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.

Renal effects of added low-dose dopamine in acute heart failure patients with diuretic resistance to natriuretic peptide.

Worsening renal function during the early phase of hospitalization is related to adverse outcomes in acute heart failure (AHF). This study aimed to clarify whether added low-dose dopamine (DA) is clinically beneficial for AHF patients with diuretic resistance to human atrial natriuretic peptide (hANP). Twenty-four AHF patients, who did not have adequate diuresis by 4 hours after administration of hANP, were randomized to a low dose of DA (1-3 µg·kg·min, n = 12) or a low dose of furosemide (10-30 mg injection, n = 12). The significant increase in mean hourly urine volume from baseline (265% ± 204% with hANP + DA; 187% ± 118% with hANP + furosemide) and improvement of dyspnea were similarly observed in both groups. Significant decreases in serum creatinine levels were observed by -14.0% ± 14.2% in the hANP + DA group compared with the hANP + furosemide group (4.5% ± 9.6%, P = 0.0011) without increases in the renotubular and myocardial markers. The incidence of worsening renal function defined as a rise in serum creatinine of >0.3 mg/dL was not observed within 3 days of admission in both groups. Added low-dose DA might not have a harmful effect on renal function and effects of diuresis and symptom relief without a significant increase in troponin-T in AHF patients with diuretic resistance to hANP.

A case of marked diuresis by combined dopamine and atrial natriuretic peptide administration without renal injury in acute decompensated heart failure.

Renal injury is an important factor for worsening outcome in acute decompensated heart failure (ADHF). An 81-year-old woman was admitted due to ADHF with dyspnea and mild peripheral edema. The patient was managed with intravenous administration of atrial natriuretic peptide (ANP) at a dose of 0.0125 µg/kg/minute, which did not control volume overload even at an increased dose of 0.025 µg/kg/minute. After a low dose of dopamine (DA) of 1.0 µg/kg/ minute was added, urine output increased markedly to 120 from 30 mL/hour. Furthermore, her heart rate decreased to 80-100 from 120 bpm and the congestion improved with a reduced brain natriuretic peptide level. Interestingly, the combination of ANP and DA therapy reduced serum creatinine as well as the levels of urinary liver-type fatty acid binding protein, a novel reno-tubular stress marker, by 98.9%, and an oxidative stress marker, urinary 8-hydroxydeoxyguanosine, by 88.2% from baseline levels. Thus, this ADHF patient, a nonresponder to ANP alone, improved without renal injury when administered combination therapy consisting of low doses of ANP and DA, suggesting that this combined therapy might be useful for better management of ADHF in patients without diuretic responses with ANP alone. Further prospective studies are warranted.