clinical study n-terminal probnp levels and tissue doppler echocardiography...

Hindawi Publishing CorporationISRN PediatricsVolume 2013 Article ID 970394 7 pageshttpdxdoiorg1011552013970394

Clinical StudyN-Terminal proBNP Levels and Tissue DopplerEchocardiography in Acute Rheumatic Carditis

Alyaa A Kotby Ghada S El-Shahed Ola A ElmasryIman S El-Hadidi and Rowaida N S El Shafey

Faculty of Medicine Pediatric Department Ain Shams University Abbasseya Square Cairo 11566 Egypt

Correspondence should be addressed to Ola A Elmasry o elmasryhotmailcom

Received 31 May 2013 Accepted 3 July 2013

Academic Editors V M Di Ciommo and G D Overturf

Copyright copy 2013 Alyaa A Kotby et alThis is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Background Rheumatic heart disease (RHD) is a leading cause of heart failure in children and young adults worldwide B-typenatriuretic peptide (BNP) is a usefulmarker of critical pediatric heart disease and its N-terminal peptide NT-proBNP is elevated incongenital and acquired heart disease in childrenAim Tomeasure NT-proBNP levels as a marker of carditis in children with acuterheumatic carditis as compared to children with quiescent RHD and healthy controlsMethods 16 children with acute rheumaticcarditis 33 children with quiescent RHD and a cohort of 30 healthy children were studied Transthoracic echocardiography wasperformed to assess valve and cardiac function Tissue Doppler echocardiography was performed for EE1015840 (ratio between mitralinflowEwave and lateralmitral annulus E1015840 wave) and systolic strainResults NT-proBNP levels were significantly higher in childrenwith acute rheumatic carditis and dropped with its resolution Strain and EE1015840 values were comparable among the three groupsConclusion NT-proBNP is significantly elevated in children with acute rheumatic carditis in the acute stage compared to childrenwith quiescent RHD and healthy subjects in the presence of comparable echocardiographic indices of LV systolic and diastolicfunction

1 Introduction

Acute rheumatic fever (ARF) and rheumatic heart disease(RHD) continue to be a major health problem in developingcountries and RHD is the leading cause of heart failure inchildren and young adults worldwide resulting in disabilityand premature death [1] 80ndash85 of children younger than 15years live in areas where rheumatic heart disease is endemic[2]

Late diagnosis is prejudicial since a bout of ARF is atherapeutic emergency While polyarthritis is the initial andmost common major manifestation carditis is the mostserious manifestation of ARF [3] and occurs in around ahalf of patients [4ndash9] within 3 weeks of onset of ARF [3]Although the initial attack can lead to severe valvular diseaseARFmight be insidious at onset and RHDmost often resultsfrom cumulative valve damage due to recurrent episodes ofARF with a paucity of clinical symptoms [1 10 11] Giventhat the efficacy and safety of antibiotic prophylaxis are wellestablished and should lead to near complete eradication of

advanced RHD when combined with broader changes suchas improved living conditions education and awareness [12ndash14] early detection of acute rheumatic carditis will allowappropriate initiation of secondary prophylaxis

No diagnostic method exists that detects onset of carditisprior to appearance of full-blown clinical or echocardio-graphic abnormalities [3] The Jones criteria introduced in1944 are clinical guidelines for the diagnosis of ARF andcarditis and since then other criteria have been put forwardto increase sensitivity and encourage investigators to stan-dardise patientsrsquo characteristics [10 15 16] However 80 yearson in the absence of any pathognomonic laboratoryimagingtest that can establish diagnosis ARF and acute rheumaticcarditis continue to be a clinical diagnosis Additionally ARFcriteria do not exclude other causes of febrile polyarthritiswhich still need to be considered in the differential diagnosis[3] adding further confusion and doubt to the final diagnosis

In 2012 the World Heart Federation published updatedcriteria for echocardiographic diagnosis of RHD Howeverthese guidelines are not intended for the diagnosis of carditis

2 ISRN Pediatrics

in the setting of ARF Whilst echocardiography is valuablein confirming established valve disease the assessment of itsseverity and screening for valve disease in geographic loca-tions with a high prevalence of RHD [17] its role in detectionof early carditis in a first episode of ARF or in establishedRHD is not as well established

Brain-type natriuretic peptide (BNP) a member of thenatriuretic peptide family is produced in cardiac myocytesand secreted into the circulation in response to cardiacvolume load causing diuresis natriuresis and vasodilatationas well as inhibition of the renin-aldosterone system andsympathetic activity [18] BNP is produced as a prohormonethat is cleaved in the circulation into active BNP and theN-terminal peptide NT-proBNP [19] Both can be assayedbut NT-proBNP has a longer plasma half-life and higherplasma concentrations [20] and therefore can give a goodestimate of BNP production NT-proBNP level was found tobe elevated in children with congenital and acquired heartdisease resulting in left and right ventricular volume andorpressure overload with the highest levels found in patientswith acute LV dysfunction due to acute myocarditis andacute cardiomyopathy while patients with chronic dilatedcardiomyopathy and those with low pressure left to rightshunt tended to have the lowest levels [21] Circulating NT-proBNP levels were also found to be significantly associatedwith themitral valve score in patients with chronic rheumaticvalve disease and significantly correlated with worseningfunctional class [22]

Recently normal values for NT-proBNP concentrationsin a large cohort of healthy 8-year-old school children fol-lowed over a 4-year period have been published [23]

11 Aim of the Study The present study was designed to eval-uate plasma NT-proBNP as a marker of carditis in patientswith acute rheumatic fever as compared to controlled quies-cent RHD and healthy controls

2 Patients and Methods

This prospective follow-up study was performed over a 2-year periodThe studywas ethically approved by the PediatricDepartment and consent was obtained from the all childrenand their parentscarers before enrollment Seventy-ninechildren were studied in 3 groups 16 patients with acuterheumatic carditis who were studied during the acute phaseof their illness and after its resolution 33 patients with knownRHD not in activity (quiescent RHD disease control group)and a cohort of 30 healthy children as a healthy control group

The diagnosis of acute rheumatic carditis was based onthe Jones criteria ARF was diagnosed when two major orone major and two minor manifestations plus evidence ofpreceding GAS infection were present Carditis was definedas the presence of a newmurmur pericardial rub tachycardiaout of proportion to fever gallop rhythmcardiomegaly recur-rent arrhythmia andor congestive heart failureWe excludedpatients with infective endocarditis and children who hadundergone previous surgical valve repair or replacement ofcardiac valves

All study candidates underwent a thorough medicalhistory physical examination routine investigations (FBCESR CRP and ASOT) 12-lead ECG and plain chest X-rayEnzyme immunoassay of plasma NT-proBNP (BiomedicaGruppe httpwwwbmgrpcom) was performed on venousblood samples

Transthoracic echocardiography examination (GE med-ical systemmdashVIVID7 Dimension N-3190mdashHorten Norway)for all study participants included M-mode measurementsLV end-diastolic and end-systolic volumes ejection frac-tion (biplane modified Simpson method) assessment of thedegree of mitral regurgitation and aortic regurgitation bycolour flow Doppler and mitral inflow velocities Pulsedwave tissue Doppler echocardiography was also performedand EE1015840 calculated Peak systolic strain and time to peaksystolic strain were measured at the left ventricle lateralseptal anterior and inferior walls at basal and mid level andthe mean values were calculated

21 Statistical Analysis Data were collected and analyzedusing Studentrsquos 119905-test andMann-Whitney test for comparisonof parametric and nonparametric data respectively andPearson and Spearmanrsquos tests for detection of correlations inparametric and nonparametric data respectively The per-formance of NT pro-BNP as a predictor of acute rheumaticcarditis and the optimal cut-off level were assessed by theROC curve A 119875 value of less than 005 was consideredsignificant

3 Results

The demographic clinical features routine laboratory datamedical treatment and type and severity of valve lesions ofthe three studied groups are shown in Table 1 In group A12 patients had recurrent acute rheumatic carditis while 7patients were in their first presentation of acute rheumaticcarditis Eleven patients in the acute rheumatic carditis group(69) were in NYHAClasses III and IV compared to none ofthe quiescent RHD group All patients with acute rheumaticfever were treated with oral prednisone and salicylates and3 patients received packed RBC transfusions for associatedanaemia

31 Echocardiography Fractional shortening and ejectionfraction were not significantly different between groups (119875 gt005) Patients in acute rheumatic carditis had signifi-cantly higher end-diastolic volumes and end-systolic volumes(Figure 1) Following resolution of the acute carditis thevalues of EDV and ESV dropped but this was not statisticallysignificant (Figure 2)

The EE1015840 (ratio between the Doppler mitral inflow Ewave(cmsec) and the PWTDI lateral mitral annulus E1015840 wave(cmsec)) was significantly increased in the acute carditisgroup (107 plusmn 53) and quiescent RHD group (76 plusmn 42)compared to controls (52 plusmn 17) (119875 lt 001)

There was no difference in systolic strain or time topeak systolic strain among the three different groups in thedifferent measured segments or between the mean strain and

ISRN Pediatrics 3

Table 1 Data of the studied groups

Variable Acute rheumatic carditis 119899 = 16 Quiescent RHD 119899 = 33 Control group 119899 = 30Age (yrs)

Mean plusmn SD (range) 1256 plusmn 19 (80ndash15) 123 plusmn 273 (60ndash16) 119 plusmn 29 (60ndash16)Males119899 10 18 17

Weight (Kg)Mean plusmn SD (range) 415 plusmn 16 (25ndash85) 399 plusmn 158 (20ndash70) 342 plusmn 127 (17ndash55)

Height (cm)Mean plusmn SD (range) 1457 plusmn 122 (125ndash163) 142 plusmn 154 (109ndash171) 1381 plusmn 188 (107ndash19)

NYHAI 4 24 0II 1 9 0III 3 0 0IV 8 0 0

Arthritis 12 0 0Chorea 2 0 0Medications

Furosemide 12 5 0Spironolactone 4 0 0Digoxin 10 4 0Captopril 10 15 0Haloperidol 2 0 0Prednisolone 16 0 0Acetyl salicylic acid 16 0 0

Valve lesionsIsolated MR 4 18 0Isolated AR 1 0 0MR and AR 11 15 0Severe MS 0 2 0

Severity of valve lesionsMR

Mild 3 23 0Moderate 7 9 0Severe 5 1 0

ARMild 7 10 0Moderate 3 5 0Severe 2 0

Pericardial effusion 11 1 0Mean LV strain ()

Mean plusmn SD (range) 209 plusmn 86 (12ndash49) 22 plusmn 3 (14ndash28) 21 plusmn 34 (17ndash277)Mean LV time to peak strain (sec)

Mean plusmn SD (range) 03 plusmn 005 (014ndash036) 032 plusmn 002 (031ndash035) 032 plusmn 001 (03ndash037)NT-proBNP (fmolmL)

Mean plusmn SD (range) 420 plusmn 223 (130ndash950) 247 plusmn 1064 (65ndash650) 116 plusmn 37 (65ndash200)Abbreviations BSA body surface area NT-proBNP N-terminal pro-brain-type natriuretic peptide NYHA New York Heart Association functional classRBCs red blood cells RF rheumatic fever SD standard deviation WBCs white blood cells

4 ISRN Pediatrics

142

607 58

832

37553553

24

538

0

25

50

75

100

125

150

EDV (mL) ESV (mL) EF ()

Group AGroup BControl

Figure 1 2D echocardiographic data Patients in acute rheumaticcarditis (Group A) had significantly higher EDV than both patientswith quiescent RHD (Group B) (119875 lt 001) and controls (119875 lt 0001)and significantly higher ESV than controls (119875 lt 0001)

142

606 58

104

49 52

0

20

40

60

80

100

120

140

160


Group AGroup Ap

Figure 2 2D echocardiographic data of patients with acute carditis(Group A) during and after resolution (Group Ap) of acute carditisThe drop in values for all 3 parameters was not statistically signifi-cant (119875 gt 005)

time to peak strain of all studied 8 LV segments in the 3 groups(119875 gt 005) (Figure 3)

32 NT-proBNP Values Patients in acute rheumatic carditishad significantly higher NT-proBNP values than patientswith quiescent RHD and controls (119875 lt 0001) Similarlypatients with quiescent RHD had significantly higher NT-proBNP values than controls (119875 lt 0001) (Table 1 Figure 4)There was no significant difference in NT-proBNP levelsbetween patients with acute rheumatic carditis presenting intheir first attack and those with recurrent rheumatic carditis(119875 gt 005)

We found a significant positive correlation between NTproBNP levels and EE1015840 ratio (119903 = 0308 119875 lt 005) EDV(119903 = 055 119875 lt 0001) and ESV (119903 = 057 119875 lt 0001)

Following resolution of the acute rheumatic carditismean plasma NT-proBNP levels dropped (1746 plusmn 65 fmolmL 119875 lt 0001) but was still significantly higher than the

control group (119875 lt 0001) An NT-proBNP plasma levelof 265 fmolmL had a sensitivity of 93 and a specificityof 929 in detecting acute carditis in patients with acuterheumatic fever using the ROC curve The area under thecurve was 0978 (Figure 5)

4 Discussion

NT-proBNP was significantly increased in children withacute rheumatic carditis compared both to children with qui-escent RHDandhealthy controlsMany of these patientswerein heart failure (NYHA class II-IV) secondary to rheumaticcarditis and worsening valve lesions with resultant volumeoverload as evidenced by significantly increased EDV andESV NT-proBNP levels dropped significantly after resolutionof the acute carditis and improvement of heart failure andvolume overload secondary to treatment Natriuretic peptidelevels are known to be reduced by treatment [24]

Similar to other studies the various conventional echo-cardiographic parameters measured in this study did nothelp to differentiate between acute rheumatic carditis andestablished chronic rheumatic heart disease without carditisClinical studies using spectral tissue Doppler for recordingmitral annular velocities have produced convincing evidenceof a positive linear relation of EE1015840 with invasively deter-mined mean LV diastolic pressure regardless of LV ejectionfraction rhythm and heart rate [25ndash27] In our patientsthere was no evidence of diastolic dysfunction as evidencedbetween the lack of any significant difference between patientgroups and controls in measured EE1015840

LV strain has been hailed as a very sensitive and volume-independentmodality for assessment ofmyocardial functionStrain imaging has been used to assessmyocardial function ina wide range of cardiac conditions It is useful in detectingearly left ventricular (LV) dysfunction in the setting ofsystemic diseases with cardiac involvement in differentiatingtransmural from nontransmural infarction and in identifyingLV contractile reserve in regurgitant valve lesions [28] Therewas no significant difference in measured LV strain amongstour patient groups and in comparison to the control groupThe echocardiographic data in our patients suggests thatrheumatic myocarditis reflected as impaired diastolic andorsystolic function is not apparent in this patient group andthat the elevated NT-proBNP was due to uncontrolled heartfailure as a consequence of the entire ldquopancarditisrdquo processof which rheumatic valve affection was probably the majorcontributor The improvement of said process was associatedwith a decline in NT-proBNP

Measurement of natriuretic peptides used in conjunctionwith other clinical information has been proven useful asa diagnostic marker to aid in the recognition of pediatriccritical heart disease in the acute care setting [29] Rheumaticcarditis occurs a few weeks after the initial infection inabout 50 of patients with acute rheumatic fever andpresents as valvulitis sometimes combined with pericarditisor myocarditis [6 30] Given the results of the current studyNT-proBNP assay might be a useful adjunct to the diagnosisof rheumatic carditis in patients presenting with noncardiacsigns of rheumatic fever Baseline levels at initial presentation

ISRN Pediatrics 5

Basal segments

Mid segments

Acute carditis Controls

Acute carditis

Anterior wallS = 237 plusmn 163



Sept

al w

all

S=275plusmn14

Sept

al w

all

S=207plusmn75

Sept

al w

all

S=225plusmn76

Inferior wallS = 166 plusmn 57



Late

ral w

all

S=233plusmn15

Quiescent RHD


Sept

al w

all

S=228plusmn52


Late

ral w

all

S=192plusmn5

Late

ral w

all

S=174plusmn04

Quiescent RHD


Sept

al w

all

S=26plusmn107


Late

ral w

all

S=20plusmn74

Controls


Sept

al w

all

S=259plusmn58


Late

ral w

all

S=22plusmn77

Late

ral w

all

S=186plusmn74

Figure 3 Peak systolic strain in the basal and mid segments of the LV anterior inferior lateral and septal walls in the 3 studied groups

ControlQuiescent RHDAcute carditis

1000

800

600

400

200

0

128200

350

NT-

proB

NP

(fmol

mL)

Figure 4 Comparison of plasma NT proBNP in studied groupsBoxes show median and interquartile ranges (IQR) between the25th and the 75th percentiles The horizontal line inside the boxrepresents the median and I bars (lines) represent the highest andlowest values (range of concentrations) The small closed squaresrepresent extreme values (more than 3 IQR) and small open circlesrepresent the outlier values (between 15 and 3 IQR)

followed by weekly serial measurements may help detect theearly onset of carditis in patients before the emergence of themore florid clinical signs of carditis

We found that a cut-off level of 265 fmolmL had areasonable high sensitivity and specificity for detecting acutecarditis in the setting of RF and RHD however there waswide overlap inNT-proBNP values between the acute carditisgroup and the quiescent RHD group Whilst elevated NT

08060402001-specificity

10

08

06

04

02

00

Sens

itivi

ty

Figure 5 Receiver-operating characteristic (ROC) curve for plasmaNT-proBNP in the diagnosis of acute rheumatic carditis The areaunder the curve was 0978 A cut of value of 265 fmolmL hasa sensitivity of 93 and specificity of 929 in detecting acuterheumatic carditis

proBNP might also be a consequence of worsening mechan-ical heart failure or complicating infective endocarditis in apatient with established rheumatic valvular disease it couldpotentially be highly suggestive of acute carditis in patientswithout history of rheumatic heart disease but presentingwith one of the major noncardiac criteria of rheumatic fever

6 ISRN Pediatrics

Given the paucity of investigations that detect earlycarditis in this patient population the absence of any specificechocardiographic findings prior to onset of valve regurgita-tion and the potential value of treatment in early rheumaticcarditis [31] this can prove to be a valuable objective investi-gation to be added to the Jones criteria

References

[1] J R Carapetis A C Steer E K Mulholland and M WeberldquoThe global burden of group A streptococcal diseasesrdquo TheLancet Infectious Diseases vol 5 no 11 pp 685ndash694 2005

[2] Population Reference Bureau ldquoworld population data sheetrdquo2008 httpwwwprborgPublicationsDatasheets20082008wpdsaspx

[3] C Weil-Olivier ldquoRheumatic fever Orphanet encyclopediardquo2004 httpwwworphanetdatapathoGBuk-RFpdf

[4] Z M A Meira E M A Goulart E A Colosimo and C C CMota ldquoLong term follow up of rheumatic fever and predictorsof severe rheumatic valvar disease in Brazilian children andadolescentsrdquo Heart vol 91 no 8 pp 1019ndash1022 2005

[5] A M Caldas M T R A Terreri V A Moises et al ldquoWhatis the true frequency of carditis in acute rheumatic fever Aprospective clinical and doppler blind study of 56 children withup to 60 months of follow-up evaluationrdquo Pediatric Cardiologyvol 29 no 6 pp 1048ndash1053 2008

[6] S K Sanyal M KThapar and S H Ahmed ldquoThe initial attackof acute rheumatic fever during childhood in North India Aprospective study of the clinical profilerdquo Circulation vol 49 no1 pp 7ndash12 1974

[7] P Vardi W Markiewicz and Y Weiss ldquoClinical-echocar-diographic correlations in acute rheumatic feverrdquo Pediatricsvol 71 no 5 pp 830ndash834 1983

[8] R S Vasan S Shrivastava M Vijayakumar R Narang B CLister and J Narula ldquoEchocardiographic evaluation of patientswith acute rheumatic fever and rheumatic carditisrdquo Circulationvol 94 no 1 pp 73ndash82 1996

[9] F E Figueroa P Valdes F Carrion et al ldquoProspective compar-ison of clinical and echocardiographic diagnosis of rheumaticcarditis long term follow up of patients with subclinicaldiseaserdquo Heart vol 85 no 4 pp 407ndash410 2001

[10] J R Carapetis M McDonald and N J Wilson ldquoAcuterheumatic feverrdquo The Lancet vol 366 no 9480 pp 155ndash1682005

[11] K SliwaM Carrington BMMayosi E Zigiriadis RMvungiand S Stewart ldquoIncidence and characteristics of newly diag-nosed rheumatic heart disease in Urban African adults insightsfrom the Heart of Soweto Studyrdquo European Heart Journal vol31 no 6 pp 719ndash727 2010

[12] M Markowitz E Kaplan R Cuttica et al ldquoAllergic reactionsto long-term benzathine penicillin prophylaxis for rheumaticfeverrdquoThe Lancet vol 337 no 8753 pp 1308ndash1310 1991

[13] P Nordet R Lopez A Duenas and L Sarmiento ldquoPreventionand control of rheumatic fever and rheumatic heart disease theCuban experience (1986ndash1996ndash2002)rdquo Cardiovascular Journalof Africa vol 19 no 3 pp 135ndash140 2008

[14] A Arguedas and E Mohs ldquoPrevention of rheumatic fever inCosta Ricardquo Journal of Pediatrics vol 121 no 4 pp 569ndash5721992

[15] National Heart Foundation of Australia and the Cardiac Societyof Australia and New Zealand ldquoDiagnosis and management

of acute rheumatic fever and rheumatic heart disease inAustralia an evidence-based reviewrdquo 2006 httpwwwheart-foundationorgauSiteCollectionDocumentsDiagnosis-Man-agement-Acute-Rheumatic-Feverpdf

[16] J R Carapetis J Paar and T Cherian ldquoStandardization of epi-demiologic protocols for surveillance of post-streptococcal se-quelae acute rheumatic fever rheumatic heart disease and acutepost-streptococcal glomerulonephritisrdquo 2006 httpwwwniaidnihgovtopicsstrepThroatDocumentsgroupasequelaepdf

[17] B Remeanyi NWilson A Steer et al ldquoWorldHeart Federationcriteria for echocardiographic diagnosis of rheumatic heartdisease-an evidence-based guidelinerdquo Nature Reviews Cardiol-ogy vol 9 no 5 pp 297ndash309 2012

[18] E A Espiner A M Richards T G Yandle and M G NichollsldquoNatriuretic hormonesrdquo Endocrinology and Metabolism Clinicsof North America vol 24 no 3 pp 481ndash509 1995

[19] A Luchner T L Stevens D D Borgeson et al ldquoDifferentialatrial and ventricular expression of myocardial BNP duringevolution of heart failurerdquo American Journal of Physiology vol274 no 5 pp H1684ndashH1689 1998

[20] R J Rodeheffer ldquoMeasuring plasma B-type natriuretic peptidein heart failure good to go in 2004rdquo Journal of the AmericanCollege of Cardiology vol 44 no 4 pp 740ndash749 2004

[21] A Nir B Bar-Oz Z Perles R Brooks A Korach and A J JT Rein ldquoN-terminal pro-B-type natriuretic peptide referenceplasma levels from birth to adolescence Elevated levels atbirth and in infants and children with heart diseasesrdquo ActaPaediatrica International Journal of Paediatrics vol 93 no 5pp 603ndash607 2004

[22] V Davutoglu A Celik M Aksoy Y Sezen S Soydinc and NGunay ldquoPlasma NT-proBNP is a potential marker of diseaseseverity and correlates with symptoms in patients with chronicrheumatic valve diseaserdquo European Journal of Heart Failure vol7 no 4 pp 532ndash536 2005

[23] G Koerbin W P Abhayaratna J M Potter S Apostoloska RD Telford and P E Hickman ldquoNTproBNP concentrations inhealthy childrenrdquo Clinical Biochemistry vol 45 pp 1158ndash11602012

[24] A Maisel C Mueller K Adams Jr et al ldquoState of the art usingnatriuretic peptide levels in clinical practicerdquo European Journalof Heart Failure vol 10 no 9 pp 824ndash839 2008

[25] S R Ommen R A Nishimura C P Appleton et al ldquoClin-ical utility of Doppler echocardiography and tissue Dopplerimaging in the estimation of left ventricular filling pressuresa comparative simultaneous Doppler-catheterization studyrdquoCirculation vol 102 no 15 pp 1788ndash1794 2000

[26] L Sundereswaran S F Nagueh S Vardan et al ldquoEstima-tion of left and right ventricular filling pressures after hearttransplantation by tissue doppler imagingrdquoAmerican Journal ofCardiology vol 82 no 3 pp 352ndash357 1998

[27] C Bruch M Grude J Muller G Breithardt and T WichterldquoUsefulness of tissueDoppler imaging for estimation of left ven-tricular filling pressures in patients with systolic and diastolicheart failurerdquo American Journal of Cardiology vol 95 no 7 pp892ndash895 2005

[28] D Y Leung and A C T Ng ldquoEmerging clinical role of strainimaging in echocardiographyrdquoHeart Lung and Circulation vol19 no 3 pp 161ndash174 2010

[29] K O Maher H Reed A Cuadrado et al ldquoB-type natriureticpeptide in the emergency diagnosis of critical heart disease inchildrenrdquo Pediatrics vol 121 no 6 pp e1484ndashe1488 2008

ISRN Pediatrics 7

[30] J Kamblock L Payot B Iung et al ldquoDoes rheumaticmyocardi-tis really exists Systematic study with echocardiography andcardiac troponin I blood levelsrdquo European Heart Journal vol24 no 9 pp 855ndash862 2003

[31] G V Herdy R S Gomes A E Silva L S Silva and V GLopes ldquoFollow-up of rheumatic carditis treated with steroidsrdquoCardiology in the Young vol 22 pp 263ndash269 2012

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2 ISRN Pediatrics

in the setting of ARF Whilst echocardiography is valuablein confirming established valve disease the assessment of itsseverity and screening for valve disease in geographic loca-tions with a high prevalence of RHD [17] its role in detectionof early carditis in a first episode of ARF or in establishedRHD is not as well established

Brain-type natriuretic peptide (BNP) a member of thenatriuretic peptide family is produced in cardiac myocytesand secreted into the circulation in response to cardiacvolume load causing diuresis natriuresis and vasodilatationas well as inhibition of the renin-aldosterone system andsympathetic activity [18] BNP is produced as a prohormonethat is cleaved in the circulation into active BNP and theN-terminal peptide NT-proBNP [19] Both can be assayedbut NT-proBNP has a longer plasma half-life and higherplasma concentrations [20] and therefore can give a goodestimate of BNP production NT-proBNP level was found tobe elevated in children with congenital and acquired heartdisease resulting in left and right ventricular volume andorpressure overload with the highest levels found in patientswith acute LV dysfunction due to acute myocarditis andacute cardiomyopathy while patients with chronic dilatedcardiomyopathy and those with low pressure left to rightshunt tended to have the lowest levels [21] Circulating NT-proBNP levels were also found to be significantly associatedwith themitral valve score in patients with chronic rheumaticvalve disease and significantly correlated with worseningfunctional class [22]

Recently normal values for NT-proBNP concentrationsin a large cohort of healthy 8-year-old school children fol-lowed over a 4-year period have been published [23]

11 Aim of the Study The present study was designed to eval-uate plasma NT-proBNP as a marker of carditis in patientswith acute rheumatic fever as compared to controlled quies-cent RHD and healthy controls

2 Patients and Methods

This prospective follow-up study was performed over a 2-year periodThe studywas ethically approved by the PediatricDepartment and consent was obtained from the all childrenand their parentscarers before enrollment Seventy-ninechildren were studied in 3 groups 16 patients with acuterheumatic carditis who were studied during the acute phaseof their illness and after its resolution 33 patients with knownRHD not in activity (quiescent RHD disease control group)and a cohort of 30 healthy children as a healthy control group

The diagnosis of acute rheumatic carditis was based onthe Jones criteria ARF was diagnosed when two major orone major and two minor manifestations plus evidence ofpreceding GAS infection were present Carditis was definedas the presence of a newmurmur pericardial rub tachycardiaout of proportion to fever gallop rhythmcardiomegaly recur-rent arrhythmia andor congestive heart failureWe excludedpatients with infective endocarditis and children who hadundergone previous surgical valve repair or replacement ofcardiac valves

All study candidates underwent a thorough medicalhistory physical examination routine investigations (FBCESR CRP and ASOT) 12-lead ECG and plain chest X-rayEnzyme immunoassay of plasma NT-proBNP (BiomedicaGruppe httpwwwbmgrpcom) was performed on venousblood samples

Transthoracic echocardiography examination (GE med-ical systemmdashVIVID7 Dimension N-3190mdashHorten Norway)for all study participants included M-mode measurementsLV end-diastolic and end-systolic volumes ejection frac-tion (biplane modified Simpson method) assessment of thedegree of mitral regurgitation and aortic regurgitation bycolour flow Doppler and mitral inflow velocities Pulsedwave tissue Doppler echocardiography was also performedand EE1015840 calculated Peak systolic strain and time to peaksystolic strain were measured at the left ventricle lateralseptal anterior and inferior walls at basal and mid level andthe mean values were calculated

21 Statistical Analysis Data were collected and analyzedusing Studentrsquos 119905-test andMann-Whitney test for comparisonof parametric and nonparametric data respectively andPearson and Spearmanrsquos tests for detection of correlations inparametric and nonparametric data respectively The per-formance of NT pro-BNP as a predictor of acute rheumaticcarditis and the optimal cut-off level were assessed by theROC curve A 119875 value of less than 005 was consideredsignificant

3 Results

The demographic clinical features routine laboratory datamedical treatment and type and severity of valve lesions ofthe three studied groups are shown in Table 1 In group A12 patients had recurrent acute rheumatic carditis while 7patients were in their first presentation of acute rheumaticcarditis Eleven patients in the acute rheumatic carditis group(69) were in NYHAClasses III and IV compared to none ofthe quiescent RHD group All patients with acute rheumaticfever were treated with oral prednisone and salicylates and3 patients received packed RBC transfusions for associatedanaemia

31 Echocardiography Fractional shortening and ejectionfraction were not significantly different between groups (119875 gt005) Patients in acute rheumatic carditis had signifi-cantly higher end-diastolic volumes and end-systolic volumes(Figure 1) Following resolution of the acute carditis thevalues of EDV and ESV dropped but this was not statisticallysignificant (Figure 2)

The EE1015840 (ratio between the Doppler mitral inflow Ewave(cmsec) and the PWTDI lateral mitral annulus E1015840 wave(cmsec)) was significantly increased in the acute carditisgroup (107 plusmn 53) and quiescent RHD group (76 plusmn 42)compared to controls (52 plusmn 17) (119875 lt 001)

There was no difference in systolic strain or time topeak systolic strain among the three different groups in thedifferent measured segments or between the mean strain and

ISRN Pediatrics 3






NYHAI 4 24 0II 1 9 0III 3 0 0IV 8 0 0











4 ISRN Pediatrics

142

607 58

832

37553553

24

538

0

25

50

75

100

125

150




142

606 58

104

49 52

0

20

40

60

80

100

120

140

160


Group AGroup Ap







4 Discussion





ISRN Pediatrics 5

Basal segments

Mid segments


Acute carditis




Sept

al w

all

S=275plusmn14

Sept

al w

all

S=207plusmn75

Sept

al w

all

S=225plusmn76




Late

ral w

all

S=233plusmn15

Quiescent RHD


Sept

al w

all

S=228plusmn52


Late

ral w

all

S=192plusmn5

Late

ral w

all

S=174plusmn04

Quiescent RHD


Sept

al w

all

S=26plusmn107


Late

ral w

all

S=20plusmn74

Controls


Sept

al w

all

S=259plusmn58


Late

ral w

all

S=22plusmn77

Late

ral w

all

S=186plusmn74



1000

800

600

400

200

0

128200

350

NT-

proB

NP

(fmol

mL)





10

08

06

04

02

00

Sens

itivi

ty



6 ISRN Pediatrics


References































ISRN Pediatrics 7








of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















ISRN Pediatrics 3






NYHAI 4 24 0II 1 9 0III 3 0 0IV 8 0 0











4 ISRN Pediatrics

142

607 58

832

37553553

24

538

0

25

50

75

100

125

150




142

606 58

104

49 52

0

20

40

60

80

100

120

140

160


Group AGroup Ap







4 Discussion





ISRN Pediatrics 5

Basal segments

Mid segments


Acute carditis




Sept

al w

all

S=275plusmn14

Sept

al w

all

S=207plusmn75

Sept

al w

all

S=225plusmn76




Late

ral w

all

S=233plusmn15

Quiescent RHD


Sept

al w

all

S=228plusmn52


Late

ral w

all

S=192plusmn5

Late

ral w

all

S=174plusmn04

Quiescent RHD


Sept

al w

all

S=26plusmn107


Late

ral w

all

S=20plusmn74

Controls


Sept

al w

all

S=259plusmn58


Late

ral w

all

S=22plusmn77

Late

ral w

all

S=186plusmn74



1000

800

600

400

200

0

128200

350

NT-

proB

NP

(fmol

mL)





10

08

06

04

02

00

Sens

itivi

ty



6 ISRN Pediatrics


References































ISRN Pediatrics 7








of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















4 ISRN Pediatrics

142

607 58

832

37553553

24

538

0

25

50

75

100

125

150




142

606 58

104

49 52

0

20

40

60

80

100

120

140

160


Group AGroup Ap







4 Discussion





ISRN Pediatrics 5

Basal segments

Mid segments


Acute carditis




Sept

al w

all

S=275plusmn14

Sept

al w

all

S=207plusmn75

Sept

al w

all

S=225plusmn76




Late

ral w

all

S=233plusmn15

Quiescent RHD


Sept

al w

all

S=228plusmn52


Late

ral w

all

S=192plusmn5

Late

ral w

all

S=174plusmn04

Quiescent RHD


Sept

al w

all

S=26plusmn107


Late

ral w

all

S=20plusmn74

Controls


Sept

al w

all

S=259plusmn58


Late

ral w

all

S=22plusmn77

Late

ral w

all

S=186plusmn74



1000

800

600

400

200

0

128200

350

NT-

proB

NP

(fmol

mL)





10

08

06

04

02

00

Sens

itivi

ty



6 ISRN Pediatrics


References































ISRN Pediatrics 7








of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















ISRN Pediatrics 5

Basal segments

Mid segments


Acute carditis




Sept

al w

all

S=275plusmn14

Sept

al w

all

S=207plusmn75

Sept

al w

all

S=225plusmn76




Late

ral w

all

S=233plusmn15

Quiescent RHD


Sept

al w

all

S=228plusmn52


Late

ral w

all

S=192plusmn5

Late

ral w

all

S=174plusmn04

Quiescent RHD


Sept

al w

all

S=26plusmn107


Late

ral w

all

S=20plusmn74

Controls


Sept

al w

all

S=259plusmn58


Late

ral w

all

S=22plusmn77

Late

ral w

all

S=186plusmn74



1000

800

600

400

200

0

128200

350

NT-

proB

NP

(fmol

mL)





10

08

06

04

02

00

Sens

itivi

ty



6 ISRN Pediatrics


References































ISRN Pediatrics 7








of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















6 ISRN Pediatrics


References































ISRN Pediatrics 7








of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















ISRN Pediatrics 7








of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of














