Predictors of responders for low-dose carperitide monotherapy in patients with acute heart failure.

Human atrial natriuretic peptide, known as carperitide, is approved for early relief of dyspnea in patients with acute heart failure (AHF). However, the diuretic effect of carperitide is sometimes insufficient for controlling volume overload. We investigated predictors for the carperitide response in patients with AHF. Forty-seven patients (age: 74 ± 10 years; left ventricular ejection fraction: 42.0% ± 15.9%) with AHF were enrolled and treated with carperitide monotherapy at a dose of 0.0125 µg/kg/min. Patients without sufficient diuresis (< 60 ml/h) or improvement of symptoms by 4 h after carperitide administration, despite increasing to twice the dose of carperitide and adding another agent, were defined as non-responders. Twenty-four (51%) patients were defined as responders and treated with low-dose carperitide monotherapy on the first day. Multiple logistic regression analysis showed that the response to carperitide monotherapy was independently predicted by serum creatinine levels and systolic blood pressure (SBP) on admission. The area under the receiver-operating characteristic curve for predicting the response to carperitide by SBP was 0.808 (95% confidence interval [0.686-0.930], sensitivity: 83.3%, specificity: 65.2%, cutoff value: 135 mmHg). Four (8.5%) patients developed asymptomatic transient hypotension. Worsening renal function occurred within 3 days of admission in three (6.4%) patients who received low-dose carperitide therapy. SBP and serum creatinine levels on admission might be useful for predicting the diuretic response to low-dose carperitide monotherapy in patients with AHF. Initial use of low-dose carperitide therapy does not have adverse effects on renal function.

Effects of early diuretic response to carperitide in acute decompensated heart failure treatment: A single-center retrospective study.

BACKGROUND: Diuretic response is a strong predictor of outcome for admitted patients of acute decompensated heart failure (ADHF). However, little is known about the effects of early diuretic response to carperitide. METHODS: We retrospectively analyzed records of 85 patients hospitalized for ADHF who received carperitide as initial treatment and <40 mg furosemide during the early period. The eligible patients were divided into good diuretic responder (GR) group and poor diuretic responder (PR) group on the basis of median urinary volume. RESULTS: The PR group demonstrated older age, lower body mass index (BMI), lower estimated glomerular filtration rate, and higher blood urea nitrogen (BUN) level, left ventricular ejection fraction, and ß-blockers prescribed at baseline than the GR group. The incidence of worsening renal function (WRF) was significantly higher in the PR group than in the GR group. There was no correlation between early intravenous furosemide dose and urinary volume (Spearman correlation, ρ = 0.111, p = 0.312). Multivariate analysis showed that the statistically significant independent factors associated with poor diuretic response to carperitide were BMI (Odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.68-0.94, p = 0.004) and BUN (OR = 1.07, 95%CI 1.01-1.15, p = 0.018). Kaplan-Meier analysis indicated a lower event-free rate in the PR group than in the GR group (log-rank, p = 0.007). CONCLUSIONS: BMI and BUN levels on admission were significant determinants of early poor diuretic response to carperitide. Early poor diuretic response to carperitide was associated with future poor outcomes.

A multicenter randomized controlled trial of surgery alone or surgery with atrial natriuretic peptide in lung cancer surgery: study protocol for a randomized controlled trial.

BACKGROUND: Postoperative cancer recurrence is a major problem following curative surgery. In a previous retrospective study of lung cancer surgery, we reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduced postoperative recurrence. We demonstrated that ANP inhibited the adhesion of cancer cells to vascular endothelium as a vasoprotective action. The objective of this study is to evaluate the effects of ANP on the incidence of postoperative cancer recurrence in lung cancer surgery. METHODS/DESIGN: The present study is a multicenter, randomized trial with two parallel groups of patients with lung cancer comparing surgery alone and surgery with ANP administration for 3 days during the perioperative period. A total of 500 patients will be enrolled from 10 Japanese institutions. The primary endpoint is 2-year relapse-free survival (RFS). The secondary endpoints are 2-year cancer-specific RFS, 5-year RFS, overall survival, the incidence of postoperative complications, and the completion rate of ANP treatment. DISCUSSION: The principal question addressed in this trial is whether ANP with its vasoprotective action can reduce cancer recurrence following lung cancer surgery. TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier: UMIN000018480 . Registered on 31 July 2015.

Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure.

BACKGROUND: In patients with acute heart failure, early intervention with an intravenous vasodilator has been proposed as a therapeutic goal to reduce cardiac-wall stress and, potentially, myocardial injury, thereby favorably affecting patients' long-term prognosis. METHODS: In this double-blind trial, we randomly assigned 2157 patients with acute heart failure to receive a continuous intravenous infusion of either ularitide at a dose of 15 ng per kilogram of body weight per minute or matching placebo for 48 hours, in addition to accepted therapy. Treatment was initiated a median of 6 hours after the initial clinical evaluation. The coprimary outcomes were death from cardiovascular causes during a median follow-up of 15 months and a hierarchical composite end point that evaluated the initial 48-hour clinical course. RESULTS: Death from cardiovascular causes occurred in 236 patients in the ularitide group and 225 patients in the placebo group (21.7% vs. 21.0%; hazard ratio, 1.03; 96% confidence interval, 0.85 to 1.25; P=0.75). In the intention-to-treat analysis, there was no significant between-group difference with respect to the hierarchical composite outcome. The ularitide group had greater reductions in systolic blood pressure and in levels of N-terminal pro-brain natriuretic peptide than the placebo group. However, changes in cardiac troponin T levels during the infusion did not differ between the two groups in the 55% of patients with paired data. CONCLUSIONS: In patients with acute heart failure, ularitide exerted favorable physiological effects (without affecting cardiac troponin levels), but short-term treatment did not affect a clinical composite end point or reduce long-term cardiovascular mortality. (Funded by Cardiorentis; TRUE-AHF ClinicalTrials.gov number, NCT01661634 .).

Renin-Angiotensin System Control for Chronic Kidney Disease Patients Undergoing Coronary Surgery.

PURPOSE: We investigated the effectiveness of active renin-angiotensin-aldosterone system (RAAS) control with human atrial natriuretic peptide (hANP) and an angiotensin II receptor blocker (ARB) in patients with chronic kidney disease (CKD) undergoing coronary artery bypass grafting (CABG). METHODS: A total of 286 consecutive patients with CKD undergoing CABG were divided into three groups: Group C (n = 50) receiving placebo, the hANP group (n = 60) receiving hANP, and the active RAAS control therapy (ARC) group (n = 56) receiving hANP plus an ARB. Renal function, brain natriuretic peptide (BNP) and RAAS parameters were analyzed. RESULTS: After 1 year, renal function parameters were better in the hANP and ARC groups compared with group C, and the dialysis rate was significantly lower (group C: 12%, hANP group: 1.7%, ARC group: 1.8%, p = 0.018) in the hANP and ARC groups. BNP levels were significantly lower in the hANP and ARC groups compared with group C (p = 0.001). There was also a significant difference of aldosterone among the groups (p = 0.023), as well as a significant difference between group C and the ARC group (p = 0.017). CONCLUSIONS: The present study showed that active RAAS control preserved renal function in patients with CKD undergoing CABG. The improved early postoperative outcome with RAAS control may lead to long-term inhibition of cardiovascular events.

Novel Therapies for Heart Failure　- Where Do They Stand?

Despite advances in therapy, patients with heart failure (HF) continue to experience unacceptably high rates of hospitalization and death, as well as poor quality of life. As a consequence, there is an urgent need for new treatments that can improve the clinical course of the growing worldwide population of HF patients. Serelaxin and ularatide, both based on naturally occurring peptides, have potent vasodilatory as well as other effects on the heart and kidneys. For both agents, phase 3 studies that are designed to determine whether they improve outcomes in patients with acute HF have completed enrollment. TRV027, a biased ligand for the type 1 angiotensin receptor with effects that extend beyond traditional angiotensin-receptor blockers is also being studied in the acute HF population. Omecamtiv mecarbil, an inotropic agent that improves myocardial contractility by a novel mechanism, and vericiguat, a drug that stimulates soluble guanylate cyclase, are both being developed to treat patients with chronic HF. Finally, despite the negative results of the CUPID study, gene transfer therapy continues to be explored as a means of improving the function of the failing heart. The basis for the use of these drugs and their current status in clinical trials are discussed. (Circ J 2016; 80: 1882-1891).

Carperitide Increases the Need for Renal Replacement Therapy After Cardiovascular Surgery.

OBJECTIVES: Acute kidney injury is a common complication after aortic surgery. Carperitide, a human atrial natriuretic peptide, was reported to be effective for preventing acute kidney injury after cardiac surgery. However, most studies were from single centers, and results of meta-analyses are subject to publication bias. The aim of the present study was to investigate whether carperitide preserved renal function in patients undergoing cardiovascular surgery. DESIGN: Retrospective cohort study. SETTING: Participating hospitals (N = 281) in a national database from 2010 to 2013. PARTICIPANTS: Adult patients (N = 47,032) who underwent cardiovascular surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main intervention variable investigated was the use of carperitide on the day of surgery. Assessed outcomes included receiving renal replacement therapy within 21 days of surgery and in-hospital mortality. Data were available for 47,032 patients, of whom 2,186 (4.6%) received carperitide on the day of surgery. Multivariate logistic regression analysis revealed that carperitide was significantly associated with a greater likelihood of receiving renal replacement therapy within 21 days of surgery, but not with in-hospital mortality. CONCLUSIONS: In patients undergoing cardiovascular surgery, carperitide significantly increased the odds of receiving renal replacement therapy within 21 days after surgery.

Carperitide Is Associated With Increased In-Hospital Mortality in Acute Heart Failure: A Propensity Score-Matched Analysis.

BACKGROUND: Carperitide (α-human A-type natriuretic peptide) has been used for more than one-half of all acute heart failure (AHF) patients in Japan. However, its clinical effectiveness is not well documented. METHODS: We retrospectively identified AHF patients presenting with acute onset or worsening of symptoms and admitted to 1 of the 3 participating hospitals. Propensity score-matched analysis was performed. The primary end point was in-hospital mortality. RESULTS: Of all of the AHF patients included in this study, 402 (38.7%) were treated with carperitide, and in-hospital mortality rate for the total cohort was 7.6%. We matched 367 pairs of patients treated with and without carperitide according to propensity score. In this matched cohort, treatment with carperitide was associated with in-hospital mortality (odds ratio [OR] 2.13, 95% confidence interval [CI] 1.17-3.85; P = .013). Potentially more harmful effects were observed in elderly patients (OR 2.93, 95% CI 1.54-5.91). CONCLUSIONS: Carperitide was significantly associated with increased in-hospital mortality rate in AHF patients. Our results strongly suggest the necessity for well designed randomized clinical trials of carperitide to determine its clinical safety and effectiveness.

Early results of human atrial natriuretic peptide infusion in non-dialysis patients with chronic kidney disease undergoing isolated coronary artery bypass grafting: the NU-HIT trial for CKD-II.

BACKGROUND: Chronic kidney disease (CKD) is an important risk factor for cardiac surgery. In the most recently reported NU-HIT trial for CKD with CKD patients underwent coronary artery bypass grafting (CABG) as subjects, carperitide was reported to be effective in terms of renal function. In the present study, a subanalysis was performed on patients registered in the NU-HIT trial for CKD from the standpoint of renin-angiotensin system, natriuresis and renal function. METHODS: 303 patients with CKD who underwent isolated CABG were divided into a group that received carperitide infusion and another group without carperitide. The renin activity, angiotensin-II, aldosterone, urine-sodium, urine- creatinine, fractional sodium excretion, renal failure index, and BNP levels. RESULTS: There were significant lower in hANP group than the placebo group, in angiotensin-II at one day postoperatively, and in aldosterone from 0 day to one month postoperatively. FENa was significantly lower in the hANP group at 3 day and one week postoperatively. CONCLUSIONS: In on pump isolated CABG patients with CKD, carperitide showed a potent natriuretic action and inhibited the renin-angiotensin system, suggesting that it prevented deterioration of postoperative renal function. Our findings raise new possibilities for the perioperative and postoperative management of patients undergoing surgery with cardiopulmonary bypass.

Efficacy and safety of short-term administration of recombinant human atrial natriuretic peptide (rhANP) for congestive heart failure: a phase II, multicentre randomized controlled dose-finding study.

WHAT IS KNOWN AND OBJECTIVE: Although the long-term infusion of ANP has proved effective to treat heart failure, no published randomized controlled study has been reported to confirm the efficacy of the short-term ANP infusion in congestive heart failure (CHF) patients. This study was designed to assess the efficacy and safety of short-term infusion of recombinant human atrial natriuretic peptide (rhANP) in CHF patients. METHODS: A total of 48 patients with CHF were enrolled and randomized into four groups, treated with standard therapy or rhANP (0·05, 0·1 or 0·2 µg/kg/min) for 1-hour infusion in addition to standard therapy. The hemodynamics were assessed for 12 h by Swan-Ganz catheter. RESULTS AND DISCUSSION: The effect of the 0·05 µg/kg/min rhANP dose group on CO was modest and transient. The 0·2 µg/kg/min rhANP dose group tended to be associated with better effect on SV, CO and dyspnoea improvement, but modest effect on PCWP and more adverse events probably attributed to the study drug. However, the 0·1 µg/kg/min rhANP infusion was well tolerated and effective both on PCWP decrease (maximum:-9·46 ± 5·81 mmHg compared with baseline (P = 0·0002) and -6·75 mmHg compared with standard therapy, the 95% confidential interval [-13·43, -0·06 mmHg] at 1 h) and CO increase (maximum: 1·02 ± 1·43 L/min [P = 0·0308] at 1 h). WHAT IS NEW AND CONCLUSION: In this small-sample study, 1-hour infusion of rhANP produced beneficial hemodynamic effects in CHF patients compared with standard therapy, and it was well tolerated. 0·1 µg/kg/min may be the optimum dose for short-term rhANP infusion to treat CHF for the further large sample trial before clinical application.

Multicenter trial of carperitide in patients with renal dysfunction undergoing cardiovascular surgery.

PURPOSE: The aim of this study was to evaluate the efficacy of carperitide in maintaining renal function during intraoperative and postoperative management of patients with renal dysfunction undergoing elective cardiovascular surgery. METHODS: The subjects were 88 patients with a preoperative serum creatinine level ≥1.2 mg/dl who underwent elective cardiovascular surgery using cardiopulmonary bypass. They were prospectively divided into a group that received carperitide from the start of surgery (carperitide group, n = 44) and a group that was not given carperitide (control group, n = 44). Carperitide infusion was initiated at the beginning of surgery and was continued for ≥5 days, with the central dose being 0.02 g/kg/min. The primary endpoint was the serum creatinine level on postoperative day (POD) 3. RESULTS: The serum creatinine levels on PODs 3, 4, and 7 were significantly lower, and creatinine clearance on PODs 2 and 3 was significantly higher in the carperitide group than in the controls. One patient in the control group and no patient in the carperitide group required continuous hemodiafiltration, but the difference was not statistically significant. CONCLUSION: Continuous low-dose infusion of carperitide from the start of cardiovascular surgery maintained renal function in patients with preoperative renal dysfunction.

Effect of low-dose human atrial natriuretic peptide on postoperative atrial fibrillation in patients undergoing pulmonary resection for lung cancer: a double-blind, placebo-controlled study.

OBJECTIVES: We previously reported that patients with preoperative B-type natriuretic peptide levels of 30 pg/mL or more have increased risk of postoperative atrial fibrillation after pulmonary resection. This study evaluated the effects of human atrial natriuretic peptide on postoperative atrial fibrillation in patients undergoing pulmonary resection for lung cancer. METHODS: A prospective, randomized study was conducted with 40 patients who had preoperative elevated B-type natriuretic peptide (≥ 30 pg/mL) and underwent a scheduled pulmonary resection for lung cancer. Results were compared between patients who received low-dose human atrial natriuretic peptide and those who received a placebo. The primary end point was the incidence of postoperative atrial fibrillation during the first 4 days after surgery. RESULTS: The incidence of postoperative atrial fibrillation was significantly lower in the human atrial natriuretic peptide group than in the placebo group (10% vs 60%; P < .001). Patients in the human atrial natriuretic peptide group also showed significantly lower white blood cell counts and C-reactive protein levels after surgery. CONCLUSIONS: Continuous infusion of low-dose human atrial natriuretic peptide during lung cancer surgery had a prophylactic effect against postoperative atrial fibrillation after pulmonary resection in patients with preoperative elevation of B-type natriuretic peptide levels. A larger sample size is needed to establish the safety and efficacy of this intervention.

[Natriuretic peptides in the therapy of acute decompensated heart failure]. / Akut dekompensierte Herzinsuffizienz: klinischer Stellenwert einer Therapie mit natriuretischen Peptiden.

Heart failure is the most frequent cause of hospitalization in elderly population. Unlike the therapy of congestive heart failure, there was only a modest progress in the medical treatment for acutely decompensated heart failure over the past several decades. Moreover, current treatment is associated with many limitations in clinical practice. The family of natriuretic peptides consists of several structurally similar polypeptides (ANP, BNP, CNP, urodilatin, DNP). ANP and BNP are the most characterized substances and represent an important compensatory mechanisms in heart failure because of their vasodilatory, natriuretic and antiproliferative effects. Nesiritide is a recombinant human BNP which has been shown to be effective in treating heart failure in several clinical trials. However, a recent meta-analysis revealed a nesiritide-associated increased 30-day-mortality rate. The results of initial small-sized trials suggest beneficial hemodynamic effects of urodilatin in decompensated heart failure. Despite of being approved for the treatment of decompensated heart failure in some countries, the clinical relevance of nesiritide is currently unclear. Urodilatin might represent a potential alternative.

Myocardial protective effect of human atrial natriuretic Peptide in cardiac surgery. -hANP Shot" in clinical safety trial-.

BACKGROUND: We studied low-dose human atrial natriuretic peptide (hANP) infusion therapy during cardiac surgery and reported the cardiac and renal protective effects. The efficacy of a bolus injection of hANP (the "hANP shot") simultaneously with induction of cardioplegia has been proven in animal experiments. In the present study the clinical effects of this "hANP shot" were examined. METHODS AND RESULTS: The subjects were 67 patients undergoing Coronary artery bypass grafting. At the time of inducing cardioplegia, 1 group received a simultaneous bolus injection of 100 µg of hANP (hANP group) and the other group received an injection of physiological saline (placebo group). The primary endpoints were (1) operative mortality and complications, and (2) the creatine kinase isoenzyme MB (CPK-MB), troponin-I, and human heart fatty acid binding protein (H-FABP) levels. The secondary endpoints were (1) the incidence of arrhythmia, and levels of (2) atrial and B-type natriuretic peptides, and cyclic guanosine monophosphate (cGMP), and (3) renin, angiotensin II, and aldosterone. Postoperative CPK-MB, troponin-I, and H-FABP levels were significantly lower in the hANP group than in the placebo group. Postoperative arrhythmia was significantly less frequent in the hANP group than in the placebo group. CONCLUSIONS: It is possible to achieve cardioprotective effects based on the safety of the "hANP shot", as well as from biomarkers of ischemia and results related to arrhythmia. The "hANP shot" should also be evaluated as a safer and new cardioprotective method for cardiac surgery.

Atrial natriuretic peptide for preventing and treating acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is common in hospitalised patients and is associated with significant morbidity and mortality. Despite recent advances, outcomes have not substantially changed in the last four decades. Atrial natriuretic peptide (ANP) has shown promise in animal studies, however randomised controlled trials (RCTs) have shown inconsistent clinical benefits. OBJECTIVES: To assess the benefits and harms of ANP for preventing and treating AKI. SEARCH STRATEGY: We searched CENTRAL, MEDLINE and EMBASE and reference lists of retrieved articles. SELECTION CRITERIA: RCTs that investigated all forms of ANP versus any other treatment in adult hospitalised patients with or "at risk" of AKI. DATA COLLECTION AND ANALYSIS: Results were expressed as risk ratios (RR) with 95% confidence intervals (CI) or mean difference (MD). Outcomes were analysed separately for low and high dose ANP for preventing or treating AKI. MAIN RESULTS: Nineteen studies (11 prevention, 8 treatment; 1,861 participants) were included. There was no difference in mortality between ANP and control in either the low or high dose prevention studies. Low (but not high) dose ANP was associated with a reduced need for RRT in the prevention studies (RR 0.32, 95% CI 0.14 to 0.71). Length of hospital and ICU stay were significantly shorter in the low dose ANP group. For established AKI, there was no difference in mortality with either low or high dose ANP. Low (but not high) dose ANP was associated with a reduction in the need for RRT (RR 0.54, 95% CI 0.30 to 0.98). High dose ANP was associated with more adverse events (hypotension, arrhythmias). After major surgery there was a significant reduction in RRT requirement with ANP in the prevention studies (RR 0.56, 95% CI 0.32 to 0.99), but not in the treatment studies. There was no difference in mortality between ANP and control in either the prevention or treatment studies. There was a reduced need for RRT with low dose ANP in patients undergoing cardiovascular surgery (RR 0.35, 95% CI 0.18 to 0.70). ANP was not associated with outcome improvement in either radiocontrast nephropathy or oliguric AKI. AUTHORS' CONCLUSIONS: ANP may be associated with improved outcomes when used in low doses for preventing AKI and in managing postsurgery AKI and should be further explored in these two settings. There were no significant adverse events in the prevention studies, however in the high dose ANP treatment studies there were significant increases hypotension and arrhythmias.

Atrial natriuretic peptide for management of acute kidney injury: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Randomized controlled trials (RCTs) with atrial natriuretic peptide (ANP) have shown inconsistent effects for renal end-points. The authors aimed to systematically review these trials to ascertain the benefit of ANP in prevention and treatment of acute kidney injury (AKI). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The authors searched MEDLINE, EMBASE, and Cochrane Renal Health Library that investigated ANP in adult patients considered with or at risk for AKI. Outcomes were analyzed separately for prevention and treatment of AKI. RESULTS: Nineteen RCTs (11 prevention, 8 treatment) involving 1861 participants were included. Pooled analysis of prevention trials showed a trend toward reduction in renal replacement therapy in the ANP group (OR = 0.45, 95% CI, 0.21 to 0.99) and good safety profile, but no improvement in mortality. For the treatment of established AKI, ANP, particularly in high doses, was associated with a trend toward increased mortality and more adverse events. Subgroup analysis of AKI after a major surgery (14 RCTs, 817 participants) showed a significant reduction in renal replacement therapy requirement in the ANP group (OR = 0.49, 95% CI, 0.27 to 0.88). Included RCTs were mostly low- or moderate-quality, underpowered studies. CONCLUSIONS: There are an insufficient number of high-quality studies to make any definite statement about the role of ANP in AKI. Analysis of the existing literature suggests ANP might be associated with beneficial clinical effects when administered in patients undergoing major surgery such as cardiovascular surgery. Its use, in low doses, should be explored further in this setting.

Multicenter prospective investigation on efficacy and safety of carperitide as a first-line drug for acute heart failure syndrome with preserved blood pressure: COMPASS: Carperitide Effects Observed Through Monitoring Dyspnea in Acute Decompensated Heart Failure Study.

BACKGROUND: Recently, vasodilators have been increasingly being recognized as useful for the treatment of acute heart failure syndromes (AHFS). Although carperitide (alpha-human atrial natriuretic peptide) has vasodilatory, diuretic and organ-protective effects, its efficacy and safety for the first-line drug treatment of AHFS have not been reported. METHODS AND RESULTS: A prospective observational study was performed in AHFS patients with preserved systolic blood pressure (SBP >or=120 mmHg), pulmonary congestion and dyspnea who were receiving carperitide monotherapy. The analysis was conducted in 1,832 patients (male: 52.7%; mean age: 75.1+/-12.7 years). The initial SBP was 151.1+/-25.7 mmHg; 62.0% were diagnosed as having acutely decompensated chronic heart failure and 78.8% were assessed as functional class III-IV according to New York Heart Association classification. Carperitide was administered at an initial dosage of 0.025-0.05 microg x kg(-1) x min(-1) in 50.4% of patients. In 1,524 patients (83.2%), carperitide monotherapy restored the acute phase and improved the degree of dyspnea as assessed using the modified Borg scale. The incidence of adverse drug reactions was 4.64%; the most frequently reported adverse reaction was hypotension (3.55%). CONCLUSION: In the present study, following carperitide monotherapy, 83.2% of AHFS patients recovered from the acute phase. Based on these findings, carperitide seems useful for the first-line drug treatment of AHFS in patients with pulmonary congestion and preserved blood pressure.

Sildenafil citrate (Viagra) enhances vasodilatation by atrial natriuretic peptide in normal dogs.

BACKGROUND: Sildenafil citrate (Viagra) is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5, which might enhance the vasorelaxant and natriuretic actions of atrial natriuretic peptide (ANP) in patients with heart failure. The objective of this study was to examine the combined effect of Viagra on hemodynamic changes during infusion of exogenous ANP. METHODS AND RESULTS: Healthy male beagles were used to assess systemic blood pressure, pulmonary artery pressure (PAP), and plasma levels of cGMP. After hemodynamic variables were measured, 0.1 microg.kg(-1).min(-1) of ANP was given during this study. One hour after initiating infusion of ANP, 2 mg/kg of sildenafil citrate or vehicle was given orally via a nasogastric tube. Hemodynamic changes were measured before and 1 h after these administrations. Mean systemic and PAP decreased during infusion of ANP, and further decreased after sildenafil citrate administration, however, mean systemic blood pressure decreased within 10 mmHg. Plasma levels of cGMP also increased after sildenafil citrate administration. CONCLUSION: In normal dogs, sildenafil citrate enhances the vasodilator effect of ANP by increasing the cGMP level, however, the concomitant use of sildenafil citrate with ANP will not induce severe hypotension.

Haemodynamic and clinical effects of ularitide in decompensated heart failure.

AIMS: Ularitide is a synthetic form of urodilatin, a natriuretic peptide produced in the kidney with vasodilating, natriuretic, and diuretic effects, that offers promise for the management of decompensated heart failure (DHF). We assessed the efficacy and safety of ularitide in treating patients with DHF. METHODS AND RESULTS: In this Phase II randomized, double-blind, placebo-controlled trial, 221 DHF patients received either placebo (n=53) or ularitide at 7.5 ng/kg/min (n=60), 15 ng/kg/min (n=53), or 30 ng/kg/min (n=55) as a 24-h continuous infusion. At 6 h, ularitide demonstrated a significant decrease in pulmonary capillary wedge pressure (P=0.052, P=0.000004, P=0.000002, respectively) and improved dyspnoea score in the 7.5, 15, and 30 ng/kg/min ularitide group (P=0.0026, P=0.0026, P=0.0013, respectively). Ularitide reduced systemic vascular resistance and increased cardiac index for the 15 and 30 ng/kg/min groups (P=0.017, P=0.00002, respectively). Systolic blood pressure (BP) decreased dose dependency. Heart rate and serum creatinine were unchanged through day 3. Most frequently reported drug-related adverse events through day 3 in all ularitide groups were dose-dependent BP decrease and hypotension. CONCLUSION: Ularitide lowered cardiac filling pressures and improved dyspnoea without apparent early deleterious effects on renal function in DHF patients. These results suggest that ularitide may play a role in the management of DHF.