Therapeutic Inhibition of Acid-Sensing Ion Channel 1a Recovers Heart Function After Ischemia-Reperfusion Injury.

BACKGROUND: Ischemia-reperfusion injury (IRI) is one of the major risk factors implicated in morbidity and mortality associated with cardiovascular disease. During cardiac ischemia, the buildup of acidic metabolites results in decreased intracellular and extracellular pH, which can reach as low as 6.0 to 6.5. The resulting tissue acidosis exacerbates ischemic injury and significantly affects cardiac function. METHODS: We used genetic and pharmacologic methods to investigate the role of acid-sensing ion channel 1a (ASIC1a) in cardiac IRI at the cellular and whole-organ level. Human induced pluripotent stem cell-derived cardiomyocytes as well as ex vivo and in vivo models of IRI were used to test the efficacy of ASIC1a inhibitors as pre- and postconditioning therapeutic agents. RESULTS: Analysis of human complex trait genetics indicates that variants in the ASIC1 genetic locus are significantly associated with cardiac and cerebrovascular ischemic injuries. Using human induced pluripotent stem cell-derived cardiomyocytes in vitro and murine ex vivo heart models, we demonstrate that genetic ablation of ASIC1a improves cardiomyocyte viability after acute IRI. Therapeutic blockade of ASIC1a using specific and potent pharmacologic inhibitors recapitulates this cardioprotective effect. We used an in vivo model of myocardial infarction and 2 models of ex vivo donor heart procurement and storage as clinical models to show that ASIC1a inhibition improves post-IRI cardiac viability. Use of ASIC1a inhibitors as preconditioning or postconditioning agents provided equivalent cardioprotection to benchmark drugs, including the sodium-hydrogen exchange inhibitor zoniporide. At the cellular and whole organ level, we show that acute exposure to ASIC1a inhibitors has no effect on cardiac ion channels regulating baseline electromechanical coupling and physiologic performance. CONCLUSIONS: Our data provide compelling evidence for a novel pharmacologic strategy involving ASIC1a blockade as a cardioprotective therapy to improve the viability of hearts subjected to IRI.

Coronary angiography of the ex-situ beating donor heart in a portable organ care system.

OBJECTIVES: To determine safety and feasibility of ex-situ coronary angiography. BACKGROUND: To cater for the perpetually growing demand for heart donors, interest in donation following circulatory death (DCD) has been rekindled. Further pursuit of donor pool expansion has led to eligibility extension to "marginal" donors who are at higher risk of coronary artery disease (CAD). Excluding CAD in potentially eligible DCD donors, for whom ante-mortem angiography is commonly not permitted, is therefore challenging. Ex-situ coronary angiography serves as an ethical and feasible diagnostic tool to assess for preclusive CAD. METHODS: We undertook a systematic review of the published literature and institutional retrospective review of case experience with ex-situ coronary angiography of donor hearts, supported by a portable organ care system. RESULTS: Combined literature and institutional case review yielded nine total cases of ex-situ coronary angiography of donor human hearts plus one experimental porcine model. Of the eight cases of ex-situ coronary angiography performed at our institute, all were conducted without complication or injury to the allograft. Two thirds of reported human cases have proceeded to successful transplantation. CONCLUSIONS: Diagnostic coronary angiography of the ex-situ beating donor heart is safe, feasible, and demonstrates novel clinical utility in mitigating subsequent transplantation of unsuitable allografts. In the setting of suspected coronary atherosclerosis of the donor heart, which may preclude favorable transplantation outcomes, ex-situ coronary angiography should be considered at eligible transplant centers.

Donation After Circulatory Death: A New Frontier.

PURPOSE OF REVIEW: To highlight the current global experience with DCD heart transplantation and explore the evolution of, and compare preservation strategies; examine early clinical outcomes, and discuss the growing use of DCD donors as a new frontier in heart transplantation. RECENT FINDINGS: The two strategies of DCD heart preservation include NMP using the OCS Heart and TA-NRP followed by either: NMP or CSS. Better understanding the limits of cold ischaemia following TA-NRP will aid in distant procurement. Asystolic warm ischaemia plays an important role in determining immediate post-operative graft function and potential need for mechanical support. Large volume DCD heart transplant units show no difference in survival between DCD and DBD donor heart transplants. In a previously non-utilised source of donor hearts, often viewed as an "unknown frontier" in heart transplantation, DCD hearts are a suitable alternative to brain-dead donor hearts and are likely to remain a permanent part of the heart transplantation landscape. Global uptake is currently increasing, and as understanding of preservation strategies and tolerable ischaemic times improve, utilisation of DCD hearts will continue to grow.

Prevention and Reversal of Frailty in Heart Failure　- A Systematic Review.

BACKGROUND: Frailty is prevalent in patients with heart failure (HF) and associated with increased morbidity and mortality. Hence, there has been increased interest in the reversibility of frailty following treatment with medication or surgery. This systematic review aimed to assess the reversibility of frailty in patients with HF before and after surgical interventions aimed at treating the underlying cause of HF. It also aimed to assess the efficacy of cardiac rehabilitation and prehabilitation in reversing or preventing frailty in patients with HF.Methods and Results:Searches of PubMed, MEDLINE and Academic Search Ultimate identified studies with HF patients undergoing interventions to reverse frailty. Titles, abstracts and full texts were screened for eligibility based on the PRISMA guidelines and using predefined inclusion/exclusion criteria in relation to participants, intervention, control, outcome and study design. In total, 14 studies were included: 3 assessed the effect of surgery, 7 assessed the effect of rehabilitation programs, 2 assessed the effect of a prehabilitation program and 2 assessed the effect of program interruptions on HF patients. CONCLUSIONS: Overall, it was found that frailty is at least partially reversible and potentially preventable in patients with HF. Interruption of rehabilitation programs resulted in deterioration of the frailty status. Future research should focus on the role of prehabilitation in mitigating frailty prior to surgical intervention.

RETRACTED: Peripheral "Right to Right" Extracoporeal Membrane Oxygenation for Right Heart Failure Following Left Ventricular Assist Device Insertion.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Authors. This abstract has been published due to a miscommunication in the ANZSCTS ASM conference supplement. It needs to be retracted as we the authors wish to submit a full length paper with updated material.

Modified composite-graft technique for aortic root replacement.

This report describes a novel modification of a self-assembled composite graft to replace the aortic root and left ventricular outflow tract (LVOT). This technique enables the implantation of a larger valve than conventional ways and simultaneous reconstruction of LVOT. This technique comprises Inspiris Resilia aortic valve and Gelweave Valsalva graft. By placing the valve in the sinus portion of the graft, the bioprosthesis that is 1 mm smaller than the graft can be accommodated, providing a proper length of the collar for LVOT reconstruction. This technique is useful for patients who require redo-aortic root replacement and have restricted LVOT.

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.

Primary Cardiac Impairment in Patients With Marfan Syndrome Undergoing a Bentall Procedure.

BACKGROUND: In this study we sought to verify the existence of primary cardiac impairment in patients with Marfan syndrome (MFS) undergoing a Bentall procedure and to explore its clinical significance. METHODS: Between October 2010 and April 2019, 164 patients with MFS and 748 patients without MFS with aortic root aneurysms underwent a Bentall procedure. Clinical characteristics and perioperative cardiac structure and function between both groups were compared after propensity score matching. Multivariate regression analysis was performed to identify factors that influenced the postoperative left ventricular ejection fraction and any adverse cardiogenic events. The midterm survival between these 2 groups were compared. RESULTS: After propensity score matching both groups had similar preoperative baseline characteristics. The MFS patients presented a higher preoperative New York Heart Association classification, larger left ventricular size, and poorer postoperative cardiac function compared with non-MFS patients. In our multivariate regression analysis MFS was associated with a lower postoperative left ventricular ejection fraction. Furthermore MFS was an independent risk factor for adverse postoperative cardiogenic events during patients' hospital stay (odds ratio, 6.243; 95% confidence interval, 1.71-22.75; P = .006). There was no difference in midterm survival between the 2 groups (P = .772). CONCLUSIONS: Clinical manifestations observed in MFS patients supported the existence of primary cardiac impairment. Because of a higher rate of postoperative cardiogenic adverse events in MFS patients, the potential impact of primary cardiac impairment in MFS should be carefully considered in cardiovascular surgery.

Percutaneous venopulmonary artery extracorporeal membrane oxygenation for right heart failure after left ventricular assist device insertion.

OBJECTIVES: Right ventricular failure after left ventricular assist device (LVAD) insertion is associated with significant mortality and morbidity. Mechanical support options include right ventricular assist devices, venoarterial extracorporeal membrane oxygenation (ECMO) and venopulmonary artery ECMO, the latter often involving central cannulation. We sought to evaluate the feasibility and early outcomes of a truly percutaneous venopulmonary artery (pVPA) ECMO strategy, with the potential advantage of bedside removal once weaned. METHODS: Data from a single tertiary centre were reviewed retrospectively from January 2014 to January 2019. During this time, 54 patients underwent LVAD insertion, with 19 requiring mechanical support for right ventricular failure. Among them, 10 patients received pVPA ECMO. Implantation of the pVPA ECMO was performed under transoesophageal echocardiography and fluoroscopy guidance, with an inflow cannula placed in the right atrium via the right femoral vein and an outflow cannula placed in the left pulmonary artery (PA) via the right internal jugular vein. RESULTS: Cannula insertion was 100% successful with no need for repositioning. Eight patients (80%) were able to be successfully weaned (at the bedside); 6 were discharged from the hospital and there were no cases of early sepsis, mediastinitis or thromboembolism. At follow-up, 5 patients had received transplants (50%), with 1 on LVAD support as destination therapy (10%). Survival was 60 ± 15% and 50 ± 16% at 6 and 12 months, respectively. CONCLUSIONS: pVPA ECMO is 100% technically feasible and is an efficient method for temporary right ventricular support after LVAD insertion with the advantage of simple bedside removal and avoidance of a PA graft remnant in the chest cavity.

Machine Learning Prediction Model for Acute Renal Failure After Acute Aortic Syndrome Surgery.

BACKGROUND: Acute renal failure (ARF) is the most common major complication following cardiac surgery for acute aortic syndrome (AAS) and worsens the postoperative prognosis. Our aim was to establish a machine learning prediction model for ARF occurrence in AAS patients. METHODS: We included AAS patient data from nine medical centers (n = 1,637) and analyzed the incidence of ARF and the risk factors for postoperative ARF. We used data from six medical centers to compare the performance of four machine learning models and performed internal validation to identify AAS patients who developed postoperative ARF. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to compare the performance of the predictive models. We compared the performance of the optimal machine learning prediction model with that of traditional prediction models. Data from three medical centers were used for external validation. RESULTS: The eXtreme Gradient Boosting (XGBoost) algorithm performed best in the internal validation process (AUC = 0.82), which was better than both the logistic regression (LR) prediction model (AUC = 0.77, p < 0.001) and the traditional scoring systems. Upon external validation, the XGBoost prediction model (AUC =0.81) also performed better than both the LR prediction model (AUC = 0.75, p = 0.03) and the traditional scoring systems. We created an online application based on the XGBoost prediction model. CONCLUSIONS: We have developed a machine learning model that has better predictive performance than traditional LR prediction models as well as other existing risk scoring systems for postoperative ARF. This model can be utilized to provide early warnings when high-risk patients are found, enabling clinicians to take prompt measures.

Long-term outcomes of the frozen elephant trunk procedure: a systematic review.

BACKGROUND: The frozen elephant trunk (FET) procedure remains an increasingly popular approach to address complex multi-segmental aortic pathologies, owing to their ability to promote false lumen thrombosis and reduce the need for second-stage operations. While the short-term outcomes of such procedures have been shown to be acceptable, much less is known regarding long-term outcomes. This systematic review evaluates long-term outcomes of the FET procedure. METHODS: Studies with at least 12 months follow-up data on FETs were identified in four electronic databases. All studies were reviewed by two independent researchers and relevant data extracted. Long-term outcomes, including overall survival, freedom from reintervention, and freedom from aortic events, were evaluated using patient data recreated from digitized Kaplan-Meier curves. RESULTS: Thirty-seven studies with 4,178 patients were identified. The majority of the studies focused solely on acute dissections. Average follow-up was 3.2 years. Overall survival at 1-, 3-, and 5-year was 89.6%, 85.2%, and 82.0%, respectively. Freedom from reintervention at the same timepoints were 93.9%, 89.3%, and 86.8%, respectively. Mortality, permanent neurological deficit and spinal cord injury were 10.2%, 7.7%, and 6.5%, respectively. CONCLUSIONS: Survival after the FET procedure is favorable, though ongoing close serial monitoring is essential to assess for the need for further reintervention. Larger multi-institutional registries are required to provide more robust evidence to better elucidate the patient cohort that would most benefit from the FET.

Multiple reoperations on the aortic valve: outcomes and implications for future potential valve-in-valve strategy.

OBJECTIVES: Surgical mortality and long-term outcomes are important considerations when determining strategies for multiple reoperations on the aortic valve (AV). With the rise of percutaneous valve-in-valve, we sought to evaluate the current outcomes of conventional surgery for AV reoperation, focusing first on the effect of the number of previous AV interventions with a subsequent analysis of the risk factors for adverse outcomes. METHODS: From January 2007 to December 2016, 316 consecutive patients underwent an open redo operation (replacement) on their AV at a single centre. It was the first AV reintervention in 263 patients (Group 1), second in 42 patients (Group 2) and third or more in 11 patients (Group 3). RESULTS: There were 230 men and 86 women, with a median age of 58 (Q1-Q3: 46-70) years. Structural valve deterioration (SVD) of the bioprosthesis (n = 136, 44%), endocarditis (n = 57, 18%) and prosthetic valve dehiscence (n = 41, 13%) were the most common reasons for reintervention. Overall, in-hospital mortality was 7.3%: 7.2% in Group 1, 4.76% in Group 2 and 18.2% in Group 3 (P = 0.233) and ranged from 3.7% for SVD to 14.0% when endocarditis was the reason for reintervention. Higher preoperative New York Heart Association (NYHA) class (III/IV) [odds ratio (OR) 15.9, P = 0.011], injury during re-entry (OR 16.9, P = 0.015), endocarditis (OR 3.7, P = 0.038) and concomitant mitral valve replacement (OR 5.6, P = 0.006) were independent risk factors for in-hospital mortality. Survival at 8 years was 79.0 ± 3.0% for the entire cohort and 88.4 ± 3.2% for re-replacement after SVD. CONCLUSIONS: Multiple AV reoperations carry an acceptable risk of early postoperative mortality, particularly for isolated valve replacements of SVD.