2024 Australia-New Zealand Expert Consensus Statement on Cardiac Amyloidosis.

Over the past 5 years, early diagnosis of and new treatments for cardiac amyloidosis (CA) have emerged that hold promise for early intervention. These include non-invasive diagnostic tests and disease modifying therapies. Recently, CA has been one of the first types of cardiomyopathy to be treated with gene editing techniques. Although these therapies are not yet widely available to patients in Australia and New Zealand, this may change in the near future. Given the rapid pace with which this field is evolving, it is important to view these advances within the Australian and New Zealand context. This Consensus Statement aims to update the Australian and New Zealand general physician and cardiologist with regards to the diagnosis, investigations, and management of CA.

Understanding Tricuspid Regurgitation Post Cardiac Transplantation; Why "Anatomical" and "Functional" Just Won't Cut It.

Tricuspid regurgitation (TR) is common after cardiac transplantation and results in poorer outcomes. Transplant recipients are at high prohibitive risk for redo surgical procedures because of risks associated with a subsequent sternotomy, immunosuppression, and renal failure. Percutaneous therapies have recently become available and may be an option for transplant recipients. However, transplant recipients have complex geometry, and there is a myriad of causes of TR posttransplant. There is a need for careful patient selection for all percutaneous valve interventions, and this is particularly true in transplant recipients who suffer from right ventricular failure and rejection and may undergo repeated endomyocardial biopsies. Cognizant of the rapid developments in this space, this review article focuses on the causes of TR, treatments, and future therapies in heart transplantation recipients to the transplant cardiologist navigate this complex area.

How do mechanical circulatory support patients die? Autopsy findings for left-ventricular assist device/total artificial heart nonsurvivors.

BACKGROUND: Although life saving for end-stage heart failure patients, permanent mechanical circulatory support (MCS) is often the proximate cause of death in those that do not survive to transplant. Autopsy remains the gold standard for diagnosing causes of death and a vital tool for better understanding underlying pathology of nonsurvivors. The aim of this study was to determine the frequency and outcomes of autopsy investigations and compare these with premortem clinical assessment. METHODS: The autopsy findings and medical records of all patients who underwent left ventricular assist device (LVAD) or total artificial heart (TAH) insertion between June 1994 and April 2022 as a bridge to transplant, but subsequently died pre-heart transplantation were reviewed. RESULTS: A total of 203 patients had a LVAD or TAH implanted during the study period. Seventy-eight patients (M=59, F=19) died prior to transplantation (age 55 [14] years, INTERMACS=2). Autopsies were conducted in 26 of 78 patients (33%). Three were limited studies. The leading contributor to cause of death was respiratory (14/26), either nosocomial infection or associated with multiorgan failure. Intracranial hemorrhage was the second most common cause of death (8/26). There was a major discrepancy rate of 17% and a minor discrepancy rate of 43%. Autopsy study added a total of 14 additional contributors of death beyond clinical assessment alone (Graphical Abstract). CONCLUSIONS: Over an observational period of 26years, the frequency of autopsy was low. To improve LVAD/TAH patient survival to transplant, better understanding as to cause of death is required. Patients with MCS have complex physiology and are at high risk of infection and bleeding complications.

The role of frailty in advanced HF and cardiac transplantation.

Frailty is a complex, multi-system condition often associated with multimorbidity. It has become an important prognostic maker across a range of conditions and is particularly relevant in patients with cardiovascular disease. Frailty encompasses a range of domains including, physical, psychological, and social. There are currently a range of validated tools available to measure frailty. It is an especially important measurement in advanced HF, because frailty occurs in up to 50% of HF patients and is potentially reversible with therapies such as mechanical circulatory support and transplantation. Moreover, frailty is dynamic, and therefore serial measurements are important. This review delves into the measurement of frailty, mechanisms, and its role in different cardiovascular cohorts. Understanding frailty will help determine patients that will benefit from therapies, as well as prognosticate outcomes.

Characteristic changes to pulsatile and steady-state load according to pulmonary hypertension classification.

It is of increasing importance to understand and predict changes to the systemic and pulmonary circulations in pulmonary hypertension (PH). To do so, it is necessary to describe the circulation in complete quantitative terms. Characteristic impedance (Zc) expresses opposition of the circulation to pulsatile blood flow. Evaluation of systemic and pulmonary Zc relationships according to PH classification has not previously been described. Prospective study of 40 clinically indicated patients referred for CMR and RHC (56 ± 18 years; 70% females, eight mPAP ≤ 25 mmHg, 16 pre-capillary [Pre-cPH], eight combined pre- and post-capillary [Cpc-PH] and eight isolated left-heart disease [Ipc-PH]). CMR provided assessment of ascending aortic (Ao) and pulmonary arterial (PA) flow, and RHC, central Ao and PA pressure. Systemic and pulmonary Zc were expressed as the relationship of pressure to flow in the frequency domain. Baseline demographic characteristics were well-matched across PH subclasses. In those with a mPAP ≤25mHg, systemic Zc and SVR were >2 times higher than pulmonary Zc and PVR. Only Pre-cPH was associated with inverse pulsatile (systemic Zc 58 [45-69] vs pulmonary Zc 70 [58-85]), but not steady-state (SVR 1101 [986-1752] vs. PVR 483 [409-557]) relationships. Patients with CpcPH and IpcPH had concordant pulsatile and steady-state relationships (Graphical Abstract). Measurement of, and the relationship between, systemic and pulmonary Zc in patients according to PH sub-classification has not previously been described. Systemic Zc was routinely higher than pulmonary Zc, except in patients with newly diagnosed Pre-cPH, where inverse pulsatile but not steady-state relationships were observed.

Tricuspid Regurgitation After Heart Transplantation: The Cause or the Result of Graft Dysfunction?

BACKGROUND: Tricuspid regurgitation (TR) is common following heart transplantation and has been shown to adversely influence patient outcomes. The aim of this study was to identify causes of progression to moderate-severe TR in the first 2 y after transplantation. METHODS: This was a retrospective, single-center study of all patients who underwent heart transplantation over a 6-y period. Transthoracic echocardiogram (TTE) was performed at month 0, between 6 and 12 mo, and 1-2 y postoperatively to determine the presence and severity of TR. RESULTS: A total of 163 patients were included, of whom 142 underwent TTE before first endomyocardial biopsy. At month 0, 127 (78%) patients had nil-mild TR before first biopsy, whereas 36 (22%) had moderate-severe TR. In patients with nil-mild TR, 9 (7%) progressed to moderate-severe TR by 6 mo and 1 underwent tricuspid valve (TV) surgery. Of patients with moderate-severe TR before first biopsy, by 2 y, 3 had undergone TV surgery. The use of postoperative extracorporeal membrane oxygenation (ECMO) in the latter group was significant (78%; P < 0.05) as was rejection profile ( P = 0.02). Patients with late progressive moderate-severe TR had a significantly higher 2-y mortality than those who had moderate-severe TR immediately. CONCLUSIONS: Overall, our study has shown that in the 2 main groups of interest (early moderate-severe TR and progression from nil-mild to moderate-severe TR), TR is more likely to be the result of significant underling graft dysfunction rather than the cause of it.

Sodium glucose co-transporter 2 inhibition with empagliflozin on metabolic, cardiac and renal outcomes in recent cardiac transplant recipients (EMPA-HTx): protocol for a randomised controlled trial.

INTRODUCTION: Cardiac 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. METHODS: The 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 DISSEMINATION: This 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 NUMBER: ACTRN12622000978763.

Rapid triage and transition to telehealth for heart transplant patients in the COVID-19 pandemic setting.

BACKGROUND: In the setting of the COVID-19 pandemic, a rapid uptake of telehealth services was instituted with the aim of reducing the spread of disease to vulnerable patient populations including heart transplant recipients. METHODS: Single-center, cohort study of all heart transplant patients seen by our institution's transplant program during the first 6 weeks of transition from in-person consultation to telehealth (23 March - 5 June 2020). RESULTS: Face-to-face consultation allocation strongly favored patients in the early post-operative period (34 vs. 242 weeks post-transplant; p < 0.001). Telehealth consultation dramatically reduced patient travel and wait times (80 min per visit saved in telehealth patients). No apparent excess re-hospitalization or mortality was seen in telehealth patients. CONCLUSIONS: With appropriate triage, telehealth was feasible in heart transplant recipients, with videoconferencing being the preferred modality. Patients seen face-to-face were those triaged to be higher acuity based on time since transplant and overall clinical status. These patients have the expected higher rates of hospital re-admission, and therefore should continue to be seen in person.

Acute Myocarditis and Pericarditis After mRNA COVID-19 Vaccinations-A Single-Centre Retrospective Analysis.

BACKGROUND: With the rapid rollout of COVID-19 vaccinations, numerous associated and suspected adverse events have been reported nationally and worldwide. Literature reporting confirmed cases of pericarditis and myocarditis following SARS-CoV-2 mRNA vaccinations has evolved, with a predominance in adolescent males following the second dose. METHODS: This was a retrospective analysis of all patients presenting to St Vincent's Hospital, Sydney, Australia with suspected COVID-19 vaccine-related myocarditis and pericarditis. The Brighton Collaboration Case Definitions of Myocarditis and Pericarditis were used to categorise patients into groups based on diagnostic certainty. Cardiac magnetic resonance imaging findings were reviewed against updated Lake Louise Criteria for diagnosing patients with suspected myocarditis. RESULTS: We report 10 cases of confirmed, possible or probable myocarditis and pericarditis. The mean age of presentation in the vaccine group was 33±9.0 years. The most common presenting symptom was pleuritic chest pain (n=8, 80%). Eight patients (80%) had electrocardiogram (ECG) abnormalities (n=6 pericarditis, n=2 myocarditis). Five patients (50%) had a minimum 24 hours of cardiac monitoring. One patient had multisystem inflammatory syndrome following vaccination (MIS-V) with severely impaired left ventricular ejection fraction and required admission to the intensive care unit. DISCUSSION AND CONCLUSION: Cardiac complications post mRNA vaccines are rare. Our case series reflects the worldwide data that vaccine-related myocarditis and pericarditis most frequently occur in young males, following the second dose of the vaccine. These cardiac side effects are mild and self-limiting, with adequate responses to oral anti-inflammatories. One patient developed a severe reaction, with no fatal cases.

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 novel method to assess valvulo-arterial load in patients with aortic valve stenosis.

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 ±â€Š9 years; 12 males; blood pressure 140/75 ±â€Š20 mmHg) with aortic stenosis on transthoracic echocardiogram (16 severe; mean gradient 45 ±â€Š16 mmHg; aortic valve area 0.8 ±â€Š0.2 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 < 0.01), irrespective of aortic stenosis severity. CONCLUSION: Difficulties in the measurement and accuracy of ventriculo-arterial coupling means that it is not routinely measured in patients with aortic stenosis. We describe a new noninvasive index that provides an accurate assessment of valvular and arterial load on the left ventricle. VAL may help detect those at risk of ventriculo-arterial coupling mismatch and assist in selection of those most likely to benefit from an invasive procedure.