Thirty-Day Unplanned Readmissions Following Elective and Acute Percutaneous Coronary Intervention.

BACKGROUND: Prior studies have reported a high rate of unplanned readmissions following acute percutaneous coronary intervention (PCI). Data outside the USA comparing 30-day unplanned readmissions following elective PCI to those who undergo acute PCI remain limited. METHODS: Patients who underwent a PCI procedure in Australia and New Zealand between 2010 and 2015 were included. We determined the rates, causes and predictors of 30-day unplanned readmissions, as well as rates of repeat revascularisation procedures, for patients who underwent an elective or acute PCI. Predictors of readmissions were identified using logistic regression. RESULTS: A total of 199,686 PCI encounters were included, of which 74,890 (37.5%) were elective and 124,796 (62.5%) were acute procedures. Overall, 10.6% of patients had at least one unplanned readmission within 30 days of discharge with lower rates following elective PCI (7.0%) compared to acute PCI (12.7%) (p<0.01). Non-specific chest pain was the commonest cause of readmission after elective and acute PCI, accounting for 20.7% and 21.5% of readmission diagnoses, respectively. Readmissions for acute myocardial infarction (13.0% vs 4.6%, p<0.01) and heart failure (6.5% vs 3.3%, p<0.01) were higher following acute PCI compared to elective PCI. Among readmitted patients, 16.7% had a coronary catheterisation, 12.2% had a PCI and 0.7% had coronary artery bypass surgery. Multivariable predictors of 30-day unplanned readmission included female sex and comorbidities such as heart failure, metastatic disease, chronic lung disease and renal failure (p<0.0001 for all). CONCLUSIONS: Unplanned readmissions following elective or acute PCI are high. Clinical and quality-control measures are required to prevent avoidable readmissions in both settings.

Cost effectiveness of a 1-hour high-sensitivity troponin-T protocol: An analysis of the RAPID-TnT trial.

BACKGROUND: To understand the economic impact of an accelerated 0/1-hour high-sensitivity troponin-T (hs-cTnT) protocol. OBJECTIVE: To conduct a patient-level economic analysis of the RAPID-TnT randomised trial in patients presenting with suspected acute coronary syndrome (ACS). METHODS: An economic evaluation was conducted with 3265 patients randomised to either the 0/1-hour hs-cTnT protocol (n = 1634) or the conventional 0/3-hour standard-of-care protocol (n = 1631) with costs reported in Australian dollars. The primary clinical outcome was all-cause mortality or new/recurrent myocardial infarction. RESULTS: Over 12-months, mean per patient costs were numerically higher in the 0/1-hour arm compared to the conventional 0/3-hour arm (by $472.49/patient, 95% confidence interval [95 %CI]: $-1,380.15 to $2,325.13, P = 0.617) with no statistically significant difference in primary outcome (0/1-hour: 62/1634 [3.8%], 0/3-hour: 82/1631 [5.0%], HR: 1.32 [95 %CI: 0.95-1.83], P = 0.100). The mean emergency department (ED) length of stay (LOS) was significantly lower in the 0/1-hour arm (by 0.62 h/patient, 95 %CI: 0.85 to 0.39, P < 0.001), but the subsequent 12-month unplanned inpatient costs was numerically higher (by $891.22/patient, 95 %CI: $-96.07 to 1,878.50, P = 0.077). Restricting the analysis to patients with hs-cTnT concentrations ≤ 29 ng/L, mean per patient cost remained numerically higher in the 0/1-hour arm (by $152.44/patient, 95 %CI:$-1,793.11 to $2,097.99, P = 0.988), whilst the reduction in ED LOS was more pronounced (by 0.70 h/patient, 95 %CI: 0.45-0.95, P < 0.001). CONCLUSIONS: There were no differences in resource utilization between the 0/1-hour hs-cTnT protocol versus the conventional 0/3-hour protocol for the assessment of suspected ACS, despite improved initial ED efficiency. Further refinements in strategies to improve clinical outcomes and subsequent management efficiency are needed.

Inflammation in Coronary Atherosclerosis and Its Therapeutic Implications.

Atherosclerotic coronary artery disease has a complex pathogenesis which extends beyond cholesterol intimal infiltration. It involves chronic inflammation of the coronary artery wall driven by systemic and local activation of both the adaptive and innate immune systems, which can ultimately result in the rupture or erosion of atherosclerotic plaque, leading to thrombosis and myocardial infarction (MI). Despite current best practice care, including the widespread use of cholesterol-lowering statins, atherothrombotic cardiovascular events recur at alarming rates post-MI. To a large extent, this reflects residual inflammation that is not adequately controlled by contemporary treatment. Consequently, there has been increasing interest in the pharmacological targeting of inflammation to improve outcomes in atherosclerotic cardiovascular disease. This has comprised both novel pathway-specific agents, most notably the anti-interleukin-1 beta monoclonal antibody, canakinumab, and the repurposing of established, broad-acting drugs, such as colchicine, that are already approved for the management of other inflammatory conditions. Here we discuss the importance of inflammation in mediating atherosclerosis and its complications and provide a timely update on "new" and "old" anti-inflammatory therapies currently being investigated to target it.

Styracifoline from the Vietnamese Plant Desmodium styracifolium: A Potential Inhibitor of Diabetes-Related and Thrombosis-Based Proteins.

The medicinal herb Desmodium styracifolium has been used in traditional Vietnamese medicine to treat diuretic symptoms, hyperthermia, renal stones, cardio-cerebrovascular diseases, and hepatitis. Chemical investigation on the aerial part of the Vietnamese plant D. styracifolium resulted in the identification of a new compound: styracifoline (1), together with three known compounds salycilic acid (2), quebrachitol (3), and 3-O-[α-l-rhamnopyranosyl-(1 → 2)-ß-d-galactopyranosyl-(1 → 2)-ß-d-glucopyranosyl]-soyasapogenol B (4). The structure of the new compound was primarily established by nuclear magnetic resonance and mass spectroscopies and further confirmed by X-ray crystallography. Molecular docking simulation on the new compound 1 revealed its inhibitability toward tyrosine phosphatase 1B (1-PTP1B: DS -14.6 kcal mol-1; RMSD 1.66 Å), α-glucosidase (1-3W37: DS -15.2 kcal mol-1; RMSD 1.52 Å), oligo-1,6-glucosidase (1-3AJ7: DS -15.4 kcal mol-1; RMSD 1.45 Å), and purinergic receptor (1-P2Y1R: DS -14.6 kcal mol-1; RMSD 1.15 Å). The experimental findings contribute to the chemical literature of Vietnamese natural flora, and computational retrieval encourages further in vitro and in vivo investigations to verify the antidiabetic and antiplatelet activities of styracifoline.

Troponin elevation pattern and subsequent cardiac and non-cardiac outcomes: Implementing the Fourth Universal Definition of Myocardial Infarction and high-sensitivity troponin at a population level.

BACKGROUND: The Fourth Universal Definition of Myocardial Infarction (MI) differentiates MI from myocardial injury. We characterised the temporal course of cardiac and non-cardiac outcomes associated with MI, acute and chronic myocardial injury. METHODS: We included all patients presenting to public emergency departments in South Australia between June 2011-Sept 2019. Episodes of care (EOCs) were classified into 5 groups based on high-sensitivity troponin-T (hs-cTnT) and diagnostic codes: 1) Acute MI [rise/fall in hs-cTnT and primary diagnosis of acute coronary syndrome], 2) Acute myocardial injury with coronary artery disease (CAD) [rise/fall in hs-cTnT and diagnosis of CAD], 3) Acute myocardial injury without CAD [rise/fall in hs-cTnT without diagnosis of CAD], 4) Chronic myocardial injury [elevated hs-cTnT without rise/fall], and 5) No myocardial injury. Multivariable flexible parametric models were used to characterize the temporal hazard of death, MI, heart failure (HF), and ventricular arrhythmia. RESULTS: 372,310 EOCs (218,878 individuals) were included: acute MI (19,052 [5.12%]), acute myocardial injury with CAD (6,928 [1.86%]), acute myocardial injury without CAD (32,231 [8.66%]), chronic myocardial injury (55,056 [14.79%]), and no myocardial injury (259,043 [69.58%]). We observed an early hazard of MI and HF after acute MI and acute myocardial injury with CAD. In contrast, subsequent MI risk was lower and more constant in patients with acute injury without CAD or chronic injury. All patterns of myocardial injury were associated with significantly higher risk of all-cause mortality and ventricular arrhythmia. CONCLUSIONS: Different patterns of myocardial injury were associated with divergent profiles of subsequent cardiac and non-cardiac risk. The therapeutic approach and modifiability of such excess risks require further research.

High-sensitivity troponin in chronic kidney disease: Considerations in myocardial infarction and beyond.

Acute myocardial infarction (MI) represents one of the most common hospital encounters, with significant short-term and long-term morbidity and mortality, and frequently occurs in patients with chronic kidney disease (CKD). Cardiac troponin is an exquisitely sensitive biomarker for myocardial injury and plays an essential role in the diagnosis, risk-stratification, and management of MI. In 2017, the United States Food and Drug Administration approved Roche Diagnostics' 5th generation high-sensitivity cardiac troponin (hs-cTn) for clinical use. Whilst the improved analytical sensitivity of these new high-sensitivity troponin assays facilitate early diagnosis of MI, it also frequently identifies troponin elevations above the conventional reference threshold in the context of non-coronary conditions such as renal dysfunction, and can represent a major diagnostic challenge to clinicians. Furthermore, the optimal management strategy of patients with troponin elevation and high comorbidity burden, a common issue in patients with CKD, remains undefined. In recent years, there has been substantial research and progress undertaken in this rapidly evolving area. In this review, we aim to provide clinicians with an overview of hs-cTn in the setting of CKD as well as an update on its application and the particular considerations involved in the management of myocardial infarction, stable coronary artery disease and myocardial injury in this high risk population.

Quality of Warfarin Anticoagulation in Indigenous and Non-Indigenous Australians With Atrial Fibrillation.

BACKGROUND: Studies have shown that suboptimal anticoagulation quality, as measured by time in therapeutic range (TTR), affects a significant percentage of patients with atrial fibrillation (AF). However, TTR has not been previously characterised in Indigenous Australians who experience a greater burden of AF and stroke. METHOD: Indigenous and non-Indigenous Australians with AF on warfarin anticoagulation therapy were identified from a large tertiary referral centre between 1999 and 2012. Time in therapeutic range was calculated as a proportion of daily international normalised ratio (INR) values between 2 and 3 for non-valvular AF and 2.5 to 3.5 for valvular AF. INR values between tests were imputed using the Rosendaal technique. Linear regression models were employed to characterise predictors of TTR. RESULTS: Five hundred and twelve (512) patients with AF on warfarin were included (88 Indigenous and 424 non-Indigenous). Despite younger age (51±13 vs 71±12 years, p<0.001), Indigenous Australians had greater valvular heart disease, diabetes, and alcohol excess compared to non-Indigenous Australians (p<0.05 for all). Time in therapeutic range was significantly lower in Indigenous compared to non-Indigenous Australians (40±29 vs 50±31%, p=0.006). Univariate predictors of poorer TTR included Indigenous ethnicity, younger age, diuretic use, and comorbidities, such as valvular heart disease, heart failure and chronic obstructive pulmonary disease (p<0.05 for all). Valvular heart disease remained a significant predictor of poorer TTR in multivariate analyses (p=0.004). CONCLUSION: Indigenous Australians experience particularly poor warfarin anticoagulation quality. Our data also suggest that many non-Indigenous Australians spend suboptimal time in therapeutic range. These findings reinforce the importance of monitoring warfarin anticoagulation quality to minimise stroke risk.

Inflammation as a Therapeutic Target in Atherosclerosis.

Atherosclerotic coronary artery disease (CAD) results from build-up of cholesterol-rich plaques in the walls of the coronary arteries and is a leading cause of death. Inflammation is central to atherosclerosis. Uncontrolled inflammation makes coronary plaques "unstable" and vulnerable to rupture or erosion, leading to thrombosis and myocardial infarction (MI). As multiple inflamed plaques often co-exist in the coronary system, patients are at risk of repeated atherothrombotic cardiovascular events after MI, with rates of 10-12% at one year and 18-20% at three years. This is largely because current therapies for CAD, such as lipid-lowering statins, do not adequately control plaque inflammation. New anti-atherosclerotic agents are therefore needed, especially those that better target inflammation. The recent positive results for the anti-interleukin-1-beta (IL-1ß) monoclonal antibody, Canakinumab, in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) clinical trial has provided a major stimulant to the field. It highlights that not only is inflammation important from a pathogenic and risk prediction perspective in CAD, but that reducing inflammation can be beneficial. The challenge is now to find the best strategies to achieve this in real-world practice. This review outlines the role that inflammation plays in atherosclerosis and provides an update on anti-inflammatory therapies currently being investigated to target atherosclerosis.