Worst lead ST deviation and resolution of ST elevation at one hour for prediction of myocardial salvage, infarct size, and microvascular obstruction in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention.

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.

Left ventricular ejection fraction and adjudicated, cause-specific hospitalizations after myocardial infarction complicated by heart failure or left ventricular dysfunction.

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.

The significance of ST-elevation in aVL in anterolateral myocardial infarction: An assessment by cardiac magnetic resonance imaging.

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.

Correlation of anteroseptal ST elevation with myocardial infarction territories through cardiovascular magnetic resonance imaging.

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.

Electrocardiographic scores of severity and acuteness of myocardial ischemia predict myocardial salvage in patients with anterior ST-segment elevation myocardial infarction.

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 2-6days after primary percutaneous coronary intervention (pPCI). LVEF was measured by echocardiography 30days 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.

Appropriateness of anteroseptal myocardial infarction nomenclature evaluated by late gadolinium enhancement cardiovascular magnetic resonance imaging.

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."

Myocardium at risk assessed by electrocardiographic scores and cardiovascular magnetic resonance - a MITOCARE substudy.

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 61years) met STEMI criteria on their admission ECG and underwent CMR within 3-5days 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.

Rhythm versus rate control in patients with newly diagnosed atrial fibrillation - Observations from the GARFIELD-AF registry.

Background: Investigate real-world outcomes of early rhythm versus rate control in patients with recent onset atrial fibrillation. Methods: The Global Anticoagulant Registry in the FIELD-AF (GARFIELD-AF) is an international multi-centre, non-interventional prospective registry of newly diagnosed (≤6 weeks' duration) atrial fibrillation patients at risk for stroke. Patients were stratified according to treatment initiated at baseline (≤48 days post enrolment), and outcome risks evaluated by overlap propensity weighted Cox proportional-hazards models. Results: Of 45,382 non-permanent atrial fibrillation patients, 23,858 (52.6 %) received rhythm control and 21,524 (47.4 %) rate control. Rhythm-controlled patients had lower median age (68.0 [Q1;Q3: 60.0;76.0] versus 73.0 [65.0;79.0]), fewer histories of stroke/transient ischemic attack/systemic embolism (9.4 % versus 13.0 %), and lower expected probabilities of death (median GARFIELD-AF death score 4.0 [2.3;7.5] versus 5.1 [2.8;9.2]). The two groups had the same median CHA2DS2-VASc scores (3.0 [2.0;4.0]) and similar proportions of anticoagulated patients (rhythm control: 66.0 %, rate control: 65.5 %). The propensity-score-weighted hazard ratios of rhythm vs rate control (reference) were 0.85 (95 % CI: 0.79-0.92, p-value < 0.0001) for all-cause mortality, 0.84 (0.72-0.97, p-value 0.020) for non-haemorrhagic stroke/systemic embolism and 0.90 (0.78-1.04, p-value 0.164) for major bleeding. Conclusion: Rhythm control strategy was initiated in about half of the patients with newly diagnosed non-valvular non-permanent atrial fibrillation. After balancing confounders, significantly lower risks of all-cause mortality and non-haemorrhagic stroke were observed in patients who received early rhythm control.

The Association of Smoking with Hospitalization and Mortality Differs According to Sex in Patients with Heart Failure Following Myocardial Infarction.

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. Materials and 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 modeling were used to study the risks of smoking on adjudicated endpoints among different sex and age categories. Results: Twenty-eight thousand seven hundred thirty-five 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 [95% CI] 1.16-1.32) than in men (HR = 1.10; 95% 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.

Cardioversion in patients with newly diagnosed non-valvular atrial fibrillation: observational study using prospectively collected registry data.

OBJECTIVE: To investigate the clinical outcomes of patients who underwent cardioversion compared with those who did not have cardioverson in a large dataset of patients with recent onset non-valvular atrial fibrillation. DESIGN: Observational study using prospectively collected registry data (Global Anticoagulant Registry in the FIELD-AF-GARFIELD-AF). SETTING: 1317 participating sites in 35 countries. PARTICIPANTS: 52 057 patients aged 18 years and older with newly diagnosed atrial fibrillation (up to six weeks' duration) and at least one investigator determined stroke risk factor. MAIN OUTCOME MEASURES: Comparisons were made between patients who received cardioversion and those who had no cardioversion at baseline, and between patients who received direct current cardioversion and those who had pharmacological cardioversion. Overlap propensity weighting with Cox proportional hazards models was used to evaluate the effect of cardioversion on clinical endpoints (all cause mortality, non-haemorrhagic stroke or systemic embolism, and major bleeding), adjusting for baseline risk and patient selection. RESULTS: 44 201 patients were included in the analysis comparing cardioversion and no cardioversion, and of these, 6595 (14.9%) underwent cardioversion at baseline. The propensity score weighted hazard ratio for all cause mortality in the cardioversion group was 0.74 (95% confidence interval 0.63 to 0.86) from baseline to one year follow-up and 0.77 (0.64 to 0.93) from one year to two year follow-up. Of the 6595 patients who had cardioversion at baseline, 299 had a follow-up cardioversion more than 48 days after enrolment. 7175 patients were assessed in the analysis comparing type of cardioversion: 2427 (33.8%) received pharmacological cardioversion and 4748 (66.2%) had direct current cardioversion. During one year follow-up, event rates (per 100 patient years) for all cause mortality in patients who received direct current and pharmacological cardioversion were 1.36 (1.13 to 1.64) and 1.70 (1.35 to 2.14), respectively. CONCLUSION: In this large dataset of patients with recent onset non-valvular atrial fibrillation, a small proportion were treated with cardioversion. Direct current cardioversion was performed twice as often as pharmacological cardioversion, and there appeared to be no major difference in outcome events for these two cardioversion modalities. For the overall cardioversion group, after adjustments for confounders, a significantly lower risk of mortality was found in patients who received early cardioversion compared with those who did not receive early cardioversion. STUDY REGISTRATION: ClinicalTrials.gov NCT01090362.

Mortality and adverse events with brand and generic clopidogrel in the US Food and Drug Administration Adverse Event Reporting System.

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<0.0001] for total FAERS, and consistent for late 2010-2017 (17.6% vs. 7.0% PRR = 0.40; 95% CI 0.37-0.45; χ2=286.2; P<0.004) PCAE cases. In contrast, GC trended to co-report more cardiac (14.6% vs. 13.3%; PRR = 1.12; 95% CI 1.0-1.25; χ2=3.5; P<0.06). The haemorrhagic (40.9% vs. 32.3%; PRR = 1.45; 95% CI 1.33-1.57; χ2=75.8; P<0.0001), and rash/dermal (5.4% vs. 4.6%; PRR = 1.20; 95% CI 1.0-1.44; χ2=3.75; P<0.05) events were also more common for GC. Thrombotic/embolic events were reported equally (at 7.0%) after each formulation. 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.

Relationship between left ventricular ejection fraction and mortality after myocardial infarction complicated by heart failure or left ventricular dysfunction.

BACKGROUND: 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. METHODS AND RESULTS: 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). CONCLUSION: 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%.