Alterations in the determinants of diastolic suction during pacing tachycardia.

In cardiomyocytes, generation of restoring forces (RFs) responsible for elastic recoil involves deformation of the sarcomeric protein titin in conjunction with shortening below slack length. At the left ventricular (LV) level, recoil and filling by suction require contraction to an end-systolic volume (ESV) below equilibrium volume (Veq) as well as large-scale deformations, for example, torsion or twist. Little is known about RFs and suction in the failing ventricle. We undertook a comparison of determinants of suction in open-chest dogs previously subjected to 2 weeks of pacing tachycardia (PT) and controls. To assess the ability of the LV to contract below Veq, we used a servomotor to clamp left atrial pressure and produce nonfilling diastoles, allowing measurement of fully relaxed pressure at varying volumes. We quantified twist with sonomicrometry. We also assessed transmural ratios of N2B to N2BA titin isoforms and total titin to myosin heavy chain (MHC) protein. In PT, the LV did not contract below Veq, even with marked reduction of volume (end-diastolic pressure [EDP], 1 to 2 mm Hg), whereas in controls ESV was less than Veq when EDP was less than approximately 5 mm Hg. In PT, both systolic twist and diastolic untwisting rate were reduced, and there was exaggerated transmural variation in titin isoform and titin-to-MHC ratios, consistent with the more extensible N2BA being present in larger amounts in the subendocardium. Thus, in PT, determinants of suction at the level of the LV are markedly impaired. The altered transmural titin isoform gradient is consistent with a decrease in RFs and may contribute to these findings.

Hemodynamic characteristics of congenital aortic stenosis: a quantitative stress echocardiography study.

BACKGROUND: Several investigators have studied the effects of exercise on pressure gradients and valve area measurements in patients with senile calcific aortic stenosis. However, there are limited data on young patients with congenital aortic stenosis. The current study was conducted to assess the dynamic effect of exercise on aortic valve area and to determine whether pressure gradients or valve area determinations correlate with duration of exercise in these patients. METHODS AND RESULTS: Twenty-five young patients with congenital aortic stenosis and 10 normal control patients performed symptom-limited bicycle exercise stress tests with quantitative 2-dimensional and Doppler analysis. Compared with normal patients, there were no significant differences in the directional changes in blood pressure, left ventricular volumes, and ejection fraction. There was no correlation between either peak instantaneous or mean transaortic pressure gradient and exercise duration. A small but statistically significant correlation was detected between the continuity equation aortic valve area and duration of exercise (r = 0.49, P =.013). Aortic valve area did not change with exercise in the patient cohort (1.5 +/- 0.6 vs 1.5 +/- 0.6; P = not significant). CONCLUSIONS: Aortic valve area does not change significantly with exercise in asymptomatic patients with congenital aortic stenosis. Consistent with prior studies, there was no correlation between the duration of exercise and the mean resting aortic valve gradient. A modest but statistically significant correlation was detected between exercise duration and aortic valve area. Further studies are required to determine whether aortic valve area measurements would provide useful adjunctive data on which to base recommendations for participation in competitive sports.

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.

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.

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.

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).

Randomized trial of an oral platelet glycoprotein IIb/IIIa antagonist, sibrafiban, in patients after an acute coronary syndrome: results of the TIMI 12 trial. Thrombolysis in Myocardial Infarction.

BACKGROUND: Inhibitors of the platelet glycoprotein IIb/IIIa receptor given intravenously have been shown to be effective in reducing ischemic complications after coronary angioplasty and in unstable angina, making this a promising new class of agents for the treatment and prevention of ischemic events in patients with acute coronary syndromes. Sibrafiban (Ro 48-3657) is an oral, peptidomimetic, selective antagonist of the glycoprotein IIb/IIIa receptor. METHODS AND RESULTS: The Thrombolysis in Myocardial Infarction (TIMI) 12 trial was a phase II, double-blind, dose-ranging trial designed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of sibrafiban in 329 patients after acute coronary syndromes. In the PK/PD cohort of TIMI 12, 106 patients were randomized to receive one of seven dosing regimens of sibrafiban, ranging from 5 mg daily to 10 mg twice daily for 28 days. In the safety cohort, 223 patients were randomized to one of four dose regimens of sibrafiban (ranging from 5 mg twice daily to 15 mg once daily) or aspirin for 28 days. High levels of platelet inhibition were achieved: mean peak values ranged from 47% to 97% inhibition of 20 micromol/L ADP-induced platelet aggregation on day 28 across the seven doses. Twice-daily dosing provided more sustained platelet inhibition (mean inhibition, 36% to 86% on day 28), whereas platelet inhibition returned to baseline levels by 24 hours with once-daily dosing. Major hemorrhage occurred in 1.5% of patients treated with sibrafiban and in 1.9% of patients treated with aspirin. Protocol-defined "minor" bleeding, usually mucocutaneous, occurred in 0% to 32% of patients in the various sibrafiban groups and in none of the patients treated with aspirin. Minor bleeding was related to total daily dose (P=.002), once- versus twice-daily dosing (P<.0001), renal function (P<.0001), and presentation with unstable angina (P<.01). CONCLUSIONS: The oral glycoprotein IIb/IIIa antagonist sibrafiban achieved effective, long-term platelet inhibition with a clear dose-response but at the expense of a relatively high incidence of minor bleeding. Oral IIb/IIIa inhibition deserves further study as a new treatment strategy in patients after acute coronary syndromes.

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.

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.

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.

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.

Restoring forces assessed with left atrial pressure clamps.

A negative pressure (P) in the fully relaxed left ventricle (LV) indicates the presence of restoring forces generated during contraction. To assess restoring forces in the intact LV under physiological filling conditions, a servomotor system was used in anesthetized open-chest dogs (n = 8) to produce nonfilling diastoles by left atrial pressure (LAP) clamping during systole such that LAP was less than left ventricular pressure (LVP) during the subsequent diastole. Steady-state LV end-diastolic pressure (EDP) was varied by volume infusion from 4.0 +/- 1.5 (+/-SD) to 12.8 +/- 2.1 mmHg. The corresponding fully relaxed LVPs increased from -2.1 +/- 1.9 to 1.1 +/- 3.2 mmHg, P < 0.001. LAP clamping increased the rate of LVP fall by 34 +/- 28% (P < 0.001) during 10 ms after the LVP dropped below the level of the LVP-LAP crossover of the preceding normal beat. During clamped beats, two-dimensional echo revealed substantial downward displacement of the mitral valve (MV) leaflets despite the reversed LA-LV gradient and absence of filling. Thus 1) restoring forces are present at low physiological EDP but absent at high physiological EDP; 2) filling retards the rate of fall of LVP; 3) even in the absence of filling, the process of LV relaxation facilitates MV opening.

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.

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.

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.

Extraskeletal Ewing's sarcoma of primary cardiac origin.

A 13-year-old boy presented with cardiac tamponade. Echocardiography revealed a large mass extending from the right and left ventricles into a large pericardial effusion. Pathology confirmed the first reported case of a primary cardiac extraskeletal Ewing's sarcoma.

Diagnosis of cardiac tamponade after cardiac surgery: relative value of clinical, echocardiographic, and hemodynamic signs.

Early detection and treatment of cardiac tamponade is crucial in management of patients after cardiac surgery. Because of the atypical features of this condition and paucity of data on relative frequency of different signs, we evaluated the sensitivity of various clinical, echocardiographic, and hemodynamic signs. We retrospectively evaluated the relative frequency of clinical, echocardiographic, and hemodynamic signs in 29 patients with cardiac tamponade after cardiac surgery. In our study 66% had a localized, posterior pericardial effusion, and the other 34% had circumferential pericardial effusion. In the whole group 24% of patients had hypotension, and pulsus paradoxus was noted in 48%, right atrial collapse in 34%, right ventricular diastolic collapse in 27%, left ventricular diastolic collapse in 65%, and left atrial collapse in 13%. Elevation with equalization of pressures was noted in 81% patients. In the patient group with circumferential pericardial effusion and cardiac tamponade 40% patients were hypotensive and 50% patients had pulsus paradoxus. RA collapse was present in 70%, RV diastolic collapse in 70%, and LV diastolic collapse in 20%. Elevated diastolic pressures with equalization of these pressures was present in 71%. In the group with regional pericardial effusion and cardiac tamponade hypotension was present in 16% and pulsus paradoxus in 47%. RA collapse was present in 16%, RV diastolic collapse in 5%, LV diastolic collapse in 89%, and LA collapse in 21% of the patients with regional tamponade. Elevated diastolic pressures with equalization of these pressures was noted in 86% of the patients. Our observations indicate that among patients who have undergone cardiac surgery the presentation of cardiac tamponade is usually atypical.(ABSTRACT TRUNCATED AT 250 WORDS)