Plasma N-terminal pro-brain natriuretic peptide: a marker of left ventricular hypertrophy in hypertrophic cardiomyopathy.

BACKGROUND: B-type natriuretic peptide is secreted mainly in the left ventricle in response to elevated wall tension. Plasma levels of the peptide correlate positively with cardiac filling pressures, making it an excellent marker for the presence of left ventricular dysfunction. In hypertrophic cardiomyopathy, enhanced production of B-type natriuretic peptide is observed. However, the relationship of the various structural and functional features present in the disease with the high plasma levels described is not yet fully clarified. In the present study, we prospectively assessed in hypertrophic cardiomyopathy the relationship of plasma NT-proBNP levels with the extent of left ventricular hypertrophy, presence of left ventricular outflow obstruction and echocardiographic parameters of left ventricular diastolic function. METHODS: The study population included 190 individuals: 53 patients with hypertrophic cardiomyopathy and well-preserved left ventricular systolic function (group A), 92 healthy relatives with no disease expression (group B), and an additional group of 46 healthy volunteers (group C) as controls for NT-proBNP levels. Groups A and B were characterized clinically and by echocardiography and compared with each other. Plasma NT-proBNP levels were measured (ECLIA-Elecsys proBNP) and compared in the 3 groups of individuals included in the study. In hypertrophic cardiomyopathy patients, correlation was sought between NT-proBNP levels, NYHA functional class and echocardiographic data. RESULTS: Groups A and B differed (p < 0.001) in septal thickness, maximal wall thickness, left ventricular hypertrophy score, left atrial size, left atrial fractional shortening, derived transmitral filling indices and plasma NT-proBNP levels (group A: 909.9 +/- 1554.2 pg/ml; group B: 40.7 +/- 45.1 pg/ml). Left ventricular diastolic size and pulmonary venous flow velocity-derived indices were similar in the 2 groups. NT-proBNP levels in group B and C (39.4 +/- 34.5 pg/ml) were similar (p = NS). In hypertrophic cardiomyopathy patients, NT-proBNP levels correlate directly with NYHA functional class (r = 0.56, p < 0.001), septal thickness (r = 0.53, p < 0.001), maximal wall thickness (r = 0.59, p < 0.001), left ventricular hypertrophy score (r = 0.63, p < 0.001), left atrial size (r = 0.32, p = 0.023) and mitral deceleration time (r = 0.46, p = 0.001) and inversely with left atrial fractional shortening (r = -0.41, p = 0.005). Functional class also correlates directly with left ventricular hypertrophy score (r = 0.39, p = 0.006), with the most symptomatic patients having the highest scores. CONCLUSIONS: In hypertrophic cardiomyopathy, plasma NT-proBNP levels depend mainly on the severity of left ventricular hypertrophy rather than on the presence of obstruction. Measurement of the peptide may help in the clinical characterization and follow-up of patients with this disease.     

B-type natriuretic peptide after percutaneous transluminal septal myocardial ablation

BACKGROUND: Plasma level of B-type natriuretic peptide is a sensitive marker of left ventricular dysfunction and the level is markedly elevated in patients with hypertrophic obstructive cardiomyopathy. Percutaneous transluminal septal myocardial ablation, a catheter-based treatment of hypertrophic obstructive cardiomyopathy, has been widely used as a new therapeutic option for the disease. This study was designed to evaluate clinical implications of natriuretic peptides after the new treatment. METHODS: Seven consecutive patients with hypertrophic obstructive cardiomyopathy unresponsive to usual medical treatments (age: 57.9+/-22.0 years) were enrolled in the study. Serial changes in atrial and B-type natriuretic peptide in plasma were examined after percutaneous transluminal septal myocardial ablation. RESULTS: Atrial and B-type natriuretic peptides levels (pg/ml, mean+/-S.D.) at baseline were higher in hypertrophic obstructive cardiomyopathy than in control (80.0+/-43.0 vs. 12.8+/-5.2, P<0.0001; 858.0+/-458.4 vs. 12.4+/-7.0, P<0.0001; respectively). Left ventricular outflow-tract pressure gradient (mmHg) immediately decreased from 115.3+/-23.3 to 30.6+/-12.4 (P<0.0001) after the treatment and concomitantly B-type natriuretic peptide level decreased (858.0+/-458.4 to 264.1+/-137.7, P=0.0084). The level re-increased and peaked at the 2nd day (634.4+/-429.6) and gradually decreased again until 4 weeks. Reduction rate of left ventricular outflow-tract pressure gradient between before and 4 weeks after percutaneous transluminal septal myocardial ablation positively correlated with that of B-type natriuretic peptide (r(2)=0.817, P=0.0053). Changes in atrial natriuretic peptide were not significant in contrast to those of B-type natriuretic peptide. CONCLUSIONS: Plasma B-type natriuretic peptide level could be useful to predict the effects of percutaneous transluminal septal myocardial ablation in patients with hypertrophic obstructive cardiomyopathy.     

The influence of age on gender-specific differences in the left ventricular cavity size and contractility in patients with hypertrophic cardiomyopathy

BACKGROUND: The aim of the study was to assess gender-specific differences in left ventricular cavity size, contractility and left ventricular outflow tract obstruction in younger and older subgroups of patients with hypertrophic cardiomyopathy. METHODS: We studied retrospectively 153 referred patients with hypertrophic cardiomyopathy (89 males and 64 females). The echocardiographically measured left ventricular end-systolic, end-diastolic dimensions, fractional shortening and occurrence of left ventricular outflow tract gradient were compared between sexes in subgroups of patients 50 years of age. RESULTS: In younger patients with hypertrophic cardiomyopathy, left ventricular end-diastolic and end-systolic dimensions were significantly smaller in females than males (41.9+/-5.8 vs. 44.7+/-5 mm P<0.01 23.4+/-5 vs. 25.2+/-5.4 mm P<0.05, respectively). Fractional shortening was comparable in both sexes (44.7+/-7.5 vs. 43.7+/-8.2% P>0.05). The left ventricular outflow tract gradient occurred in females as frequently as in males (13.3 vs. 17.6% P>0.05). In older patients with hypertrophic cardiomyopathy, left ventricular end-diastolic and end-systolic dimensions were also significantly smaller in females than males (42.5+/-6 vs. 46.3+/-3.2 mm P<0.02; 25.7+/-4.8 vs. 28.6+/-3.7 mm P<0.01, respectively). In contrast to the younger group, the fractional shortening was significantly higher in females than males (44.4+/-6.8 vs. 38.2+/-7.3% P<0.02). The left ventricular outflow tract gradient occurred in females more frequently than in males (63.2 vs. 20.8% P<0.02). CONCLUSIONS: In patients with hypertrophic cardiomyopathy, the gender-based differences in the absolute value of left ventricular cavity size persisted with aging. In older females left ventricular contractility was higher and left ventricular outflow tract gradient occurred more frequently than in males. In younger patients with hypertophic cardiomyopathy these sex-based differences were absent. The gender-specific differences in the parameters of left ventricular systolic function became apparent with increasing age.     

Cardiac natriuretic peptides in patients with hypertrophic cardiomyopathy

AIM: To study interrelation of main clinico-hemodynamic parameters and levels of natriuretic peptides (NUP) in patients with hypertrophic cardiomyopathy (HCMP). MATERIAL AND METHODS: We measured concentrations of N-terminal fragments of precursors of plasma brain and atrial natriuretic peptides (NT-proBNP and NT-proANP) and conducted complex echocardiographical examination in 94 patients (mean age 42.3 +/- 133.8 years) with obstructive (n=43) and nonobstructive (n=51) HCMP. RESULTS: Content of NUP did not depend on patients age, contractile function and dimensions of the left ventricle (LV), moderate and significant correlation between content of NT-proBNP, NT-proANP and type of ventricular filling (r=0.45 and 0.46, respectively), heart failure functional class (r=0.41 and 0.44, respectively), severity of LV hypertrophy (r=0.42 and 0.34, respectively), left atrial dimension (r=0.26 and 0.35, respectively), magnitude of pressure gradient in LV outflow tract (r=0.35 and 0.26, respectively). Degree of mitral regurgitation correlated significantly only with NT -proBNP level (r=0.34). The patients who eventually died (n=6) were characterized by higher plasma content of NUP. CONCLUSIONS: In patients with HCMP elevated plasma content of N-terminal precursors of brain and atrial natriuretic peptides are associated with severity of LV diastolic dysfunction and hypertrophy of LV as well as of hemodynamic and functional disturbances.     

Impact of gender on the left ventricular cavity size and contractility in patients with hypertrophic cardiomyopathy

BACKGROUND: The aim of the study was to assess gender-specific differences in left ventricular cavity size, contractility and left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy. METHODS: We studied retrospectively 129 referred patients with hypertrophic cardiomyopathy (77 males and 52 females). The echocardiographically measured left ventricular end-systolic, end-diastolic dimensions, fractional shortening and occurrence of left ventricular outflow tract gradient > or =30 mmHg were compared between sexes. Logistic regression analysis was used to calculate the predictive values of left ventricular dimensions and contractility for left ventricular outflow tract obstruction for each gender separately. RESULTS: Left ventricular end-diastolic and end-systolic dimensions were significantly smaller in females than males (41.7+/-5.3 vs. 45.1+/-4.9 mm, P=0.0003; 23.1+/-44 vs. 25.6+/-5.3 mm, P=0.007 respectively). On the contrary, the value of fractional shortening was comparable in both sexes (44.7+/-7.3 vs. 43.6+/-7.9%, P>0.05). The left ventricular outflow tract gradient occurred in females as frequently as in males (28.8 vs. 33.8%, P>0.05). By logistic regression analysis the predictors of left ventricular outflow tract gradient in females were left ventricular end-systolic diameter (relative risk=0.74; confidence interval (CI) 0.61 to 0.91; P=0.0038), left ventricular end-diastolic diameter (relative risk=0.82; CI 0.72 to 0.96; P=0.0061) and fractional shortening (relative risk=1.11; CI 1.01 to 1.22; P=0.036). The most potent predictor appeared to be left ventricular end-systolic dimension. In males none of these parameters identified patients with left ventricular outflow tract obstruction. Conclusions: Females with hypertrophic cardiomyopathy featured smaller left ventricular cavity size, which predisposed to left ventricular outflow tract obstruction (the most potent predictor of left ventricular outflow tract obstruction was left ventricular end-systolic dimension). Higher left ventricular contractility also determined left ventricular outflow tract gradient occurrence in females with hypertrophic cardiomyopathy. In males despite a larger left ventricular cavity size the left ventricular outflow tract obstruction occurred with a similar frequency as in females. Left ventricular outflow tract obstruction was not predicted by left ventricular cavity size or contractility in males.     

Right ventricular outflow-tract fractional shortening: an applicable measure of right ventricular systolic function.

AIMS: Assessment of right ventricular function is important. However, this is not easy to achieve due to the complex anatomy and geometry of the right ventricle, making the evaluation of its function limited. Therefore, a simple reliable and easy method is needed. This study was performed (1) to evaluate the use of right ventricular outflow tract fractional shortening obtained by M-mode echocardiography as a measure of right ventricular systolic function and (2) to determine the relationship between this parameter and other established measurements of right ventricular function such as long axis excursion. METHODS AND RESULTS: Ninety-two consecutive patients referred for echocardiographic assessment of left and right ventricular function, age mean+/-SD was 68+/-14 years, were investigated. Twenty healthy controls, age 46+/-12 years were also studied. M-mode echocardiography was used to measure right ventricular outflow tract fractional shortening and right ventricular long axis excursion. Doppler echocardiography was used for the estimation of right ventricular-right atrial pressure drop and pulmonary artery acceleration time. Right ventricular outflow tract fractional shortening (P<0.0001), right ventricular long axis excursion (P<0.0001) and pulmonary acceleration time (P<0.0001) were reduced in patients compared to controls. Right ventricular outflow tract fractional shortening correlated with long axis excursion (r=0.66 P<0.0001), pulmonary artery acceleration time (r=0.80 P<0.0001) and right ventricular-right atrial pressure drop (r=-0.53 P<0.0001). Right ventricular long axis excursion correlated with right ventricular-right atrial pressure drop though to a lesser significance (r=-0.27 P <0.001). Furthermore, right ventricular outflow tract fractional shortening was reduced in patients with pulmonary hypertension compared to patients without, this difference was not observed in the right ventricular systolic long axis excursion. CONCLUSION: Right ventricular outflow tract fractional shortening provides a simple and non-invasive measure of right ventricular systolic function. In combination with long axis excursion and Doppler velocities they should provide comprehensive assessment of right ventricular function.     

Prediction of mean pulmonary wedge pressure using doppler pulmonary venous flow variables in hypertrophic cardiomyopathy

We examined whether pulmonary venous flow variables, assessed by transthoracic Doppler echocardiography, could predict mean pulmonary wedge pressure in hypertrophic cardiomyopathy. Forty-four patients with no left ventricular systolic dysfunction (left ventricular fractional shortening > or =25%) were studied. Forty patients with systolic dysfunction (dilated cardiomyopathy group) served as control. Mitral and pulmonary venous flow velocity curves were recorded with the pulsed-Doppler method and were related to mean pulmonary wedge pressure obtained by right heart catheterization. In hypertrophic cardiomyopathy group, the systolic (r=-0.15, P=0.335) and diastolic (r=0.35, P=0.022) forward flow velocity were poorly related to mean pulmonary wedge pressure, whereas the velocity of atrial reversal (r=0.68, P<0.001) correlated well with mean pulmonary wedge pressure. In dilated cardiomyopathy group, the systolic (r=-0.51, P=0.001) and diastolic (r=0.60, P<0.001) forward flow velocity were strongly related to mean pulmonary wedge pressure. With the cut-off value set at the velocity of atrial reversal >30 cm/s in hypertrophic cardiomyopathy group, the sensitivity for predicting mean pulmonary wedge pressure >15 mmHg was 79% and the specificity was 73%. In conclusion, the atrial component of the pulmonary venous flow can be used to predict mean pulmonary wedge pressure in hypertrophic cardiomyopathy.     

Altered autonomic cardiac control in hypertrophic cardiomyopathy: Role of outflow tract obstruction and myocardial hypertrophy

Aim The goal of this study was to investigate the role of leftventricular outflow tract obstruction and myocardial hypertrophyon autonomic cardiac function in patients with hypertrophiccardiomyopathy. Methods and results The sympatho-vagal function was evaluatedby spectral analysis of heart rate variability in 28 patientswith hypertrophic obstructive cardiomyopathy, 22 patients withhypertrophic non-obstructive cardiomyopathy, 12 with systemichypertension and left ventricular hypertrophy and 28 healthysubjects. Left ventricular outflow tract pressure gradient inpatients with hypertrophic cardiomyopathy was evaluated by echo-Dopplermethods and the quantitative assessment of left ventricularhyper-trophy was based on an echocardiographic index. At rest,patients with hypertrophic non-obstructive cardiomyop-athy showednormal spectral patterns, while in patients with hypertrophicobstructive cardiomyopathy and in patients with systemic hypertensionwe observed, respectively, a significant reduction and increasein the low frequency component relative to the control (P<0·05).During tilt, the physiological increases in the low frequencycomponent, and in the low to high frequency ratio were markedlyblunted, or even reverted, only in patients with hypertrophicobstructive cardiomyopathy. In these patients, the heart rateincrease during tilt was delayed in comparison to the othergroups. Finally, in the hypertrophic obstructive cardiomyopathygroup, the impairment of sympathetic activation (lack of increasein the low frequency component during tilt) was significantlycorrelated to the echocardiographic index of left ventricularhypertrophy (r=–0·800,P<0·001) ratherthan to the left ventricular outflow tract pressure gradient(r=0·295,P: ns). Conclusion Among patients with hypertrophic cardiomyopathy,only those with outflow tract obstruction show spectral signsof altered autonomic cardiac control. Within this group, theautonomic dysfunction appears to be correlated to myocardialhypertrophy rather than to left ventricular outflow tract obstruction.     

心力衰竭患者脑钠素水平与心功能的关系

【目的】研究慢性心力衰竭患者血清脑钠素(BNP)浓度与心功能的关系。方法用酶联免疫吸附法(ELISA)测定62例慢性心力衰竭患者及20名健康对照组血清BNP浓度,采用多普勒超声心动图测定左室射血分数(LVEF)、左室短轴缩短率(FS)、左室舒张末内径(LVEDD),观察BNP水平与LVEF、FS、LVEDD的相关性。结果心衰组血清BNP浓度较对照组明显增高(P<0.01),各心衰组BNP水平差异有统计学意义,且BNP水平随NYHA分级升高而升高。BNP水平与LVEF及FS呈负相关(r=-0.62,r=-0.59,P<0.01),与LVEDD呈正相关(r=0.67,P<0.01)。结论血清CNP浓度可作为反映心功能状态的指标,并与心脏结构有关。     

Influence of left ventricular hypertrophy and function on the occurrence of ventricular tachycardia in hypertrophic cardiomyopathy.

Sixty-nine patients with hypertrophic cardiomyopathy were studied by 2-dimensional and Doppler echocardiography and 72-hour Holter monitoring to examine the relation between the degree of left ventricular (LV) hypertrophy and dysfunction and the occurrence of ventricular tachycardia (VT). Episodes of nonsustained VT were detected in 20 patients (29%). Maximal wall thickness was not different between patients with (22 +/- 5 mm) and without (21 +/- 5 mm) VT. Total hypertrophy score, calculated as the sum of 10 segmental wall thicknesses, was also similar in both groups (157 +/- 22 and 153 +/- 32 mm, respectively; p = not significant). Furthermore, no significant differences were found between the 2 groups in LV end-diastolic dimension (41 +/- 7 vs 40 +/- 6 mm), fractional shortening (33 +/- 7 vs 34 +/- 10%) and left atrial size (40 +/- 10 vs 41 +/- 11 mm). An LV outflow tract gradient was detected in 25% of patients with and 35% without VT (p = not significant). One or more Doppler indexes of diastolic function were abnormal in 70% of patients, but no difference in any of these indexes was found between those with and without VT. In summary, the occurrence of VT in hypertrophic cardiomyopathy is not related to the degree of LV hypertrophy, outflow tract gradient or dysfunction. This finding suggests a dissociation between the arrhythmogenic substrate and echocardiographic features of the disease.     

Plasma and cardiac tissue atrial and brain natriuretic peptides in experimental heart failure

Objectives. This study evaluated the role of changes in heart rate, cardiac filling pressures and cardiac tissue atrial and brain natriuretic peptides in the modulation of their plasma levels in a model of heart failure.Background. Atrial and brain natriuretic peptides constitute a dual natriuretic peptide system that regulates circulator homeostasis.Methods. The effects of 1) acute ventricular pacing, 2) acute volume expansion, and 3) volume expansion after 1 week of continuous pacing on plasma atrial and brain natriuretic peptide levels were compared in eight dogs. Atrial and ventricular tissue levels of the peptides were examined in 5 normal dogs (control group), 21 dogs paced for 1 week (group 1) and 10 dogs paced for 3 weeks (group 2).Results. Both acute pacing and volume expansion increased plasma atrial natriuretic peptide levels (from 53 ± 41 to 263 ± 143 pg/ml [mean ± SD], p < 0.01, and from 38 ± 23 to 405 ± 221 pg/ml, p < 0.001, respectively). After 1 week, there was a marked incerase in plasma levels of atrial natriuretic peptide, but the level did not increase further with volume expansion (from 535 ± 144 to 448 ± 140 pg/ml, p = 0.72). By contrast, plasma brain natriuretic peptide levels increased only modestly with acute pacing (from 12 ± 5 to 20 ± 4 to 20 ± 8 pg/ml, p < 0.05) and after pacing for 1 week (from 13 ± 4 to 48 ± 20 pg/ml, p < 0.05) but did not change with acute or repeat volume expansion. In groups 1 and 2, atrial tissue levels of atrial natriuretic peptide (1.9 ± 1.3 and 2.0 ± 0.9 ng/mg, respectively) were lower than those in the control group (11.e7 ± 6.8 ng/mg, both p < 0.001), whereas ventricular levels were similar to those in the control group. Atrial tissue brain natriuretic peptide levels in groups 1 and 2 were similar to those in the control group. However, ventricular levels in group 2 (0.018 ± 0.006 ng/mg) were increased compared with those in the control group (0.013 ± 0.006 ng/mg, p < 0.05) and in group 1 (0.011 ± 0.006 ng/mg, p < 0.05).Conclusions. Atrial and brain natriuretic peptides respond differently to changes in heart rate and atrial pressures. Reduced atrial tissue atrial natriuretic peptide levels in heart failure may indicate reduced storage after enhanced cardiac release, However, the relatively modest change in the cardiac tissue brain natriuretic peptide levels suggests that the elevated plasma levels may be mediated by mechanisms other than increased atrial pressured.     

Systolic and diastolic flow abnormalities in elderly patients with hypertensive hypertrophic cardiomyopathy

Seventeen patients with clinical and echocardiographic features of hypertensive hypertrophic cardiomyopathy of the elderly were studied to more completely characterize left ventricular systolic and diastolic function in this group. Measurements of left ventricular structure and systolic and diastolic function were made in the study patients and compared with those of age-matched control subjects. The study group had significantly greater left ventricular mass, wall thickness, shortening fraction and relative wall thickness than did the control subjects. Left ventricular end-diastolic dimension was smaller and left atrial size was not different in study patients compared with control subjects. Left ventricular filling was characterized by an increased peak atrial velocity and reduced ratio of peak early to peak atrial velocity in the study group. Left ventricular outflow velocities were elevated in 14 of the 17 study patients with peak velocities ranging from 1.2 to 5.0 m/s corresponding to a peak intraventricular gradient of 16 to 100 mm Hg. The velocity waveforms in these patients were late-peaking, similar to those described in hypertrophic obstructive cardiomyopathy. The elevated velocities were localized to the left ventricular outflow tract. These findings imply a pathophysiologic state in these elderly patients with long-standing hypertension, very similar to that in hypertrophic obstructive cardiomyopathy, and provide further support for the use of pharmacologic agents with negative inotropic properties or positive lusitropic properties in this group.     

Causal relation between the pressure gradient and left ventricular ejection time in hypertrophic cardiomyopathy

This study was designed to evaluate the relation between severity of obstruction to left ventricular outflow and left ventricular ejection time in hypertrophic obstructive cardiomyopathy. With dual catheters across the left ventricular outflow tract, the pressure gradient and corresponding left ventricular ejection time were measured in 10 patients as the pressure gradient was pharmacologically provoked or abolished, or both. The patients were studied during constant atrial pacing to avoid the potential errors introduced with heart rate correction equations. The pressure gradient was pharmacologically provoked or reduced over a range of greater than or equal to 62 mm Hg per patient. In each patient the left ventricular ejection time varied directly with the pressure gradient (mean r = 0.97, range 0.92 to 1.00). The change in magnitude of the pressure gradient varied directly with the corresponding change in the measured ejection time (mean r = 0.98, range 0.97 to 1.00). When the data from all 10 patients were pooled with use of Weissler's heart rate correction equation, the relation between the corrected left ventricular ejection time and the pressure gradient was still significant and linear (r = 0.86), but less so than in individual patients. This difference was the result of marked interpatient variability in the slope of this linear relation reflecting interpatient differences in other important factors, such as underlying myocardial contractility and stroke volume, that influence left ventricular ejection time. This study demonstrates a clear, direct and highly significant relation between the magnitude of the pressure gradient and the left ventricular ejection time in hypertrophic obstructive cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma brain natriuretic peptide level as a biochemical marker of morbidity and mortality in patients with asymptomatic or minimally symptomatic left ventricular dysfunction. Comparison with plasma angiotensin II and endothelin-1.

AIMS: To evaluate the level of plasma brain natriuretic peptide as a predictor of morbidity and mortality in patients with asymptomatic or minimally symptomatic left ventricular dysfunction. METHODS: We measured plasma levels of atrial natriuretic peptide, brain natriuretic peptide, norepinephrine, angiotensin II, and endothelin-1 and monitored haemodynamic parameters in 290 consecutive patients with asymptomatic or minimally and newly symptomatic left ventricular dysfunction (functional classes I-II, mean left ventricular ejection fraction=37%). All patients were followed up for a median period of 812 days. The Cox proportional hazards model was used to assess the association of variables with mortality and morbidity. RESULTS: At the end of the follow-up, 24 patients had suffered cardiac death and 25 had been hospitalized for worsening heart failure during the follow-up period. Among 21 variables such as clinical characteristics, treatment, haemodynamics, and neurohumoral factors, high levels of plasma brain natriuretic peptide (P<0.0001), norepinephrine (P=0.042), left ventricular end-diastolic volume index (P=0.0035), and left ventricular end-diastolic pressure (P=0.033) were shown to be independent predictors of mortality and morbidity by stepwise multivariate analysis. Moreover, only a high level of plasma brain natriuretic peptide (P<0.0001) was shown to be an independent predictor of mortality in these patients. CONCLUSIONS: These results indicate that a high plasma brain natriuretic peptide level provides information about mortality and morbidity in patients with asymptomatic or minimally symptomatic left ventricular dysfunction.     

Left atrial appendage dysfunction in chronic nonvalvular atrial fibrillation is significantly associated with an elevated level of brain natriuretic peptide and a prothrombotic state

The study tested the hypothesis that left atrial appendage (LAA) dysfunction in nonvalvular atrial fibrillation (NVAF) correlates with a prothrombotic state, and investigated whether the plasma natriuretic peptides are marker of LAA dysfunction in NVAF. Sixty-seven patients underwent transthoracic and transesophageal echocardiography. The left ventricular fractional shortening, left atrial diameter (LAD), LAA flow velocity and the grade of spontaneous echo contrast (SEC) were determined. The plasma concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), D-dimer, and thrombin-antithrombin III complex (TAT) were measured. The patients were divided into 2 groups according to LAA flow velocity: group I (LAA velocity <20 cm/s) and group II (LAA velocity > or = 20cm/s). The SEC score, D-dimer, TAT, BNP and LAD were significantly increased in group I. Based on simple linear regression analysis, SEC score (r=-0.638), LAD (r=-0.493), D-dimer (r = -0.485), BNP (r = -0.463), TAT (r = -0.455) and age (r = -0.314) were inversely correlated with LAA flow velocity. Multivariate analysis showed that SEC score (p = 0.0014) and plasma BNP level (p=0.0075) were independent negative predictors for LAA flow velocity. In conclusion, LAA dysfunction is associated with a prothrombotic state, and the plasma BNP concentration may serve as a determinant of LAA function in NVAF.     

Exercise capacity in hypertrophic cardiomyopathy depends on left ventricular diastolic function.

Some studies have demonstrated that left ventricular (LV) diastolic function is the principal determinant of impaired exercise capacity in hypertrophic cardiomyopathy (HC). In this study we sought the capability of echocardiographic indexes of diastolic function in predicting exercise capacity in patients with HC. We studied 52 patients with HC while they were not on drugs;12 of them had LV tract obstruction at rest. Diastolic function was assessed by M-mode and Doppler echocardiography by measuring: (1) left atrial fractional shortening, and the slope of posterior aortic wall displacement during early atrial emptying on M-mode left atrial tracing; and (2) Doppler-derived transmitral and pulmonary venous flow velocity indexes. Exercise capacity was assessed by maximum oxygen consumption by cardiopulmonary test during cycloergometer upright exercise. Maximum oxygen consumption correlated with the left atrial fractional shortening (r = 0.63, p <0.001), the slope of posterior aortic wall displacement during early atrial emptying (r = 0.55, p <0.001), age (r = -0.50; p <0.001), pulmonary venous diastolic anterograde velocity (r = 0.41, p <0.01), and the systolic filling fraction (r = -0.43; p <0.01). By stepwise multiple linear regression analysis, left atrial fractional shortening and the pulmonary venous systolic filling fraction were the only determinants of the maximum oxygen consumption (multiple r = 0.70; p <0.001). Exercise capacity did not correlate with Doppler-derived transmitral indexes. Thus, in patients with HC, exercise capacity was determined by passive LV diastolic function, as assessed by the left atrial M-mode and Doppler-derived pulmonary venous flow velocities.     

Atrial natriuretic peptide in chronic heart failure in the rat: a correlation with ventricular dysfunction

To assess the relation between atrial natriuretic peptide and ventricular dysfunction, we simultaneously measured both atrial and plasma immunoreactive atrial natriuretic peptide concentrations in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. When compared to controls (n = 39), rats with infarction (n = 16) had markedly elevated plasma immunoreactive atrial natriuretic peptide concentrations (1205.8 +/- 180.9 vs. 126.7 +/- 8.9 pg/ml, p less than 0.001) and reduced immunoreactive atrial natriuretic peptide concentrations in right and left atria (31.4 +/- 4.6 vs. 61.2 +/- 3.2 ng/mg, p less than 0.001; 14.9 +/- 2.2 vs. 32.7 +/- 2.4 ng/mg, p less than 0.001, respectively). Right ventricular weight increased in proportion to infarct size, and both were correlated with plasma immunoreactive atrial natriuretic peptide levels (r = 0.825, p less than 0.001 and r = 0.816, p less than 0.001, respectively). Right atrial immunoreactive atrial natriuretic peptide content was significantly higher than left in both controls and rats with infarction. Both right and left atrial immunoreactive atrial natriuretic peptide concentrations were negatively correlated with both right ventricular weight as well as plasma immunoreactive atrial natriuretic peptide concentrations (right atrium: r = -0.816, p less than 0.001, r = -0.708, p less than 0.01; left atrium: r = -0.687, p less than 0.01, r = -0.644, p less than 0.01, respectively). These results suggest that chronic stimulation of atrial natriuretic peptide release from both atria is associated with increased turnover and depleted stores of atrial natriuretic peptide in atria in proportion to the severity of heart failure. It also suggests that plasma atrial natriuretic peptide levels may be used as a reliable index of cardiac decompensation in chronic heart failure.     

肥厚型心肌病血浆BNP测定的临床意义

目的:探讨血浆B型利钠肽(BNP)水平测定在肥厚型心肌病(HCM)患者中的应用价值。方法:连续入选2005年1月至2006年12月在我科就诊的HCM患者53例,患者均行超声心动图检查和血浆BNP的测定。观察BNP水平与临床指标及超声心动图参数的关系。结果:53例中男性36例(67.9%),年龄(47.8±14.6)岁,有左心室流出道梗阻者26例(49.1%)。HCM患者的血浆BNP水平明显升高,梗阻型患者明显高于非梗阻型患者[(1 404.2±1 087.2)fmol/mL比(837.2±792.6)fmol/mL,P<0.05]。多元相关分析显示,在非梗阻型患者中与血浆BNP相关的因素为NYHA分级(r=0.696,P<0.01)、左心房内径(LAD)(r=0.617,P<0.01)、二尖瓣血流E峰与A峰比值(E/A)(r=0.988,P<0.01)、左心室舒张末内径(LVEDD)(r=0.731,P<0.05)与左心室射血分数(LVEF)(r=-0.733,P<0.05);而与梗阻型患者血浆BNP水平相关的因素为胸痛和呼吸困难的症状(r=0.418,P<0.05)与LAD(r=0.421,P<0.05)。结论:HCM患者的血浆BNP水平升高,梗阻型患者高于非梗阻型患者。对于梗阻型与非梗阻型患者,血浆BNP测定可能有不同的应用价值。     

Intraoperative Doppler echocardiography in hypertrophic cardiomyopathy: correlations with the obstructive gradient

Although significant pressure gradients can be recorded across the left ventricular outflow tract in patients with hypertrophic cardiomyopathy, controversy exists regarding the presence or absence of true obstruction. Ten patients with hypertrophic cardiomyopathy were studied at the time of septal myectomy. A sterile continuous wave Doppler transducer was placed on the ascending aorta and directed toward the left ventricular outflow tract to measure velocity simultaneously with invasive gradient measured using solid-state hub transducers by direct puncture of the left ventricle and aorta. Simultaneous Doppler velocity and invasive gradient measurements (n = 33) were made at rest, before and after myectomy and during interventions with isoproterenol, volume loading and phenylephrine. High velocity flow with a characteristic contour was recorded in patients with a significant gradient. Using the modified Bernoulli equation (gradient = 4 X velocity), a good correlation was found between the Doppler-derived gradient and the peak instantaneous gradient measured invasively (r = 0.93, y = 0.89X + 12, p = 0.0001). Changes in gradient and velocity due to interventions also correlated well (r = 0.96, y = 0.91X - 3, p = 0.0001). Continuous wave Doppler echocardiography can accurately estimate the outflow tract gradient. The magnitude, timing and contour of these high velocity flow signals support the hypothesis that true obstruction is present in patients with hypertrophic cardiomyopathy who have a significant gradient.     

The effect of the atrioventricular interval during atrioventricular sequential pacing on the hemodynamics in dynamic obstruction of the left ventricular outflow tract in dogs

The present study was performed to clarify the mechanism involved in the reduction of the pressure gradient in the left ventricular outflow tract of patients with hypertrophic obstructive cardiomyopathy when treated with atrioventricular (AV) sequential pacing. The effect of AV sequential pacing with variable AV intervals on the hemodynamics and dyssynchronous wall motion was experimentally studied using echocardiography in the dynamic obstruction of the left ventricular outflow tract created by dobutamine infusion in 17 dogs. The pressure gradient of the left ventricular outflow tract decreased with shortening of the AV interval during AV sequential pacing. Also, the dyssynchrony time, defined as the difference in the time between the intraventricular septum and posterior wall during the systolic phase recorded with M-mode echocardiography, increased with shortening of the AV interval during AV sequential pacing. However, very short AV intervals produced a significant decrease in the aortic pressure and increase in the pulmonary capillary wedge pressure. The dyssynchrony time showed a positive liner correlation with the percentage reduction in the pressure gradient of the left ventricular outflow tract (R=0.794, p<0.0001). It was concluded that dyssynchronous wall motion in the left ventricle was produced by pacing from the right ventricular apex and resulted in a reduction in the pressure gradient of the left ventricular outflow tract. Optimization of the AV interval during AV sequential pacing may play an important role in improving the hemodynamics in dynamic obstruction of the left ventricular outflow tract.