Clinical Evaluation of Pulmonary Hypertension in Systemic Sclerosis and Related Disorders: A Doppler Echocardiographic Study of 135 Japanese Patients

doi:10.1378/chest.111.1.36

Chest

Volume 111, Issue 1, January 1997, Pages 36-43

https://doi.org/10.1378/chest.111.1.36 Get rights and content

Background

Previous studies on pulmonary hypertension (PH) in systemic sclerosis and related disorders used differing patient populations, and defined PH according to different criteria. We have attempted to determine the prevalence and cause of PH in these disorders using a mainly noninvasive cardiopulmonary evaluation.

Patients and methods

One-hundred thirty-five Japanese patients with systemic sclerosis and related disorders were divided into proximal and distal scleroderma groups, with or without overlapping features of systemic lupus erythematosus (SLE) and polymyositis. They underwent multiple cardiopulmonary tests, including chest radiography, pulmonary function tests, and echocardiography to screen for pulmonary fibrosis and PH.

Results

The pulmonary artery systolic pressure was estimated by Doppler echocardiography in 80 patients (59%). PH (systolic pressure ≥40 mm Hg) was diagnosed in 28 patients by the Doppler method and in two patients by right heart catheterization (mean pressure ≥20 mm Hg). Doppler-estimated pulmonary artery pressures were significantly higher in patients with proximal scleroderma (p<0.05), and in those with an SLE/polymyositis overlap (p<0.01). The FVC was significantly reduced in the proximal scleroderma group (p<0.0005), but not in the overlap group. PH was attributable to pulmonary fibrosis in nine patients who had proximal scleroderma without overlap. Pulmonary arteriopathy was the probable cause of PH in seven patients with overlap and in four patients who had proximal scleroderma without overlap.

Conclusions

These findings suggest that proximal scleroderma predisposes patients to PH mainly because of pulmonary fibrosis, but occasionally because of pulmonary arteriopathy. An overlap of SLE/polymyositis predisposes patients to PH due to the occurrence of arteriopathy.

Section snippets

Patient Selection and Study Protocol

The initial study population consisted of 154 Japanese patients who were evaluated at the Scleroderma Clinic of Tokyo University Hospital, and who underwent multiple radiographic, echocardiographic, and pulmonary function studies between March 1990 and December 1995. Inclusion in the study required the presence of sclerodermatous skin changes or puffy, sausage-like fingers,18, 19 and a positive immunofluorescence test result for antinuclear antibodies.16, 17 We excluded 14 patients with

Characteristics of the Study Patients

Table 1 shows the characteristics of the final study population, which consisted of 135 patients (122 women and 13 men; mean age, 52.7±12.3 years). The mean period from the disease onset to the last echocardiographic study (duration of disease) was 11.6±8.7 years. Thirty-three patients with distal scleroderma did not meet the ARA diagnostic criteria for systemic sclerosis.²⁰ These patients were considered to have systemic sclerosis or related disorders on the basis of the presence of

DISCUSSION

In this study of Japanese patients with systemic sclerosis and related connective tissue disorders, Doppler-estimated pulmonary artery pressures were significantly higher in the proximal scleroderma and in the SLE/PM overlap groups. The FVC and Dco were significantly reduced in the proximal scleroderma than in the distal scleroderma group, suggesting that pulmonary fibrosis was the primary cause of PH in the proximal scleroderma group. Pulmonary arteriopathy was the probable cause of PH in the

ACKNOWLEDGMENTS

The authors are indebted to Susumu Sakurai and Tomiko Takahashi for their fine technical assistance during the echocardiographic studies. We also thank Dr. Chikuma Hamada, of the Department of Pharmacoepidemiology, for his kind advice regarding the statistical analyses.

REFERENCES (25)

YoungR.H. et al.
Pulmonary vascular changes in scleroderma
Am J Med
(1978)
UngererR.G. et al.
Prevalence and clinical correlates of pulmonary arterial hypertension in progressive systemic sclerosis
Am J Med
(1983)
CurrieP.J. et al.
Continuous wave Doppler determination of right ventricular pressure: a simultaneous Doppler-catheterization study in 127 patients
J Am Coll Cardiol
(1985)
FritzlerM.J. et al.
The CREST syndrome: a distinct serologic entity with anticentromere antibodies
Am J Med
(1980)
SchneiderP.D. et al.
Serial pulmonary function in systemic sclerosis
Am J Med
(1982)
OwensG.R. et al.
Cardiopulmonary manifestations of systemic sclerosis
Chest
(1987)
SacknerM.A. et al.
The pathophysiology of scleroderma involving the heart and respiratory system
Ann Intern Med
(1964)
SalerniR. et al.
Pulmonary hypertension in the CREST syndrome variant of progressive systemic sclerosis (scleroderma)
Ann Intern Med
(1977)
StupiA.M. et al.
Pulmonary hypertension in the CREST syndrome variant of systemic sclerosis
Arthritis Rheum
(1986)
Al-SabbaghM.R. et al.
Pulmonary arterial morphometry in systemic sclerosis: a case-control autopsy study
Arthritis Rheum
(1986)

AlpertM.A. et al.

Acute and long-term effects of nifedipine on pulmonary and systemic hemodynamics in patients with diffuse systemic sclerosis, the CREST syndrome and mixed connective tissue disease

Am J Cardiol

(1991)

AgiaG.A. et al.

Pulmonary involvement in MCTD

Am Rev Respir Dis

(1980)

Cited by (62)

Propensity Score Methods for Bias Reduction in Observational Studies of Treatment Effect
2018, Rheumatic Disease Clinics of North America
Registry and survival study in Chinese patients with idiopathic and familial pulmonary arterial hypertension
2007, Chest
Citation Excerpt :
Two-dimensional transthoracic echocardiography with Doppler flow is the most commonly used tool to screen PAH. Murata et al7 reported that systolic PAP estimated by echocardiography is often higher than that estimated by RHC. We also found a variation in results with the use of these two methods (97.8 ± 28.9 vs 89.7 ± 24.5 mm Hg, respectively; p = 0.03).
To evaluate the clinical features and survival data of patients with idiopathic pulmonary arterial hypertension (PAH) and familial PAH in Chinese patients.
Seventy-two patients with idiopathic PAH and familial PAH were enrolled in the study from 1999 to 2004 and were classified into two groups according to World Health Organization (WHO) functional class (I/II and III/IV). Clinical and hemodynamic data were recorded.
The mean age of the 72 patients was 35.9 years with female patient/male patient ratio of 2.4:1. A significant difference was identified in the clinical presentation between two WHO functional class groups at baseline. Echocardiography showed a mean pulmonary systolic pressure of 98 mm Hg. Left ventricular end-diastolic diameter was significantly smaller in the group of patients in WHO functional class III/IV than in those in class I/II group. After follow-up for a mean (± SD) duration of 40.1 ± 20.0 months, the survival rates at 1, 2, 3, and 5 years were 68.0%, 56.9%, 38.9%, and 20.8%, respectively. A significant difference was identified in survival rate between the class I/II and class III/IV groups (p = 0.02 [log rank test]).
The baseline characteristics and survival rates of our cohort study are close to those of the National Institutes of Health Registry in the 1980s, and the 1-year survival rate is obviously lower for patients in this registry than for those in the French registry between 2002 to 2003. Lack of effective treatment was the main cause of poor survival in this study. Our results support the need of an appropriate treatment strategy for this devastating disease in China.
Determinants of Pulmonary Arterial Hypertension in Scleroderma
2007, Seminars in Arthritis and Rheumatism
Citation Excerpt :
The prevalence (29%) of PAH found in this study is within the range reported by previous cross-sectional studies (4,5,16-22). In the majority of these studies, screening for PAH was similarly done by 2-dimensional echocardiography, with the RVSP cutoff values varying from 30 to 45 mm Hg (4,15,16,18,23). Studies (4,6,15,16,18,22,24) employing right heart catheterization for the diagnosis of PAH have reported lower prevalence rates compared with studies using echocardiography (ranging from 5 to 12% versus 13 to 35%, respectively).
To define risk factors associated with pulmonary arterial hypertension (PAH) in a large cohort of patients with systemic sclerosis (SSc).
SSc patients undergoing screening for PAH by means of Doppler echocardiography were identified and their charts were retrospectively reviewed. In all patients, we recorded systolic pulmonary artery pressure along with pulmonary function testing, clinical, and laboratory data. PAH was defined as right ventricular systolic pressure equal or greater than 40 mm Hg.
Of 114 SSc patients with echocardiographic measurements, PAH was found in 33 (29%) patients. In a multiple logistic regression analysis, the presence of pulmonary fibrosis on thoracic computed tomography (OR 6.78, CI 1.54 to 29.9), forced vital capacity less than 80% predicted (OR 3.03, CI 1.1 to 8.35), and duration of Raynaud’s phenomenon preceding the onset of skin changes for at least 3 years (OR 5.75, CI 1.9 to 17.41) were found to be independent predictors of PAH. Age, disease duration, disease subtype, or autoantibodies were not associated with PAH in our patients.
The present analysis identified pulmonary fibrosis and Raynaud’s phenomenon preceding SSc skin manifestations by at least 3 years as risk factors for PAH in our scleroderma cohort. Screening for PAH in these high-risk patients may detect PAH at an earlier stage and guide decisions on therapeutic interventions.
Interstitial lung disease guideline: The British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society
2008, Thorax
Right ventricle Tei-index: A tool to increase the accuracy of non-invasive detection of pulmonary arterial hypertension in connective tissue diseases
2007, European Journal of Echocardiography
Diagnostic utility of sub-maximum cardiopulmonary exercise testing in the ambulatory setting for heart failure with preserved ejection fraction
2020, Pulmonary Circulation

View all citing articles on Scopus

: Supported in part by a research grant to study mixed connective tissue disease from the Ministry of Health and Welfare of Japan.

View full text

Chest

Clinical Investigations: Pulmonary VasculatureClinical Evaluation of Pulmonary Hypertension in Systemic Sclerosis and Related Disorders: A Doppler Echocardiographic Study of 135 Japanese Patients

Background

Patients and methods

Results

Conclusions

Section snippets

Patient Selection and Study Protocol

Characteristics of the Study Patients

DISCUSSION

ACKNOWLEDGMENTS

Am J Med

Am J Med

J Am Coll Cardiol

Am J Med

Am J Med

Chest

The pathophysiology of scleroderma involving the heart and respiratory system

Ann Intern Med

Pulmonary hypertension in the CREST syndrome variant of progressive systemic sclerosis (scleroderma)

Ann Intern Med

Pulmonary hypertension in the CREST syndrome variant of systemic sclerosis

Arthritis Rheum

Pulmonary arterial morphometry in systemic sclerosis: a case-control autopsy study

Arthritis Rheum

Acute and long-term effects of nifedipine on pulmonary and systemic hemodynamics in patients with diffuse systemic sclerosis, the CREST syndrome and mixed connective tissue disease

Am J Cardiol

Pulmonary involvement in MCTD

Am Rev Respir Dis

Clinical Investigations: Pulmonary Vasculature
Clinical Evaluation of Pulmonary Hypertension in Systemic Sclerosis and Related Disorders: A Doppler Echocardiographic Study of 135 Japanese Patients