Biomedical subjects
Publications and source records attributed to P F Cohn.
Documentation of the mechanism of sudden death is described in a patient with a prolonged QT interval. Ventricular tachycardia was initiated by a ventricular premature beat (VPB) with a prematurity index similar to previous isolated VPBs. This event occurred despite the fact that the patient was receiving phenytoin sodium, a drug known to shorten the QT interval.
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To enhance the reliability of the exercise test in diagnosing both overall coronary artery disease and multivessel coronary artery disease, a discriminant function was obtained by means of stepwise linear discriminant analysis. Both electrocardiographic and nonelectrocardiographic factors were used to derive the discriminant function in a retrospective group of 231 patients, 168 of whom had angiographically defined coronary artery disease. The discriminant function converted into a simple exercise index or score was then applied to a retrospective group of 120 patients, 98 of whom had coronary artery disease. This index, combining R-wave changes with duration of ST segment depression and patient's sex, proved highly accurate in diagnosing coronary artery disease in male patients and in diagnosing the absence of coronary artery disease in female patients. When compared to standard ST segment criteria, the sensitivity and predictive value of the exercise index was significantly higher.
The cold pressor test is a potent alpha-adrenergic vasoconstrictor stimulus, but its effect on regional myocardial blood flow in patients with coronary artery disease is unknown. In this study, 17 patients with chest pain syndromes who were receiving beta-adrenergic-blocking drugs underwent regional myocardial blood flow determination by the xenon-133 technique before and after the cold pressor test. Nineteen of 28 regions analyzed were distal to significant coronary artery lesions (greater than 70% reduction of luminal diameter), while the remainder were in patients with normal coronary arteries. Patients with normal and stenotic coronary arteries had a similar increase in heart rate-pressure product, but in patients with normal coronary arteries, regional myocardial blood flow increased in nine of nine regions (average increase 11.6 +/- 1.3%, p less than 0.01) while either decreasing or remaining unchanged in 14 of 19 regions distal to coronary artery lesions (average decrease 13.6 +/- 1.6%, p less than 0.05). This difference between groups was significant (p less than 0.01), demonstrating an inappropriate reduction of regional myocardial blood flow and suggesting that alpha-adrenergic vasoconstriction may contribute to myocardial ischemia.
To determine the clinical utility and management impact of M-mode echocardiography, 182 echocardiograms were analyzed at a university teaching hospital. The physicians who ordered the echocardiograms said that 12 percent provided crucial information that was not available from other tests and that 26 percent resulted in a change in patient management. According to two independent board-certified cardiologist-reviewers, 86 percent of echocardiograms were appropriately ordered, but only 15 echocardiograms (8 percent) were actually needed for a change to a new and appropriate management. According to the reviewers, the 77 Group I M-mode echocardiograms (those ordered to evaluate left ventricular function, left atrial size, potential cardiac sources of emboli, or the possibility of bacterial endocarditis, or those ordered in patients who, according to the ordering physician, had undergone or would undergo catheterization regardless of the results of echocardiography) were less likely than the 105 Group II M-mode echocardiograms (those ordered to evaluate possible mitral valve prolapse, hypertrophic cardiomyopathy, valvular function, or the pericardium) to be ordered appropriately, to provide helpful information, or to provide crucial results. Group I echocardiograms had reviewer-assessed appropriate management impact in only one case (1 percent) compared with a 13 percent rate of management impact for Group II M-mode echocardiograms (p less than 0.01). Although echocardiography can be accurate and valuable with yields similar to those of other noninvasive procedures, 77 (42 percent) of 182 M-mode echocardiograms in this hospital could be predicted at the time of ordering to be in a low-yield group.
Sixteen asymptomatic patients with coronary artery disease and silent myocardial ischemia were studied with exercise radionuclide ventriculography. Radionuclide ventriculograms were analyzed for changes in ejection fraction globally and in three regions. Results were compared with radionuclide ventriculograms in 24 symptomatic patients. Both groups (silent myocardial ischemia and angina) were similar in prevalence of multivessel disease and previous myocardial infarction, as well as in age and sex. Global ejection fraction decreased by 0.06 in both groups during exercise; regional ejection fraction also decreased by similar amounts in the two groups. Furthermore, the percent of regions with normal ejection fraction at rest that demonstrated a decrease during exercise was identical: 19 (60%) of 33 versus 26 (60%) of 46. These exercise radionuclide ventriculographic results suggest that abnormalities in regional and global left ventricular wall motion are similar in patients with coronary artery disease with and without silent myocardial ischemia.
The diagnosis of asymptomatic coronary artery disease is increasing as a result of the widespread use of noninvasive screening techniques. Because its natural history is unknown and as there is continuing controversy over proper treatment, both primary physicians and consultant cardiologists are often unsure how to approach patients with this disorder. This uncertainty on the part of physicians, combined with the paradox of having serious heart disease without symptoms, often leads to psychologic stress in patients and their families. In a pilot study to evaluate the psychologic impact of the diagnosis of asymptomatic coronary artery disease, we elicited the reactions from 15 patients with either totally or partially asymptomatic coronary artery disease. In general, patients and spouses were surprised and concerned by the diagnosis, but most felt their physicians had been supportive in explaining the problem to them. Because patients trusted their physicians, they often changed their lifestyles markedly in regard to exercise and diet; some even underwent coronary surgery when it was recommended. Public awareness of the disorder was generally felt to be almost nonexistent. This pilot study provides insight into a subgroup of patients with potentially serious psychologic problems and the implications of these problems for their physicians.
Despite the large number of studies dealing with the natural history of angiographically defined coronary artery disease, there is still a paucity of data on the prognosis of totally asymptomatic persons. From the small number of reported studies, it appears that prognosis in selected asymptomatic patients may be better than that of symptomatic patients. However, the annual mortality rate in the subgroup of asymptomatic patients with triple vessel disease was as high as 4 to 5% in some studies that included patients with prior myocardial infarction or mild symptoms, or both. This has reinforced the views of those who advocate a more aggressive medical/surgical approach to asymptomatic patients with left main and triple vessel disease, especially if they have had a prior infarction. Although several small series of surgically treated patients have been reported to have excellent short-term survival rates, the absence of adequate control groups in nearly all of these studies has left the issue of prophylactic revascularization unresolved. Until there is more knowledge of prognosis in patients not operated on, it is likely to remain unresolved.
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In order to evaluate the effects of timolol, a new beta-adrenergic blocking agent, on exercise-induced left ventricular wall motion abnormalities, we studied nine patients with chronic, angiographically-documented coronary artery disease. A computerized technique for determining apical, anteroseptal and inferoposterior regional ejection fractions during gated radionuclide ventriculography was used to assess left ventricular dysfunction. During exercise prior to the administration of timolol, the apical regional ejection fraction fell from 0.62 +/- 0.08 to 0.51 +/- 0.08 (p less than .01). The anteroseptal ejection fraction fell from 0.50 +/- 0.08 to 0.41 +/- 0.05 (p less than .05), and the inferoposterior ejection fraction fell from 0.75 +/- 0.10 to 0.59 +/- 0.06 (p less than .05). Three days after beginning therapy with 10-30 mg of timolol, this reduction was markedly attenuated. The apical ejection fraction fell from 0.59 +/- 0.09 to 0.54 +/- 0.08 (p = NS), the anteroseptal ejection fraction fell from 0.49 +/- 0.07 to 0.47 +/- 0.18 (p = NS) and the inferoposterior ejection fraction fell from 0.62 +/- 0.06 to 0.59 +/- 0.07 (p = NS). Furthermore, several individual regions showed increases in ejection fraction. This study demonstrates a previously unreported and beneficial anti-ischemic effect of timolol.
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The increase in left ventricular ejection fraction produced by postextrasystolic potentiation or epinephrine infusion has been used to demonstrate inotropic contractile reserve in patients with coronary artery disease and a depressed ejection fraction (less than 0.50). Prior studies have shown that a change in ejection fraction of 0.10 or more after postextrasystolic potentiation or epinephrine infusion is helpful in discriminating those patients with a better short-term (1 year) prognosis whether treated medically or surgically. This study related inotropic contractile reserve to 5 year prognosis in 54 patients receiving postextrasystolic potentiation or epinephrine infusion between 1971 and 1974. Current left ventricular function in surviving patients was assessed with radionuclide ventriculograms whenever possible. Five year survival was significantly better in patients with an initial change in ejection fraction greater than 0.10 in both the surgically treated group (16 of 20 versus 5 of 15, p less than 0.01) and the medically treated group (6 of 8 versus 1 of 11, p less than 0.01). Furthermore, among the surviving patients in the surgical group, current ejection fraction in the radionuclide ventriculogram was significantly greater in patients who demonstrated inotropic contractile reserve in their 1971 to 1974 contrast left ventriculogram. These findings support the concept that coronary revascularization enhances function of ischemic but viable myocardium.
Because the New York Heart Association (NYHA) classification system categorizes patients based on subjective impression of the degree of functional compromise, a reduction in exercise might make a patient seem improved because the new lower level of ordinary activity produced fewer symptoms. To test this hypothesis, we studied three different sets of patients and compared their NYHA classes to their functional classes as determined by a new Specific Activity Scale (SAS) that is based on the metabolic equivalents of oxygen consumption required for activities the patient actually performs. Among ambulatory patients referred for exercise tests, the NYHA class was higher (i.e. indicated the patient was more limited) in 28% of patients and the SAS class was higher in 14% (p less than 0.001). Among patients interviewed at or near the time of catheterization for chest pain, the NYHA was higher in 20% and the SAS class was higher in 20% (p = NS). In both medically and surgically treated patients interviewed 1--3 yr after cardiac catheterization, the NYHA class was higher in only 4%, whereas the SAS class was higher in 28% (p less than 0.001). The SAS class was significantly more likely to be higher in patients who were not working full time and in patients who described their present activity level as sedentary or light. When the NYHA and SAS systems disagreed as to whether a patient was improved, SAS was significantly more likely to correlate with the patient's self-assessment. These findings suggest that some patients restrict their activity as their cardiac disease progresses; the resultant change in the definition of ordinary activity may reduce the apparent degree of cardiac compromise and thus give a false impression of improvement by NYHA criteria.
The effect of nifedipine on left ventricular isovolumic relaxation and diastolic filling properties and systemic and left ventricular hemodynamics was studied in 15 patients with hypertrophic cardiomyopathy. After nidefipine (10 mg sublingually), the prolonged left ventricular isovolumic relaxation time assessed by echocardiography decreased from 112 +/- 26 to 83 +/- 23 msec (p less than 0.0001), and the left ventricular pressure decay as measured by time constant T improved from 63 +/- 20 to 49 +/- 11 msec (p less than 0.05). Left ventricular filling dynamics also improved as assessed by a return toward normal in the depressed peak rate of left ventricular diastolic filling (dimension change 72 +/- 37 to 101 +/- 39 mm/sec, p less than 0.01) and the peak rate of posterior wall thinning (47 +/- 31 to 68 +/- 36 mm/sec, p less than 0.001). These changes were accompanied by hemodynamic evidence of improved diastolic function shown as a decrease in left ventricular end-diastolic pressure and a downward shift in the left ventricular diastolic pressure-dimension relationship, suggesting improved left ventricular distensibility. After nifedipine, there was a slight increase in heart rate and a decrease in systemic ventricular distensibility. After nifedipine, there was a slight increase in heart rate and a decrease in systemic arterial blood pressure, and no depression of the left ventricular percent fractional shortening or cardiac index. These data indicate that abnormal left ventricular relaxation and diastolic filling rates in hypertrophic cardiomyopathy are dynamic and favorably modified by nifedipine, and that this effect is not related to a depression of left ventricular systolic function.
To determine the incremental value of the exercise test (ETT) for diagnosing coronary artery disease (CAD), we derived a multivariate logistic regression model for the pre-ETT prediction of CAD using data from 3840 patients at Duke University. We then applied the model to 324 patients at the Brigham and Women's Hospital. Using seven clinical factors, the multivariate model had an 84% overall predictive accuracy on both the training (Duke) and the validation (Brigham) sets of patients. Three ETT factors (ST-segment change in patients not taking digitalis, absence of ST-segment change in patients taking digitalis, ETT stopped because of ECG or blood pressure changes) had incremental, significant predictive power, but overall predictive accuracy based on both clinical and ETT factors improved only to 87%. When the ETT result was important enough to move the probability of CAD across a potential therapeutic threshold, the direction of the change in probability was correct only two-thirds of the time. Thus, the ETT was of limited value in predicting the presence or absence of CAD after other easily obtainable clinical data were taken into account.
Nifedipine inhibits the slow-channel calcium current, which plays a major role in vascular smooth-muscle contraction. However, the effect of nifedipine on regional myocardial blood flow (RMBF) in patients with coronary artery disease (CAD) is unknown. In 18 patients with chest pain syndromes, RMBF was determined with xenon-133 before and after nifedipine. In patients with CAD. 25 regions were analyzed distal to significant coronary obstruction(greater than 70% reduction in luminal diameter) and eight regions were analyzed in patients with normal coronary arteries. In patients with CAD, RMBF increased in 21 of 25 regions (average 17.4 /+- 5.7%,p less than 0.01), but decreased in all eight regions in patients with normal coronary arteries, by an average of 14.4 /+- 2.3% (p less than 0.01). The difference between groups was significant (p less than 0.01). In our patients with CAD, improved RMBF appears to be related to a decrease in coronary vascular tone and suggests a physiologic basis for the beneficial effect of nifedipine in ischemic heart disease.
To evaluate the prognostic importance of anginal symptoms, 44 patients with angiographically defined coronary artery disease and no anginal symptoms at time of cardiac catheterization were selected from the Duke Harvard Collaborative Data Bank. They were "matched" with 127 symptomatic patients in the Data Bank who had similar coronary anatomy and ventricular function. Follow-up data indicated that the patients without anginal symptoms had a significantly better prognosis over a 7 year period than did those with symptoms: Annual mortality in the asymptomatic group was 2.7 percent compared with 5.4 percent in the group with angina (P 0.05). Although the patient population was a highly selective one and the matching categories were relatively broad, these results suggest that the presence of anginal symptoms may be an important independent correlate of prognosis in patients with coronary artery disease. The absence of angina did not preclude the presence of multivessel disease and did not necessarily imply a benign prognosis, because the yearly mortality rate was nearly 5 percent in the subgroup of asymptomatic patients with three vessel disease.
Decision-analytic techniques were used to evaluate the choice between an aortocoronary bypass operation and medical management in a set of hypothetical patients with coronary artery disease. The decision framework incorporates variables believed to have an important bearing on the choice of treatment. Probability estimates were obtained from two cardiologists and one cardiac surgeon. Patient preferences for the trade-off between years of survival and the quality of life as reflected by the severity of angina pectoris were made explicit by assigning utility values to alternative health outcomes. The results are expressed in terms of quality-adjusted years of life expectancy. Decision analysis favored operation for 13 of the 14 hypothetical patients, including patients with one- and two-vessel disease. The one patient for whom medical treatment was preferred had mild angina pectoris, severe left ventricular dysfunction, and a poor prognosis regardless of therapeutic modality. The results are sensitive to changes in the probability of long-term survival, but not to changes in operative mortality rates. In five patients, the physicians' clinical judgments favored medical treatment, whereas their decision-analysis-derived estimates of survival favored operation. Possible explanations for these discrepancies are discussed. A simplified cost-effectiveness analysis for patients in whom surgery was the optimal treatment indicated costs ranging from $1,500 to $250,000 per year of life gained and from $1,500 to $32,000 per quality-adjusted year of life gained.