M W Krucoff

Duke University Medical Center, Durham, North Carolina, United States

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Publications (68)344.71 Total impact

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    ABSTRACT: The cardiovascular safety of new drugs is an overarching concern for all stakeholders: the pharmaceutical industry and the US Food and Drug Administration (FDA) prior to approval and doctors and patients during postrelease drug use. Of the many cardiac safety concerns that accompany development of new drugs--including those related to vasculature and valvular tissue, the potential for myopathies, and the possibility of other electrophysiologic perturbations--the most pressing concern is the potential for ventricular arrhythmias causing sudden death.
    Clinical Pharmacology &#38 Therapeutics 08/2009; 86(1):101-4. · 6.85 Impact Factor
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    ABSTRACT: The presence of Q waves at presentation with a first acute myocardial infarction reflects a more advanced stage of the infarction process. When infarct-related artery patency (Thrombolysis in Myocardial Infarction 2 or 3 flow) is restored, resolution of ST segment elevation indicating successful myocyte reperfusion may differ according to how far the infarction process has progressed. In 144 patients with a first acute myocardial infarction treated with streptokinase in the first Hirulog Early Reperfusion Occlusion trial, information was obtained from continuous ST segment monitoring, the presenting electrocardiogram and early angiography performed at a median time of 99 min after the commencement of streptokinase (interquartile range 89-108 min). We determined how many patients had 50% ST recovery within 120 min and in how many cases it was sustained over 4h. In the 109 patients with patent infarct-related arteries, 50% ST recovery occurred in 95% of patients without vs 80% of those with initial Q waves (P=0.03), and sustained ST recovery occurred in 67% of patients without vs 47% of those with initial Q waves (P=0.03). On multivariate analysis including the time from symptom onset to streptokinase therapy, the presence of Q waves at presentation was the only predictor of failure to achieve 50% ST recovery (odds ratio 5.08, 95% confidence interval 1.29-20.01, P=0.02). TIMI 2 flow, as opposed to TIMI 3 flow, was the only predictor of failure to achieve stable ST recovery (odds ratio 2.63, 95% confidence interval 1.15-5.88,P =0.02). The presence of initial Q waves predicts slower and less complete ST recovery, reflecting reduced myocyte reperfusion, even in those with early infarct artery patency. These patients may be targeted for new therapeutic strategies to improve microvascular reperfusion.
    European Heart Journal 10/2002; 23(18):1449-55. · 14.72 Impact Factor
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    ABSTRACT: Patients undergoing percutaneous coronary intervention (PCI) for unstable coronary syndromes have substantial emotional and spiritual distress that may promote procedural complications. Noetic (nonpharmacologic) therapies may reduce anxiety, pain and distress, enhance the efficacy of pharmacologic agents, or affect short- and long-term procedural outcomes. The Monitoring and Actualization of Noetic Training (MANTRA) pilot study examined the feasibility of applying 4 noetic therapies-stress relaxation, imagery, touch therapy, and prayer-to patients in the setting of acute coronary interventions. Eligible patients had acute coronary syndromes and invasive angiography or PCI. Patients were randomized across 5 treatment groups: the 4 noetic and standard therapies. Questionnaires completed before PCI reflected patients' religious beliefs and anxiety. Index hospitalization end points included post-PCI ischemia, death, myocardial infarction, heart failure, and urgent revascularization. Mortality was followed up for 6 months after hospitalization. Of eligible patients, 88% gave informed consent. Of 150 patients enrolled, 120 were assigned to noetic therapy; 118 (98%) completed their therapeutic assignments. All clinical end points were available for 100% of patients. Results were not statistically significant for any outcomes comparisons. There was a 25% to 30% absolute reduction in adverse periprocedural outcomes in patients treated with any noetic therapy compared with standard therapy. The lowest absolute complication rates were observed in patients assigned to off-site prayer. All mortality by 6-month follow-up was in the noetic therapies group. In patients with questionnaire scores indicating a high level of spiritual belief, a high level of personal spiritual activity, a low level of community-based religious involvement, or a high level of anxiety, noetic therapies appeared to show greater reduction in absolute in-hospital complication rates compared with standard therapy. Acceptance of noetic adjuncts to invasive therapy for acute coronary syndromes was excellent, and logistics were feasible. No outcomes differences were significant; however, index hospitalization data consistently suggested a therapeutic benefit with noetic therapy. Of all noetic therapies, off-site intercessory prayer had the lowest short- and long-term absolute complication rates. Definitive demonstration of treatment effects of this magnitude would be feasible in a patient population about 4 times that of this pilot study. Absolute mortality differences make safety considerations a mandatory feature of future clinical trials in this area.
    American heart journal 12/2001; 142(5):760-9. · 4.56 Impact Factor
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    ABSTRACT: Early restoration of coronary artery patency through primary angioplasty limits infarct size and improves survival. Increasing evidence, however, suggests that microvascular obstruction is often present despite coronary artery recanalization. This may limit the benefits of reperfusion therapy. We studied the use of noninvasive markers of coronary artery reperfusion as indicators of microvascular obstruction and determinants of prognosis in 98 patients with acute myocardial infarction (AMI) who were successfully treated with primary angioplasty (Thrombolysis In Myocardial Infarction grade 3 flow and residual stenosis <30%). Plasma creatine kinase (CK) levels and 12-lead electrocardiograms were performed on admission, at 90 minutes, and at 6, 12, and 24 hours after treatment. We defined: (1) reperfusion as resolution of ST-segment elevation >50% at 90 minutes, with peak CK levels within 12 hours, and T-wave inversion within 24 hours; and (2) failed reperfusion, as the absence of these parameters. Of the 98 patients studied, 87 (88.8%) had reperfusion and 11 (11.2%) had failed reperfusion. Infarct location was anterior (versus inferior) in 9 patients in the failed reperfusion group (81.8%) compared with 41 patients in the reperfusion group (47.1%) (p <0.01). Congestive heart failure >24 hours after presentation or in-hospital death occurred in 11 patients (12.6%) in the reperfusion group versus 5 (45.5%) in the failed reperfusion group (p <0.01). One-year survival was 96.1% for the reperfusion group and 60.6% for the failed reperfusion group (p <0.0001). We conclude that the association of noninvasive markers of reperfusion better identifies patients with microvascular obstruction among those who had a "successful" primary angioplasty. Evidence of impaired microvascular reperfusion is associated with a poor in-hospital and 1-year outcome.
    The American Journal of Cardiology 08/2001; 88(4):342-6. · 3.43 Impact Factor
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    ABSTRACT: The purpose of this study was to assess whether the immediate availability of serum markers would increase the appropriate use of thrombolytic therapy. Serum markers such as myoglobin and creatine kinase, MB fraction (CK-MB) are effective in detecting acute myocardial infarction (AMI) in the emergency setting. Appropriate candidates for thrombolytic therapy are not always identified in the emergency department (ED), as 20% to 30% of eligible patients go untreated, representing 10% to 15% of all patients with AMI. Patients presenting with chest pain consistent with acute coronary syndrome were evaluated in the EDs of 12 hospitals throughout North America. In this randomized, controlled clinical trial, physicians received either the immediate myoglobin/CK-MB results at 0 and 1 h after enrollment (stat) or conventional reporting of myoglobin/CK-MB 3 h or more after hospital admission (control). The primary end point was the comparison of the proportion of patients within the stat group versus control group who received appropriate thrombolytic therapy. Secondary end points included the emergent use of any reperfusion treatment in both groups, initial hospital disposition of patients (coronary care unit, monitor or nonmonitor beds) and the proportion of patients appropriately discharged from the ED. Of 6,352 patients enrolled, 814 (12.8%) were diagnosed as having AMI. For patients having AMI, there were no statistically significant differences in the proportion of patients treated with thrombolytic therapy between the stat and control groups (15.1% vs. 17.1%, p = 0.45). When only patients with ST segment elevation on their initial electrocardiogram were compared, there were still no significant differences between the groups. Also, there was no difference in the hospital placement of patients in critical care and non- critical care beds. The availability of early markers was associated with more hospital admissions as compared to the control group, as the number of patients discharged from the ED was decreased in the stat versus control groups (28.4% vs. 31.5%, p = 0.023). The availability of 0- and 1-h myoglobin and CK-MB results after ED evaluation had no effect on the use of thrombolytic therapy for patients presenting with AMI, and it slightly increased the number of patients admitted to the hospital who had no evidence of acute myocardial necrosis.
    Journal of the American College of Cardiology 12/2000; 36(5):1500-6. · 15.34 Impact Factor
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    ABSTRACT: Early resolution of ST-segment elevation (ST-segment recovery) is associated with an improved outcome after infarction. Whether this relation is present in patients with Thrombolysis In Myocardial Infarction (TIMI) grade 2 or 3 flow (ie, patent) infarct-related arteries is not known. To examine the associations between time to achieve stable 50% ST-segment recovery assessed by continuous ECG monitoring, infarct artery flow, and infarct zone wall motion (at 48 hours), we studied 134 patients who underwent angiography at 99 (interquartile range 92 to 110) minutes after commencing streptokinase, initiated within 12 hours of onset of symptoms of myocardial infarction. Patients with TIMI 2 or 3 flow who failed to achieve early stable ST-segment recovery (50% ST-segment recovery sustained for > or 4 hours with <100 microV change in the peak lead) by 60 or 90 minutes had a higher fraction of chords in the infarct zone >2 SD below normal wall motion (TIMI 2: 55.5% vs 15.3%, P=0.006; and 56.5% vs 26.8%, P=0.01, respectively; and TIMI 3: 48.8% vs 28.3%, P=0.07; and 51.8% vs 29.9%, P=0.03, respectively). Time to stable ST-segment recovery was a multivariate predictor of infarct zone wall motion (P=0.04) independent of TIMI flow grade and the time from symptom onset to streptokinase therapy. In patients with TIMI 2 or 3 flow in infarct-related artery, early stable ST-segment recovery is associated with improved infarct zone wall motion at 48 hours. ST-segment recovery may provide additional information about the degree of myocyte reperfusion achieved in patients with a patent epicardial infarct-related artery after thrombolytic therapy.
    Circulation 05/2000; 101(18):2138-43. · 14.95 Impact Factor
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    ABSTRACT: Computer-assisted continuous monitoring of the ST-segment allows detection and quantification of recurrent ischemia in patients with acute coronary syndromes. In a substudy of the PURSUIT (Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy) trial, this technique was used to evaluate the effects of the glycoprotein IIb/IIIa inhibitor eptifibatide on the incidence and severity of recurrent ischemia, and to investigate the relationship between recurrent ischemia and the occurrence of subsequent death or myocardial (re)infarction. A total of 258 patients with unstable angina or evolving myocardial infarction without ST elevation were monitored for 24 hours during infusion with either eptifibatide or placebo with a computer-assisted 12-lead ECG-ischemia monitoring device. Recurrent ischemic episodes were identified by an automated computer algorithm. Two hundred and sixteen patients (84%) had ECG recordings suitable for analysis. Ischemic episodes were detected in 35 (33%) of the 105 eptifibatide patients and in 32 (29%) of the 111 placebo patients (not significant). No difference in ischemic burden was apparent between both treatment groups. Patients who exhibited 2 or more episodes of recurrent ischemia more frequently died or suffered a myocardial infarction, both at 7 and 30 days, as well as through the 6-month follow-up. A greater ischemic burden was significantly related to adverse outcome during the 6-month follow-up period. Real-time computer-assisted continuous multilead ECG-ischemia monitoring may help to identify patients with unstable coronary syndromes at increased risk of adverse outcome and, thus, allow for better prognostic triage and more appropriate selection of therapeutic strategies. Integration of these systems in coronary care units and emergency wards should, therefore, be recommended.
    Journal of Electrocardiology 05/2000; 33(2):127-36. · 1.36 Impact Factor
  • Critical Care Nurse 05/2000; 20(2):93-9. · 1.07 Impact Factor
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    ABSTRACT: To evaluate the relationship between perioperative ischemia and serial concentrations of D-dimer, which is a sensitive and specific marker of fibrinolytic activity. Myocardial ischemia and infarction are well-recognized complications of peripheral vascular surgery. We hypothesized that patients at increased risk of perioperative myocardial ischemia might be identified preoperatively by abnormal hemostatic indices. Prospective clinical outcomes study. A 1,124-bed tertiary care medical center.Patients: 42 ASA physical status II, III, and IV patients undergoing peripheral vascular surgery. Serial D-dimer concentrations were measured preoperatively, and at 24 and 72 hours postoperatively. Continuous 12-lead ST-segment monitoring (Mortara Instrument, Inc., Milwaukee, WI) was performed with the acquisition of a 12-lead ECG every 20 seconds for 72 hours. D-dimer measurements were performed in duplicate using the Dimer Gold assay (American Diagnostica, Greenwich CT). Ischemic episodes, as defined by continuous 12-lead ST-segment monitoring, occurred in 49% of patients. There were no demographic differences between ischemic and nonischemic groups. Although baseline D-dimer concentrations were not statistically significantly different between groups, patients experiencing perioperative myocardial ischemia generated significantly less D-dimer during the perioperative period (p = 0. 014). Patients with an impaired fibrinolytic response, as defined by reduced generation of D-dimer, experienced an increased incidence of perioperative myocardial ischemia.
    Journal of Clinical Anesthesia 04/2000; 12(2):136-41. · 1.21 Impact Factor
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    ABSTRACT: To compare the prognostic significance of reperfusion assessment by Thrombolysis in Myocardial Infarction (TIMI) flow grade in the infarct related artery and ST-segment resolution analysis, by correlating with clinical outcomes in patients with acute myocardial infarction (AMI). Angiographic assessment, based on epicardial coronary anatomy, has been considered the "gold standard" for reperfusion. The electrocardiogram (ECG) monitoring provides a noninvasive, real-time physiologic marker of cellular reperfusion and may better predict clinical outcomes. Two hundred fifty-eight AMI patients from the Thrombolytics and Myocardia Infarction phase 7 and Global Utilization of Streptokinase tPA for Occluded coronary arteries phase 1 trials were stratified based on blinded, simultaneous reperfusion assessment on the acute angiogram (divided into TIMI grades 0 & 1, TIMI grade 2 and TIMI grade 3) and ST-segment resolution analysis (divided into: <50% ST-segment elevation resolution or reelevation and > or =50% ST-segment elevation resolution). In-hospital mortality, congestive heart failure (CHF) and combined mortality or CHF were compared to determine the prognostic significance of reperfusion assessment by each modality using chi-square and Fisher's Exact tests for univariable correlation and logistic regression analysis for univariable and multivariable prediction models. By logistic regression analysis, ST-segment resolution patterns were an independent predictor of the combined outcome of mortality or CHF (p = 0.024), whereas TIMI flow grade was not (p = 0.693). Among the patients determined to have failed reperfusion by TIMI flow grade assessment (TIMI flow grade 0 & 1), the ST-segment resolution of > or =50% identified a subgroup with relatively benign outcomes with the incidence of the combined end point of mortality or CHF 17.2% versus 37.2% in those without ST-segment resolution (p = 0.06). Continuous 12-lead ECG monitoring can be an inexpensive and reliable modality for monitoring nutritive reperfusion status and to obtain prognostic information in patients with AMI.
    Journal of the American College of Cardiology 03/2000; 35(3):666-72. · 15.34 Impact Factor
  • B J Drew, M W Krucoff
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    ABSTRACT: ST-segment monitoring is underused by healthcare professionals for patients with acute coronary syndromes treated in emergency departments and intensive care units. To provide clinically practical consensus guidelines for optimal ST-segment monitoring. A working group of key nurses and physicians met in Dallas, Tex, in November 1998. Consensus was reached on who should and should not have ST monitoring, goals and time frames for ST monitoring in various diagnostic categories, what electrocardiographic leads should be monitored, what equipment requirements are needed, what strategies improve accuracy and clinical usefulness of ST monitoring, and what knowledge and skills are required for safe and effective ST monitoring. Because changes in the ST segment can shift among various electrocardiographic leads in the same person over time owing to different ischemic mechanisms, 12-lead ST monitoring is recommended. Recommended monitoring times are as follows: myocardial infarction or unstable angina, 24 to 48 hours or until patient is event-free for 12 to 24 hours; chest pain prompting a visit to an emergency department, 8 to 12 hours; catheter-based interventions with less definitive interventional outcomes requiring monitoring in an intensive unit, 6 to 12 hours; and cardiac surgery or noncardiac surgery in patients with coronary disease or risk factors, 24 to 48 hours. An ST measurement point of J + 60 ms makes it unlikely that measurement will coincide with the upslope of the T wave, even in patients with sinus tachycardia. Accurate and consistent lead placement and careful electrode and skin preparation are imperative to improve the clinical usefulness of ST monitoring.
    American Journal of Critical Care 12/1999; 8(6):372-86; quiz 387-8. · 1.60 Impact Factor
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    ABSTRACT: Background In this study we have evaluated the prognostic power of noninvasive markers of coronary artery reperfusion in patients with acute myocardial infarction who were treated with intravenous streptokinase. Methods In 967 consecutive patients with acute myocardial infarction who were treated within 6 hours of symptoms, we analyzed the prognostic power of resolution of chest pain and ST-segment elevation >50% at 90 minutes, abrupt creatine kinase rise before 12 hours, and T-wave inversion in infarct-related electrocardiographic leads within the first 24 hours after thrombolysis. Results Global in-hospital mortality rate was 12.0%. Each reperfusion marker was associated with improved outcome. Multivariate logistic regression analysis showed that 3 of the 4 markers of coronary artery reperfusion were significantly and independently associated to low in-hospital mortality rate. The presence of early T-wave inversion was associated with the lowest in-hospital mortality rate (odds ratio 0.25, confidence interval 0.10-0.56). When all markers of coronary artery reperfusion were included in the regression model, T-wave inversion (odds ratio 0.29, confidence interval 0.11-0.68) and abrupt creatine kinase rise (odds ratio 0.36, confidence interval 0.16-0.77) continued to be significantly associated with better outcome. Conclusion A systemic analysis of noninvasive markers of coronary artery reperfusion can provide the clinician with an excellent tool to predict clinical outcomes when treating myocardial infarction. (Am Heart J 1999;138:533-9.)
    American Heart Journal 09/1999; · 4.56 Impact Factor
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    ABSTRACT: Previous studies suggest that slow and/or oscillating balloon inflation during coronary angioplasty may decrease the incidence of coronary dissection and improve clinical outcomes. To compare the effect of slow oscillating versus conventional fast inflation techniques on the incidence of severe coronary dissection during angioplasty, 622 patients were randomized to slow oscillating inflation versus fast inflation. Angiographic outcomes of the procedures and in-hospital clinical events were recorded. The primary end point of severe (type C, D, E, F) dissection occurred in 7.7% of patients undergoing slow oscillation and 6.6% of patients undergoing fast inflation (p = 0.87). Major complications (death, urgent coronary artery bypass graft surgery, stroke, abrupt closure, or Q-wave myocardial infarction) occurred in 4.7% of patients undergoing slow oscillation and 3.5% of patients undergoing fast inflation (p = 0.45). The 2 inflation strategies did not differ in the pressure at which the balloon achieved full expansion, angiographic success rate, residual stenosis, and incidence of all minor and/or major complications. We conclude that there is no benefit of slow oscillating inflation over routine fast inflation in angioplasty. Slow oscillating inflation did not dilate lesions at lower pressures, decrease the incidence of dissection or severe dissection, or reduce the incidence of adverse clinical outcomes.
    The American Journal of Cardiology 04/1999; 83(5):675-80. · 3.43 Impact Factor
  • Journal of Electrocardiology 01/1999; 32:49-49. · 1.36 Impact Factor
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    ABSTRACT: A safety and efficacy study of nondrug, nondevice “noetic” medical interventions requires unique clinical trial design elements and tools. Although the precise mechanisms through which meditative or spiritual practices might influence clinical outcomes may be difficult to define, intuitively any such intervention that could meaningfully alter human physiology would be likely to be mediated through vascular tone, autonomic nervous system tone, or both. Continuous electrocardiographic monitoring in patients with coronary artery disease provides an objective, noninvasive modality through which coronary vascular insufficiency (ischemia) and spectro-temporal parameters of heart rate variability can be analyzed in an experienced core laboratory setting blinded to patient treatment assignments. We applied this approach in 150 patients with unstable angina and acute myocardial infarction undergoing invasive coronary catheterization and angioplasty who were randomized to one of five therapies (healing touch, stress relaxation training, imagery, double-blinded off-site intercessory prayer, or standard therapy) in the Monitoring & Actualization of Noetic TRAinings (MANTRA) Feasibility Pilot Study. Using a uniquely modified Marquette Electronics Tramscope 12-lead ST-Guard/MARS Holter “Unity” configuration (Milwaukee, WI), a “seamless” monitoring capability allowed monitoring to continue uninterrupted as patients went from the CCU to the catheterization lab and back to the CCU, creating a “rest-stress-recovery” data set similar to the common exercise stress test paradigm.
    Journal of Electrocardiology 01/1999; 32:22-22. · 1.36 Impact Factor
  • Journal of Electrocardiology 01/1999; 32:50-50. · 1.36 Impact Factor
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    ABSTRACT: Comparability of clinical and research data sets may be undermined if the instruments used to acquire them vary. Even when standard 12-lead electrocardiographic formats are used for monitoring, proprietary signal processing techniques and sampling intervals may differ among devices. In order to directly compare the two commercially available standard 12-lead devices with monitoring capabilities, bifurcated wires from a single standard lead set were attached to each device in elective angioplasty patients. Neither device was used as a standard; rather, a method was designed to analyze the output from each device independently, and then, if results differed, data from both monitors were reviewed by consensus to determine the source of the differences. Analysis endpoints for each study included study quality, baseline ST-segment levels, the presence of ischemia, number of ischemic episodes, peak lead location, and peak lead amplitude. Sources of differences in these endpoints visible to consensus review included variations between devices in baseline stability, noise/artifact levels, stability of the QRS complex onset, and temporal sampling intervals.
    Journal of Electrocardiology 01/1998; 30 Suppl:149-54. · 1.36 Impact Factor
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    ABSTRACT: The ability of QT interval dispersion to predict the occurrence of ventricular fibrillation (VF) after acute myocardial infarction treated with thrombolytic therapy is controversial. Continuous 12-lead electrocardiographic (ECG) monitoring for 48 hours or longer provides an opportunity to detect transient changes of QT dispersion and correlate such changes with the clinical outcome. In 543 consecutive patients enrolled in the TAMI-9 and GUSTO I studies, serial changes of the QT dispersion were analyzed in an attempt to predict the occurrence of VF with a system that monitored continuously the 12-lead ECG and stored it at least every 20 minutes. Measurements of QT dispersion were made at a median time of 2.37 hours after the onset of chest pain and at 24- and 48-hour intervals. A total of 43 patients experienced VF during the acute phase of myocardial infarction; of these patients, 33 (77%) had anterior infarcts. However, despite the higher preponderance of anterior myocardial infarcts in the VF group, patients with anterior infarcts did not have longer QT dispersion than those with other infarct locations. Similarly, no significant differences in the QT dispersion were observed at any time between the group with VF and that without. Women had increased QT dispersion in the initial and 24-hour ECG as compared with men (P = .005). However, this normalized at the 48-hour measurements. Despite this difference, there was no higher incidence of VF in female patients. In conclusion, the data suggest that QT dispersion alone is not sufficient to explain the occurrence of VF in the acute phase of myocardial infarction after thrombolytic therapy.
    Journal of Electrocardiology 01/1998; 30 Suppl:187-90. · 1.36 Impact Factor
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    ABSTRACT: Lead distributions of peak ST-segment depression were compared between patients undergoing left circumflex artery percutaneous transluminal coronary angioplasty and exercise tolerance test. Localization of peak ST-segment depression to leads V2 or V3 was 96% specific and 70% sensitive for differentiating ischemia due to occlusion of left circumflex artery occlusion from nonocclusive ischemia.
    The American Journal of Cardiology 09/1997; 80(4):512-3. · 3.43 Impact Factor

Publication Stats

1k Citations
344.71 Total Impact Points

Institutions

  • 1988–2009
    • Duke University Medical Center
      • • Division of Cardiology
      • • Department of Anesthesiology
      • • Department of Medicine
      Durham, North Carolina, United States
  • 2001
    • University of Santiago, Chile
      CiudadSantiago, Santiago, Chile
  • 2000
    • Duke University
      Durham, North Carolina, United States
  • 1999
    • University of California, San Francisco
      • School of Nursing
      San Francisco, CA, United States
    • Pontifical Catholic University of Chile
      • División Enfermedades Cardiovasculares
      CiudadSantiago, Santiago Metropolitan, Chile
  • 1995
    • University of Arkansas
      Fayetteville, Arkansas, United States
  • 1986–1991
    • Georgetown University
      • Division of Cardiology
      Washington, Washington, D.C., United States