Quality of anticoagulation with warfarin in patients with nonvalvular atrial fibrillation in the community setting.

BACKGROUND: The benefit of oral anticoagulation therapy with warfarin for stroke prevention in atrial fibrillation (AF) is directly dependent on the quality of anticoagulation (QoA), which in the US is provided predominantly in the community setting. With the emergence of new oral anticoagulation agents, the current QoA needs to be assessed. OBJECTIVES: The purpose of our study is to define the QoA with warfarin in patients with nonvalvular AF who are managed exclusively in community practices, and to compare the quality in the community setting with the quality demonstrated in the recent large randomized control trials. In addition, this study will assess the differences in the QoA based on cardiology vs primary care practices. METHODS: This is a retrospective, observational, multi-center study of 392 patients with AF in the community who were initiated on anticoagulation with warfarin for stroke prevention. International Normalized Ratio (INR) values were collected over a one-year period and the QoA was expressed as time in therapeutic range (TTR) calculated by the linear interpolation method. RESULTS: One hundred patients from cardiology practices and 292 patients from primary care were studied. During the one-year period, the overall mean TTR was 56.7%. The TTR in the primary care vs cardiology practices was 55.3% vs. 60.8% (p=0.02). Both practices had similar percent of time below therapeutic range, 29.8% vs. 29.2%. However, the primary care practice patients were above the therapeutic range 15% of the time vs. 10% in cardiology (p<0.001). There were one death secondary to intracranial bleed and one major bleed in the primary care group. There were no strokes during the study period in either group. CONCLUSION: The QoA with warfarin, as assessed by TTR, in the current community setting remains suboptimal, and there has been little to no improvement in current clinical practices. TTR should be considered when assessing the recent comparative studies evaluating novel pharmacologic agents to warfarin for the treatment of AF. SUBJECT AREAS: Arrhythmias, preventive cardiology, anticoagulation, thromboembolism, cardiovascular disease risk factors.

The impact of numeric and graphic displays of ST-segment deviation levels on cardiologists' decisions of reperfusion therapy for patients with acute coronary occlusion.

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.

Overcoming barriers to developing seamless ST-segment elevation myocardial infarction care systems in the United States: recommendations from a comprehensive Prehospital 12-lead Electrocardiogram Working Group.

BACKGROUND: Reducing time to reperfusion treatment for patients with ST-segment elevation myocardial infarction (STEMI) improves patient outcomes. Few medical systems consistently meet current benchmarks regarding timely access to treatment. Studies have widely demonstrated that prehospital 12-lead electrocardiography can facilitate early catheterization laboratory activation and is the most effective means of decreasing patients' time to treatment. METHODS: We gathered experts to examine the barriers to implementation of prehospital 12-lead electrocardiographic monitoring and transmission to in-hospital cardiologists in creating seamless STEMI care systems (STEMI-CS) and propose multidisciplinary approaches to overcoming these barriers. RESULTS AND CONCLUSIONS: Physicians, hospital systems, and emergency medical services often lack coordination of care delivery and receive fragmented funding and oversight. Clinical and regulatory guidelines do not emphasize local solutions to achieving clinical benchmarks, do not target incentives at all components of the STEMI-CS, and underemphasize risk-based approaches to protecting patient health. Integration of the multiple complex components involved in STEMI-CS is essential to improving care delivery.

Heart rate and blood pressure response in adult men and women during exercise and sexual activity.

The purpose of this study was to assess the heart rate (HR) and blood pressure (BP) response of sexual activity compared with treadmill exercise in adult men and women. Nineteen men, 55 +/- 8 years, and 13 women, 51 +/- 7 years, underwent a maximal Bruce protocol treadmill stress test followed by home-monitored sexual activity using noninvasive HR and BP recording devices. The mean treadmill times were significantly shorter than the mean times of sexual activity for men and women (p <0.001 and p = 0.002, respectively). For the men, average maximum HR, systolic BP, and HR-BP product during sexual activity were 72%, 80%, and 57% of respective measurements during treadmill exercise. For the women, maximum HR, systolic BP, and HR-BP product during sexual activity were 64%, 75%, and 48% of respective measurements during treadmill exercise. Age correlated inversely with duration of treadmill exercise (a 9-second decrease in duration per increasing year of age; p = 0.036), and with the duration of sexual activity (a 1-minute decrease in duration per increasing year of age; p = 0.024). Treadmill exercise duration predicted sexual activity duration (a 2.3-minute increase in sexual activity duration per each minute treadmill duration; p = 0.026). In conclusion, sexual activity provides modest physical stress comparable with stage II of the standard multistage Bruce treadmill protocol for men and stage I for women.

Late angiographic follow-up in adults with initial angiographic normal or minimally narrowed coronary arteries.

We identified 46 patients with angiographically normal coronary arteries and 16 patients with minor irregularities (luminal narrowing < or =30%) who had repeat coronary angiograms obtained at our institution during the subsequent 15-year period. On follow-up angiograms, 19 of 46 (41%) in the normal coronary group and 13 of 16 (81%) in the minor lesion group showed progression of coronary artery disease (CAD). Five patients (11%) with no angiographic luminal CAD at the time of their baseline angiogram developed an acute myocardial infarction during the follow-up period. Patients in group 1 progressed from no vessels with angiographic lesions to a mean of 0.70 +/- 0.90 vessels diseased and a mean angiographic narrowing of 24 +/- 34% at the time of their follow-up angiograms, yielding a CAD progression rate of 2.6% luminal narrowing per year. Patients in group 2 had a mean progression of 0.69 +/- 0.79% of their vessels and a mean progression in their narrowing of 34 +/- 21%, yielding a CAD progression rate of 6.0% luminal narrowing per year. In conclusion, CAD can manifest late, or more likely, many patients with apparently normal coronary arteries have intimal CAD undetectable by angiography.

Racial and ethnic differences in the treatment and outcome of cardiogenic shock following acute myocardial infarction.

We investigated the association between race/ethnicity on the use of cardiac resources in patients who have acute myocardial infarction that is complicated by cardiogenic shock. The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial examined the effect of reperfusion and revascularization treatment strategies on mortality. Patients screened but not enrolled in the SHOCK Trial (n = 1,189) were entered into the SHOCK registry. Of the patients in the United States registry (n = 538) who had shock due to predominant left ventricular failure, 440 were characterized as white (82%), 42 as Hispanic (8%), 34 as African-American (6%), and 22 as Asian/other (4%). The use of invasive procedures differed significantly by race/ethnicity. Hispanic patients underwent coronary angiography significantly less often than did white patients (38 vs 66%, p = 0.002). Among those patients who underwent coronary angiography, there were no race/ethnicity differences in the proportion of patients who underwent revascularization (p = 0.353). Overall in-hospital mortality (57%) differed significantly by race/ethnicity (p = 0.05), with the highest mortality rate in Hispanic patients (74% vs 65% for African-Americans, 56% for whites, and 41% for Asian/other). After adjustment for patient characteristics and use of revascularization, there were no mortality differences by race/ethnicity (p = 0.262), with all race/ethnicity subgroups benefiting equally by revascularization. In conclusion, the SHOCK registry showed significant differences in the treatment and in-hospital mortality of Hispanic patients who had cardiogenic shock, with these patients being less likely to undergo percutaneous coronary intervention. Therefore, early revascularization should be strongly considered for all patients, independent of race/ethnicity, who develop cardiogenic shock after acute myocardial infarction.

Electrocardiographic findings in cardiogenic shock, risk prediction, and the effects of emergency revascularization: results from the SHOCK trial.

OBJECTIVES: To evaluate electrocardiographic (ECG) parameters as predictors of 1-year mortality in patients developing cardiogenic shock after acute myocardial infarction (AMI), and to document associations between these ECG parameters and the survival benefit of emergency revascularization versus initial medical stabilization. BACKGROUND: Emergency revascularization reduces the risk of mortality in patients developing cardiogenic shock after AMI. The prognostic value of ECG parameters in such patients is unclear, and it is uncertain whether emergency revascularization reduces the mortality risk denoted by ECG parameters. METHODS: In a prospective substudy of 198 SHOCK (SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK) trial patients, ECGs recorded within 12 hours of shock were interpreted by personnel blinded to the patients' treatment assignment and outcome. RESULTS: The baseline heart rate was higher in non-survivors than in survivors (106 +/- 20 versus 95 +/- 24 beats/minute, P = .001). There was a significant association between the QRS duration and 1-year mortality in medically stabilized patients (115 +/- 28 ms in non-survivors versus 99 +/- 23 ms in survivors, P = .012), but not in emergently revascularized patients (110 +/- 31 versus 116 +/- 27 ms respectively, P = .343). The interaction between the QRS duration, mortality and treatment assignment was significant (P = .009). Among patients with inferior AMI, a greater sum of ST depression was associated with higher 1-year mortality in medically stabilized patients (P = .029), but not in emergently revascularized patients (P = .613, treatment interaction P = .025). On multivariate analysis, the independent mortality predictors were increasing age, elevated pulmonary capillary wedge pressure, heart rate, sum of ST depression in medically stabilized patients, and interaction (P = .016) between a prolonged QRS duration and treatment assignment. The adjusted hazard ratio for 1-year mortality per 20 ms increase in the QRS duration was 1.19 (95% CI 0.98-1.46) in medically stabilized patients and 0.81 (95% CI 0.63-1.03) in emergently revascularized patients. CONCLUSION: ECG parameters identified patients with cardiogenic shock who were at high risk. Emergency revascularization eliminated the incremental mortality risk associated with cardiogenic shock in patients with a prolonged QRS duration, or inferior AMI accompanied by precordial ST depression. Prospective assessments of the magnitude of the treatment effect based on ECG parameters are required.

Association of the timing of ST-segment resolution with TIMI myocardial perfusion grade in acute myocardial infarction.

BACKGROUND: More complete ST-segment resolution (ST res) in acute myocardial infarction (MI) has been associated with better epicardial and myocardial reperfusion as assessed with the Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG) and the TIMI myocardial perfusion grade (TMPG), respectively. However, no data exist comparing the speed of ST resolution on continuous electrocardiogram (ECG) monitoring with the TMPG on coronary angiography. We hypothesized that delayed ST res is associated with impaired TMPGs. METHODS: Continuous 12-lead ECG recordings and 60-minute angiographic data were analyzed in 120 patients with acute MI who received tenectaplase monotherapy or combination therapy with low-dose tenectaplase and eptifibatide in the Integrilin and Tenecteplase in Acute Myocardial Infarction (INTEGRITI) trial. RESULTS: More rapid ST res on continuous ECG monitoring was associated with improved TMPGs on coronary angiography performed 60 minutes after study drug administration. For TMPG 3, the median time to ST resolution was 53 minutes. For TMPG 2, 1, and 0, the corresponding times were 64 minutes, 80 minutes, and 106 minutes, respectively (P =.01 for trend). Likewise, more rapid ST res was also associated with faster epicardial flow. For TFG 3, the median time to ST resolution was 46 minutes, compared with 109 minutes for TIMI flow grades 0 to 2 (P =.001). The corresponding times for a corrected TIMI frame count < or =40 versus >40 were 52 minutes and 112 minutes, respectively (P <.001). CONCLUSIONS: Although the static ECG has been associated with epicardial and myocardial blood flow in the past, this study extends these observations to demonstrate that more rapid ST res on continuous ECG monitoring is associated with improved myocardial perfusion after thrombolytic administration.

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.

Influence of thrombolytic therapy, with or without intra-aortic balloon counterpulsation, on 12-month survival in the SHOCK trial.

BACKGROUND: The enhancement of diastolic coronary blood flow by the combination of thrombolytic therapy (TT) and intra-aortic balloon counterpulsation (IABP) in experimental studies provides a rationale for their combined use in acute myocardial infarction (MI) complicated by cardiogenic shock. We examined the relation between TT (with and without IABP) and 12-month survival in the SHould We Emergently Revascularize Occluded Coronaries for Cardiogenic ShocK (SHOCK) Trial. METHODS AND RESULTS: Among 302 patients with myocardial infarction and cardiogenic shock who were randomized in the SHOCK Trial, 16 had absolute contraindications to TT. Among 150 patients randomly assigned to initial medical stabilization (IMS), 63% received TT, as recommended per protocol, compared with 49% of 152 patients randomly assigned to emergency revascularization, in whom TT was not recommended if immediate angiography was available. IABP deployment, which was protocol-recommended, was used in 86% of patients. The rate of severe bleeding was similar in patients receiving TT and in those not receiving TT (31% vs 26%, P =.37). Among patients randomly assigned to IMS, TT was associated with improved 12-month survival (unadjusted mortality hazard ratio, 0.59; P =.01; mortality hazard ratio adjusted for age and prior MI, 0.62; P =.02). TT was not associated with improved 12-month survival among patients randomly assigned to emergency revascularization (unadjusted mortality hazard ratio, 0.93; P =.76; mortality hazard ratio adjusted for age and prior MI, 1.06, P =.81). The test for interaction of TT and randomization group P value was.16, and there was insufficient statistical power to demonstrate a differential effect of TT on 12-month survival by treatment group assignment. CONCLUSIONS: Among patients randomly assigned to IMS in the SHOCK Trial, TT was associated with improved 12-month survival and did not significantly increase the risk of severe bleeding.

The relationship of intracoronary stent placement following thrombolytic therapy to tissue level perfusion.

BACKGROUND: Stenting has been shown to improve lumen diameters and thereby improve epicardial blood flow, but the impact of stent placement on tissue level perfusion has not been well characterized. METHODS: Data were drawn from the LIMIT trial of rhuMAb CD18 (anti WBC antibody) in acute myocardial infarction (AMI). Adjunctive/rescue stenting was performed at the discretion of the investigator. The TIMI Myocardial Perfusion Grade (TMPG) was assessed and digital subtraction angiography (DSA) was used to quantify brightness of the myocardial blush. RESULTS: TIMI 3 flow was 54.2% (64/118) before stent placement, and improved to 87.2% (102/117, p < 0.001) following stent placement. Likewise, Corrected TIMI Frame Counts (CTFCs) improved from medians of 37.6 to 21 (p < 0.001). By DSA, the rate of growth in brightness also tended to be greater after stenting (2.3 +/- 0.4 Gray/sec, n = 54 vs 3.1 +/- 0.3, n = 54, p = 0.07). The incidence of TMPG 0 decreased following stent placement (25.2% (29/118) vs 14.3% (16/118), p = 0.03) and the incidence of a stain in the myocardium (TMPG 1) increased (13.5% (16/118) vs 28.6% (34/118), p = 0.004). CONCLUSION: Adjunctive stenting following thrombolytic administration in AMI improves epicardial TIMI 3 flow and TIMI frame counts as well as dye inflow into the myocardium: TMPG 0 is reduced and myocardial blush measured quantitatively by DSA tends to be brighter. However, more TMPG 1 or dye staining was present on next injection, suggesting dye outflow may be impaired.