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Introduction: The treatment of aortic valve stenosis (AS) is seeing renewed interest mainly due to the availability of transcatheter therapies. However, the number of epidemiological studies of this disease in Singapore is limited. We aimed to describe the aetiology and clinical presentation of AS in Singapore, as well as patients' attitudes toward it. Our findings may facilitate the future planning and utilisation of resources to better manage these patients.Methods: 249 consecutive patients who underwent transthoracic echocardiography (from April 1999 to April 2008) and diagnosed with severe AS were assessed. Demographic and clinical data were collected, and patients' decisions on surgery were determined.Results: The mean patient age was 71 (range 23-98) years. 50.2% of patients were male. The commonest presenting symptom was dyspnoea, and 40 (16.0%) patients had coexistent atrial fibrillation. The aetiology of AS was degenerative in 216 (86.7%), rheumatic in 11 (4.4%) and related to a bicuspid valve in 22 (8.9%) patients. The average peak velocity across the aortic valve was 4.2 ± 0.8 m/s and the mean aortic valve area was 0.76 ± 0.13 cm2. The overall mean logistic EuroSCORE was 10.7 ± 12.3. 105 (42.2%) patients who were offered surgery refused. 87 (35%) deaths were seen during the follow-up period (mean duration 14.5 months), which also saw 68 (27%) patients undergo surgery and 86 (34%) patients hospitalised for heart failure.Conclusion: Degenerative AS was the commonest aetiology in this contemporary cohort of patients. Despite the known benefits of surgery, the refusal rate for surgery remained high. [ABSTRACT FROM AUTHOR]

Although the treatment of aortic coarctation in adults with the use of stents has shown favourable results and reduced complications, there have been few studies involving elderly patients. We highlight the clinical challenges faced in the management of such patients, with attention to severe calcification at the coarctation site. The midterm results were good in our patient, showing an improvement in blood pressure control and maintenance of stent patency. [ABSTRACT FROM AUTHOR]

Introduction: Management of aortic stenosis (AS) in patients with chronic kidney disease (CKD) may often be overlooked, and this could confer poorer outcomes., Methods: Consecutive patients ( n = 727) with index echocardiographic diagnosis of moderate to severe AS (aortic valve area <1.5 cm 2 ) were examined. They were divided into those with CKD (estimated glomerular filtration rate < 60 mL/min) and those without. Baseline clinical and echocardiographic parameters were compared, and a multivariate Cox regression model was constructed. Clinical outcomes were compared using Kaplan-Meier curves., Results: There were 270 (37.1%) patients with concomitant CKD. The CKD group was older (78.0 ± 10.3 vs. 72.1 ± 12.9 years, P < 0.001), with a higher prevalence of hypertension, diabetes mellitus, hyperlipidaemia and ischaemic heart disease. AS severity did not differ significantly, but left ventricular (LV) mass index (119.4 ± 43.7 vs. 112.3 ± 40.6 g/m 2 , P = 0.027) and Doppler mitral inflow E to annular tissue Doppler e' ratio (E: e' 21.5 ± 14.6 vs. 17.8 ± 12.2, P = 0.001) were higher in the CKD group. There was higher mortality (log-rank 51.5, P < 0.001) and more frequent admissions for cardiac failure (log-rank 25.9, P < 0.001) in the CKD group, with a lower incidence of aortic valve replacement (log-rank 7.12, P = 0.008). On multivariate analyses, after adjusting for aortic valve area, age, left ventricular ejection fraction and clinical comorbidities, CKD remained independently associated with mortality (hazard ratio 1.96, 95% confidence interval 1.50-2.57, P < 0.001)., Conclusion: Concomitant CKD in patients with moderate to severe AS was associated with increased mortality, more frequent admissions for cardiac failure and a lower incidence of aortic valve replacement., (Copyright © 2024 Copyright: © 2024 Singapore Medical Journal.)

Transcatheter aortic valve implantation (TAVI) has been established as an effective treatment modality in patients with severe aortic stenosis (AS) and the uptake of TAVI is rapidly growing in the Asia-Pacific region. However, there exist a heterogeneity in the management of aortic stenosis and the use of TAVI among countries in the region. Reasons for these differences include anatomic variations, disparity in healthcare resources and infrastructure, and the lack of consensus on the optimal management of AS in the Asia-Pacific region. Hence, an Asian Pacific Society of Cardiology (APSC) working group, including a multidisciplinary group of general and interventional cardiologists, cardiac surgeons, imaging specialists, developed a position statement on the recommendations for TAVI in the management of aortic stenosis. The APSC expert panel reviewed and appraised the available evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Recommendations were developed and put to an online vote. Consensus was reached when 80% of votes for a given recommendation were in support of "agree" or "neutral." The resulting 28 statements provide guidance for clinical practitioners in the region on the use of TAVI in the treatment of patients with aortic stenosis., Competing Interests: JY received speaker's honoraria from Abbott, Biosensors, Biotronik, Boston Scientific, Edwards, GE Healthcare, Johnson & Johnson, Kaneka, Medtronic and Terumo; is a proctor for Edwards Lifesciences and Medtronic; and is on the editorial board of the Journal of Asian Pacific Society of Cardiology; this did not influence peer review. KH is a proctor for Medtronic, Edwards Lifesciences and Abbott. KWH has received speaker fees from Medtronic, Edwards Lifesciences and Abbott Vascular. SL has received honoraria and travel support from Abbott, Bayer, Bioexcel, Boehringer Ingelheim, Boston Scientific, Medtronic and Pfizer. AS is a member of the advisory board and speaker’s bureau, and proctor for Medtronic; and is a member of the speaker’s bureau and proctor for Meril Lifesciences and Boston Scientific. QNN is on the editorial board of Journal of Asian Pacific Society of Cardiology; this did not influence acceptance. TCD is a proctor for Medtronic. MC is a proctor for Edwards Lifesciences, Boston Scientific and Abbott. SHE has received consultant and speaker fees from Abbott Vascular, Philips and GE. WHY is a proctor for Medtronic, Edwards, Boston Scientific, and Abbott. YTL is a proctor for Medtronic, Edwards Lifesciences and Abbott. ELT is a proctor for Medtronic, Edwards Lifesciences and Abbott. GHLT has received speaker’s honoraria and served as a physician proctor, consultant, advisory board member, TAVR publications committee member, APOLLO trial screening committee member and IMPACT MR steering committee member for Medtronic; has received speaker’s honoraria and served as a physician proctor, consultant, advisory board member and TRILUMINATE trial anatomic eligibility and publications committee member for Abbott Structural Heart; has served as an advisory board member for Boston Scientific and JenaValve; a consultant and physician screening committee member for Shockwave Medical; a consultant for NeoChord, Peija Medical and Shenqi Medical Technology; and has received speaker’s honoraria from Siemens Healthineers. JWCT reports honoraria from AstraZeneca, Bayer, Amgen, Medtronic, Abbott Vascular, Biosensors, Alvimedica, Boehringer Ingelheim and Pfizer; research and educational grants from Medtronic, Biosensors, Biotronik, Philips, Amgen, AstraZeneca, Roche, Otsuka, Terumo and Abbott Vascular; consulting fees from Elixir, CSL Behring and Radcliffe Publishing; and is on the editorial board of Journal of Asian Pacific Society of Cardiology; this did not influence acceptance. All other authors have no conflicts of interest to declare., (© 2024 The Authors.)

Background: Echocardiographic indexes of aortic stenosis may not comprehensively reflect disease morbidity. Plasma proteomic profiling may add prognostic value in these patients., Methods and Results: Proximity extension assays (Olink) of 183 circulating cardiovascular and inflammatory proteins were performed in a prospective follow-up study of 122 asymptomatic/minimally symptomatic patients (mean±SD age, 69.1±10.9 years; 61% men) with moderate to severe aortic stenosis and preserved left ventricular ejection fraction. Protein signatures of higher-risk echocardiographic subgroups were determined. Associations of proteins with the primary composite outcome (heart failure hospitalization, progression to New York Heart Association class III-IV, or all-cause mortality) were evaluated using competing risk analyses, with aortic valve replacement being the competing risk. Network analysis unveiled mutually exclusive communities of proteins and echocardiographic parameters, connected only through NT-proBNP (N-terminal pro-B-type natriuretic peptide). Members of the tumor necrosis factor receptor superfamily (TNFRSF1A, TNFRSF1B, and TNFRSF14), and trefoil factor-3 were major hub proteins among the circulating biomarkers. Left ventricular global longitudinal strain >-15% was associated with higher levels of proteins, primarily of inflammation and immune regulation, whereas aortic valve area <1 cm 2 , E/e' >15, and left atrial reservoir strain <20% were associated with higher levels of NT-proBNP. Of 14 proteins associated with the primary end point, phospholipase-C, C-X-C motif chemokine-9, and interleukin-10 receptor subunit β demonstrated the highest hazard ratios after adjusting for clinical factors ( q <0.05)., Conclusions: Plasma proteins involved in inflammation and immune regulation were differentially expressed in patients with aortic stenosis with reduced left ventricular global longitudinal strain, and associated with adverse clinical outcomes. Their incorporation into aortic stenosis risk stratification warrants further assessment.

Alphavirus infections are transmitted by mosquitoes, but the mode of transmission for Mycobacterium ulcerans, which causes Buruli ulcer, is contested. Using notification data for Victoria, Australia, during 2017-2022, adjusted for incubation period, we show close alignment between alphavirus and Buruli ulcer seasons, supporting the hypothesis of mosquito transmission of M. ulcerans.

Objectives: Whole genome sequencing (WGS) can identify clusters, transmission patterns, and drug resistance mutations. This is important in low-burden settings such as Australia, as it can assist in efficient contact tracing and surveillance., Methods: We conducted a retrospective cohort study using WGS from 155 genomically defined drug-resistant Mycobacterium tuberculosis (DR-TB) isolates collected between 2018-2021 in Victoria, Australia. Bioinformatic analysis was performed to identify resistance-conferring mutations, lineages, clusters and understand how local sequences compared with international context., Results: Of the 155 sequences, 42% were identified as lineage 2 and 35% as lineage 1; 65.8% (102/155) were isoniazid mono-resistant, 8.4% were multi-drug resistant TB and 5.8% were pre-extensively drug-resistant / extensively drug-resistant TB. The most common mutations were observed in katG and fabG1 genes, especially at Ser315Thr and fabG1 -15 C>T for first-line drugs. Ser450Leu was the most frequent mutation in rpoB gene. Phylogenetic analysis confirmed that Victorian DR-TB were associated with importation events. There was little evidence of local transmission with only five isolate pairs., Conclusion: Isoniazid-resistant TB is the commonest DR-TB in Victoria, and the mutation profile is similar to global circulating DR-TB. Most cases are diagnosed among migrants with limited transmission. This study highlights the value of WGS in identification of clusters and resistance-conferring mutations. This information is crucial in supporting disease mitigation and treatment strategies., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: This study compares dual task (DT) gait speed between robust and frail older adults in the setting of a community-based frailty screening program., Methods: A cross-sectional study was conducted involving older adults aged 50 years or older. Participants were categorized as robust, pre-frail or frail using the FRAIL phenotype. Gait speed was measured under single task (ST) and 2 DT conditions: arithmetic (DT1) and verbal fluency (DT2) tasks. For the arithmetic task, participants counted upwards in multiples of 2, starting from 16. For the verbal fluency task, they named different animals as they walked., Results: A total of 976 participants were recruited, of which 779 were robust, 181 were pre-frail and 16 were frail. Robust participants exhibited significantly faster DT gait speeds (DT1: 1.12 (0.25)m/s; DT2: 0.97 (0.27)m/s than pre-frail/frail (PFF) participants (DT1: 0.88 (0.30)m/s); DT2: 0.78 (0.30)m/s). Robust participants also demonstrated a significantly faster ST gait speed (1.31 (0.22)m/s) vs 1.05 (0.31)m/s)., Conclusion: DT gait assessment combines both physical and cognitive domains and may serve as a more holistic tool for early frailty detection in the community. The significant differences observed in DT gait speeds highlight the need for integrating cognitive assessments into frailty screening protocols, supporting timely interventions to improve health outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

To examine protective and risk factors for Buruli ulcer (BU), we conducted a case-control study of 245 adult BU cases and 481 postcode-matched controls across BU-endemic areas of Victoria, Australia. We calculated age- and sex-adjusted odds ratios for socio-environmental, host, and behavioral factors associated with BU by using conditional logistic regression. Odds of BU were >2-fold for persons with diabetes mellitus and persons working outdoors who had soil contact in BU-endemic areas (compared with indoor work) but were lower among persons who had bacillus Calmette-Guérin vaccinations. BU was associated with increasing numbers of possums and with ponds and bore water use at residences. Using insect repellent, covering arms and legs outdoors, and immediately washing wounds were protective; undertaking multiple protective behaviors was associated with the lowest odds of BU. Skin hygiene/protection behaviors and previous bacillus Calmette-Guérin vaccination might provide protection against BU in BU-endemic areas.

Background: Buruli ulcer (BU) is a neglected tropical disease caused by infection of subcutaneous tissue with Mycobacterium ulcerans . BU is commonly reported across rural regions of Central and West Africa but has been increasing dramatically in temperate southeast Australia around the major metropolitan city of Melbourne, with most disease transmission occurring in the summer months. Previous research has shown that Australian native possums are reservoirs of M. ulcerans and that they shed the bacteria in their fecal material (excreta). Field surveys show that locales where possums harbor M. ulcerans overlap with human cases of BU, raising the possibility of using possum excreta surveys to predict the risk of disease occurrence in humans., Methods: We thus established a highly structured 12 month possum excreta surveillance program across an area of 350 km 2 in the Mornington Peninsula area 70 km south of Melbourne, Australia. The primary objective of our study was to assess using statistical modeling if M. ulcerans surveillance of possum excreta provided useful information for predicting future human BU case locations., Results: Over two sampling campaigns in summer and winter, we collected 2,282 possum excreta specimens of which 11% were PCR positive for M. ulcerans -specific DNA. Using the spatial scanning statistical tool SaTScan , we observed non-random, co-correlated clustering of both M. ulcerans positive possum excreta and human BU cases. We next trained a statistical model with the Mornington Peninsula excreta survey data to predict the future likelihood of human BU cases occurring in the region. By observing where human BU cases subsequently occurred, we show that the excreta model performance was superior to a null model trained using the previous year's human BU case incidence data (AUC 0.66 vs 0.55). We then used data unseen by the excreta-informed model from a new survey of 661 possum excreta specimens in Geelong, a geographically separate BU endemic area to the southwest of Melbourne, to prospectively predict the location of human BU cases in that region. As for the Mornington Peninsula, the excreta-based BU prediction model outperformed the null model (AUC 0.75 vs 0.50) and pinpointed specific locations in Geelong where interventions could be deployed to interrupt disease spread., Conclusions: This study highlights the One Health nature of BU by confirming a quantitative relationship between possum excreta shedding of M. ulcerans and humans developing BU. The excreta survey-informed modeling we have described will be a powerful tool for the efficient targeting of public health responses to stop BU., Funding: This research was supported by the National Health and Medical Research Council of Australia and the Victorian Government Department of Health (GNT1152807 and GNT1196396)., Competing Interests: KV, AB, JP, AV, JW, KB, MD, VB, JF, ET, PJ, SW, NG, TS No competing interests declared, (© 2023, Vandelannoote, Buultjens et al.)

Background: Regionality is often a significant factor in tuberculosis (TB) management and outcomes worldwide. A wide range of context-specific factors may influence these differences and change over time. We compared TB treatment in regional and metropolitan areas, considering demographic and temporal trends affecting TB diagnosis and outcomes., Methods: Retrospective analyses of data for patients notified with TB in Victoria, Australia, were conducted. The study outcomes were treatment delays and treatment outcomes. Multivariable Cox proportional hazard model analyses were performed to investigate the effect of regionality in the management of TB. Six hundred and eleven (7%) TB patients were notified in regional and 8,163 (93%) in metropolitan areas between 1995 and 2019. Of the 611 cases in the regional cohort, 401 (66%) were overseas-born. Fifty-one percent of the overseas-born patients in regional Victoria developed TB disease within five years of arrival in Australia. Four cases of multidrug-resistant tuberculosis were reported in regional areas, compared to 97 cases in metropolitan areas. A total of 3,238 patients notified from 2012 to 2019 were included in the survival analysis. The time follow-up for patient delay started at symptom onset date, and the event was the presentation to the healthcare centre. For healthcare system delay, follow-up time began at the presentation to the healthcare centre, and the event was commenced on TB treatment. Cases with extrapulmonary TB in regional areas have a non-significantly longer healthcare system delay than patients in metropolitan (median 64 days versus 54 days, AHR = 0.8, 95% CI 0.6-1.0, P = 0.094)., Conclusion: Tuberculosis in regional Victoria is common among the overseas-born population, and patients with extrapulmonary TB in regional areas experienced a non-significant minor delay in treatment commencement with no apparent detriment to treatment outcomes. Improving access to LTBI management in regional areas may reduce the burden of TB., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Moyo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The conventional count-based physical frailty phenotype (PFP) dichotomizes its criterion predictors-an approach that creates information loss and depends on the availability of population-derived cut-points. This study proposes an alternative approach to computing the PFP by developing and validating a model that uses PFP components to predict the frailty index (FI) in community-dwelling older adults, without the need for predictor dichotomization., Methods: A sample of 998 community-dwelling older adults (mean [SD], 68 [7] years) participated in this prospective cohort study. Participants completed a multi-domain geriatric screen and a physical fitness assessment from which the count-based PFP and the 36-item FI were computed. One-year prospective falls and hospitalization rates were also measured. Bayesian beta regression analysis, allowing for nonlinear effects of the non-dichotomized PFP criterion predictors, was used to develop a model for FI ("model-based PFP"). Approximate leave-one-out (LOO) cross-validation was used to examine model overfitting., Results: The model-based PFP showed good calibration with the FI, and it had better out-of-sample predictive performance than the count-based PFP (LOO-R 2 , 0.35 vs 0.22). In clinical terms, the improvement in prediction (i) translated to improved classification agreement with the FI (Cohen's k w , 0.47 vs 0.36) and (ii) resulted primarily in a 23% (95%CI, 18-28%) net increase in FI-defined "prefrail/frail" participants correctly classified. The model-based PFP showed stronger prognostic performance for predicting falls and hospitalization than did the count-based PFP., Conclusion: The developed model-based PFP predicted FI and clinical outcomes more strongly than did the count-based PFP in community-dwelling older adults. By not requiring predictor cut-points, the model-based PFP potentially facilitates usage and feasibility. Future validation studies should aim to obtain clear evidence on the benefits of this approach., (© 2023. The Author(s).)

Background: Intrinsic capacity (IC) and frailty are complementary in advancing disability prevention through maintaining functionality., Objectives: We examined the relationship between IC and frailty status at baseline and 1-year, and evaluated if IC decline predicts frailty onset among robust older adults. The secondary objectives investigated associations between IC, physical fitness and health-related outcomes., Design: Prospective cohort study., Setting: Community-based assessments., Participants: Older adults aged>55 years, who were independent in ambulation (walking aids permitted)., Measurements: 5 domains of IC were assessed at baseline: locomotion (Short Physical Performance Battery, 6-minute walk test), vitality (nutritional status, muscle mass), sensory (self-reported hearing and vision), cognition (self-reported memory, age- and education adjusted cognitive performance), psychological (Geriatric Depression Scale-15, self-reported anxiety/ depression). Composite IC (0-10) was calculated, with higher scores representing greater IC. Frailty status was based on modified Fried criteria, with frailty progression defined as incremental Fried score at 1-year., Results: 809 participants (67.6+6.8 years) had complete data for all 5 IC domains. 489 (60.4%) participants were robust but only 213 (26.3%) had no decline in any IC domain. Pre-frail and frail participants were more likely to exhibit decline in all 5 IC domains (p<0.05), with decremental composite IC [9 (8-9), 8 (6-9), 5.5 (4-7.5), p<0.001] across robust, prefrail and frail. IC was significantly associated with fitness performance, independent of age and gender. Higher composite IC reduced risk for frailty progression (OR=0.62, 95% CI 0.48-0.80), and reduced frailty onset among robust older adults (OR=0.53, 95% CI 0.37-0.77), independent of age, comorbidities and social vulnerability. Participants with higher IC were less likely to experience health deterioration (OR=0.70, 95% CI 0.58-0.83), falls (OR=0.76, 95% CI 0.65-0.90) and functional decline (OR=0.64, 95% CI 0.50-0.83) at 1-year., Conclusion: Declining IC may present before frailty becomes clinically manifest, increasing risk for poor outcomes. Monitoring of IC domains potentially facilitates personalized interventions to avoid progressive frailty., Competing Interests: All the authors have no conflict of interest or financial disclosure of note.

Background: The differential risk profiles associated with prefrailty may be attributable to underlying intrinsic capacity (IC)., Objectives: We examine (i) effect of a multi-domain physical exercise and nutrition intervention on pre-frailty reversal in community-dwelling older adults at 1-year, and (ii) whether IC contributes to pre-frailty reversal., Methods: Prefrail participants in this non-randomized study were invited to attend a 4-month exercise and nutritional intervention following a frailty screen in the community. Prefrailty was operationalized as (i) FRAIL score 1-2 or (ii) 0 positive response on FRAIL but with weak grip strength or slow gait speed based on the Asian Working Group for Sarcopenia cut-offs. Participants who fulfilled operational criteria for prefrailty but declined enrolment in the intervention programme served as the control group. All participants completed baseline IC assessment: locomotion (Short Physical Performance Battery, 6-minute walk test), vitality (nutritional status, muscle mass), sensory (self-reported hearing and vision), cognition (self-reported memory, age- and education adjusted cognitive performance), psychological (Geriatric Depression Scale-15, self-reported anxiety/ depression). Reversal of prefrailty was defined as achieving a FRAIL score of 0, with unimpaired grip strength and gait speed at 1-year follow-up., Results: Of 81 participants (70.0 ± 6.6 years, 79.0% female), 52 participants (64.2%) were enrolled in the multi-domain intervention, and 29 participants (35.8%) who declined intervention constituted the control group. There was no difference in age, gender and baseline composite IC between groups. Reversal to robustness at 1-year was similar between intervention and control groups (30.8% vs. 44.8% respectively, p = 0.206). Reduced prevalence of depression was observed among participants in the intervention group at 1-year relative to baseline (7.8% vs. 23.1%, p = 0.022). In multiple logistic regression, intervention had no effect on prefrailty reversal, while higher composite IC exhibited reduced likelihood of remaining prefrail at 1-year (OR = 0.67, 95% CI 0.45-1.00, p = 0.049)., Conclusion: Focusing only on the locomotion and vitality domains through a combined exercise and nutritional intervention may not adequately address component domain losses to optimize prefrailty reversal. Future studies should examine whether an IC-guided approach to target identified domain declines may be more effective in preventing frailty progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tay, Tay, Mah, Latib and Ng.)

In recent years reported cases of Buruli ulcer, caused by Mycobacterium ulcerans, have increased substantially in Victoria, Australia, with the epidemic also expanding geographically. To develop an understanding of how M. ulcerans circulates in the environment and transmits to humans we analyzed environmental samples collected from 115 properties of recent Buruli ulcer cases and from 115 postcode-matched control properties, for the presence of M. ulcerans. Environmental factors associated with increased odds of M. ulcerans presence at a property included certain native plant species and native vegetation in general, more alkaline soil, lower altitude, the presence of common ringtail possums (Pseudocheirus peregrinus) and overhead powerlines. However, only overhead powerlines and the absence of the native plant Melaleuca lanceolata were associated with Buruli ulcer case properties. Samples positive for M. ulcerans were more likely to be found at case properties and were associated with detections of M. ulcerans in ringtail possum feces, supporting the hypothesis that M. ulcerans is zoonotic, with ringtail possums the strongest reservoir host candidate. However, the disparity in environmental risk factors associated with M. ulcerans positive properties versus case properties indicates the involvement of human behavior or the influence of other environmental factors in disease acquisition that requires further study., Competing Interests: The authors have declared that no competing interests exist.

Background: Whole genome sequencing (WGS) is increasingly used by tuberculosis (TB) programs to monitor Mycobacterium tuberculosis ( Mtb ) transmission. We aimed to characterise the molecular epidemiology of TB and Mtb transmission in the low-incidence setting of Victoria, Australia, and assess the utility of WGS., Methods: WGS was performed on all first Mtb isolates from TB cases from 2017 to 2020. Potential clusters (≤12 single nucleotide polymorphisms [SNPs]) were investigated for epidemiological links. Transmission events in highly-related (≤5 SNPs) clusters were classified as likely or possible, based on the presence or absence of an epidemiological link, respectively. Case characteristics and transmission settings (as defined by case relationship) were summarised. Poisson regression was used to examine associations with secondary case number., Findings: Of 1844 TB cases, 1276 (69.2%) had sequenced isolates, with 182 (14.2%) in 54 highly-related clusters, 2-40 cases in size. Following investigation, 140 cases (11.0% of sequenced) were classified as resulting from likely/possible local-transmission, including 82 (6.4%) for which transmission was likely. Common identified transmission settings were social/religious (26.4%), household (22.9%) and family living in different households (7.1%), but many were uncertain (41.4%). While household transmission featured in many clusters ( n  = 24), clusters were generally smaller (median = 3 cases) than the fewer that included transmission in social/religious settings ( n  = 12, median = 7.5 cases). Sputum-smear-positivity was associated with higher secondary case numbers., Interpretation: WGS results suggest Mtb transmission commonly occurs outside the household in our low-incidence setting. Further work is required to optimise the use of WGS in public health management of TB., Funding: The Victorian Tuberculosis Program receives block funding for activities including case management and contact tracing from the Victorian Department of Health. No specific funding for this report was received by manuscript authors or the Victorian Tuberculosis Program, and the funders had no role in the study design, data collection, data analysis, interpretation or report writing., Competing Interests: None to declare., (© 2022 The Authors.)

Aims: Left ventricular ejection fraction is the conventional measure used to guide heart failure management, regardless of underlying etiology. Left ventricular global longitudinal strain (LV-GLS) by speckle tracking echocardiography (STE) is a more sensitive measure of intrinsic myocardial function. We aim to establish LV-GLS as a marker of replacement myocardial fibrosis on cardiovascular magnetic resonance (CMR) and validate the prognostic value of LV-GLS thresholds associated with fibrosis. Methods and results: LV-GLS thresholds of replacement fibrosis were established in the derivation cohort: 151 patients (57 ± 10 years; 58% males) with hypertension who underwent STE to measure LV-GLS and CMR. Prognostic value of the thresholds was validated in a separate outcome cohort: 261 patients with moderate-severe aortic stenosis (AS; 71 ± 12 years; 58% males; NYHA functional class I-II) and preserved LVEF ≥50%. Primary outcome was a composite of cardiovascular mortality, heart failure hospitalization, and myocardial infarction. In the derivation cohort, LV-GLS demonstrated good discrimination (c-statistics 0.74 [0.66-0.83]; P < 0.001) and calibration (Hosmer-Lemeshow χ 2 = 6.37; P = 0.605) for replacement fibrosis. In the outcome cohort, 47 events occurred over 16 [3.3, 42.2] months. Patients with LV-GLS > -15.0% (corresponding to 95% specificity to rule-in myocardial fibrosis) had the worst outcomes compared to patients with LV-GLS < -21.0% (corresponding to 95% sensitivity to rule-out myocardial fibrosis) and those between -21.0 and -15.0% (log-rank P < 0.001). LV-GLS offered independent prognostic value over clinical variables, AS severity and echocardiographic LV mass and E/e'. Conclusion: LV-GLS thresholds associated with replacement myocardial fibrosis is a novel approach to risk-stratify patients with AS and preserved LVEF., Competing Interests: The department of Cardiology at Leiden University receives unrestricted research grants from Abbott Vascular, Bayer, Biotronik, BIoventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionis and Medtronic. VD received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, MSD, Medtronic and Novartis. JJB received speaker fees from Abbott Vascular. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Le, Huang, Singh, Toh, Ewe, Tang, Loo, Bryant, Ang, Tay, Soo, Yip, Oon, Gong, Lunaria, Yong, Lee, Yeo, Chai, Goh, Ling, Ong, Richards, Delgado, Bax, Ding, Ling and Chin.)

Aims: Pulmonary artery pulsatility index (PAPi), defined as [(pulmonary artery systolic pressure - diastolic pulmonary artery pressure)/mean right atrial pressure], is a novel haemodynamic index that predicts right ventricular failure after myocardial infarction and left ventricular assist device implantation. We analysed if a low PAPi is associated with death in our 14 - ​year pulmonary arterial hypertension (PAH) registry., Methods: Consecutive patients with newly diagnosed PAH and complete haemodynamic data were prospectively enrolled into our standing registry between January 2003 and December 2016. PAPi was calculated from baseline invasive right heart catheterization data. A prognostic cut-off value was determined with a decision tree. Baseline characteristics of 'high' and 'low' PAPi groups based on this cut-off were compared, as well as odds of death and time-to-death., Results: One hundred and two patients were included. Mean age was 53 years, and 77% were women. Our multi-ethnic cohort was 64% Chinese, 23% Malay, and 10% Indian. The aetiologies were idiopathic (33%), connective tissue disease (31%), congenital heart disease (24%), and others (12%). The low PAPi group (<5.3) had a greater age (56 years vs. 49 years), lower pulmonary artery systolic pressure (71 mmHg vs. 85 mmHg), and higher mean right atrial pressure (14 mmHg vs. 6 mmHg). Mortality risk was higher in the low PAPi group (adjusted odds ratio: 2.98 and adjusted hazard ratio: 2.23). Mean right atrial pressure was the strongest predictor (hazard ratio 1.114, P = 0.009) when components of PAPi were analysed., Conclusions: Pulmonary artery pulsatility index was found to be predictive of mortality in PAH and may be a valuable marker for risk stratification. Its prognostic strength may be driven by mean right atrial pressure., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)