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Introduction The world is undergoing a demographic transition to an older population. Preventive healthcare has reduced the burden of chronic illness at younger ages but there is limited evidence that these advances can improve health at older ages. Statins are one class of drug with the potential to prevent or delay the onset of several causes of incapacity in older age, particularly major cardiovascular disease (CVD). This paper presents the protocol for the STAtins in Reducing Events in the Elderly (STAREE) trial, a randomised double-blind placebo-controlled trial examining the effects of statins in community dwelling older people without CVD, diabetes or dementia. Methods and analysis We will conduct a double-blind, randomised placebo-controlled trial among people aged 70 years and over, recruited through Australian general practice and with no history of clinical CVD, diabetes or dementia. Participants will be randomly assigned to oral atorvastatin (40 mg daily) or matching placebo (1:1 ratio). The co-primary endpoints are disability-free survival defined as survival-free of dementia and persistent physical disability, and major cardiovascular events (cardiovascular death or non-fatal myocardial infarction or stroke). Secondary endpoints are all-cause death, dementia and other cognitive decline, persistent physical disability, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, heart failure, atrial fibrillation, fatal and non-fatal cancer, all-cause hospitalisation, need for permanent residential care and quality of life. Comparisons between assigned treatment arms will be on an intention-to-treat basis with each of the co-primary endpoints analysed separately in time-to-first-event analyses using Cox proportional hazards regression models. Ethics and dissemination STAREE will address uncertainties about the preventive effects of statins on a range of clinical outcomes important to older people. Institutional ethics approval has been obtaine

The EMPEROR-Preserved trial showed that the sodium–glucose co-transporter 2 inhibitor empagliflozin significantly reduces the risk of cardiovascular death or hospitalization for heart failure (HHF) in heart failure patients with left ventricular ejection fraction (LVEF) > 40%. Here, we report the results of a pre-specified analysis that separately evaluates these patients stratified by LVEF: preserved (≥ 50%) (n = 4,005; 66.9%) or mid-range (41–49%). In patients with LVEF ≥ 50%, empagliflozin reduced the risk of cardiovascular death or HHF (the primary endpoint) by 17% versus placebo (hazard ratio (HR) 0.83; 95% confidence interval (CI): 0.71–0.98, P = 0.024). For the key secondary endpoint, the HR for total HHF was 0.83 (95%CI: 0.66–1.04, P = 0.11). For patients with an LVEF of 41–49%, the HR for empagliflozin versus placebo was 0.71 (95%CI: 0.57–0.88, P = 0.002) for the primary outcome (Pinteraction = 0.27), and 0.57 (95%CI: 0.42–0.79, P < 0.001) for total HHF (Pinteraction = 0.06). These results, together with those from the EMPEROR-Reduced trial in patients with LVEF < 40%, support the use of empagliflozin across the full spectrum of LVEF in heart failure. © 2022, The Author(s).

Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. Insight into neoatherosclerosis from OCT could improve our understanding of the mechanisms of very late stent thrombosis. The appropriate use of OCT depends on accurate interpretation and understanding of the clinical significance of OCT findings. In this Review, we summarize the state of the art in cardiac OCT and facilitate the uniform use of this modality in coronary atherosclerosis. Contributions have been made by clinicians and investigators worldwide with extensive experience in OCT, with the aim that this document will serve as a standard reference for future research and clinical application. © 2022, Springer Nature Limited.

Item does not contain fulltext, BACKGROUND: Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain. METHODS: In this double-blind trial, we randomly assigned 5988 patients with class II-IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. RESULTS: Over a median of 26.2 months, a primary outcome event occurred in 415 of 2997 patients (13.8%) in the empagliflozin group and in 511 of 2991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). This effect was mainly related to a lower risk of hospitalization for heart failure in the empagliflozin group. The effects of empagliflozin appeared consistent in patients with or without diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (407 with empagliflozin and 541 with placebo; hazard ratio, 0.73; 95% CI, 0.61 to 0.88; P<0.001). Uncomplicated genital and urinary tract infections and hypotension were reported more frequently with empagliflozin. CONCLUSIONS: Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Preserved ClinicalTrials.gov number, NCT03057951).

Background: Coronary artery disease (CAD) is the leading cause of mortality in Australian women. We identified gender differences in healthy lifestyle adherence in patients treated with percutaneous coronary intervention (PCI) for CAD. Method(s): Consecutive patients were prospectively recruited from three Australian institutions (2016-2017). The primary endpoint at 1 year follow-up was healthy lifestyle adherence defined as 3/3 of: a heart-healthy diet, being physically active and not smoking. Secondary endpoints included cardiac rehabilitation attendance, medication use and lipid levels. Result(s): From 729 participants (n=192, 26.3% women) 56% were adherent to all three lifestyle measures with no gender difference overall. Compared to men, women were less likely to smoke (7.7% versus 12.2%, p<0.001) to be physically active (61.5% versus 78.2%; p<0.0001), attend cardiac rehabilitation (58.2% versus 66.4%; p<0.045), and take statin therapy (85.4% versus 94.7%; p<0.0001). Female gender independently predicted physical inactivity (OR 2.41, 95% CI 1.57-3.68, p<0.001). Conclusion(s): Important gender differences exist in patients treated with PCI for CAD, namely, significant lower physical activity, cardiac rehabilitation attendance and statin use in women. These all represent key targets for gender-specific secondary prevention interventions.Copyright © 2020

Background: While hypo-attenuated leaflet thickening (HALT) has been extensively described following transcatheter aortic valve replacement (TAVR), it remains unclear if HALT impacts long-term prosthetic haemodynamics or predicts structural valve deterioration (SVD). Purpose(s): To determine the role of HALT and its characteristics of depth and thickness in predicting SVD. Method(s): We prospectively evaluated 186 patients who had undergone TAVR with 320-slice CT imaging for the presence of HALT, defined as hypoattenuation of bioprosthetic leaflets in diastole. All assessments were performed by two blinded operators on the 3Mensio workstation. HALT depth (thickness) was the greatest depth in the sagittal view and HALT area was the greatest area in the axial view. SVD was defined as at least one of mean gradient >=20 mmHg, increase in gradient >=10 mmHg from baseline and at least moderate valvular regurgitation. Echocardiograms at discharge, one month and annually were assessed by cardiologists blinded to HALT status. Result(s): LT prevalence was 17.7% at a median CT scan of 6 weeks. SVD occurred in 8.6% at a median follow-up of 2 years (IQR 1-3); two required valve re-intervention, five required anticoagulation that reversed moderatesevere gradient and nine had mild-moderate gradients that were closely monitored. Patients with HALT were more likely to develop SVD (39.3% vs 1.9%, p<0.01) and higher trans-valvular gradients throughout follow-up at up to 3-year follow-up. HALT affected one leaflet in 17 cases, two leaflets in 13 cases and three leaflets in 3 cases. Patients with HALT had a median cumulative thickness of 2.9 mm (IQR 1.9-4.7) and a median area of 64.2 mm2 (IQR 40.9-91.6). Threshold for the occurrence of SVD with HALT characteristics were cumulative depth of 2.4 mm (Specificity 94.1%, Sensitivity 75.0%, AUC=0.87) and cumulative area of 28 mm2 (Specificity 92.2%, Sensitivity 81.3%, AUC=0.86). Conclusion(s): HALT was associated with SVD and higher trans-val

Cardiac injury and dysfunction occur in COVID-19 patients and increase the risk of mortality. Causes are ill defined but could be through direct cardiac infection and/or inflammation-induced dysfunction. To identify mechanisms and cardio-protective drugs, we use a state-of-the-art pipeline combining human cardiac organoids with phosphoproteomics and single nuclei RNA sequencing. We identify an inflammatory "cytokine-storm", a cocktail of interferon gamma, interleukin 1beta, and poly(I:C), induced diastolic dysfunction. Bromodomain-containing protein 4 is activated along with a viral response that is consistent in both human cardiac organoids (hCOs) and hearts of SARS-CoV-2-infected K18-hACE2 mice. Bromodomain and extraterminal family inhibitors (BETi) recover dysfunction in hCOs and completely prevent cardiac dysfunction and death in a mouse cytokine-storm model. Additionally, BETi decreases transcription of genes in the viral response, decreases ACE2 expression, and reduces SARS-CoV-2 infection of cardiomyocytes. Together, BETi, including the Food and Drug Administration (FDA) breakthrough designated drug, apabetalone, are promising candidates to prevent COVID-19 mediated cardiac damage.Copyright © 2021 Elsevier Inc.

This aim of this paper is to set the scene for the need for impact assessment and return on investment in funded cardiovascular research in Australia, starting with the historical perspective on waste in health and medical research. Recently there has been a substantial move from discussion and policy about the need for research translation, into practice and application via the evolution of funding streams like the Australian Medical Research Future Fund (MRFF). Health and medical research funders play a critical role in both setting the expectations for research translation and impact and helping researchers to meet these expectations. As a leading cause of death, cardiovascular disease is a national health priority, recognised as such with a AUD$220 million MRFF allocation to the Cardiovascular Health Mission. Focussing on cardiovascular research, we address some of the barriers researchers face in prospectively planning for research translation and impact assessment, and call for an ecosystem that supports a return on investment for all stakeholders, especially the community and patient end-users.Copyright © 2021

Background: Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic cause of acute coronary syndrome (ACS) that affects women disproportionately. Previous case series have found that patients with SCAD undergoing cardiac catheterisation have high rates of iatrogenic coronary damage. We formally compared the rate of iatrogenic coronary artery dissection in women with and without SCAD undergoing cardiac catheterisation over a 11-year period. Method(s): Women with SCAD were identified by a search of the cardiac catheterisation database 2007-2017 for the keywords 'SCAD', 'spontaneous coronary artery dissection', 'spontaneous coronary dissection', and 'spontaneous dissection'. For each identified case, the medical record and the coronary angiogram images were reviewed to confirm spontaneous coronary dissection. For cases of recurrent SCAD, duplicates were removed so that each patient was included only once in this analysis. For each identified case of SCAD, a control case was chosen from women aged <70 years, without SCAD, undergoing cardiac catheterisation for an ACS during the same 10-year period. One control case was chosen to match each SCAD patient as closely as possible for age and year of cardiac catheterisation. Iatrogenic coronary dissection was defined as new, proximal, flow limiting coronary artery dissection in a different coronary segment to the presenting spontaneous coronary dissection. Result(s): Eighty-five (85) cases of women with SCAD were identified. Mean age was not different between SCAD and non-SCAD women (51+/-11 and 51+/-10 years, respectively). The SCAD group had lower rates of ST elevation myocardial infarction, lower rises in serum creatine kinase (CK) and troponin levels, lower rates of diabetes and smoking, and far less placement of stents during the procedure than the control group. The rate of additional iatrogenic dissection relating to the cardiac catheterisation procedure was 4 of 85 (4.7%) versus 0 of 85 (0%), p=0.04 in

Over the last 3 decades there have been substantial improvements in treatments aimed at reducing cardiovascular (CV) events. As these treatments have been developed, there have been parallel improvements in coronary imaging modalities that can assess plaque volumes and composition, using both invasive and noninvasive techniques. Plaque progression can be seen to precede CV events, and therefore, many studies have longitudinally assessed changes in plaque characteristics in response to various treatments, aiming to demonstrate plaque regression and improvements in high-risk features, with the rationale being that this will reduce CV events. In the past, decisions surrounding treatments for atherosclerosis have been informed by population-based risk scores for initiation in primary prevention and low-density lipoprotein cholesterol levels for titration in secondary prevention. If outcome data linking plaque regression to reduced CV events emerge, it may become possible to directly image plaque treatment response to guide management decisions.Copyright © 2022 American College of Cardiology Foundation

Background/purpose: Coronary artery disease (CAD) is common in patients undergoing transcatheter aortic valve replacement (TAVR), although its prognostic significance is questionable. Significant CAD stratified using SYNTAX score (SS) has been associated with greater mortality, yet it is unknown whether the functional impact of CAD also impacts outcomes in this cohort. DILEMMA score (DS) is a validated angiographic functional scoring tool that correlates with fractional flow reserve and instantaneous wave-free ratio. This study sought to assess the functional impact of CAD on outcomes in patients undergoing TAVR for severe aortic stenosis (AS). Methods/materials: 229 patients were included in this analysis. Patients underwent angiographic DS and SS and were classified using predefined values. The primary endpoint was one-year all-cause mortality, with secondary endpoints of 30-day major adverse cardiac and cerebrovascular events (MACCE). Result(s): The mean age was 83.9 +/- 0.5 years (55.0% female), with 11.8% all-cause mortality. CAD defined by >=30% stenosis in any vessel was not associated with adverse outcomes (HR = 1.08, p = 0.84). However, the risk of one-year mortality was greater in patients with either SS > 9 (20.8% vs. 9.4%, HR 2.34, p = 0.03) or DS > 2 (18.4% vs. 8.5%, HR = 2.28, p = 0.03). Both scoring systems were also associated with 30-day MACCE (both p < 0.05). After multivariate adjustment, independent predictors of one-year mortality were DS > 2 (HR = 2.29, p = 0.04), left ventricular ejection fraction <50% (HR 2.66, p = 0.04) and COPD (HR 2.43, p = 0.04). Conclusion(s): Our results demonstrate that angiographic functional scoring is independently predictive of both 12-month mortality and 30-day MACCE following TAVR.Copyright © 2020 Elsevier Inc.

Background: The clinical predictors and sequelae of leaflet thrombosis (LT) following transcatheter aortic valve replacement (TAVR) is still unclear. Therefore, our aim was to determine the clinical predictors and sequelae at mid-term follow-up of computed tomography (CT)-defined LT following TAVR. Methods and Results: We performed a prospective evaluation with a 320-multislice CT following TAVR for the presence of LT, defined as hypo-attenuated leaflet thickening (HALT). Four-dimensional CT image-rendering was performed to determine the presence of reduced leaflet motion (RELM). 172 patients [89 (51.7%) male, mean age 82.8 +/- 5.7 years] treated with commercially available TAVR device (Lotus 54%, CoreValve 32% and Sapien 3 14%) were included, with median CT-scan at 6.0 weeks post-TAVR. Prevalence of HALT was 14.0% (24 cases) and RELM was 9.8% (17 cases). On multivariate analysis, patients with HALT were less prescribed oral anticoagulation (OAC) (OR 9.9), received larger TAVR prostheses (OR 5.7) and higher rates of moderate-severe para-valvular regurgitation (PVR) (OR 16.3). There was no difference in clinical outcomes at a median follow-up of 2.3 years. Patients with RELM had significantly higher transvalvular gradients after discharge when compared to those without RELM. Conclusion(s): Absence of OAC, large TAVR prostheses and moderate-severe PVR were predictors for LT. Transvalvular gradients were higher in patients that developed RELM but not HALT. Further studies are warranted to determine the long-term impact of LT on TAVR durability. Graphic abstract: Prevalence of different sub-types of CT-defined LT (HALT and RELM) and the clinical predictors of developing LT following TAVR. CT computed tomography, HALT hypo-attenuated leaflet thickening, LT leaflet thrombosis, RELM reduced leaflet motion, TAVR transcatheter aortic valve replacement [Figure not available: see fulltext.].Copyright © 2021, Crown.

Familial hypercholesterolaemia (FH) is a dominant and highly penetrant monogenic disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL)-cholesterol concentration and, if untreated, leads to premature atherosclerosis and coronary artery disease (CAD). There are approximately 100,000 people with FH in Australia. However, an overwhelming majority of those affected remain undetected and inadequately treated, consistent with FH being a leading challenge for public health genomics. To further address the unmet need, we provide an updated guidance, presented as a series of systematically collated recommendations, on the care of patients and families with FH. These recommendations have been informed by an exponential growth in published works and new evidence over the last 5 years and are compatible with a contemporary global call to action on FH. Recommendations are given on the detection, diagnosis, assessment and management of FH in adults and children. Recommendations are also made on genetic testing and risk notification of biological relatives who should undergo cascade testing for FH. Guidance on management is based on the concepts of risk re-stratification, adherence to heart healthy lifestyles, treatment of non-cholesterol risk factors, and safe and appropriate use of LDL-cholesterol lowering therapies, including statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors and lipoprotein apheresis. Broad recommendations are also provided for the organisation and development of health care services. Recommendations on best practice need to be underpinned by good clinical judgment and shared decision making with patients and families. Models of care for FH need to be adapted to local and regional health care needs and available resources. A comprehensive and realistic implementation strategy, informed by further research, including assessments of cost-benefit, will be required to ensure that this new guidance benefits

Background: Echo attenuation of atherosclerotic plaque (EAP) identified with intravascular ultrasound (IVUS) has been shown to correlate with vulnerable plaque morphologies and their presence is predictive of future cardiovascular events. EAP have predominantly been assessed at a single time point and their natural history in the immediate post acute coronary syndrome (ACS) period remains unknown. We aimed to assess this and whether their presence correlated with a more modifiable plaque composition in the immediate post-ACS setting. Method(s): Serial IVUS imaging was performed in non-culprit vessels of 270 patients undergoing angiogram for ACS and at 3 month follow up. IVUS analysis of plaque burden and EAP was performed. Result(s): Baseline characteristics are described in Table 1. EAP were present at baseline in 62 patients (23%) with these patients more likely to be male (89.1% vs. 76.7%, p=0.03) but no differences in other atherosclerotic risk factors. There was no difference in baseline plaque burden between patients with EAP and those without (Percent atheroma volume [PAV] 38.9% vs. 37.8%, p=0.32). At follow up IVUS change in PAV was not statistically significantly different between patients with baseline EAP and those without (DELTAPAV 0.09% vs. -0.36%, p=0.43), and neither was there a difference in the frequency of plaque regressors (42.7% vs 50%, p=0.31). EAP had resolved in 25 patients (40%) within 3 months at the follow up IVUS. Despite contemporary post-ACS therapy 18 patients who had not had EAP present at baseline (9%) developed new EAP at the follow up IVUS. Conclusion(s): EAP were present in a quarter of ACS patients and were not associated with baseline plaque burden or a more modifiable plaque phenotype. In the setting of contemporary ACS treatments the natural history of high risk IVUS plaque characteristics such as EAP is dynamic with significant change even over a 3 month period in the post ACS setting.

Aims: Vascular inflammation inhibits local adipogenesis in pericoronary adipose tissue (PCAT) and this can be detected on coronary computed tomography angiography (CCTA) as an increase in CT attenuation of PCAT surrounding the proximal right coronary artery (RCA). In this cross-sectional study, we assessed the utility of PCAT CT attenuation as an imaging biomarker of coronary inflammation in distinguishing different stages of coronary artery disease (CAD). Methods and Results: Sixty patients with acute myocardial infarction (MI) were prospectively recruited to undergo CCTA within 48 h of admission, prior to invasive angiography. These participants were matched to patients with stable CAD (n = 60) and controls with no CAD (n = 60) by age, gender, BMI, risk factors, medications, and CT tube voltage. PCAT attenuation around the proximal RCA was quantified per-patient using semi-automated software. Patients with MI had a higher PCAT attenuation (-82.3 +/- 5.5 HU) compared with patients with stable CAD (-90.6 +/- 5.7 HU, P < 0.001) and controls (-95.8 +/- 6.2 HU, P < 0.001). PCAT attenuation was significantly increased in stable CAD patients over controls (P = 0.01). The association of PCAT attenuation with stage of CAD was independent of age, gender, cardiovascular risk factors, epicardial adipose tissue volume, and CCTA-derived quantitative plaque burden. No interaction was observed for clinical presentation (MI vs. stable CAD) and plaque burden on PCAT attenuation. Conclusion(s): PCAT CT attenuation as a quantitative measure of global coronary inflammation independently distinguishes patients with MI vs. stable CAD vs. no CAD. Future studies should assess whether this imaging biomarker can track patient responses to therapies in different stages of CAD.Copyright © 2020 Published on behalf of the European Society of Cardiology. All rights reserved.

Coronary artery disease (CAD) remains the leading cause of death worldwide. The role of hypertension, cholesterol, diabetes mellitus, and smoking in driving disease has been well recognized at a population level and has been the target of primary prevention strategies for over 50 years with substantial impact. However, in many cases, these factors alone do not provide enough precision at the individual level to allow physicians and patients to take appropriate preventive measures and many patients continue to suffer acute coronary syndromes in the absence of these risk factors. Recent advances in user-friendly chip designs, high speed throughput, and economic efficiency of genome-wide association studies complemented by advances in statistical analytical approaches have facilitated the rapid development of polygenic risk scores (PRSs). The latest PRSs combine data regarding hundreds of thousands of single-nucleotide polymorphisms to predict chronic diseases including CAD. Novel CAD PRSs are strong predictors of risk and may have application, in a complementary manner with existing risk prediction algorithms. However, there remain substantial controversies, and ultimately, we need to move forward from observational studies to prospectively and rigorously assess the potential impact if widespread implementation is to be aspired to. Consideration needs to be made of ethnicity, sex, as well as age, and risk estimate based on existing non-genomic algorithms. We provide an overview and commentary on the important advances in deriving and validating PRSs, as well as pragmatic considerations that will be required for implementation of the new knowledge into clinical practice.Copyright Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.

Background: Hypo-attenuated leaflet thickening (HALT) may occur following transcatheter aortic valve replacement (TAVR), however, it remains unclear if HALT is a predictor of haemodynamic valve deterioration (HVD). Aim(s): To determine the impact of HALT on the occurrence of HVD. Method(s): We prospectively evaluated 186 patients for the presence of HALT at a median of 6 weeks following TAVR (Interquartile-range [IQR] 4-12 weeks). HALT depth and area were measured. HVD encompassed any of the following: mean gradient >=20 mmHg with an increase in gradient >=10 mmHg from baseline, Doppler velocity index reduction >=0.1 or new moderate-to-severe valvular regurgitation. Routine echocardiograms at discharge, one month and annually, were assessed by echo-cardiologists that were blinded to the HALT status. Result(s): LT prevalence was 17.7% (33/186). HVD was present in 8.6% (16/186) at a median follow-up of 2 years (IQR 1-3); two required valve re-intervention and five required anticoagulation. HALT was the only independent predictor of HVD on multivariate analysis (OR 33.3, 95%CI 7.4-125). Patients with HALT were more likely to develop HVD, require repeat valve intervention and have higher trans-valvular gradients at up to 3-year follow-up. Patients with HALT had a median cumulative thickness of 2.9 mm (IQR 1.9-4.7) and area of 64.2 mm2 (IQR 40.9-91.6). Thresholds for HALT in predicting HVD were a cumulative depth of 2.4 mm (Specificity 94.1%, Sensitivity 75.0%, AUC = 0.87) and cumulative area of 28 mm2 (Specificity 92.2%, Sensitivity 81.3%, AUC = 0.86). Conclusion(s): HALT is an independent predictor of HVD, which exhibits specific depth and area thresholds to predict HVD. CT following TAVR may determine patients at risk of HVD.Copyright © 2021

A large body of evidence arising from recent randomized clinical trials demonstrate the association of vascular inflammatory mediators with coronary artery disease (CAD). Vascular inflammation localized in the coronary arteries leads to an increased risk of CAD-related events, and produces unique biological alterations to local cardiac adipose tissue depots. Coronary computed tomography angiography (CTA) provides a means of mapping inflammatory changes to both epi-cardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT) as independent markers of coronary risk. Radiodensity or attenuation of PCAT on coronary CTA, notably, provides indirect quantification of coronary inflammation and is emerging as a promising non-invasive imaging im-plement. An increasing number of observational studies have shown robust associations between PCAT attenuation and major coronary events, including acute coronary syndrome, and 'vulnerable' atherosclerotic plaque phenotypes that are associated with an increased risk of the said events. This review outlines the biological characteristics of both EAT and PCAT and provides an overview of the current literature on PCAT attenuation as a surrogate marker of coronary inflammation.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Radiomics, via the extraction of quantitative information from conventional radiologic images, can identify imperceptible imaging biomarkers that can advance the characterization of coronary plaques and the surrounding adipose tissue. Such an approach can unravel the underlying pathophysiology of atherosclerosis which has the potential to aid diagnostic, prognostic and, therapeutic decision making. Several studies have demonstrated that radiomic analysis can characterize coronary atherosclerotic plaques with a level of accuracy comparable, if not superior, to current conventional qualitative and quantitative image analysis. While there are many milestones still to be reached before radiomics can be integrated into current clinical practice, such techniques hold great promise for improving the imaging phenotyping of coronary artery disease.Copyright © 2021 by the authors.

Background: Women who experience vascular complications of pregnancy, including pre-eclampsia, hypertension and diabetes, are at increased risk of coronary artery disease (CAD). Yet patients and their medical providers have low awareness of the significance of these 'non-traditional' cardiovascular risk factors. We aimed to determine the prevalence and medical provider awareness of pregnancy-related cardiovascular risk factors in women with CAD. Method(s): Women aged 18-70 years treated with percutaneous coronary intervention (PCI) across three tertiary hospitals were invited to participate in a pregnancy-related telephone interview at 12 months post-PCI. Electronic medical records (EMR) were retrospectively reviewed for documentation of pregnancy-related cardiovascular risk factors in the 12 months prior to, and including, the PCI admission. Result(s): A total of 102 women (mean age 59.8+/-7.7 years) underwent PCI for CAD and completed the pregnancy history questionnaire. Approximately three-quarters (73.5%, 75/102) of women had been pregnant, of which 25.3% (19/75) had experienced vascular complications consisting of pre-eclampsia 31.5% (6/19), gestational diabetes 36.8% (7/19), and gestational hypertension 73.6% (14/19). Documentation of traditional CVD risk factors occurred in 209/211 episodes of emergency or cardiology contact (99.1%), while documentation of 'non-traditional' pregnancy-related cardiovascular risk factors occurred in 0/211 episodes of emergency or cardiology contact. Conclusion(s): More than a quarter of women treated with PCI for CAD had experienced a past pregnancy-related vascular complication. Despite vascular complications of pregnancy predicting future CAD, medical providers were not obtaining a history of these 'non-traditional' cardiovascular risk factors.Copyright © 2020

Background: Pharmacological stress testing is commonly performed for cardiovascular risk stratification in potential renal transplant candidates due to a perceived inability for these patients to exercise. We have previously reported that exercise stress testing is feasible in renal transplant candidates but the prognostic utility of exercise capacity in this patient group is not known. Purpose(s): This study prospectively evaluated the effect of exercise capacity on the risk of major adverse cardiovascular events (MACE), defined as a composite of cardiac death, non-fatal myocardial infarction, and stroke, in renal transplant candidates undergoing exercise stress echocardiography (ESE) for pre-transplant cardiovascular assessment. Method(s): We evaluated 898 consecutive patients with chronic kidney disease stage 4/5 who underwent symptom-limited treadmill ESE over 5-year mean follow-up. Exercise capacity was measured by age and sex predicted metabolic equivalents (METs). The primary outcome was achievement of predicted METs with first MACE. Cox proportional hazard multivariable modelling was used to determine MACE predictors with transplantation treated as a time-varying covariate. We also performed secondary analysis using a 7 MET threshold. Result(s): There were 106 MACE with an annual cumulative risk of 2.4%. During follow-up, 525 (58%) received transplantation. Achievement of predicted METs (48%) (hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.29-0.82, p=0.007) and transplantation (HR 0.52, 95% CI 0.30-0.91, p=0.02) were independently associated with reduced MACE. Similar results were observed using a 7 MET threshold achieved by 734 (82%) patients. Patients achieving predicted METs had no difference in MACE regardless of subsequent transplantation (HR 0.78, 95% CI 0.32-1.92, p=0.59). Patients who achieved predicted METs and did not receive transplantation had similar outcomes to those that did not achieve predicted METs and received transplantation (HR 0

Introduction Familial hypercholesterolaemia (FH) is a common, heritable and preventable cause of premature coronary artery disease, with significant potential for positive impact on public health and healthcare savings. New clinical practice recommendations are presented in an abridged guidance to assist practitioners in enhancing the care of all patients with FH. Main recommendations Core recommendations are made on the detection, diagnosis, assessment and management of adults, children and adolescents with FH. There is a key role for general practitioners (GPs) working in collaboration with specialists with expertise in lipidology. Advice is given on genetic and cholesterol testing and risk notification of biological relatives undergoing cascade testing for FH; all healthcare professionals should develop skills in genomic medicine. Management is under-pinned by the precepts of risk stratification, adherence to healthy lifestyles, treatment of non-cholesterol risk factors, and appropriate use of low-density lipoprotein (LDL)-cholesterol lowering therapies, including statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Recommendations on service design are provided in the full guidance. Potential impact on care of FH These recommendations need to be utilised using judicious clinical judgement and shared decision making with patients and families. Models of care need to be adapted to both local and regional needs and resources. In Australia new government funded schemes for genetic testing and use of PCSK9 inhibitors, as well as the National Health Genomics Policy Framework, will enable adoption of these recommendations. A broad implementation science strategy is, however, required to ensure that the guidance translates into benefit for all families with FH.

Familial hypercholesterolaemia (FH) is a common, heritable and preventable cause of premature coronary artery disease. New clinical practice recommendations are presented to assist practitioners in enhancing the care of all patients with FH. Core recommendations are made on the detection, diagnosis, assessment and management of adults, children and adolescents with FH. Management is under-pinned by the precepts of risk stratification, adherence to healthy lifestyles, treatment of non-cholesterol risk factors and appropriate use of low-density lipoprotein (LDL)-cholesterol-lowering therapies including statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. The recommendations need to be utilised using judicious clinical judgement and shared decision-making with patients and families. New government-funded schemes for genetic testing and use of PCSK9 inhibitors, as well as the National Health Genomics Policy Framework, will enable adoption of the recommendations. However, a comprehensive implementation science and practice strategy is required to ensure that the guidance translates into benefit for all families with FH.

Familial hypercholesterolaemia (FH) is a dominant and highly penetrant monogenic disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL)-cholesterol concentration and, if untreated, leads to premature atherosclerosis and coronary artery disease (CAD). There are approximately 100,000 people with FH in Australia. However, an overwhelming majority of those affected remain undetected and inadequately treated, consistent with FH being a leading challenge for public health genomics. To further address the unmet need, we provide an updated guidance, presented as a series of systematically collated recommendations, on the care of patients and families with FH. These recommendations have been informed by an exponential growth in published works and new evidence over the last 5 years and are compatible with a contemporary global call to action on FH. Recommendations are given on the detection, diagnosis, assessment and management of FH in adults and children. Recommendations are also made on genetic testing and risk notification of biological relatives who should undergo cascade testing for FH. Guidance on management is based on the concepts of risk re-stratification, adherence to heart healthy lifestyles, treatment of non-cholesterol risk factors, and safe and appropriate use of LDL-cholesterol lowering therapies, including statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors and lipoprotein apheresis. Broad recommendations are also provided for the organisation and development of health care services. Recommendations on best practice need to be underpinned by good clinical judgment and shared decision making with patients and families. Models of care for FH need to be adapted to local and regional health care needs and available resources. A comprehensive and realistic implementation strategy, informed by further research, including assessments of cost-benefit, will be required to ensure that this new guidance benefits

Fractional flow reserve (FFR) is routinely used to determine lesion severity prior to percutaneous coronary intervention (PCI). However, there is an increasing recognition that FFR may also be useful following PCI to identify mechanisms leading to restenosis and the need for repeat revascularization. Post-PCI FFR is associated with the presence and severity of stent under-expansion and may help identify peri-stent-related complications. FFR pullback may also unmask other functionally significant lesions within the target vessel that were not appreciable on angiography. Recent studies have confirmed the prognostic utility of performing routine post-PCI FFR and suggest possible interventional targets that would improve stent durability. In this review, we detail the theoretical basis underlying post-PCI FFR, provide practical tips to facilitate measurement, and discuss the growing evidence supporting its use.Copyright © 2020 Udit Thakur et al.

Introduction: The coronavirus 2019 disease (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pre-existing cardiovascular disease (CVD) increases the morbidity and mortality of COVID-19, and COVID-19 itself causes serious cardiac sequelae. Strategies to minimise the risk of viral transmission to health care workers and uninfected cardiac patients while prioritising high quality cardiac care are urgently needed. We conducted a rapid literature appraisal and review of key documents identified by the Cardiac Society of Australia and New Zealand Board and Council members, the Australian and New Zealand Society of Cardiac and Thoracic Surgeons, and key cardiology, surgical and public health opinion leaders. Main recommendations: Common acute cardiac manifestations of COVID-19 include left ventricular dysfunction, heart failure, arrhythmias and acute coronary syndromes. The presence of underlying CVD confers a five- to tenfold higher case fatality rate with COVID-19 disease. Special precautions are needed to avoid viral transmission to this population at risk. Adaptive health care delivery models and resource allocation are required throughout the health care system to address this need. Changes in management as a result of this statement: Cardiovascular health services and cardiovascular health care providers need to recognise the increased risk of COVID-19 among CVD patients, upskill in the management of COVID-19 cardiac manifestations, and reorganise and innovate in service delivery models to meet demands. This consensus statement, endorsed by the Cardiac Society of Australia and New Zealand, the Australian and New Zealand Society of Cardiac and Thoracic Surgeons, the National Heart Foundation of Australia and the High Blood Pressure Research Council of Australia summarises important issues and proposes practical approaches to cardiovascular health care delivery to patients with and without SARS-CoV-2 infection.Copyright © 20

Background. Despite the high prevalence of coronary bifurcation lesions in routine interventional cardiology practice, the best strategy for managing this challenging lesion subset remains debatable. Due to potential for complications, the routine practice of side-branch (SB) predilation is controversial. Methods. An electronic search was performed of online databases up until April 2018 for studies reporting periprocedural angiographic outcomes comparing provisional main-branch stenting with and without SB predilation. Random-effects model odds ratios (ORs) were calculated. Results. Eight studies were selected for a qualitative review, with 47.3% (1367/2890) of included subjects having angiographic outcomes following SB predilation reported. Of these, four studies included details of periangiographic outcomes comparing two groups. Bifurcation lesions stented without SB predilation demonstrated lower odds of requiring further SB intervention compared with lesions receiving upfront SB predilation (OR, 2.44; 95% confidence interval [CI], 1.71-3.47; I2=21%; P<.001). No difference was demonstrated regarding final SB TIMI flow <3, SB dissection, or intraprocedural SB occlusion. Although the odds of performing final kissing-balloon inflation were in favor of the group without SB predilation (OR, 1.62; 95%CI, 1.11-2.37; I2=61%; P=.01), there was no statistical difference in long-term major cardiovascular outcome (MACE) between the two groups (risk ratio, 1.29; 95%CI, 0.94-1.75; I2=11%; P=.33). Conclusion. SB predilation during coronary bifurcation percutaneous coronary intervention did not alter overall procedural angiographic outcomes. However, SB predilation is associated with increased SB intervention, including increased requirement for SB stenting, without demonstrable long-term MACE benefit, compared with a standard strategy without SB predilation.Copyright © 2020 HMP Communications. All rights reserved.

Background: Coronary artery disease is common in patients with severe aortic stenosis. Computed tomography-derived fractional flow reserve (CT-FFR) is a clinically used modality for assessing coronary artery disease, however, its use has not been validated in patients with severe aortic stenosis. This study assesses the safety, feasibility, and validity of CT-FFR in patients with severe aortic stenosis. Method(s): Prospectively recruited patients underwent standard-protocol invasive FFR and coronary CT angiography (CTA). CTA images were analyzed by central core laboratory (HeartFlow, Inc) for independent evaluation of CT-FFR. CT-FFR data were compared with FFR (ischemia defined as FFR <=0.80). Result(s): Forty-two patients (68 vessels) underwent FFR and CTA; 39 patients (92.3%) and 60 vessels (88.2%) had interpretable CTA enabling CT-FFR computation. Mean age was 76.2+/-6.7 years (71.8% male). No patients incurred complications relating to premedication, CTA, or FFR protocol. Mean FFR and CT-FFR were 0.83+/-0.10 and 0.77+/-0.14, respectively. CT calcium score was 1373.3+/-1392.9 Agatston units. On per vessel analysis, there was positive correlation between FFR and CT-FFR (Pearson correlation coefficient, R=0.64, P<0.0001). Sensitivity, specificity, positive predictive value, and negative predictive values were 73.9%, 78.4%, 68.0%, and 82.9%, respectively, with 76.7% diagnostic accuracy. The area under the receiver-operating characteristic curve for CT-FFR was 0.83 (0.72-0.93, P<0.0001), which was higher than that of CTA and quantitative coronary angiography (P=0.01 and P<0.001, respectively). Bland-Altman plot showed mean bias between FFR and CT-FFR as 0.059+/-0.110. On per patient analysis, the sensitivity, specificity, positive predictive, and negative predictive values were 76.5%, 77.3%, 72.2%, and 81.0% with 76.9% diagnostic accuracy. The per patient area under the receiver-operating characteristic curve analysis was 0.81 (0.67-0.95, P<0.0001). Conclusion(s): CT

The pathophysiology of coronary atherosclerosis is multifaceted. Plaque initiation and progression are governed by a complex interplay between genetic and environmental factors acting through processes such as lipid accumulation, altered haemodynamics and inflammation. There is increasing recognition that biomechanical stresses play an important role in atherogenesis, and integration of these metrics with clinical imaging has potential to significantly improve cardiovascular risk prediction. In this review, we present the calculation of coronary biomechanical stresses from first principles and computational methods, including endothelial shear stress (ESS), plaque structural stress (PSS) and axial plaque stress (APS). We discuss the current experimental and human data linking these stresses to the natural history of coronary artery disease and explore the future potential for refining treatment options and predicting future ischaemic events.Copyright © 2020 Elsevier B.V.

Objectives: To assess the predictive value of the Australian absolute cardiovascular disease risk (ACVDR) calculator and other assessment tools for identifying Australians with family histories of early onset coronary artery disease (CAD) who have coronary artery calcification. Design, setting, participants: People without known CAD were recruited at seven Australian hospitals, October 2016 - January 2019. Participants were aged 40-70 years, had a family history of early onset CAD, and a 5-year ACVDR of 2-15%. Main Outcome Measure(s): CT coronary artery calcium score greater than zero (any coronary calcification) or greater than 100 (calcification warranting lipid therapy). Result(s): 1059 participants were recruited; 477 (45%) had non-zero coronary artery calcium scores (median 5-year ACVDR, 4.8% [IQR, 2.9-7.6%]; median coronary artery calcium score, 41.7 [IQR, 8-124]); 582 (55%) did not (median 5-year ACVDR, 3.2% [IQR, 2.0-4.6%]). Of 151 participants with calcium scores of 100 or more, 116 (77%) were deemed to be at low cardiovascular risk by Australian guidelines, while 14 of 75 participants at intermediate risk (19%) had zero calcium scores. The sensitivity of the ACVDR calculator for identifying people with non-zero calcium scores (area under receiver operator curve [AUC], 0.674) was lower than that of the pooled cohort equation (AUC, 0.711; P < 0.001). ACVDR (10-year)- and Multi-Ethnic Study of Atherosclerosis (MESA)-predicted risk categories concurred for 511 participants (48%); classifications were concordant for 925 participants (87%) when the ACVDR was supplemented by calcium scores. Conclusion(s): Coronary artery calcium scoring should be considered as part of the heart health check for patients at intermediate ACVDR risk and with family histories of early onset CAD. Alternative risk calculators may better select such patients for further diagnostic testing and primary prevention therapy. Trial registration: Australian New Zealand Clinical Trials Registry

Objectives: This study sought to determine whether coronary computed tomography angiography (CCTA)-based radiomic analysis of pericoronary adipose tissue (PCAT) could distinguish patients with acute myocardial infarction (MI) from patients with stable or no coronary artery disease (CAD). Background(s): Imaging of PCAT with CCTA enables detection of coronary inflammation. Radiomics involves extracting quantitative features from medical images to create big data and identify novel imaging biomarkers. Method(s): In a prospective case-control study, 60 patients with acute MI underwent CCTA within 48 h of admission, before invasive angiography. These subjects were matched to patients with stable CAD (n = 60) and controls with no CAD (n = 60) by age, sex, risk factors, medications, and CT tube voltage. PCAT was segmented around the proximal right coronary artery (RCA) in all patients and around culprit and nonculprit lesions in patients with MI. PCAT segmentations were analyzed using Radiomics Image Analysis software. Result(s): Of 1,103 calculated radiomic parameters, 20.3% differed significantly between MI patients and controls, and 16.5% differed between patients with MI and stable CAD (critical p < 0.0006); whereas none differed between patients with stable CAD and controls. On cluster analysis, the most significant radiomic parameters were texture or geometry based. At 6 months post-MI, there was no significant change in the PCAT radiomic profile around the proximal RCA or nonculprit lesions. Using machine learning (XGBoost), a model integrating clinical features (risk factors, serum lipids, high-sensitivity C-reactive protein), PCAT attenuation, and radiomic parameters provided superior discrimination of acute MI (area under the receiver operator characteristic curve [AUC]: 0.87) compared with a model with clinical features and PCAT attenuation (AUC: 0.77; p = 0.001) or clinical features alone (AUC: 0.76; p < 0.001). Conclusion(s): Patients with acute MI have a dist

Background: To compare computed tomography coronary angiography (CTCA) with intravascular ultrasound (IVUS) in quantitative and qualitative plaque assessment. Method(s): Patients who underwent IVUS and CTCA within 3 months for suspected coronary artery disease were retrospectively studied. Plaque volumes on CTCA were quantified manually and with automated-software and were compared to IVUS. High-risk plaque features were compared between CTCA and IVUS. Result(s): There were 769 slices in 32 vessels (27 patients). Manual plaque quantification on CTCA was comparable to IVUS per slice (mean difference of 0.06 +/- 0.07, p = 0.44; Bland-Altman 95% limits of agreement -2.19-2.08 mm3, bias of -0.06 mm3) and per vessel (3.1 mm3 +/- -2.85 mm3, p = 0.92). In contrast, there was significant difference between automated-software and IVUS per slice (2.3 +/- 0.09mm3, p < 0.001; 95% LoA -6.78 to 2.25 mm3, bias of -2.2 mm3) and per vessel (33.04 +/- 10.3 mm3, p < 0.01). The sensitivity, specificity, positive and negative predictive value of CTCA to detect plaques that had features of echo-attenuation on IVUS was 93.3%, 99.6%, 93.3% and 99.6% respectively. The association of >=2 high-risk plaque features on CTCA with echo attenuation (EA) plaque features on IVUS was excellent (86.7%, 99.6%, 92.9% and 99.2%). In comparison, the association of high-risk plaque features on CTCA and plaques with echo-lucency on IVUS was only modest. Conclusion(s): Plaque volume quantification by manual CTCA method is accurate when compared to IVUS. The presence of at least two high-risk plaque features on CTCA is associated with plaque features of echo attenuation on IVUS.Copyright © 2019

Background: Familial hypercholesterolemia (FH) is a common underdiagnosed autosomal dominant lipid disorder carrying a significant risk of premature coronary artery disease. The aim of this study was to evaluate the awareness and knowledge of heterozygous FH of healthcare providers in coronary care units (CCUs). Method(s): Medical staff working in CCUs in 4 sizable metropolitan health networks in Melbourne, Australia, were requested to complete a structured anonymised questionnaire with regard to FH. The results were tabulated and analysed with the Statistical Package for the Social Sciences version 23 (IBM, New York, NY). Result(s): A total of 121 participants (67% response rate) completed the survey. Some 76% claimed to be at least modestly familiar with FH, and more than half of them adequately described FH; however, only 16% and 43%, respectively, were aware of the prevalence of FH and existence of lipid guidelines. In regard to epidemiological knowledge and update in the management of FH in CCUs, knowledge was suboptimal. In regard to FH care, General Practitioners were rated by 72% of participants as the first most efficient healthcare provider in the management of FH, and cardiologists were rated by 54% of participants as the second most efficient healthcare provider in the management of FH. Some 36% of respondents advocated a form of alert system in laboratory reports to facilitate the diagnosis of FH. Conclusion(s): This survey identified substantial gaps in the knowledge and awareness of FH among healthcare providers involved in the management of acute coronary syndrome. Focused education and clinical training are warranted to raise awareness of FH among healthcare providers working in CCUs.Copyright © 2019

Background and aims: There remains a substantial residual risk of ischaemic heart disease (IHD) despite optimal low-density lipoprotein cholesterol (LDLC) reduction. Part of this risk may be attributable to remnant cholesterol, which is carried in triglyceride-rich lipoproteins. We evaluated the relationship between remnant cholesterol and coronary atherosclerotic plaque burden assessed non-invasively by computed tomography coronary angiography (CTCA) in patients with suspected coronary artery disease (CAD). Methods and Results: This was a multicentre study of 587 patients who had a CTCA and fasting lipid profile within 3 months. Calculated remnant cholesterol was total cholesterol minus LDLC minus high-density lipoprotein cholesterol (HDLC). Significant coronary atherosclerotic burden was defined as CT-Leaman score >5 (CT-LeSc), an established predictor of cardiac events. Mean age was 61 +/- 12 years and mean pretest probability of CAD was 23.2 +/- 19.8%. LDLC levels were <1.8 mmol/L in 134 patients (23%), of whom 82% were statin-treated. Patients with CT-LeSc >5 had higher mean remnant cholesterol than those with CT-LeSc <=5 (0.76 +/- 0.36 mmol/L vs. 0.58 +/- 0.33 mmol/L, p = 0.01). On univariable analysis, remnant cholesterol (p = 0.01), LDLC (p = 0.002) and HDLC (p < 0.001) levels predicted CT-LeSc >5, whilst triglycerides (p = 0.79) had no association with CT-LeSc >5. On multivariable analysis in the subset of patients with optimal LDLC levels, remnant cholesterol levels remained predictive of CT-LeSc >5 (OR 3.87, 95% confidence interval 1.34-7.55, p = 0.004), adjusted for HDLC and traditional risk factors. Conclusion(s): Remnant cholesterol levels are associated with significant coronary atherosclerotic burden as assessed by CTCA, even in patients with optimal LDLC levels. Future studies examining whether lowering of remnant cholesterol can reduce residual IHD risk are warranted.Copyright © 2019 Elsevier B.V.