The American College of Cardiology and changing directions in cardiovascular health care: past, present and future.
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Biomedical subjects
Publications and source records attributed to S B Knoebel.
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A survey of current literature suggests an increasing interest in both the desirable and undesirable implications of a prolonged QT interval, the former perceived to be the beneficial effect of antiarrhythmic drugs that prolong the duration of ventricular action potential, and the latter considered to be a potential marker for sudden cardiac death in patients with ischemic heart disease. In addition, there has been an increasing interest in the congenital long QT syndrome associated with an apparent dysfunction of the autonomic nervous system and serious, potentially lethal ventricular arrhythmias. Circumstantial evidence suggests that these arrhythmias are due to increased dispersion of repolarization which may be aggravated by psychologic and emotional perturbations. In this review, the associations between the long QT interval, autonomic nervous system, dispersion of repolarization, antiarrhythmic drugs and ventricular arrhythmias are examined. Attention is directed to the difficulties of accurate QT measurement, problems related to the correction of the QT interval for heart rate and sex (QTc), the wide range of normal values and the modest QT alterations after various manipulations of the autonomic nervous system. Clinical conditions associated with marked, moderate and occasional QT lengthening are listed and discussed briefly in relation to the disturbances of nervous system, dispersion of ventricular repolarization and ventricular arrhythmias. It is proposed that the absence of relevant animal models of neurogenic or psychogenic QT prolongation hinders the investigation of the neurogenic factors associated with QT lengthening. QT prolongation is most often induced by antiarrhythmic drugs and ischemic heart disease. However, it is not known whether the occurrence of torsade de pointes type of ventricular tachycardia in patients treated with antiarrhythmic drugs is related to a critical drug dose or a critical degree of QTc prolongation. There is no conclusive evidence that QT lengthening has any predictive value either during the acute phase or during convalescence after myocardial infarction. Also, a serious deficiency in current knowledge is the lack of an established relation between the prolonged QT interval and the dispersion of ventricular repolarization. It is concluded that the number of unanswered questions discussed in this review still makes it difficult to judge when a prolonged QT interval is good, bad or indifferent.
The purpose of this study was to determine the potential of a clinically adaptable two-dimensional echocardiographic system using computer enhancement and a mathematically defined integrated backscatter ratio for the early detection of ischemic and infarcted myocardium. Fifteen dogs had two-dimensional echocardiograms recorded during either open chest coronary occlusion (n = 5), closed chest occlusion (n = 5), occlusion followed by reperfusion (n = 3) or sham coronary occlusion (n = 2). A serial increase in integrated backscatter ratio, representing differences in returned ultrasound intensities between a reference point and specific myocardial regions, was detected between 7 and 12 minutes of complete occlusion in 9 of 12 animals (p less than 0.05), and at minutes 18, 43 and 67 in the remaining 3 animals. Reperfusion after 20 minutes of occlusion in two studies resulted in normalization of the backscatter ratio. An increase in backscatter ratio was not detected when 5 minute occlusion periods were used or during the 5 hour sham occlusion studies. The computer enhancement techniques utilized in this study provided increased visual detail of intracardiac structures over that provided by routine two-dimensional echocardiograms; myocardial tissue was identifiable in what appeared to be echo-free segments; and boundaries that appeared as noncontiguous horizontal lines on the routine echocardiograms were identifiable as trabeculae. The results indicate that: 1) significant increases in backscatter from nonperfused myocardium are detectable echocardiographically within 12 minutes of coronary occlusion and temporal changes can be assessed in the canine model, and 2) the echocardiographic data acquisition and computer analysis system utilized provide a clinically adaptable approach to identify and map myocardial characteristics in human beings.
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Cardiac arrhythmias are ubiquitous in normal and abnormal hearts. These disorders may be life-threatening or benign, symptomatic or unrecognized. Arrhythmias may be the precursor of sudden death, a cause or effect of cardiac failure, a clinical reflection of acute or chronic disorders, or a manifestation of extracardiac conditions. Progress is being made toward unraveling the diagnostic and therapeutic problems involved in arrhythmogenesis. Many of the advances would not be possible, however, without the availability of computer technology. To preserve the proper balance and purposeful progression of computer usage, engineers and physicians have been exhorted not to work independently in this field. Both should learn some of the other's trade. The two disciplines need to come together to solve important problems with computers in cardiology. The intent of this article was to acquaint the practicing cardiologist with some of the extant and envisioned computer applications and some of the problems with both. We conclude that computer-based database management systems are necessary for sorting out the clinical factors of relevance for arrhythmogenesis, but computer database management systems are beset with problems that will require sophisticated solutions. The technology for detecting arrhythmias on routine electrocardiograms is quite good but human over-reading is still required, and the rationale for computer application in this setting is questionable. Systems for qualitative, continuous monitoring and review of extended time ECG recordings are adequate with proper noise rejection algorithms and editing capabilities. The systems are limited presently for clinical application to the recognition of ectopic rhythms and significant pauses. Attention should now be turned to the clinical goals for detection and quantification of arrhythmias. We should be asking the following questions: How quantitative do systems need to be? Are computers required for the detection of all arrhythmias? In all settings? Should we be focusing alternatively on those arrhythmias that are frequent and with clinical significance? The ultimate test of any technology is, after all, its use in advancing knowledge and patient care.
Exercise and 3 hour delayed redistribution thallium-201 myocardial perfusion imaging was performed in 107 patients including 87 patients with documented coronary artery disease and 20 patients with normal coronary arteriograms. A computer algorithm for statistical analysis and redisplay of the analog scintillation data was developed to augment the visual analysis of the standard analog image. The basic algorithm identified the myocardial area (pixel) with the most absolute counts and developed an appropriate standard deviation range from a table. All pixels in the area of the myocardium containing absolute counts below three standard deviation ranges (or approximately 6 standard deviations) were deleted from the final image. The remaining pixels were redisplayed in a digitized bimodal format and the image photographed. Two experienced observers compared visual analysis of the analog image alone and the analog image in conjunction with the computer-analyzed image for sensitivity, specificity and predictive accuracy in the detection of perfusion defects in patients with coronary artery disease and in normal subjects. Sensitivity in patients with coronary artery disease and in normal subjects. Sensitivity in patients with coronary artery disease for the analog scintillation image alone was 79 percent (69 of 87) and with computer analysis 95 percent (83 of 87). Specificity in the patients with no coronary disease was 100 percent (20 of 20) for both techniques. The predictive accuracy of the test was 83 percent (89 of 107) for the analog image alone and 96 percent (103 of 107) for the two images combined. It is concluded that use of a computer statistical analysis algorithm of thallium-201 analog myocardial perfusion images improves the accuracy of detection of perfusion defects in patients with coronary artery disease.
Computer-quantitated measurements of the Q-T intervals, the Q-T/Q-Tc ratio (Q-T/corrected Q-T) and the terminal T wave (apex to end of T [aT-eT] interval) were evaluated in resting and exercise electrocardiograms of 130 normal men with a mean age of 40 years. Pseudo-orthogonal, bipolar X, Y and Z axis leads were recorded during treadmill exercise testing, and 25 consecutive QRS-T complexes from standing rest and three exercise stages were computer-averaged. The Q-T intervals, Q-T/Q-Tc ratio and aT-eT interval measurements were then computed in the X and Z axis leads only, because the Y lead proved to be too noisy for accurate interpretation. A correlation coefficient of 0.9830 resulted between measurements made manually from the plotted, composite QRS-T complexes and those made by computer. No significant differences , in the paired sense, were found between any of the measurements. Measurements made on the Z axis lead; however, the differences in the measurements remained constant across all stages of exercise. A Q-T/Q-Tc ratio of greater than 1.08, previously reported to be a reliable indicator of coronary disease, was observed in the majority of our normal subjects during exercise. Although the Q-T interval is substantially influenced by many factors, the aT-eT interval proved not to be age- or heart rate-dependent. It appears that the aT-eT interval can be measured with a high degree of reliability during exercise and it may prove to be a relatively specific indicator of repolarization alterations that occur with myocardial ischemia.
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The purpose of this study was to examine the effect of secobarbital vs. alpha-chloralose anesthesia, and of tonic autonomic influence, upon ischemia-induced subepicardial and subendocardial bipolar electrogram changes during acute coronary artery occlusion in the open-chest dog. We found that the degree of bipolar electrogram alterations for similar reductions of regional myocardial blood flow was less in dogs anesthetized with alpha-chloralose than in those anesthetized with secobarbital. We also noted greater electrogram change when the sympathetic system was unopposed by the vagus nerves. Finally, this study demonstrates the reproducibility of ischemia-induced changes in bipolar electrograms during serial, short term, acute coronary artery occlusions.
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Proton NMR techniques were used to characterize acutely ischemic myocardial tissue from the dog. Ligation of the left anterior descending coronary artery for 30 min resulted in a consistent prolongation of the proton spin-lattice relaxation times (T1) in samples from regionally ischemic heart muscle when compared with T1 values for nonischemic areas from the same hearts. The relative prolongation of relaxation times in ischemic tissue was found to increase as the duration of ischemia was extended to 60 or 120 min. T1 values for ischemic tissue were not directly related to tissue levels of high-energy compounds, lactate, or hydrogen ions but largely reflected the increased water content of the regionally ischemic myocardium. Proton NMR analysis provides a means of identifying acute regional ischemia in heart tissue, and in the future may permit three-dimensional imaging of the heart in vivo.
The purpose of this study was to determine whether a quantitative relationship existed between a reduction in regional myocardial blood flow, measured by radiolabeled microspheres, and the degree and type of changes in myocardial activation recorded in bipolar left ventricular subepicardial and subendocardial electrograms, in open-chest dogs following acute coronary artery occlusion. We found that the degree of regional myocardial ischemia was related quantitatively to the reduction in amplitude recorded with bipolar electrograms in the subepicardium and subendocardium, and to the increase in duration of subepicardial electrograms. Other characteristics measured in electrograms did not relate to the degree of ischemia. Despite a comparable reduction in regional myocardial blood flow, subepicardial conduction delay exceeded that recorded in the subendocardium, which often exhibited accelerated conduction.
Wall thicknesses were measured and echo densities were evaluated from the left ventricular echograms of 182 patients. The echogram was considered to reflect scar tissue when 1) either the interventricular septum, the posterior left ventricular wall or the anterior left ventricular wall was less than 7 mm thick in mid-diastole and was more echo-producing than its opposing wall or another area of the same wall in a sector scan, or 2) an area of myocardium was 30% less thick than an adjacent area within a sector scan. Myocardial scarring was diagnosed by echocardiography in 52 of the 182 patients. The echocardiographic presence or absence of scarring was confirmed in 95% (173 of 182) of cases, 34 cases by microscopic examination and 139 by surgical appearance. This study shows that M-mode echocardiography is both a sensitive and specfic method for detecting myocardial scar tissue.
A formula was derived for calculating mitral valve stroke volume (MVSV) using the rate of mitral valve (MV) opening (DE slope on the MV echogram), the vertical disease between the mitral leaflet echoes early in diastole (EE), the electrocardiographic PR interval and heart rate. The formula was tested prospectively on 80 consecutive patients from whom 95 simultaneous MV echograms and either thermodilution (45) or Fick (50) cardiac outputs were obtained. Sixteen patients were normal; 54 had coronary artery disease; three had cardiomyopathy; and seven had nonrheumatic mitral regurgitation (MR). Linear regression for stroke volume was r = 0.90, SEE +/- 6, and for cardiac output r = 0.83, SEE +/- 0.5 liter for the 73 patients without MR. The presence or absence of ventricular dyssynergy did not alter statistical findings. MVSV consistently overestimated forward stroke volume for the seven patients with MR. This study shows that the MV echogram provides an accurate, widely applicable method for calculating MVSV.
Under conditions of varying flow rates, total myocardial blood flow, measured by fractional uptake of rubidium-84, using a coincidence counting system, was compared with myocardial flow measured by microspheres (15 +/- 5 micrometer). The methods were compared, open-chested, in 47 dogs: 17 during control, ten following 5 min of ligation of left anterior descending coronary artery, five following i.v. isoproterenol, six following ligation and isoproterenol, and nine after ligation plus dipyridamole. Regional flows by Rb-84 and by either Ce-141 or Cr-51 microspheres were also compared for left ventricle, as well as for nonischemic posterior wall, which served as a reference area, and for anterior wall with ligation of left anterior descending artery in the same preparations. There were no significant differences in total or regional flow measured by the two methods, nor in the estimate of ischemic area size. The data indicate that measurement of myocardial blood flow by fractional uptake of a potassium analog is a reliable method in the presence of ischemia and drug intervention. It is suggested that the inequalities of extraction ratio that occur with differing flow rates do not invalidate fractional-uptake methods over the flow ranges examined.
Echocardiographic septal and posterior wall thicknesses and the percent change with systole were measured in 146 patients with the following diagnoses: acute myocardial infarction (40), chronic coronary artery disease (49), congestive cardiomyopathy (8), atrial septal defect (20), and no cardiac disease (29). Mean diastolic thicknesses for the groups of patients with coronary artery disease and congestive cardiomyopathy were not significantly different from normal although there were abnormal values for individual patients within each group. Mean diastolic thickness of the septum was greater than normal for the group with atrial septal defect (P less than 0.02). Wall thinning with systole was associated with acute infarction or ischemia (P less than 0.0001); decreased thickening (less than normal) commonly occurred in patients with acute myocardial infarction, chronic coronary artery disease, and congestive cardiomyopathy. Patients with atrial septal defect had normal thickening with abnormal motion. Results of this study show that 1) systolic thinning is indicative of an acute event; 2) abnormal changes in systolic wall thickening occur commonly in patients with coronary artery disease or congestive cardiomyopathy; and 3) abnormal wall motion may occur without abnormal wall thickening, as the echoes of patients with atrial septal defect indicate.
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