Role of B-type natriuretic peptide and echocardiographic indices in predicting the development of acute heart failure following beta-blocker uptitration in chronic heart failure patients with left ventricular systolic dysfunction

We evaluated the role of clinical, BNP and echocardiographic left ventricular (LV) indices in predicting the development of acute heart failure (HF) following beta-blocker initiation and uptitration in 50 stable CHF patients with LVEF < 40% and creatininemia < 250 micromol/l. Use of NYHA class alone predicted the development of acute HF decompensation in only 56% and the absence of this event in 93% of patients. Use of echocardiographic indices (systolic PAP < 40 mmHg or E/A ratio < 1.4 or EDT > 145 ms) predicted the absence of acute HF decompensation in 100% of patients. Use of NYHA > 3 combined with BNP > 398 pg/ml or with echocardiographic indices (i.e. systolic PAP > 40 mmHg or E/A > 1.4 or EDT < 145 ms) predicted the development of acute HF decompensation in 100% of patients. In conclusion use of BNP and echocardiographic LV filling pressure indices in combination with NYHA class may predict beta-blocker tolerance more accurately than clinical indices alone in patients with LV systolic dysfunction (LVEF < 40%).     

Characterization of left ventricular filling abnormalities and its relation to elevated plasma brain natriuretic peptide level in acute to chronic diastolic heart failure.

BACKGROUND: Although Doppler left ventricular (LV) filling abnormalities have been extensively analyzed in patients with systolic heart failure (SHF), they have not yet been well characterized in patients with acute to chronic diastolic heart failure (DHF) in the light of plasma brain natriuretic peptide (BNP) levels. METHODS AND RESULTS: In 25 patients presenting with acute DHF and 25 with acute SHF, echo Doppler parameters and plasma BNP levels were obtained on admission and in the chronic stage. The mitral E/A ratio was lower in DHF patients than in SHF patients in the acute stage (1.3 +/-0.4 vs 1.8+/-0.9, p<0.05), and in the chronic stage of DHF the ratio decreased with plasma BNP level, but plasma BNP level was still greater than 100 pg/ml in 15 patients (60%). Among patients with DHF the plasma BNP level did not correlate with the mitral E/A ratio or deceleration time (r=0,25, p=NS; r=0,23, p=NS), but did with estimated pulmonary artery systolic pressure (r=0.64, p<0.01). CONCLUSIONS: A restrictive mitral flow velocity pattern is observed in only 25% of patients with DHF, so it is particularly important to recognize pseudonormalization in those with possible DHF. Persistently elevated plasma BNP level is not primarily caused by LV diastolic dysfunction, but by secondary alteration for hemodynamic adjustment (elevated LV end-diastolic pressure) in patients with DHF.     

Plasma brain natriuretic peptide levels in patients with rheumatic heart disease

BACKGROUND: Brain natriuretic peptide (BNP) is a cardiac hormone secreted from the ventricular myocardium as a response to ventricular volume expansion and pressure overload. Rheumatic heart disease (RHD) is still an important cause of heart failure in developing countries. AIMS: To measure BNP levels in patients with RHD and to determine whether BNP concentrations correlate with clinical and echocardiographic findings. METHODS: Eighty-eight patients with rheumatic valve disease and 24 age- and sex-matched healthy subjects were entered in the study. BNP was measured using the Triage B-Type Natriuretic Peptide test (Biosite Diagnostics, San Diego, CA). Transthoracic echocardiography was performed in all patients to assess the severity of the valve disease and for the measurement of pulmonary artery pressure. RESULTS: The plasma concentrations of BNP were significantly higher in patients with rheumatic heart disease than in control subjects (232+/-294 vs. 14+/-12 pg/ml, p<0.0001). The plasma BNP level was significantly higher in NYHA class III+IV than in class II (463+/-399 vs. 192+/-243 pg/ml, p<0.0001) and in NYHA class II than in class I (192+/-243 vs. 112+/-135 pg/ml, p<0.001). The independent determinants of higher BNP levels were NYHA functional class and systolic pulmonary artery pressure in multivariate analysis. CONCLUSION: We found increased plasma BNP levels in patients with rheumatic heart disease compared with healthy subjects.     

限制性心肌病患者血浆B 型利尿肽水平影响因素分析

目的探讨在限制性心肌病（RCM）患者中血浆B型利尿肽（BNP）的影响因素。方法入选20例经过组织活检确诊为RCM的患者。将临床、超声心动图和右心导管指标与血浆BNP水平进行相关性分析。结果 RCM患者血浆BNP水平为（792.3±1045.9）ng/L。相关性分析显示BNP与年龄、性别、心功能分级和药物治疗无显著相关;而与超声心动图左心室舒张功能指标,即二尖瓣血流峰值速度E/A比值（r=0.46）、二尖瓣E峰减速时间（r=-0.59）、等容舒张时间（r=-0.45）、组织多普勒成像二尖瓣环舒张早期速度（E′）峰值（r=-0.45）和E/E′比值（r=0.86）有显著相关性（P〈0.05）。BNP与右心导管测定的右心房压力（r=0.45）、右心室舒张末压力（r=0.56）和肺动脉楔压（r=0.46）显著相关（P〈0.05）。多因素回归分析显示二尖瓣E/E′是BNP唯一的独立相关因素（β=0.69,P〈0.05）。结论 RCM患者血浆BNP水平升高,而且与多普勒超声心动图的左心室舒张功能指标以及右心导管测定的右心室舒张压力显著相关。     

B-type natriuretic peptide level in the diagnosis of asymptomatic diastolic dysfunction.

OBJECTIVE: Brain natriuretic peptide (BNP) reflects the left ventricular pressure and volume overload. It is known that it increases in systolic dysfunction proportionally with left ventricular pressure increase. The BNP levels are well correlated with NYHA classification and prognosis. Our aim was to evaluate the predictive value of BNP in patients with diastolic dysfunction but normal systolic dysfunction demonstrated by echocardiography. METHODS: Fifty patients (mean age: 48.5+/-6.75 years; 29 males, 21 females) were included in this cross-sectional, case-controlled study. Systolic dysfunction was the exclusion criterion. The following parameters were used to evaluate diastolic function: isovolumetric relaxation time, transmitral early to late filling flow velocities (E/A) ratio, deceleration time E, pulmonary vein Doppler findings and color mitral flow propagation velocity. Diastolic dysfunction was determined in 30 hypertensive patients (Group 1), whereas 20 patients who had normal diastolic flow patterns on echocardiography (Group 2). Blood samples were taken for serum BNP level measurements. RESULTS: The BNP levels were 12.0+/-4.97 pg/ml in individuals with normal filling pattern and 66.17+/-17.56 pg/ml in individuals with abnormal filling patterns (p<0.001). The accuracy of BNP in detection of diastolic dysfunction was assessed with receiver-operating characteristic (ROC) analysis. The area under the ROC curve for BNP test accuracy in detection any abnormal diastolic dysfunction was 0.969 (95% CI, 0.909 to 1.029; p<0.001). A BNP value of 37.0 pg/ml had sensitivity of 80%, specificity of 100%, a positive predictive value of 100%, a negative predictive value of 23% and accuracy of 88% in identifying asymptomatic prolonged relaxation pattern. We found a strong correlation between left ventricular mass index and plasma BNP levels (r=0.62, p<0.05). CONCLUSION: Estimation of BNP values could be accepted as a fast and reliable blood test in the diagnosis of asymptomatic diastolic dysfunction.     

The significance of CA125 levels in patients with chronic congestive heart failure. Correlation with clinical and echocardiographic parameters

OBJECTIVE: To assess serum levels of carbohydrate antigen 125 (CA125) in patients with chronic congestive heart failure (CHF) and to assess any correlation with clinical symptoms and echocardiographic indices. PATIENTS AND METHODS: We enrolled 77 male patients (mean age: 73+/-10 years) admitted to the Cardiology Emergency Department (ED) with cardiac symptoms requiring hospitalization. Diagnosis of CHF was based upon medical history or initial echocardiographic evaluation on current admission. Serum CA125 was measured by an enzyme immunoradiometric assay, on admission and before discharge. RESULTS: The median overall CA125 value was 22.4 (11.5-48.9) U/ml. Serum CA125 levels were related to the severity of CHF [New York Heart Association (NYHA) class I: 19.2 (7.2-31) U/ml, NYHA class II: 17.6 (10-23) U/ml, NYHA class III: 32 (25-77) U/ml and NYHA class IV: 34.3 (18.6-77) U/ml (p<0.04)]. Patients in NYHA classes III and IV had significantly higher mean values of CA125, than patients in class II (p<0.005 and p<0.05, respectively). Moreover, patients with fluid congestion (pulmonary congestion, ankle edema) had higher levels of serum CA125 than patients without congestion (p=0.002 and p<0.03, respectively). Finally, levels of serum CA125 correlated weakly with right ventricular systolic pressure (RVSP) and renal function, while no significant correlation was found between CA125 and E wave deceleration time on Doppler echocardiography, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), liver function and the medical treatment prescribed. CONCLUSION: Serum CA125 is associated with the clinical severity of CHF and the symptoms and signs of fluid congestion and therefore may be a useful additional tool for the evaluation and clinical staging of these patients.     

Effects of levosimendan on coronary artery flow and cardiac performance in patients with advanced heart failure

BACKGROUND: Levosimendan has inotropic and vasodilatory effects. We investigated the effects of levosimendan on coronary flow and associated changes in neurohormonal activation and cardiac performance in patients with advanced heart failure. METHODS: Forty-two patients with NYHA III-IV and a left ventricular ejection fraction (EF) 25+/-6%, were randomised to levosimendan 0.1 microg/kg/min (n=21) or placebo for 24 h. Before and 24 h after each treatment, we assessed: the maximal velocity (Vmax), time integral (VTI) and deceleration time (DT) of the diastolic coronary flow wave (CF) in LAD using transthoracic Doppler echocardiography, pulmonary artery systolic pressure by Doppler echocardiography, E/E' ratio using Doppler imaging of mitral inflow velocity, tissue Doppler imaging of the mitral annulus and B-type natriuretic peptide (BNP) levels. RESULTS: By ANOVA, there was a greater increase in CF-Vmax (43+/-23 vs.25+/-8 cm/s), CF-DT (904+/-250 vs. 667+/-151 ms), and EF and a greater decrease in BNP, pulmonary artery systolic pressure and E/E? after levosimendan than after placebo (p<0.05). Compared to baseline, the percent changes in CF-VTI were related to the concomitant changes in EF, E/E?, and BNP after treatment with levosimendan (r=0.69, r=?0.51 and r=?0.80, p<0.05 respectively). CONCLUSION: Treatment with levosimendan improves coronary flow and microcirculation in parallel with an improvement in cardiac performance and neurohormonal activation in patients with advanced heart failure.     

Impact of clinical and echocardiographic parameters assessed during acute decompensation of chronic heart failure on 3-year survival

BACKGROUND: It is unclear whether established risk factors affecting the prognosis of chronic heart failure (CHF) have the same predictive value when assessed during acute haemodynamic decompensation of CHF. AIM: To investigate the impact of selected clinical and echocardiographic parameters assessed in patients with CHF during emergency admission due to acute CHF decompensation, on 3-year survival. METHODS: This retrospective study involved 100 consecutive patients with CHF (60 women and 40 men at the mean age of 70.4+/-9.8 years), admitted to hospital due to angina pectoris symptoms or pulmonary oedema. In the echocardiographic study performed within the first 48 hours of in-hospital stay, standard parameters as well as right ventricular systolic pressure (RVSP) were evaluated. In order to identify biological, clinical and echocardiographic factors affecting 3-year survival, both uni- and multivariable Cox proportional hazards regression analyses were carried out. RESULTS: Forty-four patients died during 3-year follow-up. Univariate regression analysis revealed that age >60 years, sodium serum concentration <140 mmol/L, RVSP >35 mmHg and reduced left ventricular ejection fraction <50% were associated with an increased risk of death. However, multivariate regression analysis showed that only age and sodium concentration were independent risk factors. CONCLUSIONS: Age of over 60 years and sodium concentration below 140 mmol/L seen during acute decompensation were found to be independent predictors of unfavourable outcome in terms of mortality in 3-year follow-up of patients with CHF.     

Value of clinical, electrocardiographic, echocardiographic and neurohumoral parameters in non-ischaemic dilated cardiomyopathy

AIM: The aim of this study was to assess the predictive value of electrocardiographic, echocardiographic and neurohumoral parameters for adverse outcomes in non-ischaemic dilated cardiomyopathy patients with sinus rhythm. METHODS: Seventy-eight patients with non-ischaemic dilated cardiomyopathy (LVEF < 40%) and sinus rhythm were enrolled. All patients underwent electrocardiographic, echocardiographic examination and coronary angiography. Blood samples for plasma NT pro-BNP levels were obtained at rest, following echocardiographic examination. Patients were followed up for clinical end points of death from worsening heart failure, sudden cardiac death and heart transplantation. RESULTS: The study population consisted of 24 (30.8%) women and 54 (69.2%) men. Forty-four patients (65.4%) suffered from clinical end points during a mean of 1278 +/- 188 days follow-up; cardiac transplantation was performed in 5 (11%), sudden cardiac death occurred in 10 (23%) and death due to worsening heart failure in 29 (66%) patients. The patients were grouped according to the presence (group 1, 44 patients) or absence (group 2, 34 patients) of clinical end points. The patients in group 1 had lower systolic blood pressures (P = 0.006) and higher NYHA functional classes (P < 0.0001). When echocardiographic parameters and NT pro-BNP values were compared, the patients in group 1 had lower left ventricular ejection fractions (P < 0.0001), higher E/A ratios (P < 0.0001), shorter E wave deceleration times (P = 0.004), pulmonary acceleration times (P < 0.0001) and isovolumetric relaxation times (P = 0.03), increased mitral regurgitant volumes (P = 0.033) and higher plasma NT pro-BNP levels (P < 0.0001). There was no significant difference between the two groups regarding electrocardiographic parameters. In univariate analysis, the prognostic predictors of life expectancy were identified as plasma NT pro-BNP, NYHA functional class, left ventricular ejection fraction, E/A ratio and E wave deceleration time. However, in multivariate analysis by logistic regression only plasma NT pro-BNP was determined as independent predictor of life expectancy (P = 0.04, HR (95% CI) = 1.0003 (1.0000-1.0007), chi2 = 3.9). CONCLUSION: Electrocardiographic parameters failed to predict clinical end points in this group of patients. Plasma NT pro-BNP is a useful biochemical marker to define the high-risk group that warrants closer follow-up in dilated cardiomyopathy patients with sinus rhythm.     

Doppler echocardiography-derived index of myocardial performance (TEI index): comparison with brain natriuretic peptide levels in various heart disease.

Plasma brain natriuretic peptide (BNP) has diagnostic and prognostic value in heart failure. Cardiac dysfunction varies from systolic or diastolic dysfunction alone to the combination of both. In the present study, Doppler echocardiographic parameters, including the Doppler echocardiography-derived index (TEI index), were compared with plasma BNP levels in 74 patients with various heart diseases. Blood sampling was performed before an echocardiographic examination was conducted. The TEI index was defined as the summation of isovolumic contraction and relaxation time divided by ejection time. In patients with left ventricular (LV) systolic dysfunction (ejection fraction <50%), the TEI index and BNP were increased significantly compared with patients with normal LV systolic function (p<0.05). Patients with a TEI index > or =0.45 showed significantly increased BNP levels compared with patients with a TEI index <0.45, irrespective of LV systolic function (241.4+/-451.2 vs 65.9+/-81.8pg/ml; p<0.05). The TEI index was significantly higher in patients with a BNP > or =73pg/ml than in patients with BNP <73pg/ml (0.57+/-0.24 vs 0.46+/-0.17; p<0.05). Other echocardiographic parameters did not correlate significantly with levels of plasma BNP. Of the echocardiographic parameters, a simple Doppler index (TEI index) that combines systolic and diastolic function can detect LV dysfunction in patients with high levels of plasma BNP in various heart diseases.     

Prognostic value of plasma brain natriuretic peptide, urea nitrogen, and creatinine in outpatients >70 years of age with heart failure

This study analyzed the relevance of plasma brain natriuretic peptide (BNP) and echocardiography in predicting cardiovascular events in a large population >70 years old with heart failure (HF). Three hundred four outpatients with HF (51.6% men, mean age 78.6) underwent transthoracic echocardiography and plasma BNP testing shortly before hospital discharge. Echocardiography was intended to reveal systolic dysfunction (left ventricular [LV] ejection fraction [EF] <50%) or diastolic dysfunction (EF > or =50% and abnormalities of ventricular relaxation). During 6-month follow-up, all-cause death and readmission were assessed. One hundred seventeen patients had diastolic dysfunction with preserved systolic LV function, and 187 had systolic dysfunction. At 6-month clinical follow-up, 33 subjects (10.9%) had died, and 62 (20.4%) needed readmission for cardiac decompensation. In all patients, univariate logistic regression demonstrated significant correlations between age (r = 0.14, p = 0.01), plasma BNP (r = 0.36, p = 0.0001), the EF (r = 0.16, p = 0.003), urea nitrogen (r = 0.35, p = 0.0001), serum creatinine (r = 0.27, p = 0.0001), and New York Heart Association (NYHA) class (r = 0.35, p = 0.0001) and the occurrence of cardiovascular events. In patients with HF in NYHA class III or IV, a BNP cut-off level of 200 pg/ml identified different outcomes (BNP <200 pg/ml in 1 of 20 events vs BNP >200 pg/ml in 55 of 85 events, p = 0.0001). In patients with HF who were >70 years old, BNP, NYHA class, and renal function predicted adverse outcome. In patients with severe HF, BNP was better than NYHA class in predicting future events.     

BNP in septic patients without systolic myocardial dysfunction

BACKGROUND: We tested our hypothesis that serum BNP levels rise in sepsis and septic shock patients as a result of an inflammatory state and not only because of left ventricular dysfunction. METHODS: Twenty-one patients with sepsis or septic shock were enrolled in the study. Echocardiography was performed in every patient on admission and at discharge. Laboratory data were evaluated on admission, during hospitalization, and at discharge. Serum IL-1beta, IL-6, TNFalpha, and BNP concentrations were determined. RESULTS: BNP values on admission (r=0.47, p=0.03), during hospitalization (r=0.64, p=0.014), and on the day of discharge (r=0.54, p=0.015) were all positively correlated with CRP values. Mean BNP (r=0.07, p=0.006) and BNP level at discharge (r=0.68, p=0.001) were also positively associated with IL-1 at discharge. Mean CRP (17.7 mg/dL+/-1.5 vs. 9.2 mg/dL+/-3.6, p=0.002), IL-6 (46.6 pg/mL+/-2.2 vs. 25.6 pg/mL+/-16.3, p=0.003), and SAPS II levels (41.3+/-4.7 vs. 33.9+/-6.5 p=0.01) were also higher in patients who died versus those who survived. No difference in BNP levels was recorded in subjects who died versus those who survived. There was no clinical or echocardiographic evidence of left ventricular systolic dysfunction (mean EF% on admission 55.1+/-21.7 vs. 61.3+/-8.6 on discharge, p=0.123). Serum BNP levels at discharge were inversely associated with EF values on admission (r=-0.475, p=0.046) and positively associated with E/A ratio on admission (r=0.565, p=0.028). No association was found between BNP values and death. CONCLUSION: BNP is positively correlated with CRP levels in septic patients without clinical or echocardiographic evidence of systolic dysfunction. No association was found between death and BNP values. It seems that, in septic patients, BNP is less accurate as a measure of ventricular dysfunction.     

Prognostic importance of comorbidities in heart failure with preserved left ventricular ejection fraction

The relative impact of comorbidities and parameters of left ventricular diastolic function on clinical outcome has not been thoroughly investigated in patients who are hospitalized for heart failure decompensation and found to have preserved ejection fraction. We identified 98 HFpEF patients among 1452 patients admitted with acute heart failure. Clinical characteristics, hemoglobin levels, estimated glomerular filtration rate (eGFR), B-type natriuretic peptide (BNP) and Doppler-echocardiographic parameters were analyzed. The primary end point of the study combined death and rehospitalization for decompensated heart failure after the index hospitalization. Mean age was 76 ± 9 years. LV ejection fraction, E/E (a) ratio, and estimated systolic pulmonary artery pressure were 61 (55-67)%, 12.9 (9.4-15.1), 40 (32-46) mmHg, respectively. BNP values, hemoglobin and eGFR were 287 (164-562) pg/mL, 11.3 (10.4-12.4) g/dL and 45 (37-74) mL/min/m(2), respectively. During a mean follow-up of 17 ± 11 months, 56% reached the primary endpoint of the study: 31 died and 24 were re-hospitalised for heart failure. Diabetes [HR = 1.76 (1.03-3.00), P = 0.039], lower systolic blood pressure [HR = 0.99 (0.97-0.99), P = 0.016], hemoglobin [HR = 0.62 (0.49-0.76), P < 0.0001], and eGFR [HR = 0.98 (0.97-0.99), P = 0.004] were associated with a poor outcome. Neither BNP nor echocardiographic parameters were correlated with outcome. Comorbidities primarily correlate with outcome in patients with HFpEF.     

Doppler-derived mitral and pulmonary venous flow variables are predictors of pulmonary hypertension in dilated cardiomyopathy

This study assessed whether Doppler-derived mitral and pulmonary venous flow parameters were predictors of pulmonary artery hypertension in patients with left ventricular dysfunction. Doppler echocardiographic examinations were performed in patients (n = 100) with dilated cardiomyopathy in sinus rhythm either symptomatic or asymptomatic before and after optimized therapy with ACE inhibitors, diuretics, and vasodilators. In case of weak or poor Doppler signals, measurable tricuspid regurgitation and pulmonary venous flow tracings were obtained after intravenous administration of 2.5 grams of Levovist at 400 mg/ml. At baseline, left ventricular ejection fraction was 30% +/- 7% and pulmonary artery systolic pressure was 48 +/- 14 mmHg. At the follow-up study carried out after 6 +/- 2 months, reversibility of pulmonary artery hypertension was apparent only in those patients exhibiting favorable changes of mitral flow curve from the restrictive or pseudonormal to impaired relaxation pattern (53 +/- 7 mmHg vs 38 +/- 8 mmHg; P < 0.0001). Numerous variables correlated significantly with pulmonary artery systolic pressure at baseline, while the correlations were generally weaker at the follow-up study. The closest correlations were found with E wave deceleration rate (r = 0.73) at baseline and with the systolic fraction of pulmonary venous flow forward peak velocities (r = -0.67) at follow-up. The stepwise regression model showed that the E wave deceleration rate and the degree of mitral regurgitation were the strongest independent predictors of pulmonary hypertension at baseline, while the ratio between pulmonary venous flow reverse and mitral wave velocities at atrial systole and ejection fraction added minor contributions, leading to a cumulative r value of 0.81. The systolic fraction was the strongest at the follow-up study, with minor contributions provided by the E wave deceleration rate and the left atrial dimension index, leading to a cumulative r value of 0.71.     

保留收缩功能性心力衰竭与B型脑钠肽及尿酸的相关性研究

目的结合超声心动图参数探讨B型脑钠肽（brain natriuretic peptide,BNP）联合尿酸（uric acid,UA）对保留收缩功能性心力衰竭诊断的临床意义。方法顺序入选130例有器质性心脏病、纽约心脏协会（New York heart association,NYHA）心功能分级I～IV级的住院患者,其超声心动图提示有不同程度的舒张功能障碍且左心室射血分数（left ventricular ejection fraction,LVEF）≥45%,检测血浆B型脑钠肽、尿酸浓度,按照NYHA分级及BNP浓度进行分组,比较患者的临床指标及超声心动图参数;分别以NYHA分级及BNP为因变量进行多元线性回归分析;对100ng/L400ng/L组较BNP〈100ng/L组的年龄、血浆UA浓度、左心房内径、左心室舒张末期内径、E/E′及左心室质量明显升高,LVEF明显降低,房性心律失常发生率明显升高,差异均有统计学意义（P〈0.01）。经多元线性回归分析仅NYHA分级及E/E′是影响血浆BNP浓度的独立相关因素（r=0.33,P〈0.01;r=0.17,P〈0.05）。100ng/L     

Brain natriuretic peptide (BNP) in coronary insufficiency: relationship with left ventricular filling and exercise tolerance

Brain natriuretic peptide (BNP) is a recently discovered peptide, secreted by the atria and ventricles in response to parietal distension. It was recently proposed as a screening test for left ventricular failure. The authors assayed this peptide at rest in 37 patients with chronic heart failure due to left ventricular systolic dysfunction and another 20 patients with various diseases (respiratory failure, cirrhosis, heart transplantation, "diastolic" heart failure) but normal left ventricular systolic function. A significant increase compared to normal values was observed not only in the group of heart failure patients, but also in patients with all other diseases. BNP was significantly higher in NYHA class IV patients. The relationship between plasma BNP levels and ejection fraction was not significant. On the other hand, a good correlation was observed between BNP and left ventricular filling parameters evaluated by cardiac Doppler: E wave deceleration time (r = -0.53, p = 0.001), E/A ratio: r = 0.57 p = 0.005) or VO2 max (r = -0.55, p < 0.005).     

Natriuretic peptides during the development of doxorubicin-induced left ventricular diastolic dysfunction

OBJECTIVES: To investigate changes in plasma atrial natriuretic peptide (ANP), N-terminal pro-atrial natriuretic peptide (NT-pro-ANP) and brain natriuretic peptide (BNP) during the development of doxorubicin-induced left ventricular systolic and diastolic dysfunction as measured by echocardiography (ECHO). DESIGN: Prospective study. SETTING: University hospital. SUBJECTS: Twenty-eight adult patients with non-Hodgkin's lymphoma, who received doxorubicin to the cumulative dose of 400-500 mg m(-2). MAIN OUTCOME MEASURES: The relationship between plasma natriuretic peptides and systolic and diastolic ECHO indices after the cumulative doxorubicin doses of 200, 400 and 500 mg m(-2). RESULTS: Left ventricular ejection fraction (LVEF, by 2D ECHO) decreased from 58 +/- 1.7 to 52.5 +/- 1.3% (P=0.036) and fractional shortening (FS) from 34.6 +/- 1.4 to 27.8 +/- 0.9% (P=0.002). Peak E wave velocity decreased from 63.3 +/- 3.2 to 51.3 +/- 2.6 cm s(-1) (P=0.008) resulting in a statistically nonsignificant decrease in E/A ratio from 1.08 +/- 0.01 to 0.85 +/- 0.07. A significant decrease was observed in the percentage of left ventricular filling during the 1/3 of diastole (1/3FF) from 42.2 +/- 1.7 to 36.5 +/- 2.0% (P < 0.001). LV end systolic diameter increased from 32 +/- 1 to 38 +/- 1 mm (P=0.011), whereas left atrial (LA) diameter remained unchanged. Peak filling rate decreased from 4.4 +/- 0.2 to 4.0 +/- 0.2 stroke volume s(-1) (SV s(-1)) (ns). Plasma levels of ANP increased from 16.4 +/- 1.3 to 22.7 +/- 2.4 pmol L(-1) (P=0.002), NT-pro-ANP from 288 +/- 22 to 380 +/- 42 pmol L(-1) (P=0.019) and BNP from 3.3 +/- 0.4 to 8.5 +/- 2.0 pmol L(-1) (P=0.020). There was a significant inverse correlation between the decrease in FS and the increases in plasma NT-pro-ANP (r= -0.524, P=0.018) and plasma BNP (r=0.462, P=0.04) and between the decrease in PFR and the increases in plasma ANP (r= -0.457, P=0.043) and plasma NT-pro-ANP (r= -0.478, P=0.033). Furthermore, after doxorubicin therapy, significant inverse correlations were observed between E/A ratio and plasma ANP (r= -0.535, P=0.008), between E/A ratio and plasma NT-pro-ANP (r= -0.432, P=0.04) and between E/A ratio and plasma BNP (r= -0.557, P=0.006) as well as between 1/3FF and plasma BNP (r= -0.493, P=0.017). There was also a trend for correlation between LA diameter and plasma BNP (r=0.395, P=0.062) and peak E wave velocity and plasma BNP (r= -0.414, P=0.05), respectively. However, no significant correlations were observed between any of the systolic parameters and natriuretic peptide levels. CONCLUSIONS: The results of this prospective study show that during the evolution of doxorubicin-induced LV dysfunction the secretion of natriuretic peptides is more closely associated with the impairment of left ventricular diastolic filling than with the deterioration of LV systolic function.     

Prognostic value of BNP for hospital mortality in elderly subjects hospitalised for acute diastolic cardiac failure

The aim of this study was to evaluate the prognostic value of BNP in elderly patients hospitalised for acute diastolic cardiac failure. 108 consecutive subjects were included, aged at least 70 years old, hospitalised for isolated acute diastolic cardiac failure. All of them had a left ventricular ejection fraction > or = 50% and evidence of diastolic dysfunction on echocardiography performed shortly after admission. The plasma BNP concentration measured in the emergency department on admission was >100 pg/ml in all of the patients except five. It was positively correlated with age (R = 0.29, p = 0.002), with the plasma creatinine level (R = 0.37, p < 0.0001) and the plasma urea level (R = 0.41, p < 0.0001). On univariate analysis, compared to the patients who survived, the 20 patients who died before discharge were significantly older (88.6 versus 84.4 years, p = 0.01), and were more often residents of a care home (60 versus 31%. p = 0.02), had a lower systolic blood pressure on admission (127 +/- 33 versus 154 +/- 30 mm Hg), a higher plasma urea level (16.8 +/- 12 versus 8.9 +/- 5 mmol/l, p = 0.002) and a higher BNP (median = 1290 pg/ml, interquartile range: 721, 3026 pg/ml versus 430 pg/ml, interquartile range: 243, 886 pg/ml). On multivariate analysis, the only factors that remained significantly associated with mortality were the BNP levels (p = 0.005) and the systolic blood pressure (p = 0.01). The negative predictive value of a BNP level < 631 pg/ml (median) for death was 94% (95% confidence interval: 91 to 97%). We conclude that BNP does have an independent prognostic value for in-hospital death in elderly subjects with acute diastolic cardiac failure.     

Accuracy of Doppler ultrasound in evaluating changes of left ventricular diastolic properties

In order to evaluate the effect of an increase in preload caused by contrast medium (Renografin-75) on Doppler echocardiographic indices of left ventricular diastolic properties, left ventricular pressure using a catheter tip micromanometer and pulsed-Doppler measurement of transmitral flow signals were measured simultaneously in 15 patients with coronary artery disease pre- and post-left ventricular angiography. After left ventricular angiography, changes in indices determined from left ventricular pressure were significant: left ventricular end-diastolic pressure increased from 17 +/- 2 mmHg to 24 +/- 2 mmHg (mean +/- SE) (P less than 0.001), maximum -dP/dt increased from 1,129 +/- 63 to 1,307 +/- 90 mmHg/sec (P less than 0.005), and time constant decreased from 73 +/- 2 to 67 +/- 1 msec (P less than 0.01). Changes in Doppler-derived indices were also significant: A/E ratio decreased from 0.99 +/- 0.08 to 0.81 +/- 0.07 (P less than 0.01), peak velocity of early diastolic filling increased from 0.61 +/- 0.03 to 0.79 +/- 0.03 M/sec (P less than 0.01), and deceleration rate increased from 3.1 +/- 0.2 to 4.6 +/- 0.2 M/sec 2 (P less than 0.01). Changes in Doppler echocardiographic indices (DR, acceleration half time, deceleration half time, and A/E ratio) were accompanied by changes in time constant and maximum -dP/dt after left ventricular angiography. However, the correlations between changes in hemodynamic indices and changes in Doppler echocardiographic indices were poor (r = 0.06 to 0.67).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ratio of peak early to late diastolic filling velocity of the left ventricular inflow is associated with left atrial appendage thrombus formation in elderly patients with acute ischemic stroke and sinus rhythm

OBJECTIVES: To investigate the useful parameters of transthoracic echocardiography (TTE) for the diagnosis of stroke subtypes in patients with acute cerebral infarction. METHODS: One hundred and one acute ischemic stroke patients met all of the following criteria; > or = 50 years of age, normal sinus rhythm on admission, and transesophageal echocardiography (TEE) within 7 days from the onset. The clinical significance of the TTE parameters on admission was examined for identifying intracardiac thrombus formation as follows: left atrial dimension, left ventricular end-diastolic dimension, percentage fractional shortening, left ventricular mass index, ratio of the transmitral inflow velocities (E/A), and deceleration time of the E wave. RESULTS: There were 28 patients with E/A > or = 1.0(70 +/- 12 years old) and 73 with E/A < 1.0 (73 +/- 10 years old). No patient showed pulmonary congestion on chest radiography. There were no significant differences in age, TTE parameters, and plasma levels of brain natriuretic peptide between the two groups. Patients with E/A > or = 1.0 had higher incidence of left atrial appendage thrombus formation and/or spontaneous echographic contrast than those with < 1.0 (25% vs 5%, p = 0.0058). There was a significant relationship between E/A and emptying flow velocity of the left atrial appendage (r = -0.569, p < 0.0001). Multivariate logistic regression analysis showed E/A was an independent predictor for left atrial appendage thrombus (risk ratio 1.531 per 0.1 increase, 95% confidence interval 1.129-2.076, p = 0.0002). CONCLUSIONS: Increased level of E/A on admission was associated with the occurrence of left atrial appendage thrombus formation in patients with acute ischemic stroke.