Decompensated Congestive Heart Failure Research Articles

The role of natriuretic peptides in heart failure

Heart failure is a clinical syndrome associated with progressive cardiac, vascular, and renal dysfunction. Regardless of the initial injury, investigations have demonstrated that neurohormones play an important role in the complex multiorgan and cellular adaptations. Natriuretic peptides play a key role in this process, antagonizing the actions of the renin-angiotensin-aldosterone system, thus promoting vasodilatation and natriuresis. Other important physiologic properties of the natriuretic peptides are prolusitropic, sympathoinhibitory, antiproliferative, anti-ischemic, anti-inflammatory, and antioxidative. Administering exogenous natriuretic peptide is a US Food and Drug Administration-approved therapy for patients with advanced decompensated congestive heart failure. Also, measuring natriuretic peptide levels has diagnostic and prognostic value. More studies are needed to define the full potential of this unique family of endogenous peptides.

Prednisone Adding to Usual Care Treatment for Refractory Decompensated Congestive Heart Failure

The aim of the present study was to determine if prednisone, a glucocorticoid, added to conventional treatment for patients with decompensated congestive heart failure (DCHF) refractory to the conventional care, results in significant relief of congestive symptoms and improvement of clinical status. Diuretic-based strategies, as the mainstay in DCHF management, are not always effective in eliciting diuresis. However, the addition of prednisone to standard care may induce potent diuresis in this clinical setting. Thirty-five patients with DCHF were enrolled in the study, and prednisone (1 mg/kg/day with maximum dosage of 60 mg/day) was added to the standard treatment. Primary endpoints were the effects on daily urine volume, patient and physician assessed dyspnea and global clinical status, and changes in renal function. The addition of prednisone induced potent diuresis with time. As a result of the diuresis, congestive symptoms improved markedly in 80% and global clinical status improved markedly in 68.6% of the DCHF patients at the end of the study (P < 0.001). The change in serum creatinine from baseline was -12.21 micromol/L (P < 0.05). Adding prednisone to conventional care in the patients with refractory DCHF induced potent diuresis accompanied by a dramatic relief of congestive symptoms and improvements in clinical status and renal function.

Combined milrinone and enteral metoprolol therapy in patients with septic myocardial depression

IntroductionThe multifactorial etiology of septic cardiomyopathy is not fully elucidated. Recently, high catecholamine levels have been suggested to contribute to impaired myocardial function.MethodsThis retrospective analysis summarizes our preliminary clinical experience with the combined use of milrinone and enteral metoprolol therapy in 40 patients with septic shock and cardiac depression. Patients with other causes of shock or cardiac failure, patients with beta-blocker therapy initiated more than 48 hours after shock onset, and patients with pre-existent decompensated congestive heart failure were excluded. In all study patients, beta blockers were initiated only after stabilization of cardiovascular function (17.7 ± 15.5 hours after shock onset or intensive care unit admission) in order to decrease the heart rate to less than 95 beats per minute (bpm). Hemodynamic data and laboratory parameters were extracted from medical charts and documented before and 6, 12, 24, 48, 72, and 96 hours after the first metoprolol dosage. Adverse cardiovascular events were documented. Descriptive statistical methods and a linear mixed-effects model were used for statistical analysis.ResultsHeart rate control (65 to 95 bpm) was achieved in 97.5% of patients (n = 39) within 12.2 ± 12.4 hours. Heart rate, central venous pressure, and norepinephrine, arginine vasopressin, and milrinone dosages decreased (all P < 0.001). Cardiac index and cardiac power index remained unchanged whereas stroke volume index increased (P = 0.002). In two patients (5%), metoprolol was discontinued because of asymptomatic bradycardia. Norepinephrine and milrinone dosages were increased in nine (22.5%) and six (15%) patients, respectively. pH increased (P < 0.001) whereas arterial lactate (P < 0.001), serum C-reactive protein (P = 0.001), and creatinine (P = 0.02) levels decreased during the observation period. Twenty-eight-day mortality was 33%.ConclusionLow doses of enteral metoprolol in combination with phosphodiesterase inhibitors are feasible in patients with septic shock and cardiac depression but no overt heart failure. Future prospective controlled trials on the use of beta blockers for septic cardiomyopathy and their influence on proinflammatory cytokines are warranted.

Acute Pulmonary Embolism Is an Independent Predictor of Adverse Events in Severe Decompensated Heart Failure Patients

Congestive heart failure (CHF) is a well-recognized risk factor for venous thromboembolism (VTE) and is associated with higher mortality in patients with an acute pulmonary embolism (PE). There are very few data on how acute PE affects the clinical course of patients with heart failure. The purpose of this study was to determine the impact of an acute PE on the short-term prognosis of patients hospitalized for decompensated CHF. This was a prospective cohort study of 198 patients admitted to a coronary care unit between July 2001 and March 2003 with severe decompensated CHF. The primary outcome measure was death or rehospitalization at 3 months. PE was confirmed in 18 of 198 patients enrolled (9.1%). The groups with and without PE were comparable with regards to demographics, the prevalence of comorbid conditions, and severity of CHF (p > 0.05). The prevalence of cancer (p = 0.0001), previous VTE (p = 0.003), and right ventricular overload (p = 0.006) was higher in the PE group. The presence of PE was also associated with a longer hospital stay (37.5 +/- 71.6 days vs 15.4 +/- 15.0 days, p = 0.001) [mean +/- SD] and a higher incidence of death or rehospitalization at 3 months (72.2% vs 43.9%, p = 0.02). In a multiple logistic regression analysis, PE remained an independent predictor of death or rehospitalization at 3 months (odds ratio, 4.0; 95% confidence interval, 1.1 to 15.1; p = 0.038). Acute PE commonly complicates the hospital course of patients with severe CHF, increasing the length of hospital stay and the chance of death or rehospitalization at 3 months.

Transient enhancement of oxidant stress and collagen turnover in patients with acute decompensated congestive heart failure

Myocardial remodeling is a crucial step for progression of heart failure. Free radical generation from failing myocardium has been proposed to be linked to myocardial remodeling. The aim of this study was to evaluate urinary excretion of 8-iso-prostaglandin F2á (8-iso-PGF2á), a reliable marker for oxidant stress in vivo, and collagen turnover in patients with acute worsening of congestive heart failure (CHF). Enrolled were 43 patients with acute worsening of CHF due to various etiologies. At their admission (acute phase) and after approximately 2 week-conventional treatment (chronic phase), we measured: (1) immunoreactive urinary 8-iso-PGF2á, (2) serum total anti-oxidant status (TAS); and (3) serum levels of procollagen type I carboxyterminal peptide (PIP) and carboxyterminal collagen type I telopeptide (CITP), biochemical markers for collagen synthesis and degradation, respectively. From acute phase to chronic phase these parameters were monitored: 335.1±245.4 to 205.3±107.4 pg/mg creatinine for urinary 8-iso-PGF2á (P<0.0001); 0.92±0.16 to 0.98±0.13 mM for TAS (P<0.01); 171.4±72.5 to 93.7±33.9 ng/ml for PIP (P<0.0001); and 7.2±3.6 to 12.6±8.4 ng/ml for CITP (P<0.0001). In conclusion, acute worsening of CHF promotes free radical generation and collagen synthesis.

WITHDRAWN: Transient enhancement of oxidant stress and collagen turnover in patients with acute decompensated congestive heart failure

WITHDRAWN: Transient enhancement of oxidant stress and collagen turnover in patients with acute decompensated congestive heart failure

Interpretation of B-type natriuretic peptide in cardiac disease and other comorbid conditions

B-Type natriuretic peptide (BNP) is elevated in states of increased ventricular wall stress. BNP is most commonly used to rule out congestive heart failure (CHF) in dyspneic patients. BNP levels are influenced by age, gender and, to a surprisingly large extent, by body mass index (BMI). In addition, it can be elevated in a wide variety of clinical settings with or without CHF. BNP is elevated in other cardiac disease states such as the acute coronary syndromes, diastolic dysfunction, atrial fibrillation (AF), amyloidosis, restrictive cardiomyopathy (RCM), and valvular heart disease. BNP is elevated in non-cardiac diseases such as pulmonary hypertension, chronic obstructive pulmonary disease, pulmonary embolism, and renal failure. BNP is also elevated in the setting of critical illness such as in acute decompensated CHF (ADHF) and sepsis. This variation across clinical settings has significant implications given the increasing frequency with which BNP testing is being performed. It is important for clinicians to understand how to appropriately interpret BNP in light of the comorbidities of individual patients to maximize its clinical utility. We will review the molecular biology and physiology of natriuretic peptides as well as the relevant literature on the utilization of BNP in CHF as well as in other important clinical situations, conditions that are commonly associated with CHF and or dyspnea.

Enhanced Oxidant Stress Under Acute Decompensated Congestive Heart Failure Exacerbates Left Ventricular Remodeling at its Stable Phase

Progression of left ventricular remodeling (LVR) is crucial for prognosis of congestive heart failure (CHF). We recently reported the enhancement of oxidant stress (OS) and collagen turnover in patients with acute decompensated CHF (AD-CHF). The aim of this study was to clarify the association between enhanced OS and LVR in such patients. Thirty-two patients were admitted into our hospital due to AD-CHF. After successful treatment, they were followed up with conventional medicines. LVR was monitored with echocardiography at admission, 2 weeks later, and 6 months later.

P6-88: Device-based monitoring of intrathoracic impedance to alert patients with chronic heart failure of cardiac decompensation: Algorithm performance and correlation with NT-proBNP

Monitoring of intrathoracic impedance reveals pulmonary fluid changes in patients (pts) with congestive heart failure (CHF). A CRT-D device (InSync Sentry™, Medtronic) that audibly alerts pts if intrathoracic impedance decreases (OptiVol™ Alert, Medtronic) may thereby facilitate the detection of CHF decompensation.

Incidence and Clinical Predictors of Pulmonary Embolism in Severe Heart Failure Patients Admitted to a Coronary Care Unit

To determine the incidence of clinical pulmonary embolism (PE) in a population with severe congestive heart failure (CHF) admitted to a coronary care unit (CCU), and to identify clinical predictors of PE in this population. Prospective, observational study performed in a CCU of a tertiary care hospital between July 2001 and March 2003. One hundred ninety-eight patients with severe decompensated CHF. Of 198 patients recruited, 18 patients (9.1%) received a diagnosis of PE during their hospitalization. Deep vein thrombosis was demonstrated in 8 of 18 patients (44.4%) with PE. Thromboprophylaxis was used by 12 of 18 patients (66.7%) with PE and 126 of 180 patients (70%) without PE (p = 0.77). Both groups were similar with respect to mean age (68.2 +/- 14.1 years vs 69.6 +/- 13.4 years [+/- SD]), proportion of male patients (61.1% vs 55.1%), markers of CHF severity (New York Heart Association functional class > II, ejection fraction < 30%, Na < 136 mEq/L, ischemic etiology), and comorbid conditions (diabetes mellitus, atrial fibrillation, chronic renal failure, hypertension) [p = not significant]. The presence of PE was significantly associated with cancer (relative risk [RR], 8.4; 95% confidence interval [CI], 3.9 to 18.1), immobilization (RR, 5.4; 95% CI, 2.0 to 14.4), previous venous thromboembolism (VTE) [RR, 4.4; 95% CI, 1.7 to 11.3], COPD (RR, 3.1; 95% CI, 1.03 to 9.2), and right ventricle (RV) abnormality (RR, 3.3; 95% CI, 1.3 to 8.0). In a multiple logistic regression analysis, only cancer (odds ratio [OR], 26.9; 95% CI, 4.9 to 146.8), RV abnormality (OR, 9.7; 95% CI, 2.2 to 42.6), and previous VTE (OR, 9.1; 95% CI, 1.28 to 64.7) remained independently associated with PE. In patients with severe decompensated CHF admitted to a CCU, the incidence of clinical PE is very high despite adequate prophylaxis. Traditional risk factors seemed to play an important role in determining the risk of PE in this population.

Beneficial effects of high doses of growth hormone in the introduction and optimization of medical treatment in decompensated congestive heart failure

Background Optimizing oral therapy in patients with unstable decompensated and/or dobutamine-dependent congestive heart failure (CHF) is a challenge. Methods and results We investigated the effects of high doses of recombinant human growth hormone (GH) in 6 patients with cardiac cachexia and unstable decompensated CHF (5 dobutamine-dependent), including its influence in the optimization of oral CHF treatment. Patients received 8 IU of subcutaneous GH per day for median 26 (range 61) days. GH improved the systolic systemic blood pressure (SSBP, in mm Hg) from median 85 (range 34) to 100 (20) ( p < .01), and the left ventricular (LV) ejection fraction (in %) from median 23 (range 22) (pretreatment) to 28 (18) (posttreatment) and 38 (28) (later) ( p < .007). The NYHA functional class improved from IV to I in 2 patients, from IV to II in 3, and from IV to II–III in one. All patients were discharged from the hospital. It was possible in the hospital to initiate and after discharge to optimize long-term CHF treatment from 37.5 to 50 mg of carvedilol in 5 patients and with higher doses of captopril (from 50 to 150 mg) in all patients. Three patients are alive after 67, 75, and 11 months of follow-up. The remaining 3 patients died from a pulmonary abscess at 9 months, septicemia at 21 months, and progressive heart failure due to unplanned withdrawal of carvedilol at 36 months. Conclusion The use of GH in patients with decompensated CHF and cardiac cachexia provided clinical stability without the need for inotropic drugs permitting introduction of nonpreviously tolerated drugs. This could represent a new option for optimizing long-term CHF therapy and discharging hospitalized patients who are dobutamine-dependent.

B-Type Natriuretic Peptide in Heart Failure

Chronic heart failure affects nearly 5 million people living in the United States, and the majority of economic burden is the result of hospitalizations for acute decompensated congestive heart failure. Patient history and symptom assessment, physical examination, and chest radiography remain the cornerstones of diagnosis and prognostic assessment. Evaluation of endogenous B-type natriuretic peptide (BNP) has emerged as a useful addition to standard methods for diagnosis and risk stratification of suspected congestive heart failure, and final diagnosis requires integration of BNP assays with traditional methods. BNP levels >500 pg/mL are more likely to be comfirmative of a primary diagnosis of heart failure and are also important predictors for long-term adverse prognosis; >100 pg/mL but <500 pg/mL suggests a reasonable likelihood for the diagnosis of heart failure but does require thoughtful exclusion of other potential confounders such as pulmonary disease resulting in right heart failure; and <100 indicates that heart failure is very unlikely. Positive physiological effects of BNP, including improvements in hemodynamics, suppression of neurohormonal activity, preservation of renal function, diuresis and natriuresis, and balanced arterial and venous dilatation have suggested that this peptide also may have therapeutic use in congestive heart failure. In clinical trials, treatment of patients with acute decompensated congestive heart failure with nesiritide, a recombinant form of human BNP, was shown to significantly reduce pulmonary capillary wedge pressure versus placebo plus standard care, as well as provide a significant improvement in dyspnea versus placebo. Diagnostic, prognostic, and therapeutic applications of BNP can be integrated easily with standard methods to provide physicians with a useful evaluation and treatment algorithm that may result in faster identification of patients likely to benefit from early therapy, including nesiritide, thereby leading to the potential for more favorable patient outcomes.

Concomitant use of nesiritide and milrinone in decompensated congestive heart failure

Milrinone and nesiritide are vasoactive agents used for the treatment of acute and chronic decompensated congestive heart failure (CHF). Milrinone is a phosphodiesterase III inhibitor that has inotropic and vasodilatory properties and acts via a cyclic adenosine monophosphate (cAMP)-mediated pathway

A Review of the Renal and Neurohormonal Effects of B‐Type Natriuretic Peptide

Adverse neurohormonal activation is an essential component in the pathogenesis of acute decompensated congestive heart failure (CHF). Consequently, blunting this activation is an important therapeutic goal. B-type natriuretic peptide (BNP) is a counterregulatory hormone produced by the ventricles in response to pressure and volume load. Endogenous BNP levels are significantly elevated in patients with acute CHF, but these levels are frequently inadequate to overcome the excess neurohormonal activation present in this condition. Infusion of nesiritide, a recombinant form of endogenous human BNP, increases circulating BNP levels by several-fold, augmenting the counterregulatory effects of this hormone. Clinical trials demonstrate that in patients with acute decompensated CHF, nesiritide produces arterial and venous vasodilation, reducing both preload and afterload; blunts adverse neurohormones, including renin, aldosterone, norepinephrine, and endothelin-1; and improves renal hemodynamics and tubular function. As a result, nesiritide quickly reduces clinical symptoms and improves mortality in patients with acute CHF.

Use of glitazones in cardiac patients: a case for B-type natriuretic peptide monitoring?

In the United States (US), approximately 4.9 million patients have congestive heart failure (CHF), and 10.9 million patients are diagnosed with diabetes mellitus. An estimated additional 5.7 million people have undiagnosed diabetes, according to statistics from 1998. The direct and indirect costs related to CHF in 2003 are estimated at 24.3 billion US dollars. Many patients have both conditions at the same time. For this reason, the effect of diabetic treatment on the course of CHF has major implications. Recently several reports have linked the use of glitazones with CHF decompensation. Therefore, a better examination of this phenomenon and the development of strategies for early detection are warranted.

Measures of heart period variability as predictors of mortality in hospitalized patients with decompensated congestive heart failure

Depressed heart rate variability (HRV) is a powerful independent predictor of a poor outcome in patients with chronic and stable congestive heart failure (CHF). However, the prognostic value of HRV analysis in patients hospitalized for decompensated CHF is not known. The aim of this study was to investigate whether HRV parameters obtained during admission for decompensated CHF could predict survival after hospital discharge. We studied 199 patients (131 men, aged 60 ± 14 years) with a previous diagnosis of New York Heart Association class III or IV CHF who were admitted to the hospital for decompensated CHF. Twenty-four–hour Holter recordings were obtained on admission, and measures of HRV were calculated in the time and frequency domain. During a mean follow-up of 312 ± 150 days, 40 patients (21.1%) died. Kaplan-Meier analysis indicated that patients with SD of the RR intervals over a 24-hour period (p = 0.027), SD of all 5-minute mean RR intervals (p = 0.043), total power (p = 0.022), and ultra–low-frequency power (p = 0.008) in the lower tertile were at a higher risk of death. In a multivariate Cox regression model, the same indexes in the lower tertile were independent predictors of mortality: SD of the RR intervals over a 24-hour period (risk ratio [RR] 2.2, 95% confidence interval [CI] 1.05 to 4.3, p = 0.036), SD of all 5-minute mean RR intervals (RR 2.1, 95% CI 1.05 to 4.2, p = 0.04), total power (RR 2.2, 95% CI 1.08 to 4.2, p = 0.03), and ultra–low-frequency power (RR 2.6, 95% CI 1.3 to 5.3, p = 0.007). Therefore, the severity of autonomic perturbations during hospital admission for CHF decompensation, as reflected by measures of overall HRV, can predict survival after hospital discharge. Together with previous studies, our findings suggest that indexes of overall HRV provide useful prognostic information in the full spectrum of CHF severity.

Economic implications of nesiritide versus dobutamine in the treatment of patients with acutely decompensated congestive heart failure

Pooled data from trials comparing nesiritide with dobutamine for treatment of acute decompensated congestive heart failure were combined with national hospital cost data in an economic model. Results indicate that the acquisition cost of nesiritide is fully offset by decreased hospital costs.

Comparison of the effects of dobutamine and nesiritide (B-type natriuretic peptide) on ventricular ectopy in acutely decompensated ischemic versus nonischemic cardiomyopathy

Congestive heart failure (CHF) involves many complex autonomic and neurohormonal responses (such as activation of the renin-angiotensin-aldosterone and sympathetic systems) that can exert deleterious effects on the heart, leading to further cardiac decompensation. Inotropic therapy with dobutamine can improve cardiac hemodynamics, but also may cause arrhythmogenesis.1,2 Nesiritide (B-type natriuretic peptide, an endogenous cardiac hormone) is a systemic arterial and venous vasodilator,3–5 and has been shown to significantly reduce symptoms and improve hemodynamics in hospitalized patients with acute decompensated CHF without increasing heart rate. Nesiritide also suppresses norepinephrine, endothelin-1, and the renin-angiotensin-aldosterone system while promoting natriuresis.6–8 In the Prospective Randomized Evaluation of Cardiac Ectopy with Dobutamine or Nesiritide Therapy (PRECEDENT) trial, dobutamine was associated with significant increases in ventricular tachycardia (VT) and heart rate, especially in patients without a history of VT, suggesting that proarrythmic effects may be due to sympathetic activation of a dormant substrate.9 In contrast, nesiritide was associated with an actual reduction in VT without an increase in heart rate. The objective of this study was to determine the differential effects of dobutamine and nesiritide on ventricular arrhythmias and on heart rate in patients with ischemic and nonischemic cardiomyopathy.

Nesiritide: a review of its use in acute decompensated heart failure.

Nesiritide (Natrecor) is a recombinant form of human B-type (brain) natriuretic peptide that has beneficial vasodilatory, natriuretic, diuretic and neurohormonal effects. The drug is administered intravenously for the management of patients with decompensated congestive heart failure (CHF). In the Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) study, patients hospitalised with acute decompensated CHF who received nesiritide had significantly greater mean reductions from baseline in pulmonary capillary wedge pressure 3 hours after starting treatment than nitroglycerin or placebo recipients (-5.8 vs -3.8 and -2 mm Hg, respectively); all patients also received standard therapy (e.g. intravenous diuretics). Improvements in other haemodynamic parameters were also seen in nesiritide recipients. In addition, significantly more nesiritide than placebo recipients reported an improvement in dyspnoea after 3 hours' treatment in VMAC, whereas there was no significant difference between nitroglycerin and placebo recipients. Improvements in global clinical status, dyspnoea and fatigue were also seen with nesiritide in another active-comparator study and in a placebo-controlled study. In VMAC, there was no significant difference between nesiritide and nitroglycerin recipients in 6-month mortality. In the other active-comparator trial, 6-month mortality was significantly lower in recipients of nesiritide 0.015 micro g/kg/min than in dobutamine recipients (although mortality was not a prespecified endpoint and this result should be interpreted with caution). In this same study, the 21-day all-cause hospital readmission rate was significantly lower with nesiritide 0.015 micro g/kg/min than with dobutamine and the duration of active drug treatment was significantly shorter with nesiritide than with dobutamine. Nesiritide is generally well tolerated. In VMAC, significantly more adverse events occurred with nitroglycerin than with nesiritide. The most common adverse events reported during the first 24 hours of therapy in nesiritide and nitroglycerin recipients included general pain, abdominal pain, catheter-related pain, headache, nausea, asymptomatic and symptomatic hypotension, nonsustained ventricular tachycardia and angina pectoris. Most episodes of symptomatic hypotension resolved spontaneously or after an intravenous volume challenge of </=250 ml. In addition, nesiritide does not appear to be proarrhythmic. Short-term intravenous infusion of nesiritide is associated with haemodynamic and symptomatic improvements in patients with acutely decompensated CHF. Nesiritide may offer tolerability and practical advantages over currently used vasodilators, inodilators and inotropes in this condition; in particular, nesiritide does not appear to have proarrhythmic effects. Nesiritide also appears to be effective and well tolerated in patients receiving concomitant beta-blocker therapy and in patients with renal insufficiency. Thus, nesiritide is a suitable first-line option for the treatment of patients with acutely decompensated CHF and is a welcome addition in an area where intravenous agents are few.

Nesiritide (Natrecor): a new treatment for acutely decompensated congestive heart failure.

The care of the patient experiencing acutely decompensated congestive heart failure requires therapies that promote vasodilation and increase cardiac output while decreasing symptomatic hypotension and dysrhythmias. Nesiritide (Natrecor) is a new type of drug, recombinant human B-type natriuretic peptide (hBNP), approved for use in acutely decompensated congestive heart failure. The neurohormonal effects of endogenous BNP are reproduced by nesiritide. Indications, dosing, administration, and review of clinical trials are presented in this article.