NT- Péptido natriurético cerebral en la evaluación de respuesta al tratamiento de la insuficiencia cardíaca con levosimendan en pacientes pediátricos / NT-brain natriuretic peptide in the assessment of response to levosimendan treatment in pediatric patients with heart failure

Introducción: El tratamiento de la insuficiencia cardiaca ha incorporado drogas inotrópicas de muy alto costo, como el levosimendan (LEVO). La evaluación de la respuesta a estas drogas en pediatría ofrece dificultades por lo que la medición de biomarcadores como la prohormona N-Terminal Péptido Natriurético Cerebral (NT-ProBNP) podrían ser de utilidad. Objetivo: describir la variación del NT-ProBNP y su correlación con parámetros ecocardiográficos en respuesta a la administración de levosimendan en pacientes pediátricos con insuficiencia cardiaca. Diseño: estudio descriptivo, observacional y prospectivo, sin intervención. Pacientes y métodos: se incluyeron pacientes con insuficiencia cardiaca de 0 a 18 años internados en terapia intensiva a los cuales se les pudo realizar dosaje de NT ProBNP pre LEVO. Se midió dicho péptido al 1°, 3° y 5° día post LEVO. Con cada determinación se realizó ecocardiograma doppler. Resultados: Se enrolaron 15 pacientes, mediana de edad 188,5 días (IQR 25-75: 56-475); de peso 5,475 kg (IQR 25-75: 2.8-7.5). El 80% fueron pacientes con reparación quirúrgica de cardiopatías congénitas, 13.3% con ventrículo único. La mediana de valor de NT ProBNPantes de la administración de LEVO fue 8924.5 pg./ml (IQR 25-75: 4096-20419,75). El 80% de la población presentó descenso en el valor de pro BNP post LEVO y en 10 (66.6%) el descenso fue mayor o igual al 30%. La evaluación global de la función miocárdica no presentó diferencias antes y después del LEVO. Conclusiones: El 66% de los pacientes presentó una disminución de al menos un 30% en los valores de NT ProBNP luego de la administración de levosimendan

Introduction: Very high-cost inotropic drugs, such as levosimendan (LEVO), have been incorporated in the treatment of heart failure. Evaluation of the response to these drugs in children is difficult and measurement of biomarkers such as the prohormone N-terminal pro b-type natriuretic peptide (NT-proBNP) may be of use. Objective: To describe variation of NT-ProBNP and its correlation with echocardiographic parameters in response to the administration of LEVO in pediatric patients with heart failure. Design: A prospective, descriptive, observational, non-interventional study. Patients and methods: Patients between 0 and 18 years of age with heart failure admitted to the intensive care unit in whom pre-LEVO NT-ProBNP levels could be measured were included. NT-ProBNP levels were measured at day 1, 3, and 5 post LEVO. At each measurement, a Doppler echocardiogram was performed. Results: 15 patients with a median age of 188.5 days (IQR 25-75: 56-475) and a weight of 5.475 kg (IQR 25-75: 2.8-7.5) were enrolled. Of the patients, 80% had undergone surgery for congenital heart defects, 13.3% with a single ventricle. Median NT-ProBNP levels before LEVO administration were 8924.5 pg./ml (IQR 25-75: 4096-20419.75). Overall, 80% of the patients had a decrease of post-LEVO NT-ProBNP levels and in 10 (66.6%) the decrease was greater than or equal to 30%. Overall evaluation of myocardial function did not show differences before and after LEVO administration. Conclusions: 66% of the patients presented with a decrease of at least 30% of NT-ProBNP levels after LEVO administration

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.

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.

Effects of anesthetic induction in patients with diastolic dysfunction.

PURPOSE: To evaluate the effects of anesthetic induction on bi-ventricular function in patients with known preoperative left ventricular (LV) diastolic dysfunction undergoing coronary artery bypass grafting surgery (CABG). METHODS: Fifty patients with diastolic dysfunction undergoing CABG were studied. Preoperative transthoracic echocardiographic (TTE) examination was performed on the day before surgery and transesophageal echocardiography (TEE) assessment was undertaken after induction of anesthesia with sufentanil, midazolam, isoflurane, and pancuronium. Mean arterial pressure (MAP) and heart rate (HR) were recorded. The diameters of the left atrium (LA) and right atrium (RA) and right ventricular (RV) end-diastolic area (EDA), end-systolic area (ESA) and fractional area change (FAC) were obtained from the apical 4-chamber view. The LV EDA, LV ESA and LV FAC were measured from a transgastric midpapillary view. Pulsed wave Doppler of the transmitral flow (TMF) and transtricuspid flow (TTF), pulmonary venous flow (PVF) and hepatic venous flow (HVF) were measured. Mitral (Em, Am) and tricuspid (Et, At) annulus velocities were assessed by tissue Doppler imaging (TDI). Assessment of diastolic dysfunction was graded from normal to severe using a validated score. RESULTS: Following induction of anesthesia, HR decreased (66 +/- 12 vs 55 +/- 9 beats.min(-1), P < 0.0001) while MAP remained unchanged (86.1 +/- 9.0 vs 85.6 +/- 26.5 mmHg, P = 0.94). The diameters of the LA, RA and RV chambers increased, and these increases were associated with opposite changes in LV dimensions. The RV FAC decreased, but the LV FAC remained unchanged. While most Doppler velocities decreased (P < 0.05), a greater reduction in the atrial components of the TMF, TTF and TDI ratios was observed. The LV diastolic function score improved after induction of anesthesia (100% of patients with a score > or = = 3 pre-induction compared to 58% of patients with a score > or = 3 post-induction; P = 0.0004). CONCLUSION: In patients with left ventricular diastolic dysfunction, cardiac dimensions and bi-ventricular filling patterns are significantly altered after induction of general anesthesia. These changes can be explained to some extent by a reduction in venous return with general anesthesia, reduced atrial contractility, and the effect of positive pressure ventilation. Although the LV diastolic function score improved after induction of anesthesia, it is difficult to dissociate this effect from that of altered loading conditions.

Effect of aldosterone antagonism on exercise tolerance, Doppler diastolic function, and quality of life in older women with diastolic heart failure.

Optimal therapy for diastolic heart failure (DHF), the most common form of heart failure in older persons, is unclear. To determine the effect of aldosterone antagonism in DHF, the authors conducted an open-label preliminary trial of spironolactone 25 mg/d in 11 women with DHF. Cardiopulmonary exercise testing, Doppler echocardiography, and a quality-of-life survey were administered at baseline and after 4 months. Peak exercise VO(2) increased by 8.3% (P=.001), the ratio of Doppler diastolic early filling velocity to mitral annulus velocity decreased by 25% (P=.02), quality-of-life score improved by 21% (P=.16 for trend), and median New York Heart Association class improved from class III to class II (P=.004). Findings from this preliminary study confirm the role of aldosterone in the pathophysiology of DHF and suggest that aldosterone antagonism may benefit such patients. These hypotheses are currently being tested in two separated National Institutes of Health-funded, randomized trials, the Spironolactone for Failure in the Elderly (SPIFFIE) and the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trials.

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 levosimendan on E/E' ratio in patients with ischemic heart failure.

BACKGROUND: Levosimendan is a novel positive inotropic calcium sensitizer agent used in acute heart failure. In acute heart failure, it improves hemodynamic parameters more favorably than the conventional positive inotropes. In this study, the effect levosimendan on E/E' ratio as a non-invasive indicator of LV filling pressure was evaluated compared to dobutamine in a prospective, randomized, patient-blind manner. METHODS: Patients with an LVEF < 40% admitting with acute heart failure attack with ischemic origin were included to this study. Patients were randomized to levosimendan (n=30, mean age: 64+/-10 years, 63% male) or dobutamine (n=32, mean age: 66+/-8 years, 54% male) groups. The ratio of the peak E wave velocity taken from mitral inflow with PW Doppler to the peak E' wave velocity taken from mitral lateral annulus with tissue Doppler was determined. Pre-treatment and 24-hour after the treatment E/E' ratios were calculated and then compared in both groups. RESULTS: Age, gender, concomitant medications were similar in both groups (p>0.05). There was no difference for pre-treatment baseline E/E' ratios between levosimendan and dobutamine groups (15.7+/-4.0 vs 15.2+/-7.5 respectively, p=0.1). There were significant reductions in post-treatment E/E' ratios in levosimendan (15.7+/-4.0 vs 9.3+/-2.8, p=0.01) and dobutamine groups (15.2+/-7.5 vs 12.9+/-5.6, p=0.04). However, the reduction in levosimendan group was greater compared to dobutamine group (p=0.01). CONCLUSIONS: Levosimendan causes a greater reduction of E/E' ratio compared to dobutamine in acute systolic left heart failure. This may explain the more favorable hemodynamic effects of levosimendan when compared to conventional positive inotropics in patients with systolic left heart failure.

Effects of anesthesia on echocardiographic assessment of left ventricular structure and function in rats.

Echocardiography is an essential diagnostic tool for accurate noninvasive assessment of cardiac structure and function in vivo. However, the use of anesthetic agents during echocardiographic studies is associated with alterations in cardiac anatomical and functional parameters. We sought to systematically compare the effects of three commonly used anesthetic agents on echocardiographic measurements of left ventricular (LV) systolic and diastolic function, LV dimensions, and LV mass in rats. Adult male Fischer 344 rats underwent echocardiographic studies under pentobarbital (PB, 25 mg/kg i.p.) (group I, n = 25), inhaled isoflurane (ISF, 1.5%) (group II, n = 25),or ketamine/xylazine (K/X, 37 mg/kg ketamine and 7 mg/kg xylazine i.p.) (group III, n = 25) anesthesia in a cross-over design. Echocardiography was also performed in an additional group of unanesthetized conscious rats (group IV, n = 5). Postmortem studies were performed to validate echocardiographic assessment of LV dimension and mass. Rats in group I exhibited significantly higher LV ejection fraction, fractional shortening, fractional area change, velocity of circumferential fiber shortening corrected for heart rate, and heart rate as compared with groups II and III. LV end-diastolic volume, end-diastolic diameter, and cross-sectional area in diastole were significantly smaller in group I compared with groups II and III. Cardiac output was significantly lower in group III compared with groups I and II. Postmortem LV mass measurements correlated well with echocardiographic estimation of LV mass for all anesthetic agents, and the correlation was best with PB anesthesia. Limited echocardiographic data obtained in conscious rats were similar to those obtained under PB anesthesia. We conclude that compared with ISF and K/X anesthesia, PB anesthesia at a lower dose yields echocardiographic LV structural and functional data similar to those obtained in conscious rats. In addition, PB anesthesia also facilitates more accurate estimation of LV mass.

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.

[Levosimendan-long-term inodilation in an infant with myocardial infarction]. / Säugling mit therapie-refraktärer suprasystemischer pulmonaler Hypertonie nach MyokardinfarktIntermittierende Stabilisierung mit Levosimendan, einem neuartigen Langzeit-Inodilatator.

An infant with myocardial infarction due to congenital stenosis of the left coronary artery with consecutive left ventricular dysfunction and mitral regurgitation developed refractory pulmonary hypertension (PHT) and recurrent PHT crises. Catecholamines to support cardiac function, or pulmonary vasodilators like inhaled nitric oxide showed no effect. Treatment with Levosimendan (Simdax), a new inodilator, combining both inotropic and pulmonary vasodilating effects, improved left ventricular dysfunction, increased cardiac index, decreased pulmonary vascular resistance and reduced frequency and extent of the PHT crises. This case may suggest the use of Levosimendan as a long-term inotropic agent and pulmonary vasodilator in children with depressed cardiac function.

Effects of torasemide on left ventricular function and neurohumoral factors in patients with chronic heart failure.

The effect of torasemide and furosemide therapy was compared in 50 patients who had chronic heart failure and symptoms [NYHA class II-III] despite long-term therapy with both low-dose furosemide and angiotensin-converting enzyme inhibitors. In this randomized 6-month, open-label trial, baseline and follow-up echocardiograms and neurohumoral assays were obtained in 25 group F patients (continued same dose of oral furosemide at 20-40 mg/day) and in 25 group T patients (received torasemide at 4-8 mg/day in place of furosemide). At 6 months, parameters were unchanged in group F whereas the group T patients had a lower left ventricular end-diastolic diameter (p<0.005) and left ventricular mass index (p<0.005) with improved Doppler filling parameters, decreased plasma B-type natriuretic concentration (p<0.001) and increased plasma concentrations of active renin (p<0.005) and aldosterone (p<0.001). The magnitude of these changes appeared dose dependent and it is suggested these favorable effects of switching from furosemide to torasemide may be related to aldosterone receptor blockade.

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.

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.

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.

Effects of 15 months of 17 beta-estradiol and dydrogesterone on systolic cardiac function according to quantitative and Doppler echocardiography in healthy postmenopausal women.

OBJECTIVE: Our goal was to investigate the short-term and intermediate effects of low-dose hormone replacement therapy on echocardiographic parameters of cardiac function in healthy postmenopausal women. STUDY DESIGN: In a prospective, controlled study 30 healthy postmenopausal women (mean age, 52 +/- 3 years) were randomly assigned to 2 groups. Women in the hormone replacement therapy group (n = 15) received 1 mg micronized 17 beta-estradiol daily sequentially combined with 5 or 10 mg dydrogesterone for 14 days of each 28-day cycle during 12 months and thereafter 2 mg 17 beta-estradiol combined with 10 mg dydrogesterone for a period of 3 months. The control group (n = 15) received no treatment. M-mode, quantitative 2-dimensional, and Doppler echocardiographic measurements were performed at baseline and within the 17 beta-estradiol phase at 3, 12, and 15 months. RESULTS: After 12 months significant differences in change between the 2 groups were found for left ventricular end-diastolic and left ventricular end-systolic diameters, left ventricular mass index, and stroke volume index. These differences were caused by changes in the control group rather than in the hormone replacement therapy group, in which no significant within-group changes were found. All other parameters measured showed no effect. CONCLUSION: Within 15 months of 17 beta-estradiol and dydrogesterone treatment no clinically relevant differences were found in the M-mode, quantitative 2-dimensional, and Doppler echocardiographic parameters measured in this study. It is suggested that 15 months of treatment probably is too short a period for detection of direct effects on the heart itself.

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.

The value of repeated echocardiographic evaluation in patients with idiopathic dilated cardiomyopathy during treatment with metoprolol or captopril.

Serial echocardiographic investigations were carried out on patients with idiopathic dilated cardiomyopathy, to evaluate treatment effects on left ventricular (LV) performance during therapy with either metoprolol or captopril. Thirty-two patients (23 males and 9 females) with mild to moderate symptoms of heart failure (NYHA II-III) and a mean age of 49 years were included in the investigation. The patients were investigated with Doppler echocardiography before treatment, after 3 and 6 months of treatment (either metoprolol or captopril) and 1 month after withdrawal of treatment. Intra- and inter-investigator reproducibility was acceptable, with a coefficient of variation of less than 5% for LV dimensions. A reduction in LV dimensions was seen in both treatment groups. In the metoprolol group there was also an increase in LV stroke volume and fractional shortening. The non-invasive data were in accordance with invasive measurements of stroke volume and LV filling pressure. In patients with idiopathic dilated cardiomyopathy and mild to moderate symptoms of heart failure, echocardiography seemed to be sufficiently reproducible to be used for determination of treatment effects in a longitudinal heart failure study. Both metoprolol and captopril were well tolerated and had favourable effects on LV performance.

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.