Assessing the Impact of Colchicine on Coronary Plaque Phenotype After Myocardial Infarction with Optical Coherence Tomography: Rationale and Design of the COCOMO-ACS Study.

INTRODUCTION: Recurrent event rates after myocardial infarction (MI) remain unacceptably high, in part because of the continued growth and destabilization of residual coronary atherosclerotic plaques, which may occur despite lipid-lowering therapy. Inflammation is an important contributor to this ongoing risk. Recent studies have shown that the broad-acting anti-inflammatory agent, colchicine, may reduce adverse cardiovascular events in patients post-MI, although the mechanistic basis for this remains unclear. Advances in endovascular arterial wall imaging have allowed detailed characterization of the burden and compositional phenotype of coronary plaque, along with its natural history and responsiveness to treatment. One such example has been the use of optical coherence tomography (OCT) to demonstrate the plaque-stabilizing effects of statins on both fibrous cap thickness and the size of lipid pools within plaque. METHODS: The Phase 2, multi-centre, double-blind colchicine for coronary plaque modification in acute coronary syndrome (COCOMO-ACS) study will evaluate the effect of colchicine 0.5 mg daily on coronary plaque features using serial OCT imaging in patients following MI. Recruitment for the trial has been completed with 64 participants with non-ST elevation MI randomized 1:1 to colchicine or placebo in addition to guideline recommended therapies, including high-intensity statins. The primary endpoint is the effect of colchicine on the minimal fibrous cap thickness of non-culprit plaque over an 18-month period. The COCOMO-ACS study will determine whether addition of colchicine 0.5 mg daily to standard post-MI treatment has incremental benefits on high-risk features of coronary artery plaques. If confirmed, this will provide new mechanistic insights into how colchicine may confer clinical benefits in patients with atherosclerotic cardiovascular disease. TRIAL REGISTRATION: ANZCTR trial registration number: ACTRN12618000809235. Date of trial registration: 11th of May 2018.

The Effect of Stent Artefact on Quantification of Plaque Features Using Optical Coherence Tomography (OCT): A Feasibility and Clinical Utility Study.

BACKGROUND: Optical coherence tomography (OCT) can detect detailed plaque features in native coronary arteries. Stent struts cause shadows that partially obscure the vessel wall, but plaque features can still be seen. We investigated the impact of stent artefact on plaque quantification and whether the plaque behind struts is associated with microvascular dysfunction. METHODS: Patients retrospectively recruited from two centres, underwent OCT pre- and post-stenting on the same vessel segment. Lipid (LA) and calcium (CA) were measured as arcs. Macrophages, microchannels and cholesterol crystals were counted. Subsequently, we determined whether stented plaque features were associated with reduced Thrombolysis in Myocardial Infarction (TIMI) flow grade in consecutive patients who underwent OCT post-stenting. RESULTS: In 52 patients the lipid arc was similar pre- vs post-stent: median (55º [13º-93º] vs. 40º [18º-87°]; difference 1º [-7º to 16º], p = NS). Pre- and post-stent lipid were strongly correlated (r = 0.92, p < 0.001). In a further 128 patients those with reduced (TIMI ≤ II) vs normal flow post percutaneous coronary intervention (PCI) showed more plaque behind struts: lipid (89º [50º-139º] vs 62º [29º-88°]; p < 0.001); and calcium (24º [6º-45º] vs 7° [0º-34º]; p = 0.031). Multivariate logistic regression analysis showed that abnormal TIMI flow post-stenting was associated with diabetes (Odds ratio [OR] 2.87, CI 1.01-8.19, p = 0.048), LA (OR 1.29, 95% CI 1.14-1.38, p < 0.001) and CA (OR 1.26, CI 1.07-1.40, p = 0.005). CONCLUSIONS: Plaque behind the struts can be accurately quantified using OCT. Furthermore, OCT plaque features in stented segments are associated with microvascular dysfunction post PCI.

A Case of Aborted Sudden Cardiac Death Due to Coronary Artery Spasm.

Coronary artery spasm remains an important yet rarely recognized cause of myocardial ischemia, which may manifest as vasospastic angina, ventricular arrhythmia, or sudden cardiac death. Here we present a case of ST-segment elevation myocardial infarction complicated by cardiac arrest secondary to coronary artery spasm, diagnosed with invasive coronary function testing.

Isolated Ventricular Septal Rupture in a Suicide Jumper.

Ventricular septal rupture is an extremely rare sequelae of blunt chest trauma, and is mostly diagnosed postmortem. We present a case of a large isolated traumatic ventricular septal rupture after a suicide attempt by jumping from a height of 5 stories, which was successfully treated with surgical closure. (Level of Difficulty: Intermediate.).

Single high-sensitivity troponin levels to assess patients with potential acute coronary syndromes.

OBJECTIVE: We tested the hypothesis that patients with a potential acute coronary syndrome (ACS) and very low levels of high-sensitivity cardiac troponin I can be efficiently and safely discharged from the emergency department after a single troponin measurement. METHODS: This prospective cohort study recruited 2255 consecutive patients aged ≥18 years presenting to the Emergency Department, Royal Perth Hospital, Western Australia, with chest pain without high-risk features but requiring the exclusion of ACS. Patients were managed using a guideline-recommended pathway or our novel Single Troponin Accelerated Triage (STAT) pathway. The primary outcome was the percentage of patients discharged in <3 hours. Secondary outcomes included the duration of observation and death or acute myocardial infarction in the next 30 days. RESULTS: The study enrolled 1131 patients to the standard cohort and 1124 to the STAT cohort. Thirty-eight per cent of the standard cohort were discharged directly from emergency department compared with 63% of the STAT cohort (p<0.001). The median duration of observation was 4.3 (IQR 3.3-7.1) hours in the standard cohort and 3.6 (2.6-5.4) hours in the STAT cohort (p<0.001), with 21% and 38% discharged in <3 hours, respectively (p<0.001). No patients discharged directly from the emergency department died or suffered an acute myocardial infarction within 30 days in either cohort. CONCLUSIONS: Among low-risk patients with a potential ACS, a pathway which incorporates early discharge based on a single very low level of high-sensitivity cardiac troponin increases the proportion of patients discharged directly from the emergency department, reduces length of stay and is safe. TRIAL REGISTRATION NUMBER: ACTRN12618000797279.

Coronary 18F-sodium fluoride PET detects high-risk plaque features on optical coherence tomography and CT-angiography in patients with acute coronary syndrome.

BACKGROUND AND AIMS: 18F-Sodium Fluoride Positron Emission Tomography (18F-NaF PET) non-invasively detects micro-calcification activity, the earliest stage of atherosclerotic arterial calcification. We studied the association between coronary 18F-NaF uptake and high-risk plaque features on intra-coronary optical coherence tomography (OCT) and CT-angiography (CTCA) and the potential application to patient-level risk stratification. METHODS: Sixty-two prospectively recruited patients with acute coronary syndrome (ACS) underwent multi-vessel OCT, 18F-NaF PET and CTCA. The maximum tissue to background ratio (TBRmax = standardised uptake value (SUV)max/SUVbloodpool) was measured in each coronary segment on 18F-NaF PET scans. High-risk plaque features on OCT and CTCA were compared in matched coronary segments. The number of patients testing positive (>2SD above the normal range) for micro-calcification activity was determined. RESULTS: In 62 patients (age, mean ± standard deviation (SD) = 61 ± 9 years, 85% male) the coronary segments with elevated 18F-NaF uptake had higher lipid arc (LA) (median [25th-75th centile]: 74° [35°-117°] versus 48° [15°-83°], p=0.021), higher prevalence of macrophages [n(%): 37 (62%) versus 89 (39%), p=0.008] and lower plaque free wall (PFW) (50° [7°-110°] versus 94° [34°-180°], p=0.027) on OCT, and a higher total plaque burden (p=0.011) and higher dense calcified plaque burden (p= 0.001) on CTCA, when compared with 18F-NaF negative segments. Patients grouped by increasing number of coronary lesions positive for microcalcification activity (0,1, ≥2) showed decreasing plaque free wall, increasing calcification and increasing macrophages on OCT (respectively p=0.008, p < 0.001 and p=0.028). CONCLUSIONS: 18F-NaF uptake is associated with high-risk plaque features on OCT and CTCA in a per-segment and per-patient analysis in subjects hospitalized for ACS.

The peri-operative management of anti-platelet therapy in elective, non-cardiac surgery.

BACKGROUND: Cardiovascular complications are important causes of morbidity and mortality in patients undergoing elective non-cardiac surgery, with adverse cardiac outcomes estimated to occur in approximately 4% of all patients. Anti-platelet therapy withdrawal may precede up to 10% of acute cardiovascular syndromes, with withdrawal in the peri-operative setting incompletely appraised. OBJECTIVES: The aims of our study were to determine the proportion of patients undergoing elective non-cardiac surgery currently prescribed anti-platelet therapy, and identify current practice in peri-operative management. In addition, the relationship between management of anti-platelet therapy and peri-operative cardiac risk was assessed. METHODS: We evaluated consecutive patients attending elective non-cardiac surgery at a major tertiary referral centre. Clinical and biochemical data were collected and analysed on patients currently prescribed anti-platelet therapy. Peri-operative management of anti-platelet therapy was compared with estimated peri-operative cardiac risk. RESULTS: Included were 2950 consecutive patients, with 516 (17%) prescribed anti-platelet therapy, primarily for ischaemic heart disease. Two hundred and eighty nine (56%) patients had all anti-platelet therapy ceased in the peri-operative period, including 49% of patients with ischaemic heart disease and 46% of patients with previous coronary stenting. Peri-operative cardiac risk score did not influence anti-platelet therapy management. CONCLUSIONS: Approximately 17% of patients undergoing elective non-cardiac surgery are prescribed anti-platelet therapy, the predominant indication being for ischaemic heart disease. Almost half of all patients with previous coronary stenting had no anti-platelet therapy during the peri-operative period. The decision to cease anti-platelet therapy, which occurred commonly, did not appear to be guided by peri-operative cardiac risk stratification.

Perioperative myocardial necrosis in patients at high cardiovascular risk undergoing elective non-cardiac surgery.

OBJECTIVE: Cardiovascular complications are important causes of morbidity and mortality in elective non-cardiac surgery. Although difficult to diagnose, perioperative myocardial infarction (MI) remains prognostically important. High-sensitivity troponin T (hs-TnT) assays allow detection of very minor damage to cardiac muscle. These assays are yet to be fully evaluated in the perioperative setting. Our aim was to determine the incidence and predictors of myocardial necrosis in patients at high cardiovascular risk undergoing elective non-cardiac surgery using hs-TnT. DESIGN: Prospective observational cohort study. PATIENTS: 352 consecutive patients undergoing elective major non-cardiac surgery prescribed antiplatelet therapy for primary or secondary cardiovascular event prevention. MAIN OUTCOME MEASURE: The incidence of elevated preoperative hs-TnT (≥14 ng/litre), hs-TnT-defined perioperative myocardial necrosis (≥ 14ng/litre and 50% increase from preoperative level), and perioperative MI were determined in relation to patient and surgical factors. RESULTS: Preoperative hs-TnT was elevated in 31% and postoperative myocardial necrosis occurred in 22% of patients. Predictors of elevated baseline hs-TnT included age (OR 1.10, p<0.001), male gender (OR 2.91, p<0.001), diabetes requiring insulin therapy (OR 4.85, p=0.004) and chronic kidney disease (OR 3.60, p<0.001). Independent predictors of perioperative myocardial necrosis were age (OR 1.07, p<0.001), intraoperative hypotension (OR 3.67, p=0.001) and orthopaedic surgery (OR 2.46, p=0.005). Only 2% of patients suffered clinically apparent MI. Elevated preoperative hs-TnT did not predict perioperative myocardial necrosis or MI. CONCLUSIONS: Perioperative myocardial damage occurs frequently in patients undergoing elective non-cardiac surgery, although the majority of events are clinically undetected. Age and intraoperative hypotension are independent predictors of myocardial necrosis in this setting.

Incidence and determinants of myocardial infarction following percutaneous coronary interventions according to the revised Joint Task Force definition of troponin T elevation.

BACKGROUND: Elevations in troponin T (TnT) occur frequently following percutaneous coronary intervention (PCI) and are associated with an adverse prognosis. The Joint ESC/ACC/AHA/WHF Task Force have released a proposal for a universal definition of myocardial infarction (MI), including diagnostic criteria for PCI associated MI. This is based on a TnT cut-point of more than three times the 99th percentile (0.03 ng/ml), which better reflects the precision of the assay. Our study investigated the incidence and predictive factors of a PCI associated MI, using the revised definition. METHODS: 325 patients were studied following PCI with stenting. TnT was collected at both 8 and 18 h following PCI in patients with either stable or unstable angina and normal baseline TnT levels. Comparison was made of both clinical and procedural characteristics of patients with and without a rise in TnT following intervention, using cut points of 0.01 and 0.03 ng/ml. RESULTS: TnT was elevated > or = 0.03 ng/ml in 27% and > or = 0.01 ng/ml in 39% of patients following PCI. Troponin elevation was significantly more likely in those patients who experienced peri-procedural ischemic symptoms or EKG changes, or in whom abciximab was used. The variables associated with a troponin rise showed a greater difference between TnT positive and negative patients when using 0.03 ng/ml compared to 0.01 ng/ml, suggesting that this may be a better definition of PCI-related MI. CONCLUSIONS: Approximately one-quarter of low risk patients experience a procedural MI according to the revised definition. Rises in troponin were significantly associated with peri-procedural ischemic symptoms and EKG changes, and abciximab use, consistent with this level of TnT reflecting true myocardial necrosis.