Peri-Coronary Adipose Tissue Is a Predictor of Stent Failure in Patients Undergoing Percutaneous Coronary Intervention.

PURPOSE: Coronary inflammation is postulated as a driver of atherosclerosis and dysfunctional arterial healing which may trigger stent failure. Pericoronary adipose tissue (PCAT) attenuation, detected on computer tomography coronary angiography (CTCA), is an emerging non-invasive marker of coronary inflammation. This propensity matched study assessed the utility of both lesion specific (PCATLesion) and standardized PCAT attenuation as assessed in the proximal RCA (PCATRCA) as a predictor of stent failure in patients undergoing elective percutaneous coronary intervention. This is the first study to our knowledge that assesses the association of PCAT with stent failure. METHODS: Patients undergoing CTCA assessment for coronary artery disease with subsequent stent insertion within 60 days and repeat coronary angiography for any clinical reason within 5 years were included in the study. Stent failure was defined as binary restenosis of >50 % on quantitative coronary angiography analysis or stent thrombosis. Both PCATLesion and PCATRCA was assessed utilizing semi-automated proprietary software on baseline CTCA. Patients with stent failure were propensity matched utilizing age, sex, cardiovascular risk factors and procedural characteristics. RESULTS: One hundred and fifty-one patients met inclusion criteria. Of these, 26 (17.2 %) had study-defined failure. A significant difference in PCATLesion attenuation between patients with and without failure was observed (-79.0 ± 12.6 vs. -85.9 ± 10.3HU, p = 0.035). There was no significant difference in PCATRCA attenuation between the two groups (-79.5 ± 10.1 vs -81.0 ± 12.3HU, p = 0.50). Univariate regression analysis showed PCATLesion attenuation was independently associated with stent failure (OR 1.06, 95 % CI 1.01-1.12, P = 0.035). CONCLUSIONS: Patients with stent failure exhibit significantly increased PCATLesion attenuation at baseline. These data suggest that baseline plaque inflammation may be an important driver for coronary stent failure.

Colchicine in the Management of Acute Coronary Syndrome: A Meta-analysis.

INTRODUCTION: Colchicine, thought to exert its effect via reduction of inflammation, has recently been studied in patients following acute coronary syndromes (ACS). We performed a meta-analysis of all available randomized controlled trials (RCTs) in this high-risk cohort, evaluating efficacy and safety. METHODS: MEDLINE, PubMed, EMBASE, clinical trial registries, and select conference proceedings were searched for RCTs comparing colchicine to placebo in patients following ACS. The primary outcome was trial-defined major adverse cardiovascular events (MACE). Secondary endpoints included stroke, myocardial infarction (MI), all-cause and cardiovascular death, and urgent revascularization. Analysis was performed at the longest available clinical follow-up. RESULTS: Two RCTs with a pooled sample size of 5540 patients with 2778 (50.1%) receiving colchicine and 2762 (49.9%) placebo were included. In order to maximize consistency, composite efficacy endpoints between trials were modified. Compared to placebo, patients receiving colchicine had reduction in study-defined composite endpoint (5.5% vs. 7.6%) OR 0.67 (95% CI 0.46-0.98, p = 0.04, I2 = 46%). Similarly, there was a significant reduction in cerebrovascular accidents (OR 0.31, 95% CI 0.14-0.69, p = 0.004, I2 = 0%) and repeat revascularization OR 0.36 (95% CI 0.14-0.90, p = 0.03, I2 = 54%). There was no difference between cardiovascular death (OR 0.92, 95% CI 0.52-1.62, p = 0.78, I2 = 0%), non-cardiovascular death OR 1.27 (95% CI 0.72-2.24, p = 0.41, I2 = 0%), MI at longest available follow-up OR 0.89 (95% CI 0.67-1.17, p = 0.39, I2 = 0%) or resuscitated cardiac arrest OR 0.88 (95% CI 0.32-2.43, p = 0.81, I2 = 0%) in those receiving colchicine. CONCLUSIONS: These data suggest colchicine, in addition to guideline-directed medical therapy following acute coronary syndrome reduces MACE, cerebrovascular accidents, and rates of urgent revascularization at 2 years of follow-up.

Impact of prehospital opioid dose on angiographic and clinical outcomes in acute coronary syndromes.

BACKGROUND: An adverse interaction whereby opioids impair and delay the gastrointestinal absorption of oral P2Y12 inhibitors has been established, however the clinical significance of this in acute coronary syndrome (ACS) is uncertain. We sought to characterise the relationship between prehospital opioid dose and clinical outcomes in patients with ACS. METHODS: Patients given opioid treatment by emergency medical services (EMS) with ACS who underwent percutaneous coronary intervention (PCI) between 1 January 2014 and 31 December 2018 were included in this retrospective cohort analysis using data linkage between the Ambulance Victoria, Victorian Cardiac Outcomes Registry and Melbourne Interventional Group databases. Patients with cardiogenic shock, out-of-hospital cardiac arrest and fibrinolysis were excluded. The primary end point was the risk-adjusted odds of 30-day major adverse cardiac events (MACE) between patients who received opioids and those that did not. RESULTS: 10 531 patients were included in the primary analysis. There was no significant difference in 30-day MACE between patients receiving opioids and those who did not after adjusting for key patient and clinical factors. Among patients with ST-elevation myocardial infarction (STEMI), there were significantly more patients with thrombolysis in myocardial infarction (TIMI) 0 or 1 flow pre-PCI in a subset of patients with high opioid dose versus no opioids (56% vs 25%, p<0.001). This remained significant after adjusting for known confounders with a higher predicted probability of TIMI 0/1 flow in the high versus no opioid groups (33% vs 11%, p<0.001). CONCLUSIONS: Opioid use was not associated with 30-day MACE. There were higher rates of TIMI 0/1 flow pre-PCI in patients with STEMI prescribed opioids. Future prospective research is required to verify these findings and investigate alternative analgesia for ischaemic chest pain.

Incidence, predictors and clinical implications of new renal impairment following percutaneous coronary intervention.

BACKGROUND: Renal impairment post-percutaneous coronary intervention (post-PCI) is a well-described adverse effect following the administration of contrast media. Within a large cohort of registry patients, we aimed to explore the incidence, predictors and clinical outcomes of renal impairment post-PCI. METHODS: The Victorian Cardiac Outcomes Registry is an Australian state-based clinical quality registry focusing on collecting data from all PCI capable centres. Data from 36 970 consecutive PCI cases performed between 2014 and 2018 were analysed. Patients were separated into three groups based on post-procedure creatinine levels (new renal impairment (NRI), defined as an absolute rise in serum creatinine>44.2 µmol/L or>25% of baseline creatinine; new renal impairment requiring dialysis (NDR), defined as worsening renal failure that necessitated a new requirement for renal dialysis; no NRI). Multivariate logistic regression analysis was performed to investigate the impact of NRI and NDR on clinical outcomes. RESULTS: 3.1% (n=1134) of patients developed NRI, with an additional 0.6% (n=225) requiring dialysis. 96.3% (n=35 611) of patients did not develop NRI. Those who developed renal impairment were more comorbid, with higher rates of diabetes (22% vs 38% vs 38%, p<0.001), peripheral vascular disease (3.4% vs 8.2% vs 11%, p<0.001), chronic kidney disease (19% vs 49.7% vs 54.2%) and severe left ventricular dysfunction (5% vs 22% vs 40%, p<0.001). Multivariable analysis found that when compared with the no NRI group, those in the combined NRI/NDR group were at a greater risk of 30-day mortality (OR 4.77; 95% CI 3.89 to 5.86, p<0.001) and 30-day major adverse cardiac events (OR 3.72; 95% CI 3.15 to 4.39, p<0.001). CONCLUSIONS: NRI post-PCI remains a common occurrence, especially among comorbid patients, and is associated with a significantly increased morbidity and mortality risk.

COlchicine to Prevent PeriprocEdural Myocardial Injury in Percutaneous Coronary Intervention (COPE-PCI): Coronary Microvascular Physiology Pilot Substudy.

Aim: In this randomized pilot trial, we aimed to assess the anti-inflammatory effect of preprocedural colchicine on coronary microvascular physiology measurements before and after PCI. Methods: Patients undergoing PCI for stable angina (SA) or non-ST-elevation myocardial infarction (NSTEMI) were randomized to oral colchicine or placebo, 6- to 24-hours before the procedure. Strict prespecified inclusion/exclusion criteria were set to ensure all patients were given the study medication, had a PCI, and had pre- and post-PCI culprit vessel invasive coronary physiology measurements. Fractional flow reserve (FFR), Index of Microvascular Resistance (IMR), Coronary Flow Reserve (CFR), and Resistive Reserve Ratio (RRR) were measured immediately before and after PCI. CMVD was defined as any one of post-PCI IMR >32 or CFR <2 or RRR <2. High-sensitive-(hs)-troponin-I, hsCRP, and leucocyte count were measured before and 24 hours after PCI. Results: A total of 50 patients were randomized and met the strict prespecified inclusion/exclusion criteria: 24-colchicine and 26-placebo. Pre-PCI coronary physiology measurements, hs-troponin-I, and hsCRP were similar between groups. Although numerically lower in patients given colchicine, the proportion of patients who developed CMVD was not significantly different between groups (colchicine: 10 (42%) vs placebo: 16 (62%), p=0.16). Colchicine patients had higher post-PCI CFR and RRR vs placebo (respectively: 3.25 vs 2.00, p=0.03 & 4.25 vs 2.75, p < 0.01). Neutrophil count was lower after PCI in the colchicine arm (p=0.02), and hsCRP post-PCI remained low in both treatment arms (1.0 mg/L vs 1.7 mg/L, p=0.97). Patients randomized to colchicine had significantly less PCI-related absolute hs-troponin-I change (46 ng/L vs 152 ng/L, p=0.01). Conclusion: In this pilot randomized substudy, colchicine given 6 to 24 hours before PCI did not statistically impact the post-PCI CMVD definition used in this study, yet it did improve post-PCI RRR and CFR measurements, with less procedure-related troponin release and less inflammation.

Colchicine and Quality of Life in Patients With Acute Coronary Syndromes: Results From the COPS Randomized Trial.

BACKGROUND: Recent data suggest that colchicine may reduce cardiovascular events among patients presenting with acute coronary syndromes. This sub-study of the Australian COPS trial aimed to assess whether colchicine affects health status outcomes. METHODS: Health status was assessed at baseline and 12-months using the EuroQol-5 Dimension 5-level (EQ-5D-5L) score and the full 19-question Seattle Angina Questionnaire (SAQ). Data were available for 786 patients (388 randomized to colchicine, 398 to placebo). RESULTS: Baseline characteristics were well matched between groups; mean age was 60.1 (SD 14.8) years, and 20 % were female. Baseline health status scores were impaired, and most parameters demonstrated significant improvement from baseline to 12-months (EQ-5D-5L Visual Analogue Score [VAS] 69.3 to 77.7; SAQ angina frequency score 83.0 to 95.3, both p < 0.001). No significant differences in adjusted mean score change among any of the EQ-5D-5L or SAQ dimensions were observed between treatment groups in either intention-to-treat or per-protocol analysis. There were borderline interactions in EQ-5D-5L scores for those with previous MI vs not, and in SAQ scores for those with obesity vs not. In categorical analysis using observed data, patients treated with colchicine were more likely to have clinically significant improvement in physical limitation score over the period (36 % improved vs. 28 %, p < 0.05). Baseline health status scores were not associated with the primary endpoint at 12 months. CONCLUSIONS: Treatment with colchicine did not appear to affect change in measures of health status following acute coronary syndromes, but it did lead to a greater likelihood of improvement in physical limitation scores. TRIAL REGISTRATION: ACTRN, ACTRN12615000861550. Registered 18/08/2015, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368973.

High-Risk Coronary Plaque Features: A Narrative Review.

Advances in coronary plaque imaging over the last few decades have led to an increased interest in the identification of novel high-risk plaque features that are associated with cardiovascular events. Existing practices focus on risk stratification and lipid monitoring for primary and secondary prevention of cardiac events, which is limited by a lack of assessment and treatment of vulnerable plaque. In this review, we summarize the multitude of studies that have identified plaque, haemodynamic and patient factors associated with risk of acute coronary syndrome. Future progress in multi-modal imaging strategies and in our understanding of high-risk plaque features could expand treatment options for coronary disease and improve patient outcomes.

Long-Term Outcomes of Unprotected Left Main Percutaneous Coronary Intervention in Centers Without Onsite Cardiac Surgery.

Unprotected left main (LM) percutaneous coronary intervention (PCI) at centers without onsite cardiac surgery remains controversial. We aimed to evaluate the effect of onsite cardiac surgery on short-term and long-term outcomes in patients who had unprotected LM PCI. We analyzed Victorian Cardiac Outcomes Registry data on consecutive patients who had unprotected LM PCI at cardiac surgical centers (SCs) and non-SCs (NSCs) between January 2014 to December 2018. Compared with the SC group (n = 594, 81%), the NSC group (n = 136) were younger (69 vs 72 years) and presented with more ST-elevation myocardial infarction (35% vs 16%) and cardiogenic shock (25% vs 15%), with higher rates of preprocedural intubation (17% vs 11%) and mechanical circulatory support (20% vs 9.3%), all p <0.01. Unadjusted in-hospital mortality (23% vs 11.4%), and 30-day major adverse cardiac events (composite of mortality, myocardial infarction, stent thrombosis, or unplanned revascularization) (26% vs 16%) were higher in NSC patients, all p <0.01. However, following multivariable adjustment, SC was neither a predictor of in-hospital mortality (odds ratio 0.68, 95% confidence interval [CI] 0.32 to 1.43, p = 0.31), 30-day mortality (odds ratio 0.70, 95% CI 0.33 to 1.48, p = 0.35) nor long-term survival at 60 months (hazard ratio 0.88, 95% CI 0.62 to 1.27, p = 0.51). Propensity score analysis confirmed the neutral effect of onsite cardiac surgery on long-term survival (hazard ratio 0.99, 95% CI 0.66 to 1.50, p = 0.97). In conclusion, patients who underwent unprotected LM PCI at NSCs presented with greater acuity of illness. Despite this, the availability of onsite cardiac surgical support was not associated with in-hospital, 30-day, or long-term outcomes underscoring the safety of LM PCI in NSCs.

Coronary Atherosclerotic Plaque Regression: JACC State-of-the-Art Review.

Over the last 3 decades there have been substantial improvements in treatments aimed at reducing cardiovascular (CV) events. As these treatments have been developed, there have been parallel improvements in coronary imaging modalities that can assess plaque volumes and composition, using both invasive and noninvasive techniques. Plaque progression can be seen to precede CV events, and therefore, many studies have longitudinally assessed changes in plaque characteristics in response to various treatments, aiming to demonstrate plaque regression and improvements in high-risk features, with the rationale being that this will reduce CV events. In the past, decisions surrounding treatments for atherosclerosis have been informed by population-based risk scores for initiation in primary prevention and low-density lipoprotein cholesterol levels for titration in secondary prevention. If outcome data linking plaque regression to reduced CV events emerge, it may become possible to directly image plaque treatment response to guide management decisions.

COlchicine to Prevent PeriprocEdural Myocardial Injury in Percutaneous Coronary Intervention (COPE-PCI): A Descriptive Cytokine Pilot Sub-Study.

BACKGROUND: High levels of inflammation pre- and post-percutaneous coronary intervention (PCI) are associated with worse outcomes. Recent trials have suggested a benefit from treating inflammation with colchicine in coronary artery disease. In this randomised pilot COPE-PCI sub-study, we aimed to determine if administration of colchicine pre-PCI, would attenuate the inflammatory effect of PCI. METHODS: PCI patients were randomised to colchicine or placebo, 6 to 24-hours pre-procedure. Study blood samples were taken immediately pre-PCI, and 24-hours post-procedure. Samples were tested for a broad array of inflammatory biomarkers including high-sensitive(hs)-CRP, leucocyte counts, and hs-troponin-. Periprocedural Myocardial Injury (PM-Injury) was defined as per the ESC Third Universal Definitions of Myocardial Infarction. RESULTS: Thirty-six were randomised to colchicine and 39 to placebo. Treatment groups were similar for baseline variables. The median time from drug administration to pre-PCI blood sampling was 18-hours. Overall inflammation was low across the patient population, pre- & post-PCI hsCRP was <1.4 mg/L. Colchicine patients had numerically lower levels of pre-PCI cytokines: IL-1ß (p = 0.01), IL-6 (p = 0.02), IL-10 (p = 0.01), IFNγ (p = 0.01), TNFα (p = 0.02) and WBC-count (p = 0.04). Post-PCI (38-hours post-drug) measures of inflammation were similar between treatment arms. Absolute troponin change (post-PCI - pre-PCI levels) was less in colchicine patients (p = 0.02). CONCLUSION: The reduction in PCI-related myocardial injury that resulted from colchicine given on median 18 h pre-PCI, was associated with numerically lower levels of inflammation pre-PCI but no difference one day post-PCI in the colchicine vs placebo groups. CLINICAL TRIAL REGISTRATION: The trial was publicly registered at www.anzctr.org.au, Trial ID: ACTRN12615000485538.

Modelling STEMI service delivery: a proof of concept study.

BACKGROUND: Access to individual percutaneous coronary intervention (PCI) centres has traditionally been determined by historical referral patterns along arbitrarily defined geographic boundaries. We set out to produce predictive models of ST-elevation myocardial infarction (STEMI) demand and time-efficient access to PCI centres. METHODS: Travel times from random addresses to PCI centres in Melbourne, Australia, were estimated using Google map application programming interface (API). Departures at 08:15 and 17:15 were compared with 23:00 to determine the effect of peak hour traffic congestion. Real-world ambulance travel times were compared with estimated travel times using Google map developer software. STEMI incidence per postcode was estimated by merging STEMI incidence per age group data with age group per postcode census data. PCI centre network configuration changes were assessed for their effect on hospital STEMI loading, catchment size, travel times and the number of STEMI cases within 30 min of a PCI centre. RESULTS: Nearly 10% of STEMI cases travelled more than 30 min to a PCI centre, increasing to 20% by modelling the removal of large outer metropolitan PCI centres (p<0.05). A model of 7 PCI centres compared favourably to the current existing network of 11 PCI centres (p=0.18 (afternoon), p=0.5 (morning and night)). The intraclass correlation between estimated travel times and ambulance travel times was 0.82, p<0.001. CONCLUSION: This paper provides a framework to integrate prehospital environmental variables, existing or altered healthcare resources and health statistics to objectively model STEMI demand and consequent access to PCI. Our methodology can be modified to incorporate other inputs to compute optimum healthcare efficiencies.

Patient Perspectives on Innovative Telemonitoring Enhanced Care Program for Chronic Heart Failure (ITEC-CHF): Usability Study.

BACKGROUND: Telemonitoring enables care providers to remotely support outpatients in self-managing chronic heart failure (CHF), but little is known about the usability and patients' willingness to engage with this technology. OBJECTIVE: This study aims to evaluate feedback from patients with CHF following participation in the Innovative Telemonitoring Enhanced Care program for CHF (ITEC-CHF) study. METHODS: The telemonitoring intervention consisted of three components: remote weight monitoring, structured telephone support, and nurse-led collaborative care. Participants were provided with electronic weighing scales (W550; ForaCare), and a computer tablet (Galaxy Tab A; Samsung). They were asked to weigh themselves on the provided scales daily. Telemonitoring was integrated with a personal assistance call service and a nurse care service according to their workflows in usual care. Feedback on the usability of ITEC-CHF was collected via survey from study participants following 6 months of receiving telemonitoring care for their body weight. Survey responses were provided on a 5-point Likert scale and through open-ended questions to determine participants' perceived benefits and barriers to using ITEC-CHF. RESULTS: A total of 67 participants (49/67, 73% male), with a mean age of 69.8 (SD 12.4) years completed the survey. The majority of participants agreed or strongly agreed that the ITEC-CHF program was easy to use (61/67, 91%), easy to navigate (51/65, 78%), useful (59/65, 91%), and made them feel more confident in managing their weight (57/67, 85%). Themes related to participants' perceptions of telemonitoring included increased support for early intervention of clinical deterioration, improved compliance to daily weighing, a sense of reassurance, and improved self-care and accountability, among others. CONCLUSIONS: ITEC-CHF was rated highly on usability and was well accepted by users as part of their routine self-management activities. Participants were willing to use telemonitoring because they perceived a broad spectrum of benefits for CHF management. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ID ACTRN 12614000916640; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366691.