Improvement of Ventricular-Arterial Coupling in Elderly Patients with Heart Failure After Beta Blocker Therapy: Results from the CIBIS-ELD Trial.

UNLABELLED: The interaction between the heart and the arterial system (ventricular-arterial coupling - VA) is an important determinant of cardiovascular performance. Vascular stiffness (Ea) and left ventricular (LV) endsystolic stiffness (Elv) augment with age and in heart failure (HF). Beta blockers (BB) are recommended therapy for patients with HF. However, data about the effects of BB on VA coupling are scarce. AIMS OF THE STUDY: TO ASSESS: 1) changes in VA after BB therapy; 2) interactions between VA and LV functions, 3) predictive factors influencing VA change. METHODS: Eight hundred seventy-seven elderly patients with HF (aged ≥ 65, NYHA ≥ II, LV ejection fraction (LVEF) ≤ 45%), treated with BB according to the CIBIS-ELD protocol of up-titration, underwent Doppler echocardiography with clinical and laboratory assessment before and after 12 weeks of BB. VA coupling was calculated as Ea/Elv ratio. RESULTS: Ventriculo-arterial interaction improved after 12 weeks of BB in elderly patients with HF. Values of Ea significantly decreased from 2.73 ± 1.16 to 2.40 ± 1.01, p < 0.001, resulting in a VA level close to the optimal range i.e. from 1.70 ± 1.05 (1.46) to 1.50 ± 0.94 (1.29), p < 0.001. A similar degree of VA change was found in the patients with ischemic and non-ischemic HF after the treatment. Improvement in the clinical stage of HF closely correlated with VA coupling change after BB (p = 0.006). The strongest predictor of VA coupling alteration during BB was the improvement in global LVEF (p < 0.001) followed by the age of patients (p = 0.014). CONCLUSIONS: The beneficial effect of BB in elderly patients with HF was achieved by optimizing VA coupling close to recommended range, associated with an improvement in LVEF and contractility.

Effect of pimobendan on echocardiographic values in dogs with asymptomatic mitral valve disease.

BACKGROUND: Pimobendan (PIMO) is a novel inodilator that has shown promising results in the treatment of advanced mitral valve disease (MVD), but little is known about its hemodynamic effects, especially regarding the mitral regurgitant volume in naturally occurring MVD. HYPOTHESIS: The addition of pimobendan to treatment decreases the regurgitant fraction (RF) in dogs with asymptomatic MVD. ANIMALS: Twenty-four client-owned dogs affected by International Small Animal Cardiac Health Council class Ib MVD. METHODS: Prospective, blinded, and controlled clinical trial. Dogs were assigned to a PIMO treatment group (n = 19) (0.2-0.3 mg/kg q12h) or a control group (n = 5). Echocardiographic evaluations were performed over a 6-month period. RESULTS: The addition of PIMO to treatment did not decrease the RF of dogs affected by asymptomatic class 1b MVD over the study period (P= .85). There was a significant increase in the ejection fraction of the PIMO treated dogs at 30 days (80.8 +/- 1.42 versus 69.0 +/- 2.76, corrected P= .0064), and a decrease in systolic left ventricular diameter (corrected P= .011) within the PIMO group compared with baseline. However, this improvement in systolic function was not sustained over the 6-month trial period. CONCLUSION AND CLINICAL IMPORTANCE: This study did not identify beneficial long-term changes in the severity of mitral regurgitation after addition of PIMO to angiotensin converting enzyme inhibitor treatment of dogs with asymptomatic MVD.

Effect of Body Position, Exercise, and Sedation on Estimation of Pulmonary Artery Pressure in Dogs with Degenerative Atrioventricular Valve Disease.

BACKGROUND: Severity of pulmonary hypertension (PH) in dogs is related to clinical signs and prognosis. HYPOTHESIS/OBJECTIVES: We hypothesized that Doppler echocardiographic (DE) indices of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) are influenced by independent factors that create clinically important variability of DE-based estimates of PH in dogs. ANIMALS: Thirty-eight client owned dogs with naturally acquired degenerative atrioventricular valve disease and tricuspid regurgitation (TR). METHODS: Dogs were prospectively enrolled, and target variables were acquired during 4 echocardiographic study periods (lateral recumbency, standing, lateral recumbency after a 6-minute walk test [6MWT], and lateral recumbency after sedation with butorphanol 0.25 mg/kg IM). Statistical methods included repeated measures ANOVA, mixed model analysis, and Chi-squared test of association. RESULTS: There was a significant increase in peak TR flow velocity (TRFV; P < 0.01) after sedation in 78% of dogs, with TRFV increasing by >0.4 m/s in 42% of dogs, independent of stroke volume. A significant effect of study period on DE-estimated PVR was not found (P = 0.15). There were negligible effects of sonographer, body position, and 6MWT on echocardiographic variables of PH. Clinically relevant cyclic variation of TRFV was found. There was an association between estimation of right atrial pressure based on subjective assessment and estimation based on cranial vena cava collapsibility (P = 0.03). CONCLUSIONS AND CLINICAL IMPORTANCE: The increase in TRFV observed with sedation could change assessment of PH severity and impact prognostication and interpretation of treatment response. Further studies with invasive validation are needed.

Recombinant Human Thyrotropin Improves Endothelial Coronary Flow Reserve in Thyroidectomized Patients with Differentiated Thyroid Cancer.

BACKGROUND: The role of thyrotropin (TSH) on the cardiovascular system has been poorly investigated. It is unknown whether the changes in the vasculature associated with thyroid diseases result from altered thyroid hormone action or whether they are a consequence of a direct effect of TSH on endothelial cells. The present study was designed to evaluate the endothelial response of coronary flow to TSH in patients with differentiated thyroid cancer (DTC) without cardiovascular risk factors. METHODS: The study population consisted of three men and seven women (Mage = 32.6 ± 8 years) who underwent total thyroidectomy for DTC. All were receiving therapy with L-thyroxine to maintain TSH within the reference range. No patient was obese, or had hypertension, diabetes, or dyslipidemia. Patients underwent standard echo-Doppler examination with evaluation of the coronary flow reserve (CFR) of the distal left anterior descending artery obtained by cold pressure test (CPT) before and 24 h after the second recombinant human TSH (rhTSH) injection. RESULTS: Left ventricular morphology and systolic and diastolic function were normal in all patients. Levels of thyroid hormones and thyroglobulin and antithyroglobulin antibodies did not differ significantly pre- versus post-rhTSH treatment, whereas TSH levels were higher after rhTSH administration. Blood pressure and heart rate were not affected by rhTSH. Coronary flow peak velocity at rest (22.3 ± 6 vs 23.2 ± 8.7; p = 0.66) did not differ between baseline and 24 h after rhTSH, while post-CPT velocity (29.3 ± 6.8 vs 34.4 ± 10.9; p < 0.05) and the CFR were higher after rhTSH administration (1.32 ± 0.2 vs. 1.53 ± 0.2; p < 0.01). CONCLUSIONS: rhTSH administration may improve the CFR after the non-pharmacological stressor CPT in DTC patients. The increase of coronary blood flow after rhTSH suggests that TSH may exert a protective effect on the coronary endothelium.

Coronary flow velocity response to adenosine characterizes coronary microvascular function in women with chest pain and no obstructive coronary disease. Results from the pilot phase of the Women's Ischemia Syndrome Evaluation (WISE) study.

OBJECTIVES: We sought to develop and validate a definition of coronary microvascular dysfunction in women with chest pain and no significant epicardial obstruction based on adenosine-induced changes in coronary flow velocity (i.e., coronary velocity reserve). BACKGROUND: Chest pain is frequently not caused by fixed obstructive coronary artery disease (CAD) of large vessels in women. Coronary microvascular dysfunction is an alternative mechanism of chest pain that is more prevalent in women and is associated with attenuated coronary volumetric flow augmentation in response to hyperemic stimuli (i.e., abnormal coronary flow reserve). However, traditional assessment of coronary volumetric flow reserve is time-consuming and not uniformly available. METHODS: As part of the Women's Ischemia Syndrome Evaluation (WISE) study, 48 women with chest pain and normal coronary arteries or minimal coronary luminal irregularities (mean stenosis = 7%) underwent assessment of coronary blood flow reserve and coronary flow velocity reserve. Blood flow responses to intracoronary adenosine were measured using intracoronary Doppler ultrasonography and quantitative angiography. RESULTS: Coronary volumetric flow reserve correlated with coronary velocity reserve (Pearson correlation = 0.87, p < 0.001). In 29 (60%) women with abnormal coronary microcirculation (mean coronary flow reserve = 1.84), adenosine increased coronary velocity by 89% (p < 0.001) but did not change coronary cross-sectional area. In 19 (40%) women with normal microcirculation (mean flow reserve = 3.24), adenosine increased coronary velocity and area by 179% (p < 0.001) and 17% (p < 0.001), respectively. A coronary velocity reserve threshold of 2.24 provided the best balance between sensitivity and specificity (90% and 89%, respectively) for the diagnosis of microvascular dysfunction. In addition, failure of the epicardial coronary to dilate at least 9% was found to be a sensitive (79%) and specific (79%) surrogate marker of microvascular dysfunction. CONCLUSIONS: Coronary flow velocity response to intracoronary adenosine characterizes coronary microvascular function in women with chest pain in the absence of obstructive CAD. Attenuated epicardial coronary dilation response to adenosine may be a surrogate marker of microvascular dysfunction in women with chest pain and no obstructive CAD.

Do beta-adrenergic blocking agents increase coronary flow reserve?

BACKGROUND: Beta-adrenergic blocking agents are the cornerstone in the treatment of coronary artery disease (CAD). The exact pathophysiologic mechanism is not clear but depends largely on the oxygen-sparing effect of the drug. Thus, the effect of metoprolol on coronary flow reserve and coronary flow velocity reserve (CFVR) was determined in patients with CAD. METHODS: Coronary blood flow velocity was measured with the Doppler flow wire in 23 patients (age: 56 +/- 10) undergoing percutaneous transluminal coronary angioplasty for therapeutic reasons. Measurements were carried out at rest, after 1-min vessel occlusion (postischemic CFVR) as well as after intracoronary adenosine (pharmacologic CFVR) before and after 5 mg intravenous metoprolol. In a subgroup (n = 15), absolute flow was measured from coronary flow velocity multiplied by coronary cross-sectional area. RESULTS: Rate-pressure product decreased after metoprolol from 9.1 to 8.0 x 10(3) mm Hg/min (p < 0.001). Pharmacologic CFVR was 2.1 at rest and increased after metoprolol to 2.7 (p = 0.002). Likewise, postischemic CFVR increased from 2.6 to 3.3 (p < 0.001). Postischemic CFVR was significantly higher than pharmacologic CFVR before as well as after metoprolol. Coronary vascular resistance decreased after metoprolol from 3.4 +/- 2.0 to 2.3 +/- 0.7 mm Hg x s/cm (p < 0.02). CONCLUSIONS: The following conclusions were drawn from this study. Metoprolol is associated with a significant increase in postischemic and pharmacologic CFVR. However, postischemic CFVR is significantly higher than pharmacologic CFVR. The increase in CFVR by metoprolol can be explained by a reduction in vascular resistance. The increase in CFVR (= increased supply) and the reduction in oxygen consumption (= decreased demand) after metoprolol explain the beneficial effect of this beta-blocker in patients with CAD.

Failure of calcium channel blockers to improve ventricular relaxation in humans.

OBJECTIVES: The objective of this study was to ascertain whether the reversal of low peak filling rates after administration of calcium channel blockers in patients with diastolic dysfunction indicates true improvement in the rate of ventricular relaxation and left ventricular end-diastolic pressure measured by invasive indexes. BACKGROUND: Depressed filling rates measured noninvasively have been associated with diastolic dysfunction, specifically abnormal relaxation of the left ventricle. There is a reversal of these low peak filling rates after administration of calcium channel blockers. METHODS: Doppler echocardiographic measurements of peak filling rates were made and invasive high fidelity manometer-tipped pressures were measured before and after administration of verapamil (0.1 mg/kg body weight) in 20 patients with coronary artery disease who had an ejection fraction > 40% and decreased peak filling rates. RESULTS: Verapamil caused significant increases in the peak filling rate, as measured by early transmitral (E) flow velocity, from 0.57 +/- 0.16 m/s to 0.77 +/- 0.15 m/s (p < 0.01), indicating reversal of decreased peak filling rates. Concomitantly, left ventricular end-diastolic pressure increased from 18.0 +/- 7.7 mm Hg to 24.1 +/- 9.0 mm Hg (p < 0.001). The time constant of relaxation was variable, with an overall significant increase from 45.8 +/- 10.4 ms to 53.2 +/- 14.6 ms (p = 0.01). CONCLUSIONS: Verapamil administered intravenously produced reversal of decreased peak filling rates in patients with coronary artery disease and normal ventricular function. However, there was an increase in left ventricular end-diastolic pressure as well as an overall prolongation of the time constant of relaxation. Therefore, changes in peak filling rates do not accurately reflect the response of ventricular relaxation to drug interactions. Thus, calcium channel blockers should be used cautiously in the empiric treatment of patients with diastolic dysfunction.

Effect of losartan on degree of mitral regurgitation quantified by echocardiography.

The objective of this study was to determine the effect of oral losartan on the degree of mitral regurgitation (MR). The regurgitant volume and effective regurgitant orifice were quantified using 3 methods (flow convergence, quantitative Doppler, and quantitative 2-dimensional echocardiography) in 32 patients (26 men, mean age 67 +/- 14 years) with MR, both at baseline and 4 hours after losartan (50 mg orally). Twenty-eight patients were also reevaluated after 1 month of continued treatment with losartan (50 mg/day). With treatment, systolic blood pressure decreased from 143 +/- 16 to 130 +/- 18 mm Hg and left ventricular end-systolic wall stress from 173 +/- 46 to 156 +/- 44 g/cm2 (both p < 0.001). With treatment, regurgitant volume decreased (from 77 +/- 28 to 64 +/- 26 ml, - 18 +/- 10%; p < 0.001) in direct relation to the effective regurgitant orifice change (from 43 +/- 16 to 37 +/- 15 mm2, -17 +/- 10%; p < 0.001) but without significant change in regurgitant gradient or duration. Wide individual variability in response was observed unrelated to the magnitude of blood pressure changes. Larger reduction in regurgitant volume was observed in patients with a marked decrease in wall stress (r = 0.47, p = 0.01) and higher baseline end-diastolic volume index (r = -0.38, p = 0.03) and regurgitant volume (r = -0.45, p = 0.01). Acute improvements were sustained and unchanged at 1 month (all p > 0.15). Treatment of MR using the angiotensin receptor antagonist losartan produces a significant and sustained decrease in the degree of MR, with decreases in regurgitant volume and effective regurgitant orifice. However, the changes are of modest and variable magnitude.

Effects of dobutamine on left ventricular diastolic performance are attenuated in patients with systemic hypertension.

We measured Doppler echocardiographic diastolic parameter during infusion of low-dose dobutamine in 14 untreated hypertensive subjects and in 14 normal controls. Low-dose dobutamine accelerated left ventricular relaxation in normal controls but not in hypertensive subjects.

Effects of long-term antihypertensive treatment with tertatolol on diastolic function in hypertensive patients with and without left ventricular hypertrophy.

UNLABELLED: We assessed the effects of long-term antihypertensive treatment with 5 mg tertatolol, a noncardioselective beta-blocker, on left ventricular hypertrophy (LVH) and diastolic function. Fifteen hypertensive patients were selected as good responders to previous treatment with tertatolol (supine blood pressure less than 140/90 mm Hg). They were divided into 2 groups: group 1 with LVH (n = 6) and group 2 without LVH (n = 9). After a one month wash-out period, all patients received 5 mg tertatolol once daily. In case of uncontrolled blood pressure (BP), the dose was doubled after 2 weeks in 10 patients. BP control was obtained in all patients. M-mode echocardiography and Doppler-echocardiography were performed under controlled conditions after BP normalization and after 6 months of treatment. Long-term BP normalization significantly reduced left ventricular mass index (LVMI) in group 1 (from 137 +/- 3 to 121 +/- 3 g/m2, P less than .01), but not in group 2 (from 120 +/- 3 to 114 +/- 4 g/m2, P = NS). After 2 weeks of effective therapy, the ratio between early and late diastolic peak flow velocity across the mitral valve (E/A ratio), significantly increased in both groups (from 0.72 +/- 0.04 to 0.87 +/- 0.06 in group 1, P less than .05; and from 1.13 +/- 0.06 to 1.26 +/- 0.07 in group 2, P less than .05). After 6 months, together with the reduction of LVMI, a further increase of E/A ratio was only observed in group 1 (to 1.30 +/- 0.12, P less than .05). IN CONCLUSION: (1) LVH contributes to left ventricular diastolic dysfunction in hypertensive patients since its reversal is able to improve diastolic filling, and (2) effective antihypertensive treatment with tertatolol improves diastolic function independently from its effect on LV mass.

Hemodynamic performance of the 21-mm Sorin Bicarbon mechanical aortic prostheses using dobutamine Doppler echocardiography.

BACKGROUND: Small-sized mechanical aortic prostheses are commonly associated with generation of high transvalvular gradients, particularly in patients with large body surface area, and can result in patient-prosthesis mismatch. This study evaluates the hemodynamic performance of 21-mm Sorin Bicarbon bileaflet mechanical prostheses using dobutamine stress echocardiography. METHODS: Fourteen patients (7 women; mean age, 63+/-8 years) who had undergone aortic valve replacement with a 21-mm Sorin Bicarbon bileaflet mechanical prosthesis 32.4+/-5.1 months previously were studied. After a resting Doppler echocardiogram, a dobutamine infusion was started at a rate of 5 microg x kg(-1) x min(-1) and increased to 30 microg x kg(-1) x min(-1) at 15-minute intervals. Pulsed- and continuous-wave Doppler echocardiographic studies were performed at rest and at the end of each increment of dobutamine. Both peak and mean velocity and pressure gradient across the prostheses were measured, and effective orifice area, discharge coefficient, and performance index were calculated. RESULTS: Dobutamine stress increased heart rate and cardiac output by 83% and 81%, respectively (both p < 0.0001), and mean transvalvular gradient increased from 15.6+/-5.5 mm Hg at rest to 35.4+/-11.9 mm Hg at maximum stress (p < 0.0001). Although the indexed effective orifice area was significantly lower in patients with a larger body surface area, this was not associated with any significant pressure gradient. The performance index of this valve was unchanged throughout the study. Regression analyses demonstrated that the mean transvalvular gradient at maximum stress was independent of all variables except resting gradient (p = 0.05). Body surface area had no association with the changes in cardiac output, transvalvular gradient at maximum stress, and effective orifice area. CONCLUSIONS: These data show that the 21-mm Sorin Bicarbon bileaflet mechanical prosthesis offers an excellent hemodynamic performance with full utilization of its available orifice when implanted in the aortic position. The lack of significant transvalvular gradient in patients with a larger body surface area suggests that patient-prosthesis mismatch is highly unlikely when this prosthesis is used.

A naturalistic study of 24-hour electrocardiographic recordings and echocardiographic findings in children and adolescents treated with desipramine.

OBJECTIVE: Recent studies assessing cardiovascular effects of desipramine (DMI) in pediatric patients consistently have found small, clinically benign, but statistically significant, increases in heart rate and electrocardiographic (ECG) conduction parameters. However, single, routine ECG recordings cannot fully assess potential infrequent rhythm disturbances. METHOD: We analyzed data from 24-hour ECG monitoring, two-dimensional Doppler echocardiography, and expert clinical cardiac examination of DMI-treated patients. Subjects were 71 children (N = 35) and adolescents (N = 36) receiving long-term treatment (means +/- SD = 1.5 +/- 1.2 years, median = 1.0 year) with DMI (means +/- SD = 3.5 +/- 1.6 mg/kg). RESULTS: Compared with previous observations in untreated healthy children. DMI-treated patients had significantly lower rates of sinus pauses and junctional rhythm, but significantly higher rates of single or paired premature atrial contractions and runs of supraventricular tachycardia. There was an association between DMI serum levels and paired premature atrial contractions, but no other associations were detected. CONCLUSIONS: These findings support the impression from previous ECG studies that DMI-associated cardiac effects in pediatric patients are quite benign. Nevertheless, it remains to be ascertained whether even minor cardiac abnormalities may predict later, evidently rare, adverse cardiovascular effects that may include sudden death.

Left ventricular diastolic function in hypertension: a 4 year follow-up study.

In order to assess the long term effects of antihypertensive treatment on left ventricular diastolic function, 26 hypertensive patients were followed up for a mean of 4.25 years with two-dimensional and Doppler echocardiography. A significant reduction in left ventricular mass index was first apparent after 9 months of therapy (mean (S.D.) 124 (22) vs. 114 (18) g/m2, P < 0.01), and this was maintained over the 4.25 year period (124 (22) vs. 117 (17) g/m2, p < 0.05). At 9 months there was no change in either isovolumic relaxation time (108 (26) vs. 108 (17) ms, P = N.S.) or left ventricular filling as assessed by peak flow velocity E/A ratio (0.94 (0.22) vs. 0.95 (0.27), P = N.S.). However, after 4.25 years there was a significant improvement in IVRT (108 (26) vs. 83 (11) ms, P < 0.01) with a trend towards an improved peak flow velocity E/A ratio, although this did not reach statistical significance (0.95 (0.27) vs. 1.02 (0.26), P = N.S.). Of the 14 patients who had an abnormal isovolumic relaxation time at baseline, 12 normalised and 2 improved. These findings suggest that left ventricular diastolic dysfunction in hypertension may be reversed by prolonged antihypertensive treatment.

Dobutamine stress Doppler echocardiography: reproducibility and physiologic left ventricular filling patterns.

Qualitatively, dobutamine stress echocardiography has become an established procedure. Quantitative results are in great demand but this is still difficult due to limited endo- and epicardial border definition. Transmitral Doppler variables are strictly quantitative and less subjective. Furthermore, ischemic alterations precede systolic ones (ischemic cascade). There are preliminary reports of the utility of dobutamine stress Doppler echocardiography, but proof of reproducibility and left ventricular filling patterns are still lacking. Fourteen healthy volunteers (10 men, 4 women, median age 25.9 years, range 21-32 years) were investigated according to the usual dobutamine stress echocardiographic protocol (5, 10, 15, 20, 30, 40 and 40 micrograms/kg/min + 0.5 mg atropine). At each titration step a standardized transmitral PW-Doppler recording with the sample volume positioned at the opened mitral leaflet tips was analyzed three times by two independent, experienced investigators. Of the early, late, and mean velocities (VmaxE, VmaxA, Vmean), time integrals (VTI-E, VTI-A, VTI), their ratios (E/A, E/A VTI), and various time intervals (Tacc, Tdec, E- and A-duration, FillT), VmaxE (0.82 to 1.09 m/s; P < 0.0001), VTI-E (16.17 to 17.19 cm; P < 0.0001) and Vmean (0.29 to 0.82 m/s; P < 0.0001) were found to have the greatest discriminatory power, commencing already at a dose of 10-15 micrograms/kg/min dobutamine. VmaxE and VTI-E demonstrated the smallest intra- and interobserver variation without any increase in variability during incremental dose titration. Assessment of the early diastolic filling pattern by Doppler echocardiography is a valuable quantitative and reproducible adjunct to conventional dobutamine stress echocardiography. Further controlled studies in coronary artery disease patients have to confirm, whether lower dobutamine doses could be used in the test and sensitivity increased due to better data acquisition in cases of limited echogenicity, less subjectivity, and earlier onset of ischemic alterations.

The acute effects of sublingual estradiol on left ventricular diastolic function in normotensive and hypertensive postmenopausal women.

AIM: limited information is available on estrogen influences on diastole. We aimed to investigate the acute effects of a single dose of sublingual 17beta-estradiol on left ventricular diastolic function in postmenopausal women. METHODS: the study included 28 women aged 55.6 +/- 6 (15 normotensive and 13 hypertensive), who underwent Doppler echocardiography and estradiol plasma levels determination before and 60 min after sublingual administration of 4 mg of 17beta-estradiol. RESULTS: there were no modifications in heart rate. Both systolic and diastolic blood pressure dropped significantly in the hypertensives and remained unchanged in normotensives. Estradiol levels were 1790 +/- 869 pg/ml in the normotensives and 2664 +/- 1490 in the hypertensives (P < 0.05). Peak early velocity, in the population as a whole, increased from 84 +/- 18 to 91 +/- 18 cm/s and the early-to-atrial velocity ratio from 1.1 +/- 0.4 to 1.4 +/- 0.6 (P < 0.0001 for both). Both acceleration and deceleration rates increased significantly (P < 0.0001). These changes were shared by all the patients. In addition, the hypertensive patients, who presented a baseline pattern characterized mainly by a grossly increased peak atrial velocity with reduction in the early-to-atrial velocity ratio, demonstrated a decrease in peak atrial velocity from 92 +/- 12 to 78 +/- 10 cm/s (P < 0.0001), associated with significant reductions in deceleration time (P < 0.0001) and pressure half time (P < 0.005). Therefore, the typical picture of impaired ventricular relaxation was favorably changed after estradiol administration. CONCLUSIONS: the sublingual administration of estradiol induces acute modifications in left ventricular diastolic function in postmenopausal women, with improvement in the age-related left ventricular relaxation pattern, and that these beneficial changes are more pronounced in hypertensive that in normotensive women.

Randomised controlled trial of postnatal sodium supplementation in infants of 25-30 weeks gestational age: effects on cardiopulmonary adaptation.

BACKGROUND: It has previously been shown that, in preterm babies, routine sodium supplementation from 24 hours after birth is associated with increased risk of oxygen dependency and persistent expansion of the extracellular compartment. OBJECTIVE: To explore whether this is mediated by a delayed fall in pulmonary artery pressure (PAP). Postnatal changes in PAP, estimated as the ratio of time to peak velocity to right ventricular ejection time, corrected for heart rate (TPV:RVET(c)), were compared in preterm infants who received routine sodium supplements that were either early or delayed. METHODS: Infants were randomised, stratified according to sex and gestation, to receive a sodium intake of 4 mmol/kg/day starting either from 24 hours after birth or when a weight loss of 6% of birth weight was achieved. Echocardiographic assessment was made on the day of delivery (day 0), and on days 1, 2, 7, and 14. Babies with congenital heart disease were excluded. RESULTS: There was no difference between the two groups in TPV:RVET(c) measured sequentially after birth. On within group testing, when compared with values at birth, the ratio was higher by day 3 in the early supplemented group, suggesting a more rapid fall in PAP compared with the late supplemented group, in whom a significant fall did not occur until day 14. CONCLUSIONS: The timing of sodium supplementation after preterm birth does not appear to affect the rate of fall in PAP as measured by the TPV:RVET(c) ratio. The previous observation linking routine sodium supplementation from 24 hours after birth with increased risk of continuing oxygen requirement therefore does not appear to be mediated by a delayed fall in PAP. Instead, the increased risk of continuing oxygen requirement is likely to be a direct consequence of persistent expansion of the extracellular compartment and increased pulmonary interstitial fluid, resulting from a sodium intake that exceeded sodium excretory capacity. This adds further weight to the view that clinical management, in this case the timing of routine sodium supplementation, should be individually tailored and delayed until the onset of postnatal extracellular volume contraction, marked clinically by weight loss.

Hemodynamic findings during exercise on a bicycle ergometer following balloon valvuloplasty of pulmonary stenosis in children and adolescents.

Eleven patients (4 female, 7 male), age range 3.3 to 24.8 years (mean 11.10 years) treated for isolated pulmonary stenosis underwent cardiac catheterization and percutaneous transluminal balloon valvuloplasty (PTVP). The right ventricular systolic pressure (RVSP) before valvuloplasty ranged from 31 to 127 mmHg (mean 79 mmHg) decreasing to 28 to 62 mmHg (mean 42 mmHg) immediately after the dilatation. The peak systolic gradient of the pulmonary valve (delta p RV-PA) before valvuloplasty ranged from 22 to 107 mmHg (mean 61 mmHg) and decreased to a range of 14 and 45 mmHg (mean 23 mmHg) immediately after the dilatation. Balloon valvuloplasty was performed using balloons of 13 to 31 mm in diameter. On 11 patients cardiac catheterization and Doppler echocardiography were repeated between 11 months and 5.3 years (mean 3.11 years) after the balloon valvuloplasty showed a further significant fall in the gradient of pressure. The right ventricular systolic pressure ranged from 20 to 51 mmHg (mean 31.7 mmHg) while the transpulmonary gradient varied from 3 to 24 mmHg (mean 11.6 mmHg). At the time of follow-up examination the patients were aged between 7.2 and 25.7 years (mean 15.9 years). On average the second catheterization was performed 3.11 years following the first hemodynamic study. The follow-up examination encompassed clinical examination, electrocardiogram, Doppler echocardiography, and right heart cardiac catheterization. During right heart cardiac catheterization the children exercised on a bicycle ergometer for three min at 50 or 100 W depending on their body surface area. During this exertion, pressures of the right ventricle and the pulmonary artery as well as heart rate and oxygen saturation were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Improvement of exercise capacity after nifedipine in patients with Eisenmenger syndrome complicating ventricular septal defect.

We investigated the potential benefit of a preferential pulmonary vasodilatory effect of nifedipine in 4 patients with Eisenmenger syndrome complicating ventricular septal defect. First-pass radionuclide scan was performed at rest to measure intracardiac shunting before and after nifedipine. Two hours after 20 mg sublingual nifedipine, right-to-left shunt increased from 16.3 +/- 1.4 to 20.4 +/- 1.5% (p less than 0.05), but systemic arterial oxygen saturation (SAO2) remained steady. With 4 weeks of maintenance nifedipine therapy, resting intracardiac shunting and SAO2 were unchanged from baseline. Symptom-limited cycle ergometry was performed before and after maintenance nifedipine with placebo control. Exercise duration was prolonged (8.7 +/- 0.6 vs. 6.8 +/- 0.9 min; p less than 0.02) and SAO2 at each stage of exercise was consistently increased in all patients after nifedipine. Cardiac output and the SAO2 at peak exercise were similar. Thus, chronic nifedipine therapy increases SAO2 on exercise and improves maximal exercise capacity in patients with Eisenmenger syndrome, which is not predicted by study of resting intracardiac shunting after acute therapy.

Baseline hemodynamic and echocardiographic indices in anesthetized calves.

The experimental calf model is used to assess mechanical circulatory support devices and prosthetic heart valves. Baseline indices of cardiac function have been established for the normal awake calf but not for the anesthetized calf. Therefore, we gathered hemodynamic and echocardiographic data from 16 healthy anesthetized calves (mean age, 189.0 +/- 87.0 days; mean body weight, 106.9 +/- 32.3 kg) by cardiac catheterization and noninvasive echocardiography, respectively. Baseline hemodynamic data included heart rate (65 +/- 12 beats per minute), mean aortic pressure (113.5 +/- 17.4 mm Hg), left ventricular end-diastolic pressure (16.3 +/- 38.9 mm Hg), and mean pulmonary artery pressure (21.7 +/- 8.3 mm Hg). Baseline two-dimensional echocardiographic data included left ventricular systolic dimension (3.5 +/- 0.7 cm), left ventricular diastolic dimension (5.6 +/- 0.8 cm), end-systolic intraventricular septal thickness (1.7 +/- 0.2 cm), end-diastolic intraventricular septal thickness (1.2 +/- 0.2 cm), ejection fraction (63 +/- 10%), and fractional shortening (37 +/- 10%). Doppler echocardiography revealed a maximum aortic valve velocity of 0.9 +/- 0.5 m/s and a cardiac index of 3.7 +/- 1.1 L/minute/m2. The collected baseline data will be useful in assessing prosthetic heart valves, cardiac assist pumps, new cannulation techniques, and robotics applications in the anesthetized calf model and in developing calf models of various cardiovascular diseases.

Hemodynamic effects of nifedipine in patients with asymptomatic aortic regurgitation: evaluation by Doppler echocardiography.

Nineteen asymptomatic patients affected by isolated chronic aortic regurgitation received 20 mg of nifedipine sublingually: the acute hemodynamic effects of nifedipine were evaluated by combined cross-sectional and Doppler echocardiography. To assess variations in the regurgitant flow volume, the flow volume across the mitral and aortic valves was calculated as the product of velocity-time integral multiplied by the orifice valve area. Flow volume across these valves represented the total stroke volume, and forward stroke volume, respectively: the regurgitant volume was obtained by calculating the difference between total and forward stroke volume. Nifedipine induced a redistribution of the two components of the total left ventricular stroke volume: regurgitant stroke volume decreased from 57 +/- 22 ml/beat to 46 +/- 21 ml/beat (P < 0.002), while forward stroke volume increased from 83 +/- 12 to 93 +/- 15 ml/beat (P < 0.0005), as a consequence of the reduction in systemic vascular resistance from 1513 +/- 378 to 1092 +/- 307 dynes.sec.cm-5 (P < 0.0001). The reduction of regurgitant volume was due to either a 24.8% decrease of the aortic-left ventricular mean pressure gradient during diastole (P < 0.008) or a 6% decrease of the diastolic time interval (P < 0.04). The effect of these acute changes on left ventricular loading was to induce a reduction in oxygen consumption which was expressed by a decrease in the double product (from 10176 +/- 1767 to 9444 +/- 1559 mmHg.beats/min; P < 0.002), in spite of a significant increase in heart rate. This study, therefore, shows the beneficial acute hemodynamic effect induced by nifedipine in asymptomatic patients affected by chronic aortic regurgitation and shows that Doppler-echocardiography is a useful instrument for the evaluation of hemodynamic changes immediately after the administration of drugs.