Quality of life metrics in LVAD patients after hemocompatibility-related adverse events.

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.

Novel heat shock protein 90 inhibitor improves cardiac recovery in a rodent model of donation after circulatory death.

OBJECTIVE: Organ donation after circulatory death (DCD) is a potential solution for the shortage of suitable organs for transplant. Heart transplantation using DCD donors is not frequently performed due to the potential myocardial damage following warm ischemia. Heat shock protein (HSP) 90 has recently been investigated as a novel target to reduce ischemia/reperfusion injury. The objective of this study is to evaluate an innovative HSP90 inhibitor (HSP90i) as a cardioprotective agent in a model of DCD heart. METHODS: A DCD protocol was initiated in anesthetized Lewis rats by discontinuation of ventilation and confirmation of circulatory death by invasive monitoring. Following 15 minutes of warm ischemia, cardioplegia was perfused for 5 minutes at physiological pressure. DCD hearts were mounted on a Langendorff ex vivo heart perfusion system for reconditioning and functional assessment (60 minutes). HSP90i (0.01 µmol/L) or vehicle was perfused in the cardioplegia and during the first 10 minutes of ex vivo heart perfusion reperfusion. Following assessment, pro-survival pathway signaling was evaluated by western blot or polymerase chain reaction. RESULTS: Treatment with HSP90i preserved left ventricular contractility (maximum + dP/dt, 2385 ± 249 vs 1745 ± 150 mm Hg/s), relaxation (minimum -dP/dt, -1437 ± 97 vs 1125 ± 85 mm Hg/s), and developed pressure (60.7 ± 5.6 vs 43.9 ± 4.0 mm Hg), when compared with control DCD hearts (All P = .001). Treatment abrogates ischemic injury as demonstrated by a significant reduction of infarct size (2,3,5-triphenyl-tetrazolium chloride staining) of 7 ± 3% versus 19 ± 4% (P = .03), troponin T release, and mRNA expression of Bax/Bcl-2 (P < .05). CONCLUSIONS: The cardioprotective effects of HSP90i when used following circulatory death might improve transplant organ availability by expanding the use of DCD hearts.

Two-Year Follow Up of the LATERAL Clinical Trial: A Focus on Adverse Events.

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.

Driveline damage and repair in continuous-flow left ventricular assist devices: A systematic review.

With mounting time on continuous-flow left ventricular assist device (CF-LVAD) support, patients occasionally sustain damage to the device driveline. Outcomes associated with external and internal driveline damage and repair are currently not well documented. We sought to evaluate the outcomes of driveline damage and its repair. Electronic search was performed to identify all relevant studies published over the past 20 years. Fifteen studies were selected for analysis comprising of 55 patients with CF-LVAD dysfunction due to driveline damage. Demographic and perioperative variables along with outcomes including survival rates were extracted and pooled for the systematic review. Most patients (53/55) were supported on HeartMate II LVAD (Abbott Laboratories, Abbott Park, IL). Internal damage was more commonly reported than external damage [69.1% (38/55) vs. 30.9% (17/55), P = .01]. Median time to driveline damage was 1.9 years [IQR 1.0, 2.5]. Most patients presented with a CF-LVAD alarm [94.5% (52/55)] and patients with internal driveline damage had a significantly higher rate of alarm activation compared to that observed for those with external damage [38/38 (100%) vs. 14/17 (82.4%), P = .04]. Patients with internal driveline dysfunction were more likely to experience component wear compared to those with external driveline dysfunction [10/38 (26.3%) vs. 0/17 (0%), P = .05]; 14.5% of patients (8/55) underwent external repair of the driveline, 5.5% (3/55) were treated with rescue tape, and 5.5% (3/55) were placed on an ungrounded cable, indicating a short-to-shield event had occurred. A total of 49.1% of patients (27/55) underwent CF-LVAD exchange, 5.5% (3/55) were weaned off the CF-LVAD to explant, and 5.5% (3/55) underwent emergent heart transplantation. The median length of hospital stay was 12 days [IQR 7, 12] and 30-day mortality rate was 14.5% (8/55). Driveline damage was more commonly reported at an internal location and despite being a well-recognized complication, mortality still appears high.

Expert Consensus Paper: Lateral Thoracotomy for Centrifugal Ventricular Assist Device Implant.

BACKGROUND: The increasing prevalence of heart failure has led to the expanded use of left ventricle assist devices (VADs) for end-stage heart failure patients worldwide. Technological improvements witnessed the development of miniaturized VADs and their implantation through less traumatic non-full sternotomy approaches using a lateral thoracotomy (LT). Although adoption of the LT approach is steadily growing, a lack of consensus remains regarding patient selection, details of the surgical technique, and perioperative management. Furthermore, the current literature does not offer prospective randomized studies or evidence-based guidelines for LT-VAD implantation. METHODS: A worldwide group of LT-VAD experts was convened to discuss these key topics openly. After a PubMed search and review with all authors, a consensus was reached and an expert consensus paper on LT-VAD implantation was developed. RESULTS: This document aims to guide clinicians in the selection of patients suitable for LT approaches and preoperative optimization. Details of operative techniques are described, with an overview of hemisternotomy and bilateral thoracotomy approaches. A review of the best surgical practices for placement of the pump, inflow cannula, and outflow graft provides advice on the best surgical strategies to avoid device malpositioning while optimizing VAD function. Experts' opinions on cardiopulmonary bypass, postoperative management, and approaches for pump exchange and explant are presented. This review also emphasizes the critical need for multidisciplinary teams and specific training. CONCLUSIONS: This expert consensus review provides a compact guide to LT for VAD implantation, from patient selection through intraoperative tips and postoperative management.

Continuous-Flow Left Ventricular Assist Devices and Valvular Heart Disease: A Comprehensive Review.

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.

Non-invasive assessment of arterial pulsatility in patients with continuous-flow left ventricular assist devices.

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.

Preoperative Risk Stratification of Right Ventricular Function Utilizing Cardiac Magnetic Resonance Imaging Compared With Echocardiographic and Hemodynamic Parameters.

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.

Exercise-induced hypoxemia predicts heart failure hospitalization and death in patients supported with left ventricular assist devices.

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 (O2 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 VO2 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.

Preoperative left atrial volume index is associated with postoperative outcomes in mitral valve repair for chronic mitral regurgitation.

OBJECTIVE: To assess determinants of left atrial reverse remodeling after mitral valve repair and to evaluate the impact of preoperative left atrial volume on postoperative outcomes. METHODS: We reviewed the records of 720 patients who underwent mitral valve repair from September 2008 to July 2015 and had preoperative measurement of left atrial volume index. We analyzed the association of preoperative left atrial volume index on early and late outcomes, and determined which baseline characteristics are associated with left atrial reverse remodeling, as measured by changes in left atrial volume index in 512 patients who had at least 1 postoperative measurement. RESULTS: The median (interquartile range) preoperative left atrial volume index was 54.0 (44.0-66.0) mL/m2. Preoperative left atrial volume index, age, body mass index, and atrial fibrillation were independently associated with the degree of left atrial reverse remodeling over the follow-up period. Reverse remodeling was greatest in patients with higher baseline left atrial volume index (P < .001), but less reverse remodeling was observed in patients with advanced age (P < .001), preoperative atrial fibrillation (P < .001), and extreme values of body mass index (P = .004), although these effects were moderately attenuated when limiting the analysis to 6-month follow-up. Secondary analysis demonstrated marginally significant effects of preoperative left atrial volume index on risks of early postoperative atrial fibrillation (P = .030) and late mortality (P = .077) after adjusting for age and sex. CONCLUSIONS: In patients with degenerative mitral valve regurgitation who had mitral valve repair, preoperative left atrial volume index was associated with extent of left atrial reverse remodeling, risk of early postoperative atrial fibrillation, and late mortality. The majority of reverse remodeling occurs within the first month after operation and is greatest in younger patients.

Active clearance of chest tubes is associated with reduced postoperative complications and costs after cardiac surgery: a propensity matched analysis.

BACKGROUND: Chest tubes are routinely used to evacuate shed mediastinal blood in the critical care setting in the early hours after heart surgery. Inadequate evacuation of shed mediastinal blood due to chest tube clogging may result in retained blood around the heart and lungs after cardiac surgery. The objective of this study was to compare if active chest tube clearance reduces the incidence of retained blood complications and associated hospital resource utilization after cardiac surgery. METHODS: Propensity matched analysis of 697 consecutive patients who underwent cardiac surgery at a single center. 302 patients served as a baseline control (Phase 0), 58 patients in a training and compliance verification period (Phase 1) and 337 were treated prospectively using active tube clearance (Phase 2). The need to drain retained blood, pleural effusions, postoperative atrial fibrillation, ICU resource utilization and hospital costs were assessed. RESULTS: Propensity matched patients in Phase 2 had a reduced need for drainage procedures for pleural effusions (22% vs. 8.1%, p < 0.001) and reduced postoperative atrial fibrillation (37 to 25%, P = 0.011). This corresponded with fewer hours in the ICU (43.5 [24-79] vs 30 [24-49], p = < 0.001), reduced median postoperative length of stay (6 [4-8] vs 5 [4-6.25], p < 0.001) median costs reduced by $1831.45 (- 3580.52;82.38, p = 0.04) and the mean costs reduced by an average of $2696 (- 6027.59;880.93, 0.116). CONCLUSIONS: This evidence supports the concept that efforts to actively maintain chest tube patency in early recovery is useful in improving outcomes and reducing resource utilization and costs after cardiac surgery. TRIAL REGISTRATION: Clinicaltrial.gov, NCT02145858, Registered: May 23, 2014.

Robotic Mitral Valve Repair: Indication for Surgery Does Not Influence Early Outcomes.

OBJECTIVE: To evaluate the outcomes of robotic mitral valve repair (MVr) by primary indication per American Heart Association guidelines for surgery: class I vs class IIa. PATIENTS AND METHODS: From January 1, 2008, through September 30, 2016, 603 patients underwent robotic MVr for severe primary mitral regurgitation. Medical records of 576 consenting patients were retrospectively reviewed to determine the primary indication for surgery. Patients were stratified into class I or class IIa, and preoperative, intraoperative, and postoperative variables were compared. RESULTS: Of 516 patients, 428 (83%) had class I indication and 88 (17%) had class IIa indication for surgery. Preoperatively, no significant differences were observed between both cohorts. Importantly, a significantly higher number of patients with class I indication underwent MVr for bileaflet prolapse (172 of 428 [40%] vs 21 of 88 [25%]; P=.03). Early MVr outcomes indicated recurrent mitral regurgitation (moderate or greater) in only 12 of 576 (2%), and no significant differences were observed between classes (P=.23). Apart from parameters for ventricular size, all other intraoperative and postoperative variables were comparable between both cohorts. CONCLUSION: Comparable outcomes were indicated across all classes of indications for MVr surgery. These results continue to support the use of this surgical technique, even in less sick patients. Early referral along with more extensive robotic MVr experience will likely result in further improvements in long-term outcomes.

Diastolic Pulmonary Gradient as a Predictor of Right Ventricular Failure After Left Ventricular Assist Device Implantation.

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.