In vivo coronary lesion differentiation with computed tomography angiography and intravascular ultrasound as compared to optical coherence tomography.

BACKGROUND: In vitro studies have shown the feasibility of coronary lesion grading with computed tomography angiography (CTA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) as compared to histology, whereas OCT had the highest discriminatory capacity. OBJECTIVE: We investigated the ability of CTA and IVUS to differentiate between early and advanced coronary lesions in vivo, OCT serving as standard of reference. METHODS: Multimodality imaging was prospectively performed in 30 NSTEMI patients. Plaque characteristics were assessed in 1083 cross-sections of 30 culprit lesions, co-registered among modalities. Absence of plaque, fibrous and fibrocalcific plaque on OCT were defined as early plaque, whereas lipid rich-plaque on OCT was defined as advanced plaque. Odds ratios adjusted for clustering were calculated to assess associations between plaque types on CTA and IVUS with early or advanced plaque. RESULTS: Normal findings on CTA as well as on IVUS were associated with early plaque. Non-calcified, calcified plaques and the napkin ring sign on CTA were associated with advanced plaque. On IVUS, fatty and calcified plaques were associated with advanced plaque. CONCLUSIONS: In vivo coronary plaque characteristics on CTA and IVUS are associated with plaque characteristics on OCT. Of note, normal findings on CTA and IVUS relate to early lesions on OCT. Nevertheless, multiple plaque features on CTA and IVUS are related to advanced plaques on OCT, which may make it difficult to use qualitative plaque assessment in clinical practice.

Computed tomography coronary angiography in patients with acute myocardial infarction and normal invasive coronary angiography.

BACKGROUND: Three to five percent of patients with acute myocardial infarction (AMI) have normal coronary arteries on invasive coronary angiography (ICA). The aim of this study was to assess the presence and characteristics of atherosclerotic plaques on computed tomography coronary angiography (CTCA) and describe the clinical characteristics of this group of patients. METHODS: This was a multicentre, prospective, descriptive study on CTCA evaluation in thirty patients fulfilling criteria for AMI and without visible coronary plaques on ICA. CTCA evaluation was performed head to head in consensus by two experienced observers blinded to baseline patient characteristics and ICA results. Analysis of plaque characteristics and plaque effect on the arterial lumen was performed. Coronary segments were visually scored for the presence of plaque. Seventeen segments were differentiated, according to a modified American Heart Association classification. Echocardiography performed according to routine during the initial hospitalisation was retrieved for analysis of wall motion abnormalities and left ventricular systolic function in most patients. RESULTS: Twenty-five patients presented with non ST-elevation myocardial infarction (NSTEMI) and five with ST-elevation myocardial infarction (STEMI). Mean age was 60.2 years and 23/30 were women. The prevalence of risk factors of coronary artery disease (CAD) was low. In total, 452 coronary segments were analysed. Eighty percent (24/30) had completely normal coronary arteries and twenty percent (6/30) had coronary atherosclerosis on CTCA. In patients with atherosclerotic plaques, the median number of segments with plaque per patient was one. Echocardiography was normal in 4/22 patients based on normal global longitudinal strain (GLS) and normal wall motion score index (WMSI); 4/22 patients had normal GLS with pathological WMSI; 3/22 patients had pathological GLS and normal WMSI; 11/22 patients had pathological GLS and WMSI and among them we could identify 5 patients with a Takotsubo pattern on echo. CONCLUSIONS: Despite a diagnosis of AMI, 80 % of patients with normal ICA showed no coronary plaques on CTCA. The remaining 20 % had only minimal non-obstructive atherosclerosis. Patients fulfilling clinical criteria for AMI but with completely normal ICA need further evaluation, suggestively with magnetic resonance imaging (MRI).

Characteristics of patients with false- ST-segment elevation myocardial infarction diagnoses.

BACKGROUND: A subgroup of patients presenting with suspected ST-elevation myocardial infarction (STEMI) have no culprit lesion during coronary angiography (false-positive STEMI). Little is known about patient- and system-related factors that are associated with false-positive STEMI. We evaluated the incidence, correlates, delay, final diagnosis, and outcome of patients with false-positive STEMI. METHODS: We studied 827 consecutive patients presenting with suspected STEMI between January 2011-September 2012. RESULTS: A false positive STEMI activation was identified in 68 patients (8.2%). Patients with false-positive STEMI were younger (57 vs 63 year; p=0.020), less often had hypercholesterolemia (19 vs 43%; p=0.001), and had a higher heart rate (82 vs 75 bpm; p=0.014). The association between these factors and false-positive STEMI activation persisted in multivariate analysis. The duration of symptoms to call was longer in false-positive STEMI patients (128 vs 83 min; p=0.030), although this did not reach statistical significance in multivariate analysis. Final diagnosis in patients with false-positive STEMI activation was particularly from unknown origin (41%). There were no significant differences in mortality at 30 days and one year between patients with STEMI and false-positive STEMI. CONCLUSION: The incidence of false-positive STEMI was 8.2% in patients suspected of STEMI. Patients with false-positive STEMI differ from STEMI patients in certain baseline characteristics and in patient delay. Interestingly, absence of coronary disease did not translate into better clinical outcome.

Independent association between symptom onset time and infarct size in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Recent studies have reported on circadian variation in infarct size in ST-elevation myocardial infarction (STEMI) patients. Controversy remains as to whether this finding indicates circadian dependence of myocardial tolerance to ischemia/reperfusion injury or that it can simply be explained by confounding factors such as baseline profile and ischemic time. We assessed the clinical impact and independent association between symptom onset time and infarct size, accounting for possible subgroup differences. From a multicenter registry, 6799 consecutive STEMI patients undergoing primary percutaneous coronary intervention (PCI) between 2004 and 2010 were included. Infarct size was measured using peak creatine kinase (CK). Infarct size exhibited circadian variation with largest infarct size in patients with symptom onset around 03:00 at night (estimated peak CK 1322 U/l; 95% confidence interval (CI): 1217-1436) and smallest infarct size around 11:00 in the morning (estimated peak CK 1071 U/l; 95% CI: 1001-1146; relative reduction 19%; p = 0.001). Circadian variation in infarct size followed an inverse pattern in patients with prior myocardial infarction (p-interaction <0.001) and prior PCI (p-interaction = 0.006), although the later did not persist in multivariable analysis. Symptom onset time remained associated with infarct size after accounting for these interactions and adjusting for baseline characteristics and ischemic time. Symptom onset time did not predict one-year mortality (p = 0.081). In conclusion, there is substantial circadian variation in infarct size, which cannot be fully explained by variations in baseline profile or ischemic time. Our results lend support to the hypothesis of circadian myocardial ischemic tolerance and suggest a different mechanism in patients with prior myocardial infarction.

Neutrophil/Lymphocyte ratio is associated with non-calcified plaque burden in patients with coronary artery disease.

BACKGROUND: Elevations in soluble markers of inflammation and changes in leukocyte subset distribution are frequently reported in patients with coronary artery disease (CAD). Lately, the neutrophil/lymphocyte ratio has emerged as a potential marker of both CAD severity and cardiovascular prognosis. OBJECTIVES: The aim of the study was to investigate whether neutrophil/lymphocyte ratio and other immune-inflammatory markers were related to plaque burden, as assessed by coronary computed tomography angiography (CCTA), in patients with CAD. METHODS: Twenty patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and 30 patients with stable angina (SA) underwent CCTA at two occasions, immediately prior to coronary angiography and after three months. Atherosclerotic plaques were classified as calcified, mixed and non-calcified. Blood samples were drawn at both occasions. Leukocyte subsets were analyzed by white blood cell differential counts and flow cytometry. Levels of C-reactive protein (CRP) and interleukin(IL)-6 were measured in plasma. Blood analyses were also performed in 37 healthy controls. RESULTS: Plaque variables did not change over 3 months, total plaque burden being similar in NSTE-ACS and SA. However, non-calcified/total plaque ratio was higher in NSTE-ACS, 0.25(0.09-0.44) vs 0.11(0.00-0.25), p<0.05. At admission, levels of monocytes, neutrophils, neutrophil/lymphocyte ratios, CD4+ T cells, CRP and IL-6 were significantly elevated, while levels of NK cells were reduced, in both patient groups as compared to controls. After 3 months, levels of monocytes, neutrophils, neutrophil/lymphocyte ratios and CD4+ T cells remained elevated in patients. Neutrophil/lymphocyte ratios and neutrophil counts correlated significantly with numbers of non-calcified plaques and also with non-calcified/total plaque ratio (r = 0.403, p = 0.010 and r = 0.382, p = 0.024, respectively), but not with total plaque burden. CONCLUSIONS: Among immune-inflammatory markers in NSTE-ACS and SA patients, neutrophil counts and neutrophil/lymphocyte ratios were significantly correlated with non-calcified plaques. Data suggest that these easily measured biomarkers reflect the burden of vulnerable plaques in CAD.

Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial.

IMPORTANCE: Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function. OBJECTIVE: To evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI). DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013. INTERVENTIONS: Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months. MAIN OUTCOMES AND MEASURES: The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure. RESULTS: At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed. CONCLUSIONS AND RELEVANCE: Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01217307.

Time of symptom onset and value of myocardial blush and infarct size on prognosis in patients with ST-elevation myocardial infarction.

In patients with ST-segment elevation myocardial infarction (STEMI), the time of onset of ischemia has been associated with myocardial infarction (MI) size. Myocardial blush grade (MBG) reflects myocardial response to ischemia/reperfusion injury, which may differ according to time of the day. The aim of our study was to explore the 24-hour variation in MBG and MI size in relation to outcomes in STEMI patients. A retrospective multicenter analysis of 6970 STEMI patients was performed. Time of onset of STEMI was divided into four 6-hour periods. STEMI patients have a significant 24-hour pattern in onset of symptoms, with peak onset around 09:00 hour. Ischemic time was longest and MI size, estimated by peak creatine kinase concentration, was largest in patients with STEMI onset between 00:00 and 06:00 hours. Both MBG and MI size were independently associated with mortality. Time of onset of STEMI was not independently associated with mortality when corrected for baseline and procedural factors. Interestingly, patients presenting with low MBG between 00:00 and 06:00 hours had a better prognosis compared to other groups. In conclusion, patients with symptom onset between 00:00 and 06:00 hours have longer ischemic time and consequently larger MI size. However, this does not translate into a higher mortality in this group. In addition, patients with failed reperfusion presenting in the early morning hours have better prognosis, suggesting a 24-hour pattern in myocardial protection.

Chronic metformin treatment is associated with reduced myocardial infarct size in diabetic patients with ST-segment elevation myocardial infarction.

PURPOSE: Increased myocardial infarct (MI) size is associated with higher risk of developing left ventricular dysfunction, heart failure and mortality. Experimental studies have suggested that metformin treatment reduces MI size after induced ischaemia but human data is lacking. We aimed to investigate the effect of metformin on MI size in patients presenting with an acute MI. METHODS: All consecutive patients (n = 3,288) presenting to our hospital with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI between January 2004 and December 2010 were included in this retrospective analysis. Patients with diabetes were divided according to metformin versus non-metformin based pharmacotherapy. MI size was estimated using peak values of serum creatine kinase (CK), myocardial band of CK (CK-MB), and troponin-T. RESULTS: We identified 677 (20.6 %) patients with diabetes, of whom 189 (27.9 %) were treated with metformin. Chronic metformin treatment was associated with lower peak levels of CK (1,101 vs. 1,422 U/L, P = 0.005), CK-MB (152 vs. 182 U/L, P = 0.018) and troponin-T (2.5 vs. 4.0 ng/L, P = 0.021) compared to non-metformin using diabetics. After adjustment for age, sex, TIMI flow post PCI, and previous MI, the use of metformin treatment remained an independent predictor of smaller MI size. Patient with diabetes treated with metformin had even smaller MI size than patients without diabetes. CONCLUSIONS: Chronic metformin treatment is associated with reduced MI size compared to non-metformin based strategies in diabetic patients presenting with STEMI. Metformin might have additional beneficial effects beyond glucose lowering efficacy.

Quantitative analysis of the impact of total ischemic time on myocardial perfusion and clinical outcome in patients with ST-elevation myocardial infarction.

Early reperfusion of the infarct-related coronary artery is an important issue in improvement of outcomes after ST-segment elevation myocardial infarction (STEMI). In this study, the clinical significance of total ischemic time on myocardial reperfusion and clinical outcomes was evaluated in patients with STEMI treated with primary percutaneous coronary intervention and thrombus aspiration and additional triple-antiplatelet therapy. Total ischemic time was defined as time from symptom onset to first intracoronary therapy (first balloon inflation or thrombus aspiration). All patients with STEMI treated with primary percutaneous coronary intervention with total ischemic times ≥30 minutes and <24 hours from 2005 to 2008 were selected. Ischemic times were available in 1,383 patients, of whom 18.4% presented with total ischemic times ≤2 hours, 31.2% >2 to 3 hours, 26.8% >3 to 5 hours, and 23.5% >5 hours. Increased ischemic time was associated with age, female gender, hypertension, and diabetes. Patients with total ischemic times <5 hours more often had myocardial blush grade 3 (40% to 45% vs 22%, p <0.001) and complete ST-segment resolution (55% to 60% vs 42%, p = 0.002) than their counterparts with total ischemic times >5 hours. In addition, patients with total ischemic times ≤5 hours had lower 30-day mortality (1.5% vs 4.0%, p = 0.032) than patients with total ischemic times >5 hours. In conclusion, in this contemporary cohort of patients with STEMI treated with primary percutaneous coronary intervention, triple-antiplatelet therapy, and thrombus aspiration, short ischemic time was associated with better myocardial reperfusion and decreased mortality. After a 5-hour period in which outcomes remain relatively stable, myocardial reperfusion becomes suboptimal and mortality increases.

Intracoronary versus intravenous administration of abciximab in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with thrombus aspiration: the comparison of intracoronary versus intravenous abciximab administration during emergency reperfusion of ST-segment elevation myocardial infarction (CICERO) trial.

BACKGROUND: administration of the glycoprotein IIb/IIIa inhibitor abciximab is an effective adjunctive treatment strategy during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Although small-scale studies have suggested beneficial effects of intracoronary over intravenous administration of abciximab, this has not been investigated in a medium-scale randomized clinical trial. METHODS AND RESULTS: a total of 534 ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration within 12 hours of symptom onset were randomized to either an intracoronary or an intravenous bolus of abciximab (0.25 mg/kg). Patients were pretreated with aspirin, heparin, and clopidogrel. The primary end point was the incidence of restored myocardial reperfusion, defined as complete ST-segment resolution. Secondary end points included myocardial reperfusion as assessed by myocardial blush grade, enzymatic infarct size, and major adverse cardiac events at 30 days. The incidence of complete ST-segment resolution was similar in the intracoronary and intravenous groups (64% versus 62%; P=0.562). However, the incidence of myocardial blush grade 2/3 was higher in the intracoronary group than in the intravenous group (76% versus 67%; P=0.022). Furthermore, enzymatic infarct size was smaller in the intracoronary than in the intravenous group (P=0.008). The incidence of major adverse cardiac events was similar in both groups (5.5% versus 6.1%; P=0.786). CONCLUSIONS: in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration, intracoronary administration of abciximab compared with intravenous administration does not improve myocardial reperfusion as assessed by ST-segment resolution. However, intracoronary administration is associated with improved myocardial reperfusion as assessed by myocardial blush grade and a smaller enzymatic infarct size.