Cekorja, B

Del Castillo, G

NUTI, RANUCCIO

PALAZZUOLI, ALBERTO

PELLEGRINI, MARCO

RUOCCO, GAETANO MARIA

Archivio della Ricerca - Università degli Studi di Siena

International Journal of Cardiology 178 (2015) 34–36Contents lists available at ScienceDirectInternational Journal of Cardiologyj ourna l homepage: www.e lsev ie r .com/ locate / i j ca rdLetter to the EditorCombined BNP and Echocardiographic assessment in interstitial lungdisease for pulmonary hypertension detection☆Alberto Palazzuoli a,⁎, Gaetano Ruocco a, Behar Cekorja b, Marco Pellegrini a,Gabriele Del Castillo a, Ranuccio Nuti aa Department of Internal Medicine, Cardiology Unit, Le Scotte Hospital University of Siena, Italyb UO Respiratory Diseases, University of Siena Italy☆ Conﬂict of interests: None declared.⁎ Corresponding author at: Department of Internal MeCardiology Section, Le Scotte Hospital, Viale Bracci, 53100E-mail address: palazzuoli2@unisi.it (A. Palazzuoli).http://dx.doi.org/10.1016/j.ijcard.2014.10.1200167-5273/© 2014 Elsevier Ireland Ltd. All rights reserveda r t i c l e i n f oArticle history:Received 11 September 2014Accepted 21 October 2014Available online 22 October 2014Keywords:Pulmonary hypertensionInterstitial lung diseaseBNPEchocardiographyto establish the exact correlation with PAP.Study design: Patients were eligible if they were admitted with aclinical and radiological diagnosis of interstitial lung disease. All patientsunderwent to: echocardiography and BNP. We included in this study120 consecutive patients affected by interstitial lung disease. Patientsrevealing PAPs N 40 mm Hg (43 patients) were then submitted to RCinvasivemeasurement to calculate PAPs, PAPmean and pulmonary vas-cular resistance (PVR). Written consent was provided by each patient.Patients were recruited from ARTEMIS-HP trial (www.clinicaltrials.gov: ID number NCT00879229).Natriuretic peptides (B-type natriuretic peptide [BNP] and NT pro-BNP) are proposed biomarkers to differentiate between cardiac and pul-monary causes of acute dyspnea [1]. Some emerging data proposed theuse in respiratory disease and particularly in patientswith acute pulmo-nary embolism and pulmonary hypertension (PH) [2].Prevalence of pulmonary hypertension (PH) in interstitial lung dis-eases (ILD) is higher in patients with severe ﬁbrosis but it may developat any stage of the disease [3,4]. Early recognition is frequently delayedfrom symptoms onset and diagnosis. For all these reasons the detectionof pulmonary arterial pressure (PAP) in patients affected to ILD is criticalfor diagnosis and clinical assessment [5]. The current gold standard forPH assessment is invasive right heart catheterization, however this proce-dure is prone to increased risk of complications and it should be carriedout in patients with evidence of PH previously identiﬁed by non-invasiveinvestigation [6]. Currently, the optimal tool to measure PH remains un-clear. The most appropriate, recognized method to detect PAP noninva-sively is trans-thoracic echocardiography, which demonstrated a goodcorrelation with invasive measurement [7]. We hypothesized that thecombination of echocardiography and BNP measurement may providea better detection of PH in patients with ILD. Thus the aims of thisstudy were: 1—to determine the accuracy of echo measurement andBNP assay in the detecting PH through building an algorithm modeldicine and Metabolic Diseases,Siena, Italy..and 2—to compare BNP and echo values with invasive measurementLaboratory analysis: Within 24 h from enrolment we measured, inall patients, BNP levels. Plasma BNP was measured with Triage BNPTest (Biosite Inc., San Diego, CA, USA); this test is an immunoassay ina single-use plastic cartridge ﬂuorescently labeledmonoclonal antibodyagainst BNP labeled with a ﬂuorescent dye and BNP. The level of BNP in12 healthy subjects was not higher than 80 pg/mL.Echocardiography: Right ventricular (RV) dimension and pulmo-nary pressure (PAPs and PAP mean) were estimated following theAmerican Society of Echocardiography criteria [8].Invasivemeasurement: For a subgroupof patientswith echocardio-graphic evidence of PH, hemodynamic results of right heart catheteriza-tion were obtained, measuring pulmonary artery pressures, pulmonaryartery WEDGE pressures and vascular resistance [9].Endpoints: 1— To establish correlations among BNP and echocardio-graphicmeasurements in the detecting PH, 2— to calculate the sensibilityand accuracy power of the echocardiographic and BNP assessments inrecognizing pulmonary hypertension, and 3 — to compare BNP andecho values with invasivemeasurement to establish the exact correlationwith PH, deﬁned as PAP mean N 25 mm Hg.Patients' characteristics: 109 patients (age 62 + 11; 46 males)fulﬁlled the inclusion criteria. ILD diagnoses included: idiopathic pulmo-nary ﬁbrosis (IPF; n = 72), sarcoidosis (n = 15), systemic sclerosis(n = 4), extrinsic allergic alveolitis (EAA; n = 2), smoking-related inter-stitial lung disease or drug-related interstitial ﬁbrosis (n = 15) andLangerhans' cell histiocytosis (n = 1). Among these patients there were43 subjects with PAPs ≥ 40 mm Hg. All patients with PAPs N 40 mm Hgunderwent RC to measure invasive parameters PAPs, PAP mean,WEDGE pressure and PVR. Of 43 catheterized patients, 34 showed PH,deﬁned as PAP mean N 25 mm Hg. BNP mean in all population was of63 pg/mL [CI: 32–96] (Table 1).Table 1Baseline characteristics of all patients with ILD included in our study. Abbreviations: BNP:B-type natriuretic peptide; FE: Ejection fraction; ILD: Interstitial lung disease; PAPd: End-diastolic pulmonary arterial pressure; PAPs: Pulmonary systolic arterial pressure; PAPm:Pulmonary arterial pressure mean; PVR: Pulmonary vascular resistance; TAPSE: Tricuspidannular plane systolic excursion.Number of the patients 109Age (year) 63 ± 11Weight (Kg) 77 ± 14Height (cm) 168 ± 11Gender (n)Male 57Female 52Risk factors and comorbidity (%)Hypertension 26%Diabetes 49%Dyslipidemia 32%Osteoporosis 76%Interstitial lung disease (n)Pulmonary idiopathic ﬁbrosis 72Sarcoidosis 15Extrinsic allergic alveolitis 4Systemic sclerosis 2Langherans cell hystiocytosis 1Other 15Lung diseases' treatment (%)Corticosteroids therapy 94Immunosuppressive therapy 17Echocardiographic parametersFE (%) 55 ± 3End-diastolic ventricular diameter (mm) 36 ± 7Right atrium area (cm2) 20 ± 3Caliber inferior cave vein (mm) 17 ± 5PAPs (mm Hg) 37 ± 12PAPs ≥ 40 mm Hg (n) 43PAP mean (mm Hg) 18 ± 7PAP mean ≥ 20 mm Hg (n) 29TAPSE (mm) 22 ± 3TAPSE ≤ 20 mm (n) 31Invasive Measurements (43 patients)PAPs (mm Hg) 45 ± 14PAP m (mm Hg) 25 ± 10WEDGE pressure (mm Hg) 12 ± 5PVR (hru) 3,21 ± 2.20Pulmonary hypertension deﬁned as invasive PAPmean ≥ 25 mm Hg (n)34BNP (pg/mL) 63 [32–96]Fig. 1. Receiver operating characteristic (Roc) curve analysis in predicting patients withPH. Logistic regression analysis evaluating ability of echocardiographic parameters (PAPsand PAP mean) and BNP to detect PH. Abbreviations: AUC: Area under the curve; BNP:B-type natriuretic peptide; CI: Conﬁdence interval; PAPs: Pulmonary systolic arterial pres-sure; PAPm: Pulmonary arterial pressuremean; PH: Pulmonary hypertension; TAPSE: Tri-cuspid annular plane systolic excursion.35A. Palazzuoli et al. / International Journal of Cardiology 178 (2015) 34–36In patients with PAPs N 40 mm Hg BNP levels were signiﬁcantly in-creased compared to patients without pulmonary hypertension(162 ± 96 vs 18 ± 7 pg/ml p = 0,004), PAPd N 20 mm Hg (205 ±118 vs 38 ± 19 pg/mL p = 0,001) and PAP mean b 25 mm Hg(128 ± 84 vs 33 ± 12 pg/ml p b 0.001). BNP was also signiﬁcantlyincreased in patients with right ventricular dysfunctionTable 2T-test evaluating BNP value changes relation to echocardiographic and invasive parameters. Absure; PAPs: Pulmonary systolic arterial pressure; PAPm: Pulmonary arterial pressure mean; TAAll patients (109)Echocardiographic parameters BNP mean (pg/mL) EchocaPAPs b 40 mm Hg 18 ± 7 PAPs ≥PAPd b 20 mm Hg 39 ± 19 PAPd ≥PAP mean b 25 mm Hg 33 ± 12 PAP meEnd diastolic diameter b 38 mm 36 ± 24 End diaTAPSE N 16 mm 21 ± 13 TAPSECatheterized patients (43)Invasive measurement BNP mean (pg/mL) InvasivPAPs b 40 mm Hg 39 ± 17 PAP ≥PAP mean b25 mm Hg 25 ± 18 PAP meWEDGE pressure b 14 mm Hg 43 ± 31 WEDGE(TAPSE b 16mm) (153±104 vs 21±13 pg/ml p b 0.001) and dilatationof RV (end-diastolic diameter ≥ 38 mm) (179 ± 115 vs 36 ± 24 pg/mlp b 0.001).In patients with invasive PAPs N 40 mm Hg and with invasive PAPmean N25 mm Hg, (n. 34) BNP levels were signiﬁcantly increased re-spect patients with invasive PAPs b 40 mm Hg (169 ± 110 vs 39 ±17 pg/ml p b 0,02) and with invasive PAP mean b 25 mm Hg (206 ±127 vs 25 ± 18 pg/ml p b 0.005). In patients with WEDGEpressure ≥ 14 mm Hg, BNP levels were signiﬁcantly higher thanpatients with WEDGE pressure b 14 mm Hg (207 ± 151 vs 43 ±31 pg/mL; p = 0.01) (Table 2).Diagnostic prediction for PH: The Roc curve analysis showed thatBNP (AUC 0.87; [CI: 0.77–0.98]; p = 0.001), PAP mean (AUC 0.89; [CI:0.80–0.98]; p = 0.001) and PAPs (AUC 0.81; [CI: 0.76–0.98]; p =0.001)were all able to detect PH. A cut-off BNP value≥ 50 pg/ml, recog-nized patients with PH, with good sensitivity (77%) and good speciﬁcity(81%) (Fig. 1). Regression analysis of the above parameters conﬁrmedthat echocardiographic measurements (PAPs, PAP mean and TAPSE)and BNP values were signiﬁcantly related (Table 3).Early detection of PH in patients with ILD is determinative to bet-ter establish prognostic impact of lung disease and to begin a speciﬁctreatment. The current European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines recommend annualechocardiographic screening in symptomatic patients [10]. Our studybreviations: BNP: B-type natriuretic peptide; PAPd: End-diastolic pulmonary arterial pres-PSE: Tricuspid annular plane systolic excursion.rdiographic parameters BNP mean (pg/mL) p-Values40 mm Hg 162 ± 96 0.00420 mm Hg 205 ± 118 0.001an ≥ 25 mm Hg 128 ± 84 0.001stolic diameter ≥ 38 mm 179 ± 115 0.001≤ 16 mm 153 ± 104 0.001e measurement BNP mean (pg/mL) p-Values40 mm Hg 169 ± 110 0.02an ≥ 25 mm Hg 206 ± 127 0.005pressure ≥ 14 mm Hg 207 ± 151 0.01Table 3Logistic regression analysis evaluating ability of echocardiographic parameters (PAPs,PAPm and TAPSE) and BNP to detect PH. Abbreviations: BNP: B-type natriuretic peptide;CI: Conﬁdence interval; OR: Odds ratio; PAPs: Pulmonary systolic arterial pressure; PAPm:Pulmonary arterial pressure mean; PH: Pulmonary hypertension; TAPSE: Tricuspid annu-lar plane systolic excursion.OR [CI] p-ValueBNP N 50 pg/mL 11.53 [3.61–24.87] 0.001PAPs ≥ 40 mm Hg 22.13 [4.47–42.17] 0.003PAP mean ≥ 25 mm Hg 10.07 [1.17–28.24] 0.04TAPSE ≤ 16 mm 6.71 [1.72–18.15] 0.00636 A. Palazzuoli et al. / International Journal of Cardiology 178 (2015) 34–36is the ﬁrst attempt to evaluate the diagnostic role of echocardiographyand BNP levels in patients with ILD and associated PH. Our ﬁndingsshowed that BNP is signiﬁcantly correlated to echo-Doppler measure-ment, particularly those patients with signs of PH or RV dysfunctionevidenced higher BNP values when compared with patients who expe-rienced normal pressure and RV function. The logistic regression analy-sis demonstrated that a cutoff of 50 pg/ml for BNP had a good sensibilityand speciﬁcity to recognize subjects with PH. The current non-invasivedata have been validated in the subgroup submitted to right heart cath-eterization (n = 43) after echocardiographic screening. In these pa-tients we demonstrated a good correlation between non-invasive andinvasive pressure assessments conﬁrming the role of BNP in the detec-tion of moderate PAP increase. All together our ﬁndings summarizedprevious reports showing that BNP is a good diagnostic indicator forPH in ILD. Echocardiographywhen used in patientswith a good acousticwindow is a reliable tool to measure PAP and early recognize PH.Recently a good correlation between hemodynamic and echocardio-graphic measurements has been evidenced in the current setting [11]conﬁrming our results. Therefore an algorithm considering laboratoryand echomeasurement could help in the identiﬁcation of those patientswith ILD affected with moderate PH.BNP has also demonstrated a prognostic impact in patients with ILDinmore recent studies: in an oriental population Song et al. [12] showedthat a combination of BNP level and PAPs measured by echocardiogra-phy may provide a better prediction of mortality than either parameteralone. In another study Corte et al. [13] demonstrated the prognosticvalue of BNP and echocardiography over the ILD population as awhole, independently of the underlying disease severity. Elevated BNPconcentration and pulmonary vascular resistance levels were linked toincreased mortality across ILD patients.Our data suggest that BNP levels and echocardiography are clinicallyuseful and easily repeatable tools for mild PH detection in patients withILD. If our preliminary results will be conﬁrmed in a larger population,an algorithm including echocardiographic measurements associatedwith a BNP cutoff N 50 pg/ml should be applied in clinical practice as apreliminary screening for invasive hemodynamic study selection.AcknowledgmentThe authors of this manuscript have certiﬁed that they comply withthe Principles of Ethical Publishing in the International Journal ofCardiology.References[1] A.S. Maisel, P. Krishnaswamy, R.M. Nowak, J. McCord, J.E. Hollander, P. Duc, T.Omland, A.B. Storrow, W.T. Abraham, A.H. Wu, P. Clopton, P.G. Steg, A. Westheim,C.W. Knudsen, A. Perez, R. Kazanegra, H.C. Herrmann, P.A. McCullough, Rapid mea-surement of B-type natriuretic peptide in the emergency diagnosis of heart failure.Breathing Not Properly Multinational Study Investigators, N. Engl. J. Med. 347(2002) 161–167.[2] P. Pruszczyk, N-terminal pro-brain natriuretic peptide as an indicator of right ven-tricular dysfunction, J. Card. 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Combined BNP and Echocardiographic assessment in interstitial lung disease for
pulmonary hypertension detection

Alberto Palazzuoli

Gaetano Ruocco

Behar Cekorja

Marco Pellegrini

Gabriele Del Castillo

Ranuccio Nuti

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International Journal of Cardiology

Combined BNP and Echocardiographic assessment in interstitial lung disease for pulmonary hypertension detection

https://usiena-air.unisi.it/retrieve/handle/11365/973690/19658/palazzuoli%202015%20int%20j%20card.pdf

Combined BNP and Echocardiographic assessment in interstitial lung disease for

pulmonary hypertension detection

Combined BNP and Echocardiographic assessment in interstitial lung disease for pulmonary hypertension detection

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