Showing papers in "Circulation in 1982"

The stunned myocardium: prolonged, postischemic ventricular dysfunction.

Abstract: Myocardial ischemia has, for many decades, been viewed as an all-or-none process that causes myocardial necrosis when prolonged and severe, but whose effects are transient when it is brief or mild. In view of the evidence that the ischemic process may "hit, run and stun," perhaps our thinking about the consequences of myocardial ischemia should be expanded. According to this formulation, an ischemic insult not of sufficient severity of duration to produce myocardial necrosis may acutely affect myocardial repolarization and cause angina (hit); but these changes wane rapidly (run), when the balance between myocardial oxygen supply and demand has been reestablished. However, the ischemia may interfere with normal myocardial function, biochemical processes and ultrastructure for prolonged periods (stun). The severity and duration of these postischemic changes depend on the length and intensity of the ischemia, as well as on the condition of the myocardium at the onset of the ischemic episode. Furthermore, it is likely that when the myocardium is repeatedly stunned, it may exhibit chronic postischemic left ventricular dysfunction, an ill-defined condition. If prolonged, chronic postischemic left ventricular dysfunction can progress to myocardial scarring and ischemic cardiomyopathy, it may be important to determine how often it can be ameliorated by permanent improvement of myocardial perfusion by surgical treatment.

Right ventricular dysplasia: a report of 24 adult cases.

Abstract: Right ventricular dysplasia is characterized by an abnormality in the development of part of the right ventricular musculature. Patients with right ventricular dysplasia may present with ventricular tachycardia, supraventricular arrhythmias, right-heart failure or asymptomatic cardiomegaly. Twenty-two adult patients with right ventricular dysplasia who had recurrent ventricular tachycardia were seen during a 7-year period. The male/female ratio was 2.7:1. The mean age at the time of hospitalization was 39 years. All but one of the patients had ventricular tachycardia of a left bundle branch block configuration. With few exceptions, the T waves were inverted over the right precordial leads. The heart was usually enlarged and the pulmonary vasculature was usually normal. In six patients who had two-dimensional echocardiograms, all showed increased right ventricular diastolic dimensions. All patients had right ventricular angiography; the diagnosis of right ventricular dysplasia was substantiated during surgery in 12 patients and at autopsy in another. Two other patients who did not have arrhythmias had right ventricular dysplasia diagnosed by right- and left-heart angiography. Our unique experience, when combined with a literature review of 34 adult cases, permits a composite clinical profile of this condition in the adult.

Oxygen utilization and ventilation during exercise in patients with chronic cardiac failure.

Abstract: Muscular work requires the integration of cardiopulmonary mechanisms for gas exchange and O2 delivery. In patients with chronic cardiac failure, the response of these mechanisms may be impaired, and the pattern of O2 utilization (VO2) and gas exchange during exercise would thus provide an objective assessment of the severity of heart failure. Accordingly, rates of air flow, O2 uptake, CO2 elimination and minute ventilation were determined during progressive treadmill exercise in 62 patients with stable heart failure. Exercise cardiac output, systemic O2 extraction and lactate production were measured directly in 40 patients with heart failure of varying severity. As the severity of heart failure increased from class A to D, there was a progressive decrease in exercise capacity (from 1157 +/- 154 to 373 +/- 157 seconds) and maximum VO2 (23 +/- 3.2 to 8.4 +/- 1.5 ml/min/kg). These decreases corresponded with the reduced maximum cardiac output and stroke volume during exercise. The appearance of anaerobic metabolism (580 +/- 17 to 157 +/- 7 seconds of exercise) and the corresponding anaerobic threshold (17 +/- 0.34 to 7.1 +/- 1.5 ml/min/kg), determined noninvasively, were reproducible and correlated with the rise in mixed venous lactate concentration. No apparent untoward effects were experienced during or after the progressive exercise test. We conclude that the measurement of respiratory gas exchange and air flow during exercise is an objective, reproducible and safe noninvasive method for characterizing cardiac reserve and functional status in patients with chronic cardiac failure.

Survival of medically treated patients in the coronary artery surgery study (CASS) registry.

Abstract: The objective of this study was to evaluate the impact on survival of the anatomic extent of obstructive coronary artery disease and of two measures of left ventricular (LV) performance. This study is based on 20,088 patients without previous coronary artery bypass graft surgery who were enrolled in the registry of the National Heart, Lung, and Blood Institute Coronary Artery Surgery Study from 1975 to 1979. The cumulative 4-year survival of medically managed patients was analyzed to determine the survival of specific subsets of patients with obstructive coronary disease. The vital status of 99.8% of the patients was known. The 4-year survival of medically treated patients with no significant obstructive disease was 97%, in contrast to 92%, 84% and 68% in patients with one-, two- and three-vessel disease, respectively. The presence of left main coronary artery disease decreased survival significantly. The 4-year survival decreased from 70% to 60% in patients with three-vessel disease when significant obstruction of the left main coronary artery was also present. Patients with significant coronary artery disease who had an ejection fraction of 50--100%, 35--49%, and 0--34% had a 4-year survival of 92%, 83% and 58%, respectively. The systolic contraction pattern was assessed in five selected segments and given a score of 1--6, with a score of 1 for normal function, increasing to 6 if an aneurysm was present. In a patient with normal LV contraction in all five segments of the LV ventricular angiogram, the LV score would equal 5. Patients with an LV score of 5--11, 12--16 and 17--30 had 4-year survivals of 90%, 71% and 53%, respectively. Patients with good LV function (a score of 5--11) had a 4-year survival of 94%, 91% and 79% for one-, two- and three-vessel disease, respectively. Patients with poor left ventricular function (score of 17--30) had a 4-year survival rate of 67%, 61% and 42% in one-, two- and three-vessel disease, respectively. Thus, LV function is a more important predictor of survival than the number of diseased vessels.

Noninvasive determination of left ventricular end-systolic stress: validation of the method and initial application.

Abstract: the method and initial application Noninvasive determination of left ventricular end-systolic stress: validation of ISSN: 1524-4539 Copyright © 1982 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online 72514 Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 1982, 65:99-108 Circulation http://circ.ahajournals.org/content/65/1/99.citation located on the World Wide Web at: The online version of this article, along with updated information and services, is

Clinical classification of cardiac deaths.

Abstract: One hundred forty-two deaths among 743 men ages 50 - 65 years who had been examined and followed 5 - 10 years were investigated and classified on the basis of clinical information from medical and non-medical observers, ECGs and autopsies. A classification based on the condition of the circulation immediately before death appears to be most relevant to studies of sudden death. In 58% of the cases, the subjects collapsed abruptly and his pulse ceased without prior circulatory collapse (arrhythmic death); in 42%, the pulse ceased only after the peripheral circulation had collapsed (deaths in circulatory failure). Thirty-three percent of arrhythmic deaths and 10% of deaths in circulatory failure occurred in a setting of clinical evidence of acute ischemic heart disease (p less than 0.005). Forty-five percent of arrhythmic deaths were preceded by chronic congestive heart failure without circulatory collapse. Ninety-three percent of final illnesses that lasted less than 1 hour ended in arrhythmic deaths; 74% lasted more than 1 day ended in deaths in circulatory failure (p less than 0.001). Eighty-eight percent of deaths that occurred outside of the hospital were arrhythmic; 71% of deaths that occurred in the hospital were deaths in circulatory failure (p less than 0.001). Ninety percent of deaths in which the primary cause of the final illness was heart disease were arrhythmic; 86% of deaths in which the primary cause was other than heart disease were deaths in circulatory failure (p less than 0.001). Ninety-one percent of deaths precipitated by an acute cardiac event were arrhythmic; 98% precipitated by acute respiratory obstruction, hemorrhage, infection, stroke or other noncardiac events were deaths in circulatory failure (p less than 0.001).

Aggravation and provocation of ventricular arrhythmias by antiarrhythmic drugs.

Abstract: Antiarrhythmic drugs may aggravate or even induce ventricular arrhythmias. This type of adverse reaction is becoming more prevalent as the use of antiarrhythmic agents becomes more widespread. In a retrospective analysis of antiarrhythmic drug action, a worsening of arrhythmia was observed in 80 of 722 (11.1%) antiarrhythmic drug tests in 53 of 155 patients being treated for ventricular tachyarrhythmias. Aggravation of arrhythmias was defined by occurrence of a fourfold increase in the frequency of ventricular premature complexes, a 10-fold increase in repetitive forms, or the first emergence of sustained ventricular tachycardia coincident with time course of action of the particular drug under study. Such aggravation was noted with each of nine drugs tested: quinidine, procainamide, disopyramide, propranolol, metoprolol, aprindine, mexiletine, tocainide and pindolol. The frequency of this complication for a specific drug ranged from 5.9-15.8%. Blood drug concentrations were consistently in the therapeutic range. A study of the variability of ventricular arrhythmia during 48-hour Holter monitoring and exercise stress testing in no instance showed arrhythmia enhancement commensurate with that defining aggravation. Our data suggest that this potentially serious complication is not readily predictable and requires a systematic approach to antiarrhythmic drug testing before a patient is prescribed a long-range maintenance program.

The effect of aortic valve replacement on survival.

Abstract: We retrospectively studied 252 operated and 47 unoperated patients with isolated aortic valve disease. Aortic valve replacement (AVR) was recommended to all patients based on clinical and hemodynamic data. Preoperative hemodynamic and angiographic data were similar in operated and unoperated cohorts. Seventy-one percent of patients received a Bjork-Shiley prosthesis. Operative mortality was 7% for the entire surgical series. For patients with predominant aortic stenosis (AS), survival at 3 years was 87% in operated and 21% in unoperated patients (p less than 0.001). For patients with predominant aortic insufficiency (AI), the 5-year survival rate was 86% in operated and 87% in unoperated patients (NS). AVR improved long-term survival in patients with AS who had normal or impaired left ventricular (LV) function. In patients with AI and normal LV function, survival was not improved after AVR, but those with LV dysfunction who were operated on tended to survive longer (NS). Long-term survival of unoperated patients with AI was better than that in unoperated patients with AS. We conclude that AVR improves long-term survival in patients with AS who were normal or abnormal LV function, and that AVR does not change long-term survival in patients with AI, although those with LV dysfunction tended to survive longer.

Frequency of provoked coronary arterial spasm in 1089 consecutive patients undergoing coronary arteriography.

Abstract: We established the incidence of coronary artery spasm provoked by 0.4 mg of methergine in 1089 consecutive patients undergoing coronary angiography. The test was performed after routine coronary arteriography. Subjects included patients with angina, both typical and atypical, patients who had recently had myocardial infarction and patients with either valvular disease or congestive cardiomyopathy. Patients with spontaneous spasm, left main narrowing or severe three-vessel disease were excluded. One hundred thirty-four patients experienced focal spasm. Focal spasm was uncommon in patients with atypical precordial pain (1.2%), angina of effort (4.3%), valvular disease (1.95%) or cardiomyopathy (0%). It occurred most often in patients with angina at rest and less often in patients with angina both at rest and induced by exercise. Spasm was provoked in 20% of patients with recent transmural infarction, but in only 6.2% of patients studied later after infarction. Spasm was superimposed on fixed atherosclerotic lesions in 60% of the patients. No serious complications were encountered. Although the patients who underwent provocation tests in this study are not representative of all patients with coronary artery disease, spasm occurred in 20% of patients who experienced a coronary event and in 15% of patients who complained of chest pain.

Sudden death in hypertrophic cardiomyopathy: a profile of 78 patients.

Abstract: The clinical profile of 78 patients with hypertrophic cardiomyopathy who died suddenly (or experienced cardiac arrest and survived) was analyzed. At the time of cardiac catastrophe, 71% of the patients were younger than 30 years of age, 54% were without functional limitation and 61% were performing sedentary or minimal physical activity. Nineteen of the 78 patients (24%) were taking propranolol in apparently adequate dosages, indicating that this drug does not provide absolute protection against sudden death. No clinical or morphologic variable was particularly reliable in identifying patients at risk for sudden death. Forty-eight of 62 patients (77%) who died suddenly had a markedly increased ventricular septal thickness of 20 mm or more; however, mean septal thickness was similar in patients who died suddenly (25.2 +/- 0.9 mm) and in age- and sex-matched control patients with hypertrophic cardiomyopathy who have survived (23.6 +/- 0.8 mm). An abnormal ECG was present as often in patients who died suddenly as in control patients who have survived, (51 or 53, 96%). In addition, no particular cardiac symptom or hemodynamic variable (such as the magnitude of left ventricular outflow tract obstruction under basal conditions or left ventricular end-diastolic pressure) was characteristic of the patients with hypertrophic cardiomyopathy who died suddenly.

Timolol-related reduction in mortality and reinfarction in patients ages 65-75 years surviving acute myocardial infarction. Prepared for the Norwegian Multicentre Study Group.

Abstract: Long-term treatment with timolol in patients ages 65--75 years who survived myocardial infarction was related to a significant reduction, compared with placebo, in overall mortality (p less than 0.05), total cardiac death (p less than 0.01), sudden death (p less than 0.05) and reinfarction (p less than 0.01). The analyses were based on 732 patients (384 taking placebo and 348 timolol) from a cohort of 1884 patients in the Norwegian multicenter timolol study. The dosage of timolol was 10 mg twice daily and the patients were followed for 12--33 months (mean 17 months). There were 83 deaths in the placebo group and 52 deaths in the timolol group, a reduction of 35.5%. There were 69 initial reinfarctions in the placebo group and 38 in the timolol group, a reduction of 39.2%. There was no difference in the reduction of mortality and reinfarction between patients 65--75 years of age and patients less than 65 years of age. The incidence of side effects, the number of withdrawals and the reasons for withdrawal were similar in older and younger patients. We conclude that age should not be a decision-making factor concerning timolol therapy in postinfarct patients.

Significance of the angiographic morphology of localized coronary stenoses: histopathologic correlations.

Abstract: Postmortem coronary angiographic morphology was correlated with histologic sections of 73 localized subtotal coronary artery stenoses (50-99% reduction of luminal diameter) to determine whether complicated or uncomplicated atherosclerotic lesions could be detected angiographically. Lesions were divided into two types, according to angiographic morphology: Type I stenoses had smooth borders, an hourglass configurations, and no intraluminal lucencies; type II stenoses had irregular borders or intraluminal lucencies. Histologic sections were also divided into two types: "uncomplicated" stenoses had fatty or fibrous plaques with intact intimal surfaces and no superimposed thrombus; "complicated" stenoses manifested plaque rupture, plaque hemorrhage, superimposed partially occluding thrombus, or recanalized thrombus. Among 35 lesions with type I angiographic morphology, four (11.4%) were complicated lesions histologically. Among the 38 stenoses showing type II angiographic morphology, 30 (78.9%) were complicated lesions. Postmortem angiography thus had a sensitivity of 88% and specificity of 79% for detecting complicated stenoses on the basis of irregular borders or intraluminal lucencies. Pathologic studies have shown that acute occlusive thrombosis of a coronary artery is usually associated with complicated atherosclerotic stenoses. Thus, complicated lesions represent a greater risk factor for acute myocardial infarction or sudden death than do uncomplicated lesions. This study suggests that coronary stenoses characterized angiographically by irregular borders or intraluminal lucencies are probably the clinically more dangerous "complicated" type.

Baroreceptor reflex control of heart rate: a predictor of sudden cardiac death.

Abstract: SUMMARY To explore the possibility that the analysis of autonomic reflexes could identify subgroups at high risk of ventricular fibrillation, we studied chronically instrumented mongrel dogs randomly divided into two groups. Twelve dogs served as controls and 17 were studied 3-4 weeks after anterior wall myocardial infarction (MI). After recovery, the dogs were given bolus i.v. injections of phenylephrine, 10 tg/kg, and nitroprusside, 100 ptg/kg, to raise or lower systolic arterial pressure 30-50 mm Hg. The RR intervals were plotted against the systolic pressure during the preceding beats, and the slope (baroreflex slope) was determined by least-squares-fit linear regression. On a subsequent day, the left circumflex coronary artery was occluded for 2 minutes, beginning with the last minute of an exercise stress test and continuing for 1 minute after the cessation of exercise (MI group only). The dogs could be divided into two groups based on their response to this test; 11 dogs (65%) had ventricular fibrillation (susceptible), whereas six dogs (35%) did not (resistant). The baroreflex slope (control 20.49 ± 8.59; resistant 10.95 ± 4.68; susceptible 4.60 ± 1.77 msec/mm Hg) and the heart rate response to a 30-mm Hg increase in arterial pressure (control - 56.5 ± 14.8; resistant -40.0 ± 12.2; susceptible - 12.9 ± 5.0 beats/min) for the susceptible dogs were significantly different from those of the control and resistant dogs. This may indicate that the resistant dogs have a greater capability to activate strong vagal reflexes, which reduce vulnerability to ventricular fibrillation. We conclude that anterior wall MI significantly attenuates the baroreceptor reflex control of heart rate and that analysis of the heart rate response to arterial pressure increases allows identification of subgroups of dogs at higher risk for ventricular fibrillation. A prospective study in patients with MI is warranted.

A scanning and transmission electron microscopic study of an infected endocardial pacemaker lead.

Abstract: We studied the pacemaker lead that had been removed from a patient who suffered three sequential episodes of Staphylococcus aureus bacteremia. This organism was recovered from the surface of the lead. Scanning electron microscopy showed differential colonization of the pacemaker lead. The metal tip, the inner surface and the internal wires were covered with a heavy biofilm of bacteria. The outer silastic surface had no biofilm adherent to it; instead, well-spaced bacterial cells were seen. These observations illustrate why infection of implantable devices persists despite intensive antibiotic chemotherapy.

Serial thallium-201 myocardial imaging after dipyridamole infusion: diagnostic utility in detecting coronary stenoses and relationship to regional wall motion.

Abstract: After a 4-minute i.v. dipyridamole infusion, 0.14 mg/kg/min, serial thallium-201 scans were obtained in 60 patients undergoing cardiac catheterization. Forty patients had significant (greater than or equal to 50% stenosis) coronary artery disease (CAD), and 20 patients had normal coronary arteries or trivial lesions. The images were graded qualitatively for thallium activity by three observers. Sensitivity was 93% (37 of 40) and specificity was 80% (16 of 20). The sensitivity and specificity of the thallium-201 study were not affected by the extent of CAD, the presence of Q waves, or propranolol therapy. Twenty-seven of 37 patients who had initial defects (73%) had complete thallium redistribution of one or more defects. Patient-by-patient analysis using a regression model of all patients showed that the fate of a segmental thallium defect predicted abnormal wall motion by angiography better than ECG Q waves. The presence of propranolol therapy or collaterals did not significantly affect the thallium redistribution results. We conclude that qualitative interpretation by multiple observers of thallium images after dipyridamole infusion is a highly sensitive and specific test for CAD. After dipyridamole, as with exercise stress, the extent of thallium redistribution is related to the degree of myocardial wall motion abnormality.

Limitation of experimental infarct size by an angiotensin-converting enzyme inhibitor.

Abstract: The effects of angiotensin-converting enzyme inhibitor (CEI) SQ14225 on infarct size and regional myocardial blood flow were studied in 21 anesthetized dogs subjected to 6 hours of coronary occlusion. An area of myocardium at risk of necrosis was determined in vivo after 15 minutes of coronary occlusion but before CEI treatment (AR1) using an autoradiographic technique and after treatment after 6 hours of coronary occlusion (AR2) using a fluorescent dye technique. An in vitro area at risk (AR8), which measures coronary bed size, was determined by injecting Monastral dye postmortem. Infarct size was determined by planimetry of unstained myocardium after incubating heart slices in triphenyltetrazolium chloride. Regional myocardial blood flow (RMBF) was measured by injecting tracer microspheres simultaneously with measurements of AR1 and AR2. In 11 saline-treated control dogs (group A), infarct size averaged 93 ± 8% of AR1, 96 i 2% of AR2 and 75 ± 6% of AR9, respectively. In 10 dogs treated with CEI (0.25 mg/kg/hour) between 30 minutes and 6 hours after coronary occlusion (group B), infarct size was smaller and averaged 68 ± 5% of AR1 (p < 0.01), 79 ± 5% of AR2 (p < 0.005), and 57 ± 7% of AR3 (p < 0.05). RMBF in the ischemic zone remained constant in group A but increased by 62 ± 26% in group B (p < 0.025). In group B, mean arterial pressure decreased from 115 ± 6 to 103 ± 7 mm Hg (p < 0.025) between 30 minutes and 6 hours after coronary occlusion and left atrial pressure decreased from 9.0 ± 1.8 to 5.7 ± 0.8 mm Hg (p < 0.0025). These measurements did not change in group A. Thus, CEI is potent in reducing infarct size in the dog after coronary occlusion. It may act by increasing collateral flow to the ischemic zone and reducing afterload.

Percutaneous transluminal coronary angioplasty immediately after intracoronary streptolysis of transmural myocardial infarction.

Abstract: Percutaneous transluminal coronary angioplasty (PTCA) was performed in 21 patients with acute myocardial infarction (AMI) treated by intracoronary infusion of streptokinase within 8 hours after the onset of symptoms. Streptolysis therapy began a mean of 3.6 +/- 1.2 hours (+/- SD) after the onset of symptoms. The vessel was occluded in 14 patients and highly stenosed in seven. After the infusion of 67,300 +/- 63,200 IU of streptokinase over 26.1 +/- 21.5 minutes, patency of the occluded vessels was reached. PTCA as performed 20-60 minutes after the end of streptokinase treatment in 19 patients and 24 and 31 hours after treatment in two patients. The dilation was successful in 17 patients (81%). The degree of vessel obstruction was reduced from 90.2 +/- 7.3% to 58.6 +/- 19.5% (area method) and from 71.4 +/- 12.4% to 39.2 +/- 19.7% (diameter method). The improvement was 31.5 +/- 18.4% and 32.2 +/- 19.3%, respectively. No reocclusion was induced by PTCA. Twenty patients were discharged. One died during hospitalization; at autopsy, the treated vessel was still patent. During the follow-up period, two reinfarctions and one asymptomatic reocclusion occurred. The clinical findings during the hospital course and the follow-up period were compared with those of a control group of 18 patients with AMI and comparable coronary stenoses who were treated only with streptokinase infusion. Four of these patients had a reinfarction during the hospital course, and three died during the follow-up period. PTCA can be performed safely and successfully immediately after intracoronary infusion of streptokinase in patients with AMI. By reducing the subtotal stenosis, this treatment contributes to the reperfusion of the ischemic myocardium, diminishes the risk of a reocclusion and seems to improve the prognosis.

Influence of heart rate and inhibition of autonomic tone on the QT interval.

Abstract: To evaluate whether heart-rate-induced changes of the QT interval are dependent on autonomic tone, we studied 13 healthy subjects, mean age 67.5 years. The maximal uncorrected QT from leads I, II, V1 and V6 was determined during atrial pacing at 90 beats/min and 130 beats/min before and after i.v. administration of propranolol, 0.1 mg/kg, and atropine, 0.02 mg/kg. Significant reductions (p less than 0.01) of QT were induced by the paced increases in heart rate before drugs (10%), after propranolol (10%) and after the combination of atropine and propranolol (9%). Propranolol caused no significant change in the QT interval when heart rate was held constant by pacing. In contrast, atropine produced rate-independent reductions of QT interval (5%) in subjects with beta-adrenergic blockade (p less than 0.05). Bazett's formula for heart-rate correction of the QT interval (QTc) was not applicable for atrial overdrive pacing, as it gave proportionately longer QTc values at higher heart rates. These results show that heart rate is a major determinant of the duration of the QT interval and that paced changes in heart rate induce QT-interval responses that are essentially uninfluenced by autonomic tone. The rate-dependent effect of the QT interval produced by elimination of cholinergic tone suggests a direct influence of cholinergic activity on the repolarization of ventricular myocardium.

Effects of alcohol use and other aspects of lifestyle on blood pressure levels and prevalence of hypertension in a working population.

Abstract: The relationship between alcohol consumption and blood pressure was studied in 491 males, ages 20-45 years, who volunteered to complete a health questionnaire and submit to standardized measurements of blood pressure, heart rate and body size. Average weekly alcohol consumption correlated with systolic pressure (r = 0.18) but not diastolic pressure. Systolic pressure increased progressively with increasing alcohol consumption, with no obvious threshold effect. In moderate and heavy drinkers (53% of the population studied), the prevalence of systolic hypertension (greater than or equal to 140 mm Hg) was four times that of teetotalers. The effect of alcohol on systolic blood pressure was independent of the effects of age, obesity, cigarette smoking and physical activity. Ex-heavy drinkers had blood pressures similar to those of teetotalers, suggesting that the effect of alcohol is reversible. Cigarette smokers had lower diastolic pressures than nonsmokers, an effect independent of obesity. The linear correlation between alcohol consumption and systolic blood pressure and the lower blood pressures in exdrinkers suggest a cause-and-effect relationship. The results indicate that alcohol ranks close to obesity as a potentially preventable cause of hypertension in the community.

Survival in subgroups of patients with left main coronary artery disease. Veterans Administration Cooperative Study of Surgery for Coronary Arterial Occlusive Disease.

Abstract: This report presents the 42-month survival experience of 91 patients with a significant lesion of the left main coronary artery in the Veterans Administration Cooperative Study of Coronary Bypass Surgery. Survival in surgical patients was significantly better than that in the medical group (p = 0.016), even after adjustments were made for two important differences in baseline characteristics--duration of angina and high risk by angiographic criteria--between the two groups (p = 0.019). Subgroups based on severity of left main stenosis and on left ventricular (LV) function showed significant trends in favor of surgery in patients with more than 75% left main stenosis and in those with abnormal LV function. A similar but nonsignificant trend was seen in the two subgroups with 50-75% stenosis or with normal LV function. The surgical benefits were not significantly different between the categories of the subgroups defined separately by stenosis and LV function. Low-, middle- and high-risk subgroups based on four noninvasive clinical predictors also showed significantly improved survival with surgery in the high-risk group. The low-risk groups showed a slight, nonsignificant disadvantage with surgical treatment. These data support the view that patients with left main disease are not a homogeneous group. High- and low-risk subgroups with different outcomes and responses to treatment can be delineated by angiographic or clinical criteria. For most patients with left main disease, coronary artery bypass grafting offers improved longevity.

Prostacyclin-induced acute pulmonary vasodilation in primary pulmonary hypertension.

Abstract: To evaluate the effects of prostacyclin (prostaglandin I2) on pulmonary vascular tone in primary pulmonary hypertension (PPH), we performed right-heart catheterization on seven patients with PPH and made hemodynamic measurements before and after infusing incremental doses of prostacyclin. In maximal doses of 2-12 mg/kg/min (mean 5.7 +/0 3.1 ng/kg/min), prostacyclin reduced mean pulmonary arterial pressure from 62 +/- 15 to 55 +/- 16 mm Hg (p less than 0.05) and total pulmonary resistance from 17.1 +/- 8.7 to 9.7 +/- 5.9 units (p less than 0.005), and increased cardiac output from 4.22 +/- 1.64 to 6.57 +/- 2.04 l/min (p less than 0.01). Heart rate increased from 83 +/- 13 to 94 +/- 11 beats/min (p = 0.1) and mean systemic arterial pressure decreased from 90 +/- 12 to 77 +/- 4 mm Hg (p = 0.055). Three patients who received a continuous infusion of prostacyclin for 24-48 hours had sustained reductions in total pulmonary resistance during the infusion period. These data demonstrate that prostacyclin can increase cardiac output and reduce pulmonary arterial pressure and resistance in PPH.

Detection of left ventricular thrombus by two-dimensional echocardiography: sensitivity, specificity, and causes of uncertainty.

Abstract: To define the sensitivity, specificity and predictive accuracy of two-dimensional echocardiographic detection of left ventricular thrombus, the echocardiograms of 78 patients who had independent proof of the presence or absence of a left ventricular thrombus were interpreted without knowledge of any clinical data. The presence of thrombus was established by autopsy in four patients, by aneurysmectomy in three, and by indium-111 platelet imaging in 15; the absence of thrombus was proved by autopsy in 55 patients and by aneurysmectomy in one patient. The characteristics of true-positive and false-positive echocardiograms, interobserver variability, and clinical features associated with proved thrombus were also defined. The echocardiogram was positive for thrombus in 22 patients, equivocal in seven and negative in 49. For detection of thrombus, a positive or equivocal echocardiogram had a sensitivity of 95% (21 of 22), a specificity of 86% (48 of 56), and a predictive value of 72% (21 of 29); the predictive value of a negative study was 98% (48 of 49). Considering positive and equivocal studies separately, the predictive value of a positive study was 86% (19 of 22), while that of an equivocal study was only 29% (two of seven). Compared with patients who had no thrombus, patients with proved thrombus had a higher prevalence of electrocardiographic transmural anterior infarction (86% vs 13%), left ventricular aneurysm (73% vs 5%), and clinical systemic emboli (36% vs 7%) (all p less than 0.05). These clinical features help to identify a subset of patients most likely to have left ventricular thrombi who may benefit from echocardiography. Two-dimensional echocardiography is highly sensitive in detecting left ventricular thrombus, but false-positive studies are relatively common. Several echocardiographic criteria derived from analysis of the true and false positives in this study may help minimize diagnostic errors.

Microvascular spasm in the cardiomyopathic Syrian hamster: a preventable cause of focal myocardial necrosis.

Abstract: The cardiomyopathic Syrian hamster develops focal myocardial necrosis beginning at 1 month of age, which leads to eventual ventricular failure within 1 year. The pathogenesis of this myocytolytic necrosis is unknown. Based on the nature of the cell necrosis, cytochemical evidence of vascular alterations, and the sensitivity of the hamsters to catecholamines and other vasoactive substances, we believe that the cardiomyopathy may be mediated by abnormalities of the microcirculation. Nonetheless, until the present study, no significant changes have been observed in these vessels. To elucidate the pathogenesis of this disease, we perfused living cardiomyopathic hamsters with silicone rubber solutions, which revealed numerous areas of microvascular constriction, diffuse vessel narrowing and luminal irregularity. Fixed structural lesions in these vessels could not be demonstrated. Pretreatment of young hamsters with verapamil during the period when they normally develop myocardial necrosis prevented myocytolytic lesions and abolished microvascular hyperreactivity. We believe that focal, transient spasm of small blood vessels, probably secondary to vasoactive substances, may cause myocytolytic necrosis (a form of reperfusion injury) in this model. This may also be a multifactorial disease with myocellular as well as vascular abnormalities leading to myocardial degeneration. The similarity of this disease to human and experimental cardiomyopathy suggests that microvascular spasm may be a common denominator of many different cardiomyopathic syndromes.

Evaluation of a QRS scoring system for estimating myocardial infarct size. I. Specificity and observer agreement.

Abstract: We evaluated a simplified version of a previously developed QRS scoring system for estimating infarct size using observations of Q- and R-wave durations and R/Q and R/S amplitude ratios in the standard 12-lead ECG. Groups of subjects with a minimal likelihood of having myocardial infarcts and minimal likelihood of having common noninfarction sources of QRS modification were studied to establish the specificity of each of the 37 criteria. Only two criteria required modification to achieve 95% specificity. These 37 criteria form the basis of a 29-point QRS scoring system. A 98% specificity was achieved when a score of more than 2 points was required to identify a myocardial infarct. Fifty patients were studied to determine the intra- and interobserver agreement with this scoring system. Each criterion achieved at least 91% intra- and interobserver agreement. These impressive levels of specificity and observer agreement must be matched by high sensitivity of the scoring system and a good correlation between the point score and infarct size in patients with proven infarcts if the point score is to be useful for detecting and sizing infarcts. Sensitivity and correlation between point score and infarct size are evaluated in later studies in this series. The standard ECG is inexpensive and can be obtained repetitively and noninvasively; its QRS complex may be an important means of estimating the size, presence and location of myocardial infarcts.

Exacerbation of vasotonic angina pectoris by propranolol.

Abstract: Using a double-blind protocol, we investigated the use of propranolol in patients with coronary artery spasm as assessed by subjective and objective variables. Both low-dose (40 mg every 6 hours) and high-dose (160 mg every 6 hours) propranolol were administered. At both doses, the duration of angina attacks was significantly prolonged but the frequency was not. We conclude that propranolol at doses up to 160 mg every 6 hours as single therapy is frequently detrimental in angina pectoris due to coronary artery spasm and should not be used as the sole treatment of this disorder.

Measurement of absolute left ventricular volume from gated blood pool studies.

Abstract: A new method for obtaining absolute left ventricular volume from gated blood pool studies was evaluated in a torso phantom and in 35 patients who also underwent single-plane contrast ventriculography. Gated 400 left anterior oblique and static anterior views were acquired. Left ventricular volume at end-diastole was given by the ratio of the attenuation-corrected end-diastolic count rate from the gated study to the count rate per milliliter from a blood sample. Attenuation correction was made by dividing the end-diastolic count rate by e ud, where u = the linear attenuation coefficient of water and d = the distance from the skin marker to the center of the left ventricle in the anterior view divided by sin 400 to yield the depth of left ventricle in the left anterior oblique view. In the phantom studies, the correlation between radionuclide and true volume was 0.99 (radionuclide = 1.03 true − 3 ml); the standard error of the estimate was 8 ml. In the patient studies, the radionuclide end-diastolic volume was used to calibrate the left ventricular time-activity curve, yielding left ventricular volume throughout the cardiac cycle. The correlation between radionuclide and angiographic enddiastolic volume was 0.95 (radionuclide = 0.97 angiographic + 3 ml); the standard error of the estimate was 36 ml. The correlation between radionuclide and angiographic end-systolic volume was 0.95 (radionuclide − 1.01 angiographic + I ml); the standard error of the estimate was 33 ml. This method permits direct determination of absolute left ventricular volume without assumptions about the shape of the ventricle or the necessity of using regression equations to convert volume “units” to true volume.

Experimental validation of quantitative coronary arteriography for determining pressure-flow characteristics of coronary stenosis.

Abstract: SUMMARY The applicability of classic fluid dynamic equations to tapering stenoses in vasoactive, flexible coronary arteries in vivo and the validity of quantitative coronary arteriography was tested by comparing experimentally measured and x-ray-predicted pressure gradients at equal flows for left circumflex stenoses in five dogs chronically instrumented with a balloon. occluder, flow probe, and proximal and distal catheters for.injection of contrast media or recording distal coronary pressure. Arterial borders on cut-film orthogonal arteriograms were digitized and computer processed into a three-dimensional reconstruction of the stenosis. The total pressure gradient was calculated from stenosis dimensions using classic fluid dynamic equations. Over the full range of flow, the correlation of x-ray-predicted and experimentally measured pressure gradient for 51 separate stenoses was y = 1.11x ± 0.75, r = 0.95, p < 0.001, with a standard deviation about the regression line of 9.4 mm Hg and with 95% of x-ray-predicted values falling within ± 18.5 mm Hg of the experimentally measured values (95.% confidence limits). Mean experimentally measured and x-ray-predicted pressure gradients were 10.1 7.7 mm Hg (± SD) and 10.9 ± 5.6 mmn Hg at low flow and 48.2 ± 23.1 mm Hg and 55.8 ± 28.8 mm Hg at high flow, respectively. The mean difference was 3.9 ± 4.3 mm Hg at rest flow and 11.9 ± 10.5 mm Hg at high flow. For all data over the entire range of flows, the frequency distribution of differences between x-ray-predicted and experimentally measured gradients was a bell-shaped curve with a peak, or mean difference, of ± 4 mm Hg, a standard deviation of ± 9.8 mm Hg and 95% confidence limits for individual values of ± 19.6 mm Hg. These data demonstrate the validity of applying classic fluid dynamic theory to tapering stenoses in vivo. Quantitative coronary arteriography on the average or in individual instances approximately predicts the pressure gradient-flow characteristics of coronary arterial stenoses in intact animals. However, as indicated by the above measures of variability, there is considerable scatter in x-ray predictions that limits its applicability to individual clinical cases. We believe that this scatter is a result of difficulties in visually tracing arterial borders on arteriograms and can most likely be reduced by automatic border recognition techniques.

Blood flow reductions in stenosed canine coronary arteries: vasospasm or platelet aggregation?

Abstract: In 67 dogs with a 60-80% coronary stenosis produced by an external constricting plastic ring, blood flow measured with an electromagnetic flowmeter showed cyclical flow reductions of varying magnitude and duration, and then an abrupt return to control flow. In 45 dogs, heparin did not prevent these flow reductions, but ibuprofen (Motrin) or indomethacin abolished them. With incremental doses of each of these drugs, the cyclical flow reduction and the platelet function in vitro were diminished proportionately. In 10 more dogs, during low flow, pinching or poking the narrowed vessel suddenly restored normal flow. Topical application of papaverine and nitroglycerin proximal to the stenosis did not abolish the cyclic flow reduction, although a transient fall in systemic pressure indicated that they had been absorbed. Seven dogs had the constricting cylinder and flow probe chronically implanted for 4-6 weeks. A single oral dose of aspirin, 20 mg/kg, abolished their cyclic flow reductions for 2-4 days. In five dogs with 70% stenosis in the circumflex coronary artery, coronary arteriography was performed before coronary flow reduction and when coronary blood flow was low. This showed that there was a considerable additional reduction in the size of the mechanically constricted lumen during spontaneous flow reduction. In one dog, a nonopacified mass was dislodged from the area of constriction in 67 msec and this restored the lumen to its control diameter. Similar rapid clearing was filmed in two more dogs. In no case was vasospasm observed. These results suggest that obstruction from platelets aggregated in the narrowed lumen caused the cyclic flow reductions.

Intermittent brief periods of ischemia have a cumulative effect and may cause myocardial necrosis.

Abstract: We investigated the effects of brief intermittent periods of ischemia on myocardial viability. Brief periodic coronary occlusions were produced up to 18 times by inflating and deflating the balloon of an intracoronary No. 2F catheter for periods of 15, 10 or 5 minutes, followed by 15-minute periods of reperfusion. Creatine kinase (CK) release, triphenyl tetrazolium chloride staining, and light and electron microscopy were used to detect the presence of myocardial necrosis. For the study of CK release, blood was taken from the great cardiac vein and the aorta before and at 5-minute intervals during each left anterior descending coronary occlusion, as well as during and 1, 5, 10 and 15 minutes after balloon deflation. In seven of 24 dogs with 15-minute occlusions, in five of 21 dogs with 10-minute occlusions, and in three of 32 dogs with 5-minute occlusions, small but distinct areas of subendocardial necrosis were present. In all dogs with morphologic proof of necrosis, there was periodic release of CK into the great cardiac vein, which peaked immediately after reperfusion, reflecting CK washout. Thus, brief periods of ischemia, which when single do not cause necrosis, have a cumulative effect and may cause myocardial necrosis. This mechanism of necrosis may be relevant clinically in patients with frequent anginal episodes. Since many dogs of this study did not have any myocardial necrosis, the findings also suggest that intermittent reperfusion has a beneficial effect and may prevent necrosis, even when total occlusion time exceeds 200 minutes.

A comparison of the acute and long-term hemodynamic effects of ventricular inhibited and atrial synchronous ventricular inhibited pacing.

Abstract: Sixteen patients treated with a noninvasively programmable pacemaker were examined after a prolonged period of ventricular inhibited (VVI) and atrial synchronous ventricular inhibited (VDD) pacing. Maximal working capacity was determined by bicycle ergometry. Atrial and ventricular rates, brachial artery cuff pressure and breathing rate were determined at rest and during exercise. There was a mean increase in working capacity of 24% with VDD compared with VVI pacing (p less than 0.001). Thirteen of the patients were catheterized. During VDD pacing, cardiac output was significantly higher, particularly during exercise (+/- 32%) due to the capability of heart rate increase and despite a substantial compensatory stroke volume increase during VVI pacing. Arteriovenous oxygen difference was much higher during VVI pacing, reaching 164 +/- 14 ml/l during the highest work load, while the corresponding level during VDD pacing was 140 +/- 14 ml/l (p less than 0.001). During exercise, arterial blood lactate was significantly higher during VVI than during VDD pacing. Heart size was significantly smaller, 568 +/- 98 vs 530 +/- 96 ml/m2 BSA (p less than 0.05), during VDD pacing a questionnaire was completed by the patients to evaluate subjective symptoms and pacemaker preference. This part of the study favored the VDD mode of pacing. The conclusion of this study is that VDD pacing is superior to VVI pacing.