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The aim of this study was to investigate cardiomyocyte Ca2+ handling and contractile function in freshly excised human atrial tissue from diabetic and non‐diabetic patients undergoing routine surgery. Multicellular trabeculae (283 ± 20 μm in diameter) were dissected from the endocardial surface of freshly obtained right atrial appendage samples from consenting surgical patients. Trabeculae were mounted in a force transducer at optimal length, electrically stimulated to contract, and loaded with fura‐2/AM for intracellular Ca2+ measurements. The response to stimulation frequencies encompassing the physiological range was recorded at 37°C. Myofilament Ca2+ sensitivity was assessed from phase plots and high potassium contractures of force against [Ca2+]i. Trabeculae from diabetic patients (n = 12) had increased diastolic (resting) [Ca2+]i (p = 0.03) and reduced Ca2+ transient amplitude (p = 0.04) when compared to non‐diabetic patients (n = 11), with no difference in the Ca2+ transient time course. Diastolic stress was increased (p = 0.008) in trabeculae from diabetic patients, and peak developed stress decreased (p ≤ 0.001), which were not accounted for by reduction in the cardiomyocyte, or contractile protein, content of trabeculae. Trabeculae from diabetic patients also displayed diminished myofilament Ca2+ sensitivity (p = 0.018) compared to non‐diabetic patients. Our data provides evidence of impaired calcium handling during excitation‐contraction coupling with resulting contractile dysfunction in atrial tissue from patients with type 2 diabetes in comparison to the non‐diabetic. This highlights the importance of targeting cardiomyocyte Ca2+ homeostasis in developing more effective treatment options for diabetic heart disease in the future. [ABSTRACT FROM AUTHOR]

The disrupted organisation of the ryanodine receptors (RyR) and junctophilin (JPH) is thought to underpin the transverse tubule (t-tubule) remodelling in a failing heart. Here, we assessed the nanoscale organisation of these two key proteins in the failing human heart. Recently, an advanced feature of the t-tubule remodelling identified large flattened t-tubules called t-sheets, that were several microns wide. Previously, we reported that in the failing heart, the dilated t-tubules up to ~1 μm wide had increased collagen, and we hypothesised that the t-sheets would also be associated with collagen deposits. Direct stochastic optical reconstruction microscopy (dSTORM), confocal microscopy, and western blotting were used to evaluate the cellular distribution of excitation-contraction structures in the cardiac myocytes from patients with idiopathic dilated cardiomyopathy (IDCM) compared to myocytes from the non-failing (NF) human heart. The dSTORM imaging of RyR and JPH found no difference in the colocalisation between IDCM and NF myocytes, but there was a higher colocalisation at the t-tubule and sarcolemma compared to the corbular regions. Western blots revealed no change in the JPH expression but did identify a ~50% downregulation of RyR (p = 0.02). The dSTORM imaging revealed a trend for the smaller t-tubular RyR clusters (~24%) and reduced the t-tubular RyR cluster density (~35%) that resulted in a 50% reduction of t-tubular RyR tetramers in the IDCM myocytes (p < 0.01). Confocal microscopy identified the t-sheets in all the IDCM hearts examined and found that they are associated with the reticular collagen fibres within the lumen. However, the size and density of the RyR clusters were similar in the myocyte regions associated with t-sheets and t-tubules. T-tubule remodelling is associated with a reduced RyR expression that may contribute to the reduced excitation-contraction coupling in the failing human heart. [ABSTRACT FROM AUTHOR]

Acute cellular rejection after cardiac transplantation surgery is routinely monitored by pathological assessment of haematoxylin and eosin (H&E) histology of endomyocardial biopsies (EMB). Unfortunately, there is considerable variation in the diagnosis of rejection that has been attributed to the subjectivity involved in assessing the degree of (a) inflammatory infiltrate and (b) myocyte damage. In this work, we sought to investigate the potential of high contrast confocal microscopy for numerically assessing inflammatory infiltrate and myocyte damage in EMB histology. Confocal microscopy was used to capture images from EMB fluorescently labelled for nuclei (DAPI), f‐actin (phalloidin), troponin‐T (anti‐body), and extracellular matrix and cell border (wheat germ agglutinin). Images from 28 biopsy procedures were captured. Standard pathological grading of H&E histology identified the following rejection gradings: 6 0R, 16 1R, 6 2R and no 3R. Confocal imaging was able to identify equivalent features of rejection provided by H&E histology but at higher contrast facilitating quantification. Lymphocytic infiltrate was calculated as the ratio of non‐myocyte nuclei to total nuclei. This metric was found to be significantly higher in the biopsies from 2R patients compared to both 1R and 0R patients (P <.05). Myocyte damage was quantified as the loss of troponin‐T labelling normalised to f‐actin labelling. This metric of myocyte damage found significantly lower amounts of troponin‐T in the biopsies from 2R patients compared to those with a 0R rejection grading (P <.05). Confocal imaging and simple image processing routines show potential for numerically assessing both inflammatory infiltrate and myocyte damage in endomyocardial biopsy. [ABSTRACT FROM AUTHOR]

The natural history of a systemic right ventricle after an atrial switch procedure has yet to be fully characterised. We describe the case of the longest surviving patient at our institution who underwent a Mustard Baffle correction for dextro‐transposition of great arteries in childhood. Over following decades he was reviewed regularly with deteriorating systemic right ventricle function. At around 50 years of age he developed worsening heart failure on maximal medical therapy. He was subsequently assessed for cardiac transplantation which he underwent successfully at the age of 55 years. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 71-year-old man with exertional dyspnoea in the setting of stage IV metastatic melanoma. It describes the treatment, examination, and surgery underwent by the patient, which include melanoma excision and sentinel node biopsy, right groin completion lymph node dissection, and small bowel resection. The benefit of a combination of surgical metastasectomy and post-operative immunotherapy with pembrolizumab is discussed.

Objective: Patients with Fontan physiology may eventually require heart transplantation (HT). We determined the rates and outcomes of HT in a national, population-based multicentre study.Methods: From 1990 to 2015, 1369 patients underwent the Fontan procedure as recorded in the Australia and New Zealand Fontan Registry. We identified those who underwent HT and analysed their outcomes. We compared rates of HT between two catchment areas. In area 1 (n=721), patients were referred to the national paediatric HT programme or its associated adult programme. In area 2 (n=648), patients were referred to the national paediatric HT programme or one of the other adult HT programmes.Results: Mean follow-up time post-Fontan was 11±8 years. Freedom from Fontan failure was 74%±3.9% at 20 years. HT was performed in 34 patients. Patients living in area 1 were more likely to have HT (4.0%, 29/721 vs 0.8%, 5/648, p<0.001) with a cumulative proportion of 3.4% vs 0.7% at 10 years and 6.8% vs 1.2% at 20 years (p=0.002). Area 1 patients were more likely to undergo HT (hazard ratio 4.7, 95% CI 1.7 to 13.5, p=0.003) on multivariable regression. Post-HT survival at 1, 5 and 10 years was 91%, 78% and 71%, respectively. Compared with other patients with congenital heart disease (n=87), Fontan patients had similar in-hospital outcomes and long-term survival.Conclusions: Although HT after the Fontan procedure can be achieved with excellent outcomes, most patients with Fontan failure do not undergo HT. Significant regional differences in rates of HT in Fontan patients exist. [ABSTRACT FROM AUTHOR]