Thomas Killip

Unstable angina pectoris: National cooperative study group to compare surgical and medical therapy: II. In-Hospital experience and initial follow-up results in patients with one, two and three vessel disease

Abstract A prospective randomized study comparing intensive medical therapy with urgent coronary bypass surgery for the acute management of patients with unstable angina pectoris was carried out by nine cooperating medical centers under the auspices of the National Heart, Lung, and Blood Institute. Between 1972 and 1976, a total of 288 patients were entered into the study. All patients had transient S-T or T wave changes, or both, in the electrocardiogram during pain; 90 percent had pain at rest in the hospital, and 76 percent had multivessel coronary disease. The medically and surgically treated patients were comparable with respect to clinical, electrocardiographic and angiographic characteristics and left ventricular function. During the total study period, the hospital mortality rate was 5 percent in the surgical group and 3 percent in the medical group (difference not significant). The rate of in-hospital myocardial infarction was 17 and 8 percent in the respective groups (P In the 1st year after hospital discharge class III or IV angina (New York Heart Association criteria) was more common in medically than in surgically treated patients with one vessel disease (22 percent versus 3 percent, P The results indicate that patients with unstable angina pectoris can be managed acutely with intensive medical therapy, including the administration of propranolol and long-acting nitrates in pharmacologic doses, with adequate control of pain in most patients and no increase in early mortality or myocardial infarction rates. Later, elective surgery can be performed with a low risk and good clinical results if the patients angina fails to respond to intensive medical therapy.

Unstable angina pectoris: National cooperative study group to compare medical and surgical therapy

A preliminary report is presented of a prospective randomized trial conducted by eight cooperative institutions under the auspices of the National Heart and Lung Institute to compare the effectiveness of medical and surgical therapy in the management of the acute stages of unstable angina pectoris. To date 150 patients have been included in the randomized trial, 80 assigned to medical and 70 to surgical therapy; the clinical presentation, coronary arterial anatomy and left ventricular function in the two groups are similar. Some physicians have been reluctant to prescribe medical or surgical therapy by a random process, and the eithical basis of the trial has been questioned. Since there are no hard data regarding the natural history and outcome of therapy for unstable angina pectoris, randomization appears to provide a rational way of selecting therapy. Furthermore, subsets of patients at high risk may emerge during the process of randomization. The design of this randomized trial is compared with that of another reported trial. Thus far, the study has shown that it is possible to conduct a randomized trial in patients with unstable angina pectoris, and that the medical and surgical groups have been similar in relation to the variables examined. The group as a whole presented with severe angina pectoris, either as a crescendo pattern or as new onset of angina at rest, and 84 percent had recurrence of pain while in the coronary care unit and receiving vigorous medical therapy. It is anticipated that sufficient patients will have been entered into the trial within the next 12 months to determine whether medical or surgical therapy is superior in the acute stages of unstable angina pectoris.Abstract A preliminary report is presented of a prospective randomized trial conducted by eight cooperative institutions under the auspices of the National Heart and Lung Institute to compare the effectiveness of medical and surgical therapy in the management of the acute stages of unstable angina pectoris. To date 150 patients have been included in the randomized trial, 80 assigned to medical and 70 to surgical therapy; the clinical presentation, coronary arterial anatomy and left ventricular function in the two groups are similar. Some physicians have been reluctant to prescribe medical or surgical therapy by a random process, and the ethical basis of the trial has been questioned. Since there are no hard data regarding the natural history and outcome of therapy for unstable angina pectoris, randomization appears to provide a rational way of selecting therapy. Furthermore, subsets of patients at high risk may emerge during the process of randomization. The design of this randomized trial is compared with that of another reported trial. Thus far, the study has shown that it is possible to conduct a randomized trial in patients with unstable angina pectoris, and that the medical and surgical groups have been similar in relation to the variables examined. The group as a whole presented with severe angina pectoris, either as a crescendo pattern or as new onset of angina at rest, and 84 percent had recurrence of pain while in the coronary care unit and receiving vigorous medical therapy. It is anticipated that sufficient patients will have been entered into the trial within the next 12 months to determine whether medical or surgical therapy is superior in the acute stages of unstable angina pectoris.

Prodromata in Acute Myocardial Infarction

One hundred patients admitted to a coronary care unit with acute myocardial infarction were interviewed from a structured questionnaire to evaluate the incidence and significance of prodromal symptoms. Prodromata occurred in 65% of the subjects; this is the highest incidence ever recorded. Chest pain was the most common symptom. Characteristically it was recurrent and progressive. Patients with prodromata in contrast to those without warning are more likely to have an anterior or anterolateral infarction and the damage is more likely to be nontransmural than transmural. Prodromata have a striking relationship to pre-existing angina. Patients with angina rarely are hospitalized for acute infarction without warning. Emotional stress was not correlated with the definitive attack of cardiac infarction but was associated with the development of prodromata in some patients. These observations suggest that acute myocardial infarction is usually the culmination of a dynamic pre-coronary process.

Mode of onset of atrial fibrillation in man

Abstract The mode of onset of atrial fibrillation has been recorded 18 times in 14 patients during continuous monitoring of an electrocardiogram. An atrial premature discharge preceded the onset of atrial fibrillation in all 14 episodes of relapse from sinus rhythm. In 10 of these the premature P wave was followed immediately by atrial fibrillation. In 4 the premature P wave appeared to initiate a brief run of atrial tachycardia (less than 6 beats) which accelerated to atrial fibrillation. In 4 observations, atrial fibrillation developed from established atrial flutter. The atrial rate gradually accelerated from approximately 300 per minute, and irregular, rapid atrial response characteristic of atrial fibrillation appeared. In 1 patient this event occurred during carotid sinus massage. The relative prematurity of ectopic atrial beats was evaluated by calculating the coupling index, defined as the ratio of the coupling interval (P-P) to the preceding cycle length. The mean coupling index of the 14 atrial premature contractions which initiated atrial fibrillation was .48 ± .03 (S.E.M.). The mean coupling index for atrial premature contractions which were not followed by atrial fibrillation was .65 ± .02 in the patients who subsequently developed atrial fibrillation, and .68 ± .01 in a similar group of patients with ectopic atrial activity who did not develop fibrillation. The difference between the mean coupling indices of those P waves which initiated atrial fibrillation and those which did not is highly significant (p It is concluded that a spontaneously occurring atrial premature impulse may initiate atrial fibrillation. In some instances the fibrillation is preceded by an accelerating atrial tachycardia. The propensity of a premature impulse to initiate fibrillation is related to its relative prematurity, expressed as the coupling index. When the coupling index is less than .50, the change of atrial fibrillation is high; when it is greater than .60, the chance of atrial fibrillation following that particular premature P wave is small. The observation that atrial fibrillation may follow a properly timed ectopic discharge is consistent with the experimental delineation of an atrial vulnerable period. Possible relationships between focal ectopic activity, atrial tachycardias, and atrial fibrillation are discussed.

Unstable angina pectoris: National cooperative study group to compare medical and surgical therapy. I. Report of protocol and patient population

A preliminary report is presented of a prospective randomized trial conducted by eight cooperative institutions under the auspices of the National Heart and Lung Institute to compare the effectiveness of medical and surgical therapy in the management of the acute stages of unstable angina pectoris. To date 150 patients have been included in the randomized trial, 80 assigned to medical and 70 to surgical therapy; the clinical presentation, coronary arterial anatomy and left ventricular function in the two groups are similar. Some physicians have been reluctant to prescribe medical or surgical therapy by a random process, and the eithical basis of the trial has been questioned. Since there are no hard data regarding the natural history and outcome of therapy for unstable angina pectoris, randomization appears to provide a rational way of selecting therapy. Furthermore, subsets of patients at high risk may emerge during the process of randomization. The design of this randomized trial is compared with that of another reported trial. Thus far, the study has shown that it is possible to conduct a randomized trial in patients with unstable angina pectoris, and that the medical and surgical groups have been similar in relation to the variables examined. The group as a whole presented with severe angina pectoris, either as a crescendo pattern or as new onset of angina at rest, and 84 percent had recurrence of pain while in the coronary care unit and receiving vigorous medical therapy. It is anticipated that sufficient patients will have been entered into the trial within the next 12 months to determine whether medical or surgical therapy is superior in the acute stages of unstable angina pectoris.Abstract A preliminary report is presented of a prospective randomized trial conducted by eight cooperative institutions under the auspices of the National Heart and Lung Institute to compare the effectiveness of medical and surgical therapy in the management of the acute stages of unstable angina pectoris. To date 150 patients have been included in the randomized trial, 80 assigned to medical and 70 to surgical therapy; the clinical presentation, coronary arterial anatomy and left ventricular function in the two groups are similar. Some physicians have been reluctant to prescribe medical or surgical therapy by a random process, and the ethical basis of the trial has been questioned. Since there are no hard data regarding the natural history and outcome of therapy for unstable angina pectoris, randomization appears to provide a rational way of selecting therapy. Furthermore, subsets of patients at high risk may emerge during the process of randomization. The design of this randomized trial is compared with that of another reported trial. Thus far, the study has shown that it is possible to conduct a randomized trial in patients with unstable angina pectoris, and that the medical and surgical groups have been similar in relation to the variables examined. The group as a whole presented with severe angina pectoris, either as a crescendo pattern or as new onset of angina at rest, and 84 percent had recurrence of pain while in the coronary care unit and receiving vigorous medical therapy. It is anticipated that sufficient patients will have been entered into the trial within the next 12 months to determine whether medical or surgical therapy is superior in the acute stages of unstable angina pectoris.

Identification of high risk subsets of acute myocardial infarction

To Identify the patient at high risk after acute myocardial Infarction data on 400 patients obtained from the Myocardial Infarction Research Units Cooperative Data Bank were examined. Patients were grouped according to clinical findings as follows: uncomplicated (class 1, 81 patients); mild to moderate failure (class II, 150 patients); severe failure with pulmonary edema (class III, 17 patients); and severe failure with shock (class IV, 152 patients). Hemodynamic data Including pulmonary capillary wedge pressure and cardiac output were available In all patients. High risk subsets within clinical classes I, II and IV were Identifiable. In class I, nonsurvivors had significantly (P <0.05) higher values for pulmonary capillary wedge pressure (16 mm Hg) and heart rate (96 beats/min); nonsurvivors In class II also had a significant (P <0.01) elevation In pulmonary capillary wedge pressure (23 mm Hg); and In class IV the high risk subset was characterized (P <0.01) by pulmonary capillary wedge pressure (21 mm Hg), heart rate (100 beats/min), cardiac Index (1.6 liters/min per m2), stroke index (14 cc/m2) and stroke work index (12 g-m/m2). Discrimlnant function analysis using pulmonary capillary wedge pressure and heart rate predicted mortality In classes I to III with 72 percent accuracy; a similar equation representing stroke work index, pulmonary capillary wedge pressure and cardiac Index had an 83 percent rate of accuracy in class IV patients. interclass comparison of the last three measurements indicated that the data differed significantly among classes, thus signifying a spectrum of ventricular impairment after Infarction that was commensurate with the clinical presentation. However, in individual patients the clinical examination did not consistently reflect the degree of ventricular dysfunction. Thus, careful bedside examination together with hemodynamic monitoring of wedge pressure, cardiac output and heart rate serve to identify the high risk patient after acute myocardial infarction.

Arterial oxygen tension in acute myocardial infarction. Serial analysis of clinical state and blood gas changes

Abstract The arterial hypoxemia frequently present in acute myocardial infarction was compared with simultaneous clinical examination on 177 occasions throughout 40 episodes of infarction and recovery. The arterial oxygen tension and the increment with 28 per cent oxygen were found to correlate with clinical severity. The daily arterial carbon dioxide, pH, and lactate studies did not accurately reflect changes in clinical course. The complex physiologic derangements are discussed. Arterial blood gas analysis is a safe and useful tool for evaluating the clinical course and management of acute myocardial infarction.

A simple bedside method for transvenous intracardiac pacing

Abstract A simple and effective method for transvenous intracardiac pacing is presented, utilizing a flexible, platinum-tipped, Tefloncoated, braided stainless steel wire electrode inserted percutaneously. The advantages of the technique over those using the semirigid cardiac catheter electrodes are discussed. The technique permits intracardiac electrode placement without the necessity of fluoroscopic control and avoids the hazard of cardiac perforation. The procedure may be applied at the bedside with ease and speed, even in the most urgent clinical situation. Several cases in which this method of intracardiac pacing has been successfully employed are outlined and the absence of complications to date is stressed.

Serum Digitalis and Arrhythmia in Patients Undergoing Cardiopulmonary Bypass

To assess the possible role of digitalis in the etiology of arrhythmia following cardiopulmonary bypass, serum digoxin or digitoxin was determined serially by radioimmunoassay in 24 chronically digitalized patients undergoing open-heart surgery. After an initial fall during bypass probably secondary to intraoperative fluid, serum digitalis rebounded, rising to or surpassing the preoperative value in 21 of the 24 patients studied. Peak rebound serum digitalis occurred an average of 13 hours following onset of bypass. Eight patients receiving maintenance digoxin developed arrhythmia postbypass at or near the peak of the rebound. The arrhythmia subsided as the peak was passed. Mean serum digoxin at the time of arrhythmia was 1.3 ± 0.2 (SD) ng/ml. A significantly higher (P < 0.001) value than the value of 0.07 ± 0.03 ng/ml found in patients without arrhythmia. Occurrence of arrhythmia could not be correlated with diagnosis, clinical status, cardiac size, blood gas, or serum electrolyte values. In 77 control subjects with ECG evidence of digoxin toxicity, mean serum digoxin level was 3.1 ± 0.9 (SD) ng/ml. Since arrhythmia occurred at serum levels of digitalis lower than those observed in patients toxic to the drug who had not undergone cardiopulmonary bypass, and since the arrhythmia subsided as the serum level declined, and since the levels were higher in patients who had arrhythmia postbypass than in those who did not, this study suggests that myocardial sensitivity to the toxic effects of digitalis is increased in the first 24 hours following cardiopulmonary bypass.

Unstable angina pectoris: National cooperative study group to compare surgical and medical therapy: III. Results in patients with S-T segment elevation during pain

Abstract A prospective randomized study comparing intensive medical therapy with urgent coronary bypass surgery for the acute management of patients with unstable angina pectoris was carried out by nine cooperating medical centers under the auspices of the National Heart, Lung, and Blood Institute. Between 1972 and 1976, a total of 288 patients were entered into the study; 79 of these (27 percent of the total study group) with 70 percent or more fixed obstruction in one or more coronary arteries had episodes of pain at rest associated with transient S-T segment elevation. Forty-two were randomized to medical and 37 to surgical therapy. The hospital mortality rate was 4.8 percent for the medical and 5.4 percent for the surgical group (difference not significant). The rate Of in-hospital myocardial infarction was 12 percent in the medical and 14 percent in the surgical group (difference not significant). During the 1st and 2nd years of follow-up, 25 percent in the medical and 15 percent in the surgical group complained of New York Heart Association class III or IV angina (difference not significant). During an average follow-up period of 42 months 45 percent of the medically treated patients later underwent surgery to relieve unacceptable angina. In the medical group 65 percent were working full- or part-time at the end of 1 year and 61 percent at the end of 2 years of follow-up; comparable figures for the surgically treated group were 63 and 68 percent. The results indicate that patients with unstable angina pectoris with transient S-T segment elevation during pain at rest with fixed obstruction of 70 percent or more in one or more coronary arteries do not differ significantly from patients with pain at rest associated with transient S-T segment depression or T wave inversion. The condition of such patients can be stabilized, and they can be managed with a maximal medical program including propranolol and long-acting nitrates in pharmacologic doses with good control of pain in most and no increase in rate of early mortality or myocardial infarction. Later, elective surgery can be performed with a lower risk and good clinical results if the patients angina fails to respond to intensive medical therapy.