Reduced Exercise Capacity and Stress-Induced Pulmonary Hypertension in Patients With Scleroderma

doi:10.1378/chest.130.1.176

Chest

Volume 130, Issue 1, July 2006, Pages 176-181

https://doi.org/10.1378/chest.130.1.176 Get rights and content

Objectives

We sought to determine the incidence of stress-induced pulmonary artery (PA) systolic hypertension in a referral population of patients with scleroderma, and to examine the relation between stress-induced pulmonary systolic hypertension and exercise capacity in this population.

Background

Early detection of patients with scleroderma at risk for pulmonary hypertension (PHTN) could lead to more timely intervention and thus reduce morbidity and improve mortality. The change in PA systolic pressure (PASP) with exercise provides a possible tool for such detection.

Methods

Sixty-five patients with scleroderma (9 men and 56 women; mean age 51 ± 12 years [SD]), normal resting PASP, and normal resting left ventricular function underwent exercise Doppler echocardiography using a standard Bruce protocol. Tricuspid regurgitation velocity was measured before and after exercise. Exercise variables including workload achieved in metabolic equivalents (METS), total exercise time, percentage of target heart rate achieved, and PASP at rest and within 60 s after exercise were recorded.

Results

Thirty patients (46%) demonstrated an increase in PASP to > 35 mm Hg plus an estimated right atrial pressure of 5 mm Hg. Postexercise PASP inversely correlated to both the maximum workload achieved (r = − 0.34, p = 0.006) and exercise time (r = − 0.31, p = 0.01). In women, the correlation was more significant (r = − 0.38, p = 0.003). Patients in the lowest quartile of exercise time, with the least cardiac workload achieved, produced the highest postexercise PASP.

Conclusion

Stress-induced PHTN is common in patients with scleroderma, even when resting PASP is normal. Stress Doppler echocardiography identifies scleroderma patients with an abnormal rise in PASP during exertion. Peak PASP is linearly related to exercise time and maximum workload achieved. Measurement of PASP during exercise may prove to be a useful tool for the identification of future resting PHTN.

Section snippets

Patients

The study included consecutive patients from February 2003 to April 2004 18 years old with a rheumatologist-established diagnosis of scleroderma by standard criteria.¹⁵ Patients were referred as part of their routine follow-up care. Both, patients with diffuse systemic sclerosis or limited scleroderma (CREST syndrome [calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia]) were accepted. PASP was normal or only mildly elevated at rest (PASP ≤ 35 mm Hg plus

Results

All patients had normal wall motion at baseline. There were no clinical signs of heart failure on physical examination. The vast majority of patients had no left ventricular hypertrophy. Diabetes (n = 1) and hypertension (n = 6) were infrequent. Resting diastolic function was normal (Table 1). Pulmonary function data were available for 57 patients (87%; Table 1). Right atrial pressure was estimated at 5 mm Hg for all patients. No patients complained of exertional chest pain. Thirty patients

Discussion

In this study, we demonstrate that stress-induced pulmonary systolic hypertension in patients with scleroderma is highly prevalent, and is associated with reduced exercise capacity, decreased maximum cardiac workload, and decreased adjusted Dlco. While our data do not directly examine the mechanism underlying these relations, they do suggest that determinants of exercise capacity in scleroderma patients may vary from those variables that govern more traditional populations undergoing exercise

Acknowledgment

The authors thank Dr. Irfan Yusufzai for his assistance in data collection and management.

References (26)

MurataI et al.
Clinical evaluation of pulmonary hypertension in systemic sclerosis and related disorders: a Doppler echocardiographic study of 135 Japanese patients
Chest
(1997)
HommaA et al.
Pulmonary artery systolic pressures estimated by echocardiogram vs cardiac catheterization in patients awaiting lung transplantation
J Heart Lung Transplant
(2001)
BossoneE et al.
Range of tricuspid regurgitation velocity at rest and during exercise in normal adult men: implications for the diagnosis of pulmonary hypertension
J Am Coll Cardiol
(1999)
MinaiOA et al.
Manifestations of scleroderma pulmonary disease
Clin Chest Med
(1998)
BelmanMJ
Exercise training in chronic obstructive pulmonary disease
Clin Chest Med
(1986)
Mac GregorAJ et al.
Pulmonary hypertension in systemic sclerosis: risk factors for progression and consequences for survival
Rheumatology (Oxford)
(2001)
OudizRJ
Cardiac catheterization in pulmonary arterial hypertension: a guide to proper use
Adv Pulm Hypertension
(2002)
DentonCP et al.
Comparison of Doppler echocardiography and right heart catheterization to assess pulmonary hypertension in systemic sclerosis
Br J Rheumatol
(1997)
BossoneE et al.
Diagnostic value of resting tricuspid regurgitation velocity and right ventricular ejection flow parameters for the detection of exercise induced pulmonary arterial hypertension
Int J Card Imaging
(2000)
RaesideDA et al.
Pulmonary artery pressure measurement during exercise testing in patients with suspected pulmonary hypertension
Eur Respir J
(2000)

RaesideDA et al.

Ambulatory pulmonary artery pressure monitoring during sleep and exercise in normal individuals and patients with COPD

Thorax

(2002)

PalevskyHI

Exercise and the pulmonary circulation

(1986)

BevegardS et al.

Circulatory studies in well trained athletes at rest and during heavy exercise, with special reference to stroke volume and the influence of body position

Acta Physiol Scand

(1963)

Cited by (104)

Pulmonary artery pressure–perfusion relation during exercise in patients with chronic thromboembolic pulmonary hypertension using pulmonary arteriography and right-heart catheterization
2023, IJC Heart and Vasculature
In pulmonary hypertension (PH), pulmonary artery pressure (PAP) does not increase to pulmonary perfusion (PP) < 50%. During exercise, PAP may be increased even at PP > 50% for the early detection of PP disorders. The relationship between PP estimated by pulmonary angiography (PAG) and PAP was evaluated in patients with chronic thromboembolic PH (CTEPH) treated by balloon pulmonary angioplasty with near-normal PH.
Thirty-one patients (age 60 ± 11 years) with CTEPH underwent catheterization at rest and during exercise. Each segmental PP was determined by visualization of its segmental pulmonary artery and graded from 0 to 3 in the PAG. PP was estimated as the percentage PAG (%PAG) score–%summed total of all segmental PP/the full score-54.
The mean PAP (mPAP) increased from 28 ± 6 mmHg to 46 ± 10 mmHg during exercise. Transpulmonary pressure gradient, the value of mPAP with the pulmonary artery wedge pressure substituted at peak exercise, was negatively correlated with %PAG score (rs = -0.56, p < 0.001) and elevated at > 50% PP.
The PAP-PP relationship at peak exercise was correlated, shifting from the relationship at rest, and the PAP started to rise with PP > 50%.
Exercise-induced pulmonary hypertension in HIV patients: Association with poor clinical and immunological status
2021, Vascular Pharmacology
Exercise-induced pulmonary hypertension (Ex-PH) may represent the earliest sign of pulmonary arterial hypertension (PAH) in human immunodeficiency virus (HIV) patients. We investigated its association with clinical and immunological status, virologic control, and response to antiviral therapy.
In 32 consecutive HIV patients with either low (n = 29) or intermediate probability (n = 3) of PH at rest, we evaluated the association of isolated ExPH with: time to HIV diagnosis; CD4+ T-cell count; clinical progression to acquired immunodeficiency syndrome (AIDS); development of resistance to antiretroviral therapy (ART); HIV RNA levels; time to beginning of ART; current use of protease inhibitors; combination of ART with boosters (ritonavir or cobicistat); immuno-virologic response to ART; and ART discontinuation.
Isolated ExPH at stress echocardiography (ESE) was defined as absence of PH at rest and systolic pulmonary arterial pressure (sPAP) >45 mmHg or a >20 mmHg increase during low-intensity exercise cardiac output (<10 L/min).
In our cohort, 22% (n = 7) of the enrolled population developed ExPH which was inversely related to CD4+ T-cell count (p = 0.047), time to HIV diagnosis (p = 0.014) and time to onset of ART (p = 0.041). Patients with ExPH had a worse functional class than patients without ExPH (p < 0.001). ExPH and AIDS showed a trend (p = 0.093) to a direct relationship. AIDS patients had a higher pulmonary vascular resistance compared to patients without ExPH (p = 0.020) at rest echocardiography.
The presence of isolated ExPH associates with a worse clinical status and poor immunological control in HIV patients. Assessment of ExPH by ESE may help identify subgroups of HIV patients with a propensity to develop subclinical impairment of pulmonary circulation following poor control of HIV infection.
Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary circulation in patients with systemic sclerosis
2019, Advances in Medical Sciences
Citation Excerpt :
SSc patients often experience dyspnea with exercise. Alkotob et al. [19] and Mininni et al. [20] revealed that exercise-induced increases in TRPG on echocardiogram commonly occur in SSc, but RHC was not performed to confirm these findings. Steen et al. [12] evaluated 54 SSc patients and revealed an increase in exercise TRPG > 20 mmHg in 44% of them.
Pulmonary hypertension (PH) is an ominous complication in systemic sclerosis patients (SSc) and echocardiography is a screening tool for its detection. The goal of this study was to assess the reliability of resting and exercise echo Doppler parameters with data obtained by right heart catheterization (RHC).
We included 91 patients (84 F, 53.3 ± 15.2 years) with SSc. Transthoracic echocardiography followed by exercise Doppler-echocardiography (EDE) were performed. A positive EDE was defined as a ≥20 mmHg increase in tricuspid regurgitation peak gradient (TRPG). RHC with exercise was performed in positive EDE patients and/or in subjects with resting TRPG > 31 mmHg.
Finally, RHC was performed in 20 patients. The correlation for the echocardiography and invasive measurement of systolic (sPAP) and mean (mPAP) pulmonary artery pressure was r = 0.66 (p = 0.001) and r = 0.7 (p = 0.001), respectively. We also found significant correlation between echocardiography and invasive measurement of exercise sPAP r = 0.68 (p = 0.001) and exercise mPAP r = 0.67 (p = 0.002). There was a correlation between pulmonary vascular resistance (PVR) assessed by echocardiography and measured by RHC r = 0.49, p = 0.027. The equation derived within our population was: PVR by echocardiography = 9.6*TRV/TVI_RVOT+0.068. We also performed ROC analysis to predict PVR > 2 WU. Our results highlight that sPAP has the highest AUC (0.802, 95% CI 0.585–1).
Doppler resting and exercise echocardiography may provide a reliable, noninvasive method for determining resting and exercise sPAP, mPAP, and PVR in SSc patients, although it may underestimate or overestimate these values in some individuals. Doppler echocardiography does not replace RHC for definite hemodynamic assessment of suspected PH.
The Right Heart International Network (RIGHT-NET): Rationale, Objectives, Methodology, and Clinical Implications
2018, Heart Failure Clinics
Pulmonary Circulation on the Crossroads Between the Left and Right Heart in Systemic Sclerosis: A Clinical Challenge for Cardiologists and Rheumatologists
2018, Heart Failure Clinics
Citation Excerpt :
Exercise echocardiography is a noninvasive tool to estimate pulmonary hemodynamics during exercise and is useful to assess abnormalities of pulmonary vascular function as well as the state of the right heart, although it does not have an established role in the management of SSc patients. A main issue in SSc is the high percentage of patients showing exercise PH during exercise stress echocardiography, which clearly overestimates the subset of SSc patients who will develop PAH.63–66 PAP is dependent, however, not only on PVR, which is abnormally increased in PAH, but also on left atrial pressure and CO, as shown both in healthy subjects67 and in SSc.51
Stressing the Cardiopulmonary Vascular System: The Role of Echocardiography
2018, Journal of the American Society of Echocardiography
The cardiopulmonary vascular system represents a key determinant of prognosis in several cardiorespiratory diseases. Although right heart catheterization is considered the gold standard for assessing pulmonary hemodynamics, a comprehensive noninvasive evaluation including left and right ventricular reserve and function and cardiopulmonary interactions remains highly attractive. Stress echocardiography is crucial in the evaluation of many cardiac conditions, typically coronary artery disease but also heart failure and valvular heart disease. In stress echocardiographic applications beyond coronary artery disease, the assessment of the cardiopulmonary vascular system is a cornerstone. The possibility of coupling the left and right ventricles with the pulmonary circuit during stress can provide significant insight into cardiopulmonary physiology in healthy and diseased subjects, can support the diagnosis of the etiology of pulmonary hypertension and other conditions, and can offer valuable prognostic information. In this state-of-the-art document, the topic of stress echocardiography applied to the cardiopulmonary vascular system is thoroughly addressed, from pathophysiology to different stress modalities and echocardiographic parameters, from clinical applications to limitations and future directions.

View all citing articles on Scopus

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

Supported in part by National Institutes of Health General Clinical Research Center grant MO1RR06192.

There are no conflicts of interest or financial disclosures for any of the authors.

View full text

Chest

Original ResearchReduced Exercise Capacity and Stress-Induced Pulmonary Hypertension in Patients With Scleroderma

Objectives

Background

Methods

Results

Conclusion

Section snippets

Patients

Results

Discussion

Acknowledgment

Chest

J Heart Lung Transplant

J Am Coll Cardiol

Clin Chest Med

Clin Chest Med

Pulmonary hypertension in systemic sclerosis: risk factors for progression and consequences for survival

Rheumatology (Oxford)

Cardiac catheterization in pulmonary arterial hypertension: a guide to proper use

Adv Pulm Hypertension

Comparison of Doppler echocardiography and right heart catheterization to assess pulmonary hypertension in systemic sclerosis

Br J Rheumatol

Diagnostic value of resting tricuspid regurgitation velocity and right ventricular ejection flow parameters for the detection of exercise induced pulmonary arterial hypertension

Int J Card Imaging

Pulmonary artery pressure measurement during exercise testing in patients with suspected pulmonary hypertension

Eur Respir J

Ambulatory pulmonary artery pressure monitoring during sleep and exercise in normal individuals and patients with COPD

Thorax

Exercise and the pulmonary circulation

Circulatory studies in well trained athletes at rest and during heavy exercise, with special reference to stroke volume and the influence of body position

Acta Physiol Scand

Original Research
Reduced Exercise Capacity and Stress-Induced Pulmonary Hypertension in Patients With Scleroderma