Cardiorenal syndrome in acute decompensated heart failure

Cardiorenal syndrome (CRS) commonly occurs during treatment of acute decompensated heart failure (ADHF) and is associated with poor clinical outcome. The pathophysiology of CRS entails a complex interaction between hemodynamic alterations, including reduced renal perfusion, increased venous pressure and activation of multiple neurohormonal systems. Attempts to effectively treat congestion while preserving renal function in ADHF are often met with limited clinical success and often require therapeutic decisions that reflect a compromise between potential benefits and harm. At present, there is no evidence-based intervention specifically targeted at renal function. Recent Phase III randomized trials, using novel agents in patients with ADHF, have largely failed to demonstrate any benefits of therapy on renal and clinical outcomes. Early diagnosis of CRS using novel markers of tubular injury may allow for timely interventions and attenuate progression. Future studies are needed to further elucidate the pathophysiology of this complex syndrome and identify new potential targets for effective evidence-based treatments.     

Nesiritide: a new drug for the treatment of decompensated heart failure

Nesiritide, a recombinant human B-type natriuretic peptide, is the first in a new drug class for the treatment of decompensated heart failure. The drug binds to receptors in the vasculature, kidney, adrenal gland, and brain, and overcomes resistance to endogenous BNP present in patients with CHF. Nesiritide administration leads to a rapid and balanced vasodilatory effect, which results in a significant decrease in right and left ventricular filling pressures and systemic vascular resistance and at the same time in an increase in stroke volume and cardiac output without a change in heart rate. These early hemodynamic changes result in a rapid improvement in symptoms of heart failure. In addition, nesiritide lowers aldosterone, catecholamines, and endothelin-1 levels and its effect on the kidney leads to an increased natriuresis and diuresis without effect on serum potassium or renal function. Prior to its approval for clinical use, nesiritide was studied in 10 different clinical trials involving 941 patients with moderate and severe CHF, including elderly patients, patients with both systolic and diastolic dysfunction, and patients with arrhythmias, renal insufficiency, and acute ischemic syndrome. In comparative studies with available vasoactive therapies frequently used for treatment of patients with decompensated heart failure, nesiritide was proven comparable in efficacy to inotropic drugs such as dobutamine, but superior in safety. In a recent study, nesiritide was found to be more effective and better tolerated than the vasodilator, nitroglycerin. The most common side effects expected with the use of nesiritide are headaches and decrease in blood pressure. At the recommended dose of nesiritide, headache was reported during the first 24 hours of treatment in 8% of patients and symptomatic hypotension in 4% of patients, compared to 20% and 5% in nitroglycerin-treated patients.     

老年急性失代偿性心力衰竭合并肾功能不全60例治疗体会

目的：探讨利尿剂或血液净化疗法治疗老年急性失代偿性心力衰竭合并肾功能不全的疗效及预后。方法：60例年龄≥60岁的急性心衰合并急性肾损伤患者,在常规利尿剂应用无效基础上,40例用利尿剂加量治疗,20例用血液净化治疗。观察利尿剂或血液净化治疗前后肾功能、血气分析、尿量及血浆B型脑利钠肽（BNP）浓度变化;90d内死亡、再住院率及肾功能变化。结果：利尿剂加量组或血液净化组在治疗前后血肌酐、尿素氮、血pH、碳酸氢根、24h尿量及血浆BNP水平均有改善（P〈0.05）;两组治疗48h后血液净化组较利尿剂加量组血肌酐、尿素氮及BNP浓度明显下降（P〈0.01）,SaO2、24h尿量明显上升（P〈0.01）。随访90d后,利尿剂加量组22例（55.0%）肾功能恢复,90d再住院15例（37.5%）,死亡7例（17.5%）;血液净化组12例（60.0%）肾功能恢复,90d再住院5例（25.0%）,死亡3例（15.0%）。结论：血液净化疗法改善老年急性失代偿性心力衰竭合并肾功能不全的疗效及预后优于单纯利尿剂治疗。     

肾功能不全对心力衰竭预后的影响

目的探讨肾功能不全对心力衰竭预后的影响。方法根据肾功能将心力衰竭患者分为心肾综合征组70例和单纯心力衰竭组131例，观察其治疗和预后情况。结果心肾综合征组与单纯心力衰竭组相比，年龄、血肌酐、水肿发生率，糖尿病和高血压患病率及住院天数显著增高（P〈0．05或0．01），血红蛋白浓度显著降低（P〈0．01）；而2组间性别、心力衰竭时间、心功能、冠心病及高脂血症的患病率差异无显著性。随访心肾综合征组生存率明显低于单纯心力衰竭组（P〈0．001），在成功应用血管紧张素转换酶抑制剂的患者中也有类似关联。Cox回归模型分析显示，心功能分级、射血分数、血肌酐水平和血红蛋白浓度与心力衰竭死亡独立相关。结论肾功能不全明显增加心力衰竭病死率。     

Clinical characteristics of emergency department heart failure patients initially diagnosed as non-heart failure

Background

Since previous studies suggest the emergency department (ED) misdiagnosis rate of heart failure is 10–20% we sought to describe the characteristics of ED patients misdiagnosed as non-decompensated heart failure in the ED.

Methods

We analyzed a prospective convenience sample of 439 patients at 4 emergency departments who presented with signs or symptoms of decompensated heart failure. Patients with a cardiology criterion standard diagnosis of decompensated heart failure and an ED diagnosis of decompensated heart failure were compared to patients with a criterion standard of decompensated heart failure but no ED diagnosis of decompensated heart failure. Two senior cardiology fellows retrospectively determined the patient's heart failure status during their acute ED presentation. The Mann-Whitney u-test for two groups, the Kruskall-Wallis test for multiple groups, or Chi-square tests, were used as appropriate.

Results

There were 173 (39.4%) patients with a criterion standard diagnosis of decompensated heart failure. Among those with this criterion standard diagnosis of decompensated heart failure, discordant patients without an ED diagnosis of decompensated heart failure (n = 58) were more likely to have a history of COPD (p = 0.017), less likely to have a previous history of heart failure (p = 0.014), and less likely to have an elevated b-type natriuretic peptide (BNP) level (median 518 vs 764 pg/ml; p = 0.038) than those who were given a concordant ED diagnosis of decompensated heart failure. BNP levels were higher in those with a criterion standard diagnosis of decompensated heart failure than in those without a criterion standard diagnosis (median 657 vs 62.7 pg/ml). However, 34.6% of patients with decompensated heart failure had BNP levels in the normal (<100 pg/ml; 6.1%) or indeterminate range (100–500 pg/ml; 28.5%).

Conclusion

We found the ED diagnoses of decompensated heart failure to be discordant with the criterion standard in 14.3% of patients, the vast majority of which were due to a failure to diagnose heart failure when it was present. Patients with a previous history of COPD, without a previous history of heart failure and with lower BNP levels were more likely to have an ED misdiagnosis of non-decompensated heart failure. Readily available, accurate, objective ED tests are needed to improve the early diagnosis of decompensated heart failure in ED patients.     

The ASCEND-HF trial: an acute study of clinical effectiveness of nesiritide and decompensated heart failure

Nesiritide has been approved by the US FDA for the treatment of acute decompensated heart failure since 2001. Subsequently, two meta-analyses questioned its impact on mortality and association with worsening renal function. Therefore, the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure trial was designed to assess the safety and efficacy of nesiritide in acute decompensated heart failure based on clinically relevant outcomes. In this article, the important findings and lessons learned from this landmark study are reviewed and potential evolving roles for nesiritide and natriuretic peptides in the future of heart failure therapy are proposed.     

Role of tolvaptan in acute decompensated heart failure

Acute decompensated heart failure accounts for more than 1 million hospitalizations in the USA every year. Currently, the most common treatment for symptom relief is the use of loop diuretics, despite recent concerns for potential adverse effects. With the growing understanding of the role of neurohormonal dysregulation in the pathophysiology of heart failure, there has been increasing interest in novel pharmacologic therapies targeting specific neurohormonal axes. Serum arginine vasopressin is a potent vasoconstrictor, as well as an antidiuretic, and serum concentrations are upregulated in heart failure. Tolvaptan, a vasopressin receptor antagonist, has been shown to improve diuresis and symptom relief without adversely affecting renal function, and may be a promising novel therapeutic agent in the growing population of patients with heart failure.     

Nesiritide: trials and tribulations

Standard therapy for acute decompensated heart failure, a major health problem, consists of intravenous diuretics, vasodilators, and positive inotropic agents. Nesiritide, a recombinant form of human B-type natriuretic peptide, is the only drug specifically approved for this indication. Recent meta-analyses have reported an increased risk of worsening renal function and 30-day mortality with nesiritide administration. These data understandably require physicians to carefully reevaluate their current use of nesiritide in patients with acute decompensated heart failure. In performing this reevaluation, it is important to consider our understanding of the underlying disease state, the limitations and results of these meta-analyses, and new data that provide additional insight into the possible risks and benefits associated with nesiritide therapy. Until additional therapeutic trials are conducted, therapeutic choices must be based on symptomatic and hemodynamic improvement and limited, imperfect available data, which may continue to support the use of nesiritide for its established indication.     

New advances and novel treatments in heart failure

As briefly summarized in this report, the prevalence of heart failure is high and it will continue to rise as the population ages. There will be over 1 million hospitalizations for acutely decompensated heart failure this year. The goals of treatment for patients with acutely decompensated heart failure are to lower cardiac filling pressures, remove fluids and improve symptoms of dyspnea, decrease vascular resistance, and increase cardiac output without activating the RAAS. There are few guidelines for the treatment of individuals with acutely decompensated heart failure and many different agents have been used in patients with this disease. Many of these drugs are not completely effective and may lead to serious adverse events. BNP is a natural protein produced by myocardial cells in response to ventricular distension, and its level is dramatically increased in patients with heart failure. The results of several recent clinical trials have shown that administration of nesiritide is safe and highly effective for the initial treatment of patients with acutely decompensated heart failure and can help physicians and nurses meet treatment goals for the management of patients with this serious condition.     

Glucocorticoids improve renal responsiveness to atrial natriuretic peptide by up-regulating natriuretic peptide receptor-A expression in the renal inner medullary collecting duct in decompensated heart failure

In heart failure, the renal responsiveness to exogenous and endogenous atrial natriuretic peptide (ANP) is blunted. The mechanisms of renal hyporesponsiveness to ANP are complex, but one potential mechanism is decreased expression of natriuretic peptide receptor-A (NPR-A) in inner medullary collecting duct (IMCD) cells. Newly emerging evidence shows that glucocorticoids could produce potent diuresis and natriuresis in patients with heart failure, but the precise mechanism is unclear. In the present study, we found dexamethasone (Dex) dramatically increased the expression of NPR-A in IMCD cells in vitro. The NPR-A overexpression induced by Dex presented in a time- and dose-dependent manner, which emerged after 12 h and peaked after 48 h. The cultured IMCD cells were then stimulated with exogenous rat ANP. Consistent with the findings with NPR-A expression, Dex greatly increased cGMP (the second messenger for the ANP) generation in IMCD cells, which presented in a time- and dose-dependent manner as well. In rats with decompensated heart failure, Dex dramatically increased NPR-A expression in inner renal medulla, which was accompanied by a remarkable increase in renal cGMP generation, urine flow rate, and renal sodium excretion. It is noteworthy that Dex dramatically lowered plasma ANP, cGMP levels, and left ventricular end diastolic pressure. These favorable effects induced by Dex were glucocorticoid receptor (GR)-mediated and abolished by the GR antagonist 17β-hydroxy-11β-[4-dimethylamino phenyl]-17α-[1-propynyl]estra-4,9-dien-3-one (RU486). Collectively, glucocorticoids could improve renal responsiveness to ANP by up-regulating NPR-A expression in the IMCD and induce a potent diuretic action in rats with decompensated heart failure.     

Intravenous diuretic day-care treatment for patients with heart failure

Fluid overload is a common manifestation of decompensated chronic heart failure. This paper reports on a pilot study that investigated whether intravenous (i.v.) furosemide administered on a cardiology day ward for three successive days was effective in improving the symptoms of patients with fluid overload and chronic heart failure. The results showed that 94.1% of patients reported an improvement in their breathlessness, with a marked weight loss in 88.2% of patients. There were no marked changes in blood pressure or renal function. Hospital admission was avoided in 94.1% of cases. The study concluded that i.v. diuretic treatment given in a hospital day-care setting is safe and effective, and that it reduces the need for hospital admissions. As a consequence, this reduces the associated financial costs of hospitalisation.     

肝细胞生长因子对急性失代偿性心力衰竭模型小鼠的保护

背景:肝细胞生长因子是一种心肌营养因子,具有很强的抑制心肌细胞凋亡与心室重构,促血管内皮细胞有丝分裂作用.目的:观察肝细胞生长因子对急性失代偿性心力衰竭模型小鼠的保护作用.方法:将50只昆明小鼠随机分为5组:正常对照组、慢性心力衰竭组、急性失代偿性心力衰竭组、慢性心力衰竭治疗组、急性失代偿性心力衰竭治疗组.采用尾静脉注射阿霉素建立慢性心力衰竭小鼠模型,第7周尾静脉注射细菌脂多糖制作急性失代偿性心力衰竭模型,随后慢性心力衰竭治疗组、急性失代偿性心力衰竭治疗组同时给予尾静脉注射肝细胞生长因子干预.结果与结论:与慢性心力衰竭组比较,慢性心力衰竭治疗组心室壁厚度、左室射血分数值明显增加,白细胞介素6减少,脑钠肽下降,Bax蛋白表达减少,Bcl-2蛋白表达增加,心肌细胞凋亡明显减少(P < 0.01或0.05).与急性失代偿性心力衰竭组比较,急性失代偿性心力衰竭治疗组心室壁厚度、左室射血分数值明显增加,脑钠肽表达下调,白细胞介素6明显下降,Bcl-2蛋白表达增加,Bax蛋白表达减少(P < 0.01或0.05).说明肝细胞生长因子通过抗炎性因子作用,抗心肌细胞凋亡作用明显改善急性失代偿性心力衰竭小鼠的心脏功能.     

肝细胞生长因子对急性失代偿性心力衰竭模型小鼠的保护

背景：肝细胞生长因子是一种心肌营养因子,具有很强的抑制心肌细胞凋亡与心室重构,促血管内皮细胞有丝分裂作用。目的：观察肝细胞生长因子对急性失代偿性心力衰竭模型小鼠的保护作用。方法：将50只昆明小鼠随机分为5组：正常对照组、慢性心力衰竭组、急性失代偿性心力衰竭组、慢性心力衰竭治疗组、急性失代偿性心力衰竭治疗组。采用尾静脉注射阿霉素建立慢性心力衰竭小鼠模型,第7周尾静脉注射细菌脂多糖制作急性失代偿性心力衰竭模型,随后慢性心力衰竭治疗组、急性失代偿性心力衰竭治疗组同时给予尾静脉注射肝细胞生长因子干预。结果与结论：与慢性心力衰竭组比较,慢性心力衰竭治疗组心室壁厚度、左室射血分数值明显增加,白细胞介素6减少,脑钠肽下降,Bax蛋白表达减少,Bcl-2蛋白表达增加,心肌细胞凋亡明显减少（P〈0.01或0.05）。与急性失代偿性心力衰竭组比较,急性失代偿性心力衰竭治疗组心室壁厚度、左室射血分数值明显增加,脑钠肽表达下调,白细胞介素6明显下降,Bcl-2蛋白表达增加,Bax蛋白表达减少（P〈0.01或0.05）。说明肝细胞生长因子通过抗炎性因子作用,抗心肌细胞凋亡作用明显改善急性失代偿性心力衰竭小鼠的心脏功能。     

Effect of nesiritide on renal function in patients admitted for decompensated heart failure

BACKGROUND: Studies addressing the effect of nesiritide on renal function in patients hospitalized for decompensated heart failure (HF) are limited, with conflicting results. AIM: To study the effect of nesiritide on renal function in patients admitted for acute decompensated HF. METHODS: We retrospectively reviewed charts of patients admitted with decompensated HF, comparing those who received nesiritide along with conventional therapy vs. those who received conventional therapy alone. Serum creatinine levels and body weight were measured on admission, and were compared with levels at day 3 to estimate deterioration in renal function. Worsening renal function (WRF) was defined as a rise in serum creatinine of > or =0.3 mg/dl from baseline, with final creatinine level >1.5 mg/dl. RESULTS: We reviewed 206 charts (116 controls, 90 nesiritide group). WRF developed in 28/90 (31.1%) in the nesiritide group and 37/116 (31.9%) controls (p = 1.0). Mean change in creatinine in the nesiritide group was 0.15 +/- 0.37 mg/dl, compared to 0.17 +/- 0.25 mg/dl in controls (p = 0.75). Using an alternative cut-off increase in serum creatinine of > or =0.5 mg/dl, 16/90 (17.7%) patients in the nesiritide group developed WRF compared to 18/116 (15.5%) controls (p = 0.80). If WRF was defined as elevation in serum creatinine levels by > or =0.3 mg/dl anytime during hospitalization, the incidence of WRF in the nesiritide group remained similar to that of controls (42.2% vs. 41.3%, p = 0.90). On multivariate analysis, nesiritide therapy was not associated with WRF (OR 0.8, 95% CI 0.4-1.6, p = 0.48). DISCUSSION: We failed to detect any significant risk of WRF in patients treated with nesiritide compared to conventional therapy in patients with decompensated HF during index hospitalization. Larger randomized, placebo-controlled trials are required to further elucidate the effect of nesiritide on renal function in these patients.     

Loop diuretics in acute heart failure: beyond the decongestive relief for the kidney

Current goals in the acute treatment of heart failure are focused on pulmonary and systemic decongestion with loop diuretics as the cornerstone of therapy. Despite rapid relief of symptoms in patients with acute decompensated heart failure, after intravenous use of loop diuretics, the use of these agents has been consistently associated with adverse events, including hypokalemia, azotemia, hypotension, and increased mortality. Two recent randomized trials have shown that continuous infusions of loop diuretics did not offer benefit but were associated with adverse events, including hyponatremia, prolonged hospital stay, and increased rate of readmissions. This is probably due to the limitations of congestion evaluation as well as to the deleterious effects linked to drug administration, particularly at higher dosage. The impaired renal function often associated with this treatment is not extensively explored and could deserve more specific studies. Several questions remain to be answered about the best diuretic modality administration, global clinical impact during acute and post-discharge period, and the role of renal function deterioration during treatment. Thus, if loop diuretics are a necessary part of the treatment for acute heart failure, then there must be an approach that allows personalization of therapy for optimal benefit and avoidance of adverse events.     

Nesiritide for the treatment of decompensated heart failure

Heart failure is the leading cause of hospitalizations in the USA, and is associated with significant morbidity, mortality and resource utilization. Established therapies for chronic heart failure have been shown to improve outcomes, but treatment for decompensated heart failure remains largely empiric. Nesiritide (Natrecor^®) is a synthetic analog of human B-type natriuretic peptide, a peptide released by the ventricular myocardium in response to increased wall tension. The physiologic effects of human B-type natriuretic peptide include natriuresis, vasodilation and neurohormonal modulation. In clinical trials, nesiritide has been shown to decrease cardiac filling pressures, increase cardiac index, and improve the clinical status of patients with acute decompensated heart failure. Compared with other available intravenous agents for heart failure, nesiritide is effective, generally well-tolerated with few adverse effects, and does not require invasive monitoring during administration. Nesiritide has proven to be an effective new treatment for patients with decompensated heart failure.     

Nesiritide for the treatment of decompensated heart failure

Heart failure is the leading cause of hospitalizations in the USA, and is associated with significant morbidity, mortality and resource utilization. Established therapies for chronic heart failure have been shown to improve outcomes, but treatment for decompensated heart failure remains largely empiric. Nesiritide (Natrecor) is a synthetic analog of human B-type natriuretic peptide, a peptide released by the ventricular myocardium in response to increased wall tension. The physiologic effects of human B-type natriuretic peptide include natriuresis, vasodilation and neurohormonal modulation. In clinical trials, nesiritide has been shown to decrease cardiac filling pressures, increase cardiac index, and improve the clinical status of patients with acute decompensated heart failure. Compared with other available intravenous agents for heart failure, nesiritide is effective, generally well-tolerated with few adverse effects, and does not require invasive monitoring during administration. Nesiritide has proven to be an effective new treatment for patients with decompensated heart failure.     

超声造影对肝移植患者术前肾功能评估的初步应用

目的探讨超声造影对肝移植患者术前肾功能评价的应用价值。方法对我院76例肝移植患者行术前肾脏超声造影检查,包括肝硬化代偿期患者25例,肝硬化失代偿期患者36例,肝肾综合症患者15例;正常对照组28例。造影剂为SonoVue,用ACQ软件对造影图像中皮质部位进行分析,观察指标为造影剂到达时间(AT)、达峰时间(TTP)及达峰强度(PI)。结果各项观察指标在肝硬化代偿组与正常对照组无明显差异(P>0.05);肝硬化失代偿期组患者TTP较正常组及肝硬化代偿组明显延长,PI明显降低(P<0.05);肝肾综合征组AT、TTP较肝硬化失代偿组进一步延长,PI进一步降低(P<0.05)。结论超声造影有助于肝移植术前肝硬化患者肾功能评价。     

Intermittent outpatient nesiritide infusion reduces hospital admissions in patients with advanced heart failure

Recombinant B-type natriuretic peptide (BNP) is a therapeutic modality in patients with decompensated congestive heart failure. Retrospectively tested are the effects of intermittent outpatient nesiritide infusion on symptoms, hospital readmission rates, endogenous BNP, and renal function in patients with advanced heart failure. Twenty-four patients in heart failure in New York Heart Association (NYHA) classes III-IV received a 6- to 8-hour intermittent nesiritide outpatient infusion (0.01 mcg/kg/min continuously intravenously) once weekly for a total duration of 3 months in addition to standard medical therapy. Data were analyzed retrospectively to compare hospital readmission rates, endogenous BNP levels, blood urea nitrogen, and creatinine levels 1 year before and up to 12 months after starting treatment. All patients tolerated nesiritide infusions well with no significant adverse events. At the end of the observation period, NYHA classes had improved 1 class in 16 patients and 2 classes in 4 patients and remained unchanged in 4 patients. There was a significant reduction in hospital readmissions within 1 year with nesiritide treatment compared with the year before (0.94 +/- 0.8 vs 3.6 +/- 2.2, P < .005). No significant changes were seen regarding endogenous BNP levels (1002 +/- 870 vs 1092 +/- 978 pg/mL, P = .95), blood urea nitrogen levels (45 +/- 28 vs 45 +/- 26 mg/dL, P = .96), and a tendency of slightly elevated creatinine levels that did not differ significantly compared with prior levels (1.76 +/- 0.85 vs 1.1 +/- 0.56 mg/dL, P = .5). Intermittent outpatient nesiritide treatment resulted in improved symptoms and reduced hospital readmission rates without a significant decline in renal function in patients with advanced heart failure but did not alter endogenous BNP levels.     

Management of acute heart failure exacerbation.

Patients with decompensated heart failure should be managed in an aggressive and proactive manner, using predominantly hemodynamic and end-organ function goals. This management is in contrast to the chronic maintenance therapy of patients with heart failure, where a neuroendocrine approach is indicated. Underlying anatomic targets for intervention should be sought aggressively and addressed. Patients who prove resistant to standard measures should be considered for early referral to heart transplant centers for more definitive measures, including evaluation for heart transplantation and mechanical circulatory support if necessary.