2024 CSANZ Position Statement on Indications, Assessment and Monitoring of Structural and Valvular Heart Disease With Transthoracic Echocardiography in Adults.

Transthoracic echocardiography (TTE) is the most widely available and utilised imaging modality for the screening, diagnosis, and serial monitoring of all abnormalities related to cardiac structure or function. The primary objectives of this document are to provide (1) a guiding framework for treating clinicians of the acceptable indications for the initial and serial TTE assessments of the commonly encountered cardiovascular conditions in adults, and (2) the minimum required standard for TTE examinations and reporting for imaging service providers. The main areas covered within this Position Statement pertain to the TTE assessment of the left and right ventricles, valvular heart diseases, pericardial diseases, aortic diseases, infective endocarditis, cardiac masses, pulmonary hypertension, and cardiovascular diseases associated with cancer treatments or cardio-oncology. Facilitating the optimal use and performance of high quality TTEs will prevent the over or under-utilisation of this resource and unnecessary downstream testing due to suboptimal or incomplete studies.

Recurrent Takotsubo Syndrome: How Frequent, and How Does It Present?

BACKGROUND: Recurrent Takotsubo syndrome (TS) is not uncommon but experience with TS recurrence is inherently limited by the infrequency of the condition itself and incomplete long-term follow-up. There is limited published data on the clinical features and outcomes of patients with recurrent TS. We aimed to describe the clinical characteristics and outcomes of patients with recurrent TS in a large Auckland cohort. METHOD: The clinical profile, in-hospital, and long-term outcomes were prospectively assessed in consecutive patients with recurrent TS presenting to Auckland's three major hospitals between January 2006 and January 2023. RESULTS: During the study period, 472 TS patients were identified. Of the 467 patients discharged alive after the index event, 45 (9.6%) patients (mean age 62.3±11.0 years), all women, experienced recurrent TS. Median time interval from index event to the first recurrence was 3.14 years (range 27 days to 13.8 years). In 27 (60%) of the 45 patients, the subsequent events involved a stressor (physical triggers, n=8; emotional triggers, n=19). The stressor type differed between the index and recurrent event in 18 (40%) of the 45 patients. Thirteen (28.9%) had a different echocardiographic variant of TS at first recurrence. All patients with recurrent TS were discharged alive. Four patients died late after discharge from the first recurrence, all but one from a non-cardiac cause. CONCLUSIONS: One in 10 patients with TS experience recurrent events. These may occur many years later, and both the stressor type and the echocardiographic variant may be different at the recurrent event.

Inexpensive DIY Bioprinting in a Secondary School Setting.

Bioprinting is a technique that allows custom printing of cell-laden tissue using the principle of three-dimensional (3D) printing. The technique has various applications, ranging from tissue engineering to materials science. Bioprinting is an attractive topic for science, technology, engineering, and math education due to its novelty and interdisciplinary nature. Nonetheless, a basic commercial bioprinter could cost several thousand U.S. dollars. There have been attempts to construct low-cost do-it-yourself bioprinters for research purpose. However, those methods required expertise, uncommon reagents, and professional equipment, making it difficult for teachers and students in secondary schools to replicate. Here, we demonstrate how teachers and students in a secondary school can convert a 3D printer into a bioprinter for conducting a hands-on bioprinting activity using secondary school-available resources. Briefly, an open-source Creality Ender 3 V2 3D printer in a school was converted into a bioprinter using 3D-printed parts and other readily available materials. Cell-laden bioink and support medium were made using school-available reagents. The bioprinter can be easily constructed and operated by teachers and students who do not have prior knowledge in coding and engineering. We used the bioprinter to print a coronary artery model and an algae-laden artificial leaf. The photosynthetic activity of the artificial leaf could be observed and investigated using a hydrogen carbonate indicator. The work described in this paper could make bioprinting available, comprehensible, and enjoyable to secondary school students, opening a door for inexpensive innovative teaching and learning activities using bioprinting in secondary schools.

External Validation of a Clinical Score to Differentiate Takotsubo Syndrome From Non-ST-Elevation Myocardial Infarction in Women.

BACKGROUND AND AIMS: Clinical presentation of Takotsubo Syndrome (TS) mimics acute coronary syndrome (ACS). A score to differentiate TS from ACS would be helpful to facilitate appropriate investigation and management. We have previously developed a clinical score (NSTE-Takotsubo Score) to distinguish women with non-ST-segment elevation myocardial infarction (NSTEMI) from TS with non-ST-segment elevation (NSTE-TS). This study sought to assess the diagnostic validity of this score in an external validation cohort. METHODS: The external cohort consisted of women with NSTE-TS (n=110) and NSTEMI (n=113) from two major tertiary hospitals in New Zealand. The five variables in the arithmetic score (range -6 to +5) and their relative weights are: T-wave inversion (TWI) in ≥6 leads (3 points), recent stress (2 points), diabetes mellitus (DM) (-1 point), prior cardiovascular disease (CVD) (-2 points) and presence of ST depression (-3 points). Two clinicians blinded to the diagnoses calculated the score using clinical and electrocardiogram (ECG) data on day 1 post-admission. RESULTS: The NSTE-Takotsubo Score discriminated well between NSTE-TS and NSTEMI. The sensitivity and specificity of a score ≥1 to distinguish NSTE-TS from NSTEMI were 78% and 85%, respectively. The area under the receiver operator curve was 0.78 (95% CI 0.72 to 0.84). CONCLUSION: In an external validation cohort, the NSTE-Takotsubo Score was easy to apply and useful to identify women likely to have NSTE-TS on day 1 post-admission.

Drug-Initiated Activity Metabolomics Identifies Myristoylglycine as a Potent Endogenous Metabolite for Human Brown Fat Differentiation.

Worldwide, obesity rates have doubled since the 1980s and in the USA alone, almost 40% of adults are obese, which is closely associated with a myriad of metabolic diseases such as type 2 diabetes and arteriosclerosis. Obesity is derived from an imbalance between energy intake and consumption, therefore balancing energy homeostasis is an attractive target for metabolic diseases. One therapeutic approach consists of increasing the number of brown-like adipocytes in the white adipose tissue (WAT). Whereas WAT stores excess energy, brown adipose tissue (BAT) can dissipate this energy overload in the form of heat, increasing energy expenditure and thus inhibiting metabolic diseases. To facilitate BAT production a high-throughput screening approach was developed on previously known drugs using human Simpson-Golabi-Behmel Syndrome (SGBS) preadipocytes. The screening allowed us to discover that zafirlukast, an FDA-approved small molecule drug commonly used to treat asthma, was able to differentiate adipocyte precursors and white-biased adipocytes into functional brown adipocytes. However, zafirlukast is toxic to human cells at higher dosages. Drug-Initiated Activity Metabolomics (DIAM) was used to investigate zafirlukast as a BAT inducer, and the endogenous metabolite myristoylglycine was then discovered to mimic the browning properties of zafirlukast without impacting cell viability. Myristoylglycine was found to be bio-synthesized upon zafirlukast treatment and was unique in inducing brown adipocyte differentiation, raising the possibility of using endogenous metabolites and bypassing the exogenous drugs to potentially alleviate disease, in this case, obesity and other related metabolic diseases.

Spontaneous coronary artery dissection: insights from computed tomography coronary angiography follow-up.

METHODS: Patients with SCAD on invasive coronary angiography who underwent a follow-up CTCA between 2010 and 2018 at our institute were included. CTCA was reported by two cardiologists-one with knowledge of the SCAD location, and a second blinded. Assessment of dissection healing were made and optimal timing of CTCA was also calculated. RESULTS: A total of 32 patients with 38 non-contiguous SCAD lesions were included (mean age 50.5 ± 8.8 years, 65.6% women). The left circumflex artery was the most commonly affected vessel (34.2%), and 71.1% of lesions occurred in distal or branch vessels. Median time that CTCA was performed was 40.5 days from the index event, and 25 of 38 lesions had healed (65.8%). On blinded reporting, the sensitivity and specificity of CTCA for assessment of dissection healing was 72% and 53.8%, respectively. The optimal timing of CTCA to assess healing was 80 days (AUC 0.774, p=0.006; sensitivity 76.9%, specificity 84.0%). When early CTCA was performed (<80 days), 21 of 24 lesions (87.5%) were unhealed, whereas late CTCA (≥80 days) showed healing in 10 of 14 lesions (71.4%). CONCLUSION: The usefulness of CTCA in diagnosing SCAD remains challenging due to limitations in spatial and temporal resolution, particularly in distal vessels. The optimal timing of CTCA to assess dissection healing was 80 days.

Type of Stressor and Medium-Term Outcomes After Takotsubo Syndrome: What Becomes of the Broken Hearted? (ANZACS-QI 59).

BACKGROUND: Takotsubo syndrome (TS) is often triggered by an acute physical or emotional stressor. We hypothesised that medium-term prognosis may be better for TS patients with an associated emotional stressor than for those with an acute physical illness. METHODS: We identified consecutive TS patients presenting in New Zealand (2006-2018). The clinical presentation and outcomes of TS patients according to types of stressor (physical, emotional or no stressor) were assessed. Post-discharge survival after TS was compared with age- and gender-matched patients after myocardial infarction (MI) and people in the community without known cardiovascular disease (CVD). RESULTS: Of 632 TS patients (95.9% women, mean age 65.0±11.1 years), 27.4% had an associated acute physical stressor, 46.4% an emotional stressor and 26.2% no evident stressor. In-hospital mortality was similar for each group (1.7%, 1.2%, 0.3% respectively, p=0.29). In a median 4.4 years post-discharge there were 54 deaths (53 non-cardiac). Compared with patients without known CVD, TS patients with physical stress and those with MI were less likely to survive (HR 4.46, 95%CI 3.10-6.42; HR 4.23, 95%CI 3.81-4.70 respectively) but survival for TS patients associated with emotional stress or no stressor was similar (HR 1.11, 95%CI 0.66-1.85; HR 1.08, 95%CI 0.54-2.18, respectively). Recurrence was similar among the three groups (p=0.14). CONCLUSION: Takotsubo syndrome associated with physical stressor has a post-discharge mortality risk as high as after MI. In contrast, prognosis for TS triggered by an emotional stressor is excellent, and similar to that of those without known CVD.

A Decade of Transcatheter Aortic Valve Implantation in New Zealand: Growth and Inequalities.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an effective treatment increasingly performed for severe aortic stenosis. Developing nationwide accessibility to TAVI can be met with barriers that result in treatment disparities. OBJECTIVES: This nationwide retrospective study aimed to review the first decade of TAVI in New Zealand and identify potential inequalities. METHODS: All patients undergoing TAVI in a New Zealand public hospital between 2008 and 2018 were included. Demographic and geographic details were analysed and TAVI rates were age standardised using census data. One-year survival was compared between groups. RESULTS: A total of 952 patients were included in our study. The mean age was 80.0±7.5 years and women accounted for nearly half of all patients (42.5%). The age-standardised TAVI rate in New Zealand increased from 15 per million in 2013 to 49 per million in 2018. Since 2013, there has been a disproportionate growth in TAVI rates between different ethnicities. TAVI rates for Europeans grew from 16 to 66 per million compared to 7 to 8 per million for Pacific people and 3 to 5 per million for Maori. Despite nationwide access to TAVI in 2018, significant geographic heterogeneity remains, ranging from 2.0 to 12.8 procedures per 100,000 people between regions. One-year (1-yr) survival for Maori were significantly worse than Europeans (80.1% vs 93.9%, HR 4.2, 95%CI: 1.6-11.5, p=0.004) despite being younger (67.9 vs 80.6 years, p<0.05). CONCLUSION: There are significant geographical and ethnic variations in TAVI rates in New Zealand. Maori had worse one-year survival than European patients following TAVI.

A comparison of the clinical features and outcomes of Takotsubo syndrome across five metropolitan hospitals in New Zealand.

AIM: Takotsubo syndrome (TS) mimics acute coronary syndrome but has a distinct pathophysiology. This study aimed to compare and contrast the clinical presentation, management and outcomes of patients with TS in five large New Zealand hospitals. METHODS: We identified 632 consecutive patients presenting to the five major tertiary hospitals in New Zealand (Middlemore Hospital, Auckland City Hospital, North Shore Hospital, Christchurch Hospital and Dunedin Hospital) between January 2006 and June 2018 and obtained clinical, laboratory, electrocardiography, echocardiography, coronary angiography and long-term follow-up data. RESULTS: Six hundred and thirty-two consecutive patients with TS (606 women, mean age 65.0+11.1 years) were included. An associated stressor was identified in two-thirds of patients, and emotional triggers were more frequent than physical triggers (62.9% and 37.1%, respectively). Overall, 12.7% of patient had depression and 11.7% anxiety but this was more common in patients from Christchurch Hospital (20.4% and 23.4%, respectively). The in-hospital mortality among the five hospitals ranges between 0 to 2.0%. The mean follow-up was 4.9+3.4 years (median 4.4 years). Fifty-four people died post-discharge, all but one from a non-cardiac cause. Forty patients had recurrent TS. Mortality post-discharge (p=0.63) and TS recurrence (p=0.38) did not differ significantly among the five hospitals. CONCLUSION: In this large New Zealand TS cohort, the clinical characteristics and presentation were similar among the five hospitals. A subset of patients had a complicated in-hospital course, but late deaths were almost all from non-cardiac causes and recurrence was infrequent. Mortality post-discharge and recurrence was similar between the hospitals.

CSANZ Imaging Council Position Statement on Echocardiography Services During the COVID-19 Pandemic.

This Cardiac Society of Australia and New Zealand (CSANZ) Imaging Council Position Statement aims to guide local, regional and national clinical practice, and facilitate resource and echocardiographic service planning appropriately during the current COVID-19 global pandemic. General considerations include workforce arrangements and contingency plans, patient risk assessment for COVID-19 and level of care (personal protective equipment) for staff. Both outpatient and inpatient settings are addressed, including specific considerations in the in-patient setting including scanning protocols, screening modalities and indications for echocardiograms in the context of COVID-19 infection.

A Score to differentiate Takotsubo syndrome from non-ST-elevation myocardial nfarction in women at the bedside.

Objective: A score to distinguish Takotsubo syndrome (TS) from acute coronary syndrome would be useful to facilitate appropriate patient investigation and management. This study sought to derive and validate a simple score using demographic, clinical and ECG data to distinguish women with non-ST elevation myocardial infarction (NSTEMI) from NSTE-TS. Methods: The derivation cohort consisted of women with NSTE-TS (n=100) and NSTEMI (n=100). Logistic regression was used to derive the score using ECG values available on the postacute ward round on day 1 post-hospital admission. The score was then temporally validated in subsequent consecutive patients with NSTE-TS (n=40) and NSTEMI (n=70). Results: The five variables in the score and their relative weights were: T-wave inversion in ≥6 leads (+3), recent stress (+2), diabetes (-1), prior cardiovascular disease (-2) and ST-depression in any lead (-3). When calculated using ECG values obtained at admission, discrimination between conditions was very good (area under the curve (AUC) 0.87 95% CI 0.83 to 0.92). The optimal score cut-point of ≥1 to predict NSTE-TS had 73% sensitivity and 90% specificity. When applied to the validation cohort at admission, AUC was 0.82 (95% CI 0.75 to 0.90) and positive and negative predictive values were 78% and 81%, respectively. On day 1 post-admission, AUC was 0.92 (95% CI 0.87 to 0.97), with positive and negative predictive values of 77% and 91%, respectively. Conclusion: This NSTE-TS score is easy to use and may prove useful in clinical practice to distinguish women with NSTE-TS from NSTEMI. Further validation in external cohorts is needed.

Design of a Long-Acting and Selective MEG-Fatty Acid Stapled Prolactin-Releasing Peptide Analog.

Anorexigenic peptides offer promise as potential therapies targeting the escalating global obesity epidemic. Prolactin-releasing peptide (PrRP), a novel member of the RFamide family secreted by the hypothalamus, shows therapeutic potential by decreasing food intake and body weight in rodent models via GPR10 activation. Here we describe the design of a long-acting PrRP using our recently developed novel multiple ethylene glycol-fatty acid (MEG-FA) stapling platform. By incorporating serum albumin binding fatty acids onto a covalent side chain staple, we have generated a series of MEG-FA stapled PrRP analogs with enhanced serum stability and in vivo half-life. Our lead compound 18-S4 exhibits good in vitro potency and selectivity against GPR10, improved serum stability, and extended in vivo half-life (7.8 h) in mouse. Furthermore, 18-S4 demonstrates a potent body weight reduction effect in a diet-induced obesity (DIO) mouse model, representing a promising long-acting PrRP analog for further evaluation in the chronic obesity setting.

Prognostic Value of Global Longitudinal Strain in Hypertrophic Cardiomyopathy: A Systematic Review of Existing Literature.

OBJECTIVES: The association of left ventricular global longitudinal strain (LV-GLS) with clinical outcomes in patients with hypertrophic cardiomyopathy (HCM) has been examined in multiple studies. The authors conducted a systematic review aimed at summarizing and critically appraising the current evidence. BACKGROUND: HCM is a common genetic cardiovascular disease with an estimated prevalence of 1 in 500 patients. LV-GLS derived from speckle tracking echocardiography is a sensitive noninvasive method of assessing regional left ventricular function. Several studies have suggested association of abnormal LV-GLS with outcomes in HCM patients. METHODS: A computerized literature search of all English language publications in the PubMed and EMBASE databases was made looking at all randomized and nonrandomized studies conducted on patients with HCM where association of LV-GLS with clinical outcomes was studied. We then manually searched the reference lists of included articles. The Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PRISMA) of reporting systematic reviews was used. RESULTS: Our search yielded a total of 14 observational studies published between 2009 and 2017 with a total of 3,154 patients with HCM. Eleven of the 14 studies included a composite cardiac outcome which included mortality as their primary outcome of interest and 3 of the 14 studies looked at association of LV-GLS with ventricular arrhythmias and/or implantable cardiac defibrillator discharge. We noted wide variability in inclusion, methodology, follow-up, and consequently effect estimates, which was not conducive to performing a meta-analysis. However, despite the variation, all studies revealed a degree of association of abnormal LV-GLS with poor cardiac outcomes. CONCLUSIONS: Our systematic review of more than 3000 HCM patients suggests an association of abnormal LV-GLS with adverse composite cardiac outcomes and ventricular arrhythmias.

Postdischarge outcome after Takotsubo syndrome compared with patients post-ACS and those without prior CVD: ANZACS-QI 19.

Objective: Takotsubo syndrome (TS) mimics acute coronary syndrome (ACS) but has a distinct pathophysiology. While in-hospital adverse outcomes appear similar to those presenting with an ACS, data on longer term postdischarge risk are conflicting. This study sought to assess the long-term prognosis of patients discharged alive after TS. Methods: The clinical profile and in-hospital and long-term outcomes were prospectively assessed in consecutive patients with TS. Survival in patients with TS was compared with two representative age-matched and gender-matched comparison cohorts: a hospitalised ACS cohort and a community cohort without known cardiovascular disease (CVD). Results: Two hundred and-twenty-five patients with TS (216 women, mean age 63.7±11.8 years) were included. In-hospital mortality was 1.8% and 1.9% for patients with TS and ACS, respectively. Of the 219 patients with TS with postdischarge follow-up, at a mean follow-up of 4.8±3.2 years, there were 19 (8.3%) deaths, 18 of which were from non-cardiac causes. When compared with the cohort without prior CVD, postdischarge patients with TS were at increased mortality risk (HR 2.00, 95% CI 1.26 to 3.17, p=0.003), but mortality in postdischarge patients with ACS was over threefold higher (HR 3.43, 95% CI 2.97 to 3.96, p<0.0001). Conclusions: In-hospital mortality for patients diagnosed with TS and ACS was similar. However, while postdischarge survivors of TS had a long-term survival which was poorer than for a community-based cohort without known CVD, their survival was better than for postdischarge survivors of an ACS event. Late deaths in patients with TS were almost all from non-cardiac causes.

A novel inhibitor of inducible NOS dimerization protects against cytokine-induced rat beta cell dysfunction.

BACKGROUND AND PURPOSE: Beta cell apoptosis is a major feature of type 1 diabetes, and pro-inflammatory cytokines are key drivers of the deterioration of beta cell mass through induction of apoptosis. Mitochondrial stress plays a critical role in mediating apoptosis by releasing cytochrome C into the cytoplasm, directly activating caspase-9 and its downstream signalling cascade. We aimed to identify new compounds that protect beta cells from cytokine-induced activation of the intrinsic (mitochondrial) pathway of apoptosis. EXPERIMENTAL APPROACH: Diabetogenic media, composed of IL-1ß, IFN-γ and high glucose, were used to induce mitochondrial stress in rat insulin-producing INS1E cells, and a high-content image-based screen of small molecule modulators of Casp9 pathway was performed. KEY RESULTS: A novel small molecule, ATV399, was identified from a high-content image-based screen for compounds that inhibit cleaved caspase-9 activation and subsequent beta cell apoptosis induced by a combination of IL-1ß, IFN-γ and high glucose, which together mimic the pathogenic diabetic milieu. Through medicinal chemistry optimization, potency was markedly improved (6-30 fold), with reduced inhibitory effects on CYP3A4. Improved analogues, such as CAT639, improved beta cell viability and insulin secretion in cytokine-treated rat insulin-producing INS1E cells and primary dispersed islet cells. Mechanistically, CAT639 reduced the production of NO by allosterically inhibiting dimerization of inducible NOS (iNOS) without affecting its mRNA levels. CONCLUSION AND IMPLICATIONS: Taken together, these studies demonstrate a successful phenotypic screening campaign resulting in identification of an inhibitor of iNOS dimerization that protects beta cell viability and function through modulation of mitochondrial stress induced by cytokines.

A comprehensive web tool for toehold switch design.

Motivation: Toehold switches are a class of RNAs with a hairpin loop that can be unfolded upon binding a trigger RNA, thereby exposing a ribosome binding site (RBS) and permitting translation of the reporter protein. They have been shown very useful in detecting a variety of targets including RNAs from Zika and Ebola viruses. The base complementation between the toehold switch and the trigger RNA also makes it sensitive to sequence variations. Design of toehold switches involves a series of considerations related to their sequence properties, structures and specificities. Results: Here we present the first comprehensive web tool for designing toehold switches. We also propose a score for predicting the efficacy of designed toehold switches based on properties learned from ∼180 experimentally tested switches. Availability and implementation: The toehold switch web tool is available at https://yiplab.cse.cuhk.edu.hk/toehold/.

Seasonal variation in Takotsubo syndrome compared with myocardial infarction: ANZACS-QI 16.

BACKGROUND: The incidence of myocardial infarction (MI) is characterised by seasonal variation, with a winter peak and summer trough. Takotsubo syndrome (TS) mimics MI, but is thought to have a distinct aetiology and may exhibit a reversed pattern of seasonal variation. This study investigated the seasonal variation in the incidence of TS in comparison to MI. METHODS: Two hundred and sixty consecutive patients with TS (95% women, median age 66 years) admitted between March 2004 and December 2016 in the Auckland region of New Zealand were identified. The study population was grouped into three-month intervals (seasons) according to the date of admission to analyse for potential seasonal variations in the incidence. The TS cohort was compared with 36,376 patients who presented with acute MI in the Auckland region (40% women, median age 71 years) between March 2004 and December 2016. RESULTS: The onset of TS differed as a function of season (p=0.02), with the events most frequent in summer (n=77, 30%) and least so in winter (n=46, 18%). In contrast, incidence of MI also varied by season (p=0.0003), with highest events in winter and lowest in summer. CONCLUSION: The pattern of seasonal variation in TS is reversed compared with MI, with peaks during summer.

The Significance of Equivocal Exercise Treadmill ECG for Intermediate Risk Chest Pain Assessment - Insight From Coronary CT Angiography Data.

BACKGROUND: Exercise treadmill test (ETT) is commonly the first-line investigation in troponin-negative chest pain patients. Inconclusive results are common and often lead to repeated functional testings. Coronary computed tomographic angiography (CCTA) has excellent negative predictive value for coronary artery disease detection and may play an important role in their diagnostic workup. We aim to analyse ETT and CCTA findings to understand their modern roles in intermediate risk chest pain population with inconclusive ETT. METHODS: Patients who underwent both ETT and CCTA at our institution between August 2011 and February 2013 were retrospectively investigated. The ETTs were blindly reviewed, with equivocal ETTs defined as any indeterminate results not strictly adhering to ACC/AHA guidelines for positive ETT. Baseline demographics, clinical characteristics and investigation results were collated. Follow-up outcome data for subsequent investigations, representations, major cardiac adverse events (MACE) and unexpected revascularisations were also analysed. RESULTS: 346 consecutive patients were identified (age 57±10years, 53% females, body mass index (BMI) 28±4, Dukes Clinical Score 48±30%, mean follow-up 2.1±0.4years). The ETT was positive in 31%, equivocal in 54% and negative in 15%. Obstructive coronary artery disease (CAD) prevalence was 25% (29% males, 13% females). Those with negative ETTs had obstructive CAD in 8%, with no adverse outcomes during follow-up. Obstructive CAD was seen in 20% with "equivocal" ETTs and 29% with "positive" ETTs. In females, obstructive CAD prevalence was low, and similar in those with equivocal or positive ETT (16% and 11% respectively). In males, obstructive CAD was almost 50% in those with positive ETT (p=0.005). CONCLUSIONS: Obstructive CAD was found in one in five "equivocal" ETTs, hence, not all should be considered negative. Obstructive CAD was only found in one in three "positive" ETTs, hence not all should proceed to invasive angiography. CCTA may be an important gatekeeper test in those with low-intermediate pre-test probability of obstructive CAD.