High probability ventilation-perfusion scan in primary pulmonary hypertension

The perfusion lung scan is a valuable noninvasive tool in the evaluation of patients with pulmonary arterial hypertension of undetermined cause and for the exclusion of occult large-vessel pulmonary thromboembolism. Peripheral patchy defects have been reported in primary pulmonary hypertension (PPH) but there are no well documented reports of segmental or larger perfusion defects. A case of a 55-year-old male with severe pulmonary hypertension of unknown etiology who had persistent high probability perfusion scan patterns over a period of two years is reported. No evidence of thromboembolism was present on pulmonary angiography. A discussion of the case and a review of the literature on the role of lung scan in PPH are presented. Most patients with PPH have normal or low probability perfusion scans; high probability scans occur rarely.

tttrL".or primary pulmonary hype rtension (PPH) , consists of di ff use patchy peripheral defects.Perfusion defects o r a lobar or segmental nature have not bt:en wdl docume nted in PPH .The present case is rqxirtcd lo denwnstrate that multiple seg mental defects typiL•al pf pulmonary unboli may be present in ;1 paticnl with nonthrombocmholic pulmonary hypertension.

CASE PRESENTATION
A 55-year-old Caucasian male with a IO pack-year smoi..ing history presented with gradually progress ive exertional dyspnea and a single episode of exertional syncope.He had a past history of systemic hypertension and a long history of Raynaud•s phenomenon .Physical examination revealed e levated venous pre ••sure.right ventricular lift.right ventricular fourth hea11 sound and a systolic murmur of tricuspid regurgitation over the right sternal border.Electrocardiography showed typical findings of right ventricular hy pe11rophy.A chest radiograph showed canJiomegaly and large pu lmonary arteries (Figure 1 ).Transthoracic cchocan.liogramrevealed normal left ventricle size and function.and a markedly dilated right ventricle with a severe reduction in ri ght ventricular systolic function.Severe tricuspid regurgitation was presL:nt and paradoxic motion of interventricular septum was seen.Pulmonary artery systolic pressure was estimated by trnnsvalvular flow velocity to be in excess of 90 mmHg .A six-view technetium-99m macroaggregated albumin pe rfusion lung scan showed multiple.bil ateral.triangular wedgeshaped segmental and subscgmental defects (Figure 2).1.\\ Xenon ventilation scan showed mild asymmetry but no segmental ventilatory abnormalities.and therefore established the presence of multiple areas of ventilation-perfusion mismatch (Figure 2. bottom).Subsequent ventilation perfusion scans done at an interval of one week and one month were unchanged from the tirst study.No evidence of dee p  total lung capacity 61 % predicted; and carbon monox ide di ffusing capacity of the lu ng 19.4 mL/min/rnmHg (80% predicted).Arterial blood gases showed pH 7 .42,PaC02 32 mm! Ig.Pa02 7 1 mm Hg and bicarbonate 21 mmo l/L.No mediasti nal or parenchymal abnonna lities were identified on an unin fused computed tomography (CT) scan or the chest.Pulmonary ai1ery angiography was not performed.The patient was initially treated with intravenous heparin followed by adequate long tenn anticoagulation with oral warfar in therapy.
The patient returned two yl:an; later with increa sing dy spnea and worsening right-sided heai1 failure.Med ications included lisinopril.furosemide.ranitidinc and warfarin.
Erythrocyte sedimentation rate, DNA.extractable nuclear antigens and anticentromere antibodies were all negative.Po,itive ANA may indicate a disease process such as progressive systemic sc lerosis or CREST (calcinosis cutis.Raynaud's phenomenon, esophageal motility disorder, scle rodactyly and telangiectasia) syndrome, but no clinical or laboratory evidence of an underlying collagen vascular disease was found.A repeat CT scan of the chest faikd to show any rncdiastinal or parcnchy111al abnormalities.

DISCUSSION
T his is a well documented case of a false pnsitive perfusion lung scan in a patient with severe pulmonary artery hype rten.,ion of undetermined origin.Our patient has either PPH or pulmonary arterial hypertension associated with col - There was 110 c1•ide11cc of recent or c/im11ic tlil'omhocmholi.Top Rig/it side: Bottom Lc/i sit!<' lagen vascular disease li111ited to the pulmonary vasculature.The cl inical picture and pulmonary ang iogram are consisten t ~-ith PPH.Perfusion lung scans are used as a guide to fu rther evaluation of patients with pulmonary hype rte nsion who may have chronic large vessel thromhoemholism amenable to thromboendarterectomy.The value or the perfusion scan as a screening investigation before angiography has been finnly established.D' Alonzo et al (I) reported a series of25 patients with chronic pulmonary hypertension .All eight patients in whom thromboembolic disease was established on subsequent angiography had hi gh probability scans, whereas scans were nonnal or low probability in patients with PPH.Powe et al (2) reviewed their experience with 58 patients who were evaluated for pulmonary arterial hypertension.Thirtyfour patients had a definitive diagnosis made by open lung biopsy, angiography and/or autopsy.All eight patients with thromboembolism had high probability scans.None of the 13 patients with PPH had a high probability scan.Three of the 13 patients who had nonembolic secondary pulmonary hypertension had high probability scans, but they also had significant underlying thoracic disease known to alter pulmonary perfusion.Ryan et al (3) reviewed the perfusion scans in 25 consecutive patients with chronic thromboembolic pulmonary hypertension diagnosed on pulmonary angiography.All of the perfusion scans were abnormal, although they were noted to underestimate the severity of pulmonary arterial hypcrtcn.\illn.Moser et al (4) published the largest series on the role of perfusion lung scanning as a guide to angiography in pulmonary arterial hypertension.Th is group reported that ;mgiography should be pe1formed in patients with pulmonary hypertension who have a segmental or larger pe1fusion defect.Their series incl uded 64 patients with PPH and 46 patients with chronic thromboembolic pulmonary hypertension.On evaluating the perfusion lung scans of these I I 0 patients, no segmental defects were noted on the scans of 64 patients with PPH, whereas all 46 patients with thrombocmbolic hyperte nsion had one or more defects that were segmental or larger in size.
Rece ntly one other case of a scan-angiographic disparity was reported in which a false positive pc,fusion scan occurred in a patient with PPH.Worsley et al (5) retrospectively studied the records of 35 patients with PPH.One of the patients had high probability ventilation-perfusion scan but no thro111boembolis111 on pulmonary angiography.However, this repo11 does not include any clinical details of this case and there is no infom1atio11 lln how the angiography was reviewed or whether the perfusion defects were segmental or persistent.
Our patient 111eets the criteria for PPH , although thi s is essentially a diagnosis of exclusion.There are no spec ific hi stopathological lesions of PPH and the diagnosis of thi s di sease req uires the close integration of clinical sym ptoms.laboratory investigations and histopathological findings (6,7).A full range of pulmonary hypertensive lesions including plexogenic arteriopathy, the hallmark of PPH. is pn;sent in patients with long standing pulmonary hypertension secondary to congenital and acquired cardiac conditions.collagen vasc ular disorders and chronic major vesse l thrombocmbolic pulmonary hypertension (8.9).The incidence of positive ANA has been reported in 14 to 29%, of cases in vari ous registries ( I 0, 11 ).T he persistently positive perfusion scan in our patient shows that, although most patients with PPH have normal or low probability perfusion scans, there will be rare patients who have high probability scans.