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Background: Hemocompatibility-related adverse events (HRAE) negatively influence survival. However, no study has examined the impact of these events on health-related quality of life (HRQOL) and functional outcomes following continuous-flow left ventricular assist device implantation (CF-LVAD). We assessed the impact of HRAE events on HRQOL and hypothesized that HRAE's adversely impact HRQOL and functional outcomes., Methods: INTERMACS database identified patients undergoing primary CF-LVAD implantation from 2008 to 2017. HRAEs included stroke, non-surgical bleeding, hemolysis, and pump thrombosis and were identified as defined in the literature. HRAEs were further stratified as Tier 1-2 and disabling stroke events. Time-series analysis was executed for HRAE patients with values pre-HRAE, post-HRAE, and closest to 12 months follow up. Local polynomial regression curves modeling individual patients were superimposed into "spaghetti" plots., Results: All HRQOL and functional metrics improved in patients over time, despite HRAE complications. However, these patient metrics were significantly reduced compared to the non-HRAE cohort. Advanced data visualization techniques noted a decline after experiencing an HRAE with a subsequent recovery to baseline levels or higher. Six-minute walk test (6MWT) was noted to be most affected in the post-HRAE period but recovered similar to other metrics., Conclusions: The burden of HRAE following CF-LVAD implantation did not negatively impact the quality of life. However, the 6MWT did not increase in the post-HRAE period in all HRAE patients. Improvement of heart failure symptoms after CF-LVAD coupled with optimal management following the HRAE act to preserve the enhanced quality of life., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: The LATERAL trial validated the safety and efficacy of the thoracotomy approach for implantation of the HeartWare HVAD System, leading to Food and Drug Administration approval. We sought to analyze 24-month adverse event (AE) rates, including a temporal analysis of the risk profile, associated with the thoracotomy approach for the HVAD system., Methods: AEs from the LATERAL trial were evaluated over 2 years postimplant. Data was obtained from the Interagency Registry for Mechanically Assisted Circulatory Support database for 144 enrolled United States and Canadian patients. Temporal AE profiles were expressed as events per patient year., Results: During 162.5 patient years of support, there were 25 driveline infections (0.15 events per patient year), 50 gastrointestinal bleeds (0.31 events per patient year), and 21 strokes (0.13 events per patient year). Longitudinal AE analysis at follow-up intervals of <30 and 30 to 180 days, and 6 to 12 and 12 to 24 months revealed the highest AE rate at <30 days, with a decrease in total AEs within the first 6 months. After 6 months, most AE rates either stabilized or decreased through 2 years, including a 95% overall freedom from disabling stroke., Conclusions: Two-year follow-up of the LATERAL trial revealed a favorable morbidity profile in patients supported with the HVAD system, as AE rates were more likely to occur in the first 30 days postimplant, and overall AE rates were significantly reduced after 6 months. Importantly, 2-year freedom from disabling stroke was 95%. These data further support the improving AE profile of patients on long-term HVAD support. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02268942.

Accurate right ventricle functional analysis prior to mechanical circulatory support continues to be valuable for preoperative stratification of patients at risk for developing right ventricular (RV) failure. While cardiac magnetic resonance imaging (CMR) remains the gold standard, CMR is limited by availability and patient-specific contraindications. Further investigation of other imaging modalities would be beneficial as it may serve as a surrogate to identifying RV systolic dysfunction. A single-center, retrospective study including 29 patients with advanced heart failure was performed. All patients underwent ventricular functional analysis with both CMR and echocardiography, and 19 patients underwent right heart catheterization. Predictability with multimodal assessment of RV function was determined using logistic regression methods. Of the 29 participants, 10 had severe RV dysfunction. Tricuspid annular plane of systolic excursion was a modest predictor of RV dysfunction with odd ratio (OR) of 0.07 (0.01-0.72) and c-statistic of 0.79. Invasive hemodynamic measurement of cardiac index by thermodilution method was also predictive of RV dysfunction but failed to reach statistical significance (OR of 0.03, <0.001-1.28) with c-statistic of 0.83. The role of invasive hemodynamic data in predicting RV function compared with CMR should be further explored among patients with advanced heart failure.

Following implantation of continuous-flow left ventricular assist devices, mechanical off-loading results in improved resting hemodynamics; however, peak exercise capacity generally does not increase substantially. This study evaluated patients supported by continuous-flow left ventricular assist devices who were invasively monitored during exercise to define parameters that underpin exercise capacity and outcomes. A review of all patients supported by continuous-flow left ventricular assist devices who underwent supine bicycle ergometry exercise testing with measurement of pulmonary gas exchange during right heart catheterization for evaluation of dyspnea at one institution between 2007 and 2018 was performed (n = 22). The primary outcome of this investigation was death or heart failure hospitalization. Although resting filling pressures were relatively preserved, resting cardiac index (Fick) was low (2.1 ± 0.5 mL/kg/min). An impaired cardiac output reserve was present in 75% of patients. On univariate modeling, patients with supine exercise-induced hypoxemia (O 2 saturation <90%) experienced significantly diminished hospitalization-free survival (unadjusted hazard ratio = 11.0, confidence interval = 2.4-57.2, p = 0.003), which persisted despite adjustment for right heart catheterization peak VO 2 and peak cardiac output (adjusted hazard ratio = 25, confidence interval = 3.6-322, p = 0.001). Our findings suggest that supine exercise testing provides additional prognostic utility in the continuous-flow left ventricular assist device population.

Mechanical circulatory support with implantable durable continuous-flow left ventricular assist devices (CF-LVADs) represents an established surgical treatment option for patients with advanced heart failure refractory to guideline-directed medical therapy. CF-LVAD therapy has been demonstrated to offer significant survival, functional, and quality-of-life benefits. However, nearly one-half of patients with advanced heart failure undergoing implantation of a CF-LVAD have important valvular heart disease (VHD) present at the time of device implantation or develop VHD during support that can lead to worsening right or left ventricular dysfunction and result in development of recurrent heart failure, more frequent adverse events, and higher mortality. In this review, we summarize the recent evidence related to the pathophysiology and treatment of VHD in the setting of CF-LAVD support and include a review of the specific valve pathologies of aortic insufficiency (AI), mitral regurgitation (MR), and tricuspid regurgitation (TR). Recent data demonstrate an increasing appreciation and understanding of how VHD may adversely affect the hemodynamic benefits of CF-LVAD support. This is particularly relevant for MR, where increasing evidence now demonstrates that persistent MR after CF-LVAD implantation can contribute to worsening right heart failure and recurrent heart failure symptoms. Standard surgical interventions and novel percutaneous approaches for treatment of VHD in the setting of CF-LVAD support, such as transcatheter aortic valve replacement or transcatheter mitral valve repair, are available, and indications to intervene for VHD in the setting of CF-LVAD support continue to evolve., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Long-term use of continuous-flow left ventricular assist devices may have negative consequences for autonomic, cardiovascular and gastrointestinal function. It has thus been suggested that non-invasive monitoring of arterial pulsatility in patients with a left ventricular assist device is highly important for ensuring patient safety and longevity. We have developed a novel, semi-automated frequency-domain-based index of arterial pulsatility that is obtained during suprasystolic occlusions of the upper arm: the 'cuff pulsatility index'., Purpose: The purpose of this study was to evaluate the relationship between the cuff pulsatility index and invasively determined arterial pulsatility in patients with a left ventricular assist device., Methods: Twenty-three patients with a left ventricular assist device with end-stage heart failure (six females: age = 65 ± 9 years; body mass index = 30.5 ± 3.7 kg m -2 ) were recruited for this study. Suprasystolic occlusions were performed on the upper arm of the patient's dominant side, from which the cuff pressure waveform was obtained. Arterial blood pressure was obtained from the radial artery on the contralateral arm. Measurements were obtained in triplicate. The relationship between the cuff pressure and arterial blood pressure waveforms was assessed in the frequency-domain using coherence analysis. A mixed-effects approach was used to assess the relationship between cuff pulsatility index and invasively determined arterial pulsatility (i.e. pulse pressure)., Results: The cuff pressure and arterial blood pressure waveforms demonstrated a high coherence up to the fifth harmonic of the cardiac frequency (heart rate). The cuff pulsatility index accurately tracked changes in arterial pulse pressure within a given patient across repeated measurements., Conclusions: The cuff pulsatility index shows promise as a non-invasive index for monitoring residual arterial pulsatility in patients with a left ventricular assist device across time.

Background Diastolic pulmonary gradient (DPG) was proposed as a better marker of pulmonary vascular remodeling compared with pulmonary vascular resistance (PVR) and transpulmonary gradient (TPG). The prognostic significance of DPG in patients requiring a left ventricular assist device (LVAD) remains unclear. We sought to investigate whether pre-LVAD DPG is a predictor of survival or right ventricular (RV) failure post-LVAD. Methods and Results We retrospectively reviewed 268 patients who underwent right heart catheterization before LVAD implantation from 2007 to 2017 and had pulmonary hypertension because of left heart disease. Patients were dichotomized using DPG ≥7 mm Hg, PVR ≥3 mm Hg, or TPG ≥12 mm Hg. The associations between these parameters and all-cause mortality or RV failure post LVAD were assessed with Cox proportional hazards regression and Kaplan-Meier analyses. After a mean follow-up time of 35 months, elevated DPG was associated with increased risk of RV failure (hazard ratio [HR]: 3.30; P=0.004, for DPG ≥7 versus DPG <7), whereas elevated PVR (HR 1.85, P=0.13 for PVR ≥3 versus PVR <3) or TPG (HR 1.47, P=0.35, for TPG ≥12 versus TPG <12) were not associated with the development of RV failure. Elevated DPG was not associated with mortality risk (HR 1.16, P=0.54, for DPG ≥7 versus DPG <7), whereas elevated PVR, but not TPG, was associated with higher mortality risk (HR 1.55; P=0.026, for PVR ≥3 versus PVR <3). Conclusions Among patients with pulmonary hypertension because of left heart disease requiring LVAD support, elevated DPG was associated with RV failure but not survival, while elevated PVR predicted mortality post LVAD implantation.

Despite the growing acceptance of left ventricular assist device (LVAD) therapy to improve survival and quality of life in heart failure (HF) patients, uncertainties persist regarding the definition of a successful implant. We sought to define an innovative approach to assess success and subsequently compare preoperative variables affecting outcomes. From January 2007 to 2015, 278 patients underwent LVAD implantation. Median age at implant was 62 years and 81% patients were males. Indication for support was bridge-to-transplantation in 36% patients and the etiology of HF was ischemic in 49% patients. Based on clinically relevant and accepted standards, we defined successful LVAD implant as someone who was alive or transplanted at 2 years, had two or less readmissions in the first year, had no major adverse events in the first year, and had a New York Heart Association class of ≤ II at 6 months. Follow-up was obtained for a median of 1.7 years for a total of 605 patient-years-of-support. Based on our criteria, 81/278 (29%) patients were defined as having a successful implant. Univariate predictors of LVAD failure included destination therapy indication (hazard ratio [HR] = 2.11 [1.24, 3.58]), ischemic cardiomyopathy (HR = 1.73 [1.02, 2.94]), and a higher left ventricular ejection fraction (HR = 1.54 [1.07, 2.22]). After multivariable analysis, only destination therapy indication (HR = 2.2 [1.28, 3.78]) was found to be independently predictive of success failure. Despite an overall trend toward improved outcomes on device therapy, our criteria classified only one-third of patients as successful. Continued improvements in adverse event profiles, appropriate patient selection, and optimal time of implantation, together hold the key to improve outcomes after LVAD therapy.

Objective: To examine the frequency and outcomes of patients requiring renal replacement therapy (RRT) early after left ventricular assist device (LVAD) implantation., Patients and Methods: We examined use of in-hospital RRT and outcomes in consecutive adults who underwent continuous-flow LVAD implantation from February 15, 2007, through August 8, 2017. Logistic regression was used to examine predictors of RRT. The associations of RRT with outcomes were examined using Cox proportional hazards regression., Results: Of 354 patients who underwent LVAD implantation, 54 (15%) required in-hospital RRT. Patients receiving RRT had higher preoperative Charlson Comorbidity Index values (median, 5 vs 4; P=.03), Model for End-Stage Liver Disease scores (mean, 19.0 vs 14.5; P<.001), right atrial pressure (mean, 19.1 vs 13.4 mm Hg; P<.001), and estimated 24-hour urine protein levels (median, 357 vs 174 mg; P<.001) and lower preoperative estimated glomerular filtration rate (eGFR) (median, 43 vs 57 mL/min; P<.001) and measured GFR using 125 I-iothalamate clearance (median, 33 vs 51 mL/min; P=.001) than those who did not require RRT. Approximately 40% of patients with eGFR less than 45 mL/min/1.73 m 2 and 24-hour urine protein level greater than 400 mg required RRT vs 6% with eGFR greater than45 mL/min/1.73 m 2 and without significant proteinuria. Lower preoperative eGFR, higher estimated 24-hour urine protein level, higher right atrial pressure, and longer cardiopulmonary bypass time were independent predictors of RRT after LVAD implantation. Of patients requiring in-hospital RRT, 18 (33%) had renal recovery, 18 (33%) required outpatient hemodialysis, and 18 (33%) died before hospital discharge. After median (Q1, Q3) follow-up of 24.3 (8.9, 49.6) months, RRT was associated with increased risk of death (adjusted hazard ratio [HR], 2.86; 95% CI, 1.90-4.33; P<.001) and gastrointestinal bleeding (adjusted HR, 4.47; 95% CI, 2.57-7.75; P<.001)., Conclusion: In-hospital RRT is associated with poor prognosis after LVAD. A detailed preoperative assessment of renal function before LVAD may be helpful in risk stratification and patient selection., (Published by Elsevier Inc.)

Background: Previous studies on readmissions after left ventricular assist device (LVAD) implantation have focused on hospital readmissions after dismissal from the index hospitalization. Because few data exist, the purpose of this study was to examine intensive care unit (ICU) readmissions in patients during their initial hospitalization for LVAD implantation to determine reasons for, factors associated with, and incidence of mortality after ICU readmission., Methods: A retrospective analysis was performed from February 2007 to March 2015 of patients at our institution receiving first-time LVAD implantation. After LVAD implantation, patients dismissed from the ICU who then required ICU readmission before hospital dismissal were compared to those not requiring ICU readmission before hospital dismissal with respect to preoperative, intraoperative, and postoperative factors., Results: Among 287 LVAD patients, 266 survived their initial ICU admission, of which 49 (18.4%) required ICU readmission. The most common reasons for readmission were bleeding and respiratory failure. Factors found to be univariably associated with ICU readmission were preoperative hemoglobin, preoperative aspartate aminotransferase, preoperative atrial fibrillation, preoperative dialysis, longer cardiopulmonary bypass times, and higher intraoperative allogeneic blood transfusion requirements. Multivariable analysis revealed ICU readmission to be independently associated with preoperative dialysis (odds ratio, 12.86; 95% confidence interval, 3.16-52.28; P < .001). Overall mortality at 1 year was 22.6%. Survival after hospital dismissal was worse for patients who required ICU readmission during the index hospitalization (adjusted hazard ratio, 2.35; 95% confidence interval, 1.15-4.81; P = .019)., Conclusions: ICU readmission after LVAD implantation occurred relatively frequently and was significantly associated with 1-year mortality after hospital dismissal. These data can perhaps be used to identify subsets of LVAD patients at risk for ICU readmission and may lead to implementation of practice changes to mitigate ICU readmissions. Future larger and prospective studies are warranted.

Background: The HeartWare centrifugal-flow ventricular assist device system (HVAD) is a viable option for treatment of advanced heart failure. There is a growing trend toward the use of less invasive techniques in cardiac surgery, and the thoracotomy technique for HVAD implantation may provide benefits not available with conventional approaches., Methods: The LATERAL trial is a multicenter, prospective, non-randomized, single-arm trial that utilized data from 144 patients enrolled in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database at 26 centers in the United States and Canada. The primary composite end-point was success at 180 days defined as alive on the originally implanted device and free from disabling stroke (modified Rankin Scale score >3), transplanted or explanted for recovery. The key secondary end-point was mean length of initial hospital stay., Results: The primary end-point was successfully achieved in 88.1% of patients and was significantly greater than the pre-defined performance goal of 77.5% set from historical sternotomy data (p = 0.0012). The key secondary end-point-mean length of initial hospital stay -was 18 days and was significantly shorter than the pre-defined performance goal of 26.1 days obtained from historical sternotomy data (p < 0.0001). The adverse event profile further demonstrated the safety of the thoracotomy approach. The overall patient survival was good, and bleeding requiring reoperation was significantly less frequent than that observed in previous studies using the sternotomy approach., Conclusions: This prospective clinical trial provides validation that implantation of the HVAD system via the thoracotomy approach used in the LATERAL study represents a safe and effective alternative to median sternotomy in selected patients intended for a bridge-to-transplant indication., (Copyright © 2019. Published by Elsevier Inc.)

Importance: Left ventricular assist device (LVAD) therapy improves myocardial function, but few patients recover sufficiently for explant, which has focused attention on stem cells to augment cardiac recovery., Objective: To assess efficacy and adverse effects of intramyocardial injections of mesenchymal precursor cells (MPCs) during LVAD implant., Design, Setting, and Participants: A randomized phase 2 clinical trial involving patients with advanced heart failure, undergoing LVAD implant, at 19 North American centers (July 2015-August 2017). The 1-year follow-up ended August 2018., Interventions: Intramyocardial injections of 150 million allogeneic MPCs or cryoprotective medium as a sham treatment in a 2:1 ratio (n = 106 vs n = 53)., Main Outcomes and Measures: The primary efficacy end point was the proportion of successful temporary weans (of 3 planned assessments) from LVAD support within 6 months of randomization. This end point was assessed using a Bayesian analysis with a predefined threshold of a posterior probability of 80% to indicate success. The 1-year primary safety end point was the incidence of intervention-related adverse events (myocarditis, myocardial rupture, neoplasm, hypersensitivity reactions, and immune sensitization). Secondary end points included readmissions and adverse events at 6 months and 1-year survival., Results: Of 159 patients (mean age, 56 years; 11.3% women), 155 (97.5%) completed 1-year of follow-up. The posterior probability that MPCs increased the likelihood of successful weaning was 69%; below the predefined threshold for success. The mean proportion of successful temporary weaning from LVAD support over 6 months was 61% in the MPC group and 58% in the control group (rate ratio [RR], 1.08; 95% CI, 0.83-1.41; P = .55). No patient experienced a primary safety end point. Of 10 prespecified secondary end points reported, 9 did not reach statistical significance. One-year mortality was not significantly different between the MPC group and the control group (14.2% vs 15.1%; hazard ratio [HR], 0.89; 95%, CI, 0.38-2.11; P = .80). The rate of serious adverse events was not significantly different between groups (70.9 vs 78.7 per 100 patient-months; difference, -7.89; 95% CI, -39.95 to 24.17; P = .63) nor was the rate of readmissions (0.68 vs 0.75 per 100 patient-months; difference, -0.07; 95% CI, -0.41 to 0.27; P = .68)., Conclusions and Relevance: Among patients with advanced heart failure, intramyocardial injections of mesenchymal precursor cells, compared with injections of a cryoprotective medium as sham treatment, did not improve successful temporary weaning from left ventricular assist device support at 6 months. The findings do not support the use of intramyocardial mesenchymal stem cells to promote cardiac recovery as measured by temporary weaning from device support., Trial Registration: clinicaltrials.gov Identifier: NCT02362646.

Background Left ventricular (LV) hemodynamic assessment has been sparsely performed in patients supported on continuous-flow LV assist devices (cf LVADs ). Insight into dynamic changes of left heart parameters during ramp studies may improve LV assist device optimization and evaluate pathology. Methods and Results To complement right heart catheterization, a novel technique for left heart catheterization in patients with a cf LVAD was developed. Patients implanted with cf LVAD s underwent hemodynamic ramp left heart catheterization and right heart catheterization with transthoracic echocardiography. Continuous aortic and LV pressures were measured along with right atrial, pulmonary artery, and pulmonary capillary wedge pressures. A novel index, the transaortic gradient ( TAG ) was established. Thirty eight patients with cf LVADs were evaluated at a median of 446 days (interquartile range, 183-742) after device implant. During left heart catheterization performed for hemodynamic optimization, drop-in LV end-diastolic pressure and pulmonary capillary wedge pressure were associated with a rise in TAG . A range was identified for TAG (20-40 mm Hg) as providing the most optimal level of hemodynamic offloading. Pathologic states deviated from normal responses to ramp. LV assist device thrombosis was associated with an inability to increase in TAG during speed ramp. Significant aortic insufficiency was associated with a marked increase in LV end-diastolic pressure despite a concomitant decrease in pulmonary capillary wedge pressure with increasing LV assist device speeds. Conclusions Inclusion of left heart catheterization to a typical right heart catheterization LV assist device ramp protocol imparted unique insights to optimize cf LVAD speeds in different clinical scenarios. A novel index, the TAG was defined and provided additional resolution to optimized offloading.

Aim: The lungs-and particularly the alveolar-capillary membrane-may be sensitive to continuous flow (CF) and pulmonary pressure alterations in heart failure (HF). We aimed to investigate long-term effects of CF pumps on respiratory function., Methods and Results: We conducted a retrospective study of patients with end-stage HF at our institution. We analysed pulmonary function tests [e.g. forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 )] and diffusing capacity of the lung for carbon monoxide (D LCO ) from before and after left ventricular assist device (LVAD) implantation and compared them with invasive haemodynamic studies. Of the 274 patients screened, final study analysis involved 44 patients with end-stage HF who had CF LVAD implantation between 1 February 2007 and 31 December 2015 at our institution. These patients [mean (standard deviation, SD) age, 50 (9) years; male sex, n = 33, 75%] received either the HeartMate II (Thoratec Corp.) pump (77%) or the HeartWare (HeartWare International Inc.) pump. The mean (SD) left ventricular ejection fraction was 21% (13%). At a median of 237 days post-LVAD implantation, we observed significant D LCO decrease (-23%) since pre-implantation (P < 0.001). ΔD LCO had an inverse relationship with changes in pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP) from pre-LVAD to post-LVAD implantation: ΔD LCO to ΔPCWP (r = 0.50, P < 0.01) and ΔD LCO to ΔRAP (r = 0.39, P < 0.05). We observed other reductions in FEV 1 , FVC, and FEV 1 /FVC between pre-LVAD and post-LVAD implantation. In mean (SD) values, FEV 1 changed from 2.3 (0.7) to 2.1 (0.7) (P = 0.005); FVC decreased from 3.2 (0.8) to 2.9 (0.9) (P = 0.01); and FEV 1 /FVC went from 0.72 (0.1) to 0.72 (0.1) (P = 0.50). Landmark survival analysis revealed that ΔD LCO from 6 months after LVAD implantation was predictive of death for HF patients [hazard ratio (95% confidence interval), 0.60 (0.28-0.98); P = 0.03]., Conclusions: Pulmonary function did not improve after LVAD implantation. The degree of D LCO deterioration is related to haemodynamic status post-LVAD implantation. The ΔD LCO within 6 months post-operative was associated with survival., (© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

The gold standard for noninvasive blood pressure (BP) measurement, the Doppler technique, does not provide systolic blood pressure (SBP) and diastolic blood pressure (DBP) and may limit therapy outcomes. To improve patient care, we tested specifically designed experimental BP (ExpBP) monitor and the Doppler technique by comparing noninvasive measures to the intraarterial (I-A) BP in 31 patients with end-stage heart failure (4 females) 2.6 ± 3.4 days post-LVAD implantation (20 HeartMate II and 11 HeartWare). Bland-Altman plots revealed that the ExpBP monitor overestimated mean arterial pressure (MAP) by 1.2 (4.8) mm Hg (mean difference [standard deviation]), whereas the Doppler by 6.7 (5.8) mm Hg. The ExpBP SBP was overestimated by 0.8 (6.1) mm Hg and DBP by 1.9 (5.3) mm Hg compared with the respective I-A pressures. Both techniques achieved similar measurement reliability. In the measurement "success rate" expressed as a frequency (percent) of readable BP values per measurement attempts, Doppler accomplished 100% vs. 97%, 97%, and 94% of successful detections of MAP, SBP, and DBP provided by the ExpBP monitor. The ExpBP monitor demonstrated higher accuracy in the MAP assessment than the Doppler in addition to providing SBP and DBP in majority of subjects. Improved BP control may help to mitigate related neurologic adverse event rates.

Background: The FOXO3a (forkhead box O3a)-BNIP3 (B-cell lymphoma 2/adenovirus E1B 19kDa interacting protein 3) pathway modulates mitochondrial dynamics and function and contributes to myocardial remodeling in rodent models of heart failure. We sought to investigate the expression of this pathway along with the expression of mitochondrial biogenesis (PGC-1α [peroxisome proliferator-activated receptor-γ coactivator-1α]), dynamics (DRP-1 [dynamin-related protein 1], OPA-1 [optic atrophy 1], and MFN 2 [mitofusin 2]), and oxidative phosphorylation (citrate synthase and electron transport chain complexes) markers and COX IV (cytochrome C oxidase) activity in myocardium from patients with valvular or ischemic heart disease and heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF)., Methods and Results: Subepicardial left ventricular biopsies (10×1×1 mm 3 ) were obtained at aortic valve replacement (HFpEF AVR , n=5; and HFrEF AVR , n=4), coronary artery bypass grafting (HFpEF CABG , n=5; and HFrEF CABG , n=5), or left ventricular assist device implantation (HFrEF LVAD , n=4). Subepicardial biopsies from patients with normal left ventricular function (n=2) and from donor hearts (n=3) served as controls (normal). Relative to normal, mitochondrial fragmentation and cristae destruction were evident, and mitochondrial area was decreased in HFpEF; 1.00±0.09 versus 0.71±0.08; P=0.016. These mitochondrial morphological changes were more pronounced in HFrEF (0.54±0.06); P=0.002 HFpEF versus HFrEF. BNIP3 (monomer+dimer) expression was increased in HFpEF (3.99±2.44) and in HFrEF (5.19±1.70) relative to normal; P=0.004 and P<0.001, respectively. However, BNIP3 monomer was increased in HFrEF (4.32±1.43) compared with normal (0.99±0.06) and HFpEF (1.97±0.90); P=0.001 and 0.004, respectively. The HFrEF group uniquely showed increase in DRP-1 expression (1.94±0.38) and decreases in PGC-1α expression (0.61±0.07) and COX IV activity (0.70±0.10) relative to normal; P=0.013, P<0.001, and P<0.001, respectively, with no significant change in electron transport chain complexes expression., Conclusions: These findings in human myocardium confirm studies in rodents where contractile dysfunction is associated with activation of the FOXO3a-BNIP3 pathway and altered mitochondrial dynamics, biogenesis, and function.

Continuous-flow left ventricular assist devices (CF-LVADs) have revolutionized the management of patients with advanced heart failure. Alternative implant strategies are increasingly used for device placement. We reviewed our experience from the Mechanical Circulatory Support Research Network registry with the HeartWare centrifugal CF-LVAD (HVAD). From May 2004 to August 2015, 1,150 patients underwent primary CF-LVAD implantation at our institutions. Within this group, a total of 283 patients (25%) were implanted with the HVAD. A minimally invasive left lateral thoracotomy (MILT) implant strategy was used in 53 patients (20%), of which 22 (42%) were implanted off-pump. Median age at implant was 59 years and 183 patients (65%) were implanted as bridge-to-transplantation. Follow-up was 100% complete for a total of 302 patient-years of support. In-hospital mortality was 4.9% (14 patients), and was comparable between the conventional sternotomy (CS) and MILT cohorts (p = 0.15). Patients in the MILT cohort had a shorter median length of stay (p < 0.01) and had a lower incidence of postimplant pump thrombus (p = 0.02). Cumulative survival at the end of follow-up reached 84%, and was comparable between the two groups (p = 0.298). Multivariate analysis identified preoperative bilirubin level as the only independent predictor of survival. Surgical technique had no impact on survival. In this large, multicenter experience, data demonstrate excellent survival and adverse event profiles for patients supported with the HVAD technology, regardless of surgical implant technique. With constant advancements in device technology along with our increasing clinical experience with the newer techniques, minimally invasive LVAD implantation continues to evolve as a valuable alternative to CS in selected patients.

Although improvement in cardiac output and hemodynamic parameters is routinely demonstrated in patients implanted with continuous-flow left ventricular assist devices (CF-LVADs), improvement in exercise capacity is inconsistently seen. Our purpose was to determine whether native cardiac factors, LVAD factors, or comorbid factors were associated with lack of improvement. Review of all patients undergoing preimplant cardiopulmonary exercise testing (CPET) and CPET on LVAD therapy at one institution was performed between 2007 and 2014 (n = 49). Comprehensive assessment of echocardiographic parameters, right heart catheterization data, medications, and comorbid illness was undertaken. There was no mean improvement in peak oxygen consumption (VO2; 11.8-12.4 ml/kg/min; p = 0.26), although exercise time (5.1 [46% predicted] to 5.8 min [56% predicted]; p = 0.02) and nadir of the ratio of minute ventilation to carbon dioxide production slope (VE/VCO2; 39-36; p = 0.001) improved. Factors most strongly associated with improvement in VO2 were Heartmate II pulsatility index (PI; R = 0.48; p = 0.001), power (R = -0.40; p = 0.009), pump flow (R = -0.40; p = 0.008), and pump speed (R = -0.32; p = 0.04). Peak heart rate (HR) was also associated with improvement in VO2 (R = 0.41; p = 0.004). Left ventricular ejection fraction (LVEF; R = 0.004; p = 0.77), right ventricular (RV) function (R = 0.22; p = 0.28), and aortic valve opening (R = 0.20; p = 0.57) were not associated with improvement in VO2. Our data suggest that less reliance on LVAD support was modestly associated with improvement in exercise capacity. Further studies should seek to determine the optimal level of device support prospectively in relation to exercise capacity.

Objective: To investigate differences in invasive hemodynamic parameters and outcomes in patients with and without heart failure (HF) symptoms after left ventricular assist device (LVAD) implantation., Patients and Methods: We performed a single-center retrospective analysis of 51 symptomatic patients and 50 patients with resolved HF symptoms who underwent right-sided heart catheterization (RHC) after LVAD implantation from March 1, 2007, through June 30, 2016. Patient characteristics and outcomes including all-cause mortality and right ventricular (RV) failure were compared between groups., Results: Fifty-one patients had development of HF symptoms after LVAD implantation and underwent RHC a mean ± SD of 243.7±288 days postoperatively. Fifty asymptomatic LVAD recipients underwent routine RHC 278.6±205 days after implantation. Compared with patients who had resolved HF symptoms, symptomatic patients were older, more likely to be male, and more likely to have ischemic cardiomyopathy. Symptomatic patients had higher right atrial pressure (P<.001), mean pulmonary arterial pressure (P<.001), and pulmonary capillary wedge pressure (P<.001). Improvements in right atrial pressure, mean pulmonary arterial pressure, and pulmonary capillary wedge pressure before and after LVAD implantation were less remarkable in symptomatic patients. The frequency of RV dysfunction was significantly higher among symptomatic patients than patients with resolved HF symptoms (P=.001). Symptomatic patients displayed significantly higher risk of all-cause mortality (hazard ratio, 3.0; 95% CI, 1.3-6.5; P=.007) and RV failure (hazard ratio, 6.2; 95% CI, 1.3-29.7; P=.02) independent of other predictors of outcome., Conclusion: Patients with recurrent HF symptoms after LVAD implantation display more profound hemodynamic derangements, greater burden of RV failure, and increased rates of all-cause mortality compared with LVAD recipients with resolved HF symptoms., (Copyright © 2018 Mayo Foundation for Medical Education and Research. All rights reserved.)

Background: Adults with congenital heart disease represent an expanding and unique population of patients with heart failure (HF) in whom the use of mechanical circulatory support (MCS) has not been characterized. We sought to describe overall use, patient characteristics, and outcomes of MCS in adult congenital heart disease (ACHD)., Methods: All patients entered into the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) between June 23, 2006, and December 31, 2015, were included. Patients with ACHD were identified using pre-operative data and stratified by ventricular morphology. Mortality was compared between ACHD and non-ACHD patients, and multivariate analysis was performed to identify predictors of death after device implantation., Results: Of 16,182 patients, 126 with ACHD stratified as follows: systemic morphologic left ventricle (n = 63), systemic morphologic right ventricle (n = 45), and single ventricle (n = 17). ACHD patients were younger (42 years ± 14 vs 56 years ± 13; p < 0.0001) and were more likely to undergo device implantation as bridge to transplant (45% vs 29%; p < 0.0001). A higher proportion of ACHD patients had biventricular assist device (BiVAD)/total artificial heart (TAH) support compared with non-ACHD patients (21% vs 7%; p < 0.0001). More ACHD patients on BiVAD/TAH support were INTERMACS profile 1 compared with patients on systemic left ventricular assist device (LVAD) support (35% vs 15%; p = 0.002). ACHD and non-ACHD patients with LVADs had similar survival; survival was worse for patients on BIVAD/TAH support. BiVAD/TAH support was the only variable independently associated with mortality (early phase hazard ratio 4.4; 95% confidence interval, 1.8-11.1; p = 0.001). For ACHD patients receiving MCS, ventricular morphology was not associated with mortality., Conclusions: ACHD patients with LVADs have survival similar to non-ACHD patients. Mortality is higher for patients requiring BiVAD/TAH support, potentially owing to higher INTERMACS profile. These outcomes suggest a promising role for LVAD support in ACHD patients as part of the armamentarium of therapies for advanced HF., (Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Device indications have changed for placement of continuous-flow left ventricular assist devices (CF-LVADs). We performed a multicenter analysis evaluating temporal variations in outcomes after CF-LVAD implantation., Methods & Results: We retrospectively defined 3 time intervals to reflect changes in CF-LVAD technology (period 1, 2004-2009; period 2, 2010-2012; and period 3, 2012-2014). A total of 1,064 patients (Heartmate II [HMII] = 835; Heartware [HVAD] = 229) underwent CF-LVAD implantation from May 2004 to October 2014. Device utilization was different between periods: period 1: HMII = 134 (100%); period 2: HMII = 480 (88%) and HW = 63 (12%); and period 3: HMII = 221 (57%) and HW = 166 (43%); P < .001. Despite few baseline group differences, adjusted survivals were similar among the time periods (P = .96). Adjusted multivariable analysis revealed age (per 10-year increase) and Interagency Registry for Mechanically Assisted Circulatory Support category (1 vs all others) as the only independent predictors of mortality: P < .001 and P = .008, respectively. Furthermore, it also showed the later periods to be at an increased risk of adverse events: 1) pump thrombosis (periods 2 and 3); and 2) gastrointestinal bleeding (period 3)., Conclusions: Despite significant differences in device types, indications, and patient characteristics, post-implantation survivals were similar across time intervals. The most recent cohort seems to be at an increased risk of gastrointestinal bleeding and pump thrombosis., (Published by Elsevier Inc.)

Background: Diabetes mellitus (DM) is a risk factor for morbidity and mortality in patients with heart failure. The effect of DM on post-left ventricular assist device (LVAD) implantation outcomes is unclear. This study sought to investigate whether patients with DM had worse outcomes than patients without DM after LVAD implantation and whether LVAD support resulted in a better control of DM., Methods and Results: We retrospectively reviewed 341 consecutive adults who underwent implantation of LVAD from 2007 to 2016. Patient characteristics and adverse events were studied and compared between patients with and without DM. One hundred thirty-one patients (38%) had DM. Compared with patients without DM, those with DM had higher rates of ischemic cardiomyopathy, LVAD implantation as destination therapy, and increased baseline body mass index. In a proportional hazards (Cox) model with adjustment for relevant covariates and median follow-up of 16.1 months, DM was associated with increased risk of all-cause mortality (hazard ratio, 1.73; 95% confidence interval: 1.18-2.53; P =0.005) and increased risk of nonfatal LVAD-related complications, including a composite of stroke, pump thrombosis, and device infection (hazard ratio, 2.1; 95% confidence interval: 1.35-3.18; P =0.001). Preoperative hemoglobin A1c was not significantly associated with mortality or adverse events among patients with DM. LVAD implantation resulted in a remarkable decrease in hemoglobin A1c levels (7.4±1.9 pre-LVAD versus 6.0±1.5 and 6.3±1.4 after 3 and 12 months post-LVAD, respectively; P <0.0001) and a significant reduction in requirements of DM medications., Conclusions: DM is associated with increased rates of all-cause mortality and major adverse events despite favorable glycemic control after LVAD implantation., (© 2017 American Heart Association, Inc.)

Objectives: This study examined patient outcomes after left ventricular assist device (LVAD) implantation across a range of center surgical volumes., Background: In order for a center to qualify for reimbursement, Centers for Medicare and Medicaid Services (CMS) requires it to implant ≥10 LVADs or total artificial hearts over a 3-year period. The impact of center LVAD surgical volumes on patient outcomes has not been thoroughly scrutinized., Methods: Center volumes were provided for 7,416 patients undergoing LVAD implantation who were enrolled in INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). Center LVAD volume was categorized as either very low (≤10 implants/year, n = 617), low (11 to 30 implants/year, n = 2,561), medium (31 to 50 implants/year, n = 2,458), or high (>50 implants/year, n = 1,750). The main outcome of interest was patient survival based on center volume derived from Kaplan-Meier and multivariate Cox regression., Results: Overall survival was associated with center volume (p = 0.003), as follows: 71 ± 1.8% (very low volume), 81 ± 0.8% (low volume), 83 ± 0.8% (medium volume), and 79 ± 1.0% (high volume) at 1 year. Compared with medium volume centers, the 90-day mortality was higher in very low volume (odds ratio [OR]: 1.35; p = 0.04) and high volume (OR: 1.28; p = 0.018) VAD centers. The adjusted hazard ratios (HRs) for mortality were 1.32 (95% confidence interval [CI]: 1.11 to 1.56), 1.07 (95% CI: 0.95 to 1.21), and 1.17 (95% CI: 1.03 to 1.30) for very low, low, and high volume centers, respectively. Center volume did not predict mortality (p = 0.25; n = 3,688) in INTERMACS profile 1 patients (patients who had sustained cardiogenic shock) and profile 2 patients (patients with progressive hemodynamic decline despite inotropes)., Conclusions: Center volume correlates with post-VAD survival, with worse survival noted at very-low volume centers. These findings suggest that current U.S. VAD center standards warrant reconsideration., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Durability of the percutaneous driveline is critical for the optimal long-term support of patients after left ventricular assist device (LVAD) implantation. There are no data specifically examining the durability of major repair for driveline fracture or its effect on patient outcomes. Between May 2004 and August 2014, 560 patients underwent implantation with the HeartMate II LVAD at our respective institutions. Median age at LVAD implantation was 59 years (range 18-82 years) and 465 patients (83%) were male. The indication for LVAD implantation was bridge to transplant (BTT) in 296 patients (53%). Follow-up was available in all early survivors (n = 519) for a total of 940 patient-years of support (median 1.1 years, max. 10.4 years). Percutaneous driveline fracture was identified in 17 patients (3.2%), eight of whom were implanted as destination therapy. Median time from LVAD implantation to driveline fracture was 1.3 years (range, from 4 months to 3.8 years). Two of these patients underwent device exchange as primary treatment, while 15/17 (88%) underwent repair. Three of these 15 patients required a driveline reintervention, including device exchange (n = 1), rerepair (n = 1), and ungrounded cables (n = 1). Median time of support after driveline repair was 10 months (range from 3 months to 5.4 years). There were no late deaths after driveline repair during the follow-up period with 14/15 patients (93%) active on support and one having undergone transplant. The incidence of percutaneous driveline fracture after HeartMate II LVAD implantation is low (3.9%). The majority of driveline repairs for driveline fracture are durable with reintervention required in a minority of patients. There was no adverse effect of driveline fracture requiring repair on late outcome noted in this series with all patients either active on support or transplanted at last follow-up.

Renal function improves early after left ventricular assist device (LVAD) implantation but later decline has been observed. We sought to determine the occurrence and evaluate possible causes for this decline. In 62 consecutive patients with HeartMateII LVAD with available calculated glomerular filtration rate (GFR, ml/min/1.73 m) 1 year after implant, GFR was assessed repeatedly and possible predictors for decline from 3 to 12 months were investigated. Post-mortem renal specimens for patients supported with an LVAD were evaluated. GFR 54.5 ± 19.5 at admission increased to 66.4 ± 22.3 preoperatively and to 79.2 ± 30.1 ~1 month after implantation. Subsequently at ~3 months GFR declined to 74.7 ± 25.4, at ~6 months to 68.8 ± 23.1, and ~1 year after implant to 63.9 ± 17.7. Glomerular filtration rate at 1 year was significantly lower (p < 0.0001, p < 0.0001, p = 0.005) than GFR 1, 3, and 6 months after implant. Early rise in GFR after surgery was not associated with late decline. Shorter bypass time (β = -0.09, p = 0.048) and higher albumin 3 months after LVAD (β = 14.4, p = 0.025) were significantly associated with less later decline in GFR. Arteriosclerosis was identified in autopsy renal specimens. In conclusion, early gains in renal function after LVAD implant are not sustained in many patients. Patient, device, and operative factors may influence long-term renal function in these patients.

Background: Axial configuration (AC) and centrifugal configuration (CC) left ventricular assist devices (LVAD) have different flow characteristics, and whether the interaction between device flow configuration and the pre-operative left ventricular internal diastolic diameter (LVIDD) mediates adverse events after LVAD implantation is unknown., Methods: We queried 9,424 continuous-flow LVAD recipients who received LVADs from April 2008 to June of 2015 in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). The pre-operative LVIDD * flow configuration interaction term was tested in multivariable models to determine its relationship to adverse events., Results: The pre-operative LVIDD * flow configuration interaction was a significant predictor of device thrombosis. As the LVIDD increased, the risk of AC device thrombosis increased compared with CC devices (p = 0.0099). At 7.0 cm, the hazard ratio (HR) for AC device thrombosis compared with the CC device was 1.61 (95% confidence interval [CI], 1.17-2.22; p = 0.004) and continued to rise as the LVIDD increased. The LVIDD * flow configuration interaction did not predict stroke, gastrointestinal bleeding, or patient survival. In multivariable models, the hazard of stroke was higher with the CC device regardless of the LVIDD (HR, 1.96; 95% CI, 1.64-2.36; p < 0.0001). Adjusted analyses showed LVAD implantation into a larger left ventricle was associated with a lower risk of death (HR, 0.90; 95% CI, 0.85-0.95; p = 0.0004) per centimeter of LVIDD., Conclusions: Our study suggests that the pre-operative LVIDD, flow configuration, and interaction terms should be considered individually when choosing the appropriate LVAD to mitigate the rates of device thrombosis, stroke, and death., (Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Analyses of the HeartMate II left ventricular assist device are routinely performed after explant if returned to the manufacturer. Findings from manufacturer-reported pump analyses have not been correlated with pre-explant serum lactate dehydrogenase (LDH) values., Methods: Between May 2004 and December 2014, 502 patients underwent primary HeartMate II implantation. Seventy pumps were explanted in 58 patients and returned to the manufacturer for pump analysis: 51 (73%) for suspected pump thrombosis, 12 (17%) for device-related infection, and 7 (13%) for percutaneous lead fracture. Median time from implant to explant was 12.4 months (range, 1 to 57 months)., Results: Pump thrombus was confirmed in 53 of 70 pumps (76%). Stratified by major clinical indications for explant of suspected pump thrombus or infection and lead fracture, the presence of pump thrombus was identified in 47 of 51 (92%) and 6 of 19 (32%), respectively. The median of 1) all LDH values, 2) maximum LDH values, and 3) interval change in LDH between 6 and 2 months before device explant were 1,061, 1,940, and -27 IU/L with thrombus present and 533, 504, and 13 IU/L in the absence of thrombus. Density estimation of LDH concentrations identified that a LDH value of 1,155 IU/L in the 6 months preceding pump thrombus had a 78% sensitivity and 90% specificity for findings of pump thrombus at the time of pump analysis., Conclusions: Pre-explant LDH concentrations significantly correlated with findings on manufacture-performed pump analysis. These data validate LDH surveillance as an important clinical tool for identification of pump thrombus., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Earlier studies have demonstrated disparities in patients undergoing left ventricular assist device (LVAD) implantation when stratified according to sex and race. Because very few data exist from large investigations, we reviewed data from the registry of the Mechanical Circulatory Support Research Network., Methods: Between May 2004 and September 2014, 734 patients underwent primary LVAD implantation at our institutions. Median age at implant was 57 (range 18 to 82) years and there were 577 males (80%). Race included Caucasian (C) in 586 patients (82%), African-American (AA) in 112 (16%), and other (O) in 21 (3%). Between sexes, significant pre-operative differences most commonly included median age at implant (males 60 years, females 57 years), ischemic etiology (53% vs 35%) and mean INTERMACS profile (2.9 vs 2.5). Between races, significant pre-operative differences most commonly included median age at implant (C = 61 vs AA = 51 vs O = 51), New York Heart Association functional class (85% vs 100% vs 92%) and ischemic etiology (55% vs 24% vs 40%)., Results: There were no significant differences in survival at 1, 3 or 5 years by sex or race. Similarly, there were no differences in time-related freedom from stroke, drive-line infection, gastrointestinal bleeding or pump thrombus by sex or race. After controlling for differences, neither sex nor race was associated with survival (p = 0.09 and p = 0.18, respectively), stroke (p = 0.28 and p = 0.21), drive-line infection (p = 0.9 and p = 0.92), gastrointestinal bleed (p = 0.48 and p = 0.45) or pump thrombus (p = 0.99 and p = 0.8)., Conclusions: In this large, multi-institutional analysis, although some pre-operative clinical characteristics varied, they did not translate into any significant differences in late survival or complications while on LVAD support., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Recommended structured clinical practices including implant technique, anti-coagulation strategy, and pump speed management (PREVENT [PREVENtion of HeartMate II Pump Thrombosis Through Clinical Management] recommendations) were developed to address risk of early (<3 months) pump thrombosis (PT) risk with HeartMate II (HMII; St. Jude Medical, Inc. [Thoratec Corporation], Pleasanton, CA). We prospectively assessed the HMII PT rate in the current era when participating centers adhered to the PREVENT recommendations., Methods: PREVENT was a prospective, multi-center, single-arm, non-randomized study of 300 patients implanted with HMII at 24 participating sites. Confirmed PT (any suspected PT confirmed visually and/or adjudicated by an independent assessor) was evaluated at 3 months (primary end-point) and at 6 months after implantation., Results: The population included 83% men (age 57 years ± 13), 78% destination therapy, and 83% Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profile 1-3. Primary end-point analysis showed a confirmed PT of 2.9% at 3 months and 4.8% at 6 months. Adherence to key recommendations included 78% to surgical recommendations, 95% to heparin bridging, and 79% to pump speeds ≥9,000 RPMs (92% >8,600 RPMs). Full adherence to implant techniques, heparin bridging, and pump speeds ≥9,000 RPMs resulted in a significantly lower risk of PT (1.9% vs 8.9%; p < 0.01) and lower composite risk of suspected thrombosis, hemolysis, and ischemic stroke (5.7% vs 17.7%; p < 0.01) at 6 months., Conclusions: Adoption of all components of a structured surgical implant technique and clinical management strategy (PREVENT recommendations) is associated with low rates of confirmed PT., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Temporary circulatory support (TCS) is used to stabilize patients in critical cardiogenic shock and bridge patients to a durable ventricular assist device (VAD). Whether TCS confers increased risk at the time of VAD implant is unknown., Methods: Prospectively collected data from five institutions was retrospectively reviewed. All profile 1 through profile 3 patients implanted with a continuous-flow VAD (n = 804) were categorized into three groups: TCS (n = 68); non-TCS profile 1 (n = 70); and non-TCS profile 2-3 (n = 666)., Results: End-organ function and hemodynamics were worse before TCS than in non-TCS profile 1 patients: creatinine (1.7 ± 0.1 mg/dL versus 1.3 ± 0.06 mg/dL, p = 0.003); and right atrial pressure (16 ± 0.8 mm Hg versus 13 ± 1.1 mm Hg, p = 0.048). The TCS restored cardiac output before durable VAD (4.9 ± 0.2 L/min), and was comparable to profile 2-3 patients (4.3 ± 0.05 L/min) and better than profile 1 patients (4.0 ± 0.2 L/min, p = 0.002). Markers of hepatic function such as bilirubin were impaired before VAD in TCS and profile 1 patients (2.0 ± 0.2 mg/dL) compared with profile 2 and 3 patients (1.1 ± 0.03, p < 0.001). The incidence of postoperative right ventricular failure necessitating a right VAD was 21% for TCS patients and non-TCS profile 1 patients compared with 2% for profile 2-3 patients (p < 0.001). Profile 1 and TCS patients had similar 1-year survival (70% and 77%, p = 0.57), but inferior survival as compared with profile 2 and 3 patients (82%, p < 0.001). On multivariable analysis, TCS increased the hazard of death twofold., Conclusions: Temporary circulatory support restores hemodynamics and reverses end-organ dysfunction. Nevertheless, these patients have high residual risk with postoperative morbidity and mortality that parallels profile 1 patients without TCS. Caution is suggested in downgrading risk for TCS patients with improved hemodynamic stability., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Limited data exist on outcomes in patients ≥70 years of age supported with the use of continuous-flow left ventricular assist devices (LVADs)., Methods: Data on 1149 continuous-flow LVAD recipients was queried from the Mechanical Circulatory Support Research Network. Groups were assigned based on age: ≥70 years ("older patients") and <70 years. The primary outcome was survival at one-year based on age grouping., Results: Compared with younger patients (54.3 ± 11.2 y; n = 986), older patients (73.4 ± 3.0 y) constituted only 14% of LVAD implants. Older patients had similar rates of device thrombosis (P = .47) and stroke (P = .44), but survival-free of gastrointestinal bleeding (GIB) at 1 year was lower compared with younger patients (58% vs 69%; P < .01). Unadjusted survival at 1 year in older patients was 75% compared with 84% in younger patients, and at 2 years 65% versus 73% (P = .18). Age ≥70 years was not associated with increased mortality (adjusted hazard ratio [aHR] 0.94, 95% confidence interval [CI] 0.70-1.26; P = .67). Preoperative creatinine (aHR 1.57, 95% CI: 1.30-1.89, P < .0001), bilirubin (aHR 1.22, 95% CI 1.05-1.42; P = .010), and ischemic cardiomyopathy (aHR 1.43, 95% CI 1.11-1.84; P = .005) portended increased risk of death. In older patients, the only predictor of mortality was creatinine (HR 2.1, 95% CI 1.2-3.4; P = .007). Creatinine ≥1.4 mg/dL was associated with a 1-year survival of 65%, compared with 84% when the creatinine was <1.4 mg/dL (P = .009)., Conclusion: Age >70 years is an important consideration when assessing LVAD risk, but other correlates may be more predictive of LVAD survival. Older patients without renal dysfunction have survival similar to younger patients. Older patients should be counseled about age-correlated risks, including higher rates of GIB., (Copyright © 2016 Elsevier Inc. All rights reserved.)

As ventricular-assist devices (VADs) are increasingly employed in heart failure management, a leading cause of mortality, new literature is consistently published on less-invasive implantation techniques. Although early perioperative outcomes have been shown to be favorable with minimally invasive left thoracotomy (LT) approaches compared with conventional sternotomy (CS), studies comparing long-term outcomes are lacking. We set out to evaluate long-term follow up between LT and CS approach. In a single center, retrospective review, data on patients with similar demographic profiles were collected. HeartWare (HVAD) implantation was performed by either CS or LT. Analysis was performed on perioperative adverse outcomes, and 6 month postoperative adverse events. Primary objectives of the study included comparative outcomes of morbidity and mortality between both groups at 180 days postimplantation. Eighty-one (n = 81) bridge to transplant (BTT) patients underwent CS or LT HVAD implantation. Perioperative transfusion (p = 0.04) favored the LT cohort compared with CS, with a median of 6 units and 8 units transfused for each group, respectively. No survival difference was observed between both groups at 6 months postimplantation (p = 0.52). Clinical outcomes at an average of 6 month follow up showed no difference in adverse events, including common postoperative VAD complications such as infection and right heart failure. Miniaturization of LVAD size and improvement in technology has allowed expansion of interest in alternative surgical approaches for HVAD implantation. For BTT patients, no difference in early outcome was observed 6 months after implantation using a left LT versus CS technique.

Purpose of Review: Advanced heart failure is a chronic, systemic disease, which affects other organs in ways that are incompletely understood. Patients with advanced heart failure commonly develop congestive hepatopathy, which may lead to progressive hepatic injury and fibrosis. Because the independent adverse effects of hepatic dysfunction on early and late outcomes after continuous flow left ventricular assist devices have also not been entirely demonstrated, we review its impact on this patient population., Recent Findings: Although early mortality is increased in patients with significantly elevated total bilirubin before implant, early improvement in hepatic function is consistently observed following left ventricular assist device (LVAD) implantation, and this early improvement remains stable during late follow-up. Furthermore, a growing experience with expanded application of LVAD therapy in special patient populations, such as those with restrictive cardiomyopathy or congenital heart disease, demonstrates improved outcomes with LVAD compared with continued medical therapy. Although these outcomes are encouraging in the context of hepatic dysfunction not being considered a precluding factor in isolation, careful patient selection and preoperative optimization should be employed to ensure acceptable risk and a durable outcome., Summary: Significant preoperative hepatic dysfunction can increase early mortality in patients undergoing LVAD implant, but long-term outcomes in early survivors demonstrate improvement in measures of hepatic function, which is maintained during follow-up. Numerous perioperative considerations are imperative to optimize to ensure a durable outcome with LVAD in these patients.

Background: Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) patient profiles and modifiers are descriptors of patient illness severity before durable ventricular assist device implantation. It is unknown how individual U.S. institutions and practitioners assign profiles and if modifiers improve on risk discrimination., Methods: Respondents (n = 212) to a web-based survey answered questions about the INTERMACS profile assignment process in their institution. For 5 hypothetical clinical scenarios, respondents assigned the best profile. The INTERMACS registry (2009-2014) was queried, and hazard ratio (HR) (95% confidence interval [CI]) for mortality between profiles as well as based on the presence of temporary circulatory support (TCS), frequent flyer (FF), or arrhythmia modifiers was calculated., Results: Respondents included 131 (62%) cardiologists, 30 (14%) surgeons, and 51 (24%) physician extenders/coordinators. Institutional INTERMACS profile assignment was variable (63% assigned by cardiologists/surgeons; 10% by research coordinators; 27% by physician extenders). Profile assignments in hypothetical patient scenarios were heterogeneous, especially for contiguous profiles. The 1-year survivals for Profiles 1, 2, and 3 were 77 ± 1.2%, 80 ± 0.7%, and 84 ± 0.7% (p < 0.001). Although Profile 1 patients had worse adjusted survival than Profile 3 patients (p = 0.001), survival for Profile 1 patients vs Profile 2 patients was similar (adjusted HR = 1.01 [95% CI = 0.88-1.12]). The TCS (adjusted HR = 1.1 [95% CI = 0.94-1.2]) and arrhythmia (adjusted HR = 1.1 [95% CI = 0.97-1.2]) modifiers were not predictive of mortality, but the FF modifier was (HR = 1.3 [95% CI = 1.02-1.63])., Conclusions: Substantial heterogeneity exists in the process and assignment of INTERMACS profiles. This heterogeneity could affect mortality estimates used for risk stratification. Only the FF modifier appears to improve risk discrimination beyond that of known risk factors. Adding objective descriptors may reduce profile heterogeneity., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The concept of biventricular support with durable centrifugal pumps is evolving, and the surgical strategy and best practice guidelines for implantation of right-sided devices are still unknown. We present optimal strategy for bilateral HeartWare continuous-flow ventricular assist device (HVAD) implantation in a series of four patients. Patients were implanted with the HVAD pumps simultaneously or sequentially. This report offers a perspective on surgical considerations such as right ventricular positioning, implications related to potential risks of obstruction from the tricuspid apparatus, the role if any of downsizing the outflow anastomosis, and considerations for speed adjustments. In this series, one patient died on support and three patients experienced pump thrombosis requiring device revision. All other patients survived until orthotopic heart transplantation, although one of these patients died from perioperative complications, 2 days posttransplantation. Surgical management of patients with medically refractory biventricular heart failure remains challenging and associated with a high incidence of pump thrombosis. Best practice guidelines from experts' consensus are still needed to address this challenging population.

Objectives: We review differences in the incidence and timing of adverse events in patients implanted with continuous-flow left ventricular assist devices (LVADs), using the Mechanical Circulatory Support Research Network registry., Methods: From May 2004 to September 2014, a total of 734 patients (591 men; median age: 59 years) underwent primary continuous-flow LVAD implantation at our institutions. Patients implanted with the HeartMate II (HMII) (560 [76%] patients), compared with the HeartWare ventricular assist device (HVAD; 174 [24%]) were more often receiving destination therapy (47% vs 20%; P < .01), had a lower preoperative creatinine level (1.2 vs 1.3; P = .01), and had less median preoperative right ventricular dysfunction (mild vs moderate; P < .01). Ischemic etiology, prior sternotomy, and median INTERMACS profile were similar., Results: Overall mortality was 54 of 734 (7.4%); 41 of 560 (7.3%) in the HMII group, and 13 of 174 (7.5%) in the HVAD group (P = .95). Follow-up was available in 100% of early survivors for a median of 1 year (max: 10 years) and a total of 1120 patient-years of support (HMII: 940 patient-years [median: 1.1 years, max: 5.3 years] and HVAD: 180 patient-years [median: 0.6 year, max: 10.4 years]). On multivariable analysis, GI bleeding (P = .63), any infection (P = .32), driveline infection (P = .10), and pump thrombus (P = .64) were similar between devices while HeartWare HVAD was associated with higher risk of stroke (HR: 1.8, [1.25, 2.5], P = .003)., Conclusions: In this pooled analysis, a trend was found for higher incidence of percutaneous driveline infections in patients treated with the HMII; a higher incidence of stroke and time-related cumulative risk of any infection and stroke was found in patients treated with the HVAD, which was independently associated with higher stroke risk., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

The management of concomitant aortic and aortic valve disease with left ventricular assist device (LVAD) implantation for patients with severe cardiomyopathy is challenging, and has not been established given the complexity of LVAD surgery with concomitant aortic interventions. A 45-year-old patient presented to our institution with end-stage heart failure symptoms and non-ischemic cardiomyopathy. The patient was found to have a bicuspid aortic valve, severe native aortic regurgitation, a significant ascending aortic aneurysm, and severely depressed left ventricular (LV) function requiring two inotropes. He underwent a successful hemiarch repair of the ascending aortic aneurysm using a back table outflow graft anastomosis technique, and subsequent placement of a HeartWare Ventricular Assist Device (HVAD) with concomitant aortic valve closure with a modified Park's stitch. The patient did well postoperatively and is currently listed for heart transplantation.

Background: The use of continuous flow (CF) left ventricular assist devices (LVAD) as a bridge to orthotopic heart transplantation (OHT) has increased. This study examined survival outcomes after CF-LVAD explantation and OHT using marginal donors., Methods: Adults undergoing OHT with or without LVAD explant using marginal donors between 2007 and 2014 were identified in the Scientific Registry for Transplant Recipients database. A previously validated donor risk score was used to define marginal donors. Patients were stratified into four groups based on utilization of a marginal donor with or without LVAD explantation at OHT. Graft survival was analyzed at 1 and 5 years., Results: Overall, 7,798 patients with OHT were analyzed. Whereas 1,862 patients (24%) underwent direct OHT utilizing marginal donors, only 626 patients (30% [group A]) underwent OHT with LVAD explant (HeartMate II [Thoratec, Pleasanton, CA], n =581, 93%; HVAD [HeartWare, Framingham, MA], n = 45, 7%) and 1,236 (70%) underwent direct OHT (group B). Standard donors were utilized for 2,334 patients with CF-LVAD explant (group C), and 3,602 patients underwent direct OHT (group D). Utilization of marginal donors in patients undergoing LVAD explantation was associated with decreased posttransplant graft survival (p < 0.001). After adjusting for recipient age, sex, listing status at OHT, body mass index, creatinine, and duration of LVAD support, Cox regression analysis found that patients bridged with LVADs, recipients receiving transplants from marginal donors, recipients with highest age and body mass index, and highest creatinine were at increased risk of graft failure (all p < 0.01)., Conclusions: Utilization of marginal donors in patients undergoing CF-LVAD explantation and OHT is associated with reduced early and late graft survival. These findings support cautionary use of marginal donors in patients bridged with CF-LVAD., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Readmissions after continuous flow left ventricular assist devices implantation are common. We compared the frequency and etiology of readmissions between two continuous flow left ventricular assist devices 6 months after implant. We retrospectively assessed readmissions in 81 patients who received a bridge to transplant HeartMate-II (HM-II) n = 35, 43% or HeartWare (HW) n = 46, 57%, from 2009 to 2014. Readmissions were divided into cardiac, infection, gastrointestinal bleeding, stroke, pump thrombosis, and miscellaneous profiles. Age, gender, creatinine, INTERMACS profiles were comparable between groups (p > 0.05). Sixty-one patients accounted for 141 readmissions. At 6 months, the overall readmission rate was higher among HM-II versus HW recipients (2.3 ± 1.7 vs. 1.4 ± 1.3; p = 0.024). Multiple readmissions (≥2) occurred more frequently in HM-II recipients (HM-II 23, 66% vs. HW 20, 44%; p = 0.047) which accounted for 87% of overall readmission frequency. Cardiac profile was the most common reason for readmission (HM-II = 15, HW = 17; p = 0.95). Readmission for arrhythmia (HM-II = 10, HW = 3; p = 0.021) and overall infection rate (0.49 ± 0.70 vs. 0.17 ± 0.68; p = 0.001) were more common among HM-II recipients; however, other readmission profiles were comparable between devices (p > 0.05). Readmission frequency, multiple readmissions, and clinical profile characteristics were different between HM-II and HW recipients.

Background: The risk of device-related adverse events leading to death is abundant and ever-present after left ventricular assist device (VAD) implantation. Very few data specifically examine the causes of death related to length of time after VAD implantation., Methods: Between October 2004 and February 2013, 493 patients (395 male, 80%) underwent primary continuous-flow VAD implantation at our institutions. The median age at implantation was 60 years (range, 18-79 years), and 301 patients (62%) underwent bridge to transplantation., Results: Follow-up was available for all patients (median, 13 months) for a total of 717 patient-years of support. There were 132 deaths during follow-up (median, 8 months; early, 5.5 years) after VAD implantation. The patients were grouped according to temporal occurrence of deaths: (1) early (30-day or index hospitalization) in 34 of 132 patients (26%), (2) between hospital dismissal and 6 months in 29 of 132 patients (22%), (3) 6 months to 1 year in 14 of 132 patients (11%), and (4) after 1 year in 55 of 132 patients (42%). The causes of death (%) at each time period are presented; the most common early cause was right ventricular failure/multisystem organ failure in 18 of 34 patients (61%); from dismissal to 6 months, and 6 months to 1 year, cerebral hemorrhage in 6 of 29 patients (21%) and 4 of 14 patients (29%), respectively; after 1 year, cerebral hemorrhage in 12 of 55 patients (22%) and right ventricular failure/multisystem organ failure in 11 of 55 patients (20%)., Conclusions: The causes of death vary according to time after VAD implantation. Understanding the temporal relationship of causes of mortality after VAD implantation is critical to the identification of varying specific risks in an effort to avoid morbidity, which may ultimately detract from a durable VAD outcome., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The use of mechanical circulatory support to treat patients with congestive heart failure has grown enormously, recently surpassing the number of annual heart transplants worldwide. The current generation of left ventricular assist devices (LVADs), as compared with older devices, is characterized by improved technologies and reduced size. The result is that minimally invasive surgery is now possible for the implantation, explantation, and exchange of LVADs. Minimally invasive procedures improve surgical outcome; for example, they lower the rates of operative complications (such as bleeding or wound infection). The miniaturization of LVADs will continue, so that minimally invasive techniques will be used for most implantations in the future. In this article, we summarize and describe minimally invasive state-of-the-art implantation techniques, with a focus on the most common LVAD systems in adults., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: Right ventricular (RV) dysfunction contributes to mortality in chronic heart failure (HF). However, the molecular mechanisms of RV failure remain poorly understood, and RV myocardial biomarkers have yet to be developed., Methods and Results: We performed RNA sequencing (RNA-seq) on 22 explanted human HF RVs and 5 unused donor human heart RVs (DON RV) and compared results to those recently reported from 16 explanted human LVs We used Bowtie-Tophat for transcript alignment and transcriptome assembly, DESeq for identification of differentially expressed genes (DEGs) and Ingenuity for exploration of gene ontologies. In the HF RV, RNA-seq identified 130,790 total RNA transcripts including 13,272 protein coding genes, 10,831 long non-coding RNA genes and 8,605 pseudogenes. There were 800-1000 DEGs between DON and HF RV comparison groups with differences concentrated in cytoskeletal, basement membrane, extracellular matrix (ECM), inflammatory mediator, hemostasis, membrane transport and transcription factor genes, lncRNAs and pseudogenes. In an unbiased approach, the top 10 DEGs SERPINA3, SERPINA5, LCN6, LCN10, STEAP4, AKR1C1, STAC2, SPARCL1, VSIG4 and F8 exhibited no overlap in read counts between DON and HF RVs, high sensitivities, specificities, predictive values and areas under the receiver operating characteristic curves. STEAP4, SPARCL1 and VSIG4 were differentially expressed between RVs and LVs, supporting their roles as RV-specific myocardial biomarkers., Conclusions: Unbiased, comprehensive profiling of the RV transcriptome by RNA-seq suggests structural changes and abnormalities in inflammatory processes and yields specific, novel HF RV vs HF LV myocardial biomarkers not previously identified by more limited transcriptome profiling approaches., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Mitral valve regurgitation (MR) is prevalent in patients with heart failure. Because very few data exist examining the influence of significant pre-operative MR on outcomes after left ventricular assist device (LVAD) implantation, we evaluate our experience., Methods: Between October 1996 and August 2013, 756 patients underwent primary LVAD implantation at our institutions. Of these, 508 patients received a continuous-flow LVAD and represent the contemporary cohort for this analysis. Devices implanted included the HeartMate II in 410 patients (81%) and HeartWare HVAD in 98 patients (19%). Based on availability of pre-operative echocardiography, 491 patients were divided into 2 study groups according to degree of pre-operative MR; 189 patients (39%) had moderate to severe or greater MR (MR group), and 302 (61%) had less than moderate to severe MR (less MR group). Median age at operation (60 years in MR group vs 58 years in less MR group, p = 0.19), male sex (78% in MR group vs 81% in less MR group, p = 0.42), and ischemic etiology (46% in MR group vs 51% in less MR group, p = 0.35) were similar between groups., Results: There were 40 early deaths (7.9%), and follow-up was available in all 468 early survivors for 641 patient-years of support. Patients in the MR group had higher late survival (2 years, 75%; 4 years, 65%) compared with patients in the less MR group (2 years, 66%; 4 years, 48%; p < 0.04). Cox proportional hazards model confirmed the independent interaction between MR and late survival (hazard ratio 0.62, p = 0.04)., Conclusions: There was improved survival in patients with severe pre-operative MR after continuous-flow LVAD implantation in our cohort. These findings may lend insight into the possible lack of value of addressing significant MR at the time of LVAD implantation., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: The present report describes the authors' initial experience with implantation of the Heartware left ventricular assist devices (HeartWare Inc., Framingham, MA). via a minimally invasive surgical approach without cardiopulmonary bypass. A detailed overview of the anesthesiologist's role during the procedure, characteristics of the patient population, and short-term clinical outcomes are provided, and the clinical considerations that influence the decision to implant this device via an off-pump minimally invasive approach are outlined., Design: Retrospective medical record review., Setting: University hospital., Participants: Thirteen patients with advanced heart failure deemed candidates for off-pump minimally invasive left ventricular Heartware implantation as a bridge to heart transplantation., Interventions: The Heartware left ventricular assist device was implanted in all 13 patients via a minimally invasive approach., Measurements and Main Results: One patient required unplanned cardiopulmonary bypass to control bleeding around the left ventricular outflow cannula. The average operating room time was 249.8 minutes±46.2 minutes. Six of 13 patients required no intraoperative red blood cell transfusions. Seven patients were extubated within 12 hours after surgery. Two patients required reintubation within 48 hours. No patients required reoperation for bleeding. Average intensive care unit and hospital lengths of stay were 7.2±3.9 days and 13.4±3.6 days, respectively. There were no in-hospital deaths., Conclusions: Minimally invasive off-pump left ventricular Heartware implantation is an emerging alternative to placement by midline sternotomy. The authors speculate, based on their limited experience, that an off-pump thoracic strategy may be a desirable option for some patients and that clinical outcomes may be non-inferior to placement by midline sternotomy with cardiopulmonary bypass., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Minimally invasive left thoracotomy (MILT) and off-pump implantation strategies have been anecdotally reported for implantation of the HeartWare ventricular assist device (HVAD). We analyzed our experience with off-pump MILT implantation techniques and compared early in-hospital outcomes with conventional on-pump sternotomy (CS) implantation strategy., Methods: Between January 2013 and February 2014, 51 patients underwent HVAD implantation and were included in this study. Thirty-three patients had CS, whereas 18 patients underwent off-pump MILT. To compare outcomes of these techniques, a multivariate analysis using propensity score modeling was performed after adjusting for age, INTERMACS, Kormos and Leitz-Miller (LM) scores., Results: Mean age at implant was 57 (range 18 to 69) years, and overall in-hospital mortality was 8%. Univariate analysis revealed a statistically significant reduction in days on inotropes (p = 0.04), and a trend toward reduced intra-operative blood product administration (p = 0.08) in the MILT group. There was no difference in intensive-care-unit length of stay (p = 0.5), total length of stay (p = 0.76), post-operative blood product administration (p = 0.34) and total time on mechanical ventilation (p = 0.32). After adjusting for age, INTERMACS profile and Kormos and LM scores, no statistically significant differences were observed between the MILT and CS groups., Conclusions: An off-pump MILT implantation strategy can be utilized as a safe surgical approach for patients undergoing HVAD implantation. Further large collaborative studies are needed to identify advantages of the MILT approach., (Published by Elsevier Inc.)

Advances in mechanical circulatory support have significantly expanded the treatment options for patients with heart failure, whether acute or chronic. There are numerous devices available that offer patients short-, intermediate-, and long-term duration of support depending on their clinical needs and cardiac recovery. Each device has its own technical considerations and the decision which device to use depends on several factors, including what is available, the degree of support required, and expected duration of support. Additional issues that need to be considered in choosing level of support include right heart function, respiratory failure, and multi-organ derangements. A widespread availability of short-term ventricular assist devices and timely institution for effective hemodynamic support will translate into improved patient outcomes whether that is successful transfer to a tertiary care facility or recovery of inherent cardiac function. Implantable ventricular assist devices have and will continue to evolve into smaller and more durable devices, and the future for patients with advanced heart failure looks ever-more promising.