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Durable continuous-flow left ventricular assist devices (cfLVADs) demonstrate superior survival, cardiac functional status, and overall quality of life compared to medical therapy alone in advanced heart failure. Previous studies have not considered the impact arterial compliance may have on pump performance or developed arterial pressure. This study assessed the impact of alterations in arterial compliance, preload, and afterload on continuous-flow pump function and measured hemodynamics using an in-vitro pulsatile mock circulatory loop. Decreased arterial compliance was associated with a significant increase in arterial pressure pulsatility which was not evident in the flow pulsatility, as displayed in pump flow waveforms. There were marked changes in the pump flow waveforms due to the significant alteration in the aortoventricular gradient during diastole according to the changes in compliance. This study demonstrates that changes in systemic blood pressure, afterload, and left ventricular contractility each significantly affects the flow waveform. The association of hypertension with lower aortic compliance results in markedly decreased diastolic flow rates which may be important in contributing to a greater risk of adverse events under cfLVAD support.

Heart failure (HF) is one of the most prevalent life-threatening cardiovascular diseases in which 6.5 million people are suffering in the USA and more than 23 million worldwide. Mechanical circulatory support of HF patients can be achieved by implanting a left ventricular assist device (LVAD) into HF patients as a bridge to transplant, recovery or destination therapy and can be controlled by measurement of normal and abnormal pulmonary arterial wedge pressure (PAWP). While there are no commercial long-term implantable pressure sensors to measure PAWP, real-time non-invasive estimation of abnormal and normal PAWP becomes vital. In this work, first an improved Harris Hawks optimizer algorithm called HHO+ is presented and tested on 24 unimodal and multimodal benchmark functions. Second, a novel fully Elman neural network (FENN) is proposed to improve the classification performance. Finally, four novel 18-layer deep learning methods of convolutional neural networks (CNNs) with multi-layer perceptron (CNN-MLP), CNN with Elman neural networks (CNN-ENN), CNN with fully Elman neural networks (CNN-FENN), and CNN with fully Elman neural networks optimized by HHO+ algorithm (CNN-FENN-HHO+) for classification of abnormal and normal PAWP using estimated HVAD pump flow were developed and compared. The estimated pump flow was derived by a non-invasive method embedded into the commercial HVAD controller. The proposed methods are evaluated on an imbalanced clinical dataset using 5-fold cross-validation. The proposed CNN-FENN-HHO+ method outperforms the proposed CNN-MLP, CNN-ENN and CNN-FENN methods and improved the classification performance metrics across 5-fold cross-validation with an average sensitivity of 79%, accuracy of 78% and specificity of 76%. The proposed methods can reduce the likelihood of hazardous events like pulmonary congestion and ventricular suction for HF patients and notify identified abnormal cases to the hospital, clinician and cardiologist for emergency action, which can diminish the mortality rate of patients with HF.

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.), Central Illustration

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.

There is accumulating evidence that novel glucose-lowering agents infer potent cardiovascular and renal benefits. Therefore, it is imperative to reassess the management of post-transplant diabetes mellitus and consider the role of newer agents. With improved transplant-related survival and high prevalence of post-transplant diabetes, management of long-term complications such as diabetes are increasingly important. There are limited guidelines to assist in choice of appropriate agents after solid organ transplantation. Traditional therapies including insulin and sulfonylureas may still have a role; however, other agents should be considered prior. The evidence of novel glucose-lowering agents in post-transplant care is limited, and most studies have focused on kidney transplant recipients. While there are some parallels between renal and cardiac transplant recipients, the potential cardiovascular benefits, particularly on cardiac fibrosis are unique to cardiac transplantation. The treatment of diabetes, with a focus on additional cardiac and renal benefits, needs to be brought to the forefront of post-transplant care with incorporation of recent evidence outside of transplantation. The role for novel glucose-lowering agents in cardiac transplant recipients will be explored, with a summary of available evidence.

Over the past decade, transcatheter mitral valve replacement (TMVR) technologies have evolved with the objective of improving outcomes for patients with severe mitral regurgitation (MR) deemed unsuitable for conventional mitral valve surgery. Although the safety and efficacy of transcatheter edge-to-edge mitral valve repair (TEER) is well-established, there is a sense amongst innovators that a major advantage of TMVR may be to offer a more complete solution for the correction of MR in patients whose complex anatomy means that the likelihood of achieving grade 0 or 1 MR with TEER is low. However, abrupt correction of MR in a poorly prepared left ventricle poses a number of unique haemodynamic challenges, particularly when sudden elimination of regurgitant flow causes a relative increase in left ventricular (LV) afterload. Rapid reduction in LV cavity size following MR elimination may itself result in relative LV outflow tract obstruction (LVOTO), irrespective of the intrinsic risk of LVOTO associated with TMVR. Nevertheless, TMVR on a beating heart affords the opportunity to study real-time invasive cardiac indices in high-risk patients with acute reversal of severe MR.

There is accumulating evidence that novel glucose-lowering agents infer potent cardiovascular and renal benefits. Therefore, it is imperative to reassess the management of post-transplant diabetes mellitus and consider the role of newer agents. With improved transplant-related survival and high prevalence of post-transplant diabetes, management of long-term complications such as diabetes are increasingly important. There are limited guidelines to assist in choice of appropriate agents after solid organ transplantation. Traditional therapies including insulin and sulfonylureas may still have a role; however, other agents should be considered prior. The evidence of novel glucose-lowering agents in post-transplant care is limited, and most studies have focused on kidney transplant recipients. While there are some parallels between renal and cardiac transplant recipients, the potential cardiovascular benefits, particularly on cardiac fibrosis are unique to cardiac transplantation. The treatment of diabetes, with a focus on additional cardiac and renal benefits, needs to be brought to the forefront of post-transplant care with incorporation of recent evidence outside of transplantation. The role for novel glucose-lowering agents in cardiac transplant recipients will be explored, with a summary of available evidence.

Cardiorenal syndrome (CRS) contributes significantly to morbidity and mortality in patients requiring mechanical circulatory support and transplantation. There are no validated markers to predict major adverse kidney events (MAKEs), for which simultaneous heart-kidney transplant (SHKT) could offer improved survival. We evaluate renal histology in predicting MAKEs in transplant-listed patients.We identified 18 patients with renal histology consistent with CRS from 655 consecutive heart transplant-listed patients between 2010 and 2019. Biopsies were analyzed for glomerular, tubular, interstitial, and arteriolar changes tallied to give a biopsy chronicity score. The primary outcome, MAKE, was a composite of death, need for renal replacement therapy (RRT), or estimated glomerular filtration rate decline50%. These were evaluated at 2 time points: before and following the transplant. Secondary outcomes included the individual components of the composite outcomes and the need for short-term RRT following the transplant.The mean age was 52.3 y, 22% were female. Five patients did not survive to transplant. One patient underwent successful SHKT. MAKE occurred in 8 of 18 before the transplant and in 8 of 13 following the transplant. Neither outcome was predicted by baseline biochemistry. The biopsy chronicity score was significantly higher in patients with MAKE before transplant (4.3 versus 1.7,A higher biopsy chronicity score was associated with adverse kidney endpoints, raising its potential utility over standard biochemistry in considering SHKT referral.

Background and Aim: The left ventricle (LV) faces a dual afterload in patients with aortic stenosis (AS) – both from the valve and vasculature. Together they form the global LV load. Two cardiac magnetic resonance (CMR) techniques have been described to quantify global LV load: (1) valvulo-arterial impedance instantaneous (ZVA-INS) and (2) valvulo-arterial load (VAL). The purpose of this study was to evaluate concordance (if any) between ZVA-INS and VAL. Methods: Twenty AS patients were compared (80 ± 9 years; 12 males; 80% severe). Aortic flow velocity data was obtained during breath-hold using through-plane PC Qflow imaging. ZVA-INS was determined as the relationship of aortic pressure and maximum aortic valve (AV) gradient to ascending aorta flow velocity in the time domain. VAL was determined as the relationship of aortic pressure to ascending aorta flow velocity in the frequency domain. Values from both methods were compared against total arterial compliance (TAC). Results: Global LV load was significantly higher when assessed by ZVA-INS (3990±1795 dynes.s.cm³) than VAL (946±318 dynes.s.cm³) (R=0.941; R²=0.886; F=109.2; P

Low flow and suction alarms are provided to alert caregivers of changes in left ventricular assist device pump function but may be reset in clinical practice. We investigated the incidence and underlying causes of these alarms as well as their prognostic significance. HeartWare ventricular assist device patients (n = 113) were divided into quartiles based on their frequency of low flow and suction alarms. Survival and adverse events (thrombus, stroke, bleeding, and right heart failure) were compared between quartiles. Low flow alarms peaked in the first few months of pump support before dropping down to near negligible levels. Suction alarm frequency remained relatively constant throughout pump support. Although pump speeds (p < 0.001) and flow (p = 0.01) decreased over time, there was an increase in suction alarm frequency (p = 0.018), with no changes in low flow alarms. Patients with smaller body size (p = 0.016) and lower pump flows (p = 0.008) had higher frequencies of low flow alarms on multiple regression (p < 0.001). Patients with the highest low flow alarm frequency demonstrated poorer survival (p = 0.026). There was no relationship between suction alarm frequency and survival. There was also no relationship between either low flow or suction alarm frequency with strokes, gastrointestinal bleeds, pump thrombus, or right ventricular failure. Duration of alarm and intervention in response to the alarm was not assessed in this study. Further studies examining alarm duration and responses may inform future pump alarm algorithms.

OBJECTIVES: This study aimed to determine the safety and efficacy of combined low-dose everolimus and low-dose tacrolimus compared with standard-dose tacrolimus in attenuating left ventricular hypertrophy (LVH) after orthotopic heart transplantation (OHT). BACKGROUND: Calcineurin inhibitors (CNIs) such as tactrolimus are important in preventing cardiac allograft rejection and reducing mortality after OHT. However CNIs are causatively linked to the development of LVH, and are associated with nephrotoxicity and vasculopathy. CNI-sparing agents such as everolimus have been hypothesized to inhibit adverse effects of CNIs. METHODS: In this prospective, randomized, open-label study, OHT recipients were randomized at 12 weeks after OHT to a combination of low-dose everolimus and tacrolimus (the RADTAC group) or standard-dose tacrolimus (the TAC group), with both groups coadministered mycophenolate and prednisolone. The primary endpoint was LVH indexed as the change in left ventricular mass (DeltaLVM) by cardiovascular magnetic resonance (CMR) imaging from 12 to 52 weeks. Secondary endpoints included CMR-based myocardial performance, T1 fibrosis mapping, blood pressure, and renal function. Safety endpoints included episodes of allograft rejection and infection. RESULTS: Forty stable OHT recipients were randomized. Recipients in the RADTAC group had significantly lower tacrolimus levels compared with the TAC group (6.5 +/- 3.5 mug/l vs. 8.6 +/- 2.8 mug/l; p = 0.02). The mean everolimus level in the RADTAC group was 4.2 +/- 1.7 mug/l. A significant reduction in LVM was observed in the RADTAC group compared with an increase in LVM in the TAC group (DeltaLVM = -13.0 +/- 16.8 g vs. 2.1 +/- 8.4 g; p < 0.001). Significant differences were also noted in secondary endpoints measuring function and fibrosis (Delta circumferential strain = -2.9 +/- 2.8 vs. 2.1 +/- 2.3; p < 0.001; DeltaT1 mapping values = -32.7 +/- 51.3 ms vs. 26.3 +/- 90.4 ms; p = 0.003). No significant differences were observed in blood pressure (Delta mean arterial pressure = 4.2 +/- 18.8 mm Hg vs. 2.8 +/- 13.8 mm Hg; p = 0.77), renal function (Delta creatinine = 3.1 +/- 19.9 mumol/l vs. 9 +/- 21.8 mumol/l; p = 0.31), frequency of rejection episodes (p = 0.69), or frequency of infections (p = 0.67) between groups. CONCLUSIONS: The combination of low-dose everolimus and tacrolimus compared with standard-dose tacrolimus safely attenuates LVH in the first year after cardiac transplantation with an observed reduction in CMR-measured fibrosis and an improvement in myocardial strain.

Background Thirst is a common and troublesome symptom of patients with chronic heart failure (CHF). To date, there are no interventions to help alleviate thirst in this cohort. Chewing gum is a novel intervention, which has been tested in people undergoing haemodialysis, also prescribed with a fluid restricted therapy. The aim of this study was to determine the effect of chewing gum on the level of thirst in the short-term (average of 24 hours each day for 4 days) and in the longer-term (Days 7, 14 and 28) individuals with CHF. Methods Seventy-one (71) individuals with CHF on oral loop diuretics were randomised to chewing gum (n=36) or control (n=35) for 2 weeks. Both groups were assessed for their level of thirst at Days 1–4, 7, 14 and 28. Results Significant improvements in the level of thirst of those who received chewing gum compared to the control group at Day 4 (p=0.04) and Day 14 (p=0.02) were observed. Conclusion Chewing gum provided relief from thirst in the short-term and in the longer term. This trial provides important information to inform future clinical trials on ways to relieve thirst.

Health related quality of life (HRQoL) is rarely routinely measured in the clinical setting. In the absence of patient reported data, clinicians rely on proxy and informal estimates to support clinical decisions. This study compares clinician estimates (proxy) with patient reported HRQoL in patients with advanced heart failure and examines factors influencing discrepancies. Seventy-five patients with heart failure, (22 females, 53 males) completed the EQ-5D-5L questionnaire. Thirty-nine clinicians (11 medical, 23 nursing, 5 allied health) completed the proxy version (V1) producing 194 dyads. Correlation was assessed using Spearman’s rank tests, systematic bias was examined with Bland–Altman analyses. Inter-rater agreement at the domain level, was investigated using linear weighted Kappa statistics while factors influencing the IRG were explored using independent student t-tests, analysis of variance and regression. There was a moderate positive correlation between clinician HRQoL estimates and patient reported utility (r = 0.38; p

Background: Endomyocardial biopsy (EMB) is the gold standard method for surveillance of acute cardiac allograft rejection (ACAR) despite its invasive nature. Cardiovascular magnetic resonance (CMR)–based myocardial tissue characterization allows detection of myocarditis. The feasibility of CMR-based surveillance for ACAR-induced myocarditis in the first year after heart transplantation is currently undescribed. Methods: CMR-based multiparametric mapping was initially assessed in a prospective cross-sectional fashion to establish agreement between CMR- and EMB-based ACAR and to determine CMR cutoff values between rejection grades. A prospective randomized noninferiority pilot study was then undertaken in adult orthotopic heart transplant recipients who were randomized at 4 weeks after orthotopic heart transplantation to either CMR- or EMB-based rejection surveillance. Clinical end points were assessed at 52 weeks. Results: Four hundred one CMR studies and 354 EMB procedures were performed in 106 participants. Forty heart transplant recipients were randomized. CMR-based multiparametric assessment was highly reproducible and reliable at detecting ACAR (area under the curve, 0.92; sensitivity, 93%; specificity, 92%; negative predictive value, 99%) with greater specificity and negative predictive value than either T1 or T2 parametric CMR mapping alone. High-grade rejection occurred in similar numbers of patients in each randomized group (CMR, n=7; EMB, n=8; P =0.74). Despite similarities in immunosuppression requirements, kidney function, and mortality between groups, the rates of hospitalization (9 of 20 [45%] versus 18 of 20 [90%]; odds ratio, 0.091; P =0.006) and infection (7 of 20 [35%] versus 14 of 20 [70%]; odds ratio, 0.192; P =0,019) were lower in the CMR group. On 15 occasions (6%), patients who were randomized to the CMR arm underwent EMB for clarification or logistic reasons, representing a 94% reduction in the requirement for EMB-based surveillance. Conclusions: A noninvasive CMR-based surveillance strategy for ACAR in the first year after orthotopic heart transplantation is feasible compared with EMB-based surveillance. Registration: HREC/13/SVH/66 and HREC/17/SVH/80. Australian New Zealand Clinical Trials Registry: ACTRN12618000672257.

INTRODUCTION Ventricular function in elderly patients with aortic stenosis is impeded both by restricted aortic flow and arterial stiffening. A number of patients continue to have exertional intolerance after relief of aortic valvular obstruction due to unrecognized ventriculo-arterial coupling mismatch. HYPOTHESIS Quantification of valvulo-arterial load (VAL), using a simultaneous applanation tonometry/cardiac magnetic resonance (CMR) technique, can accurately assess the relative contributions of aortic stiffness and valve gradient in older patients with aortic stenosis. METHODS Elderly patients with aortic stenosis underwent a simultaneous applanation tonometry/CMR protocol. CMR provided left ventricular volume and aortic flow simultaneously with radial applanation tonometry pressure acquisition. Central aortic pressure was derived by transformation of the radial applanation tonometry waveform. VAL was determined as the relationship of derived aortic pressure to CMR aortic flow in frequency domain (central illustration). RESULTS Twenty patients (age 80 ± 9 years; 12 males; blood pressure 140/75 ± 20 mmHg) with aortic stenosis on transthoracic echocardiogram (16 severe; mean gradient 45 ± 16 mmHg; aortic valve area 0.8 ± 0.2 cm2) were enrolled. Derived aortic pressure and flow waveforms correlated well with invasive data. Increased VAL was significantly associated with advanced age (P = 0.04) and raised SBP (P

Left ventricular assist devices (LVADs) can provide mechanical support for a failing heart as a bridge to transplant and destination therapy. Physiological control systems for LVADs should be designed to respond to changes in hemodynamic across a variety of clinical scenarios and patients by automatically adjusting the heart pump speed. In this study, a novel adaptive physiological control system for an implantable heart pump was developed to respond to interpatient and intrapatient variations to maintain the left-ventricle-end-diastolic-pressure (LVEDP) in the normal range of 3 to 15 mmHg to prevent ventricle suction and pulmonary congestion. A new algorithm was also developed to detect LVEDP from pressure sensor measurement in real-time mode. Model-free adaptive control (MFAC) was employed to control the pump speed via simulation of 100 different patient conditions in each of six different patient scenarios, and compared to standard PID control. Controller performance was tracked using the sum of the absolute error (SAE) between the desired and measured LVEDP. The lower SAE on control tracking performance means that the measured LVEDP follows the desired LVEDP faster and with less amplitude oscillations, preventing ventricle suction and pulmonary congestion (mean and standard deviation of SAE (mmHg) for all 600 simulations were 18813 ± 29345 and 24794 ± 28380 corresponding to MFAC and PID controller, respectively). In four out of six patient scenarios, MFAC control tracking performance was better than the PID controller. This study shows the control performance can be guaranteed across different patients and conditions when using MFAC over PID control, which is a step toward clinical acceptance of these systems.

BACKGROUND: Ventricular assist devices (VADs) have provided a temporising solution to many individuals with refractory heart failure (HF) while awaiting a suitable donor for heart transplantation which remains the gold standard in treatment. Many of the discussions around VADs involve ongoing morbidity; however, one aspect of VADs that is often overlooked is the utility of their log files. We decided to review the literature for mentions of the clinical utility of VAD log files. METHODS: A keyword search was utilised on PUBMED using the terms ‘Ventricular Assist Device’ and ‘Log files’. Perhaps unsurprisingly, this search only yielded 4 results with further articles being discovered through the bibliography of these publications. RESULTS: The 4 identified articles provided basic information on log files, particularly with reference to the HVAD. Logs can be categorised into three types—data (pump parameters), events (changes in parameters) and alarms (abnormal function). Using a combination of these logs, we can readily identify abnormal pump operation such as the development and progression of pump thrombosis, suction events and gastrointestinal bleeding. However, the research potential of log files was not discussed in these publications, particularly as it pertains to areas such as studying speed modulation and pulsatility in VADs. CONCLUSIONS: VADs are an important staple in the treatment of patients with refractory HF. Log files provide a treasure-trove of information and knowledge that can be utilised for clinical benefit. Furthermore, log files provide an excellent tool for conducting research into device functionality. Current literature on the clinical utility of log files is sparse with much untapped potential.

IntroductionCardiac transplantation (CTx) is a life-saving operation that can improve the quality and length of a recipient’s life. Immunosuppression medication, required to prevent rejection, can result in adverse metabolic and renal effects. Clinically significant complications include metabolic effects such as diabetes and weight gain, renal impairment, and cardiac disease such as allograft vasculopathy and myocardial fibrosis. Sodium glucose co-transporter 2 (SGLT2) inhibitors are a class of oral medication that increase urinary excretion of glucose. In patients with type 2 diabetes, SGLT2 inhibitors improve cardiovascular, metabolic and renal outcomes. Similar benefits have been shown in patients with heart failure and reduced ejection fraction irrespective of diabetes status. In patients with post-transplant diabetes mellitus, SGLT2 inhibitors improve metabolic parameters; however, their benefit and safety have not been evaluated in randomised prospective studies. This study will potentially provide a novel therapy to improve or prevent complications (diabetes, kidney failure and heart fibrosis) that occur with immunosuppressive medications.MethodsThe EMPA-HTx study is a randomised, placebo-controlled trial of the SGLT2 inhibitor empagliflozin 10 mg daily versus placebo in recent CTx recipients. One hundred participants will be randomised 1:1 and commence the study medication within 6–8 weeks of transplantation with treatment and follow-up until 12 months after transplantation. Demographic information, anthropomorphic measurements, pathology tests and cardiac magnetic resonance (CMR) scan will be recorded at baseline and follow-up. Patients will be reviewed monthly during the study until 12 months post-CTx and data will be collected for each patient at each study visit. The overall aim of the study is to assess the safety and efficacy of empagliflozin in CTx recipients. The primary outcome is glycaemic improvement measured as change in glycated haemoglobin and/or fructosamine. Key secondary outcomes are cardiac interstitial fibrosis measured by CMR and renal function measured by estimated glomerular filtration rate.Ethics and disseminationThis study has been approved by St Vincent’s Hospital Human Research Ethics Committee (2021/ETH12184). The findings will be presented at national and international scientific meetings and published in peer-reviewed journals.Trial registration numberACTRN12622000978763.

Background: In light of decreased intracranial hemorrhage with direct oral anticoagulants and concerns about their safety in continuous flow left ventricular assist devices, we conducted an ex vivo study of thrombus formation using multiple anticoagulation agents. Methods: A continuous flow left ventricular assist device (HeartWare ventricular assist device) hemocompatibility loop was run using human blood under 7 conditions: control (no anticoagulation or antiplatelet); in vitro addition of aspirin; in vitro addition of apixaban at low dose (equivalent 2.5 mg twice daily); addition of apixaban at high dose (equivalent 5 mg twice daily); patients on warfarin; patients on apixaban (5 mg twice daily); and patients on dabigatran (150 mg twice daily). The primary outcome was time to formation of intrapump thrombosis. Secondary outcomes were reduction in clotting times over 1 hour, hemolysis, reduced platelet aggregation, and von Willebrand activity. Results: Twenty-one runs were completed. Times to thrombosis in median (interquartile range) were control, 131 (127–134.5); in vitro aspirin, 124 (114.5–137); and patients on dabigatran, 131 (130.5–135.5) minutes, respectively. Times in patients on warfarin were, 137 (136.5–143.5); in vitro low-dose apixaban, 141 (138.5–142); and patients on apixaban, 140 (138–142.5) minutes, respectively. No thrombus formed in the in vitro high-dose apixaban group. There were no significant differences between the individual groups. When all apixaban groups were compared with nonapixaban groups, the time to thrombosis formation was significantly longer, 143 (137–150) versus 133.5 (128.5–140) minutes, P =0.02. There were similar changes in lactate dehydrogenase levels and other secondary end points. Conclusions: In an in vitro study of anticoagulation using human blood in a mock loop with a HeartWare HVAD, we demonstrated similar thrombosis times for apixaban and warfarin. Time to clotting was longer in the combined apixaban groups compared with combined other groups, but thrombosis times between individual groups were not significantly different.

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.), Graphical abstract, Paravalvular leak can complicate transcatheter aortic valve replacement with important prognostic implications. Correction of defects requires…

Aortic regurgitation (AR), mitral regurgitation (MR), and tricuspid regurgitation (TR) after continuous-flow left ventricular assist device (LVAD) are common and may increase with prolonged LVAD support. The aim of this study was to simulate severe valvular regurgitation (AR, MR, and TR) within a 4-elemental pulsatile mock circulatory loop (MCL) and observe their impact on isolated LVAD and biventricular assist device (BiVAD) with HeartWare HVAD. Aortic regurgitation, MR, and TR were achieved via the removal of one leaflet from bileaflet mechanical valve from the appropriate valves of the left or right ventricles. The impact of alteration of LVAD pump speed (LVAD 2200-4000 RPM, right ventricular assist device [RVAD] 2400 RPM) and altered LVAD preload (10-25 mm Hg) was assessed. With each of the regurgitant valve lesions, there was a decrease in isolated LVAD pump flow pulsatility. Isolated LVAD provided sufficient support in the setting of severe MR or TR compared with control, and flows were enhanced with BiVAD support. In severe AR, there was no benefit of BiVAD support over isolated LVAD, and actual loop flows remained low. High LVAD flows combined with low RVAD flows and dampened aortic pressures are good indicators of AR. The 4-elemental MCL successfully simulated several control and abnormal valvular conditions using various pump speeds. Current findings are consistent with conservative management of MR and TR in the setting of mechanical support, but emphasize the importance of the correction of AR.

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.

BACKGROUND Despite advances in device technology and treatment strategies, infection remains a major cause of adverse events (AEs) in mechanical circulatory support (MCS) patients. To characterize the epidemiology of MCS infection, we examined the type, location, and timing of infection in the International Society for Heart and Lung Transplantation Registry (ISHLT) for Mechanically Assisted Circulatory Support (IMACS) over 3 years, 2013 to 2015. METHODS Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) definitions were used to categorize AE infections occurring in MCS patients within IMACS. The IMACS infection variables were mapped to ISHLT definitions for infection where feasible. Three categories of MCS infection were defined as ventricular assist device (VAD) specific, VAD related, and non-VAD. RESULTS There were 10,171 patients enrolled from January 2013 through December 2015. Infection was the most common AE, with 3,788 patients (37%) experiencing ≥ 1 infection, and 6,758 AE infections reported overall. Non-VAD infection was the largest category, 4,501: 34.0% pneumonias, 30.6% non-VAD-related bloodstream infections (BSIs), 24.15% urinary tract infections (UTIs), and 10.2% gastrointestinal infections. VAD-specific infection was the second largest category, 1,756: 82.9% driveline, 12.8% pocket, and 4.3% pump/or cannula infections. VAD-related infection was the smallest category, 501: 47.5% BSIs, 47.5% mediastinitis, and 5.0% mediastinitis/pocket infections. All 3 categories were more frequently reported ≤ 3 months after implant. CONCLUSIONS Non-VAD infection, including pneumonia, BSI, UTI, and gastrointestinal infection, was the leading category of infection in MCS patients and the most frequently reported ≤ 3 months after implant. These results provide evidence to support resourcing and strengthening infection prevention strategy early after implantation in MCS.

Right ventricular failure following left ventricular assist devices implantation is a serious complication associated with high mortality. In patients with or at high risk of developing right ventricular failure, biventricular support is recommended. Because univentricular support is associated with high survival rates, biventricular support is often undertaken as a last resort. With the advent of newer right ventricular and biventricular systems under design and testing, better differentiation is required to ensure optimal patients care. Clear guidelines on patient selection, time of intervention and device selection are required to improve patient outcomes.

Objectives This is a systematic review summarizing the procedural characteristics and outcomes of ventricular assist device (VAD)–related ventricular tachycardia (VT) ablation. Background Drug-refractory VT refractory commonly develops post-VAD implantation. Procedural and outcome data come from small series or case reports. Methods An electronic search was performed using major databases. Primary outcomes were VT recurrence, mortality, and cardiac transplantation. Secondary endpoints were acute procedural success and procedural complications. Results Eighteen studies were included, with a total of 110 patients (mean age 59.6 ± 11 years, 89% men; VT storm 34%). Scar-related re-entry was the predominant mechanism of VT (90.3%) and cannula-related VT in 19.3% cases. Electroanatomical mapping interference occurred in 1.8% of cases; there were no reports of catheter entrapment. Noninducibility of clinical VT was achieved in 77.9%; procedural complications occurred in 9.4%. At a mean follow-up of 263.5 ± 267.0 days, VT recurred in 43.6%, 23.4% underwent cardiac transplant, and 48.1% died. There were no procedural-related deaths and no death was directly related to ventricular arrhythmia. In follow-up, there was a significant reduction in implantable cardioverter-defibrillator therapies or shocks (57.1% vs. 23.8%). Ablation allowed VT storm termination in 90% of patients. Conclusions VAD-related VT is predominantly related to pre-existing intrinsic myocardial scar rather than inflow cannula site insertion. Catheter ablation is a reasonable treatment strategy, albeit with expectedly high rate of recurrence, transplantation, and mortality related to severe underlying disease.

BACKGROUND The aim of this study was to validate our previous finding that frailty predicts early mortality in patients with advanced heart failure (AHF) and that including cognition in the frailty assessment enhances the prediction of mortality. METHODS Patients with AHF referred to our Transplant Unit between November 2015 and April 2020 underwent physical frailty assessment using the modified Fried physical frailty (PF) phenotype as well as cognitive assessment using the Montreal Cognitive Assessment (MOCA) to identify patients who were cognitively frail (CogF). We assessed the predictive value of the 2 frailty measures (PF ≥ 3 of 5 = frail; CogF ≥ 3 of 6 = frail) for pretransplant mortality. RESULTS 313 patients (233 male, 80 female; age 53 ± 13 years) were assessed. Of these, 224 patients (72%) were nonfrail and 89 (28%) were frail using the PF. The cognitive frailty assessment identified an additional 30 patients as frail: 119 (38%). Frail patients had significantly increased mortality as compared to nonfrail patients. Ventricular assist device and heart transplant-censored survival at 12 months was 92 ± 2 % for nonfrail and 69 ± 5% for frail patients (p < 0.0001) using the CogF instrument. CONCLUSIONS This study validates our previously published findings that frailty is prevalent in patients with advanced heart failure referred for heart transplantation. Physical frailty predicts early mortality. The addition of cognitive assessment to the physical assessment of frailty identifies an additional cohort of patients with a similarly poor prognosis.

Background: Modern ventricular assist devices (VADs) use a continuous flow design. It has been suggested that a lack of pulsatility contributes to a range of adverse outcomes including pump thrombus, gastrointestinal bleeding and stroke. To better assess the role of pulsatility in these adverse events, we first require a clear definition of ‘pulsatility’ in the setting of a severely impaired ventricle and a modern continuous flow VAD. Methods: A literature review was conducted to elucidate the understanding of pulsatility in modern VAD literature. Search engines used included PUBMED, EMBASE and the Cochrane library. Articles were appraised on three aspects: Whether they mentioned pulsatility; whether they mentioned which pulsatility measure was used and finally which methodology was used to obtain the value. Results: Of 354 articles reviewed, only 13 met our broad inclusion criteria. Of these articles, the most cited measure was pulsatility index (PI) – used by 11 of the publications. The methodology used to obtain the value was not uniform and five articles did not clearly state it. Other measures included pulse pressure and surplus haemodynamic energy. The majority of articles did not directly discuss pulsatility in the setting of patient-pump interaction. Conclusion: Most publications did not provide a definition for pulsatility. In those that did, the most common measure was PI. Measuring PI was not standardised. Few papers addressed the impact of intrinsic ventricular function and arterial compliance on pulsatility. We suggest that future publications adopt a uniform definition which encompasses both patient and pump characteristics.

Secondary mitral regurgitation (MR) and heart failure are mutually dependent. Secondary MR occurs as a consequence of heart failure in patients with impaired left ventricular (LV) function, decreasing cardiac efficiency, accelerating a decline in contractility and worsening the already dismal prognosis of these patients. Advances in transcatheter techniques have now given promise to improved survival, outcomes, and quality of life for patients with advanced heart failure and secondary MR. Although transcatheter edge-to-edge repair is well established, transapical transcatheter mitral valve implantation (TMVI) may represent a more durable solution for correction of secondary MR without the need for cardiopulmonary bypass. Correction of MR, however, is thought to acutely increase LV afterload due to the elimination of low afterload regurgitant flow. In high-risk patients, this may cause acute decompensated heart failure. Off-pump TMVI on a beating heart poses a number of unique challenges, but also the opportunity to study invasive haemodynamic indices in high-risk heart failure patients for the first time. In the following discussion, we review the acute haemodynamic changes during off-pump TMVI in patients with heart failure in order to better guide optimal patient selection and management.

Purpose Hemolysis is an important complication of ventricular assist device (VAD) therapy. Several studies have postulated that chronic hemolysis may be a cause of adverse outcomes in patients with VADs, but consistent definitions and clinical outcome data are lacking. Methods We conducted a single-center retrospective cohort study examining survival to transplantation in patients who underwent VAD implantation from 2010-2020. Baseline demographics, renal function, echocardiographic, and cardiac catheterization data for the first 12 months of VAD therapy or until transplantation were collected. Additionally, all available lactate dehydrogenase (LDH) values were collected over this time frame and means were calculated for each patient. Results VADs were implanted in 166 patients, 19% female and 87% left-sided devices. Patients with mean LDH above the upper limit of normal for our laboratory's LDH assay of 440 units/liter (U/L) were more likely to die prior to transplantation compared to those with mean LDH Conclusion Mean LDH above the normal range was an independent and significant predictor of mortality in patients with VADs awaiting transplantation at our center over the last decade. While concomitant severe liver or RV dysfunction can raise LDH, chronic hemolysis is an important potential etiology for our observations. Further work is needed to define chronic hemolysis and its impact on outcomes in patients with VADs.

Purpose Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy providing hemodynamic support to patients with advanced cardiorespiratory compromise. Following orthotopic heart transplantation (HTX), primary graft failure (PGF), especially wherein there is significant right ventricular dysfunction, can necessitate such intensive support to bridge to recovery or additional therapy. Marginal donors are used to increase the donor pool given the excess of candidates in most jurisdictions. Methods We conducted a single-center retrospective cohort study examining HTX from donation after brain death (DBD) donors that required post-operative ECMO for PGF from January 2008 - September 2020. Donor and recipient information were collected including demographics, renal function, echocardiographic measurements, biopsy data, and outcome measures. Marginal donor hearts were identified according to validated criteria including use of donor triiodothyronine (T3), donor left ventricular ejection fraction 60 years old, and donor ischemic time >6 hours or >4 hours if donor age >40 years old. Results Overall, 376 DBD HTX were performed, of which 126 involved marginal donor hearts (33.3%). ECMO was required in 81 (21.4%) of these patients, 42 (51.9%) of which involved marginal donor hearts. Thus, ECMO rates were 15.5% and 33.3% in non-marginal and marginal donor hearts, respectively. Overall, ECMO was successfully weaned in 75 (92.6%) and 62 (76.5%) survived their index HTX admission. Among patients who received non-marginal organs, 36 (92.3%) had ECMO weaned and 31 (79.5%) survived their index HTX admission versus 39 (92.9%) and 31 (73.8%) for these endpoints respectively among patients receiving marginal organs. Conclusion Our center's experience indicates that ECMO can provide satisfactory outcomes in HTX patients requiring advanced hemodynamic support post-operatively for PGF. Marginal donor hearts were more likely to require ECMO support post-operatively but had comparable and acceptable rates of index-admission survival compared to non-marginal cases. Further work is needed to evaluate outcome differences as efforts are made to expand the donor pool around the world.

Background: Aortic stenosis (AS) is no longer considered to be a disease of fixed left ventricular (LV) afterload, but rather, functions as a series circuit, with important contributions from both the valve and vasculature. Patients with AS are typically elderly, with hypertension and a markedly remodelled aorta. The arterial component is sizeable, and yet, quantifying this to-date has been difficult to determine. We compared measurement of aortic pressure, flow and global LV load using a cardiac magnetic resonance (CMR)/applanation tonometry (AT) technique to uncouple ventriculo-arterial (VA) interactions. Methods: 20 healthy elderly patients and 20 with AS underwent a CMR/AT protocol. CMR provided LV volume and aortic flow simultaneously with AT pressure acquisition. Aortic pressure was derived by transformation of the AT waveform. Systemic vascular resistance (SVR) and global LV load were determined as the relationship of pressure to flow in the frequency domain. Values from both cohorts were compared. Results: AS patients were older (p ​

Background: Vasoplegia has been shown to be associated with increased morbidity and mortality in patients undergoing cardiac surgery. It has been previously stated that low pulsatile states as seen with current left ventricular assist devices (LVADs) may contribute to vasoplegia post LVAD-explant and heart transplant. We sought to examine the literature regarding vasoplegia in the post-operative setting for patients undergoing LVAD explant and heart transplant. Method: A literature review was conducted to firstly define vasoplegia in the setting of LVAD patients, and secondly to better understand the relationship between vasoplegia and LVAD explantation in the postoperative heart transplant patient cohort. A keyword search of ‘vasoplegia’ OR ‘vasoplegic’ AND ‘transplant’ was used. Search engines used were PubMed, Cochrane Library, ClinicalTrials.gov , Ovid, Scopus and grey literature. Results: 17 studies met the selection criteria for review. Three key themes emerged from the literature. Firstly, there is limited consensus regarding the definition of vasoplegia. Secondly, patients with LVADs experienced higher rates of vasoplegia following heart transplant than their counterparts and thirdly, increased cardiopulmonary bypass time was associated with a higher rate of vasoplegia. Conclusion: Vasoplegia is not clearly defined in the literature as it pertains to the LVAD patient cohort. Patients bridged with LVADs appear to have higher rates of vasoplegia, however the aetiology of this is unclear and may be associated with continuous flow physiology or prolonged cardiopulmonary bypass time. A universal definition will aid in risk stratification, early recognition and management.

Aortic valve stenosis (AS) is no longer considered to be a disease of fixed left ventricular (LV) afterload (due to an obstructive valve), but rather, functions as a series circuit with important contributions from both the valve and ageing vasculature. Patients with AS are frequently elderly, with hypertension and a markedly remodelled aorta. The arterial component is sizable, and yet, the contribution of ventricular afterload has been difficult to determine. Arterial stiffening increases the speed of propagation of the blood pressure wave along the central arteries (estimated as the pulse wave velocity), which results in an earlier return of reflected waves. The effect is to augment blood pressure in the proximal aorta during systole, increasing the central pulse pressure and, in turn, placing even greater afterload on the heart. Elevated global LV afterload is known to have adverse consequences on LV remodelling, function and survival in patients with AS. Consequently, there is renewed focus on methods to estimate the relative contributions of local versus global changes in arterial mechanics and valvular haemodynamics in patients with AS. We present a review on existing and upcoming methods to quantify valvulo-arterial impedance and thereby global LV load in patients with AS.