Coronary patency after intravenous infusion of recombinant tissue-type plasminogen activator in acute myocardial infarction.

The relation between coronary patency after infusion of recombinant tissue-type plasminogen activator (rt-PA) and clinical and laboratory findings was assessed in patients with acute myocardial infarction. This study focused primarily on information available early in the hospitalization phase. Data were available for 243 patients who received the full dose of rt-PA and who had assessable coronary angiograms 90 min after the start of the intravenous infusion. The infarct-related vessel was scored by an independent assessment committee as being patent in 65% of patients. The left anterior descending coronary artery was involved in 53% of patients, and proximal localization of the infarct-related vessel occurred in 65%. In the majority of patients (85%), the infusion was started within 4 h of the acute event. Neither the angiographic location of the infarct-related vessel nor electrocardiographic evidence of infarct severity or location appeared to have a bearing on thrombolysis with rt-PA. Multivariate logistic regression analysis identified three independent predictors of coronary patency: hematocrit 43 to 47%, blood plasminogen level greater than or equal to 90% of normal and serum alkaline phosphatase greater than or equal to 82% of the local upper normal limit. In addition, the use of intravenous nitrates suggests a positive association with patency.

Relative value of clinical variables, bicycle ergometry, rest radionuclide ventriculography and 24 hour ambulatory electrocardiographic monitoring at discharge to predict 1 year survival after myocardial infarction.

The relative value of predischarge clinical variables, bicycle ergometry, radionuclide ventriculography and 24 hour ambulatory electrocardiographic monitoring for predicting survival during the first year in 351 hospital survivors of acute myocardial infarction was assessed. Discriminant function analysis showed that in patients eligible for stress testing the extent of blood pressure increase during exercise slightly improved the predictive accuracy beyond that of simple clinical variables (history of previous myocardial infarction, persistent heart failure after the acute phase of infarction and use of digitalis at discharge), whereas radionuclide ventriculography and 24 hour electrocardiographic monitoring did not. The predictive value for mortality was 12% with clinical variables alone and 15% with the stress test added. Radionuclide ventriculography and 24 hour electrocardiographic monitoring were slightly additive to clinical information in the whole group of patients independent of the eligibility for stress testing (predictive value for mortality 24% with clinical variables alone and 26% with radionuclide ejection fraction and 24 hour electrocardiographic monitoring added). It is concluded that the appropriate use of simple clinical variables and stress testing is sufficient for risk stratification in postinfarction patients, whereas radionuclide ventriculography and 24 hour electrocardiographic monitoring should be limited to patients not eligible for stress testing.

Increased serum levels of fibrinogen degradation products due to treatment with recombinant tissue-type plasminogen activator for acute myocardial infarction are related to bleeding complications, but not to coronary patency. European Co-operative Study Groups for rt-PA.

The association of increasing serum levels of fibrinogen degradation products after recombinant tissue-type plasminogen activator (rt-PA) therapy with bleeding and early coronary patency was assessed in 242 patients with acute myocardial infarction. After administration of 5,000 IU heparin, a median of 40 mg (range 35 to 60) of double chain rt-PA was given intravenously in 90 min. Bleeding occurred in 62 patients; in 73% of patients it was observed within the 1st 24 h and 84% of events consisted of hematoma or prolonged bleeding, or both, at puncture sites. Bleeding events occurred 2.12 times as often in patients with serum levels of fibrinogen degradation products greater than 85 mg/liter as in patients with serum levels less than 22 mg/liter (95% confidence interval 1.01 to 4.43). The infarct-related coronary vessel was patent in 65% of patients at 90 min after the start of rt-PA infusion. In patients with high serum levels of fibrin(ogen) degradation products, coronary patency at 90 min after the start of rt-PA infusion was not better (13% less, 95% confidence interval - 33%, 13%) than in patients with low serum levels. This uncoupling of thrombolytic effect in terms of coronary patency and systemic fibrinogenolysis confirms the experimentally demonstrated fibrin specificity of double chain rt-PA in human subjects. Because fibrin specificity of single chain rt-PA is at least similar to that of double chain rt-PA, the observations in this analysis most likely hold also for single chain rt-PA.(ABSTRACT TRUNCATED AT 250 WORDS)

A model of asynchronous left ventricular relaxation predicting the bi-exponential pressure decay.

A new model for the pressure relaxation of the left ventricle is proposed. The model presumes that the myocardium relaxes asynchronously, but that when regions begin to relax, after a delay, the local wall stress decays as a mono-exponential process. This formulation results in an apparently bi-exponential process (two time constants) which has been previously reported. It is shown that the ratio of the two time constants (T2/T1) can be interpreted as the fraction of the myocardium which relaxes synchronously. Data are presented illustrating the Model during transient coronary occlusion in patients undergoing percutaneous transluminal coronary angioplasty.

Interaction of left ventricular relaxation and filling during early diastole in human subjects.

Seventeen patients with coronary artery disease were studied with cineangiography and simultaneous tip manometry at resting heart rate and maximal tachycardia induced by atrial pacing. During early diastole, defined as the interval from the opening of the mitral valve to the point of minimal left ventricular pressure, 20 percent of total ventricular filling took place at resting heart rate, but 62 percent occurred during tachycardia. Minimal pressure was significantly correlated with the time constant of pressure decay during the isovolumic phase (r = 0.75 at resting heart rate and r = 0.81 during tachycardia). The measured minimal pressure could be predictd by extrapolating the exponential decay of ventricular isovolumic pressure to the time of occurence of the minimal pressure, which occurred on average 2.7 time constants from the peak negative rate of change of pressure. At resting heart rate the time constant of relaxation was inversely correlated with ventricular inflow volume (r = -0.64) and inflow rate (r = -0.72). It is concluded that left ventricular relaxatin has a relevant role in early diastolic pressure-volume relations and increases during tachycardia.

Direct method for determining regional myocardial shortening after bypass surgery from radiopaque markers in man.

A new method is described for determining localized epicardial shortening in regions newly perfused after saphenous vein bypass grafting. Four to six radiopaque markers are sutured to the ventricular epicardium in pairs, 2 cm apart and 0 to 3 cm distal to the coronary anastomosis. Shortening fraction and time to onset of shortening are reported in 56 patients examined noninvasively with use of cinefluorography 1 week to 6 months after operation. The right coronary bypass region showed the greatest improvement in shortening fraction in 6 months (from 10.1 to 16.7 percent); the left anterior descending region showed the least (but still significant) improvement (from 8.6 to 11.5 percent). Paradoxical systolic expansion occurred predominantly in the region of the left anterior descending coronary bypass (95 percent of all such occurrences). Measurement error, observer variability and beat to beat variability were less important than the physiologic changes in the postoperative period. This technique is a direct method providing heretofore unavailable follow-up information on localized shortening in newly perfused myocardium after coronary bypass grafting.

Effect of flecainide on regional left ventricular wall motion after acute intravenous, acute oral and chronic oral administration late after coronary artery bypass grafting.

Epicardial marker motion was measured in 14 patients before flecainide administration, immediately after an intravenous dose of 2 mg/kg over 15 minutes (maximum 150 mg) and 15 minutes thereafter. Platinum epicardial markers had been implanted more than 4 years earlier at the time of coronary artery bypass grafting. Maximal and minimal marker separation (Lmax and Lmin) during the cardiac cycle were measured and regional shortening fraction (Lmax - Lmin)/Lmax) was determined as a percentage. After intravenous flecainide, a significant increase in end-diastolic (immediately after 2.8%; after 15 minutes 2.1%) and end-systolic (3.6% and 3.2%) regional dimensions was observed, together with a decrease in regional myocardial shortening (9.3% and 9.0%). One week later, after a single oral dose of 200 mg of flecainide, Lmax and Lmin had increased 2.4% and 2.7%, while regional myocardial shortening did not differ significantly from baseline values. In 10 patients measurements were repeated after 6 weeks of chronic oral treatment with 300 mg/day. Despite plasma flecainide levels similar to those after intravenous administration, no significant changes in end-diastolic and end-systolic dimensions or regional shortening fraction were observed. Thus, acute intravenous or oral flecainide administration increases regional end-diastolic and end-systolic dimensions, but only intravenous administration decreases regional shortening fraction. Values during chronic administration indicate that regional myocardial function is more affected at the time of rising or acutely changing flecainide plasma levels than when stable plasma levels are achieved.

Afterload reduction with nifedipine in aortic insufficiency.

The acute hemodynamic effects of nifedipine were assessed in 12 patients with severe aortic insufficiency during control conditions and 30 minutes after administration of nifedipine (20 mg sublingually). Left ventricular end-diastolic pressure decreased from 19 +/- 8 (mean +/- standard deviation) to 9 +/- 5 mm Hg (probability [p] less than 0.0001), mean aortic pressure from 98 +/- 12 to 80 +/- 9 mm Hg (p less than 0.00001), systemic vascular resistance from 1,135 +/- 280 to 794 +/- 176 dynes . s. cm-5 (p less than 0.0002) and rate-pressure product from 11,732 +/- 1,727 to 10,022 +/- 1,103 mm Hg beats/min (p less than 0.01). Forward cardiac index increased by 24 percent, from 3.8 +/- 1.1 to 4.4 to 0.8 liters/min per m2 (p less than 0.04). Left ventricular end-diastolic volume, ejection fraction and total stroke work index did not change significantly. Regurgitant fraction, measured in five patients, changed parallel with systemic vascular resistance. Left ventricular function was maintained while both preload and afterload were decreased. Regurgitant flow was moderated and myocardial oxygen demand decreased. This hemodynamically favorable condition, due to nifedipine, is clinically important and suggests the need for further therapeutic trials.

Nifedipine in the treatment of unstable angina, coronary spasm and myocardial ischemia.

The effects of nifedipine, a potent calcium antagonist, were studied in patients with unstable angina, coronary spasm and myocardial ischemia. Data from two separate groups of patients studied in the cardiac catheterization laboratory indicate that intracoronary injection of nifedipine promptly reversed coronary spasm--whether provoked or spontaneous--in five of six patients. In other patients, direct intracoronary injection of the drug was compared with intravenous administration. After intracoronary injection, local mechanical cardiac action virtually ceased, and the ventricular wall became thinner during systole. Thus, a specific inhibitory action on contractile energy expenditure could be demonstrated in the presence of increased coronary flow. This "oxygen-sparing" effect was tested in a group of 31 patients with symptomatic unstable angina whose pain at rest, with ST-T changes, had not responded to 8 hours of treatment with maximal beta adrenergic blockade, nitrates and bed rest. The addition of 6 X 10 mg of nifedipine rendered 27 of these patients asymptomatic within 1.5 hours. In the four patients who did not respond, coronary arteriography demonstrated severely stenotic lesions. Two of the four patients subsequently responded to intraaortic balloon pumping and bypass surgery; one patient had a myocardial infarction and one who had a 90 percent reduction in the diameter of the left main coronary artery, died. It is concluded that nifedipine should be added to beta adrenergic blockade therapy if the latter does not appear to be immediately effective. This combination has not been shown to cause any hemodynamic deterioration, and only a minority of the patients treated sustained a myocardial infarction during the first 3 months of follow-up. The use of nifedipine in unstable angina deserves further clinical evaluation.

Comparison of preoperative, operative and postoperative variables in asymptomatic or minimally symptomatic patients to severely symptomatic patients three years after coronary artery bypass grafting: analysis of 423 patients.

During a follow-up period of 3 years, among a consecutive series of 423 patients who gave informed consent for recatheterization both 1 and 3 years after coronary artery bypass grafting, the incidence of severely symptomatic patients with New York Heart Association class III or IV was 19% (79 of 423). The predictive value of approximately 80 clinical, angiographic and perioperative variables was too low to be of clinical value. Adverse clinical outcome was associated with a high closure rate of the grafts. Forty-six percent of the patients could not undergo reoperation because of unsuitable coronary anatomy. With intensive medical therapy half of these patients improved to functional class I or II, while of those patients who were reoperable 32% improved to class I or II with intensive pharmacologic treatment instead of reoperation. The nonresponders underwent reoperation, which resulted in improvement of symptoms to functional class I or II in most (83%).

Prediction of mortality during the first year after acute myocardial infarction from clinical variables and stress test at hospital discharge.

The predictive value of a predischarge symptom-limited stress test was studied in 405 consecutive survivors of acute myocardial infarction (AMI). Three hundred patients performed bicycle ergometry; 105 could not perform it. Among these latter 105 patients, the stress test was contraindicated in 43 because of angina or heart failure and in 62 because of noncardiac limitations. One-year survival was 44% in the "cardiac-limited" group (19 of 43) and 92% in the "non-cardiac-limited" group (57 of 62). One-year survival among the patients who performed an exercise test at discharge was 93% (280 out of 300). The best stress test predictor of mortality by univariate analysis was the extent of blood pressure (BP) increase: 42 +/- 24 mm Hg in 280 survivors vs 21 +/- 14 mm Hg in 20 nonsurvivors (p less than 0.001). Among the 212 patients in whom BP increased 30 mm Hg or more, mortality was 3% (n = 6), while it was 16% (n = 14) among the 88 patients in whom BP increased less than 30 mm Hg. Angina, ST changes and arrhythmias were not as predictive. Stepwise discriminant function analysis showed inadequate BP increase to be an independent predictor of mortality. A high-risk group can be identified at discharge on clinical grounds in patients unable to perform a stress test, whereas intermediate- and low-risk groups can be identified by the extent of BP increase during exercise.

Acute coronary thrombolysis with recombinant human tissue-type plasminogen activator: initial patency and influence of maintained infusion on reocclusion rate.

An intravenous infusion of 40 mg of recombinant tissue-type plasminogen activator (rt-PA) was given intravenously over 90 minutes to 123 patients with acute myocardial infarction (AMI) of less than 4 hours' duration. A coronary angiogram was recorded at the end of the infusion in 119 patients. Central assessment of the angiograms revealed a patent infarct-related artery in 78 patients (patency rate 66%, 95% confidence limits 57 to 74%). Patients with a patent infarct-related artery at the first angiogram were randomized in a double-blind manner to receive a subsequent 6-hour infusion of either 30 mg of rt-PA or placebo. All patients had received an initial bolus of 5,000 IU of heparin and then 1,000 IU/hour until a second angiogram was recorded 6 to 24 hours after the start of the second perfusion. At central assessment of the second coronary angiogram the reocclusion rate was 2 of 36 patients who received rt-PA at the second infusion and 3 of 37 patients not receiving this drug (or the 2 groups combined 7%, 95% confidence limits 2 to 15%). Three of 60 patients (5%, 95% confidence limits 1 to 14%) with patent arteries on both previous angiograms had a later occlusion as judged on the angiogram recorded at hospital discharge. No difference in late reocclusion rates between the 2 treatment groups was observed.

Regional myocardial shortening in relation to graft-reactive hyperemia and flow after coronary bypass surgery.

Extent of regional shortening of myocardium in areas newly perfused by bypass grafting was determined in 56 patients by a new technique employing four to six radiopaque markers sutured in pairs to the epicardium near the coronary anastomosis. Paradoxical systolic expansion (PSE) was manifest in 16 regions (a 12% incidence) during the follow-up period, and six of these showed spontaneous remission. All cases of PSE were in the region of the left anterior descending artery. Correlation between graft flow measured during operation and regional shortening during the postoperative period revealed that the development of PSE could not be predicted from the hemodynamic measurements. In the majority of cases postoperative myocardial infarction could also be excluded as an explanation. At 1 year after operation most grafts were patent in PSE regions but collaterals, apparent preoperatively, could not be visualized. Excluding PSE, shortening fraction (ratio of shortening to maximum marker separation) for all graft regions at 1 week was 9.8%; 1 month, 12.8%; 3 months, 13.3%; and six months, 13.9%. Average graft flow was 56 ml. per minute and average reactive hyperemia was 25% with 37% of grafts showing no response. For those regions that did not develop PSE there was a positive correlation between shortening fraction and flow that became significant (null hypothesis: r = 0) when reactive hyperemia exceeded 20%. Correlation was greatest at 1 week and 1 month, but became nonsignificant at 6 months. These results are consistent with a simple interpretation of reactive hyperemia: Graft-reactive hyperemia is related to the dependence of viable tissue on the functioning of the graft.

Coronary artery bypass surgery; a stimulus to modify existing risk factors?

Coronary arterial atherosclerosis is known to be associated with the risk factors of a positive family history, smoking, systemic hypertension, diabetes mellitus, and elevated serum cholesterol levels. Modification of these risk factors, where possible, is prudent. The risk factor data of 226 (212 men, 14 women) subjects who underwent coronary artery bypass surgery for symptomatic obstructive coronary artery disease are presented. Prior to surgery, an attempt was made to educate the subjects in regard to the risk factors and they were urged to modify these factors. All underwent repeat evaluation one year after operation. Although over half of the subjects had had a prior myocardial infarction and all had had aortocoronary bypass surgery, strong stimuli to modify risk factors, there was little modification of the risk factors of smoking and serum cholesterol. There was some modification of the hypertension risk factor. This study documents the need for a very early approach in life to prevent acquiring risk factors and the need for more research into better methods of behavior modification in the adult population.

Orthotopic canine heart transplantation: left ventricular contractility during chronic rejection.

Myocardial left ventricular contractility is assessed in 8 orthotopic heart-transplanted dogs during chronic rejection by a noninvasive method. The mean circumferential velocity of shortening (Vcf) is calculated from endocardial marker motion on cinefilms. A model for chronic rejection after cardiac transplantation was obtained by histocompatibility matching in DLA identical Beagle littermates. No immunosuppressive treatment was used. All dogs eventually died of chronic rejection; mean survival time was 112.5 days. LV contractility shows the following pattern: Chronic rejection causes an important contractility decrease (P less than 0.001) with two significant drops: (1) from the week preoperative to the first week after transplantation (P less than 0.02) and (2) from week terminal minus one to the terminal week (P less than 0.01). This study describes the technique and the changes in Vcf observed over a period of time in a predictable model.

The role of the personal computer in the cardiac catheterization laboratory: an integrated approach to information management.

A personal computer-based data management system for the cardiac catheterization laboratory is described. This is a cooperative effort on the part of the Dutch academic hospitals, through the Interuniversity Cardiology Institute, to put in place a more uniform structure for data collection and reporting in the context of cooperative studies. The major design criteria included the necessity that the system provide a clear and present benefit to the users in terms of their day-to-day work. This requires a practical data entry package together with a full reporting capability, including management tools for supervision of the catheterization laboratory in general. Ancillary activities include quantitative analysis of ventriculograms and an elementary statistics package with graphics. To facilitate supportability of the system, commercially available packages for data base management, text processing, and communications have been used to advantage. After a prototype test phase involving two centers, five other centers have been equipped with similar systems and used successfully in the majority.

[Regional myocardial shortening and blood flow through the graft after aorto-coronary bypass surgery]. / Raccourcissement myocardique régional et débit sanguin des greffons après chirurgie de pontage aorto-coronarien.

In 56 patients operated on for coronary artery bypass grafting the relation between regional epicardial shortening, bypass flow, reactive hyperemia, and time postoperative was determined. Regional shortening in the newly perfused region was measured by a new technique employing four to six radiopaque markers sutured in pairs to the epicardium juxtaposed by 2 cm, and from 0 to 3 cm distal to the coronary anastomosis. Marker pairs were filmed sequentially at each follow up. Excluding dyskinesia, shortening fraction (ratio of shortening to maximum marker separation) for all graft regions at 1 week was 9.8 p. 100, 1 month 12.8 p. 100, 3 months 13.3 p. 100, and 6 months 13.9 p. 100. Average graft flow was 56 ml/mn and average reactive hyperemia was 25 p. 100 with 37 p. 100 of grafts having no response. There was a positive correlation between shortening fraction and flow, becoming significant (null hypothesis: r = 0) when reactive hyperemia exceeded 20 p. 100. Correlation was greatest at 1 week and 1 month, but became non-significant at 6 months implicating other factors such as new collateral development, bypass closure, new infarction, or altered medical therapy. It appears that bypass flow and reactive hyperemia do have a certain predictive value as to regional shortening up to 1 to 3 months postoperative.