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We previously showed that implementing algorithms for managing diabetes in acute coronary syndrome was associated with improved inpatient glycaemic control and increased sodium-glucose cotransporter 2 (SGLT2) inhibitor prescriptions. The present study performed 1 year later found that inpatient hyperglycaemia had relapsed to pre-intervention rates, although SGLT2 inhibitor prescriptions remained increased. We discuss the challenges of improving inpatient glycaemic control., (© 2021 Royal Australasian College of Physicians.)

Sodium-glucose cotransporter 2 inhibitors can improve heart failure outcomes, however, the effects on left ventricular (LV) function remain unclear. This prospective observational study aimed to investigate whether initiating empagliflozin therapy was associated with improved LV diastolic function following an acute coronary syndrome (ACS) in patients with type 2 diabetes (T2D). Patients with ACS and T2D were identified during hospitalisation in a cardiology unit. Empagliflozin was initiated at discharge in eligible patients (i.e. HbA1c > 7%) without contraindications or precautions. Transthoracic echocardiography was performed during admission and after 3-6 months. Changes in echocardiographic parameters were compared between patients initiated on empagliflozin versus not initiated on empagliflozin (control). There were 22 patients in each group (n = 44). Baseline characteristics, medications and echocardiographic parameters were similar except HbA1c (empagliflozin: 9.8 ± 1.6% versus control: 6.6 ± 0.7%, p < 0.001). Baseline LV global longitudinal strain (GLS) (empagliflozin: - 12.4 ± 2.8 versus control: - 13.0 ± 3.6%) and ejection fraction (51.1 ± 11.3 versus 54.9 ± 10.8%) were similar. The difference in change from baseline to follow-up was significant for LV mass index (empagliflozin: - 14.1 ± 21.6 versus control: 3.6 ± 18.7 g/m 2 , p = 0.006), left atrial volume index (- 2.1 ± 8.1 versus 3.4 ± 9.5 ml/m 2 , p = 0.045), mitral valve E-wave velocity (- 0.14 ± 0.23 versus 0.03 ± 0.16 m/s, p = 0.007) and average E/e' (- 2.1 ± 2.6 versus 0.9 ± 3.4, p = 0.002). There were no significant between-group differences in change for LV GLS, ejection fraction and volume. In patients with ACS and T2D, addition of empagliflozin to ACS therapy at discharge was associated with a reduction in LV mass and favourable changes in diastolic function parameters. Further studies are warranted to investigate these findings.

Recent cardiovascular safety trials on sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists have demonstrated the significant cardiovascular and renal benefits of these medications. Diabetes organisations have revised their medication guidelines to include a focus on disease outcomes for cardiovascular disease, heart failure and renal disease. This article summarises latest evidence, guideline recommendations and current Australian Pharmaceutical Benefits Scheme requirements., (© 2020 Royal Australasian College of Physicians.)

Objectives High-sensitivity (hs) cardiac troponin (cTn) assays can quantitate small fluctuations in cTn concentration. Determining biological variation allows calculation of reference change values (RCV), to define significant changes. We assessed the short- and long-term biological variation of cardiac troponin I (cTnI) in healthy individuals and patients with renal failure requiring haemodialysis or cardiomyopathy. Methods Plasma samples were collected hourly for 4 h and weekly for seven further weeks from 20 healthy individuals, 9 renal failure patients and 20 cardiomyopathy patients. Pre- and post-haemodialysis samples were collected weekly for 7 weeks. Samples were analysed using a hs-cTnI assay (Abbott Alinity ci-series). Within-subject biological variation (CVI), analytical variation (CVA) and between-subject biological variation (CVG) was used to calculate RCVs and index of individuality (II). Results For healthy individuals, CVI, CVA, CVG, RCV and II values were 8.8, 14.0, 43.1, 45.8% and 0.38 respectively for short-term, and 41.4, 14.0, 25.8, 121.0% and 1.69 for long-term. For renal failure patients, these were 2.6, 5.8, 50.5, 17.6% and 0.30 respectively for short-term, and 19.1, 5.8, 11.2, 55.2% and 1.78 for long-term. For cardiomyopathy patients, these were 4.2, 10.0, 65.9, 30.0% and 0.16 respectively for short-term, and 17.5, 10.0, 63.1, 55.8% and 0.32 for long-term. Mean cTnI concentration was lower post-haemodialysis (15.2 vs. 17.8 ng/L, p < 0.0001), with a 16.9% mean relative change. Conclusions The biological variation of cTnI is similar between end-stage renal failure and cardiomyopathy patients, but proportionately greater in well-selected healthy individuals with very low baseline cTnI concentrations.

Background: Infective endocarditis (IE) is associated with significant morbidity and mortality. Non-adherence to IE guidelines and recommendations is frequent, and may adversely impact patient outcomes., Aim: To assess the impact of non-adherence to components of existing IE guidelines and recommendations on a composite outcome consisting of any of the following: mortality, unplanned cardiac surgery, embolic event or relapse of positive blood culture within six months of diagnosis., Methods: A single centre, retrospective cohort study., Results: Amongst 157 patients, there was inconsistent adherence to: initial diagnosis of an infective condition (87%), timely administration of antimicrobial therapy (82%), appropriateness of predominant antimicrobial regime (94%), appropriate management of the portal of entry (86%), multidisciplinary input (75%), end of antimicrobial therapy repeat echocardiography (60%) and adherence to indications for surgery (76%). Inpatient mortality was 12.1% (n = 19) and the composite adverse outcome occurred in 36 (22.9%) patients. In multivariate logistic regression analysis, infection of prosthetic device (adjusted odds ratio [95% confidence interval]; 2.43 [1.07-5.50]) and non-adherence to surgical guidelines (aOR 3.67 [1.60-8.47]) were significantly associated with an adverse outcome., Conclusions: Our data suggests that adherence to differing components of IE management guidelines and recommendations varies and that non-adherence to surgical aspects of guidelines has the biggest impact in determining outcomes., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Outcomes after coronary artery bypass graft (CABG) surgery have improved due to advances in surgical technique and post-operative care. We aimed to describe contemporary clinical characteristics and short-term post-operative outcomes in diabetic patients undergoing CABG surgery., Methods: A retrospective analysis of patients who underwent CABG surgery over a 4.5-year period in a Western Australian tertiary hospital was performed in September 2019. The cohort was stratified according to pre-operative diabetes status., Results: A total of 1327 patients underwent CABG surgery, of which 572 (43.1%) had diabetes. Diabetic patients were more likely to be female (24.7% vs. 13.9%, p < 0.001) and have dyslipidaemia (83.0% vs. 68.1%, p < 0.001), hypertension (82.0% vs. 68.7%, p < 0.001), raised body mass index (29.8 ± 5.6 vs. 28.7 ± 5.1 kg/m 2 , p < 0.001), prior myocardial infarction (62.8% vs. 54.8%, p = 0.004), prior stroke (8.6% vs. 5.0%, p = 0.010), congestive cardiac failure (20.2% vs. 15.1%, p = 0.014), reduced estimated glomerular filtration rate (86.7 ± 36.1 vs. 90.8 ± 32.1 ml/min/1.73 m 2 , p = 0.036) and three-vessel coronary artery disease (74.8% vs. 67.3%, p = 0.003). Post-operative wound infections (3.1% vs. 1.5%, p = 0.022), new dialysis requirement (2.9% vs. 1.0%, p = 0.009) and 30-day hospital admission (13.1% vs. 8.5%, p = 0.007) was more likely in diabetic patients, but not myocardial infarction (3.0% vs. 2.0%, p = 0.247), stroke (1.4% vs. 0.8%, p = 0.286) or 30-day mortality (2.4% vs. 1.7%, p = 0.354). No significant differences were detected in short-term outcomes between patients with non-insulin (n = 398) versus insulin treated (n = 174) diabetes., Conclusions: Diabetic patients continue to represent a higher-risk cohort, highlighting the need for further strategies to reduce short-term adverse outcomes following CABG surgery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Diabetes India. All rights reserved.)

Background: Exercise training is an important component of multidisciplinary heart failure management. However, the effects of aerobic training (AT) versus resistance training (RT) on cardiac function in patients with heart failure with reduced ejection fraction are not well defined. The aim of this study was to evaluate the impact of these exercise modalities on echocardiographic parameters., Methods: Participants with stable heart failure with reduced ejection fraction (ejection fraction < 50%) were randomized to 12 weeks of AT, RT, or untrained control. Exercise was performed at matched relative intensities of each training modality (50%-70% of maximum). Echocardiography and cardiopulmonary exercise testing were performed at baseline and after 12 weeks of training., Results: Thirty-eight participants were randomized, and 12 in each group completed the intervention (mean age, 61.5 ± 1.7 years; 89% men). Peak oxygen consumption increased from 14.5 ± 1.3 to 17.2 ± 1.6 ml · min -1 · kg -1 after AT and from 13.7 ± 1.2 to 16.4 ± 1.1 ml · min -1 · kg -1 after RT (P < .001 for both). In the AT group, there was a decrease in septal e' (from 0.052 ± 0.004 to 0.041 ± 0.004 m/sec) and increases in E/e' ratio (from 18.2 ± 3.1 to 23.8 ± 3.5), left atrial volume (from 86 ± 9 to 99 ± 10 mL), and right ventricular end-diastolic area (from 18 ± 1 to 20 ± 1 cm 2 ; P < .05 for all), but these were unchanged in the control and RT groups. There were no significant changes in left ventricular diameters or volumes or right ventricular fractional area change after exercise., Conclusions: There is a differential effect of AT versus RT on some echocardiographic parameters in patients with heart failure with reduced ejection fraction. AT was associated with evidence of worsening myocardial diastolic function, whereas this was not apparent after RT. Further studies are indicated to investigate the long-term clinical significance of these adaptations., (Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aim: Diabetes mellitus is associated with increased risk of adverse outcomes following acute coronary syndrome. Translating evidence-based recommendations into practice is necessary to improve outcomes. We evaluated whether implementing algorithms to guide inpatient care improved glycaemic control, and increased use of sodium-glucose co-transporter 2 (SGLT2) inhibitors and lipid-lowering medication in a tertiary cardiac unit., Method: A 3-month audit (phase 1) was conducted to evaluate hyperglycaemia and dyslipidaemia management, and medication prescriptions. Consecutive people with diabetes admitted for acute coronary syndrome were prospectively identified. Target blood glucose level was defined as 5-10 mmol/l. A multidisciplinary committee designed and implemented decision-support algorithms plus education. A 3-month post-implementation audit (phase 2) was conducted., Results: There were 104 people in phase 1 and 101 in phase 2, with similar characteristics [HbA 1c 64 ± 20 mmol/mol vs. 61 ± 21 mmol/mol (8.0 ± 1.8% vs. 7.8 ± 1.9%]. Post implementation, the incidence of blood glucose levels > 10 mmol/l was lower [phase 1: 46.4% vs. phase 2: 31.8%, rate ratio (RR) = 0.77, 95% confidence intervals (CI) 0.60-0.98; P = 0.031], without a difference in blood glucose levels < 5mmol/l (phase 1: 4.9% vs. phase 2: 4.5%, RR = 1.20, 95% CI 0.70-2.08; P = 0.506). SGLT2 inhibitor prescriptions increased significantly (baseline to discharge: 12.5% to 15.4% vs. 7.9% to 24.8%; P = 0.007) but high-intensity statin prescriptions did not (baseline to discharge: 35.6% to 72.1% vs. 40.6% to 85.1%; P = 0.074). Prescription rates of non-statin lipid-lowering medications were not significantly increased., Conclusions: Implementing decision-support algorithms was associated with improved inpatient glycaemic control and increased use of cardioprotective therapies at discharge in people with diabetes and acute coronary syndrome., (© 2019 Diabetes UK.)

The diagnosis of acute myocardial injury requires a rise and/or fall of cardiac troponin (cTn) on serial testing, with at least one concentration above the 99 th percentile value of a normal reference population according to the recently published Fourth Universal Definition of Myocardial Infarction .1 However, the magnitude of change in cTn that constitutes a significant rise and/or fall was again not specified in detail. High-sensitivity cardiac troponin (hs-cTn) assays can measure ten-fold lower concentrations of cTn with more precision than older assays, and can accurately quantify cTn in more than 50% of healthy individuals with a coefficient of variation of less than 10% at the 99 th percentile. These hs-cTn assays are also able to detect the normal variations in cTn results that are due to biological variability. Understanding and quantifying the normal variations in cTn is important as this would allow significant changes to be better defined. Numerous studies have sought to investigate the biological variability of cTn over the last ten years. Such studies are usually conducted in healthy individuals, however individuals with chronic cardiac disease or chronic renal failure have also been examined. These studies have yielded varying results in regards to significant change values for cTn. In light of the recent redefinition for myocardial infarction, the purpose of this mini-review is to revisit the biological variability of cTn. In particular, we outline concepts for determining a significant change value, review the results of previous studies on the biological variation of cTn and discuss potential considerations for clinical practice., Competing Interests: Competing Interests: None declared., (The contents of articles or advertisements in The Clinical Biochemist – Reviews are not to be construed as official statements, evaluations or endorsements by the AACB, its official bodies or its agents. Statements of opinion in AACB publications are those of the contributors. Print Post Approved - PP255003/01665. Copyright © 2005 The Australasian Association of Clinical Biochemists Inc. No literary matter in The Clinical Biochemist – Reviews is to be reproduced, stored in a retrieval system or transmitted in any form by electronic or mechanical means, photocopying or recording, without permission. Requests to do so should be addressed to the Editor. ISSN 0159 – 8090.)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a unique class of oral anti-hyperglycaemic medications that act to reduce glucose reabsorption in the renal proximal tubules, thereby enhancing urinary glucose excretion. Large randomized placebo-controlled trials in people with diabetes at high cardiovascular risk have demonstrated that SGLT2 inhibitors reduce heart failure hospitalization within months of commencing therapy. These findings are of considerable interest, as diabetes is associated with an increased risk of both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. In addition, left ventricular (LV) hypertrophy and impaired diastolic function is thought to be more prevalent in people with diabetes. Although many hypotheses have been proposed, the underlying mechanisms through which SGLT2 inhibitors reduce the risk of heart failure in people with diabetes are not fully understood. Given the rapid reduction in heart failure hospitalization, it is conceivable that the benefits of SGLT2 inhibitors are due to favourable haemodynamic and metabolic effects on LV function. Several clinical studies have been conducted to investigate the effect of SGLT2 inhibitors on LV structure and function and have found that LV mass index and diastolic function improve following SGLT2 inhibitor therapy in people with type 2 diabetes. If these findings are confirmed in future studies utilizing novel cardiac imaging modalities and large randomized controlled trials, then this will bring new hope for the prevention and management of heart failure with preserved ejection fraction, for which no current treatments have been shown to reduce mortality. At the present time, SGLT2 inhibitors are indicated for the treatment of type 2 diabetes; however, the results of ongoing trials in participants with heart failure but without diabetes are eagerly awaited. The purpose of this review is to summarize current knowledge regarding the effects of SGLT2 inhibitors on LV function, particularly the findings from clinical studies, proposed biological mechanisms, and future directions., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: Patent foramen ovale (PFO) is a potential mechanism for paradoxical embolism in cryptogenic ischaemic stroke or transient ischaemic attack (TIA). PFO is typically demonstrated with agitated saline ("bubble study", BS) during echocardiography. We hypothesised that the BS is frequently requested in patients that have a readily identifiable cause of stroke, that any PFO detected is likely incidental, and its detection often does not alter management., Methods: This was a retrospective observational study of patients with recent ischaemic stroke/TIA referred for a BS. Patient demographics, stroke risk factors, vascular/cerebral imaging results and transoesophageal echocardiogram (TOE) reports were recorded. A "modified" Risk of Paradoxical Embolism (RoPE) score was calculated. Change in management was defined as antiplatelet/anticoagulant therapy alteration or referral for PFO closure. Bubble Study complications were recorded., Results: Among 715 patients with ischaemic stroke/TIA referred for a BS, 8.7% had atrial fibrillation and 9.2% had carotid stenosis ≥70%. At least three stroke risk factors were present in 39.3% and only 47.1% of patients screened had a "modified" RoPE score of >5. A PFO was detected in 248 patients of whom only 31% (77/248) had a subsequent change in management. Of BS performed, 1/924 patients (0.1%) suffered a TIA as a complication., Conclusions: The echocardiographic BS is frequently performed in patients that have a readily identifiable cause of stroke and whose PFO unlikely relates to the stroke/TIA. Bubble Study findings resulted in a change in management in the minority. The procedure is safe but the complication rate warrants informed consent., (Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.)

The risk of atherosclerotic cardiovascular disease (ASCVD) can be significantly reduced in patients with diabetes who are undergoing low-density lipoprotein cholesterol-reducing therapies. However, the elevated triglyceride levels seen in diabetic dyslipidaemia can contribute to residual ASCVD risk. Icosapent ethyl (IPE) has recently been shown to substantially reduce major cardiovascular events in high-risk patients with hypertriglyceridaemia who are undergoing statin therapy. In a real-world study of patients with diabetes and acute coronary syndrome (ACS), 17.1% were found to be eligible for treatment with IPE based on Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) criteria. A significant proportion of patients with diabetes and ACS merit receiving IPE therapy, with important implications for evolving clinical practice guidelines and best standard of care., (© 2019 John Wiley & Sons Ltd.)

Background The Framingham Risk Score estimates the 10-year risk of cardiovascular events. However, it performs poorly in older adults. We evaluated the incremental benefit of adding high-sensitivity cardiac troponin I (hs-cTnI) to the Framingham Risk Score. Methods and Results The HIMS (Health in Men Study) is a cohort study of community-dwelling men aged 70 to 89 years in Western Australia. Participants were identified from the electoral roll, with a subset undergoing plasma analysis. Hs- cTnI (Abbott Architect i2000 SR ) was measured in 1151 men without prior cardiovascular disease. The Western Australia Data Linkage System was used to identify incident cardiovascular events. After 10 years of follow-up, 252 men (22%) had a cardiovascular event ( CVE +) and 899 did not (CVE-). The Framingham Risk Score placed 148 (59%) CVE + and 415 (46%) CVE- in the high-risk category. In CVE - men, adding hs- cTnI affected the risk categories of 244 (27.2%) men, with 64.8% appropriately reclassified to a lower and 35.2% to a higher category, which decreased the number of high-risk men in the CVE- to 39%. In CVE + men, adding hs- cTnI affected the risk categories of 61 (24.2%), with 50.8% appropriately reclassified to a higher and 49.2% to a lower category and 82.5% remaining above the 15% risk treatment threshold. The net reclassification index was 0.305 ( P<0.001). Adding hs- cTnI increased the C-statistic modestly from 0.588 (95% CI , 0.552-0.624) to 0.624 (95% CI , 0.589-0.659) and improved model fit (likelihood ratio test, P<0.001). Conclusions Adding hs- cTnI to the Framingham Risk Score provided incremental prognostic benefit in older men, especially aiding reclassification of individuals into a lower risk category.

Familial hypercholesterolaemia (FH) is a dominantly inherited disorder of low-density lipoprotein (LDL) catabolism, which if untreated causes lifelong elevated LDL-cholesterol (LDL-c), accelerated atherosclerosis and premature cardiovascular disease. Recent evidence suggests the prevalence of heterozygous FH is ∼1:220, making FH the most common autosomal dominant condition. Lowering LDL-c with statin and lifestyle therapy reduces the risk of cardiovascular events. Furthermore, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors significantly lower LDL-c in addition to statin therapy, and early outcome data suggest improved vascular outcomes with these agents in FH patients in addition to statins. However, the vast majority of people with FH still remain undiagnosed. The onus is on clinicians to identify kindreds with FH, as PCSK9 inhibitors, although expensive, are funded for patients with FH in Australia. Multiple strategies for detecting FH have been proposed. The detection of index cases can be achieved through applying electronic screening tools to general practice databases, universal screening of children during immunisation, and targeted screening of patients with premature cardiovascular disease. Advances in genomic technology have decreased costs of genetic testing, improved the understanding of the pathogenesis of FH and facilitated cascade screening. However, awareness of FH amongst clinicians and the general public still requires optimisation. This review outlines recent advances in FH detection, including emerging strategies and challenges for the next decade., (Copyright © 2018 Royal College of Pathologists of Australasia. All rights reserved.)

Dyslipidaemia is an important modifiable risk factor contributing to the increased risk of atherosclerotic cardiovascular disease in diabetes. However, determining when to initiate statin therapy in young adults with type 1 diabetes mellitus (T1DM) can often be challenging. This is due to a relative paucity of data in this area to guide management and for developing T1DM-specific risk engines. Current recommendations from international guidelines offer differing approaches to cardiovascular risk stratification and management of dyslipidaemia in T1DM. We present a clinical vignette and comment on the use of nontraditional methods of cardiovascular risk stratification. The strategy for managing dyslipidaemia in young T1DM should be individualized, and recommendations from guidelines should serve to inform clinical judgement., (© 2018 John Wiley & Sons, Ltd.)

Ehlers-Danlos Syndrome comprises a heterogeneous group of heritable connective tissue disorders resulting from various gene mutations. We present an unusual case of vascular Ehlers-Danlos Syndrome with distinctive physical characteristics and a cardiomyopathy with features suggesting isolated left ventricular non-compaction. The cardiac features represent the first report of a cardiomyopathy associated with a mutation in the COL3A1 gene. This case also illustrates the multi-system nature of Ehlers-Danlos Syndrome and the complexity of managing patients with the vascular subtype., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To investigate the relationship between hearing loss and cardiovascular disease risk factors., Design: Cross-sectional study., Methods: Participants were recruited between May 2010 and December 2015 and answered a health and risk factor questionnaire. Physical and biochemical assessments were performed., Setting: A community-based population., Participants: A total of 5107 participants born within the years 1946-1964 enrolled in the Busselton Healthy Ageing Study., Main Outcome Measures: Hearing was assessed behaviourally through the best ear pure-tone average (500, 1000, 2000, 4000 Hz), low-frequency average (250, 500, 1000 Hz) and high-frequency average (4000, 8000 Hz). Self-reported hearing loss, tinnitus and hyperacusis were assessed via questionnaire. Cardiovascular risk factors were assessed via a patient-completed questionnaire and objective measurements including blood pressure, body mass index, waist circumference, lipid profile and glycated haemoglobin., Results: Of the participants, 54% were female, with the mean age of 58 years (range 45-69 years). Age, sex and family history of hearing loss were consistently strong determinants of hearing loss outcomes. After adjusting for these, obesity, current smoking, peripheral arterial disease and history of cardiovascular disease were significantly associated with pure-tone, low-frequency and high-frequency hearing loss. In addition, high blood pressure, triglyceride and glycated haemoglobin were significantly associated with low-frequency hearing loss. There was a graded association between hearing loss and Framingham Risk Score for cardiovascular risk (P<0.001)., Conclusions: Established cardiovascular disease and individual and combined cardiovascular disease risk factors were found to be associated with hearing loss. Future research should prospectively investigate whether targeting cardiovascular disease can prevent hearing loss., (© 2017 John Wiley & Sons Ltd.)