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Mitchell W Krucoff

Publications and source records attributed to Mitchell W Krucoff.

At least 19 recordsLinked to original sources
PubMed2006

Real-time detection and alerting for acute ST-segment elevation myocardial ischemia using an implantable, high-fidelity, intracardiac electrogram monitoring system with long-range telemetry in an ambulatory porcine model.

OBJECTIVES: The purpose of this study was to evaluate feasibility of using real-time, high-fidelity, intracardiac electrogram monitoring from a permanently implantable ischemia detection system (IIDS), with long-range telemetry capability to detect ST-segment shifts associated with acute or subacute coronary occlusion in a porcine model. BACKGROUND: Early identification of coronary occlusion with ST-segment elevation could profoundly accelerate the timing of revascularization and improve clinical outcomes. METHODS: This paper reports the first investigation using real-time, high-fidelity, intracardiac electrogram monitoring from a permanently IIDS, with long-range telemetry capability. This IIDS was tested in an ambulatory porcine model, with acute coronary occlusion precipitated by stent thrombosis. Two overlapping copper stents were implanted in the left anterior descending (n = 3), the circumflex (n = 3), or the right coronary artery (n = 2) of juvenile farm pigs. Monitoring was carried using telemetry from the IIDS. RESULTS: All stented pigs had acute ST-segment elevation event(s) triggering the alerting thresholds of the IIDS. All triggered events were confirmed to be caused by thrombosis of the copper stent(s), and well correlated to infarct age and location. Four of the 8 pigs died from ventricular fibrillation, recorded by the IIDS at a mean time of 70 +/- 121 h after ST-segment alert. The sensitivity and specificity of alerting for ST-segment shift, associated with thrombotic coronary occlusion, were 100% and 100%, respectively. CONCLUSIONS: This study demonstrates the ability of an implantable ischemia detection system to detect ST-segment elevation from coronary occlusion in a porcine model of ST-segment elevation myocardial infarction. ST-segment elevation was sufficient to trigger alerting thresholds in all 3 epicardial coronary distributions. Such a system, with real-time alerting capability, could advance the time frame of reperfusion therapy and potentially prevent, rather than interrupt, acute myocardial infarction in patients with coronary artery disease.

Acute Disease↗
PubMed2006

Results of the first clinical study of adjunctive CAldaret (MCC-135) in patients undergoing primary percutaneous coronary intervention for ST-Elevation Myocardial Infarction: the randomized multicentre CASTEMI study.

AIMS: To examine the safety and efficacy of intravenous caldaret in patients with large acute ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: STEMI patients (n=387) with > or =10 mm summed ST-deviation on electrocardiogram were randomized to receive a 48 h infusion of caldaret 57.5 mg [lower dose (LD)], caldaret 172.5 mg [higher dose (HD)], or placebo, starting before PCI. Both HD and LD were well tolerated. In 247 patients with pre-PCI TIMI 0/1, there was no effect of HD or LD on single photon emission computed tomography infarct size or ejection fraction assessed at Day 7 and Day 30. Subgroup analyses suggest that future work in patients with anterior MI might be warranted. CONCLUSION: This first human experience with caldaret prior to direct PCI for large STEMI shows a good safety profile. No evidence of efficacy was discerned. Subgroup analyses in anterior MI patients showed some effects in endpoints studied, however, these findings require confirmation in a further study if a drug effect is to be established.

Angioplasty, Balloon, Coronary↗
PubMed2006

Novel electrocardiogram configurations and transmission procedures in the prehospital setting: effect on ischemia and arrhythmia determination.

AIM: The aims of this report are to (1) describe a novel prehospital 12-lead electrocardiogram (ECG) configuration and transmission procedure used in the Synthesized Twelve-lead ST Monitoring and Real-time Tele-electrocardiography Study and to (2) report on the frequency of arrhythmias in field ECGs compared with the first hospital ECG. METHODS: The Synthesized Twelve-lead ST Monitoring and Real-time Tele-electrocardiography Study is a 5-year randomized clinical trial ending in 2008. All emergency vehicles responding to 911 calls in Santa Cruz County, Calif, have been equipped with portable monitor defibrillators with a special study software that (1) synthesizes a 12-lead ECG from 5 electrodes, (2) measures ST amplitudes in all 12 leads every 30 seconds, and (3) automatically transmits an ECG to the target emergency department if there is a change in ST amplitude of 200 microV in 1 lead or more or 100 microV in 2 contiguous leads or more lasting 2.5 minutes. An initial ECG is transmitted by paramedics, which activates the software. Subsequent transmissions of ST event ECGs occur automatically without paramedic decision making. RESULTS: Prehospital ECGs had a greater frequency of arrhythmias than the first hospital ECG in the group as a whole (n = 433; 33.3% vs 28.9%; P < or = .001), as well as the subgroup with acute coronary syndrome (n = 185; 30.3% vs 26.5%; P < or = .001). More tachyarrhythmias occurred in the field and slightly more bradyarrhythmias occurred at the time of the first hospital ECG. CONCLUSIONS: Prehospital continuous 12-lead ST-segment ischemia monitoring with computer-assisted automatic mobile telephone transmission of ST event ECGs to the target hospital is feasible. More arrhythmias occur in the prehospital phase than are evident on the first hospital ECG.

Adult↗
PubMed2005

A dynamic model forecasting myocardial infarct size before, during, and after reperfusion therapy: an ASSENT-2 ECG/VCG substudy.

AIMS: Serial forecasts of final myocardial infarct (MI) size during fibrinolytic treatment (Rx) of ST-elevation MI would allow the identification of high-risk patients with a predicted major loss of viable myocardium, at a point when treatment may still be modified. We investigated a model for such forecasting, using time and the ECG. METHODS AND RESULTS: We collected 234 patients with ST-elevation MI, without signs of previous MI, bundle branch block, or hypertrophy. MI size was determined by the Selvester score and was "forecasted" at: admission with patients stratified by delay time and an ECG acuteness score into three groups (EARLY, DISCORDANT, and LATE); 90 min after Rx by > or =70% ST-recovery or not and occurrence of "reperfusion peaks"; 4 h after Rx by ST re-elevations. EARLY patients had smaller final infarct sizes than LATE (9.4 vs. 20%, P=0.01). EARLY patients with > or =70% ST-recovery without a reperfusion peak had smaller infarct sizes than those with (3.1 vs. 12.5%, P=0.001). EARLY patients without ST re-elevations had smaller infarct sizes (1.5%) than those with some (9%) or many re-elevations (12%), P<0.001. CONCLUSION: Final infarct size can be forecasted using delay time and serial ECGs. Serially updated forecasts seem especially important when both clock-time and initial ECG- signs indicate earliness.

Aged↗
PubMed2005

Distal microcirculatory protection during percutaneous coronary intervention in acute ST-segment elevation myocardial infarction: a randomized controlled trial.

CONTEXT: Atheromatous and thrombotic embolization during percutaneous coronary intervention (PCI) in acute myocardial infarction is common and may result in microcirculatory dysfunction, the prevention of which may improve reperfusion success, reduce infarct size, and enhance event-free survival. OBJECTIVE: To determine whether protection of the distal microcirculation from thromboembolic debris liberated during primary PCI results in improved reperfusion and decreased infarct size. DESIGN, SETTING, AND PATIENTS: Prospective randomized controlled trial at 38 academic and community-based institutions in 7 countries enrolling 501 patients aged 18 years or older with ST-segment elevation myocardial infarction (STEMI) presenting within 6 hours of symptom onset and undergoing primary PCI or rescue intervention after failed thrombolysis. INTERVENTIONS: Patients were randomized between May 20, 2002, and November 21, 2003, to receive PCI with a balloon occlusion and aspiration distal microcirculatory protection system vs angioplasty without distal protection. MAIN OUTCOME MEASURES: Coprimary end points were ST-segment resolution (STR) measured 30 minutes after PCI by continuous Holter monitoring and infarct size measured by technetium Tc 99m sestamibi imaging between days 5 and 14. Secondary end points included major adverse cardiac events. RESULTS: Among 252 patients assigned to distal protection, aspiration was performed in 97% (242/251), all angioplasty balloon inflations were fully protected in 79% (193/245), and visible debris was retrieved from 73% (182/250). Complete STR was achieved in a similar proportion reperfused with vs without distal protection (63.3% [152/240] vs 61.9% [148/239], respectively; absolute difference, 1.4% [95% confidence interval, -7.7% to 10.5%; P = .78]), and left ventricular infarct size was similar in both groups (median, 12.0% [n = 229] vs 9.5% [n = 208], respectively; P = .15). Major adverse cardiac events at 6 months occurred with similar frequency in the distal protection and control groups (10.0% vs 11.0%, respectively; P = .66). CONCLUSIONS: A distal balloon occlusion and aspiration system effectively retrieves embolic debris in most patients with acute STEMI undergoing emergent PCI. Nonetheless, distal embolic protection did not result in improved microvascular flow, greater reperfusion success, reduced infarct size, or enhanced event-free survival.

Aged↗
PubMed2005

Comparison of ST-segment resolution with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy versus fibrinolytic alone (data from four clinical trials).

We compared combination fibrinolytic plus glycoprotein IIb/IIIa inhibitor therapy with stand-alone fibrinolysis with respect to speed and stability of reperfusion in patients who had acute ST-segment elevation myocardial infarction; data were obtained from 654 patients in 4 trials (Integrilin to Manage Platelet Aggregation to Combat Thrombosis in Acute Myocardial Infarction, Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction, Integrilin and Tenecteplase in Acute Myocardial Infarction, and the Fifth Global Use of Strategies to Open Occluded Coronary Arteries) that compared thrombolytics plus lamifiban, eptifibatide, or abciximab with standard thrombolysis. We found significantly faster and more stable ST-segment recovery with combination therapy starting at 60 minutes (56.7% vs 48.0% with >/=50% ST-segment resolution, p = 0.03) and sustained over 180 minutes after drug administration; this transient benefit may suggest a time frame when more optimal percutaneous coronary intervention can be performed.

Abciximab↗
PubMed2005

Clinical utility of the Food and Drug Administration Electrocardiogram Warehouse: a paradigm for the critical pathway initiative.

Although there are rising public expectations about the prospects for new therapies based on advances in biomedical discoveries, the rate of new product submissions to the Food and Drug Administration (FDA) has not been increasing. Alarmingly, over the past 6 years, there has been a 30% decline in submissions. The reasons for this are multifactorial and include new science not at its full potential, mergers/business arrangements have decreased candidates, chronic disease is harder to study, the failure rate has not improved, and rapidly escalating costs and complexity. Notably, societal investment in research and development to improve the drug approval process has been lacking in contrast to the large investments, both private and public, in basic research and specific product advances. The Critical Path Initiative has been developed by the FDA to combat many of these issues. This initiative is designed to be collaborative between government, academic, industry, and patient groups. The partnership is designed to expand product opportunities by sharing existing knowledge and data, allowing the development of enabling standards, to improve drug development and approval. A central tenant of Critical Path is a focus on the evaluative science of the drug approval process, including both efficacy and safety measures. The FDA Electrocardiogram Warehouse is 1 example where a government resource could be used by a confluence of groups to improve the science surrounding important components of the drug approval process such as cardiac safety evaluation.

Critical Pathways↗
PubMed2004

Assessment of derived 12-lead electrocardiograms using general and patient-specific reconstruction strategies at rest and during transient myocardial ischemia.

Twelve-lead ST-segment monitoring is a widely used tool for capturing focal ischemia and transient intermittent episodes. However, continuous registration of all 10 electrodes is impractical in clinical settings. This study investigated the accuracy of 2 derived 12-lead strategies that required 6 electrodes, including all limb leads, and 2 precordial leads by using population-based (generalized) and individualized (patient-specific) reconstruction coefficients to derive the additional 4 chest leads. A total of 26,880 simultaneous digital conventional 12-lead generalized and patient-specific electrocardiograms were monitored over 112 hours in 39 patients during percutaneous coronary intervention, including 159 balloon occlusions in 63 arteries, to test accuracy at rest and during ischemia. Occlusion duration was 78 seconds (range 42 to 96) in the left main coronary in 2 patients, the left anterior descending artery in 15, the right coronary artery in 10, the circumflex artery in 2, and graft segments in 5 patients. Average summated 12-lead ST deviation over the study population at baseline was 377 microV (range 104 to 1,718), which increased at peak ischemia to an average of 1,086 microV (range 282 to 4,099). Median absolute differences at peak ischemic ST deviation were 25 microV in lead V(1), 0 microV in lead V(2), 35 microV in lead V(3), 34 microV in lead V(4), 0 microV in lead V(5), 11 microV in lead V(6), and 114 microV for summated 12-lead ST deviation with the generalized method and 7 microV in lead V(1), 4 microV in lead V(2), 1 muV in lead V(3), 5 microV in lead V(4), 4 microV in lead V(5), 9 microV in lead V(6), and 83 microV for the summated 12-lead ST deviation with the patient-specific method. Limb leads (I, II, III, aVR, aVL, and aVF) were identical in all patients. Thus, generalized and patient-specific methods derived from 12-lead electrocardiography using actual limb and 2 precordial electrodes accurately derived the additional chest leads at rest and during ischemia. These approaches appear to be more practical than conventional 10-electrode monitoring but preserve high accuracy.

Aged↗
PubMed2004

Practice standards for electrocardiographic monitoring in hospital settings: an American Heart Association scientific statement from the Councils on Cardiovascular Nursing, Clinical Cardiology, and Cardiovascular Disease in the Young: endorsed by the International Society of Computerized Electrocardiology and the American Association of Critical-Care Nurses.

The goals of electrocardiographic (ECG) monitoring in hospital settings have expanded from simple heart rate and basic rhythm determination to the diagnosis of complex arrhythmias, myocardial ischemia, and prolonged QT interval. Whereas computerized arrhythmia analysis is automatic in cardiac monitoring systems, computerized ST-segment ischemia analysis is available only in newer-generation monitors, and computerized QT-interval monitoring is currently unavailable. Even in hospitals with ST-monitoring capability, ischemia monitoring is vastly underutilized by healthcare professionals. Moreover, because no computerized analysis is available for QT monitoring, healthcare professionals must determine when it is appropriate to manually measure QT intervals (eg, when a patient is started on a potentially proarrhythmic drug). The purpose of the present review is to provide 'best practices' for hospital ECG monitoring. Randomized clinical trials in this area are almost nonexistent; therefore, expert opinions are based upon clinical experience and related research in the field of electrocardiography. This consensus document encompasses all areas of hospital cardiac monitoring in both children and adults. The emphasis is on information clinicians need to know to monitor patients safely and effectively. Recommendations are made with regard to indications, timeframes, and strategies to improve the diagnostic accuracy of cardiac arrhythmia, ischemia, and QT-interval monitoring. Currently available ECG lead systems are described, and recommendations related to staffing, training, and methods to improve quality are provided.

Arrhythmias, Cardiac↗
PubMed2004

Feasibility of endovascular cooling as an adjunct to primary percutaneous coronary intervention (results of the LOWTEMP pilot study).

In a nonrandomized feasibility study of therapeutic hypothermia in acute myocardial infarction, 18 patients were treated with endovascular cooling (Alsius, Irvine, California) as adjunctive therapy to primary percutaneous coronary intervention to assess measures of infarct size (area under the curve creatinine kinase-MB and technetium-99m single-photon emission computed tomography sestamibi) and the quality of myocardial perfusion (continuous ST-segment monitoring). Periprocedural endovascular cooling successfully decreased core body temperature (median 33.5 degrees C) and was well tolerated, which supports the evaluation of adjunctive hypothermia in pivotal trials to limit infarct size and decrease reperfusion injury.

Angioplasty, Balloon, Coronary↗
PubMed2004

Improved speed and stability of ST-segment recovery with reduced-dose tenecteplase and eptifibatide compared with full-dose tenecteplase for acute ST-segment elevation myocardial infarction.

OBJECTIVES: This sub-study of the Integrilin and Tenecteplase in Acute Myocardial Infarction (INTEGRITI) trial evaluated of the impact of combination reperfusion therapy with reduced-dose tenecteplase plus eptifibatide on continuous ST-segment recovery and angiographic results. BACKGROUND: Combination therapy with reduced-dose fibrinolytics and glycoprotein IIb/IIIa inhibitors for ST-segment elevation myocardial infarction improves biomarkers of reperfusion success but has not reduced mortality when compared with full-dose fibrinolytics. METHODS: We evaluated 140 patients enrolled in the INTEGRITI trial with 24-h continuous 12-lead ST-segment monitoring and angiography at 60 min. The dose-combination regimen of 50% of standard-dose tenecteplase (0.27 microg/kg) plus high-dose eptifibatide (2 boluses of 180 microg/kg separated by 10 min, 2.0 microg/kg/min infusion) was compared with full-dose tenecteplase (0.53 microg/kg). RESULTS: The dose-confirmation regimen of reduced-dose tenecteplase plus high-dose eptifibatide was associated with a faster median time to stable ST-segment recovery (55 vs. 98 min, p = 0.06), improved stable ST-segment recovery by 2 h (89.6% vs. 67.7%, p = 0.02), and less recurrent ischemia (34.0% vs. 57.1%, p = 0.05) when compared with full-dose tenecteplase. Continuously updated ST-segment recovery analyses demonstrated a modest trend toward greater ST-segment recovery at 30 min (57.7% vs. 40.6%, p = 0.13) and 60 min (82.7% vs. 65.6%, p = 0.08) with this regimen. These findings correlated with improved angiographic results at 60 min. CONCLUSIONS: Combination therapy with reduced-dose tenecteplase and eptifibatide leads to faster, more stable ST-segment recovery and improved angiographic flow patterns, compared with full-dose tenecteplase. These findings question the relationship between biomarkers of reperfusion success and clinical outcomes.

Coronary Angiography↗
PubMed2004

Combining baseline clinical descriptors and real-time response to therapy: the incremental prognostic value of continuous ST-segment monitoring in acute myocardial infarction.

BACKGROUND: Clinical descriptors and ST-segment recovery variables hold prognostic information for clinical outcome after thrombolysis for acute myocardial infarction (MI). We sought to define the incremental prognostic value of continuous 12-lead ST-segment monitoring variables to clinical risk descriptors identified by the Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries (GUSTO-I) trial 30-day mortality analysis. METHODS: Of 1,777 patients enrolled in continuous ST-segment substudies from the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI-9), GUSTO-I, Duke University Clinical Cardiology Study (DUCCS-II), Integrilin to manage Platelet Aggregation to Combat Thrombus in Acute Myocardial Infarction (IMPACT-AMI), Promotion of Reperfusion by Inhibition of Thrombin During Myocardial Infarction Evolution (PRIME), and Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction (PARADIGM) trials, 825 patients qualified for assessment of time to recovery. ST recovery variables analyzed were time to stable ST-recovery and late ST elevation. Patients who were at low clinical risk (n = 261) had no high-risk descriptors, and patients at high clinical risk (n = 564) had at least 1 of these high-risk descriptors: age >or=70 years, systolic blood pressure or=90 beats/min, anterior MI, or previous MI. High (n = 90), moderate (n = 318), and low (n =417) ST-risk groups were defined by the presence of both slow ST recovery and late ST elevation, one or the other, or neither, respectively. End points analyzed were inhospital death and combined death, reinfarction, or congestive heart failure. RESULTS: There was a trend toward increased mortality rate in the high-clinical/high-ST-risk group. For the composite end point, ST subgrouping resulted in significant event stratification in both patients at low and high clinical risk. In multivariable analysis, age and heart rate were independent predictors of both mortality and the composite end point. Late ST elevation added incremental prognostic information. CONCLUSION: Age, heart rate, and late ST elevation are powerful, independent predictors of adverse clinical outcome. Continuous monitoring allows noninvasive assessment of the response to therapy. Consequently, this technique will enhance the potential to risk-stratify individual patients in a real-time setting.

Aged↗