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.

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.

Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials.

AIMS: Recent randomized trials demonstrated a benefit of low-dose colchicine added to guideline-based treatment in patients with recent myocardial infarction or chronic coronary disease. We performed a systematic review and meta-analysis to obtain best estimates of the effects of colchicine on major adverse cardiovascular events (MACE). METHODS AND RESULTS: We searched the literature for randomized clinical trials of long-term colchicine in patients with atherosclerosis published up to 1 September 2020. The primary efficacy endpoint was MACE, the composite of myocardial infarction, stroke, or cardiovascular death. We combined the results of five trials that included 11 816 patients. The primary endpoint occurred in 578 patients. Colchicine reduced the risk for the primary endpoint by 25% [relative risk (RR) 0.75, 95% confidence interval (CI) 0.61-0.92; P = 0.005], myocardial infarction by 22% (RR 0.78, 95% CI 0.64-0.94; P = 0.010), stroke by 46% (RR 0.54, 95% CI 0.34-0.86; P = 0.009), and coronary revascularization by 23% (RR 0.77, 95% CI 0.66-0.90; P < 0.001). We observed no difference in all-cause death (RR 1.08, 95% CI 0.71-1.62; P = 0.73), with a lower incidence of cardiovascular death (RR 0.82, 95% CI 0.55-1.23; P = 0.34) counterbalanced by a higher incidence of non-cardiovascular death (RR 1.38, 95% CI 0.99-1.92; P = 0.060). CONCLUSION: Our meta-analysis indicates that low-dose colchicine reduced the risk of MACE as well as that of myocardial infarction, stroke, and the need for coronary revascularization in a broad spectrum of patients with coronary disease. There was no difference in all-cause mortality and fewer cardiovascular deaths were counterbalanced by more non-cardiovascular deaths.

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.

Colchicine in Patients With Acute Coronary Syndrome: The Australian COPS Randomized Clinical Trial.

BACKGROUND: Inflammation plays a crucial role in clinical manifestations and complications of acute coronary syndromes (ACS). Colchicine, a commonly used treatment for gout, has recently emerged as a novel therapeutic option in cardiovascular medicine owing to its anti-inflammatory properties. We sought to determine the potential usefulness of colchicine treatment in patients with ACS. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial involving 17 hospitals in Australia that provide acute cardiac care service. Eligible participants were adults (18-85 years) who presented with ACS and had evidence of coronary artery disease on coronary angiography managed with either percutaneous coronary intervention or medical therapy. Patients were assigned to receive either colchicine (0.5 mg twice daily for the first month, then 0.5 mg daily for 11 months) or placebo, in addition to standard secondary prevention pharmacotherapy, and were followed up for a minimum of 12 months. The primary outcome was a composite of all-cause mortality, ACS, ischemia-driven (unplanned) urgent revascularization, and noncardioembolic ischemic stroke in a time to event analysis. RESULTS: A total of 795 patients were recruited between December 2015 and September 2018 (mean age, 59.8±10.3 years; 21% female), with 396 assigned to the colchicine group and 399 to the placebo group. Over the 12-month follow-up, there were 24 events in the colchicine group compared with 38 events in the placebo group (P=0.09, log-rank). There was a higher rate of total death (8 versus 1; P=0.017, log-rank) and, in particular, noncardiovascular death in the colchicine group (5 versus 0; P=0.024, log-rank). The rates of reported adverse effects were not different (colchicine 23.0% versus placebo 24.3%), and they were predominantly gastrointestinal symptoms (colchicine, 23.0% versus placebo, 20.8%). CONCLUSIONS: The addition of colchicine to standard medical therapy did not significantly affect cardiovascular outcomes at 12 months in patients with ACS and was associated with a higher rate of mortality. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12615000861550.

Gender Differences in Healthy Lifestyle Adherence Following Percutaneous Coronary Intervention for Coronary Artery Disease.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of mortality in Australian women. We identified gender differences in healthy lifestyle adherence in patients treated with percutaneous coronary intervention (PCI) for CAD. METHODS: Consecutive patients were prospectively recruited from three Australian institutions (2016-2017). The primary endpoint at 1 year follow-up was healthy lifestyle adherence defined as 3/3 of: a heart-healthy diet, being physically active and not smoking. Secondary endpoints included cardiac rehabilitation attendance, medication use and lipid levels. RESULTS: From 729 participants (n=192, 26.3% women) 56% were adherent to all three lifestyle measures with no gender difference overall. Compared to men, women were less likely to smoke (7.7% versus 12.2%, p<0.001) to be physically active (61.5% versus 78.2%; p<0.0001), attend cardiac rehabilitation (58.2% versus 66.4%; p<0.045), and take statin therapy (85.4% versus 94.7%; p<0.0001). Female gender independently predicted physical inactivity (OR 2.41, 95% CI 1.57-3.68, p<0.001). CONCLUSION: Important gender differences exist in patients treated with PCI for CAD, namely, significant lower physical activity, cardiac rehabilitation attendance and statin use in women. These all represent key targets for gender-specific secondary prevention interventions.

Utility of Zwolle Risk Score in Guiding Low-Risk STEMI Discharge.

BACKGROUND: Despite emerging evidence suggesting that selected patients presenting with ST-segment elevation myocardial infarction (STEMI) treated successfully with primary percutaneous coronary intervention (PPCI) may be considered for early discharge, STEMI patients are typically hospitalised longer to monitor for serious complications. METHODS: We assessed the feasibility of identifying low-risk STEMI patients in our institution for early discharge using the Zwolle risk score (ZRS). We evaluated consecutive STEMI patients who underwent successful PPCI within the period 1 January 2016 to 31 December 2017. Low-risk was defined as ZRS≤3. Demographic, angiographic characteristics, length of stay (LOS), and 30-day major adverse cardiovascular events (MACE) defined as cardiac death, stroke, congestive cardiac failure, and non-fatal myocardial infarction, were recorded. RESULTS: There were 183 STEMI patients in our study cohort (mean age 62.0±12.2 years, 77.0% male). The median ZRS was 2 (interquartile range 1-4) with 132 (72.1%) patients classified as low-risk. The overall 30-day MACE and mortality rates were 10.4% and 3.3% respectively. None of the 35 (26.5%) low-risk patients who were discharged within 72 hours experienced MACE at 30 days. Low-risk STEMI patients had significantly shorter median LOS (86.3 vs. 93.2 hours, p=0.002), lower 30-day MACE (4.5% vs. 25.5%, p<0.0001) and mortality (0% vs. 11.8%, p<0.0001) compared to high-risk group (ZRS>3). Receiver operating characteristic (ROC) curve analyses for ZRS in predicting 30-day MACE and mortality yielded C-statistics of 0.79 (95%CI 0.68-0.90, p<0.0001) and 0.98 (95%CI 0.95-1.00, p<0.0001) respectively. CONCLUSION: Low-risk STEMI patients stratified by Zwolle risk score, who were treated successfully with PPCI, experienced low 30-day MACE and mortality rates, indicating that early discharge may be safe in these patients. Larger studies are warranted to evaluate the safety of ZRS-guided early discharge of STEMI patients, as well as the economic and psychological impacts.

Effects of Different Telemonitoring Strategies on Chronic Heart Failure Care: Systematic Review and Subgroup Meta-Analysis.

BACKGROUND: Telemonitoring studies in chronic heart failure are characterized by mixed mortality and hospitalization outcomes, which have deterred the uptake of telemonitoring in clinical practice. These mixed outcomes may reflect the diverse range of patient management strategies incorporated in telemonitoring. To address this, we compared the effects of different telemonitoring strategies on clinical outcomes. OBJECTIVE: The aim of this systematic review and subgroup meta-analysis was to identify noninvasive telemonitoring strategies attributing to improvements in all-cause mortality or hospitalization outcomes for patients with chronic heart failure. METHODS: We reviewed and analyzed telemonitoring strategies from randomized controlled trials (RCTs) comparing telemonitoring intervention with usual care. For each strategy, we examined whether RCTs that applied the strategy in the telemonitoring intervention (subgroup 1) resulted in a significantly lower risk ratio (RR) of all-cause mortality or incidence rate ratio (IRR) of all-cause hospitalization compared with RCTs that did not apply this strategy (subgroup 2). RESULTS: We included 26 RCTs (N=11,450) incorporating 18 different telemonitoring strategies. RCTs that provided medication support were found to be associated with a significantly lower IRR value than RCTs that did not provide this type of support (P=.01; subgroup 1 IRR=0.83, 95% CI 0.72-0.95 vs subgroup 2 IRR=1.02, 95% CI 0.93-1.12). RCTs that applied mobile health were associated with a significantly lower IRR (P=.03; IRR=0.79, 95% CI 0.64-0.96 vs IRR=1.00, 95% CI 0.94-1.06) and RR (P=.01; RR=0.67, 95% CI 0.53-0.85 vs RR=0.95, 95% CI 0.84-1.07). CONCLUSIONS: Telemonitoring strategies involving medication support and mobile health were associated with improvements in all-cause mortality or hospitalization outcomes. These strategies should be prioritized in telemonitoring interventions for the management of patients with chronic heart failure.

The Effects of Telemonitoring on Patient Compliance With Self-Management Recommendations and Outcomes of the Innovative Telemonitoring Enhanced Care Program for Chronic Heart Failure: Randomized Controlled Trial.

BACKGROUND: Telemonitoring enables care providers to remotely support outpatients in self-managing chronic heart failure (CHF), but the objective assessment of patient compliance with self-management recommendations has seldom been studied. OBJECTIVE: This study aimed to evaluate patient compliance with self-management recommendations of an innovative telemonitoring enhanced care program for CHF (ITEC-CHF). METHODS: We conducted a multicenter randomized controlled trial with a 6-month follow-up. The ITEC-CHF program comprised the provision of Bluetooth-enabled scales linked to a call center and nurse care services to assist participants with weight monitoring compliance. Compliance was defined a priori as weighing at least 4 days per week, analyzed objectively from weight recordings on the scales. The intention-to-treat principle was used to perform the analysis. RESULTS: A total of 184 participants (141/184, 76.6% male), with a mean age of 70.1 (SD 12.3) years, were randomized to receive either ITEC-CHF (n=91) or usual care (control; n=93), of which 67 ITEC-CHF and 81 control participants completed the intervention. For the compliance criterion of weighing at least 4 days per week, the proportion of compliant participants in the ITEC-CHF group was not significantly higher than that in the control group (ITEC-CHF: 67/91, 74% vs control: 56/91, 60%; P=.06). However, the proportion of ITEC-CHF participants achieving the stricter compliance standard of at least 6 days a week was significantly higher than that in the control group (ITEC-CHF: 41/91, 45% vs control: 23/93, 25%; P=.005). CONCLUSIONS: ITEC-CHF improved participant compliance with weight monitoring, although the withdrawal rate was high. Telemonitoring is a promising method for supporting both patients and clinicians in the management of CHF. However, further refinements are required to optimize this model of care. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12614000916640; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366691.

Different patients, different outcomes: A case-control study of spontaneous coronary artery dissection versus acute coronary syndrome.

INTRODUCTION: There is progressive interest worldwide in spontaneous coronary artery dissection (SCAD). To identify a SCAD cohort and compare risk factors, presentation, and management outcomes compared to acute coronary syndrome (ACS) matched controls. METHODS: Retrospective analysis was performed from 2000 to 2015. Clinical data included a neuropsychiatric history, with management and clinical outcomes assessed at 12 months. Patients were matched on a 1:3 case-control basis according to type of ACS. Twenty-two SCAD patients were matched to 66 controls by ACS type (ST-elevation myocardial infarction 45%, Non-ST-elevation myocardial infarction 41%, unstable angina 14%). RESULTS: The SCAD group were more likely female (77.3% vs 19.7%, P < 0.0001), of younger age (48.7 ± 10.7 years vs 61.3 ± 10.6 years, P < 0.0001) with no cases of diabetes (0% vs 33.3%, P = 0.002), compared to controls. SCAD patients had a high prevalence of anxiety, depression or previous neuropsychiatric history (52.4% SCAD vs 1.5% ACS, P < 0.0001). A conservative revascularization strategy with stenting was performed in a minority of SCAD patients (13.6% SCAD vs 83.3% ACS, P < 0.0001), with no significant difference in cumulative major adverse cardiac or cerebrovascular events (MACCE) of death, stroke, re-admission, or repeat angiography rates between both groups (13.6% SCAD vs 27.3% ACS P = NS). CONCLUSION: SCAD affects young females with a paucity of cardiovascular risk factors. The major risk factor for SCAD was a history of anxiety, depression, or neuropsychiatric illness. A conservative approach to SCAD revascularization led to similar MACCE when compared to ACS controls undergoing guideline revascularization at 12 months.

The Index of Microcirculatory Resistance Postpercutaneous Coronary Intervention Predicts Left Ventricular Recovery in Patients With Thrombolyzed ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The index of microcirculatory resistance (IMR), an invasive measure of microvascular function, has been shown to correlate with clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study is to evaluate the predictive value of IMR on left ventricular recovery in patients undergoing a pharmacoinvasive strategy for STEMI. METHODS: The index of microcirculatory resistance was assessed following percutaneous coronary intervention (PCI) in 31 patients with STEMI who were initially managed with thrombolysis. Other markers of microvascular function such as coronary flow reserve (CFR), TIMI flow grade, corrected TIMI frame count (cTFC), and ST-segment resolution were also recorded. All indices were evaluated against measures of left ventricular function and recovery 3 months postindex event. RESULTS: The IMR correlated with left ventricular function, as assessed by wall motion score and ejection fraction at 3-month follow-up (r = 0.652, P = 0.005; r = -0.452, P = 0.011, respectively). The traditional methods of assessing microvascular function, such as CFR, TIMI flow grade, cTFC, and ST-segment resolution did not correlate with wall motion score and ejection fraction at 3 months. Post-PCI IMR was significantly lower in those patients with left ventricular recovery at 3 months (18 U vs 39 U, P < 0.001). The optimal cut-off value for post-PCI IMR and left ventricular recovery was 32 U. In patients in whom the IMR was greater than 32 U, the percent change in ejection fraction was significantly lower than in those patients in whom the IMR was less than 32 U (2 ± 11 vs 12 ± 8, P = 0.012). CONCLUSIONS: In patients presenting with STEMI initially managed with thrombolysis and subsequently undergoing PCI, IMR correlates with measures of left ventricular function and has the potential to predict left ventricular recovery at 3 months.

Fractional flow reserve-guided management in stable coronary disease and acute myocardial infarction: recent developments.

Coronary artery disease (CAD) is a leading global cause of morbidity and mortality, and improvements in the diagnosis and treatment of CAD can reduce the health and economic burden of this condition. Fractional flow reserve (FFR) is an evidence-based diagnostic test of the physiological significance of a coronary artery stenosis. Fractional flow reserve is a pressure-derived index of the maximal achievable myocardial blood flow in the presence of an epicardial coronary stenosis as a ratio to maximum achievable flow if that artery were normal. When compared with standard angiography-guided management, FFR disclosure is impactful on the decision for revascularization and clinical outcomes. In this article, we review recent developments with FFR in patients with stable CAD and recent myocardial infarction. Specifically, we review novel developments in our understanding of CAD pathophysiology, diagnostic applications, prognostic studies, clinical trials, and clinical guidelines.

Fractional flow reserve vs. angiography in guiding management to optimize outcomes in non-ST-segment elevation myocardial infarction: the British Heart Foundation FAMOUS-NSTEMI randomized trial.

AIM: We assessed the management and outcomes of non-ST segment elevation myocardial infarction (NSTEMI) patients randomly assigned to fractional flow reserve (FFR)-guided management or angiography-guided standard care. METHODS AND RESULTS: We conducted a prospective, multicentre, parallel group, 1 : 1 randomized, controlled trial in 350 NSTEMI patients with ≥1 coronary stenosis ≥30% of the lumen diameter assessed visually (threshold for FFR measurement) (NCT01764334). Enrolment took place in six UK hospitals from October 2011 to May 2013. Fractional flow reserve was disclosed to the operator in the FFR-guided group (n = 176). Fractional flow reserve was measured but not disclosed in the angiography-guided group (n = 174). Fractional flow reserve ≤0.80 was an indication for revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). The median (IQR) time from the index episode of myocardial ischaemia to angiography was 3 (2, 5) days. For the primary outcome, the proportion of patients treated initially by medical therapy was higher in the FFR-guided group than in the angiography-guided group [40 (22.7%) vs. 23 (13.2%), difference 95% (95% CI: 1.4%, 17.7%), P = 0.022]. Fractional flow reserve disclosure resulted in a change in treatment between medical therapy, PCI or CABG in 38 (21.6%) patients. At 12 months, revascularization remained lower in the FFR-guided group [79.0 vs. 86.8%, difference 7.8% (-0.2%, 15.8%), P = 0.054]. There were no statistically significant differences in health outcomes and quality of life between the groups. CONCLUSION: In NSTEMI patients, angiography-guided management was associated with higher rates of coronary revascularization compared with FFR-guided management. A larger trial is necessary to assess health outcomes and cost-effectiveness.