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The percutaneous management of chronic total occlusions (CTO) is a well-established sub-specialty of Interventional Cardiology, requiring specialist equipment, training, and techniques. The heterogeneity of approaches in CTO has led to the generation of multiple algorithms to guide operators in their management. The evidence base for management of CTOs has suffered from inconsistent descriptive and quantitative terminology in defining the nature of lesions and techniques utilised, as well as seemingly contradictory data about improvement in ventricular function, symptoms of angina, and mortality from large-scale registries and randomised controlled trials. Through this review, we explore the history of CTO management and its supporting evidence in detail, with an outline of limitations of CTO-percutaneous coronary intervention and a look at the future of this growing field within cardiology. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are effective therapies for numerous cancers, but have been associated with atherosclerotic cardiovascular disease (ASCVD). This study aimed to identify predictors for ASCVD events among cancer patients treated with ICIs and the cardiovascular risk factor (CVRF) control of those who developed ASCVD. A single-centre retrospective study of 366 cancer patients who received ICIs from 2018 to 2020 was performed. Demographic, baseline CVRF, cancer history, and ICI regimen data were obtained from medical records. The primary end point of ASCVD events was defined as myocardial infarction, coronary revascularisation, ischaemic stroke, or acute limb ischaemia. Cox proportional multivariable modelling and competing risks analysis were performed to assess ASCVD predictors. Descriptive analysis was performed to describe CVRF management among those who developed ASCVD events. Over a median follow-up of 3.4 years (2.8–4.3), 26 patients (7.1%) experienced 27 ASCVD events (seven myocardial infarction, one coronary revascularisation, 13 ischaemic stroke, and six acute limb ischaemia events). There were 226 (61.8%) cancer-related deaths and no cardiac deaths. History of ASCVD before ICI initiation was independently associated with ASCVD events on traditional Cox modelling (hazard ratio [HR] 4.00; 95% confidence interval [CI] 1.79–8.91; p<0.01) and competing risks analysis (HR 4.23; 95% CI 1.87–9.60; p<0.01). A total of 17 patients developed ASCVD events after ICI cessation (median 1.4 years). Among those with ASCVD events, 12 had prior ASCVD, 16 had hypertension, nine had hypercholesterolaemia, and four had diabetes, and nine were actively smoking. Variable prescription of cardiovascular preventative therapies was noted. History of ASCVD was associated with subsequent ASCVD events among patients treated with ICIs, which could occur even after active treatment was stopped. Identification and aggressive management of modifiable CVRFs should be considered throughout cancer survivorship in patients who received ICI treatment. [ABSTRACT FROM AUTHOR]

The management of adult patients with anomalous aortic origin of the right coronary artery (ARCA) from the left aortic sinus poses important challenges. The presence of symptoms or documented ischaemia, the anatomical characteristics of the ostium, and the course of the coronary determine decision-making. A retrospective review was performed of all cases of surgical management of ARCA at a single centre. The primary endpoints were mortality and myocardial infarction at 30 days. Secondary endpoints included recurrence of symptoms, freedom from re-intervention, and mortality during long-term follow-up. From October 2019 to August 2023, 15 adult patients underwent surgery for ARCA; 13 patients were included in this study (mean age 53.9±11.1 years; 10 female). A slit-like orifice, a long intramural segment, and an interarterial course were found in all patients. Twelve (12) patients (92.3%) were symptomatic: nine with angina, combined with dyspnoea on exertion in seven. One (1) patient had history of pre-syncope. One (1) patient presented with out-of-hospital cardiac arrest. All patients underwent formal unroofing of the orifice and intramural portion of the ARCA; five patients had a concomitant procedure. No 30-day mortality nor myocardial infarction was recorded. At a mean follow-up of 20.1±12.8 months, all patients were alive. One (1) patient (7.6%) developed recurrent dyspnoea; investigations showed no ischaemia. No repeated interventions were required. Surgical unroofing of anomalous coronary artery in the adult is safe and effective; correction of both the slit-like orifice and intramural portion of the anomaly provides a durable result in patients with ARCA. [ABSTRACT FROM AUTHOR]

Type 4a myocardial infarction (T4aMI), defined as myocardial injury associated with percutaneous coronary intervention (PCI), is associated with a poor prognosis and there is conflicting evidence regarding the effectiveness of remote ischaemic conditioning (RIC) in its prevention. This review aimed to determine the effect of RIC on stable and unstable angina patients. A systematic review was conducted in PubMed and Central database. Outcome measures were: changes in peak troponin, creatine kinase myocardial band (CKMB), C-reactive protein (CRP) level, incidence of T4aMI, and major adverse cardiovascular event (MACE). Data were meta-analysed and reported as standardised mean difference (SMD) and odds ratio (OR). Risk of bias was assessed with the Risk of Bias 2 (RoB2) tool. Fifteen studies with no significant risk of bias were included. Peak troponin level was reduced in the RIC group, particularly after excluding a study with low statin use, while CKMB and CRP levels resulted in a non-significant SMD between the groups. The incidence of T4aMI was significantly lower in the intervention group (OR 0.714; p=0.026); this finding was also seen in subgroups of elective PCI, pre-conditioning, and high statin use. Incidence of MACE also only reached statistically significant protective effects with OR <1 in similar subgroups. No substantial heterogeneity was found and the funnel plot did not show publication bias. Remote ischaemic conditioning in elective PCI patients has been proven to be potentially beneficial in reducing peak troponin levels and risk of T4aMI and MACE. [ABSTRACT FROM AUTHOR]

Cardiogenic shock (CS) is a serious complication of acute myocardial infarction (MI) and is associated with significant mortality. We describe a contemporary, real-world cohort of patients with ST-elevation MI (STEMI) and CS, including 30-day mortality and clinically relevant predictors of mortality. All patients presenting with STEMI who were treated with percutaneous coronary intervention (PCI) in New Zealand (2016 to 2020) were identified from the Aotearoa New Zealand All Cardiology Services Quality Improvement (ANZACS-QI) registry and stratified based on their Killip class on arrival to the cardiac catheterisation laboratory. Primary outcome was 30-day all-cause mortality. Multivariable analysis was used to identify predictors of mortality prior to PCI and to develop a mortality scoring system. In total, 6,649 patients were identified, including 192 (2.9%) Killip IV (CS) patients. Thirty-day mortality was 47.5% in patients with CS, 14.6% in those with heart failure without shock, and 3% in those without heart failure. Independent predictors of 30-day mortality for patients with CS were: estimated glomerular filtration rate <60 mL/min/1.73m2 (relative risk [RR] 1.89, 95% confidence interval [CI] 1.39–2.58), cardiac arrest (RR 1.54, 95% CI 1.15–2.06), diabetes (RR 1.31, 95% CI 1.01–1.70), female sex (RR 1.32, 95% CI 1.01–1.72), femoral arterial access (RR 1.42, 95% CI 1.06–1.90) and left main stem culprit (RR 2.16, 95% CI 1.65–2.84). A multivariable Shock score was developed which predicts 30-day mortality with good global discrimination (area under the curve 0.79, 95% CI 0.73–0.85). In this national cohort, the 30-day mortality for STEMI patients presenting with CS treated with PCI remains high, at nearly 50%. The ANZACS-QI Shock score is a promising tool for mortality risk stratification prior to PCI but requires further validation. [ABSTRACT FROM AUTHOR]

The Impella (Abiomed, Danvers, MA, USA) temporary percutaneous left ventricular assist device is increasingly used as mechanical circulatory support in patients with acute myocardial infarction–cardiogenic shock (AMICS) or those undergoing high-risk protected percutaneous coronary intervention (PCI). The optimal weaning regimen remains to be defined. We implemented a structured weaning protocol in a series of 10 consecutive patients receiving Impella support for protected PCI or AMICS treated with PCI in a high volume non-cardiac surgery centre. Weaning after revascularisation was titrated to native heart recovery using both haemodynamic and echocardiographic parameters. Ten patients (eight male, two female; aged 43–70 years) received Impella support for AMICS (80%) or protected PCI (20%). Cardiogenic shock was of Society for Cardiac Angiography & Interventions grade C–E of severity in 80%, and median left ventricular end-diastolic pressure was 31 mmHg. Protocol implementation allowed successful weaning in eight of 10 patients with a median support time of 29 hours (range, 4–48 hours). Explantation was associated with an increase in heart rate (81 vs 88 bpm; p=0.005), but no significant change in Cardiac Index (2.9 vs 2.9 L/min/m2), mean arterial pressure (79 vs 82 mmHg), vasopressor requirement (10% vs 10%), or serum lactate (1.0 vs 1.0). Median durations of intensive care and hospital stay were 3 and 6 days, respectively. At 30 days, the mortality rate was 20%, with median left ventricular ejection fraction of 40%. A structured and dynamic weaning protocol for patients with AMICS and protected PCI supported by the Impella device is feasible in a non-cardiac surgery centre. Larger studies are needed to assess generalisability of such a weaning protocol. [ABSTRACT FROM AUTHOR]

Adults <55 years of age comprise a quarter of all acute coronary syndromes (ACS) hospitalisations. There is a paucity of data characterising this group, particularly sex differences. This study aimed to compare the clinical and risk profile of patients with ACS aged <55 years with older counterparts, and measure short-term outcomes by age and sex. The study population comprised patients with ACS enrolled in the AUS-Global Registry of Acute Coronary Events (GRACE), Cooperative National Registry of Acute Coronary Syndrome Care (CONCORDANCE) and SNAPSHOT ACS registries. We compared clinical features and combinations of major modifiable risk factors (hypertension, smoking, dyslipidaemia, and diabetes) by sex and age group (20–54, 55–74, 75–94 years). All-cause mortality and major adverse events were identified in-hospital and at 6-months. There were 16,658 patients included (22.3% aged 20–54 years). Among them, 20–54 year olds had the highest proportion of ST-elevation myocardial infarction compared with sex-matched older age groups. Half of 20–54 year olds were current smokers, compared with a quarter of 55–74 year olds, and had the highest prevalence of no major modifiable risk factors (14.2% women, 12.7% men) and of single risk factors (27.6% women, 29.0% men), driven by smoking. Conversely, this age group had the highest proportion of all four modifiable risk factors (6.6% women, 4.7% men). Mortality at 6 months in 20–54 year olds was similar between men (2.3%) and women (1.7%), although lower than in older age groups. Younger adults with ACS are more likely to have either no risk factor, a single risk factor, or all four modifiable risk factors, than older patients. Targeted risk factor prevention and management is warranted in this age group. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the medium-term prognostic implications of cardiac magnetic resonance (CMR) imaging in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA). A systematic literature search of Embase, PubMed, and The Cochrane Library was performed. Eligible studies reported outcomes of CMR-assessed MINOCA with a mean follow-up period of >6 months. The primary endpoint was all-cause death. Secondary endpoints included cardiac death, reinfarction, and cardiovascular rehospitalisation. The pooled effect sizes with 95% confidence interval (CIs) were estimated using a random effect model. A total of 3,050 patients from twenty-one studies were included in the meta-analysis. The prevalence of myocarditis, "true" myocardial infarction, Takotsubo cardiomyopathy, and normal CMR imaging was 36%, 25%, 14%, and 19%, respectively. Pooled data showed that the annualised event rates for all-cause mortality, cardiac mortality, reinfarction, and cardiovascular rehospitalisation were 1.01% (95% CI 0.59%–1.51%), 0.06% (95% CI 0.00%–0.39%), 0.68% (95% CI 0.18%–1.38%), and 5.67% (95% CI 3.11%–8.85%), respectively. Compared with patients with a diagnosis of myocarditis on CMR, patients with Takotsubo cardiomyopathy (RR 7.11; 95% CI 3.04–16.66) and "true" myocardial infarction (RR 3.82; 95% CI 1.65–8.86) were associated with a significantly higher risk of all-cause mortality, whereas a similar risk of all-cause mortality was observed in patients with normal imaging (RR 1.01; 95% CI 0.28–3.59). No association was found between CMR diagnoses and the risk of secondary endpoints in MINOCA. In patients with MINOCA assessed by CMR, the overall absolute incidence rates of mortality and reinfarction were low. However, certain imaging diagnoses were associated with a higher risk of all-cause mortality, with most deaths attributed to non-cardiac causes. Additionally, these patients experienced a high burden of cardiovascular rehospitalisation. PROSPERO (CRD42022323615). [ABSTRACT FROM AUTHOR]

Recent clinical trials have demonstrated that sodium-glucose cotransporter 2 inhibitors (SGLT2i), which were previously only indicated in treatment of type 2 diabetes mellitus (T2DM), can markedly reduce heart failure hospitalisation (HFH), with less striking potential reductions in acute coronary syndromes and cardiac arrhythmias. To evaluate the impact of SGLT2i on cardiovascular outcomes in real-world practice, we performed a retrospective cohort analysis on South Australian (SA) data. A total of 842 individuals with T2DM receiving SGLT2i were identified from SA public hospitals between 2011 and 2019. Episodes of care were temporally matched with those of 3,128 individuals with T2DM not receiving SGLT2i (control). Baseline characteristics were adjusted using inverse probability treatment weighting. The incidence of cardiovascular events at 12 and 24 months was evaluated using coded (International Classification of Diseases, Tenth Revision, Australian Modification [ICD-10-AM]) data. The primary outcome of HFH was lower with SGLT2i use at 12 months (adjusted hazard ratio [HR adj ] 0.44; 95% confidence interval [CI] 0.29–0.68; p<0.001) and 24 months. There were also lower hospitalisations due to acute myocardial infarction (HR adj 0.42; 95% CI 0.21–0.85; p=0.015) and atrial or ventricular arrhythmias (HR adj 0.29; 95% CI 0.14–0.59; p=0.001), with no difference observed in hospitalisation due to ischaemic cerebrovascular events. There was no difference in all-cause mortality at 12 months but interestingly a higher rate at 24 months (HR adj 2.08; 95% CI 1.59–2.72; p<0.001). Despite this, similar reductions in cardiovascular outcomes were observed at 24 months. Use of SGLT2i in patients with T2DM in SA was associated with reductions in cardiovascular events even before their recent Pharmaceutical Benefits Scheme (PBS) listing for heart failure. Furthermore, this analysis supports that SGLT2i play a role not only in HFH reduction but also in reducing coronary and tachyarrhythmic events. This real-world evidence supports the use of SGLT2i as broadly protective cardiovascular drugs. [ABSTRACT FROM AUTHOR]

The aim was to increase cardiac rehabilitation (CR) uptake using a novel intervention, Rehabilitation Support Via Postcard (RSVP), among patients with acute myocardial infarction discharged from two major hospitals in Hunter New England Local Health District (HNELHD), New South Wales, Australia. The RSVP trial was evaluated using a two-armed randomised controlled trial design. Participants (N=430) were recruited from the two main hospitals in HNELHD, and enrolled and randomised to either the intervention (n=216) or control (n=214) group over a six-month period. All participants received usual care; however, the intervention group received postcards promoting CR attendance between January and July 2020. The postcard was ostensibly written as an invitation from the patient's admitting medical officer to promote timely and early uptake of CR. The primary outcome was CR attendance at outpatient HNELHD CR services in the 30-days post-discharge. Fifty-four percent (54%) of participants who received RSVP attended CR, compared to 46% in the control group; however this difference was not statistically significant (odds ratio [OR]=1.4, 95% confidence interval [CI]=0.9–2.0, p =0.11). Exploratory post-hoc analysis among four sub-groups (i.e., Indigeneity, gender, age and rurality), found that the intervention significantly increased attendance in males (OR=1.6, 95%CI=1.0–2.6, p =0.03) but had no significant impact on attendance for other sub-groups. While not statistically significant, postcards increased overall CR attendance by 8%. This strategy may be useful to increase attendance, particularly in men. Alternative strategies are necessary to increase CR uptake among women, Indigenous people, older people and people from regional and remote locations. [ABSTRACT FROM AUTHOR]

Diagnosis of acute myocardial infarction (AMI) requires a combination of elevated cardiac troponins, and clinical or echocardiographic evidence of coronary ischaemia. Identification of patients with a high likelihood of coronary plaque rupture (Type 1 myocardial infarction [MI]) is crucial as it is these patients for whom coronary intervention has been well-established to provide benefit and reduce subsequent coronary ischemic events. However, high-sensitivity cardiac troponin (hs-cTn) assays have increasingly identified patients with hs-cTn elevations not due to Type 1 MI where recommendations for ongoing care are currently limited. Understanding the profile and clinical outcomes for these patients may inform the development of an emerging evidence-base. Using two previously published studies (hs-cTnT study n=1,937, RAPID-TnT study n=3,270) and the Fourth Universal Definition of MI, index presentations of patients to South Australian emergency departments with suspected AMI, defined by high sensitivity cardiac troponin T (hs-cTnT) greater than the upper reference limit (14 ng/L) and without obvious corresponding ischaemia on electrocardiogram (ECG), were classified as either Type 1 MI (T1MI), Type 2 MI (T2MI), acute myocardial injury (AI), or chronic myocardial injury (CI). Patients with non-elevated hs-cTnT (defined as <14 ng/L) were excluded. Outcomes assessed included death, MI, unstable angina, and non-coronary cardiovascular events within 12 months. In total, 1,192 patients comprising 164 (13.8%) T1MI, 173 (14.5%) T2MI/AI, and 855 (71.7%) CI were included. The rate of death or recurrent acute coronary syndrome was greatest in patients with T1MI, but also occurred with moderate frequency in Type 2 MI/AI and CI (T1MI: 32/164 [19.5%]; T2MI/AI: 24/173 [13.1%]; CI:116/885 [13.6%]; p=0.008). Of all the deaths observed, 74% occurred among those with an initial index diagnostic classification of CI. After adjusting for age, gender and baseline comorbidities, the relative hazard ratios for non-coronary cardiovascular readmissions were similar across all groups: Type 2 MI/AI: 1.30 (95% confidence interval 0.99–1.72, p=0.062); CI: 1.10 (95% confidence interval 0.61–2.00, p=0.75). Non-T1MI accounted for the majority of patients presenting with elevated hs-cTnT without ischaemia on ECG. Patients with T1MI had the highest rates of death or recurrent AMI; however patients with T2MI/AI and CI experienced a substantial rate of non-coronary cardiovascular re-hospitalisations. [ABSTRACT FROM AUTHOR]

Guidelines recommend management with an invasive coronary angiogram in acute coronary syndromes (ACS), but most studies excluded patients with advanced chronic kidney disease (CKD). Our aims were to describe, in a comprehensive ACS cohort, the incidence of CKD, coronary angiography utilisation and outcomes, according to CKD stage. National datasets were used to identify hospitalised ACS patients (2013 to 2018) in the Northern region of New Zealand. CKD stage was obtained from a linked laboratory dataset. Outcomes included all-cause and cause-specific mortality, and non-fatal myocardial infarction, heart failure and stroke. Thirty-eight percent (38%) of the 23,432 ACS patients had CKD stage 3 or higher: 2,403 (10%) had stages 4/5 CKD. Overall 61% received coronary angiography. Compared with normal renal function the adjusted rate of coronary angiography was lower in CKD stage 3b (RR 0.75, 95% confidence intervals [CIs] 0.69, 0.82) and stages 4/5 without dialysis (RR 0.41, 95% CIs 0.36, 0.46), but similar for those on dialysis (RR 0.89, 95% CIs 0.77, 1.02). All-cause mortality (mean follow-up 3.2 years) increased with CKD stage from 8% (normal kidney function) to 69% (stages 4/5 CKD without dialysis). Compared with coronary angiography, the adjusted all-cause and CVD mortality risks were higher in those without coronary angiography, except for those on dialysis, where these risks converged. Invasive management fell below an eGFR of 45 mL/min (≤ stage 3b), and nearly half of all deaths occurred in these patients. Clinical trials are needed to assess the role of invasive management in ACS and advanced CKD. [ABSTRACT FROM AUTHOR]

Aortic valve (AV) thrombosis is an uncommon but ominous complication in patients managed with mechanical circulatory support (MCS) devices. In this systematic review, we summarised the data on clinical presentations and outcomes in such patients. We searched articles on PubMed and Google Scholar, reporting at least one adult patient with aortic thrombosis on MCS support and where the individual patient data could be extracted. We grouped the patients by the type of MCS (temporary or durable), and the type of the AV (prosthetic, surgically modified, or native) We identified reports on six patients with aortic thrombus on short-term MCS, and on 41 patients on durable left ventricular assist devices (LVADs). On temporary MCS, AV thrombus typically causes no symptoms and is found incidentally pre- or intra-operatively. For those with durable MCS, the occurrence of aortic thrombus forming on prosthetic or surgically modified valves appears to be more related to the intervention on the valve, rather than from the presence of LVAD. The mortality in this group was 18%. In patients with native AV on durable LVAD support, 60% of patients presented with acute myocardial infarction, acute stroke, or acute heart failure, and mortality in this cohort was 45%. In terms of management, heart transplantation was most successful. While the outcomes of aortic thrombosis were good in patients where temporary MCS was used in the setting of aortic valve surgery, patients with native AV who develop this complication on durable LVAD have high morbidity and mortality. Cardiac transplantation should be strongly considered in eligible candidates because other therapies provide inconsistent results. [ABSTRACT FROM AUTHOR]

Heart failure is an important cause of morbidity and mortality. More than 20 years ago, special interest was drawn to cell therapy as a means of restoring damaged hearts to working condition. But progress has not been straightforward as many of our initial assumptions turned out to be wrong. In this review, we critically examine the last 20 years of progress in cardiac cell therapy and focus on several of the popular beliefs surrounding cell therapy to illustrate the mechanisms involved in restoring heart function after cardiac injury. Are they true or false? [ABSTRACT FROM AUTHOR]

Ischaemic heart disease is the primary cause of death worldwide with myocardial infarction (MI) contributing to significant morbidity and mortality. The human heart has a limited capacity to regenerate and the significant loss of cardiomyocytes after MI can overwhelm this limited innate regenerative capability. This is in part compensated for by the creation of collagen-rich scar tissue. Therapeutic angiogenesis is an exciting prospect that can assist cardiac regeneration after MI with various approaches having been explored. This review will focus on results from clinical growth factor trials, and the lack of clinical translation. Inconsistencies in results from these may be due to heterogeneity within patient selection and an incomplete understanding of therapeutic differences between isoforms of active agents. The technology used has also evolved with recombinant protein and, subsequently, gene therapy being utilised. Innovative therapeutic designs, such as combinatorial therapies, might help to resolve these issues in the future. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality worldwide and the primary underlying risk factor for heart failure. Despite decades of research and clinical trials, there are no drugs currently available to prevent organ damage from acute ischaemic injuries of the heart. In order to address the increasing global burden of heart failure, drug, gene, and cell-based regeneration technologies are advancing into clinical testing. In this review we highlight the burden of disease associated with AMI and the therapeutic landscape based on market analyses. New studies revealing the role of acid-sensitive cardiac ion channels and other proton-gated ion channels in cardiac ischaemia are providing renewed interest in pre- and post-conditioning agents with novel mechanisms of action that may also have implications for gene- and cell-based therapeutics. Furthermore, we present guidelines that couple new cell technologies and data resources with traditional animal modelling pipelines to help de-risk drug candidates aimed at treating AMI. We propose that improved preclinical pipelines and increased investment in drug target identification for AMI is critical to stem the increasing global health burden of heart failure. [ABSTRACT FROM AUTHOR]

Clinical presentation of Takotsubo Syndrome (TS) mimics acute coronary syndrome (ACS). A score to differentiate TS from ACS would be helpful to facilitate appropriate investigation and management. We have previously developed a clinical score (NSTE-Takotsubo Score) to distinguish women with non-ST-segment elevation myocardial infarction (NSTEMI) from TS with non-ST-segment elevation (NSTE-TS). This study sought to assess the diagnostic validity of this score in an external validation cohort. The external cohort consisted of women with NSTE-TS (n=110) and NSTEMI (n=113) from two major tertiary hospitals in New Zealand. The five variables in the arithmetic score (range -6 to +5) and their relative weights are: T-wave inversion (TWI) in ≥6 leads (3 points), recent stress (2 points), diabetes mellitus (DM) (-1 point), prior cardiovascular disease (CVD) (-2 points) and presence of ST depression (-3 points). Two clinicians blinded to the diagnoses calculated the score using clinical and electrocardiogram (ECG) data on day 1 post-admission. The NSTE-Takotsubo Score discriminated well between NSTE-TS and NSTEMI. The sensitivity and specificity of a score ≥1 to distinguish NSTE-TS from NSTEMI were 78% and 85%, respectively. The area under the receiver operator curve was 0.78 (95% CI 0.72 to 0.84). In an external validation cohort, the NSTE-Takotsubo Score was easy to apply and useful to identify women likely to have NSTE-TS on day 1 post-admission. [ABSTRACT FROM AUTHOR]

Previous studies examining temporal variations in cardiovascular care have largely been limited to assessing weekend and after-hours effects. We aimed to determine whether more complex temporal variation patterns might exist in chest pain care. This was a population-based study of consecutive adult patients attended by emergency medical services (EMS) for non-traumatic chest pain without ST elevation in Victoria, Australia between 1 January 2015 and 30 June 2019. Multivariable models were used to assess whether time of day and week stratified into 168 hourly time periods was associated with care processes and outcomes. There were 196,365 EMS chest pain attendances; mean age 62.4 years (standard deviation [SD] 18.3) and 51% females. Presentations demonstrated a diurnal pattern, a Monday–Sunday gradient (Monday peak) and a reverse weekend effect (lower rates on weekends). Five temporal patterns were observed for care quality and process measures, including a diurnal pattern (longer emergency department [ED] length of stay), an after-hours pattern (lower angiography or transfer for myocardial infarction, pre-hospital aspirin administration), a weekend effect (shorter ED clinician review, shorter EMS off-load time), an afternoon/evening peak period pattern (longer ED clinician review, longer EMS off-load time) and a Monday–Sunday gradient (ED clinician review, EMS offload time). Risk of 30-day mortality was associated with weekend presentation (Odds ratio [OR] 1.15, p=0.001) and morning presentation (OR 1.17, p<0.001) while risk of 30-day EMS reattendance was associated with peak period (OR 1.16, p<0.001) and weekend presentation (OR 1.07, p<0.001). Chest pain care demonstrates complex temporal variation beyond the already established weekend and after-hours effect. Such relationships should be considered during resource allocation and quality improvement programs to improve care across all days and times of the week. [ABSTRACT FROM AUTHOR]

The pleiotropic action of ticagrelor, with effects in addition to platelet inhibition, has been shown to improve endothelial function in patients with coronary artery disease. These positive effects are possibly adenosine mediated. This study investigated the association of ticagrelor therapy and coronary artery flow reserve in survivors of myocardial infarction (MI). This was an exploratory, cross-sectional, open substudy of PROFLOW. High-risk individuals with a history of MI were identified. Coronary flow reserve (CFR) was measured non-invasively in the left anterior descending artery using transthoracic Doppler echocardiography. Coronary flow velocity was measured at rest and at maximal flow after induction of hyperaemia by intravenous infusion of adenosine at 140 μg/kg/min. Patients receiving ticagrelor (n=75) were compared with those not receiving ticagrelor (n=506), using simple and multiple linear regression models. Most patients in both groups were treated with aspirin (97% in the ticagrelor and 94% in the non-ticagrelor group). Adjustment for traditional risk factors was conducted. The mean age at study inclusion was 68.5±6.8 years, and most patients were male (81.8%). The simple linear regression analysis showed ticagrelor treatment to be significantly associated with increased CFR: ticagrelor 2.95±0.76 (mean±SD), non-ticagrelor 2.70±0.77, (coefficient 0.25; 95% CI 0.063–0.438; p=0.009). This association was significant in two of the three multiple linear regression models with increasing numbers of variables: Model 1 (0.28; 0.06–0.50; p=0.014), Model 2 (0.26; 0.03–0.48; p=0.025), and borderline significant in Model 3 (0.21; –0.01 to 0.43; p=0.058). Ticagrelor treatment was associated with increased CFR in this high-risk population. Increased CFR may be a clinically important therapeutic effect of ticagrelor in addition to platelet inhibition. [ABSTRACT FROM AUTHOR]

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. 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. 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). Unplanned readmissions following elective or acute PCI are high. Clinical and quality-control measures are required to prevent avoidable readmissions in both settings. [ABSTRACT FROM AUTHOR]

The National Heart Foundation of Australia's (NHFA) Warning Signs campaign ran between 2010 and 2013. This study examines trends in Australian adults' ability to name heart attack symptoms during the campaign and in the years following. Using the NHFA's HeartWatch data (quarterly online surveys) for adults aged 30–59 years, we conducted an adjusted piecewise regression analysis comparing trends in the ability to name symptoms during the campaign period plus one year lag (2010–2014) to the post-campaign period (2015–2020) Over the study period, there were 101,936 Australian adults surveyed. Symptom awareness was high or increased during the campaign period. However, there was a significant downward trend in each year following the campaign period for most symptoms (e.g., chest pain: adjusted odds ratio [AOR] =0.91, 95%CI: 0.56–0.80; arm pain: AOR=0.92, 95%CI: 0.90–0.94). Conversely, the inability to name any heart attack symptom increased in each year following the campaign (3.7% in 2010 to 19.9% in 2020; AOR=1.13, 95%CI: 1.10–1.15); these respondents were more likely to be younger, male, have less than 12 years of education, identify as Aboriginal and/or Torres Strait Islander Peoples, speak a language other than English at home and have no cardiovascular risk factors. Awareness of heart attack symptoms has decreased in the years since the Warning Signs campaign in Australia, with 1 in 5 adults currently unable to name a single heart attack symptom. New approaches are needed to promote and sustain this knowledge, and to ensure people act appropriately and promptly if symptoms occur. [ABSTRACT FROM AUTHOR]

Recent studies suggest that the risk factor profile of patients presenting with ST elevation myocardial infarction (STEMI) is changing. The aim is to determine if there has been a shift of cardiovascular risk factors to cardiometabolic causes in the first presentation STEMI population. We analysed data from a STEMI registry from a large tertiary referral percutaneous coronary intervention centre to determine the prevalence and trends of the modifiable risk factors of hypertension, diabetes, smoking and hypercholesterolaemia. Consecutive first presentation STEMI patients between January 2006 to December 2018. Among the 2,366 patients included (mean age 59, SD 12.66, 80% male) the common risk factors were hypertension (47%), hypercholesterolaemia (47%) current smoking (42%) and diabetes (27%). Over the 13 years, patients with diabetes (20% to 26%, OR 1.09 per year, CI 1.06–1.11, p<0.001) and patients with no modifiable risk factors increased (9% to 17%, OR 1.08, CI 1.04–1.11, p<0.001). Concurrently there was a fall in prevalence of hypercholesterolaemia, (47% to 37%, OR 0.94 per year, CI 0.92–0.96, p<0.001) and smoking (44% to 41%, OR 0.94, CI 0.92–0.96, p<0.001) but no significant change in rates of hypertension (53% to 49%, OR 0.99, CI 0.97–1.01, p=0.25). The risk factor profile of first presentation STEMI has changed over time with a reduction in smoking and a concurrent rise in patients with no traditional risk factors. This suggests the mechanism of STEMI may be changing and further investigation of potential causal factors is warranted for the prevention and management of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Green space reduces cardiovascular disease (CVD) risk, but few studies examine what types of green space matter, which is an important consideration as cities densify and apartments become more common. Participants were 86,727 in houses and 17,998 in apartments from the 45 and Up Study (Sax Institute) baseline survey with 10 years of linked hospitalisation and death data used to define: (i) all-cause; and (ii) CVD-mortality; (iii) fatal and non-fatal CVD events; and (iv) acute myocardial infarction (AMI). Associations with total green space, tree canopy cover and open grass within 1.6 km buffers were assessed using survival analysis adjusted for potential confounders. Mean percentage green space indicators were all higher among participants in houses than in apartments. Among residents of houses, a 10% increase in total green space was associated with reduced risk of CVD mortality (HR 0.97, 95%CI 0.95–1.00). A 10% increase in tree canopy cover was associated with reduced risks of all-cause mortality (HR 0.97, 95%CI 0.95–0.99), CVD mortality (HR 0.96, 95%CI 0.93–0.98), and fatal or non-fatal AMI (HR 0.93, 95%CI 0.89–0.96). In contrast, a 10% increase in open grass was associated with an increased risk of fatal or non-fatal AMI (HR 1.15, 95%CI 1.09–1.20) in residents of houses. Among residents of apartments, a 10% increase in total green space was associated with increased risk of all-cause mortality (HR 1.04, 95%CI 1.00–1.08) and CVD mortality (HR 1.03, 95%CI 1.00–1.08). Urban reforestation may be a population-level intervention to protect cardiovascular health, especially for people living in houses. The intersection of urban greening and cardiovascular health among residents of apartments warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Air pollution is a consequence of industrial development that is exacerbated as a result of population growth, and urbanisation.Aim: The goal of the study is to investigate the effects of air pollution on the number of cases of acute myocardial infarction (AMI) according to gender using the Zero-inflated Poisson Regression model in Hamadan, Iran.Methods: The study used an ecological design, and data collected from March 2016 to September 2020 in Hamadan were included. The intended response was the number of cases of AMI recorded in the investigated period. The time lag of the pollutants was used to investigate the effect of air pollution on the number of AMIs.Results: The number of AMI recorded for men and women was 1,195 and 553, respectively. The average age (±SD) for men and women was 64.60 (±12.27) and 70.98 (±11.79) years, respectively. According to the air quality index in Hamadan, the values of particulate matter (PM)2.5, SO2, O3, and CO were below moderate levels. Also, according to NO2 and PM10, the air quality index of Hamadan was in the very unhealthy mode just for 2 and 3 days, respectively. The O3 and NO2 are significant positive effects on AMI among men. But, PM2.5, PM10, and SO2 are negative impacts on hospitalisation in men due to AMI. For women, PM2.5 and O3 had positive effects on AMI. But, NO2 and PM10 had a significant negative impact on hospitalisation in women during different time lags.Conclusions: The results of the study showed that if the analyses are based on gender, the responses to pollutants are different and hence the stratified analysis is important. [ABSTRACT FROM AUTHOR]

Coronary artery calcification is prevalent in coronary heart disease with its progression being predictive of future adverse cardiac events. Its presence is considered to be a marker of interventional procedural complexity. Several adjunctive percutaneous coronary intervention tools, such as modifying balloons, atherectomy devices and intravascular lithotripsy, now exist to successfully treat calcified lesions. In this state-of-the-art review, a step-wise progression of strategies is described to modify coronary plaque, from well-recognised techniques to techniques that should only be considered when standard manoeuvres have proven unsuccessful. Technology has advanced greatly over the past few decades and we discuss how future technologies might shape percutaneous intervention. [ABSTRACT FROM AUTHOR]

Objective: Cardiac troponins (cTn) have been used historically to estimate infarct size in ST elevation myocardial infarction (STEMI). Within a resource constrained health care environment, cTn could therefore be used for prioritisation of patients for cardiac imaging, in particular echocardiography. We aimed to determine how useful routinely collected cTn would be in predicting significant left ventricular (LV) impairment.Methods: All patients in the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry with their first episode of STEMI between January 2013 and November 2018, who had high sensitivity troponin T measured, were included. We excluded patients with no left ventricular ejection fraction (LVEF) assessment, known LV dysfunction, or prior myocardial infarction.Results: In total, 3,698 patients were included in the analysis. A higher mean hsTnT (admission and peak) was seen in patients with more severely impaired LV function but there was significant overlap in the range of hsTnT between the different LVEF categories. Cardiac troponins demonstrated poor discriminative ability to either predict or exclude significant LV impairment (LVEF <40%). At an optimal cutpoint of 3,405 ng/L, peak hsTnT had a sensitivity of 56.5% (95% confidence interval [CI] 42-62%), a specificity of 65.3% (95% CI 62-79%) and an area under the receiver operating curve of 0.62 (95% CI 0.60-0.64).Conclusion: This is the largest study comparing clinically measured troponin levels and LV function in patients presenting with STEMI. A definite, but weak, association was seen between peak troponin and the degree of LV dysfunction, with significant overlap in troponin levels between levels of myocardial dysfunction. Routinely acquired troponin is not suitable for clinical use as a method of prioritising patients for cardiac imaging. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Low ankle-brachial index (ABI) is an established risk factor for long-term cardiovascular outcomes in patients with acute myocardial infarction (AMI), and brachial-ankle pulse wave velocity (ba-PWV) may also be a risk factor. However, there is a significant overlap between low ABI and high ba-PWV. The purpose of this retrospective study was to examine whether increased ba-PWV was associated with long-term clinical outcomes in AMI patients with normal ABI.Methods: We included 932 AMI patients with normal ABI and divided them into the high PWV group (≥1,400 cm/s; n=646) and the low PWV group (<1400 cm/s; n=286) according to the ba-PWV values measured during the AMI hospitalisation. The primary endpoint was the major adverse cardiovascular events (MACE) defined as the composite of all-cause death, nonfatal myocardial infarction, and hospitalisation for heart failure.Results: During the median follow-up duration of 541 days (Q1: 215 days-Q3: 1,022 days), a total of 154 MACE were observed. The Kaplan-Meier curves showed that MACE was more frequently observed in the high PWV group than in the low PWV group (p<0.001). The multivariate Cox hazard analysis revealed that high ba-PWV was significantly associated with MACE (hazard ratio [HR] 1.587; 95% CI 1.002-2.513; p=0.049) after controlling multiple confounding factors.Conclusions: High ba-PWV was significantly associated with long-term adverse events in AMI patients with normal ABI. Our results suggest the usefulness of PWV as a prognostic marker in AMI with normal ABI. [ABSTRACT FROM AUTHOR]

Background: Recently, the impact of the lack of standard modifiable risk factors, including hypertension, diabetes, dyslipidaemia, and current smoking, has been investigated in ST-segment elevation myocardial infarction (MI). The present study aimed to evaluate clinical characteristics and prognosis of the patients with no standard risk factors in acute MI.Methods: This bi-centre registry included 1,093 patients with acute MI undergoing percutaneous coronary intervention. The participants were divided into two groups: patients having at least one of the four standard risk factors and those having none of the risk factors. The study endpoints included major adverse cardiovascular events (MACE) (death, recurrent MI, and stroke) and major bleeding events during hospitalisation. Any MACE and major bleeding events after discharge were also evaluated as an exploratory analysis.Results: Of 1,093 patients, 64 (5.9%) had none of the four standard risk factors. The patients with no standard risk factors were likely to present with Killip class IV and cardiac arrest. The rate of in-hospital MACE was higher in patients with no risk factors than in their counterparts (25.0% vs 9.9%; p<0.001), whereas the incidence of in-hospital major bleeding was not significantly different between the two groups (9.4% vs 6.7%; p=0.44). Active cancer and autoimmune/inflammatory diseases were often found in patients with no standard risk factors. After discharge, no significant differences were observed in the risks of MACE and major bleeding events between the two groups.Conclusions: No standard modifiable risk factors were not uncommon and were associated with poor short-term outcomes in patients with acute MI. [ABSTRACT FROM AUTHOR]

Background: Troponin positive chest-pain with unobstructed coronary arteries (TPCP-UCA), occurs in 6% of cases of patients presenting with acute coronary syndrome (ACS). Whilst TPCP-UCA patients are known to be younger with less cardiovascular risk factors when compared to obstructive coronary disease (MICAD), no validated methods exist to reliably delineate these two conditions prior to coronary angiography.Methods: We analysed 142 patients with MICAD and 127 patients with TPCP-UCA from 2015 to 2019. Several key predetermined clinical, biochemical and electrocardiograph (ECG) parameters, as well as Global Registry of Acute Coronary Events (GRACE) score, were collected for all patients. All TPCP-UCA patients underwent cardiac magnetic resonance imaging (cMRI).Results: Patients with TPCP-UCA were younger than MICAD (44 vs 68 yrs, p<0.01), and with less cardiac risk factors of hypertension (31% vs 68%, p<0.01), hypercholesterolaemia (23% vs 56%, p<0.01), diabetes (11% vs 45%, p<0.01), prior ischaemic heart disease (8% vs 42%, p<0.01) and smoking history (29% vs 50%, p<0.01). Peak troponin (MICAD 2,084.5 ng/L vs TPCP-UCA 847.0 ng/L, p=0.02), serial-to-initial troponin ratio (MICAD 13.5 vs TPCP-UCA 5.1, p<0.01), and peak-to-initial troponin ratio (MICAD 69.6 vs TPCP-UCA 14.0, p<0.01) were all higher in the MICAD group. GRACE scores were significantly different across the two cohorts (TPCP UCA 74 vs MICAD 106, p<0.01), with a receiver operator characteristic (ROC) curve statistic of 0.794 (95% CI 0.739-0.850). On ECG analysis, MICAD had greater prevalence and sum of ST depression (40% vs 19% p<0.01; 1.6 mm vs 0.44 mm, p<0.01) and T wave inversion (37% vs 17%, p<0.01), whilst TPCP-UCA had greater presence of PR depression (20% vs 3% p<0.01), and longer repolarisation (T wave peak to end 89 ms vs 83 ms, p=0.04; T wave peak to end/corrected QT 0.208 ms vs 0.193 ms, p=0.03). All TPCP-UCA patients underwent cMRI. Aetiology was found in 82% of cases, with the leading diagnosis being myocarditis (58%), followed by infarction (8%), whilst 18% had a normal cMRI.Conclusions: TPCP-UCA is an important differential for patients presenting with ACS, and has several key demographic, biochemical and electrocardiographic differences. The present findings are hypothesis generating, thus prospective studies are required to determine and validate potential clinical utility. [ABSTRACT FROM AUTHOR]

Background: Limited data exist regarding the significance of peripheral arterial disease (PAD) in patients with acute coronary syndrome (ACS).Methods: We evaluated 16,922 consecutive ACS patients who were prospectively included in a national ACS registry. The co-primary endpoint included 30 days major adverse cardiovascular event (MACE) (re-infarction, stroke, and/or cardiovascular death) and 1-year mortality.Results: PAD patients were older (70±11 vs 63±13; p<0.01), male predominance (80% vs 77%; p=0.01), and more likely to sustain prior cardiovascular events. PAD patients were less likely to undergo coronary angiography (69% vs 83%; p<0.001) and revascularisation (80% vs 86%; p<0.001). Patients with PAD were more likely to sustain 30-day MACE (22% vs 14%; p<0.001) and mortality (10% vs 4.4%; p<0.001), as well as re-hospitalisation (23% vs 19%; p=0.001). After adjusting for potential confounders, PAD remained an independent predictor of 30-day MACE (odds ratio [OR], 1.6 [95% confidence interval (CI), 1.24-2.06]). Patients with compared to those without PAD had 2.5 times higher 1-year mortality rate (22% vs 9%; p<0.001). Co-existence of PAD remained an independent predictor of 1-year mortality after adjustment for potential confounders by multivariable regression analysis (OR, 1.62; 95% CI, 1.4-1.9). PAD was associated with a significant higher 1-year mortality rate across numerous sub-groups of patients including type of myocardial infarction (ST-elevation myocardial infarction vs non-ST-elevation myocardial infarction), and whether the patient underwent revascularisation.Conclusions: Acute coronary syndrome with concomitant PAD represents a high-risk subgroup that warrants special attention and a more tailored approach. [ABSTRACT FROM AUTHOR]

Background: Clopidogrel in combination with aspirin after acute coronary syndromes (ACS) reduces recurrent ischaemic events compared to aspirin alone. Further reductions in events have been demonstrated when clopidogrel is replaced by ticagrelor or prasugrel albeit with increases in bleeding. There are few studies documenting the patterns of use of P2Y12 inhibitors or their association with outcomes in the Australian population.Aims: To describe the patterns of use of each P2Y12 inhibitor and to determine the associations between initial P2Y12 inhibitor use and outcomes.Methods: Data were extracted from Cooperative National Registry of ACS, Guideline Adherence and Clinical Events (CONCORDANCE)-a prospective database of patients presenting to 43 sites across Australia with ACS. Patients were stratified based on first antiplatelet agent received. Baseline clinical characteristics were compared between these patient groups and hospital investigations, management as well as in-hospital and 12 months outcomes (death, a composite of cardiac-related death, myocardial infarction, and stroke, and major bleeding) were compared between the three treatment cohorts after adjustment for differences in baseline characteristics.Results: Mean ages of the clopidogrel (n=7,537), ticagrelor (n=1,878), and prasugrel (n=347) cohorts were 65, 63, and 58 yrs respectively (p<0.0001), the mean Global Registry of Acute Coronary Events (GRACE) risk scores were 107, 104, and 102 (p=0.0016). The ticagrelor and prasugrel cohorts were more likely to receive percutaneous coronary intervention (PCI) (clopidogrel 52%, ticagrelor 66%, prasugrel 88%, p<0.0001), and evidence based medications (≥4 guideline indicated medications: clopidogrel 76%, ticagrelor 82%, prasugrel 93%, p<0.0001). Patients treated with ticagrelor and prasugrel were less likely to experience in-hospital death (clopidogrel 2.5%, ticagrelor 1.4%, prasugrel 1.2%, p=0.05), major adverse cardiac events (MACE) (clopidogrel 5.1%, ticagrelor 3.0%, prasugrel 3.5% [p=0.01]), or bleeding (clopidogrel 8.4%, ticagrelor 4.6%, prasugrel 7.5% [p<0.001]) compared to clopidogrel. These differences were no longer apparent after multivariable adjustment. There was no difference in outcomes between cohorts at 12 months.Conclusions: In Australia, ticagrelor and prasugrel are used in younger patients who are more likely to undergo percutaneous coronary intervention (PCI) and receive evidence based therapy. Patients receiving clopidogrel were more likely to experience in hospital ischaemic or bleeding events but this was explained by their higher baseline risk. Selection of therapy was not associated with any difference in outcomes at 12-month follow-up, but our findings suggest there is room for improvement towards guideline-driven usage of P2Y12 inhibitors. [ABSTRACT FROM AUTHOR]

Toll-like receptor 3 (TLR3) is an important member of the innate immune response receptor toll-like receptors (TLRs) family, which plays a vital role in regulating immune response, promoting the maturation and differentiation of immune cells, and participating in the response of pro-inflammatory factors. TLR3 is activated by pathogen-associated molecular patterns and damage-associated molecular patterns, which support the pathophysiology of many diseases related to inflammation. An increasing number of studies have confirmed that TLR3, as a crucial medium of innate immunity, participates in the occurrence and development of cardiovascular diseases (CVDs) by regulating the transcription and translation of various cytokines, thus affecting the structure and physiological function of resident cells in the cardiovascular system, including vascular endothelial cells, vascular smooth muscle cells, cardiomyocytes, fibroblasts and macrophages. The dysfunction and structural damage of vascular endothelial cells and proliferation of vascular smooth muscle cells are the key factors in the occurrence of vascular diseases such as pulmonary arterial hypertension, atherosclerosis, myocardial hypertrophy, myocardial infarction, ischaemia/reperfusion injury, and heart failure. Meanwhile, cardiomyocytes, fibroblasts, and macrophages are involved in the development of CVDs. Therefore, the purpose of this review was to explore the latest research published on TLR3 in CVDs and discuss current understanding of potential mechanisms by which TLR3 contributes to CVDs. Even though TLR3 is a developing area, it has strong treatment potential as an immunomodulator and deserves further study for clinical translation. [ABSTRACT FROM AUTHOR]

Background: Whilst the left ventricular ejection fraction (LVEF) remains the primary echocardiographic measure widely utilised for risk stratification following myocardial infarction (MI), it has a number of well recognised limitations. The aim of this study was to compare the prognostic utility of a composite echocardiographic score (EchoScore) composed of prognostically validated measures of left-ventricular (LV) size, geometry and function, to the utility of LVEF alone, for predicting survival following MI.Methods: Retrospective data on 394 consecutive patients with a first-ever MI were included. Comprehensive echocardiography was performed within 24 hours of admission for all patients. EchoScore consisted of LVEF<50%, left atrial volume index>34 mL/m2, average E/e >14, E/A ratio>2, abnormal LV mass index, and abnormal LV end-systolic volume index. A single point was allocated for each measure to derive a score out of 6. The primary outcome measure was all-cause mortality.Results: At a median follow-up of 24 months there were 33 deaths. On Kaplan-Meier analysis, a high EchoScore (>3) displayed significant association with all-cause mortality (log-rank χ2=74.48 p<0.001), and was a better predictor than LVEF<35% (log-rank χ2=17.01 p<0.001). On Cox proportional-hazards multivariate analysis incorporating significant clinical and echocardiographic predictors, a high EchoScore was the strongest independent predictor of all-cause mortality (HR 6.44 95%CI 2.94-14.01 p<0.001), and the addition of EchoScore resulted in greater increment in model power compared to addition of LVEF (model χ2 56.29 vs 44.71 p<0.001, Harrell's C values 0.83 vs 0.79).Conclusions: A composite echocardiographic score composed of prognostically validated measures of LV size, geometry, and function is superior to LVEF alone for predicting survival following MI. [ABSTRACT FROM AUTHOR]

Percutaneous treatment of heavily calcified coronary lesions remains a challenge for interventional cardiologists with increased risk of incomplete lesion preparation, suboptimal stent deployment, procedural complications, and a higher rate of acute and late stent failure. Adequate lesion preparation through calcium modification is crucial in optimising procedural outcomes. Several calcium modification devices and techniques exist, with rotational atherectomy the predominant treatment for severely calcified lesions. Novel technologies such as intravascular lithotripsy are now available and show promise as a less technical and highly effective approach for calcium modification. Emerging evidence also emphasises the value of detailed characterisation of calcification severity and distribution especially with intracoronary imaging for appropriate device selection and individualised treatment strategy. This review aims to provide an overview of the non-invasive and invasive evaluation of coronary calcification, discuss calcium modification techniques and propose an algorithm for the management of calcified coronary lesions. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) after acute Stanford type A aortic dissection (STAAD) surgery has a high mortality rate. Clarifying what type of renal artery problem (dynamic obstructive renal artery, DORA, or static obstructive renal artery, SORA) secondary to STAAD benefits from true lumen opening is helpful in providing a reference for the indication of renal artery intervention.Methods: From May 2018 to December 2019, 292 acute STAAD patients who underwent aortic surgery were enrolled in this study. DORA, SORA, and renal malperfusion were diagnosed according to preoperative aortic enhanced computed tomography (CTA). Renal artery problems secondary to STAAD were divided into three types: type 1, normal renal artery; type 2, DORA; and type 3, SORA. Acute kidney injury was divided into three stages: Stage 1, Stage 2, and Stage 3, according to 2012 Kidney Disease: Improving Global Outcomes (KDIGO). The primary endpoint was all-cause 30-day in-hospital death, and the secondary endpoint was postoperative dialysis requirement. Univariate and multivariate analyses were performed to assess the difference among the three types.Results: Postoperative AKI occurred in 154 of 292 (52.7%) patients, and postoperative dialysis was present in 27 of 292 (9.2%) patients with STAAD. Postoperative AKI and dialysis were significantly more prevalent in the SORA group (AKI: 71% in SORA group vs 51.5% in DORA group vs 22.2% in normal group; postoperative dialysis: 22.2% in SORA group vs 5.4% in DORA group vs 6.1 in normal group). Thirty-day (30-day) mortality was also significantly higher in the SORA group (Log-rank test, p=0.012). Preoperative acute myocardial infarction and body mass index were the independent risk factors for 30-day mortality. Static obstructive renal artery, cardiopulmonary bypass time, and renal blood cell transfusion >3 units were the independent risk factors for postoperative dialysis requirement.Conclusion: Static obstructive renal artery led to higher 30-day in-hospital mortality and more postoperative dialysis. Open surgery reduced renal ischaemia injury caused by DORA, but it could not reduce renal ischaemia injury caused by SORA. [ABSTRACT FROM AUTHOR]

Background: International Classification of Disease (ICD) codes are central for identifying myocardial infarction (MI) in administrative hospitalisation data, however validation of MI subtype codes is limited. We measured the sensitivity and specificity of ICD-10-AM (Australian Modification) codes for ST-elevation MI (STEMI) and non-STEMI (NSTEMI).Methods: A sample of MI admissions was obtained from a dataset containing all MI hospitalisations in Western Australia (WA) for 2003, 2008 and 2013. Clinical data were collected from hospital medical records (n=799 patients). Cases were classified by ICD-10-AM codes for STEMI, NSTEMI and unspecified MI, and compared to clinical classification from review of available electrocardiographs (ECGs) and cardiac biomarkers (n=660). Sensitivity and specificity for ICD-10-AM coding versus clinical classification was measured, stratified by calendar year of discharge.Results: The majority of classifiable cases had MI recorded in the principal diagnosis field (STEMI n=293, 84.2%; NSTEMI n=202, 74.3%; unspecified MI n=20, 50.0%). Overall sensitivity of the ICD-10-AM STEMI code was 86.3% (95% CI 81.7-90.0%) and was higher when restricted to MI as a principal versus secondary diagnosis (88.8% vs 66.7%). Comparable values for NSTEMI were 66.7% (95% CI 61.5-71.6%), and 68.8% vs 61.4% respectively. Between 2003 and 2013, sensitivity for both MI subtypes increased: 80.2-89.5% for STEMI, and 51.2-73.8% for NSTEMI. Specificity was high for NSTEMI throughout (88.2% 95% CI 84.1-91.6%), although improving over time for STEMI (68.1-76.4%).Conclusions: The sensitivity and specificity of ICD-10-AM codes for MI subtypes in hospitalisation data are generally high, particularly for principal diagnosis cases. However, the temporal improvement in sensitivity in coding of MI subtypes, particularly NSTEMI, may necessitate modification to trend studies using administrative hospitalisation data. [ABSTRACT FROM AUTHOR]

Objectives: Approximately 5-10% of patients presenting for percutaneous coronary intervention (PCI) have concurrent atrial fibrillation (AF). To what extent AF portends adverse long-term outcomes in these patients remains to be defined.Methods: We analysed data from the multicentre Melbourne Interventional Group Registry from 2014-2018. Patients were identified as being in AF or sinus rhythm (SR) at the commencement of PCI. The primary endpoint was long-term mortality, obtained via linkage with the National Death Index.Results: 13,286 procedures were included, with 800 (6.0%) patients in AF and 12,486 (94.0%) in SR. Compared to SR, patients with AF were older (72.9±10.9 vs 64.1±12.0 p<0.001) and more likely to have comorbidities including diabetes mellitus (31.3% vs 25.0% p<0.001), hypertension (74.4% vs 65.1% p<0.001) and moderate to severe left ventricular systolic dysfunction (36.6% vs 19.5% p<0.001). Atrial fibrillation was associated with an increased risk of in-hospital mortality (11.0% vs 2.5% p<0.001) and MACE (composite of all-cause mortality, myocardial infarction, or target vessel revascularisation) (11.9% vs 4.2% p<0.001). In-hospital major bleeding was more common in the AF group (3.1% vs 1.0% p<0.001). On Cox proportional hazards modelling, AF was an independent predictor of long-term mortality (adjusted HR 1.38 95% CI 1.11-1.72 p<0.004) at a mean follow-up of 2.3±1.5 years.Conclusions: Preprocedural AF is common among patients presenting for PCI. Preprocedural AF is associated with high-rates of comorbid illnesses and portends higher risk of short- and long-term outcomes including mortality underscoring the need for careful evaluation of its risks prior to PCI. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the safety and feasibility of rotational atherectomy (RA) in patients with severe aortic stenosis (AS).Background: Heavily calcified coronary lesions are commonly encountered in elderly patients with severe AS who are being considered for transcatheter aortic valve implantation. The use of RA in these patients is controversial as they may be at a higher risk of complications.Methods: We retrospectively enrolled patients with severe AS who underwent RA across two hospitals from March 2010 to September 2019. Patients with severe AS prior to or within 8 weeks of RA were included.Results: Twenty-seven (27) consecutive patients (83±5.2 yrs 63% male) with severe AS (peak velocity 4.1±0.5 m/s, mean gradient 40.0±10.2 mmHg) were enrolled and 31 lesions were treated with RA across 30 separate procedures. Three (3) (11.1%) patients had left ventricular ejection fraction ≤30%. Nine (9) (30%) procedures involved percutaneous coronary intervention of multiple arteries, with most lesions in the right coronary artery (51.6%) and left anterior descending artery (32.3%). Three (3) (9.7%) lesions were in the left main stem. RA-facilitated stenting was successful in all lesions. There were no episodes of coronary perforation or slow-flow/no-reflow. There was one episode of coronary dissection in an artery that did not undergo RA, which was successfully treated with a drug-eluting stent. There were no deaths within 30 days and three deaths (11.1%) within 1 year.Conclusions: Rotational atherectomy in patients with severe AS is feasible and has a low rate of procedural complications. [ABSTRACT FROM AUTHOR]

Background: Renal disease confers a strong independent risk for morbidity and mortality after percutaneous coronary intervention (PCI). We evaluated the relationship between baseline pre-procedural renal function and outcomes following PCI.Methods: We examined 45,287 patients who underwent PCI in British Columbia. We evaluated all-cause mortality and target vessel revascularisation (TVR) at 2 years. Pre-procedural renal impairment was categorised by creatinine clearance (CrCl, mL/min): CrCl≥90 (n=14,876), 90>CrCl≥60 (n=10,219), 60>CrCl≥30 (n=14,876), 30>CrCl≥0 (n=2,594) and dialysis (n=579).Results: Declining CrCl values less than 60 mL/min were progressively associated with greater mortality: 60>eGFR≥30 (HR=2.01, 95% CI 1.71-2.37, p<0.001); 30>eGFR≥0 (HR=4.10, 95% CI 3.39-4.95, p<0.001); and dialysis (HR=6.22, 95% CI 5.07-7.63, p<0.001). A reduction in eGFR was not associated with TVR in non-dialysis patients. However, dialysis was a strong independent predictor for TVR (HR=1.69, 95% CI 1.37-2.08, p<0.001). This was confirmed in propensity-matched analyses where, dialysis was strongly associated with TVR (HR=1.53, 95% CI 1.24-1.89, p<0.001). This association was consistently seen in stratified analyses for diabetic versus non-diabetic patients; stent length >30 mm versus <30 mm; stent diameter >3 mm versus <3 mm; and receipt of bare metal stents versus drug-eluting stents.Conclusions: This study indicates the association with declining renal function and mortality in patients undergoing PCI. Whilst renal disease was not associated with increased TVR in non-dialysis patients, dialysis-dependence was a strong independent predictor for increased TVR. [ABSTRACT FROM AUTHOR]

Objective: To assess whether outcomes following percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) for left main coronary artery (LMCA) disease differ between men and women.Background: Current guidelines recommend either PCI or CABG for patients with unprotected LMCA disease and low-to-intermediate anatomical complexity. However, it is unclear whether these guidelines apply to women, who are underrepresented in clinical trials.Methods: An electronic search was performed to identify studies reporting sex-specific outcomes after PCI versus CABG in patients with LMCA disease. Trial level hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled by random-effects modelling.Results: Eight (8) studies met inclusion criteria, comprising 13,066 patients (24.3% women). In both sexes, there was no difference between PCI and CABG with respect to the primary composite endpoint of death, myocardial infarction or stroke (HR in women: 1.03, 95% CI 0.76-1.40; HR in men: 1.04, 95% CI 0.92-1.17). However, both sexes were more likely to require repeat revascularisation after PCI. There was no interaction between sex and treatment effect for the primary composite endpoint nor for the individual outcomes of death, stroke and repeat revascularisation. However, in women the risk of myocardial infarction was higher after PCI compared with CABG (HR 1.84, 95% CI 1.06-3.18), with a trend toward the opposite in men (HR 0.78, 95% CI 0.54-1.13; p-interaction=0.01).Conclusion: Percutaneous coronary intervention and CABG have a comparable risk of the composite outcome of death, stroke or myocardial infarction in patients undergoing revascularisation for LMCA disease, with no significant interaction between sex and treatment effect. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have shown that 123I-metaiodobenzylguanidine (MIBG) scintigraphy, an index of cardiac sympathetic nervous (CSN) activity, is useful for predicting prognosis in patients with heart failure. However, the factors influencing the CSN activity of patients with severe aortic stenosis (AS) remain unclear.Methods: We enrolled 91 patients with severe AS who underwent 123I-MIBG scintigraphy, coronary computed tomography (CCT), and transthoracic echocardiography. When CCT angiography (CCTA) showed an obstructive epicardial artery, invasive coronary angiography was performed within 1 week of CCTA.Results: There were 21 male and 70 female patients with a mean age of 84±5 years. Eighty-five (85) patients (93%) had hypertension and 13 patients (14%) had diabetes. Two (2) patients (2%) had previous myocardial infarction and eight (9%) had a previous coronary intervention. All patients had severe AS: aortic valve area was 0.63±0.18 cm2 and the mean pressure gradient was 56±19 mmHg. Regarding 123I-MIBG parameters, early heart-to-mediastinum (H/M) ratio was 3.1±0.5, delayed H/M ratio was 2.8±0.6, and the washout rate (WR) was 35%±13%. Multivariable linear regression analysis showed that coronary artery disease (β=-0.30, p=0.002) was an independent predictor of delayed H/M ratio, and that aortic valve area (β=-0.20, p=0.048) was an independent predictor of WR.Conclusions: Our findings suggest that coronary artery disease is an independent predictor of delayed H/M ratio, and aortic valve area is an independent predictor of WR in patients with severe AS. [ABSTRACT FROM AUTHOR]

Background: Heart failure is increasing in prevalence, creating a greater public health and economic burden on our health care system. With a rising proportion of hospitalisations for heart failure with preserved ejection fraction (HFpEF) compared to heart failure with reduced ejection fraction (HFrEF) and lack of proven therapies for HFpEF, patient characterisation and defining clinical outcomes are important in determining optimal management of heart failure patients. There is scarce Australian-specific data with regards to the burden of disease of patients with HFpEF which further limits our ability to appropriately manage this syndrome.Aim: To determine the characteristics, management practices and outcomes of patients with HFpEF compared to patients diagnosed with HFrEF.Method: Data was sourced from the Victorian Cardiac Outcomes Registry-Heart Failure (VCOR-HF) snapshot of patients admitted with acute heart failure to one of 16 Victorian health services between 2014-2017 over one consecutive month annually. Outcomes measured were in-hospital mortality, and 30-day readmission and mortality.Results: Of the 1,132 HF patients, 436 patients were diagnosed with HFpEF and were more likely to be female (59%) and older (81.5±9.8 vs 73.2±14.5 years). They were also more likely to have hypertension (80%), atrial fibrillation (59.9%), chronic obstructive airways disease (36.2%) and chronic kidney disease (68.8%). Patients with HFrEF were more likely to have ischaemic heart disease with a history of previous myocardial infarction (36.6%), percutaneous coronary intervention and cardiac bypass surgery (35.2%). There were no significant differences in 30-day mortality between HFpEF and HFrEF (10.2% vs 7.8%; p=0.19, respectively) and 30-day readmission rates (22.1% vs 25.9%; p=0.15, respectively).Conclusion: VCOR-HF Snapshot data provides important insight into the burden of acute heart failure. Whilst patients with HFpEF and HFrEF have differing clinical profiles, morbidity, mortality and re-admission rates are similar. [ABSTRACT FROM AUTHOR]

Background: Takotsubo syndrome (TS) is often triggered by an acute physical or emotional stressor. We hypothesised that medium-term prognosis may be better for TS patients with an associated emotional stressor than for those with an acute physical illness.Methods: We identified consecutive TS patients presenting in New Zealand (2006-2018). The clinical presentation and outcomes of TS patients according to types of stressor (physical, emotional or no stressor) were assessed. Post-discharge survival after TS was compared with age- and gender-matched patients after myocardial infarction (MI) and people in the community without known cardiovascular disease (CVD).Results: Of 632 TS patients (95.9% women, mean age 65.0±11.1 years), 27.4% had an associated acute physical stressor, 46.4% an emotional stressor and 26.2% no evident stressor. In-hospital mortality was similar for each group (1.7%, 1.2%, 0.3% respectively, p=0.29). In a median 4.4 years post-discharge there were 54 deaths (53 non-cardiac). Compared with patients without known CVD, TS patients with physical stress and those with MI were less likely to survive (HR 4.46, 95%CI 3.10-6.42; HR 4.23, 95%CI 3.81-4.70 respectively) but survival for TS patients associated with emotional stress or no stressor was similar (HR 1.11, 95%CI 0.66-1.85; HR 1.08, 95%CI 0.54-2.18, respectively). Recurrence was similar among the three groups (p=0.14).Conclusion: Takotsubo syndrome associated with physical stressor has a post-discharge mortality risk as high as after MI. In contrast, prognosis for TS triggered by an emotional stressor is excellent, and similar to that of those without known CVD. [ABSTRACT FROM AUTHOR]