recipients demonstrated a shift toward a pro-angiogenic phenotype in the angiopoietin axis that is significantly associated with GIB and may be linked to low pulse pressure.

Preoperative higher right ventricular stroke work index increases the risk of de novo aortic insufficiency after continuous-flow left ventricular assist device implantation

During continuous-flow left ventricular assist device (CF-LVAD) support, hemodynamic shear stress causes a burden on aortic valve (AV) leaflets, leading to de novo aortic insufficiency (AI). This study investigated the influence of preoperative hemodynamic parameters on de novo AI in CF-LVAD recipients. We reviewed 125 patients who underwent CF-LVAD implantation without concomitant AV surgery between 2005 and 2018. De novo AI was defined as moderate or severe AI in those with none or trivial preoperative AI. During mean 30 ± 16 months of CF-LVAD support, de novo AI-free rate was 86% and 67% at 1 and 2 years, respectively. Multivariable analysis showed that higher right ventricular stroke work index (RVSWI) (hazard ratio, 1.12 /g/m2/beat; 95% confidence interval, 1.00–1.20; p = 0.047) and trivial grade AI (hazard ratio, 2.8; 95% confidence interval, 1.2–6.4; p = 0.020) were independent preoperative risk factors for de novo AI. The longitudinal analysis using generalized mixed effects model showed that higher RVSWI was associated with continuous AV closure after LVAD implantation (Odd ratio, 1.20/g/m2/beat; 95% confidence interval, 1.00–1.43 /g/m2/beat; p = 0.047). Right heart catheterization revealed that preoperative RVSWI was positively correlated with postoperative pump flow index in patients with continuously closed AV (r = 0.44, p = 0.04, n = 22). Preoperative higher RVSWI was a significant risk factor for de novo AI following CF-LVAD implantation. In patients with preserved right ventricular function, postoperative higher pump flow may affect AI development via hemodynamic stress on the AV.

Gastrointestinal bleeding on continuous-flow left ventricular assist device therapy.

While technological advances in the field of continuous-flow left ventricular assist device (CF-LVAD) are constantly being made, CF-LVAD recipients are still subjected to a relatively high rate of LVAD-related adverse events, with post-LVAD gastrointestinal bleeding (GIB) being the most common one. GIB is associated with a significant impairment in quality of life, multiple hospital admissions, blood transfusion requirements and possibly death. Furthermore, of those patients who bled once, many will experience recurrent GIB events, which further aggravates their discomfort. While some medical and endoscopic treatment options are available, evidence regarding their benefit remains largely equivocal, with all related studies based on data from registries rather than clinical trials. Although having a major impact on LVAD recipients, an effective and validated pre-implant screening options to predict GIB events post-implant are scarce. This review focuses on the aetiology, incidence, risk factors, treatment options and the effect of new generation devices on post-LVAD GIB.

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.

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.

Prognostic Value of Peak Oxygen Uptake in Patients Supported With Left Ventricular Assist Devices (PRO-VAD)

ObjectivesThe purpose of this study was to examine whether peak oxygen uptake (pVO2) and other cardiopulmonary exercise test (CPET)-derived variables could predict intermediate-term mortality in stable continuous flow LVAD recipients. BackgroundpVO2 is a cornerstone in the selection of patients for heart transplantation, but the prognostic power of pVO2 obtained in patients treated with a left ventricular assist device (LVAD) is unknown. MethodsWe collected data for pVO2 and outcomes in adult LVAD recipients in a retrospective, multicenter study and evaluated cutoff values for pVO2 including: 1) values above or below medians; 2) grouping patients in tertiles; and 3) pVO2 ≤14 ml/kg/min if the patient was not treated with beta-blockers (BB) or pVO2 ≤12 ml/kg/min if the patient was taking BB therapy. ResultsNine centers contributed data from 450 patients. Patients were 53 ± 13 years of age; 78% were male; body mass index was 25 ± 5 kg/m2 with few comorbidities (stroke: 11%; diabetes: 18%; and peripheral artery disease: 4%). The cause of heart failure (HF) was most often nonischemic (66%). Devices included were the HeartMate II and 3 (Abbott); and Heartware ventricular assist devices Jarvik and Duraheart (Medtronic). The index CPET was performed at a median of 189 days (154-225 days) after LVAD implantation, and mean pVO2 was 14.1 ± 5 ml/kg/min (47% ± 14% of predicted value). Lower pVO2 values were strongly associated with poorer survival regardless of whether patients were analyzed for absolute pVO2 in ml/kg/min, pVO2 ≤12 BB/14 ml/kg/min, or as a percentage of predicted pVO2 values (P ≤ 0.001 for all). For patients with pVO2 >12 BB/14 and ventilation/carbon dioxide relationship (VE/VCO2) slope <35, the 1-year survival was 100%. ConclusionsEven after LVAD implantation, pVO2 has prognostic value, similar to HF patients not supported by mechanical circulatory support devices. (PROgnostic Value of Exercise Capacity Measured as Peak Oxygen Uptake [pVO2] in Recipients of Left Ventricular Assist Devices [PRO-VAD]; NCT04423562)

Does Size Matter for Female Continuous-flow LVAD Recipients? A Translational Approach to a Decade Long Question.

Females have increased risk of right-ventricular failure (RVF) and 3 month mortality after left-ventricular assist device (LVAD) implantation. In this translational study, we tested the hypothesis that sex differences in outcomes are driven by pump-induced LV size-volume mismatch, due to a negative impact on interventricular septal (IVS) interdependence. Adult continuous-flow LVAD recipients from the International Society For Heart And Lung Transplantation Mechanically Assisted Circulatory Support registry (n = 15,498) were studied to determine association of female sex with outcomes of 3 month mortality and RVF. Female sex was associated with smaller preimplant left-ventricular end-diastolic diameter (6.5 vs. 6.9 cm, p < 0.001), increased 3 month mortality (odds ratio [OR]: 1.42, p < 0.001) and RVF (OR: 1.18, p = 0.005). Smaller left-ventricular end-diastolic diameter was associated with worse outcomes after LVAD implantation (OR for mortality: 1.20, p < 0.001; RVF: 1.09, p < 0.001), and attenuated the association of female sex with these outcomes. In test bench heart phantoms (n = 4), the IVSs of smaller hearts demonstrated abnormal leftward shift earlier than larger hearts (volume change at IVS shift: 40 [95% confidence interval: 30-52] vs. 50 [95% confidence interval: 48-69] ml). Smaller LV size partially mediates worse post-LVAD outcomes for female patients, due to lower volume thresholds for adverse IVS shifting.

Psychosocial Risk and Its Association With Outcomes in Continuous-Flow Left Ventricular Assist Device Patients.

Advanced heart failure therapies such as left ventricular assist device (LVAD) implantation require intricate follow-up and complex care. We sought to explore the burden of psychosocial risk factors among patients with LVAD and their impact on postimplant outcomes using the Interagency Registry for Mechanically Assisted Circulatory Support. Adult patients in the Interagency Registry for Mechanically Assisted Circulatory Support requiring durable LVAD between 2008 and 2017 were included. Individuals were determined to have psychosocial risk if they had one of the following: (1) limited social support; (2) limited cognition; (3) substance abuse (alcohol and drug); (4) severe psychiatric disease (including major depression and other major psychiatric diagnosis); and (5) repeated noncompliance. Univariate and multivariate Cox proportional hazard regression models were used to analyze predictors of survival and complications. A total of 15 403 continuous-flow LVAD recipients were included. A total of 3163 (20.5%) had one or more psychosocial risk factors. The most prevalent psychosocial risk factor was substance abuse in 1941 (12.6%) recipients. Patients with psychosocial risk factors were significantly younger at LVAD implant, less likely to be White, and less likely to be female compared with those without psychosocial risk, P<0.001 for all. Patients with psychosocial risk were significantly more likely to receive an LVAD as destination therapy, P<0.001. In adjusted models, patients with psychosocial risk were at increased hazards for device-related infection, gastrointestinal bleeding, pump thrombosis, and readmission and reduced hazards for cardiac transplantation (P<0.05 for all). There was no statistically significant difference in survival on pump support or stroke. Psychosocial risk is an important component of patient selection for advanced heart failure therapies. Addressing these specific components may help improve access to advanced therapies and post-LVAD outcomes.

Characteristics and outcomes of gastrointestinal bleeding in patients with continuous-flow left ventricular assist devices: A systematic review.

Gastrointestinal bleeding (GIB) is a common adverse event after continuous-flow left ventricular assist device (CF-LVAD) implantation. We sought to evaluate patterns of GIB development and related outcomes in CF-LVAD recipients. An electronic search was performed to identify all articles related to GIB in the setting of CF-LVAD implantation. A total of 34 studies involving 1087 patients were pooled for analysis. Mean patient age was 60 years (95% CI 57-64) and 24% (95% CI 21-28%) were female. The mean time from CF-LVAD implantation to the first GIB was 54 days (95% CI 24-84) with 40% (95% CI 34-45%) of patients having multiple episodes of GIB. Anemia was present in 75% (95% CI 41-93%) and the most common etiology of bleeding was arteriovenous malformations (36% [95% CI 24-50%]). The mean duration of follow-up was 14.6 months (95% CI 6.9-22.3) during which the all-cause mortality rate was 21% (95% CI 12-36%) and the mortality rate from GIB was 4% (95% CI 2-9%). Thromboembolic events occurred in 32% (95% CI 22-44%) of patients with an ischemic stroke rate of 16% (95% CI 3-51%) and a pump thrombosis rate of 8% (95%CI 3-22%). Heart transplantation was performed in 31% (95% CI 18-47%) of patients, after which 0% (95% CI 0-10%) experienced recurrent GIB. GIB is a major source of morbidity among CF-LVAD recipients. While death due to GIB is rare, cessation of anticoagulation during treatment increases the risk of subsequent thrombotic events. Heart transplant in these patients appears to reliably resolve the risk of future GIB.

Outcomes of Left Ventricular Assist Device Implantation with Mitral Regurgitation with and without Concomitant Mitral Operation

The clinical impact of mitral valve procedures (MVP) at time of left ventricular assist device (LVAD) is not well understood. We examined the association of MVP, according to severity of MR, with long term survival and quality of life metrics. Continuous-flow LVAD recipients with MR from the 2008-2017 INTERMACS registry were included in the analysis. Patients with concomitant MVP were compared to those without intervention, stratified by severity of MR. Descriptive analyses, hazard modeling, and Kaplan-Meier analyses were used to examine associations between intervention and clinical outcomes. 6360 (40.0%) mild, 5592 (35.2%) moderate, and 3936 (24.8%) severe MR cases were included. MVP was not associated with improved survival for mild (median: 80.7 months for MVP vs. 55.0 months for non-MVP, P=0.49, HR 0.65 [95%:0.34-1.23]), moderate (58.8 vs. 49.3 months, P=0.31, HR 0.90 [0.57-1.42]), or severe MR (76.8 vs 49.7 months, P=0.15, HR 1.08 [0.73-1.59]). MVP was not associated with differential risk for device failure, bleeding, arrhythmia, thrombotic, right heart failure, or renal failure. There were no differences in Kansas City Cardiomyopathy Questionnaire with or without MVP for mild, moderate, or severe MR at 1- or 2-years after implantation. Concomitant MVP with LVAD implantation was not associated with mortality, adverse events, or objective quality of life metrics. The role of concomitant MVP with LVAD implantation must be carefully considered.

Association Between Neurohormone Levels and Exercise Testing Measures in Patients with Mechanical Circulatory Supports.

Continuous-flow left ventricular assist device (CF-LVAD) recipients exhibit impaired exercise capacity. Long-term continuous blood flow also elevates norepinephrine (NE) and aldosterone (Aldo) levels. However, the relationship between exercise capacity and neurohormonal activation has not been elucidated. Our study objective was to assess the association between cardiopulmonary exercise testing (CPT) measures and neurohormonal levels in CF-LVAD recipients. Symptom-limited CPT on a treadmill, using the modified Bruce protocol was performed in 15 CF-LVAD recipients. Norepinephrine and Aldo levels were measured, and the association between their levels and CPT measures were assessed. Peak VO2 (13.6 ml/kg/min) and percent age, sex predicted VO2 max (49.4%), and oxygen pulse (O2 pulse) (9.0 ± 4.0 ml/beat) were low, whereas minute ventilation/carbon dioxide output (VE/VCO2) slope (35) was elevated. In addition, VO2 at anaerobic threshold (VO2 AT), and O2 pulse values negatively correlated with NE levels. Norepinephrine levels positively correlated with chronotropic responses and heart rate (HR) recovery. Aldo levels in CF-LVAD recipients were not related to any CPT measures. Continuous-flow left ventricular assist device recipients exhibited impaired exercise capacity and chronotropic incompetence (CI). Despite the association of NE levels with chronotropic responses at peak exercise, neither NE levels nor chronotropic responses predicted peak VO2. This suggests that CI may not be the primary factor responsible for the low peak VO2. O2 pulse, which is a combined measure for stroke volume and peripheral oxygen extraction during exercise, was an independent predictor of peak VO2. Future studies should examine the contribution of peripheral factors to exercise capacity limitations.

Predictors of Warfarin Time in Therapeutic Range after Continuous‐Flow Left Ventricular Assist Device

Patients with a continuous-flow left ventricular assist device (CF-LVAD) require anticoagulation with a vitamin K antagonist to prevent thromboembolic events. Fluctuations in the international normalized ratio are associated with both increased thrombotic and bleeding episodes. To date, risk factors for low time in therapeutic range (TTR) among ambulatory patients with a CF-LVAD have not been explored. A retrospective single-center analysis of 121 patients implanted with a CF-LVAD was performed. International normalized ratios were systematically recorded from the initial postdischarge outpatient visit to 12months of time on the device. Risk factors for low TTR were evaluated using a multivariable linear regression analysis. Each of the 21 independent variables was entered into a stepwise regression designed to minimize the Akaike information criteria. In the multivariable analysis, the model output revealed that every 1-year increase in age was associated with a 0.4% increase in TTR (p=0.008), and every 1 mile further from clinic was associated with a 0.08% increase in TTR (p=0.03). Female sex was associated with a 10.1% decrease in TTR (p=0.04), type 2 diabetes was associated with an 11.5% decrease in TTR (p=0.006), and prior warfarin use was associated with an 8.3% decrease in TTR (p=0.03). In CF-LVAD recipients receiving warfarin, increasing age and distance from clinic are independent predictors of higher TTR. Female sex, type 2 diabetes, and prior warfarin use are independent predictors of lower TTR.

Long-Term Continuous-Flow Left Ventricular Assist Device Support After Left Ventricular Outflow Tract Closure.

Aortic valve insufficiency can be addressed during continuous-flow left ventricular assist device (CF-LVAD) implantation by performing aortic valve repair or replacement, or patch closure of the left ventricular outflow tract (LVOT). However, few studies have examined the safety of long-term CF-LVAD support after LVOT closure. From November 2003 through March 2016, 16 patients with advanced chronic heart failure underwent CF-LVAD implantation and concomitant LVOT closure for severe aortic insufficiency. We compared their long-term outcomes with those of 510 CF-LVAD recipients without concomitant LVOT closure. Total support time was 26.1 patient-years in the LVOT-closure group and 938.6 patient-years in the CF-LVAD-only group. Survival at 30 days, 6 months, 1 year, and 2 years was similar for CF-LVAD-only patients (90.4%, 80.6%, 74.3%, 67.5%) and LVOT-closure patients (81.3%, 81.3%, 75.0%, 68.8%; p = 0.59). There were no deaths related to LVOT closure. The event rate per patient-year for neurologic dysfunction (ND) was 0.23 in the LVOT-closure group (6 ND events) and 0.20 in the CF-LVAD-only group (136 ND events; p = 0.97). We conclude that for select patients with aortic insufficiency who are undergoing CF-LVAD implantation, LVOT closure produces acceptable outcomes and, therefore, is a viable option.

Preimplant Phosphodiesterase-5 Inhibitor Use Is Associated With Higher Rates of Severe Early Right Heart Failure After Left Ventricular Assist Device Implantation.

Background Early right heart failure (RHF) occurs commonly in left ventricular assist device (LVAD) recipients, and increased right ventricular (RV) afterload may contribute. Selective pulmonary vasodilators, like phosphodiesterase-5 inhibitors (PDE5i), are used off-label to reduce RV afterload before LVAD implantation, but the association between preoperative PDE5i use and early RHF after LVAD is unknown. Methods and Results We analyzed adult patients from the INTERMACS registry (Interagency Registry for Mechanically Assisted Circulatory Support) who received a continuous flow LVAD after 2012. Patients on PDE5i were propensity-matched 1:1 to controls. The primary outcome was the incidence of severe early RHF, defined as the composite of death from RHF within 30 days, need for RV assist device support within 30 days, or use of inotropes beyond 14 days. Of 11 544 continuous flow LVAD recipients, 1199 (10.4%) received preoperative PDE5i. Compared to controls, patients on PDE5i had higher pulmonary artery systolic pressure (53.4 mm Hg versus 49.5 mm Hg) and pulmonary vascular resistance (2.6 WU versus 2.3 WU; P<0.001 for both). Before propensity matching, the incidence of severe early RHF was higher among patients on PDE5i than in controls (29.4% versus 23.1%; unadjusted odds ratio (OR), 1.32; 95% CI, 1.17-1.50). This association persisted after propensity matching (PDE5i, 28.9% versus control 23.7%; OR, 1.31; 95% CI, 1.09-1.57), driven by a higher incidence of prolonged inotropic support. Similar results were observed across a wide range of subgroups stratified by markers of pulmonary vascular disease and RV dysfunction. Conclusions Patients treated with preoperative PDE5i had markers of increased RV afterload and HF severity compared to unmatched controls. Even after propensity matching, patients receiving preimplant PDE5i therapy had higher rates of post-LVAD RHF.

Effect of Angiotensin II Inhibitors on Gastrointestinal Bleeding in Patients With Left Ventricular Assist Devices

BackgroundAngiotensin II receptor activation may result in angiogenesis, and ultimately arteriovenous malformations (AVM), through transforming growth factor (TGF)-β and angiopoietin-2 pathway activation. ObjectivesThe goal of this study was to determine whether angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) were associated with lower risk of major gastrointestinal bleeds (GIB) and AVM-related GIBs in continuous-flow left ventricular assist device (CF-LVAD) patients. MethodsThe authors reviewed HeartMate II CF-LVAD recipients between January 2009 and July 2016. Major GIBs were endoscopically confirmed requiring ≥2 U of packed red blood cells or resulting in death. ACE inhibitor/ARB dose was abstracted from medical records. ACE inhibitor/ARB exposure status was landmarked at 30 days post-operatively to avoid immortal time bias. Fine and Gray hazard models assessed the impact of ACE inhibitor/ARB therapy on major GIB and AVM-related GIB, whereas standard Cox regression assessed the impact on mortality, adjusting for baseline variables. ResultsOne-hundred and eleven patients were included with a mean 2.1 ± 1.4 years follow-up. Patients who received an ACE inhibitor/ARB within 30 days post-operatively had a 57% reduction in the risk of major GIB (adjusted hazard ratio [aHR]: 0.43; 95% confidence interval [CI]: 0.19 to 0.97; p = 0.042) and a 63% reduction in the risk of AVM-related GIB (aHR: 0.37; 95% CI: 0.16 to 0.84; p = 0.017). When the mean daily post-operative lisinopril-equivalent ACE inhibitor/ARB dose was >5 mg, the risk of major GIB decreased in a dose-threshold manner (aHR: 0.28; 95% CI: 0.09 to 0.85; p = 0.025). ConclusionsACE inhibitor/ARB therapy is associated with a protective effect of developing GIBs in CF-LVAD patients, with a dose threshold of >5 mg of daily lisinopril equivalence, possibly due to prevention of AVM formation.

Digoxin Restores Angiogenic Equilibrium in CF- LVAD Patients

Purpose Gastrointestinal bleeding (GIB) in patients supported by Continuous-Flow Left Ventricular Assist Devices (CF-LVAD) is most commonly caused by gastrointestinal angiodysplasia (GIAD). It has been postulated that the abnormal hemodynamic profile in CF-LVAD patients can cause splanchnic submucosal hypoperfusion and activate a Hypoxia Inducible Factor (HIF)1-alpha /Angiopoietins (Ang) signaling cascade that triggers pathological neoangiogenesis. Specifically, it has been established in CF-LVAD recipients that the increased levels of Ang-2, decreased Ang-1 and resultant increase in the ratio of Ang-2/Ang-1, presents angiogenic switch that may favor GIAD development. We have recently shown that use of digoxin, a potent inhibitor of HIF1-alpha, is associated with a significant reduction in GIAD related GIB in CF-LVAD patients. We now hypothesize that dysregulation of Ang-2 and Ang-1 levels in patients with CF-LVADs can be restored by digoxin treatment. Methods Blood samples were collected from 10 patients supported with CF-LVAD before and 2 weeks after they were started on digoxin. Ang-1 and Ang-2 was measured in patients’ serum by ELISA. Statistical difference between the groups was tested with paired t-test. Results Digoxin treatment in CF-LVAD patients decreased Ang-2 (14.1 to 8.8 ng/ml, p=0.015) and increased Ang-1 levels (11.6 to 29.8 ng/ml, p=0.002), reversing angiogenic switch (Fig.1). Conclusion Digoxin may restore angiogenic equilibrium in patients supported by CF-LVADs. The relevance of this finding for development of GIB needs to be prospectively studied.

Prediction of GIB Using R2 CHA2DS2 VASc Risk Score

Purpose Continuous flow left ventricular assist device (CF-LVAD) support has been associated with high rates of gastrointestinal bleeding (GIB). We analyzed the ability of the R2CHA2DS2 VASc scoring system to predict GIB in patients on CF-LVAD support. Methods We performed a retrospective review of 526 patients who underwent implantation of CF-LVADs from November 2003 through March 2016 at our center. The R2 CHA2DS2 VASc score was calculated preoperatively for each patient, and logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to determine whether this risk score predicted GIB. Additional analyses were performed using the R2 CHA2DS2 VASc score to identify etiologies and locations of GIB. Results R2CHA2DS2 VASc score was calculated for 519 patients; 7 patients were excluded due to incomplete data. Average score was 5.1±1.4 (Figure). A total of 218 GIB event occurred in 140 patients; 48 experienced a recurrent GIB. Median time to GIB event was 78 days (interquartile range = 36.5-2298.75 days). The most common etiology was atriovenous malformations (72 events in 50 patients). The R2 CHA2DS2 VASc score successfully predicted GIB (Odds ratio [OR]=1.4, p=0.001) and was especially significant for GIB from ulcers (OR=1.4, p=0.002) and AVMs (OR=1.5, p=0.001) in the stomach (OR=1.3, p=0.004) and duodenum (OR=1.5, p=0.02; Table). ROC curve analysis resulted in an area under the curve of 0.63. Conclusion The R2 CHA2DS2 VASc risk score accurately predicted GIB events in CF-LVAD recipients from AVMs and ulcers in the stomach and duodenum. This may be useful in the selection and management of patients being considered for LVAD implantation.

Novel Model to Predict Gastrointestinal Bleeding During Left Ventricular Assist Device Support.

Gastrointestinal bleeding (GIB) is a leading cause of morbidity during continuous-flow left ventricular assist device (CF-LVAD) support. GIB risk assessment could have important implications for candidate selection, informed consent, and postimplant therapeutic strategies. The aim of the study is to derive and validate a predictive model of GIB in CF-LVAD patients. CF-LVAD recipients at the Utah Transplantation Affiliated Hospitals program between 2004 and 2017 were included. GIB associated with a decrease in hemoglobin ≥2 g/dL was the primary end point. A weighted score comprising preimplant variables independently associated with GIB was derived and internally validated. A total of 351 patients (median age, 59 years; 82% male) were included. After a median of 196 days, GIB occurred in 120 (34%) patients. Independent predictors of GIB included age >54 years, history of previous bleeding, coronary artery disease, chronic kidney disease, severe right ventricular dysfunction, mean pulmonary artery pressure <18 mm Hg, and fasting glucose >107 mg/dL. A weighted score termed Utah bleeding risk score, effectively stratified patients based on their probability of GIB: low (0-1 points) 4.8%, intermediate (2-4) 39.8%, and high risk (5-9) 83.8%. Discrimination was good in the development sample (c-index: 0.83) and after internal bootstrap validation (c-index: 0.74). The novel Utah bleeding risk score is a simple tool that can provide personalized GIB risk estimates in CF-LVAD patients. This scoring system may assist clinicians and investigators in designing tailored risk-based strategies aimed at reducing the burden posed by GIB in the individual CF-LVAD patient and healthcare systems.