Left ventricular response to exercise in aortic stenosis: an exercise echocardiographic study

BACKGROUND: While normal at rest, left ventricular (LV) systolic function may become abnormal during exercise in patients with aortic stenosis. Once contraindicated in patients with aortic stenosis, exercise testing is now recommended in asymptomatic patients with aortic stenosis to elicit symptoms and thereby ascertain the need for aortic valve replacement. However, the clinical significance of an abnormal LV response to exercise in asymptomatic patients with aortic stenosis remains unknown. OBJECTIVE: The aim of this study was to evaluate the clinical implications of an abnormal LV response during exercise in the setting of aortic stenosis. METHODS: We monitored the LV response to exercise by 2D-Doppler echocardiography during a symptom limited semirecumbent bicycle exercise in 50 patients with tight aortic stenosis (aortic valve area < or = 1.0 cm(2)) and a normal LV systolic function (LV ejection fraction, EF > or = 50%) and followed them for an average of 11 months. RESULTS: Twenty patients had an abnormal LV response to exercise with a mean decrease in LV EF from 64 +/- 10 to 53 +/- 12% while 30 patients had a normal LV response to exercise with a mean increase in LV EF from 62 +/- 7 to 70 +/- 8%. Patients with an abnormal LV response during exercise were more likely to develop symptoms during exercise than patients with a normal LV response: 80% versus 27% (P< 0.0001). The survival free of cardiac events was significantly lower in patients with abnormal LV response to exercise than in patients with a normal response (P = 0.03). CONCLUSION: Exercise echocardiography provides objective data that facilitate interpretation of exercise elicited symptoms in asymptomatic patients with severe aortic stenosis. In addition, an abnormal LV response to exercise may predict a poor outcome.     

Left ventricular volume and ejection fraction response to exercise in aortic regurgitation

To test the hypothesis that left ventricular (LV) performance in aortic regurgitation (AR) can be more completely characterized by measurement of LV volumes in addition to ejection fraction (EF), 27 asymptomatic patients (Group 1), and 22 symptomatic patients (Group 2), and 10 control subjects were studied at rest and during upright bicycle exercise using the first-pass technique and a multicrystal scintillation camera. LV end-diastolic volume was measured by the area-length method. In the control group end-diastolic volume increased 14%, end-systolic volume decreased 22%, and EF increased 22% with exercise. In contrast, in Group 1 patients with AR, end-diastolic volume was elevated at rest and during exercise. The 18% decrease in end-diastolic volume during exercise was significantly different from the control response (p less than 0.01). End-systolic volume was also elevated at rest and during exercise, but the 30% decrease during exercise was a response not significantly different from the control. Although mean EF increased 15% in these patients, EF at peak exercise was significantly lower than that in the controls. In Group 2 patients with AR, resting EF was reduced, the EF response to exercise was abnormal, and end-diastolic and end-systolic volume responses to exercise were significantly different from those in Group 1: end-diastolic volume did not change and end-systolic volume increased. In contrast to the fairly uniform volume responses among all Group 1 patients, there were 2 subgroups based on volume changes within Group 2: 7 of 22 had a decrease in end-diastolic volume and end-systolic volume during exercise and 8 of 22 showed an increase in end-diastolic and end-systolic volume during exercise. In conclusion, LV volumes at rest and exercise give more information about LV functional reserve in symptomatic patients with AR than do EF responses alone, and may be useful in separating symptomatic patients who show a normal end-systolic volume response to exercise from those in whom worsening failure develops during exercise.     

The relation between myocardial ischemia and the ejection fraction response to exercise in patients with normal or abnormal resting left ventricular function

This study examines the relation between myocardial ischemia and the left ventricular (LV) ejection fraction (EF) response to exercise in patients with normal or abnormal resting EF. We studied 69 patients aged 25 to 78 years (mean 52 years) by radionuclide ventriculography (at rest and during peak upright exercise) and by exercise thallium-201 imaging. In 27 patients with resting EF less than 50%, the EF response to exercise was normal (greater than or equal to 5% increase) in 13 patients and abnormal in 14. The thallium scans showed reversible defects in 11 of the 14 patients (79%) with abnormal response but none in any of the patients with normal responses (p = 0.0001). In the 42 patients with resting EF greater than or equal to 50%, the EF response to exercise was normal in 23 and abnormal in 19. Reversible defects were present in 13 of the 19 patients (68%) with abnormal response and in only 3 of 23 patients (13%) with normal response (p = 0.0001). Therefore, an abnormal EF response to exercise was seen in 11 of 11 patients with resting EF less than 50% and in 13 of 16 patients (81%) with resting EF greater than or equal to 50% who had reversible thallium defects; normal EF responses were seen in 13 of the 16 patients (81%) with resting EF less than 50% and in 20 of 26 patients (77%) with resting EF greater than or equal to 50% who had no reversible thallium defects. Thus, in patients with abnormal resting LV function an abnormal EF response to exercise suggests the presence of myocardial ischemia rather than a nonspecific response to stress.     

Radionuclide angiographic evaluation of left ventricular performance at rest and during exercise in patients with aortic regurgitation

Radionuclide angiographic evaluation of LV performance at rest and during exercise in patients with AR have shown that an abnormal EF response to exercise may be observed in asymptomatic patients with normal resting LV function. The EF response to exercise has been correlated with a number of clinical and exercise measurements; important among these are the slope of the systolic pressure-to-end-systolic volume, end-systolic volume, cardiac index, pulmonary capillary wedge pressure, and wall stress. The changes in the regurgitant fraction, EF, and LV volume have shown considerable individual variability; they have also allowed a better understanding of the circulatory responses during exercise. Radionuclide angiography provides a reliable and reproducible method of measuring the rest LVEF that is important in the timing and the outcome of valve replacement. The value of the EF response to exercise in patient management is not yet clear; it is possible that other radionuclide-derived measurements at rest or during exercise, such as the systolic pressure-to-end-systolic volume relationship, and the end-systolic volume may provide complementary information to that provided by the EF.     

Left ventricular pressure/volume relationship in aortic regurgitation

In this study we examined the left ventricular pressure/volume relationship in 39 patients with moderate or severe aortic regurgitation (AR) and 15 normal subjects. The patients with AR were divided into two groups; patients with normal resting ejection fraction (EF greater than or equal to 50%, group I, n = 21) and patients with abnormal EF (group II, n = 18). The patients in group I were younger (p less than 0.005), exercised to a higher workload, and had better exercise tolerance than patients in group II (p less than 0.01). The patients' exercise heart rate and blood pressure were not significantly different between the two groups. During exercise tests nine patients in group I and seven patients in group II had normal EF response (greater than or equal to 5% increase) (p = NS). The peak systolic blood pressure to end-systolic volume index ratio (SBP/ESVI) was higher in normal subjects than in patients in groups I and II, at rest it was (4.3 +/- 1.0 vs 2.6 +/- 1.2 vs 1.6 +/- 0.8, respectively, p less than 0.0001) and during exercise it was (7.6 +/- 1.8 vs 4.2 +/- 1.4 vs 2.6 +/- 1.3, respectively, p less than 0.0001). The resting SBP/ESVI ratio was below the lower normal limit in 12 patients (57%) in group I and in 16 patients (89%) in group II. Also, the exercise SBP/ESVI ratio was below the lower normal limit in 17 patients (81%) in group I and all of the patients (100%) in group II. Multivariate discriminant analysis identified the change in SBP/ESVI (F = 34.8) and resting end-diastolic volume (F = 6.7) as independent predictors of the EF response to exercise. Thus, most patients with AR, including those with normal resting EF or normal EF response to exercise, have abnormal SBP/ESVI at rest or during exercise.     

Comparison of effects of isometric and supine bicycle exercise on left ventricular performance in patients with aortic regurgitation and normal ejection fraction at rest

The effects of handgrip and supine bicycle exercise on hemodynamics and left ventricular (LV) performance were compared in 25 patients with moderate to severe aortic regurgitation (AR) and normal LV ejection fraction at rest (greater than or equal to 50%) and in 10 control subjects. In both groups, heart rate, systolic blood pressure, rate-pressure product, and LV output were higher during supine bicycle exercise. Compared with the controls, in patients with AR, stroke volume was unchanged during supine bicycle exercise. LV end-diastolic volume increased during handgrip exercise but was unchanged during supine bicycle exercise. LV end-systolic volume increased and ejection fraction decreased during both forms of exercise. Of 25 patients with AR, 15 (60%) during handgrip exercise and 19 (76%) during supine bicycle exercise had an abnormal ejection fraction response (p less than 0.05). In patients with moderate to severe AR and normal LV ejection fraction at rest, both handgrip and supine bicycle exercise induced LV dysfunction. An abnormal LV ejection fraction response occurred more often with supine bicycle exercise. Handgrip exercise may be a useful alternative method for detecting LV dysfunction in patients with AR in whom adequate bicycle exercise cannot be accomplished.     

Relation between left ventricular functional reserve during exercise and resting systolic loading conditions in chronic aortic regurgitation

The relation between systolic loading conditions at rest and left ventricular (LV) functional response to exercise was assessed in 31 patients with aortic regurgitation (AR) (20 asymptomatic, 11 symptomatic) and 10 control subjects. Peak and end-systolic wall stress determined from echocardiography and cuff systolic pressure at rest were used as indirect measures of LV systolic loading and were compared with LV ejection fraction response to handgrip and bicycle exercise by radionuclide ventriculography. Both peak and end-systolic wall stress were significantly higher in both asymptomatic (164 +/- 33 and 90 +/- 25 X 10(3) dynes/cm2) and symptomatic (196 +/- 33 and 134 +/- 17 X 10(3) dynes/cm2) patients with AR than in the control subjects (125 +/- 22 and 61 +/- 14 X 10(3) dynes/cm2 p less than 0.01), and correlated inversely with the changes in LV ejection fraction during handgrip (r = -0.63 and r = -0.73) and bicycle (r = -0.68 and r = 0.87) exercise. In patients with AR, resting systolic loading conditions closely reflect LV functional reserve during exercise.     

Left ventricular ejection fraction response during exercise in asymptomatic systemic hypertension

To study the effect of mild-to-moderate elevations in diastolic blood pressure (BP) on systolic left ventricular (LV) function, 28 hypertensive patients and 20 normal subjects underwent upright exercise first-pass radionuclide angiography. All were asymptomatic, had normal rest and exercise electrocardiographic findings and no evidence of LV hypertrophy or coronary artery disease. LV function at rest was similar in the 2 groups, but with exercise hypertensive patients had a greater end-systolic volume (69 +/- 19 vs 51 +/- 19 ml, p less than 0.002) and lower ejection fraction (EF) (0.59 +/- 0.09 vs 0.72 +/- 0.07, p less than 0.0001), stroke volume (101 +/- 28 vs 130 +/- 36 ml, p less than 0.005) and peak oxygen uptake (23 +/- 7 vs 33 +/- 9 ml/kl/min, p less than 0.05). Hypertensive patients were separated into 3 groups: group 1-12 patients with an increase in EF with exercise greater than or equal to 0.05; group 2-7 patients with a change in EF with exercise less than 0.05; and group 3-9 patients with a decrease in EF with exercise greater than or equal to 0.05. Group 3 hypertensive patients were older, had a higher heart rate at rest and lower peak oxygen uptake. Rest LV function was similar in the 3 hypertensive subgroups, but exercise end-systolic volumes were higher in groups 2 and 3. Exercise thallium-201 images was normal in all but 1 of 14 hypertensive group 2 or 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Risk stratification of single or double vessel coronary artery disease and impaired left ventricular function using exercise radionuclide angiography

Patients with 3-vessel coronary artery disease (CAD) and normal left ventricular (LV) function have a worse prognosis if they manifest ischemia during exercise testing. The present study determines if exercise radionuclide angiography can aid in the risk stratification of patients with 1- or 2-vessel CAD and impaired LV function (ejection fraction less than 50%). Sixty-five consecutive patients with these findings were followed for a median duration of 24 months (range 12 to 49). Eleven of the 65 patients (17%) had severely ischemic exercise radionuclide angiograms, defined as: a decrease in ejection fraction with exercise; greater than or equal to 1.0 mm of ST-segment depression; and peak exercise workload less than or equal to 600 kg-m/min. During follow-up 11 patients had initial significant cardiac events: 4 cardiac deaths, 1 cardiac arrest, 4 myocardial infarctions and 2 bypass or angioplasty procedures for unstable angina greater than or equal to 3 months after the exercise study. Four of 11 patients (36%) with severely ischemic exercise radionuclide angiograms had events, compared to 7 of 54 patients (13%) without ischemic radionuclide angiograms. Event-free survival at 18 months was 73% for patients with severe exercise ischemia versus 92% for those without ischemia (p less than 0.05). Univariate analysis showed that severe ischemia on radionuclide angiography was the only variable of several tested that significantly predicted future cardiac events (chi-square = 8.16, p less than 0.005). Among patients with 1- or 2-vessel CAD and impaired resting LV function, severe ischemia on exercise radionuclide angiography identifies a subgroup at high risk for future cardiac events.     

Comparison of ambulatory left ventricular ejection fraction and blood pressure in systemic hypertension in patients with and without increased left ventricular mass.

To evaluate the effects of long-standing systemic hypertension on left ventricular (LV) function during daily activities, ambulatory radionuclide monitoring of LV ejection fraction (EF) and blood pressure was performed during exercise and other structured activities in 31 hypertensive patients. Patients were divided into 3 groups based on the absence of LV hypertrophy (group 1 [n = 16], LV mass 107 +/- 12 g/m2), presence of LV hypertrophy without electrocardiographic changes (group 2 [n = 10], LV mass 141 +/- 8 g/m2) and LV hypertrophy with associated electrocardiographic changes (group 3 [n = 5], LV mass 158 +/- 9 g/m2). The groups were similar with respect to age, baseline medication, treated and untreated blood pressure, resting EF and treadmill exercise time. Patients in group 3 had the longest history of hypertension. Peak filling rate was normal in group 1 (2.9 +/- 0.4 end-diastolic volume/s), but reduced at rest in groups 2 (2.4 +/- 0.4) and 3 (2.1 +/- 0.3). Patients in group 1 had normal EF responses to exercise and mental stress testing, as well as during routine ambulatory activities. Patients in group 2 had a blunted EF response to exercise, and those in group 3 had a significantly abnormal response. Both group 2 and 3 patients demonstrated abnormal EF responses to mental stress, as well as cold pressor testing in association with significant increases in mean arterial pressure and marked reduction in diastolic filling rate. Decreases in EF were also observed during routine patient monitoring in 3 group 3 patients and 4 group 2 patients. These events were associated with significantly increased blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prediction of mortality in patients with left ventricular hypertrophy by clinical,exercise stress,and echocardiographic data

OBJECTIVES: This study evaluated the clinical, exercise stress test, and echocardiographic predictors of mortality and cardiac events in patients with left ventricular hypertrophy (LVH). BACKGROUND: Left ventricular hypertrophy is associated with an increased risk of cardiovascular morbidity and mortality. METHODS: Symptom-limited treadmill exercise echocardiography was performed for evaluation of coronary artery disease in 483 patients (age, 66 +/- 11 years; 281 men) with LVH. End points during follow-up were all-cause mortality and hard cardiac events (cardiac death and nonfatal myocardial infarction [MI]). RESULTS: Forty-six patients died and 14 had nonfatal MI. The cumulative mortality rate was higher in patients with abnormal exercise echocardiography (3% vs. 0.4% at one year, 11.7% vs. 3.7% at three years, and 18.3% vs. 9.5% at five years, p < 0.001). In a sequential multivariate analysis model of clinical, exercise test, and rest and exercise echocardiographic data, incremental predictors of mortality were workload (hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3 to 0.9), rate pressure product (HR, 0.7; 95% CI, 0.5 to 0.9), left ventricular (LV) mass index (HR, 1.4; 95% CI, 1.1 to 1.8), and failure to increase ejection fraction (EF) with exercise (HR, 2.1; 95% CI, 1.1 to 3.8). Predictors of cardiac events were history of coronary artery bypass grafting (HR, 2.6; 95% CI, 1.2 to 5.4), lower exercise rate-pressure product (HR, 0.6; 95% CI, 0.5 to 0.8), resting wall motion score index (HR, 1.4; 95% CI, 1.1 to 1.8), and failure to increase EF with exercise (HR, 3.3; 95% CI, 1.6 to 6.9). CONCLUSIONS: In patients with LVH, LV mass index and EF response to exercise are independent predictors of mortality, incremental to clinical and exercise test data and resting LV function. A normal exercise echocardiogram predicts a relatively low mortality rate during the following three years.     

Comparative effects of propranolol and verapamil alone and in combination on left ventricular function and volumes in patients with chronic exertional angina: a double-blind, placebo-controlled, randomized, crossover study with radionuclide ventriculography

With the use of equilibrium radionuclide ventriculography the effects on left ventricular (LV) function of 160 mg oral propranolol daily and 360 mg verapamil daily alone and in combination were compared in 18 patients with chronic exertional angina. A randomized, double-blind, placebo-controlled, crossover protocol was used. The reduction in exercise rate-pressure product induced by the combination (118 +/- 28 mm Hg/min) was significantly greater (p less than .05) than that by propranolol (135 +/- 27 mm Hg/min) or verapamil alone (163 +/- 28 mm Hg/min). In patients at rest, neither single nor combined therapy altered global or regional left ventricular ejection fractions (EFs). Verapamil, but not propranolol, increased (p less than .05) cardiac volumes of resting subjects; used in combination, no further increase in LV volume occurred. With placebo, exercise global EF did not decrease from the level at rest and therefore no drug effect could be demonstrated for this parameter of LV function. By an evaluation of normalized regional EF measurements the combination was shown to reduce exercise-induced hypokinesis (placebo 52 +/- 20%, combination 61 +/- 23%; p less than .01). No significant improvement was noted with propranolol or verapamil alone; only the combination prevented a significant increase in end-systolic and end-diastolic volumes during exercise. Thus, propranolol and verapamil, used alone in moderate doses, exert no beneficial effect on exercise LV function as measured by EF and volume changes, and resting function deteriorates slightly with verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular response to isometric exercise and its value in predicting the change in ventricular function after mitral valve replacement for mitral regurgitation

Reduced left ventricular (LV) afterload and its effect on the resting ejection fraction may lead to over-estimation of LV function in mitral regurgitation (MR). To evaluate LV function during increased afterload of the heart, an isometric handgrip test was performed during cardiac catheterization in 15 patients with mitral regurgitation (MR group) and in 9 normal subjects (normal group). Twelve months after successful mitral valve replacement (MVR) the patients were recatheterized, and the value of preoperative stress testing in predicting the change in resting ventricular function after surgery was estimated.Isometric exercise caused an increase in end-systolic wall stress, a measure of ventricular afterload, in both the MR group and the control group (p < 0.001). The ejection fraction remained unchanged in the control group, but decreased from 0.58 ± 0.08 to 0.53 ± 0.08 in the MR group (p < 0.001). After MVR, end-systolic wall stress increased significantly (p < 0.001) and the ejection fraction decreased from 0.58 ± 0.05 to 0.51 ± 0.1 (p < 0.05). A positive correlation existed between the change in the ejection fraction during preoperative stress testing and the change in the resting ejection fraction after MVR (r = 0.65, p < 0.01). In 8 patients whose resting ejection fraction was within normal limits (> 0.55) preoperatively, the ejection fraction was depressed (< 0.55) 1 year after surgery. In all but 1 of these patients the isometric exercise revealed the reduced ventricular response to afterload stress preoperatively (decrease of the ejection fraction > 0.03 during exercise). Therefore, the isometric exercise-induced change in LV function appears to predict the influence of MVR on LV function.     

Left ventricular filling in sickle cell anemia

M-mode echocardiography was performed on 11 normal black subjects and 38 patients with sickle cell anemia while they were at rest to evaluate their left ventricular (LV) systolic and diastolic function. The patients with sickle cell anemia were also evaluated by radionuclide exercise tests and, based on their ejection fraction (EF) response, were separated into 2 groups: a group with a normal EF response to exercise (73 +/- 9%, mean +/- standard deviation) and a group with an abnormal EF response to exercise (53 +/- 9%). Computer-assisted analysis of the M-mode echocardiograms identified abnormalities of diastolic function (impaired left ventricular filling) in patients with sickle cell anemia compared with the normal subjects. The abnormal EF response group had significantly more impaired diastolic function and did less exercise than the normal EF response group. Both groups of patients had a decrease in left ventricular end-diastolic volume during exercise. The patients with sickle cell anemia had abnormalities of systolic and diastolic function on echocardiographic and radionuclide testing. The abnormalities in diastolic and systolic function assumed greater significance at the increased heart rates associated with exercise, accounting for the decrease in left ventricular end-diastolic volume and the abnormal EF response, and contributed to exercise intolerance in patients with sickle cell anemia.     

Long-term effect of mexiletine on left ventricular function and relation to suppression of ventricular arrhythmia.

The effects of oral mexiletine on left ventricular (LV) ejection fraction (EF) and ventricular arrhythmias--and a possible relation between these effects--were evaluated during 3 months of therapy in 29 patients with chronic ventricular premature complexes (VPCs) and a moderately reduced to normal LVEF by 24-hour Holter monitoring and by radionuclide ventriculography at rest and during maximum tolerable exercise testing. After an average titration period of 13 days, a mean daily mexiletine dose of 739 mg was maintained throughout the treatment. At the end of titration and after 3 months of treatment, patients with a baseline LVEF less than or equal to 40% (group 2) responded with a median reduction of the hourly VPC rate by 90 and 81%, respectively, compared with 79 and 72% in those with a baseline LVEF greater than 40% (group 1). Couplets and runs of ventricular tachycardia were almost completely suppressed in nearly all patients. A single patient had a proarrhythmic increase in VPCs during treatment. Compared with baseline, there were no significant changes in resting or exercise LVEF after 1 or 3 months of treatment in either of the 2 groups of patients. No correlation was found between treatment-induced changes in arrhythmia frequency and in resting EF. No symptoms of congestive heart failure developed. The study confirms that long-term use of mexiletine is efficacious and relatively free of cardiac depressant effects even in patients with diminished LV function.     

Left ventricular function in asymptomatic patients with severe aortic regurgitation: relation to clinical parameters and exercise performance

The optimal time for valve replacement in asymptomatic patients with severe aortic regurgitation is uncertain and is usually based on changing patterns in the ECG, radiographic heart size, or decreasing effort tolerance. The relationship between these parameters and changes in left ventricular function however has not been defined. In this study 28 patients, ages 20 to 66 years (mean 35 years) underwent gated pool radionuclide imaging at rest and at submaximal exercise (to greater than 85% maximum heart rate predicted for age) to quantitate ejection fraction (EF) and severity of aortic regurgitation. All patients had a 12-lead ECG and chest x-ray and 18 patients underwent echocardiography and maximal treadmill exercise testing. Severity of left ventricular hypertrophy on ECG was assessed by the Estes scoring system, heart size was expressed as cardiothoracic ratio (CTR). Echocardiograms were analyzed with respect to left ventricular end-systolic diameter (LVESD) and fractional shortening. EF was below the normal range at rest (<0.45%) in only 6 patients (21%), but was abnormal during exercise in 18 patients (64%). Reduction in EF on exercise by 20% was judged to represent significant deterioration and occurred in 12 patients (43%), all of whom had an EF of less than 0.45% on exercise. Comparison of ECG, heart size, echocardiogram, exercise performance, and resting EF in this group of 12 patients with the remaining 16 patients showed no significant differences. In the group as a whole, stress EF was abnormal in 14 of 19 patients (73%) with an Estes score of 5 or greater, and was significantly lower (p < 0.05, mean 0.42) than in patients with an Estes score less than 5 (mean 0.52). There was no significant correlation between EF at rest or during exercise and any of the other parameters. Severity of aortic regurgitation (regurgitant fraction) showed poor correlation with heart size and LVESD (r = 0.24 and 0.32, respectively). It is concluded that abnormalities of left ventricular function can be demonstrated on exercise in a significant proportion of patients with aortic regurgitation despite the absence of symptoms, and that these changes cannot be predicted by readily available clinical parameters or by assessment of resting left ventricular function. Gated pool imaging may be a sensitive method for detection of early changes in LV function in these patients, but its value in assessing the timing of valve replacement requires serial investigation.     

Prospective evaluation of doxorubicin cardiotoxicity by rest and exercise radionuclide angiography

The role of rest and exercise radionuclide angiography (RNA) in predicting the cardiotoxic effects of doxorubicin was assessed prospectively in 48 patients who received a mean total doxorubicin dose of 522 mg/m2 (range 480 to 600). Thirty-three of these patients also received cyclophosphamide (mean 5,220 mg/m2). Left ventricular (LV) ejection fraction (EF) at rest progressively decreased from the baseline value of 55 +/- 9% to 52 +/- 8% after 338 mg/m2 to 47 +/- 8% after completion of doxorubicin therapy (p less than 0.001). In 42 patients (88%) EF at rest decreased after doxorubicin administration. Although no patient had known prior heart disease, the EF response to exercise was abnormal in 11 patients before doxorubicin. EF at rest after doxorubicin was significantly lower (41 +/- 6% vs 49 +/- 8%, p less than 0.02) in these 11 patients than in the 29 patients in whom the pretreatment EF response to exercise was normal, and in 4 of the 11 patients congestive heart failure developed. While age was an independent risk factor, cyclophosphamide did not appear to enhance the cardiotoxicity of doxorubicin. By multivariate analysis, age (p = 0.01) and EF at the midcourse of doxorubicin therapy (p less than 0.001) were the most significant predictors of final EF after completion of doxorubicin therapy; neither rest nor exercise EF before doxorubicin appreciably improved the predictive value of age and EF at midcourse of therapy. Thus, some depression of LV function occurs in most patients receiving doxorubicin, and patients with abnormal baseline function appear to be at greater risk of clinical congestive heart failure after doxorubicin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long‐Term Outcome in Asymptomatic Patients with Severe Aortic Regurgitation,Normal Left Ventricular Ejection Fraction,and Severe Left Ventricular Dilatation

Background: Although the guidelines consider severe left ventricular (LV) dilatation a class IIaC indication for surgery in asymptomatic patients with severe aortic regurgitation (AR) and normal LV function, the optimal management remains controversial. We aimed to assess the LV enlargement, hypertrophy and function, and the outcomes in these patients by the presence of severe LV dilatation at baseline. Methods: From our 20‐year database, we identified all asymptomatic patients with severe AR and LV ejection fraction (EF) >50% and ≥2 echocardiograms ≥1 year apart. LV end‐diastolic diameter >70 mm or LV end‐systolic diameter >50 mm or LV end‐systolic diameter index >25 mm/m² defined severe LV dilatation. A composite end point included onset of symptoms or LV dysfunction. Results: Eighty‐four patients (52 ± 18 years, 61 men) were enrolled and followed‐up for 7.1 ± 5.1 years. Two groups were defined: 22 patients with and 62 patients without severe LV dilatation at baseline. The progression of LV dilatation and hypertrophy, and the LVEF at last exam were similar in both groups. Twelve of 22 and 34 of 62 patients (P = 0.59) reached the end point. Vasodilators did not modify the progression of LV enlargement/hypertrophy. Ten of 22 and 25 of 62 patients (P = 0.45) underwent surgery and had similar postoperative LV diameters, mass, EF. Conclusions: The progression of LV enlargement/hypertrophy and outcomes in asymptomatic patients with severe AR, normal LV function, and severe LV dilatation or the postoperative LV parameters were not influenced by the severe LV dilatation, suggesting that a close follow‐up could delay surgery in this population. (Echocardiography 2010;27:915‐922)     

Effects of severity of mitral stenosis on left and right ventricular function at rest and during exercise

Few studies have assessed the effect of severity of mitral stenosis (MS) on ventricular function. Using equilibrium radionuclide ventriculography to measure ejection fraction and volume changes, 63 patients were studied during supine, symptom-limited exercise. To more carefully assess the 12 patients with MS and impaired left ventricular function, 2 groups of patients were formed. Group I (n = 51) had a normal (less than 50%) resting left ventricular (LV) ejection fraction (EF) and group II (n = 12) had an abnormally low (less than 50%) resting LVEF. Both groups were divided into mild (greater than 1.4 cm2), moderate (1.1-1.4 cm2) and severe (less than 1.0 cm2) MS. There were no differences in mean rest or exercise LVEF for group I. Exercise LVEF increased significantly (p less than 0.05) from rest with mild MS, but not with moderate or severe MS. The decrease in exercise LVEF was due to a decrease in exercise end-diastolic volume of 9 +/- 23% and 15 +/- 18% for moderate and severe MS, respectively. Exercise end-systolic volume decreased normally for all degrees of MS severity. Exercise right ventricular (RV)EF did not increase for any degree of MS severity due to an increase in end-systolic volume. All patients in group II had an RVEF of less than 40%. For this group, severity of MS had no effect on resting LVEF and the response to exercise was similar to group I. We conclude that in patients with MS, resting LVEF is unaffected by MS severity whereas exercise LVEF decreases with increased severity of MS due to impaired diastolic filling.(ABSTRACT TRUNCATED AT 250 WORDS)