Echocardiographic surrogate of left ventricular stroke work in a model of brain stem death donors.

BACKGROUND: The commonest echocardiographic measurement, left ventricular ejection fraction, can not necessarily predict mortality of recipients following heart transplantation potentially due to afterload dependency. Afterload-independent left ventricular stroke work index (LVSWI) is alternatively recommended by the current guideline; however, pulmonary artery catheters are rarely inserted in organ donors in most jurisdictions. We propose a novel non-invasive echocardiographic parameter, Pressure-Strain Product (PSP), as a potential surrogate of catheter-based LVSWI. This study aimed to investigate if PSP could correlate with catheter-based LVSWI in an ovine model of brain stem death (BSD) donors. The association between PSP and myocardial mitochondrial function in the post-transplant hearts was also evaluated. METHODS: Thirty-one female sheep (weight 47 ± 5 kg) were divided into two groups; BSD (n = 15), and sham neurologic injury (n = 16). Echocardiographic parameters including global circumferential strain (GCS) and global radial strain (GRS) and pulmonary artery catheter-based LVSWI were simultaneously measured at 8-timepoints during 24-h observation. PSP was calculated as a product of GCS or GRS, and mean arterial pressure for PSPcirc or PSPrad, respectively. Myocardial mitochondrial function was evaluated following 6-h observation after heart transplantation. RESULTS: In BSD donor hearts, PSPcirc (n = 96, rho = .547, p < .001) showed the best correlation with LVSWI among other echocardiographic parameters. PSPcirc returned AUC of .825 to distinguish higher values of cardiomyocyte mitochondrial function (cut-off point; mean value of complex 1,2 O2 Flux) in post-transplant hearts, which was greater than other echocardiographic parameters. CONCLUSIONS: PSPcirc could be used as a surrogate of catheter-based LVSWI reflecting mitochondrial function.

HeartMate 3 implantation with an emphasis on the biventricular configuration.

OBJECTIVES: Right ventricular failure following implantation of a durable left ventricular assist device (LVAD) is a major driver of mortality. Reported survival following biventricular (BiVAD) or total artificial heart (TAH) implantation remains substantially inferior to LVAD alone. We report our outcomes with LVAD and BiVAD HeartMate 3 (HM3). METHODS: Consecutive patients undergoing implantation of an HM3 LVAD between November 2014 and December 2021, at The Alfred, Australia were included in the study. Comparison was made between the BiVAD and LVAD alone groups. RESULTS: A total of 86 patients, 65 patients with LVAD alone and 21 in a BiVAD configuration underwent implantation. The median age of the LVAD and BiVAD groups was 56 years (Interquartile range 46-62) and 49 years (Interquartile range 37-55), respectively. By 4 years after implantation, 54% of LVAD patients and 43% of BiVAD patients had undergone cardiac transplantation. The incidence of stroke in the entire experience was 3.5% and pump thrombosis 5% (all in the RVAD). There were 14 deaths in the LVAD group and 1 in the BiVAD group. The actuarial survival for LVAD patients at 1 year was 85% and BiVAD patients at 1 year was 95%. CONCLUSIONS: The application of HM 3 BiVAD support in selected patients appears to offer a satisfactory solution to patients requiring biventricular support.

Mitral Valve Regurgitation After Lung Transplantation: Aetiology, Management and Outcome.

BACKGROUND: Problematic mitral regurgitation (MR) may develop following lung transplantation (LTx). There is limited information on the management of MR in LTx patients, as such we sought to evaluate our centre's experience. METHODS: From 2000 to 2019, 1,054 patients underwent LTx at our centre (896 bilateral, 158 single). We identified patients in whom significant MR developed at any point post-LTx. The aetiology of MR, management and outcome were retrospectively analysed. RESULTS: Eight (8) patients developed severe MR post-LTx, six following bilateral LTx and two following single LTx. Lung transplantation indications included interstitial lung disease (n=5), chronic obstructive pulmonary disease (n=2) and pulmonary arterial hypertension (n=1). Severe MR occurred intraoperatively (n=1), postoperative day 1 (n=1) with the remaining six cases between 80 and 263 days post-LTx. The aetiology was noted to be due to severe left ventricular dysfunction following unmasking of a chronically pulmonary hypertension-related under-preloaded left ventricle in one case, and in the remaining seven patients causes included myxomatous degeneration, ischaemic MR, and functional MR due to annular dilatation. In the patient with intraoperative severe MR, the MR became mild with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and in the remaining seven patients a variety of procedures were used, including mitral valve repair, valve replacement and transcatheter edge-to-edge mitral valve repair. All patients survived the mitral procedure. Two (2) deaths occurred at 12.9 years (stroke) and 5 years (cancer) from mitral valve surgery. CONCLUSIONS: Development of significant mitral valve regurgitation is a rare but morbid complication after lung transplantation. This may represent the progressive natural history of pre-existing degenerative mitral valve disease and rarely, early after transplantation may be related to changes in ventricular geometry. Management of severe MR can follow the same management approach as in the non-transplant community, with the expectation of similarly good results.

Compromised right ventricular contractility in an ovine model of heart transplantation following 24 h donor brain stem death.

BACKGROUND: Heart failure is an inexorably progressive disease with a high mortality, for which heart transplantation (HTx) remains the gold standard treatment. Currently, donor hearts are primarily derived from patients following brain stem death (BSD). BSD causes activation of the sympathetic nervous system, increases endothelin levels, and triggers significant inflammation that together with potential myocardial injury associated with the transplant procedure, may affect contractility of the donor heart. We examined peri-transplant myocardial catecholamine sensitivity and cardiac contractility post-BSD and transplantation in a clinically relevant ovine model. METHODS: Donor sheep underwent BSD (BSD, n = 5) or sham (no BSD) procedures (SHAM, n = 4) and were monitored for 24h prior to heart procurement. Orthotopic HTx was performed on a separate group of donor animals following 24h of BSD (BSD-Tx, n = 6) or SHAM injury (SH-Tx, n = 5). The healthy recipient heart was used as a control (HC, n = 11). A cumulative concentration-effect curve to (-)-noradrenaline (NA) was established using left (LV) and right ventricular (RV) trabeculae to determine ß1-adrenoceptor mediated potency (-logEC50 [(-)-noradrenaline] M) and maximal contractility (Emax). RESULTS: Our data showed reduced basal and maximal (-)-noradrenaline induced contractility of the RV (but not LV) following BSD as well as HTx, regardless of whether the donor heart was exposed to BSD or SHAM. The potency of (-)-noradrenaline was lower in left and right ventricles for BSD-Tx and SH-Tx compared to HC. CONCLUSION: These studies show that the combination of BSD and transplantation are likely to impair contractility of the donor heart, particularly for the RV. For the donor heart, this contractile dysfunction appears to be independent of changes to ß1-adrenoceptor sensitivity. However, altered ß1-adrenoceptor signalling is likely to be involved in post-HTx contractile dysfunction.

The frequent insignificance of a "significant" p-value.

Null hypothesis significance testing (NHST) and p-values are widespread in the cardiac surgical literature but are frequently misunderstood and misused. The purpose of the review is to discuss major disadvantages of p-values and suggest alternatives. We describe diagnostic tests, the prosecutor's fallacy in the courtroom, and NHST, which involve inter-related conditional probabilities, to help clarify the meaning of p-values, and discuss the enormous sampling variability, or unreliability, of p-values. Finally, we use a cardiac surgical database and simulations to explore further issues involving p-values. In clinical studies, p-values provide a poor summary of the observed treatment effect, whereas the three-number summary provided by effect estimates and confidence intervals is more informative and minimizes over-interpretation of a "significant" result. p-values are an unreliable measure of the strength of evidence; if used at all they give only, at best, a very rough guide to decision making. Researchers should adopt Open Science practices to improve the trustworthiness of research and, where possible, use estimation (three-number summaries) or other better techniques.

Spontaneous echo contrast mimicking aortic root thrombus in a patient supported with extracorporeal membrane oxygenation.

Aortic root spontaneous echo contrast is a rare but significant finding. We report a 31-year-old female who was placed on venoarterial extracorporeal membrane oxygenation emergently for acute mitral regurgitation secondary to papillary muscle rupture. Following stabilization, subsequent transesophageal echocardiography suggested aortic root thrombus and prompted emergent surgery. However, further inspection with intraoperative transesophageal echocardiography revealed a spontaneous echo contrast which aided us in the intraoperative decision making.

Suicide right ventricle after lung transplantation for pulmonary vascular disease.

A 27-year-old female with Eisenmenger's syndrome underwent closure of a patent ductus arteriosus, closure of a perimembranous ventricular septal defect and mid muscular defect and bilateral lung transplantation. Her immediate postoperative course was complicated by severe right ventricular outflow tract (RVOT) obstruction resulting in hemodynamic collapse, a condition described as suicide right ventricle. The patient was placed on central Veno-Arterial Extra-Corporeal Membrane Oxygenation as a bridge to the relief of RVOT obstruction which included a right ventricular outflow muscle resection and a right ventricle outflow tract patch. The patient made an uneventful recovery.

Donor Lung Procurement by Surgical Fellow With an Expectation of High Rate of Lung Utilisation.

There is an ever increasing demand for donor lungs in patients waiting for transplantation. Lungs of many potential donors will be rejected if the standard criteria for donor assessment are followed. We have expanded our donor lung pool by accepting marginal donors and establishing a donation after circulatory death program. We have achieved comparable results using marginal donors and accepting donor lungs following donation after circulatory death. We present our assessment and technical guidelines on lung procurement taking into consideration an increasingly complex cohort of lung donors. These guidelines form the basis of the lung procurement training program involving surgical Fellows at the Alfred Hospital in Melbourne, Australia.

ECMO as a bridge to non-transplant cardiac surgery.

Cardiac surgery performed on patients in cardiogenic shock is associated with a high mortality and morbidity. This review outlines the current role of preoperative veno-arterial extra corporeal membrane oxygenation to allow hemodynamic stability and organ recovery before definitive cardiac surgery.

Successful Bridge to Orthotopic Cardiac Transplantation with Implantation of a HeartWare HVAD in Management of Systemic Right Ventricular Failure in a Patient with Transposition of the Great Arteries and Previous Atrial Switch Procedure.

A clinical case is described of a patient with a history of dextro-transposition of the great arteries (d-TGA) and prior atrial switch procedure who developed significant pulmonary hypertension whilst awaiting orthotopic cardiac transplantation. The increase in his pulmonary pressures necessitated de-listing for cardiac transplantation. A strategy of ventricular assist device (VAD) placement was then employed which provided improvement in his systemic cardiac output with left atrial off-loading to provide pulmonary vascular remodelling and consequently reduction in pulmonary vascular resistance (PVR). He was supported for a period of 408 days prior to successful orthotopic cardiac transplantation. A small number of cases with this abnormality undergoing VAD implantation have been described. Mechanical circulatory support has an important role in some patients with congenital heart disease.

Incremental Value of Three-Dimensional Transesophageal Echocardiography over the Two-Dimensional Technique in the Assessment of a Thrombus in Transit through a Patent Foramen Ovale.

We report a case of a right atrial thrombus traversing a patent foramen ovale into the left atrium, where three-dimensional transesophageal echocardiography provided considerable incremental value over two-dimensional transesophageal echocardiography in its assessment. As well as allowing us to better spatially characterize the thrombus, three-dimensional transesophageal echocardiography provided a more quantitative assessment through estimation of total thrombus burden.

Is a Bioprosthetic Valve in the Aortic Position Desirable with a Continuous Flow LVAD?

Commissural fusion of the native aortic valve in a patient with a continuous flow left ventricular assist device (LVAD) is a known phenomenon. This may result in aortic insufficiency (AI) leading to symptomatic heart failure. In patients with AI at the time of LVAD implantation, repairing, or replacing the aortic valve is advisable. We describe a patient who had a severe dilated cardiomyopathy and moderate AI who underwent implantation of an LVAD and aortic valve replacement with a bioprosthesis that subsequently developed commissural fusion which was found at the time of heart transplantation. This case highlights the conundrum of the management of AI in patients requiring LVAD support.

Pericardial Synovial Sarcoma: A Rare Clinical Entity.

Synovial sarcoma is an extremely rare form of primary malignancy of the pericardium. We present a case of primary synovial sarcoma of the pericardium followed by a review of the literature.

Left Ventricular Assist Device (LVAD) as a Bridge to Recovery for Tachycardia-Mediated Cardiomyopathy.

A case is described of cardiogenic shock that occurred following use of sotalol in a patient with severe left ventricular dysfunction. The patient required left ventricular assist device (LVAD) placement with subsequent myocardial recovery to a degree that allowed eventual device removal following 140 days of support.

Procurement of lungs for transplantation following donation after circulatory death: the Alfred technique.

INTRODUCTION: Donation after circulatory death (DCD) is an evolving method for lung transplantation (LTx) with results comparable to donation after brain death (DBD). MATERIALS AND METHODS: DCD lung transplant program requires a systematic approach for an efficient utilization of hospital resources. The surgical techniques have been developed to minimize the ischemic time during lung procurement. We have presented our management protocol and the surgical techniques as used at the Alfred Hospital in Melbourne, Australia. RESULTS: We have transplanted 92 recipients with lungs procured from 91 donors over an 8 year period from May 2006 to July 2014. This accounted for an extra 19% lung transplant operations performed during this time period. Operative mortality was 1% and 8 year survival was 71% in DCD lung recipients. CONCLUSIONS: DCD lung transplantation provides an additional significant pool of lung donors with satisfactory short and long term outcomes.

Reconstructing the infected aortic root with antibiotic impregnated biological glue.

Prosthetic valve dehiscence and persistent infection are two complications following reconstruction of the aortic root in destructive endocarditis. A technique is described involving the principles of aggressive debridement, closure of large abscess cavities with biological material incorporating a slurry of antibiotic-impregnated biological sealant, and replacement of the aortic valve with an aortic allograft valve. This strategy appears to have been successful in preventing persistent endocarditis and valve dehiscence in a limited number of patients.

Mechanical circulatory assist as a bridge to heart retransplantation in adolescents.

We report our experience with an adolescent patient who required complex management leading to retransplantation for coronary allograft vasculopathy and also review the role of ventricular assist device support in patients with this clinical entity.

Long-term right ventricular support with a centrifugal ventricular assist device placed in the right atrium.

This case series outlines the technique and results of right ventricular assist device (RVAD) support with the off-label use of the centrifugal HeartWare HVAD (HeartWare Inc., Framingham, MA, USA) for long-term support. Four patients in our institution have been implanted with BiVADs, using the Heartware device as the RVAD, and supported for between 117 days and 772 days. Three of the patients have been successfully supported for over 18 months. Three patients have successfully been transplanted and one patient remains on the device, now approaching two years of support. None of the patients have had RVAD device-related complications.

Perspective: Will blood-informed design signal the fourth generation of cardiac assist devices?

Mechanical circulatory support devices have profoundly transformed the management of severe cardiothoracic disorders. While heart transplantation is the gold standard therapy for end stage heart disease, long-term mechanical support devices are a viable alternative for those ineligible and/or those awaiting organ availability. Major technological advancements were made over first five decades of development, resulting in improved durability and survival with reduced adverse events. However, gains have tapered recently for various complications (e.g., internal bleeding; multi-system organ failure) which collectively represent a significant proportion of disability and/or mortality. Further, in light of mature ventricular assist devices failing during clinical trials or even after clinical approval (Class I withdrawals), it is timely to consider: are our pre-clinical assessment protocols, vital in the design and development of mechanical circulatory support devices, providing a realistic and reliable profile of future clinical performance? This commentary explores this question and analyses development pathways through the lens of the various disciplines involved in the pre-clinical assessment of mechanical circulatory support technologies: limitations in approaches to benchtop blood testing, computational design and simulation, and animal testing are discussed as likely contributors to some of the common hemocompatibility-related adverse events. While it is acknowledged that some shortcomings are pragmatic in nature, possible solutions are presented that will only be realised through truly transdisciplinary and open approaches that challenge the current nature of medical device development. We suggest that these can and must be overcome to diminish hemocompatibility-related adverse events and will potentially demarcate the fourth-generation of cardiac assist devices.