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International audience; Background: Smoking has been associated with higher morbidity and mortality following myocardial infarction (MI), but reports of the impact on morbidity and mortality for females and elderly patients experiencing MI complicated with left ventricular dysfunction or overt heart failure are limited. Methods: In an individual patient data meta-analysis of high-risk MI patients, the association of smoking with hospitalizations and death were investigated. Weighted Cox proportional hazard modelling were used to study the risks of smoking on adjudicated endpoints among different sex and age categories. Results: 28,735 patients from the CAPRICORN, EPHESUS, OPTIMAAL and VALIANT trials were assessed. After weighting, smokers (N=18,148) were unfrequently women (29.2%) and a minority were above ≥80 years (9.8%). Smoking was significantly more associated with all-cause hospitalizations in women (hazard ratio (HR) 1.24; 95% confidence interval (CI) 1.16-1.32) than in men (HR=1.10; CI 1.05-1.16) resulting in a significant interaction between smoking and sex (p=0.005). Smoking was predictive of all-cause mortality homogenously across age categories (p for interaction=0.25) and sex (p for interaction=0.58). Conclusions: The influence of smoking on morbidity differed according to sex following high-risk MI. The deleterious impact of smoking on hospitalization appeared particularly potent in women, which should further reinforce preventive strategies in females.

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Background ECG changes after revascularization predicts improved outcome for patients with ST‐elevation myocardial infarction (STEMI). Worst lead residual (WLR) ST deviation and resolution of worst lead ST elevation (rST elevation) are simple measures that can be obtained early after PCI. The objective of the current study was to investigate whether simple ECG measures, obtained one hour following PCI, could predict cardiac magnetic resonance (CMR)‐derived myocardial salvage index (MSI), infarct size (IS), and microvascular obstruction (MVO) in patients with STEMI included in the MITOCARE trial. Methods The MITOCARE trial included 165 patients with a first‐time STEMI presenting within six hours of symptom onset. The current analysis included patients that had an ECG recorded at baseline and one hour after PCI and underwent CMR imaging after 3–5 days. Independent core laboratories determined WLR ST deviation, rST elevation, and the CMR variables (MSI, IS, and MVO). Results 83 patients with a mean age of 61 years were included. 83.1% were males and 41% had anterior infarctions. In logistic regression models, WLR ST deviation was a statistically significant predictor of IS (OR 2.2, 95% CI 1.3–3.8) and MVO (OR 2.8, 95% CI 1.5–5.2), but not of MSI (OR 0.8, 95% CI 0.5–1.2). rST elevation showed a trend toward a significant association with IS (OR 0.3, 95% CI 0.1–1.0), but not with the other CMR variables. Conclusion WLR ST deviation one hour after PCI was a predictor of IS and MVO. WLR ST deviation, a measure easily obtained from ECGs following PCI, may provide important prognostic information in patients with STEMI. publishedVersion

Background Anteroseptal ST elevation myocardial infarction (STEMI) is traditionally defined on the electrocardiogram (ECG) by ST elevation (STE) in leads V1-V3, with or without involvement of lead V4. It is commonly taught that such infarcts affect the basal anteroseptal myocardial segment. While there are suggestions in the literature that Q waves limited to V1-V4 represent predominantly apical infarction, none have evaluated anteroseptal ST elevation territories. We compared the distribution of the myocardium at risk (MaR) in STEMI patients presenting with STE limited to V1-V4 and those with more extensive STE (V1-V6). Methods We identified patients in the MITOCARE study presenting with a first acute STEMI and new STE in at least two contiguous anterior leads from V1 to V6. Patients underwent cardiac magnetic resonance (CMR) imaging three to five days after acute infarction. Results Thirty-two patients met inclusion criteria. In patients with STE in V1-V4 (n = 20), myocardium at risk (MaR) > 50% was seen in 0%, 85%, 75%, 100%, and 90% in the basal anteroseptal, mid anteroseptal, apical anterior, apical septal segments, and apex, respectively. The group with STE in V1-V6 (n = 12), MaR > 50% was seen in 8%, 83%, 83%, 92%, and 83% of the same segments. Conclusions Patients with acute STEMI and STE in leads V1-V4, exhibit MaR in predominantly apical territories and rarely in the basal anteroseptum. We found no evidence to support existence of isolated basal anteroseptal or septal STEMI. “Anteroapical” infarction is a more precise description than “anteroseptal” infarction for acute STEMI patients exhibiting STE in V1-V4.

Introduction: The myocardium at risk (MaR) represents the quantitative ischemic area destined to myocardial infarction (MI) if no reperfusion therapy is initiated. Different ECG scores for MaR have been developed, but there is no consensus as to which should be preferred. Objective: Comparisons of ECG scores and Cardiac Magnetic Resonance (CMR) for determining MaR. Methods: MaR was determined by 3 different ECG scores, and by CMR in ST-segment elevation MI (STEMI) patients from the MITOCARE cardioprotection trial. The Aldrich score (AL) is based on the number of leads with ST-elevation for anterior MI and the sum of ST-segment elevation for inferior MI on the admission ECG. The van Hellemond score (VH) considers both the ischemic and infarcted component of the MaR by adding the AL and the QRS score, which is an estimate of final infarct size. The Hasche score is based on the maximal possible infarct size determined from the QRS score on the baseline ECG. Results: Ninety-eight patients (85% male, mean age 61. years) met STEMI criteria on their admission ECG and underwent CMR within 3-5. days after STEMI. Mean MaR by CMR was 41.2. ±. 10.2 and 30.3. ±. 7.2 for anterior and inferior infarcts, respectively. For both anterior and inferior infarcts the Aldrich (18.2. ±. 5.1 and 18.6. ±. 6.0) and Hasche (25.3. ±. 9.8 and 26.4. ±. 8.8) scores significantly underestimated MaR compared to MaR measured by CMR. In contrast, MaR by the van Hellemond score (37.0. ±. 14.2 and 31.7. ±. 12.8) was comparable to CMR. Conclusion: We tested the performance of the electrocardiographic estimation of myocardium area at risk by Aldrich, Hasche and van Hellemond ECG scores in comparison to MaR measured by CMR in STEMI patients. MaR by the van Hellemond score and CMR were comparable, while Aldrich and Hasche underestimated MaR.

Background: Reduced left ventricular ejection fraction (LVEF) after acute myocardial infarction (MI) increases risk of cardiovascular (CV) hospitalizations, but evidence regarding its association with non-CV outcome is scarce. We investigated the association between LVEF and adjudicated cause-specific hospitalizations following MI complicated with low LVEF or overt heart failure (HF). Methods: In an individual patient data meta-analysis of 19,740 patients from 3 large randomized trials, Fine and Gray competing risk modeling was performed to study the association between LVEF and hospitalization types. Results: The most common cause of hospitalization was non-CV (n = 2,368 for HF, n = 1,554 for MI, and n = 3,703 for non-CV). All types of hospitalizations significantly increased with decreasing LVEF. The absolute risk increase associated with LVEF ≪25% (vs LVEF ≫35%) was 15.5% (95% CI 13.4-17.5) for HF, 4.7% (95% CI 3.0-6.4) for MI, and 10.4% (95% CI 8.0-12.8) for non-CV hospitalization. On a relative scale, after adjusting for confounders, each 5-point decrease in LVEF was associated with an increased risk of HF (hazard ratio [HR] 1.15, 95% CI 1.12-1.18), MI (HR 1.06, 95% CI 1.03-1.10), and non-CV hospitalization (HR 1.03, 95% CI 1.01-1.05). Conclusions: In a high-risk population with complicated acute MI, the absolute risk increase in non-CV hospitalizations associated with LVEF ≪25% was two thirds of the absolute risk increase in HF hospitalizations and twice the absolute risk increase in MI hospitalizations. LVEF was an independent predictor of all types of hospitalization and appears as an integrative marker of sicker patient status. acceptedVersion

Aims Clopidogrel is commonly used even after expiring patents. The brand clopidogrel (BC) was dealt by single company, while numerous manufacturers produce generic clopidogrel (GC). There are no convincing data to compare the safety of different formulations. Therefore, the data yielded from international, uniform, government-mandated registries may be useful. Methods and results We assessed primary causative adverse events (PCAE) after BC and GC in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The outcomes were divided into death, cardiac, thrombotic/embolic, haemorrhagic, and rash/dermal complications. These primary endpoints were then examined by proportional reporting ratios (PRR) and chi-square (χ2). Among total FAERS (n = 9 466 679) reports, overall BC (n = 88 863) cases were more common than after GC (n = 36 559). When triaged by PCAE role, BC (n = 18 328) was also more abundant than GC (n = 3987). The reported death rates were more than doubled after BC [18.4% vs. 7.0%; PRR = 0.38; 95% confidence interval (95% CI) 0.32–0.43; χ2=369.7; P Conclusion The PCAE profiles differ with BC and GC in FAERS. While deaths reports were higher, the rates of cardiac, haemorrhagic, and skin complications were less common for BC. Despite expected reporting bias, this may indicate that the manufacturers of GC are reluctant to report deaths to the FDA. However, the overall adverse event profile suggests potentially better safety of BC over GC formulations.

Background: Anterolateral myocardial infarction (MI) is traditionally defined on the electrocardiogram by ST-elevation (STE) in I, aVL, and the precordial leads. Traditional literature holds STE in lead aVL to be associated with occlusion proximal to the first diagonal branch of the left anterior descending coronary artery. However, concomitant ischemia of the inferior myocardium may theoretically lead to attenuation of STE in aVL. We compared segmental distribution of myocardial area at risk (MaR) in patients with and without STE in aVL. Methods: We identified patients in the MITOCARE study presenting with a first acute MI and new STE in two contiguous anterior leads from V1 to V6, with or without aVL STE. Patients underwent cardiac magnetic resonance imaging 3-5 days after acute infarction for quantitative assessment of MaR. Results: A total of 32 patients met inclusion criteria; 13 patients with and 19 without STE in lead aVL. MaR > 20% at the basal anterior segment was seen in 54% of patients with aVL STE, and 11% of those without (p = 0.011). MaR > 20% at the apical inferior segment was seen in 62% and 95% of patients with and without aVL STE, respectively (p = 0.029). The total MaR was not different between groups (44% ± 10% and 39% ± 8.3% respectively, p = 0.15). Conclusion: Patients with anterior STEMI and concomitant STE in aVL have less MaR in the apical inferior segment and more MaR in the basal anterior segment.

Background Terminal “QRS distortion” on the electrocardiogram (ECG) (based on Sclarovsky-Birnbaum's Grades of Ischemia Score) is a sign of severe ischemia, associated with adverse cardiovascular outcome in ST-segment elevation myocardial infarction (STEMI). In addition, ECG indices of the acuteness of ischemia (based on Anderson-Wilkins Acuteness Score) indicate myocardial salvage potential. We assessed whether severe ischemia with or without acute ischemia is predictive of infarct size (IS), myocardial salvage index (MSI) and left ventricular ejection fraction (LVEF) in anterior versus inferior infarct locations. Methods In STEMI patients, the severity and acuteness scores were obtained from the admission ECG. Based on the ECG patients were assigned with severe or non-severe ischemia and acute or non-acute ischemia. Cardiac magnetic resonance (CMR) was performed 2–6 days after primary percutaneous coronary intervention (pPCI). LVEF was measured by echocardiography 30 days after pPCI. Results ECG analysis of 85 patients with available CMR resulted in 20 (23%) cases with severe and non-acute ischemia, 43 (51%) with non-severe and non-acute ischemia, 17 (20%) with non-severe and acute ischemia, and 5 (6%) patients with severe and acute ischemia. In patients with anterior STEMI (n = 35), ECG measures of severity and acuteness of ischemia identified significant and stepwise differences in myocardial damage and function. Patients with severe and non-acute ischemia had the largest IS, smallest MSI and lowest LVEF. In contrast, no difference was observed in patients with inferior STEMI (n = 50). Conclusions The applicability of ECG indices of severity and acuteness of myocardial ischemia to estimate myocardial damage and salvage potential in STEMI patients treated with pPCI, is confined to anterior myocardial infarction.

Identifying risk factors for specific modes of death in patients with heart failure (HF) or left ventricular (LV) dysfunction after acute myocardial infarction (MI) may help to avert events. We sought to evaluate LV ejection fraction (LVEF) as a prognosticator of specific death modes.In an individual patient data meta-analysis of four merged trials (CAPRICORN, EPHESUS, OPTIMAAL, and VALIANT), Cox modelling was performed to study the association between baseline LVEF from 19,740 patients and types of death during follow-up. Over a median follow-up of 707 days 3419 deaths occurred. The distribution pattern for mode of death was similar across categories (LVEF 25%, LVEF 25-35%, and LVEF 35%). In multivariable models, the risk of all types of death increased with decreasing LVEF. If compared to LVEF 35%, LVEF 25% was associated with a 113% increased risk of sudden death (hazard ratio (HR) 2.13, 95% confidence interval (CI) 1.53-2.98), a 170% increased risk of HF death (HR 2.70, 95% CI 1.83-3.98), a 66% increased risk of other cardiovascular (CV) death (HR 1.66, 95% CI 1.14-2.42), and a 90% increased risk of non CV death (HR 1.90, 95% CI 1.15-3.14).In patients with HF or LV dysfunction after acute MI, low LVEF is a ubiquitous risk marker associated with death regardless of type. The different modes of death are fairly equally represented throughout the categories of LVEF and sudden death remains a significant mode of death also in patients with LVEF 35%.

BACKGROUND: In traditional literature, it appears that "anteroseptal" MIs with Q waves in V1-V3 involve basal anteroseptal segments although studies have questioned this belief.METHODS: We studied patients with first acute anterior Q-wave (>30ms) MI. All underwent late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (MRI).RESULTS: Those with Q waves in V1-V2 (n=7) evidenced LGE >50% in 0%, 43%, 43%, 57%, and 29% of the basal anteroseptal, mid anteroseptal, apical anterior, apical septal segments, and apex, respectively. Patients with Q waves in V1-V3 (n=14), evidenced involvement was 14%, 43%, 43%, 50%, and 7% of the same respective segments. In those with extensive anterior Q waves (n=7), involvement was 0%, 71%, 57%, 86%, and 86%.CONCLUSIONS: Q-wave MI in V1-V2/V3 primarily involves mid- and apical anterior and anteroseptal segments rather than basal segments. Data do not support existence of isolated basal anteroseptal or septal infarction. "Anteroapical infarction" is a more appropriate term than "anteroseptal infarction."

Obstructive sleep apnea (OSA) and obesity are often present concomitantly. Their potential contribution to inflammation remains an ongoing debate. The objectives of this study were to investigate whether variables of sleep-disordered breathing are associated with levels of myeloid-related protein-8/14 (MRP-8/14) or C-reactive protein (CRP), and to characterize how adiposity interacts with these associations in individuals evaluated for possible OSA.Consecutive individuals referred to Lovisenberg Diakonale Hospital's sleep laboratory between 1st October 2009 and 1st March 2010 were included. We characterized the biomarker distribution sampled the morning after sleep and related these to clinical characteristics and variables recorded during polygraphy or polysomnography.Of the total study population of 222 individuals, 161 (72.5%) were diagnosed with OSA (apnea-hypopnea index (AHI)or = 5/h). In baseline models (multiple median regression adjusted for age and sex), AHI was independently associated with MRP-8/14 (P=0.025) and CRP (P0.001). The associations were attenuated after the addition of body mass index (BMI), but remained statistically significant for CRP (P=0.025). However, in final models adjusted for additional factors (systolic blood pressure, cholesterol:high-density lipoprotein ratio, glycosylated haemoglobin, smoking, and cardiovascular disease), only average oxygen saturation for MRP-8/14 (P=0.028) and oxygen desaturation index (ODI) for CRP (P=0.037) remained independent predictors of inflammation, whereas AHI lost its predictive value (MRP-8/14; P=0.30 and CRP; P=0.092). The association between several variables of sleep-disordered breathing and inflammation were stronger in individuals with a higher BMI (P for interaction0.05 for AHI, nadir oxygen saturation, and time90% oxygen saturation).No definitive indication of independent immunological activity resulting from apneas and hypopneas was found in final models adjusted for other factors associated with inflammation, whereas average oxygen saturation for MRP-8/14 and ODI for CRP remained statistically significant predictors. Interactions were observed between BMI and several variables of sleep-disordered breathing on MRP-8/14 and CRP levels.

Cardiac troponins (cTn) are to date the most sensitive and specific biochemical markers of myocardial injury. Abnormal breathing patterns in patients with obstructive sleep apnea (OSA) may cause myocardial cell stress detectable by novel cTn assays. The objectives of this study were to investigate whether a new single-molecule cTnI (S-cTnI) assay and a commercially available high-sensitivity cTnT (hs-cTnT) assay would detect myocyte injury in individuals evaluated for possible OSA, and to explore their relation to variables of disordered breathing during sleep.Consecutive individuals referred to Lovisenberg Diakonale Hospital's sleep laboratory between 1 October 2009 and 1 March 2010 were included. We measured cTn in specimens collected the morning after sleep and studied these in relation to variables recorded during polygraphy or polysomnography.All 222 (100 %) individuals had measurable cTn levels using either assay. Stratified into categories according to the apnea-hypopnea index (AHI), patients with OSA (AHI ≥5) had a different distribution of S-cTnI (P = 0.036) and hs-cTnT (P = 0.002) compared to those without (AHI5). The median (quartiles 1-3) were 3.0 (1.9-6.0) versus 2.3 (1.6-3.8) ng/l for S-cTnI, and 7.0 (5.5-8.7) versus 6.2 (4.9-7.2) ng/l for hs-cTnT. However, in multiple median regression analyses adjusted for conventional predictors, neither S-cTnI (P = 0.57) nor hs-cTnT (P = 0.80) were significantly associated with AHI.This study reveals no association independent of conventional predictors between OSA and myocardial cell injury measured by S-cTnI and hs-cTnT assays. Our findings support a search for novel biomarkers for prognostication of OSA.

Circulating levels of cardiac troponin I (cTnI) after ST-segment elevation myocardial infarction (STEMI) are associated with infarct size and chronic left ventricular dysfunction, but the relation to clinical end points and biochemical measures of global cardiac function remains less well defined.One thousand sixty-six patients receiving primary percutaneous coronary intervention (PCI) in the PROTECTION AMI trial were studied in a post hoc analysis. Cardiac troponin I was measured at several time points during the index hospitalization, and patients were followed up for 3 months before reassessment including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and left ventricular ejection fraction (LVEF) measurements.The median (quartile 1-3) cTnI levels were 0.4 (0.1-0.4) μg/L at admission, 33.1 (12.8-72.1) μg/L after 16 to 24 hours, and 9.1 (3.9-17.5) μg/L after 70 to 80 hours. In adjusted models, all post-PCI single points, peak, and area under curve were found to be independently associated with clinical events, NT-proBNP118 pmol/L, or LVEF40% (P for all.001). When cTnI was added to a baseline risk model for prediction of clinical events, the C statistic improved from 0.779 to 0.846 (16-24 hours) and 0.859 (70-80 hours). Quantified by integrated discrimination improvement, the addition of cTnI significantly augmented prediction ability (relative integrated discrimination improvement 44%-154%; P for all ≤.001). Consistent improvements in discrimination of NT-proBNP118 pmol/L and LVEF40% were observed.Cardiac troponin I measured after primary PCI for STEMI is independently associated with clinical outcomes and cardiac function through 3-month follow-up. These results suggest that cTnI levels are a useful risk stratification tool in STEMI patients.