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Biomedical subjects

E Braunwald

Publications and source records attributed to E Braunwald.

At least 253 records · Page 14Linked to original sources
PubMed1987

Intracoronary thallium-201 scintigraphy after thrombolytic therapy for acute myocardial infarction compared with 10 and 100 day intravenous thallium-201 scintigraphy.

Thallium-201 imaging has been utilized to estimate myocardial salvage after thrombolytic therapy for acute myocardial infarction. However, results from recent animal studies have suggested that as a result of reactive hyperemia and delayed necrosis, thallium-201 imaging may overestimate myocardial salvage. To determine whether early overestimation of salvage occurs in humans, intracoronary thallium-201 scans 1 hour after thrombolytic therapy were compared with intravenous thallium-201 scans obtained approximately 10 and 100 days after myocardial infarction in 29 patients. In 10 patients with angiographic evidence of coronary reperfusion, immediate improvement in thallium defects and no interim clinical events, there was no change in imaging in the follow-up studies. Of nine patients with coronary reperfusion but no initial improvement of perfusion defects, none showed worsening of defects in the follow-up images. Six of these patients demonstrated subsequent improvement at either 10 or 100 days after infarction. Seven of 10 patients with neither early evidence of reperfusion nor improvement in perfusion defects had improvement of infarct-related perfusion defects, and none showed worsening. In conclusion, serial scanning at 10 and 100 days after infarction in patients with no subsequent clinical events showed no worsening of the perfusion image compared with images obtained in acute studies. Therefore, there is no evidence that thallium-201 imaging performed early in patients with acute myocardial infarction overestimates improvement.

Acute Disease↗
PubMed1987

A cost-effectiveness model for coronary thrombolysis/reperfusion therapy.

A model was designed to examine the relations between incremental costs and benefits of coronary thrombolysis/reperfusion therapy. The model allows for the study of intravenous and intracoronary streptokinase, intravenous tissue plasminogen activator and primary angioplasty. Three strategies for the management of reocclusion are also compared. It was found that each of the following four variables can be responsible for a 2- to 15-fold variation in the costs per additional survivor: 1) the quantity of jeopardized myocardium, 2) the duration of coronary occlusion before the onset of therapy, 3) the time required from the onset of therapy until reperfusion is achieved, and 4) the reocclusion management strategy. Therapeutic strategies involving intravenous administration of thrombolytic agents were found to be consistently more cost effective than were strategies involving intracoronary administration of thrombolytic agents and primary angioplasty. In patients with a large or moderate-sized infarct, proper selection of intravenous protocols and reocclusion management strategies leads to costs of $7,000 to $100,000/additional survivor, costs that are similar to those of many generally accepted medical practices. Substantially higher costs per additional survivor are incurred with the routine use of thrombolytic therapy in patients with a small infarct or the routine use of coronary artery bypass surgery to reduce the risk of reocclusion after successful thrombolytic therapy. Decisions regarding which patients should receive thrombolysis/reperfusion therapy depend on society's willingness to pay for its incremental benefits.

Angioplasty, Balloon↗
PubMed1987

The effect of intravenous thrombolytic therapy on left ventricular function: a report on tissue-type plasminogen activator and streptokinase from the Thrombolysis in Myocardial Infarction (TIMI Phase I) trial.

In Phase I of the NHLBI trial of Thrombolysis in Myocardial Infarction (TIMI), 290 patients admitted within 7 hr after onset of acute infarction were randomly assigned to intravenous treatment with either streptokinase (SK) or recombinant tissue-type plasminogen activator (rt-PA). Left ventricular function was measured from contrast ventriculograms in 145 patients with both pretreatment and predischarge studies analyzable. Regional wall motion in the infarct site was measured by the centerline method and expressed in units of standard deviations (SDs) from the mean motion in 52 normal subjects. Patients treated with rt-PA (n = 77) achieved a significantly higher reperfusion rate after 90 min of treatment. Perfusion of the infarct-related artery improved from visual grade 0 or 1 (total occlusion or penetration without perfusion) to grade 2 or 3 (partial or full reperfusion) in 62% receiving rt-PA vs 31% receiving SK (n = 68) (p less than .001). However, the ejection fraction did not change significantly from before treatment to before discharge in either treatment group (+0.7 +/- 6.7% vs +1.0 +/- 8.3%, respectively). A small but significant increase in regional wall motion was observed in each of the two groups (+0.4 +/- 0.8 vs +0.3 +/- 0.8 SD/chord, respectively; each p less than .001 compared with baseline). This was countered by declines in the hyperkinesis of the noninfarct region (-0.3 +/- 1.0 SD/chord [p = .01] compared with baseline and -0.2 +/- 1.0 SD/chord [p = .23], respectively). Analysis of the combined groups revealed that the ejection fraction increased only in patients who achieved reperfusion by 90 min after onset of therapy or who had subtotal occlusions initially. There was greater recovery of left ventricular function in patients who achieved reperfusion earlier vs later than 4 hr after symptom onset and in patients with vs without some collateral circulation to the infarct-related artery.

Cardiac Catheterization↗
PubMed1987

Hemodynamic benefits and prolonged survival with long-term captopril therapy in rats with myocardial infarction and heart failure.

To determine whether the hemodynamic profile of chronic heart failure secondary to myocardial infarction could be altered, captopril was administered to female Wistar rats 3 weeks after coronary artery ligation and continued for 3 months. Captopril reduced left ventricular mass, prevented the increase in right ventricular mass observed with increasing infarct size, lessened the increase in left ventricular end-diastolic pressure, and reduced mean arterial pressure and total peripheral resistance, whereas cardiac output and heart rate were maintained. The end-diastolic volume of treated rats with moderate infarcts was significantly less than that of untreated rats, and therefore the ejection fraction index was significantly increased. In rats given captopril until death or for a period of up to 1 year, survival was significantly prolonged, particularly in those rats with moderate-sized infarcts.

Animals↗
PubMed1986

Implications for acute intervention related to time of hospital arrival in acute myocardial infarction.

The time from onset of symptoms to arrival in the hospital emergency room (ER) was studied in 778 patients randomized into a study of acute myocardial infarction (AMI) size limitation. Patients at relatively high risk of death after AMI (including those with preexisting diabetes mellitus, systemic hypertension or congestive heart failure), women and older patients arrived significantly later in the ER than did patients without these characteristics. A significantly higher mortality rate was observed in patients who arrived late, i.e., those who arrived more than 2 hours after the onset of chest pain, even though patients with hemodynamic compromise (bradycardia, hypotension) tended to arrive earlier. The difference in long-term mortality between those who arrived early (within 2 hours of onset of chest pain) and those who arrived late was accounted for by the baseline differences between these 2 groups. These baseline differences may influence the effects of early interventions in AMI. In addition, these findings have implications for education of high-risk patients who could benefit the most from aggressive early intervention.

Age Factors↗
PubMed1986

Digoxin therapy and mortality after myocardial infarction. Experience in the MILIS Study.

Recent studies have led to controversy about whether long-term digoxin therapy after confirmed or suspected myocardial infarction increases mortality. We analyzed the mortality experience in 903 patients enrolled in the Multicenter Investigation of Limitation of Infarct Size (MILIS). As in previous studies, the decision to treat or not to treat with digoxin was made by the patient's personal physician on the basis of the usual clinical indications. Cumulative mortality was 28 percent for the 281 digoxin-treated patients as compared with 11 percent for the 622 patients who did not receive digoxin (P less than 0.001; follow-up interval, six days to 36 months; mean, 25.1 months). However, patients treated with digoxin had more base-line characteristics predictive of mortality than did their counterparts. Adjustment for these differences with two separate applications of the Cox method yielded P values of 0.14 and 0.34 for tests of difference in mortality, providing no evidence for a significant excess mortality associated with digoxin. Thus, the findings in the MILIS population do not support the assertion that digoxin therapy is excessively hazardous after infarction, but the existence of an undetected harmful effect can only be excluded with a randomized study. Until the results of such a study are available, we recommend careful consideration of whether any treatment of ventricular dysfunction is actually needed, consideration of alternatives to digoxin therapy, and restriction of digoxin use to the subgroup of patients (with severe chronic congestive failure and a dilated left ventricle) previously shown to have a beneficial clinical response.

Clinical Trials as Topic↗
PubMed1986

Role of reflex sympathetic withdrawal in the hemodynamic response to an increased inotropic state in patients with severe heart failure.

Newer positive inotropic agents used in the treatment of severe heart failure not only increase cardiac contractility, but also cause peripheral vasodilation. It is not known to what extent this vasodilation is due to a direct peripheral action of the drug, as opposed to reflex withdrawal of sympathetic tone secondary to an augmented inotropic state. In 16 patients with severe heart failure, a 48 hour intravenous infusion of milrinone, a positive inotropic vasodilator drug, resulted in an increase in stroke volume index from 26 +/- 2 to 34 +/- 3 ml/m2 (p less than 0.001), a reduction in forearm vascular resistance measured by venous plethysmography from 43 +/- 5 to 27 +/- 3 U (p less than 0.003) and an increase in forearm venous capacitance from 2.1 +/- 0.2 to 2.9 +/- 0.2 ml/100 ml (p less than 0.001). To determine whether a withdrawal of sympathetic tone contributed to this vasodilation, milrinone was infused directly into the left main coronary artery in eight of the patients, thereby eliminating any direct vascular effects of the drug. Intracoronary milrinone (50 micrograms/min) caused an increase in peak positive first derivative of pressure (658 +/- 49 to 784 +/- 68 mm Hg/s; p less than 0.01) and stroke volume index (20 +/- 2 to 25 +/- 3 ml/m2; p less than 0.0001), which was associated with a reduction in plasma norepinephrine from 540 +/- 101 to 423 +/- 90 pg/ml (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Administration Schedule↗
PubMed1986

Effect of verapamil on infarct size in dogs subjected to coronary artery occlusion with transient reperfusion.

Reocclusion after successful coronary reperfusion occurs in 15 to 35% of patients receiving thrombolytic therapy for acute myocardial infarction. The present study was designed to simulate the clinical situation of reocclusion and determine whether verapamil might be effective in reducing myocardial necrosis and preserving high energy phosphates in this setting. Pentobarbital-anesthetized, open chest dogs underwent occlusion of the left anterior descending coronary artery for 2 hours followed by 1 hour of reperfusion and a further 4 hours of coronary artery occlusion. Treatment with verapamil (intravenous bolus dose of 0.2 mg/kg body weight followed by infusion of 0.56 +/- 0.14 mg/kg per h) was begun 1 hour after occlusion and infusion was continued for the remainder of the experiment. The dose of verapamil was adjusted to lower mean arterial pressure to approximately 90 mm Hg. The area at risk was determined by intraatrial injection of monastral blue dye and the area of necrosis was assessed by triphenyltetrazolium chloride staining. In vivo myocardial needle biopsy for determination of adenosine triphosphate and creatine phosphate was performed at the end of the experiment. The area of the left ventricle at risk was similar in both groups (control [n = 8], 20.2 +/- 1.6% versus verapamil-treated [n = 9], 23.1 +/- 2.9%; p = NS). The area of necrosis expressed as a percent of the area at risk was reduced in the verapamil-treated group compared with the control group (43.3 +/- 5.0% versus 63.1 +/- 6.8%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1986

Survival of patients with severe congestive heart failure treated with oral milrinone.

The safety and efficacy of long-term oral milrinone therapy were evaluated over a 2 1/2 year period in 100 patients who had severe congestive heart failure despite conventional therapy. Long-term oral milrinone therapy (27 +/- 8 mg/day initial dose) was well tolerated; drug-related side effects occurred in only 11% of patients and led to drug withdrawal in only 4% of patients. Of 94 patients evaluated after 1 month of therapy, 51% had improved by at least one New York Heart Association functional class. Despite hemodynamic and clinical improvements, life table analysis showed a 39% mortality rate at 6 months and a 63% mortality rate at 1 year of therapy. Characteristics at study entry that predicted death within 6 months included more advanced functional class, impaired renal function, lower right ventricular ejection fraction, presence of nonsustained ventricular tachycardia on 24 hour ambulatory electrocardiography, more impaired baseline hemodynamic function and absence of clinical improvement after 1 month of milrinone therapy. Multivariate analysis selected lower baseline cardiac index and aortic systolic pressure as the most significant variables in predicting death; patients who died of progressive heart failure had less frequent use of antiarrhythmic drugs and greater increases in furosemide and milrinone doses during long-term follow-up than did those who died suddenly. Thus, although milrinone is well tolerated and produces early symptomatic benefits in approximately half of patients with congestive heart failure refractory to conventional therapy, there is no evidence that it improves the high baseline mortality in this disorder.

Administration, Oral↗
PubMed1986

Separation of the direct myocardial and vasodilator actions of milrinone administered by an intracoronary infusion technique.

To determine the relative contributions of milrinone's positive inotropic and vasodilator actions in patients with severe congestive heart failure, the drug was administered by constant infusion directly into the left main coronary artery of 11 patients with New York Heart Association functional class III or IV heart failure. Intracoronary infusion of milrinone at rates up to 50 micrograms/min had no effect on mean arterial pressure or systemic vascular resistance but resulted in dose-related increases in peak positive dP/dt (+21%), stroke volume index (+18%), and stroke work index (+21%) and decreases in heart rate (-3%), mean right atrial pressure (-25%), and left ventricular end-diastolic pressure (-17%). In eight patients, intravenous administration (75 micrograms/kg) after the intracoronary infusion resulted in significant decreases in mean arterial pressure (-14%) and systemic vascular resistance (-40%), further increase in stroke volume index compared with intracoronary administration, and further decreases in mean right atrial and left ventricular end-diastolic pressures compared with intracoronary administration. These data indicate that milrinone exerts both positive inotropic and vasodilator actions that contribute significantly to the drug's overall hemodynamic effect.

Adult↗
PubMed1986

Intravenous recombinant tissue-type plasminogen activator in patients with acute myocardial infarction: a report from the NHLBI thrombolysis in myocardial infarction trial.

The efficacy and safety of a 3 hr, 80 mg intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA) were investigated in 47 patients with acute myocardial infarction. Coronary angiography, performed before the administration of rt-PA and for 90 min thereafter, demonstrated that 37 patients had total coronary occlusion before therapy. After 90 min of rt-PA (50 mg), reperfusion of the infarct-related artery was observed in 25 patients (68%). Continuous infusions of heparin for anticoagulation were administered for 8 to 10 days. Of 36 patients who underwent follow-up coronary cineangiography, 21 had initially presented with total occlusion and had experienced reperfusion at 90 min. Sustained perfusion of the infarct-related artery was observed in 14 (67%) of these 21 initially reperfused patients. Late angiography was performed in nine patients who initially demonstrated subtotal occlusion of the infarct-related artery; sustained perfusion was observed in eight (89%). Significant bleeding was observed in 15 patients (32%). A hematoma at the site of the acute catheterization accounted for most instances of significant bleeding (11/15, 73%). Administration of rt-PA resulted in a significant decline in fibrinogen and plasminogen while amounts of fibrin(ogen) degradation products rose. In no patient, however, did fibrinogen levels decline to less than 140 mg/dl. Thus, rt-PA, administered as a brief 80 mg intravenous infusion, is capable of restoring blood flow in a high proportion of patients with acute myocardial infarction due to total coronary obstruction. Declines in plasma fibrinogen and plasminogen are observed. If combined with heparin anticoagulation and invasive vascular procedures, significant bleeding is a common complication.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗