Barriers to and Facilitators of Implementing Guidelines for Detecting Familial Hypercholesterolaemia in Australia.

BACKGROUND: Familial hypercholesterolaemia (FH) is a genetic condition that is a preventable cause of premature cardiovascular morbidity and mortality. High-level evidence and clinical practice guidelines support preventative care for people with FH. However, it is estimated that less than 10% of people at risk of FH have been detected using any approach across Australian health settings. The aim of this study was to identify the implementation barriers to and facilitators of the detection of FH in Australia. METHODS: Four, 2-hour virtual focus groups were facilitated by implementation scientists and a clinicians as part of the 2021 Australasian FH Summit. Template analysis was used to identify themes. RESULTS: There were 28 workshop attendees across four groups (n=6-8 each), yielding 13 barriers and 10 facilitators across three themes: (1) patient related, (2) provider related, and (3) system related. A "lack of care pathways" and "upskilling clinicians in identifying and diagnosing FH" were the most interconnected barriers and facilitators for the detection of FH. CONCLUSIONS: The relationships between barriers and facilitators across the patient, provider, and system themes indicates that a comprehensive implementation strategy is needed to address these different levels. Future research is underway to develop a model for implementing the Australian FH guidelines into practice.

Australian Atherosclerosis Society Position Statement on Lipoprotein(a): Clinical and Implementation Recommendations.

This position statement provides guidance to cardiologists and related specialists on the management of adult patients with elevated lipoprotein(a) [Lp(a)]. Elevated Lp(a) is an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). While circulating Lp(a) levels are largely determined by ancestry, they are also influenced by ethnicity, hormones, renal function, and acute inflammatory events, such that measurement should be done after accounting for these factors. Further, circulating Lp(a) concentrations should be estimated using an apo(a)-isoform independent assay that employs appropriate calibrators and reports the results in molar units (nmol/L). Selective screening strategies of high-risk patients are recommended, but universal screening of the population is currently not advised. Testing for elevated Lp(a) is recommended in all patients with premature ASCVD and those considered to be at intermediate-to-high risk of ASCVD. Elevated Lp(a) should be employed to assess and stratify risk and to enable a decision on initiation or intensification of preventative treatments, such as cholesterol lowering therapy. In adult patients with elevated Lp(a) at intermediate-to-high risk of ASCVD, absolute risk should be reduced by addressing all modifiable behavioural, lifestyle, psychosocial and clinical risk factors, including maximising cholesterol-lowering with statin and ezetimibe and, where appropriate, PCSK9 inhibitors. Apheresis should be considered in patients with progressive ASCVD. New ribonucleic acid (RNA)-based therapies which directly lower Lp(a) are undergoing clinical trials.

National Heart Foundation of Australia: position statement on coronary artery calcium scoring for the primary prevention of cardiovascular disease in Australia.

INTRODUCTION: This position statement considers the evolving evidence on the use of coronary artery calcium scoring (CAC) for defining cardiovascular risk in the context of Australian practice and provides advice to health professionals regarding the use of CAC scoring in primary prevention of cardiovascular disease in Australia. Main recommendations: CAC scoring could be considered for selected people with moderate absolute cardiovascular risk, as assessed by the National Vascular Disease Prevention Alliance (NVDPA) absolute cardiovascular risk algorithm, and for whom the findings are likely to influence the intensity of risk management. (GRADE evidence certainty: Low. GRADE recommendation strength: Conditional.) CAC scoring could be considered for selected people with low absolute cardiovascular risk, as assessed by the NVDPA absolute cardiovascular risk algorithm, and who have additional risk-enhancing factors that may result in the underestimation of risk. (GRADE evidence certainty: Low. GRADE recommendation strength: Conditional.) If CAC scoring is undertaken, a CAC score of 0 AU could reclassify a person to a low absolute cardiovascular risk status, with subsequent management to be informed by patient-clinician discussion and follow contemporary recommendations for low absolute cardiovascular risk. (GRADE evidence certainty: Very low. GRADE recommendation strength: Conditional.) If CAC scoring is undertaken, a CAC score > 99 AU or ≥ 75th percentile for age and sex could reclassify a person to a high absolute cardiovascular risk status, with subsequent management to be informed by patient-clinician discussion and follow contemporary recommendations for high absolute cardiovascular risk. (GRADE evidence certainty: Very low. GRADE recommendation strength: Conditional.) CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: CAC scoring can have a role in reclassification of absolute cardiovascular risk for selected patients in Australia, in conjunction with traditional absolute risk assessment and as part of a shared decision-making approach that considers the preferences and values of individual patients.

Lipoprotein apheresis and PCSK9 inhibitors for severe familial hypercholesterolaemia: Experience from Australia and New Zealand.

INTRODUCTION: Severe familial hypercholesterolaemia (FH) causes premature disability and death due to atherosclerotic cardiovascular disease and is refractory to standard lipid-lowering therapies. Lipoprotein apheresis (LA) has long been a standard of care for patients with severe FH, but is invasive, expensive and time-consuming for patients and their caregivers. Newer drug therapies, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, may reduce the need for LA. MATERIALS AND METHODS: We audited the records of 16 patients (eight homozygous, eight heterozygous) treated with LA in Australia and New Zealand, 14 of whom subsequently commenced PCSK9 inhibitor therapy. LA was performed by cascade filtration in all centres. RESULTS: LDL-cholesterol was acutely lowered by 69 ± 7% in patients with homozygous FH and by 72 ± 9% in those with heterozygous FH, representing time-averaged reductions of 36 ± 12% and 34 ± 5%, respectively. LA was well-tolerated, and patients reported comparable quality of life to population and disease-related norms. After commencement of PCSK9 inhibitors, four of seven patients with homozygous FH had meaningful biochemical responses, with a reduction in the frequency of LA permitted in one patient and complete cessation in another. Four of seven patients with heterozygous FH were able to be managed without LA after commencing PCSK9 inhibitors. CONCLUSION: While PCSK9 inhibitors have reduced the need for LA, some patients with severe FH continue to require LA, and will require it for the foreseeable future. However, emerging therapies, including angiopoetin-like 3 inhibitors, may further reduce the need for LA.

Gaps in the Care of Familial Hypercholesterolaemia in Australia: First Report From the National Registry.

BACKGROUND: Familial hypercholesterolaemia (FH) is under-diagnosed and under-treated worldwide, including Australia. National registries play a key role in identifying patients with FH, understanding gaps in care and advancing the science of FH to improve care for these patients. METHODS: The FH Australasia Network has established a national web-based registry to raise awareness of the condition, facilitate service planning and inform best practice and care services in Australia. We conducted a cross-sectional analysis of 1,528 FH adults enrolled in the registry from 28 lipid clinics. RESULTS: The mean age at enrolment was 53.4±15.1 years, 50.5% were male and 54.3% had undergone FH genetic testing, of which 61.8% had a pathogenic FH-causing gene variant. Only 14.0% of the cohort were family members identified through cascade testing. Coronary artery disease (CAD) was reported in 28.0% of patients (age of onset 49.0±10.5 years) and 64.9% had at least one modifiable cardiovascular risk factor. The mean untreated LDL-cholesterol was 7.4±2.5 mmol/L. 80.8% of patients were on lipid-lowering therapy with a mean treated LDL-cholesterol of 3.3±1.7 mmol/L. Among patients receiving lipid-lowering therapies, 25.6% achieved an LDL-cholesterol target of <2.5 mmol/L without CAD or <1.8 mmol/L with CAD. CONCLUSION: Patients in the national FH registry are detected later in life, have a high burden of CAD and risk factors, and do not achieve guideline-recommended LDL-cholesterol targets. Genetic and cascade testing are under-utilised. These deficiencies in care need to be addressed as a public health priority.

Ischemic stroke/transient ischemic attack events and carotid artery disease in the absence of or with minimal coronary artery calcification: Results from the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: The association between minimally elevated coronary artery calcification (CAC) and cerebrovascular disease is not well known. We assessed whether individuals with minimal CAC (Agatston scores of 1-10) have higher ischemic stroke or transient ischemic attack (TIA) frequencies compared with those with no CAC. We also investigated the relative prevalence of carotid atherosclerosis in these two groups. METHODS: A total of 3924 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) without previous cardiovascular events, including stroke, and with baseline CAC scores of 0-10 were followed for the occurrence of incident ischemic stroke/TIA. We used carotid ultrasound to detect carotid artery plaques and to measure the intima-media thickness (IMT). RESULTS: During a median follow-up of 13.2 years, 130 participants developed incident ischemic stroke/TIA. There was no significant difference in the ischemic stroke/TIA incidence between those with minimal CAC and no CAC (3.7 versus 2.7 per 1000 person-years). In participants with minimal CAC, we observed a significant association of the condition with an internal carotid artery (ICA) that had a greater-than-average IMT (ICA-IMT; ß = 0.071, p = 0.001) and a higher odds ratio (OR) for carotid artery plaques (OR 1.46; with a 95% confidence interval [CI] of 1.18-1.80; p < 0.001). CONCLUSIONS: A CAC score of 0-10 is associated with a low rate of ischemic stroke/TIA, and thus a minimal CAC score is not a valuable predictive marker for ischemic stroke/TIA. A minimal CAC score may, however, provide an early and asymptomatic sign of carotid artery disease.

Pragmatic approach to chest pain patients discharged with undetectable high-sensitivity troponin T and normal electrocardiogram: the STABS + CT protocol.

A strategy that discharges chest pain patients with negative high-sensitivity troponin and non-ischaemic electrocardiography changes may still result in 0.44% of patients experiencing myocardial infarction within 30 days. We observed that a pragmatic approach that systematically discharged 25 patients on cardio-protective medications of aspirin, metoprolol and atorvastatin followed with prompt (<10 days) coronary computed tomography angiography resulted in no major adverse cardiac event and adverse drug reaction 30 days post-presentation. The strategy resulted in three patients (12%) ultimately diagnosed with likely unstable angina, which required planned coronary intervention in two patients and medical management in one patient. No unplanned readmissions for chest pains were noted from initial presentation through to 6-month follow up.

Design of the Familial Hypercholesterolaemia Australasia Network Registry: Creating Opportunities for Greater International Collaboration.

Familial Hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipoprotein metabolism that leads to premature coronary heart disease. There are over 65,000 people estimated to have FH in Australia, but many remain undiagnosed. Patients with FH are often under-treated, but with early detection, cascade family testing and adequate treatment, patient outcomes can improve. Patient registries are key tools for providing new information on FH and enhancing care worldwide. The development and design of the FH Australasia Network Registry is a crucial component in the comprehensive model of care for FH, which aims to provide a standardized, high-quality and cost-effective system of care that is likely to have the highest impact on patient outcomes. Informed by stakeholder engagement, the FH Australasia Network Registry was collaboratively developed by government, patient and clinical networks and research groups. The open-source, web-based Rare Disease Registry Framework was the architecture chosen for this registry owing to its open-source standards, modular design, interoperability, scalability and security features; all these are key components required to meet the ever changing clinical demands across regions. This paper provides a high level blueprint for other countries and jurisdictions to help inform and map out the critical features of an FH registry to meet their particular health system needs.

A new model of care for familial hypercholesterolaemia: what is the role of cardiology?

Familial hypercholesterolaemia (FH) is a co-dominantly inherited disorder that causes marked elevation in plasma cholesterol and premature coronary heart disease. There are at least 45,000 people with FH in Australia and New Zealand, but most remain undiagnosed and undertreated. To bridge this gap in coronary prevention the FH Australasia Network has developed a model of care for FH. We present the executive summary, with a commentary contrasting the recommendations with other international guidelines and highlighting the role of the cardiologist.

Out-of-office and central blood pressure for risk stratification: a cross-sectional study in patients treated for hypertension.

BACKGROUND: Central blood pressure (BP) predicts mortality independent of office brachial BP. Whether central BP may be useful to differentiate BP control requires examination and was the first aim of this study. Secondly, we sought to determine the variability in central BP among patients from different categories of BP control [controlled hypertension (CH), masked hypertension (MH), white coat (WCHT) and uncontrolled hypertension (UH)]. MATERIALS AND METHODS: We assessed patients with uncomplicated hypertension using measurement of central BP (SphygmoCor 8.1), brachial BP and 24-h ambulatory BP monitoring. BP control was defined according to guidelines using office BP and 24-h BP. RESULTS: Of the 201 patients (63 ± 8 years, 51% men), 67 (33%) were classified as CH; 59 (29%) with MH; 31 (15%) with WCHT; and 44 (22%) with UH. There were no differences in central BP parameters (augmentation pressure, augmentation index, pulse pressure) between patients with CH and MH or between patients with WCHT and UH (P > 0·05 for all). However, there was significant overlap in central systolic BP between BP control categories. For example, 27% of patients with normal brachial systolic BP had central systolic BP above age- and gender-specific normal values, including patients from three classifications of BP control (CH: n = 27; MH: n = 22; and WCHT: n = 4). CONCLUSION: Office central BP alone cannot delineate categories of BP control. However, given the high degree of variability in central BP among patients from different categories of BP control, measurement of central BP may result in significant reclassification of risk related to BP.

Familial hypercholesterolaemia: a model of care for Australasia.

Familial hypercholesterolaemia (FH) is a dominantly inherited disorder present from birth that causes marked elevation in plasma cholesterol and premature coronary heart disease. There are at least 45,000 people with FH in Australia and New Zealand, but the vast majority remains undetected and those diagnosed with the condition are inadequately treated. To bridge this major gap in coronary prevention the FH Australasia Network (Australian Atherosclerosis Society) has developed a consensus model of care (MoC) for FH. The MoC is based on clinical experience, expert opinion, published evidence and consultations with a wide spectrum of stakeholders, and has been developed for use primarily by specialist centres intending starting a clinical service for FH. This MoC aims to provide a standardised, high-quality and cost-effective system of care that is likely to have the highest impact on patient outcomes. The MoC for FH is presented as a series of recommendations and algorithms focusing on the standards required for the detection, diagnosis, assessment and management of FH in adults and children. The process involved in cascade screening and risk notification, the backbone for detecting new cases of FH, is detailed. Guidance on treatment is based on risk stratifying patients, management of non-cholesterol risk factors, safe and effective use of statins, and a rational approach to follow-up of patients. Clinical and laboratory recommendations are given for genetic testing. An integrative system for providing best clinical care is described. This MoC for FH is not prescriptive and needs to be complemented by good clinical judgment and adjusted for local needs and resources. After initial implementation, the MoC will require critical evaluation, development and appropriate modification.

The impact of performing spirometry on shunting across a patent foramen ovale.

Transient changes in intrathoracic pressure can alter left and right intra-atrial pressures, and may provoke shunting of blood across a patent foramen ovale (PFO). Spirometry causes a transient rise and subsequent fall in intrathoracic pressure that, if performed following a dive on compressed air, could raise the risk of decompression illness by arterialisation of venous bubbles across a PFO. To assess whether spirometry can provoke right-to-left shunting across a patent foramen ovale, a subject with a known PFO, previously identified by bubble contrast transthoracic echocardiography, where shunting was only evident on performing a Valsalva manoeuvre, underwent re-examination whilst performing spirometry. Right-to-left shunting was not evident at rest, but was provoked by performing spirometry. If spirometry is to be performed within two hours of surfacing, this should be regarded as a potential risk for decompression illness.