Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke.

BACKGROUND: Surgical occlusion of the left atrial appendage has been hypothesized to prevent ischemic stroke in patients with atrial fibrillation, but this has not been proved. The procedure can be performed during cardiac surgery undertaken for other reasons. METHODS: We conducted a multicenter, randomized trial involving participants with atrial fibrillation and a CHA2DS2-VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating greater risk of stroke) who were scheduled to undergo cardiac surgery for another indication. The participants were randomly assigned to undergo or not undergo occlusion of the left atrial appendage during surgery; all the participants were expected to receive usual care, including oral anticoagulation, during follow-up. The primary outcome was the occurrence of ischemic stroke (including transient ischemic attack with positive neuroimaging) or systemic embolism. The participants, research personnel, and primary care physicians (other than the surgeons) were unaware of the trial-group assignments. RESULTS: The primary analysis population included 2379 participants in the occlusion group and 2391 in the no-occlusion group, with a mean age of 71 years and a mean CHA2DS2-VASc score of 4.2. The participants were followed for a mean of 3.8 years. A total of 92.1% of the participants received the assigned procedure, and at 3 years, 76.8% of the participants continued to receive oral anticoagulation. Stroke or systemic embolism occurred in 114 participants (4.8%) in the occlusion group and in 168 (7.0%) in the no-occlusion group (hazard ratio, 0.67; 95% confidence interval, 0.53 to 0.85; P = 0.001). The incidence of perioperative bleeding, heart failure, or death did not differ significantly between the trial groups. CONCLUSIONS: Among participants with atrial fibrillation who had undergone cardiac surgery, most of whom continued to receive ongoing antithrombotic therapy, the risk of ischemic stroke or systemic embolism was lower with concomitant left atrial appendage occlusion performed during the surgery than without it. (Funded by the Canadian Institutes of Health Research and others; LAAOS III ClinicalTrials.gov number, NCT01561651.).

Left ventricular assist devices: yesterday, today, and tomorrow.

The shortcomings of expense, power requirements, infection, durability, size, and blood trauma of current durable LVADs have been recognized for many years. The LVADs of tomorrow aspire to be fully implantable, durable, mitigate infectious risk, mimic the pulsatile nature of the native cardiac cycle, as well as minimize bleeding and thrombosis. Power draw, battery cycle lifespan and trans-cutaneous energy transmission remain barriers to completely implantable systems. Potential solutions include decreases in pump electrical draw, improving battery lifecycle technology and better trans-cutaneous energy transmission, potentially from Free-range Resonant Electrical Energy Delivery. In this review, we briefly discuss the history of LVADs and summarize the LVAD devices in the development pipeline seeking to address these issues.

Impact of 2016 UNOS pediatric heart allocation policy changes on VAD utilization, waitlist, and post-transplant survival outcomes in children with CHD versus Non-CHD.

AIMS: We analyzed the impact of the revised pediatric heart allocation policy on types of ventricular assist device (VAD) utilization, and waitlist (WL) and post-heart transplant (HT) survival outcomes in congenital heart disease (CHD) versus non-CHD patients before (Era-1) and after (Era-2) pediatric heart allocation policy implementation. METHODS: We retrospectively reviewed the UNOS database from December 16, 2011, through March 31, 2021, for patients < 18 years old and listed for primary HT. We compared the differences observed between Era-1 and Era-2. RESULTS: 5551 patients were listed for HT, of whom 2447(44%) were in Era-1 and 3104(56%) were in Era-2. CHD patients were listed as status 1A unchanged, but the number of patients listed as status 1B decreased in Era-2, whereas the number of non-CHD patients listed as status 1A decreased, but status 1B increased. In Era-2 compared to Era-1, both temporary (1% to 4%, p < .001) and durable VAD (13.6% to 17.8%, p < .001) utilization increased, and the transplantation rate per 100-patient years increased in both groups. The median WL period for CHD patients increased marginally from 70 to 71 days (p = .06), whereas for non-CHD patients it decreased from 61 to 54 days (p < .001). Adjusted 90-day WL survival increased from 84% to 88%, p = .016 in CHD, but there was no significant change in non-CHD patients (p = .57). There was no significant difference in 1-year post-HT survival in CHD and non-CHD patients between Era-1 and Era-2. CONCLUSIONS: In summary, after the revised heart allocation policy implementation, temporary and durable VAD support increased, HT rate increased, waitlist duration marginally increased in the CHD cohort and decreased in the non-CHD cohort, and 90-day WL survival probability improved in children with CHD without significant change in 1-year post-HT outcomes. Future studies are needed to identify changes to the policy that may further improve the listing criteria to improve WL duration and post-HT survival.

Contemporary outcomes of durable ventricular assist devices in adults with congenital heart disease as a bridge to heart transplantation.

OBJECTIVES: This study aimed to compare the clinical characteristics, risk factors, and overall survival outcomes in adults with congenital heart disease (ACHD) bridged to transplantation with a ventricular assist device (VAD) versus no-VAD. METHODS: The study included 894 ACHD patients aged ≥18 years listed for primary heart transplantation between 2010 and 2019 from the United Network for Organ Sharing database. Primary outcomes were waitlist and 1-year post-transplant mortality between VAD and no-VAD ACHD patients. RESULTS: Of 894 ACHD patients included in the study, 91(10.1%) had VAD support at the time of listing. Patients who needed VAD support were mostly males, heavier, and had higher pulmonary artery pressure than the no-VAD group at the listing. The overall waitlist mortality was 38% in the VAD group than 17% in the no-VAD group (p < 0.01). ECMO use was associated with significantly higher mortality than either group. There was no significant difference in 1-year post-transplant mortality between VAD versus no-VAD at the time of transplant (15% vs. 17%; p = 0.66). Multivariate regression analysis found that BMI <20 kg/m2 (hazard ratio (HR) 1.1; p = 0.01), bilirubin >2 mg/dl (HR 1.1; p = 0.03), creatinine >2 mg/dl (HR 1.3; p = 0.04) and ECMO at transplant (HR 1.4; p = 0.03) increased early post-transplant mortality. CONCLUSIONS: The one-year post-transplant mortality rate was no different for ACHD patients that received VAD versus no-VAD. These findings suggest that a VAD should be considered an option to support ACHD patients as a bridge to heart transplantation.

Prospective Multicenter Study of Myocardial Recovery Using Left Ventricular Assist Devices (RESTAGE-HF [Remission from Stage D Heart Failure]): Medium-Term and Primary End Point Results.

BACKGROUND: Left ventricular assist device (LVAD) unloading and hemodynamic support in patients with advanced chronic heart failure can result in significant improvement in cardiac function allowing LVAD removal; however, the rate of this is generally considered to be low. This prospective multicenter nonrandomized study (RESTAGE-HF [Remission from Stage D Heart Failure]) investigated whether a protocol of optimized LVAD mechanical unloading, combined with standardized specific pharmacological therapy to induce reverse remodeling and regular testing of underlying myocardial function, could produce a higher incidence of LVAD explantation. METHODS: Forty patients with chronic advanced heart failure from nonischemic cardiomyopathy receiving the Heartmate II LVAD were enrolled from 6 centers. LVAD speed was optimized with an aggressive pharmacological regimen, and regular echocardiograms were performed at reduced LVAD speed (6000 rpm, no net flow) to test underlying myocardial function. The primary end point was the proportion of patients with sufficient improvement of myocardial function to reach criteria for explantation within 18 months with sustained remission from heart failure (freedom from transplant/ventricular assist device/death) at 12 months. RESULTS: Before LVAD, age was 35.1±10.8 years, 67.5% were men, heart failure mean duration was 20.8±20.6 months, 95% required inotropic and 20% temporary mechanical support, left ventricular ejection fraction was 14.5±5.3%, end-diastolic diameter was 7.33±0.89 cm, end-systolic diameter was 6.74±0.88 cm, pulmonary artery saturations were 46.7±9.2%, and pulmonary capillary wedge pressure was 26.2±7.6 mm Hg. Four enrolled patients did not undergo the protocol because of medical complications unrelated to the study procedures. Overall, 40% of all enrolled (16/40) patients achieved the primary end point, P<0.0001, with 50% (18/36) of patients receiving the protocol being explanted within 18 months (pre-explant left ventricular ejection fraction, 57±8%; end-diastolic diameter, 4.81±0.58 cm; end-systolic diameter, 3.53±0.51 cm; pulmonary capillary wedge pressure, 8.1±3.1 mm Hg; pulmonary artery saturations 63.6±6.8% at 6000 rpm). Overall, 19 patients were explanted (19/36, 52.3% of those receiving the protocol). The 15 ongoing explanted patients are now 2.26±0.97 years after explant. After explantation survival free from LVAD or transplantation was 90% at 1-year and 77% at 2 and 3 years. CONCLUSIONS: In this multicenter prospective study, this strategy of LVAD support combined with a standardized pharmacological and cardiac function monitoring protocol resulted in a high rate of LVAD explantation and was feasible and reproducible with explants occurring in all 6 participating sites. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01774656.

Role of implantable cardioverter-defibrillator in patients awaiting heart transplant in the continuous-flow left ventricular assist device era.

Implantable cardioverter-defibrillators (ICDs) have been shown to have survival advantage in advanced heart failure patients. Few studies have evaluated the role of ICDs in patients supported with continuous-flow left ventricular assist devices (CFVADs). We aimed to evaluate the impact of ICD and CFVAD on heart transplant (HTx) waiting list survival. We queried the United Network for Organ Sharing (UNOS) thoracic transplant database between years 2007 and 2016 for patients aged ≥ 18 years listed for HTx. Patients receiving devices other than CFVAD were excluded. Patients were divided into groups-with and without CFVAD and further subdivided into groups-with and without ICD use. Kaplan-Meier curves were used to evaluate the survival outcomes. There were 34 860 patients listed for HTx during study period of which 11 481 (32%) had a CFVAD and 26 139 (75%) had an ICD. Within CFVAD group, patients with ICD were older, more likely male, with higher creatinine and listed as UNOS status 1A. In the No-CFVAD group, 1-year waitlist survival was significantly better with ICD use (81% vs. 73%, P < .0001); however, in CFVAD patients, 1-year survival with ICD use was comparable to No-ICD use (95% vs. 94%, P = .1). Use of ICD is associated with significantly better heart transplant waitlist survival in patients not supported by CFVAD. In patients supported with CFVAD, the ICD does not offer additional survival benefit.

Association of temporal trends in neutrophil lymphocyte ratio on left ventricular assist device patient outcomes.

Neutrophil to lymphocyte ratio (NLR) can predict mortality/complications in left ventricular assist device (LVAD) patients; however, the prognostic value of longitudinal NLR measurements has not been well studied. Here, we examine the mortality/complication incidence in patients with chronically increased NLR verses patients with acutely elevated NLR as a predictor of patient outcomes. This retrospective analysis included 102 patients who underwent LVAD implantation from 2016 to 2018 at a single center. The NLR was calculated at the time of surgery, and at 30 and 90 days after surgery. The NLR values were grouped into categorical data: low, normal (put in range), and high. Patients were classified in 2 groups based on change in their NLR values from surgery to 90 days; the H90 group had sustained increase of NLR over 90-days and the N90 group had normalization of NLR at 90-days. Actuarial survival the between study groups was measured using Kaplan-Meier curves. The N90 group had 50 patients (median age 58 (48-66) years, 21% female) at the time of LVAD placement. Group H90 had 52 patients (median age 64 (52-68) years, 16% female). Median age, body mass index (BMI), bilirubin, creatinine, and BNP at time of implant as well as type of device and implant strategy were comparable between the study groups. The post implant survival for N90 group was significantly better than the H90 group at 1 year (93% vs. 80%) and 2 years (90% vs. 67%) (log-rank P = .001). Early post LVAD survival in patients with elevated NLR over 90 days postoperatively was significantly worse compared to patients who normalized the NLR at 90 days.

Validation of a Novel NeurOs Cerebral Oximetry Monitor Against the INVOS Monitor During Cardiac Surgery.

OBJECTIVES: To compare the performance of a novel NeurOs cerebral oximetry monitor against the INVOS monitor during the entire intraoperative phase of cardiac surgery, including periods of known fluctuation in brain oxygenation, such as preoxygenation, induction, cannulation, and cardiopulmonary bypass. DESIGN: This study was a prospective, nonrandomized, healthcare-provider and outcome-assessor blinded study. SETTING: Tertiary care university hospital; single institutional study. PARTICIPANTS: Twenty-three patients who underwent cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Both self-adhesive INVOS sensors and the assembled NeurOs sensors were placed accordingly when the patient arrived in the operating room. MEASUREMENTS AND MAIN RESULTS: Ten out of 13 cases under the normal mode and eight out of the 10 cases under the high- sensitivity mode showed significant correlations between the NeurOs and INVOS groups (p < 0.05, r value from 0.24-0.88). When all cases were combined, NeurOs demonstrated significant correlation with INVOS (r = 0.5, 95% confidence interval [CI] 0.44-0.56, p < 0.01 for normal mode; r = 0.69, 95% CI 0.64 to 0.74, p < 0.01 for high-sensitivity mode) in both modes. To evaluate the data diversity, the authors performed a cluster analysis and found much less variation existed in the NeurOs normal mode when compared with INVOS (standard deviation [SD] 16.6% in INVOS, 4% in NeurOs normal mode) but similar patterns in the high-sensitivity mode (SD 17.6% in INVOS, 15.2% in NeurOs high-sensitivity mode). Bland-Altman plot analysis showed that most of the data fell between ± 1.96 SD lines, which demonstrated good consistency between these two methods under both modes of NeurOs (-28.8 to 30.8 in the normal mode; -36.6 to 32.7 in high-sensitivity mode). In the normal mode of NeurOs monitoring, receiver operating characteristic analysis suggested a 2% cutoff point was most optimal from the baseline for detecting hyperoxia (sensitivity 73%; specificity 66%) and minus 1% (sensitivity 66%; specificity 67%) for detecting hypoxia. Whereas in the high-sensitivity mode, the optimal cutoff point was 3% from baseline for detecting hyperoxia (sensitivity 75%; specificity 68%), and minus 3% for detecting hypoxia (sensitivity 90%; specificity 45%). CONCLUSIONS: In conclusion, the novel NeurOs system was found to correlate with INVOS cerebral oximetry measurements during cardiac surgery.

Aortic root replacement with Medtronic Freestyle bioprosthesis: 25-year experience.

BACKGROUND: Stentless porcine bioprothesis is a surgical strategy to treat aortic root disease. Use has been limited due to the concern for long-term valve degeneration. This study evaluated the perioperative and late outcomes of patients with aortic root disease requiring root replacement. METHODS: A total of 409 patients underwent aortic root replacement by a single surgeon using a stentless porcine bioroot between February 1996 and May 2020. The cohort was divided into two groups (age ≤65 and >65 years). Descriptive statistics were used to analyze the data and Kaplan-Meier curves used to evaluate long-term outcomes. RESULTS: Patients age >65 years were more likely to be female (p = .01), have hypertension (p = .01), require circulatory arrest (p = .01), and have concomitant coronary artery bypass grafting (CABG) (p = .04). Baseline creatinine >1.8 (p = .20), diabetes (p = .06), and ejection fraction (p = .20) were similar between groups. The 1-, 5-, and 10-year survival for patients age ≤65 years were 92%, 87%, and 69%, respectively, significantly better than patients age >65 (88%, 73%, and 43%, respectively) (p < .01, Figure 1). The 1-, 5-, and 10-year freedom from reoperation for patients ≤65 years were 99%, 97%, and 93% versus 99%, 98%, and 96% in patients age >65 years, respectively (p = .24). CONCLUSION: Patients with aortic root disease can be treated with acceptable perioperative outcomes, long-term survival, and low reoperation rates using a stentless porcine bioprothesis. It should be considered irrespective of age due to its excellent durability and freedom from anti-coagulation requirement.

Device Therapy and Arrhythmia Management in Left Ventricular Assist Device Recipients: A Scientific Statement From the American Heart Association.

Left ventricular assist devices (LVADs) are an increasingly used strategy for the management of patients with advanced heart failure with reduced ejection fraction. Although these devices effectively improve survival, atrial and ventricular arrhythmias are common, predispose these patients to additional risk, and complicate patient management. However, there is no consensus on best practices for the medical management of these arrhythmias or on the optimal timing for procedural interventions in patients with refractory arrhythmias. Although the vast majority of these patients have preexisting cardiovascular implantable electronic devices or cardiac resynchronization therapy, given the natural history of heart failure, it is common practice to maintain cardiovascular implantable electronic device detection and therapies after LVAD implantation. Available data, however, are conflicting on the efficacy of and optimal device programming after LVAD implantation. Therefore, the primary objective of this scientific statement is to review the available evidence and to provide guidance on the management of atrial and ventricular arrhythmias in this unique patient population, as well as procedural interventions and cardiovascular implantable electronic device and cardiac resynchronization therapy programming strategies, on the basis of a comprehensive literature review by electrophysiologists, heart failure cardiologists, cardiac surgeons, and cardiovascular nurse specialists with expertise in managing these patients. The structure and design of commercially available LVADs are briefly reviewed, as well as clinical indications for device implantation. The relevant physiological effects of long-term exposure to continuous-flow circulatory support are highlighted, as well as the mechanisms and clinical significance of arrhythmias in the setting of LVAD support.

Intrapericardial Left Ventricular Assist Device for Advanced Heart Failure.

BACKGROUND: Mechanical circulatory support with a left ventricular assist device (LVAD) is an established treatment for patients with advanced heart failure. We compared a newer LVAD design (a small intrapericardial centrifugal-flow device) against existing technology (a commercially available axial-flow device) in patients with advanced heart failure who were ineligible for heart transplantation. METHODS: We conducted a multicenter randomized trial involving 446 patients who were assigned, in a 2:1 ratio, to the study (centrifugal-flow) device or the control (axial-flow) device. Adults who met contemporary criteria for LVAD implantation for permanent use were eligible to participate in the trial. The primary end point was survival at 2 years free from disabling stroke or device removal for malfunction or failure. The trial was powered to show noninferiority with a margin of 15 percentage points. RESULTS: The intention-to treat-population included 297 participants assigned to the study device and 148 participants assigned to the control device. The primary end point was achieved in 164 patients in the study group and 85 patients in the control group. The analysis of the primary end point showed noninferiority of the study device relative to the control device (estimated success rates, 55.4% and 59.1%, respectively, calculated by the Weibull model; absolute difference, 3.7 percentage points; 95% upper confidence limit, 12.56 percentage points; P=0.01 for noninferiority). More patients in the control group than in the study group had device malfunction or device failure requiring replacement (16.2% vs. 8.8%), and more patients in the study group had strokes (29.7% vs. 12.1%). Quality of life and functional capacity improved to a similar degree in the two groups. CONCLUSIONS: In this trial involving patients with advanced heart failure who were ineligible for heart transplantation, a small, intrapericardial, centrifugal-flow LVAD was found to be noninferior to an axial-flow LVAD with respect to survival free from disabling stroke or device removal for malfunction or failure. (Funded by HeartWare; ENDURANCE ClinicalTrials.gov number, NCT01166347 .).

Combined Heart-Kidney Transplant Versus Sequential Kidney Transplant in Heart Transplant Recipients.

OBJECTIVES: In patients with reduced kidney function there are no established guidelines to suggest combined heart-kidney transplant (HKTx) versus sequential kidney transplant (SKTx) using preoperative value of estimated glomerular filtration (eGFR). METHODS: The United Network for Organ Sharing database was queried from 2000 to 2015 to evaluate survival of HKTx and SKTx population stratified by preoperative eGFR rate <45 mL/min. Aim of the study was to assess the eGFR rate that is most beneficial to perform a concomitant or a SKTx at time of transplant evaluation. RESULTS: In our analysis, patients who required SKTx are recipients that, after heart transplantation, developed or worsened kidney insufficiency due to calcineurin inhibitor nephrotoxicity. In recipients with eGFR <30 or dialysis, a total of 545 received HKTx and 80 received SKTx. The median waiting time between heart and kidney transplant in SKTx group was 6 years. The overall post-transplant survival was 81% and 80% and 75% and 59% at 5 and 1 years for the HKTx and SKTx groups, respectively (P = .04). In recipients with eGFR from 30 to 44, a total of 107 received HKTx and 112 received SKTx. The median waiting time between heart and kidney transplant in SKTx group was 4 years. Overall post-transplant survival showed no statistically significant differences in HKTx group (n=107) compared with SKTx group (n=112) and was 90% and 95% at 1 year and 74% and 52% at 5 years, respectively (P = .4) . CONCLUSIONS: To optimize organ and patient survival, eGFR value can be utilized to discern between HKTx versus SKTx in patients with decreased renal function at the time of heart transplantation. Patients with eGFR<30 or in dialysis presented better survival with HKTx, while both SKTx and HKTx are suitable for patients with eGFR between 30 and 45.

Risk Factors and Outcomes in Redo Coronary Artery Bypass Grafting.

BACKGROUND: Reoperative coronary artery bypass grafting (redo-CABG) has declined during the last decade, while use of percutaneous coronary intervention (PCI) has increased. The aim of this retrospective study was to evaluate risk factors, in-hospital mortality, and long-term survival between first-time CABG and redo-CABG. METHODS: From January 2009 to December 2015, 2,581 patients underwent first-time CABG procedures while 132 underwent isolated redo-CABG. Logistic regression was used to identify risk factors predictive of redo-CABG and after propensity matching the in-hospital morbidity and long-term all-cause mortality were compared. RESULTS: Risk factors for redo-CABG were prior PCI, dyslipidaemia, diabetes and hypertension. After propensity matching there were no significant differences between the redo-CABG (n = 126) and first-time CABG groups (n = 232) in baseline characteristics. The adjusted in-hospital mortality was 3.1% for redo-CABG and 2.1% for first-time CABG (p = 0.55). Redo-CABG required significantly more intraoperative red blood cells (p = 0.03), platelets (p < 0.001), cryoprecipitate (p < 0.007) and fresh frozen plasma (p < 0.001) than first-time CABG. There was no significant difference in reoperation for bleeding (p = 0.72), prolonged ventilation (p = 0.98), postoperative stroke (p = 0.92) or dialysis (p = 0.44). The survival at 1, 3 and 5 years for redo-CABG was 93.5%, 90%, and 85% respectively, and 95.5%, 94.5%, 93% for first-time CABG, respectively (p = 0.2). CONCLUSIONS: Prior PCI after first time CABG and the risk factors for atherosclerotic disease are predictive for redo-CABG. An increased use of blood products is required during redo-CABG. After propensity matching, in-hospital mortality and long-term survival for redo-CABG is comparable to first-time operation. Re-sternotomy does not impact the survival in redo-CABG.

Impact of QRS Duration and Ventricular Pacing on Clinical and Arrhythmic Outcomes in Continuous Flow Left Ventricular Assist Device Recipients: A Multicenter Study.

OBJECTIVES: Wide QRS duration and ventricular pacing are common in recipients of continuous-flow left ventricular assist devices (CF-LVADs) but their impact on outcomes remains unclear. We assessed the clinical and arrhythmic outcomes of CF-LVAD patients with wide QRS or right ventricular (RV) pacing at baseline, compared with those with narrow QRS and those with continued cardiac resynchronization therapy (CRT). METHODS AND RESULTS: A total of 520 patients (57 ± 13 years) with an implantable cardioverter-defibrillator (ICD) (n = 240) or CRT-defibrillator (n = 280) who underwent CF-LVAD implantation at 5 centers in 2007-2015 were studied. Patients were divided into 3 groups: ICD-N (QRS ≤120 ms; n = 134), ICD-W (QRS >120 ms; n = 106), and CRT (n = 280). Mortality, hospitalization, and ventricular arrhythmia (VA) incidence were compared among the groups. Baseline QRS duration was different among the groups (100 ± 13 [ICD-N] vs 155 ± 26 [ICD-W] vs 159 ± 29 ms [CRT]; P < .0001). In the ICD-W group, 37 (35%) had >80% RV pacing at baseline. Median biventricular pacing in the CRT group was 96%. Over 523 days of CF-LVAD support, Kaplan-Meier analysis showed no difference in survival among groups (log rank P = .9). According to multivariate Cox regression, wide QRS duration and RV pacing were not associated with survival. QRS narrowed during CF-LVAD support in the ICD-W and CRT groups but was not associated with improved survival (P = .9). No differences were noted among the groups in hospitalizations (P = .9), VA (P = .2), or ICD shocks (P = .06). CONCLUSIONS: In this large CF-LVAD cohort, a wide QRS duration, high percentage of RV pacing at baseline, and changes in QRS duration after LVAD implantation were not associated with survival. Continued CRT after CF-LVAD implantation also was not associated with improved survival or HF hospitalizations.

High shear induces platelet dysfunction leading to enhanced thrombotic propensity and diminished hemostatic capacity.

Thrombosis and bleeding are devastating adverse events in patients supported with blood-contacting medical devices (BCMDs). In this study, we delineated that high non-physiological shear stress (NPSS) caused platelet dysfunction that may contribute to both thrombosis and bleeding. Human blood was subjected to NPSS with short exposure time. Levels of platelet surface GPIbα and GPVI receptors as well as activation level of GPIIb/IIIa in NPSS-sheared blood were examined with flow cytometry. Adhesion of sheared platelets on fibrinogen, von Willibrand factor (VWF), and collagen was quantified with fluorescent microscopy. Ristocetin- and collagen-induced platelet aggregation was characterized by aggregometry. NPSS activated platelets in a shear and exposure time-dependent manner. The number of activated platelets increased with increasing levels of NPSS and exposure time, which corresponded well with increased adhesion of sheared platelets on fibrinogen. Concurrently, NPSS caused shedding of GPIbα and GPVI in a manner dependent on shear and exposure time. The loss of intact GPIbα and GPVI increased with increasing levels of NPSS and exposure time. The number of platelets adhered on VWF and collagen decreased with increasing levels of NPSS and exposure time, respectively. The decrease in the number of platelets adhered on VWF and collagen corresponded well with the loss in GPIbα and GPVI on platelet surface. Both ristocetin- and collagen-induced platelet aggregation in sheared blood decreased with increasing levels of NPSS and exposure time. The study clearly demonstrated that high NPSS causes simultaneous platelet activation and receptor shedding, resulting in a paradoxical effect on platelet function via two distinct mechanisms. The results from the study suggested that the NPSS could induce the concurrent propensity for both thrombosis and bleeding in patients.

Myocardial protection with complementary dose of modified Del Nido cardioplegia during heart transplantation.

Myocardial protection during heart transplantation is achieved by a first dose of heart preservation solution during donor heart harvesting, while there is no consensus about the management of complementary doses during implantation in the recipient. We describe a preliminary case series where modified Del Nido Cardioplegia was used as complementary dose at the time of donor heart implantation.

Changing demographics of heart donors: The impact of donor drug intoxication on posttransplant survival.

Recent reports have shown an increase in the number of organ donors from drug intoxication. The impact of donor drug use on survival after cardiac transplant remains unclear. The aim of our study was to illustrate changes in donor death mechanisms and assess the impact on posttransplant survival. We queried United Network of Organ Sharing thoracic transplant and deceased donor databases to identify patients undergoing heart transplantation between 2005 and 2015. We evaluated annual trends in donor death mechanisms. Recipients were propensity matched (drug-intoxicated-non-drug-intoxicated = 1:2) and posttransplant survival was compared using Kaplan-Meier curves. In total, 19 384 donor hearts were used for transplant during the period (donor age 31.6 ± 11.8 years, 72% male). Use of drug-intoxicated donors increased from 2% (2005) to 13% (2015) and decreased from blunt injury (40%-30%) and intracranial hemorrhage (29%-25%). After propensity matching, posttransplant survival of drug-intoxicated donor hearts was 90%, 82%, and 76% at 1, 3, and 5 years, which was similar to non-drug-intoxicated. Heart transplants using drug-intoxicated donors have significantly increased; however, they have not adversely affected posttransplant survival. Hearts from drug-intoxicated donors should be carefully evaluated and considered for transplant.

Biomarker enhanced risk prediction for development of AKI after cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is a common post-cardiac surgery complication and influences patient morbidity and prognosis. This study was designed to identify preoperative candidate urine biomarkers in patients undergoing cardiac surgery. METHODS: A prospective cohort study of adults undergoing cardiac surgery at increased risk for AKI at a single hospital between July 2010 and September 2012 was performed. The primary outcome was the development of AKI, defined as an absolute serum creatinine (SCr) level increase ≥ 0.5 mg/dL or a ≥ 50% relative increase within 72 h of surgery. A secondary outcome was development of AKI defined by Kidney Disease Improving Global Outcomes (KDIGO). Urine collected by voiding within 4 h prior to surgery was used for proteomic analysis and confirmatory enzyme linked immunosorbent assays (ELISAs) studies. Biomarkers were tested for AKI-prediction using Cox and Snell R2, area under the receiver operating curve (AUROC), and percent of corrected classifications. To evaluate the added effect of each candidate biomarker on AKI discrimination, receiver operator characteristic (ROC) curves, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were calculated. RESULTS: Forty-seven of 755 patients met screening criteria including 15 with AKI. Proteomic analysis identified 29 proteins with a significant ≥2-fold change. Confirmatory ELISA measurements of five candidate markers showed urinary complement factor B (CFB) and histidine rich glycoprotein (HRG) concentrations were significantly increased in patients with AKI. By multivariate analysis, NRI, and IDI the addition of CFB and HRG to the standard clinical assessment significantly improved risk prediction for the primary outcome. Only HRG was a significant predictor in the 21 patients with AKI defined by KDIGO criteria. CONCLUSIONS: Pre-operative urine measurement of CFB or HRG significantly enhanced the current post-surgery AKI risk stratification for more restrictive definition of AKI. HRG, but not CFB or clinical risk stratification, predicted AKI defined by KDIGO. The ability of these biomarkers to predict risk for dialysis-requiring AKI or death could not be reliably assessed in our study due to a small number of patients with either outcome.

Regional Cerebral Oxygen Saturation Level Predicts 30-Day Mortality Rate After Left Ventricular Assist Device Surgery.

OBJECTIVE: Left ventricular assist device (LVAD) surgery is complex, high risk, and expensive. The authors' hypothesis is baseline regional cerebral oxygen saturation (rSO2) might be a predictor of postoperative clinical outcomes. DESIGN: Retrospective review of 210 consecutive continuous flow LVAD patients between 2008 and 2014. The primary measure is 30-day mortality rate and secondary measures include modified major adverse cardiocerebral events (MACE), length of stay (LOS), and intensive care unit (ICU) stay. Multiple logistic regression models were applied to examine if a binary outcome variable, such as 30-day mortality and MACE, is associated with rSO2 at baseline. Log-linear model was used to examine whether LOS or ICU stay hours is associated with rSO2 at baseline. SETTING: Single institution, academic hospital. PARTICIPANTS: Patients who received LVAD surgery ​at Jewish Hospital, Louisville, KY. INTERVENTIONS: All patients received LVAD surgery. Cerebral oximetry monitoring was used in both the preoperative and intraoperative periods. MEASUREMENTS AND MAIN RESULTS: The authors found that higher rSO2 at baseline is associated with lower 30-day mortality with an odds ratio of 0.94 and 95% confidence interval (0.888, 0.995) for every 1% increase of rSO2. For secondary outcomes, baseline rSO2 was not significantly associated with MACE, requirement for postoperative renal failure/dialysis, reoperation for bleeding, and LOS or ICU hours. CONCLUSIONS: Regional cerebral oxygen saturation levels at baseline are significantly associated with 30-day mortality after LVAD surgeries.

Mechanistic insight of platelet apoptosis leading to non-surgical bleeding among heart failure patients supported by continuous-flow left ventricular assist devices.

Non-surgical bleeding (NSB) is the most common clinical complication in heart failure (HF) patients supported by continuous-flow left ventricular assist devices (CF-LVADs). In this study, oxidative stress and alteration of signal pathways leading to platelet apoptosis were investigated. Thirty-one HF patients supported by CF-LVADs were divided into bleeder (n = 12) and non-bleeder (n = 19) groups. Multiple blood samples were collected at pre-implant (baseline) and weekly up to 1-month post-implant. A single blood sample was collected from healthy subjects (reference). Production of reactive oxygen species (ROS) in platelets, total antioxidant capacity (TAC), oxidized low-density lipoproteins (oxLDL), expression of Bcl-2 and Bcl-xL, Bax and release of cytochrome c (Cyt.c), platelet mitochondrial membrane potential (Δψ m), activation of caspases, gelsolin cleavage and platelet apoptosis were examined. Significantly elevated ROS, oxLDL and depleted TAC were evident in the bleeder group compared to non-bleeder group (p < 0.05). Platelet pro-survival proteins (Bcl-2, Bcl-xL) were significantly reduced in the bleeder group in comparison to the non-bleeder group (p < 0.05). Translocation of Bax into platelet mitochondria membrane and subsequent release of Cyt.c were more prevalent in the bleeder group. Platelet mitochondrial damage, activation of caspases, gelsolin cleavage, and ultimate platelet apoptosis in the bleeder group were observed. Oxidative stress and activation of both intrinsic and extrinsic pathways of platelet apoptosis may be linked to NSB in CF-LVAD patients. Additionally, biomarkers of oxidative stress, examination of pro-survivals and pro-apoptotic proteins in platelets, mitochondrial damage, caspase activation, and platelet apoptosis may be used to help identify HF patients at high risk of NSB post-implant.