Jun 2, 2001 - Kook-Jin Chun M.D., Seong Ho Kim, M.D., Byung Jae An, M.D.,. Sang Hyun Kim, M.D., Jae Kyung Ha, M.D., Taek Jong Hong M.D., and Yung ...
The Korea n J ourna l of Inte rnal Me dic ine Vol. 16, No. 2, J une , 2001
S u r v iv a l a n d P r o g n o s t ic Fa ct o r s in P a t ie n t s w it h P r im a ry P u lm o n a ry Hy p e rt e n s io n Ko o k- J in C h u n M . D . , S e o n g H o Kim , M . D . , By u n g J a e A n , M . D . , S a n g Hy u n Kim , M . D . , J a e Ky u n g H a , M . D . , T a e k J o n g H o n g M . D . , a n d Y u n g W o o S h in M . D . De p a rt m e nt o f In t e rn a l M e d ic in e , Co lle g e o f M e d ic in e , Pu s a n N a t io n a l U n iv e rs ity , Pu s a n , Ko re a O b j e c t iv e s : P rim a ry p u lm o n a ry hy p e rt e n s io n ( P PH) t h a t a f f e c t s p re d o m in a n t ly y o u n g a n d p ro d u c t iv e p e o p le is a p ro g re s s iv e f a t a l d is e a s e o f u n k n o w n c a u s e . T h e o bj e c t iv e s o f t h is s t u d y w e re t o c h a ra c t e riz e m o rt a lity in p a t ie n t s w it h PP H a n d t o in v e s t ig a t e t h e f a c t o rs a s s o c ia t e d w it h t h e ir s u rv iv a l. M e t h o d s : T h irt e e n p a t ie n t s w it h P P H w e re e n ro lle d b e t w e e n 1 9 8 8 a n d 1 9 9 6 a n d f o llo w e d - u p t h ro u g h J u ly 1 9 9 9 . M e a s u re m e n t s a t d ia g n o s is in c lu d e d h e m o d y n a m ic a n d p u lm o n a ry f u n c t io n v a ria b le s in a d d it io n t o in f o rm a t io n o n d e m o g ra p h ic d a t a a n d m e d ic a l h is t o ry . R e s u lt s : 1 ) T h e m e a n a g e o f t h e p a t ie n t s w it h P PH e n ro lle d in t o t h e s t u d y w a s 3 6 . 1 ±9 . 3 y e a rs w it h f e m a le p re d o m in a n c e . 2 ) T h e e s t im a t e d m e d ia n s u rv iv a l w a s 3 .4 ±0 . 6 y e a rs . 3 ) De c re a s e d c a rd ia c in d e x w a s t h e o n ly s ig n if ic a n t p re d ic t o r o f m o rt a lity ( Co x p ro p o rt io n a l h a z a rd s m o d e l) . C o n c l u s io n : Pa t ie n t s w it h P P H h a v e a p o o r s u rv iv a l e x p e c t a n cy . In t h is lim it e d s t u d y w it h a s m a ll n u m b e r o f p a t ie n t s , m o rt a lity is la rg e ly a s s o c ia t e d w it h d e c re a s e d c a rd ia c in d e x . Ke y W o rd s : Primary pulm onary hypertension; S urvival; Prognosis
INT R O D UC T IO N Primary pulmonary hypertension (PPH) is an uncommon disease that affects predominantly young and productive people 1 - 3 ) . Although important conceptual advances and information about the pathogenesis, histopathology, characterization and management of PPH have been generated in the past decade, many questions remain to be answered. Part of the reason for the lack of complete knowledge in this regard is a rare entity and a short mean survival of 2 to 4 years 2 - 5 ) . Patients with a survival period > 5 to 10 years have also been well documented5 - 9 ) and even spontaneous regression of the disease, although uncommon, has been described 10 - 1 1) . We analyzed determinants associated with the survival and prognosis of patients with PPH. Address reprint requests to : Kook-Jin Chun, M.D., Department of Internal Medicine, Pusan National University, 1- 10 Amidong, SeoGoo, Pusan 602- 739, Korea
MA T E R IA LS A N D MET HO DS 1. Materials The study series included 13 patients in whom PPH was diagnosed at our institution between 1988 and 1996 and who were followed- up through J uly 1999. As in other studies, the PPH was diagnosed by a thorough workup, including clinical history, physical examination, laboratory tests, chest radiography, ECG, pulmonary function tests, echocardiography, radionuclide perfusion lung scan and cardiac catheterization. Criteria used to establish the diagnosis of PPH include a mean pulmonary arterial pressure of more than 25 mmHg at rest or 30 mmHg during exercise, a normal pulmonary capillary wedge pressure (PCWP) and absence of other disease known to cause or to be associated with secondary pulmonary hypertension1 2 ) . Particular care was taken to exclude patients with evidence of congenital heart disease or acquired valvular or myo75
K.J. Chun, S.H. Kim, B.J. An, S.H. Kim, J.K. Ha, T.J. Hong, Y.W. Shin
cardial disease, obstructive or restrictive lung disease, or both, parasitic disease involving the lung, pulmonary thromboembolic and clearly defined collagen vascular disease and the antiphospholipid syndrome. 2. He modyna mic meas ureme nts Cardiac output and cardiac index were measured by the thermodilution method and pulmonary artery pressure, PCWP, right atrial pressure, right ventricular pressure and oxygen saturation were obtained by a Swan- Ganz catheter. The radial artery was also cannulated with a needle for arterial oxygen blood sampling. We did not evaluate the hemodynamic data after taking a vasodilator drug during cardiac catheterization. 3 . Treatment Some patients in this study had been taking a vasodilator and diuretics. All patients were not treated with coumadin. 4 . Statistical ana lys is For the survival analysis, we used the initial clinical and hemodynamic characteristics by cardiac catheterization as an index for determining survival. All values are expressed as mean±S D. The Kaplan- Meier method was used to estimate overall survival distribution and Cox proportional hazards model was used to examine the relation between survival and variables. A p value < 0.05 was significant in all analysis.
R E S U LT S 1. Clinica l cha racte ristics The mean age of the patients with PPH entered into the study was 36.1± 9.3 years and women were predominant (female/male ratio 1.75:1). None of the patients had histories of appetite suppressant drug use and 3 were cigarette smokers. Of the women of reproductive age, one had taken oral contraceptive and none had a family history of familial pulmonary hypertension. The frequency of symptoms at diagnosis was dyspnea 100%, syncope 2 (16.7%), chest pain 2 (16.7%), effort related palpitation 1 (8.3%), hoarseness 4 (30.7%) and leg edema 3 (23.1%). The functional status of the patients at diagnosis according to the New York Heart Association (NYHA) classification was as follows; 8.3% of the patients 76
Ta ble 1. Ba s e line c ha ra cte ris tic s N=13 Age , yea rs Sex Ma le Fe ma le Smoking Fa mily History NYHA class I II III IV Syncope Chest pa in Pa lpitation Hoa rse ness Pe riphe ra l ede ma
36.1± 9.3 3 (23.1%) 10 (76.9%) 3 (23.1%) 0 (0 %) 1 5 5 2 2 2 1 4 3
(8.3%) (4 1.7%) (4 1.7%) (16.7%) (16.7%) (16.7%) ( 8.3%) (30.7%) (23.1%)
NYHA, New York Hea rt Association.
were in class I, 4 1.7% in class II, 4 1.7% in class III and 16.7% in class IV (Table 1). Mean time from onset of the first symptom to diagnosis of PPH was 4.2 years (range 0 to 9.6). 2. La boratory findings The chest radiograph showed the typical changes associated with pulmonary hypertension, namely prominence of the main pulmonary artery in all patients and enlarged hilar vessels. The mean cardiothoracic ratio was 0.6. The ECG showed a sinus rhythm and evidence of right ventricular hypertrophy in all cases. The echocardiogram confirmed right ventricular hypertrophy and showed variable degrees of right ventricular enlargement. A lung perfusion scan was performed in 8 patients and was considered to be normal in 4 (50%) and showed diffuse bilateral patchy pattern in 4 (50%). The mean hemoglobin and hematocrit levels were 13.9± 5 g/dL and 4 1.7±4.5%, respectively. The total platelet count was normal. The antinuclear antibody test was negative in all cases. 3 . Pulmonary function and Hemodynamic findings Pulmonary function tests were performed in all cases and there was no evidence of abnormal obstructive and restrictive patterns. Mean pulmonary artery pressure was 66.8 mmHg, elevated right atrial pressure (7.1 mmHg) with normal PCWP and reduced cardiac index (2.31 L/min/m)2 ) were noted (Table 2).
