1. How to Screen for PAH in Scleroderma-Spectrum Disorders
Dinesh Khanna, MD Professor of Medicine, Division of Rheumatology, Department of Medicine Director, Scleroderma Program University of Michigan Medical Center Ann Arbor, MI

2. PAH is a Frequent Complication of SSc
Hachulla et al.
Avouac et al.
Vonk et al.
Phung et al.
de Azevedo et al.
Coral-Alvarado et al.
Kumar et al.
Pope et al.
Gindzienska et al.
Chang et al.
Yamane et al.
Combined
Twelve individual studies reported PAH prevalence ranging from 3.6% to 32% in patients with SSc
The pooled prevalence estimate of PAH in patients with SSc was 13%
In patients with DLCO < 60%, the prevalence is 19%
0.0 20 40 60
Prevalence, % (95% confidence interval)
Study prevalence estimate (relative size of box equals relative weight)
Pooled prevalence estimate
Figure adapted from Yang X, Markedian J, Sanders KN, et al. Prevalence of pulmonary arterial hypertension in patients with connective tissue diseases: a systematic review of the literature. Clin Rheumatol. 2013; 32: Coghlan JG, Denton CP, Grünig E, et al. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis. 2014;73:

3. Patients With PAH-CTD Have a Poorer Survival Than IPAH Patients
Data from patients enrolled in the REVEAL Registry cohort
100
p < 0.001 80
IPAH
PAH-CTD
Yr 1
88%
80%
Yr 3
74%
57%
Yr 5
64%
44%
Yr 7
36% 60
Survival (%) 40
IPAH (n = 1201) 20
PAH-CTD (n = 742) 1 2 3 4 5 6 7
Time from diagnosis (years)
No. at risk:
IPAH
PAH-CTD
415
257
553
342
600
344
609
329
538
276
415
203
268
138
143 67
Benza RL, Miller DP, Barst RJ, et al. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest 2012; 142:

4. Screening of Scleroderma-Spectrum Disorders
HOW OFTEN
Annually
HOW TO SCREEN
Resting echocardiography, PFT, and NT-proBNP or DETECT algorithm
(if DLCO < 60%)
IF ABNORMAL
Send for RHC
DLCO = diffusing capacity of the lung for carbon monoxide, RHC = right heart catheterization
PFT = pulmonary function tests; NT-proBNP – n-terminal pro-brain natriuretic peptide
Khanna D, Gladue H, Channick R, et al. Recommendations for screening and detection of connective-tissue disease associated pulmonary arterial hypertension. Arthritis Rheum. 2013;65(12):
Hoeper M, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(suppl 25):D42-D50. Galiè N, Humbert M, Vachiery JL, et al ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015;46:
Galiè N, Humbert M, Vachiery J-L, et al ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2016;37:

5. Guidelines Recommend Annual Screening with Resting Echocardiography for Asymptomatic Patients
2013 Recommendations for CTD-PAH
2013 WSPH Nice symposium
2015 ESC/ERS Guidelines
Khanna D, Gladue H, Channick R, et al. Recommendations for screening and detection of connective-tissue disease associated pulmonary arterial hypertension. Arthritis Rheum. 2013;65(12):
Hoeper M, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(suppl 25):D42-D50.
Galiè N, Humbert M, Vachiery JL, et al ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015;46:
Galiè N, Humbert M, Vachiery J-L, et al ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2016;37:

6. Guidelines Recommend Annual Screening for Asymptomatic Patients with DLCO < 60% and Disease Duration > 3 years with DETECT Algorithm
2013 Recommendations for CTD-PAH
2013 WSPH Nice symposium
2015 ESC/ERS Guidelines
DLCO = diffusing capacity of the lung for carbon monoxide
Khanna D, Gladue H, Channick R, et al. Recommendations for screening and detection of connective-tissue disease associated pulmonary arterial hypertension. Arthritis Rheum. 2013;65(12):
Hoeper M, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(suppl 25):D42-D50.
Galiè N, Humbert M, Vachiery JL, et al ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015;46:
Galiè N, Humbert M, Vachiery J-L, et al ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2016;37:

7. DETECT: Two-step Decision Tree for Screening SSc Patients
DETECT: Evidence-based screening algorithm for PAH in SSc patients
Step 1
Step 2
RHC for diagnosis of presence / absence of PAH
6 non-echo variables:
FVC % pred./DLCO % pred.
Anti-centromere antibodies
Telangiectasias
NT-proBNP
ECG: Right axis deviation
Serum urate (uric acid)
Step 1 total risk score plus 2 echo variables:
Right atrium area
TR velocity
YES
YES
Is total risk score > 300?
Is total risk score > 35? NO NO
No referral for echo
No referral for RHC
Coghlan JG, Denton CP, Grünig E, et al. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis. 2014;73:

8. Conclusions
PAH is a frequent complication of SSc and is associated with a particularly poor prognosis
Screening of SSc patients facilitates early detection of PAH and improves long term outcomes
Evidence-based screening algorithms have been published that improves the detection of PAH-SSc and is recommended by different guidelines