Arthur D. Hagan

A Randomized Trial of Intracoronary Streptokinase in the Treatment of Acute Myocardial Infarction

Fifty patients with acute myocardial infarction were randomly assigned to receive either intracoronary streptokinase or standard (control) therapy within about three hours after the onset of pain. Coronary perfusion was reestablished in 19 of 24 patients receiving streptokinase. Streptokinase alleviated pain (as indicated by differences in subsequent morphine use). The Killip class was significantly improved after therapy with streptokinase, as were changes in radionuclide ejection fraction between Days 1 and 10 in surviving patients (+3.9 vs. -3.0 per cent, P less than 0.01). The echocardiographic wall-motion index also showed greater improvement after streptokinase treatment (P less than 0.01). Streptokinase therapy was associated with rapid evolution of electrocardiographic changes, which were essentially complete within three hours after therapy, but loss of R waves, ST elevation, and development of Q waves in the convalescent period were greater in the control group (P less than 0.01). The time required to reach peak plasma enzyme concentrations was significantly shorter after streptokinase. The incidence of early and late ventricular arrhythmias was not affected by treatment. We conclude that intracoronary streptokinase appears to have a beneficial effect on the early course of acute myocardial infarction.

Evaluation of size and dynamics of the inferior vena cava as an index of right-sided cardiac function.

To define normal criteria of size and dynamics of the inferior vena cava (IVC) and its clinical value in assessing right-sided cardiac function, 2-dimensional (2-D) and M-mode echocardiography (echo) were performed in 175 subjects, who were classified into 3 groups: group 1-80 normal subjects; group IIA--65 patients with documented right-sided cardiac disease, and group IIB--30 patients with cardiac disease but no right-sided abnormality. The IVC was adequately imaged in 175 of 185 subjects (95%). There was good correlation between M-mode and 2-D echo (r = 0.84) and long- and short-axis (r = 0.88) measurements. The IVC diameter during expiration was: group 1-9 to 28 mm (mean 18.2 +/- 4.6); group IIA--15 to 40 mm (mean 23.1 +/- 4.8) and group IIB-8-24 mm (mean 15.6 +/- 3.7). Collapsibility index (inspiratory decrease in diameter) was: group I-37 to 100% (mean 55.8 +/- 15.9); group IIA--0 to 39% (mean 13.5 +/- 10.5); and group IIB--44 to 100% (mean 60.4 +/- 13.1). A and V waves could be measured in 120 of 151 cases (79%). Both A and V waves were less than 125% of its diameter in group I. The A wave was absent in 34 patients; 30 (88%) were in atrial fibrillation. Among 8 patients with tricuspid regurgitation, 5 (63%) had V waves greater than 125%. There was no correlation between diameter or collapsibility index and age, sex, rhythm or body surface area.(ABSTRACT TRUNCATED AT 250 WORDS)

Multicenter reperfusion trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: Controlled comparison with intracoronary streptokinase

The recent establishment of a firm therapeutic role for reperfusion in acute myocardial infarction has stimulated interest in the development of more ideal thrombolytic agents. Anisoylated plasminogen streptokinase activator complex (APSAC) is a new plasminogen activator possessing properties that are promising for intravenous thrombolytic application in acute myocardial infarction. To assess the reperfusion potential of intravenous APSAC, a multi-center, angiographically controlled reperfusion trial was performed. An approved thrombolytic regimen of intracoronary streptokinase served as a control. Consenting patients with clinical and electrocardiographic signs of acute myocardial infarction were studied angiographically and 240 qualifying patients with documented coronary occlusion (flow grade 0 or 1) were randomized to treatment in less than 6 h of symptom onset (mean 3.4 h, range 0.4 to 6.0) with either intravenous APSAC (30 U in 2 to 4 min) or intracoronary streptokinase (160,000 U over 60 min). Both groups also received heparin for greater than or equal to 24 h. Reperfusion was evaluated angiographically over 90 min and success was defined as advancement of grade 0 or 1 to grade 2 or 3 flow. Rates of reperfusion for the two treatment regimens were 51% (59 of 115) at 90 min after intravenous APSAC and 60% (67 of 111) after 60 min of intracoronary streptokinase (p less than or equal to 0.18). Reperfusion at any time within the 90 min was observed in 55 and 64%, respectively (p less than or equal to 0.16). Time to reperfusion occurred at 43 +/- 23 min after intravenous and 31 +/- 17 min after intracoronary therapy. The success of intravenous therapy was dependent on the time to treatment: 60% of APSAC patients treated within 4 h exhibited reperfusion compared with 33% of those treated after 4 h (p less than or equal to 0.01). Reperfusion rates were also dependent on initial flow grade (p less than or equal to 0.0001): 48% (81 of 168) for grade 0 (APSAC = 43%, streptokinase = 54%), but 78% for grade 1 (APSAC = 78%, streptokinase = 77%). APSAC given as a rapid injection was generally well tolerated, although the median change in blood pressure at 2 to 4 min was greater after APSAC than after streptokinase (-10 versus -5 mm Hg). Mean plasma fibrogen levels fell more at 90 min after the sixfold higher dose of APSAC than after streptokinase (to 32 versus 64% of control). Reported bleeding events were more frequent after APSAC but occurred primarily at the site of catheter insertion and no event was intracranial.(ABSTRACT TRUNCATED AT 400 WORDS)

A randomized trial of intravenous and intracoronary streptokinase in patients with acute myocardial infarction.

The clinical effects of intravenous streptokinase in patients with acute myocardial infarction were compared with those of intracoronary streptokinase in a randomized, prospective study. Comparisons were also made with a historical control group. Fifty patients were entered into the study at 2.4 +/- 1.2 hr after onset of pain, and 27 were assigned to intravenous and 23 to intracoronary therapy. The doses of streptokinase averaged 212,000 U ic and 845,000 U iv (0.75 X 10(6) U/5 hr, n = 14 or 10(6) U/1 hr, n = 13). Results of studies of the two intravenous dosage schedules were similar and so were combined. Streptokinase was administered at 2.8 +/- 1.0 hr after onset of pain in the intravenous and at 4.3 +/- 1.4 hr in the intracoronary drug group (p less than .001). Convalescent (day 10) radionuclide ejection fractions were 54 +/- 14% for the intravenous and 50 +/- 16% for the intracoronary drug group. Change in ejection fraction from day 1 to 10 tended to be greater after intravenous drug: 5.1% (p less than .08) vs 1.2% (NS). Semiquantitative regional wall motion indexes in the infarct zone showed significant and similar modest improvement from admission to day 10 in both groups (p less than .02). Accelerated enzyme-release kinetics were noted after both therapies. Times of peak enzyme levels for patients on intravenous and intracoronary drug were, respectively, 12.5 +/- 5.0 and 11.5 +/- 4.3 hr for creatine kinase MB isoenzyme and 31.7 +/- 11.8 and 28.1 +/- 12.7 hr for lactic dehydrogenase (LDH). Peak LDH-1 level was lower in patients receiving intravenous drug than in the historical control group (p less than .05). Electrocardiographically summed ST segments diminished rapidly after therapy in both groups; Q wave development was similar and overall R wave loss was equivalent and less extensive compared with in historical control subjects. Infarct pain requiring morphine was diminished similarly in both treatment groups. Incidence of early arrhythmias and heart failure also did not differ. Posttherapy ischemic events and early surgery tended to be more common in the intracoronary group and bleeding was more common in the intravenous group. Intravenous drug did not decrease early hospital mortality (intravenous drug = 5, historical control = 4, intracoronary drug = 1); the differences in this parameter among groups were not significant. At convalescent angiographic evaluation, anterograde perfusion was present in 73% of those receiving intravenous and 76% of those receiving intracoronary drug.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical Correlates in Hypertensive Patients With Left Ventricular Hypertrophy Diagnosed With Echocardiography

Seventy-three hypertensive patients were evaluated with M mode and two dimensional echocardiography. Left ventricular hypertrophy was found in 37 patients (51 percent); 29 had concentric hypertrophy and the remaining 8 had disproportionate septal thickening. Factors that did not influence the distribution of patients in the group with left ventricular hypertrophy and normal subjects included (1) duration of hypertension, (2) level of blood pressure, (3) age, (4) body surface area, and (5) race. More of the patients who had a normal left ventricular mass (32 or 89 percent) than of those who had hypertrophy (22 or 59 percent) were receiving two or more antihypertensive drugs. Electrocardiography was very insensitive in identifying left ventricular hypertrophy in these patients. The presence of increased left ventricular mass was associated with a greater incidence of other target organ disease.

Correlation of regional myocardial blood flow and function with myocardial infarct size during acute myocardial ischemia in the conscious pig.

Regional myocardial function and blood flow were determined for 48 hours after permanent occlusion of the left circumflex coronary artery in conscious swine. Systolic wall thickening and end‐diastolic wall thickness (EDWTh) were correlated with regional myocardial flow (RMBF) at 15 minutes, 24 and 48 hours after occlusion. Both regional function and blood flow were compared with the extent of myocardial necrosis (determined histologically) after 48 hours in functionally distinct zones. Group 1 (control zones) was characterized by increased systolic wall thickening, EDWTh, RMBF and had no necrosis. Group 2 (marginal zones) had depressed systolic wall thickening (35 ± 3% [mean ± SEM] of preocclusion level at 48 hours) and RMBF (64 ± 6% of preocclusion values), transiently decreased EDWTh and 46 ± 5% necrosis. In Group 3 (ischemic zones), all values were greatly reduced: systolic wall thickening was 3.6 ± 1.2%, EDWTh 76 ± 8% and RMBF 25 ± 9% of preocclusion values; necrosis was 90 ± 5%. Groups 2 and 3 had increased RMBF at 24 and 48 hours from that at 15 minutes after occlusion; however, in neither case was systolic wall thickening greater than that at 15 minutes after occlusion. We conclude that there is close correlation between RMBF, systolic wall thickening and the extent of necrosis present after 48 hours of coronary artery occlusion in the conscious swine; subsequent increases in RMBF to the marginal zone after occlusion are not accompanied by improved regional function.

Detection of ischemic wall dysfunction: Comparison between M-mode echocardiography and sonomicrometry☆

The quantification of regional ventricular function by M-mode echocardiography was compared to that by sonomicrometry in 10 closed-chest, sedated swine during temporary occlusions of the left circumflex coronary artery. Wall thickening during systole (%WT) was calculated to quantitate regional myocardial function, and percentage of fractional shortening (%FS) was calculated from both sonomicrometer tracings and M-mode echocardiograms. Ventricular dimensions at end diastole and end systole were also compared before and after 2 minutes of coronary artery occlusion. Both techniques detected significant changes in wall thickness, %WT, and %FS after occlusion. Changes in %WT during coronary artery occlusion detected by M-mode echocardiography and sonomicrometry had a significant linear relationship (p less than 0.05). Discrepancy between the two techniques in the measurement of wall thickness at end diastole was attributed to the difficulty in measuring relatively small distances with M-mode echocardiograms. However, we conclude that the clinical M-mode echocardiogram is capable of detecting acute regional wall dysfunction associated with ischemia.

Long-term follow-up after intracoronary streptokinase for myocardial infarction: A randomized, controlled study

Intracoronary streptokinase (SK) may have beneficial effects on the in-hospital course of acute myocardial infarction (MI), but long-term outcome is unknown. We evaluated the outpatient course of 50 MI patients, randomly treated with either SK (n = 24) or standard therapy (n = 26), who presented within 2.7 +/- 0.7 hours of symptoms. Coronary reperfusion occurred in 19 (79%) SK patients. Survivors were followed for a mean of 18.7 months (range 11 to 28.5); information was current in 48 patients (96%). Both groups received antiplatelet therapy for 3 months. A total of five deaths occurred in the control group and two in the SK group, including one posthospital death in each. Nonfatal MIs totaled five in control patients and three in SK patients, including five posthospital MIs (three control, one SK). Differences in major events (death or nonfatal MI) favoring SK did not quite reach statistical significance (10 control vs 5 SK). Bypass surgery was performed in seven SK and four control patients (NS). Angina occurred in more control (15) than SK (six) patients (p less than 0.01), and more control patients used long-acting nitrates (14 control, three SK; p less than 0.01). Palpitations were noted by nine control and one SK patient (p less than 0.01), and documented late arrhythmias were present in four control patients and no SK survivors (p less than 0.05). Symptoms suggestive of heart failure were present in seven control and one SK patient (p less than 0.01); two control patients were hospitalized for failure. Use of beta blockers, calcium channel blockers, and other cardiac medications did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiographic criteria for normal newborn infants

Echocardiograms were obtained from 200 normal newborn infants ranging from 6 to 10 pounds in weight and from 10 to 72 hours in age. A continuous recording technique is described employing a 5 MHz transducer. Criteria have been established for a normal echocardiographic profile in the full-term neonate. This profile consists of obtaining quantitative measurements of mitral valve excursion and velocity, tricuspid valve excursion and velocity, pulmonary artery diameter, aortic root diameter, left atrial diameter, and interventricular septal thicknesses. In addition, qualitative assessment is made of the septal contour, position of the aortic root to pulmonary artery, continuity of mitral valve with posterior aortic root, and continuity of tricuspid valve with anterior aortic root. No correlation was found between the magnitude of any one parameter and either body surface area or weight. The establishment of normal echocardiographic criteria for the newborn may be expected to significantly facilitate application of this noninvasive technique to infants born with congenital heart disease.

Double Outlet Right Ventricle

Double outlet right ventricle is a rare congenital cardiac malformation that appears to result from lack of conotruncal inversion, failure of leftward conoventricular shift and persistance of a subaortic conus [1, 2]. The anomaly is classified into two categories: those hearts with and those without pulmonary stenosis [3, 4]. The obstruction to pulmonary blood flow may be either valvular, subvalular, supravalvular, or a combination of these [5]. The great arteries in double outlet right ventricle are either side by side (aorta on the right), d-malposed (aorta anterior and to the right of the pulmonary artery), 1-malposed (aorta anterior and to the left of the pulmonary artery), or normally related [6]. The persistence of a subaortic conus prevents the normal leftward shift of the aorta and aortic valve. Thus, the aorta remains to the right of the pulmonary artery and muscle tissue (bilateral conus) separates the mitral and tricuspid valves from the aortic valve and pulmonic valve (Figures 1 & 2). The anomaly is further classified by the position of the ventricular septal defect. The ventricular septal defect may be related to (1) the aortic valve (subaortic), (2) the pulmonic valve (subpulmonic) (TaussigBing anomaly), (3) to both semilunar valves (doubly committed) or (4) to neither semilunar valve (remote) [7]. In those hearts with a subaortic ventricular septal defect, pulmonic stenosis is a common feature. In addition, hearts with a subpulmonic ventricular septal defect may have an associated coarctation of the aorta or mitral valve anomalies. These mitral valve anomalies include mitral stenosis, atresia, or straddling mitral valve [8].