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.

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 99th 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 quantitate cTn in more than 50% of healthy individuals with a coefficient of variation of less than 10% at the 99th 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.

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.