Background: Cardiovascular disease (CVD) is the leading cause of mortality in New Zealand, with significant inequities affecting Māori and Pacific peoples. Familial hypercholesterolaemia (FH) affects approximately 1 in 313 individuals globally, yet over 90% remain undiagnosed. Standard polygenic risk scores (PRS) derived from European cohorts may not be portable to diverse ancestries. We developed the HoloQ Omniscan Waka Te Ira, a custom Illumina Global Screening Array (GSA) v3 enriched with FH mutations, coronary artery disease (CAD) PRS markers, and network medicine-derived content. Methods: We customised the GSA v3 by adding 43,437 single nucleotide polymorphisms (SNPs) targeting FH and CAD. Content included 6,717 unique variants in primary FH genes; 14,005 pathogenic or likely pathogenic cardiovascular and pharmacogene variants; and 5,845 copy number variant probes. We further incorporated 5,232 network medicine derived CAD SNPs, 14,806 rare variants for a multiancestry PRS, and 407 globally diverse and population-specific variants. The final design comprised 47,027 target SNPs. Validation utilised large-scale genotype and whole-genome sequencing (WGS) datasets with PRS benchmarking. Results: In a large European-ancestry dataset, we observed high recovery for common PRS loci but low recovery for population-specific founder variants. The array captured 938 (84%) of all pathogenic or likely pathogenic FH variants catalogued in ClinVar, representing a 26.4% expansion beyond the standard backbone array. WGS validation identified additional carriers of rare high impact variants present only in the custom content. The selected CAD PRS model achieved an adjusted area under the receiver operating characteristic curve of 0.786. Conclusion: The HoloQ Omniscan Waka Te Ira enhances detection of clinically relevant FH variants and provides robust PRS coverage. The low recovery of population-specific alleles underscores the necessity of this custom array for equitable genomic medicine in New Zealand's multi-ethnic population. ### Competing Interest Statement The authors have declared no competing interest. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of UK Biobank gave ethical approval for this work under a signed MTA with Te Whatu Ora Waitematā I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

BACKGROUND:Macrotroponin is an important cause of discrepancy between current high-sensitivity cardiac troponin (hs-cTn) assays, however, its clinical significance is unclear. This study examined the effects of macrotroponin and repeat testing by different hs-cTnI assays in a cohort of community patients with elevated hs-cTnI.METHODS:The first residual serum specimen from each patient in the community admitted to hospital with elevated hs-cTnI (Siemens hs-cTnI Centaur) was retested after immunoglobulin depletion and by 5 other hs-cTn assays. Low recovery of cTnI (<40%) following immunoglobulin depletion was considered as macrotroponin. A retrospective chart review was performed for these participants. Investigator-adjudicated diagnosis served as the reference standard.RESULTS:In our cohort of community patients with elevated troponin (n = 188), participants with macrotroponin (n = 99) often had a multifactorial or indeterminate myocardial injury (56% vs 25%) and were less likely to have acute coronary syndrome (9% vs 28%). On repeat testing of cTn on other platforms, better diagnostic performance (c-statistics) for ischemic and non-ischemic cardiac causes was observed on the Beckman Access hs-cTnI (0.74; 95% confidence interval [CI] 0.67-0.81) or the Abbott hs-cTnI Architect (0.75; CI 0.68-0.82) compared to the Siemens hs-cTnI Vista (0.62; CI 0.54-0.70; P < 0.05). This could be attributed to differences in assay reactivity for macrotroponin. Interestingly, better diagnostic performance was observed in patients without macrotroponin. Although a small number of deaths occurred (n = 16), participants with macrotroponin had better overall survival.CONCLUSIONS:In the low-risk setting, the presence of macrotroponin was clinically associated with multifactorial or indeterminate causes of troponin elevation.

Abstract Elevated triglycerides and non-HDL-cholesterol (C) are risk factors for atherosclerotic cardiovascular disease (ASCVD). AROANG3 is a RNA interference therapy targeting hepatocyte production of angiopoietin-like protein 3 (ANGPTL3), a regulator of lipoprotein metabolism. This Phase 1 trial (NCT03747224) investigated single and repeat doses of AROANG3 in healthy volunteers and repeat doses in subjects with hepatic steatosis. AROANG3 was well tolerated without adverse changes in liver fat in steatotic subjects. In healthy volunteers, ARO-ANG3 produced reductions in ANGPTL3 (mean − 45% to -78%) 12 weeks post-dose. Concurrent reductions in triglycerides (median 34% to 54%) and nonHDL-C (mean 18% to 29%) were observed with the 3 highest doses. Reduced LDL-C was seen with repeat dosing. The data support ANGPTL3 as a potential therapeutic target for treatment of ASCVD.

Macrotroponin is a complex formed between endogenous cardiac troponin autoantibodies and circulating cardiac troponin (cTn). It is a recognised cause of discrepancy between current high sensitivity troponin (hs-cTn) assays; and immunoglobulin-bound (macrotroponin) and unbound cTn can coexist in varying proportions in the acute setting. Increasingly it is considered when laboratory cTn results do not match a patient's clinical picture. However, despite the better understanding of macrotroponin as an analytical interference, its clinical significance remains unclear. The aim of this study was to determine the potential impact of macrotroponin on the use of cTn as a long-term prognostic marker. We repeated cTnI testing after polyethylene glycol (PEG) precipitation on consecutive participants (n=159) with a first elevated cTn above 0.2 μg/L during their hospital admission episode. Because this paper is looking at outcomes in years, the initial data were generated at a time when non-hs-cTn assays were in use. We divided the cohort into two groups based on an exploratory PEG recovery cut-off of <34.6% to indicate the presence of possible macrotroponin and compared the overall and cardiovascular related mortality. The median follow-up time for the overall cohort was 8.35 years (8.32-8.40 interquartile range) with no difference between the two groups. The overall median survival was 8.1 years. Our findings indicate a hazard ratio of 0.54 (0.32-0.91 95% CI) for all-cause mortality and 0.48 (0.24-0.95) for cardiovascular mortality in patients with possible macrotroponin compared to those patients with troponin elevation without evidence of macrotroponin, after adjustment for common cardiovascular disease risk factors. Furthermore, an association was observed between PEG% recovery and all-cause mortality (p<0.05). This study showed that patients with macrotroponin have comparatively favourable long-term all-cause and cardiovascular mortality in a cohort of patients with elevated troponin. We illustrate the importance of recognising cTn results as being a summation of heterogeneous components, including those bound to antibodies, and the potential role of macrotroponin to further improve our interpretation and use of cTn as a biomarker.

Background. Each year, approximately 5000 New Zealanders are admitted to hospital with first-time acute coronary syndrome (ACS). The Multi-Ethnic New Zealand Study of Acute Coronary Syndromes (MENZACS) is a prospective longitudinal cohort study embedded within the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry in six hospitals. The objective of MENZACS is to examine the relationship between clinical, genomic, and cardiometabolic markers in relation to presentation and outcomes post-ACS. Methods. Patients with first-time ACS are enrolled and study-specific research data is collected alongside the ANZACS-QI registry. The research blood samples are stored for future genetic/biomarker assays. Dietary information is collected with a food frequency questionnaire and information about physical activity, smoking, and stress is also collected via questionnaire. Detailed family history, ancestry, and ethnicity data are recorded on all participants. Results. During the period between 2015 and 2019, there were 2015 patients enrolled. The mean age was 61 years, with 60% of patients aged <65 years and 21% were female. Ethnicity and cardiovascular (CV) risk factor distribution was similar to ANZACS-QI: 13% Māori, 5% Pacific, 5% Indian, and 74% NZ European. In terms of CV risk factors, 56% were ex-/current smokers, 42% had hypertension, and 19% had diabetes. ACS subtype was ST elevation myocardial infarction (STEMI) in 41%, non-ST elevation myocardial infarction (NSTEM) in 54%, and unstable angina in 5%. Ninety-nine percent of MENZACS participants underwent coronary angiography and 90% had revascularization; there were high rates of prescription of secondary prevention medications upon discharge from hospital. Conclusion. MENZACS represents a cohort with optimal contemporary management and will be a significant epidemiological bioresource for the study of environmental and genetic factors contributing to ACS in New Zealand’s multi-ethnic environment. The study will utilise clinical, nutritional, lifestyle, genomic, and biomarker analyses to explore factors influencing the progression of coronary disease and develop risk prediction models for health outcomes.

AIMSWe investigated the relationship between clinically assessed left ventricular ejection fraction (LVEF) and survival in a large, heterogeneous clinical cohort.METHODS AND RESULTSPhysician-reported LVEF on 403 977 echocardiograms from 203 135 patients were linked to all-cause mortality using electronic health records (1998-2018) from US regional healthcare system. Cox proportional hazards regression was used for analyses while adjusting for many patient characteristics including age, sex, and relevant comorbidities. A dataset including 45 531 echocardiograms and 35 976 patients from New Zealand was used to provide independent validation of analyses. During follow-up of the US cohort, 46 258 (23%) patients who had undergone 108 578 (27%) echocardiograms died. Overall, adjusted hazard ratios (HR) for mortality showed a u-shaped relationship for LVEF with a nadir of risk at an LVEF of 60-65%, a HR of 1.71 [95% confidence interval (CI) 1.64-1.77] when ≥70% and a HR of 1.73 (95% CI 1.66-1.80) at LVEF of 35-40%. Similar relationships with a nadir at 60-65% were observed in the validation dataset as well as for each age group and both sexes. The results were similar after further adjustments for conditions associated with an elevated LVEF, including mitral regurgitation, increased wall thickness, and anaemia and when restricted to patients reported to have heart failure at the time of the echocardiogram.CONCLUSIONDeviation of LVEF from 60% to 65% is associated with poorer survival regardless of age, sex, or other relevant comorbidities such as heart failure. These results may herald the recognition of a new phenotype characterized by supra-normal LVEF.

Background: Angiopoietin-like protein 3 (ANGPTL3) regulates triglyceride (TG) and lipoprotein (LP) metabolism by inhibiting liver and endothelial LP lipases and reduces plasma LDL-C. In Phase 1 Study AROANG1001 (NCT03747224), single and multiple doses of RNA interference therapeutic ARO-ANG3 (100, 200, or 300 mg; n=36) in healthy volunteers substantially reduced ANGPTL3, LDL-C, and other LPs (AHA 2019) compared with placebo (n=16). Purpose: We report preliminary results following repeat doses (days 1 and 29) of ARO-ANG3 in patients with heterozygous familial hypercholesterolemia (FH) with elevated LDL-C despite statin therapy and average LDL-C of 130 mg/dL. An additional group (non-FH patients) had LDL-C > 70 mg/dL despite statin therapy. Methods: Seventeen FH patients received open-label, subcutaneous, ARO-ANG3 100 mg (n=6), 200 mg (n=6), or 300 mg (n=5). Nine non-FH, high risk patients with elevated LDL-C not at goal received either 200 mg ARO-ANG3 (n=6) or placebo (n=3) using a randomized double-blind design. Pharmacodynamic markers included serum ANGPTL3, LDL-C, TG, and others. Results: Results are reported as of 04 May 2020. In FH patients, ARO-ANG3 significantly reduced mean ANGPTL3 levels between 62-92% at week 16 in a dose-dependent manner (Table). LDL-C (23-37%) and TG (25-43%) were consistently reduced at all doses (Table). The mean percent reductions in non-FH patients for ANGPTL3 (85%), LDL-C (28%), and TG (29%) were comparable to those in FH patients, despite their initially lower LDL-C at baseline. As of 15 May 2020, there were no drug-related serious or severe adverse events (AEs) or discontinuations and most AEs were mild. The most common AEs reported in subjects receiving ARO-ANG3 were respiratory tract infection (30% of subjects) and injection site AEs (13% of subjects). Conclusions: In FH and non-FH patients, repeat doses of ARO-ANG3 significantly reduced ANGPTL3, LDL-C, and TG, with favorable safety.

Arrowhead Pharmaceuticals, PI for AROANG1001.

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Background: The New Zealand health system has a wealth of electronic-based data that are readily available for research. This data can be used for a variety of clinical applications such as detecting new disease phenotypes, performing embedded cohort studies, and developing prediction models using artificial intelligence and machine learning. Method: A total of 75,000 patients who had undergone an echocardiogram between 2009 and 2018 at Waitemata District Health Board (WDHB) were identified from an Excelera database. Using SQL and Python, these data were linked with other electronic databases containing ICD10 codes, laboratory data, electrocardiogram meta-data, e-referrals, clinic letters, electronic discharge summaries, and Pyxis inpatient prescribing data. Deep learning-based neural networks were used to remove patient identifiers from free-text data, with up to 99.7% accuracy. Machine-learning algorithms were applied to the dataset and predictions were made for various outcomes such as mortality, echocardiogram results, direct current (DC) cardioversion efficacy, and genetic disorders such as familial hyperlipidaemia. Results: Mortality and age of mortality can be predicted with a high level of accuracy (AUC 0.92, F-measure 0.93, precision 97%, recall 90%, Phi 0.53, R2 0.77). Pathology found on echocardiography could be predicted (AUC 0.79, F-measure 0.94, precision 89%, recall 99%, Phi 0.22). Important features for prediction of DC cardioversion for atrial fibrillation (AF) were identified as duration since AF onset and left atrial dimensions; both features were subsequently added to e-referral forms at WDHB. Conclusion: Artificial intelligence has great potential for clinical application within the New Zealand health system, particularly due to the availability of high-quality electronic health records.

Background: Biomarker analysis is a cornerstone of diagnostic and prognostic assessment in acute coronary syndromes (ACS). Significant variability in biomarker levels over the acute phase response of ACS has been demonstrated. However, their use as predictors in prognostic risk models often fails to account for influence of time on measured levels. This study aimed to assess the timing of research blood sampling in relation to patient presentation and clinical care, and the factors implicated in delayed sampling. Method: Multi-Ethnic New Zealand study of Acute Coronary Syndromes (MENZACS) is a multicentre, longitudinal case–control study in adults hospitalised with first-time acute ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), or unstable angina (UA). Data were derived from the MENZACS research module and the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry. Results: Of 1,573 patients enrolled in MENZACS, 915 had NSTEMI/UA, and 657 STEMI. The median time to research blood sampling for NSTEMI/UA was 72 hours (interquartile range [IQR], 48–120) and 48 hours for STEMI (IQR, 30–72). Age, prior cardiovascular disease, day of admission, hospital transfer, admission to MENZACS hospital, signs/symptoms of acute heart failure, and percutaneous coronary intervention procedure, all influenced the timing of blood sampling (all p < 0.001). Logistic and patient-related factors were associated with differences in timing between patients with NSTEMI/UA and those with STEMI. Conclusion: Patient and logistics factors influenced timing of blood sampling in ACS. Detailed knowledge of these factors to ensure that biomarker results are appropriately interpreted within their temporal context in research studies is important.

Introduction Screening patients for cardiovascular disease has not been widely advocated due to cost implications and is reserved for high risk or symptomatic patients. We undertook an exploratory study to evaluate the promising low-cost methods for screening, including genetic risk scoring (GRS), advanced ECG (A-ECG), echocardiography and metabolomics. Methods 78 patients underwent advanced 5-min ECG and echocardiography, including global longitudinal strain (GLS), and echocardiographic calcium scoring (eCS). A GRS of 27 SNPs (GRS27) related to coronary disease and 3 SNPs for atrial fibrillation was used, as well as hs-troponin (Abbott, Singulex, Roche), NTproBNP (Roche) testing and targeted plasma metabolomics using GC-MS. Results were correlated with the presence of coronary artery disease (CAD) (CT coronary angiography (CTCA)), measures of left ventricular hypertrophy (LVH) (echocardiography and CTCA), and LV systolic dysfunction (LVSD) (echocardiography). Results LV dysfunction was accurately identified by using either A-ECG (AUC 0.97, 0.89 to 0.99) or NTproBNP. eCS demonstrated accurate discrimination of CAD (AUC 0.84, 95% CI 0.72 to 0.92, p < 0.0001. Troponin I (Abbott/Singulex) had the highest sensitivity and accuracy for the detection of LVH measured by either CT or echocardiography (AUC 0.85, 95% CI 0.73 to 0.92), however specificity was reduced by the presence of LV systolic dysfunction. Metabolomics and A-ECG identified underlying abnormal mechanisms related to both LVH (glycine metabolism) and LV dysfunction, (Citric Acid cycle). Metabolomics provided incidental utility by identifying metformin adherence and nutritional biomarkers. Conclusion A multi-omic approach to screening can be achieved at relatively low cost, and high accuracy, but will need to be evaluated in larger populations to prove its utility.

Aim: Next Generation sequencing (NGS) has recently identified Titin truncation variants (TTNtv) to be causative in numerous cases of familial dilated cardiomyopathy (DCM). Identifying the underlying molecular cause aids in cascade screening, risk stratification and a pathway for future therapeutic options. Phenotypic characteristics of patients with TTNtv are not fully described. We present a large Maori kindred with a highly penetrant TTNtv causing DCM. Method: 7 male family members affected by early onset DCM were identified. 28 inherited heart disease genes were sequenced on an Illumina MiSeq in the proband. Cardioclassifier https://www.cardioclassifier.org/ (Imperial College London, 2017) was used for variant calling. Advanced ECG (A-ECG) analysis was used to compare TTNtv carriers and a DCM cohort with unknown TTNtv status. Results: The proband was heterozygote for a nonsense TTNtv in the I band (Chr2 c.41880G > A), identified by Cardioclassifier as likely pathogenic. This co-segregated with family members with DCM and was absent in unaffected individuals. Paroxysmal atrial fibrillation and a rate related cardiomyopathy was the presenting hallmark in several family members. The proband had a ventricular fibrillation arrest at the time of pulmonary vein isolation. Two family members have undergone cardiac transplantation and one has been listed for transplantation. A-ECG Spatial QRS-T angle indicated a higher risk for ventricular arrhythmia, in family members with arrhythmic events. Conclusion: TTNtv presented as a highly penetrant pathogenic variant associated with DCM in this kindred. Both atrial and ventricular arrhythmias were common in carriers. TTNtv population frequencies should be further explored in indigenous Maori populations, who have high burden of unexplained DCM and possible founder effects.

The conventional use of high-sensitivity troponins (hs-troponins) is for diagnosing myocardial infarction however they also have a role in chronic disease management. This pilot study assessed the relationship of hs-troponins with echocardiographic markers of left ventricular hypertrophy (LVH) and structural heart disease (SHD). Patients undergoing computer gomography (CT) coronary angiogram for low-intermediate risk chest pain and healthy volunteers were recruited. Hs-troponins Singulex I, Abbott I and Roche T and N-terminal pro-brain natriuretic peptide (NT-proBNP) were evaluated in relation to SHD parameters including left ventricular hypertrophy (LVHEcho) and left atrial enlargement (LAEEcho) on echocardiography. 78 subjects who underwent echocardiography were included in this study. C-statistics (95% confidence interval) of the four biomarkers for predicting LVHEcho were 0.84 (0.72–0.92), 0.84 (0.73–0.92), 0.75 (0.63–0.85) and 0.62 (0.49–0.74); for LAEEcho 0.74 (0.6–0.85), 0.78 (0.66–0.88), 0.55 (0.42–0.67) and 0.68 (0.62–0.85); and composite SHD 0.79 (0.66–0.88), 0.87 (0.75–0.94), 0.62 (0.49–0.73) and 0.74 (0.62–0.84) respectively. Optimal cut points for SHD were >1.2 ng/L, >1.6 ng/L, >8 ng/L and >18 pmol/L respectively. These results advocate the potential role of hs-troponins as screening tools for structural heart disease with theranostic implications.

AbstractIntroductionTicagrelor is widely considered superior to clopidogrel however a pharmacogenetic substudy of PLATO indicated that the majority of this difference is due to genetic nonresponders to clopidogrel. We evaluated patient outcomes following genotyping for CYP2C19 in a propensity matched acute coronary syndrome cohort treated with either clopidogrel, ticagrelor or aspirin monotherapy.MethodsICD10 coding identified 6,985 acute coronary syndrome patients at Waitematā District Health Board over a five year period (2012-2016). Ticagrelor was subsidised by The Pharmaceutical Management Agency of New Zealand in July 2013. Patients were genotyped for CYP2C19 *2, *3 and *17 alleles using the Nanosphere Verigene analyser and treatment was tailored accordingly. Logistic regression and nearest neighbour propensity matching was employed in a 1:3 fashion with each treatment group to balance patient characteristics.ResultsA total of 146 patients were genotyped and compared with 438 matched patients taking either clopidogrel, ticagrelor or aspirin monotherapy. Post July 2013 clopidogrel was prescribed more often in responders than in those without genotype information (68 vs 39%, χ2 9, 95% CI 4 to 34, p=0.003). Conversely, ticagrelor was used more frequently in clopidogrel nonresponders. Mortality with personalised treatment was equivalent to ticagrelor (HR 0.8, 95% CI 0.3 to 1.8) but higher in those treated with clopidogrel (HR 2.3, 95 % CI 1 to 5.3). Readmissions with ACS were higher in nonresponders treated with clopidogrel versus those treated with genotype appropriate dual antiplatelet therapy (HR 3.9, 95% CI 0.8 to 18, p =0.03).ConclusionPersonalised antiplatelet management was equivalent to ticagrelor with respect to all-cause mortality and ACS readmissions. It also led to more appropriate use of both clopidogrel and ticagrelor and potential cost savings.

BACKGROUND:Increased spatial QRS-T angle has been shown to predict appropriate implantable cardioverter defibrilIator (ICD) therapy in patients with left ventricular systolic dysfunction (LVSD). We performed a retrospective cohort study in patients with left ventricular ejection fraction (LVEF) 31-40% to assess the relationship between the spatial QRS-T angle and other advanced ECG (A-ECG) as well as echocardiographic metadata, with all-cause mortality or ICD implantation for secondary prevention. METHODS:534 patients ≤75 years of age with LVEF 31-40% were identified through an echocardiography reporting database. Digital 12-lead ECGs were retrospectively matched to 295 of these patients, for whom echocardiographic and A-ECG metadata were then generated. Data mining was applied to discover novel ECG and echocardiographic markers of risk. Machine learning was used to develop a model to predict possible outcomes. RESULTS:49 patients (17%) had events, defined as either mortality (n = 16) or ICD implantation for secondary prevention (n = 33). 72 parameters (58 A-ECG, 14 echocardiographic) were univariately different (p<0.05) in those with vs. without events. After adjustment for multiplicity, 24 A-ECG parameters and 3 echocardiographic parameters remained different (p<2x10-3). These included the posterior-to-leftward QRS loop ratio from the derived vectorcardiographic horizontal plane (previously associated with pulmonary artery pressure, p = 2x10-6); spatial mean QRS-T angle (134 vs. 112°, p = 1.6x10-4); various repolarisation vectors; and a previously described 5-parameter A-ECG score for LVSD (p = 4x10-6) that also correlated with echocardiographic global longitudinal strain (R2 = - 0.51, P < 0.0001). A spatial QRS-T angle >110° had an adjusted HR of 3.4 (95% CI 1.6 to 7.4) for secondary ICD implantation or all-cause death and adjusted HR of 4.1 (95% CI 1.2 to 13.9) for future heart failure admission. There was a loss of complexity between A-ECG and echocardiographic variables with an increasing degree of disease. CONCLUSION:Spatial QRS-T angle >110° was strongly associated with arrhythmic events and all-cause death. Deep analysis of global ECG and echocardiographic metadata revealed underlying relationships, which otherwise would not have been appreciated. Delivered at scale such techniques may prove useful in clinical decision making in the future.

Aim: The use of scout transthoracic echocardiography (sTTE), and machine learning enhancements of conventional tools, e.g. A-ECG or biomarkers could be a low cost solution to waiting lists. We evaluated the use of A-ECG as a prescreen for a sTTE and full TTE. Method: 169 patients waiting for >12 months on a low risk echocardiography waiting list were allocated to either A-ECG or human read ECG screening. Patients with normal ECGs underwent a 5-min sTTE, but proceeded to TTE if ≥moderate structural heart disease (major SHD) was found. A-ECG was compared to human read ECGs and the resultant sTTE or TTE. Results: 99 patients were allocated to A-ECG and 70 to human screened ECGs. 28 patients did not attend. A-ECG streamed 40 patients to sTTE, 3 (8%) had a major SHD. Human ECGs streamed 34 patients to sTTE, 12 (35%) had a major SHD (Z score 2.9, p = 0.004). A-ECG streamed 43 patients to TTE, 7 (35%) were normal or had minor SHD. Human ECGs streamed 24 to TTE, 5 (21%) were normal or had minor SHD (Z score -1.9, p = 0.06). Overall accuracy of A-ECG exceeded a human reader (A-ECG; Sens 81%, Spec of 92% vs Human Sens 79% Spec 65%) for detecting major SHD. Cohens kappa demonstrated greater agreement between A-ECG and echo than human read ECGs, 0.43 vs 0.09. Conclusion: Low risk patients referred for echocardiography could effectively be screened with A-ECG and a 5-min sTTE. This has the potential to radically reduce waiting lists, and cost.

Aim: Conventional resting echocardiography has only modest predictive value in detecting the presence of coronary artery disease (CAD). Novel low cost enhancements such as global longitudinal strain, and an echocardiographic calcium score could improve the predictive power of a resting echocardiogram. We performed a pilot study to evaluate these tools. Method: 56 patients undergoing CT coronary angiography (CTCA) had a resting 2D echocardiogram performed (Philips CX50), which included left ventricular global longitudinal strain (GLS) (Philips QLab), and an echocardiographic calcium score (eCS) which included evaluation of calcium deposits in the aortic root, aortic and mitral valves and annulus and subvalvular apparatus. A-ECG, troponin, BNP and genetic biomarkers were also collected. Results: 29 (52%) of patients had CAD detected by CTCA, 9 (16%) had a stenosis ≥50% in ≥1 vessel. GLS was available on 37 (66%) of patients. GLS ≤18 had a sensitivity of 82% and specificity of 70% (AUC 0.82, 95% CI 0.66 to 0.93, p < 0.0001). eCS had a sensitivity of 100%, and specificity of 68% (AUC 0.9, 95% CI 0.79 to 0.97, p < 0.0001) in the prediction of CAD. The eCS score increased with graded severity of CAD in a dose dependent fashion. Duke and ACC/AHA clinical risk scores had an AUC 0.66 and 0.53 respectively for the same patients. Conclusion: Both global longitudinal strain and a novel echocardiographic calcium score had greater value than conventional clinical risk scores in predicting CAD on CTCA. Both eCS and GLS could be incorporated into a 5-min 2D echocardiogram.

Introduction Two-dimensional strain analysis is a powerful analysis modality, however, clinical utilization has been limited by variability between different analysis systems and operators. We compared strain in adults and children using vendor-specific and vendor-independent software to evaluate variability. Methods One hundred and ten subjects (50/110 pediatric, 80/110 normal left ventricular function) had echocardiograms with a General Electric ultrasound scanner between September 2010 and January 2012. Left ventricular longitudinal strain was derived with EchoPAC (General Electric, v10.8.1), a vendor-specific software, and Velocity Vector Imaging (Siemens, v3.5), which is vendor-independent. Three independent readers analyzed all the echocardiograms yielding 330 datasets. Results Mean left ventricular global longitudinal Lagrangian strain was −18.1 ± SD 4.4% for EchoPAC and −15.3 ± SD 4.1% for Velocity Vector Imaging. Velocity Vector Imaging yielded lower absolute global longitudinal Lagrangian strain by mean 2.9 (±SD 2.7, p < 0.0001), and lower regional longitudinal strain. These differences persisted in normal subjects versus those with cardiomyopathy. Longitudinal strain differences were slightly higher in the pediatric cohort. There was no significant difference in inter-observer longitudinal strain and a small difference in intra-observer strain between analysis systems. On repeat measurements, a significant change in global longitudinal Lagrangian strain occurred after the difference exceeded 3–5 strain points for EchoPAC and Velocity Vector Imaging, respectively. Conclusion Velocity Vector Imaging produces lower left ventricular longitudinal strain values versus EchoPAC for the same echo images. Both systems have similar inter-observer variability, Velocity Vector Imaging slightly higher intra-observer variability. A statistically significant change in global longitudinal Lagrangian strain occurs with changes >3–5 strain points on repeat measurements. Strain values between the systems are not interchangeable.