Concomitant tricuspid valve surgery in patients with significant tricuspid regurgitation undergoing left ventricular assist device implantation: A systematic review and meta-analysis.

BACKGROUND: Significant tricuspid regurgitation (TR) is a predictor of right heart failure (RHF) and increased mortality following left ventricular assist device (LVAD) implantation, however the benefit of tricuspid valve surgery (TVS) at the time of LVAD implantation remains unclear. This study compares early and late mortality and RHF outcomes in patients with significant TR undergoing LVAD implantation with and without concomitant TVS. METHODS: A systematic search of four electronic databases was conducted for studies comparing patients with moderate or severe TR undergoing LVAD implantation with or without concomitant TVS. Meta-analysis was performed for primary outcomes of early and late mortality and RHF. Secondary outcomes included rate of stroke, renal failure, hospital and ICU length of stay. An overall survival curve was constructed using aggregated, reconstructed individual patient data from Kaplan-Meier (KM) curves. RESULTS: Nine studies included 575 patients that underwent isolated LVAD and 308 patients whom received concomitant TVS. Both groups had similar rates of severe TR (46.5% vs. 45.6%). There was no significant difference seen in risk of early mortality (RR 0.90; 95% CI, 0.57-1.42; p = 0.64; I2 = 0%) or early RHF (RR 0.82; 95% CI, 0.66-1.19; p = 0.41; I2 = 57) and late outcomes remained comparable between both groups. The aggregated KM curve showed isolated LVAD to be associated with overall increased survival (HR 1.42; 95% CI, 1.05-1.93; p = 0.023). CONCLUSIONS: Undergoing concomitant TVS did not display increased benefit in terms of early or late mortality and RHF in patients with preoperative significant TR. Further data to evaluate the benefit of concomitant TVS stratified by TR severity or by other predictors of RHF will be beneficial.

Comparing left ventricular assist device inflow cannula angle between median sternotomy and thoracotomy using 3D reconstructions.

BACKGROUND: Left ventricular assist device (LVAD) implantation via thoracotomy has many potential advantages compared to conventional sternotomy, including improved inflow cannula (IFC) positioning. We compared the difference in IFC angles, postoperative, and long-term outcomes for patients with LVADs implanted via thoracotomy and sternotomy. METHODS: A single-center, retrospective analysis of 14 patients who underwent thoracotomy implantation was performed and matched with 28 patients who underwent sternotomy LVAD implantations for a total of 42 patients. Inclusion required a minimum LVAD support duration of 30 days and excluded concomitant procedures. A postoperative CT-chest was used to measure the angle the between the IFC and mitral valve in two-dimensions and results were compared with three-dimensional reconstruction using the same CT chest. Outcome data were extracted from medical records. RESULTS: There was no significant difference in gender, INTERMACS score, BMI, or age between the two groups. Median cardiopulmonary bypass time was longer in the thoracotomy group compared to the sternotomy group, 107 min (86-122) versus 76 min (56-93), p < 0.01. 3D reconstructions revealed less deviation of the IFC away from the mitral valve in devices implanted via thoracotomy compared to sternotomy, median (IQR) angle 16.3° (13.9°-21.0°) versus 23.2° (17.9°-26.4°), p < 0.01. Rates of pump thrombosis, stroke, and gastrointestinal bleeding were not significantly different. CONCLUSIONS: Devices implanted via thoracotomy demonstrated less deviation away from mitral valve. However, there was no difference in morbidity between the two approaches. 3D reconstruction of the heart is an innovative technique to measure angulation and is clinically advantageous when compared to 2D imaging.

Anatomical human fitting of the BiVACOR total artificial heart.

BACKGROUND: BiVACOR is a novel total artificial heart (TAH) utilizing a single centrifugal magnetically levitated rotor with the ability to modulate pulsatile flow. The device has been successfully tested in a bovine model. We undertook a multicenter anatomical and virtual fitting study of the BiVACOR in patients undergoing heart transplantation. METHODS: 10 patients were recruited across two heart transplant centers. A sterilized 1:1 titanium model of the device was inserted into the patient's chest post heart explant, prior to implantation of the donor heart. Measurements were recorded in situ. The device was then removed. Following this, retrospective 3D reconstructions were created from computed tomography chest scans to simulate a virtual fitting. RESULTS: Mean age was 53 years (range 38-67). Mean BMI was 28 (range 20-37). Heart failure etiology was varied-with ischemic cardiomyopathy being the most common. Mean spine-to-sternum distance at the tenth thoracic vertebrae (T10) was 14 cm (range 11-18). Mean aorta to aortic Port distance was 0.2 cm (range 0-0.5). Mean pulmonary artery to pulmonary artery port distance was 4.2 cm (range 1-7). The device fitted suitably in all patients without gross distortion to the geometry between native vessel/chamber and port. CONCLUSIONS: This study described the anatomical and virtual fitting of the BiVACOR TAH. The device fit well within the chest cavities of all 10 patients, who represented a variety of body morphologies and heart failure etiology.

Using Intravascular Lithotripsy to Facilitate Transfemoral Arterial Access for Transcatheter Aortic Valve Implantation.

Peripheral vascular assessment is important in pre-procedural planning for transcatheter aortic valve implantation (TAVI). While alternative vascular access sites have been used in patients with hostile iliofemoral anatomy, femoral access has been established as the superior access method for procedural outcomes. Intravascular lithotripsy (IVL) can facilitate transfemoral access for TAVI in patients with calcific stenoses of the iliofemoral arteries. This How-To-Do-It article describes the procedural planning and methods for performing IVL in these patients.

Coronary Artery Fistula Involving the RCA, LAD, and the Main Pulmonary Artery.

We present a case of a complex congenital coronary artery fistula between the right coronary artery, left anterior descending artery, and the main pulmonary artery complicated by massive aneurysms and a left-to-right shunt. We highlight the multimodality approach to assessment and the importance of individualized management of complex coronary fistulas.

Heart Transplantation From DCD Donors in Australia: Lessons Learned From the First 74 Cases.

Heart transplantation from donation after circulatory death (DCD) donors has the potential to substantially increase overall heart transplant activity. The aim of this report is to review the first 8 y of our clinical heart transplant program at St Vincent's Hospital Sydney, to describe how our program has evolved and to report the impact that changes to our retrieval protocols have had on posttransplant outcomes. Since 2014, we have performed 74 DCD heart transplants from DCD donors utilizing a direct procurement protocol followed by normothermic machine perfusion. Changes to our retrieval protocol have resulted in a higher retrieval rate from DCD donors and fewer rejections of DCD hearts during normothermic machine perfusion. Compared with our previously reported early experience in the first 23 transplants, we have observed a significant reduction in the incidence of severe primary graft dysfunction from 35% (8/23) to 8% (4/51) in the subsequent 51 transplant recipients ( P < 0.01). The only withdrawal time interval significantly associated with severe primary graft dysfunction was the asystolic warm ischemic time: 15 (12-17) versus 13 (11-14) min ( P < 0.05). One- and 5-y survival of DCD heart transplant recipients was 94% and 88%, comparable to that of a contemporary cohort of donation after brain death recipients: 87 and 81% ( P -value was not significant). In conclusion, heart transplantation from DCD donors has become a major contributor to our overall transplant activity accounting for almost 30% of all transplants performed by our program in the last 2 y, with similar DCD and donation after brain death outcomes.

A systematic review and meta-analysis of clinical trials of thyroid hormone administration to brain dead potential organ donors.

OBJECTIVES: To review all published clinical studies of thyroid hormone administration to brain-dead potential organ donors. METHODS: A search of PubMed using multiple search terms retrieved 401 publications including 35 original reports describing administration of thyroid hormone to brain-dead potential organ donors. Detailed review of the 35 original reports led to identification of two additional publications not retrieved in the original search. The 37 original publications reported findings from 16 separate case series or retrospective audits and seven randomized controlled trials, four of which were placebo-controlled. Meta-analysis was restricted to the four placebo-controlled randomized controlled trials. RESULTS: Whereas all case series and retrospective audits reported a beneficial effect of thyroid hormone administration, all seven randomized controlled trials reported no benefit of thyroid hormone administration either alone or in combination with other hormonal therapies. In four placebo-controlled trials including 209 donors, administration of thyroid hormone (n=108) compared with placebo (n=101) had no significant effect on donor cardiac index (pooled mean difference, 0.15 L/min/m²; 95% confidence interval -0.18 to 0.48). The major limitation of the case series and retrospective audits was the lack of consideration of uncontrolled variables that confound interpretation of the results. A limitation of the randomized controlled trials was that the proportion of donors who were hemodynamically unstable or marginal in other ways was too small to exclude a benefit of thyroid hormone in this subgroup. CONCLUSIONS: The findings of this systematic review do not support a role for routine administration of thyroid hormone in the brain-dead potential organ donor. Existing recommendations regarding the use of thyroid hormone in marginal donors are based on low-level evidence.

Splinters in the fingernails, heart and brain: thromboembolic complications of non-bacterial thrombotic endocarditis despite treatment with a direct-acting oral anticoagulant.

Non-bacterial thrombotic endocarditis (NBTE) is a rare condition characterized by non-infectious vegetations affecting the cardiac valves. Although systemic thromboembolism is a commonly associated condition, antiphospholipid syndrome is less common. Nevertheless, treatment generally involves long-term anticoagulation. We report a case of a patient with previously undiagnosed NBTE who suffered systemic thromboembolic events despite pre-existing treatment with a direct-acting oral anticoagulant.

Smaller rectus femoris size measured by ultrasound is associated with poorer outcomes after cardiac surgery.

OBJECTIVE: We sought to evaluate the association of low rectus femoris cross-sectional area (RFCSA) with hospital length of stay and poorer outcomes in patients undergoing cardiac surgery. METHODS: A single right-leg RFCSA was measured with ultrasound preoperatively and baseline characteristics, clinical data, and outcomes recorded. Patients were categorized as low rectus femoris muscle size (lowRF) or normal rectus femoris muscle size (normalRF), if they were in the lowest quartile or not, respectively. All analyses were performed on both body surface area (BSA)- and sex-adjusted RFCSA. RESULTS: One hundred eight-four patients had a RFCSA measured with a mean of 5.01 cm2 (1.41 cm2), and range of 0.71 to 8.77 cm2. When analyzing the BSA-adjusted RFCSA, we found the lowRF group had a longer hospital stay, 11.0 days [7.0-16.3] versus 8.0 days [6.0-10.0] for the normalRF group (P < .001), and a greater proportion of extended hospital stay (≥18.5 days) of 19.6% compared with 6.2% (P = .010). When the RFCSA was adjusted for sex, the lowRF group had a greater length of hospital stay, 9.0 days [7.0-14.5] versus 8.0 days [6.0-11.0] (P = .049). In both the BSA- and sex-adjusted RFCSA, the lowRF group suffered greater morbidity and were more likely discharged to a destination other than home. In multivariate analyses adjusting for European System for Cardiac Operative Risk Evaluation II, BSA-adjusted lowRF but not sex-adjusted lowRF was independently associated with log-transformed hospital length of stay. LowRF was not independently associated with increased major morbidity and death for both BSA and sex-adjusted RFCSA. CONCLUSIONS: Low RFCSA has a significant association with increased hospital length of stay, morbidity, and nonhome discharge in patients undergoing cardiac procedures. TRIAL REGISTRY NUMBER: ACTRN12620000678998.

Impact of frailty on mortality and morbidity in bridge to transplant recipients of contemporary durable mechanical circulatory support.

BACKGROUND: Frailty is associated with adverse outcomes in advanced heart failure. We studied the impact of frailty on postoperative outcomes in bridge to transplant (BTT) durable mechanical circulatory support (MCS) recipients. METHODS: Patients undergoing left ventricular assist device (LVAD, n = 96) or biventricular support (BiV, n = 11) as BTT underwent frailty assessment. Frailty was defined as ≥ 3 physical domains of the Fried's Frailty Phenotype (FFP) or ≥ 2 physical domains of the FFP plus cognitive impairment on the Montreal Cognitive Assessment (MoCA). RESULTS: No difference in mortality at 360 days was observed in frail (n = 6/38, 15.8%) vs non-frail (n = 4/58, 6.9%) LVAD supported patients, p = 0.19. However, there was a significant excess mortality in frail BiV (n = 4/5) vs non-frail BiV (n = 0/6) supported patients, p = 0.013. In all patients, frail patients compared to non-frail patients experienced longer intensive care unit stay, 12 vs 6 days (p < 0.0001) and hospital length of stay, 48 vs 27 days (p < 0.0001). There was no difference in hemocompatibility and infection related adverse events. The majority (n = 22/29, 75.9%) of frail patients became non-frail following MCS; contrastingly, a minority (n = 3/42, 7.1%) became frail from being non-frail (p = 0.0003). CONCLUSIONS: Abnormal markers of frailty are common in patients undergoing BTT-MCS support and those used herein predict mortality in BiV-supported patients, but not in LVAD patients. These findings may help us better identify patients who will benefit most from BiV-BTT therapy.

Intermittent Papillary Muscle Suction: A Rare Cause of Left Ventricular Assist Device Low Flow.

Low flow alarms represent a management challenge in patients with left ventricular assist devices because they are often a consequence of complex patient-device interactions. We present a case of intermittent suction of the postero-medial papillary muscle into the left ventricular assist device inflow cannula during diastole, causing low flows. This case highlights the importance of a systematic approach and use of multiple investigation modalities in making an accurate diagnosis. (Level of Difficulty: Advanced.).

The impact of frailty on mortality after heart transplantation.

BACKGROUND: Frailty is prevalent in the patients with advanced heart failure; however, its impact on clinical outcomes after heart transplantation (HTx) is unclear. The aim of this study was to assess the impact of pre-transplant frailty on mortality and the duration of hospitalization after HTx. METHODS: We retrospectively reviewed the post-transplant outcomes of 140 patients with advanced heart failure who had undergone frailty assessment within the 6-month interval before HTx: 43 of them were frail (F) and 97 were non-frail (NF). RESULTS: Post-transplant survival rates for the NF cohort at 1 and 12 months were 97% (93-100) and 95% (91-99) (95% CI), respectively. In contrast, post-transplant survival rates for the F cohort at the same time points were 86% (76-96) and 74% (60-84) (p < 0.0008 vs NF cohort), respectively. The Cox proportional hazards regression analysis demonstrated that pre-transplant frailty was an independent predictor of post-transplant mortality with a hazard ratio of 3.8 (95% CI: 1.4-10.5). Intensive care unit and hospital length of stay were 2 and 7 days longer in the F cohort (both p < 0.05), respectively, than in the NF cohort. CONCLUSIONS: Frailty within 6 months before HTx is independently associated with increased mortality and prolonged hospitalization after transplantation. Future research should focus on the development of strategies to mitigate the adverse effects of pre-transplant frailty.

Plugging Paravalvular Leak in Transcatheter Aortic Valves.

Paravalvular leak can complicate transcatheter aortic valve replacement with important prognostic implications. Correction of defects requires complex planning and execution. Multiple or irregular lesions, calcified annulus, and high sealing skirts on self-expandable devices are especially challenging. Such defects may be approximated using malleable vascular closure devices. (Level of Difficulty: Intermediate.).

Outcomes of Donation After Circulatory Death Heart Transplantation in Australia.

BACKGROUND: Transplantation of hearts retrieved from donation after circulatory death (DCD) donors is an evolving clinical practice. OBJECTIVES: The purpose of this study is to provide an update on the authors' Australian clinical program and discuss lessons learned since performing the world's first series of distantly procured DCD heart transplants. METHODS: The authors report their experience of 23 DCD heart transplants from 45 DCD donor referrals since 2014. Donor details were collected using electronic donor records (Donate Life, Australia) and all recipient details were collected from clinical notes and electronic databases at St. Vincent's Hospital. RESULTS: Hearts were retrieved from 33 of 45 DCD donors. A total of 12 donors did not progress to circulatory arrest within the pre-specified timeframe. Eight hearts failed to meet viability criteria during normothermic machine perfusion, and 2 hearts were declined due to machine malfunction. A total of 23 hearts were transplanted between July 2014 and April 2018. All recipients had successful implantation, with mechanical circulatory support utilized in 9 cases. One case requiring extracorporeal membrane oxygenation subsequently died on the sixth post-operative day, representing a mortality of 4.4% over 4 years with a total follow-up period of 15,500 days for the entire cohort. All surviving recipients had normal cardiac function on echocardiogram and no evidence of acute rejection on discharge. All surviving patients remain in New York Heart Association functional class I with normal biventricular function. CONCLUSIONS: DCD heart transplant outcomes are excellent. Despite a higher requirement for mechanical circulatory support for delayed graft function, primarily in recipients with ventricular assist device support, overall survival and rejection episodes are comparable to outcomes from contemporary brain-dead donors.

Enhanced preservation of the rat heart after prolonged hypothermic ischemia with erythropoietin-supplemented Celsior solution.

BACKGROUND: The cardioprotective efficacy of erythropoietin (EPO) has been widely documented in rodent models of acute coronary syndrome. We sought to evaluate its cardioprotective potential as an adjunct to Celsior cardioplegia in a rodent model of prolonged hypothermic global ischemia-reperfusion injury. METHODS: Isolated working rat hearts were subjected to 6 or 10 hours of hypothermic ischemic storage in Celsior cardioplegic solution. Celsior was supplemented with EPO over a dose range of 0 to 5 units/ml, as well as with glyceryl trinitrate (0.1 mg/ml) and zoniporide (1 µmol/liter). Myocardial functional recovery was determined after 45 minutes of reperfusion, then left ventricular tissue was prepared for Western blotting. RESULTS: The presence of EPO in Celsior dose-dependently improved recovery of myocardial function after 6 hours ischemic storage time (cardiac output recovery: 52.5 ± 11.3% vs 2.5 ± 0.4%; EPO: 5 units/ml vs 0 units/ml; p < 0.05). This functional benefit was associated with decreased lactate dehydrogenase released into coronary effluent and enhanced phosphorylation of STAT3, all of which were completely abrogated by pre-treatment with stattic, a selective inhibitor of STAT3 activation. When the ischemic storage time was extended to 10 hours, additive beneficial effects on myocardial function were seen when EPO was used in combination with the cardioprotective agents glyceryl trinitrate and zoniporide. CONCLUSIONS: EPO has demonstrated cardioprotective efficacy in a rodent model of ischemia-reperfusion injury simulating cardiac allograft preservation, which appears to be mediated via activation of the SAFE cytoprotective signaling pathway.

A recombinant human neuregulin-1 peptide improves preservation of the rodent heart after prolonged hypothermic storage.

BACKGROUND: Donor hearts are subjected to ischemia-reperfusion injury during transplantation. Recombinant human neuregulin (rhNRG)-1 peptide attenuates myocardial injury in various animal models of cardiomyopathy. Supplementing the organ-storage solution, Celsior (C), with glyceryl trinitrate (GTN) and cariporide improves cardiac preservation after hypothermic storage. We hypothesized that the addition of rhNRG-1 to C would improve cardiac preservation after hypothermic storage and provide incremental benefit in combination with GTN and cariporide. METHODS: An isolated working rat heart model was used. To assess the effect of rhNRG-1, hearts were stored for 6 hr at 4°C in C ± rhNRG-1 (14 nM). To assess the effect of using a combination of prosurvival kinase activators on cardiac preservation, the ischemic storage time was extended to 10 hr and hearts stored in C ± rhNRG-1 (14 nM) ± GTN (0.1 mg/mL) ± Cariporide (10 µM). Hearts were subsequently reperfused, cardiac function remeasured, and tissue collected for protein analysis and immunohistochemistry. Optimal timing of rhNRG-1 administration was also assessed. RESULTS: rhNRG-1 supplemented C improved functional recovery after 6 hr of storage (cardiac output recovery [mean ± SEM]: control 1.4% ± 0.6%; rhNRG-1+C 21.1% ± 7.9%; P<0.05). After 10-hr storage, no improvement in functional recovery was observed with rhNRG-1, GTN, or cariporide alone; however, GTN combined with cariporide did improve recovery (P<0.01), which was further enhanced by the addition of rhNRG-1 (P<0.01). Functional improvements were accompanied by increased phosphorylation of Akt, ERK1/2, STAT3, and GSK-3ß and reduced cleaved caspase-3 (P<0.01). CONCLUSIONS: rhNRG-1 given together with other activators of prosurvival pathways improves preservation of the rat heart and shows promise for increasing the cold-ischemic life of donor hearts in transplantation.

Usefulness of extracorporeal membrane oxygenation for early cardiac allograft dysfunction.

BACKGROUND: Owing to persisting donor shortages, the use of "marginal hearts" has increased. Because patients who receive a marginal heart may require hemodynamic support in the early post-operative period, extracorporeal membrane oxygenation (ECMO) may be used until recovery of acute graft dysfunction. METHODS: A retrospective file review of 124 primary adult heart transplant patients from 2003 to 2008 was conducted. We compared 17 patients who received post-transplant ECMO support with 107 transplant recipients without ECMO. Donor and recipient pre-transplant, intra-operative, and post-transplant clinical variables to 6 months after transplant were compared. RESULTS: Pre-operative demographics of the 2 groups were similar. Eight (47%) of the patients in the ECMO group received marginal donor hearts, compared with 1 (1%) in the non-ECMO group (p < 0.05). There were 3 early deaths in the ECMO group (2 of whom had received optimal donor hearts), resulting in lower Day 30 ECMO survival of 82.4% vs 100% for non-ECMO, respectively (p < 0.001), and 6-month survival of 82.4% vs 95.6%, respectively (p < 0.02). Most of the difference in survival was in patients who required salvage ECMO despite normal pre-transplant donor LV function. The rate of early dialysis was higher in the ECMO group, at 18% vs 6% at Day 3, but there was no difference between the 2 groups by Day 7. Pre-discharge ventricular function was normal in all discharged ECMO patients and all but 1 non-ECMO patient. ECMO patients had a longer intensive care unit stay (8.9 ± 3.4 vs 4.8 ± 5.4 days, p < 0.005), but there was a slightly shorter ward stay, resulting in a similar overall hospitalization length of stay (22.9 ± 8.3 vs 25.1 ± 25.2 days). CONCLUSIONS: ECMO allows for salvage of acute graft dysfunction and may allow use of marginal donor hearts. Survival rates are lower in patients who require ECMO compared with optimal donors, but early cardiac dysfunction normalizes in most without long-term cardiac or renal sequelae. Despite longer ventilation times, overall hospitalization is not prolonged.

Primary graft failure after heart transplantation.

Primary graft failure (PGF) is a devastating complication that occurs in the immediate postoperative period following heart transplantation. It manifests as severe ventricular dysfunction of the donor graft and carries significant mortality and morbidity. In the last decade, advances in pharmacological treatment and mechanical circulatory support have improved the outlook for heart transplant recipients who develop this complication. Despite these advances in treatment, PGF is still the leading cause of death in the first 30 days after transplantation. In today's climate of significant organ shortages and growing waiting lists, transplant units worldwide have increasingly utilised "marginal donors" to try and bridge the gap between "supply and demand." One of the costs of this strategy has been an increased incidence of PGF. As the threat of PGF increases, the challenges of predicting and preventing its occurrence, as well as the identification of more effective treatment modalities, are vital areas of active research and development.