Faculty Bibliography

The study purpose is to determine whether numeric and/or graphic ST measurements added to the display of the 12-lead electrocardiogram (ECG) would influence cardiologists' decision to provide myocardial reperfusion therapy. Twenty ECGs with borderline ST-segment deviation during elective percutaneous coronary intervention and 10 controls before balloon inflation were included. Only 5 of the 20 ECGs during coronary balloon occlusion met the 2007 American Heart Association guidelines for ST-elevation myocardial infarction (STEMI). Fifteen cardiologists read 4 sets of these ECGs as the basis for a "yes/no" reperfusion therapy decision. Sets 1 and 4 were the same 12-lead ECGs alone. Set 2 also included numeric ST-segment measurements, and set 3 included both numeric and graphically displayed ST measurements ("ST Maps"). The mean (range) positive reperfusion decisions were 10.6 (2-15), 11.4 (1-19), 9.7 (2-14), and 10.7 (1-15) for sets 1 to 4, respectively. The accuracies of the observers for the 5 STEMI ECGs were 67%, 69%, and 77% for the standard format, the ST numeric format, and the ST graphic format, respectively. The improved detection rate (77% vs 67%) with addition of both numeric and graphic displays did achieve statistical significance (P < .025). The corresponding specificities for the 10 control ECGs were 85%, 79%, and 89%, respectively. In conclusion, a wide variation of reperfusion decisions was observed among clinical cardiologists, and their decisions were not altered by adding ST deviation measurements in numeric and/or graphic displays. Acute coronary occlusion detection rate was low for ECGs meeting STEMI criteria, and this was improved by adding ST-segment measurements in numeric and graphic forms. These results merit further study of the clinical value of this technique for improved acute coronary occlusion treatment decision support.

CONTEXT/BACKGROUND:Acute ST-segment elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality. In experimental models of MI, erythropoietin reduces infarct size and improves left ventricular (LV) function. OBJECTIVE:To evaluate the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with STEMI. DESIGN, SETTING, AND PATIENTS/METHODS:A prospective, randomized, double-blind, placebo-controlled trial with a dose-escalation safety phase and a single dose (60,000 U of epoetin alfa) efficacy phase; the Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction (REVEAL) trial was conducted at 28 US sites between October 2006 and February 2010, and included 222 patients with STEMI who underwent successful percutaneous coronary intervention (PCI) as a primary or rescue reperfusion strategy. INTERVENTION/METHODS:Participants were randomly assigned to treatment with intravenous epoetin alfa or matching saline placebo administered within 4 hours of reperfusion. MAIN OUTCOME MEASURE/METHODS:Infarct size, expressed as percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging performed 2 to 6 days after study medication administration (first CMR) and again 12 ± 2 weeks later (second CMR). RESULTS:In the efficacy cohort, the infarct size did not differ between groups on either the first CMR scan (n = 136; 15.8% LV mass [95% confidence interval {CI}, 13.3-18.2% LV mass] for the epoetin alfa group vs 15.0% LV mass [95% CI, 12.6-17.3% LV mass] for the placebo group; P = .67) or on the second CMR scan (n = 124; 10.6% LV mass [95% CI, 8.4-12.8% LV mass] vs 10.4% LV mass [95% CI, 8.5-12.3% LV mass], respectively; P = .89). In a prespecified analysis of patients aged 70 years or older (n = 21), the mean infarct size within the first week (first CMR) was larger in the epoetin alfa group (19.9% LV mass; 95% CI, 14.0-25.7% LV mass) than in the placebo group (11.7% LV mass; 95% CI, 7.2-16.1% LV mass) (P = .03). In the safety cohort, of the 125 patients who received epoetin alfa, the composite outcome of death, MI, stroke, or stent thrombosis occurred in 5 (4.0%; 95% CI, 1.31%-9.09%) but in none of the 97 who received placebo (P = .04). CONCLUSIONS:In patients with STEMI who had successful reperfusion with primary or rescue PCI, a single intravenous bolus of epoetin alfa within 4 hours of PCI did not reduce infarct size and was associated with higher rates of adverse cardiovascular events. Subgroup analyses raised concerns about an increase in infarct size among older patients. TRIAL REGISTRATION/BACKGROUND:clinicaltrials.gov Identifier: NCT00378352.

BACKGROUND: Current guidelines define cardiac troponin I (TnI) as an indicator of necrosis when the concentration exceeds the 99% upper limit of a healthy reference population, a reference value near the assay's lowest detectable level. We assessed the utility of a modified TnI cutoff point derived from a population at low risk for coronary artery disease (CAD) and evaluated its utility in determining acute myocardial infarction (MI). METHODS: A modified TnI cutoff point was derived by the receiver operating characteristic (ROC) curve from 737 consecutive patients who underwent serial TnI measurements for exclusion of MI. Creatinine kinase isoenzyme MB (CK-MB) evolutionary change was used to define MI. The new derived cutoff point was validated using another subset of 320 patients who were evaluated for MI. RESULTS: ROC-derived TnI cutoff point (A) was 0.65 mug/L, and its performance was compared to the recommended cutoff point ([B] 0.15 mug/L). Cutoff point A had greater specificity (94.5% vs. 86.9%, p < 0.001) but slightly lower sensitivity (96.5% vs. 100%, p < 0.01). Cutoff point A provided significantly greater positive predictive value (PPV) for MI (74.1% vs. 55.5%, p < 0.0001) and fewer false-positive errors, while preserving comparable negative predictive value (NPV) (98.9% vs. 100%). CONCLUSION: A higher cutoff point derived from a reference population of patients at low risk for CAD may improve the TnI performance assay. The PPV for diagnosis of MI was significantly higher and false-positive values were fewer without affecting the NPV. The more reliable diagnosis of MI may have resulted, which, in turn, may have significant clinical and economic implications.

BACKGROUND:Multiple studies have shown that the exercise electrocardiogram (ECG) is less accurate for predicting ischemia, especially in women, and there is additional evidence to suggest that heart size may affect its diagnostic accuracy. HYPOTHESIS/OBJECTIVE:The purpose of this investigation was to assess the diagnostic accuracy of the exercise ECG based on heart size. METHODS:We evaluated 1,011 consecutive patients who were referred for an exercise nuclear stress test. Patients were divided into two groups: small heart size defined as left ventricular end diastolic volume (LVEDV) <65 mL (Group A) and normal heart size defined as LVEDV ≥65 mL (Group B) and associations between ECG outcome (false positive vs. no false positive) and heart size (small vs. normal) were analyzed using the Chi square test for independence, with a Yates continuity correction. LVEDV calculations were performed via a computer-processing algorithm. SPECT myocardial perfusion imaging was used as the gold standard for the presence of coronary artery disease (CAD). RESULTS:Small heart size was found in 142 patients, 123 female and 19 male patients. There was a significant association between ECG outcome and heart size (χ(2) = 4.7, p = 0.03), where smaller hearts were associated with a significantly greater number of false positives. CONCLUSIONS:This study suggests a possible explanation for the poor diagnostic accuracy of exercise stress testing, especially in women, as the overwhelming majority of patients with small heart size were women.

BACKGROUND:Inflammation has been shown to be a major component in the pathophysiology of acute coronary syndrome (ACS). In patients presenting with acute myocardial infarction (AMI), a critical component of the ACS spectrum, multiple coronary arteries are involved during this inflammatory process. In addition to the coronary vasculature, the inflammatory cascade has also been shown to affect the carotid arteries and possibly the aorta. PURPOSE/OBJECTIVE:To assess the involvement of the aorta during AMI by cardiac magnetic resonance (CMR). METHODS:We prospectively evaluated the aortic wall by CMR in 123 patients. 78 patients were enrolled from the emergency department (ED), who presented with chest pain and were classified as either: (1) AMI: elevated troponin levels and typical chest pain or (2) non-cardiac chest pain (CP): negative troponins and a normal stress test or normal cardiac catheterization. We compared these 2 groups to a group of 45 asymptomatic diabetic patients. The descending thoracic aortic wall area (AWA) and maximal aortic wall thickness (AWT) were measured using a double inversion recovery T-2 weighted, ECG-gated, spin echo sequence by CMR. RESULTS:Patients with AMI were older, more likely to smoke, had a higher incidence of claudication, and had higher CRP levels. The AWA and maximal AWT were greater in patients who presented to the ED with ACS (2.11+/-0.17 mm(2), and 3.17+/-0.19 mm, respectively) than both patients presenting with non-cardiac CP (1.52+/-0.58 mm(2), p<0.001; and 2.57+/-0.10 mm, p<0.001) and the diabetic patients (1.38+/-0.58 mm(2), p<0.001; and 2.30+/-0.131 mm, p<0.001). The difference in the aortic wall characteristics remained significant after correcting for body mass index, hyperlipidemia, statins and C-reactive protein. There was no difference in maximal AWT or AWA between patients with non-cardiac CP and patients with diabetes. CONCLUSION/CONCLUSIONS:Patients with AMI have a significantly greater maximal aortic wall thickness and area compared to patients with non-cardiac CP. Longitudinal studies are needed to assess whether this increase is due to inflammation or a higher atherosclerotic burden.

The coronary vasodilatory effect of dipyridamole is competitively blocked by caffeine. The purposes of this study were to (1) assess the incidence of having detectable serum caffeine and (2) evaluate whether an intensive caffeine history screening strategy was superior to routine history screening before dipyridamole myocardial perfusion imaging. One hundred ninety-four patients who were randomized to an intensive or a routine screening history strategy were prospectively evaluated. Serum caffeine levels were determined in all patients. Outcomes data, including death, nonfatal myocardial infarction, and history of revascularization, were obtained at 24 months. Nearly 1 in 5 patients (19%) who screened negative by history had detectable serum caffeine. In patients who screened negative by history, there was no statistically significant difference in the percentage of caffeine seropositivity between the intensive and routine arms (16% vs 22%, respectively, p = 0.31). The incidence of combined end points of death, myocardial infarction, or revascularization was 22.9% and 7.3% in patients with and without detectable serum caffeine, respectively (p = 0.01). In conclusion, despite initial negative results on screening by history, a considerably high percentage of patients had positive serum caffeine levels. These results do not support the use of an intensive screening strategy. Detectable serum caffeine was associated with a higher incidence of adverse outcomes.

BACKGROUND:Antiplatelet therapy is the principal component of the antithrombotic regimen after acute myocardial infarction. It remains unclear whether additional chronic oral anticoagulation (OAC) improves outcomes. We set out to evaluate the risk and benefit of long-term OAC after myocardial infarction. METHODS:We pooled 10 randomized clinical trials comparing warfarin-containing regimens (OAC) with or without aspirin with non-OAC regimens with or without aspirin (No OAC) for patients with recent infarction. The primary endpoint was all-cause mortality. Other endpoints included recurrent infarction, stroke, and major bleeding. We calculated the odds ratio (OR) (fixed effect, OR <1 indicates benefit for OAC) for death and other ischemic and hemorrhagic complications at the longest interval of follow-up available. RESULTS:Among 24,542 patients, 14,062 were assigned to OAC and 10,480 to no OAC. The patients were followed for 3-63 months, for 89,562 patient-years. Death occurred in 2424 patients (9.9%), 1279 OAC patients, and 1145 in the no OAC group, OR 0.97 (95% confidence interval [CI], 0.88-1.05), P=.43. Similarly, there was no effect on recurrent infarction. Stroke occurred in 578 patients (2.4%), 271 in the OAC group and 307 in the no OAC group, OR 0.75 (95% CI, 0.63-0.89), P=.001. There was substantially more major bleeding (OR 1.83 [95% CI, 1.50-2.23], P <.001) in the OAC group. Separate analyses, performed for patients (n=11,920) randomized to aspirin versus aspirin and OAC yielded very similar results. CONCLUSION/CONCLUSIONS:As compared with placebo or aspirin, OAC with or without aspirin does not reduce mortality or reinfarction, reduces stroke, but is associated with significantly more major bleeding.

BACKGROUND:In patients with sarcoidosis, sudden death is a leading cause of mortality, which may represent unrecognized cardiac involvement. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) can detect minute amounts of myocardial damage. We sought to compare DE-CMR with standard clinical evaluation for the identification of cardiac involvement. METHODS AND RESULTS/RESULTS:Eighty-one consecutive patients with biopsy-proven extracardiac sarcoidosis were prospectively recruited for a parallel and masked comparison of cardiac involvement between (1) DE-CMR and (2) standard clinical evaluation with the use of consensus criteria (modified Japanese Ministry of Health [JMH] guidelines). Standard evaluation included 12-lead ECG and at least 1 dedicated non-CMR cardiac study (echocardiography, radionuclide scintigraphy, or cardiac catheterization). Patients were followed for 21+/-8 months for major adverse events (death, defibrillator shock, or pacemaker requirement). Patients were predominantly middle-aged (46+/-11 years), female (62%), and black (73%) and had chronic sarcoidosis (median, 7 years) and preserved left ventricular ejection fraction (median, 56%). DE-CMR identified cardiac involvement in 21 patients (26%) and JMH criteria in 10 (12%, 8 overlapping), a >2-fold higher rate for DE-CMR (P=0.005). All patients with myocardial damage on DE-CMR had coronary disease excluded by x-ray angiography. Pathology evaluation in 15 patients (19%) identified 4 with cardiac sarcoidosis; all 4 were positive by DE-CMR, whereas 2 were JMH positive. On follow-up, 8 had adverse events, including 5 cardiac deaths. Patients with myocardial damage on DE-CMR had a 9-fold higher rate of adverse events and an 11.5-fold higher rate of cardiac death than patients without damage. CONCLUSIONS:In patients with sarcoidosis, DE-CMR is more than twice as sensitive for cardiac involvement as current consensus criteria. Myocardial damage detected by DE-CMR appears to be associated with future adverse events including cardiac death, but events were few, and this needs confirmation in a larger cohort.