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Respiratory Medicine (2005) 99, 329–336

KEYWORDChronicthromboempulmonaryhypertensiPrimary puhypertensiPulmonaryhypertensiChestroentogen

0954-6111/$ - sdoi:10.1016/j.r

�Correspondiof Medicine, Ke35, Shinjukukufax: +81-3-3353

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Descriptive patterns of severe chronic pulmonaryhypertension by chest radiography

Toru Satoh�, Shingo Kyotani, Yoshiaki Okano, Norifumi Nakanishi,Takeyoshi Kunieda

Department of Medicine, Division of Cardiology and Pulmonary Circulation,National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan

Received 9 January 2004; accepted 13 August 2004

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Summary Background: To find chest roentgenographic (CXR) features to helpdifferentiate two representative diseases with severe chronic pulmonary hyperten-sion (PH).

Study subjects: Thirty-six consecutive patients with chronic thromboembolic PH(CTEPH), 38 with primary PH (PPH), and 37 with left heart disease and PH.

Methods: CXRs were reviewed about 6 features (left 2nd arc protrusion, rightdescending pulmonary artery diameter (rPAD), cardiothoracic ratio (CTR), right 2ndarc width, avascular area and pleural abnormality). Hemodynamic data and thedegree of tricuspid regurgitation (TR) on echocardiography were compared with CXRfindings.

Results: The diagnostic pattern of CTEPH was the presence of one of two findings,an avascular area or marked rPAD (420mm) together with pleuritic change. Thediagnostic pattern of PPH was one of the two features; without pleuriticabnormality, marked left 2nd arc protrusion (410mm) or moderate left 2nd arcprotrusion (5–10mm) with marked rPAD (o20mm). The sensitivity for the diagnosisof CTEPH among the three diseases was 78% and specificity was 92%. The sensitivityfor the diagnosis of PPH was 45% and specificity was 88%. CTR and right 2nd arc widthwere related to the degree of TR in CTEPH and PPH.

Conclusions: Characteristic roentgenographic findings can help differentiate twofrequent diseases associated with chronic pulmonary hypertension and reflect theseverity of disease.& 2004 Elsevier Ltd. All rights reserved.

Elsevier Ltd. All rights reserv

nary Division, Departmentf Medicine, Shinanomachin. Tel.: +81-3-3353-1211;

.keio.ac.jp (T. Satoh).

Introduction

Primary and chronic thromboembolic pul-monary hypertension (PH) are two major diseases

ed.

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associated with severe chronic PH. These tworepresentative diseases have very similar clinicalpresentation and results of various laboratory tests,but are very different in their treatment. Patientswith primary pulmonary hypertension (PPH) arebeginning to have a better prognosis with theintroduction of continuous epoprostenol infusion1,2

and many patients with chronic thromboembolicpulmonary hypertension (CTEPH) can be cured bypulmonary thromboendarterectomy.3 In view oftheir different pathologic processes, there may becharacteristic chest radiographic findings in eachentity that can be used to help differentiate them,though some features are shared. Simple radio-graphic recognition would lead to early diagnosticdeduction of the disease, reducing the cost andrelieving the burden on the patients from unneces-sary examinations.

Chest radiographic findings characteristic inprimary4,5 and thromboembolic6 PH have beenreported in detail separately. Differentiation ofthe two entities by chest roentogenography wasthought difficult in several series7,8 but waspursued vigorously with somewhat satisfactoryresults by Anderson et al.9 They, however, includedacute and chronic varieties in their cases ofthromboembolic PH, and failed to pick up impor-tant features such as proximal pulmonary arterialdilatation caused by severe intimal thickening inthe chronic cases.

We, therefore, evaluated chest roentgenogramsto identify characteristic findings in 38 consecutivepatients with PPH and 36 with CTEPH with definitefinal diagnosis and hemodynamic measurement. Wealso evaluated chest roentgenograms in patientswith left heart disease and PH to differentiate PPH,CTEPH and secondary PH due to left heart disease.We then compared the findings in these threecategories and defined the diagnostic patterns forthe former two PH diseases. In addition, thevariables measured in roentgenograms were quan-tified and compared with hemodynamic parametersto relate the roentgenographic findings to theseverity of disease.

Table 1 Patient characteristics.

Disease Number Age (y/o) Sex (m/f) Weight

CTEPH 36 52714 19/17 5579PPH 38 35715 13/25 5479LHD 37 56715 21/16 56710

CTEPH: chronic thromboembolic pulmonary hypertension; LHD: lartery pressure; Number: number of patients; PCWP: pulmohypertension; PVR: pulmonary vascular resistance; y/o: years old

Methods

Study patients

Patients from the three categories were studiedretrospectively. Patients with CTEPH consisted of36 consecutive patients who were diagnosed byradionuclide perfusion lung scan, computed tomo-graphy and pulmonary angiography with hemody-namic measurement.8 All patients had more thanmoderate hypoxia and multiple perfusion defectson radionuclide perfusion lung scan, suggestingcentral type pulmonary embolism. Patients withPPH were 38 consecutive patients with hemody-namic measurement by right heart catheterizationwho were defined as having PH unexplained by anysecondary causes, based on the criteria of theNational Institutes of Health registry on PPH.10 Thethird group consisted of patients with left heartdisease and PH who had equivalent age, sex andpulmonary pressure as the group of patients withCTEPH. They included 23 patients with valvularheart disease and 12 with idiopathic cardiomyo-pathy, which were diagnosed by echocardiographyand cardiac catheterization. Detailed patient char-acteristics are presented in Table 1. Patients withPPH were younger, had a larger proportion offemale patients and had higher pulmonary arterypressure.

Chest roentgenographic evaluation

The radiographs were taken by computed radio-graphy (FCR AC-3, Fuji Medical Systems, Co., Ltd.,Tokyo, Japan). Tube voltage was 120 kV, tubecurrent was 200mA and phototimer was 30–40ms.Films were exposed during suspension of respira-tion at deep inspiration. The focus-film distance inthe PA projection was 1.8m with the patientupright.

Two of the authors (T.S. and S.K.) evaluated thechest roentgenographs retrospectively withoutknowing the patient names. The measured

(kg) MPA (mm Hg) PVR (unit) PCWP (mm Hg)

45714 1378 87361712 1779 97638714 472 2178

eft heart disease; m/f: male/female; mPA: mean pulmonarynary capillary wedge pressure; PPH: primary pulmonary. Some values are presented as mean7SD.

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Figure 1 Evaluated signs and measured variables in chestroentgenographs. Following six signs and measurementswere determined in chest roentgenographs taken withthe patient standing. (1) Degree of left 2nd arcprotrusion. (2) Right descending pulmonary artery dia-meter. (3) Cardiothoracic ratio. (4) Width of right 2ndarc. (5) Avascular area. (6) Pleural sign. For details seetext.

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variables in study patients were compared betweenthe two authors by Student’s t-test. There were nosignificant differences between the two for all themeasured variables. Therefore, the two measuredvalues were averaged and used for the followingevaluation. The chest roentgenographs evaluatedwere taken within one week of cardiac catheter-ization and hemodynamic measurement. The mea-sured variables are demonstrated in Fig. 1: (1) Thedegree of left 2nd arc protrusion: the distance fromthe farthest protruding point of the left 2nd arcperpendicular to the line between the lowest pointof the left 1st arc and the uppermost point of theleft 3rd arc. (2) The width of the right descendingpulmonary artery. (3) The cardiothoracic ratio: thepercent ratio of the cardiac silhouette width to thethoracic width. (4) The width of the right 2nd arc:the distance from the farthest right point of theright 2nd arc perpendicular to the vertebral body.(5) Avascular area: paucity of vasculature incontrast to vasculature in the contralateral lungfield. (6) Pleural sign: old pleuritic shadow pre-sumably due to pulmonary infarction.

Hemodynamic and echocardiographicevaluation

Right heart catheterization was performed throughthe right internal jugular vein or the right femoral

vein. The mean right atrial pressure and the meanpulmonary artery pressure were compared with thechest roentgenographic findings. Echocardiographywas performed within one week of cardiac cathe-terization. The degree of tricuspid regurgitation(TR) was graded from 1 to 4 according to observa-tion in the parasternal short axis and apex 4-chamber views based on the standard criteria11, forcomparison with the findings of chest X-rays.

Statistical analysis

Chest roentgenographic features were comparedamong the three groups by Scheffe’s multiplecomparison analysis or w2-test. Sensitivity wascalculated by dividing the number of true positivecases by the number of positive cases. Specificitywas calculated as dividing the number of truenegative cases by the number of negative casesamong the three groups.

Results

Average values of and frequency of presenceof each roentgenographic finding

Detailed results are presented in Table 2. (1) Thedegree of left 2nd arc protrusion was greater inPPH. (2) The right descending pulmonary artery waswider in chronic thromboembolic and primary PHthan in left heart disease. (3) Pleural sign wasrecognized more frequently in CTEPH and left heartdisease. (4) The cardiothoracic ratio (CTR) was notdifferent among the three. (5) An avascular areawas only found in CTEPH. (6) The width of the right2nd arc was not statistically significantly differentamong the three groups.

Differential diagnosis of chronicthromboembolic and primary pulmonaryhypertension

1. CTEPH: The presence of avascular area (Fig. 2)was only found in this entity and in 15 out of the 36patients. It was decided as the first diagnosticpattern. As the right descending pulmonary arterywas more prominent in diameter and the pleuriticsigns were seen more frequently in this group, thenext diagnostic pattern for CTEPH was the width ofthe right descending pulmonary artery diametermore than 20mm together with pleuritic abnorm-ality (Fig. 3). It was seen in 13 out of the remaining21 patients without avascular area in the throm-boembolic group, 5 out of 38 patients with PPH and

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Table 2 Chest roentgenographic findings.

CTEPH PPH LHD

lt2ndArc (mm) 4.873.6 6.673.4* 3.475.1rtPA (mm) 2176* 2074* 1673CTR (%) 5476 58713 5979rt2ndArc (mm) 28712 30715 34717Avascular area 15/36* 0/38 0/37Pleuritic scar 21/36* 12/38 19/37*

CTEPH: chronic thromboembolic pulmonary hypertension; CTR: cardiothoracic ratio; LHD: left heart disease; lt2ndArc: degreeof left second arc protrusion; PPH: primary pulmonary hypertension; rtPA: diameter of right descending pulmonary artery;rt2ndArc: width of right 2nd arc. Values for first 4 items are presented as mean7SD. Avascular area and pleuritic scar arepresented as the frequency of the presence of each finding. See text for details.*Po0.05.

Figure 2 Avascular area. Chest X-ray of 45-year-old man.Mean pulmonary artery pressure was 38mm Hg. Vascularmarkings in the left upper and middle lung fields aresparse compared to those in the corresponding right lung.

Figure 3 Marked right descending pulmonary arterydilatation with pleural abnormality. Chest X-ray of 44-year-old woman. Mean pulmonary artery pressure was43mm Hg. There are bilateral lower pleural changes withenlarged right descending pulmonary artery diameter of20mm.

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1 out of 37 patients with left heart disease. If wedefine owning one of these 2 roentgenographicpatterns as the diagnostic features for CTEPH, thesensitivity among these 3 diseases was 78% and thespecificity was 92%. The positive predictive valuewas 82% and the negative predictive value was 97%(Table 3).

2. PPH: Left second arc protrusion of more than10mm (Fig. 4) was found in 3 patients in CTEPH, 7in PPH and 3 in left ventricular disease. Left secondarc protrusion of more than 5mm with rightdescending pulmonary arterial diameter more than

20mm without pleural abnormality was found 3 inthromboembolism, 10 in PPH and no patient in leftventricular disease and pulmonary hypertension.When the presence of one of these two roentgeno-graphic findings was defined as the diagnosticpattern for PPH, the sensitivity among these threedisease groups was 45% and the specificity 88%. Thepositive predictive value was 65% and the negativepredictive value 88%.

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Table 3 Roentgenographic diagnostic criteria.

Findings CTEPH PPH LHD

Avascular area or rtPAX20mm and pleuritic scar 28/36 5/38 1/37Without pleural change, lt2ndArcX10mm or lt2ndArcX5mm and rtPAX20mm 6/36 17/38 3/37

CTEPH: chronic thromboembolic pulmonary hypertension; LHD: left heart disease; lt2ndArc: degree of left second arcprotrusion; PPH: primary pulmonary hypertension; rtPA: diameter of right descending pulmonary artery; Frequency in presenceof each finding is shown.

Figure 4 Marked left second arc protrusion. Chest X-rayof 34-year-old woman. Mean pulmonary artery pressurewas 75mm Hg. Protruded distance of left 2nd arc was12mm.

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Mean pulmonary artery pressure androentgenographic findings

The relations of mean pulmonary artery pressurewith left 2nd arc protrusion, and with cardiothor-acic ratio, among the three groups are depictedin Fig. 6. The degree of left 2nd arc protrusionwas significantly correlated with mean pul-monary artery pressure only in the left heartdisease group. The cardiothoracic ratio showedsignificant correlations with mean pulmonary ar-tery pressure in the CTEPH and left heart diseasegroup (Fig. 5).

Degree of TR and roentgenographic findings

The degree of TR was significantly correlated withcardiothoracic ratio and right second arc diameterin CTEPH and PPH (Fig. 6).

Discussion

The authors tried to identify characteristic patternsin chest roentgenograms to differentiate tworepresentative diseases associated with severechronic pulmonary hypertension (PH); chronicthromboembolic pulmonary hypertension (CTEPH)and primary pulmonary hypertension (PPH). CTEPHwas associated with a pathognomonic avasculararea, pleuritic scarring and right descending pul-monary arterial dilatation. PPH cases showed moreprominent left 2nd arc protrusion and moderateright descending pulmonary arterial dilatation. Bycombining these findings, the authors have selectednew roentgenographic diagnostic patterns forchronic PH. The pattern of CTEPH is the existenceof one of two findings; an avascular area or rightdescending pulmonary artery diameter more than20mm together with pleural abnormality. Thediagnostic pattern of PPH is the existence of oneof the following 2 features; left 2nd arc protrusionmore than 10mm or left 2nd arc protrusion of morethan 5mm with right descending pulmonary arterydiameter more than 20mm without pleural ab-normality. Using these features, sensitivity andspecificity for CTEPH between the two precapillaryPH diseases even with left heart disease wassatisfactory, and for PPH specificity was good andsensitivity fair.

Diseases associated with severe chronic PH areusually detected and diagnosed by history taking,physical examination and electrocardiography.Then the cause of PH will be sought and deter-mined after careful differential diagnosis. Fre-quently encountered diseases associated with PHare left heart disease, PPH, pulmonary parenchy-mal disease, Eisenmenger syndrome, CTEPH,

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Figure 5 Relation of mean pulmonary arterial pressure with left 2nd arc protrusion and cardiothoracic ratio in three PHdiseases. Mean pulmonary artery pressure and the other two roentgenographic variables were correlated by linearregression analysis. Left 2nd arc protrusion only reflected the degree of pulmonary hypertension in left heart disease.Cardiothoracic ratio represented the severity of pulmonary hypertension in CTEPH and left heart disease. CTEPH:chronic thromboembolic pulmonary hypertension; CTR: cardiothoracic ratio; LHD: left heart disease; lt2ndArc: leftsecond arc; mPA: mean pulmonary artery pressure; PPH: primary pulmonary hypertension.

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hypoventilation syndrome, high output cardiacfailure and other rare diseases.12 Among the firstfive common etiologies, pulmonary parenchymaldisease can be differentiated by chest roentogen-ography. Left heart disease and Eisenmengersyndrome can ordinarily be diagnosed by echocar-diography. The differential diagnosis of CTEPH andPPH is rather difficult and requires further studiessuch as perfusion lung scan, which is available onlyat certain institutions. If chest X-ray, which isperformed in most clinics, can help differentiatethe cause of severe chronic PH, it will make furtherscrutiny more smooth and efficient.

There have been many studies concerning chestX-ray findings in patients with PH in general,13 butvery few reports have documented the roentgeno-graphic features of respective PH diseases orcompared the findings. Kanemoto et al. performeda pioneering study on the roentgenographic findingsin patients with PPH, claiming that main pulmonaryartery protrusion was marked and had a roughcorrelation with pulmonary arterial pressure, andthat CTR correlated with right atrial pressure and

right heart failure in PPH.4 However, in our study,left 2nd arc protrusion was prominent but did notcorrelate with pulmonary arterial pressure, andCTR did not correlate with right atrial pressure butwith tricuspid regurgitation. The correlation coeffi-cients between the main pulmonary artery dilata-tion and mean pulmonary arterial pressure andbetween CTR and right atrial pressure that Kane-moto et al. reported were 0.31 and 0.37, barelysignificant. Anderson et al. classified PH patientsaccording to pulmonary arterial dilatation andcardiomegaly, and revealed that patients withnormal pulmonary arterial and cardiac configura-tion had the worst prognosis.9 Our roentgeno-graphic patterns demonstrated high specificity fordiagnosis of PPH but low sensitivity, suggesting thatthe existence of main pulmonary artery protrusionand a large CTR signifies severe PPH, but lessmarked protrusion or a normal CTR does not ruleout PPH. CTR and right atrial pressure werecorrelated in patients with CTEPH in our study.

The roentgenographic findings found in CTEPHpatients were studied in detail by Woodruff et al.6

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Figure 6 Relation of degree of tricuspid regurgitation with cardiothoracic ratio and right 2nd arc width. Cardiothoracicratio and right 2nd arc width reflected the degree of tricuspid regurgitation in CTEPH and PPH. CTEPH: chronicthromboembolic pulmonary hypertension; CTR: cardiothoracic ratio; LHD: left heart disease; rt2ndArc: right secondarc; PPH: primary pulmonary hypertension.

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They reported that the signs frequently found inCTEPH were cardiomegaly (86%), oligemia (68%),right descending pulmonary artery enlargement(55%), effusion (23%) and pleural thickening (14%).We recognized similar findings with almost thesame frequency. We showed that oligemia was verypathognomonic to differentiate CTEPH from anyother PH diseases and that right descendingpulmonary artery enlargement was prominent inCTEPH compared to PH due to left heart disease.Pleuritic change was more frequent in CTEPH thanin PPH. By combining these findings, CTEPH can bediagnosed with good sensitivity and specificity. Intwo representative precapillary PH diseases, CTRand right 2nd arc width correlated with the degreeof tricuspid regurgitation. In CTEPH in particular,CTR correlated with mean pulmonary arterialpressure and right atrial pressure, indicating thatcardiomegaly well reflects the severity of thedisease.

Anderson et al. evaluated and compared thecharacteristic roentgenographic findings demon-strated in PPH and CTEPH and reported that

patients with PPH had an enlarged pulmonaryartery but those with CTEPH had pathognomonicoligemia9 without pulmonary arterial dilatation.Their study patients had less severe PH and seemedto include patients with acute pulmonary embolismwith less intimal thickening of the pulmonaryartery, resulting in failure to demonstrate dilata-tion of the right descending pulmonary artery as animportant finding in CTEPH. Patients with PPH hadgreater left 2nd arc protrusion owing to greaterpulmonary hypertension, and those with CTEPHshowed a wider branched pulmonary artery result-ing from thickened pulmonary intima. They alsoreported that some of the PPH patients with theworst prognosis had normal pulmonary arterydiameter and CTR on chest roentogenography,indicating the lower sensitivity of roentgenographicdiagnosis of PPH, consistent with our results.

CTR and mPA were significantly correlated inCTEPH and LHD, but not in PPH. This is partlybecause pulmonary artery pressures in patientswith CTEPH and LHD were distributed over a widerange, but those in patients with PPH were

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distributed within in a higher range, leading to thedifferent statistical significance among those dis-ease states. Essentially, CTR may be weaklycorrelated with the degree of PH regardless ofthe etiology.

CTR was well correlated with the degree of TRbut not the mean right atrial pressure, although TRand right atrial pressure had a weak significantcorrelation. Right atrial pressure is sometimeselevated in right heart failure but TR is notprominent when pulmonary hypertension is rapidlyprogressive. CTR is more influenced by chronicdilatation of right atrium and ventricle.

As a study limitation, the radiographic findingscannot lead to a definitive diagnosis, though theymay be helpful for reaching a tentative diagnosisand to direct further diagnostic plans. When CTEPHis suspected from the radiographic findings, thenCT scanning is preferred for the next diagnosticmethod, because CT is now the most accurate andnon-invasive diagnostic tool.14

Conclusion

Characteristic chest roentgenographic featureswere sought to help differentiate two chronicpulmonary hypertension. Chronic thromboembolicpulmonary hypertension had a pathognomonicavascular area, pleuritic scarring and right des-cending pulmonary artery dilatation. Primary pul-monary hypertension had more prominent left 2ndarc protrusion and moderate right descendingpulmonary artery dilatation. By combining thesefindings, new roentgenographic diagnostic patternsfor chronic pulmonary hypertension were deter-mined. The former had good specificity and fairsensitivity and the latter had satisfactory sensitiv-ity and specificity among them and PH due to leftheart disease. Cardiac dilatation associated withpulmonary hypertension reflected the degree oftricuspid dilatation.

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