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Pneumo-Reuma senza frontiere La diagnosi precoce diipertensione polmonare XlIL Congresso Italiano dellaSocietà Italiana di...
CTDs• PAH may complicate a number of  autoimmune diseases, such as  – Systemic sclerosis  – Systemic lupus erythematosus a...
MULTIPLE MECHANISMS LEADING TO PH IN CTDsDue to CRDs and/or                                  Due to pulmonary hypoxemia (l...
Differential diagnosis of “PH”                    CTD                              Pulmonary arterial hypertension (PAH)  ...
Updated clinical classification of      pulmonary hypertensionGalie’ N, et al. Eur Respir J 2009   Sergio Harari
Updated clinical classification of     pulmonary hypertensionGalie’ N, et al. Eur Respir J 2009   Sergio Harari
Updated clinical classification of    pulmonary hypertensionGalie’ N, et al. Eur Respir J 2009   Sergio Harari
IDIOPATHIC AND SYSTEMIC SCLEROSIS              ASSOCIATED PULMONARY ARTERIAL              HYPERTENSION                    ...
CTD PAH: data from registries                            399 SSc (68%)                            110 SLE (18%)           ...
SSc PAH• In SSc frequency  estimated between  7.5 and 12%  (variable between 4  and 38% depending  on the study  considere...
Lo screening è efficace per diagnosticare la                malattia                            No screening1             ...
Detection of milder disease with screening                          Systemic Sclerosis1                                   ...
Prognosis of “routine practice” and “detected” PAH-                    SSc patients                       100%            ...
Key problems for clinicians Is interstitial lung disease present?Is pulmonary hypertension present? Is it clinically si...
Is pulmonary hypertension or        fibrosis present? Symptoms misleading Chest radiography insensitive Sensitive marke...
HRCT can sometimes creates itsown problemsIs disease clinically significant?
When does a minor abnormality become             “disease”?
SSc PAH: risk factorsSteen V. J Clin Rheumatol 2005      Sergio Harari
Predictors of PAH in SSc Allanore Y et al, A&R 2008   Cavagna L et al, J Rheumatol 2010                                   ...
The relationship between DLCO and the development of SSc-associated PAH. Serial falls in       DLCO are predictive of the ...
NON INVASIVE MARKERS OF PAH           PROGNOSIS Functional class (NYHA/WHO) Biochemical markers (uric acid, BNP, TnT/I)...
ASSESSMENT OF PAH SEVERITY        BIOLOGICAL MARKERSBiological markers of disease severity       Uric acid       B-type ...
ASSESSMENT OF PAH SEVERITY                                                     URIC ACID                                  ...
ASSESSMENT OF PAH SEVERITY                                              URIC ACID               100                  Male ...
ASSESSMENT OF PAH SEVERITY                                     NATRIURETIC PEPTIDES                                Baselin...
ASSESSMENT OF PAH SEVERITY                          TROPONIN TTorbicki A, et al. Circulation 2003    Sergio Harari
ASSESSMENT OF PAH SEVERITY  EXERCISE : 6-MIN WALK TEST     Miyamoto et al. AJRCCM 2000; 161:487-492   Sergio Harari
ASSESSMENT OF PAH SEVERITY                   EXERCISE : 6-MIN WALK TESTMiyamoto et al. AJRCCM 2000; 161:487-492        Ser...
ASSESSMENT OF PAH SEVERITY         CARDIO-PULMONARY EXERCISE TESTINGWensel et al. Circulation 2002; 106:319-324   Sergio H...
Uses of exercise testing in lung           disease Is exercise capacity impaired and is it  consistent with symptoms? Is...
Criteri per diagnosi di PH dalla misurazione della velocità diflusso del rigurgito tricuspidale
• CTD-APAH patients have  – better hemodynamics but higher prevalence of    pericardial effusion  – lower 6-MWD  – Higher ...
Why is PH/PAH-SSc so difficult          to treat?• Older patients• Interstitial lung disease• Left ventricular diastolic d...
Take home messages• PAH may frequently complicate CTDs• Among CTDs, Systemic Sclerosis-associated  PAH represents a unique...
http://www.pulmonaryrarediseases.com
Sclerodermia e ipertensione polmonare
Sclerodermia e ipertensione polmonare
Sclerodermia e ipertensione polmonare
Sclerodermia e ipertensione polmonare
Sclerodermia e ipertensione polmonare
Sclerodermia e ipertensione polmonare
Sclerodermia e ipertensione polmonare
Sclerodermia e ipertensione polmonare
Sclerodermia e ipertensione polmonare
Sclerodermia e ipertensione polmonare
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Sclerodermia e ipertensione polmonare

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Sclerodermia e ipertensione polmonare

  1. 1. Pneumo-Reuma senza frontiere La diagnosi precoce diipertensione polmonare XlIL Congresso Italiano dellaSocietà Italiana di Reumatologia Milano 21-24 Novembre 2012 Sergio Harari U.O. Pneumologia e UTIR Servizio di Emodinamica e Fisiopatologia Respiratoria Osp. San Giuseppe - Milano
  2. 2. CTDs• PAH may complicate a number of autoimmune diseases, such as – Systemic sclerosis – Systemic lupus erythematosus and anti- phospholipids syndrome – Mixed connective tissue disease – Rheumatoid arthritis• Most data come from cohorts of SSc patients because PAH is a frequent occurrence in this disease• • Sergio Harari
  3. 3. MULTIPLE MECHANISMS LEADING TO PH IN CTDsDue to CRDs and/or Due to pulmonary hypoxemia (lung vascular remodeling fibrosis+++) PAH Hypoxic PH PH in CTDsDue to left-heart disease CTEPHPost-capillary PH
  4. 4. Differential diagnosis of “PH” CTD Pulmonary arterial hypertension (PAH) Pulmonary Interstitial lung veno-occlusive disease (ILD) disorder (PVOD) Chronic Myocardial thromboembolic involvement pulmonary hypertension (CTEPH) OthersPH = pulmonary hypertension Sergio Harari
  5. 5. Updated clinical classification of pulmonary hypertensionGalie’ N, et al. Eur Respir J 2009 Sergio Harari
  6. 6. Updated clinical classification of pulmonary hypertensionGalie’ N, et al. Eur Respir J 2009 Sergio Harari
  7. 7. Updated clinical classification of pulmonary hypertensionGalie’ N, et al. Eur Respir J 2009 Sergio Harari
  8. 8. IDIOPATHIC AND SYSTEMIC SCLEROSIS ASSOCIATED PULMONARY ARTERIAL HYPERTENSION IPAH 200 Pathogenesis includes Angiogenesis  Inflammation Autoimmunity anti-endothelial cell 60 antibodies anti-fibroblast antibodiesPerspectives 40  Identification of target antigens  Characterisation of function SScPAH Tamby MC et al. Thorax 2005; 60 : 765-772. Mouthon et al, Eur Resp J 2005;
  9. 9. CTD PAH: data from registries 399 SSc (68%) 110 SLE (18%) 52 MCTD (9%) 28 RA (5%)Chung L et al, Chest 2010 Sergio Harari
  10. 10. SSc PAH• In SSc frequency estimated between 7.5 and 12% (variable between 4 and 38% depending on the study considered)Mukerjee D, et al. ARD 2003 Sergio Harari
  11. 11. Lo screening è efficace per diagnosticare la malattia No screening1 With screening2 100 100 80 75% 80 Patients (%) Patients (%) 63% 60 60 44% 39% 40 40 24% 28% 20 12% 20 11% 1% 0 0 I II III IV II III IV WHO FC WHO FC1Hachulla et al. Arthritis Rheum 2005; 2Humbert et al. Am J Respir Crit Care Med 2006 Sergio Harari
  12. 12. Detection of milder disease with screening Systemic Sclerosis1 HIV infection2 Previously Newly Previously Newly known diagnosed known diagnosed PAH PAH PAH PAH (n=29) (n=18) (n=30) (n=5)mPAP (mmHg) 49 ± 17 30 ± 9 46 ± 13 30 ± 9CI (L/min/m2) 2.8 ± 0.7 3.2 ± 1.0 3.0 ± 0.8 3.6 ± 0.8PVR (d.s.cm-5) 1007 ± 615 524 ± 382 800 ± 320 320 ± 240 1. Hachulla E, et al. Arthritis Rheum 2005;52:3792-800. 2. Sitbon O, et al. Am J Respir Crit Care Med 2008;177:108-13. Sergio Harari
  13. 13. Prognosis of “routine practice” and “detected” PAH- SSc patients 100% p = 0.0037 HR = 4.15 100 81% (95% CI 1.47 - 11.71) 73% 90 80 64% 70 75% Survival (%) 60 Detected PAH-SSc 50 40 31% 30 25% Routine 20 17% practice PAH-SSc 10 0 1 year 3 years 5 years 8 years Years of follow-up Humbert M, et al. Arthritis Rheum 2011; Epub ahead of print. Sergio Harari
  14. 14. Key problems for clinicians Is interstitial lung disease present?Is pulmonary hypertension present? Is it clinically significant? Sergio Harari
  15. 15. Is pulmonary hypertension or fibrosis present? Symptoms misleading Chest radiography insensitive Sensitive markers include pulmonary function tests, echocardiography, right heart catheterization Sergio Harari
  16. 16. HRCT can sometimes creates itsown problemsIs disease clinically significant?
  17. 17. When does a minor abnormality become “disease”?
  18. 18. SSc PAH: risk factorsSteen V. J Clin Rheumatol 2005 Sergio Harari
  19. 19. Predictors of PAH in SSc Allanore Y et al, A&R 2008 Cavagna L et al, J Rheumatol 2010 Sergio Harari
  20. 20. The relationship between DLCO and the development of SSc-associated PAH. Serial falls in DLCO are predictive of the development of future PAH, suggesting that DLCO monitoring could form part of a screening strategy for PAH in SSc. Redrawn from Steen et al.51 DLCO, diffusion capacity for carbon monoxide; PAH, pulmonary arterial hypertension; SSc, systemic sclerosis. Lau E M et al. Eur Heart J 2011;32:2489-2498Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2011. For permissions please email: journals.permissions@oup.com
  21. 21. NON INVASIVE MARKERS OF PAH PROGNOSIS Functional class (NYHA/WHO) Biochemical markers (uric acid, BNP, TnT/I) Echocardiography (PE, Tei index, RV-LV function) Exercise studies (6-min walk test, CPET) Hemodynamic variables (RAP, CO, SvO2) Sergio Harari
  22. 22. ASSESSMENT OF PAH SEVERITY BIOLOGICAL MARKERSBiological markers of disease severity  Uric acid  B-type naturetic peptide  Cardiac troponin T
  23. 23. ASSESSMENT OF PAH SEVERITY URIC ACID 12 +Serum uric acid levels (mg/dl) 10 * 8 6 * p < 0.05 vs control 4 & class II + p < 0.05 vs 2 control, class II & class III 0 Control NYHA II NYHA III NYHA IV (n = 30) (n = 5) (n = 72) (n = 13) Nagaya N, et al. Am J Respir Crit Care Med 1999; 160:478-492
  24. 24. ASSESSMENT OF PAH SEVERITY URIC ACID 100 Male 100 Female 80 80Survival (%) < 8.9 mg/dl 60 (median) 60 < 6.4 mg/dl (median) 40 40 20  8.9 mg/dl 20  6.49 mg/dl 0 0 0 2 4 6 8 10 12 0 2 4 6 8 10 12 Time (years) Nagaya N, et al. Am J Respir Crit Care Med 1999; 160:478-492 Sergio Harari
  25. 25. ASSESSMENT OF PAH SEVERITY NATRIURETIC PEPTIDES Baseline BNP Follow-up BNP 100 100 Survival rate (%) BNP < 180 pg/ml 80 BNP < 150 pg/ml 80 60 60 40 BNP  150 pg/ml 40 20 20 BNP  180 pg/ml 0 0 0 12 24 36 48 0 12 24 36 48 Time (months) Time (months)Nagaya N, et al. Circulation 2000; 102:865-70. Sergio Harari
  26. 26. ASSESSMENT OF PAH SEVERITY TROPONIN TTorbicki A, et al. Circulation 2003 Sergio Harari
  27. 27. ASSESSMENT OF PAH SEVERITY EXERCISE : 6-MIN WALK TEST Miyamoto et al. AJRCCM 2000; 161:487-492 Sergio Harari
  28. 28. ASSESSMENT OF PAH SEVERITY EXERCISE : 6-MIN WALK TESTMiyamoto et al. AJRCCM 2000; 161:487-492 Sergio Harari
  29. 29. ASSESSMENT OF PAH SEVERITY CARDIO-PULMONARY EXERCISE TESTINGWensel et al. Circulation 2002; 106:319-324 Sergio Harari
  30. 30. Uses of exercise testing in lung disease Is exercise capacity impaired and is it consistent with symptoms? Is exercise impairment related to lung disease alone or do other conditions contribute? What physiological mechanisms contribute to exercise impairment? Prescription of exercise training program or oxygen during exerciseMed Clin N Am 1990; 4:634 Sergio Harari
  31. 31. Criteri per diagnosi di PH dalla misurazione della velocità diflusso del rigurgito tricuspidale
  32. 32. • CTD-APAH patients have – better hemodynamics but higher prevalence of pericardial effusion – lower 6-MWD – Higher BNP levels – Lower DLCO• SSc-APAH vs other CTDs have – Similar hemodynamics but – Higher BNP and lower DLCO Sergio Harari
  33. 33. Why is PH/PAH-SSc so difficult to treat?• Older patients• Interstitial lung disease• Left ventricular diastolic dysfunction• Right ventricular diastolic dysfunction• More severe structural vasculopathy• Key outcome measures may differ (6 MWT-RHC ?)• More inflammation Sergio Harari
  34. 34. Take home messages• PAH may frequently complicate CTDs• Among CTDs, Systemic Sclerosis-associated PAH represents a unique phenotype for clinical presentation and outcome• Screening of PAH is mandatory in SSc patients at any time of the disease course• A big effort is needed in identifying the earliest predictors of this complication in order to make the most of the new therapeutic armamentarium• A multidisciplinary management may improve diagnosis and outcome Sergio Harari
  35. 35. http://www.pulmonaryrarediseases.com

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