Hilaire De Geest

Coronary Thrombolysis with Tissue-Type Plasminogen Activator in Patients with Evolving Myocardial Infarction

Tissue-type plasminogen activator is a naturally occurring, clot-selective activator of fibrinolysis. We recently reported that human tissue-type plasminogen activator isolated from a Bowes-melanoma-tissue-culture supernate lysed coronary thrombi in dogs without depleting circulating fibrinogen or alpha 2-antiplasmin, in contrast to the case with streptokinase and urokinase. In the present study coronary thrombolysis, confirmed angiographically, was induced within 19 to 50 minutes with intravenous or intracoronary tissue-type plasminogen activator in six of seven patients with evolving myocardial infarction. Circulating fibrinogen, plasminogen, and alpha 2-antiplasmin were not depleted by this agent, in contrast to the case in the two patients subsequently given streptokinase. In the one patient in whom lysis was not inducible with tissue-type plasminogen activator, it was also not inducible with streptokinase. These observations indicate that clot-selective coronary thrombolysis can be induced in patients with evolving myocardial infarction by means of tissue-type plasminogen activator, without concomitant induction of a systemic lytic state. Definition of its therapeutic benefit must await greater availability of the agent and the performance of appropriate clinical trials.

Ultrastructural correlates of left ventricular contraction abnormalities in patients with chronic ischemic heart disease: Determinants of reversible segmental asynergy postrevascularization surgery

The relationships between structural alterations and left ventricular (LV) contraction abnormalities were studied in patients with coronary artery disease (CAD). Transmural biopsies of the LV anterior free wall were taken during aortocoronary bypass surgery (CABG) in 62 patients. When preoperative anterior wall motion (AWM) was reduced, significant myocardial cell degeneration was found in patients with as well as without previous anterior infarction (MI). The amount of myocardial fibrosis was increased only in patients with ECG evidence of previous anterior MI (p less than 0.001). In a second series of 139 CAD patients, cineventriculograms performed before and 8 months after CABG were examined. In patients with patent grafts to the LV anterior wall not previously infarcted, reduced AWM became normal. In patients with previous anterior MI the outcome of AWM was unpredictable (usually unimproved). Thus the histologic correlate of reduced AWM in segments not previously infarcted was progressive loss of contractile material in otherwise viable myocardial cells. Some reversibility was suggested by restoration of resting function after CABG. Unpredictable results in segments associated with pathologic Q waves appear related to the fibrous component of these previously infarcted areas.

Short-term effects of early intravenous treatment with a beta-adrenergic blocking agent or a specific bradycardiac agent in patients with acute mycardial infarction receiving thrombolytic therapy

OBJECTIVES This study was conducted to explore mechanisms that could explain the possible clinical benefit of early administration of a beta 1-selective adrenoreceptor blocking agent or a bradycardiac drug as adjunct to thrombolysis in acute myocardial infarction. BACKGROUND The effects of beta-blockers given concomitantly with thrombolytic therapy in patients with acute myocardial infarction have not been fully examined. The potential role of specific bradycardiac agents lacking negative inotropism as an alternative to beta-blockers in this setting has never been studied in humans. METHODS In a double-blind study, we examined the effects of early intravenous and continued oral administration of a beta-blocker (atenolol), a specific bradycardiac agent (alinidine) or placebo on left ventricular function, late coronary artery patency, infarct size, exercise capacity and incidence of arrhythmias. RESULTS A total of 292 patients with acute myocardial infarction of < or = 5 h duration and without contraindications to thrombolytic or beta-blocker therapy were studied. Of these, 100 were allocated to treatment with atenolol (5 to 10 mg intravenously followed by 25 to 50 mg orally every 12 h), 98 to alinidine (20 to 40 mg intravenously followed by 20 to 40 mg orally every 8 h) and 94 to placebo. All patients received 100 mg of alteplase over 3 h and full intravenous heparinization. No significant differences in coronary artery patency, global ejection fraction or regional wall motion were observed at 10 to 14 days among the three groups. Likewise, enzymatic and scintigraphic infarct size were also very similar. Neither atenolol nor alinidine was associated with a significant reduction in the incidence of arrhythmias during the 1st 24 h. No significant differences in clinical events were observed, with the exception of a greater incidence of nonfatal pulmonary edema in the atenolol group (6% vs. 1% in the alinidine group and 0% in the placebo group, p = 0.021). CONCLUSIONS In the absence of contraindications, the administration of a beta-blocker or a specific bradycardiac agent together with thrombolytic therapy was safe. In this limited number of patients, these agents did not appear to enhance myocardial salvage or preservation of left ventricular function or to reduce the incidence of major arrhythmias in the early phase of infarction.

Frequency of angina pectoris and coronary artery disease in severe isolated valvular aortic stenosis

A consecutive series of 192 patients (121 men and 71 women, mean age 59 years, range 28 to 82) with isolated, severe valvular aortic stenosis was with isolated, severe valvular aortic stenosis was analyzed retrospectively to determine the relation of angina pectoris and coronary risk factors to angiographically significant coronary artery disease (CAD). Significant CAD (diameter reduction greater than or equal to 50%) was found in 47 patients (24%). Angina was present in 83% of them, but it was also found in 61% of the non-CAD patients. This symptom had as a result a low positive predictive value (31%). Of the patients without angina (n = 65) 12% had significant CAD. The negative predictive value of angina alone was thus 88%. By using multivariate logistic regression, a risk score could be calculated based on angina, age and sex, which increased the negative predictive value to 95%. It was concluded that coronary arteriography can only be omitted in severe aortic valvular stenosis, when patients have no angina and when they are less than 40 years of age for men and less than 50 years for women. For all other cases, coronary arteriography should be recommended.

The Left Ventricular Ejection Time in Elderly Subjects

The left ventricular ejection time (LVET) was studied by means of the carotid artery tracing in 512 elderly subjects (205 male and 307 female) who were between 60 and 90 years old (mean age, 70.5 years). A highly significant correlation was found between heart rate (HR) and LVET. The data on these aged subjects were compared and analyzed with the results previously reported concerning young and middle-aged adults. A small but significant increase of LVET with aging, independent of changes in HR and blood pressure, could be demonstrated by multiple regression analysis. A statistically significant difference existed between the sexes. The influence on LVET of parameters other than HR was small.

Safety and efficacy of low dose simvastatin in cardiac transplant recipients treated with cyclosporine

Hyperlipidemia is common in heart transplant patients. Lipid-lowering therapy poses special problems, yet may be important because accelerated graft atherosclerosis is the major factor limiting long-term survival. Simvastatin 5 mg/day was started > 6 months after surgery in 26 consecutive cardiac transplant recipients with a total serum cholesterol level of > 250 mg/dl. The dose of simvastatin was increased in 5-mg increments until total serum cholesterol fell below 220 mg/dl or until side effects developed or up to a maximal dose of 20 mg/day. The final average daily dose was 10 mg. Changes in serum lipid levels after 6 months of therapy were compared with data from a matched and concurrent control group of heart transplant patients not taking simvastatin. Immunosuppression for both groups consisted of CsA, AZA, and corticosteroids. In the simvastatin-treated group, the serum level of total cholesterol decreased by 27% from 315pm53 to 230pm38 mg/dl (P<0.0001), low density lipoprotein cholesterol decreased by 40% from 205pm30 to 123pm32 mg/dl (P<0.0001), and triglycerides decreased by 21% from 177pm89 to 140pm49 mg/dl (P<0.01). There was no significant change in high density lipoprotein cholesterol level. Body weight and CsA blood levels remained stable. Steroid intake decreased during the study period to a similar extent in both the treated and the control groups. In the control group, no significant changes in serum lipid levels were observed. Two patients experienced a mild form of myotoxicity. In one other patient simvastatin treatment was stopped after an acute pancreatitis of uncertain etiology developed. Low dose simvastatin effectively lowers total serum cholesterol, low density lipoprotein cholesterol, and triglycerides in heart transplant patients. With due precautions, the safety profile of the drug in this patient population seems reasonable.

On the value of apex cardiography for timing intracardiac events

Abstract The left apex cardiogram was recorded in the dog by means of a pulse transducer with an infinite time constant. The time relation between the left apex cardiogram and left ventricular and aortic pressure tracings (recorded by means of high fidelity micromanometers) and their first time derivatives (dp/dt) was studied. Both the onset of the upstroke and the protodiastolic nadir of the left apex cardiogram and of the left ventricular pressure curve were found to occur nearly simultaneously. This close relation was preserved during various acutely induced hemodynamic changes and during right and left ventricular pacing. The E point of the left apex cardiogram occurred simultaneously with the peak dp/dt of the left ventricular pressure, or followed it with a time lag of 2 to 35 msec. Diastolic waves also occurred simultaneously. It is concluded that the left apex cardiogram provides a reliable noninvasive technique for the timing of intracardiac events.

Dynamic electrocardiography and ventricular pauses of 3 seconds and more : etiology and therapeutic implications

A total of 2350 consecutive Holter recordings revealed that 53 patients had ventricular asystole of 3 seconds or more. The diagnoses based on the longest pauses were: sinus arrest in 19; AV block in 5; slow atrial fibrillation in 29. Symptoms occurred in 45 and were absent in 8 patients. Associated heart disease was present in only 33 cases. A pacemaker was implanted in 7 out of 8 asymptomatic patients. Ventricular asystole of 3 seconds or more is proposed as a definite indication for the implantation of a permanent pacemaker.

Diagnostic value of clinical history, exercise testing and atrial pacing in patients with chest pain

Abstract The clinical history and the electrocardiographic response to graded exercise testing and atrial pacing were correlated with the presence or absence of severe coronary artery disease, as demonstrated by coronary angiography, in 70 patients. A clinical history of angina pectoris was a very sensitive (90 percent) but less specific (80 percent) predictor of severe coronary artery disease, ischemic S-T segment depression greater than or equal to 1 mm was the most accurate electrocardiographic predictor. When this criterion was used, the graded exercise test was less sensitive (65 vs. 72 percent) but more specific (83 vs. 70 percent) than atrial pacing. Results of a discriminant function analysis of several possible predictors of severe coronary artery disease indicated that atrial pacing does not contribute significantly to the diagnosis in patients submitted to a graded exercise test.

Immediate and follow-up results of the conservative coronary angioplasty strategy for unstable angina pectoris

To assess the results of a conservative coronary angioplasty strategy in unstable angina pectoris, the records of 1,421 consecutive patients without previous myocardial infarction undergoing a first percutaneous transluminal coronary angioplasty (PTCA) between 1986 and 1990 were reviewed. Of these patients, 631 had unstable and 790 had stable angina pectoris. Only after an intense effort to medically control symptoms, the unstable patients underwent PTCA at an average of 15.4 days (range 1 to 76) after hospital admission. Primary clinical success was achieved in 91.7% of patients with unstable and in 94.4% of those with stable angina pectoris (p = not significant). In-hospital mortality rates were 0.3 and 0.1%, respectively (p = not significant). Nonfatal in-hospital event rates for acute myocardial infarction, cerebrovascular accident and coronary bypass surgery were only slightly higher in patients with unstable angina pectoris; however, the difference from the stable group was significant when all events were combined (9 vs 5.9%; p less than 0.04). During 6-month follow-up, no significant difference in adverse events was found between the groups. The respective rates for the unstable and stable groups were 0.4 and 0.2% for death, 5.5 and 5.1% for major nonfatal events, and 17.7 and 20.1% for repeat PTCA. These results suggest that use of a conservative PTCA strategy in the treatment of patients with unstable angina pectoris results in favorable and similar immediate and 6-month outcomes compared with those in patients with stable angina pectoris.