Showing papers in "Circulation in 1984"

Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation

Abstract: We evaluated the accuracy of a noninvasive method for estimating right ventricular systolic pressures in patients with tricuspid regurgitation detected by Doppler ultrasound. Of 62 patients with clinical signs of elevated right-sided pressures, 54 (87%) had jets of tricuspid regurgitation clearly recorded by continuous-wave Doppler ultrasound. By use of the maximum velocity (V) of the regurgitant jet, the systolic pressure gradient (delta P) between right ventricle and right atrium was calculated by the modified Bernoulli equation (delta P = 4V2). Adding the transtricuspid gradient to the mean right atrial pressure (estimated clinically from the jugular veins) gave predictions of right ventricular systolic pressure that correlated well with catheterization values (r = .93, SEE = 8 mm Hg). The tricuspid gradient method provides an accurate and widely applicable method for noninvasive estimation of elevated right ventricular systolic pressures.

The relationships among ventricular arrhythmias, left ventricular dysfunction, and mortality in the 2 years after myocardial infarction.

Abstract: We examined the relationships among ventricular arrhythmias, left ventricular dysfunction, and mortality after the occurrence of myocardial infarction in 766 patients who enrolled in a nine-hospital study and underwent two special tests. Frequency and repetitiveness of ventricular premature depolarizations (VPDs) were determined by computer analysis of predischarge 24 hr electrocardiographic recordings. The left ventricular ejection fraction (LVEF) was determined by radionuclide ventriculography and dichotomized at its optimal value of 30%. Frequency of VPDs was divided into three categories: (1) less than one per hour, (2) one to 2.9 per hour, and (3) three or more per hour. Repetitiveness of VPDs was also divided into three categories: (1) no repetitive VPDs, (2) paired VPDs, and (3) VPD runs. These variables were related, one at a time and jointly, to total mortality and to deaths caused by arrhythmias. The hazard ratios for dying in the higher or highest risk stratum vs the lower or lowest stratum for each variable (adjusted for the effects of the others) were: LVEF below 30%, 3.5; VPD runs, 1.9; and VPD frequency of three or more per hour, 2.0. There were no significant interactions among the three variables with respect to effects on the risk of mortality. There was a suggestion of an interaction between each risk variable and time after infarction. LVEF below 30% was a better predictor of early mortality (less than 6 months) and the presence of ventricular arrhythmias was a better predictor of late mortality (after 6 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Primary pulmonary hypertension: natural history and the importance of thrombosis.

Abstract: A long-term retrospective follow-up study was made of 120 patients (33 male, 87 female patients) with primary pulmonary hypertension--diagnosed by strict clinical and hemodynamic criteria--to obtain a better understanding of the natural history and possible pathogenetic mechanisms of the disease. The mean age at diagnosis was 34 (3 to 64) years, but only 24 patients (21%) remained alive 5 years later. Lung tissue obtained at autopsy from 56 patients revealed two major pathologic types: thromboembolic pulmonary hypertension in 32 patients (57%) and plexogenic pulmonary arteriopathy in 18 (32%). Thus, in more than half the patients undergoing autopsy the major histologic feature was thrombi without any evidence of plexiform lesions. The two groups were similar with respect to their clinical and hemodynamic features and short survival. Of the variables tested for prognostic importance by stepwise multivariate analysis, only two were significant: pulmonary arterial oxygen saturation (p less than .00001) and anticoagulant therapy (p = .01). Anticoagulant therapy is recommended for patients with primary pulmonary hypertension.

Continuous measurement of left ventricular volume in animals and humans by conductance catheter.

Abstract: An eight-electrode conductance catheter previously developed by us and used to determine stroke volume in dogs was applied in human beings and dogs to measure absolute left ventricular volume quantitatively. For calibration we developed the formula V(t) = (1/alpha)(L2/sigma b)G(t) - Vc, where V(t) is time-varying left ventricular volume, alpha is a dimensionless constant, L is the electrode separation, sigma b is the conductivity of blood obtained by a sampling cuvette, and G(t) is the measured conductance within the left ventricular cavity. Vc is a correction term caused by the parallel conductance of structures surrounding the cavity and is measured in two ways. The first method, applicable in the anesthetized animal, consists of temporary reduction of volume to zero by suction. The second method uses a transient change in sigma b by injection of a small bolus of hypertonic saline (dogs) or 10 ml of cold glucose (humans) into the pulmonary artery. The validity of the formula was previously established for the isolated postmortem canine heart. The predicted linearity, slope constant alpha, and accuracy of Vc for the left ventricle in vivo were investigated by comparing the conductance volume data with results from independent methods: electromagnetic blood flow measurement for stroke volume and indicator dilution technique for ejection fraction (dogs), thermal dilution for cardiac output (12 patients), and single-plane cineventriculography for V(t) (five patients). In all comparisons, linear regression showed high correlation (from r = .82 [n = 46] to r = .988 [n = 20]) while alpha, with one exception, ranged from 0.75 to 1.07 and the error in Vc ranged from 0.5% to 16.5% (mean 7%). After positioning of the catheter, no arrhythmias were observed. It is concluded that the conductance catheter provides a reliable and simple method to measure left ventricular volume, giving an on-line, time-varying signal that is easily calibrated. Together with left ventricular pressure obtained through the catheter lumen, the instrument may be used for instantaneous display of pressure-volume loops to facilitate assessment of left ventricular pump performance.

Pulsed Doppler echocardiographic determination of stroke volume and cardiac output: clinical validation of two new methods using the apical window.

Abstract: Two methods of measuring stroke volume and cardiac output with pulsed Doppler two-dimensional echocardiography were developed and validated against the thermodilution technique in 39 patients, 33 of which were in an intensive care unit. With the use of the apical four-chamber view, a mitral inflow method combined the velocity of left ventricular inflow at the mitral anulus with the cross-sectional area of the anulus calculated from its diameter at middiastole (area = pi r2). From the apical five-chamber view a left ventricular outflow method combined the velocity of left ventricular outflow with the cross-sectional area of the aortic anulus calculated from its diameter during early systole (parasternal long-axis view). Measurements with the mitral inflow and left ventricular outflow methods were obtained in 35 of 39 (90%) and 39 of 39 (100%) patients, respectively. Validation of the mitral method excluded patients with mitral regurgitation (n = 11) and validation of the left ventricular outflow method excluded those with aortic regurgitation (n = 4). Good correlations were observed between thermodilution and Doppler measurements of stroke volume and cardiac output for both the mitral anulus method (R = .96 and .87, respectively) and the left ventricular outflow method (R = .95 and .91, respectively). The results of the two methods correlated well with each other in patients without regurgitant valve lesions. A greater interobserver variability was observed with the mitral anulus method, which was related solely to greater variability in measuring the annular diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI Type II Coronary Intervention Study.

Abstract: In the National Heart, Lung and Blood Institute Type II Coronary Intervention Study, patients with Type II hyperlipoproteinemia and coronary artery disease (CAD) were placed on a low-fat, low-cholesterol diet and then were randomly allocated to receive either 6 g cholestyramine four times daily or placebo. This double-blind study evaluated the effects of cholestyramine on the progression of CAD as assessed by angiography. Diet alone reduced the low-density lipoprotein cholesterol 6% in both groups. After randomization, low-density lipoprotein cholesterol decreased another 5% in the placebo group and 26% in the cholestyramine-treated group. Coronary angiography was performed in 116 patients before and after 5 years of treatment. CAD progressed in 49% (28 of 57) of the placebo-treated patients vs 32% (19 of 59) of the cholestyramine-treated patients (p less than .05). When only definite progression was considered, 35% (20 of 57) of the placebo-treated patients vs 25% (15 of 59) of the cholestyramine-treated patients exhibited definite progression; the difference was not statistically significant. However, when this analysis was performed with adjustment for baseline inequalities of risk factors, effect of treatment was more pronounced. Of lesions causing 50% or greater stenosis at baseline, 33% of placebo-treated and 12% of cholestyramine-treated patients manifested lesion progression (p less than .05). Similar analyses with other end points (percent of baseline lesions that progressed, lesions that progressed to occlusion, lesions that regressed, size of lesion change, and all cardiovascular end points) all favored the cholestyramine-treated group, but were not statistically significant. Thus, although the sample size does not allow a definitive conclusion to be drawn, this study suggests that cholestyramine treatment retards the rate of progression of CAD in patients with Type II hyperlipoproteinemia.

Exercise cardiac output is maintained with advancing age in healthy human subjects: cardiac dilatation and increased stroke volume compensate for a diminished heart rate.

Abstract: To assess the effect of age on cardiac volumes and function in the absence of overt or occult coronary disease, we performed serial gated blood pool scans at rest and during progressive upright bicycle exercise to exhaustion in 61 participants in the Baltimore Longitudinal Study of Aging. The subjects ranged in age from 25 to 79 years and were free of cardiac disease according to their histories and results of physical, resting and stress electrocardiographic, and stress thallium scintigraphic examinations. Absolute left ventricular volumes were obtained at each workload. There were no age-related changes in cardiac output, end-diastolic or end-systolic volumes, or ejection fraction at rest. During vigorous exercise (125 W), cardiac output was not related to age (cardiac output [1/min] = 16.02 + 0.03 [age]; r = .12, p = .46). However, there was an age-related increase in end-diastolic volume (end-diastolic volume [ml] = 86.30 + 1.48 [age]; r = .47, p = .003) and stroke volume (stroke volume [ml] = 85.52 + 0.80 [age]; r = .37, p = .02), and an age-related decrease in heart rate (heart rate [beats/min] = 184.66 - 0.70 [age]; r = -.50, p = .002). The dependence of the age-related increase in stroke volume on diastolic filling was emphasized by the fact that at this high workload end-systolic volume was higher (end-systolic volume [ml] = 3.09 + 0.65 [age]; r = .45, p = .003) and ejection fraction lower (ejection fraction = 88.48 - 0.18 [age]; r = -.33, p = .04) with increasing age. These findings indicate that although aging does not limit cardiac output per se in healthy community-dwelling subjects, the hemodynamic profile accompanying exercise is altered by age and can be explained by an age-related diminution in the cardiovascular response to beta-adrenergic stimulation.

Maximal coronary flow and the concept of coronary vascular reserve.

Abstract: CORONARY FLOW can usually be increased above resting levels by reactive hyperemia after transient coronary arterial occlusion,'-\" exercise,7 11, 1421 pacing,22-26 or injection of agents like dipyridamole,' 17. 18 20 21. 27-37 other vasodilating -7. 10, 11. 30. 38 agents,5 or hyperosmolar iodinated contrast media.4 693 If the stimulus produces maximal coronary vasodilatation, then the increment of coronary flow above the resting level will be maximal. This increment, often termed the \"coronary vascular reserve,\" is beginning to be measured in human beings to give information about the coronary vascular bed.9 13, 15. 17. 19-29. 33A3 However, it is easy to misinterpret the information, so that it is important to understand the basic physiology that underlies the concept of coronary vascular reserve.

Comparison of late changes in internal mammary artery and saphenous vein grafts in two consecutive series of patients 10 years after operation.

Abstract: Postoperative angiographic studies were carried out at 1 month, 1 year, and 10 years in two groups of patients: 238 patients with saphenous vein (SV) grafts and 40 patients with internal mammary artery (IMA) grafts. Cumulative patency was better in IMA grafts, both at 1 year (88.5% vs 76.4%) and at 10 years (84.1% vs 52.8%). Atheromatous changes in patent grafts at 10 years were frequent in SV grafts (29/66 or 43.9%) and uncommon in IMA grafts (1/19 or 5.2%; p less than .02). Attrition rate (11.8%) during the first year in IMA grafts (representing our initial experience with IMA grafts) was comparable to that of SV grafts (15.2%) in a group of patients operated on after 2 years of experience. Therefore, early attrition rate may be related to both experience and type of conduit. Later, at 10 years, the conduit itself appears to be the dominant factor. Furthermore, patients who received IMA grafts had a better survival rate at 10 years (84.3% vs 70%) than those who underwent SV bypass grafting.

Prosthetic valve endocarditis.

Abstract: Fifty-three (3.6%; actuarially 4.1% at 48 months) of 1465 consecutive in-hospital survivors of valve replacement from 1975 to July 1979 (aortic, mitral, or aortic and mitral, only one untraced) developed prosthetic valve endocarditis (PVE). Incremental risk factors for developing PVE were native valve endocarditis (p less than .0001), black race (p = .0001), mechanical prosthesis (vs bioprosthesis) (p = .005), male sex (p = .04), and longer cardiopulmonary bypass time (p = .09). In general, the hazard function for developing PVE was greatest at 3 weeks after valve replacement. Patients with native valve endocarditis had a tendency to develop PVE early after valve replacement, as did patients in whom mechanical prostheses were used. PVE associated with Staphylococcus epidermidis tended to appear within 6 months of valve replacement, whereas streptococcal PVE tended to appear later after valve replacement. PVE took an atypical form in some patients, but patients with possible PVE (n = 6) had the same findings as those with certain PVE (n = 47). In 11 patients bacteriologic confirmation of PVE was not obtained. The typical prosthetic and periprosthetic characteristics of PVE were present in 30 of the 40 cases in which observations were possible. PVE is a serious condition; 34 (64%) of our 53 patients died. Most deaths occurred within 3 months of the first evidence of PVE. Recovery of some patients is possible with appropriate medical and surgical treatment, but more intense preventive measures are indicated.

Triple control of relaxation: implications in cardiac disease.

Abstract: EARLY DETECTION of impaired relaxation has been emphasized recently for the evaluation of global and regional ventricular function in patients with heart disease. Although early relaxation abnormalities have been found in various cardiac diseases, the underlying mechanisms are not as yet fully understood. Given the recent progress in our understanding of relaxation of the heart,' these mechanisms can now be discerned

Exercise intolerance in patients with chronic heart failure: role of impaired nutritive flow to skeletal muscle.

Abstract: The maximal exercise capacity of patients with chronic heart failure is frequently reduced. To investigate whether this exercise intolerance is caused by inadequate nutritive flow to skeletal muscle, we compared cardiac outputs, leg blood flow, and leg metabolism during maximal bicycle exercise in seven patients with normal maximal oxygen uptake (VO2) (greater than 20 ml/min/kg; group A), eight patients with heart failure and moderately reduced maximal VO2 (15 to 18 ml/min/kg; group B), and eight patients with heart failure and markedly reduced maximal VO2 (less than 14 ml/min/kg; group C). As the severity of exercise intolerance increased from group A to group C there was a progressive decline in cardiac output and leg blood flow at any given workload accompanied by a progressive decline in maximal cardiac output (liters/min) (A, 12.4 +/- 1.0; B, 8.7 +/- 0.9; C, 5.5 +/- 0.7), maximal leg flow (liters/min) (A, 4.0 +/- 0.3; B, 2.6 +/- 0.4; C, 1.4 +/- 0.2), and maximal leg VO2 (ml/min) (A, 564 +/- 49; B, 403 +/- 41; C, 213 +/- 35 ml/min). All patients terminated exercise because of severe leg fatigue. At termination of exercise, all three groups exhibited similar marked levels of leg O2 extraction (%) (A, 80 +/- 2; B, 83 +/- 3; C, 89 +/- 1) and high femoral-arterial lactate gradients (mg/dl) (A, 15.4 +/- 2.6; B, 18.3 +/- 3.5; C, 19.2 +/- 3.6), suggesting that exercise was limited when a critical level of muscle underperfusion was reached. These data suggest that the reduced maximal exercise capacity of patients with chronic heart failure is primarily due to impaired nutritive flow to skeletal muscle and resultant muscular fatigue.

The influence of changes in lipid values induced by cholestyramine and diet on progression of coronary artery disease: results of NHLBI Type II Coronary Intervention Study.

Abstract: The National Heart, Lung and Blood Institute Type II Coronary Intervention Study, a double-blind, placebo-controlled trial, evaluated the efficacy of reduction in cholesterol levels induced by cholestyramine on progression of coronary artery disease (CAD). The rate of CAD progression in patients treated with cholestyramine plus diet was compared with that of patients treated with placebo plus diet. CAD progression was defined angiographically. Significant decrease in total cholesterol (TC) and low-density lipoprotein cholesterol (LDLc) and increases in high-density lipoprotein cholesterol (HDLc), as well as in HDLc/TC and HDLc/LDLc ratios, were observed with cholestyramine. HDLc change was due to increase in HDL2A and HDL2B. When the relationship between CAD progression and lipid changes was examined independent of specific treatment group, a significant inverse relationship was found between progression at 5 years and the combination of an increase in HDLc and a decrease in LDLc; changes in HDLc/TC and HDLc/LDLc were the best predictors of CAD change. While the testing of these relationships independent of treatment group was not part of the initial study design, the trends were observed in both the placebo-treated and cholestyramine-treated groups. Moreover, with multivariate analysis, the effect of cholestyramine treatment on CAD progression was eliminated by adding changes in HDLc/TC to the regression model. These findings support the hypothesis that increases in HDLc and decreases in TC (or LDLc) can prevent or delay CAD progression.

Autonomic mechanisms in ventricular fibrillation induced by myocardial ischemia during exercise in dogs with healed myocardial infarction. An experimental preparation for sudden cardiac death.

Abstract: The relationship between activity of the autonomic nervous system, myocardial ischemia, and malignant arrhythmias has been investigated in a new experimental preparation for sudden death. Fifty-seven dogs were chronically instrumented and studied under control conditions (n = 15) and 1 month after production of an anterior myocardial infarction (n = 42). The protocol consisted in occluding the left circumflex coronary artery for 2 min, commencing at the last minute of an exercise stress test and extending through the first minute after cessation of exercise. With this protocol, ventricular fibrillation was observed in 40% of normal dogs and 66% of dogs with infarction. In 14 dogs with infarction, left stellectomy reduced the incidence of ventricular fibrillation to zero (p less than .001). The reflex changes in heart rate elicited within the first minute of ischemia during exercise in the animals that survived (from 204 +/- 14 to 198 +/- 31 beats/min, -6) were opposite those in animals that had ventricular fibrillation (from 208 +/- 24 to 229 +/- 30 beats/min, +21) (p less than .05). The ischemia-induced reduction in heart rate despite continuation of exercise suggests the presence in the dogs that survived of active vagal reflexes that may have played an important role in the maintenance of cardiac electrical stability. This preparation has the potential to induce ventricular fibrillation consistently in conscious animals by the interaction of a few clinically relevant factors (acute myocardial ischemia, submaximal exercise and its cessation, sympathetic and vagal reflexes, and heart rate) and offers the possibility of acquiring further insights into the mechanisms of malignant arrhythmias and evaluating novel strategies for targeted prevention.

Mechanisms by which epinephrine augments cerebral and myocardial perfusion during cardiopulmonary resuscitation in dogs.

Abstract: The goals of this study were to quantify the effects of epinephrine on myocardial and cerebral blood flow during conventional cardiopulmonary resuscitation (CPR) and CPR with simultaneous chest compression-ventilation and to test the hypothesis that epinephrine would improve myocardial and cerebral blood flow by preventing collapse of intrathoracic arteries and by vasoconstricting other vascular beds, thereby increasing perfusion pressures. Cerebral and myocardial blood flow were measured by the radiolabeled microsphere technique, which we have previously validated during CPR. We studied the effect of epinephrine on established arterial collapse during CPR with simultaneous chest compression-ventilation with the abdomen bound or unbound. Epinephrine reversed arterial collapse, thereby eliminating the systolic gradient between aortic and carotid pressures and increasing cerebral perfusion pressure and cerebral blood flow while decreasing blood flow to other cephalic tissues. Epinephrine produced higher cerebral and myocardial perfusion pressures during CPR with simultaneous chest compression-ventilation when the abdomen was unbound rather than bound because abdominal binding increased intracranial and venous pressures. In other experiments we compared the effect of epinephrine on blood flow during 1 hr of either conventional CPR or with simultaneous chest compression-ventilation with the abdomen unbound. Epinephrine infusion during conventional CPR produced an average cerebral blood flow of 15 ml/min . 100 g (41 +/- 15% of control) and an average myocardial blood flow of 18 ml/min . 100 g (15 +/- 8% of control). In our previous studies, cerebral and myocardial blood flow were less than 3 +/- 1% of control during conventional CPR without epinephrine. Although flows during CPR with simultaneous chest compression-ventilation without epinephrine were initially higher than those during conventional CPR, arterial collapse developed after 20 min, limiting cerebral and myocardial blood flow. The use of epinephrine throughout 50 min of CPR with simultaneous chest compression-ventilation maintained cerebral blood flow at 22 +/- 2 ml/min . 100 g (73 +/- 25% control) and left ventricular blood flow at 38 +/- 9 ml/min . 100 g (28 +/- 8% control). The improved blood flows with epinephrine correlated with improved electroencephalographic activity and restoration of spontaneous circulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Assessment of diastolic function: suggested methods and future considerations.

Abstract: RECENT STUDIES in diseased hearts have demonstrated that diastolic dysfunction may precede abnormalities in systolic ventricular performance. Therefore, it is important to critically review methods currently being used in the assessment of diastolic function. Many review articles and symposia that express differing points of view have been published recently. '-5 Several of the controversies stem from a misunderstanding of basic principles of physics and mathematics, the use of inappropriate analyses, and the desire to develop simple indexes of diastolic function. The emphasis here will therefore be on the development of relationships between pertinent physiologic parameters, the applications of various mathematic models, and suggestions of topics requiring further study. In particular, attention will be focused on methods for the assessment of chamber stiffness, myocardial stiffness, and the time constant of relaxation since these are important factors involved during shifts in the pressure-volume relationship after drug intervention or pacing-induced angina.

Reduction of coronary reserve: a mechanism for angina pectoris in patients with arterial hypertension and normal coronary arteries

Abstract: The pathogenesis of angina pectoris in patients with left ventricular hypertrophy secondary to arterial hypertension and with normal coronary arteries remains uncertain. We measured coronary blood flow (argon method) in 12 control subjects and in 16 patients with arterial hypertension at rest and after intravenous administration of dipyridamole (0.5 mg/kg). In the patients with arterial hypertension, coronary blood flow response to dipyridamole was markedly reduced (p less than .001 as compared with control values). During coronary vasodilation there was a linear correlation between coronary resistance and left ventricular end-diastolic pressure (r = .67, p less than .001). Left ventricular catheter biopsy specimens did not reveal alterations in myocardial microvasculature. These findings suggest that reduction of coronary reserve may be an important contributor to the pathogenesis of angina pectoris in these patients.

Coronary thrombolysis with recombinant human tissue-type plasminogen activator: a prospective, randomized, placebo-controlled trial.

Abstract: Forty-five patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were prospectively randomized, two for one, to treatment of acute coronary thrombosis with intravenous recombinant human tissue-type plasminogen activator (rt-PA) or placebo. Each of five additional consecutive patients was treated with a high dose of rt-PA for 2 hr. Twenty-five of 33 patients (75%) receiving 0.5 to 0.75 mg/kg of rt-PA over 30 to 120 min had angiographically proven recanalization within 90 min of initiation of therapy. Only one of 14 patients given placebo had spontaneous recanalization within 45 min (p less than .001). Thirteen placebo-treated patients were crossed over to the intracoronary rt-PA group. Nine (69%) exhibited subsequent recanalization within 45 min. Levels of circulating fibrinogen decreased after treatment with rt-PA by an average of only 8% of baseline values. None of the patients manifested a depletion of fibrinogen level to below 100 mg/dl. Six patients who were completely unresponsive to rt-PA were subsequently treated with intracoronary streptokinase and none responded. Thus, either intravenous or intracoronary rt-PA induced coronary thrombolysis without eliciting clinically significant fibrinogenolysis in patients with evolving myocardial infarction due to thrombotic coronary occlusion.

Quantification of regional myocardial blood flow in vivo with H215O.

Abstract: Using H215O (half-life = 2.1 min) we demonstrated that a modification of the tissue autoradiographic approach permitted quantitation of myocardial blood flow in open-chest dogs by direct assay of myocardial tissue and that noninvasive estimation with positron-emission tomography (PET) delineated relative myocardial blood flow in intact dogs. In open-chest anesthetized dogs, the single-pass extraction fraction of H215O averaged 96 +/- 5% at flows of 80 to 100 ml/100 g/min. This high extraction fraction did not differ significantly over the range of 12 to 238 ml/100 g/min. Myocardial blood flow calculated after a 60 sec intravenous infusion of H215O and direct analysis of tissue correlated well with results obtained with microspheres (r = .94, n = 9 dogs). Subsequently the approach was adapted for preliminary use with PET. Estimation of myocardial content of radiolabeled H2O after intravenous infusion of 20 to 30 mCi of H215O was corrected for vascular pool radioactivity with the use of tomographic data obtained after administration of C15O by inhalation to label red blood cells. Tomograms obtained in vivo in six dogs with either normal or reduced regional blood flow correlated closely with the tomographically detectable distribution of 68Ga-labeled microspheres (r = .93) and with postmortem microsphere distribution (r = .95). The technique accurately reflects myocardial blood flow. With the use of PET, rapid sequential noninvasive estimation of relative regional myocardial blood flow has been demonstrated that should ultimately permit improved objective assessment of nutritional blood flow in patients in response to medical and surgical interventions designed to augment perfusion.

Coumadin and aspirin in prevention of recurrence after transluminal coronary angioplasty: a randomized study.

Abstract: To determine the influence of adjunctive treatment with coumadin or aspirin on recurrence rate after percutaneous transluminal coronary angioplasty (PTCA), 248 patients in whom PTCA was assessed to be a primary success were randomized to either 325 mm aspirin daily or to coumadin treatment sufficient to maintain a prothrombin time 2 to 2.5 times the control value. The follow-up protocol included stress testing and coronary angiographic examinations 3 to 6 months after PTCA. All patients were followed for at least 9 months. Of the 122 patients randomized to coumadin 44 (36%) had recurrent stenoses as opposed to 34/126 (27%) of patients on aspirin, a difference that did not reach statistical significance at the .05 level. However, patients with at least a 6 month history of angina demonstrated a significantly different response to adjunctive treatment in that 19/43 (44%) of coumadin patients as compared with 10/48 (21%) of aspirin patients had recurrent stenoses (p less than .05). Thus, coumadin was not shown to be more effective than aspirin as adjunctive treatment after PTCA, while aspirin was shown to be superior to coumadin in patients with a longer history of angina.

The value of lesion cross-sectional area determined by quantitative coronary angiography in assessing the physiologic significance of proximal left anterior descending coronary arterial stenoses.

Abstract: The results of previous work from this laboratory have shown a poor correlation between percent stenosis (determined visually with calipers) and the coronary reactive hyperemic response (an index of maximal coronary vasodilator capacity) determined during cardiac surgery. This study was performed to determine whether other parameters of lesion severity could predict the reactive hyperemic response and thus the hemodynamic significance of coronary stenoses in human beings. Twenty-three patients with lesions in the proximal left anterior descending coronary artery were studied. To account for differences in expected vessel size, patients with large diagonal branches (greater than one-half the diameter of the left anterior descending artery) arising before the lesion were excluded. Computer-assisted quantitative coronary angiography was used to measure percent diameter stenosis, percent area stenosis, and minimal stenosis cross-sectional area. With a pulsed Doppler velocity probe, reactive hyperemic responses were recorded after a 20 sec coronary occlusion of the left anterior descending artery at cardiac surgery before cardiopulmonary bypass and were quantified by the peak/resting velocity ratio (normal greater than 3.5:1). Percent area stenosis ranged from 7% to 54% for vessels with normal reactive hyperemic responses and from 27% to 94% for vessels with abnormal reactive hyperemic responses. With both percent diameter stenosis and percent area stenosis there was substantial overlap between vessels with normal and abnormal reactive hyperemic responses. In contrast, nine of nine vessels with normal reactive hyperemic responses had lesion minimal cross-sectional areas of greater than 3.5 mm2 and 13 of 14 vessels with abnormal reactive hyperemic responses had minimal cross-sectional areas of less than 3.5 mm2.(ABSTRACT TRUNCATED AT 250 WORDS)

Independent determinants of operative mortality for patients with aortic dissections.

Abstract: A 20 year (1963 to 1982) surgical experience including 175 consecutive patients with aortic dissections was analyzed by logistic discriminant analyses to identify predictors of high operative risk. The patient population had characteristics similar to those in large autopsy series. Sixty-nine percent had type A and 58% had acute dissections. The intimal tear was located in the ascending aorta in 60% of the patients, the descending aorta in 27%, and the transverse arch in 13%. The overall operative mortality rate was 23 +/- 3%. The operative mortality rates were substantially lower between 1977 and 1982: mortality in patients with acute type A dissections, 7 +/- 5%; in those with chronic type A, 11 +/- 7%; in those with acute type B, 13 +/- 12%; and in those with chronic type B, 11 +/- 11%. After preliminary univariate screening, the following factors were determined to be significant independent predictors of operative mortality (in rank order of declining predictive power): type A patients (n = 121), renal dysfunction, tamponade, renal/visceral ischemia, and operative date; type B patients (n = 54), rupture, renal/visceral ischemia, and age; all patients (n = 175), renal dysfunction, renal/visceral ischemia, site of tear (ascending less than descending less than arch), tamponade, operative date, and pulmonary disease. Interestingly, several variables had no important bearing on operative mortality, including type (acute vs chronic) of dissection, age, previous operation, rupture, stroke, paraplegia, Marfan's syndrome, concomitant aortic valve replacement and/or coronary artery bypass grafting, site of tear, and whether or not the tear was resected in type A patients; emergency operation, hypertension, previous cardiac symptoms, paraplegia, site of tear, and resection of tear in type B patients; and, when all patients were considered together, age, sex, cardiac symptoms, prior operation, stroke, paraplegia, acute myocardial infarction, acute aortic regurgitation, Marfan's syndrome, and tear resection. These data allow calculation of any individual patient's operative risk and document that the operative mortality rate today is relatively low for all patients with aortic dissections, irrespective of type or acuity. Earlier surgical referral of patients with acute type A or acute type B dissection before irreversible major end-organ ischemia and/or infarction is probably in part responsible for the substantially improved results since 1977.

The effects of daily exercise on susceptibility to sudden cardiac death.

Abstract: The purpose of this study was to investigate the effects of daily exercise on susceptibility to sudden cardiac death. A 2 min coronary occlusion was initiated during the last minute of an exercise stress test and continued for 1 min after cessation of exercise in chronically instrumented dogs with a healed anterior wall myocardial infarction. Thirteen dogs developed ventricular fibrillation (VF; susceptible), while five did not (resistant). Before the exercise plus ischemia test, the baroreflex was evaluated with a bolus injection of phenylephrine (10 micrograms/kg). The changes in heart rate caused by a 30 mm Hg increase in systolic arterial pressure as well as the slopes of either heart rate or RR interval plotted against systolic arterial pressure were significantly lower in dogs that developed VR (resistant, -49.6 +/- 7.8; susceptible, -15.3 +/- 6.4 beats/min; p less than .001). Four resistant and eight susceptible animals were then placed on a 6 week daily exercise program, while eight susceptible dogs had an equal period of rest. At the end of the 6 week period the exercise plus ischemia test was repeated; no susceptible animal that performed daily exercise developed VF, and all but one of the rested animals did. Daily exercise improved baroreflex control of heart rate in the susceptible group but not in the resistant group. Rest did not alter baroreflex function (change in heart rate after 30 mm Hg increase in systolic arterial pressure: after 6 weeks of exercise, resistant -43.3 +/- 18.9 beats/min, susceptible -60.8 +/- 16.6 beats/min; after 6 weeks of rest, susceptible 27.4 +/- 11.0 beats/min). We conclude that daily exercise prevents VF induced by acute myocardial ischemia in a subpopulation of dogs that were previously identified as susceptible to sudden cardiac death. Exercise also altered the autonomic control of the heart, possibly decreasing sympathetic and/or increasing parasympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)

Family history of heart attack as an independent predictor of death due to cardiovascular disease.

Abstract: Although a family history of ischemic heart disease is a well-accepted risk factor for cardiovascular disease, only three prospective studies--all in men--have examined the predictive strength of a positive family history after adjusting for other heart disease risk factors. The present analysis is based on a 9 year follow-up of 4014 men and women from 40 to 79 years old who resided in Rancho Bernardo, CA, and who reported no known cardiovascular disease in response to a standardized interview. At baseline 38% of this group reported a family history of a heart attack in a parent, sibling, or child; 15% of those with a positive family history in a first-degree relative indicated that the heart attack had occurred before the relative was 50 years old. Younger men (less than 60 years) with a positive family history at any age had significantly higher mean blood pressures and total plasma cholesterol levels; older men were more likely to have diabetes mellitus. Younger women with a positive family heart attack to subsequent cardiovascular death was determined by the Cox model after adjusting for age, systolic blood pressure, total plasma cholesterol level, obesity, cigarette smoking, personal history of diabetes, and estrogen use (in women). In men, but not in women, a positive family history of heart attack was independently predictive of death from all causes and from cardiovascular and ischemic heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of ventricular arrhythmias initiated by programmed ventricular stimulation: the importance of the type of ventricular arrhythmia induced and the number of premature stimuli required.

Abstract: An increasing number of premature ventricular stimuli are being used during programmed stimulation of the heart in the investigation of patients with documented or suspected ventricular arrhythmias. To analyze the significance of the different types of ventricular arrhythmias that are initiated, we evaluated in a prospective study the effect of from one to four ventricular premature stimuli in 52 patients without (non-VT group) and 50 patients with (prior-VT group) documented ventricular tachycardia or ventricular fibrillation. More than half of the patients in the prior-VT group had coronary heart disease. In the majority of patients of the non-VT group the heart was normal. In 44 of the 50 patients in the prior-VT group the clinically documented ventricular arrhythmia was initiated by programmed ventricular stimulation of the heart. In 88% of these 44 patients, one or two ventricular premature beats were required to initiate the clinical arrhythmia. A ventricular arrhythmia could be initiated in 31 of the 52 patients in the non-VT group. The ventricular arrhythmias included nonsustained monomorphic ventricular tachycardia (two patients), six to 25 complexes of sustained polymorphic ventricular tachycardia (24 patients), and ventricular fibrillation (five patients). In 70% of patients in the non-VT group three or four ventricular premature beats were required to initiate the ventricular arrhythmia. Our results indicate that not only the number of extrastimuli required to initiate ventricular arrhythmias but also the type of ventricular arrhythmia initiated differed between the two groups of patients. Nonsustained polymorphic ventricular tachycardia and ventricular fibrillation are nonspecific responses to aggressive stimulation protocols.

Left ventricular performance, regional blood flow, wall motion, and lactate metabolism during transluminal angioplasty.

Abstract: The response of left ventricular function, coronary blood flow, and myocardial lactate metabolism during percutaneous transluminal coronary angioplasty (PTCA) was studied in a series of patients undergoing the procedure. From four to six balloon inflation procedures per patient were performed with an average duration per occlusion of 51 +/- 12 sec (mean +/- SD) and a total occlusion time of 252 +/- 140 sec. Analysis of left ventricular hemodynamics in 19 patients showed that the relaxation parameters, peak negative rate of change in pressure, and early time constants of relaxation, responded earliest to short-term coronary occlusion (peak effect at 17 +/- 7 sec) while other parameters, such as peak pressure, left ventricular end-diastolic pressure, and peak positive rate of change in pressure, responded more gradually, suggesting a progressive depression of myocardial mechanics throughout the procedure. Left ventricular angiograms, available for 14 patients, indicated an early onset of asynchronous relaxation concurrent with the early response in peak negative dP/dt and the time constant of early relaxation. All hemodynamic functions fully recovered within minutes after the end of PTCA. Mean blood flow in the great cardiac vein and proximal coronary sinus and the hyperemic response were measured in 20 patients. Before PTCA mean flow in the great cardiac vein was 69 +/- 17 ml/min and in the coronary sinus it was 129 +/- 34 ml/min. Reactive hyperemia (great cardiac vein) was 55% after the first PTCA and 91% after the third. A more pronounced reaction was observed when the residual functional coronary stenosis was reduced in subsequent dilatations. Arteriovenous lactate difference appeared constant during the first two occlusions (control +0.11 mmol/liter, first PTCA -0.87 mmol/liter, and second PTCA -0.82 mmol/liter) and did not increase during subsequent occlusions. Within minutes after the procedure lactate balance was again positive, demonstrating the reversibility of the metabolic disturbances after repeated ischemia. The results of this study indicate that there is no permanent dysfunction of global or regional myocardial mechanics, myocardial blood flow, or lactate metabolism after PTCA with four to six coronary occlusions of 40 to 60 sec.

Intra-atrial reentry as a mechanism for atrial flutter induced by acetylcholine and rapid pacing in the dog.

Abstract: In the isolated blood-perfused canine heart we produced episodes of rapid atrial flutter by continuous infusion of acetylcholine and rapid pacing. The spread of excitation during atrial flutter was mapped with the aid of two endocavitary mapping electrodes containing 960 leads and recording from 192 different sites simultaneously. The flutter maps clearly showed that intra-atrial reentry was the mechanism responsible for the arrhythmia. However, the localization and size of the intra-atrial circuits differed from case to case even in the same heart. The orifices of the venae cavae or the atrioventricular ring did not serve as a central anatomic obstacle for circus movement. We also failed to identify a special role of the internodal pathways in the formation of the loop. Instead, the intra-atrial circuits could be found everywhere, provided sufficient atrial mass was available to accommodate the circuit. The diameter of the circuits varied between 1.5 and 3 cm at a cycle length between 65 and 155 msec. The average conduction velocity of the circulating impulse varied between 60 and 80 cm/sec. Spontaneous termination of atrial flutter frequently occurred and was based on local conduction block in a narrow part of the circuit. Another interesting aspect of these studies is the finding that during continuous circus movement of the impulse, the amount of myocardium that is activated may vary considerably. This marked periodicity in excited tissue mass during atrial flutter could adequately explain the continuously undulating baseline or typical sawtoothlike F waves as seen in the surface electrocardiogram during atrial flutter.

Fast-Fourier transform analysis of signal-averaged electrocardiograms for identification of patients prone to sustained ventricular tachycardia.

Abstract: Electrocardiograms obtained from patients during arrhythmia-free intervals do not identify those prone to sustained ventricular tachycardia (VT) despite the occult delayed activation that is presumably present. To determine whether frequency-domain analysis facilitates detection of this hallmark of predisposition to VT, fast-Fourier transform analysis (FFTA) procedures were developed and tested with a computer-generated mathematical model. The FFTA approach developed allows inherent limitations of high-gain amplification and a priori filtering used commonly for time-domain analysis to be avoided. After demonstrating that FFTA detected low-amplitude oscillatory waveforms in signal-averaged recordings in the frequency domain, the procedure was applied to signal-averaged X, Y, and Z lead recordings from the following three groups of patients: group I, patients with prior myocardial infarction and episodic sustained VT (n = 16); group II, patients with prior myocardial infarction without overt sustained VT (n = 35); and group III, normal control subjects (n = 10). Results of FFTA demonstrated significant (p less than .0001) differences in the decibel drop at 40 Hz and the area under the curve from the fundamental frequency to the frequency at which the spectral amplitude was decreased by 60 dB for both the terminal 40 msec of the QRS and ST segment in patients in group I compared with those in groups II and III, in whom results were similar. Results were independent of QRS duration (r = .2), left ventricular ejection fraction (r = .19), and complexity of spontaneous ventricular ectopy. Thus, patients known to manifest sustained VT also exhibited relatively greater high-frequency content in arrhythmia-free intervals in the terminal QRS and ST segment than those without VT (88%, 15%, and 0% in groups I through III, respectively). FFTA offers promise for the noninvasive detection of patients at risk for the development of sustained VT.

Rethrombosis after reperfusion with streptokinase: importance of geometry of residual lesions.

Abstract: We tested the hypothesis that lesion rethrombosis after streptokinase reperfusion is related to luminal size of the residual stenosis. Two independent techniques of analyzing coronary angiograms, quantitative coronary angiography and computer-based videodensitometry, were used to estimate the size of the residual lumen immediately after discontinuation of streptokinase. These techniques were selected because they provide independent estimates of cross-sectional area of a lesion with high degrees of reproducibility and minimal observer variability. Twenty-four patients who had undergone successful reperfusion with streptokinase were studied. Seven patients had lesion rethrombosis documented either on a repeat angiogram, at autopsy, or, in one case, by the fact that the patient had an acute transmural infarction resulting in death. Vessel patency was documented by repeat coronary angiography 8 to 14 days after initial streptokinase reperfusion in the other 17 patients. As assessed by quantitative coronary angiography, seven of 13 patients (54%) with minimal luminal cross-sectional areas of less than 0.4 mm2 had rethrombosis. None of the 11 patients with lumens greater than 0.4 mm2 had rethrombosis. In the 17 patients with vessels that remained patent the size of the residual lesion at repeat catheterization was compared with its size immediately after reperfusion with streptokinase. Over the intervening 8 to 14 day interval, an average percentage increase in minimal cross-sectional area of 116 +/- 34% was observed. In seven patients minimal luminal cross-sectional area more than doubled. Integrated optical density, an index of the severity of coronary stenosis derived from computer-based videodensitometry, was also useful in identifying a subgroup of patients at high risk for rethrombosis of lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Nifedipine therapy for patients with threatened and acute myocardial infarction: a randomized, double-blind, placebo-controlled comparison.

Abstract: Preliminary clinical and laboratory observations suggest that nifedipine might prevent progression of threatened myocardial infarction by reversing coronary spasm or might limit necrosis during the course of acute myocardial infarction. We screened 3143 patients with ischemic pain of greater than 45 min duration and randomly assigned 105 eligible patients with threatened myocardial infarction and 66 with acute myocardial infarction to receive nifedipine (20 mg orally every 4 hr for 14 days) or placebo plus standard care. Treatment was started 4.6 +/- 0.1 hr after the onset of pain. Infarct size index was calculated by the MB-creatine kinase (CK) method and expressed as CK-geq/m2 +/- SE. The incidence of progression to infarction among patients with threatened myocardial infarction was not significantly altered by nifedipine (36 of 48 [75%] for placebo-treated and 43 of 57 [75%] for nifedipine-treated patients). Furthermore, infarct size index was similar among placebo- and nifedipine-treated patients (16.9 +/- 1.5 MB-CK-geq/m2, n = 65, and 17.0 +/- 1.5 MB-CK-geq/m2, n = 68, respectively) with threatened myocardial infarction who exhibited infarction and for those with acute myocardial infarction. Among the 171 eligible patients randomly assigned to drug or placebo, 6 month mortality did not differ significantly (8.5% for placebo vs 10.1% for nifedipine, NS), but mortality in the 2 weeks after randomization was significantly higher for nifedipine-treated patients (0% for placebo compared with 7.9% for nifedipine, p = .018).(ABSTRACT TRUNCATED AT 250 WORDS)