Eugene Braunwald

Effect of Infarct Artery Patency on Prognosis After Acute Myocardial Infarction

BACKGROUND In patients with acute myocardial infarction (MI), early restoration of patency of the infarct-related artery (IRA) leads to preservation of left ventricular function and improved clinical outcome. However, there is evidence that the benefits associated with a patent IRA are out of proportion to the observed improvement in ventricular function and may result not only from salvage of ischemic myocardium but also from the opening of the IRA beyond a narrow postinfarct time window. The objectives of this study were (1) to assess the effect of IRA patency on outcome of patients after acute MI with left ventricular dysfunction while controlling for differences in left ventricular ejection fraction and the extent of coronary disease and (2) to determine the effect of angiotensin-converting enzyme (ACE) inhibitor therapy on patients with patent as well as occluded infarct arteries. METHODS AND RESULTS The Survival and Ventricular Enlargement (SAVE) study consisted of 2231 patients with a documented MI and a left ventricular ejection fraction < or = 40%. They were randomized to the ACE inhibitor captopril (50 mg TID) or placebo 3 to 16 days after MI and were followed for an average of 3.5 years. Left ventricular ejection fraction, measured with radionuclide left ventriculography, was repeated at the end of the follow-up period. The 946 patients in whom the patency of the IRA was established before randomization form the basis of this study. At cardiac catheterization averaging 4.2 days after infarction, 30.7% of patients had an initially occluded IRA. After revascularization, 162 of the 946 patients (17.1%) were left with an occluded IRA at the time of randomization. The 162 patients with persistently occluded IRAs and 784 with patent IRAs had similar clinical baseline characteristics, but those with occluded arteries had a slightly lower ejection fraction than the 784 patients with patent infarct arteries (30% versus 32%, P = .01). Cox proportional-hazards analyses showed that the independent predictors of all-cause mortality were hypertension (relative risk [RR] 1.94, P < .001), number of diseased coronary arteries (RR 1.68, P < .001), occluded IRA (RR 1.49, P = .039), ejection fraction (RR 1.36, P < .001), age (RR 1.10, P = .030), and use of beta-adrenergic receptor blocking agents (RR 0.60, P = .007). Independent predictors of a composite end point consisting of cardiovascular mortality, morbidity, or reduction of ejection fraction of > or = 9 units were occluded IRA (odds ratio [OR] 1.73, P = .002), hypertension (OR 1.71, P < .001), number of diseased vessels (OR 1.38, P < .001), ejection fraction (OR 1.18, P = .003), use of beta-adrenergic receptor blocking agents (OR 0.67, P = .007), and randomization to captopril (OR 0.70, P = .009). CONCLUSIONS IRA patency within 16 days after MI predicts a favorable clinical outcome, independent of the number of obstructed coronary arteries or of left ventricular function. The beneficial effect of ACE inhibition is independent of patency status of the IRA. These findings support the need for additional, prospective clinical trials of late reperfusion in MI patients.

The Hemodynamics of the Left Side of the Heart as Studied by Simultaneous Left Atrial, Left Ventricular, and Aortic Pressures; Particular Reference to Mitral Stenosis

At operation the hemodynamics of the left side of the heart were studied in six patients without mitral stenosis, and in eight patients with mitral stenosis, by means of simultaneous needle puncture of the left atrium, left ventricle, and aorta. This technic permits analysis of the various phases of the cardiac cycle in normal subjects and in patients with mitral stenosis. The fundamental hemodynamic expression of mitral stenosis is the presence of an elevated left atrioventricular filling pressure sure gradient, which ranged from 4 to 20 mm. Hg, and after valvulotomy fell in relation to the adequacy of the procedure.

A study of the electrocardiogram and vectorcardiogram in congenital heart disease

Abstract 1.1. The electrocardiograms and spatial vectorcardiograms of 135 patients with congenital heart disease, in whom the diagnosis was well established, were analyzed. Our findings were compared with those of other authors. 2.2. No pathognomonic electrocardiographic or vectorcardiographic pattern is associated with any particular anatomic lesion. 3.3. Both the electrocardiogram and the vectorcardiogram, but particularly the latter, are of considerable aid in the differential diagnosis of the various malformations by indicating the dominant type of ventricular hypertrophy present. 4.4. In general, patients with the tetralogy of Fallot, pulmonic stenosis, interatrial septal defect, and Eisenmengers complex show right ventricular hypertrophy; those with tricuspid atresia, subaortic or aortic stenosis, and coarctation of the aorta show left ventricular hypertrophy, while those with uncomplicated patent ductus arteriosus, interventricular septal defect, and idiopathic dilatation of the pulmonary artery show a normal balance of electrical forces. 5.5. The determination of electrical axis from the standard electrocardiographic leads is found to be of little value in determining the type of ventricular hypertrophy present.

Electrocardiographic, enzymatic and scintigraphic criteria of acute myocardial infarction as determined from study of 726 patients (a MILIS study)

Methods for detecting acute myocardial infarction (AMI) were compared in a prospective study of 726 patients with pain presumed to be caused by ischemia that lasted 30 minutes or longer and was associated with electrocardiographic changes (ST-segment deviation greater than or equal to 0.1 mV and/or new Q waves or left bundle branch block). Using MB-CK values of more than 12 IU/liter as the standard criterion for detection of AMI, 639 patients (88%) were judged to have AMI. Total plasma CK values, technetium-99m stannous pyrophosphate images 48 to 72 hours after admission, and serial 12-lead electrocardiograms over 10 days were analyzed by investigators blinded to other clinical and laboratory data. For detection of AMI, total CK, electrocardiograms (ECGs) and pyrophosphate imaging were all highly accurate and sensitive (total CK accuracy 97%, ECG 92%, pyrophosphate 88%; total CK sensitivity 98%, ECG 96% and pyrophosphate 91%). However, both pyrophosphate and ECG were less specific than total CK (p less than 0.01) (total CK specificity 89%, pyrophosphate 64% and ECG 59%). The sensitivity (p less than 0.05) and accuracy (p less than 0.01) of total CK and pyrophosphate for those patients with Q-wave development were slightly greater than for those in whom Q waves did not evolve. The ECG was less accurate (p less than 0.02) and pyrophosphate was less specific (p less than 0.04) in patients with prior MI compared with those with initial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

A study of the electrocardiogram and vectorcardiogram in congenital heart disease. III. Electrocardiographic and vectorcardiographic findings in various malformations.

Abstract 1. 1. The electrocardiograms and spatial vectorcardiograms of 135 patients with congenital heart disease, in whom the diagnosis was well established, were analyzed. Our findings were compared with those of other authors. 2. 2. No pathognomonic electrocardiographic or vectorcardiographic pattern is associated with any particular anatomic lesion. 3. 3. Both the electrocardiogram and the vectorcardiogram, but particularly the latter, are of considerable aid in the differential diagnosis of the various malformations by indicating the dominant type of ventricular hypertrophy present. 4. 4. In general, patients with the tetralogy of Fallot, pulmonic stenosis, interatrial septal defect, and Eisenmengers complex show right ventricular hypertrophy; those with tricuspid atresia, subaortic or aortic stenosis, and coarctation of the aorta show left ventricular hypertrophy, while those with uncomplicated patent ductus arteriosus, interventricular septal defect, and idiopathic dilatation of the pulmonary artery show a normal balance of electrical forces. 5. 5. The determination of electrical axis from the standard electrocardiographic leads is found to be of little value in determining the type of ventricular hypertrophy present.

Right Bundle-Branch Block. Hemodynamic, Vectorcardiographic and Electrocardiographic Observations

The time intervals between the onset of ventricular depolarization and of right ventricular contraction were studied in 36 patients, by means of cardiac catheterization, and were correlated with their vectorcardiograms and electrocardiograms. The onset of right ventricular contraction was delayed in six subjects without heart disease but with the electrocardiographic picture of right bundle-branch block. The onset of right ventricular contraction was found to be normal in 10 of 15 patients with right ventricular hypertrophy with the electrocardiographic picture of right bundle branch block. This indicates that this electrocardiographic configuration is not necessarily accompanied by delayed right ventricular contraction.

Comparison of left ventricular function and infarct size in patients with and without persistently positive technetium-99m pyrophosphate myocardial scintigrams after myocardial infarction: Analysis of 357 patients☆

One hundred nine patients with persistently positive technetium-99m pyrophosphate (Tc-99m-PPi) myocardial scintigrams 6 months after acute myocardial infarction (MI) (Group A) and 185 patients without such persistently positive scintigrams (Group B) were compared with regard to enzymatically determined infarct size, early and late measurements of left ventricular (LV) function determined by radionuclide ventriculography, and preceding clinical course during the 6 months after MI. The CK-MB-determined infarct size index in Group A (17.4 +/- 10.6 g-Eq/m2) did not differ significantly from that in Group B (16.0 +/- 14.6 g-Eq/m2). Similarly, myocardial infarct areas in the 2 groups, determined by planimetry of acute Tc-99m-PPi scintigrams in those patients with well-localized 3+ or 4+ anterior pyrophosphate uptake, were not significantly different (35.7 +/- 13.4 vs 34.4 +/- 13.1 cm2, respectively). However, patients in Group A had significantly lower LV ejection fractions than those in Group B, both within 18 hours of the onset of MI (0.42 +/- 0.14 vs 0.49 +/- 0.14, p less than 0.01) and at 3 months after MI, both at rest (0.42 +/- 0.14 vs 0.51 +/- 0.14, p less than 0.01) and at maximal symptom-limited supine bicycle exercise (0.44 +/- 0.17 vs 0.51 +/- 0.17, p less than 0.01). Peak exercise levels achieved in the 2 groups were not significantly different. Furthermore, patients in Group A demonstrated a greater incidence of congestive heart failure during the initial hospital admission (41 vs 24%; p less than 0.01) and a greater requirement for digoxin (p less than 0.05) and furosemide (p less than 0.01) after discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart failure updates

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Current Status of Measurements and Efforts to Reduce Myocardial Infarct Size in Man

Ischemic heart disease represents the most common serious health problem of contemporary Western society. In this country alone, more than 675,000 patients die each year from ischemic heart disease and its complications, approximately 1,300,000 patients develop a myocardial infarct, and countless more suffer from congestive heart failure secondary to ischemic myocardial damage. Acute myocardial infarction thus remains the most common cause of inhospital deaths in this country, indeed in the Western world. Inhospital deaths of patients with acute myocardial infarction result mainly from primary arrhythmias and from pump failure [1]. Whereas death due to arrhythmias has been reduced by modern monitoring techniques and more vigorous prophylaxis and treatment, the death rate following mechanical failure manifested by cardiogenic shock and/or pulmonary edema is still very high. These syndromes have been found to be associated with larger infarcts than those exhibited by other patients who succumbed to myocardial infarction, but who did not die as a consequence of pump failure [2, 3]. The prognosis for patients with larger infarcts is distinctly worse than it is for those with smaller infarcts [3].