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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 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.

Background Acute coronary syndrome (ACS) events and the ongoing burden of disease can have a significant impact on the subsequent life-course of working age people. Methods We report 12-month clinical outcomes for 10,822 patients hospitalized with first-time ACS between 2015-2016 and enrolled in the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry, with a focus on people of working age (defined as Results Nearly half (48%) of first-time ACS occurred in people of working age. Compared to those >65 years, these patients had a high burden of cardiovascular risk factors, and were more likely to be male (75% vs 60%), to be of non-European ethnicity (36% vs 15%), and to be living in areas of high deprivation. Subsequent clinical events were common in the younger patients, with 15% dying or being readmitted for cardiovascular causes within 12 months despite high rates of angiography (96%), revascularization (74%) and evidence-based medical therapy at the time of the index ACS event. Conclusions The high risk factor burden and subsequent high rate of clinical events in working age patients reinforces the need for a longer-term focus on strategies to improve clinical outcomes following first-time ACS.

New Zealand has a multiethnic population and a national cardiac inherited disease registry (Cardiac Inherited Disease Registry New Zealand [CIDRNZ]). Ancestry is reflected in the spectrum and prevalence of genetic variants in long QT syndrome (LQTS).The purpose of this study was to study the genetic testing yield and mutation spectrum of CIDRNZ LQTS probands stratified by self-identified ethnicity.A 15-year retrospective review of clinical CIDRNZ LQTS probands with a Schwartz score of ≥2 who had undergone genetic testing was performed.Of the 264 included LQTS probands, 160 (61%) reported as European, 79 (30%) NZ Māori and Pacific peoples (Polynesian), and 25 (9%) Other ethnicities, with comparable clinical characteristics across ethnic groups (cardiac events in 72%; age at presentation 28±19 years; corrected QT interval 512±55 ms). Despite comparable testing (5.3±1.4 LQTS genes), a class III-V LQTS variant was identified in 35% of Polynesian probands as compared with 63% of European and 72% of Other probands (P.0001). Among variant-positive CIDRNZ LQTS probands (n=148), Polynesians were more likely to have non-missense variants (57% vs 39% and 25% in probands of European and Other ethnicity, respectively; P=.005) as well as long QT syndrome type 1-3 variants not reported elsewhere (71% vs European 22% and Other 28%; P.0001). Variants found in multiple probands were more likely to be shared within the same ethnic group; P.01).Genetic testing of Polynesian LQTS probands has a lower diagnostic yield, despite comparable testing and clinical disease severity. Rare LQTS variants are more common in Polynesian LQTS probands. These data emphasize the importance of increasing the knowledge of genetic variation in the Polynesian population.

Background The relative proportion of each cardiac inherited disease (CID) causing resuscitated sudden cardiac arrest (RSCA) on a population basis is unknown. Objectives This study describes the profile of patients with CIDs presenting with RSCA; their data were collected by the national Cardiac Inherited Diseases Registry New Zealand (CIDRNZ). Methods Data were collated from CIDRNZ probands presenting with RSCA (2002 to 2018). Results CID was identified in 115 (51%) of 225 RSCA cases: long QT syndrome (LQTS) (n = 48 [42%]), hypertrophic cardiomyopathy (HCM) (n = 28 [24%]), Brugada syndrome (BrS) (n = 16 [14%]), catecholaminergic polymorphic ventricular tachycardia (CPVT) (n = 9 [8%]), arrhythmogenic right ventricular cardiomyopathy (ARVC) (n = 9 [8%]), and dilated cardiomyopathy (n = 5 [4%]). Seventy-one (62%) of 115 were male. Of 725 probands from the CIDRNZ with CID, the proportion presenting with RSCA was: CPVT, 9 (53%) of 17; BrS, 16 (33%) of 49; ARVC, 9 (25%) of 36; LQTS, 48 (20%) of 238; dilated cardiomyopathy, 5 (9%) of 58; and HCM, 28 (8%) of 354. Incident activity was: normal everyday activities, 44 (40%); exercising, 33 (30%); concurrent illness, 13 (12%); sleeping, 10 (9%); drugs/medication, 9 (8%); and emotion, 2 (2%). LQTS and CPVT predominated in those 24 years of age, 49 (64%) of 76. For those >40 years of age, HCM was the most common (33%) CID. A genetic diagnosis in patients with CID was made in 48 (49%) of 98 tested. Diagnosis by age range was as follows: age 1 to 14 years, 78%; age 15 to 24 years, 53%; age 25 to 39 years, 54%; and age >40 years, 26%. Conclusions The commonest CID identified after RSCA was LQTS; the most common CID cause of RSCA for those >40 years of age was HCM. CPVT was the CID most likely to present with RSCA and HCM the least. Genetic yield decreases with age. Only one-third of RSCA cases due to CID occurred while exercising.

Aims Clinical registry-derived data are widely used to represent patient populations. In New Zealand (NZ), a national registry—the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry—aims to include all patients undergoing coronary angiography; other acute coronary syndrome (ACS) patients are also registered but without complete capture. This study compares national hospitalization data of all first-time ACS admissions in NZ with patients in the ANZACS-QI registry, to investigate the use of clinical registry-derived data in research and in assessing clinical care. Methods and results Patients admitted with first-time ACS in the NZ National Hospitalisation Dataset between 1 January 2015 and 31 December 2016 were included. Clinical characteristics and time to 12-month clinical outcomes were compared between patients captured and not-captured in the registry. A total of 16 569 patients were admitted with first-time ACS, median age 69 years, 61% male; 60% (n = 9918) were enrolled in ANZACS-QI. Registry-captured patients were younger, more often male, and with a lower comorbidity burden than non-captured patients. Overall, 16% patients died within 12 months, 15% experienced a non-fatal cardiovascular (CV) readmission, and 28% either died or were readmitted. Patients not captured in the registry were more than twice as likely to have experienced death or a non-fatal CV readmission within 12 months as captured patients. Conclusions First-time ACS patients captured in the ANZACS-QI registry had very different clinical characteristics and outcomes than those not captured. Cardiovascular registry-derived data are dependent on registry design and may not be representative of the wider patient population; this must be considered when using registry-derived data.

ObjectiveFollowing acute coronary syndrome (ACS), patients are managed long-term in the community, yet few tools are available to guide patient-clinician communication about risk management in that setting. We developed a score for predicting cardiovascular disease (CVD) risk among patients managed in the community after ACS.MethodsAdults aged 30–79 years with prior ACS were identified from a New Zealand primary care CVD risk management database (PREDICT) with linkage to national mortality, hospitalisation, pharmaceutical dispensing and regional laboratory data. A Cox model incorporating clinically relevant factors was developed to estimate the time to a subsequent fatal or non-fatal CVD event and transformed into a 5-year risk score. External validation was performed in patients (Coronary Disease Cohort Study) assessed 4 months post-ACS.ResultsThe PREDICT-ACS cohort included 13 703 patients with prior hospitalisation for ACS (median 1.9 years prior), 69% men, 58% European, median age 63 years, who experienced 3142 CVD events in the subsequent 5 years. Median estimated 5 year CVD risk was 24% (IQR 17%–35%). The validation cohort consisted of 2014 patients, 72% men, 92% European, median age 67 years, with 712 CVD events in the subsequent 5 years. Median estimated 5-year risk was 33% (IQR 24%–51%). The risk score was well calibrated in the derivation and validation cohorts, and Harrell’s c-statistic was 0.69 and 0.68, respectively.ConclusionsThe PREDICT-ACS risk score uses data routinely available in community care to predict the risk of recurrent clinical events. It was derived and validated in real-world contemporary populations and can inform management decisions with patients living in the community after experiencing an ACS.

Background To review long QT syndrome molecular autopsy results in sudden unexplained death in young (SUDY) between 2006 and 2013 in New Zealand. Methods Audit of the LQTS molecular autopsy results, cardiac investigations and family screening data from gene-positive families. Results During the study period, 365 SUDY cases were referred for molecular autopsy. 128 cases (35%) underwent LQTS genetic testing. 31 likely pathogenic variants were identified in 27 cases (21%); SCN5A (14/31, 45%), KCNH2 (7/31, 22%), KCNQ1 (4/31, 13%), KCNE2 (3/31, 10%), KCNE1 (2/31, 7%), KCNJ2 (1/31, 3%). Thirteen variants (13/128, 10%) were ultimately classified as pathogenic. Most deaths (63%) occurred during sleep. Gene variant carriage was more likely with a positive medical history (mostly seizures, 63% vs 36%, p = 0.01), amongst females (36% vs 12%, p = 0.001) and whites more than Maori (31% vs 0, p = 0.0009). Children 1–12 years were more likely to be gene-positive (33% vs 14%, p = 0.02). Family screening identified 42 gene-positive relatives, 18 with definitive phenotypic expression of LQTS/Brugada. 76% of the variants were maternally inherited (p = 0.007). Further family investigations and research now support pathogenicity of the variant in 13/27 (48%) of gene-positive cases. Conclusion In New Zealand, variants in SCN5A and KCNH2, with maternal inheritance, predominate. A rare variant in LQTS genes is more likely in whites rather than Maori, females, children 1–12 years and those with a positive personal and family history of seizures, syncope or SUDY. Family screening supported the diagnosis in a third of the cases. The changing classification of variants creates a significant challenge.

Arrhythmic SNPs and Risk of Cardiac Arrest in HCM Introduction The accurate prediction of the risk of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) remains elusive. Corrected QT interval (QTc) duration is a known risk factor in various cardiac conditions. Single nucleotide polymorphisms (SNPs) have been linked to QTc length, and to SCD. Here we investigated the role of 21 candidate SNPs in QTc duration and SCD events in patients with HCM. Methods and Results This HCM registry-based study included patients with an ECG, medical history, first SCD event data, and DNA available. Each individual SNP was assessed using logistic regression for associations with 2 outcomes: a prolonged QTc ( ≥440 milliseconds), and first SCD event (SCD, resuscitated cardiac arrest, and appropriate implantable cardioverter defibrillator (ICD) shock for ventricular fibrillation/ventricular tachycardia (VF/VT). In 272 HCM patients, there were 31 SCD events (8 SCD, 9 resuscitated cardiac arrest, 14 ICD shocks for VF/VT; 11%). A QTc ≥ 500 milliseconds was associated with SCD events on multivariate analysis (odds ratio [OR] = 4.0, 95% confidence interval [CI], 1.19–12.02, P = 0.016). In 228 Caucasian patients, 2 SNPs in the NOS1AP gene (rs10494366 and rs12143842) were associated with a prolonged QTc after correction for multiple testing. This remained significant after adjustment for current age, sex, and ≥1 SCD risk factor (OR 1.59 per copy of the minor allele, 95% CI 1.08–2.39, P = 0.022, and OR 1.63, 95% CI 1.09–2.49, P = 0.020, respectively). No SNPs were directly associated with SCD events. Conclusion SNPs in the NOS1AP gene influence QTc interval duration but we have not demonstrated a direct association with the risk of SCD.

Aim: Our understanding of heart failure in younger patients is limited. The Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) database, which consisted of 24 prospective observational studies and 7 randomized trials, was used to investigate the clinical characteristics, treatment, and outcomes of younger patients. Methods and Results: Patients were stratified into six age categories: < 40 (n = 876), 40–49 (n = 2638), 50–59 (n = 6894), 60–69 (n = 12 071), 70–79 (n = 13 368), and ≥80 years (n = 6079). Of 41 926 patients, 2.1, 8.4, and 24.8% were younger than 40, 50, and 60 years of age, respectively. Comparing young ( < 40 years) against elderly (≥80 years), younger patients were more likely to be male (71 vs. 48%) and have idiopathic cardiomyopathy (63 vs. 7%). Younger patients reported better New York Heart Association functional class despite more severe left ventricular dysfunction (median ejection fraction: 31 vs. 42%, all P < 0.0001). Comorbidities such as hypertension, myocardial infarction, and atrial fibrillation were much less common in the young. Younger patients received more disease-modifying pharmacological therapy than their older counterparts. Across the younger age groups ( < 40, 40–49, and 50–59 years), mortality rates were low: 1 year 6.7, 6.6, and 7.5%, respectively; 2 year 11.7, 11.5, 13.0%; and 3 years 16.5, 16.2, 18.2%. Furthermore, 1-, 2-, and 3-year mortality rates increased sharply beyond 60 years and were greatest in the elderly (≥80 years): 28.2, 44.5, and 57.2%, respectively. Conclusion: Younger patients with heart failure have different clinical characteristics including different aetiologies, more severe left ventricular dysfunction, and less severe symptoms. Three-year mortality rates are lower for all age groups under 60 years compared with older patients.

To investigate regional variations in the detection of sudden death syndromes across New Zealand by assessing registrations in the national Cardiac Inherited Diseases Registry New Zealand (CIDRNZ).The CIDRNZ has been a national entity since 2009, with a hub in Auckland and locally funded regional coordinators (Midland, Central) linked with multidisciplinary cardiac genetic teams. Registration is consent-based and voluntary, and involves the collection of clinical/genetic information and permits genetic testing and research. Registry data were extracted from the CIDRNZ in October 2015 and results are expressed as registrations per 100,000 people by district health board area.The CIDRNZ has 1,940 registrants from 712 families, 46% of whom are definitely or probably affected by cardiac inherited disease. There are clear regional differences in registration frequencies between regions and between the North and South Islands, both for overall registrations (56/100,000 and 14/100,000, respectively; p0.001) and for long QT syndrome registrations (15/100,000 and 6/100,000, respectively; p0.001). Regions with local coordinators have the highest number of registrations.The detection of sudden death syndromes in New Zealand through a cardiac genetic registry is possible but much work is needed to improve regional variation in the detection/reporting of these conditions across the country.

Background Cardiovascular (CV) risk factor profiles of people experiencing acute coronary syndromes (ACS) vary with age, and in New Zealand (NZ), Māori and people of Pacific Island descent typically present with ACS at a younger age. We aimed to explore age- and ethnicity-related differences in CV risk factors in a large NZ cohort with first-time ACS. Methods The All NZ Acute Coronary Syndrome Quality Improvement program (ANZACS-QI) registry collects comprehensive data for patients admitted with ACS at NZ hospitals. This analysis includes patients with no prior atherosclerotic CV disease enrolled from 1 July, 2012 to 30 June, 2015. Results 14,190 patients had confirmed ACS, 8493 (60%) patients with no prior CVD comprised the study cohort. The mean age was 64 years, 25% were aged 2 ), and higher total cholesterol:HDL ratios (≥4.0, 70% vs 50%), all p 2 (67%) and higher median HbA1c than older patients with diabetes (69mmol/mol vs 55mmol/mol). Māori and people of Pacific Island descent were overrepresented in the younger age group; these patients had a very high risk factor burden. Conclusions A quarter of NZ patients admitted to hospital with a first-time CV disease event are aged 2 , and 16% have diabetes.

The accurate prediction of the risk of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) remains elusive. Corrected QT interval (QTc) duration is a known risk factor in various cardiac conditions. Single nucleotide polymorphisms (SNPs) have been linked to QTc length, and to SCD. Here we investigated the role of 21 candidate SNPs in QTc duration and SCD events in patients with HCM.This HCM registry-based study included patients with an ECG, medical history, first SCD event data, and DNA available. Each individual SNP was assessed using logistic regression for associations with 2 outcomes: a prolonged QTc ( ≥440 milliseconds), and first SCD event (SCD, resuscitated cardiac arrest, and appropriate implantable cardioverter defibrillator (ICD) shock for ventricular fibrillation/ventricular tachycardia (VF/VT). In 272 HCM patients, there were 31 SCD events (8 SCD, 9 resuscitated cardiac arrest, 14 ICD shocks for VF/VT; 11%). A QTc ≥ 500 milliseconds was associated with SCD events on multivariate analysis (odds ratio [OR] = 4.0, 95% confidence interval [CI], 1.19-12.02, P = 0.016). In 228 Caucasian patients, 2 SNPs in the NOS1AP gene (rs10494366 and rs12143842) were associated with a prolonged QTc after correction for multiple testing. This remained significant after adjustment for current age, sex, and ≥1 SCD risk factor (OR 1.59 per copy of the minor allele, 95% CI 1.08-2.39, P = 0.022, and OR 1.63, 95% CI 1.09-2.49, P = 0.020, respectively). No SNPs were directly associated with SCD events.SNPs in the NOS1AP gene influence QTc interval duration but we have not demonstrated a direct association with the risk of SCD.

Aim: To investigate the relationship between heart rate and survival in patients with heart failure (HF) and coexisting atrial fibrillation (AF). Methods and Results: Patients with AF included in the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) meta-analysis were the main focus of this analysis (3259 patients from 17 studies). The outcome was all-cause mortality at 3 years. Heart rate was analysed as a categorical (tertiles; T1 ≤77 b.p.m., T2 78–98 b.p.m., T3 ≥98 b.p.m.) and continuous variable. Cox proportional hazard models were used to compare the risk of all-cause death between tertiles of baseline heart rate. Patients in the highest tertile were more often female, less likely to have an ischaemic aetiology or diabetes, had a lower ejection fraction but higher blood pressure and New York Heart Association (NYHA) class. Higher heart rate was associated with higher mortality in patients with sinus rhythm (SR) but not in those in AF. In patients with heart failure and reduced ejection fraction (HF-REF) and AF, death rates per 100 patient years were lowest in the highest heart rate tertile (T1 18.9 vs. T3 15.9) but this difference was not statistically significant (P = 0.10). In patients with heart failure and preserved ejection fraction (HF-PEF), death rates per 100 patient years were highest in the highest heart rate tertile (T1 14.6 vs. T3 16.0, P = 0.014). However, after adjustment for other important prognostic variables, higher heart rate was no longer associated with higher mortality in HF-PEF (or HF-REF). Conclusions: In this meta-analysis of patients with HF, heart rate does not have the same prognostic significance in patients in AF as it does in those in SR, irrespective of ejection fraction or treatment with beta-blocker.

Long QT syndrome is the most commonly recognised cause of sudden cardiac death in children. With a prevalence of 1 in 2000, family screening is identifying large numbers of hitherto asymptomatic gene carriers in the community, about a third of whom have a normal QT interval. The mainstay of treatment is long term uninterrupted beta blocker therapy, a treatment with many potential side effects. This article reviews the evidence and suggests a cohort who may, after assessment in a specialised cardiac-genetic clinic, be spared this treatment because of very low baseline risk. These are asymptomatic boys and prepubertal girls with a heart rate corrected QT interval persistently less than 470 ms who do not indulge in high risk activities (especially swimming) and do not have a missense mutation in the c-loop region of the KCNQ1 (long QT 1) gene.

Background Disease-modifying single nucleotide polymorphisms (SNPs) can help explain incomplete penetrance and variable expressivity in congenital long QT syndrome (LQTS) by altering susceptibility to arrhythmias. Objective The purpose of this study was to assess multiple arrhythmia SNPs (in 16 genes) in a distinct cohort of LQTS patients to identify modifier SNPs influencing the risk of sudden death. Methods This study included 273 patients with LQTS from the New Zealand Cardiac Inherited Disease Registry (154 long QT type 1, 96 long QT type 2, and 23 long QT type 3), including 31 patients who had experienced death or resuscitated sudden cardiac death (RSCD). Patients were genotyped for 29 SNPs and tested for associations with clinical events and QTc length. Caucasian (n = 220) and Pacific Islander/New Zealand Maori (n = 53) ethnic groups were analyzed separately. This subgroup of Polynesian ancestry has not been previously studied for LQTS in either presentation or outcome. Results In Caucasians, four SNPs at two risk loci ( NOS1AP : rs12143842 and rs16847548; and KCNQ1: rs10798 and rs8234) were significantly associated with clinical events after correction for multiple testing. Patients homozygous for the risk allele of rs12143842 had an increased risk of death/RSCD [hazard ratio 10.15, 95% confidence interval (2.38, 43.34), q=0.045). Several other SNPs showed trends toward association with QTc length and clinical events. Conclusion This study demonstrates that SNPs in NOS1AP and KCNQ1 are associated with an increased risk of cardiac events in LQTS patients, with the hazard ratio suggesting they have significant potential in clinical risk stratification.

Background Long QT syndrome (LQTS) prevalence is estimated at 4 of 10,000 based on community electrocardiogram (ECG) screening, about which there is disagreement regarding efficacy, accuracy, cost-effectiveness, and practicality. Family studies of autosomal dominant conditions such as LQTS have revealed 8–9gene-positive family members per proband. Objective To evaluate a cardiac/genetic registry and family screening program as a tool to identify LQTS in the community. Methods Possible LQTS probands were referred to the New Zealand Cardiac Inherited Disease service. The registry was first established in the northern region (population 2.03 million), including central Auckland (population 0.46 million). After clinical evaluation, genetic testing and family cascade screening were initiated. Genotype-positive individuals were classified as definite LQTS, and others were classified as definite or probable LQTS by clinical and ECG criteria. Results One hundred twelve probands were identified (presentation: 7 sudden death, 82 cardiac event, 16 ECG abnormality, and 7 sudden death of a family member). Following cascade screening, 309 patients with LQTS were identified (248 definite and 61 probable). Two hundred twenty patients had LQTS-causing mutations identified (120 [55%] LQT1, 78 [35%] LQT2, 19 [9%] LQT3, 1 [0.5%] LQT 5, and 2 [1%] LQT7). Thus far, an average of 2.1 definitely or probably affected family members have been identified per proband. The community detection rate is 1.5 of 10,000 for the whole region and 2.2 of 10,000 in Auckland. Conclusions A high level of community detection of LQTS is possible using a clinical registry. With adequate resourcing, this has the potential to be an effective alternative to community ECG screening.