Genetic Testing Yield and Clinical Characteristics of Hypertrophic Cardiomyopathy in Understudied Ethnic Groups: Insights From a New Zealand National Registry.

BACKGROUND: Aotearoa/New Zealand has a multiethnic population. Patients with hypertrophic cardiomyopathy (HCM) are enrolled in the national Cardiac Inherited Diseases Registry New Zealand. Here, we report the characteristics of Cardiac Inherited Diseases Registry New Zealand HCM probands with and without pathogenic or likely pathogenic (P/LP) genetic variants for HCM, and assess genetic testing yield and variant spectrum by self-identified ethnicity. METHODS: Probands with HCM and enrolled in Cardiac Inherited Diseases Registry New Zealand who have undergone clinical genetic testing over a 17-year period were included. Clinical data, family history, and genetic test results were analyzed. RESULTS: Of 336 probands, 121 (36%) were women, 220 (66%) were European ethnicity, 41 (12%) were Maori, 26 (8%) were Pacific people, and 49 (15%) were other ethnicities. Thirteen probands (4%) presented with sudden death and 19 (6%) with cardiac arrest. A total of 134 (40%) had a P/LP variant identified; most commonly in the MYBPC3 gene (60%) followed by the MYH7 gene (24%). A P/LP variant was identified in 27% of Maori or Pacific probands versus 43% European or other ethnicity probands (P=0.022); 16% of Maori or Pacific probands had a variant of uncertain significance identified, compared with 9% of European or other ethnicity probands (P=0.092). Women more often had a P/LP variant identified than men (48% versus 35%; P=0.032), and variant-positive probands were younger at clinical diagnosis than variant of uncertain significance/variant-negative probands (39±17 versus 50±17 years; P<0.001) and more likely to have experienced cardiac arrest or sudden death events over their lifetime (P=0.002). CONCLUSIONS: Carriage of a P/LP variant in HCM probands is associated with presentation at younger age, and cardiac arrest or sudden death events. Maori or Pacific probands were less likely to have a P/LP variant identified than European or other ethnicity probands.

Sex differences in outcomes after acute coronary syndrome vary with age: a New Zealand national study.

AIMS: This study investigated age-specific sex differences in short- and long-term clinical outcomes following hospitalization for a first-time acute coronary syndrome (ACS) in New Zealand (NZ). METHODS AND RESULTS: Using linked national health datasets, people admitted to hospital for a first-time ACS between January 2010 and December 2016 were included. Analyses were stratified by sex and 10-year age groups. Logistic and Cox regression were used to assess in-hospital death and from discharge the primary outcome of time to first cardiovascular (CV) readmission or death and other secondary outcomes at 30 days and 2 years. Among 63 245 people (mean age 69 years, 40% women), women were older than men at the time of the ACS admission (mean age 73 vs. 66 years), with a higher comorbidity burden. Overall compared with men, women experienced higher rates of unadjusted in-hospital death (10% vs. 7%), 30-day (16% vs. 12%) and 2-year (44% vs. 34%) death, or CV readmission (all P < 0.001). Age group-specific analyses showed sex differences in outcomes varied with age, with younger women (<65 years) at higher risk than men and older women (≥85 years) at lower risk than men: unadjusted hazard ratio of 2-year death or CV readmission for women aged 18-44 years = 1.51 [95% confidence interval (CI) 1.21-1.84] and aged ≥85 years = 0.88 (95% CI 0.83-0.93). The increased risk for younger women was no longer significant after multivariable adjustment whereas the increased risk for older men remained. CONCLUSION: Men and women admitted with first-time ACS have differing age and comorbidity profiles, resulting in contrasting age-specific sex differences in the risk of adverse outcomes between the youngest and oldest age groups.

Prognostic modelling of clinical outcomes after first-time acute coronary syndrome in New Zealand.

OBJECTIVE: The Multi-Ethnic New Zealand Study of Acute Coronary Syndromes (MENZACS) was established to investigate the drivers of secondary events after first-time acute coronary syndrome (ACS), including addressing inequitable outcomes by ethnicity. Herein, the first clinical outcomes and prognostic modelling approach are reported. METHODS: First, in 28 176 New Zealanders with first-time ACS from a national registry, a clinical summary score for predicting 1-year death/cardiovascular readmission was created using Cox regression of 20 clinical variables. This score was then calculated in the 2015 participant MENZACS study to represent clinical risk. In MENZACS, Cox regression was used to assess N-terminal pro-B-type natriuretic peptide (NT-proBNP) as a prognostic marker for death/cardiovascular readmission in four models, adjusting for (1) age and sex; (2) age, sex, ethnicity; (3) clinical summary score; (4) clinical summary score and ethnicity. RESULTS: Of the 2015 MENZACS participants (mean age 61 years, 79% male, 73% European, 14% Maori, 5% Pacific people), 2003 were alive at discharge. Of the 2003, 416 (20.8%) experienced all-cause death/cardiovascular readmission over a median of 3.5 years. In a simple model, age, male sex, Maori ethnicity and NT-proBNP levels were significant predictors of outcome. After adjustment for the clinical summary score, which includes age and sex, NT-proBNP and ethnicity were no longer statistically significant: log2(NT-proBNP) hazard ratio (HR) 1.03, 95% confidence interval (95% CI) 0.98 to 1.08, p=0.305; Maori ethnicity HR 1.26, 95% CI 0.97 to 1.62, p=0.084. CONCLUSIONS: In 2015 patients with first-time ACS, recurrent events were common (20.8%). Increasing NT-proBNP levels and Maori ethnicity were predictors of death/cardiovascular readmission, but not after adjustment for the 20 clinical risk factors represented by the clinical summary score. TRIAL REGISTRATION NUMBER: ACTRN12615000676516.

Acute coronary syndrome registry enrolment status: differences in patient characteristics and outcomes and implications for registry data use (ANZACS-QI 36).

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.

Outcomes for working age patients after first-time acute coronary syndrome - ANZACS-QI 35.

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 <65 years). 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.

Development and validation of a cardiovascular risk score for patients in the community after acute coronary syndrome.

OBJECTIVE: Following 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. METHODS: Adults 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. RESULTS: The 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. CONCLUSIONS: The 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.

Clinical Characteristics and Burden of Risk Factors Among Patients With Early Onset Acute Coronary Syndromes: The ANZACS-QI New Zealand National Cohort (ANZACS-QI 17).

BACKGROUND: Cardiovascular (CV) risk factor profiles of people experiencing acute coronary syndromes (ACS) vary with age, and in New Zealand (NZ), Maori 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 <55years, and 66% were male. Those aged <55years were more likely than older patients to be current smokers (48% vs 19%), have higher body mass index (BMI) (48% vs 34% with BMI≥30kg/m2), and higher total cholesterol:HDL ratios (≥4.0, 70% vs 50%), all p<0.001. Sixteen per cent of those <55years had diabetes; these patients often had a BMI≥30kg/m2 (67%) and higher median HbA1c than older patients with diabetes (69mmol/mol vs 55mmol/mol). Maori 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 <55years. Younger patients have a very high risk factor burden: half are current smokers, half have a BMI≥30kg/m2, and 16% have diabetes.

Known and missing left ventricular ejection fraction and survival in patients with heart failure: a MAGGIC meta-analysis report.

AIMS: Treatment of patients with heart failure (HF) relies on measurement of LVEF. However, the extent to which EF is recorded varies markedly. We sought to characterize the patient group that is missing a measure of EF, and to explore the association between missing EF and outcome. METHODS AND RESULTS: Individual data on 30 445 patients from 28 observational studies in the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) project were used to compare the prevalence of co-morbidities and outcome across three groups of HF patients: those with missing EF (HF-mEF), reduced EF (HF-REF), and preserved EF (HF-PEF). A total of 29% had HF-mEF, 52% HF-REF, and 19% HF-PEF. Compared with patients in whom EF was known, patients with HF-mEF were older, had a greater prevalence of COPD and previous stroke, and were smokers. Patients with HF-mEF were less likely to receive evidence-based treatment than those with HF-REF. Adjusted mortality in HF-mEF was similar to that in HF-REF and greater than that in HF-PEF at 3 years [HF-REF, hazard ratio (HR) 1.03, 95% confidence interval (CI) 0.95-1.12); HF-PEF, HR 0.78, 95% CI 0.71-0.86]. CONCLUSION: Missing EF is common. The short- and long-term outcome of patients with HF-mEF is poor and they exhibit different co-morbidity profiles and treatment patterns compared with patients with known EF. HF patients with missing EF represent a high risk group.