Pulmonary hypertension in isolated aortic stenosis

J

THoRAc CARDIOVASC SURG

1988;95:603-7

Pulmonary hypertension in isolated aortic stenosis Hemodynamic correlations and follow-up The clinical, hemodynamic, and angiographic data on 92 patients with severe isolated aortic stenosis were reviewed to determine the incidence and mechanism of pulmonary hypertension. The status of each of these patients was determined 1 to 8 years after diagnosis by cardiac catheterization. Patients were divided into three groups on the basis of the pulmonary artery systolic pressure: group 1 (::::;30 mm Hg), 46 patients; Group 2 (31 to 50 mm Hg), 31 patients; and Group 3 (>50 mm Hg), 15 patients. The prevalence of pulmonary hypertension was 50% (46/92) and that of severe pulmonary hypertension, 16% (15/92). There was no significant difference in age, aortic valve gradient, or valve area among the three groups. There was a significant positive correlation in left ventricular end-diastolic pressure (group 1, 15.5 ± 7.2 mm Hg; group 2, 23.3 ± 8.1 mm Hg; and group 3, 29.5 ± 5.8 mm Hg; R = 0.56, p < 0.01). There was also a significant negative correlation in left ventricular ejection fraction (group 1, 67.5 % ± 14 %; group 2, 62.3 % ± 13.8 %; and group 3 49.9 % ± 18.3 %; R = 0.43, p < 0.01). Of the 92 patients, 85 had aortic valve replacement with four (4.7%) hospital deaths. FoUow-upshowed exceUent symptomatic relief in aU three groups. Thirteen of the 15 patients in group 3, with severe pulmonary hypertension, had aortic valve replacement. There were no hospital deaths and only one noncardiac death at follow-up in Group 3 patients, and 11 of the 12 surviving patients were in New York Heart Association functional class I. We conclude that pulmonary hypertension is common in isolated aortic stenosis and is related to an elevated left ventricular end-diastolic pressure, frequently with preserved systolic function. Surgical results are exceUent.

Lewis W. Johnson, MD, Mary Beth Hapanowicz, RN, Carlo Buonanno, MD, Michael A. Bowser, MD, Mehdi A. Marvasti, MD, and Frederick B. Parker, Jr., MD, Syracuse. N. Y.

Although the pathophysiology of aortic stenosis and the accompanying left ventricular dysfunction has been extensively studied,':' less attention has been focused on pulmonary hypertension in patients with isolated aortic stenosis. We, therefore, attempted to determine (l) the incidence of pulmonary hypertension in aortic stenosis, (2) the mechanism of the development of pulmonary hypertension, and (3) the risk and effects of operations on patients with this condition. To answer these questions, we reviewed the clinical records and hemodynamic and angiographic data of patients with severe, isolated aortic stenosis studied in From Crouse Irving Memorial Hospital and SUNY Health Science Center at Syracuse, Syracuse, N.Y. Received for publication Jan. 23, 1987. Accepted for publication March 17, 1987. Address for reprints: Lewis W. Johnson, MD, 736 Irving Ave., Syracuse, NY 13210.

our laboratory from 1977 through 1984. Ninety-two patients fulfilled the criteria for inclusion in the study. The patients were divided into three groups based on the pulmonary artery systolic pressure: normal, mildly elevated, and severely elevated. The status of each of these patients was determined in 1985, 1 to 8 years after initial diagnosis by cardiac catheterization. Methods Case histories of all patients with isolated aortic stenosis from 1977 through 1984 with a mean systolic gradient of at least 50 mm Hg and a calculated aortic valve area of 0.7 em? or less detected by cardiac catheterization were reviewed. Only patients with complete studies including simultaneous aortic valve gradients, left ventriculography, supravalvular aortic angiography, and selective coronary arteriography were included. Excluded from the analysis were those patients with mitral valve disease or more than mild aortic regurgitation and those with a history of myocardial infarction or with segmental contraction abnormalities resulting from coronary artery disease. However, the analysis includes patients with coronary

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The Journal of Thoracic and Cardiovascular Surgery

Johnson et al.

Table I. Group 3: Severe pulmonary hypertension Case No.

Age (yr)

PAP (mmHg)

PVR (Wood units)

AVG (mmHg)

AVA (em']

LVEDP (mmHg)

EF (%)

I

62 72 50 73 71 57 70 60 69 61 81 59 69 55 59

72/29 51/20 74/39 79/25 67/34 51/25 51/25 74/30 92/40 82/32 78/29 53/25 83/29 55/17 65/27

4.7 2.6 3.5 3.3 3.5 1.5 2.2 3.8 5.1 7.1 3.0 3.5 3.8 0.8 1.6

25 84 82 78 54 60 119 107 46 66 65 90 104 50 58

0.5 0.47 0.45 0.8 0.49 0.9 0.5 0.4 0.6 0.42 0.8 0.5 0.55 0.8 0.6

30 31 35 22 33 23 28 33 38 29 22 31 18 33 36

76 24 59 32 43 56 62 54 14 66 79 57 37 46

2 3 4 5 6 7 8 9 10 II

12 13 14 15

44

Operation

Yes

Follow-up

I

No

CD

Yes Yes Yes Yes Yes Yes Yes

I I I I I I I

No

Yes Yes Yes Yes Yes

CD NCD I I I III

Legend: PAP. Pulmonary artery systolic pressure. PVR. Pulmonary vascular resistance. AVG. Aortic valve gradient. AVA, Aortic valve area. LVEDP. Left ventricular end-diastolic pressure. EF. Ejection fraction. Follow-up: New York Heart Association functional classes I to IV. CD. Cardiac death. NCD. Noncardiac death.

artery disease without left ventricular dysfunction caused by coronary artery disease. Ninety-two patients met these criteria. Each patient had right heart and retrograde left heart catheterization. The left ventricle was entered by the brachial approach. Systemic aortic pressure was measured by a second arterial catheter placed percutaneously in the right femoral artery and advanced to a position in the ascending aorta. Pressures were measured by standard fluid-filled angiographic catheters. Cardiac output was measured by the Fick method simultaneously with the gradient recording. The aortic valve area was calculated by the Gorlin formula.' Left ventriculograms were done in a single-plane right anterior oblique projection and the ejection fraction was calculated by the area-length method." Significant aortic regurgitation was excluded by aortograms in the left anterior oblique position in all patients. Selective coronary arteriograms were performed by the Judkins or Sones technique. Catheterization data were reviewed with special attention to pulmonary artery pressure, left ventricular end-diastolic pressure, aortic valve gradient measured by planimetry, pulmonary vascular resistance, and left ventricular ejection fraction. The patients were divided into three groups according to the level of pulmonary artery systolic pressure at the time of cardiac catheterization: group 1, normal pulmonary artery pressure (pulmonary artery systolic pressure .::::;30 mm Hg); group 2, mild pulmonary hypertension (pulmonary artery systolic pressure 31 to 50 mm Hg); group 3, severe pulmonary hypertension (pulmonary artery systolic pressure >50 mm Hg). Aortic valve replacement was performed with extracorporeal circulation, moderate hypothermia, and cold cardioplegia. The status of each of these patients was determined in late 1985, 1 to 8 years after cardiac catheterization; the average follow-up duration was 4 years. Follow-up information was obtained from the referring physician and by telephone contact

with the patient or a member of the patient's family. Information obtained included subsequent hospitalizations, cardiac catheterizations, cardiac operations, and present symptoms (chest pain, congestive heart failure, or syncope). In patients who died, an attempt was made to determine the cause of death. Information about in-hospital death was obtained from a review of hospital records. If an autopsy was performed, the report was reviewed. No patients were lost to follow-up. Statistical analysis of the differences among groups was performed by an analysis of variance; correlation between variables was examined by simple regression analysis. Probability values of less than 0.05 were considered significant. Where analysis of variance showed a statistically significant difference among the three groups, Duncan's multiple range test was used to check for significance between pairs of groups.

Results There were 64 male and 28 female patients. The average age at cardiac catheterization was 62.9 years (range 33 to 83 years). Forty-six patients had normal pulmonary artery pressures (group 1), 31 had mild elevation of the pulmonary artery pressure (group 2), and 15 had severe pulmonary hypertension (group 3). Of the 92 patients, 85 had aortic valve replacement. Of the remaining seven, one died suddenly while awaiting valve replacement, three died of progressive congestive heart failure, and three were in New York Heart Association class I. Among the 85 undergoing aortic valve replacement, there were four hospital deaths (4.7%). Among the 81 patients surviving aortic valve replacement, there were eight late deaths, two cardiac and six noncardiac. Of the 73 patients alive after aortic

Volume 95 Number 4 April 1988

605

Pulmonary hypertension in isolated aortic stenosis

Table II. Hemodynamic data PVR

No. Group I

46

Group 2

31

Group 3

15

p Values

1-2 2-3 1-3

Age (yr)

PAP (mm Hg)

60.9 ± 10.2 65.3 ± 8.9 64.5 ± 8.3

25.1 ± 3.6 39.4 ± 4.9 68.5 ± 13.6

NS NS NS

AVG (mmHg)

AVA

units)

1.1 ±0.5 1.9 ±0.8 3.5 ± 1.5

64.5 ± 13.9 72.1 ±14.2 72.5 ±25.6

0.70 ±0.18 0.67 ±0.18 0.59 ±O.16

NS NS NS

NS NS

(Wood

0.01 0.01 0.01

(em')

0.05

LVEDP (mmHg)

15.5 ±7.2 23.2 ±8.1 29.5 ±5.8 0.01 0.01 0.01

EF (%)

67.5 ± 14.0 62.3 ± 13.8 49.9 ± 18.3

NS 0.01 0.01

Legend: PAP, Pulmonary artery systolic pressure. PVR, Pulmonary vascular resistance. AVG, Aortic valve gradient. AVA, Aortic valve area. LVEDP, Left ventricular end-diastolic pressure. EF, Ejection fraction.

valve replacement, 69 were in class I-II and four were class III-IV. Group 1: Normal pulmonary artery pressure. Cardiac catheterization data. Pulmonary artery systolic pressure was 25.1 ± 3.6 mID Hg (mean ± standard deviation). Pulmonary vascular resistance was 1.1 ± 0.48 Wood units. The mean aortic valve gradient, measured with a planimeter, was 64.5 ± 13.9 mID Hg and the calculated aortic valve area was 0.7 ± 0.18 em', Left ventricular end-diastolic pressure was 15.5 ± 7.2 mID Hg and left ventricular ejection fraction was 67.5% ± 14.0%. Follow-up data. Of the 46 patients in group 1, four patients were not operated on and 42 had aortic valve replacement. Of these four not having an operation, two died, one of progressive congestive heart failure and the other suddenly two years after cardiac catheterization. When reevaluated, the other two patients not having an operation were in class I-II. Three of the 42 undergoing aortic valve replacement died in the hospital (7.7%) of respiratory failure, endocarditis, and a bleeding diathesis. Among the 39 patients surviving aortic valve replacement, there were five deaths, one cardiac and four noncardiac. Of the 34 remaining patients, 31 were in class I-II and three were in class III-IV. Group 2: Mild pulmonary hypertension. Cardiac catheterization data. Pulmonary artery systolic pressure was 39.4 ± 4.9 mID Hg. Pulmonary vascular resistance was 1.9 ± 0.84 Wood units. The mean aortic valve gradient, measured with a planimeter, was 72.1 ± 14.2 mID Hg and the calculated aortic valve area was 0.67 ± 0.18 em'. Left ventricular end-diastolic pressure was 23.2 ± 8.1 mID Hg and left ventricular ejection fraction was 62.3% ± 13.8%.

Follow-up data. Of the 31 patients in Group 2, one patient did not have an operation and was in class I at follow-up. Among the 30 patients undergoing aortic valve replacement, there was one hospital death (3.3%), caused by myocardial infarction with associated cardiogenic shock. Among the remaining 29 patients, there were two late deaths (one cardiac and one noncardiac). All surviving patients were in class I-II. Group 3: Severe pulmonary hypertension (Table I).

Cardiac catheterization data. Pulmonary artery systolic pressure was 68.5 ± 13.5 mID Hg. Pulmonary vascular resistance was 3.5 ± 1.5 Wood units. Mean aortic valve gradient, measured with a planimeter, was 72.5 ± 25.6 mID Hg and the calculated aortic valve area was 0.59 ± 0.16 em'. Left ventricular end-diastolic pressure was 29.5 ± 5.8 mID Hg and left ventricular ejection fraction was 49.9 ± 18.3%. Follow-up data. Of the 15 patients in group 3, two patients did not have an operation. One of these died suddenly 2 days after cardiac catheterization and one died 2 years later of congestive heart failure. Among the 13 patients having aortic valve replacement, there were no hospital deaths. One of these 13 patients died of prostatic carcinoma. Of the surviving 12 patients, 11 were in class I and one was in class III. This symptomatic patient also has severe chronic obstructive pulmonary disease. Comparison of groups 1, 2, and 3 (Table II). The patients' ages were not significantly different in the three groups. Pulmonary vascular resistances were significantly higher with increased pulmonary artery pressure. There was a trend toward a higher gradient and smaller valve area.

The Journal of Thoracic and Cardiovascular Surgery

606 Johnson et al.

There was a significant positive correlation between the pulmonary artery systolic pressure and left ventricular end-diastolic pressure (group 1, 15.5 ± 7.2 mm Hg; group 2, 23.3 ± 8.1 mm Hg; and group 3, 29.5 ± 5.8 mm Hg; R = 0.56, P < 0.01). There was a negative correlation between pulmonary artery systolic pressure and left ventricular ejection fraction (group 1,67.5% ± 14%; group 2, 62.3% ± 13.8%; and group 3, 49.9% ± 18.3%; R = 0.43, P < 0.01).

Discussion The prevalence of pulmonary hypertension in aortic stenosis has varied from 11% to 46%.2,10-18 Fifty percent of the patients in this study of isolated aortic stenosis had elevation of pulmonary artery pressure and 16% had severe pulmonary hypertension. We were careful to exclude patients with any mitral valve disease, more than mild aortic regurgitation, or left ventricular dysfunction caused by associated coronary artery disease. Some critically ill patients with aortic stenosis and pulmonary hypertension who did not have left ventriculography or aortography were excluded; therefore, the incidence of pulmonary hypertension associated with aortic stenosis in general may be even higher. The mechanism of the development of pulmonary hypertension appears to be related to an elevation of left ventricular filling pressure. All of our group 3 patients had an elevated left ventricular end-diastolic pressure (29.5 ± 5.8 mm Hg). Systolic dysfunction, as evidenced by a decreased ejection fraction below 50%, occurred in less than half of the patients with severe pulmonary hypertension. There was evidence of some reactive pulmonary hypertension manifested by an elevated pulmonary vascular resistance but not to the extent seen in mitral stenosis. This may be due to the chronicity of the elevation of pulmonary venous pressure in mitral compared with aortic stenosis. The prognosis of patients with aortic stenosis and pulmonary hypertension without valve replacement has been reported to be poor. McHenry and associates" studied 15 patients with severe pulmonary hypertension and elevated pulmonary vascular resistance associated with aortic stenosis. Four patients died suddenly shortly after catheterization, three died while awaiting the operation, and eight had an urgent operation and survived. Three patients had postoperative cardiac catheterization and each had a marked decrease in pulmonary vascular resistance. This experience led to the recommendation of urgent operation in patients with aortic stenosis complicated by pulmonary hypertension, particularly in association with left ventricular failure. One of our patients in group 3 with severe pulmonary

hypertension died suddenly 2 days after catheterization. Copeland and colleagues'? followed up a large group of patients after aortic valve replacement and found that preoperative pulmonary hypertension adversely affected long-term prognosis. Kirsh and co-workers'? found poorer long-term results after aortic valve replacement in patients with pulmonary hypertension. The surgical results in our group 3 patients were excellent. There were no operative deaths. The I to 8 year follow-up revealed no cardiac deaths, the only death being due to cancer. Of the 12 patients followed up for 1 to 8 years, 11 were in class I. We conclude that pulmonary hypertension is common in adult patients with isolated aortic stenosis. The mechanism may be related to an elevated left ventricular end-diastolic pressure, frequently with preserved systolic function. Operative mortality is low in this group of patients and long-term symptomatic results after aortic valve replacement appear to be excellent. We gratefully acknowledge the statistical advice of Dr. Robert Gilbert and the secretarial assistance of Gail Ogden, CMA. REFERENCES I. Gorlin R, McMillen IKR, Medd WE, Matthews MB, Daley R. Dynamics of the circulation in aortic valvular disease. Am J Med 1955;18:855-70. 2. Braunwald E, Goldblatt A, Aygen MM, Rockoff SO, Morrow AG. Congenital aortic stenosis: clinical and hemodynamic findings in 100 patients. Circulation 1963; 27:426-50.

3. Gunther S, Grossman W. Determinants of ventricular function in pressure-overload hypertrophy in man. Circulation 1979;59:679-88. 4. Carabello BA, Green LH, Grossman W, Cohn LH, Koster JK, Collins JJ Jr. Hemodynamic determinants of prognosis of aortic valve replacement in critical aortic stenosis and advanced congestive heart failure. Circulation 1980;62:42-8. 5. Huber 0, Grimm J, Koch R, Krayenbuehl HP. Determinants of ejection performance in aortic stenosis. Circulation 1981;64:126-34. 6. Dineen E, Brent BN. Aortic valve stenosis: comparison of patients with to those without chronic congestive heart failure. Am J Cardiol 1986;64: 126-39, 7. Peterson KL, Tsugi J, Johnson A, DiDonna J, LeWinter M. Diastolic left ventricular pressure volume and stressstrain relations in patients with valvular aortic stenosis and left ventricular hypertrophy. Circulation 1978;58:7789.

8. Gorlin R, Gor/in SG. Hydraulic formula for calculation of the stenotic mitral valve, other cardiac valves and central circulatory shunts. Am Heart J 1951;41:1-29.

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9. Kennedy JW, Trenholme SE, Kasser IS. Left ventricular volume and mass from single plane cineangiograms: a comparison of anteroposterior and right anterior oblique methods. Am Heart J 1970;80:343-52. 10. Lee SJK, Jonsson B, Bevegard S, Karlof I, Astrom H. Hemodynamic changes at rest and during exercise in patients with aortic stenosis of varying severity. Am Heart

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heart: observations in a catheterization material. Scand J Clin Lab Invest 1973;31 :409-18. 13. Shrivastava S, Tandon R. Congenital aortic stenosis with severe pulmonary arterial hypertension. Indian Heart J 1981;33:47-51. 14. McHenry R, Rice J, Matloff HJ, Flamm MD. Pulmo-

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