B-type Natriuretic Peptide Ratio Research Articles

Urinary cGMP (Cyclic Guanosine Monophosphate)/BNP (B-Type Natriuretic Peptide) Ratio, Sacubitril/Valsartan, and Outcomes in Heart Failure With Reduced Ejection Fraction: An Analysis of the PARADIGM-HF Trial.

The ratio of ucGMP (urinary cyclic guanosine monophosphate) to BNP (B-type natriuretic peptide) is thought to reflect the responsiveness of tissues to natriuretic peptides. We examined the relationship between ucGMP/BNP ratio and clinical outcomes, the effect of sacubitril/valsartan, compared with enalapril, on the ucGMP/BNP ratio, and the efficacy of sacubitril/valsartan on clinical outcomes according to baseline ucGMP/BNP ratio in PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). ucGMP/BNP ratio was available at baseline (N=2031), 1 month (N=1959), and 8 months after randomization (N=1746). The primary outcome was a composite of heart failure hospitalization or cardiovascular death. Compared with the lowest tertile of baseline ucGMP/BNP ratio, patients in the higher tertiles had a lower risk of the primary outcome (tertile 1, reference; tertile 2, hazard ratio 0.57 [95% CI, 0.45-0.71]; tertile 3, hazard ratio, 0.54 [0.43-0.67]). Compared with baseline, the ucGMP/BNP ratio at 1 month and 8 months after randomization was higher with sacubitril/valsartan than with enalapril: ratio of geometric mean ratios at 1 month, 1.38 (95% CI, 1.27-1.51) and 8 months, 1.32 (95% CI, 1.20-1.45), and this difference was consistent across tertiles of ucGMP/BNP ratio at baseline (Pinteraction=0.19 and 0.91, respectively). The effect of sacubitril/valsartan, compared with enalapril, was consistent across tertiles of ucGMP/BNP ratio at baseline for all outcomes (Pinteraction ≥0.31). In patients with heart failure and reduced ejection fraction, higher ucGMP/BNP ratio was associated with better outcomes. Sacubitril/valsartan increased the ucGMP/BNP ratio, compared with enalapril, and the effect of sacubitril/valsartan on clinical outcomes was not modified by baseline ucGMP/BNP ratio. URL: https://www. gov; Unique Identifier: NCT01035255.

BNP on Admission Combined with Imaging Markers of Multimodal CT to Predict the Risk of Cardioembolic Stroke.

Background The aim of the study was to find the potential roles of B-type natriuretic peptide (BNP) and imaging markers on distinguishing cardioembolic (CE) stroke from non-CE stroke, so as to provide useful information for making individualized endovascular treatment (EVT) plan for the patients with acute ischemic stroke (AIS). Methods The patients with unilateral anterior circulation large vessel occlusion who underwent EVT between March 2016 and December 2021 were analyzed in this study, retrospectively. The risk factors, laboratory test indicators, imaging parameters, and other factors were compared between the CE group and non-CE group. Logistic regression was used to analyze the risk factors of CE stroke. ROC curves were used to assess the values of different parameters on distinguishing CE stroke from non-CE stroke. The relationships between BNP and imaging parameters were assessed using the Spearman correlation analysis. Results 160 patients were enrolled in the study and divided into the CE group (n = 66) and non-CE group (n = 94). BNP (odds ratio (OR) = 1.004; 95% CI, 1.001-1.009; p = 0.038), MMR (OR = 0.736; 95% CI, 0.573-0.945; p = 0.016), NIHSS (OR = 1.150; 95% CI, 1.022-1.294; p = 0.020), and AF (OR = 556.968; 95% CI, 51.739-5995.765; p < 0.001) were the independent predictive factors of CE stroke. The area under the curve (AUC) of BNP and mismatch ratio (MMR) were 0.846 (95% CI (0.780-0.898), p < 0.001) and 0.636 (95% CI (0.633-0.779), p < 0.001), respectively. The cut-off value of BNP was 249.23 pg/mL with the sensitivity of 74.24% and the specificity of 82.98%. BNP combined with MMR improved the predictive value for CE stroke. The AUC of the combination was 0.858 with the sensitivity of 84.85% and the specificity of 73.40%. BNP was correlated with 4D CTA collateral score, MMR, clot burden score, final infarct volume, infarct core volume, and ischemic penumbra volume (all, p < 0.05). Conclusion BNP on admission combined with MMR is valuable for the risk prediction of CE stroke, which will promote the further screening of the high-risk patients with CE stroke and provide more diagnostic information for clinicians.

Association of B-type natriuretic peptide with rapid progression in patients with aortic stenosis.

Rapid progression of aortic stenosis (AS) is associated with poor outcomes, and the impact of B-type natriuretic peptide (BNP) on AS progression remains unknown. The purpose of the present study was to investigate the association between BNP level and the AS progression rate. From January 2016 to June 2021, 200 AS patients with progression who had at least two transthoracic echocardiograms with a maximum interval of 180 days were retrospectively analyzed. Rapid progression of AS was defined as the annual increase of aortic jet velocity (Vmax) ≥0.3 m/s/year. For analyses, both the log-transformed BNP and the BNP ratio were used. The linear regression and binary logistic regression analyses were used to determine the association between BNP and the AS progression. At a median echocardiographic follow-up of 595 days, the annual median (interquartile) progression of Vmax was 0.26 (0.09-0.58) m/s/year. Patients with rapid progression had higher age, log BNP, and higher percentage of diabetes and male gender. Higher tertiles of log BNP and BNP ratio had more rapid increase in Vmax (p = 0.018 and 0.033, respectively). BNP ratio significantly correlated with Vmax progression in univariate and multivariate linear regression analyses (p < 0.001 and p = 0.001, respectively). Moreover, both the univariate and multivariate binary logistic regression analyses showed that the log BNP and BNP ratio were associated with the rapid progression of AS (p < 0.050 for all). Higher BNP was independently associated with the rapid progression of AS.

NT-proBNP/BNP ratio for prognostication in European Caucasian patients enrolled in a heart failure prevention programme.

AimsGuidelines support the role of B‐type natriuretic peptide (BNP) and amino‐terminal pro‐BNP (NT‐proBNP) for risk stratification of patients in programmes to prevent heart failure (HF). Although biologically formed in a 1:1 ratio, the ratio of NT‐proBNP to BNP exhibits wide inter‐individual variability. A report on an Asian population suggests that molar NT‐proBNP/BNP ratio is associated with incident HF. This study aims to determine whether routine, simultaneous evaluation of both BNP and NT‐proBNP is warranted in a European, Caucasian population.Methods and ResultsWe determined BNP and NT‐proBNP levels for 782 Stage A/B HF patients in the STOP‐HF programme. The clinical, echocardiographic, and biochemical associates of molar NT‐proBNP/BNP ratio were analysed. The primary endpoint was the adjusted association of baseline molar NT‐proBNP/BNP ratio with new‐onset HF and/or progression of left ventricular dysfunction (LVD). We estimated the C‐statistic, integrated discrimination improvement, and the category‐free net reclassification improvement metric for the addition of molar NT‐proBNP/BNP ratio to adjusted models. The median age was 66.6 years [interquartile range (IQR) 59.5–73.1], 371 (47.4%) were female, and median molar NT‐proBNP/BNP ratio was 1.91 (IQR 1.37–2.93). Estimated glomerular filtration rate, systolic blood pressure, left ventricular mass index, and heart rate were associated with NT‐proBNP/BNP ratio in a linear regression model (all P < 0.05). Over a median follow‐up period of 5 years (IQR 3.4–6.8), 247 (31.5%) patients developed HF or progression of LVD. Log‐transformed NT‐proBNP/BNP ratio is inversely associated with HF and LVD risk when adjusted for age, gender, diabetes, hypertension, vascular disease, obesity, heart rate, number of years of follow‐up, estimated glomerular filtration rate, and baseline NT‐proBNP (odds ratio 0.71, 95% confidence interval 0.55–0.91; P = 0.008). However, molar NT‐proBNP/BNP ratio did not increase the C‐statistic (Δ −0.01) and net reclassification improvement (0.0035) for prediction of HF and LVD compared with NT‐proBNP or BNP alone. Substitution of NT‐proBNP for BNP in the multivariable model eliminated the association with HF and LVD risk.ConclusionsThis study characterized, for the first time in a Caucasian Stage A/B HF population, the relationship between NT‐proBNP/BNP ratio and biological factors and demonstrated an inverse relationship with the future development of HF and LVD. However, this study does not support routine simultaneous BNP and NT‐proBNP measurement in HF prevention programmes amongst European, Caucasian patients.

Association of Natriuretic Peptide Levels After Transcatheter Aortic Valve Replacement With Subsequent Clinical Outcomes

Among those with aortic stenosis, natriuretic peptide levels can provide risk stratification, predict symptom onset, and aid decisions regarding the timing of valve replacement. Less is known about the prognostic significance and potential clinical utility of natriuretic peptide levels measured after valve replacement. To determine the associations of elevated B-type natriuretic peptide (BNP) levels after transcatheter aortic valve replacement (TAVR) and change in BNP levels between follow-up time points with risk of subsequent clinical outcomes. In this cohort study, patients with severe symptomatic aortic stenosis at intermediate, high, or prohibitive surgical risk for aortic valve replacement who underwent TAVR from the PARTNER IIA cohort, PARTNER IIB cohort, SAPIEN 3 intermediate-risk registry, and SAPIEN 3 high-risk registry were included. B-type natriuretic peptide levels were obtained at baseline and discharge as well as 30 days and 1 year after TAVR. For each measurement, a BNP ratio was calculated using measured BNP level divided by the upper limit of normal for the assay used. Outcomes were evaluated in landmark analyses out to 2 years. Data were collected from April 2011 to January 2019. All-cause death, cardiovascular death, rehospitalization, and the combined end point of cardiovascular death or rehospitalization. Among 3391 included patients, 1969 (58.1%) were male, and the mean (SD) age was 82 (7.5) years. Most patients had a BNP ratio greater than 1 at each follow-up time point, including 2820 of 3256 (86.6%) at baseline, 2652 of 2995 (88.5%) at discharge, 1779 of 2209 (80.5%) at 30 days, and 1799 of 2391 (75.2%) at 1 year. After adjustment, every 1-point increase in BNP ratio at 30 days (approximately equivalent to an increase of 100 pg/mL in BNP) was associated with an increased hazard of all-cause death (adjusted hazard ratio [aHR], 1.11; 95% CI, 1.07-1.15), cardiovascular death (aHR, 1.16; 95% CI, 1.11-1.21), and rehospitalization (aHR, 1.08; 95% CI, 1.03-1.14) between 30 days and 2 years. Among those with a BNP ratio of 2 or more at discharge, after adjustment, every 1-point decrease in BNP ratio between discharge and 30 days was associated with a decreased hazard of all-cause death (aHR, 0.92; 95% CI, 0.88-0.96) between 30 days and 2 years. Elevated BNP levels after TAVR was independently associated with increased subsequent mortality and rehospitalizations. Further studies to determine how best to mitigate this risk are warranted.

P4666Higher BNP levels after transcatheter aortic valve implantation are associated with increased mortality and hospitalizations

Abstract Background Among patients with aortic stenosis (AS), the adverse association between increased B-type natriuretic peptide (BNP) levels and worse clinical outcomes, including mortality and hospitalization after valve replacement, has been demonstrated. However, little attention has been paid to the clinical consequences of BNP levels after valve replacement, which may have implications for medical therapy prescribed after the procedure. Purpose Evaluate the association between BNP levels after transcatheter aortic valve implantation (TAVI) and subsequent mortality and hospitalizations. Methods Among intermediate, high, and extreme risk patients with severe symptomatic AS who received TAVI for native valve AS in the PARTNER II and S3 clinical trials or registries, we included 3260 patients who had BNP measured at baseline. Patients from sites which measured NTproBNP were excluded. To account for factors that influence BNP levels, we developed a regression equation–including age, sex, BMI, creatinine, study site, and the upper limit of normal of the BNP assay used for a given measurement–to determine expected BNP. BNP ratio was determined pre-TAVR and at discharge, 30 days, and 1 year and calculated as the actual BNP/expected BNP. Using a landmark approach, the relationships between (1) BNP ratio at 30 days or (2) delta BNP ratio between discharge and 30 days and subsequent outcomes between 30 days and 1 year were assessed. The primary outcome was a composite of cardiovascular (CV) mortality or hospitalization. Adjustment was made for 20 baseline and post-procedural factors known to influence outcomes. Results Higher BNP ratio at 30 days was associated with higher CV mortality or hospitalization between 30 days and 1 year (adjusted hazard ratio [aHR] 1.07 per increase of 1 in the BNP ratio, 95% CI 1.04–1.10, p&lt;0.001), whereas baseline BNP ratio was not (p=0.38). A similar relationship was shown for the components of this composite: CV mortality (aHR 1.08, 95% CI 1.04–1.12, p&lt;0.001) and hospitalizations (aHR 1.04, 95% CI 1.01–1.08, p=0.01). Adjusted for discharge BNP ratio and other factors, a greater decrease in BNP ratio between discharge and 30 days was also associated with lower CV mortality or hospitalization between 30 days and 1 year (aHR 0.95 per decrease of 1 in the BNP ratio, 95% CI 0.92–0.99, p=0.006). Similar relationships were observed for all-cause mortality and when examining the relationship between 1 year BNP ratio and outcomes between 1 and 2 years. Conclusion Higher BNP ratio after TAVI is associated with higher subsequent all-cause and CV mortality and hospitalizations, whereas baseline BNP ratio was not. Greater decrease in BNP ratio between discharge and 30 days is associated with better outcomes. Further investigation is warranted to understand these findings and determine whether intensification of medical therapy to decrease BNP after TAVR may improve patient outcomes. Acknowledgement/Funding The PARTNER 2 Trial was funded by Edwards Lifesciences

B-Type Natriuretic Peptide Clinical Activation in Aortic Stenosis: Impact on Long-Term Survival

This study was conducted to define the association between serum B-type natriuretic peptide (BNP) activation andsurvival after the diagnosis of aortic stenosis (AS). In AS, the link between BNP levels and clinical outcome is in dispute. Failure to account for the normal shifting ofBNP ranges with aging in men and women, not using hard endpoints (survival), and not enrolling large series ofpatients have contributed to the uncertainty. A program of prospective measurement of BNP levels with Doppler echocardiographic AS assessment during the same episode of care was conducted. BNP ratio (measured BNP/maximal normal BNP value specific to age and sex) >1 defined BNP clinical activation. In 1,953 consecutive patients with at least moderate AS (aortic valve area 1.03 ± 0.26 cm(2); mean gradient 36±19 mm Hg), median BNP level was 252 pg/ml (interquartile range: 98 to 592 pg/ml); BNP ratio 2.46 (interquartile range 1.03 to 5.66); ejection fraction (EF) 57% ± 15%, and symptoms present in 60% of patients. After adjustment for all survival determinants, BNP clinical activation (BNP ratio >1) independently predicted mortality after diagnosis (p< 0.0001; hazard ratio [HR]: 1.91; 95% CI: 1.55 to 2.35) and provided incremental power to the survival predictive model (p<0.0001). Eight-year survival was 62 ± 3% with normal BNP levels, 44± 3% with BNP ratio of 1 to 2 (adjusted HR: 1.49; 95% CI: 1.17 to 1.90), 25 ± 4% with BNP ratio of 2 to 3 (adjusted HR: 2.12; 95% CI: 1.63 to2.75), and 15 ± 2% with BNP ratio of≥3 (adjusted HR: 2.43; 95% CI: 1.94 to 3.05). This strong link to survivalwas confirmed in asymptomatic patients with normal EF (adjusted HR: 2.35 [95% CI: 1.57 to 3.56] for BNPclinical activation and 2.10 [95% CI: 1.32 to 3.36] for BNP ratio of 1 to 2, 2.25 [95% CI: 1.31 to 3.87] for BNP ratio of 2 to 3, 3.93 [95% CI: 2.40 to 6.43] for BNP ratio of≥3). Aortic valve replacement was associated with survival improved by a similarly high margin (p= 0.54) with BNP ratio of<2 (HR: 0.68; 95% CI: 0.52 to 0.89; p= 0.003) or BNP ratio of>2(HR: 0.56; 95% CI: 0.47 to 0.66; p< 0.0001). In this large series of patients with AS, BNP clinical activation was associated with excess long-term mortality incrementally and independently of all baseline characteristics. Higher mortality with higher BNP clinical activation, even in asymptomatic patients, emphasizes the importance of appropriate clinical interpretation of BNP levels in managing patients with AS.

Processed B-Type Natriuretic Peptide Is a Biomarker of Postinterventional Restenosis in Ischemic Heart Disease

Restenosis, a condition in which the lesion vessel renarrows after a coronary intervention procedure, remains a limitation in management. A surrogate biomarker for risk stratification of restenosis would be welcome. B-type natriuretic peptide (BNP) is secreted in response to pathologic stress from the heart. Its use as a biomarker of heart failure is well known; however, its diagnostic potential in ischemic heart disease is less explored. Recently, it has been reported that processed forms of BNP exist in the circulation. We hypothesized that circulating processed forms of BNP might be a biomarker of ischemic heart disease. We characterized processed forms of BNP by a newly developed mass spectrometry-based detection method combined with immunocapture using commercial anti-BNP antibodies. Measurements of processed forms of BNP by this assay were found to be strongly associated with presence of restenosis. Reduced concentrations of the amino-terminal processed peptide BNP(5-32) relative to BNP(3-32) [as the index parameter BNP(5-32)/BNP(3-32) ratio] were seen in patients with restenosis [median (interquartile range) 1.19 (1.11-1.34), n = 22] vs without restenosis [1.43 (1.22-1.61), n = 83; P < 0.001] in a cross-sectional study of 105 patients undergoing follow-up coronary angiography. A sensitivity of 100% to rule out the presence of restenosis was attained at a ratio of 1.52. Processed forms of BNP may serve as viable potential biomarkers to rule out restenosis.

Diverse Molecular Forms of Plasma B-Type Natriuretic Peptide in Heart Failure

Recent studies have shown that not only plasma B-type natriuretic peptide (BNP)-32, but also plasma proBNP-108 is increased in heart failure (HF), and that the current BNP-32 assay kit crossreacts with proBNP-108. It also was shown that both BNP-32 and proBNP-108 were higher in HF than in normal. The proBNP-108/total BNP (BNP-32 + proBNP-108) ratio was widely distributed and patients with HF with ventricular overload had higher proBNP-108/total BNP ratio than HF patients with atrial overload. Consistent with this finding, proBNP-108 was the major molecular form in ventricular tissue, and BNP-32 was the major molecular form in atrial tissue. In addition, proBNP-108 was the major molecular form of BNP in pericardial fluid. The proBNP-108/total BNP ratio increased with deterioration of HF and decreased with improvement of HF. Thus, not only BNP-32, but also proBNP-108 is increased in HF and the proBNP-108/total BNP ratio also rises in association with pathophysiological conditions such as ventricular overload. A new hypothesis that O-glycosylation at Thr71 in a region close to the cleavage site impairs proBNP-108 processing was proposed. In the future, the precise mechanism of increased proBNP-108 in HF should be elucidated.

The cyclic guanosine monophosphate/B‐type natriuretic peptide ratio and mortality in advanced heart failure

Attenuation of the effects of natriuretic peptides has been demonstrated in animal models but studies in humans are scarce, particularly concerning renal attenuation. We investigated the attenuation of B-type natriuretic peptide (BNP) in chronic advanced heart failure (HF). We included 62 outpatients with HF and severe left ventricular systolic dysfunction. Cases had at least one hospital admission or emergency department visit for acute HF in the previous year and were in NYHA class III/IV despite optimized therapy. The individual age- and sex-matched controls were symptomatically controlled (NYHA I and II). We collected 24 h urine and a blood sample from all patients. Plasma BNP and plasma (pcGMP) and urine cyclic guanosine monophosphate (ucGMP) were measured. Patients were followed for 3 months for hospital admission or all-cause death. ucGMP to plasma BNP (ucGMP/BNP) ratio was attenuated in cases vs. controls [median (IQR): 8354 (4293-16,456) vs. 12,693 (6896-22,851)]. There were no differences in pcGMP to BNP (pcGMP/BNP) ratio or urine cGMP excretion. Patients with worse outcome had lower pcGMP/BNP [260 (86-344) vs. 381 (244-728) in patients without adverse outcome events] and lower ucGMP/BNP [4146 (2207-9363) vs. 10,922 (7495-19,971)]. Renal NP's second messenger production is attenuated in advanced HF. Patients with worse outcome have lower ucGMP/BNP and pcGMP/BNP ratios.

B-Type Natriuretic Peptide and Impedance Cardiography at the Time of Routine Echocardiography Predict Subsequent Heart Failure Events

Background Detection of heart failure (HF) in stable outpatients can be difficult until an overt event occurs. This study sought to determine whether the combination of B-type natriuretic peptide (BNP) and impedance cardiography (ICG) could be used in a nonacute clinical setting to risk stratify and predict HF-related events in stable outpatients. Methods and Results Patients undergoing routine outpatient echocardiography underwent ICG and BNP testing and were followed for one year for HF-related events (Emergency Department [ED] visit or hospitalization due to HF or all-cause death). A total of 524 patients were analyzed, resulting in 57 HF-related events; 16 ED visits, 17 hospitalizations, and 24 all-cause deaths. Using Cox regression analyses, BNP and systolic time ratio index (STRI) by ICG proved to be the strongest predictors of future HF-related events. Patients with a BNP >100 pg/ml and STRI >0.45 sec -1 had a significantly lower event-free survival rate than those with a high BNP and low STRI (67% versus 89%, P=.001). In patients with LV dysfunction only, if both BNP and STRI values were high, the relative risk of a HF-related event increased by 12.5 (95 % C.I. 4.2-36.7), when compared with patients with a low BNP and low STRI (P<.001). Conclusions In a nonacute clinical setting, both BNP and ICG testing can provide unique predictive power of long-term HF-related events in a stable cohort of patients with and without LV dysfunction.

Altered sodium intake affects plasma concentrations of BNP but not proBNP in healthy individuals and patients with compensated heart failure

Plasma B-type natriuretic peptide (BNP) and proBNP are promising markers for treatment of heart failure (HF), but the intra-individual biological variation is high. We investigated whether changes in sodium intake and posture contribute to this variation. A total of 12 healthy individuals and 12 patients with medically treated compensated HF were examined after 1 week of low (70 mmol [1.61 g] per day) and 1 week of high (250 mmol [5.75 g] per day) sodium intake. Plasma volume and plasma concentrations of BNP and proBNP were determined after 1 h in seated and 1 h in supine position. In healthy individuals, the plasma BNP concentration increased significantly on high sodium intake with a ratio (high sodium/low sodium) of 2.00 (1.32-3.03, P = 0.004). The corresponding values for HF patients were 1.69 (1.25-2.29, P = 0.003). The plasma BNP concentration changed modestly by a posture change, with a plasma BNP ratio (supine/seated) of 1.15 (1.07-1.14, P = 0.001) and 1.06 (0.99-1.24, P = 0.088) in healthy subjects and HF patients, respectively. Plasma proBNP concentrations were neither significantly affected by posture nor by sodium intake. Sodium intake has a considerable effect on plasma BNP and therefore contributes to the intra-individual variability. We suggest dietary sodium intake to be standardized at least 3 days prior to blood sampling for the determination of plasma BNP.

B-type natriuretic peptide levels predict outcome after neonatal cardiac surgery

Neonates undergoing cardiac surgery are at high risk for adverse outcomes. B-type natriuretic peptide is used as a biomarker in patients with cardiac disease, but the predictive value of B-type natriuretic peptide after cardiac surgery in neonates has not been evaluated. Therefore, the objective of this study was to determine the predictive value of perioperative B-type natriuretic peptide levels for postoperative outcomes in neonates undergoing cardiac surgery. Plasma B-type natriuretic peptide determinations were made before and 2, 12, and 24 hours after surgery in 36 consecutive neonates. B-type natriuretic peptide levels and changes in perioperative B-type natriuretic peptide were evaluated as predictors of postoperative outcome. B-type natriuretic peptide levels at 24 hours were lower than preoperative levels (24-h/pre B-type natriuretic peptide ratio < 1) in 29 patients (81%) and higher (24-h/pre B-type natriuretic peptide ratio > or = 1) in 7 patients (19%). A 24-hour/pre B-type natriuretic peptide level of 1 or greater was associated with an increased incidence of low cardiac output syndrome (100% vs 34%, P = .002) and fewer ventilator-free days (17 +/- 13 days vs 26 +/- 3 days, P = .002), and predicted the 6-month composite end point of death, an unplanned cardiac operation, or cardiac transplant (57% vs 3%, P = .003). A 24-hour/pre B-type natriuretic peptide level of 1 or greater had a sensitivity of 80% and a specificity of 90% for predicting a poor postoperative outcome (P = .003). In neonates undergoing cardiac surgery, an increase in B-type natriuretic peptide 24 hours after surgery predicts poor postoperative outcome.

Acute Phosphodiesterase 5 Inhibition Mimics Hemodynamic Effects of B-Type Natriuretic Peptide and Potentiates B-Type Natriuretic Peptide Effects in Failing But Not Normal Canine Heart

The aim of this work was to test whether acute phosphodiesterase 5 (PDE5) inhibition via sildenafil (SIL) mimics and/or potentiates cardiorenal effects of exogenous natriuretic peptide (NP) infusion. Heart failure (HF) is often accompanied by elevated NP secretion yet blunted responsiveness. Such NP resistance may, in part, relate to increased cyclic guanosine monophosphate (cGMP) catabolism by PDE5. Dogs (n = 7) were studied before and after tachypacing-induced HF. Animals received 30-min infusion of B-type natriuretic peptide (BNP) (2 mug/kg bolus, 0.02 mug/kg/min), and on a separate day SIL (1 mg/kg, intravenous), followed by BNP (SIL + BNP). Phosphodiesterase 5 activity was measured in lung, vasculature, and kidney. At baseline (non-failing), BNP lowered central venous, pulmonary capillary wedge, diastolic, mean pulmonary artery, and mean arterial pressure. Sildenafil had no effects, and SIL + BNP was similar to BNP alone. In contrast, SIL lowered these pressures similarly to BNP in dogs with HF, and SIL + BNP was additive in further reducing pulmonary pressures over BNP alone. Plasma cGMP/plasma BNP ratio was markedly reduced with HF, indicating NP resistance. Sildenafil plus BNP increased this ratio in HF, but had no effect in non-failing animals. Sildenafil had no independent diuretic/natriuretic effects nor did it enhance BNP effects under baseline or HF conditions. In HF, PDE5 activity was significantly increased in the systemic and pulmonary vasculature and in the kidney. The PDE5 activity in systemic and pulmonary vasculature increases in HF rendering hemodynamic responses to PDE5 inhibition identical to those from BNP infusion. Natriuretic peptide desensitization in HF relates, in part, to increased PDE5 activity, supporting a therapeutic role for PDE5 inhibition.