Cost-effectiveness of adding a non-invasive acoustic rule-out test in the evaluation of patients with symptoms suggestive of coronary artery disease: rationale and design of the prospective, randomised, controlled, parallel-group multicenter FILTER-SCAD trial.

INTRODUCTION: Most patients with symptoms suggestive of chronic coronary syndrome (CCS) have no obstructive coronary artery disease (CAD) and better selection of patients to be referred for diagnostic tests is needed. The CAD-score is a non-invasive acoustic measure that, when added to pretest probability of CAD, has shown good rule-out capabilities. We aimed to test whether implementation of CAD-score in clinical practice reduces the use of diagnostic tests without increasing major adverse cardiac events (MACE) rates in patients with suspected CCS. METHODS AND ANALYSIS: FILTER-SCAD is a randomised, controlled, multicenter trial aiming to include 2000 subjects aged ≥30 years without known CAD referred for outpatient assessment for symptoms suggestive of CCS. Subjects are randomised 1:1 to either the control group: standard diagnostic examination (SDE) according to the current guidelines, or the intervention group: SDE plus a CAD-score. The subjects are followed for 12 months for the primary endpoint of cumulative number of diagnostic tests and a safety endpoint (MACE). Angina symptoms, quality of life and risk factor modification will be assessed with questionnaires at baseline, 3 months and 12 months after randomisation. The study is powered to detect superiority in terms of a reduction of ≥15% in the primary endpoint between the two groups with a power of 80%, and non-inferiority on the secondary endpoint with a power of 90%. The significance level is 0.05. The non-inferiority margin is set to 1.5%. Randomisation began on October 2019. Follow-up is planned to be completed by December 2022. ETHICS AND DISSEMINATION: This study has been approved by the Danish Medical Agency (2019024326), Danish National Committee on Health Research Ethics (H-19012579) and Swedish Ethical Review Authority (Dnr 2019-04252). All patients participating in the study will sign an informed consent. All study results will be attempted to be published as soon as possible. TRIAL REGISTRATION NUMBER: NCT04121949; Pre-results.

Safety of Same-Day Discharge After Percutaneous Coronary Intervention in Selected Patients With Non-ST Elevation Acute Coronary Syndrome.

OBJECTIVES: We aimed to investigate the safety of same-day discharge (SDD) after percutaneous coronary intervention (PCI) for non-ST segment elevation acute coronary syndrome (NSTEACS), and to investigate the reduction in duration of hospitalization achievable by SDD. BACKGROUND: Previous studies have established the safety of SDD after elective PCI, while the safety of SDD after non-elective PCI for acute coronary syndrome has only been sparsely studied. METHODS: A single-center, observational, retrospective study of 923 consecutive procedures in patients with NSTEACS who had PCI was performed. The procedures were divided into 2 groups based on postprocedural management: SDD (n = 195) and non-SDD (n = 728). RESULTS: No differences were seen in the total number of adverse events at 1 month (1.5% SDD vs 1.4% non-SDD; P=.74), 3 months (2.5% SDD vs 2.3% non-SDD; P=.80), and 6 months (3.5% SDD vs 3.3% non-SDD; P=.84) after discharge, and there were no deaths in the SDD group. No difference was found in unplanned rehospitalizations within 6 months (20.5% SDD vs 25.3% non-SDD; P=.17), while unplanned revascularizations were more frequent in non-SDD patients (5.6% SDD vs 13.4% non-SDD; P<.01). Median duration of hospitalization was 1.3 days shorter for SDD patients than for non-elderly, uncomplicated non-SDD patients. CONCLUSIONS: SDD after PCI in a selected group of NSTEACS patients was associated with low rates of adverse events, unplanned rehospitalizations, and revascularizations. SDD was associated with a shorter hospitalization duration.

Clinical outcome following late reperfusion with percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Up to 40% of patients with ST-segment elevation myocardial infarction (STEMI) present later than 12 hours after symptom onset. However, data on clinical outcomes in STEMI patients treated with primary percutaneous coronary intervention 12 or more hours after symptom onset are non-existent. We evaluated the association between primary percutaneous coronary intervention performed later than 12 hours after symptom onset and clinical outcomes in a large all-comer contemporary STEMI cohort. METHODS: All STEMI patients treated with primary percutaneous coronary intervention in eastern Denmark from November 2009 to November 2016 were included and stratified by timing of the percutaneous coronary intervention. The combined clinical endpoint of all-cause mortality and hospitalisation for heart failure was identified from nationwide Danish registries. RESULTS: We included 6674 patients: 6108 (92%) were treated less than 12 hours and 566 (8%) were treated 12 or more hours after symptom onset. During a median follow-up period of 3.8 (interquartile range 2.3-5.6) years, 30-day, one-year and long-term cumulative rates of the combined endpoint were 11%, 17% and 25% in patients treated 12 or fewer hours and 21%, 29% and 37% in patients treated more than 12 hours (P<0.001 for all) after symptom onset. Late presentation was independently associated with an increased risk of an adverse clinical outcome (hazard ratio 1.42, 95% confidence interval 1.22-1.66; P<0.001). CONCLUSIONS: Increasing duration from symptom onset to primary percutaneous coronary intervention was associated with an increased risk of an adverse clinical outcome in patients with STEMI, especially when the delay exceeded 12 hours.

Early Systolic Lengthening in Patients With ST-Segment-Elevation Myocardial Infarction: A Novel Predictor of Cardiovascular Events.

Background Early systolic lengthening (ESL) may occur in ischemic myocardial segments with reduced contractile force. We sought to evaluate the prognostic potential of ESL in patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods and Results We prospectively enrolled 373 patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. All patients underwent a speckle tracking echocardiographic examination a median of 2 days (interquartile range, 1-3 days) after the percutaneous coronary intervention. We assessed a novel viability index, the ESL index, defined as follows: [-100×(peak positive systolic strain/peak negative strain in cardiac cycle)]. We also calculated ESL duration, defined as time from onset of QRS complex on the ECG to time of peak positive systolic strain. Both parameters were averaged from 18 myocardial segments. During a median follow-up of 5.3 years (interquartile range, 2.5-6.0 years), 145 (39%) experienced major adverse cardiovascular events, a composite of incident heart failure, new myocardial infarction, and all-cause mortality. The ESL index and ESL duration were significantly increased in culprit lesion areas (6.7±6.2% versus 5.0±4.1% and 43±33 ms versus 33±24 ms, respectively; P<0.001 for both). In Cox proportional hazard models, the ESL index (hazard ratio, 1.27 per 1% increase; 95% CI, 1.13-1.43; P<0.001) and ESL duration (hazard ratio, 1.49 per 1-ms increase; 95% CI, 1.15-1.92; P=0.002) yielded prognostic information on major adverse cardiovascular events. Both associations remained significant after adjusting for clinical, echocardiographic, and invasive confounders. Conclusions Assessment of ESL after primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction yields independent and significant prognostic information on the future risk of cardiovascular events.

Clinical outcome following late reperfusion with percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Up to 40% of patients with ST-segment elevation myocardial infarction (STEMI) present later than 12 hours after symptom onset. However, data on clinical outcomes in STEMI patients treated with primary percutaneous coronary intervention 12 or more hours after symptom onset are non-existent. We evaluated the association between primary percutaneous coronary intervention performed later than 12 hours after symptom onset and clinical outcomes in a large all-comer contemporary STEMI cohort. METHODS: All STEMI patients treated with primary percutaneous coronary intervention in eastern Denmark from November 2009 to November 2016 were included and stratified by timing of the percutaneous coronary intervention. The combined clinical endpoint of all-cause mortality and hospitalisation for heart failure was identified from nationwide Danish registries. RESULTS: We included 6674 patients: 6108 (92%) were treated less than 12 hours and 566 (8%) were treated 12 or more hours after symptom onset. During a median follow-up period of 3.8 (interquartile range 2.3-5.6) years, 30-day, one-year and long-term cumulative rates of the combined endpoint were 11%, 17% and 25% in patients treated 12 or fewer hours and 21%, 29% and 37% in patients treated more than 12 hours (P<0.001 for all) after symptom onset. Late presentation was independently associated with an increased risk of an adverse clinical outcome (hazard ratio 1.42, 95% confidence interval 1.22-1.66; P<0.001). CONCLUSIONS: Increasing duration from symptom onset to primary percutaneous coronary intervention was associated with an increased risk of an adverse clinical outcome in patients with STEMI, especially when the delay exceeded 12 hours.

Presence of post-systolic shortening is an independent predictor of heart failure in patients following ST-segment elevation myocardial infarction.

Following an ischemic event post systolic shortening (PSS) may occur. We investigated the association between PSS in patients with ST-segment elevation myocardial infarction (STEMI) following primary percutaneous coronary intervention (pPCI) and occurrence of cardiovascular events at follow-up. A total of 373 patients admitted with STEMI and treated with pPCI were prospectively included in the study cohort. All patients were examined by echocardiography a median of 2 days after admission (interquartile range, 1-3 days). PSS was measured by color tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) in six myocardial walls from all three apical projections. During a median follow-up period of 5.4 years (interquartile range, 4.1-6.0 years), 180 events occurred: 59 deaths, 70 heart failures (HF) and 51 new myocardial infarctions (MI). In multivariable analysis adjusting for: age, sex, peak troponin, left ventricle ejection fraction, TIMI flow grade, left ventricle mass index, hypertension and diabetes, presence of PSS by TDI in the culprit region was associated with a nearly twofold increased risk of HF (HR 1.90, 95% CI 1.02-3.53, P = 0.043) and the risk of HF increased incrementally with increasing numbers of walls displaying PSS. The increased risk of HF was confirmed when assessing the post-systolic index by STE (HR 1.29 95% CI 1.09-1.53, P = 0.003, per 1% increase). A regional analysis showed that PSS by TDI in the septal wall was the strongest predictor of HF (HR 1.77, 95% CI 1.08-2.92, P = 0.024). Presence of PSS was not associated with increased risk of death or MI. In patients with STEMI treated with pPCI, the presence of PSS examined by TDI and STE provides prognostic information on development of HF. Presence of PSS in the septal wall is the strongest predictor of HF.

Osteoprotegerin improves risk detection by traditional cardiovascular risk factors and hsCRP.

OBJECTIVE: To evaluate the association of plasma osteoprotegerin (OPG) to hospitalisation for ischaemic heart disease (IHD), ischaemic stroke and all-cause mortality, and the effect of combining plasma OPG and high-sensitivity C-reactive protein (hsCRP). DESIGN: OPG and hsCRP concentrations were measured at baseline in a large Danish prospective community-based population study. SETTING: The 4th Copenhagen City Heart Study. PARTICIPANTS: 5863 men and women aged 20-95 were recruited from the general population. MAIN OUTCOME MEASURES: Combined end-point of IHD, ischaemic stroke or all-cause mortality. RESULTS: During a median follow-up of 7.8 years (IQR 7.3-8.3), 1270 subjects (21.7%) reached the combined end-point. A twofold increase in plasma OPG was a significant predictor of the combined end-point (univariable HR 1.85, 95% CI 1.75 to 1.96; p<0.001). In a multivariable Cox-regression model containing age, male sex, hypertension, diabetes, hypercholesterolaemia, present or former smoking, glomerular filtration rate, prior IHD, prior ischaemic stroke, hsCRP and plasma OPG, high concentrations of hsCRP and plasma OPG were independent predictors of the combined end-point. The two biomarkers interacted statistically (p<0.001). Compared to low hsCRP and low OPG (n=1927), either high hsCRP or high OPG (univariable HR 2.38, 95% CI 2.02 to 2.80, p<0.001; n=2816), or both high hsCRP and high OPG (univariable HR 5.13, 95% CI 4.29 to 6.13, p<0.001; n=775) conferred increased risk of the combined end-point. CONCLUSIONS: OPG is an independent predictor of the combined end-point of hospitalisation of IHD, ischaemic stroke and all-cause mortality. The combination of plasma OPG and hsCRP provides more prognostic information than the individual effect of the two biomarkers.

Level of complement activity predicts cardiac dysfunction after acute myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: The positive effect of reperfusion after ST-elevation myocardial infarction (STEMI) can be reduced by ischemic/reperfusion (I/R) injury.Mannose-binding-lectin (MBL) and soluble C5b-9 (membrane-attack-complex) are involved in complement-driven cell lysis and may play a role in human myocardial I/R injury. We evaluated the potential association between MBL and sC5b-9 in plasma and subsequent cardiac dysfunction in patients with STEMI treated with primary percutaneous coronary intervention (pPCI). METHODS: The study included 74 STEMI-patients with acute occlusion of the left anterior descending coronary artery who were successfully treated with pPCI. Cardiac dysfunction was defined as left ventricular ejection fraction LVEF < 35%. RESULTS: Patients with subsequent LVEF < 35% had significantly higher median MBL and lower sC5b-9 compared to patients with LVEF > or = 35%. After adjustment of the multivariate logistic regression analysis, the odds for reduced LVEF was 5.5 (95% CI:1.5-19.3; p = 0.01) for patients with MBL > or = 800 mcg/L, and 5.0 (95% CI 1.4-18.4; p = 0.01) for patients with sC5b-9 < or = 160 mcg/L. CONCLUSION: High plasma MBL and low plasma sC5b-9 are independently associated with increased risk of cardiac dysfunction in STEMI patients treated with pPCI, probably due to increased complement activity during the ischemic and reperfusion process. The predictive value of low peripheral plasma sC5b-9 may be explained by an accumulation and activation of sC5b-9 in the infarcted myocardium.