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Background: Extensive evidence from single-center studies indicates that a subset of patients with chronic advanced heart failure (HF) undergoing left ventricular assist device (LVAD) support show significantly improved heart function and reverse structural remodeling (ie, termed "responders"). Furthermore, we recently published a multicenter prospective study, RESTAGE-HF (Remission from Stage D Heart Failure), demonstrating that LVAD support combined with standard HF medications induced remarkable cardiac structural and functional improvement, leading to high rates of LVAD weaning and excellent long-term outcomes. This intriguing phenomenon provides great translational and clinical promise, although the underlying molecular mechanisms driving this recovery are largely unknown.Methods: To identify changes in signaling pathways operative in the normal and failing human heart and to molecularly characterize patients who respond favorably to LVAD unloading, we performed global RNA sequencing and phosphopeptide profiling of left ventricular tissue from 93 patients with HF undergoing LVAD implantation (25 responders and 68 nonresponders) and 12 nonfailing donor hearts. Patients were prospectively monitored through echocardiography to characterize their myocardial structure and function and identify responders and nonresponders.Results: These analyses identified 1341 transcripts and 288 phosphopeptides that are differentially regulated in cardiac tissue from nonfailing control samples and patients with HF. In addition, these unbiased molecular profiles identified a unique signature of 29 transcripts and 93 phosphopeptides in patients with HF that distinguished responders after LVAD unloading. Further analyses of these macromolecules highlighted differential regulation in 2 key pathways: cell cycle regulation and extracellular matrix/focal adhesions.Conclusions: This is the first study to characterize changes in the nonfailing and failing human heart by integrating multiple -omics platforms to identify molecular indices defining patients capable of myocardial recovery. These findings may guide patient selection for advanced HF therapies and identify new HF therapeutic targets. [ABSTRACT FROM AUTHOR]

Among the estimated 6.2 million Americans living with heart failure (HF), ≈5%/y may progress to advanced, or stage D, disease. Advanced HF has a high morbidity and mortality, such that early recognition of this condition is important to optimize care. Delayed referral or lack of referral in patients who are likely to derive benefit from an advanced HF evaluation can have important adverse consequences for patients and their families. A 2-step process can be used by practitioners when considering referral of a patient with advanced HF for consideration of advanced therapies, focused on recognizing the clinical clues associated with stage D HF and assessing potential benefits of referral to an advanced HF center. Although patients are often referred to an advanced HF center to undergo evaluation for advanced therapies such as heart transplantation or implantation of a left ventricular assist device, there are other reasons to refer, including access to the infrastructure and multidisciplinary team of the advanced HF center that offers a broad range of expertise. The intent of this statement is to provide a framework for practitioners and health systems to help identify and refer patients with HF who are most likely to derive benefit from referral to an advanced HF center. [ABSTRACT FROM AUTHOR]

Background: Metabolic remodeling in heart failure contributes to dysfunctional lipid trafficking and lipotoxicity. Acyl coenzyme A synthetase-1 (ACSL1) facilitates long-chain fatty acid (LCFA) uptake and activation with coenzyme A (CoA), mediating the fate of LCFA. The authors tested whether cardiac ACSL1 overexpression aids LCFA oxidation and reduces lipotoxicity under pathological stress of transverse aortic constriction (TAC).Methods: Mice with cardiac restricted ACSL1 overexpression (MHC-ACSL1) underwent TAC or sham surgery followed by serial in vivo echocardiography for 14 weeks. At the decompensated stage of hypertrophy, isolated hearts were perfused with 13C LCFA during dynamic-mode 13C nuclear magnetic resonance followed by in vitro nuclear magnetic resonance and mass spectrometry analysis to assess intramyocardial lipid trafficking. In parallel, acyl CoA was measured in tissue obtained from heart failure patients pre- and postleft ventricular device implantation plus matched controls.Results: TAC-induced cardiac hypertrophy and dysfunction was mitigated in MHC-ACSL1 hearts compared with nontransgenic hearts. At 14 weeks, TAC increased heart weight to tibia length by 46% in nontransgenic mice, but only 26% in MHC-ACSL1 mice, whereas ACSL1 mice retained greater ejection fraction (ACSL1 TAC: 65.8±7.5%; nontransgenic TAC: 45.9±7.3) and improvement in diastolic E/E'. Functional improvements were mediated by ACSL1 changes to cardiac LCFA trafficking. ACSL1 accelerated LCFA uptake, preventing C16 acyl CoA loss post-TAC. Long-chain acyl CoA was similarly reduced in human failing myocardium and restored to control levels by mechanical unloading. ACSL1 trafficked LCFA into ceramides without normalizing the reduced triglyceride storage in TAC. ACSL1 prevented de novo synthesis of cardiotoxic C16- and C24-, and C24:1 ceramides and increased potentially cardioprotective C20- and C22-ceramides post-TAC. ACLS1 overexpression activated AMP activated protein kinase at baseline, but during TAC, prevented the reduced LCFA oxidation in hypertrophic hearts and normalized energy state (phosphocreatine:ATP) and consequently, AMP activated protein kinase activation.Conclusions: This is the first demonstration of reduced acyl CoA in failing hearts of humans and mice, and suggests possible mechanisms for maintaining mitochondrial oxidative energy metabolism by restoring long-chain acyl CoA through ASCL1 activation and mechanical unloading. By mitigating cardiac lipotoxicity, via redirected LCFA trafficking to ceramides, and restoring acyl CoA, ACSL1 delayed progressive cardiac remodeling and failure. [ABSTRACT FROM AUTHOR]

Background: In nonrandomized, open-label studies, a transcatheter interatrial shunt device (IASD, Corvia Medical) was associated with lower pulmonary capillary wedge pressure (PCWP), fewer symptoms, and greater quality of life and exercise capacity in patients with heart failure (HF) and midrange or preserved ejection fraction (EF ≥40%). We conducted the first randomized sham-controlled trial to evaluate the IASD in HF with EF ≥40%.Methods: REDUCE LAP-HF I (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) was a phase 2, randomized, parallel-group, blinded multicenter trial in patients with New York Heart Association class III or ambulatory class IV HF, EF ≥40%, exercise PCWP ≥25 mm Hg, and PCWP-right atrial pressure gradient ≥5 mm Hg. Participants were randomized (1:1) to the IASD versus a sham procedure (femoral venous access with intracardiac echocardiography but no IASD placement). The participants and investigators assessing the participants during follow-up were blinded to treatment assignment. The primary effectiveness end point was exercise PCWP at 1 month. The primary safety end point was major adverse cardiac, cerebrovascular, and renal events at 1 month. PCWP during exercise was compared between treatment groups using a mixed-effects repeated measures model analysis of covariance that included data from all available stages of exercise.Results: A total of 94 patients were enrolled, of whom 44 met inclusion/exclusion criteria and were randomized to the IASD (n=22) and control (n=22) groups. Mean age was 70±9 years, and 50% were female. At 1 month, the IASD resulted in a greater reduction in PCWP compared with sham control (P=0.028 accounting for all stages of exercise). Peak PCWP decreased by 3.5±6.4 mm Hg in the treatment group versus 0.5±5.0 mm Hg in the control group (P=0.14). There were no peri-procedural or 1-month major adverse cardiac, cerebrovascular, and renal events in the IASD group and 1 event (worsening renal function) in the control group (P=1.0).Conclusions: In patients with HF and EF ≥40%, IASD treatment reduces PCWP during exercise. Whether this mechanistic effect will translate into sustained improvements in symptoms and outcomes requires further evaluation.Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02600234. [ABSTRACT FROM AUTHOR]

Cardiac arrest in patients on mechanical support is a new phenomenon brought about by the increased use of this therapy in patients with end-stage heart failure. This American Heart Association scientific statement highlights the recognition and treatment of cardiovascular collapse or cardiopulmonary arrest in an adult or pediatric patient who has a ventricular assist device or total artificial heart. Specific, expert consensus recommendations are provided for the role of external chest compressions in such patients. [ABSTRACT FROM AUTHOR]

Initial invasive versus conservative management of stable ischemic heart disease patients with a history of heart failure or left ventricular dysfunction: insights from the ISCHEMIA trial. As Morgan et al also point out, ISCHEMIA was designed to study patients without significant LVD,[3] but because 7.7% of patients randomized had HF/LVD, our study provided a unique opportunity to explore the treatment effect of an invasive strategy in such patients with moderate or severe ischemia. In our analysis of patients with heart failure (HF) or left ventricular dysfunction (LVD), we reported lower rates of the composite of cardiovascular death, myocardial infarction, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest and the secondary composite outcome of cardiovascular death or myocardial infarction in patients assigned to the invasive strategy as compared with the conservative strategy.[1] Morgan et al correctly point out that our results were driven by a small number of patients with LVD (ejection fraction [EF] <45%) in the HF/LVD group, and we agree that these findings should be interpreted with caution. [Extracted from the article]

Initial invasive versus conservative management of stable ischemic heart disease patients with a history of heart failure or left ventricular dysfunction: insights from the ISCHEMIA trial. The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial did not report evidence of a differential treatment effect on the primary outcome with respect to baseline left ventricular (LV) function.[1] Lopes et al now present a subgroup analysis of patients who had previous diagnoses of heart failure (HF) or LV dysfunction, defined as an LV ejection fraction (EF [LVEF]) <45%.[2] This is a high-risk population that does worse than their counterparts with preserved LV function (eg, higher overall risk of cardiovascular death, myocardial infarction, and all-cause death or HF [15.0% vs 6.9%] than in the overall trial population), as is also shown here. In patients without a history of HF (the majority), an initial invasive strategy had no impact on the primary outcome, regardless of LVEF (Figure 3A in Lopes et al[2]). [Extracted from the article]

The article discusses the advancement which has taken place in the mechanical circulatory support (MCS) technology. It states that the survival and the quality of life of the heart failure patients have been increased due to the accelerated usage of left ventricular assist devices (LVADs). It further discusses the novel pump design which has changed the structure of heart disease programs and has improved clinical outcomes.

Background: Evidence suggests that the ischemic etiology of heart failure (HF) is a predictor of mortality in patients receiving guidline directed medical therapy as well as in patients undergoing heart transplantation. Little is known about the impact of the ischemic etiology of HF in patients undergoing left ventricular assist device (LVAD) placement. Therefore, we investigated this underexplored gap in knowledge. Methods: The National Inpatient Sample Database was queried from 2009-2014 to identify all hospitalizations in patients aged ≥18 years with the LVAD placement. The primary outcome was in-hospital all-cause mortality. The differences in outcomes between ischemic (ICM) and non-ischemic cardiomyopathy (NICM) in LVAD placement were examined using complex samples multivariable logistic or generalized linear model regressions. Results: The study population included 3,511patients that underwent LVAD placement from 2009 to 2014. Of these, 1,880 (53.5 %) had ICM, while 1631 (46.5 %) had NICM. Patients in the ICM group were older and had a higher prevalence of several major comorbidities. Patients with ICM were found to have a significantly higher risk of hemorrhage requiring transfusion (OR1.29, 95% CI 1.08 to 1.53), vascular complications requiring surgery (OR 1.58 95% CI 1.10 to 2.28) and postoperative ST-segment myocardial infarction (OR 7.38 95% CI 5.33 to 10.24). There was no difference between ICM and NICM cohorts with regards to in-hospital mortality, ischemic stroke, acute kidney injury, postoperative sepsis, respiratory complications, hemopericardium, cardiac tamponade or hemolytic anemia. Conclusion: We found that ischemic etiology of heart failure did not impact in-hospital mortality in patients undergoing LVAD placement but was a predictor of perioperative complications including bleeding requiring transfusion, vascular complications, and postoperative myocardial infarction. [ABSTRACT FROM AUTHOR]

Introduction: Sustained ventricular arrhythmias (VA) are common in heart failure patients receiving continuous flow left ventricular assist devices (LVAD). Available studies evaluating the impact of VA on clinical outcomes in LVAD recipients have been single center and limited by small sample size Hypothesis: We report the first multicenter study to assess the incidence, predictors, and outcomes associated with VA in LVAD patients Methods: Analysis was performed on 408 patients who underwent LVAD implantation at 5 centers from 2007-2015. VA was defined as sustained ventricular tachyarrhythmias lasting >30 sec or requiring ICD therapy. Effects of pre- and post-LVAD VA on survival was assessed using Kaplan-Meier analysis. Results: Of 408 LVAD patients (Age 60 years), 254 (62%) had pre-LVAD VA (PreVA) and 154 (38%) did not (No-PreVA). At baseline, the PreVA group had greater male sex (85 vs 75%, p=0.02), amiodarone use (44 vs 31%, p=0.01), LV diastolic dimensions (7.1 vs 6.8 cm, p=0.01) and atrial arrhythmias (AA) (57 vs 45%, p=0.03). Compared to the No-PreVA group, the PreVA group had significantly higher incidence of post-LVAD VA (73 vs 37%, p< 0.0001), AA (63 vs 42%, P<0.0001), and ICD shocks (42 vs 32%, p=0.001) but similar rates of hospitalization (0.5 vs 0.5/100 days, p=0.7). During a median follow-up of 478 days, 35% of patients died in both groups. Kaplan-Meier analysis showed no difference in survival between the groups (Log Rank p=0.1: Fig 1). Those who had both pre- and post-LVAD VA had similar survival as patients without any VA (Log rank p=0.1). Conclusions: In this large, multicenter LVAD cohort, PreVA was associated with a significantly higher incidence of post-LVAD VA and ICD shocks. PreVA was not significantly associated with survival or all-cause hospitalizations. [ABSTRACT FROM AUTHOR]

Introduction: Sarcopenia is the age-related deterioration in skeletal muscle mass and function, which can be accelerated by chronic comorbidities. The prevalence in advanced systolic heart failure (HF) and impact on HF health status are currently uncertain. Sarcopenia diagnostic criteria from the Foundation for the National Institutes of Health (FNIH) and European Working Group on Sarcopenia in Older People (EWGSOP) have not been applied to HF cohorts. Hypothesis: We hypothesized that at the time of left ventricular assist device (LVAD) implantation systolic HF patients have prevalent sarcopenia, and that sarcopenia is associated with poorer nutritional and HF health status. Methods: We recruited 18 adults with systolic HF ±21 days from LVAD implantation. All underwent whole-body dual X-ray absorptiometry (DXA) to calculate appendicular lean mass (ALM). Subjects also underwent a 3-day food recall, Simplified Nutritional Appetite Questionnaire (SNAQ), Kansas City Cardiomyopathy Questionnaire (KCCQ) for HF health status, handgrip strength and blood testing. Sarcopenia was defined by 2 ALM criteria: FNIH – males <19.75kg, females <15.02kg; EWGSOP – males <7.26kg/m2, females <5.5kg/m2. Linear regression determined relationships between appendicular lean mass and age, weight, handgrip strength, KCCQ summary score, SNAQ score, 24-hour protein intake, and key blood variables, without/with adjustment for sex and height. Results: Sarcopenia was diagnosed in 5 subjects (28%) by FNIH criteria and an additional 5 (10 total, 56%) by EWGSOP criteria (Figure). There were unadjusted associations between lower appendicular lean mass and lower handgrip strength; higher SNAQ score (higher malnutrition risk); lower sodium; and lower hemoglobin. After adjustment for sex and height, lower lean mass remained associated with lower hemoglobin. Lower appendicular lean mass was also independently associated with higher (more favorable) KCCQ scores. Conclusions: As many as half of advanced systolic HF patients meet standard DXA criteria for sarcopenia. Lower appendicular lean mass is independently associated with lower hemoglobin but does not appear to be associated with poorer HF status. [ABSTRACT FROM AUTHOR]

Introduction: Decreased cardiac output is often thought to be the main determinant of renal dysfunction in patients with heart failure. However, large cohort studies are lacking to show these correlations in patients with end stage heart failure. Methods: We selected all adult patients between 2007-2016 who were listed for heart transplant (n=11,030) after excluding those on life support, inotropes, nitric oxide, total artificial heart, percutaneous mechanical or ECMO support, dialysis dependent, biventricular or only right ventricular assist device support and with prior heart or kidney transplant using the United Network for Organ Sharing database. We evaluated associations between renal function and three hemodynamic parameters: 1) cardiac index (CI), 2) mean pulmonary artery pressure (mPA) and 3) pulmonary vascular resistance (PVR) using robust regression models. Results: Average age of patients was 53.5±12.3 years (23% females) with mean estimated glomerular filtration rate (eGFR) of 71.7±26.2 mL/min/1.73m2. Nearly half (49%) of the patients had left ventricular assist devices (LVAD) with mPA pressure of 26.2±9.9 mmHg and average CI of 2.4±0.7. There was an inverse correlation between mPA pressure and eGFR (p<0.001) however no association between CI and eGFR (p=0.853); or between PVR and eGFR (p=0.989). After multivariate adjustment, mPA pressure was inversely correlated with eGFR (p<0.001). Subgroup analysis of individuals with LVADs (N=5,417) showed similar results with significant inverse relations between mPA and eGFR (p= 0.008) and no significant correlation between PVR or CI and eGFR (p>0.2 for both). Analysis restricted to individuals with low CI (< 1.8 L/min/m2) and PVR < 4 Woods Units (n=8376) also showed inverse linear correlation between mPA pressures up to 45 mmHg and eGFR (p<0.001). Conclusions: Among patients with end stage heart failure, higher mPA pressure and not the lower cardiac index are cross-sectionally related to lower eGFR values. [ABSTRACT FROM AUTHOR]

Introduction: Patients at increased risk of complications following LVAD placement are admitted to the hospital for hemodynamic optimization prior to LVAD implantation, which can include adjustment of medical therapy and/or placement of an IABP. Hypothesis: Prior to LVAD placement patients treated with an IABP during hemodynamic optimization will have similar outcomes despite worse baseline characteristics compared with patients treated medically. Methods: This single-center study included 199 non-inotrope dependent patients who underwent durable LVAD implantation between January 1st, 2007 and April 10th 2017. Hemodynamic data was collected retrospectively. Patients who received an IABP were compared to those who did not. Stage 2 or 3 acute kidney injury, right ventricular failure, and 30 day mortality was compared between patients with and without and IABP. Results: The mean age was 62.7 and 82.9% were male; 72 (36.2%) received an IABP. Baseline characteristics between groups were similar. Patients treated with an IABP had worse INTERMACS profiles and worse baseline hemodynamic parameters. The incidence of the primary composite endpoint was similar between patients who had an IABP and those who did not (23.6% vs 19.7%; p=0.517), as were each of the individual endpoints: stage 2 or 3 acute kidney injury (18.1% vs 14.2%; p=0.472), right ventricular failure (13.9% vs 13.4%; p=0.796), and 30 day mortality (6.9 % vs 3.2%; p=0.226). Patients treated with an IABP had greater relative reductions in mean right atrial pressure (-24.1% vs -5.9%; p=0.044), pulmonary artery systolic (-11.7% vs +3.3%; p=<0.001), diastolic (-17.0% vs +12.0%; p=0.015), and mean pressures (-15.2% vs 0.5%; p=<0.001). Conclusions: Despite worse hemodynamic parameters and INTERMACS profile at baseline, ambulatory heart failure patients who received an IABP prior to LVAD implantation did not have an increased incident of stage 2 or 3 acute kidney injury, right ventricular failure, or 30 day mortality, and had more favorable reductions in right atrial and pulmonary artery pressures. These results suggest that the use of the IABP prior to LVAD implantation in non-inotrope dependent patients with poor baseline hemodynamics may mitigate the risk of postoperative complications. [ABSTRACT FROM AUTHOR]

Purpose: Older age is a well-known risk factor following implantation of a left ventricular assist device. We examined the effect of heart failure etiology in this higher risk population after implantation of the HeartWareTM HVADTM System as destination therapy in the ENDURANCE Supplemental trial Methods: This is a post-hoc analysis of patients older than 65 supported by the HVAD from the ENDURANCE Supplemental trial. Patients were separated into two groups, those with an ischemic heart failure (n=106) and those with non-ischemic heart failure (n=43) and examined for differences in adverse events and 2-year survival. Results: Patients with ischemic heart failure were significantly more likely to be male with a history of prior cardiac surgeries (Table 1). The ischemic group experienced more non-device related infections (p=0.03) and acute renal dysfunction (p=0.01). (Table 2). Two-year survival was significantly reduced in the ischemic group (p=0.0005) (Figure 1). Conclusions: Patients in the experimental arm of the ENDURANCE Supplemental trial who were older than 65 with ischemic heart failure had significantly reduced survival despite having similar rates of serious adverse events. Further investigation is required to determine how patient management strategies may be modified to address this high-risk patient cohort. [ABSTRACT FROM AUTHOR]

Background: Morbidly obese patients with end-stage heart failure (HF) are routinely ineligible for heart transplantation. Left ventricular assist devices (LVAD) are commonly used in an attempt to assist weight loss prior to a heart transplant ("bridge to weight loss"), however this strategy often fails. Hypothesis: Bariatric surgery has been used in LVAD patients to assist in weight loss. We aimed to study trends in bariatric surgery use, patient characteristics, and outcomes following bariatric procedures in patients with LVAD. Methods: Using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS), we identified patients with LVADs who underwent bariatric procedures in United States hospitals from 2010-2015. Baseline characteristics and in-hospital outcomes were analyzed. Results: A total of 45 patients with LVAD underwent bariatric surgery with an increase of procedures over the time period analyzed. All patients had body mass index (BMI) greater than 40 kg/m2. Patients were mostly men (77.8%) and white (42.9%), with an average age of 45.7 years. A summary of the baseline characteristics can be found in Table 1. All of the interventions were performed in urban and teaching hospitals. Average length of stay was estimated at 10 days (4.94-15.5). There was no incidence of gastrointestinal bleeding. Other bleeding complications were described in 33.3% of patients. Renal dysfunction occurred in 22.2% and infection in 11.1% of cases. Overall stroke or pump thrombosis was not reported. There was no in-hospital mortality. Conclusions: We report the first nationwide evidence for the use of bariatric procedures in patients with LVADs. Despite the incidence of some periprocedural complications, no major adverse events such as stroke or death were reported. Further studies are needed to understand predictors of poor outcomes to possibly detect patients in whom bariatric surgery may have a major impact. [ABSTRACT FROM AUTHOR]

Introduction: The use of left ventricular assist devices (LVAD) in patients with end-stage heart failure (HF) requires identification of those patients who will derive the most benefit from therapy while avoiding adverse events. Patients with a past or ongoing history of substance abuse may not be deemed candidates for VAD therapy due to a perceived risk of poor compliance and subsequent adverse events. There is paucity of published data to guide this ethical decision. Methods: Using the Healthcare Cost and Utilization Project Nationwide Readmissions Database (HCUP-NRD), we identified patients who underwent VAD implantation in US hospitals from 2010-2014. We used ICD-9-CM codes to classify patients with alcohol abuse, drug abuse, polysubstance abuse and no substance abuse. Multivariate analysis models were generated to compare readmission rates and specific outcomes in patients with substance abuse against a cohort of patients without substance abuse. Results: An estimated total of 7988 patients were included in our analysis. Of these, 221 patients had a history of substance abuse. Alcohol was the most common substance abused (n=146), followed by drug abuse (cocaine, marijuana, opioid, amphetamine or hallucinogen) (n=46), and 11 patients had polysubstance abuse. Compared to the cohort with no substance abuse, there was no difference in 90-day readmission rates in patients with drug abuse (OR 1.23, 95% CI 0.55-2.77; p 0.616) or polysubstance abuse (OR 1.02; 95% CI 0.14-7.28; p 0.983). Patients with alcohol abuse had a lower 90-day readmission rate (OR 0.5; 95% CI 0.27-0.96; p 0.037). Other outcomes analyzed such as length of stay, costs, bleeding, renal dysfunction, or stroke, were not higher in the groups with substance abuse. Conclusions: Our results suggest that patients with substance abuse do not have a greater readmission rate and are not at higher risk of common VAD-associated complications. Limiting access to LVAD therapy in patients with a substance abuse history might be an unnecessary restriction. Larger studies, including those that capture loss to follow-up, are needed to confirm these findings and aid in the decision-making for this population. [ABSTRACT FROM AUTHOR]

Introduction: Despite the impressive improvement in survival for patients with advanced heart failure afforded by LVADs, peak exercise capacity remains severely impaired. Hypothesis: We sought to identify which hemodynamic parameters most highly correlated with peak VO2 in LVAD supported patients. Methods: Patients referred for routine post-VAD hemodynamic assessment and optimization from 12/2017-5/2018 at a single medical center were considered for participation. Twenty two patients supported by axial flow pumps (n=10) and fully magnetically levitated centrifugal flow pumps (n=12) underwent upright incremental bicycle exercise with respiratory gas analysis and Swan Ganz monitoring. Hemodynamic measurements, mixed venous saturation, and BP assessed with a Terumo device were recorded every 3 minutes during exercise. Linear correlations were performed between peak VO2 (ml/min) and peak Fick CO, peak device flow, the assumed intrinsic cardiac output derived as Fick CO-device flow , peak pressure differential across the LVAD (ΔMAP-PCWP), peak pressure differential across RV (mean PA-RAP), and SVR. Results: There were 21 men and 1 woman. Eight patients had CAD and 14 patients had dilated cardiomyopathy. Average age was 61.1±13 yrs. The indication was bridge to transplant in 18 and destination therapy in 4 patients. The average pump speed of the axial flow pumps was 9400±141 RPM and 5392±254 rpm in the centrifugal group. Fick CO had the greatest correlation with peak VO2 with an R value of 0.9 and p<0.001 followed by intrinsic CO (R=0.77; p<0.01). Peak device flow weakly correlated to peak VO2 (R=0.349, p <.01). There tended to be a inverse correlation with the ΔMAP-PCWP to peak VO2 but it was not significant (R=-.24; p=0.06) Conclusions: LVAD supported patients have severely impaired exercise capacity. The Fick cardiac output and the presumed contribution from the native heart are the best predictors of peak exercise performance. [ABSTRACT FROM AUTHOR]

Introduction: Sleep-disordered breathing (SDB) has been associated with increased risk of adverse events in patients with heart failure (HF). However, the impact of SDB on patients with left ventricular assist device (LVAD) remains unclear. Methods: We prospectively enrolled 50 patients with HeartMateII who were examined their respiratory disturbance index (RDI) by portable sleep monitoring. The patients were divided into 2 groups, SDB (RDI>15, n=12) and no-SDB (RDI<15, n=38), based on the existence of moderate SDB, or not. The patients were followed-up for the occurrence of adverse events (arrhythmia, cerebrovascular, hemolysis, bleeding, infection, and death) after enrollment. Results: There were no significant differences between 2 groups in gender, body mass index, etiology of cardiac disease, medical therapy. In addition, there were no significant difference between 2 groups in echocardiographic and hemodynamic parameters. Age [53±4 vs 42±2 , p=0.02], Brain natriuretic peptide [324 (132-627) pg/ml vs 88 (51-185) pg/ml, p=0.009] and eGFR [60±27 ml/min vs 86±31 ml/min, p=0.01] were higher in Group SDB than Group no-SDB. The prevalence of VTa after enrollment was higher in Group SDB during follow-up period; 160±70 days [4 (33%)vs 2 (5%), p=0.02]. On Cox proportional hazard analysis, the presence of SDB was a significant predictor (Hazard ratio 6.5, 95% confidence interval 1.28-47.19, p=0.03) for VTa. The patients with VTa in Group no-SDB had occurred once VTa event. The patients in Group SDB developed multiple VTa events which required both repeated cardioversion and various anti-arrhythmic medical therapies. Conclusions: Some patients with HF still have SDB even after LVAD implantation. The result of this study suggested that SBD in patients with LVAD is associated with the occurrence of VTa. Neurohumoral hyperactivation due to SBD may trigger the VTa and some interventions to SBD may be effective to suppress VTa in patients with LVAD. [ABSTRACT FROM AUTHOR]

Background: Since 1968, heart transplantation has become the definitive treatment for patients with end-stage heart failure. In this study, we aim to investigate heart transplantation trends and outcomes over the past 50 years. Methods: From January 6, 1968 to December 2017, 1703 adult patients underwent heart transplant at Stanford Hospital. Our primary end point was all cause mortality and secondary end points included infection, rejection within one year requiring hospitalization, and graft failure. Results: Average recipient age (48±12.8 years) and donor age (29.7±11.5 years) significantly increased over time (p <.0001). Recent patients were more likely to have diabetes (n=350, 30.1%), chronic obstructive pulmonary disease (n=95, 8.2%), prior sternotomy (n=347, 28.5%), and be on dialysis preoperatively (n=39, 3.4%) (p ≤.0002). There were 101 re-transplants (5.9%), and 181 patients (15.7%) had a ventricular assist device preoperatively, which was more frequent during recent decades (p <.0001). Average listed wait time was 147.5±243 days. Distance organ travelled was 130±153.2 miles, and total ischemic time was 207.9±59 minutes, both increased over time (p <.0001). Median hospital length of stay was 14 days. The most common perioperative infection was pneumonia (n=75, 6.5%). A total of 268 patients (22%) had rejection requiring hospitalization within one year, and 105 patients (8.7%) had graft failure during follow up. Average length of follow up was 6.8±6.9 years, and most recent ejection fraction was 59.1±11%. Overall median survival was 8.4 years. Each decade, median survival improved from 1.5 years (1968-1977) to 10.8 years (1998-2007), with 74% survival at ten years for the most recent decade (p <.0001). Age-adjusted hazard ratio significantly decreased by each decade (p <.005). At 20 years, the adjusted probability of survival from 1968 to 2007 by decade was 4.2%, 11.3%, 20.8%, and 30%. Conclusions: In this half-century retrospective study from one of the largest heart transplant programs in the U.S., long-term survival after heart transplantation has significantly improved over the decades, despite increased recipient and donor age, recipient comorbidities, technical complexity, procurement distance, and total allograft ischemic time. [ABSTRACT FROM AUTHOR]

Background: Careful selection of heart transplant candidates is vital to optimize organ utilization and maximize post-transplant survival especially in highly heterogenic cohorts with underrepresented subgroups. Purpose: To evaluate the performance of a novel artificial intelligence method for assessing post-cardiac transplant survival in high risk and other underrepresented subgroups. Methods: "Trees of Predictors" (ToPs) is a machine learning method built on the principle that for specific subgroups of patients some features are more predictive of survival than other features, some features are more predictive for survival for a particular time horizon than for other time horizons. ToPs uses artificial intelligence to divide the population into subgroups (clusters) and discover these specific features and the specific predictors that perform best for each cluster. We tested ToPs performance on high risk heart transplant recipients such as elderly > 69 years, diabetics and recipients of a left ventricular assist device (LVAD) and other underrepresented recipients such as women who were included in the United Network for Organ Sharing (UNOS) database. Results: ToPs was applied to 51,971 adult patients included in the UNOS database between 1985 and 2015 for whom post-transplant follow up was available. Compared to commonly used risk assessment scores including risk-stratification score (RSS), donor risk index (DRI), and the index for mortality prediction after cardiac transplantation (IMPACT) as well as common machine learning methods, ToPs had better predictive accuracy for all study subgroups and time horizons post-transplant. C-index ± standard deviation for each score and time horizon is depicted in Table 1. Conclusion: For high risk and other underrepresented post cardiac transplant patients, ToPs provide improved survival prediction at all-time horizons via a personalized, non-linear and time specific approach to risk assessment. [ABSTRACT FROM AUTHOR]

Introduction: The use of continuous flow-ventricular assist devices (CF-VAD) in patients with heart failure continues to grow. CF-VAD implanted patients are at increased risk for complications, especially thrombosis and non-surgical bleeding, contributing to morbidity and mortality. This study aimed to identify potential biomarkers of hemostatic dysregulation that could predict thrombotic and hemorrhagic risk in CF-VAD patients. One such biomarker is microparticles (MP) generated from cellular activation. Methods: This study followed 16 patients implanted with a HeartMate II for one year. Blood samples were drawn at routine clinic visits beginning immediately after implant. Levels of platelet (P; CD41+), leukocyte (W; CD45+), erythrocyte (R; CD235+) and endothelial (E; CD146+) MPs were measured using flow cytometry. Platelet count, leukocyte count and INR were obtained from medical records. Blood samples from healthy individuals served as controls. Patient aggregate data was compared with normal values in terms of group means and statistical parameters. Results: Levels of all four microparticle subtypes were elevated in the CF-VAD patients (PMPs p <0.0001; WMPs p <0.0001; RMPs p <0.0003; EMPs p <0.0002) relative to healthy normals. While platelet counts fluctuated widely in individual patients, circulating platelet counts correlated with PMP levels (p =0.02). No correlations were noted between platelet count and other cellular microparticle subtypes or with leukocyte count or INR. Conclusion: This study demonstrates that CF-VAD implanted patients exhibit cellular activation resulting in the generation of specific microparticles of different origin. Platelet microparticle levels correlate with circulating platelet counts and may primarily contribute to the observed pathogenesis of the hemostatic process in these patients. [ABSTRACT FROM AUTHOR]

Introduction: Atrial fibrillation (AF) and heart failure (HF) often coexist but little is known on how AF burden associates with subsequent episodes of HF. Hypothesis: The aim of this study is to quantitatively assess the short- and long-term association of AF burden with subsequent episodes of HF events in cardiac resynchronization therapy (CRT) patients with reduced ejection fraction. Methods: A cohort study of CRT patients enrolled in the Medtronic Product Surveillance Registry with at least 90 days of Cardiac Compass data were included in the study. Time-dependent Cox regression was used to evaluate the association of short- and long-term AF burden. Short-term AF burden was defined as the change in the daily AF burden compared to the moving AF burden average since the time of implant. Long-term AF burden was defined as the overall average AF burden since the time of implant. Each patient with HF was matched to 2 control patients without HF event based on age, gender, year of implant and CRT defibrillation capability. Other covariates included intrathoracic impedance and ventricular pacing percentage. Results: Among 542 patients, 177 developed HF over an average follow-up of 24 ± 11 months. Short-term AF burdenwas associated with subsequent HF events (adjusted hazard ratio [aHR] for an increase in 1 hour/day of AF burden 1.05, 95% confidence interval [CI] 1.03-1.08, p-value <0.01). In contrast, there was no association between long-term AF burden and subsequent HF events (aHR for an increase in 1 hour/day of AF burden 1.01, 95% CI 0.99-1.03, p-value 0.28). The reduction of intrathoracic impedance was associated with subsequent HF events (aHR 0.85 for an increase in an ohm of intrathoracic impedance, 95% CI 0.83-0.86, p-value = <0.01). Conclusion: Every hour of increased AF burden is associated with a 5% increased risk of HF over the subsequent week (short-term), independent of intrathoracic impedance. These findings quantitate the association of AF burden with HF events and are consistent with a causal effect AF on HF episodes due to the temporal direction of the association. [ABSTRACT FROM AUTHOR]

Introduction: Implantable cardioverter defibrillators (ICD) and cardiac resynchronization therapy (CRT) for the treatment of heart failure with reduced ejection fraction (HFrEF) should only be considered after 3 to 6 months of optimal guideline-directed medical therapy (GDMT). This includes heart failure approved beta-blockers (HF-BB), ace inhibitors (ACE-I) or angiotensin II receptor blockers (ARB), and mineralocorticoid receptor antagonists (MRA) for select patients. Our study attempts to characterize the rates of GDMT delivery prior to device implantation in an urban academic hospital and identify potential quality improvement targets. Hypothesis: Prescription rates of HF-BB, ACE-I or ARB, and MRAs will be low prior to device implantation. Methods: We conducted a retrospective analysis of patients who underwent de novo ICD or CRT device implantation at our institution from January 2015 to July 2017. Charts were reviewed to obtain demographics, comorbidities, laboratory, imaging, and medication reconciliation data. We evaluated the rates of any GDMT use on admission as well as rates of two-drug and three-drug regimens. Results: Among 144 patients scheduled for ICD or CRT (mean age 60; 67% male; mean LVEF 27%), 83% were on a HF-BB, 83% were on an ACE-I/ARB, and 31% were on an MRA. Two-drug regimens (HF-BB and ACE-I /ARB) were seen in 69%, and three-drug regimens (HF-BB, ACE-I/ARB, and MRA) in 22%. Only 42% of HF-BBs and 26% of ACE-I/ARB were prescribed at ≥ 50% of the maximal dose. There was no significant difference in GDMT rates between men and women. In addition, the rate of GDMT did not differ from admission to discharge. Conclusion: The data indicate that patients admitted for heart failure device therapy are not receiving optimal GDMT. This presents an opportunity to assess the quality of care delivery at a juncture in the patient's treatment course. [ABSTRACT FROM AUTHOR]

Introduction: Ventricular arrhythmias are common in patients with advanced heart failure and a continuous flow left ventricular assist device (CF-LVAD) and result in a drop in device output, increased risk of device thrombosis and, if sustained, may lead to right heart failure. However, the effect of an implantable cardioverter defibrillator (ICD) on mortality in patients with CF-LVAD is not known and there is no consensus about the role of an ICD in these patients. Methods: We conducted a systematic literature review and meta-analysis to assess the effect of an ICD on mortality for patients with advanced heart failure and CF-LVAD. PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase were searched from inception through March 2018. Original studies of patients with a CF-LVAD that compared mortality among those with and without an ICD were included. The primary outcome was mortality. The analysis was done using a random-effects model. Hazard ratios are expressed with 95% confidence intervals (CIs). Results: Eight observational studies with a total of 5982 patients met inclusion criteria. An ICD was present in 3064 (51.2%) patients and there was no ICD in 2918 (48.8%) patients. Propensity score matching was done on the largest two observational studies with a total number of 5160 (86.2%) patients to ensure a targeted cohort with similar baseline characteristics. CF-LVAD was used as a bridge to heart transplantation in 73.7%. Meta-analysis showed no difference in mortality for patients using CF-LVAD with and without an ICD (HR: 0.94, 95% confidence interval (CI): [0.66 - 1.22]; p=0.203, I2=28.3%) Conclusions: Having an ICD was not associated with improved mortality for advanced heart failure patients with a CF-LVAD. However all included studies were observational. Randomized controlled study is needed to determine the effect of an ICD in patients with a CF-LVAD. [ABSTRACT FROM AUTHOR]