GASTROENTEROLOGY

1991;100:520-528

Pulmonary Hypertension Complicating Portal Hypertension: Prevalence and Relation to Splanchnic Hemodynamics ANTOINE HADENGUE, MOHAMED DIDIER LEBREC, and JEAN-PIERRE Service d’HBpatologie and Unite de Recherches HBpital Beaujon, Clichy, France

The prevalence of pulmonary hypertension in 507 patients hospitalized with portal hypertension but without known pulmonary hypertension who underwent cardiac catheterization was prospectively studied. Ten (2%) of these patients, 6 of whom were clinically asymptomatic, had primary pulmonary hypertension. Second, 26 patients with symptomatic pulmonary hypertension complicating portal hypertension were reviewed. Pulmonary hypertension occurred later after diagnosis of portal hypertension in patients with a surgical shunt (10 patients) than in those without a shunt (147 rf:49 vs. 44 + 27 months; P < 0.0001). Cardiac index correlated inversely with pulmonary arterial pressure (r = -0.45; P < 0.01) and was lower in the 5 patients who died of pulmonary hypertension than in the 5 who died of liver failure (1.52 f 0.14 vs. 3.69 + 1.88 Urnin. m’; P < 0.05). Third, systemic and splanchnic hemodynamics were compared in 285 patients with alcoholic cirrhosis and 29 controls. No significant relation was found between elevated pulmonary vascular resistance and increased portal pressure, azygos blood flow, or cardiac index. Pulmonary hypertension is considerably more frequent than was previously estimated in patients with portal hypertension. The risk of developing pulmonary hypertension could increase with the duration of portal hypertension without any clear relation to the degree of portal hypertension, hepatic failure, or amount of blood shunted. ulmonary hypertension has been reported in 0.25%-0.73% of patients with portal hypertension, a prevalence that excludes fortuitous coincidence (l-4). However, the prevalence of pulmonary hypertension in patients with portal hypertension has been estimated only in retrospective clinical or au-

P

KAMAL BENHAYOUN, BENHAMOU de Physiopathologie

Hkpatique, INSERM U 24,

topsy studies (l-4). Pulmonary hypertension has been reported in patients with cirrhotic portal hypertension and in patients with noncirrhotic portal hypertension (5-10). Thus, pulmonary hypertension appeared to be linked to portosystemic shunting by a cause-and-effect relationship. Several putative mechanisms have been proposed for the increased pulmonary resistance in patients with portal and pulmonary hypertension, mainly repeat embolization of pulmonary arteries by microthrombi (4,6,9,11), alteration in the pulmonary vascular bed by some unidentified vasoconstrictor substance originating from the gut and escaping liver inactivation (1,2,12,13), and the role of the hyperkinetic systemic circulation (14,15). Prognosis of pulmonary hypertension associated with portal hypertension is thought to be poor (2,16-l 8). In the present study we first estimated the prevalence of pulmonary hypertension in 507 consecutive patients with portal hypertension who underwent cardiac catheterization between January 1984 and June 1988. Second, we reviewed our 26 patients with pulmonary hypertension associated with portal hypertension and determined which factors from those assessing the severity of liver failure or pulmonary hypertension predicted the cause of death. Third, we compared our 26 patients with pulmonary hypertension with 285 patients with alcoholic cirrhosis and 29 controls without pulmonary or portal hypertension, all of whom underwent invasive hemodynamic studies of the systemic and splanchnic circulations. This comparison was meant to find a link, if any, between pulmonary hypertension and the degree of liver failure and hemodynamic derangements known to occur during portal hypertension. o 1991by

the American Gastroenterological 0016-5085/91/$3.00

Association

February 1991

PULMONARY HYPERTENSION IN PORTAL HYPERTENSION

Patients and Methods Patients With Portal Hypertension in Prospective Hemodynamic Study Between January 1985 and June 1988, 507 patients with portal hypertension underwent cardiac catheterization in our unit at the time of transvenous liver biopsy (19). Patients in whom pulmonary hypertension was known or clinically suspected before the hemodynamic study were excluded from this group to exclude a possible selection bias due to the interest of our unit in pulmonary hypertension. Liver biopsy was performed using the transvenous procedure either because of a coagulation disorder or the presence of ascites or for hemodynamic assessment of portal hypertension. Heart catheterization was performed as part of the routine hemodynamic study. The cause of portal hypertension was alcoholic cirrhosis in 285 of the 507 patients, hepatitis B surface antigen (HBsAg)-positive chronic hepatitis or cirrhosis in 82, cryptogenic cirrhosis in 48, primary biliary cirrhosis in 12, portal vein thrombosis in 7, hepatic schistosomiasis in 2, hemochromatosis in 2, Wilson’s disease in 3, and undetermined in 66. All patients were asked whether they had dyspnea or syncopes. In this group of 507 patients, pulmonary pressures and cardiac output were measured prospectively, allowing calculation of the prevalence of pulmonary hypertension. In addition, systemic and splanchnic hemodynamics were compared in 285 of these 507 patients who had alcoholic cirrhosis. The hepatic venous pressure gradient, a reliable reflection of portal pressure in patients with alcoholic cirrhosis (201, was measured in all 285 alcoholic patients, and azygos blood flow, an index of superior portosystemic collateral blood flow, was measured in 131 of them. The severity of cirrhosis was estimated using Pugh’s score (21). In the 285 patients with alcoholic cirrhosis, the mean Pugh’s score was 8.5 ? 2.2 (66 patients were grade A, 130 were grade B, and 89 were grade C according to Pugh’s modified Child classification). Criteria for Primary Pulmonary Hypertension Both in patients studied prospectively and in patients with previously known pulmonary hypertension, primary pulmonary hypertension was diagnosed using the criteria of the Patient Registry for the Characterization of Primary Pulmonary Hypertension (3,22): (a) no history of drug abuse or use of drugs known to induce pulmonary arterial hypertension; (b) mean pulmonary arterial pressure 2 25 mm Hg without pulmonary artery pressure gradient during heart catheterization; (c) pulmonary wedge pressure I 13 mm Hg; and (d) in all patients, cardiac and pulmonary evaluation, including clinical examination, chest radiograph, electrocardiogram, and blood gas analysis while breathing room air that did not identify a cause of secondary pulmonary hypertension. Patients With Symptomatic Hypertension

Pulmonary

From 1967 to 1988, 26 patients with symptomatic pulmonary hypertension associated with portal hyperten-

521

sion were admitted to the Hopital Beaujon. Characteristics of the first 9 patients have been previously published (2). In 4 of these patients, pulmonary hypertension had been overlooked until prospective hemodynamic study. In these 26 patients, to meet criteria of primary pulmonary hypertension as defined above, the following specific additional investigations were performed: cardiac ultrasonography in 12 patients, lung perfusion scanning in 16, pulmonary angiography in 8, and pulmonary function tests in 4. All 26 patients underwent liver biopsy and had portal hypertension, evidenced by increased hepatic venous pressures or the presence of esophageal varices. Three patients were lost to follow-up. Of the remaining 23 patients, 14 died from 1967 to 1988. Follow-up data were collected from hospital charts or town registries and included date and cause of death for the patients who died. Con fro1 Patients Twenty-nine patients with normal hepatic venous pressures and normal liver architecture underwent transvenous liver biopsy and cardiac catheterization during the same period. Twelve were alcoholic patients, studied beyond 10 days after alcohol withdrawal and who had mild steatosis. The other patients, who underwent liver biopsy because of unexplained alterations in liver test results or before treatment for lymphoma, had a normal liver or mild steatosis. None of these patients had evidence of heart-andlung disease in clinical history, chest radiograph, or electrocardiogram. Hemodynamic

Studies

No patient had gastrointestinal bleeding within the previous 7 days, had taken any vasoactive substance within the previous 72 hours, had oral temperature > 37.5”C, or had hepatic encephalopathy at the time of the hemodynamic study. Hemodynamic studies were performed according to methods previously described (23). Briefly, after an overnight fast, subjects were sedated with meperidine hydrochloride, 50 mg, IM, and rested supine for 1 hour. In all patients, a Swan-Ganz catheter (Baxter Healthcare Corp., Irvine, CA) was used for measurements of pulmonary and atria1 pressures and determination of cardiac output in triplicate. Arterial pressure was monitored using an oscillotonometric device (Dinamap, Critikon, Inc., Tampa, FL), and heart rate was determined by continuous monitoring. Systemic and pulmonary vascular resistances were calculated according to the following formulas: Systemic Vascular Resistance (dyne/s . cm5) = (Mean Arterial Pressure - Right Atria1 Pressure) x 80/Cardiac Output; Pulmonary Vascular Resistance (dyne/s . cm5) = (Mean Pulmonary Pressure - Pulmonary Wedge Pressure) x 80/ Cardiac Output. The gradient between wedged and free hepatic venous pressures (hepatic venous pressure gradient) was measured using a 7F catheter introduced into a right hepatic vein. Azygos blood flow was measured by continuous thermodilution using a catheter introduced into the arch of the azygos vein. Details of this procedure have been described elsewhere (23).

522

GASTROENTEROLOGY

HADENGUE ET AL.

Review of the Literature

All published cases [excluding our 9 previously published patients (2)] with coexistent portal hypertension and pulmonary hypertension were collected using Medline and Pascal computerized data files. From 1951 to 1987, 73 cases of this association have been published (5-10,24-50). Diagnosis was ascertained by a hemodynamic study in 50 patients and/or by an autopsy study with histological examination of pulmonary arterioles in 48 patients. Both hemodynamic and autopsy studies had been performed in 25 patients. Statistical Analysis

Simple linear regression with Spearman’s correlation coefficient and one-way analysis of variance with unpaired Student’s t test were used where appropriate. Results Patients With Portal Hypertension in Prospective Hemodynamic Study

Among the 507 patients who underwent cardiac catheterization at the time of transvenous liver biopsy, 10 (1.97%) met the diagnostic criteria for coexistent portal and pulmonary hypertension and had no other detectable cardiac or pulmonary cause of pulmonary hypertension. Nine of these 10 patients with pulmonary hypertension had alcoholic cirrhosis. The last patient had HBsAg-positive cirrhosis. Six of them had no dyspnea. Four of them had complained of exertional dyspnea, which had been overlooked until the hemodynamic study. Mean pulmonary arterial pressure and pulmonary vascular resistance were lower in this group than in the group of 26 patients in whom pulmonary hypertension was suspected before the hemodynamic study (28.0 + 4.0 vs. 49.5 + 16.1 mm Hg and 258 + 111 vs. 661 & 400 dyne/s . cm5). In the 285 patients with alcoholic cirrhosis, Pugh’s score correlated with the hepatic venous pressure gradient (r = 0.31; P < O.OOl),azygos blood flow (r = 0.28; P < O.Ol),and cardiac index (r = 0.40; P < 0.0001). However, pulmonary arterial pressure and resistance did not correlate with Pugh’s score (r = 0.14 and r = 0.15,respectively), hepatic venous pressure (r = 0.10and r = 0.06, respectively), or azygos blood flow (r = -0.02 and r = -0.14, respectively) . Normal Controls

Pulmonary arterial pressure and vascular resistance were not significantly different in controls without portal hypertension or in patients with alcoholic cirrhosis. However, patients with cirrhosis

Vol. 100,No. 2

tended to have lower pulmonary vascular resistance than normal controls (80 + 41 vs. 95 ? 46 dyne/ s * cm5; P = 0.06). The distribution of patients with cirrhosis and of normal controls according to the level of pulmonary vascular resistance is shown in Figure 1.

Patients With Symptomatic Pulmonary Hypertension

Portal and

Table 1 shows hemodynamic data in our 26 patients with symptomatic pulmonary hypertension, followed by those of the 6 patients with asymptomatic pulmonary hypertension. The main clinical features, hemodynamic findings, and survival times from the time of recognition of pulmonary hypertension in our 26 patients with symptomatic pulmonary hypertension are compared with those of the 50 patients reported in the literature in whom a hemodynamic study was performed and shown in Table 2. Portal hypertension was recognized before pulmonary hypertension in 24 of our patients; in 2, pulmonary and portal hypertension were diagnosed simultaneously. Sex ratio calculated from literature patients contrasted with male predominance in our patients. (male-female ratio, 1.6:1 in our patients; l.l:l in the literature). Our patients were older than those reported in the literature (46 + 15 vs. 35 r 14 years). The 16 patients with alcoholic cirrhosis were older than the whole group (51 + 9 vs. 46 + 15 years) and more often males than females (male-female ratio, 2.1:1).

Normal controls Patients with cirrhosis 3 E

.s

30

z

%

20

&

o-40

41-60

81-120

121-160

161.200

201-240

241.260

Pulmonary vascular resistance (dyn/s.cmS) Figure 1. Repartition of the patients with cirrhosis (n = 285; H) and normal controls (n = 29; a) according to the level of pulmonary vascular resistance. The number of patients for each level of pulmonary vascular resistance is expressed as a percentage of the total group.

February 1991

PULMONARY HYPERTENSION IN PORTAL HYPERTENSION

523

Table 1. Hemodynamic Results in 32 Patients with Pulmonary Hypertension Associated with Portal Hypertension

Patient

Hepatic venous pressure gradient (mm Hg)

Pulmonary arterial pressure (mm Hg)

-

1"

2” 3” 4” 5” 6” 7” aa 9” 10” 11” 12” 13” 14” 15” 16” 17” la” 19” 20” 21” 22” 23b 24b 25* 26’ 27’ 28” 29” 30” 31’ 32”

11

a 15 15 26 14 11 a 6 16

24

16 a 29 19 18 20

Pulmonary wedge pressure

Pulmonary vascular resistance

Systemic vascular resistance

(mm &I

(dyne3zm-5)

(dyne.s.cm-5)

(L.min-‘.m-‘)

-

50 a3 60 59 100 40 40 65 61 49 37 50 50 28 48 47 45 35 60 31 37 48 40 45 28 50 26 29 25 25 25 26

-

Cardiac index

-

3.26 -

-

496

-

2.7

6 2 13 5 a 7

2.84 1.42 4.7 1.7 6.85 1.63 1.77 4.3 7.89 2.05 3.49 3.65 2.33 3.08 3.7 4.07 2.28 4.30 5.55 3.78 3.07 3.75 3.91

11

12 4 a 10 11 a 10 6 5 13 11 11

12 a 12 11

-

1010 -

1186

-

765 1042 413 1169 141 1049 914 440 116 1578 264 367 754 510 485 170 a72 349 324 344 554 347 384

696

2954

1206 816 1405 369

904

1128 a89

a38 688 724 1508 990 863

“Patients with pulmonary hypertension known before prospective hemodynamic study. bPatients without known pulmonary hypertension before the hemodynamic study with hitherto overlooked exertional dyspnea. “Patients without known pulmonary hypertension before the hemodynamic study without exertional dyspnea.

Alcoholic cause

cirrhosis

of portal

was nearly

hypertension

twice

in our

more often the

patients

than

in

In our patients, the distribution of the cases of pulmonary hypertension among the different causes of portal hypertension seemed to mirror the general prevalence of each of these causes at our hospital (Table 2). Although three patients from the literature but none of our patients had primary biliary cirrhosis, no conclusion can be drawn from the available data because of the low numbers of patients reported. In Table 3, clinical and hemodynamic features of patients with pulmonary hypertension are compared according to the presence or absence of a surgical portosystemic shunt. In our 10 patients (38%) who had undergone surgical portosystemic shunting, the interval between diagnosis of portal and pulmonary hypertension was significantly longer than in patients who had not undergone surgery (147 + 49 vs. 44 + 27 months; P < 0.0001). The interval between the first

those from the literature.

clinical symptom of pulmonary hypertension and diagnosis was also significantly longer in the 10 patients who underwent surgical shunting than in those who did not (43 + 44 vs. 7 + 10 months). However, cardiac index, pulmonary arterial pressure, pulmonary vascular resistance, and time of survival from diagnosis of pulmonary hypertension were not different in patients who had or had not undergone surgical shunting. In our 26 patients with coexistent portal and pulmonary hypertension,

cardiac

index

correlated

inversely

-0.45; P < 0.01). However, pulmonary arterial pressure and resistance did not correlate with Pugh’s score, hepatic venous pressure gradient, or azygos blood flow. Pulmonary arterial pressure and resistance were not different in patients who had or had not undergone surgical portosystemic shunting. Among the 14 patients who died, 10 died within 12 months. The remaining 4 patients died 61 k 37 with

pulmonary

arterial

pressure

(r =

524

GASTROENTEROLOGY Vol. 100, No. 2

HADENGUE ET AL.

Table 2. Clinical and Hemodynamic Characteristics and Survival Times in Our 26 Patients With Coexistent Portal and Pulmonary Hypertension (HGpital Beaujon, 1967-1988) and in the 50 Patients Reported in the Literature Our patients

Patients from the literature (n = 50)

(n = 26) 46 f 15"

Age(~4 Sex (M/F) Cause of portal hypertension Alcoholic cirrhosis Posthepatitic cirrhosis Primary biliary cirrhosis Cryptogenic cirrhosis Nodular regenerative hyperplasia Portal vein thrombosis Other Surgical portocaval shunt Interval between diagnosis of portal and pulmonary hypertension (mo) Interval between first symptom and diagnosis of pulmonary hypertension Symptoms or physical findings Exertional dyspnea Exertional syncope Thoracic pain Hemoptysia Accentuated pulmonic sound Systolic murmur Cardiac failure Right ventricular hypertrophy visible on radiograph Prominent pulmonary arteries visible on radiograph Cardiomegaly visible on radiograph Mean pulmonary arterial pressure (mm Hg) Cardiac index (Umin.m’) Pulmonary wedge pressure (mm Hg) Pulmonary vascular resistance (dyne/s.cm5) Survival time from time of diagnosis in the patients who died (mo) “Mean 2 SD. bNo. of patients Data available dData available “Data available ‘Data available data available *Data from the

35 e14 27123

16/10

17(34%) 11(22%)

16(60%) 4(150/b) 0

3 (6%) 8(16%) 0

4(15%) 1(4%) 1(4%1 0

(mo)

7(14%)

10(38%) 84 f 63 21k 31

4(8%) 23/50*(46%) 70 2 68" 18 f 2gd

25(96%) 8 (29%) 4(150/b)

33/37 (89%) 7/37 (19%) 4/37 (11%)

1(4%) 17(65%) 12(46%)

4/37 (11%) 23/37 (62%) 23/37 (62%) lo/37 (27%) 35/38 (92%) 34/39 (87%) 28139 (72%) 56 f 15 3.39 + 0.90' 9 f 38 739 2 386 13 f 13'

4(16%) 20(770/b) 21(81%) 19(73%) 49 f 16 3.35 t 1.71 8f3 6612 400 19 2 32*

with the symptom or physical finding/no. of patients for whom the information was available. for 40 patients. for 39 patients. for 19 patients. for 21 patients. for 34 patients. 14 patients who died between diagnosis of pulmonary hypertension and June 1988.

months after the diagnosis of pulmonary hypertension was made. Among the 10 patients who died within 1 year, 5 died of causes directly related to liver failure, 5 of causes likely to be related to pulmonary hypertension (cardiac failure or sudden death excluding gastrointestinal hemorrhage). Survival did not correlate with age, Pugh’s score, hepatic venous pressure gradient, pulmonary arterial pressure, pulmonary vascular resistance, or cardiac index. However, those patients who died of a cause related to pulmonary hypertension, when compared with those who died from causes related to liver failure, had significantly lower Pugh’s scores (7 + 1 vs. 12 f 1, P < O-05), hepatic venous pressure gradient (8 + 2 vs. 14 + 2 mm Hg), cardiac index (1.52 + 0.14 vs. 3.69 f 1.88 L * min-’ . m-‘; P < 0.05) and significantly higher pulmonary arterial pressure (65 + 25 vs. 37 f 7 mm Hg; P < 0.05) and pulmonary vascular

resistance

(1045

f

50

vs.

465

k 295

dyne/s * cm5;

P < 0.05).

Discussion Pulmonary hypertension is thought to be rarely associated with portal hypertension. However, the reported data were calculated from retrospective autopsy studies (1,s) or by comparing the number of patients with known pulmonary and portal hypertension with the number of patients admitted with portal hypertension alone during the same period (2). In the present study, the prevalence of pulmonary hypertension was close to 2%, about three times the highest previous estimation. This estimation is based on data provided by systematic cardiac catheterization in 507 consecutive patients hospitalized with portal hyper-

February 1991

Table 3. Comparison of Patients With Portal Hypertension Potiacaval Shunting

PULMONARY HYPERTENSION IN PORTAL HYPERTENSION

and Pulmonary Hypertension

With or Without Surgical

Our patients With surgical portacaval shunt (n = 10) Interval between diagnosis of portal and pulmonary hypertension (mo) Interval between first symptom and diagnosis of pulmonary hypertension (mo) Mean pulmonary arterial pressure (mm Hg) Cardiac index (L min-‘.m-‘) Pulmonary vascular resistance (dyi7ew2m+) Survival time from time of diagnosis in the patients who died (mol

147 2 49" 43 * 48 * 3.77 k 567 2 412

44 10 2.05 325 49

525

Patients from the literature

Without surgical portacaval shunt (n = 16)

44k 7 f 49 f 3.2 k 623 f

With surgical portacaval shunt (n = 23)

27'

lllk

67

lo* 19 1.63 455

15 f 53 f 3.4 f 771 r

21 14 1 451

25 2 34

12 2 0

Without surgical portacaval shunt (n = 27)

28 f 386 20 k 34 59 2 16 3.37 It 0.82 689 f 275 14 2 15

“Mean rf: SD. *Significantly different from patients with portacaval shunt.

tension of all causes, predominantly alcoholic cirrhosis. Two possible biases in our study of the prevalence of pulmonary hypertension in patients with portal hypertension should be considered. On the one hand, the patients in whom transvenous liver biopsy has been performed might have not been representative of patients with portal hypertension in general: if pulmonary hypertension occurs late during the course of portal hypertension and if our patients who underwent hemodynamic study at the time of transvenous liver biopsy were more severely ill, the prevalence of pulmonary hypertension might have been overestimated in our study. However, the mean Pugh’s score was 8.5 f 2.2 in our patients with alcoholic cirrhosis who underwent transvenous liver biopsy, which is not different from the mean Pugh’s score in the whole group of patients admitted at our institution with cirrhosis. This is probably a result of the fact that transvenous liver biopsy, a safe and readily available procedure in our hospital, is extensively performed in our patients (19). Indisputably, our estimation of the prevalence of pulmonary hypertension is relevant to hospitalized patients with portal hypertension who could differ from a population of patients with asymptomatic portal hypertension. On the other hand, we excluded from this prospective work all patients referred to our hemodynamic Unit with a clinically suspected diagnosis of pulmonary hypertension (8 patients from January 1985 to June 1988) to avoid a selection bias due to our interest in pulmonary hypertension. Therefore, the actual prevalence of primary pulmonary hypertension in patients with portal hypertension may in fact have been underestimated in the present work. Obviously, our investigations led to the detection of asymptomatic pulmonary hypertension. We believe,

however, that clinicians should identify this association more often if they are aware that the actual prevalence of pulmonary hypertension during portal hypertension is higher than previously estimated. Thus, among 10 patients with coexisting portal hypertension and pulmonary hypertension who were identified in our prospective work, 4 complained of exertional dyspnea that had been hitherto overlooked, and 6 were completely asymptomatic. Mean pulmonary vascular resistance was lower in this group than in the group of 26 patients with symptomatic pulmonary hypertension, which could suggest that the patients identified during our prospective study were at an earlier stage. The clinical relevance of hemodynamitally defined, mild pulmonary hypertension in patients with portal hypertension, which remains to be established, depends on two issues. First, does mild pulmonary hypertension progress to a more severe disease in these patients ? To our knowledge, no answer to this question is available in the literature. However, in 3 of our 26 patients with symptomatic pulmonary hypertension, pulmonary pressure had been measured 2-4 years before inclusion in the present study. Pulmonary pressure had markedly increased from the first to the second determination (from 18 + 9 to 47 + 13 mm Hg, mean + SD), while all three patients became dyspneic. This finding suggests that a rapid progression of pulmonary hypertension can be observed in patients with portal hypertension. Second, can aggressive therapy of pulmonary hypertension at an early stage benefit patients with portal hypertension? Although it has been suggested that vasodilators could benefit patients with idiopathic primary pulmonary hypertension if administered before pulmonary arterial resistance is fixed (51), this possibility remains to be explored in patients with coexistent portal and pulmonary hyperten-

526

GASTROENTEROLOGY

HADENGLIE ET AL.

sion. However, preliminary data suggest that pulmonary vascular resistance could be more sensitive to vasodilators in patients with portal and pulmonary hypertension than in those with primary pulmonary hypertension alone (52,53). Our 26 patients with coexistent portal and pulmonary hypertension were older than those reported in the literature and were more often males than females. This is probably related to alcoholic cirrhosis being the predominant cause of portal hypertension in our patients. Other causes of portal hypertension remained uncommon causes of pulmonary hypertension in our patients. The high prevalence of uncommon causes of portal hypertension in patients reported in the literature might be explained by the interest in reporting uncommon diseases. Consistent with the view that portal hypertension by itself, and not liver failure, causes pulmonary hypertension in these patients, the degree of liver failure as estimated by Pugh’s score did not correlate with pulmonary vascular resistance in our patients. Surgical portosystemic shunting was considered to be a risk factor for the development of pulmonary hypertension (2,241. This has been suggested by the large proportion of surgical shunts in patients with portal and pulmonary hypertension reported in the literature. A prospective study by Senior et al. (24) also reported the occurrence of pulmonary hypertension in 6 of 11 patients 2-l 7 years after creation of a surgical portacaval shunt. However, in the present study as well as in the literature, patients with surgical portacaval shunts did not differ from those without a shunt with respect to hemodynamic characteristics or time of survival after the diagnosis of pulmonary hypertension. It is interesting to note that the interval between diagnosis of portal and pulmonary hypertension was significantly longer in patients with surgical shunts (averaging more than 10 years in our patients) than in those without surgical shunts. Conceivably, patients who were selected for and survived surgical portosystemic shunting escaped variceal hemorrhage and ascites, but remained exposed for years to an increased risk for pulmonary hypertension. This is consistent with the observation that, whether shunting procedures are performed or not, portal hypertension usually precedes pulmonary hypertension by several years: portal hypertension was diagnosed before pulmonary hypertension in > 90% of our patients. Surgical portosystemic shunts do not differ in essence from spontaneous portosystemic collaterals. Surgical shunts only derivate larger quantities of blood from portal tributaries to systemic circulation. However, neither in our patients with pulmonary hypertension nor in patients with alcoholic cirrhosis without known pulmonary hypertension was pulmo-

Vol. 100, No. 2

nary pressure or resistance correlated to azygos blood flow, a reliable index of superior portosystemic collateral circulation. In addition, our hemodynamic results do not support the hypothesis that pulmonary hypertension might result from the hyperkinetic circulation known to occur in patients with portal hypertension and to be exaggerated by surgical shunting. In fact, mean values for pulmonary vascular resistance were lower in patients with alcoholic cirrhosis than in controls. Thus, our results do not suggest that surgical shunting by itself was a major risk factor in our patients, but rather that patients with surgical shunts remained longer exposed to a risk that seems common to all patients with surgical as well as spontaneous portacaval circulation. Survival from the time of diagnosis of pulmonary hypertension appeared difficult to predict in our patients: 5 died within 1 month of diagnosis, 10 survived 2 years or more, and 2 survived > 10 years, without any clear relation to the degree of liver failure or pulmonary hypertension. Cardiac index was usually < 2 Wmin * m* in patients who died from causes related to pulmonary hypertension and was normal or elevated in those who died of liver failure. Prospective studies are needed to identify definite prognostic factors in patients with pulmonary hypertension associated with portal hypertension. However, in our experience, a low cardiac index, although not predictive of survival, should be considered indicative of a higher risk of complications related to pulmonary hypertension than complications related to cirrhosis itself. We conclude that portal hypertension with portacaval shunting, either surgical or spontaneous, is an important risk factor for the development of pulmonary hypertension. This risk factor seems to affect susceptible individuals independently of liver failure, portal pressure, or amount of blood shunted. The number of patients with portal hypertension who develop pulmonary hypertension could increase with the duration of portal hypertension. Finally, cardiac index might be predictive of the cause of death, but not of survival, in patients with pulmonary hypertension complicating portal hypertension.

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February 1991

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PULMONARY HYPERTENSION IN PORTAL HYPERTENSION

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Received September 8,1989. Accepted August 10,199O. Address requests for reprints to: Antoine Hadengue, M.D., INSERM U 24, HBpital Beaujon, Clichy, France.

Pulmonary hypertension complicating portal hypertension: prevalence and relation to splanchnic hemodynamics.

The prevalence of pulmonary hypertension in 507 patients hospitalized with portal hypertension but without known pulmonary hypertension who underwent ...
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