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Biomedical subjects

F H Sheehan

Publications and source records attributed to F H Sheehan.

At least 55 records · Page 3Linked to original sources

Late outcome of survivors of out-of-hospital cardiac arrest with left ventricular ejection fractions greater than or equal to 50% and without significant coronary arterial narrowing.

In a retrospective survey of 1,195 survivors of out-of-hospital ventricular fibrillation, 43 patients were identified in whom left ventricular ejection fraction was greater than or equal to 0.50 and in whom no coronary artery stenosis of greater than or equal to 50% luminal diameter were present. Thirteen (30%) of these patients had hypokinesia on left ventriculography, and 20 patients (47%) had a persistently abnormal electrocardiogram. Seven patients (16%) had recurrent out-of-hospital cardiac arrest during an average follow-up of 86 +/- 54 months. The presence of either wall motion or electrocardiographic abnormalities defined patients with a several-fold higher risk of recurrent cardiac arrest than those without such abnormalities. The risk for recurrent cardiac arrest within 5 years was 30% in those with abnormal electrocardiograms versus 5% in the others (p less than 0.03). Age was an independent predictor of recurrent cardiac arrest in this group (p less than 0.01); surprisingly, recurrent cardiac arrest was occurring more often among younger patients. Although cardiac arrest is unusual in patients without major structural heart disease, its recurrence in such survivors is common. Patients at relatively high risk for recurrent ventricular fibrillation can be identified by their youth and by abnormalities detected on the surface 12-lead electrocardiogram or by contrast left ventriculography.

Adult↗

Early beneficial effect of streptokinase on left ventricular function in acute myocardial infarction.

The effect of intravenous streptokinase therapy on the time course of functional recovery was investigated in a controlled study of 64 patients randomized within 3 hours after the onset of acute myocardial infarction (AMI). Contrast ventriculography was performed 1 to 4 days after AMI and repeated 5 weeks later. Wall motion was analyzed by the centerline method in the central infarct, peripheral infarct and noninfarct regions. In patients with ventriculographic data at the early catheterization, streptokinase-treated patients had less severe hypokinesia in the central infarct region than control patients (-2.9 +/- 0.9 [n = 29] vs -3.4 +/- 0.7 standard deviations below normal [n = 21], p less than 0.05). The benefit of streptokinase was more marked in the peripheral infarct region (-1.5 +/- 0.7 vs -2.1 +/- 0.6, p less than 0.001). As a result, the ejection fraction was slightly higher in treated versus control groups (46 +/- 10 vs 43 +/- 7%, respectively; difference not significant). At 5 weeks, function in the streptokinase and control groups had diverged further because of continued improvement in the streptokinase-treated patients. This study shows that streptokinase benefits left ventricular (LV) function by 1 to 4 days after AMI, earlier than previously reported. The benefit was not limited to the peripheral infarct region, where ischemia might have been less severe, but was also seen in the central infarct region. The implication is that thrombolytic therapy can improve LV function during the period of myocardial stunning, while myocardial function is still recovering.

Adult↗

Prehospital thrombolysis in acute myocardial infarction.

The benefit and risk of prehospital thrombolysis for acute myocardial infarction (AMI) were evaluated in a double-blind randomized trial. Patients presenting less than 4 hours after symptom onset received 2 million units of urokinase as an intravenous bolus either before (group A, n = 40) or after (group B, n = 38) hospital admission. The mean time interval from onset of symptoms to thrombolytic therapy was 85 +/- 51 minutes in group A and 137 +/- 50 minutes in group B (p less than 0.0005). In 91% of the patients, thrombolytic therapy was administered less than 3 hours after symptom onset. Complication rates during the pre- and in-hospital period were low and did not differ between groups. Three patients died (1 in group A, 2 in group B) from reinfarction 7 to 14 days after admission. Left-sided cardiac catheterization before discharge revealed a patency rate in the infarct-related artery of 61% in group A and 67% in group B (difference not significant). Global left ventricular function and regional wall motion at the infarct site did not differ significantly between group A and B (ejection fraction 51 +/- 10%, n = 28 vs 53 +/- 14%, n = 28; wall motion -2.3 +/- 1.3 vs -2.2 +/- 1.1 standard deviation, respectively). Also, peak creatine kinase did not differ significantly (838 +/- 634 U/liter in group A vs 924 +/- 595 U/liter in group B). Prehospital thrombolysis using a bolus injection of urokinase has a low risk when performed by a trained physician with a mobile care unit. The saving of 45 minutes in the early stage of an acute infarction through prehospital thrombolysis did not appear to be important for salvage of myocardial function.

Ambulances↗

Influence of coronary arterial thrombus location on left ventricular function in acute myocardial infarction.

In 238 patients with acute myocardial infarction studied during intracoronary streptokinase therapy, the circumferential extent of left ventricular hypokinesis was measured by 5 methods and correlated with the location of the infarct-related coronary artery segment and with 1-year survival. Of the 5 methods, 1 focused only on the infarct region, and 4 varied in the complexity of the noise filter. Hypokinetic segment length measurements by all 5 methods correlated significantly with the location of occlusion along the left anterior descending coronary artery. No method yielded measurements that correlated with occlusion location along the right coronary artery. Measurements by all methods correlated significantly with survival, but the method that focused on the infarct region performed least well. Thus, the circumferential extent of hypokinesis in patients with acute myocardial infarction is greater for proximal than mid- or distal occlusions of the left anterior descending but not the right coronary artery. Survival is influenced by the function of periinfarct and noninfarct regions and by the function of the infarct region. Complex noise filters provide no advantage over simpler filters in measuring the extent of hypokinesis.

Coronary Angiography↗

[The thrombolysis treatment of acute myocardial infarct at the site of the emergency. A randomized double-blind study].

Two million units of urokinase were administered intravenously as a bolus, either before (group I, n = 40) or after hospital admission (group II, n = 38), to 66 men and 12 women (mean age 55 +/- 8 years) with typical symptoms of acute myocardial infarction of less than 4 hours' duration. Time elapsed between onset of symptoms and urokinase administration averaged 85 +/- 51 min for group I and 137 +/- 50 min for group II (P less than 0.005). The complication rate was low, both during the pre-hospital and the hospital phases, without any significant differences between the two groups. The rate of open infarct vessels (by angiography before discharge from hospital) was 61% for group I and 67% for group II (no significant difference). Global left ventricular function, regional wall motion in the infarct area and maximal creatinekinase values did not significantly differ between the two groups (ejection fraction 51 +/- 10% and 53 +/- 14%, respectively; creatinekinase 838 +/- 634 U/l and 924 +/- 595 U/l, respectively). The data indicate that thrombolytic pre-hospital treatment carried a low risk. The gain of 45 min, however, seems to be of secondary importance in any significant diminution of the acute infarction size.

Coronary Angiography↗

Comparison of immediate invasive, delayed invasive, and conservative strategies after tissue-type plasminogen activator. Results of the Thrombolysis in Myocardial Infarction (TIMI) Phase II-A trial.

To assess the value and timing of percutaneous transluminal coronary angioplasty (PTCA) after thrombolytic therapy for acute myocardial infarction (AMI), 586 patients in the Thrombolysis in Myocardial Infarction Study Phase II-A were randomized among three treatment strategies, one using immediate coronary arteriography followed by PTCA if appropriate (immediate invasive strategy group, n = 195), a second that deferred angiography and PTCA for 18-48 hours (delayed invasive strategy group, n = 194), and a third, more conservative, approach in which PTCA was used only if ischemia occurred spontaneously or at the time of predischarge exercise testing (conservative strategy group, n = 197). Predischarge contrast left ventricular ejection fraction, the primary study end point, was similar among the patients in all three treatment groups and averaged 49.3%. The finding of a patent infarct-related artery at the time of predischarge arteriography was equally common among the patients in the three groups (mean, 83.7%); however, the mean residual infarct artery stenosis was greater in the patients in the conservative strategy group (67.2%) as compared with the patients in the immediate invasive (50.6%) and the delayed invasive strategy groups (47.8%) (p less than 0.001). Immediate invasive strategy led to a higher rate of coronary artery bypass graft surgery (CABG) after PTCA (7.7%) than did delayed invasive and conservative strategies (2.1% and 2.5%, respectively; p less than 0.01). Furthermore, among patients not undergoing CABG during the first 21 days, blood transfusion of more than 1 unit was used in 13.8% of the patients in the immediate invasive strategy group, 3.1% of the patients in the delayed invasive strategy group, and 2.0% of the patients in the conservative strategy group (p less than 0.001). At 1-year follow-up, the three treatment groups had similar cumulative rates of mortality (8.7%, pooled over all groups), fatal and nonfatal reinfarction (8.5%), combined death and reinfarction (14.5%), and CABG (17.2%), although the cumulative performance rate of PTCA remained higher in the invasive groups (immediate invasive strategy group, 75.8%; delayed invasive strategy group, 64.3%; and conservative strategy group, 23.9%; p less than 0.001). Thus, because conservative strategy achieves equally good short- and long-term outcome with less morbidity and a lower use of PTCA, it seems to be the preferred initial management strategy.

Aged↗

Factors influencing accuracy in left ventricular volume determination.

The accuracy with which left ventricular volume is determined from contrast ventriculograms depends on the care with which the analysis protocol is followed. Therefore, the effect of variations in the method used for calculating the correction factor (CF) that adjusts for magnification and image distortion on volume calculation was measured. The results showed that error in the CF is caused by (in order of decreasing importance): filming the calibration figure at a different magnification mode from that of the ventriculogram, at a different height from the table than the level of the ventricle, or with the image intensifier at a different height than used during ventriculography; use of a calibration figure less than half the size of the ventricle; calculation of the CF from only 1 band pair of a banded catheter; or placement of the calibration figure at the periphery rather than the center of the imaging field. Error in volume determination was proportional to error in the CF. With care, the error in volume can be reduced to that due to interobserver variability in tracing the endocardial contours.

Calibration↗

Left ventricular dysfunction in acute myocardial infarction due to isolated left circumflex coronary artery stenosis.

The characteristics of regional and global left ventricular dysfunction due to isolated left circumflex (LC) artery stenosis were determined from the contrast ventriculograms of 52 patients studied during acute myocardial infarction. In patients with a left dominant coronary circulation (35%), the severity, circumferential extent and location of hypokinesia resembled those of right coronary artery stenosis. However, in patients with a right dominant or balanced circulation (65%), the location of LC artery-related hypokinesia varied over the entire left ventricular contour, overlapping with the territories of the left anterior descending and right coronary arteries. The method for measuring the severity of hypokinesia was adjusted to take into account the wide territory of the LC artery. This enhanced the sensitivity of the method, particularly in the right anterior oblique view, as indicated by the greater severity of hypokinesia measured (-2.5 +/- 0.9 vs -1.8 +/- 1.1 standard deviations by our previously published method, p less than 0.001). However, the overlap of the artery territories may make it difficult to selectively measure the dysfunction due to stenosis of an artery of interest in patients with multiple infarctions. The circumferential extent of hypokinesia due to LC artery thrombosis was greater in the left than the right anterior oblique view. When averaged over both views, the size of the dysfunctional segment approached that due to left anterior descending coronary artery thrombosis, exceeding the size previously reported. These results suggest that current eligibility criteria for thrombolytic therapy select patients with extensive LC artery beds.

Cineradiography↗

Evolution of left ventricular function after intracoronary thrombolysis for acute myocardial infarction.

The temporal evolution of left ventricular (LV) function after intracoronary streptokinase therapy for acute myocardial infarction (AMI) was assessed from the data of 264 patients who had complete occlusion of either the left anterior descending or the right coronary artery before treatment. Angiography was performed immediately, and at 3 days and 6 months after AMI in 91%, 71% and 47% of the study group, respectively. Wall motion was measured by the centerline method. In patients with sustained reperfusion, the ejection fraction decreased at 3 days (delta = -2.0 +/- 9.9%, n = 134, p = 0.02) and recovered later (from 54 +/- 12% acutely to 57 +/- 12% at 6 months, n = 82, p less than 0.05). These changes in global function were associated with a marked regression in hyperkinesis in the noninfarcted wall by 3 days, and delayed recovery of wall motion in the infarct region (delta = 0.2 +/- 0.9 at 3 days, p = 0.055; 1.0 +/- 1.2 at 6 months, p less than 0.001). Patients without reperfusion or with reocclusion had a more severe decrease in ejection fraction at 3 days, and little or no subsequent functional recovery. The length of the hypokinetic segment increased significantly by 3 days but subsequently diminished to slightly less than the acute value. It is concluded that full recovery of ischemically impaired myocardium takes greater than 3 days, but compensatory hyperkinesis regresses earlier so that global LV function deteriorates by the third day. Variability or deterioration of LV function early after AMI need not be due to infarct extension; it can reflect regression of hyperkinesis in the noninfarcted region.

Angiography↗

Limitations in the interpretation of rest-exercise ejection fraction changes after early thrombolytic therapy during acute myocardial infarction.

The effect of exercise on left ventricular wall motion in the infarct and noninfarct regions, and their contribution to the global ejection fraction response to exercise was evaluated in 24 patients studied at least 2 weeks following thrombolytic therapy for acute myocardial infarction. To achieve this goal, a nonstandard protocol was used: contrast ventriculography was performed at rest and immediately following 3 minutes of supine bicycle exercise at 50 watts. Wall motion in the infarct and noninfarct regions was measured using the centerline method. The global ejection fraction response to exercise correlated poorly with the exercise response of motion in the infarct region (r = 0.38). In 15 of the 24 patients, the function of the infarct and noninfarct regions changed in opposing directions, and in only 8 (53%) of these did the global ejection fraction response follow the exercise response of motion in the infarct region. The motion of the noninfarct region was the predominant influence on the ejection fraction response in the other 7 patients. Subgroup analysis revealed that the global ejection fraction response was more dependent on the response of motion in the anterior wall (r = 0.71, p less than 0.001) than in the inferior wall (r = 0.16), regardless of infarct location. The regional wall motion response to exercise also better distinguished reperfused from nonreperfused patients than did the ejection fraction response. These results indicate that the global ejection fraction response to exercise may be an unreliable indicator of the functional status of the infarct region.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Improved survival up to four years after early coronary thrombolysis.

The long-term prognosis after thrombolytic therapy in patients with acute myocardial infarction (AMI) is unknown. This question was investigated in a 4-year follow-up study of 227 patients. According to the status of reperfusion at the end of the acute catheterization, the patients were divided into a patent (n = 171) and an occluded (n = 56) group. Both hospital and 4-year mortality rates were significantly reduced in the patent group by 13 and 14%, respectively (p less than or equal to 0.005 for both). Baseline variables known to be important for prognosis did not differ between the 2 groups. Patients with a patent infarct artery who underwent early acute coronary artery bypass grafting (CABG) had a greater survival (p less than 0.10) and better left ventricular function (p less than 0.01) than did patients with a patent infarct artery who did not undergo CABG. This difference was associated with a lower frequency of fatal reinfarction and cardiogenic shock in the CABG group. Thus, survival is improved up to 4 years after successful thrombolysis and appears to be further enhanced by early CABG.

Cardiac Catheterization↗

Use of a satellite-assisted computer link for long-distance research collaboration.

Research collaboration between investigators located at some distance from each other is not only possible but also feasible. By using satellite-assisted computer-to-computer links, researchers across the United States and overseas work with the staff and facilities of the Cardiovascular Research and Training Center (CVRTC) in the University of Washington, Seattle. This report presents the mechanics, advantages, and results of using such an approach to collaborate with distant colleagues.

Cardiovascular Diseases↗

Early recovery of left ventricular function after thrombolytic therapy for acute myocardial infarction: an important determinant of survival.

Thrombolytic therapy for acute myocardial infarction reduces early mortality, but full recovery of left ventricular function after reperfusion is delayed. Therefore, the relations among reperfusion, survival and the time course of left ventricular functional recovery were examined in 226 patients treated with intracoronary streptokinase; 77% (134 patients) had sustained reperfusion and 31 patients had no reperfusion or had reocclusion by day 3. Wall motion was measured from contrast ventriculograms performed in the acute period and 3 days later in the central and peripheral infarct regions and the noninfarct region by the centerline method in 165 patients. Patients with reperfusion had better survival (p less than 0.05, mean follow-up 4.5 years) and a higher ejection fraction at 3 days (52 +/- 12 versus 46 +/- 10%, p less than 0.02) attributable to a significantly different change in peripheral infarct region function between the acute and 3 day studies (0.1 +/- 1.0 versus -0.3 +/- 0.9 SD, p less than 0.05). These early functional changes were significant in patients with anterior myocardial infarction and showed similar trends in those with inferior myocardial infarction. On Cox regression analysis, function measured at 3 days was more predictive of survival than was function measured acutely (chi square for acute ejection fraction = 11.48 versus 24.59 at 3 days). Although, as previously reported, greater than 45% of total recovery of left ventricular function occurs later, the ejection fraction achieved by day 3 is already predictive of survival. Thus, the mechanism by which successful thrombolytic therapy enhances survival is improvement of regional and global left ventricular function early after acute myocardial infarction.

Coronary Circulation↗

Recovery of left ventricular function after myocardial infarction can be predicted immediately after thrombolysis by semiquantitative intracoronary thallium and technetium pyrophosphate scintigraphy.

The accuracy with which intracoronary thallium and technetium pyrophosphate scintigraphy during intracoronary thrombolysis predicts myocardial salvage was studied in 58 patients with acute myocardial infarction by comparing the acute scintigraphic findings with subsequent left ventricular function. Scintigrams obtained before and immediately after thrombolysis were interpreted by three independent observers using a scoring system. Regional wall motion in the infarct area was determined from left ventricular (LV) cine angiograms using the center-line method. Patients with mild hypokinesis (hypokinesis less than or equal to -2 SD from normal) could be distinguished from those with severe hypokinesis (hypokinesis greater than -2 SD) using the prethrombolysis thallium score with an accuracy of 83%. Accuracy using the post-thrombolysis score was 76%. When the post-thrombolysis thallium and technetium pyrophosphate scores were combined, differentiation was possible in 91% of all patients studied, and in 100% of patients with anterior myocardial infarction. Thus, analysis of combined thallium and technetium pyrophosphate scintigraphy accurately predicts recovery of LV function after thrombolysis and may be helpful in deciding whether acute percutaneous transluminal coronary angioplasty or bypass surgery should be performed after thrombolysis.

Cardiac Output↗

The Western Washington Intravenous Streptokinase in Acute Myocardial Infarction Randomized Trial.

Three hundred sixty-eight patients were randomly assigned to receive intravenous streptokinase (IVSK) (n = 191) or standard therapy (n = 177) to determine the efficacy of IVSK in the treatment of acute myocardial infarction. The mean time to treatment was 3.5 hr. At 14 days there were 12 deaths in the treatment group (6.3%) and 17 deaths in the control group (9.6%) (p = .23). Early mortality was related to infarct location. Fourteen day mortality for anterior infarctions was 10.4% for treatment with IVSK and 22.4% for control patients (p = .06) and was similar for IVSK-treated patients with inferior infarctions, 4.0% vs 1.8% (p = .32). For those randomized under 3 hr, 14 day mortality tends to be lower in treated patients, 5.2% vs 11.5% (p = .11). There was significant improvement in long-term survival for patients with anterior infarction; 2 year survival was 81% for IVSK-treated patients and 65% for control patients (p = .05). There was no improvement in survival for patients with inferior myocardial infarction (p = .27). We conclude that patients with anterior myocardial infarction have improved survival when treated within the first 6 hr of symptoms. Patients with inferior infarction do not appear to have improved survival with thrombolytic therapy. Some of this improvement in survival in patients with anterior infarction may be due to a higher frequency of revascularization procedures in the treatment group.

Aged↗

Intravenous streptokinase for acute myocardial infarction. Effects on global and regional systolic function.

The Western Washington Intravenous Streptokinase Trial randomized 368 patients with acute myocardial infarction to receive either intravenous streptokinase or standard therapy. The ventriculograms and coronary angiograms obtained in 170 patients 10.4 +/- 7.4 days after infarction were analyzed to evaluate the effects of thrombolytic therapy on global and regional systolic function. Streptokinase treatment resulted in a higher patency rate of the infarct-related artery (68.5%) than did standard therapy (44.8%) (p = 0.003). Ejection fraction was higher in streptokinase-treated patients (54% vs. 51%, p = 0.056), and the difference was most marked in patients with anterior myocardial infarction (53% vs. 44%, p = 0.03). Regional wall motion was measured by the centerline method and expressed in mean +/- SD motion in 52 normal subjects. There was a trend toward better function of the infarct zone in streptokinase-treated patients (SD, -2.48 vs. -2.70, p = 0.24). Additionally, streptokinase-treated patients had significantly better wall motion of noninfarct areas (SD, 0.36 vs. -0.08, p = 0.02). Treatment effects on function of noninfarct regions were most apparent in the subset of patients with multivessel disease. Thus, intravenous streptokinase preserves left ventricular function in patients with acute myocardial infarction. This benefit includes favorable effects on the function of regions remote from the site of infarction.

Cardiac Catheterization↗

Coronary thrombolysis with intravenous urokinase in patients with acute myocardial infarction.

Regional left ventricular wall motion, about two to three weeks after acute myocardial infarction (MI), is perhaps the best clinical measure of myocardial salvage and limitation of infarct size by thrombolytic therapy. Normal or only slightly depressed wall motion at the site of infarction indicates significant limitation of infarct size, whereas markedly abnormal wall motion indicates irreversible myocardial damage. Early studies found significant improvement in regional wall motion in only 40 percent of patients undergoing successful intracoronary thrombolytic therapy after the onset of symptoms of acute MI. Why only 40 percent of these reperfused patients demonstrated salvage of ischemic myocardium could not be answered at that time. Animal experiments show that the duration of coronary occlusion is an important factor in determining myocardial salvage after reperfusion. To study whether this time dependency also exists under clinical circumstances in patients with coronary artery disease, the relationship between regional wall motion (as an index of infarct size) and the time to thrombolytic therapy after the onset of symptoms (as an index of duration of coronary occlusion) was examined. After showing that such time dependency does indeed exist in patients with acute MI, the efficacy and safety of intravenous bolus injections of urokinase were then demonstrated.

Coronary Disease↗