Activity of the neurohormonal system and its relationship to autonomic abnormalities in decompensated heart failure.

BACKGROUND: The syndrome of congestive heart failure (CHF) entails complex autonomic and hormonal responses. Profound abnormalities in autonomic function, characterized by sympathetic overactivity and parasympathetic withdrawal, exert direct deleterious effects on the heart and contribute to progressive circulatory failure. We investigated the relationship of heart rate variability (HRV) with levels of neurohormones in plasma. METHODS AND RESULTS: We studied 64 patients admitted to the hospital for treatment of decompensated CHF (mean age, 59 +/- 2 years; New York Heart Association class III [72%] and IV [28%]). Time- and frequency-domain HRV indices were obtained from 24-hour Holter recordings. Neurohormonal activation was assessed by measuring plasma renin activity and aldosterone and norepinephrine levels. In the time domain, norepinephrine correlated negatively with average NN interval (r = -.34; P =.007), SDNN (r = -.35; P =.005), and SDANN (r = -.36; P =.004). In the frequency domain, norepinephrine was negatively associated with the total power (r = -.39; P =.001) and ultralow power (r = -.43; P =.0005). No correlation was found between indices indicative of parasympathetic modulation, except for a borderline correlation with the high-frequency power (r = -.25; P =.048). CONCLUSIONS: Reduced HRV may be associated with increased norepinephrine levels in patients with severe CHF. The ability of long-term HRV parameters to reflect in part the activation of diverse hormonal systems may explain their greater prognostic power for risk stratification in patients with CHF.     

Relationship between cardiac metaiodobenzylguanidine uptake and hemodynamic, functional and neurohormonal parameters in patients with heart failure.

BACKGROUND: Sympathetic activation plays a pivotal role in heart failure attributing to the disease process and symptoms of the patient. Myocardial sympathetic activity can be visualized using radioiodinated metaiodobenzylguanidine 123I-MIBG, a structural analogue of norepinephrine (NE). AIM OF THE STUDY: We investigated whether a relation exists between myocardial MIBG uptake and different functional, hemodynamic and neurohormonal parameters in patients with chronic heart failure. METHODS AND RESULTS: The study comprised 52 patients with stable congestive heart failure functional class II or III and left ventricular ejection fractions of <35%. The heart/mediastinum ratio (H/M ratio) was calculated to quantify myocardial MIBG uptake. A significant correlation was found between peak oxygen consumption and maximal exercise duration as exercise parameters and H/M ratio of MIBG (R, respectively, 0.36 and 0.4, P<0.05). From all other measured parameters, only plasma NE showed a significant correlation with the H/M ratio of MIBG. CONCLUSION: Cardiac sympathetic activity, as measured by myocardial MIBG uptake, is correlated with peak exercise parameters.     

Echocardiographic ejection fraction in patients with acute heart failure: correlations with hemodynamic, clinical, and neurohormonal measures and short-term outcome

BACKGROUND: Although echocardiographic ejection fraction (EF) is frequently used for the estimation of left ventricular contractility in patients with acute heart failure, its exact role and correlations with clinical, hemodynamic, and neurohormonal variables of cardiac contractility is not known. METHODS: Patients (343) with acute heart failure, enrolled into two prospective placebo-controlled hemodynamic studies of tezosentan, and in whom EF was available at baseline, were included. Outcome was evaluated in a subset of 94 patients who were enrolled in the placebo arms of the studies. RESULTS: Higher echocardiographic EF was correlated with older age, increased incidence of hypertension and atrial fibrillation, and female gender. We observed weak correlation between EF and cardiac output or cardiac power and no correlation with wedge pressure, and the change in hemodynamic variables over time. Higher EF was correlated with more baseline leukocytosis and higher plasma levels of endothelin-1 and blood urea nitrogen, while lower EF was related to higher baseline B-type natriuretic peptide (BNP). We observed no overall correlations between EF and outcome. CONCLUSIONS: In patients with acute heart failure, echocardiographic EF is weakly correlated with hemodynamic measures of left ventricular contractility and outcome; hence, it should be interpreted cautiously when evaluating patients admitted due to acute heart failure.     

Short-term effects of levosimendan and prostaglandin E1 on hemodynamic parameters and B-type natriuretic peptide levels in patients with decompensated chronic heart failure

BACKGROUND: Both levosimendan and prostaglandin E1 (PGE1) have beneficial effects on hemodynamic parameters and outcome compared to dobutamine in decompensated chronic heart failure (CHF). AIMS: We compared short-term effects of levosimendan versus PGE1 on hemodynamic parameters and B-type natriuretic peptide levels (BNP) in patients with decompensated CHF. METHODS AND RESULTS: 73 patients (cardiac index < 2.5 L/min/m2, pulmonary capillary wedge pressure (PCP) >15 mmHg) with decompensated CHF were randomised to treatment with either a 24 h-infusion of levosimendan (n=38) or a chronic infusion of PGE1 (n = 35). Hemodynamic parameters and BNP were measured at baseline, 24 and 48 h, BNP levels were also measured after 1 week. Baseline characteristics including concomitant medication were similar in both groups. Levosimendan and PGE1 increased cardiac output (CO) after 24 and 48 h. Levosimendan increased CO twice as much as PGE1 (24 h: Levosimendan +1.1 +/- 0.1 L/min, PGE1 +0.6 +/- 0.1 L/min, p < 0.001). Both drugs produced a comparable reduction in PCP and pulmonary artery pressure after 24 and 48 h. Levosimendan decreased BNP by 28% after 24 h and 22% after 48 h, but effects disappeared after 1 week. In contrast, PGE1 decreased BNP by 15% after 48 h (no change at 24 h), but a decrease of 20% was sustained at 1 week. CONCLUSIONS: The differential beneficial effects of levosimendan (greater increase in CO) and PGE1 (sustained decrease in BNP) may have a potential impact on clinical outcome.     

Hemodynamic effects of levosimendan added to dobutamine in patients with decompensated advanced heart failure refractory to dobutamine alone

A 24-hour infusion of levosimendan was added to dobutamine in 18 patients (aged 63 +/- 9 years) hospitalized for management of decompensated New York Heart Association functional class IV heart failure refractory to a continuous 24-hour infusion of dobutamine (10 microg/kg/min) and furosemide (10 mg/hour); the primary study end point was a >or=40% increase in cardiac index and a >or=25% decrease in pulmonary capillary wedge pressure compared with pretreatment measurements.The primary end point was reached in one of the patients treated with dobutamine alone versus 7 patients (39%) treated with levosimendan and dobutamine combined (p = 0.008), whereas at 24 hours, the combined treatment was associated with a 0.76 +/- 0.78 L/min/m(2) (p = 0.001) mean increase in cardiac index and a 6.4 +/- 7.3 mm Hg (p = 0.002) mean decrease in pulmonary capillary wedge pressure compared with measurements obtained after 24 hours of dobutamine infusion alone. Symptoms were alleviated in all patients, and all but 3 were discharged from the hospital.     

左西孟旦治疗老年缺血性心肌病所致急性失代偿性心力衰竭的疗效和安全性分析

目的探讨左西孟旦治疗老年缺血性心肌病所致急性失代偿性心力衰竭患者的疗效和安全性。方法选择老年缺血性心肌病所致急性失代偿性心力衰竭患者60例,根据治疗方法随机分为左西孟旦组30例和常规治疗组30例。2组患者治疗前和治疗后1周分别测定血压、心率、左心室射血分数、血浆N末端钠尿肽前体和肌酐水平,并进行疗效和安全性比较。结果左西孟旦组治疗后左心室射血分数明显高于常规治疗组,血浆N末端钠尿肽前体水平明显低于常规治疗组(36.5%vs 34.0%,1872.9ng/L vs 2499.6ng/L,P0.05)。左西孟旦组与常规治疗组治疗后血压、心率和肌酐水平比较,差异无统计学意义(P0.05)。结论老年缺血性心肌病导致的急性失代偿性心力衰竭患者使用左西孟旦后,左心室射血分数升高,N末端钠尿肽前体水平降低,而血压、心率和肾功能并无异常,证实了左西孟旦治疗老年缺血性心肌病导致的急性失代偿性心力衰竭患者安全有效。     

Blunted sympathetic response in diabetic patients with decompensated congestive heart failure.

BACKGROUND: The risk for congestive heart failure is strongly increased in diabetes, and the prognosis of diabetic patients with established heart failure is worse compared to nondiabetic patients. Heart failure entails complex alterations in autonomic and neurohormonal responses, which exert a direct deleterious effect on the heart and contribute to progressive circulatory failure. Altered neurohumoral physiology may underlie the poor prognosis of diabetic patients with heart failure. METHODS: We studied 88 patients (mean age 61+/-13 years) admitted for decompensated heart failure. Neurohormonal and cytokine profiles, including plasma renin activity, aldosterone, norepinephrine, endothelin-1, tumor necrosis factor-alpha, and interleukin-6, were obtained in all patients. In addition, a 24-h Holter recording was performed, and time and frequency domain heart rate variability indices were calculated. RESULTS: Of 88 patients, 48 were classified as having diabetes based on history, diet therapy, or use of oral hypoglycemic agents or insulin. The only difference in the neurohormonal and cytokine profile between the diabetic and nondiabetic groups was a significantly lower norepinephrine level in diabetic patients (668+/-64 vs. 489+/-50 pg/ml, P=0.009). Heart rate variability analysis revealed that the low-frequency power in normalized units (an index of sympathetic modulation) was significantly lower in diabetic patients (4.7+/-1.4 vs. 5.9+/-0.9, P=0.04). No significant differences occurred in any of the time (the percentage of RR intervals with >50 ms variation and the square root of mean squared differences of successive RR intervals) or frequency domain (high frequency power) indices of parasympathetic modulation between the two groups. CONCLUSIONS: Patients with diabetes mellitus exhibit a blunted sympathetic response during heart failure decompensation. Blunted sympathetic activation in the setting of symptomatic heart failure may impair the ability of the myocardium to compensate and contribute to the high incidence of symptomatic heart failure among diabetic patients.     

左西孟旦、米力农与多巴酚丁胺治疗急性失代偿心力衰竭患者临床疗效及安全性评价

【摘要】目的：探讨左西孟旦、米力农和多巴酚丁胺三种药物治疗急性失代偿心力衰竭患者的临床疗效和安全性。方法：将我院2015年7月~2017年7月间收治的急性失代偿心力衰竭患者随机分为左西孟旦组、米力农组和多巴酚丁胺组,,每组50 例,并分别给予左西孟旦、米力农与多巴酚丁胺治疗3d。比较治疗前后三组的疗效、心功能指标(LVIDd、LVEF、FS)、血清学指标(NT-proBNP、ET-1、NE)、血流动力学指标(PCWP、PAMP、RAP、SVR)以及不良反应发生率。结果：治疗后,西孟旦组的有效率显著高于米力农组和多巴酚丁胺组(P&lt;0.05);三组的LVIDd、LVEF、FS、NT-proBNP、ET-1、NE、PCWP、PAMP、RAP、SVR水平均显著优于治疗前(P&lt;0.05);米力农组和多巴酚丁胺组的LVEF、FS、NT-proBNP、ET-1、NE水平均显著低于左西孟旦组(P&lt;0.05),PCWP、PAMP与SVR水平均显著高于左西孟旦组(P&lt;0.05);三组间的LVIDd、RAP水平比较差异无统计学意义(P&gt;0.05);左西孟旦组的不良反应发生率明显低于米力农组和多巴酚丁胺组(P&lt;0.05)。结论：左西孟旦治疗急性失代偿期心力衰竭患者的疗效显著,且安全性高,值得临床推广。     

Effects of levosimendan on markers of left ventricular diastolic function and neurohormonal activation in patients with advanced heart failure

In this randomized, placebo-controlled study, it was found that a 24-hour levosimendan infusion improves echocardiographic markers of abnormal left ventricular diastolic function (transmitral flow patterns and mitral annulus velocities, as assessed by transthoracic pulse-wave Doppler and tissue Doppler imaging, respectively) and reduces substances of excessive neurohormonal activation (plasma B-type natriuretic peptide and interleukin-6) in patients with advanced heart failure. Moreover, levosimendan-treated patients had fewer events and longer progression-free survival during a 5-month follow-up compared with those who received placebo. Thus, levosimendan seems to be effective in improving left ventricular diastolic function and reducing neurohormonal activation in patients with severe heart failure.     

Levosimendan produces an additional clinical and hemodynamic benefit in patients with decompensated heart failure successfully submitted to a fluid removal treatment

A pivotal role in treating decompensated heart failure (HF) is played by inotropes and calcium sensitizers such as levosimendan. In this study, the authors evaluated whether levosimendan could determine further clinical and hemodynamic benefits in 31 HF patients (New York Heart Association [NYHA] class III or IV), after successful treatment with diuretics (n=15) or ultrafiltration (n=16). Systolic, diastolic, dicrotic, and mean arterial pressures; systemic vascular resistance (SVR); some classic hemodynamic variables (cardiac output [CO], stroke volume [SV], dP/dt(max) ); and indices of cardiovascular system performance (cardiac cycle efficiency [CCE], cardiac power output) have been assessed by the pressure recording analytical method (PRAM), a minimally invasive monitoring system, before levosimendan infusion, at the end of treatment (EoT), and 36?hours after EoT (post-36). A significant increase in CCE, CO, SV, and dP/dt(max) and a significant decrease in diastolic and dicrotic arterial pressures and in SVR have been observed at EoT and at post-36. After the addition of levosimendan, a further reduction in signs and symptoms of HF and NYHA class was observed. Five patients showed an opposite trend of several hemodynamic parameters without any significant clinical improvement (nonresponders). In conclusion, most HF patients treated with diuretics or ultrafiltration receive additional clinical and hemodynamic benefits from levosimendan. The characterization of nonresponders could help in optimizing its use.     

Effects of levosimendan versus dobutamine on left atrial function in decompensated heart failure

BACKGROUND:

Although the effects of levosimendan on the left ventricle (LV) have been studied, its effect on left atrial (LA) function is poorly understood, despite its key role in optimizing LV function.

OBJECTIVE:

To compare the effects of levosimendan and dobutamine on LA and LV function in patients with decompensated heart failure (DHF).

METHODS:

Seventy-four patients (mean [± SD] age 64±10 years) with DHF and an LV ejection fraction of 35% or lower were randomly assigned to receive levosimendan (n=37) or dobutamine (n=37). LA active emptying fraction, LA passive emptying fraction (PEF) and the ratio of mitral inflow early diastolic velocity to annulus velocity (E/e) were evaluated with pulsed wave and tissue Doppler imaging along with plasma B-type natriuretic peptide (BNP) level measurements before and after drug infusion.

RESULTS:

The ejection fraction was significantly increased in both groups. The levosimendan group had a greater decrease in BNP and a greater increase in active emptying fraction at 24 h compared with the dobutamine group. The PEF, E/e and deceleration time of the E wave were significantly improved in the levosimendan group, but not in the dobutamine group. Levosimendan-induced percentage change of BNP was significantly correlated with the percentage change of E/e and PEF (r=0.48 [P<0.005] and r=−0.38 [P<0.05], respectively).

CONCLUSIONS:

In patients with DHF, levosimendan and dobutamine both improve LV systolic function. However, levosimendan also improves LV diastolic function and LA performance in parallel with a greater improvement in neurohormonal activation compared with dobutamine.