Mechanical unloading versus neurohumoral stimulation on myocardial structure and endocrine function In vivo

BACKGROUND-Mechanical load and humoral stimuli such as endothelin (ET) and angiotensin II (Ang II) are potent modulators of cardiac structure and endocrine function, specifically gene expression and production and release of atrial natriuretic peptide (ANP). We define the contribution of mechanical load compared with neurohumoral stimulation in vivo with specific focus on myocardial and circulating ANP during chronic myocardial unloading produced by thoracic inferior vena caval constriction (TIVCC). METHODS AND RESULTS-TIVCC was produced by banding the IVC for 10 days in 7 dogs, whereas in the 6 control dogs, the band was not constricted. TIVCC was characterized by a decrease in cardiac output, right atrial pressure, and left ventricular (LV) end-diastolic diameter and marked activation of ET and Ang II in plasma and atrial and ventricular myocardium. Despite neurohumoral stimulation, LV mass index and myocyte diameters in unloaded hearts decreased, reflecting myocyte atrophy. The total number of myocytes in the LV remained unchanged. Atrial stores of ANP increased, but plasma ANP did not change, in association with a trend toward ANP gene expression to decrease in unloaded hearts. CONCLUSIONS-Chronic mechanical unloading of the heart results in myocardial atrophy and lack of activation of ANP synthesis despite marked neurohumoral stimulation by the growth promoters ET and Ang II.     

Relationship between plasma atrial natriuretic peptide concentration and atrial pressure in acute and chronic heart failure

Several reports have demonstrated a close correlation between plasma atrial natriuretic peptide (ANP) concentration and atrial pressure in stable heart diseases. However, few studies have investigated whether plasma ANP concentration is a noninvasive indicator of hemodynamic parameters during the treatment of heart failure. Thus, we have studied the relationship between peripheral plasma ANP concentration and concurrent hemodynamic variables during the treatment of heart failure, and, in order to determine whether secretion of ANP is stimulated in this disease condition, we compared the plasma ANP concentration in the pulmonary artery with that in the peripheral veins. Studies were performed in each of 9 patients with acute heart failure due to myocardial infarction (Group A) or chronic heart failure (Group B), who were matched as closely as possible for treatment, age, sex and cardiac output. In group A, no significant correlation was found between plasma ANP levels and any measured hemodynamic variables. In group B, peripheral plasma ANP concentrations were significantly correlated with left atrial pressure (r = 0.82, p less than 0.01), but not with right atrial pressure (r = 0.56, p greater than 0.05). Furthermore, in group B ANP levels in pulmonary arterial plasma were consistently higher than those in peripheral venous plasma, whereas in group A the opposite was observed in expired cases. These results suggest that measurement of peripheral plasma ANP is a useful noninvasive method for estimating left atrial pressure during the treatment of chronic heart failure. However, plasma ANP concentration may not be a valid means of estimating hemodynamic parameters in acute heart failure due to myocardial infarction. In such cases, the increased secretion of ANP was not obvious, and there may be other factors, in addition to atrial pressure, that regulate cardiac secretion of ANP.     

Effect of angiotensin-converting enzyme inhibition on sympathetic tone in patients with mild to moderate heart failure

Sixteen patients with mild to moderate heart failure were examined to investigate whether sympathetic deactivation plays a role in the improvement in the failing heart by chronic angiotensin converting enzyme (ACE) inhibition. Measurements, including echocardiography, blood examinations, neurohumoral samplings (atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine), and spectral heart rate variability analysis by Holter electrocardiography, were carried out before and 6 months after the administration of lisinopril (5-10 mg/day). Quality of life assessment was accomplished by the Specific Activity Scale (SAS) questionnaire. Treatment with lisinopril for 6 months resulted in a significant reduction in systolic blood pressure. The left ventricular diastolic dimension significantly decreased and fractional shortening significantly increased on echocardiography. Of the 16 patients, 8 had improvement in their symptoms as measured by the SAS. Lisinopril did not significantly reduce the plasma norepinephrine concentration, but there was a significant reduction in the plasma ANP and BNP concentrations. In the heart rate power spectral analysis, total spectral power, high-frequency components and low/high frequency ratios did not change significantly with lisinopril. The mechanism by which ACE inhibitors improve mild to moderate heart failure is not by suppressing sympathetic activity.     

Neurohumoral prediction of left-ventricular morphologic response to beta-blockade with metoprolol in chronic left-ventricular systolic heart failure

BACKGROUND: In order to tailor therapy in heart failure, a solution might be to develop sensitive and reliable markers that can predict response in individual patients or monitor effectiveness of therapy. AIMS: To evaluate neurohumoral factors as markers for left-ventricular (LV) antiremodelling from metoprolol treatment in patients with chronic LV systolic heart failure. METHODS: Forty-one subjects randomised to placebo or metoprolol were studied with magnetic resonance imaging and blood samples to measure LV dimensions and ejection fraction, epinephrine, norepinephrine, plasma renin activity, aldosterone, atrial (ANP) and brain natriuretic peptides, arginine-vasopressin and endothelin-1 at baseline, 5 weeks and 6 months after randomisation. RESULTS: Baseline ANP was identified as sole independent marker for changes in LV end-diastolic (deltaLVEDVI: r=-0.70, P=0.002), and end-systolic (deltaLVESVI: r=-0.53, P=0.03) volumes during metoprolol treatment. Change in ANP during the study was an independent marker for deltaLVEDVI: r=0.66, P=0.004, and deltaLVESVI: r=0.69, P=0.002 in the entire metoprolol group, but at the individual patient level, results were less clear. CONCLUSION: The pre-treatment plasma level of ANP may be a predictor of LV antiremodelling from treatment with metoprolol in patients with chronic heart failure. However, the potential for individual neurohumoral monitoring of the effects on LV dimensions during beta-blockade appears limited.     

The modulating actions of sulfonylurea on atrial natriuretic peptide release in experimental acute heart failure

OBJECTIVES: This study defined the modulating actions of sulfonylurea on acute release of atrial natriuretic peptide (ANP) in experimental acute heart failure. BACKGROUND: Sulfonylurea drugs, blockers of cardioprotective ATP-sensitive K(+) (K(ATP)) channels, may increase the risk of early cardiovascular mortality. In cardiovascular diseases such as acute heart failure, early release of ANP is essential for cardiorenal homeostasis. Although K(ATP) channels regulate secretion of hormones, such as insulin, it is unknown whether sulfonylureas interfere with ANP release in acute heart failure. METHODS: The effects of acute administration of glyburide (0.3 mg/kg), a prototype sulfonylurea, on ANP release and sodium excretion were measured in vivo in a canine model of pacing-induced acute heart failure characterized by acute atrial stretch. Immunoreactivity, in atrial tissue, for ANP and the K(ATP) channel subunit, Kir6.2, was determined using specific antibodies. RESULTS: With increased left atrial pressure in heart failure, plasma levels of ANP increased rapidly and peaked within 25+/-3 min. Glyburide delayed the time required for peak plasma ANP secretion to 48+/-5 min. This resulted in reduced natriuresis from 84+/-17 microEq/min in the absence of glyburide, to 34+/-9 microEq/min in the presence of glyburide. However, glyburide did not alter the renal natriuretic responsiveness to exogenously administered ANP in normal dogs. In atrial tissue, both ANP and the K(ATP) channel subunit, Kir6.2, displayed strong immunoreactivity and co-localization. CONCLUSIONS: Glyburide delays release of ANP in acute heart failure resulting in impaired natriuresis. This cannot be ascribed to an antinatriuretic effect on the kidney, but rather may be due to interference with K(ATP) channel-dependent ANP secretion from the atrium. Such adverse outcome of sulfonylurea drug use could reduce the compensatory capacity to preserve cardiorenal homeostasis in acute heart failure.     

Relationship between left atrial appendage function and plasma concentration of atrial natriuretic peptide.

BACKGROUND: It has been reported that the most intensely granuled cardiocytes secreting atrial natriuretic peptide (ANP) are located in the atrial appendages. AIMS: To evaluate the mechanisms of ANP release in congestive heart failure. METHODS AND RESULTS: The relationship between ANP and left atrial appendage (LAA) function was evaluated in 36 patients who underwent both transoesophageal echocardiography and cardiac catheterization. ANP level correlated positively with mean pulmonary capillary wedge pressure (mPCWP; r=0.75, P<0.0001), whereas it showed no significant correlation with the mean right atrial pressure. mPCWP correlated positively with the maximal LAA area (LAAa; r=0.79, P<0.0001) and negatively with the LAA ejection fraction during atrial contraction (LAA-EF; r=-0.61, P<0.0001) and peak late diastolic LAA emptying flow velocity (LAAF; r=-0.69, P<0.0001). ANP level correlated negatively with the LAA-EF (r=-0.56, P<0.001) and with LAAF (r=-0.61, P<0.0001). ANP level correlated more closely with the LAAa (r=0.79, P<0.0001) than with maximal LA volume (r=0.34, P<0.05). Multiple stepwise regression analysis selected LAAa as the only factor independently related to the plasma concentration of ANP (ANP=-22.4+28.6 LAAa, r=0.79, P<0.0001). CONCLUSIONS: We conclude that the factor most predictive for ANP in patients with left-sided cardiac dysfunction is distension of the LAA wall rather than elevation in the LA pressure or distension of the body of LA. This is consistent with the known distribution of ANP-secreting cardiocytes.     

Neurohumoral profiles in patients with hypertrophic cardiomyopathy: differences to hypertensive left ventricular hypertrophy.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD) have increased concentrations of various neurohumoral factors. Thus, the aim of the present study was to evaluate the differences in the neurohumoral profiles of HCM and HHD. METHODS AND RESULTS: Plasma concentrations of epinephrine, norepinephrine, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), angiotensin II and endothelin-1 were measured in 40 patients with HCM, 35 with HHD, and 15 controls. Additionally, the concentrations of these neurohumoral factors in the coronary sinus and aortic root were measured in 12 HCM patients and 10 controls. Plasma concentrations of norepinephrine, ANP and BNP were significantly higher in HCM than HHD and controls. In HCM, there was no significant correlation between the left ventricular mass index and any neurohumoral factor. The plasma BNP concentration significantly correlated with left intraventricular pressure gradient in HCM. There were significant differences in the plasma concentrations of ANP and BNP between HCM with and without left ventricular diastolic dysfunction. Transcardiac production of BNP was significantly higher in patients with obstructive HCM than in those with non-obstructive HCM. CONCLUSIONS: The significant neurohumoral differences between HCM and HHD were the plasma concentrations of norepinephrine, ANP and BNP. In HCM patients, the plasma BNP concentration may reflect the intraventricular pressure gradient and left ventricular diastolic dysfunction whereas the plasma ANP concentration reflects only the left ventricular diastolic dysfunction.     

Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure

OBJECTIVES: We sought to evaluate the effects of spironolactone on neurohumoral factors and left ventricular remodeling in patients with congestive heart failure (CHF). BACKGROUND: Aldosterone (ALD) promotes collagen synthesis and structural remodeling of the heart. Spironolactone, an ALD receptor antagonist, is reported to reduce mortality in patients with CHF, but its influence on left ventricular remodeling has not been clarified. METHODS: Thirty-seven patients with mild-to-moderate nonischemic CHF were randomly divided into two groups that received treatment with spironolactone (n = 20) or placebo (n = 17). We measured left ventricular volume and mass before treatment and after four months of treatment. We also measured the plasma levels of neurohumoral factors, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), as well as plasma procollagen type III aminoterminal peptide (PIIINP), a marker of myocardial fibrosis. RESULTS: Left ventricular volume and mass were significantly decreased and ejection fraction was significantly increased in the spironolactone group, while there were no changes in the placebo group. Plasma levels of ANP, BNP and PIIINP were significantly decreased after spironolactone treatment, but were unchanged in the placebo group. There was a significant positive correlation between the changes of PIIINP and changes of the left ventricular volume index (r = 0.45, p = 0.045) as well as the left ventricular mass index (r = 0.65, p = 0.0019) with spironolactone treatment. CONCLUSIONS: These findings indicate that four months of treatment with spironolactone improved the left ventricular volume and mass, as well as decreased plasma level of BNP, a biochemical marker of prognosis and/or ventricular hypertrophy, suggesting that endogenous aldosterone has an important role in the process of left ventricular remodeling in nonischemic patients with CHF.     

The concentration of atrial natriuretic peptide (ANP) in plasma and atrial tissue of canines with acute heart failure induced by reversible aortic or mitral regurgitation

We have established an easily reversible acute heart failure model in beagle canines by reversible aortic or mitral regurgitation (AR or MR). To cause reversible AR, a basket catheter was inserted into the left ventricle from the apex and fixed at the aortic valve in 10 canines. To cause MR, a basket catheter was inserted into the left atrium via the pulmonary vein and fixed at the mitral valve in 10 canines. The regurgitation by AR or MR was caused by extending the tip basket wire, and the recovery from the regurgitation was immediately possible by closing it. Left atrial pressure (LAP), right atrial pressure (RAP) and pulmonary artery pressure (PAP) were increased significantly during AR or MR, and decreased to the normal level after the release of AR or MR. Using these reversible acute heart failure models, the effects of both advancing and restoring acute heart failure by the secretion of ANP were examined by observing the changes of ANP concentration and its molecular forms in the plasma and left atrial tissue in the same canine. Plasma ANP concentration showed a reversible change. In group analysis, plasma ANP concentration did not correlate with LAP or RAP, but in each canine it showed high correlations with LAP (r = 0.70 approximately 0.94, 0.82 +/- 0.07) and RAP (r = 0.60 approximately 0.93, 0.79 +/- 0.08), having a different slope in each regression line. The ANP concentration in the atrial tissue was decreased during AR or MR, but the low level was maintained after AR or MR. The main molecular form of ANP in the plasma was alpha-ANP and that in the tissue was gamma-ANP. In summary, the tissue storage of ANP was decreased because the ANP secretion caused by stimulation of acute heart failure exceeded its production. The ANP secretion was decreased by the subsequent elimination of heart failure, but the production was not stimulated rapidly, because the tissue content remained unchanged.     

Activation of neurohumoral systems following acute myocardial infarction.

Previous studies have indicated that patients with an acute myocardial infarction have marked activation of all neurohumoral systems on admission to the hospital. This activation begins to subside within the first 72 hours so that by 7-10 days, all plasma neurohormones have returned to normal. The only documented exceptions were found to occur in patients with left ventricular dysfunction and overt heart failure, where both plasma renin activity and atrial natriuretic peptide were increased, and in patients with left ventricular dysfunction but no overt heart failure, where only atrial natriuretic peptide was increased. Although these studies suggest that neurohumoral activation rarely occurs at the time of hospital discharge, they were small and may have missed an important subgroup of patients with persistent neurohumoral activation. In the Survival and Ventricular Enlargement (SAVE) study, 522 patients had plasma neurohumoral levels measured at a mean of 12 days postinfarction. All SAVE patients had left ventricular dysfunction (left ventricular ejection fraction less than or equal to 40%), but no overt heart failure. In this group of patients, all neurohumoral levels (plasma renin activity, norepinephrine, arginine vasopressin, and atrial natriuretic peptide) were found to be increased compared with age-matched control subjects. These results indicate that, in fact, a subgroup of patients without overt heart failure has persistent neurohumoral activation at the time of hospital discharge postinfarction, and that this activation involves several neurohumoral systems. Since patients with persistent neurohumoral activation postinfarction are likely those most at risk of developing complications and the ones most likely to benefit from pharmacologic interventions blunting the effects of neurohumoral activation, measurement of predischarge neurohumoral levels may be useful.     

慢性心力衰竭患者心钠素水平及与心功能关系的观察

目的探讨心钠素(ANP)在慢性心力衰竭发生与发展过程中的意义及与心功能的关系。方法选择35例慢性心力衰竭患者和32例正常对照,采用放射免疫法测定其血浆ANP水平,应用彩色多普勒超声心动图测定左心室收缩末期内径(LVSd)、左心室舒张末期内径(LNDd)、左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)及心动周期中二尖瓣舒张晚期心室充盈峰速度(A)与二尖瓣舒张早期心室充盈峰速度(E)的比值(A／E),观察ANP水平与心功能之间的关系。结果心力衰竭患者血浆ANP水平比健康对照组明显升高(P<0．001),且随着心功能程度的不断加重,ANP水平逐渐升高．依次为心功能Ⅱ级<心功能Ⅲ级<心功能Ⅳ级(P<0．05-0．001)。ANP水平与LVEF、LVFS呈负相关,r值分别为0．76(P<0．01)、-0．72(P<0．01);与LVSd、LVDd及A／E呈正相关,r值分别为0．65(P<0．01)、0．79(P<0．01)、0．72(P<0．01)。结论慢性心力衰竭进展中,ANP水平与心力衰竭的严重程度密切相关,能够反映不同的心功能状态,为慢性心力衰竭的诊断与治疗提供参考依据。     

Systemic and regional vascular effects of atrial natriuretic peptide in a rat model of chronic heart failure

Summary To characterize the systemic and regional vascular effects of atrial natriuretic peptide (ANP) in chronic heart failure, central hemodynamics, regional blood flow and plasma ANP levels were determined in a rat model of myocardial infarction and failure and in sham-operated animals. Measurements were made in the conscious state before and after intravenous rANP [99-126] (8 g bolus followed by continuous infusion of 1.0 g/kg/min). With this protocol, ANP significantly decreased cardiac output, right atrial, left ventricular enddiastolic and arterial pressures and there were increases in heart rate, systemic and intestinal vascular resistances in sham animals. Renal blood flow per gram of tissue was unchanged with ANP, but when expressed as a percentage of cardiac output, increased significantly, indicating a preferential renal vasodilatory effect of ANP. In rats with infarction and failure, this dose did not alter cardiac output or arterial pressure, but decreased right atrial and left ventricular blood flow. Although significantly reduced as compared to the control group, renal blood flow was not improved with ANP in the heart failure group. ANP plasma levels of the heart failure group were elevated at baseline (p<0.01), and increased 5–10 times after infusion of rANP. Thus, in rats with chronic heart failure, the renal vascular effects of ANP are blunted, which may, in part, explain the failure of ANP to restore the altered volume homeostasis in heart failure despite elevated ANP plasma levels. However, the effects on venous return were preserved which, in turn, improved cardiac performance via a reduction of preload.Supported by the Deutsche Forschungsgemeinschaft (DFG, Dr 148/3-1)     

Long-term treatment with neutral endopeptidase inhibitor improves cardiac function and reduces natriuretic peptides in rats with chronic heart failure

OBJECTIVE: Increased secretion of atrial and brain natriuretic peptide (ANP and BNP) from hearts is known to exhibit favorable effects in patients and animals with heart failure, and inhibition of neutral endopeptidase (NEP), an enzyme that degrades ANP and BNP, may further increase these peptide levels. However, it is still unknown whether such elevation of the ANP and BNP may offer a therapeutic benefit to the progression of chronic heart failure (CHF). We examined the effects of ONO-9902, a novel NEP inhibitor, on changes in hemodynamic parameters, NEP activity and neurohumoral factors in rats with CHF induced by left coronary artery ligation (CAL). METHODS: Male Wistar rats (220-240 g) were subjected to induction of acute myocardial infarction by CAL. Rats were orally treated with ONO-9902 (300 mg/kg/day) from the 1st to 6th week after the operation. Hemodynamic and/or biochemical assessments were performed at the 1st and 6th weeks after the operation. RESULTS: A single administration of ONO-9902 inhibited the plasma and kidney NEP activities and thereby further augmented the elevation of plasma ANP concentration in rats with CAL at the 1st week after the operation. In rats with CAL at the 6th week after the operation, the left ventricular end-diastolic pressure (LVEDP) increased and cardiac output index (COI) decreased as compared with those of sham-operated rats. These changes were accompanied by marked increases in the plasma ANP, BNP and endothelin-1 (ET-1). Chronic treatment with ONO-9902 attenuated the increase in LVEDP and the decrease in COI. These changes were associated with a decrease in plasma ANP, BNP and ET-1 concentrations. CONCLUSIONS: The results suggest that chronic treatment with NEP inhibitor improves depressed cardiac function in rats with CHF. ONO-9902 may offer a new and possible therapeutic approach in patients with CHF.     

Relationship between left ventricular wall stress and ANP gene expression during the evolution of rapid ventricular pacing-induced heart failure in the dog

We have recently described a modified model of progressive rapid ventricular pacing-induced heart failure which evolves over a period of 38 days. To further characterize left ventricular remodeling during the progression of heart failure, we assessed left ventricular geometry, wall stress, and atrial natriuretic peptide (ANP) gene expression and protein content during control conditions, asymptomatic left ventricular dysfunction, and overt congestive heart failure (CHF). Although asymptomatic left ventricular dysfunction was characterized by a significant increase in systolic and diastolic left ventricular dimension (+30% and +6%, respectively, P<0.05 each) and a marked increase in left ventricular systolic wall stress (+68%, P<0.01), left ventricular ANP gene expression was unchanged as compared to control. In contrast, strong left ventricular ANP gene expression (+449%, P<0.05) was observed during overt CHF in the absence of further significant increases in left ventricular systolic wall stress. The onset of strong left ventricular ANP gene expression was associated with increased ANP content (+88%, P<0.05) and left ventricular mass index (+13%, P<0.05). In contrast, left atrial ANP gene expression and left ventricular diastolic wall stress increased progressively during asymptomatic left ventricular dysfunction (+39%, P=n.s. and +131%, P<0.01) and overt CHF (+76% and +336% vs. control, P<0.01 each). Progressive rapid ventricular pacing is associated with the induction of left ventricular ANP gene expression and protein synthesis exclusively during overt CHF. The current studies provide new insight into the temporal pattern of ANP-activation and the disparity between left ventricular systolic wall stress and ANP-activation in a large animal model of progressive CHF.     

Heart failure and atrial fibrillation: current concepts and controversies.

Heart failure and atrial fibrillation are very common, particularly in the elderly. Owing to common risk factors both disorders are often present in the same patient. In addition, there is increasing evidence of a complex, reciprocal relation between heart failure and atrial fibrillation. Thus heart failure may cause atrial fibrillation, with electromechanical feedback and neurohumoral activation playing an important mediating role. In addition, atrial fibrillation may promote heart failure; in particular, when there is an uncontrolled ventricular rate, tachycardiomyopathy may develop and thereby heart failure. Eventually, a vicious circle between heart failure and atrial fibrillation may form, in which neurohumoral activation and subtle derangement of rate control are involved. Treatment should aim at unloading of the heart, adequate control of ventricular rate, and correction of neurohumoral activation. Angiotensin converting enzyme inhibitors may help to achieve these goals. Treatment should also include an attempt to restore sinus rhythm through electrical cardioversion, though appropriate timing of cardioversion is difficult. His bundle ablation may be used to achieve adequate rate control in drug refractory cases.     

Role of atrial natriuretic peptide in congestive heart failure due to chronic diabetes.

OBJECTIVE: It is now believed that diabetes sensitizes the myocardium so that superimposed hypertension with its attendant vascular changes results in progressive myocyte damage leading ultimately to congestive heart failure. In this regard, remarkable progress has been made within the past few years with a family of closely related peptides, the atrial natriuretic peptides (ANPs), which are involved in the regulation of plasma volume. Any changes in their levels and/or action can be seen to participate in the development of diabetes-induced congestive heart failure. While the literature reasonably supports the evidence for a defect in the ANP-receptor coupling system in hypertensive and diabetic animals, it is not as clear that this is the cause for heart failure. The present article attempts to demonstrate evidence for causality. DESIGN: The present article summarizes existing knowledge on the involvement of ANP in the induction of fluid imbalance. In particular, the role of ANP in congestive heart failure, hypertension, diabetes and congestive heart failure in diabetes is examined. Recent data in experimental hypertensive-diabetic rats, obtained from this laboratory have also been described here. MAIN RESULTS: There are now several reports which indicate high plasma ANP concentrations in both patients and animals with heart failure, thus implicating a role for this peptide. The present paper deals with ANP-induced molecular changes in kidney basolateral membranes in congestive heart failure due to chronic diabetes. CONCLUSION: Congestive heart failure in diabetes with hypertension may be due to uncoupling of the ANP-receptor effector system in the kidney basolateral membrane. It is possible that other neurohumoral agents through a wide variety of activities may also contribute to the pathophysiology of this disease.     

Atrial natriuretic peptide predicts impaired atrial remodeling and occurrence of late postoperative atrial fibrillation after surgery for symptomatic aortic stenosis

BACKGROUND: Aortic stenosis (AS) and atrial fibrillation (AF) are commonly encountered in clinical practice. Natriuretic peptides (NP) are endogenous cardiac hormones, which have been shown to increase in patients with heart failure, and valvular or congenital heart disease. We aimed to determine the association between atrial NP (ANP) and late postoperative AF after surgery for AS along with temporal changes in plasma ANP levels and left atrial (LA) volumes. METHODS: 22 patients (16 males/6 females, mean age: 61 years) with symptomatic AS and 8 healthy volunteers (5 males/3 females) were enrolled into our study. All the patients studied underwent transthoracic echocardiography, which was repeated during the follow-up. N-terminal ANP (N-ANP) was studied initially and at the 2-month follow-up. Postoperatively, the patients were followed up for 12 months for AF attacks. RESULTS: Patients with AS had significantly higher levels of N-ANP, left ventricular (LV) end-diastolic pressure, E/A ratio, LV mass and LA volumes compared to the controls. Patients with postoperative AF attacks were significantly older, had higher N-ANP levels and LV end-diastolic pressure in addition to higher LA volumes and longer symptom duration compared to patients without AF. Age at the time of operation (p = 0.011) and N-ANP at the 2nd month (p = 0.047) were found to be independent predictors for late AF attacks during follow-up in regression analysis. Besides, N-ANP (p < 0.001) at the 2-month follow-up independently predicted impaired LA remodeling. CONCLUSION: ANP might be an important factor to identify AS patients at risk for late postoperative AF attacks.     

卡维地洛治疗扩张型心肌病心力衰竭疗效观察

目的　评价第三代 β受体阻滞剂卡维地洛治疗扩张型心肌病 (DCM)心力衰竭的临床疗效。方法　 6 2例 DCM心力衰竭患者在接受常规治疗 (洋地黄、利尿剂、血管紧张素转换酶抑制剂 )病情稳定后 ,随机分为卡维地洛组和美多心安组。均从小剂量 (卡维地洛组 ,2 .5 m g bid;美多心安组 ,6 .2 5 m g bid)缓慢递增。检测治疗前后 DCM患者左心室功能和结构的变化以及血液中内皮素 - 1(ET- 1)、心钠素 (ANP)和血管紧张素 (Ang )的改变。结果　治疗 6个月后 ,两组心脏功能分级均明显改善 ,左心室射血分数 (L VEF)、短轴缩短率 (FS)、左心室射血前期与射血时间比(PEP/ L VET)、舒张早期峰值血流速度 (PFVE)、舒张早期峰值血流速度与舒张晚期峰值血流速度比 (PFVE/ PF-VA)均明显增加 ,卡维地洛组较美多心安组 L VEF增加更为明显。两组左心房内径 (L AD)、左心室收缩末期内径(L VSD)、左心室舒张末期内径 (L VDD)明显减小 ,卡维地洛组 L VSD减小较美多心安组更明显。治疗后血浆中ET- 1、ANP和 Ang 均明显降低。结论　卡维地洛和美多心安都能够改善 DCM心力衰竭患者左心室收缩和舒张功能 ,逆转左心室重构 ,卡维地洛较美多心安疗效更佳。     

Evaluation of impaired left ventricular ejection fraction and increased dimensions by multiple neurohumoral plasma concentrations.

BACKGROUND: A range of neurohumoral substances have been suggested as diagnostic markers in heart failure. It is, however, undetermined which marker has the greatest diagnostic potential, and whether additional information is gained by a comprehensive neurohumoral evaluation. AIMS: The purpose of the study was to compare the value of epinephrine, norepinephrine, renin activity, aldosterone (ALDO), atrial (ANP) and brain (BNP) natriuretic peptides, arginine-vasopressin and endothelin (ENDO) as markers for left ventricular (LV) dimensions and ejection fraction (LVEF) in patients with systolic heart failure. METHODS: Forty-eight patients with symptomatic heart failure were examined with blood samples and magnetic resonance imaging along with 20 age and gender-matched normal controls. RESULTS: In multiple regression analyses, BNP was the strongest independent marker for LV end-diastolic (r=0.71, P<0.0001), and end-systolic (r=0.75, P<0.0001) volumes, myocardial mass (r=0.69, P<0.0001), and LVEF (r=-0.78, P<0.0001). ANP was a supplementary independent marker for LV end-diastolic (r=0.76, P<0.0001) and end-systolic (r=0.78, P<0.0001) (ANP and BNP combined) volumes, ENDO for myocardial mass [r=0.71, P<0.0001 (ENDO/BNP)], and ALDO for LVEF [r=-0.81, P<0.0001 (ALDO/BNP)]. CONCLUSION: BNP is the strongest marker for LV dimensions and LVEF in patients with systolic heart failure. However, a comprehensive neurohumoral evaluation may add some information to the diagnosis.     

Atrial natriuretic peptide in a rat model of cardiac failure. Atrial and ventricular mRNA, atrial content, plasma levels, and effect of volume loading

This study examined the relation between synthesis, atrial storage, and plasma levels of atrial natriuretic peptide (ANP), and it examined plasma ANP levels and hemodynamic output in response to volume expansion in a rat model of myocardial infarction and failure. Arterial ANP concentrations did not correlate linearly with infarct size, but they did show an abrupt increase when infarct size exceeded 30% of the left ventricle, similar to the abrupt increase of left ventricular end-diastolic pressure with infarct size greater than 30%. Consequently, a close relation was found between plasma ANP levels and left ventricular end-diastolic pressure (n = 23, r = 0.89, p less than 0.001). Atrial ANP content per gram of tissue but not ANP content per pair of atria was reduced in rats with large infarcts (greater than 40%, p less than 0.05 vs. control animals). ANP mRNA level per pair of atria (related to total atrial RNA), determined by liquid hybridization (controlled by northern blot analysis), was increased by 38% in infarcted rats (p less than 0.05 vs. controls), but the ratio of atrial ANP mRNA relative to atrial beta-actin mRNA levels was not increased. Right and left ventricular ANP mRNA level increased by 90% and 380%, respectively, far exceeding the concomitant increase in beta-actin mRNA (+26% in the left ventricle). Plasma ANP increased with volume loading in controls and rats with moderate infarcts but not in rats with large infarcts despite a similar increase in right atrial pressure (compared with control animals); thus, the relation of delta ANP/delta right atrial pressure exerted by volume loading decreased in rats with large infarcts. Similarly, the response of cardiac output and renal blood flow (determined by radioactive microspheres) to volume loading was attenuated in rats with large infarcts. Thus, in this model of chronic cardiac failure, the activation of the ANP system is closely coupled with the increase in intracardiac pressures without correlating linearly to the extent of myocardial loss. Second, in severe cardiac failure, additional stimulation such as volume loading may elicit only an attenuated ANP secretion response, for example, due to saturation of the ANP receptor sensing system or to a limited transformation rate of pro-ANP. Third, the increase in atrial ANP synthesis and the increase in atrial ANP gene expression seems limited; however, substantial specific ANP gene expression occurs in the ventricles, which, in turn, may contribute to increased plasma ANP levels in chronic heart failure.