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The substantial and growing prevalence of heart failure, which remains the leading cause of preventable hospitalisation worldwide, has brought heart failure prevention into sharp focus. Although this condition has historically been characterised by impaired cardiac function, mounting evidence has underscored its complex and multisystem pathobiology. Epidemiological studies have indicated that other forms of cardiovascular disease, along with kidney and metabolic dysfunction, frequently and increasingly contribute to heart failure onset. Clinical trials have additionally demonstrated the power of several new pharmacotherapies to simultaneously modify cardiovascular, kidney, and metabolic (CKM) health. This convergence of epidemiology and therapy highlights deeply interconnected mechanisms of disease, identifying CKM diseases—and their pathophysiological and sociostructural antecedents—as important but often under-recognised targets for heart failure prevention. Herein, we illustrate that positioning heart failure prevention within the broader context of CKM health provides an actionable framework for patients, health-care professionals, health systems, communities, and policy makers.

Purpose of Review Lowering low-density lipoprotein (LDL)-cholesterol reduces cardiovascular risk. International lipid management guidelines recommend LDL-cholesterol goals or thresholds for initiating lipid-lowering therapy. However, contemporary real-world studies have shown that many high- and very high-risk patients are not attaining LDL-cholesterol goals and are not receiving intensive lipid-lowering therapies. In this review, recent examples of implementation strategies for optimising lipid management are discussed. Recent Findings Implementation studies are heterogenous in their strategies and design. At the clinician level, multidisciplinary team-based care (including multidisciplinary lipid clinics), pharmacist- or nurse-led interventions, decision-support algorithms or protocols, and educational initiatives have shown potential to improve lipid management. Various strategies to improve patient adherence to lipid-lowering therapies have demonstrated at least short-term efficacy, including education, shared decision-making, behavioural support and nudges. Electronic health records can be leveraged at low cost to identify patients requiring initiation or intensification of lipid-lowering therapies, but the optimal method of integrating automated alerts or nudges to influence decision-making requires further research. Moreover, telehealth and remote care delivery models can improve access to healthcare and facilitate lipid-lowering. Summary Multifaceted strategies with a systematic approach to targeting clinician, patient and system related factors can be successful in improving lipid management. Future implementation research should evaluate longer-term outcomes and follow implementation science theories, models and/or frameworks at all stages. By doing so, ongoing implementation studies will help researchers better understand the impact, sustainability and scalability of strategies, and where barriers and facilitators to lipid management may exist in other contexts.

Despite its commonality in routine clinical practice, the approach to a diagnosis of atherosclerotic coronary artery disease remains complex and, in part, contentious. The traditional dogma linking ischaemia to hard clinical outcomes has been questioned and reframed over the years; rather than being a predictor of hard clinical outcomes, the degree of ischaemia may simply be a marker of atherosclerotic disease burden. A renewed interest in the imaging of plaque burden has spawned the contemporary role of CT imaging for not only diagnosis and prognosis, but also for dictating downstream management. As the technology develops and evidence expands, decisions on investigative modalities remain centred around patient factors, local availability, test performance and cost. This review summarizes the available methods for diagnosis in the symptomatic patient and provides an overview of the current evidence behind functional and anatomical approaches.

Background Despite great promise, trials that ascertain patient clinical data from electronic health records (EHR), referred to here as “EHR-sourced” trials, are limited by uncertainty about how existing trial sites and infrastructure can be best used to operationalize study goals. Evidence is needed to support the practical use of EHRs in contemporary clinical trial settings. Main text We describe a demonstration project that used EHR data to complement data collected for a contemporary multi-center pharmaceutical industry outcomes trial, and how a central coordinating center supported participating sites through the technical, governance, and operational aspects of this type of activity. We discuss operational considerations related to site selection, data extraction, site performance, and data transfer and quality review, and we outline challenges and lessons learned. We surveyed potential sites and used their responses to assess feasibility, determine the potential capabilities of sites and choose an appropriate data extraction strategy. We designed a flexible, multimodal approach for data extraction, enabling each site to either leverage an existing data source, create a new research datamart, or send all data to the central coordinating center to produce the requisite data elements. We evaluated site performance, as reflected by the speed of contracting and IRB approval, total patients enrolled, enrollment yield, data quality, and compared performance by data collection strategy. Conclusion While broadening the type of sites able to participate in EHR-sourced trials may lead to greater generalizability and improved enrollment, sites with fewer technical resources may require additional support to participate. Central coordinating center support is essential to facilitate the execution of operational processes. Future work should focus on sharing lessons learned and creating reusable tools to facilitate participation of heterogeneous trial sites.

Recent analyses suggest the incidence of acute coronary syndrome is declining in high- and middle-income countries. Despite this, overall rates of non-ST-elevation myocardial infarction (NSTEMI) continue to rise. Furthermore, NSTEMI is a greater contributor to mortality after hospital discharge than ST-elevation myocardial infarction (STEMI). Patients with NSTEMI are often older, comorbid and have a high likelihood of multivessel coronary artery disease (MVD), which is associated with worse clinical outcomes. Currently, optimal treatment strategies for MVD in NSTEMI are less well established than for STEMI or stable coronary artery disease. Specifically, in relation to percutaneous coronary intervention (PCI) there is a paucity of randomized, prospective data comparing multivessel and culprit lesion-only PCI. Given the heterogeneous pathological basis for NSTEMI with MVD, an approach of complete revascularization may not be appropriate or necessary in all patients. Recognizing this, this review summarizes the limited evidence base for the interventional management of non-culprit disease in NSTEMI by comparing culprit-only and multivessel PCI strategies. We then explore how a personalized, precise approach to investigation, therapy and follow up may be achieved based on patient-, disease- and lesion-specific factors.

Non-adherence to medication is a global health problem with far-reaching individual-level and population-level consequences but remains unappreciated and under-addressed in the clinical setting. With increasing comorbidity and polypharmacy as well as an ageing population, cardiovascular disease and medication non-adherence are likely to become increasingly prevalent. Multiple methods for detecting non-adherence exist but are imperfect, and, despite emerging technology, a gold standard remains elusive. Non-adherence to medication is dynamic and often has multiple causes, particularly in the context of cardiovascular disease, which tends to require lifelong medication to control symptoms and risk factors in order to prevent disease progression. In this Review, we identify the causes of medication non-adherence and summarize interventions that have been proven in randomized clinical trials to be effective in improving adherence. Practical solutions and areas for future research are also proposed.In this Review, Bosworth and colleagues describe the causes of medication non-adherence, discuss interventions that have been clinically shown to improve adherence and identify areas for future research.

ObjectivesWe aimed to assess the healthcare costs and impact on the economy at large arising from emergency medical services (EMS) treated non-traumatic shock.DesignWe conducted a population-based cohort study, where EMS-treated patients were individually linked to hospital-wide and state-wide administrative datasets. Direct healthcare costs (Australian dollars, AUD) were estimated for each element of care using a casemix funding method. The impact on productivity was assessed using a Markov state-transition model with a 3-year horizon.SettingPatients older than 18 years of age with shock not related to trauma who received care by EMS (1 January 2015–30 June 2019) in Victoria, Australia were included in the analysis.Primary and secondary outcome measuresThe primary outcome assessed was the total healthcare expenditure. Secondary outcomes included healthcare expenditure stratified by shock aetiology, years of life lived (YLL), productivity-adjusted life-years (PALYs) and productivity losses.ResultsA total of 21 334 patients (mean age 65.9 (±19.1) years, and 9641 (45.2%) females were treated by EMS with non-traumatic shock with an average healthcare-related cost of $A11 031 per episode of care and total cost of $A280 million. Annual costs remained stable throughout the study period, but average costs per episode of care increased (Ptrend=0.05). Among patients who survived to hospital, the average cost per episode of care was stratified by aetiology with cardiogenic shock costing $A24 382, $A21 254 for septic shock, $A19 915 for hypovolaemic shock and $A28 057 for obstructive shock. Modelling demonstrated that over a 3-year horizon the cohort lost 24 355 YLLs and 5059 PALYs. Lost human capital due to premature mortality led to productivity-related losses of $A374 million. When extrapolated to the entire Australian population, productivity losses approached $A1.5 billion ($A326 million annually).ConclusionThe direct healthcare costs and indirect loss of productivity among patients with non-traumatic shock are high. Targeted public health measures that seek to reduce the incidence of shock and improve systems of care are needed to reduce the financial burden of this syndrome.

Background: Hypertriglyceridaemia is commonly encountered in clinical practice and is associated with an increased risk of cardiovascular disease and acute pancreatitis. General practitioners play a central role in treating patients with hypertriglyceridaemia, ultimately with the aim of preventing associated complications. Objective: The aim of this paper is to provide a contemporary approach to the management of patients with hypertriglyceridaemia in Australian primary care. Discussion: Hypertriglyceridaemia is often attributable to secondary causes, which should be identified and addressed. Healthy lifestyle modifications targeting diet, exercise, alcohol consumption and weight are fundamental. Statins should be prescribed according to cardiovascular risk assessment and can reduce triglyceride levels. Icosapent ethyl is subsidised on the Pharmaceutical Benefits Scheme and is recommended to reduce cardiovascular risk in statin-treated patients with cardiovascular disease and mild-to-moderate fasting hypertriglyceridaemia (1.7-5.6 mmol/L). In patients with severe hypertriglyceridaemia (>5.6 mmol/L), intensive triglyceride-lowering with lifestyle modifications and pharmacotherapy is recommended to reduce pancreatitis risk. Specialist referral should be considered for severe cases of hypertriglyceridaemia or when primary genetic causes are suspected.

Obesity and pericardial adipose tissue are independent risk factors for atrial fibrillation (AF) and adverse cardiac structural remodeling. The effect of weight reduction on pericardial adipose tissue and cardiac structure remains unknown. We prospectively performed cardiac magnetic resonance imaging on 87 participants with AF undergoing either structured weight management (intervention) or general lifestyle advice (control). We measured pericardial adipose tissue, atrial and ventricular volumes, and myocardial mass at baseline and 12 months. In total, 69 participants underwent baseline and 12-month follow-up cardiac magnetic resonance imaging (intervention n = 36 and controls n = 33). From baseline to 12 months, weight loss (kg, mean [95% CI]) was greater in the intervention group from 101.5 kg (97.2-105.8 kg) to 86.5 kg (81.2-91.9 kg) as compared with controls from 102.6 kg (97.2-108.1 kg) to 98.7 kg (91.0-106.3 kg) (time-group interaction P < .001). The intervention group showed a reduction in left atrial volumes (mL) from 105.0 mL (98.9-111.1 mL) to 96.4 mL (91.6-101.1 mL), whereas the change in the control group was from 108.8 mL (99.6-117.9 mL) to 108.9 mL (99.8-118.0 mL) (time-group interaction P < .001). There was a decline in pericardial adipose tissue (cm3) from 140.9 cm3 (129.3-152.4 cm3) to 118.8 cm3 (108.1-129.6 cm3) and myocardial mass (g) from 137.6 g (128.1-147.2 g) to 123.1 g (114.5-131.7 g) in the intervention group, whereas the change in the control group was from 143.2 cm3 (124.6-161.7 cm3) to 147.2 cm3 (128.9-165.4 cm3) for pericardial adipose tissue and 138.3 g (124.8-151.8 g) to 140.7 g (127.4-154.1 g) for myocardial mass (both variables, time-group interaction P < .001). Weight reduction results in favorable structural remodeling and a reduction in pericardial adipose tissue burden.

Anacetrapib, a cholesteryl ester transfer protein (CETP) inhibitor previously under development, exhibited an usually extended terminal half‐life and large food effect and accumulated in adipose tissue. Other CETP inhibitors have not shown such effects. Obicetrapib, a potent selective CETP inhibitor, is undergoing Phase III clinical development. Dedicated assessments were conducted in pre‐clinical and Phase I and II clinical studies of obicetrapib to examine the pharmacokinetic issues observed with anacetrapib. After 9 months of dosing up to 50 mg/kg/day in cynomolgus monkeys, obicetrapib was completely eliminated from systemic circulation and not detected in adipose tissue after a 13‐week recovery period. In healthy humans receiving 1–25 mg of obicetrapib, the mean terminal half‐life of obicetrapib was 148, 131, and 121 h at 5, 10, and 25 mg, respectively, and food increased plasma levels by ~1.6‐fold with a 10 mg dose. At the end of treatment in Phase II trials, mean plasma levels of obicetrapib ranged from 194.5 ng/mL with 2.5 mg to 506.3 ng/mL with 10 mg. Plasma levels of obicetrapib decreased by 92.2% and 98.5% at four and 15 weeks post‐treatment, respectively. Obicetrapib shows no clinically relevant accumulation, is minimally affected by food, and has a mean terminal half‐life of 131 h for the 10 mg dose. These data support once daily, chronic dosing of obicetrapib in Phase III trials for dyslipidemia management.