Utilising organs from hepatitis C virus PCR-positive donors in Western Australia.

We transplanted six solid organs from three hepatitis C virus (HCV) polymerase chain reaction (PCR)-positive donors during 2018-2023. Recipients were treated with glecaprevir/pibrentasvir or sofosbuvir/velpatasvir for 4-12 weeks, with all six achieving sustained virological response without significant adverse events. As occurs in other jurisdictions, solid organ transplants from HCR PCR-positive donors can be safely utilised in Australia.

Outcomes of Cardiac Transplantation in Western Australia - A Contemporary Single Centre Experience.

BACKGROUND: Cardiac transplantation remains the gold standard therapy for select patients with end-stage heart failure and outcomes have improved significantly over the past few decades. We report the 5-year contemporary experience of cardiac transplantation in Western Australia, one of the most remote transplant centres worldwide. METHODS: Patients undergoing isolated cardiac transplant at Fiona Stanley Hospital (FSH) from February 2015 until April 2021 were included. Donor details were collected using donor electronic records (Donate Life, Australia). Recipient data was collated from electronic medical records at FSH and the Australia and New Zealand Society of Cardiothoracic Surgery database. The primary outcome measure was all-cause mortality. Secondary outcome measures included postoperative intensive care and total hospital length of stay and rates of acute kidney injury, rejection, serious infections, and cardiac allograft vasculopathy. Frailty indices were also assessed. RESULTS: A total of 60 patients were included (mean age 53±14 yrs, 66.7% male). The commonest indication for transplant was a non-ischaemic cardiomyopathy (46.7%). Mean donor age was 35±12 years and median donor ischaemia time was 171 minutes (IQR=138-240). After median follow-up of 3.7 years, there were no mortalities. Postoperative renal failure occurred in 21 (35.0%) patients, pneumonia in four (6.7%), deep sternal wound infection in three (5.1%), acute rejection in 17 (28.3%) and cardiac allograft vasculopathy (CAV) in 23 (38.3%). CONCLUSION: With recipient and donor criteria comparable to national and international standards, compounded by the challenges of geographic isolation, we report the first published data on contemporary outcomes post isolated cardiac transplantation in Western Australia.

Cardiac allograft vasculopathy: Insights on pathogenesis and therapy.

Cardiac allograft vasculopathy (CAV) is a unique accelerated form of coronary vascular disease affecting heart transplant recipients. This complication is a significant contributor to medium- to long-term post-transplant morbidity and mortality. There is a high prevalence of CAV with approximately one in three patients developing CAV by 5 years post-transplant. Morphologically, CAV is characterized by concentric coronary intimal hyperplasia in both the epicardial arteries and intramural microvasculature. Although several immune and non-immune factors have been identified, their precise pathogenic mechanisms, interactions, and relative importance in the development of CAV are not well defined. The advent of improved imaging surveillance modalities has resulted in earlier detection during the disease process. However, overall management of CAV remains challenging due to paucity of treatment. This review aims to discuss key concepts on the pathogenesis of CAV and current management strategies, focusing on the use of mammalian target of rapamycin inhibitors.

Safety and Efficacy Outcomes of Combined Leadless Pacemaker and Atrioventricular Nodal Ablation for Atrial Fibrillation Using a Single Femoral Puncture Approach.

BACKGROUND: Atrioventricular nodal (AVN) ablation with permanent pacemaker (PPM) insertion is indicated for rate control in patients with atrial fibrillation (AF) who remain unresponsive to rate or rhythm control strategies. The leadless PPM (Micra Transcatheter Pacing System [TPS], Medtronic, Minneapolis, MN, USA) has the advantage of eliminating transvenous lead and pacemaker pocket-related complications. The aim of this case series was to determine the outcomes of patients who had undergone combined Micra TPS and AVN ablation, performed via a single femoral approach. METHOD: A retrospective review was undertaken on patients who had undergone concurrent procedures, across two major hospitals in Perth, Western Australia. Procedural details were obtained from a cardiac devices database whilst patient demographics and clinical information were determined from medical records. RESULTS: Fourteen (14) patients underwent concurrent Micra TPS insertion and AVN ablation for symptomatic AF. The average age was 73±9.2 years, and 43% of them were males. There was no acute procedural/device related complication. Over a median follow-up duration of 9 months (36% completing 12-month follow-up), there was no incidence of device complications, in particular device dislodgement, malfunction or infection. One patient had a resuscitated ventricular fibrillation (VF) arrest event with new onset cardiomyopathy during follow-up and required Micra TPS removal. One patient died at 33 days post procedure from a non-cardiac cause. Device performance was excellent with stable sensing and pacing thresholds during the follow-up period. CONCLUSION: Our study has shown that combined leadless PPM (Micra TPS) implantation and AVN ablation using a single femoral approach is feasible, with good safety and efficacy profile in the short-medium term. Long-term data involving larger cohorts is needed to confirm the findings of this study and determine the clinical usefulness of this combined approach.

Bacteriology and clinical outcomes of patients with culture-positive pleural infection in Western Australia: A 6-year analysis.

BACKGROUND AND OBJECTIVE: Pleural infection is a clinical challenge; its microbiology can be complex. Epidemiological and outcome data of pleural infection in adult Australians are lacking. We describe the bacteriology and clinical outcomes of Australian adults with culture-positive pleural infection (CPPI) over a 6-year period. METHODS: Cases with CPPI were identified through Western Australian public hospitals electronic record. Culture isolates, admission dates, vital status, co-morbidities, radiology, blood and pleural fluid tests were extracted. RESULTS: In total, 601 cases (71.4% males; median age: 63 years (IQR: 50-74); median hospital stay 13 days) involving 894 bacterial isolates were identified. Hospital-acquired (HA)-CPPI was defined in 398 (66.2%) cases, community-acquired (CA)-CPPI in 164 (27.3%) cases and the remaining classified as oesophageal rupture/leak. Co-morbidities, most frequently cancer, were common (65.2%). Radiological evidence of pneumonia was present in only 43.8% of CA-CPPI and 27.3% of HA-CPPI. Of the 153 different bacterial strains cultured, Streptococcus species (32.9%) especially viridans streptococci group were most common in CA-CPPI, whereas HA-CPPI was most often associated with Staphylococcus aureus (11.6%) and Gram-negative (31.9%) infections. Mortality was high during hospitalization (CA-CPPI 13.4% vs HA-CPPI 16.6%; P = 0.417) and at 1 year (CA-CPPI 32.4% vs HA-CPPI 45.5%; P = 0.006). CONCLUSION: This is the first large multicentre epidemiological study of pleural infection in Australian adults and includes the largest cohort of HA-CPPI published to date. CPPI is caused by a diverse range of organisms which vary between CA and HA sources. CPPI is a poor prognostic indicator both in the short term and in the subsequent 12 months.

Pleurodesis outcome in malignant pleural mesothelioma.

Few data exist on the pleurodesis outcome in patients with malignant pleural mesothelioma (MPM). A retrospective review of the Western Australian Mesothelioma Registry over 5 years revealed 390 evaluable patients. Only a subset of patients (42.3%) underwent pleurodesis, surgically (n=78) or by bedside instillation of sclerosants (n=87). Surgical pleurodesis showed no advantages over bedside pleurodesis in efficacy (32% vs 31% failures requiring further drainage, p=0.98), patient survival (p=0.52) or total time spent in hospital from procedure till death (p=0.36). No clinical, biochemical or radiographic parameters tested adequately predict pleurodesis outcome.

The Prevalence and Characteristics of Arrhythmic Mitral Valve Prolapse in Patients With Unexplained Cardiac Arrest.

BACKGROUND: There is growing evidence that mitral valve prolapse (MVP) is associated with otherwise unexplained cardiac arrest (UCA). However, reports are hindered by the absence of a systematic ascertainment of alternative diagnoses. OBJECTIVES: This study reports the prevalence and characteristics of MVP in a large cohort of patients with UCA. METHODS: Patients were enrolled following an UCA, defined as cardiac arrest with no coronary artery disease, preserved left ventricular ejection fraction, and no apparent explanation on electrocardiogram. A comprehensive evaluation was performed, and patients were diagnosed with idiopathic ventricular fibrillation (IVF) if no cause was found. Echocardiography reports were reviewed for MVP. Patients with MVP were divided into 2 groups: those with IVF (AMVP) and those with an alternative diagnosis (nonarrhythmic MVP). Patient characteristics were then compared. The long-term outcomes of AMVP were reported. RESULTS: Among 571 with an initially UCA, 34 patients had MVP (6%). The prevalence of definite MVP was significantly higher in patients with IVF than those with an alternative diagnosis (24 of 366 [6.6%] vs 5 of 205 [2.4%]; P = 0.03). Bileaflet prolapse was significantly associated with AMVP (18 of 23 [78%] vs 1 of 8 [12.5%]; P = 0.001; OR: 25.2). The proportion of patients with AMVP who received appropriate implantable cardioverter-defibrillator therapies over a median follow-up of 42 months was 21.1% (4 of 19). CONCLUSIONS: MVP is associated with otherwise UCA (IVF), with a prevalence of 6.6%. Bileaflet prolapse appears to be a feature of AMVP, although future studies need to ascertain its independent association. A significant proportion of patients with AMVP received appropriate implantable cardioverter-defibrillator therapies during follow-up.

Changing epidemiology of bloodstream infection pathogens over time in adult non-specialty patients at an Australian tertiary hospital.

The epidemiology of bloodstream infections (BSI) has been changing over time in developed countries. However, overview reports of BSI trends are limited in Australia. This descriptive epidemiological study analysed general and age-group specific trends, and antimicrobial susceptibility patterns of blood culture isolates between 2001 and 2009 in non-specialty adult patients at an Australian tertiary referral centre. A total of 3,051 isolates from 2,172 patients (60% males) were analysed. Both community onset (1,790 isolates, 59%) and hospital onset (1,261 isolates, 41%) BSIs were included. The mean age of patients was 59 ± 20 years; 930 patients (43%) were 70 years of age or over. Overall, 1,493 (49%) gram positive bacteria, 1,389 (46%) gram negative bacteria and 169 (5.5%) fungi were isolated. The proportion of gram negative isolates increased over the 9 years, (44% to 53%, P = 0.006) whilst gram positives decreased (49% to 45%, P = 0.045). These trends were significant in community onset infections but not hospital onset infections, and also in adult patients aged 20 years to less than 70 years but not in the elderly (≥70 years). Gram negative pathogens were most prevalent amongst the elderly (53% in the ≥70 years age group, P<0.0001 vs. 41% in the ≥20 to <70 years age group), attributable to an age-dependent increase in Escherichia coli infections and a decrease in Staphylococcus aureus infections (P<0.0001 for both). Most gram negative isolates remained susceptible to commonly prescribed antibiotics. By contrast, methicillin-resistant S. aureus rates decreased from 54% in 2001 to 28% in 2009 (P=0.007). This study found that gram negative BSIs appeared to be re-emerging, particularly in community onset infections and also amongst the younger patients at the study institution. Such epidemiological trends have important implications for antimicrobial choices for the treatment of undifferentiated sepsis.

Post-Myocardial Infarction Ventricular Septal Defect Successfully Treated with Impella as Bridge to Cardiac Transplantation.

A 63-year-old female presented late with anterior ST-elevation myocardial infarction and cardiogenic shock. This was complicated by acute ventricular septal defect with large left-to-right shunt. An Impella CP was inserted on day seven with rapid haemodynamic improvement. This facilitated bridge to cardiac transplant on day twelve post-MI.

Pulmonary Hypertension Due to Left Heart Disease-A Practical Approach to Diagnosis and Management.

Pulmonary hypertension (PH) due to left heart disease (LHD) is a frequent complication of heart failure (HF) and is associated with exercise intolerance, poor quality of life, increased risk of hospitalisations, and reduced overall survival. Since the recent Sixth World Symposium on Pulmonary Hypertension in 2018, there have been significant changes in the hemodynamic definitions and clinical classification of PH-LHD. PH-LHD can be subdivided into (1) isolated postcapillary PH (IpcPH) and (2) combined precapillary and postcapillary PH (CpcPH). This categorisation of PH-LHD is important because CpcPH shares certain pathophysiologic, clinical, and hemodynamic characteristics with pulmonary arterial hypertension and is associated with worse outcomes compared with IpcPH. A systematic approach using clinical history and noninvasive investigations is required in the diagnosis of PH-LHD. Right heart catheterisation with and without provocative testing is performed in expert centres and is indicated in selected individuals. Although the definition of IpcPH and CpcPH is based on measurements made with right heart catheterisation, distinguishing between these two entities is not always necessary. Despite strong evidence for medical therapy in patients with pulmonary arterial hypertension, those options have limited benefit in PH-LHD. Expert PH centres in Canada have been established to provide ongoing care for the more complex patient subgroups.

Mitral valve-in-valve implantation during pregnancy.

A 32-year-old, 11-week pregnant African woman with known rheumatic heart disease presented to the emergency department with worsening shortness of breath on exertion. She had undergone a double bioprosthetic valve replacement and left atrial appendage resection 8 years prior for severe mitral stenosis, moderate mitral regurgitation and moderate aortic regurgitation. A transo-oesophageal echocardiography at this presentation confirmed a morphologically calcified and stenosed mitral bioprosthesis, with moderate stenosis of her aortic bioprosthesis. Her multidisciplinary team, including cardiologists, cardiothoracic surgeons and obstetricians, came to a consensus decision to proceed with a transseptal transcatheter valve implantation within the mitral valve prosthesis (valve-in-valve implantation). Transthoracic echocardiography performed 2 months post procedure showed satisfactory mitral valve gradients and at 30 weeks' gestation, she successfully delivered her fifth child. 2 years later, the valve in valve complex is still functioning well.

Left Atrial Intramural Hematoma Post-Ablation of Supraventricular Tachycardia: A Rare Complication Treated Successfully.

We report successful management of left atrial hematoma after ablation of supraventricular tachycardia. A 43-year-old female patient experienced chest pain immediately after radiofrequency ablation of a symptomatic left posterolateral accessory pathway. Transthoracic echocardiography demonstrated a large mass occupying the left atrium. Computed tomography and transesophageal echocardiography results were consistent with posterolateral intramural hematoma. She became hemodynamically unstable, requiring emergent surgery. The mass resolved completely by 6 weeks. (Level of Difficulty: Beginner.).

Cardiovascular Testing Detects Underlying Dysfunction in Childhood Leukemia Survivors.

PURPOSE: Childhood leukemia survivors commonly develop late-onset cardiovascular disease after treatment with anthracyclines. Resting echocardiogram is the standard procedure for monitoring cardiac health but this method may not be sensitive enough to detect subclinical injury. Exercise echocardiography may provide a viable alternative. METHODS: Nineteen (9 males; age, 19 ± 3 yr) anthracycline-treated survivors of childhood leukemia and 17 (8 males) healthy individuals of similar age (22 ± 2 yr) were recruited. All survivors had normal resting echocardiography upon recruitment. Exercise echocardiography was performed using contemporary imaging techniques. Flow-mediated dilation (FMD), body composition, and cardiorespiratory fitness (V˙O2peak) were assessed to determine predisposition to additional disease. RESULTS: Mitral valve peak flow velocity in late diastole (interaction, P = 0.007) increased from rest in survivors (P = 0.023) and controls (P = 0.020) immediately postexercise but did not recover again in the survivors (exercise-recovery, P = 0.784) after recuperation. Consequently, E/A ratio (interaction, P < 0.001) was lower in the survivors at recovery (P < 0.001). Survivors had reduced FMD (7.88 ± 1.70 vs 9.65 ± 2.83; P = 0.030), maximal and recovery HR (P = 0.001; P < 0.001), minute ventilation (P < 0.001), and V˙O2peak (absolute, 2.64 ± 0.62 vs 3.14 ± 0.74 L·min, P = 0.034; relative, 36.78 ± 11.49 vs 45.14 ± 6.80 mL·kg·min; P = 0.013) compared with controls. They also had higher total body fat (percentage, P = 0.034; mass, P = 0.024) and fat mass in the central (P = 0.050), peripheral (P = 0.039) and visceral (P < 0.001) regions. Survivors matched controls with regard to height (173.0 ± 7.8 cm vs 173.8 ± 9.1 cm; P = 0.796), body mass (76.16 ± 19.05 kg vs 70.07 ± 13.96 kg; P = 0.287) and body mass index (25.2 ± 5.1 vs 22.9 ± 2.7; P = 0.109). CONCLUSIONS: Exercise echocardiography unmasked subclinical diastolic dysfunction that may indicate late anthracycline toxicity in apparently healthy survivors of childhood leukemia. Presence of secondary risk factors indicates increased predisposition to comorbidities and highlights the importance of assessing cardiovascular health during follow-up.

Multidisciplinary Code Shock Team in Cardiogenic Shock: A Canadian Centre Experience.

BACKGROUND: Cardiogenic shock (CS) is associated with high mortality. We report on a "Shock Team" approach of combined interdisciplinary expertise for decision making, expedited assessment, and treatment. METHODS: We reviewed 100 patients admitted in CS over 52 months. Patients managed under a Code Shock Team protocol (n = 64, treatment) from 2016 to 2019 were compared with standard care (n = 36, control) from 2015 to 2016. The cohort was predominantly male (78% treatment, 67% control) with a median age of 55 years (interquartile range [IQR], 43-64) for treatment vs 64 years (IQR, 48-69) for control (P = 0.01). New heart failure was more common in the treatment group: 61% vs 36%, P = 0.02. Acute myocardial infarction comprised 13% of patients in CS. There were no significant differences between treatment and control in markers of clinical acuity, including median left ventricular ejection fraction (18% vs 20%), prevalence of moderate-severe right ventricular dysfunction (64% vs 56%), median peak serum lactate (5.3 vs 4.7 mmol/L), acute kidney injury (70% vs 75%), or acute liver injury (50% vs 31%). Inotropes, dialysis, and invasive ventilation were required in 92%, 33%, and 66% of patients, respectively. Temporary mechanical circulatory support was used in 45% of treatment and 28% of control patients (P = 0.08). There were no significant differences in median hospital length of stay (17.5 days), 30-day survival (71%), or survival to hospital discharge (66%). Over 240 days (IQR, 14,847) of median follow-up, survival was 67% for treatment vs 42% for control (hazard ratio, 0.53; 95% confidence interval, 0.28-0.99; P = 0.03). CONCLUSION: A multidisciplinary Code Shock Team approach for CS is feasible and may be associated with improved long-term survival.

CONTEXTE: Le choc cardiogénique (CC) est associé à une mortalité élevée. Nous décrivons une approche où la prise de décision, l'évaluation rapide des cas et le traitement sont confiés à une « équipe de choc ¼ interdisciplinaire. MÉTHODOLOGIE: Nous avons examiné les cas de 100 patients hospitalisés en raison d'un CC sur une période de 52 mois. Les patients pris en charge par une équipe interdisciplinaire selon un protocole d'intervention déclenché par un code-choc (n = 64, groupe traité) de 2016 à 2019 ont été comparés à des patients ayant reçu des soins courants (n = 36, groupe témoin) de 2015 à 2016. Les patients de la cohorte étaient majoritairement de sexe masculin (78 % dans le groupe traité, 67 % dans le groupe témoin) et l'âge médian était de 55 ans (intervalle interquartile [IIQ] : 43-64) au sein du groupe traité par rapport à 64 ans (IIQ : 48-69) au sein du groupe témoin (p = 0,01). Les nouveaux cas d'insuffisance cardiaque étaient plus fréquents dans le groupe traité : 61 % vs 36 % (p = 0,02). Les patients hospitalisés en raison d'un CC avaient subi un infarctus aigu du myocarde dans 13 % des cas. Aucune différence significative n'a été relevée entre le groupe traité et le groupe témoin au chapitre des marqueurs d'acuité clinique, y compris la fraction médiane d'éjection ventriculaire gauche (18 % vs 20 %), la prévalence d'une dysfonction modérée ou sévère du ventricule droit (64 % vs 56 %), la concentration maximale médiane de lactate sérique (5,3 vs 4,7 mmol/l), l'insuffisance rénale aiguë (70 % vs 75 %) ou l'insuffisance hépatique aiguë (50 % vs 31 %). L'administration d'inotropes, la dialyse et la ventilation effractive ont été nécessaires chez 92 %, 33 % et 66 % des patients, respectivement. Une assistance circulatoire mécanique temporaire a été utilisée chez 45 % des patients du groupe traité et 28 % des patients du groupe témoin (p = 0,08). Aucune différence significative n'a été notée en ce qui concerne la durée médiane des hospitalisations (17,5 jours), la survie à 30 jours (71 %) ou la survie à la sortie de l'hôpital (66 %). Au cours d'une période de suivi médiane de 240 jours (IIQ : 14 847), le taux de survie était de 67 % dans le groupe traité vs 42 % dans le groupe témoin (rapport des risques instantanés : 0,53; intervalle de confiance à 95 % : 0,28-0,99; p = 0,03). CONCLUSION: Dans les cas de CC, l'intervention d'une équipe interdisciplinaire déclenchée par un code-choc est réalisable et pourrait être associée à une amélioration de la survie à long terme.

Structural basis for the high specificity of a Trypanosoma congolense immunoassay targeting glycosomal aldolase.

BACKGROUND: Animal African trypanosomosis (AAT) is a neglected tropical disease which imposes a heavy burden on the livestock industry in Sub-Saharan Africa. Its causative agents are Trypanosoma parasites, with T. congolense and T. vivax being responsible for the majority of the cases. Recently, we identified a Nanobody (Nb474) that was employed to develop a homologous sandwich ELISA targeting T. congolense fructose-1,6-bisphosphate aldolase (TcoALD). Despite the high sequence identity between trypanosomatid aldolases, the Nb474-based immunoassay is highly specific for T. congolense detection. The results presented in this paper yield insights into the molecular principles underlying the assay's high specificity. METHODOLOGY/PRINCIPAL FINDINGS: The structure of the Nb474-TcoALD complex was determined via X-ray crystallography. Together with analytical gel filtration, the structure reveals that a single TcoALD tetramer contains four binding sites for Nb474. Through a comparison with the crystal structures of two other trypanosomatid aldolases, TcoALD residues Ala77 and Leu106 were identified as hot spots for specificity. Via ELISA and surface plasmon resonance (SPR), we demonstrate that mutation of these residues does not abolish TcoALD recognition by Nb474, but does lead to a lack of detection in the Nb474-based homologous sandwich immunoassay. CONCLUSIONS/SIGNIFICANCE: The results show that the high specificity of the Nb474-based immunoassay is not determined by the initial recognition event between Nb474 and TcoALD, but rather by its homologous sandwich design. This (i) provides insights into the optimal set-up of the assay, (ii) may be of great significance for field applications as it could explain the potential detection escape of certain T. congolense strains, and (iii) may be of general interest to those developing similar assays.