ABC | Volume 110, Nº3, March 2018

Original Article Almeida Junior et al BNP, echo and clinical evaluation in heart failure Arq Bras Cardiol. 2018; 110(3):270-277 in the recent PROTECT trial, 36 a similar strategy of guiding treatment according to amino-terminal-Pro-BNP levels against standard of care resulted in decreased incidence of events, improvement in quality of life and in cardiac remodeling. However, that trial was conducted in an outpatient setting, involving very few heart failure patients in more advanced functional classes. In the present study, we used a cut-off point of 400 pg/mL for BNP as a marker of congestion, since this value was employed in previous studies. 14,35 We have observed that BNP levels > 400 pg/mL had a poor prediction performance to identify elevation in LAP, similar to other physical findings or chest radiography performances when taken individually. No valuable information on filling pressures was observed when BNP levels were below 400 pg/mL. Using the AUC, we found that BNP levels of 1000 pg/mL had the best specificity to predict LAP ≥ 15 mm Hg. Therefore, we have also utilized this cut-off value in our subsequent combined analysis. Patients with moderate or severe renal impairment had higher BNP values, in our study the mean values of urea and creatinine were only slightly elevated and should not have influenced the results. Although there is a time difference between the change in ventricular filling pressures and the corresponding change in BNP levels, this time lapse does not seem to have clinical significance. The half-life of BNP is short, about 20 minutes, and, in addition, the treatment-induced decrease in pulmonary capillary pressure leads to a rapid reduction in BNP levels (30 to 50 pg/mL/hour). Combining tools to estimate congestion In patients with intermediate BNP levels (100-500 pg/mL), adding the information about the presence of S3 increases the positive predictive value from 54% to 80%. 37 A recent study with 50 patients utilized a very similar strategy to our study, comparing a CS, BNP and a hand carried ultrasound in estimating elevation of ventricular filling pressures, but the gold standard in that study was right heart catheterization. 14 As in ours, that study used a cut-off value for BNP > 400 pg/mL and for PCWP ≥15 mm Hg as referencing parameters. The clinical symptom score had very little predictive utility for an elevated PCWP. Combining the information of jugular venous pressure, BNP and ultrasound, the best diagnostic characteristics for predicting elevated LV filling pressure was achieved (AUC 0.98). In our study, combining the findings of physical examination with chest radiography and BNP augmented progressively the sensitivity (64%, 82% and 91%, respectively) for detecting an elevated LAP, achieving a positive predictive value of 81%, although with a poor specificity. Still, combining these tools showed a modest power in predicting high filling pressures (AUC: 0.62). Thus, ours and the study by Goonewardena et al. 14 showed that clinical examination and BNP are not fully capable to precisely detect elevated filling pressures, and echocardiographically-derived hemodynamic assessment can reliably be incorporated into clinical practice of ADHF, avoiding the traditional invasive right heart catheterization method. The increasing utilization of hand carried ultrasound can be of great value in this area. Study limitations Wehaveusedtheechocardiogramasthegold-standardmethod for defining filling pressures instead of right heart catheterization. Nonetheless, hemodynamic echocardiogram‑derived parameters are well validated in the medical literature when correlated with invasive measurements. 38-40 We primarily use the lateral annulus to measure E/e' ratio. Although the most recent recommendations suggest using the mean of the lateral and septal annulus values, this was mainly validated in normal subjects. The most recent 2016 guideline of the American Society of Echocardiography and the European Association of Cardiovascular Imaging recognizes that at times only the lateral e’ or septal e’ velocity is available, and it is clinically valid. Inaddition,wedidnot followpatients during thehospitalization or in the post-discharge period to observe whether the initial hemodynamic profile was compatible with the clinical course. Conclusions In this study, we showed that in ADHF patients, clinical assessment alone or in conjunction with chest radiography and BNP may lead to inaccurate estimation of echocardiographically-derived hemodynamic profiling. Author contributions Conception and design of the research and Analysis and interpretationofthedata:AlmeidaJuniorGLG,ClausellN,GarciaMI, Esporcatte R, Rangel FOD, Rocha RM, Silva Neto LB, Silva FB, GorgulhoPCC, XavierSS; Acquisitionof data: Almeida JuniorGLG, Garcia MI; Statistical analysis: Almeida Junior GLG, Clausell N, Silva FB, Xavier SS; Obtaining financing: Almeida Junior GLG; Writing of the manuscript: Almeida Junior GLG, Clausell N, Garcia MI, Xavier SS; Critical revision of the manuscript for intellectual content: Almeida Junior GLG, Clausell N, Garcia MI, Rangel FOD, Xavier SS. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding There were no external funding sources for this study. Study Association This article is part of the thesis of Doctoral submitted by Gustavo Luiz Gouvêa de Almeida Junior, from Universidade Federal do Rio Grande do Sul. Ethics approval and consent to participate This study was approved by the Ethics Committee of the Hospital Pró-Cardíaco under the protocol number 021/10 (CAAE:0021.1.346.001-10). All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study. 275