Purpose To create a cohort with high specificity for moderate and severe rheumatic heart disease (RHD) in New Zealand, not reliant on International Classification of Diseases discharge coding. To describe the demography and cardiac profile of this historical and contemporary cohort.
Design and participants Retrospective identification of moderate or severe RHD with disease onset by 2019. Case identification from the following data sources: cardiac surgical databases, RHD case series, percutaneous balloon valvuloplasty databases, echocardiography databases, regional rheumatic fever registers and RHD clinic lists. The setting for this study was a high-income country with continued incidence of acute rheumatic fever (ARF).
Findings to date A Registry cohort of 4959 patients was established. The initial presentation was RHD without recognised prior ARF in 41%, and ARF in 59%. Ethnicity breakdown: Māori 38%, Pacific 33.5%, European 21.9%, other 6.7%. Ethnic disparities have changed significantly over time. Prior to 1960, RHD cases were 64.3% European, 25.3% Māori and 6.7% Pacific. However, in contrast, from 2010 to 2019, RHD cases were 10.7% European, 37.4% Māori and 47.2% Pacific.
Follow-up showed 32% had changed region of residence within New Zealand from their initial presentation. At least one cardiac intervention (cardiac surgery, transcatheter balloon valvuloplasty) was undertaken in 64% of the cohort at a mean age of 40 years. 19.8% of the cohort had multiple cardiac interventions. At latest follow-up, 26.9% of the cohort died. Of those alive, the mean follow-up is 20.5+19.4 years. Māori and Pacific led governance groups have been established to provide data governance and oversight for the registry.
Future plans Detailed mortality and morbidity of the registry cases will be defined by linkage to New Zealand national health data collections. The contemporary cohort of the registry will be available for future studies to improve clinical management and outcomes for the 3450 individuals living with chronic RHD.
- Valvular heart disease
- Public health
- Cardiac surgery
- Adult cardiology
Data availability statement
Data are available on reasonable request. Data sharing will be enabled post the planned analysis with the New Zealand NMDS.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
STRENGTHS AND LIMITATIONS OF THIS STUDY
The Aotearoa New Zealand Rheumatic Heart Disease (RHD) registry methodology has very high disease specificity for RHD with all included cases confirmed by review of clinical records.
The high specificity of the registry will allow accurate evaluation of historical and contemporary RHD mortality and morbidity by linkage to New Zealand national mortality and hospital admission data sets.
A limitation of the registry is its retrospective nature and low sensitivity for total RHD.
Māori and Pacific-led governance groups have been established to provide data governance and oversight for the registry.
The contemporary cohort of the registry will be available for future studies to improve clinical management and outcomes for the approximately 3450 individuals living with chronic RHD in Aotearoa New Zealand.
Acute rheumatic fever (ARF) has been extensively chronicled in New Zealand, as highlighted by the vast bibliography listed in the Heart Foundation New Zealand Guidelines for Rheumatic Fever: Diagnosis, Management and Secondary Prevention of Acute Rheumatic Fever and Rheumatic Heart Disease (RHD) of 2014.1 The New Zealand primary prevention programme began in 2011, with a reduction in ARF incidence observed by 2014, however, in recent years, ARF incidence has plateaued, with widening ethnic disparities inequitably impacting Pacific peoples and Māori.2 3
It is known that if an individual has an episode of ARF with mild or no carditis and then receives 10 years of secondary prophylaxis with penicillin, the outcomes, including cardiac outcomes, are very good.1 Many such patients are discharged from medical follow-up at age 21 years in New Zealand.1 4
When ARF leads to severe RHD, even with good secondary prophylaxis, the outcomes are often poor and the cardiac course is determined by progressive valve changes (valve regurgitation and stenosis) and cardiac muscle changes (ventricular dysfunction) evolving over years. Heart failure, endocarditis, atrial fibrillation, stroke and premature mortality occur in many people with RHD.1 Well-timed cardiac valve operations can limit the adverse effects of valve dysfunction. However, valve replacements and the need for lifelong anticoagulation confer additional clinical risk for individuals with severe RHD.1 4 In summary, ARF lasts for weeks but chronic RHD lasts for a lifetime.
ARF recurrences lead to worsening RHD.1 Adherence to secondary prophylaxis following ARF for children in New Zealand is high due to enrolment in regional RF registers, which facilitate the delivery of benzathine penicillin secondary prophylaxis by community nursing teams. However, adherence by adolescents and young adults is often challenging. New Zealand regional register data demonstrates that recurrences are more likely to occur in these older age groups.5
Current global disease estimates for RHD are 40 million cases and 340 000 deaths in 2019.6 With a few notable exceptions, there are limited studies of regional disease burden of RHD. Studies in Fiji,7 Australia8 and countries in the African continent9–12 have shown the burden of severe RHD within their setting. The mean age of death from RHD in Ethiopia is 25 years, and in Fiji is 39 years. The REMEDY study in Africa led by Liesl Zühlke provided powerful data of the burden of RHD in low-income and middle-income countries.10 13 14 Major adverse outcomes and therapeutic indicators of severe RHD were investigated, including heart failure, endocarditis, the proportion of patients receiving warfarin after prosthetic valve replacements, atrial fibrillation, stroke and premature death. The data showed very poor patient outcomes for severe RHD.13 14
In contrast to the extensive data pertaining to ARF, the burden of chronic RHD in New Zealand is not well defined. International Classification of Diseases (ICD) hospitalisation and national mortality data estimate 150–200 deaths per year and 600–800 admissions per year for RHD.15 However, there have been long-standing concerns regarding the poor positive predictive value of ICD valvular heart disease codes for RHD.16 17 Some New Zealand RHD surgical outcomes are known,18 and there is historical19 and more contemporary New Zealand data describing RHD in pregnancy.20
One New Zealand study estimated the mean age of death of RHD at 55 years.2 21 A more recent study has shown a breakdown of mortality for RHD by ethnicity being 55 years for Pacific populations, 59 years for Māori and 80 years for Europeans.2 The latter figure is likely due to RHD in New Zealand European adults who were diagnosed with mild RHD several decades ago. To date, access to, and engagement in, care and the quality of medical and surgical management of RHD have not been systematically evaluated in New Zealand.
The aim of the registry is to describe the demographics, care and outcomes of people with moderate and severe RHD in New Zealand. We aimed to create a baseline cohort with very strong positive predictive value for RHD. In addition, data linkage with the baseline cohort to the National Minimum Data Set (NMDS), National Mortality Collection and Pharmaceutical Collection could be performed to define the morbidity and mortality due to RHD, along with hospitalisation and treatment trends.
This is a retrospective cohort study of all cases of significant RHD across New Zealand, to create a contemporary cohort of patients to form ‘The Aotearoa New Zealand Rheumatic Heart Disease Registry’. Significant RHD is defined as any case identified with moderate or severe valve disease at any time point.
The registry includes individuals with significant RHD diagnosed prior to 31 December 2019. Follow-up data were included until the end of 2020.
Patients were identified from multiple data sources, as listed in table 1. Duplication was avoided by linkage to the National Health Index (NHI) number, a unique identifier assigned to every person who uses health and disability services in New Zealand. The NHI system was created in 1992. Definitions of categories were established by three investigators (ET, BM and NW). For all data sources, clinical records of all patients were examined by the research team to establish whether the patient had RHD. One investigator (ET) provided oversight of data entry for consistency.
Eligibility and inclusions
All cases with moderate or severe RHD at any time point.
ARF cases with moderate or severe carditis confirmed via echocardiography.
Residing in New Zealand.
Congenital mitral valve prolapse.
Mild RHD (includes mild latent RHD detected by screening programmes and those found in echocardiographic databases).
Isolated tricuspid regurgitation (TR) in the absence of rheumatic mitral or aortic valve changes.
Bicuspid aortic valve.
Isolated aortic stenosis (AS). AS coded as rheumatic was excluded if the surgical description emphasised degenerative valvar changes, unless there was a clear past history of ARF and/or rheumatic changes on the mitral valve including histopathological changes on the explanted valve.
Overseas residents from the South Pacific Islands with RHD referred for cardiac surgery in New Zealand, unless there was evidence that they came to reside in New Zealand postoperatively.
The data sources to establish the RHD registry are shown in table 1.
Cases were entered into the Registry during the years 2018–2020. The minimum dataset was collated into a Microsoft Excel spreadsheet, and stored in a password-protected folder. The minimum dataset fields are described in online supplemental table 1. Serial echocardiographic data were not recorded. Clinical data were restricted to that available at the time the case was entered into the registry unless identified from a later data source.
Patient and public involvement
Regional research locality agreements from participating District Health Boards (DHBs) involved wide consultation including with Māori for the public good of the formation of the Registry. In addition, Māori and Pacific led Governance groups have now been established to provide oversight for future utility of the Registry.
The multidisciplinary background of the investigators included clinical disciplines caring for patients with RHD. This informed the research question, which was to address the gap in knowledge of health outcomes for moderate and severe patients with RHD in New Zealand. Of note, Dr Anneka Anderson, coinvestigator has led previous qualitative research on the lived experiences of patients with ARF and RHD in New Zealand.22
Patients were not directly involved in recruitment or study conduct. Dissemination of findings will be guided by the Māori and Pacific Governance groups, which include community representatives.
Minimum data set fields descriptors
The original source data or the demographics page on the hospital electronic records. Ethnicity is self-designated in the New Zealand health system. Defined ethnicity groups include Māori ethnicity, Pacific ethnicity (Samoan, Tongan, Niuean, Rarotongan, Fijian, other Pacific included Tokelauan, Tuvaluan, Tahitian), European ethnicity (New Zealand European also known as Pākehā, other European ethnicities) and ‘other’ ethnicities (Chinese, Indian, Middle Eastern, other Asian and no ethnicity recorded).
Type and date of presentation
Presentation type was defined as one of:
Chronic RHD—first presentation with moderate or severe RHD without a clear history of ARF episode. Presentation varied widely including those with severe disease requiring cardiac surgery, presentation of RHD in pregnancy and the detection of moderate or severe RHD during school echocardiographic screening studies.23–25
ARF with moderate or severe carditis—meeting New Zealand Heart Foundation Guidelines11definition of ARF at the time of initial presentation (or retrospectively from history of a medically confirmed episode), or entered from a regional ARF database. Both initial and recurrent episodes of ARF were coded in this category.
Acute on chronic rheumatic fever—a first recognised episode of ARF but with unequivocal chronic RHD changes identified on echocardiography or clinical presentation. This also includes ‘missed cases’ of ARF where the clinical records revealed a previous presentation consistent with ARF but not identified by the health professionals at that time.
Indolent carditis—insidious onset of ARF with slow progression, without evidence of recovery from the acute phase of illness.1
Unknown—patients where the details of the initial presentation could not be determined.
The patient’s address at the time of initial diagnosis was used to define their region of domicile or DHB at presentation.
If the ARF episode was only recorded ‘as a child’, the patient’s 10th birthday was used as the presentation date, this being the approximate median age of ARF presentations.1 4 Where an age at the time of the ARF episode was specified but not a date, the patient’s birthday of that age was used. Where only a year of presentation was recorded, this was assigned to the first day of that year or first day of the recorded month if a year and month was identified. If none of this detail was available, the date was recorded as unknown.
Valve disease and severity details
Valve gradings assigned: nil, mild, moderate or severe. 0 or trivial or no=nil; trivial-mild=mild; mild to moderate=moderate; moderate to severe=severe; torrential=severe. Where grading was not included in the body or conclusion of the echocardiogram report, it was presumed ‘nil’.
Valve disease and severity were based on the echocardiogram at the time of initial diagnosis, the echocardiogram immediately prior to surgery (where applicable) or the surgical report. As RHD (and the carditis of ARF) evolve over time, the registry recorded the severest grading of the index valve involved. A ‘severity date’ was recorded. The echocardiogram at latest follow-up, if available, was included. Serial echocardiographic data were not collected.
Mitral stenosis (MS): recorded as nil unless the severity of MS was defined.
Multivalve disease is common in RHD. A second left-sided heart valve was recorded as rheumatic for all such cases whether the disease severity was mild, moderate or severe. Tricuspid disease was also recorded as rheumatic if there was mild or greater TR.
RHD surgical details
Limited surgical data were collected including dates of surgery, valves operated and type of surgery. Dates of surgery included only RHD-related surgical dates. Inclusions: first and redo valve RHD surgery, and cardiac transplantation due to complications from RHD. Exclusions: non-valve-related complications including wound infection, delayed chest closure or other minor complications that do not result in permanent sequelae.
Follow-up date was defined as the date of the most recent cardiology or other clinical letter. The patient DHB of domicile at most recent follow-up was recorded. If they had relocated overseas, the country to which they moved was recorded. Discharge from medical follow-up was recorded. Where it appeared that the patient repeatedly did not attend follow-up without a clear reason, they were deemed ‘lost to follow-up’. Patient deaths were recorded.
Numerical data were expressed as mean and SD for parametric data, and median for non-parametric data. χ2 test was used for categorical variables presented as counts and percentages. Generalised linear model was carried out for comparing age between ARF and RHD groups.
Findings to date
The cohort comprises 4959 individuals. Table 2 shows the demography of the registry, by gender, ethnicity and age at clinical presentation.
Type of first presentation
The type of presentation was not able to be determined in 7% of cases (349/4959) due to missing clinical information. Of the remaining 4610, the first presentation was RHD without a recognised prior episode of ARF in 41% (1892/4610). The first presentation was ARF in 59% (2718/4610), of whom 96.1% (2612/2718) were first episodes, 3.8% (103) were acute on chronic presentation and 0.1% (3) indolent carditis.
Decade of presentation by ethnicity
Figure 1 shows presentation by ethnicity and by decade. The year of presentation was identifiable from available records in 89.4% (4436/4959) of the cohort. The proportion of Māori ethnicity by decade increased from 25.3% pre-1960 to 37.4% in the most recent decade. The proportion of Pacific ethnicities steadily rose over each decade from 6.7% pre-1960 to 47.2% currently. In contrast, the ethnicity dominantly affected by RHD prior to 1960 was NZ European at 64.3%, decreasing to 10.7% in 2010–2019. Online supplemental table 2 details the numbers and proportions of cases by ethnicity and decade.
Online supplemental table 3 records the numbers and percentage of the cohort residing within each region at presentation and at latest follow-up. At the time of the most recent recorded follow-up, 89.7% of cases were residing in the North Island and 6.8% residing in the South Island. 53% of the cohort resided in the greater Auckland region (Auckland Waitemata and Counties Manukau DHBs) at follow-up. Compared with their region at presentation, 32% (1328 of 4089) of the cohort resided in a different region at latest follow-up.
Registry data sources
For the total cohort, 38% (1868) of patients were identified from more than one data source for entry into the registry and 62% (3091) were identified from a single source.
The source datasets for those identified from a single data source are shown in online supplemental figure 1). The proportion of the cohort identified solely from ICD discharge data was less than 2%.
RHD valve type at presentation
Online supplemental table 4 details the numbers of each valve category, and the proportion with associated TR.
Of the cohort, 64% (3196/4959) had at least one cardiac intervention (cardiac surgery, transcatheter balloon valvuloplasty or transcatheter valve replacement) (figure 3). The mean (SD) age at initial procedure was 40.7 (19.9) years (range 2–85 years). Of these 3196 patients, 88.7% had cardiac surgery only, 5.6% had cardiac surgery and a transcatheter balloon valvuloplasty or valve replacement, 5.6% had balloon valvuloplasty only and 0.1% had isolated transcatheter valve replacement (figure 3).
Online supplemental figure 2 shows the cardiac interventions by valve type. Online supplemental table 5 details the cardiac interventions excluding valvular cardiac surgical procedures. Note that for those with isolated MS, 91% (335/368) had initial Percutaneous Mitral Balloon Valvuloplasty (PMBV) (online supplemental tables 4 and 5).
In total, 19.8% (981/4959) of the cohort had between two and eight interventions. The second intervention occurred after a mean time of 11 years (range 0 days to 51 years). Of those who had multiple interventions, 738 patients had two interventions, 194 had three interventions, 36 had four interventions, 10 patients had five interventions and 1 patient each had six, seven and eight total interventions. Overall, 95.4% (1232) of multiple interventions were repeat cardiac surgery.
A total of 4107 cardiac surgeries were performed on 3015 patients, 268 patients had valve repair/valvotomy without subsequent valve replacement and 246 patients had initial valve repair/valvotomy with subsequent valve replacement. Valve replacements (at any operation) occurred in 2588 patients, including 2021 prosthetic valves, 520 bioprosthetic valves and 47 unknown type of replacement. The details of valve replacement types are shown in online supplemental table 6.
Of the cohort, 1336 (26.9%) are deceased and 173 have relocated overseas, with 3450 patients alive and residing in New Zealand. Of these, 73.8% (2545) have recorded clinical follow-up with a mean (SD) duration of 20.5 years (19.4 years), range 1 month to 79 years. There were 9.4% (326) who were medically discharged from follow-up and 16.8% (579) appeared to be lost to medical follow-up at the time of entry to the registry.
The primary analysis of the Registry will be the linkage to NMDS to define the health burden of significant RHD, namely the morbidity and mortality of moderate and severe RHD in New Zealand. Mortality data recorded in the Registry will be linked with the mortality data from the New Zealand Ministry of Health coded mortality collection26 The NMDS mortality data provide the cause of death and other contributing causes. Risk factors for mortality will be calculated. The morbidity of RHD of the cohort will be examined by linkage to the NMDS hospital admissions for expected and unexpected morbidity of RHD. Expected morbidity includes the prevalence of heart failure, atrial fibrillation, endocarditis and stroke. This New Zealand data will allow comparisons with previously reported Registries of RHD.8 13 14 Linkage to pharmaceutical data sets will potentially give insights of the contemporary registry cohort with respect to oral anticoagulant therapy and antiarrhythmic therapy.
Beyond this initial establishment and analysis phase, there are many potential uses for the registry as approved by the Māori and Pacific governance groups. The registry will be used to interrogate the equity and quality of care for RHD in New Zealand in a contemporary subset of the registry, by comparing to the New Zealand RF/RHD guidelines for recommended best practice care for patients with RHD.1 The registry cohort could be combined with the recently announced national rheumatic fever register to help improve and maintain secondary prevention of ARF across the country. The registry will evolve to a prospective registry of those alive with significant RHD to be known as the Aotearoa RHD registry. The registry may form the basis for multiple future studies by groups including but not limited to researchers, civil societies and patient groups, non-government organisations and the New Zealand Ministry of Health. Such endeavours have the potential to help address current RHD ethnic inequities and improve outcomes for those living with chronic RHD in New Zealand. This will contribute to fulfilling Te Tiriti o Waitangi obligations to Māori enabling the monitoring and improvement of RHD health outcomes.27
This collaborative study involves investigators from diverse medical specialties including Nursing, Children’s and Adult Cardiac Services, Paediatrics, General Medicine, Infectious Diseases, Māori Health and Public Health. An additional strength is the national collaboration involving nearly all health districts in New Zealand particularly regional cardiac centres.
High specificity of RHD cases in the registry
The registry methodology ensured that cases entered have a very high specificity for significant RHD, avoiding potential misclassification by relying solely on ICD discharge data.16 17 We found a high specificity for RHD for cases identified from the cardiac surgical, mitral valvuloplasty, previous RHD case series and regional rheumatic fever registers. In contrast, echocardiography database searches were problematic. The search terms ‘RHD’, ‘Rheumatic Heart Disease’, ‘Rheumatic Fever’, ‘ARF’ and ‘Mitral stenosis were often useful for searching. In comparison, the terms ‘moderate’ or ‘severe mitral regurgitation’ or ‘aortic regurgitation’ resulted in large lists of undifferentiated adult valve disease. Echocardiographic searching was a labour-intensive process and the usefulness varied with different echocardiographic software reporting systems.
The Aotearoa New Zealand Registry will provide data similar to the Northern Territory, Australia dataset of similar methodology where patients with a high specificity for ARF and RHD entered over a 20-year period were later linked to Australian national data sets for both known medical complications of RHD but also with other known health outcomes.28
Decade and ethnicity data
The methodology used demonstrated a doubling of cases of significant RHD in the last two decades. This may be attributable to true disease increase but also reflects population increase, heightened recognition of ARF/RHD, and wider application of echocardiography and utilisation of cardiac surgery.
The changes in the ethnic makeup of the cohort over time are significant. The absolute number and proportion of Māori and Pacific with significant RHD has increased over the last three decades, mirroring the well-documented increase in ARF over that time period.1 2 15 21 29 The proportion and absolute numbers of cases of RHD in those of European ethnicity has fallen steadily over the last five decades and is currently low.
The late Professor Dian Lennon, paraphrasing clinicians from the USA, described RHD as the long shadow of rheumatic fever. The sobering implication of this ‘long shadow’ is that the lives of young Māori and Pacific individuals with recently acquired chronic heart disease from ARF will continue to be affected by the morbidity of RHD and premature mortality for decades. In summary, the registry highlights the continued unacceptable ethnic inequities of the burden of RHD in New Zealand.27
Cardiac characteristics of the registry
The cardiac disease burden of people identified with significant RHD in the Registry is high, with 64% of cases having undergone cardiac interventions, often multiple and predominantly cardiac surgery.8 10 13 14 The mean age at first intervention was 40 years. The dominant intervention was a prosthetic valve replacement. PMBV for isolated MS accounted for a minority of the interventions reflecting that isolated MS was less common than isolated valvular regurgitation or mixed valve pathology.
Mobility of patients with RHD
In this cohort, we found at least 32% of patients had moved region. This spatial mobility and being ‘lost to follow-up’ in the context of ARF/RHD management has been shown to adversely affect outcomes.22 The registry did not record changes of residence within the same region, which may be equally problematic. This has important implications ensuring optimal ongoing medical management and for adherence to secondary prophylaxis. The high level of interregional mobility also supports the urgent need for a nationally coordinated ARF/RHD patient management system.
A limitation of the registry is its retrospective nature and low sensitivity for total RHD. In particular, underascertainment is more likely for individuals with mild cardiac involvement at baseline and who have not had subsequent RHD-related hospitalisation events and/or accessed healthcare services.
Data availability statement
Data are available on reasonable request. Data sharing will be enabled post the planned analysis with the New Zealand NMDS.
Patient consent for publication
This study involves human participants and was approved by Health and Disability Ethics Committee (HDEC) for New ZealandReference Number: 17/STH/111Locality agreements from the participating District Health Boards and research teams were obtained. Participants gave informed consent to participate in the study before taking part.
We are very grateful for the Māori governance group (Chair: Dr Matire Harwood) and Pacific governance group (Chair: Dr Malaki Ofanoa) engagement and future oversight of the Registry. We thank the following collaborators in regional cardiac, paediatric and public health centres for access to regional RHD data sets: Dr Ailsa Tuck, Leanne Hulse, Dr Claire McLintock, Professor Peter Ruygrok, Dr Arthur Coverdale, Noelle Balbas, Ming Cen, Jenna Turton-Lane, Dr Andrew To, Dr Ross Nicholson, Associate Professor Andrew Kerr, Andrew McLachlan, Belinda Paku, Dr John Malcolm, Leanne Ruck, Dr Rajesh Nair, Mr Adam El Gamel, Bruce Atkins, Jana Rowlands, Kelsey Simpson, Jacque Roberts, Dr Sarka Davidkova, Tina Lees, Dr Shaun Grant, Associate Professor Gerry Devlin, Tom Mortlemore, Sandi French, Dr Kai Steinmann, Sarah McKinley, Dr Andrew Aitken, Mr Sean Galvin, Catherine Goggin, Dr Craig Thornley, Angela Holmes, Dr Melissa Kerdemelidis, Dr Paul Bridgeman, Vicky Ray, Dr James Pemberton, Dr Dominic Parry, Ramanen Sugunesegran, Rachel Reddy. We thank Megan Upjohn, Dr Jodie Hayward, Evangeline Liddicoat, Dr Nicole Stonestreet, Dr Fa Thongsamak and Smriti Gupta for data entry. We thank Dug Yeo Han, statistician, for confirmation of accuracy of investigator data analysis. We thank Charlene Nell for providing expert assistance with manuscript preparation.
Contributors ET contributed to study design, regional locality applications, led data collection and data analysis, contributed to interpretation of findings and drafting of the manuscript. BM, NW contributed as senior authors, supervising all aspects of the study, including conception of the study, ethics application, study design, study conduct, analysis planning, interpretation of findings and manuscript preparation. RW, AA, BP, SJ contributed to study design, interpretation of the findings and critically revised the manuscript. ML contributed to interpretation of data and critically revised the manuscript. ET and NW are the guarantors for the analyses.
Funding This research received funding from the Green Lane Research and Education Fund, the Heart Foundation of New Zealand and the A+Charitable Trust.
Disclaimer The funders of this study had no influence on the study design, analyses or interpretation and reporting of results.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.