Biomedical subjects
B Massie
Publications and source records attributed to B Massie.
Ventricular arrhythmias in patients undergoing noncardiac surgery. The Study of Perioperative Ischemia Research Group.
OBJECTIVE: To determine the incidence, clinical predictors and prognostic importance of perioperative ventricular arrhythmias. DESIGN: Prospective cohort study (Study of Perioperative Ischemia). SETTING: University-affiliated Department of Veterans Affairs Medical Center, San Francisco, Calif. SUBJECTS: A consecutive sample of 230 male patients, with known coronary artery disease (46%) or at high risk of coronary artery disease (54%), undergoing major noncardiac surgical procedures. MEASUREMENTS: We recorded cardiac rhythm throughout the preoperative (mean = 21 hours), intraoperative (mean = 6 hours), and postoperative (mean = 38 hours) periods using continuous ambulatory electrocardiographic monitoring. Adverse cardiac outcomes were noted by physicians blinded to information about arrhythmias. MAIN RESULTS: Frequent or major ventricular arrhythmias (greater than 30 ventricular ectopic beats per hour, ventricular tachycardia) occurred in 44% of our patients: 21% preoperatively, 16% intraoperatively, and 36% postoperatively. Compared with the preoperative baseline, the severity of arrhythmia increased in only 2% of patients intraoperatively but in 10% postoperatively. Preoperative ventricular arrhythmias were more common in smokers (odds ratio [OR], 4.1; 95% confidence interval [CI], 1.2 to 15.0), those with a history of congestive heart failure (OR, 4.1; 95% CI, 1.9 to 9.0), and those with electrocardiographic evidence of myocardial ischemia (OR, 2.2; 95% CI, 1.1 to 4.7). Preoperative arrhythmias were associated with the occurrence of intraoperative and postoperative arrhythmias (OR, 7.3; 95% CI, 3.3 to 16.0, and OR, 6.4; 95% CI, 2.7 to 15.0, respectively). Nonfatal myocardial infarction or cardiac death occurred in nine men; these outcomes were not significantly more frequent in those with prior perioperative arrhythmias, albeit with wide CIs (OR, 1.6; 95% CI, 0.4 to 6.2). CONCLUSION: Almost half of all high-risk patients undergoing noncardiac surgery have frequent ventricular ectopic beats or nonsustained ventricular tachycardia. Our results suggest that these arrhythmias, when they occur without other signs or symptoms of myocardial infarction, may not require aggressive monitoring or treatment during the perioperative period.
Correlates of aortic distensibility in chronic aortic regurgitation and relation to progression to surgery.
Aortic distensibility decreases with increasing age. Patients with chronic aortic regurgitation eject a large stroke volume into the proximal aorta. A decrease in distensibility of the aorta may impose a higher afterload on the left ventricule and may contribute to deterioration of left ventricular function over time. Accordingly, aortic distensibility was measured in 33 patients aged 13 to 73 years who had chronic isolated aortic regurgitation with minimal or no symptoms. Ascending aortic diameter was measured 4 cm above the aortic valve by two-dimensional echocardiography and pulse pressure was measured simultaneously by sphygmomanometry. Aortic distensibility was calculated as (Change in aortic diameter between systole and diastole/End-diastolic diameter)/Pulse pressure. Left ventricular systolic wall stress and mass were derived from standard M-mode echocardiographic measurements. Left ventricular volumes and ejection fraction were measured by radionuclide ventriculography. Aortic distensibility decreased logarithmically with increasing age (r = -0.62, p less than 0.001) and also correlated inversely with systolic wall stress, left ventricular mass and end-diastolic volume. Patients who eventually underwent aortic valve replacement for symptoms of left ventricular dysfunction had significantly lower aortic distensibility than did those who did not yet require valve replacement: 0.09 +/- 0.08 vs. 0.22 +/- 0.19 x 1/100 (1/mm Hg) (p less than 0.05). Thus, the reduced aortic distensibility that occurs with increasing age may contribute to the gradual left ventricular dilation and dysfunction seen in patients with chronic aortic regurgitation.
Congestive heart failure: survival trial of antiarrhythmic therapy (CHF STAT). The CHF STAT Investigators.
This study is a prospective, double-masked, randomized, clinical trial to determine the effect of anti-arrhythmic drug therapy on mortality in patients with congestive heart failure and ventricular arrhythmia. Patients will be assigned to receive either amiodarone or placebo. Eligible patients include those with ischemic and nonischemic congestive heart failure (New York Heart Association class III or VI) and with 10 or more ventricular premature beats per hour. All patients must have shortness of breath with minimal exertion or paroxysmal nocturnal dyspnea, a left ventricular internal dimension (LVIDd) by echocardiogram of 55 mm or greater (> or = 55 mm) or a CT ratio of greater than 0.5, and an ejection fraction of 40% of less. Patients will be entered into the study for 2.5 years and followed for an additional 2 years. Drug therapy will be continued for all patients throughout the entire study unless adverse reactions occur that necessitate individualized treatment. The expectation is that 674 patients are to be entered into the study from 25 participating centers. This sample size will allow for the detection of a 33% decrease in 2-year mortality (20% vs. 30%) in the treated patients as compared to those in the placebo group with a power of 0.90 and a two-sided alpha level of 0.05. Intermittent Holter monitoring, radionuclide ventriculograms, pulmonary function tests, echocardiograms, and blood tests, including arterial blood gases, will be required for each patient. The study analysis will address differences in total mortality, cardiac mortality, and sudden cardiac death between patients receiving anti-arrhythmic drug therapy and those receiving placebo. Other factors to be examined include the effects of antiarrhythmic therapy on suppression of arrhythmias, on ejection fraction, and relation of ischemic events to mortality.
Energetics of acute pressure overload of the porcine right ventricle. In vivo 31P nuclear magnetic resonance.
In vivo 31P nuclear magnetic resonance (NMR) spectroscopy of the right ventricular (RV) free wall was employed to determine (a) whether phosphorus energy metabolites vary reciprocally with workload in the RV and (b) the mechanisms that limit RV contractile function in acute pressure overload. In 20 open-chest pigs, phosphocreatine (PCr)/ATP ratio (an index of energy metabolism inversely related to free ADP concentration), myocardial blood flow (microspheres), and segment shortening (sonomicrometry, n = 14) were measured at control (RV systolic pressure 31 +/- 1 mm Hg), and with pulmonary artery constriction to produce moderate pressure overload (RV systolic pressure 45 +/- 1 mm Hg), and maximal pressure overload before overt RV failure and systemic hypotension (RV systolic pressure 60 +/- 1 mm Hg). With moderate pressure overload, PCr/ATP declined to 89% of control (P = 0.01), while contractile function increased. Adenosine (n = 10, mean dose 0.16 mg/kg-min) increased RV blood flow by an additional 41% without increasing PCr/ATP, indicating that coronary reserve was not depleted and that the decrease in PCr/ATP from control was not due to ischemia. With maximal pressure overload and incipient RV failure, PCr/ATP fell further to 81% of control and RV blood flow did not increase further, even with adenosine. Thus: (a) The decline in PCr/ATP with moderate RV pressure overload, without evident ischemia or contractile dysfunction, supports the positive regulation of oxidative phosphorylation by ATP hydrolysis products. (b) Depletion of RV coronary flow reserve accompanies the onset of RV failure at maximal pressure overload.
Effects of stopping long-term vasodilator therapy in patients with chronic aortic insufficiency.
We studied the effects of stopping long-term vasodilator therapy in 17 patients with chronic stable aortic insufficiency. These patients received hydralazine for 37 +/- 15 months (mean +/- SD) and, as a result, had experienced a significant decrease in left ventricular volumes. All patients were followed clinically and ten of the patients underwent serial radionuclide evaluation at baseline, while receiving drug, and at 20 +/- 7 months after stopping drug therapy. No patient showed evidence of acute clinical deterioration when drug therapy was stopped. The rate of progression to valve replacement due to onset of symptoms or left ventricular dysfunction was not significantly different from that previously reported in a population with similar characteristics. Left ventricular size, however, returned to levels similar to baseline after drug therapy was stopped. We conclude that long-term vasodilator therapy may be discontinued in patients with chronic stable aortic insufficiency without causing clinical deterioration or significant alteration in rate of progression to valve replacement.
Effects of long-term vasodilator therapy on electrocardiographic abnormalities in chronic aortic regurgitation.
Electrocardiographic abnormalities develop in patients with chronic aortic regurgitation (AR). Although vasodilator drugs may reduce left ventricular (LV) volume overload, the effects of such therapy on electrocardiographic abnormalities have not been previously evaluated. Accordingly, electrocardiograms were analyzed before and after double-blind, randomized administration of either hydralazine or placebo in 54 patients with chronic AR. These patients were without limiting symptoms and had preserved ejection fraction on entry in the study. The magnitude of ST-segment depression and Romhilt-Estes point score for LV hypertrophy were assessed. Baseline ST depression and LV hypertrophy scores in the placebo and hydralazine groups were not significantly different. At follow-up, after a mean of 19 +/- 6 months, there was a significant reduction in ST depression in patients taking hydralazine (n = 28) compared with patients given placebo (n = 26): -0.023 +/- 0.044 vs 0.029 +/- 0.055 mV, respectively (p = 0.0001); and in the LV hypertrophy score (-1.1 +/- 2.2 vs 0.9 +/- 2.3 points, respectively; p = 0.002). Hydralazine-treated patients also had significant decreases in LV end-diastolic and end-systolic volume indexes, and a significant increase in ejection fraction. These results suggest that such vasodilator therapy may be beneficial in patients with chronic AR.
Affinity purification of active subunit 1 of herpes simplex virus type 1 ribonucleotide reductase exhibiting a protein kinase activity.
Herpes simplex virus (HSV) ribonucleotide reductase is formed by the association of two distinct dimeric subunits, R1 and R2. Attempts to purify either the HSV holoenzyme or its R1 subunit in their active form have been unsuccessful until now. The C terminus of the R2 protein being involved in the association with R1, the synthetic nonapeptide corresponding to this terminus, impedes the formation of the holoenzyme by competing with R2 for a critical site on R1. Based upon these observations, we developed an affinity chromatographic procedure to purify the R1 protein from HSV-1-infected baby hamster kidney cells. Specific binding of R1 to an affinity column made by linking the peptide HSV R2-(326-337) to Affi-Gel 10, followed by specific elution with an excess of an analogous peptide exhibiting a higher affinity for R1 yielded, in a single step, highly purified R1 protein. The purified R1 preparations contained approximately 95% of intact R1, the remaining 5% consisting of two R1 copurifying proteolytic breakdown products. The purified R1 protein exhibited a high reductase specific activity when mixed with an excess of the R2 subunit. Moreover, in vitro kinase assays revealed that the purified R1 protein of HSV-1 possesses an autophosphorylating activity also able to phosphorylate alpha-casein and histone II-S. The intrinsic protein kinase activity of HSV R1 is associated with its unique N-terminal domain which is absent from all other reductase subunits 1 and contains consensus motifs found in Ser/Thr protein kinases. A preliminary characterization of the kinase activity of the R1 protein of HSV-1 ribonucleotide reductase is presented.
Metabolic and functional consequences of blunted myocardial reactive hyperemia.
This study determined whether the rapidity of myocardial metabolic and contractile recovery after brief coronary occlusion depends upon the intensity of reactive hyperemia. We also tested the hypothesis that coronary flow rate modulates contractility after brief myocardial ischemia, independent of changes in phosphorus metabolites. Eight open-chest pigs were studied with phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy with 14 s time resolution. After a 29-s anterior descending coronary occlusion, peak Doppler coronary flow velocity was alternately unrestricted (normal hyperemia, 443 +/- 40% of control) or limited to 159 +/- 9% of control. During 29 s coronary occlusion, phosphocreatine-to-inorganic phosphate ratio (PCr/Pi) and systolic segment shortening in the ischemic region fell to 28 +/- 4 and 7 +/- 7% of control, respectively. With normal hyperemia, PCr/Pi and segment shortening recovered within 29 s. With blunted hyperemia, recovery of both parameters was delayed an additional 29-43 s, associated with reduced subendocardial blood flow (measured with radioactive microspheres) and persistent intracellular acidosis. However, the relationship between segment shortening and PCr/Pi was unaffected by the intensity of reactive hyperemia. Thus blunted reactive hyperemia significantly delays metabolic and contractile recovery from brief ischemia, probably via transient maldistribution of transmural perfusion. However, coronary blood flow rate does not independently modulate contractility after brief reversible ischemia.
Dipyridamole thallium-201 scintigraphy as a preoperative screening test. A reexamination of its predictive potential. Study of Perioperative Ischemia Research Group.
BACKGROUND: We examined the value of dipyridamole thallium-201 (201Tl) scintigraphy as a preoperative screening test for perioperative myocardial ischemia and infarction. METHODS AND RESULTS: We prospectively studied 60 patients undergoing elective vascular surgery. We performed 201Tl scintigraphy preoperatively and blinded all treating physicians to the results. Historical, clinical, laboratory, and physiological data were gathered throughout hospitalization. Myocardial ischemia was assessed during the intraoperative period using continuous 12-lead electrocardiography (ECG) and transesophageal echocardiography (TEE) and during the postoperative period using continuous two-lead ambulatory ECG. Adverse cardiac outcomes (cardiac death, myocardial infarction, unstable angina, severe ischemia, or congestive heart failure) were assessed daily throughout hospitalization. Twenty-two patients (37%) had defects that improved or reversed on delayed scintigrams (redistribution defects), 18 (30%) had persistent defects, and 20 (33%) had no defects on 201Tl scintigraphy. There was no association between redistribution defects and adverse cardiac outcomes: 54% (seven of 13) of adverse outcomes occurred in patients without redistribution defects, and the risk of an adverse outcome was not significantly increased in patients with redistribution defects (relative risk 1.5, 95% confidence interval 0.6-3.9, p = 0.43). Consistent with these findings, there was also no association between redistribution defects and perioperative ischemia: 54% (19 of all 35) of perioperative ECG and TEE ischemic episodes and 58% (14 of 24) of severe ischemic episodes occurred in patients without redistribution defects. The sensitivity of 201Tl scintigraphy for perioperative ischemia and adverse outcomes ranged from 40% to 54%, specificity from 65% to 71%, positive predictive value from 27% to 47% and negative predictive value from 61% to 82%. CONCLUSIONS: These results differ from those of previous studies and suggest that the routine use of 201Tl scintigraphy for preoperative screening of patients undergoing vascular surgery may not be warranted.
In vivo phosphorus-31 spectroscopic imaging in patients with global myocardial disease.
The goals of this study were to determine whether abnormalities in phosphorus metabolism could be noninvasively detected using phosphorus-31 nuclear magnetic resonance spectroscopy in patients with dilated cardiomyopathy and left ventricular hypertrophy, and whether these patient groups could be distinguished from each other based on parameters obtained using this technique. Seventeen patients and 14 control subjects were studied using nuclear magnetic resonance spectroscopy. Spectra were obtained from the human heart at rest using 3-dimensional spectroscopic imaging as a localization technique. Data were acquired over an average volume of 48 cc in 26.3 minutes using a 2 tesla imaging and spectroscopy unit. The ratio of phosphocreatine to adenosine triphosphate was 0.89 +/- 0.88 (mean +/- standard error) in normal subjects and did not differ significantly in patients with dilated cardiomyopathy or left ventricular hypertrophy. A prominent peak in the phosphodiester region was seen much more frequently in patients with dilated cardiomyopathy, resulting in significantly higher ratios of phosphodiester to phosphocreatine (1.28 +/- 0.35) and phosphodiester to adenosine triphosphate (0.79 +/- 0.18) in this group compared to normal subjects (0.33 +/- 0.08 and 0.29 +/- 0.08, respectively). However, the various patient groups could not be reliably distinguished from each other based on spectral patterns. These studies demonstrate the feasibility of performing phosphorus-31 nuclear magnetic resonance spectroscopic imaging in patients with myocardial disease. The initial results indicate that, under resting conditions, the ratio of phosphocreatine to adenosine triphosphate is not consistently altered in patients with severe global cardiomyopathies or hypertrophy. Phosphodiesters are elevated in some patients with dilated cardiomyopathy, a finding that may signify abnormal phospholipid metabolism in this condition.
Epicardial and endocardial localized 31P magnetic resonance spectroscopy: evidence for metabolic heterogeneity during regional ischemia.
Previous studies have noted that myocardial blood flow and high energy phosphates are heterogeneous across the myocardial wall during ischemia. In order to determine whether differences in metabolites between the subendocardium and subepicardium could be detected using 31P magnetic resonance spectroscopy, the Fourier series window (FSW) experiment was implemented on a porcine model of graded regional ischemia. FSW experiments using a planar phantom showed a 46% improvement in localization to the subendocardium compared to a one-pulse experiment. Animal studies of graded ischemia demonstrated a gradient in the phosphocreatine to inorganic phosphate ratio in the myocardium that paralleled the gradient in blood flow. These studies demonstrate the ability of spatially localized 31P magnetic resonance spectroscopy to detect regional changes in myocardial high energy phosphates localized to the subepicardium and subendocardium.
Left ventricular hypertrophy reversal with labetalol and propranolol: a prospective randomized, double-blind study.
Hypertensive patients with left ventricular hypertrophy (LVH) have increased cardiovascular morbidity and mortality. Experimental studies indicate the importance of both the alpha and beta components of the adrenergic nervous system in the development and reversal of LVH. Therefore labetalol (L), a combined alpha and beta blocker, and propranolol (P), a nonselective beta blocker, were evaluated in a randomized, double-blind study of 35 hypertensive patients with echocardiographic evidence of LVH. Following 2 weeks of placebo, L or P was titrated as needed and tolerated to maximum total daily doses of 1600 mg and 640 mg, respectively. A thiazide diuretic was added if necessary for blood pressure control. M-mode echocardiograms were performed at baseline and after 1, 3, 6, and 12 months of blood pressure control. The echocardiograms were read independently by two blinded observers for end-diastolic dimension and wall thicknesses, and left ventricular mass. Fractional shortening, cardiac output, and peripheral vascular resistance were derived using standard formulas. Both drugs reduced blood pressure significantly and comparably. Significant changes in the echocardiographic measurements were observed as early as 1 month and usually persisted throughout the study. Both drugs decreased posterior wall thickness; however, only the decrease in propranolol group achieved statistical significance. Septal wall thickness was reduced by L at 3 and 12 months. End-diastolic dimension increased significantly in the L-treated group at 3, 6, and 12 months of therapy, whereas P had no effect on this measurement.(ABSTRACT TRUNCATED AT 250 WORDS)
High level expression in 293 cells of the herpes simplex virus type 2 ribonucleotide reductase subunit 2 using an adenovirus vector.
The herpes simplex viruses (HSV-1 and HSV-2) encode a ribonucleotide reductase consisting of two non-identical subunits (RR1 and RR2) which associate to form the active holoenzyme. To facilitate the purification and subsequent biochemical characterization of this enzyme, we have cloned the small subunit 2 of the HSV-2 ribonucleotide reductase (RR2HSV-2) in a helper-independent adenovirus type 5 vector under the control of the adenovirus type 2 major late promoter. After infection of 293 cells with the recombinant virus, the amount of RR2HSV-2 protein produced was eightfold higher than in HSV-2-infected cells. The specific activities of the RR2HSV-2 recombinant subunit and the RR2HSV-2 protein in HSV-2-infected cells were determined by their mixing with saturating amounts of isolated RR1HSV-1 subunit. By comparison of the relative amount of each RR2HSV-2 subunit with its specific activity, we calculated that the recombinant protein intrinsic activity was similar to that of the protein produced in HSV-2-infected cells. These results demonstrated that the adenovirus expression vector is a good system to produce an active RR2HSV-2 subunit in fairly high amounts.
Myocardial high-energy phosphates in reactive hyperemia.
This study used 31P nuclear magnetic resonance (NMR) spectroscopy to determine whether the magnitude and duration of myocardial reactive hyperemia (RH) reflect a commensurate derangement of myocardial high-energy phosphate (HEP) metabolism, or if coronary blood flow (CBF) and HEP metabolism are dissociated during RH. Twelve open-chest anesthetized pigs were studied during and after 24 s occlusion of the anterior descending coronary artery. CBF velocity was measured with a Doppler probe. NMR time resolution (4.8 s) was obtained by summing corresponding short blocks of data from multiple occlusions. During occlusion, phosphocreatine (PCr) declined to 65 +/- 5% (mean +/- SE) of control accompanied by increased spectral intensity of the Pi + phosphomonester region. By 20 s of reflow, HEPs had returned to control levels, but CBF was still elevated at 282 +/- 18% of control and remained elevated for an additional 53 +/- 7 s, during which 44 +/- 6% of total RH flow occurred. Therefore, the control of CBF is not closely coupled to the levels of myocardial HEPs during RH and the duration of RH does not reflect prolonged depletion of myocardial HEPs.
Dynamic relation between myocardial contractility and energy metabolism during and following brief coronary occlusion in the pig.
Changes in high-energy phosphate metabolism may be important in the regulation of myocardial contractile function during ischemia. This study sought to determine the dynamic relation between myocardial contractile function and high-energy phosphate metabolism during and following brief (24-second) coronary occlusion, when large and rapid changes in both parameters occur. Eight anesthetized, open-chest pigs were instrumented with a Doppler flow probe and occluder on the anterior descending coronary artery, segment length crystals in the anterior left ventricular wall, and a surface coil for phosphorus-31 nuclear magnetic resonance spectroscopy. Phosphorus-31 spectra were reconstructed with a 4.8-second time resolution by summing corresponding short blocks of data from multiple occlusions. Metabolic and functional parameters were unchanged during the first 4.8 seconds of occlusion. During the remainder of occlusion, phosphocreatine progressively declined to 66 +/- 3% of control, inorganic phosphate rose to 170 +/- 8% of control, and segment shortening fell to 25 +/- 9% of control. A strong linear correlation was found between dynamic changes in segment shortening and phosphocreatine (r2 = 0.97), inorganic phosphate (r2 = 0.96), and the ratio of phosphocreatine to inorganic phosphate (r2 = 0.98) during occlusion. At any level of the ratio between phosphocreatine and inorganic phosphate, segment shortening was greater during reflow than during occlusion. The close, dynamic relation between segment shortening and phosphorus metabolites supports the regulation of contractility by changes in energy metabolism or its by-products during ischemia. During reactive hyperemia, the high coronary flow rate may be an independent factor modulating contractility.
Relationship between myocardial metabolites and contractile abnormalities during graded regional ischemia. Phosphorus-31 nuclear magnetic resonance studies of porcine myocardium in vivo.
The mechanisms responsible for changes in myocardial contractility during regional ischemia are unknown. Since changes in high-energy phosphates during ischemia are sensitive to reductions in myocardial blood flow, it was hypothesized that myocardial function under steady-state conditions of graded regional ischemia is closely related to changes in myocardial high-energy phosphates. Therefore, phosphorus-31 nuclear magnetic resonance spectroscopy was employed in an in vivo porcine model of graded coronary stenosis. Simultaneous measurements of regional subendocardial blood flow, high-energy phosphates, pH, and myocardial segment shortening were made during various degrees of regional ischemia in which subendocardial blood flow was reduced by 16-94%. During mild reductions in myocardial blood flow (subendocardial blood flow = 83% of nonischemic myocardium), only the ratio of phosphocreatine to inorganic phosphate (PCr/Pi), Pi, and [H+] were significantly changed from control. PCr, ATP, and PCr/ATP were not significantly reduced from control with mild reductions in blood flow. Changes in myocardial segment shortening were most closely associated with changes in PCr/Pi (r = 0.94). Pi and [H+] were negatively correlated with segment shortening (r = -0.64 and -0.58, respectively) and increased over twofold when blood flow was reduced by 62%. Thus, these data demonstrate that PCr/Pi is sensitive to reductions in myocardial blood flow and closely correlates with changes in myocardial function. These data are also consistent with a role for Pi or H+ as inhibitors of myocardial contractility during ischemia.
Chronic aortic insufficiency: factors associated with progression to aortic valve replacement.
STUDY OBJECTIVE: To determine whether the initial measurement of clinical variables in patients with chronic stable aortic insufficiency is helpful in identifying patients at risk for earlier progression to aortic valve replacement. DESIGN: Prospective analysis of a cohort of patients for a median follow-up time of 44 months (range, 8 to 57). SETTING: Referral-based cardiology clinics at two university hospitals and their affiliated Veterans Administration medical centers. PATIENTS: Cohort of 50 asymptomatic or minimally symptomatic patients with chronic aortic insufficiency and left ventricular enlargement. Patients had preserved left ventricular ejection fraction at rest and no evidence of coronary artery disease or significant noncardiac illness. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Baseline evaluation included a history and physical examination, chest roentgenogram. M-mode echocardiogram, treadmill test, and radionuclide angiogram done at rest and during supine bicycle exercise. Ten patients progressed to surgery because of the onset of limiting symptoms or objective evidence of left ventricular dysfunction, or both; the overall rate was 4% +/- 3% per year. The Breslow and Mantel-Cox statistics were used to compute survival (surgery-free) dichotomized by prognostic variables. The progression to surgery was earlier in patients with left ventricular end-diastolic volume indices of 150 cc/m2 or more, end-systolic volume indices of 60 cc/m2 or more, a left ventricular ejection fraction at maximal exercise of less than 0.50, or an end-systolic wall stress of 86 dynes/cm2 or more. CONCLUSIONS: Patients at higher and lower risk for early progression to aortic valve replacement can be identified through the measurement of left ventricular size and function. This information can be used to decide the frequency and intensity of follow-up evaluation in these patients.