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Background: Aortic stenosis (AS) and mitral regurgitation (MR) result in different patterns of left ventricular remodeling and hypertrophy., Objectives: We characterized left ventricular wall stress (LVWS) profiles in pressure and volume-overloaded systems, examined the relationship between baseline LVWS and cardiac remodeling, and assessed the acute effects of valve intervention on LVWS using invasive pressures combined with cardiac magnetic resonance (CMR) imaging measures of left ventricular volumes/mass., Methods: A total of 47 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR) and 15 patients with severe MR undergoing MitraClip (MC) underwent a 6-minute walk test (6MWT), transthoracic echocardiogram, and CMR before their procedures. Catheters in the left ventricle were used to record hemodynamic changes before and after valve/clip deployment. This was integrated with CMR data to calculate LVWS before and after intervention., Results: The TAVR group demonstrated significant reductions in systolic LVWS post procedure (median 24.7 Pa [IQR: 14 Pa] pre vs median 17.3 Pa [IQR: 12 Pa] post; P < 0.001). The MC group demonstrated significant reductions in diastolic LVWS (median 6.4 Pa [IQR: 5 Pa] pre vs median 4.3 Pa [IQR: 4.1 Pa] post; P = 0.021) with no significant change in systolic LVWS (30.6 ±1.61 pre vs 33 ±2.47 Pa post; P = 0.16). There was an inverse correlation between baseline systolic LVWS and 6MWT in the TAVR group (r = -0.31; P = 0.04)., Conclusions: TAVR results in significant reductions in systolic LVWS acutely. MC results in significant reductions in diastolic LVWS. Higher baseline systolic LVWS in TAVR is associated with shorter 6MWT suggesting that in AS, LVWS may be a useful marker of early decompensation., Competing Interests: Funding Support and Author Disclosures Prof Taylor is supported by an National Health and Medical Research Council (NHMRC) Leadership Investigator grant and A/Professor Dion Stub is supported by National Heart Foundation and NHMRC Research Fellowships. All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Worldwide, the cardiology profession has an under-representation of women. We assessed medical students' perceptions of cardiology as a career choice with the aim of identifying barriers to gender diversity., Method: An anonymous survey was distributed to medical students studying at three Australian medical universities. Questions pertained to demographics, year and stage of medical training, desire to pursue cardiology, and perceived barriers to a cardiology career. Results were analysed according to identified gender and desire to pursue or not pursue a cardiology career. Multivariable logistic regression evaluated for independent associations. The primary outcome were barriers identified to pursuing a career in cardiology., Results: From 127 medical student respondents (86.6% female, mean age 25.9±4.8 years), 37.0% stated they wanted to pursue a career in cardiology (39.1% of women versus 23.5% of men, p=0.54). The top four perceived barriers to a cardiology career included: poor work-life balance (92/127, 72.4%), physician training process (63/127, 49.6%), on-call requirements (50/127, 39.4%) and lack of flexibility (49/127, 38.6%), with no gender differences. Women were more likely to report gender-related barriers (37.3% versus 5.9%, p=0.01) and less likely to identify procedural aspects as a barrier (5.5% women versus 29.4% men, p=0.001). Students in their pre-clinical years were more likely to want a career in cardiology (odds ratio 3.0, 95% confidence interval 1.2-7.7, p=0.02)., Conclusions: A high proportion of female and male medical students want to pursue a career in cardiology with both genders identifying major barriers of poor work-life balance, lack of flexibility, on-call requirements and the training process., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Streptococcus pyogenes is a leading cause of infection-related morbidity and mortality. A reinvigorated vaccine development effort calls for new clinically relevant human S pyogenes experimental infection models to support proof of concept evaluation of candidate vaccines. We describe the initial Controlled Human Infection for Vaccination Against S pyogenes (CHIVAS-M75) study, in which we aimed to identify a dose of emm75 S pyogenes that causes acute pharyngitis in at least 60% of volunteers when applied to the pharynx by swab., Methods: This observational, dose-finding study was done in a clinical trials facility in Melbourne (VIC, Australia). Groups of healthy volunteers aged 18-40 years, at low risk of complicated S pyogenes disease, and without high type-specific anti-emm75 IgG antibodies against the challenge strain were challenged and closely monitored as inpatients for up to 6 days, and then as outpatients for 6 months. Antibiotics were started upon diagnosis (clinical signs and symptoms of pharyngitis and a positive rapid molecular test) or after 5 days in those without pharyngitis. Rapid test results were confirmed by standard bacterial culture. After a sentinel participant, cohorts of five and then ten participants were challenged, with protocol-directed dose-escalation or de-escalation for subsequent cohorts. The primary outcome was the proportion of participants at each dose level with pharyngitis by day 5 after challenge. The study is registered with ClinicalTrials.gov, NCT03361163., Findings: Between July 10, 2018, and Sept 23, 2019, 25 healthy adults were challenged with emm75 S pyogenes and included in analyses. Pharyngitis was diagnosed in 17 (85%; 95% CI 62-97) of 20 participants at the starting dose level (1-3 × 10 5 colony-forming units [CFU]/mL). This high proportion prompted dose de-escalation. At the lower dose level (1-3 × 10 4 CFU/mL), pharyngitis was diagnosed in one of five participants. Immunological, biochemical, and microbiological results supported the clinical picture, with acute symptomatic pharyngitis characterised by pharyngeal colonisation by S pyogenes accompanied by significantly elevated C-reactive protein and inflammatory cytokines (eg, interferon-γ and interleukin-6), and modest serological responses to streptolysin O and deoxyribonuclease B. There were no severe (grade 3) or serious adverse events related to challenge., Interpretation: We have established a reliable pharyngitis human infection model with reassuring early safety findings to accelerate development of vaccines and other interventions to control disease due to S pyogenes., Funding: Australian National Health and Medical Research Council., Competing Interests: Declaration of interests JBD is the inventor of technologies related to the development of S pyogenes vaccines; the University of Tennessee Research Foundation has licensed these technologies to Vaxent, of which JBD is the chief scientific officer and a member. MP and MFG are inventors on patents related to S pyogenes vaccines, and Griffith University (Gold Coast, QLD, Australia) has licensed some of these technologies to Olymvax Pharmaceuticals (China). NJM is an inventor on a patent related to S pyogenes analytical methods and compositions. MJW has a patent pending related to S pyogenes vaccines. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Timor-Leste is one of the poorest countries in the world. The East Timor Hearts Fund is a charitable organisation involving Australian cardiologists providing outreach screening and access to cardiac interventions., Aims: To assess ten years of clinical volume, demographics and patient outcomes. Our intention was to identify existing limitations to facilitate planning for further capacity building over the next decade., Methods: The East Timor Hearts Fund database was sectioned into 2-year intervals (2009/2010, 2011/2012, 2013/2014, 2015/2016 and 2017/2018). Demographics and clinical outcomes of patients were compared, with subgroup analysis of adult (>18 years old), paediatric and interventional patients., Results: Over 10 years, 2050 patient encounters have occurred; 1119 (54.6%) encounters occurred in 2017/2018; 73.6% of patients were assessed in the capital Dili. Rheumatic and congenital cardiac diseases remain very common (39.1% of adult new patients and 74.2% of paediatric new patients), with 1.4% of new patients exhibiting both pathologies. The number of new patients with rheumatic or congenital heart disease tripled in 2017/2018 compared to 2009/2010 (99 vs 34 patients, P < 0.0001). Paediatric case volume increased over 10-fold over 10 years (288 new patients in 2017/2018 vs 24 in 2009/2010, P < 0.0001), with corresponding increase in proportion of paediatric interventions (59.4% in 2017/2018 vs 25.0% in 2009/2010, P = 0.027). For patients undergoing intervention (n = 87), post-procedural complications and mortality are extremely low (3.4% and 1.1%, respectively), with all eligible patients attending at least one post-procedure appointment., Conclusion: Demand for cardiac services in Timor-Leste is rising exponentially, with inequitable geographic coverage. Rheumatic and congenital cardiac diseases remain priorities for assessment, and paediatric case volume is increasing. Patients undergoing intervention experience good medical outcomes., (© 2019 Royal Australasian College of Physicians.)

Background: The World Health Organisation previously recommended routine screening in school-aged children in countries with a high prevalence of rheumatic heart disease (RHD); however, it is unclear if screening-detected (latent) valve disease will inevitably evolve to a pathological lesion. Understanding the natural history of latent RHD is essential prior to recommendation of screening in endemic areas. Studies documenting the progression of latent RHD have had contrasting conclusions about the pathogenicity of latent valvular lesions. This review provides estimates of rates of progression of latent RHD., Methods and Findings: In this systematic review and meta-analysis, we searched EMBASE, MEDLINE, Global Index Medicus, Africa Wide, Cochrane Database of Systematic Reviews and Global Health Database for studies published before April 30, 2019. Study data were extracted from all studies which reported follow-up data on progression of latent valve lesions. Studies with control cohorts were used to calculate comparative prevalence ratios. This study is registered with PROSPERO, number CRD42019119427. We identified 12 studies reporting follow-up data on latent RHD for 950 people in 9 countries. The estimated pooled prevalence rate for progression per year of latent RHD was 5%/year (95% CI 2-8). Eight studies reported on the progression of borderline latent RHD with an estimated pooled prevalence of 2%/year (95% CI 0-4). Three studies included control groups. There was a significant increase in the risk of progression of valvular disease in the latent group compared with controls (RR = 3.57 (95%CI = 1.65-7.70, P = 0.001). The overall risk of bias was low. Given most studies included penicillin administration we were unable to document the natural history of latent RHD. Furthermore, we were unable to perform a sensitivity analysis to determine the effect of administering penicillin prophylaxis on progression of valve disease given prescription of penicillin was not standardised., Conclusion: Latent RHD has a slow rate of progression but it is significantly higher compared to controls, with definite latent RHD having a higher rate of progression compared with borderline latent disease. There are a massive number of individuals at risk for RHD in the developing world as well as logistical challenges of screening and delivering penicillin prophylaxis. The low rate of progression from untargeted screening may be an important consideration in resource-constrained environments., Competing Interests: The authors have declared that no competing interests exist.

Aims: This study aims to determine if traditional markers of disadvantage [female sex, low socio-economic status (SES), and remoteness] are associated with lower prescription of evidence-based therapy and higher mortality among patients with moderate-severe heart failure with reduced ejection fraction., Methods and Results: We recruited 452 consecutive class II-III heart failure with reduced ejection fraction patients. Baseline clinical data were recorded prospectively. The primary outcome was the association of female sex on overall survival. Secondary outcomes included association between evidence-based therapy delivery and sex and association of SES and remoteness on heart failure therapy and survival. The Australian Bureau of Statistics generated all indices. Median follow-up was 37.9 months. One hundred and nine patients (24.3%) were women. There was no difference in overall survival based on sex (hazard ratio = 1.19, 95% confidence interval: 0.74-1.92, 0.48). There was no difference in prescription of beta-blockers [χ 2 (1) = 0.91, 0.66], angiotensin-converting enzyme inhibitors [χ 2 (1) = 0.001, 0.97], nor aldosterone antagonists [χ 2 (1) = 2.71, 0.10]. There was no difference in rates of primary prevention implantable cardioverter-defibrillator implantation in men compared with women [χ 2 (1) = 0.35, 0.56]. Neither higher SES nor inner city residence conferred an overall survival benefit., Conclusions: In this Australian cohort of heart failure patients, delivery of care and likelihood of death are comparable between the sexes, SES groups, and rural vs. city residents., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: The effects of empagliflozin on cardiac structure and function are not known., Aims: To examine the changes in cardiac structure and function following the addition of empagliflozin in patients with type 2 (T2D) diabetes using cardiac magnetic resonance (CMR) imaging., Methods: Twenty patients attending a specialist diabetes service recommended for treatment with empagliflozin, and 8 control patients with T2D on stable glucose lowering therapy were recruited for cardiac imaging. Participants underwent CMR scans at baseline and 6 months. Inclusion criteria were established T2D, age < 75 years, estimated glomerular filtration rate ≥45 mL/min/1.73 m 2 ., Results: 17 of 20 in the empagliflozin group, and all of 8 in the control group completed the study. Empagliflozin therapy was associated with reduction in left ventricular end diastolic volume 155 mL (137 mL, 174 mL) at baseline to 145 mL (125 mL, 165 mL) at 6 months, P < 0.01, compared with the control group 153 mL (128 mL, 179 mL) at baseline and 158 mL (128 mL, 190 mL), not significant. There were no differences in measures of left ventricular mass, ejection fraction, heart rate or markers of cardiac fibrosis at baseline and 6 months in either group., Conclusions: This is the first CMR study to examine the effects of empagliflozin on cardiac function and structure, showing evidence of reduced end diastolic volume. This is likely to reflect change in plasma volume, and may explain the reduced cardiovascular death and heart failure seen in the EMPA-REG OUTCOME trial., (© 2019 Royal Australasian College of Physicians.)

Objectives: This study sought to determine the long-term right atrial (RA) electrical and structural changes in a subgroup from the CAMERA-MRI (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction-Magnetic Resonance Imaging) study., Background: Catheter ablation (CA) is successful in restoring ventricular function in patients with atrial fibrillation (AF) and otherwise unexplained cardiomyopathy, as demonstrated in the randomized study of CA versus rate control (CAMERA-MRI). It is unknown if this is associated with atrial remodeling., Methods: Detailed electroanatomical (EA) mapping of the RA using CARTO3 and a force sensing catheter was performed at initial CA and electively at least 12 months after CA in patients with >90% reduction in AF burden following ablation. Bipolar voltage, fractionation, and conduction velocity were collected in 4 segments together with echo and cardiac magnetic resonance imaging., Results: Fifteen patients (mean age 59.1 ± 6.8 years) underwent repeat RA EA mapping. At a mean follow-up of 23.4 ± 11.9 months, left ventricular (LV) ejection fraction improved from 33.6 ± 3.2% to 54.1 ± 3.2% (p = 0.001), RA area decreased from 28.4 ± 2.0 cm 2 to 20.8 ± 1.2 cm 2 (p < 0.001), and left atrial area decreased from 32.9 ± 2.3 cm 2 to 26.8 ± 1.4 cm 2 (p = 0.007). On EA mapping, RA bipolar voltage increased from 1.6 ± 0.1 mV to 1.9 ± 0.1 mV (p = 0.04). Tissue voltage increased across all regions, which achieved statistical significance at the posterior (p = 0.002) and septal (p = 0.01) segments. There was a significant decrease in complex fractionated electrograms from 21.7 ± 3.5% to 8.3 ± 1.8% (p = 0.002); however, no significant change occurred in global or regional conduction velocities (p = 0.5)., Conclusions: Recovery of atrial electrical and structural changes was observed following restoration of sinus rhythm and recovery of LV function in patients who underwent CA for persistent AF and LV systolic dysfunction. The randomized CAMERA MRI study demonstrated significant improvement in LV systolic function with AF ablation compared with rate control. The present study demonstrated reverse electrical and structural atrial recovery in concert with recovery of LV systolic function at 2 years post-AF ablation. This may partially explain the long-term success of CA in patients with AF and otherwise unexplained cardiomyopathy., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: In patients with non-ischaemic cardiomyopathy (NICM), the mortality benefit of a primary prevention implantable cardioverter-defibrillator (ICD) has been challenged. Left ventricular (LV) scar identified by cardiac magnetic resonance (CMR) imaging is associated with a high risk of malignant arrhythmia in NICM. We aimed to determine the impact of LV scar on the mortality benefit from a primary prevention ICD in NICM., Methods and Results: We recruited 452 consecutive heart failure patients [New York Heart Association (NYHA) Class II/III] with NICM and LV ejection fraction ≤35% from a state-wide CMR service. All patients fulfilled European Society of Cardiology guidelines for primary prevention ICD implantation; however, the decision to implant was at the treating physician's discretion. Baseline clinical and CMR data were recorded prospectively and heart failure mortality risk (MAGGIC score) was calculated. The primary study outcome measurement was all-cause mortality based on presence or absence of ICD, stratified by LV scar. Median follow-up was 37.9 months and there was no difference in MAGGIC score between those who did and did not receive a primary prevention ICD (19.30 ± 5.46 vs. 18.90 ± 5.67, P = 0.50). In patients without LV scar, ICD implantation was not associated with improved mortality [hazard ratio (HR) = 1.22, 95% confidence interval (CI): 0.53-2.78, P = 0.64]. In patients with LV scar, ICD implantation was independently associated with reduced mortality (HR = 0.45, 95% CI: 0.26-0.77, P = 0.003)., Conclusions: In patients with NICM, primary prevention ICD implantation is only associated with reduced mortality in patients with LV scar. This may enable more effective selection of NICM patients for ICD implantation compared with current guidelines.

Objectives: This study sought to determine if diffuse ventricular fibrosis improves in patients with atrial fibrillation (AF)-mediated cardiomyopathy following the restoration of sinus rhythm., Background: AF coexists in 30% of heart failure (HF) patients and may be an underrecognized reversible cause of left ventricular systolic dysfunction. Myocardial fibrosis is the hallmark of adverse cardiac remodeling in HF, yet its reversibility is unclear., Methods: Patients with persistent AF and an idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%) were randomized to catheter ablation (CA) or ongoing medical rate control as a pre-specified substudy of the CAMERA-MRI (Catheter Ablation versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction-an MRI-Guided Multi-centre Randomised Controlled Trial) trial. All patients had cardiac magnetic resonance imaging scans (including myocardial T1 time), serum B-type natriuretic peptide, 6-min walk tests, and Short Form-36 questionnaires performed at baseline and 6 months. Sixteen patients with no history of AF or left ventricular systolic dysfunction were enrolled as normal controls for T1 time., Results: Thirty-six patients (18 in each treatment arm) were included in this substudy. Demographics, comorbidities, and myocardial T1 times were well matched at baseline. At 6 months, patients in the CA group had a significant reduction in myocardial T1 time from baseline compared with the medical rate control group (-124 ms; 95% confidence interval [CI]: -23 to -225 ms; p = 0.0176), although it remained higher than that of normal controls at 6 months (p = 0.0017). Improvements in myocardial T1 time with CA were associated with significant improvements in absolute LVEF (+12.5%; 95% CI: 5.9% to 19.0%; p = 0.0004), left ventricular end-systolic volume (p = 0.0019), and serum B-type natriuretic peptide (-216 ng/l; 95% CI: -23 to -225 ng/l; p = 0.0125)., Conclusions: The improvement in LVEF and reverse ventricular remodeling following successful CA of AF-mediated cardiomyopathy is accompanied by a regression of diffuse fibrosis. This suggests timely treatment of arrhythmia-mediated cardiomyopathy may minimize irreversible ventricular remodeling., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) and left ventricular systolic dysfunction (LVSD) frequently co-exist despite adequate rate control. Existing randomized studies of AF and LVSD of varying etiologies have reported modest benefits with a rhythm control strategy., Objectives: The goal of this study was to determine whether catheter ablation (CA) for AF could improve LVSD compared with medical rate control (MRC) where the etiology of the LVSD was unexplained, apart from the presence of AF., Methods: This multicenter, randomized clinical trial enrolled patients with persistent AF and idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%). After optimization of rate control, patients underwent cardiac magnetic resonance (CMR) to assess LVEF and late gadolinium enhancement, indicative of ventricular fibrosis, before randomization to either CA or ongoing MRC. CA included pulmonary vein isolation and posterior wall isolation. AF burden post-CA was assessed by using an implanted loop recorder, and adequacy of MRC was assessed by using serial Holter monitoring. The primary endpoint was change in LVEF on repeat CMR at 6 months., Results: A total of 301 patients were screened; 68 patients were enrolled between November 2013 and October 2016 and randomized with 33 in each arm (accounting for 2 dropouts). The average AF burden post-CA was 1.6 ± 5.0% at 6 months. In the intention-to-treat analysis, absolute LVEF improved by 18 ± 13% in the CA group compared with 4.4 ± 13% in the MRC group (p < 0.0001) and normalized (LVEF ≥50%) in 58% versus 9% (p = 0.0002). In those undergoing CA, the absence of late gadolinium enhancement predicted greater improvements in absolute LVEF (10.7%; p = 0.0069) and normalization at 6 months (73% vs. 29%; p = 0.0093)., Conclusions: AF is an underappreciated reversible cause of LVSD in this population despite adequate rate control. The restoration of sinus rhythm with CA results in significant improvements in ventricular function, particularly in the absence of ventricular fibrosis on CMR. This outcome challenges the current treatment paradigm that rate control is the appropriate strategy in patients with AF and LVSD. (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction [CAMERA-MRI]; ACTRN12613000880741)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

An 81 year-old female with severe aortic stenosis was admitted electively to determine her anatomic suitability for trans-catheter aortic valve implantation (TAVI). Transthoracic echocardiogram prior to referral confirmed critical aortic stenosis with a mean transaortic valve gradient of 106mmHg, aortic valve area (AVA) 0.6cm(2) and dimensionless index (DI) 0.18. She reported a significant symptom burden with New York Heart Association Class III dyspnoea, four episodes of syncope in the month prior to admission and exertional chest pain., (Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)