Durable ventricular assist devices for patients with advanced heart failure: the New Zealand experience.

AIMS: The prevalence of heart failure in New Zealand is increasing. A small number of select patients with predicted poor short-term survival are candidates for advanced heart failure therapies such as transplantation and durable mechanical circulatory support (MCS). The aim of our study was to introduce left ventricular assist devices (LVADs) to the wider clinicians and highlight their role in managing patients with advanced heart failure in New Zealand. METHOD: A retrospective audit of all ventricular assist device (VAD) recipients from January 2005 to December 2022 was conducted. Data were collated using electronic medical and paper records. The primary outcome was survival to transplantation or successful explant of VAD. RESULTS: Thirty-nine patients received VADs; 32 were male and seven female. Mean age was 45 years (range 10-64 years). Most recipients were NZ European (25), six were Maori, four were Pacific peoples and four were of other ethnicities. The majority of LVADs were implanted for those with dilated cardiomyopathy (67%). At the time of data collection, 24 (62%) had survived to heart transplantation, seven (18%) died while on VAD support, five from right ventricular failure and two from strokes, one patient had their VAD explanted due to recovery and seven (18%) VAD recipients continue on support awaiting transplant. CONCLUSION: This audit has provided an opportunity to inform New Zealand clinicians of our durable MCS programme and the expanding role of VAD support in patients with advanced heart failure. The programme will need to continue to audit and report its practice in order to provide equitable allocation of this very limited resource to a growing population in need.

Correcting bias in cardiac geometries derived from multimodal images using spatiotemporal mapping.

Cardiovascular imaging studies provide a multitude of structural and functional data to better understand disease mechanisms. While pooling data across studies enables more powerful and broader applications, performing quantitative comparisons across datasets with varying acquisition or analysis methods is problematic due to inherent measurement biases specific to each protocol. We show how dynamic time warping and partial least squares regression can be applied to effectively map between left ventricular geometries derived from different imaging modalities and analysis protocols to account for such differences. To demonstrate this method, paired real-time 3D echocardiography (3DE) and cardiac magnetic resonance (CMR) sequences from 138 subjects were used to construct a mapping function between the two modalities to correct for biases in left ventricular clinical cardiac indices, as well as regional shape. Leave-one-out cross-validation revealed a significant reduction in mean bias, narrower limits of agreement, and higher intraclass correlation coefficients for all functional indices between CMR and 3DE geometries after spatiotemporal mapping. Meanwhile, average root mean squared errors between surface coordinates of 3DE and CMR geometries across the cardiac cycle decreased from 7 ± 1 to 4 ± 1 mm for the total study population. Our generalised method for mapping between time-varying cardiac geometries obtained using different acquisition and analysis protocols enables the pooling of data between modalities and the potential for smaller studies to leverage large population databases for quantitative comparisons.

Impaired calcium handling mechanisms in atrial trabeculae of diabetic patients.

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.

MITEA: A dataset for machine learning segmentation of the left ventricle in 3D echocardiography using subject-specific labels from cardiac magnetic resonance imaging.

Segmentation of the left ventricle (LV) in echocardiography is an important task for the quantification of volume and mass in heart disease. Continuing advances in echocardiography have extended imaging capabilities into the 3D domain, subsequently overcoming the geometric assumptions associated with conventional 2D acquisitions. Nevertheless, the analysis of 3D echocardiography (3DE) poses several challenges associated with limited spatial resolution, poor contrast-to-noise ratio, complex noise characteristics, and image anisotropy. To develop automated methods for 3DE analysis, a sufficiently large, labeled dataset is typically required. However, ground truth segmentations have historically been difficult to obtain due to the high inter-observer variability associated with manual analysis. We address this lack of expert consensus by registering labels derived from higher-resolution subject-specific cardiac magnetic resonance (CMR) images, producing 536 annotated 3DE images from 143 human subjects (10 of which were excluded). This heterogeneous population consists of healthy controls and patients with cardiac disease, across a range of demographics. To demonstrate the utility of such a dataset, a state-of-the-art, self-configuring deep learning network for semantic segmentation was employed for automated 3DE analysis. Using the proposed dataset for training, the network produced measurement biases of -9 ± 16 ml, -1 ± 10 ml, -2 ± 5 %, and 5 ± 23 g, for end-diastolic volume, end-systolic volume, ejection fraction, and mass, respectively, outperforming an expert human observer in terms of accuracy as well as scan-rescan reproducibility. As part of the Cardiac Atlas Project, we present here a large, publicly available 3DE dataset with ground truth labels that leverage the higher resolution and contrast of CMR, to provide a new benchmark for automated 3DE analysis. Such an approach not only reduces the effect of observer-specific bias present in manual 3DE annotations, but also enables the development of analysis techniques which exhibit better agreement with CMR compared to conventional methods. This represents an important step for enabling more efficient and accurate diagnostic and prognostic information to be obtained from echocardiography.

Systematic Comparison of Left Ventricular Geometry Between 3D-Echocardiography and Cardiac Magnetic Resonance Imaging.

Aims: Left ventricular (LV) volumes estimated using three-dimensional echocardiography (3D-echo) have been reported to be smaller than those measured using cardiac magnetic resonance (CMR) imaging, but the underlying causes are not well-understood. We investigated differences in regional LV anatomy derived from these modalities and related subsequent findings to image characteristics. Methods and Results: Seventy participants (18 patients and 52 healthy participants) were imaged with 3D-echo and CMR (<1 h apart). Three-dimensional left ventricular models were constructed at end-diastole (ED) and end-systole (ES) from both modalities using previously validated software, enabling the fusion of CMR with 3D-echo by rigid registration. Regional differences were evaluated as mean surface distances for each of the 17 American Heart Association segments, and by comparing contours superimposed on images from each modality. In comparison to CMR-derived models, 3D-echo models underestimated LV end-diastolic volume (EDV) by -16 ± 22, -1 ± 25, and -18 ± 24 ml across three independent analysis methods. Average surface distance errors were largest in the basal-anterolateral segment (11-15 mm) and smallest in the mid-inferoseptal segment (6 mm). Larger errors were associated with signal dropout in anterior regions and the appearance of trabeculae at the lateral wall. Conclusions: Fusion of CMR and 3D-echo provides insight into the causes of volume underestimation by 3D-echo. Systematic signal dropout and differences in appearances of trabeculae lead to discrepancies in the delineation of LV geometry at anterior and lateral regions. A better understanding of error sources across modalities may improve correlation of clinical indices between 3D-echo and CMR.

Nanoscale Organisation of Ryanodine Receptors and Junctophilin-2 in the Failing Human Heart.

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.

Loss of troponin-T labelling in endomyocardial biopsies of cardiac transplant patients is associated with increased rejection grading.

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.

Comparison of percutaneous MitraClip versus mitral valve surgery for severe mitral regurgitation: a meta-analysis: Mitraclip and mitral valve surgery meta-analysis.

AIMS: Mitral valve surgery (MVS) is the gold-standard treatment for severe symptomatic mitral regurgitation. Percutaneous mitral valve interventions such as the MitraClip procedure offer another dimension to its management particularly in high-risk patients. We meta-analysed the outcomes of MitraClip and MVS. METHODS AND RESULTS: PubMed, MEDLINE, Embase, Cochrane and Scopus from 1980/01-2019/06 were searched for eligible studies. Data were extracted and pooled using random-effects models. After screening 959 studies and reviewing 21 full-text articles, nine studies totalling 640 MitraClip and 531 MVS (91% valve repair) procedures were included in the meta-analysis. MitraClip patients were older, with a higher prevalence of previous cardiac surgery, coronary disease and a higher EuroSCORE (all p<0.05) than MVS patients. Pooled operative mortality was similar for MitraClip, 3%, versus MVS, 5%, odds ratio (OR): 0.58, 95%, CI: 0.28-1.19, as well as at 1 year mortality, OR: 1.09, CI: 0.71-1.68 and 3-year mortality, OR: 1.08, CI: 0.72-0.163. MitraClip patients had higher rates of early and late significant mitral regurgitation (MR) and more cardiovascular readmissions, while MVS had higher rates of in-hospital bleeding and pacemaker implantation (all p<0.05). CONCLUSIONS: MitraClip patients had a higher baseline risk than MVS, but there were no significant differences in short- and long-term mortality. MitraClip patients had higher rates of cardiovascular admissions and significant MR post-operatively, while MVS patients had more procedural complications.

Characteristics and Outcomes of Patients With Severe Aortic Stenosis Discussed by the Multidisciplinary "Heart Team" According to Treatment Allocation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an alternative and effective contemporary intervention to surgical aortic valve replacement (SAVR) for patients with severe aortic valve disease at increased surgical risk. Guidelines recommend a multidisciplinary "Heart Team" (MHT) review of patients considered for a TAVI procedure, but this has been little studied. We reviewed the characteristics, treatments and outcomes of such patients reviewed by the MHT at our centre. METHODS: Data on consecutive patients with severe aortic valve stenosis discussed by the Auckland City Hospital MHT from June 2011 to August 2016 were obtained from clinical records. Patient characteristics, treatment and outcomes were analysed using standard statistical methods. RESULTS: Over the 5-year period 243 patients (mean age 80.2 ± 8.0 years, 60% male) were presented at the MHT meeting. TAVI was recommended for 200, SAVR for 26 and medical therapy for 17 patients, with no significant difference in mean age (80.2 ± 8.3, 80.4 ± 6.1, 80.4 ± 7.3 years, respectively) or EuroSCORE II (6.5 ± 4.7%, 5.3 ± 3.6%, 6.7 ± 4.3%, respectively). Over time, there was an increase in the number of patients discussed and treated, with no change in their mean age, but the mean EuroSCORE II significantly decreased (TAVI p = 0.026, SAVR p = 0.004). Survival after TAVI and SAVR was similar to that of the age-matched general population, but superior to medical therapy p = 0.002 (93% (n = 162), 84% (n = 21) and 73% (n = 18) at one year and 85% (n = 149), 84% (n = 21) and 54% (n = 13) at 2 years, respectively). CONCLUSIONS: An increasing number of patients were discussed at the MHT meeting with the majority undergoing TAVI, with a similar age and EuroSCORE II to those allocated SAVR or medical therapy. Survival following TAVI and SAVR was superior to medical therapy and similar to the age-matched general population. These findings suggest that the MHT process is robust, consistent and appropriately allocating a limited treatment resource.

Socio-Economic Disparity is Not Linked to Outcome Following Heart Transplantation in New Zealand.

BACKGROUND: Socio-economic deprivation (SED) is emerging as a risk factor for acute graft rejection (AR) and reduced survival of heart transplant (HT) recipients. The study aim was to evaluate any association between SED status of HT recipients and the development of early AR and long-term survival in New Zealand. METHODS: This was a retrospective cohort study. Over a 30-year period, 329 HT recipients were identified from the Australian and New Zealand Heart Transplant Registry. All patients were divided into two groups according to the 2013 New Zealand Deprivation Index (NZDep2013) Score. Heart transplant recipients with NZDep2013 scores of 1,030 and above that corresponded to the eighth, ninth and tenth NZDep2013 deciles were allocated to the higher SED group and those with NZDep2013 scores below 1,030 to the lower SED group. RESULTS: The incidence of early AR in the higher SED group was 1.158/person-years and in the lower SED group 1.156/person-years. The crude incidence rate ratio was 1.0 (95% CI: 0.71-1.44; p = 0.9997). The prevalence of early AR in the higher SED group was 1.13/person-years and 1.15/person-years in the lower SED group. The crude prevalence rate ratio was 0.98/person-year (95% CI: 0.68-1.41/person-years; p = 0.468). In the higher SED group, mortality was 5.6/100 person-years (95% CI: 4.3-7.4/100 person-years) and 5.2/100 person-years (95% CI: 4.3-6.3/100 person-years) in the lower SED group. The adjusted mortality rate ratio estimate was 1.2 (95% CI: 0.8-1.7; p = 0.426). The higher and lower SED groups had similar survival (p = 0.196). CONCLUSION: Socio-economic disparity in New Zealand HT recipients has no negative impact on the development of AR or survival.

Outcomes of patients with ST elevation myocardial infarction in the era of second-generation drug eluting stents; five-year follow-up.

AIM: The second-generation everolimus and zotarolimus drug eluting stents (DES) have shown superiority for repeat revascularisation and safety to the first-generation devices for stable patients. However, the benefit of those devices in the setting of ST elevation myocardial infarction (STEMI) has remained questionable due to concern regarding stent thrombosis (ST) seen with the first-generation devices. We review the outcomes of patients with STEMI treated in our centre at a time when the second-generation DES became the standard of care. METHODS: All patients who presented to our institution with STEMI and underwent emergency percutaneous intervention (PCI) in 2012 with second-generation DES were identified. Case notes and electronic records were reviewed. Patients undergoing staged PCI to non-culprit lesions were excluded. Patients who died during the primary cardiac event with cardiogenic shock were also excluded. RESULTS: A total of 399 patients (mean age 65+/-12, 274 (76%) male) were identified. Thirty-five patients (8.7%) died during hospitalisation with cardiogenic shock and were excluded from the subsequent analysis. A further 35 patients died during follow-up. Patients received a mean of 1.15 DES. Median follow-up time was 4.7 years. Median door to reperfusion time was 90 minutes. The all-cause mortality rate for STEMI survivors was 9.6%. Cardiac mortality rate was 3.6%. Thirty-one patients (8.5%) re-presented with symptoms leading to repeat coronary angiography. In-stent restenosis (ISR) was observed only in eight patients (2.2%). The significant factors associated with re-presentation were smoking and medication non-compliance. CONCLUSION: Early mortality rates following emergency PCI for STEMI remain high despite low reperfusion times. The five-year follow-up data would suggest that STEMI survivors have good outcomes with the second-generation DES.

Natural history of a systemic right ventricle.

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.

Large Left Ventricular Outflow Tract Pseudoaneurysm Closed Percutaneously From a Novel Apical Approach.

An incidental finding of a large left ventricular outflow tract pseudoaneurysm in a 74-year-old man, with high surgical risk, was managed with a novel, fully percutaneous, left ventricular apical approach. The pseudoaneurysm defect and the apical puncture site were successfully closed with Amplatzer septal occluders with successful positioning, as demonstrated on cardiac computed tomography at 6 weeks follow-up. (Level of Difficulty: Intermediate.).

Patent Foramen Ovale Closure Versus Medical Therapy for Cryptogenic Stroke: Meta-Analysis of Randomised Trials.

BACKGROUND: Patent foramen ovale (PFO) is a common anatomic variant associated with cryptogenic stroke. Percutaneous PFO closure in these patients to prevent recurrent neurological events has been controversial for decades, and mixed results have been reported from past and recent observational and randomised studies. This meta-analysis of randomised trials aims to compare the efficacy and safety of PFO closure with medical therapy for cryptogenic stroke patients. METHODS: Medline, PubMed, EMBASE, Scopus and Cochrane were searched from January 1980 to September 2017 by two authors independently to include original randomised trials comparing PFO closure with medical therapy for secondary stroke prevention. Relevant study and baseline characteristics and outcomes were extracted and pooled using random-effects models. RESULTS: Amongst 619 articles searched giving 10 full-texts assessed, six studies reporting five randomised trials and totalling 1,829 PFO closure and 1,611 medical therapy patients were included. Pooled hazards ratios (95% confidence interval, p-value) ischaemic stroke, transient ischaemic attack (TIA) and composite neurovascular or mortality events were 0.41 (0.19-0.90, p=0.03), 0.77 (0.51-1.14, p=0.19) and 0.60 (0.44-0.81, p<0.001) for PFO closure compared to medical therapy. Any adverse events, major bleeding and all-cause mortality were similar between modalities (p=0.37-0.95), however PFO closure had higher rates of new onset atrial fibrillation at 4.6 times (p<0.001). CONCLUSION: Our meta-analysis found that, in patients with cryptogenic stroke, percutaneous PFO closure is beneficial at reducing ischaemic stroke and composite neurovascular or mortality events, with a higher incidence of new atrial fibrillation, compared to medical therapy.