Relation between left ventricular shape and exercise capacity in patients with left ventricular dysfunction.

OBJECTIVES: The aim of this study was to identify dynamic predictors of exercise duration in patients with systolic left ventricular dysfunction and to test the hypothesis that left ventricular shape is an independent determinant of exercise duration in these patients. BACKGROUND: Measurements of left ventricular volumes and ejection fraction at rest do not predict exercise capacity in patients with systolic left ventricular dysfunction. Left ventricular shape at rest has been reported to be an independent determinant of exercise duration in these patients. The significance of alterations in left ventricular shape that occur during dynamic exercise has not been investigated. METHODS: Twenty-one patients with a documented ejection fraction < 40% performed symptom-limited graded upright bicycle exercise with simultaneous quantitative two-dimensional echocardiography. End-diastolic volume, end-systolic volume, stroke volume, ejection fraction and sphericity index were measured at rest and peak exercise. RESULTS: Eleven patients exercised beyond stage II (6 min, 50 W), averaging 8.9 +/- 1.9 min; 10 patients were unable to complete stage II, averaging 4.9 +/- 0.9 min. No patient developed clinical evidence of ischemia during the exercise period. Of the echocardiographic variables considered, only end-systolic and end-diastolic sphericity indexes at peak exercise (r = 0.809 and 0.711, respectively) and the change in end-systolic sphericity index during exercise (r = 0.697) were strongly correlated with exercise duration. CONCLUSIONS: Conventional descriptors of left ventricular function are poor predictors of exercise capacity. Dynamic changes in heart shape correlate strongly with exercise duration and may be important determinants of exercise capacity in patients with systolic left ventricular dysfunction.

Validation of global and segmental left ventricular contractile function using gated planar technetium-99m sestamibi myocardial perfusion imaging.

OBJECTIVES: The purpose of this study was to test the hypothesis that segmental wall motion analysis determined from gated planar technetium-99m sestamibi myocardial imaging is reproducible and agrees well with echocardiographic data. BACKGROUND: Technetium-99m sestamibi is a new radiopharmaceutical recently approved for myocardial perfusion imaging. Its advantages include a dosimetry that allows use of a dose 10 to 15 times higher than that of thallium-201. As a result, myocardial counts are markedly improved and images can be collected in a gated mode to potentially allow assessment of global and segmental ventricular function. However, the reproducibility and accuracy of technetium-99m sestamibi imaging for measurement of global and segmental left ventricular function have not been evaluated or compared with those of a standard ventricular function technique, such as echocardiography. METHODS: We studied 136 patients referred for clinical technetium-99m sestamibi imaging. One-day rest-stress planar technetium-99m sestamibi protocols were used, gating the stress images. After technetium-99m sestamibi imaging, all patients had standard rest two-dimensional echocardiography. Global and segmental technetium-99m sestamibi and echocardiographic left ventricular contraction was graded qualitatively as normal or abnormal using a four-point grading system. RESULTS: Interobserver and intraobserver agreement was extremely high for global and segmental technetium-99m sestamibi wall motion analysis, with absolute agreements ranging from 0.92 to 1.00 and corresponding kappa values of 0.74 to 1.00 (p < 0.00001). Agreement with global and segmental echocardiographic wall motion was similarly very high, with absolute agreements ranging from 0.93 to 1.00 and corresponding kappa values of 0.75 to 1.00 (p < 0.00001). CONCLUSIONS: Gated technetium-99m sestamibi cardiac imaging provides information with regard to rest global and segmental left ventricular systolic function that is highly reproducible and agrees very well with results of two-dimensional echocardiography.

Observations suggesting a high incidence of exercise-induced severe mitral regurgitation in patients with mild rheumatic mitral valve disease at rest.

OBJECTIVES: The aim of this study was to determine the hemodynamic effects of upright bicycle ergometry in symptomatic patients with mild, mixed mitral stenosis and regurgitation. BACKGROUND: Patients with seemingly mild rheumatic mitral valve disease often complain of exertional dyspnea or fatigue. These symptoms are usually ascribed to flow-dependent increases in the gradient across the stenotic mitral valve. Although catheterization studies in these patients may demonstrate an increase in mitral valve gradient proportional to an increase in cardiac output, this approach does not specifically address the underlying mechanism of any observed increases in mitral gradient or left atrial (i.e., pulmonary capillary wedge) pressure. Exercise echocardiography is uniquely suited to the dynamic assessment of exercise-induced hemodynamic changes. METHODS: Fourteen symptomatic patients with exertional dyspnea and mild mitral stenosis and regurgitation at rest performed symptom-limited upright bicycle ergometry with quantitative two-dimensional, Doppler and color Doppler echocardiographic analysis. RESULTS: Average pulmonary artery systolic pressure in the 13 patients with adequate spectral signals of tricuspid regurgitation increased from 36 +/- 5 mm Hg (mean +/- SD) at rest to 63 +/- 14 mm Hg at peak exercise (p < 0.001). The mean transmitral pressure gradient in all patients increased from 4.5 +/- 1.4 mm Hg at rest to 12.7 +/- 2.7 mm Hg at peak exercise (p < 0.001). Five patients developed severe mitral regurgitation during exercise. CONCLUSIONS: Patients with exertional dyspnea and mild mitral stenosis and regurgitation at rest demonstrate a marked increase in pulmonary artery systolic pressure and mean transmitral pressure gradient during dynamic exercise. In a subset of these patients, marked worsening of mitral regurgitation appears to be the underlying mechanism of this hemodynamic deterioration. Because of the small sample size, this novel observation must be considered preliminary with respect to the true prevalence of exercise-related development of severe mitral regurgitation. If additional studies confirm the importance of this phenomenon, it has important implications for the management of patients with rheumatic mitral valve disease.

Serial assessment of left ventricular function and mass after orthotopic heart transplantation: a 4-year longitudinal study.

Long-term changes in left ventricular performance and geometry in the transplanted human heart have been incompletely described. Therefore, two-dimensional echocardiograms were performed on 22 recipients of an orthotopic heart transplant at 1 month (32 +/- 20 days), 1 year (11 +/- 3 months) and 4 years (54 +/- 9 months) after transplantation. All studies were performed at a time when the patient had no pathologic evidence of rejection. Ten healthy men served as a normal control group. Over 4 years of follow-up, mean systolic blood pressure in the study patients increased from 121 +/- 12 (p = NS vs. values in the control group) to 139 +/- 11 mm Hg (p less than 0.05 vs. both control values and values at 1 month); mean diastolic blood pressure increased from 72 +/- 7 (p = NS vs. normal values in the control group) to 93 +/- 8 mm Hg (p less than 0.05 vs. both control values and values at 1 month). Left ventricular end-systolic volume increased from 42 +/- 10 (p = NS vs. control values) to 51 +/- 14 ml (p less than 0.05 vs. both control values and values at 1 month) and end-diastolic volume increased from 103 +/- 28 (p = NS vs. control values) to 112 +/- 27 ml (p less than 0.05 vs. control values) over 4 years. Left ventricular mass and ejection fraction did not change significantly within the patient cohort and remained similar to that found in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Papillary muscle fractional shortening is a determinant of heart shape in patients with prior myocardial infarction.

To examine the relation between papillary muscle fractional shortening and heart shape, we performed quantitative echocardiography in 20 patients with prior myocardial infarction and 20 normal control subjects. Papillary muscle fractional shortening was markedly depressed in infarction patients and there was a high degree of correlation between papillary muscle fractional shortening and left ventricular shape, which was evident over a wide range of ejection fraction and shape.

Evaluation of the significance of a transvalvular catheter on aortic valve gradient in aortic stenosis: a direct hemodynamic and Doppler echocardiographic study.

We studied 18 patients with aortic stenosis undergoing routine cardiac catheterization to determine the effect of a transvalvular catheter on transaortic pressure gradients. By measuring the Doppler gradients before and after the withdrawal of the pigtail catheter, we demonstrated significant increases in the peak instantaneous and mean gradients when the catheter straddled the valve, an effect that was more pronounced with increasing severity of stenosis.

Relation between left ventricular shape and Doppler filling parameters in patients with left ventricular dysfunction secondary to coronary artery disease.

Left ventricular (LV) shape is an independent predictor of exercise capacity in patients with systolic LV dysfunction. Recent studies suggest that end-systolic LV shape is related to the generation of restoring forces during contraction that facilitate filling at lower LV pressure during subsequent diastole. To test the hypothesis that preservation of a more elliptical LV shape would be associated with a distribution of diastolic inflow characterized by increased early relative-to-late filling, 32 outpatients with coronary artery disease and ejection fraction < 40% underwent quantitative 2-dimensional and Doppler echocardiography. LV volumes, ejection fraction, and eccentricity index were measured as were standard Doppler indexes of LV filling. Simple and multiple linear regression models were used to examine relations between LV shape and Doppler measurements. LV eccentricity at end-systole correlated strongly with the Doppler atrial filling fraction (r = -0.670; p < 0.001) and the ratio of early-to-late flow velocity integrals (r = 0.648; p < 0.001). No other 2-dimensional echocardiographic variable was significantly correlated with any other Doppler index of LV filling. Thus, LV shape at end-systole appears to be an important determinant of diastolic filling patterns. In patients with systolic LV dysfunction, preservation of a more elliptical chamber is associated with a diastolic inflow pattern characterized by increased early relative-to-late diastolic filling.

Effect of enalapril therapy on left ventricular mass and volumes in asymptomatic chronic, severe mitral regurgitation secondary to mitral valve prolapse.

Quantitative 2-dimensional and Doppler echocardiography was used to assess the longitudinal effects of angiotensin-converting enzyme inhibition in asymptomatic patients with chronic, severe mitral regurgitation due to mitral valve prolapse. Over a 6-month period, angiotensin-converting enzyme inhibition therapy resulted in significant reductions in left ventricular volumes and mass in association with a minor reduction in regurgitant fraction.

Left ventricular systolic torsion and early diastolic filling by echocardiography in normal humans.

This study describes a novel 2-dimensional echocardiographic technique to measure left ventricular (LV) systolic twist in humans and relates this measure to early ventricular filling. LV twist is the counterclockwise rotation of the left ventricle during systole when viewed from the apex. The effect of ventricular twist has been postulated to store potential energy, which ultimately aids in diastolic recoil, leading to ventricular suction. The generated negative early diastolic pressures may augment early ventricular filling. We measured ventricular twist in 40 patients with normal transthoracic echocardiograms. End-systolic twist was determined by measuring rotation of the anterolateral papillary muscle about the center of the ventricle. LV filling was assessed by analysis of transmitral Doppler flow velocities. The mean value obtained was 9 +/- 7 degrees of rotation. Twist measurements were highly reproducible with an intraobserver correlation coefficient of r = 0.881, p <0.001. The magnitude of ventricular twist was strongly correlated positively with acceleration of the mitral E-wave (r = 0.75; p <0.0001) and negatively with the mitral E-wave acceleration time (r = -0.83; p <0.0001).

Effects of percutaneous mitral valvuloplasty on left ventricular mass and volume.

The response of left ventricular (LV) geometry to altered loading conditions after mitral valvuloplasty has been incompletely described. Therefore, 15 patients with rheumatic mitral stenosis were studied using quantitative 2-dimensional echocardiography a mean of 1 +/- 2 months before and 11 +/- 5 months after percutaneous balloon mitral valvuloplasty. Mitral valve area (Gorlin) increased in all patients, from 1.0 +/- 0.3 to 1.9 +/- 0.5 cm2 (p less than 0.01). Mitral regurgitation (1+/4+) developed in 3 patients, and increased by 1 grade in 1 patient as a consequence of mitral valvuloplasty. After valvuloplasty, there were significant increases in LV end-diastolic volume (69 +/- 22 to 82 +/- 26 ml, p less than 0.01), stroke volume (34 +/- 13 to 46 +/- 19 ml, p less than 0.05) and mass (181 +/- 46 to 200 +/- 42 ml, p less than 0.005). LV end-systolic volume and ejection fraction did not change significantly. LV mass-to-volume ratio was unchanged (5.6 +/- 1.5 to 5.8 +/- 1.4 g/ml, p = not significant). Quantitatively similar results were obtained when these changes were indexed to body surface area. Thus, successful mitral valvuloplasty was associated with significant increases in LV end-diastolic volume and mass. These findings suggest that increased preload may be a stimulus to myocardial growth.

Effects of exercise on left ventricular performance determined by echocardiography in chronic, severe mitral regurgitation secondary to mitral valve prolapse.

Data on the effects of exercise on left ventricular (LV) volumes and ejection performance in patients with severe mitral regurgitation (MR) are limited. With use of a matched-pairs design, 10 asymptomatic patients with chronic, severe MR and normal LV systolic function who were not receiving vasodilator therapy (group 1) and 10 matched normal control subjects with no structural heart disease (group 2) performed symptom-limited upright bicycle ergometry with quantitative echocardiographic analysis. An additional 8 patients with severe, chronic MR and normal LV systolic function who were receiving vasodilator therapy at the time of testing (group 3) were studied for comparison. The 3 cohorts exercised for similar periods of time. Group 1 and 3 patients had similar end-diastolic volumes at rest, both of which were significantly greater than those of normal controls. Although resting LV end-systolic volume was greater in groups 1 and 3 than in normal controls, the 3 groups had similar relative percent reductions in end-systolic volume during exercise (30 +/- 12%, 32 +/- 13%, and 30 +/- 24%; p = NS). A similar percent increase in LV ejection fraction was also observed in all 3 cohorts (18 +/- 9%, 15 +/- 9%, and 14 +/- 6%; p = NS). Forward stroke volume increased significantly in group 1 (59 +/- 21 and 71 +/- 18 ml; p <0.001) and in group 3 (59 +/- 17 and 68 +/- 13 ml; p < 0.05). Thus, in asymptomatic patients with chronic, severe MR and normal LV ejection fraction at rest, there is an improvement in LV ejection fraction and an increase in forward stroke volume during exercise. These effects are comparable to those observed in normal controls. Directional differences in the cohort receiving no activity therapy were indistinguishable from either patients receiving vasodilator therapy or normal control subjects.

Clinical, echocardiographic and Doppler correlates of clinical instability with onset of atrial fibrillation.

To identify clinical and Doppler echocardiographic correlates of instability with the onset of atrial fibrillation (AF), 87 consecutive patients with new-onset AF who had echocardiograms recorded during that hospital admission while in sinus rhythm were studied. Reviewers who were blinded to echocardiographic and Doppler data classified 51 patients (59%) as unstable because of the development of angina, congestive heart failure, syncope or hypotension with the onset of AF. Echocardiographic and Doppler data on transmitral blood flow velocity were analyzed by a single reviewer who was blinded to other clinical data. Multiple logistic regression analysis identified 3 variables as independent predictors of clinical instability with the onset of AF: (1) history of prior myocardial infarction (p less than 0.02); (2) echocardiographic evidence of left ventricular dysfunction (p less than 0.03); and (3) Doppler evidence of increased atrial filling fraction (p less than 0.0001). An atrial filling fraction threshold of 0.40 had a sensitivity for predicting clinical instability of 80% and a specificity of 72%. These data are consistent with the hypothesis that patients who are more dependent on the atrial contribution to ventricular filling are at increased risk of instability with AF due to the loss of atrial systole.

Prediction of major cardiac events after peripheral vascular surgery using dipyridamole echocardiography.

Patients undergoing peripheral vascular surgery are at increased risk of postoperative cardiac complications. To evaluate the role of dipyridamole echocardiography in predicting major cardiac events, 109 unselected patients undergoing elective peripheral vascular surgery were prospectively studied. Preoperative dipyridamole echocardiograms were interpreted by an echocardiographer unaware of all clinical data. Patients were followed up until hospital discharge by research physicians without knowledge of dipyridamole echocardiography results. Outcomes were classified using strict predefined criteria by reviewers unaware of other clinical and echocardiographic data. Of the 109 patients, 9 (8%) had positive studies defined as development of new regional wall motion abnormalities or worsening of preexistent wall motion abnormalities. Of these 9 patients, 7 had postoperative events, including 3 cardiac deaths, 1 nonfatal myocardial infarction, 2 with unstable angina, and 1 with pulmonary edema. Only 1 event occurred among the 100 patients with negative studies. The sensitivity and specificity of dipyridamole echocardiography for predicting cardiac events after vascular surgery were 88 and 98%, respectively; the positive and negative predictive values were 78 and 99%. The relative risk of having a cardiac event if dipyridamole echocardiography was abnormal was 78 (95% confidence interval, 11 to 564; p less than 0.0001). If these results are extended and confirmed by other investigators, preoperative dipyridamole echocardiography may be an important screening test for patients undergoing elective peripheral vascular surgery.

Prevalence of pulmonary hypertension in limited and diffuse scleroderma.

STUDY OBJECTIVES: To characterize the prevalence of undiagnosed pulmonary hypertension in patients with limited and diffuse scleroderma. DESIGN: Prospective cross-sectional study. SETTING: University-based outpatient clinic. PATIENTS: Thirty-four consecutive patients with limited (n = 29) or diffuse (n = 5) scleroderma but without the clinical diagnosis of pulmonary hypertension. MEASUREMENTS AND RESULTS: All patients had 12-lead ECGs and two-dimensional and Doppler echocardiograms. The pulmonary artery systolic pressure (PAs) was calculated as the sum of the Doppler transtricuspid pressure gradient and the right atrial pressure as estimated by the caval respiratory index. Thirty-three patients (97%) had adequate spectral signals of tricuspid regurgitation. The velocity of tricuspid regurgitation ranged from 1.6 to 4.5 m/s. The calculated PAs ranged from 15 to 95 (mean +/- SD = 30 +/- 14 mm Hg). Twelve patients (35% of the total cohort) had pulmonary hypertension defined as PAs of 30 mm Hg or greater. CONCLUSIONS: Undiagnosed elevation of PAs is common in patients with scleroderma. Noninvasive assessment of PAs can be performed accurately in most patients independent of clinical signs of pulmonary hypertension. If successful treatment strategies are identified, it may be possible to identify patients early in the development of pulmonary hypertension and intervene before significant end-organ damage occurs.

Effect of short-term medroxyprogesterone acetate on left ventricular mass: role of insulin-like growth factor-1.

Previous studies using 17beta-estradiol and medroxyprogesterone acetate (MPA) have shown that hormone replacement therapy (HRT) increases left ventricular mass (LVM). To determine if insulin-like growth factor-1 (IGF-1) is associated with the increase in LVM, we measured IGF-1 and IGF-binding protein-3 (IGFBP-3) levels in 19 postmenopausal women before and after 8 weeks of oral treatment with MPA 5 mg/d. LVM was measured by two-dimensional echocardiography. Changes in IGF-1, IGFBP-3, and LVM from baseline were analyzed by paired ttest. Regression analysis was used to determine if changes in the IGF-1 axis with MPA treatment affect the increase in LVM. LVM increased 4.4% during the study (P = .006 vbaseline). IGF-1 increased 17% with MPA (P = .008), whereas IGFBP-3 did not change. The IGF-1/IGFBP-3 ratio increased 16.8% (P = .0003). Regression analysis of LVM with IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 ratio suggested that IGF-1 during MPA therapy explains 2.4% and the IGF-1/IGFBP-3 ratio explains 3.2% of the variation in LVM. There was no effect of IGFBP-3 on LVM. Most of the variation in LVM with MPA (90.5%) was explained by baseline LVM. The IGF-1/IGFBP-3 ratio on MPA treatment was inversely related to the change in LVM: women with a lower LVM at baseline had the greatest increase in LVM with MPA. These findings suggest that MPA increases IGF-1 and LVM. Because the increase in IGF-1 with MPA treatment explains a fraction of the increase in LVM, other mechanisms must also be operative.

A visual pathway that mediates fear-conditioned enhancement of acoustic startle.

Eighty rats received 10 light-shock pairings on two successive days. Seventy-two h after the final training session, subjects received lesions directed at the primary visual areas (deep and superficial layers of the superior colliculus, dorsal lateral geniculate nucleus, pretectal nuclei, visual cortex and thalamic reticular nucleus) and at the nuclei of the lateral lemniscus and reticularis pontis caudalis, proposed components of a primary acoustic startle circuit in the rat. Control animals were sham operated. One day later, all animals were tested for startle by presenting noise bursts of 3 different intensities in the presence or absence of the light conditioned stimulus. Potentiated startle (the difference between light-noise vs noise-alone trials) was significantly attenuated or eliminated by lesions directed at the dorsal nucleus of the lateral geniculate, deep layers of the superior colliculus, visual cortex, and the posteroventral region of the nucleus of the lateral lemniscus. Lesions directed at pretectal nuclei, superficial layers of the superior colliculus, thalamic reticular nucleus, nucleus reticularis pontis caudalis or dorsal nucleus of the lateral lemniscus did not attenuate potentiated startle. The results suggest that the visual pathway that mediates potentiated startle goes from the retina to the dorsal lateral geniculate nucleus to visual cortex to deep layers of superior colliculus and down to the postero-ventral region of the lateral lemniscus where acoustic startle is modulated.

Effect of short-term hormone replacement therapy on left ventricular mass and contractile function.

OBJECTIVE: To determine the effect of hormone replacement therapy (HRT) on cardiac structure and function and whether these changes are related to changes in blood volume. DESIGN: Open-label pilot study. SETTING: Academic medical center. PATIENT(S): Eighteen healthy postmenopausal women. INTERVENTION(S): We administered medroxyprogesterone acetate orally, 5 mg/d for 2 months followed by 2 months of oral sequential 17beta-estradiol, 1 mg/d plus medroxyprogesterone acetate, 10 mg/d for the last 12 days of each month. MAIN OUTCOME MEASURE(S): Cardiac output, stroke volume, heart rate, end diastolic volume, end systolic volume, ejection fraction, and left ventricular mass were measured by echocardiography; blood and plasma volumes were measured using 125I-albumin dilution. RESULT(S): Cardiac output, stroke volume, left ventricular mass, end diastolic volume, and ejection fraction increased by 12.8%, 11.7%, 9.4%, 7.2%, and 10.9%, respectively, by 16 weeks. End systolic volume decreased, whereas heart rate was unaffected. There was a significant increase in blood volume (5.2%) and plasma volume (4.8%) from baseline during treatment, which could explain the increased cardiac output but not the increased ejection fraction. CONCLUSION(S): Hormone replacement therapy causes modest but significant increases in cardiac output, ejection fraction, and left ventricular mass. These pilot data suggest a direct myocardial effect of HRT that is preload independent.

The ability of vegetation size on echocardiography to predict clinical complications: a meta-analysis.

To clarify whether echocardiographic detection of a vegetation 10 mm or larger in size in patients with left-sided infective endocarditis poses an increased risk for complications, we performed a meta-analysis of English-language publications identified by a computerized search of the key words infective endocarditis and echocardiography. A pooled odds ratio was calculated by using the Robins, Greenland, and Breslow estimate of variance. The pooled odds ratio for increased risk of systemic embolization in the presence of a vegetation >10 mm (10 studies, 738 patients) was 2.80 (95% confidence interval [CI] 1.95 to 4.02; p < 0.01). The odds ratio of requiring valve-replacement surgery (seven studies, 549 patients) was 2.95 (95% CI 1.90 to 4.58; p < 0.01). The odds ratio of death (six studies, 476 patients) was 1.55 (95% CI 0.92 to 2.60; p = 0.10). Thus this analysis supports the hypothesis that echocardiographically detected left-sided vegetations >10 mm pose a significantly increased risk of (1) systemic embolization and (2) a need for valve-replacement surgery than cases where either no or smaller vegetations are detected.

Stress echocardiography in valvular heart disease.

Stress echocardiography has been widely accepted as an important diagnostic and prognostic tool in the assessment of known or suspected coronary artery disease. Its use in valvular heart disease, to date, has been more limited, but is continuing to grow as the technology and the understanding of valvular disorders progress. In this article, we will review the current literature regarding the use of both exercise and pharmacological stress testing in conjunction with echocardiography in the settings of native and prosthetic mitral and aortic valve disease. We will also discuss the limitations of this modality and touch upon possible future areas of investigation.