Michael J A Williams

• MD FRACP FACC FCSANZ
• Professor at University of Otago

aim: There are limited data on the prevalence of calcific aortic valve disease (CAVD) in Māori and known inequities in outcomes after aortic valve intervention. Our study aimed to investigate the prevalence of CAVD in Māori. methods: Data from initial clinically indicated echocardiograms performed between 2010 to 2018 in patients aged ≥18 years wer...

Background A staging system for aortic stenosis (AS) based upon the extent of cardiac damage has been proposed to better stratify risk and evaluate the benefit of aortic valve intervention (AVI), especially in those with moderate AS. We sought to evaluate the prognostic value of this staging system. Methods Data from initial clinically indicated ec...

Background: Patients with ischemic heart disease (IHD) require frequent monitoring, as the transition from stable disease to acute life-threatening events remains largely unpredictable. Currently available tests are either not sensitive enough to detect early changes or not easily incorporated into routine clinical practice. MicroRNAs (miRNAs), sma...

Aims Cohort studies have demonstrated associations between calcific aortic valve disease (CAVD) and Lp(a). As Lp(a) is almost entirely genetically determined, in this study, we aim to determine whether Lp(a), when predicted from genetic data, is associated with CAVD and major adverse cardiovascular events (MACEs). Methods and results Patients unde...

Objective Preoperative exercise training, or prehabilitation, aims to optimize cardiorespiratory fitness before surgery to reduce the risk of adverse perioperative events and delayed recovery. However, traditional exercise such as walking and cycling can be difficult for people with degenerative joint diseases of the lower limbs, such as osteoarthr...

Background: Previous studies have demonstrated relatively slow rates of progression of early calcific aortic valve disease (CAVD), which encompasses aortic sclerosis (ASc) and mild aortic stenosis (AS). The potential evolution to clinically significant AS is unclear and we therefore examined the long-term outcomes of patients with ASc and mild AS...

Background Cohort studies have demonstrated associations between calcific aortic valve disease (CAVD) and Lp(a). As Lp(a) is almost entirely genetically determined, with the increasing clinical availability of genetic information, we aimed to determine if Lp(a), when predicted from genetic data, is associated with CAVD and major adverse cardiovascu...

Background: High levels of Lp(a; lipoprotein[a]) are associated with multiple forms of cardiovascular disease. Lp(a) consists of an apoB100-containing particle attached to the plasminogen homologue apo(a). The pathways for Lp(a) clearance are not well understood. We previously discovered that the plasminogen receptor PlgRKT (plasminogen receptor w...

Objective The recommended duration of dual anti-platelet therapy (DAPT) following acute coronary syndrome (ACS) varies from 1 month to 1 year depending on the balance of risks of ischaemia and major bleeding. We designed paired ischaemic and major bleeding risk scores to inform this decision. Methods New Zealand (NZ) patients with ACS investigated...

Exercise is painful and difficult to perform for patients with severe lower-limb osteoarthritis; consequently, reduced physical activity contributes to increased cardiometabolic disease risk. The aim of this study was to characterize the acute and adaptive cardiovascular and metabolic effects of two low or no impact therapies in patients with sever...

Objective: We investigated whether childhood social isolation was associated with retinal neural layer changes in adulthood, and whether this association was independent of other childhood or adulthood risk factors, including adult social isolation. Methods: Participants were members of the Dunedin Multidisciplinary Health and Development Study,...

Objective Cardiac troponins (cTn) have been used historically to estimate infarct size in ST elevation myocardial infarction (STEMI). Within a resource constrained health care environment, cTn could therefore be used for prioritisation of patients for cardiac imaging, in particular echocardiography. We aimed to determine how useful routinely collec...

Non-ischemic diabetic heart disease (NiDHD) is characterised by diastolic dysfunction and decreased or preserved systolic function, eventually resulting in heart failure. Accelerated apoptotic cell death due to alteration of molecular signalling pathways due to dysregulation in microRNAs (miRNAs) plays a significant role in the development of NiDHD...

Background : Quality of life is a key outcome after coronary revascularization for ischemic heart disease in the modern era. 6-12 months after coronary revascularization, recovery from the intervention itself, especially coronary artery bypass grafting, is no longer the key determinant of quality of life, while the benefits (or lack thereof) of rev...

Background Suspected myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) occurs in ≈5% to 10% of patients with MI referred for coronary angiography. The prognosis of these patients may differ to those with MI and obstructive coronary artery disease (MI-CAD) and those without a MI (patients without known history of MI [No-MI])....

Background/Purpose Spontaneous coronary artery dissection (SCAD) is an underdiagnosed and poorly understood condition that frequently affects younger women without cardiovascular risk factors. In this project we aimed to describe the present landscape of SCAD in New Zealand (NZ). Methods All patients in NZ who were admitted to hospital with a diag...

Importance Inflammation promotes cardiovascular disease and anti-inflammatory treatment reduces cardiovascular events in patients with chronic coronary syndrome. Chronic kidney disease (CKD) is a risk factor for cardiovascular disease. It is unclear how inflammation mediated by interleukin 6 (IL-6) in patients with CKD is linked to cardiovascular d...

Background The heart has an intrinsic ability to regenerate, orchestrated by progenitor or stem cells. However, the relative complexity of non-resident cardiac progenitor cell (CPC) therapy makes modulation of resident CPCs a more attractive treatment target. Thiamine analogues improve resident CPC function in pre-clinical models. In this double bl...

Background and aims: The last two decades in New Zealand have seen increased availability of primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) and early invasive coronary angiography (ICA) for other high-risk acute coronary syndrome (ACS) patients. One metric to assess the clinical appropriaten...

Long-chain acylcarnitines (LCACs) are known to directly alter cardiac contractility and electrophysiology. However, the acute effect of LCACs on human cardiac function is unknown. We aimed to determine the effect of LCAC 18:1, which has been associated with cardiovascular disease, on the contractility and arrhythmia susceptibility of human atrial m...

Aims/hypothesis Diabetes mellitus causes a progressive loss of functional efficacy in stem cells, including cardiac progenitor cells (CPCs). The underlying molecular mechanism is still not known. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate genes at the post-transcriptional level. We aimed to determine if diabetes mellitus i...

Introduction: Hand-held isometric dynamometry is a convenient alternative to gold standard isokinetic dynamometry for the assessment of skeletal muscle strength. The purpose of this study was to quantify the absolute and relative reliability of hand-held dynamometry, for the measurement of lower-limb isometric strength in patients with severe hip a...

Background Some studies have suggested a lower mortality in obese subjects with cardiovascular disease. The aim of this study was to evaluate the relationship between body mass index (BMI) and outcomes in patients with acute coronary syndrome (ACS). Methods The study included 13,742 patients undergoing coronary angiography for ACS between 2012 and...

Multiple receptors have been implicated in lipoprotein(a) (Lp(a)) uptake, yet each receptor only partially accounts for the uptake, and no endocytic pathway has been described for Lp(a) internalisation to date. In this study, we define macropinocytosis as the endocytic pathway responsible for internalising Lp(a). In liver and macrophage cells, Lp(a...

Background: Acetylcholine (ACh) plays a crucial role in the function of the heart. Recent evidence suggests that cardiomyocytes possess a non-neuronal cholinergic system (NNCS) that comprises of choline acetyltransferase (ChAT), choline transporter 1 (CHT1), vesicular acetylcholine transporter (VAChT), acetylcholinesterase (AChE) and type-2 muscari...

Background Countries with a high incidence of coronavirus 2019 (COVID-19) reported reduced hospitalisations for acute coronary syndromes (ACS) during the pandemic. This study describes the impact of a nationwide lockdown on ACS hospitalisations in New Zealand (NZ), a country with a low incidence of COVID-19. Methods All patients admitted to a NZ H...

Objective Past studies have suggested a potential “J shaped” relationship between infrarenal aortic diameter and both cardiovascular disease (CVD) prevalence and all cause mortality. However, screening programmes have focused primarily on large (aneurysmal) aortas. In addition, aortic diameter is rarely adjusted for body size, which is particularly...

Background: The adipocytokine resistin is released from epicardial adipose tissue (EAT). Plasma resistin and EAT deposition are independently associated with atrial fibrillation (AF). The EAT secretome enhances arrhythmia susceptibility and inotropy of human myocardium. Therefore, we aimed to determine the effect of resistin on the function of hum...

Cardiopulmonary exercise testing is performed increasingly for cardiorespiratory fitness assessment and pre‐operative risk stratification. Lower limb osteoarthritis is a common comorbidity in surgical patients, meaning traditional cycle ergometry‐based cardiopulmonary exercise testing is difficult. The purpose of this study was to compare cardiopul...

Aim: We aimed to investigate the correlation between epicardial adipose tissue (EAT) and body mass index (BMI) in different ethnic groups in New Zealand. Methods: The study included 205 individuals undergoing open heart surgery. Māori and Pacific groups were combined to increase statistical power. EAT was measured using 2D echocardiography. Res...

Type 2 diabetes has a strong association with the development of cardiovascular disease, which is grouped as diabetic heart disease (DHD). DHD is associated with the progressive loss of cardiovascular cells through the alteration of molecular signalling pathways associated with cell death. In this study, we sought to determine whether diabetes indu...

The coronavirus 2019 (COVID-19) pandemic requires significant changes to standard operating procedures for non-COVID-19 related illnesses. Balancing the benefit from standard evidence-based treatments with the risks posed by COVID-19 to patients, healthcare workers and to the population at large is difficult due to incomplete and rapidly changing i...

Changes in whole blood DNA methylation levels at several CpG sites have been associated with circulating blood lipids, specifically high-density lipoprotein and triglycerides. This study performs a discovery and validation epigenome-wide association study (EWAS) for circulating lipoprotein(a) [Lp(a)], an independent risk factor for cardiovascular d...

Background The availability of an accurate continuous cuffless blood pressure (BP) monitor would provide an alternative to both invasive continuous BP and 24-hour intermittent cuff-based BP monitors. We investigated the accuracy of a cuffless beat to beat (BtB) device compared to both invasive BP (iBP) and brachial cuff BP (cBP) measurements. Meth...

Background Coronary heart disease remains one of the leading causes of mortality and morbidity in New Zealand (NZ) and globally. The All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) programme includes the CathPCI registry which records all those referred for diagnostic coronary angiography (DCA) and percutaneous coronary inte...

Aims: Epicardial adipose tissue (EAT) deposition has a strong clinical association with atrial arrhythmias; however, whether a direct functional interaction exists between EAT and the myocardium to induce atrial arrhythmias is unknown. Therefore, we aimed to determine whether human EAT can be an acute trigger for arrhythmias in human atrial myocar...

Plasma lipoprotein(a) [Lp(a)] levels are largely determined by variation in the LPA gene which codes for apolipoprotein(a) [apo(a)]. Genome-wide association studies (GWAS) have identified nonsynonymous variants in LPA that associate with low Lp(a) levels although their effect on apo(a) function is unknown. We investigated two such variants, R990Q a...

Background: Cardiac surgery risk scoring systems predict operative mortality but not outcomes related to preoperative frailty. The aim of this study was to assess frailty in a cohort of older cardiac surgery patients as a predictor of postoperative outcomes. Methods: Prospective data was collected on patients 65 years of age and older undergoing...

Myocardial pathology results in significant morbidity and mortality, whether due to primary cardiomyopathic processes or secondary to other conditions such as ischemic heart disease. Cardiac imaging techniques characterise the underlying tissue directly, by assessing a signal from the tissue itself, or indirectly, by inferring tissue characteristic...

Introduction Myocardial Infarction (MI) with Non-Obstructive Coronary Arteries (MINOCA) is now a recognised MI subtype. A 2013 systematic review of MINOCA literature indicated that MINOCA prognosis is favourable compared to those with MI and obstructive coronary artery disease (MICAD), but healthy controls were not included. With the growth of rece...

Aim: Prompt access to cardiac defibrillation and reperfusion therapy improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). The study aim was to describe the 'patient' and 'system' delay in patients who receive acute reperfusion therapy for ST-elevation myocardial infarction (STEMI) in New Zealand. Methods: In 201...

Background and objective Chronic lung disease is associated with impaired endothelial function and this may be a risk factor for poor cardiovascular health. It is unknown if there is an association between lung and endothelial function in the general population. We investigated associations between lung and endothelial function in a population‐base...

Background: The All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry was designed to collect data on all coronary angiograms and percutaneous coronary interventions (PCI) in New Zealand, and all acute coronary syndromes (ACS) associated with these procedures. This study compares the completeness of capture in ANZACS-QI...

Background The diabetic heart undergoes remodelling contributing to an increased incidence of heart failure in individuals with diabetes at a later stage. The molecular regulators that drive this process in the diabetic heart are still unknown. Methods Real-time (RT) PCR analysis was performed to determine the expression of cardiac specific microR...

Macroscopic deposition of epicardial adipose tissue (EAT) has been strongly associated with numerous indices of obesity and cardiovascular disease risk. In contrast, the morphology of EAT adipocytes has rarely been investigated. We aimed to determine whether obesity-driven adipocyte hypertrophy, which is characteristic of other visceral fat depots,...

Objective Recently, the prevalence of abdominal aortic aneurysm (AAA) using screening strategies based on elevated cardiovascular disease (CVD) risk was reported. AAA was defined as a diameter ≥30 mm, with prevalence of 6.1% and 1.8% in men and women respectively, consistent with the widely reported AAA predominant prevalence in males. Given the ob...

Objective The medium-term outcome and cause of death in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) is not well characterised. The aim of this study was to compare mortality and rates of recurrent events in post myocardial infarction (MI) patients with obstructive coronary artery disease (CAD) and in patients...

Objectives To examine associations between periodontitis at ages 32 and 38 and a range of early cardiometabolic risk biomarkers at age 38. Methods Periodontal probing depth and bleeding on probing data collected during the age‐32 and age‐38 assessments in the Dunedin Multidisciplinary Health and Development Study were used to quantify periodontal...

Increased apoptosis and premature cellular ageing of the diabetic heart underpin the development of diabetic heart disease. The molecular mechanisms underlying these pathologies are still unclear. Here we determined the role of pro-senescence microRNA (miR)-34a in accelerating the ageing of the diabetic heart. RT-PCR analysis showed a significant i...

Background: To describe the long-term mortality of a complete national cohort of acute coronary syndrome (ACS) patients enrolled in 2002, to compare this with a national age, sex and Māori ethnicity matched population, and to assess the influence of baseline factors on the 12-year mortality. Methods: We reviewed 721 patients with a discharge dia...

Aim: The aim of this report is to provide hospitals in New Zealand with data about their own outcomes for percutaneous coronary intervention (PCI) procedures and allow comparisons with other New Zealand units and with international data. Methods: All PCI procedures (n=5,033) were identified in nine public hospital catheterisation laboratories be...

Background/objectives: Endothelial dysfunction predicts mortality but it is unknown whether childhood obesity predicts adult endothelial dysfunction. The aim of this study was to determine whether anthropometric indices of body fat in childhood, adolescence and early midlife are associated with endothelial dysfunction in early midlife. Subjects/m...

Aims: To audit the management of ST-segment elevation myocardial infarction (STEMI) patients admitted to a New Zealand Hospital over three 14-day periods to review their number, characteristics, management and outcome changes over a decade. Methods: The acute coronary syndrome (ACS) audits were conducted over 14 days in May of 2002, 2007 and 201...

People with type 1 diabetes (T1D) have lower exercise capacity (V̇O2max) than their age-matched nondiabetic counterparts (CON), which might be related to cardiac autonomic dysfunction. We examined whether Heart Rate Variability (HRV; indicator of cardiac autonomic modulation) was associated with exercise capacity in those with and without T1D. Twen...

L ipoprotein(a) [Lp(a)] is an independent risk factor for developing cardiovascular disease. 1 Lp(a) comprises a low-density lipoprotein (LDL) with its apolipoprotein B (apoB) moiety linked to apolipoprotein(a) [apo(a)]. 2 Apo(a) has its evolutionary origin from plasminogen 3 and shows homology to other plasminogen-related growth factors. 4 Lp(a) i...

Background: Emerging evidence suggests that microRNAs (miRs) could be a potential biomarker to identify early molecular alterations in the heart. HDL are the major carriers for miRs into the circulation. This study tested whether changes in the level of HDL could affect the diagnostic sensitivity of miRs. Methods and results: Peripheral blood sa...

Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). Methods and Re...

Aim: Microangiopathy due to endothelial dysfunction is a major contributing factor to the development of diabetes-induced cardiovascular disease (CVD). Dysregulation of endothelial-specific microRNAs (miRs) is correlated with impaired angiogenesis and cell survival. We investigated the profile of two angiomiRs, miR-126, and miR-132, in the plasma...

Aortic valve stenosis (AS) is a major cause of morbidity and mortality, with no effective medical therapies. Investigation into the underlying biology of AS in humans is limited by difficulties in obtaining healthy valvular tissue for use as a control group. However, micro-ribonucleic acids (miRNAs) are stable in post-mortem tissue. We compared val...

The All New Zealand Acute Coronary Syndrome Quality Improvement programme (ANZACS-QI) uses a web-based system to create a clinical registry of patients with acute coronary syndrome (ACS) and other cardiac problems admitted to hospitals across New Zealand. This detailed clinical registry is complemented by parallel analyses of, and individual linkag...

Background: Abdominal aortic aneurysm (AAA) continues to be a significant health burden yet few countries have implemented a comprehensive screening programme. Screening typically places emphasis on men aged over 65 years; however, there is concern that other at-risk groups may be underidentified. The present study examined three potential screeni...

Background Several sequence variants are known to have effects on serum levels of non–high-density lipoprotein (HDL) cholesterol that alter the risk of coronary artery disease. Methods We sequenced the genomes of 2636 Icelanders and found variants that we then imputed into the genomes of approximately 398,000 Icelanders. We tested for association...

Introduction Routine measurement of cardiac biomarkers such as troponin T (TnT) is recommended perioperatively, especially in high-risk vascular surgery. Long-term prognosis is worse even in those with nonspecific perioperative myocardial injury. However, a clear understanding of these biomarker profiles and how they should affect patient managemen...

Background Inflammation of the aortic wall is recognised as a key pathogenesis of abdominal aortic aneurysm (AAA). This study was undertaken to determine whether inflammatory cytokines could be used as biomarkers for the presence of AAA. Methods and Results Tissue profiles of 27 inflammatory cytokine were examined in AAA (n=14) and nonaneurysmal (...

Objectives Remote ischemic preconditioning (RIPC) involves the phenomenon whereby transient episodes of limb ischemia induced by cuff inflation provide cardioprotection. The effectiveness of RIPC in vascular surgery is uncertain. This randomized, controlled trial was designed to investigate the potential of two episodes of RIPC to provide myocardia...

Aim: We wished to determine the mortality burden of valvular heart disease (VHD) in New Zealand, and how it changed prior to the introduction of transcatheter aortic valve replacement. Method: Patient-level cause of death data from 1988 to 2007 were used to examine trends in VHD mortality rates over time. Our outcome measure was death, where the...

Aim: The New Zealand Cardiac Clinical Network and the Ministry of Health recommend a "3-day door-tocatheter target" for acute coronary syndromes (ACS) admissions, requiring that at least 70% of ACS patients referred for invasive coronary angiography (ICA) undergo this within 3 days of hospital admission. We assessed the variability in use of ICA,...

Aims: The first New Zealand Acute Coronary Syndrome (ACS) national audit of 2002 was a collaborative effort between clinicians and nurses, and demonstrated important limitations to Non ST-elevation ACS patient (NSTEACS) care. A momentum for change was created. Subsequent audits in 2007 and 2012 allow assessment over time. Methods: Over 14 days i...

We were interested to read the recent article by Martinsson et al1 on the changing epidemiology of aortic stenosis (AS) in Sweden between 1989 and 2009. This highlights the growing burden of AS on healthcare systems, with increasing numbers of AS diagnoses and procedures. In addition to the valid points in the accompanying editorial,2 we wish to ra...

Background: Radial arterial (RA) and femoral arterial (FA) access rates for invasive coronary angiography (ICA) vary widely internationally. The European Society of Cardiology (ESC) suggests default RA is feasible. We aim to investigate the variation in RA rates across all New Zealand public hospitals. Methods and results: Patient characteristic...

Previous studies examining blood pressure change over time have modeled an average population trajectory. Recent research among older adults suggests there may be subgroups with different blood pressure trajectories. Identifying subgroups at risk of developing adult hypertension early in life can inform effective risk reduction efforts. We sought t...

People with diabetes tend to develop heart disease at a younger age than the age-matched non-diabetic population. We along with others have reported a variety of cellular alterations in diabetic heart due to increase in oxidative stress, reduced survival kinase, defects in calcium homeostasis and substrate metabolism, accumulation of advanced glyca...

Aortic stenosis (AS) is a progressive condition leading to heart failure and death without treatment. No medical therapy currently exists for AS, and a major management challenge is deciding on the correct timing of aortic valve replacement. MicroRNAs (miRNAs) are short noncoding RNAs that are stable in the circulation. We wished to use miRNAs as b...

To compare exercise capacity and cardiovascular response to exercise in elderly individuals with coronary artery disease (CAD) who attend ongoing community-based maintenance cardiac rehabilitation (CR) versus age- and gender-matched healthy "very active" (HVA; ≥ 2000 kcal/week) and healthy "less active" (HLA; <2000 kcal/week) individuals. Sixty-thr...

We aimed to assess differences in patient management, and outcomes, of Australian and New Zealand patients admitted with a suspected or confirmed acute coronary syndrome (ACS). We used comprehensive data from the binational Australia and New Zealand ACS 'SNAPSHOT' audit, acquired on individual patients admitted between 00.00 hours on 14 May 2012 to...

Reasons for low attendance at maintenance cardiac rehabilitation (CR) programs remain largely unknown. Using the Health Belief Model as a theoretical framework, this study compared the motivations and barriers for attending a community-based CR maintenance program in high attenders (HA), low attenders (LA) and non-attenders (NA) with coronary arter...

Elevated levels of lipoprotein(a) [Lp(a)] are a well established risk factor for developing cardiovascular disease (CVD). While Lp(a) levels are thought to be independent of other plasma lipoproteins, some trials have reported a positive association between Lp(a) and high density lipoproteins (HDL). Whether Lp(a) has a direct effect on HDL is not k...

The Cardiac Society of Australia and New Zealand (CSANZ) and the Australia and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) have joined together to provide recommendations for institutions and individual operators to assess their ability to initiate and maintain a transcatheter valve program. Transcatheter aortic valve replacement...

Cardiac rehabilitation (CR) graduates are encouraged to attend maintenance programs to promote long-term physical activity and preserve gains in function. This study describes the characteristics, attendance and physical function of community-based maintenance CR participants, compared to primary prevention participants. In this cross-sectional stu...

Background Previous studies have documented the prevalence of abdominal aortic aneurysm (AAA) during transthoracic echocardiography but the effect of such screening on subsequent vascular interventions remains unclear.AimTo determine the utility of opportunistic selective screening for AAA in a contemporary large series of patients having transthor...