How Will Our Practice Change After the CLEAR Outcomes Trial?

PURPOSE OF REVIEW: Bempedoic acid is a novel therapeutic agent that is designed to reduce levels of low-density lipoprotein cholesterol (LDL-C). The purpose of this review is to provide the background for development of bempedoic acid, findings from clinical trials and to discuss clinical implications. RECENT FINDINGS: Bempedoic acid inhibits ATP citrate lyase within the liver and reduces cholesterol synthesis, with the potential to avoid muscle symptoms experienced by patients treated with statins. Early clinical studies demonstrated that administration of bempedoic acid resulted in lowering of LDL-C by 20-30% as monotherapy and by 40-50% when combined with ezetimibe, in addition to lowering of high sensitivity C-reactive protein by 20-30%. The CLEAR Outcomes trial of high cardiovascular risk patients, with elevated LDL-C levels and either unable or unwilling to take statins demonstrated that bempedoic acid reduced the rate of major adverse cardiovascular events. A greater incidence of elevation of hepatic transaminase and creatinine, gout, and cholelithiasis were consistently observed in bempedoic acid-treated patients. Bempedoic acid presents an additional therapeutic option to achieve more effective lowering of LDL-C levels and reduction in cardiovascular risk.

Impact of PCSK9 inhibitors on coronary atheroma phenotype following myocardial infarction: insights from intravascular imaging.

PURPOSE OF REVIEW: The aim of this study was to review the impact of combination lipid lowering with statins and proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors on coronary atherosclerosis using serial intravascular imaging. RECENT FINDINGS: Early studies using intravascular ultrasound established the ability of increasingly intensive lipid lowering to both slow progression and ultimately promote regression of coronary disease. More recent clinical trials that have employed serial imaging with optical coherence tomography have permitted the ability to evaluate the impact of intensive lipid lowering on compositional features associated with plaque vulnerability. In particular, the combination of intensive statin and PCSK9 inhibitor therapy promotes plaque stability in patients following an acute coronary syndrome. SUMMARY: More intensive lipid lowering using the combination of statins and PCSK9 inhibitors promote plaque regression in addition to promoting calcification, fibrous cap thickening and reductions in plaque lipid. These plaque-stabilizing effects underscore the benefits of combination therapy on cardiovascular events and highlight the importance of combination lipid-lowering therapy.

Prescribing Trends and Health Care Expenditure of P2Y12 Prescriptions in Australia Over the Last Decade.

BACKGROUND: Dual antiplatelet therapy (DAPT) is guideline therapy following acute coronary syndrome (ACS). Novel, potent P2Y12 inhibitors have been developed and studied but it is unclear how this evidence has been incorporated into patient care. We sought to describe the prescribing trends and health care costs of P2Y12therapy in Australia over the last decade. METHOD: The latest statistical data collected by the Pharmaceutical Benefit Scheme (PBS), Australia, was reviewed. PBS codes for coronary indications were selected. Yearly total prescriptions and cost were then compared between all three P2Y12 inhibitors. Linear trend modelling was used to observe general trends over the data collection period. RESULTS: Total yearly P2Y12 scripts have more than doubled between 2010 (403,880 scripts) and 2020 (994,826 scripts). Clopidogrel is the most prescribed P2Y12 inhibitor and has been for the last decade. Ticagrelor represents 26.2% of total prescriptions but accounts for 75% of PBS spending. More than $30 million is spent on ticagrelor every year with a cost per MACE prevented of $72,637. Prasugrel was the least prescribed agent but was 41% cheaper per major adverse cardiac event (MACE) prevented than ticagrelor before being removed from the Australian market. Without prasugrel available, clopidogrel scripts have increased 10% and ticagrelor scripts remain stable. CONCLUSION: Clopidogrel remains the most prescribed P2Y12 agent in Australia, despite emergence of more potent P2Y12 inhibitors. Ticagrelor is increasingly prescribed but represents a disproportionately large burden of spending. Whilst prasugrel is the most efficacious, cheaper than ticagrelor and guideline recommended P2Y12 inhibitor after ACS, it represented the minority of scripts before being withdrawn. Rather than use of a potent P2Y12 agent, clinicians are reverting to prescribing clopidogrel.

Perspectives on the success of plasma lipidomics in cardiovascular drug discovery and future challenges.

INTRODUCTION: Plasma lipidomics has emerged as a powerful tool in cardiovascular drug discovery by providing insights into disease mechanisms, identifying potential biomarkers for diagnosis and prognosis, and discovering novel targets for drug development. Widespread application of plasma lipidomics is hampered by technological limitations and standardization and requires a collaborative approach to maximize its use in cardiovascular drug discovery. AREAS COVERED: This review provides an overview of the utility of plasma lipidomics in cardiovascular drug discovery and discusses the challenges and future perspectives of this rapidly evolving field. The authors discuss the role of lipidomics in understanding the molecular mechanisms of CVD, identifying novel biomarkers for diagnosis and prognosis, and discovering new therapeutic targets for drug development. Furthermore, they highlight the challenges faced in data analysis, standardization, and integration with other omics approaches and propose future directions for the field. EXPERT OPINION: Plasma lipidomics holds great promise for improving the diagnosis, treatment, and prevention of CVD. While challenges remain in standardization and technology, ongoing research and collaboration among scientists and clinicians will undoubtedly help overcome these obstacles. As lipidomics evolves, its impact on cardiovascular drug discovery and clinical practice is expected to grow, ultimately benefiting patients and healthcare systems worldwide.

Optimal Medical Therapy for Stable Ischemic Heart Disease in 2024: Focus on Blood Pressure and Lipids.

Hypertension and dyslipidemia are 2 highly prevalent and modifiable risk factors in patients with stable ischemic heart disease. Multiple lines of evidence demonstrate that lowering blood pressure and low-density lipoprotein cholesterol improves clinical outcomes in patients with ischemic heart disease. Accordingly, clinical guidelines recommend intensive treatment targets for these high-risk patients. This article summarizes the pathophysiology, supporting evidence, and treatment recommendations for management of hypertension and dyslipidemia among patients with manifest ischemic heart disease and points to future research and unmet clinical needs.

Cardiology patients are unaware of the benefits of seasonal influenza immunization.

Seasonal influenza immunization reduces the risk of cardiovascular events. Patients with established cardiovascular disease (CVD) derive a greater benefit than those without, yet up to 50 % do not take up the immunization. Patient perceptions and beliefs are known to inform immunization behaviors, yet the immunization related beliefs of patients with CVD have not been described. Objective: To describe beliefs, perceptions and behaviors regarding influenza immunization in patients with CVD. Methods: We undertook a cross-sectional, voluntary and anonymous survey of 181 cardiology inpatients and outpatients attending three large hospitals in Victoria. Results: Median age was 64, 35.0 % were female and 24.2 % spoke a language other than English at home. Over one-third-(34.5 %) of respondents did not receive the seasonal influenza immunization in the prior year. Only half (54.2 %) of patients agreed that their heart condition placed them at higher risk of complications and serious illness if they contracted influenza. Nearly a quarter of patients (24.0 %) were concerned about side effects while 1 in 10 patients raised cost as a barrier despite being free-of-charge in Australia. If asked to receive the seasonal influenza immunization, 86 % patients would agree if their cardiologist recommended it. Conclusion: Despite guideline recommendations, most cardiology patients are uninformed of the cardiovascular benefits of seasonal influenza immunization with many unaware they are at higher risk of influenza-related illness. The vast majority of patients would accept the immunization if recommended by their cardiologist highlighting their important role in improving uptake.

Asymptomatic coronary artery disease in ischaemic stroke survivors: A systematic review and meta-analysis.

BACKGROUND: Ischaemic stroke and coronary artery disease share risk factors and stroke survivors experience a high rate of cardiac events. Recent work suggests a high burden of asymptomatic coronary artery disease (CAD) in ischaemic stroke survivors. Thus, we performed this systematic review and meta-analysis to A) estimate the prevalence of CAD in ischaemic stroke survivors without known CAD and B) evaluate the association between coronary atherosclerosis and future major adverse cardiovascular events (MACE) in stroke survivors. PATIENTS AND METHODS: We conducted a systematic review and meta-analysis according to the PRISMA statement. We included studies investigating acute ischaemic stroke or transient ischaemic attack where participants underwent anatomical assessment of all coronary arteries. For objective B) we included studies that reported an association between coronary atherosclerosis and MACE. Two reviewers used the Newcastle-Ottawa Scale to assess risk of bias. We used random-effects modelling for our analyses. RESULTS: We identified 2983 studies of which 17 were included. These studies had a total of 6862 participants between 2008 and 2022. The pooled prevalence of any coronary atherosclerosis was 66.8% (95% CI 57.2%-75.1%) with substantial heterogeneity (I2 = 95.2%). The pooled prevalence of obstructive (>50%) stenosis was 29.3% with substantial heterogeneity (I2 = 91%). High-risk coronary anatomy (triple vessel disease or left main stenosis) was found in 7.0% (95% CI 4%-12%) with high heterogeneity I2 = 72%. One study examined high-risk plaques and found a prevalence of 5.9%. Five studies reported the association of coronary atherosclerosis with future MACE. The presence of obstructive CAD confers a HR of 8.0 (95% CI 1.7-37.1, p = 0.007) for future MACE. DISCUSSION AND CONCLUSIONS: Asymptomatic CAD is common in ischaemic stroke survivors. The presence and severity of asymptomatic CAD strongly associates with the risk of future MACE. Further evaluation of the benefits of routine coronary assessment in ischaemic stroke is warranted.

Variation of computed tomography-derived extracellular volume fraction and the impact of protocol parameters: A systematic review and meta-analysis.

BACKGROUND: Cardiac computed tomography quantification of extracellular volume fraction (CT-ECV) is an emerging biomarker of myocardial fibrosis which has demonstrated high reproducibility, diagnostic and prognostic utility. However, there has been wide variation in the CT-ECV protocol in the literature and useful disease cut-offs are yet to be established. The objectives of this meta-analysis were to describe mean CT-ECV estimates and to estimate the effect of CT-ECV protocol parameters on between-study variation. METHODS: We conducted a meta-analysis of studies assessing CT-ECV in healthy and diseased participants. We used meta-analytic methods to pool estimates of CT-ECV and performed meta-regression to identify the contribution of protocol parameters to CT-ECV heterogeneity. RESULTS: Thirteen studies had a total of 248 healthy participants who underwent CT-ECV assessment. Studies of healthy participants had high variation in CT-ECV protocol parameters. The pooled estimate of CT-ECV in healthy participants was 27.6% (95%CI 25.7%-29.4%) with significant heterogeneity (I2 â€‹= â€‹93%) compared to 50.2% (95%CI 46.2%-54.2%) in amyloidosis, 31.2% (28.5%-33.8%) in severe aortic stenosis and 36.9% (31.6%-42.3%) in non-ischaemic dilated cardiomyopathies. Meta-regression revealed that CT protocol parameters account for approximately 25% of the heterogeneity in CT-ECV estimates. CONCLUSION: CT-ECV estimates for healthy individuals vary widely in the literature and there is significant overlap with estimates in cardiac disease. One quarter of this heterogeneity is explained by differences in CT-ECV protocol parameters. Standardization of CT-ECV protocols is necessary for widespread implementation of CT-ECV assessment for diagnosis and prognosis.

Computed tomography coronary angiography assessment of left main coronary artery stenosis severity.

BACKGROUND: Angiographic assessment of left main coronary artery (LMCA) stenosis severity can be unreliable. In cases of ambiguity, intravascular ultrasound (IVUS) can be utilised with a minimal lumen area (MLA) of ≥6 â€‹mm2 an accepted threshold for safe deferral of revascularization. We sought to assess whether quantitative computer tomography coronary angiography (CTCA) measures could assist clinicians making LMCA revascularization decisions when compared with IVUS as gold standard. METHODS: Consecutive patients undergoing IVUS assessment of angiographically intermediate LMCA stenosis were included. All patients had undergone 320-slice CTCA <90 days prior to IVUS imaging. Offline quantitative assessment of IVUS- and CT-derived measures were undertaken with the cohort divided into those with significant (s-LMCA) versus non-significant (ns-LMCA) disease using the accepted IVUS threshold. RESULTS: Fifty-eight patients were included, with no difference in mean age (61.5 â€‹± â€‹12.2 vs. 59.7 â€‹± â€‹11.9 years, p â€‹= â€‹0.57), diabetic status (24.2% vs 16.0%, p â€‹= â€‹0.44) or other baseline demographics between groups. Patients with ns-LMCA had larger CT luminal area (8.64 â€‹± â€‹3.91 vs. 5.41 â€‹± â€‹1.54 â€‹mm2, p â€‹< â€‹0.001), larger minimal lumen diameter (MLD) (3.25 â€‹± â€‹0.74 vs. 2.56 â€‹± â€‹0.38 â€‹mm, p â€‹< â€‹0.001) and lower area stenosis (45.74 â€‹± â€‹18.10 vs. 60.93 â€‹± â€‹14.68%, p â€‹= â€‹0.001). There was a significant positive correlation between CTCA and IVUS MLA (r â€‹= â€‹0.68, p â€‹< â€‹0.001) and MLD (r â€‹= â€‹0.67, p â€‹< â€‹0.001). ROC analysis demonstrated CTCA MLA cut-off <8.29 â€‹mm2 provides the greatest negative predictive value and sensitivity in predicting the presence of significant LMCA disease. CONCLUSION: CTCA derived MLA and MLD have a strong correlation with IVUS. A CTCA derived MLA cut-off <8.29 â€‹mm2 showed greatest clinical utility for predicting the need for further assessment, based on IVUS gold standard.

Candida parapsilosis bone marrow infection in an immunocompetent patient.

Background: We discuss a case of an immunocompetent patient who presented with fever and tachypnoea, found to have Candida parapsilosis bone marrow infection, cultured on bone marrow aspirate sample. Candida parapsilosis is an opportunistic yeast pathogen that typically affects immunocompromised individuals, or occurs in patients with apparent introduced source; neither of these factors were present for this case. Bone marrow aspirates and trephines are not regular investigations for fever; however they can be useful diagnostic aids as evidenced in this case. Case report: An 83-year-old woman presenting with fevers and tachypnoea was being treated for a systemic bacterial infection, however was unresponsive to empirical antibiotic therapy. To exclude an occult malignancy, an 18-fluorodeoxyglucose positron emission tomography scan was conducted. Significant bone marrow uptake was noted, prompting a bone marrow aspirate and trephine to investigate for a hematological malignancy. While the trephine biopsy was benign, a culture of the aspirate grew Candida parapsilosis. Intravenous antifungal therapy was initiated; however, the patient did not improve despite targeted therapy likely due to delays in diagnosis, and was palliated. Conclusion: Our case seeks to demonstrate a novel case whereby a bone marrow aspirate culture provided a conclusive diagnosis of invasive Candida parapsilosis bone marrow infection, and guided treatment in an immunocompetent patient. It is important for clinicians to consider invasive fungal infections in febrile patients regardless of immune status. Additionally, when performing a bone marrow aspirate and trephine on a febrile patient, we recommend including aspirate fungal cultures to investigate for an invasive fungal infection.

Cardiologists' knowledge and perceptions of the seasonal influenza immunisation.

BACKGROUND: Seasonal influenza immunisation reduces cardiovascular events in high-risk patients, but 50% do not receive routine immunisation. The perceptions and current role of cardiologists in recommending and prescribing influenza immunisation has not been well described. METHODS: We used an exploratory sequential mixed methods design. Semi-structured interviews of 10 cardiologists were performed to identify themes for quantitative evaluation. 63 cardiologists undertook quantitative evaluation in an online survey. The interviews and surveys addressed (a) attitudes and behaviours regarding influenza immunisation and (b) preventative care in cardiology. RESULTS: One quarter (25.4%, n = 16) of cardiologists recommended influenza immunisation to all patients. Less than half (49.2%, n = 31) recommended influenza immunisation to secondary prevention patients. Almost 1/3 of respondents (31.7%, n = 20) were uncertain or unaware of the guidelines regarding influenza immunisation and patients with cardiac disease. Most cardiologists believed that general practitioners were responsible for ensuring patients received influenza immunisation (76.2%, n = 48). CONCLUSIONS: Despite reducing cardiovascular events in high-risk patients, influenza immunisation is not widely recommended by cardiologists. Further clinician education is needed to address the knowledge gaps which prevent recommendation and uptake of this guideline directed treatment.

Severe Adult Rotavirus Gastroenteritis: A Rare Case with Multi-Organ Failure and Critical Management.

BACKGROUND Infectious diarrheal illnesses such as rotavirus gastroenteritis are significant contributors to childhood morbidity and mortality, especially in low socio-demographic index regions. Major advances in addressing this issue include sanitation and clean water initiatives, as well as rotavirus immunization. In Australia, a robust vaccination program has significantly reduced childhood rotavirus infections, leading to decreased hospitalizations and mortality. However, cases of adult rotavirus still occur, and although these adult patients usually do not require interventional management, it is possible for them to present critically unwell and require resuscitation. CASE REPORT A previously well 65-year-old man presented to the Emergency Department febrile and hypotensive with severe diarrhea attributed to rotavirus. Clinically, he presented with mixed hypovolemic and septic shock. Despite initial resuscitation, he had multiple severe acute end-organ complications, secondary to poor perfusion. He acquired an acute kidney injury, type-2 myocardial infarction, and ischemic hepatic injury. The mainstay of management was rapid fluid resuscitation, continuous renal replacement therapy, and monitoring in the Intensive Care Unit; however, it was crucial to empirically treat for other causes of shock. CONCLUSIONS To the best of our knowledge, there is a scarcity of reports documenting the management of severe rotavirus gastroenteritis in adults. We recommend advising elderly patients to avoid contact with individuals with diarrheal illnesses, especially rotavirus gastroenteritis. Clinicians should also promote awareness regarding the potential severity of a disease that is typically managed conservatively, and be aware that intervention can be required in severe gastroenteritis.

Provocation testing in congenital long QT syndrome: A practical guide.

Congenital long QT syndrome (LQTS) is a hereditary cardiac channelopathy with an estimated prevalence of 1 in 2500. A prolonged resting QT interval corrected for heart rate (QTc interval) remains a key diagnostic component; however, the QTc value may be normal in up to 40% of patients with genotype-positive LQTS and borderline in a further 30%. Provocation of QTc prolongation and T-wave changes may be pivotal to unmasking the diagnosis and useful in predicting genotype. LQTS provocation testing involves assessment of repolarization during and after exercise, in response to changes in heart rate or autonomic tone, with patients with LQTS exhibiting a maladaptive repolarization response. We review the utility and strengths and limitations of 4 forms of provocation testing-stand-up test, exercise stress test, epinephrine challenge, and mental stress test-in diagnosing LQTS and provide some practical guidance for performing provocation testing. Ultimately, exercise testing, when feasible, is the most useful form of provocation testing when considering diagnostic sensitivity and specificity.