Ipertensione

polmonare nelle

malattie reumatiche

Annalisa Fiorella

UO Cardiologia SS Annunziata Taranto

Galiegrave N et al Eur Heart J and Eur Respir J 2009

GaliegraveN et al Eur Heart J and Eur Respir J 2009

Recommendations for PAWP at rest

bull The cutoff for pre-capillary PH should remain at 15 mmHg because this value has been used in almost all clinical trials generating evidence for the safety and efficacy of PAH-targeted therapies in patients fulfilling these criteria

bull Invasive hemodynamics need to be placed in clinical and echocardiographic context with regard to probability of existence of left heart disease

bull The working group recommends zeroing the pressure transducer at the midthoracic line in a supine patient halfway between the anterior sternum and the bed surface This represents the level of the left atrium

Coghlan Arthritis Rheum 2013 Apr65(4)1074-84 doi 101002art37838

Galiegrave N et al Eur Heart J and Eur Respir J 2009

GaliegraveN et al Eur Heart J and Eur Respir J 2009

Recommendations for PAWP at rest

bull The cutoff for pre-capillary PH should remain at 15 mmHg because this value has been used in almost all clinical trials generating evidence for the safety and efficacy of PAH-targeted therapies in patients fulfilling these criteria

bull Invasive hemodynamics need to be placed in clinical and echocardiographic context with regard to probability of existence of left heart disease

bull The working group recommends zeroing the pressure transducer at the midthoracic line in a supine patient halfway between the anterior sternum and the bed surface This represents the level of the left atrium

Coghlan Arthritis Rheum 2013 Apr65(4)1074-84 doi 101002art37838

GaliegraveN et al Eur Heart J and Eur Respir J 2009

Recommendations for PAWP at rest

bull The cutoff for pre-capillary PH should remain at 15 mmHg because this value has been used in almost all clinical trials generating evidence for the safety and efficacy of PAH-targeted therapies in patients fulfilling these criteria

bull Invasive hemodynamics need to be placed in clinical and echocardiographic context with regard to probability of existence of left heart disease

bull The working group recommends zeroing the pressure transducer at the midthoracic line in a supine patient halfway between the anterior sternum and the bed surface This represents the level of the left atrium

Coghlan Arthritis Rheum 2013 Apr65(4)1074-84 doi 101002art37838

Recommendations for PAWP at rest

bull The cutoff for pre-capillary PH should remain at 15 mmHg because this value has been used in almost all clinical trials generating evidence for the safety and efficacy of PAH-targeted therapies in patients fulfilling these criteria

bull Invasive hemodynamics need to be placed in clinical and echocardiographic context with regard to probability of existence of left heart disease

bull The working group recommends zeroing the pressure transducer at the midthoracic line in a supine patient halfway between the anterior sternum and the bed surface This represents the level of the left atrium

Coghlan Arthritis Rheum 2013 Apr65(4)1074-84 doi 101002art37838

bull A mPAP between 21-24 mmHg may be not normal in these cases It has been proposed to use the term of ldquoBorderlinerdquo elevation of PAP

bull ldquoBorderlinerdquo elevation of PAP is frequently observed in Groups 2 and 3 however the meaning of this observation is unknown and has no therapeutic implications

bull ldquoBorderlinerdquo elevation of PAP is also observed in scleroderma patients screened for PH Recent data support that a substantial number of these patients develop manifest PAH in the F-U

ldquoBorderlinerdquo PH

Hoeper et allJacc Vol 62 No 25 Suppl D 2013

Long-term Follow-up of lsquorsquoborderlinersquorsquo PH in Scleroderma

Coghlan Arthritis Rheum 2013 Apr65(4)1074-84 doi 101002art37838

37 had Borderline PAP at baseline

Long-term Follow-up of lsquorsquoborderlinersquorsquo PH in Scleroderma

Coghlan Arthritis Rheum 2013 Apr65(4)1074-84 doi 101002art37838

37 had Borderline PAP at baseline

How do we handle ldquoborderlinerdquo PH

bull We recognize ldquoborderlinerdquo elevation of PAP is a hemodynamic definition with mPAP at RHC of 21 to 24 mm Hg

bull In scleroderma Patients we consider ldquoborderlinerdquo elevation of PAP as a risk marker for progression to PHa risk marker for progression to PH

bull Therapeutic implications remain unknown

Task Force recommendations

Coghlan Arthritis Rheum 2013 Apr65(4)1074-84 doi 101002art37838

Galiegrave N et al Eur Heart J and Eur Respir J 2009

1 Pulmonary arterial hypertension

2 PH ass with left heart disease

3 PH ass with lung diseases

4 PH due to chronic TE disease

5 Miscellaneous

35

79

10

15

6

Mixed

PH Epidemiology in an Echo lab (Armadale study)

Gabbay et al Am J Resp Crit Care Med 2007175A713

Prevalence of PH (SPAPgt 40 mmHg) among 4579 pts 105

Pulmonary Arterial Hypertension (group 1)Associated Conditions

1Pulmonary Arterial Hypertension11 Idiopathic PAH12 Heritable PAH121 BMPR2122 ALK-1ENGSMAD9CAV1KCNK3123 Unknown13 Drugs and toxins induced

14 Associated with141 Connective tissue disease142 HIV infection143 Portal hypertension144 Congenital Heart diseases (table)145 Schistosomiasis

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Non-invasive assessment of PH

Hoeper et allJacc Vol 62 No 25 Suppl D 2013

PH PresentPeak TRV

(ms)ePASP (mmHg)

Additional Echo Signs of

PHRE

Unlikely lt28 lt35 No I-B

Possiblelt28 lt35 Yes IIa-C

29 ndash 34 36 ndash 50 NoYes IIa-C

Likely gt34 gt50 NoYes I-B

Table 9 Arbitrary Echo Criteria for estimating the presence of PH based on TRV an assumed RAP of 5 mmHg and additional Echo variables suggestive of PH

Galiegrave N et al Eur Heart J and Eur Respir J 2009

increased velocity of pulmonary valve regurgitation short AcT increased dimensions of RH chambers abnormal shape and function of the IVS increased RV wall thickness and dilated main PA

Hoeper et allJacc Vol 62 No 25 Suppl D 2013

Cateterismo cardiaco destro

Permette di misurare quanto descritto nella definizione funzionale della PAH

mPAP gt25 mmHg a riposo o gt30 mmHg in corso di esercizio

Gaine et al Lancet 1998352719

IP all rsquoEcocardiogramma gt PAPs 30-50 mmHg velocitagrave del rigurgito tricuspidalico di 2834 msec (PADx 5 mmHg)

European Heart Journal 2004 252253

Screening can be effective in identifying earlier disease

1

24

75

12Pa

tie

nts

(

)

63

0

20

40

60

80

100

I II III IV

100

80

60

40

20

0

n = 8(44) n = 5

(28) n = 2

(11)

II III IV

Pa

tie

nts

39

Hachulla E et al Arthritis Rheum 2005 523698-700 Humbert M et al Am J Respir Crit Care Med 2006 1731023-30

No screening With screening

WHO class WHO class

Survival Daily practice vs screening

Humbert Arthritis Rheum 2011 Nov63(11)3522-30

Screening

1 Pulmonary arterial hypertension

2 PH ass with left heart disease

3 PH ass with lung diseases

4 PH due to chronic TE disease

5 Miscellaneous

35

79

10

15

6

Mixed

PH Epidemiology in an Echo lab (Armadale study)

Gabbay et al Am J Resp Crit Care Med 2007175A713

Prevalence of PH (SPAPgt 40 mmHg) among 4579 pts 105

Pulmonary Arterial Hypertension (group 1)Associated Conditions

1Pulmonary Arterial Hypertension11 Idiopathic PAH12 Heritable PAH121 BMPR2122 ALK-1ENGSMAD9CAV1KCNK3123 Unknown13 Drugs and toxins induced

14 Associated with141 Connective tissue disease142 HIV infection143 Portal hypertension144 Congenital Heart diseases (table)145 Schistosomiasis

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Non-invasive assessment of PH

Hoeper et allJacc Vol 62 No 25 Suppl D 2013

PH PresentPeak TRV

(ms)ePASP (mmHg)

Additional Echo Signs of

PHRE

Unlikely lt28 lt35 No I-B

Possiblelt28 lt35 Yes IIa-C

29 ndash 34 36 ndash 50 NoYes IIa-C

Likely gt34 gt50 NoYes I-B

Table 9 Arbitrary Echo Criteria for estimating the presence of PH based on TRV an assumed RAP of 5 mmHg and additional Echo variables suggestive of PH

Galiegrave N et al Eur Heart J and Eur Respir J 2009

increased velocity of pulmonary valve regurgitation short AcT increased dimensions of RH chambers abnormal shape and function of the IVS increased RV wall thickness and dilated main PA

Hoeper et allJacc Vol 62 No 25 Suppl D 2013

Cateterismo cardiaco destro

Permette di misurare quanto descritto nella definizione funzionale della PAH

mPAP gt25 mmHg a riposo o gt30 mmHg in corso di esercizio

Gaine et al Lancet 1998352719

IP all rsquoEcocardiogramma gt PAPs 30-50 mmHg velocitagrave del rigurgito tricuspidalico di 2834 msec (PADx 5 mmHg)

European Heart Journal 2004 252253

Screening can be effective in identifying earlier disease

1

24

75

12Pa

tie

nts

(

)

63

0

20

40

60

80

100

I II III IV

100

80

60

40

20

0

n = 8(44) n = 5

(28) n = 2

(11)

II III IV

Pa

tie

nts

39

Hachulla E et al Arthritis Rheum 2005 523698-700 Humbert M et al Am J Respir Crit Care Med 2006 1731023-30

No screening With screening

WHO class WHO class

Survival Daily practice vs screening

Humbert Arthritis Rheum 2011 Nov63(11)3522-30

Screening

Pulmonary Arterial Hypertension (group 1)Associated Conditions

1Pulmonary Arterial Hypertension11 Idiopathic PAH12 Heritable PAH121 BMPR2122 ALK-1ENGSMAD9CAV1KCNK3123 Unknown13 Drugs and toxins induced

14 Associated with141 Connective tissue disease142 HIV infection143 Portal hypertension144 Congenital Heart diseases (table)145 Schistosomiasis

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Non-invasive assessment of PH

Hoeper et allJacc Vol 62 No 25 Suppl D 2013

PH PresentPeak TRV

(ms)ePASP (mmHg)

Additional Echo Signs of

PHRE

Unlikely lt28 lt35 No I-B

Possiblelt28 lt35 Yes IIa-C

29 ndash 34 36 ndash 50 NoYes IIa-C

Likely gt34 gt50 NoYes I-B

Table 9 Arbitrary Echo Criteria for estimating the presence of PH based on TRV an assumed RAP of 5 mmHg and additional Echo variables suggestive of PH

Galiegrave N et al Eur Heart J and Eur Respir J 2009

increased velocity of pulmonary valve regurgitation short AcT increased dimensions of RH chambers abnormal shape and function of the IVS increased RV wall thickness and dilated main PA

Hoeper et allJacc Vol 62 No 25 Suppl D 2013

Cateterismo cardiaco destro

Permette di misurare quanto descritto nella definizione funzionale della PAH

mPAP gt25 mmHg a riposo o gt30 mmHg in corso di esercizio

Gaine et al Lancet 1998352719

IP all rsquoEcocardiogramma gt PAPs 30-50 mmHg velocitagrave del rigurgito tricuspidalico di 2834 msec (PADx 5 mmHg)

European Heart Journal 2004 252253

Screening can be effective in identifying earlier disease

1

24

75

12Pa

tie

nts

(

)

63

0

20

40

60

80

100

I II III IV

100

80

60

40

20

0

n = 8(44) n = 5

(28) n = 2

(11)

II III IV

Pa

tie

nts

39

Hachulla E et al Arthritis Rheum 2005 523698-700 Humbert M et al Am J Respir Crit Care Med 2006 1731023-30

No screening With screening

WHO class WHO class

Survival Daily practice vs screening

Humbert Arthritis Rheum 2011 Nov63(11)3522-30

Screening

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Non-invasive assessment of PH

Hoeper et allJacc Vol 62 No 25 Suppl D 2013

PH PresentPeak TRV

(ms)ePASP (mmHg)

Additional Echo Signs of

PHRE

Unlikely lt28 lt35 No I-B

Possiblelt28 lt35 Yes IIa-C

29 ndash 34 36 ndash 50 NoYes IIa-C

Likely gt34 gt50 NoYes I-B

Table 9 Arbitrary Echo Criteria for estimating the presence of PH based on TRV an assumed RAP of 5 mmHg and additional Echo variables suggestive of PH

Galiegrave N et al Eur Heart J and Eur Respir J 2009

increased velocity of pulmonary valve regurgitation short AcT increased dimensions of RH chambers abnormal shape and function of the IVS increased RV wall thickness and dilated main PA

Hoeper et allJacc Vol 62 No 25 Suppl D 2013

Cateterismo cardiaco destro

Permette di misurare quanto descritto nella definizione funzionale della PAH

mPAP gt25 mmHg a riposo o gt30 mmHg in corso di esercizio

Gaine et al Lancet 1998352719

IP all rsquoEcocardiogramma gt PAPs 30-50 mmHg velocitagrave del rigurgito tricuspidalico di 2834 msec (PADx 5 mmHg)

European Heart Journal 2004 252253

Screening can be effective in identifying earlier disease

1

24

75

12Pa

tie

nts

(

)

63

0

20

40

60

80

100

I II III IV

100

80

60

40

20

0

n = 8(44) n = 5

(28) n = 2

(11)

II III IV

Pa

tie

nts

39

Hachulla E et al Arthritis Rheum 2005 523698-700 Humbert M et al Am J Respir Crit Care Med 2006 1731023-30

No screening With screening

WHO class WHO class

Survival Daily practice vs screening

Humbert Arthritis Rheum 2011 Nov63(11)3522-30

Screening

Non-invasive assessment of PH

Hoeper et allJacc Vol 62 No 25 Suppl D 2013

PH PresentPeak TRV

(ms)ePASP (mmHg)

Additional Echo Signs of

PHRE

Unlikely lt28 lt35 No I-B

Possiblelt28 lt35 Yes IIa-C

29 ndash 34 36 ndash 50 NoYes IIa-C

Likely gt34 gt50 NoYes I-B

Table 9 Arbitrary Echo Criteria for estimating the presence of PH based on TRV an assumed RAP of 5 mmHg and additional Echo variables suggestive of PH

Galiegrave N et al Eur Heart J and Eur Respir J 2009

increased velocity of pulmonary valve regurgitation short AcT increased dimensions of RH chambers abnormal shape and function of the IVS increased RV wall thickness and dilated main PA

Hoeper et allJacc Vol 62 No 25 Suppl D 2013

Cateterismo cardiaco destro

Permette di misurare quanto descritto nella definizione funzionale della PAH

mPAP gt25 mmHg a riposo o gt30 mmHg in corso di esercizio

Gaine et al Lancet 1998352719

IP all rsquoEcocardiogramma gt PAPs 30-50 mmHg velocitagrave del rigurgito tricuspidalico di 2834 msec (PADx 5 mmHg)

European Heart Journal 2004 252253

Screening can be effective in identifying earlier disease

1

24

75

12Pa

tie

nts

(

)

63

0

20

40

60

80

100

I II III IV

100

80

60

40

20

0

n = 8(44) n = 5

(28) n = 2

(11)

II III IV

Pa

tie

nts

39

Hachulla E et al Arthritis Rheum 2005 523698-700 Humbert M et al Am J Respir Crit Care Med 2006 1731023-30

No screening With screening

WHO class WHO class

Survival Daily practice vs screening

Humbert Arthritis Rheum 2011 Nov63(11)3522-30

Screening

Hoeper et allJacc Vol 62 No 25 Suppl D 2013

PH PresentPeak TRV

(ms)ePASP (mmHg)

Additional Echo Signs of

PHRE

Unlikely lt28 lt35 No I-B

Possiblelt28 lt35 Yes IIa-C

29 ndash 34 36 ndash 50 NoYes IIa-C

Likely gt34 gt50 NoYes I-B

Table 9 Arbitrary Echo Criteria for estimating the presence of PH based on TRV an assumed RAP of 5 mmHg and additional Echo variables suggestive of PH

Galiegrave N et al Eur Heart J and Eur Respir J 2009

increased velocity of pulmonary valve regurgitation short AcT increased dimensions of RH chambers abnormal shape and function of the IVS increased RV wall thickness and dilated main PA

Hoeper et allJacc Vol 62 No 25 Suppl D 2013

Cateterismo cardiaco destro

Permette di misurare quanto descritto nella definizione funzionale della PAH

mPAP gt25 mmHg a riposo o gt30 mmHg in corso di esercizio

Gaine et al Lancet 1998352719

IP all rsquoEcocardiogramma gt PAPs 30-50 mmHg velocitagrave del rigurgito tricuspidalico di 2834 msec (PADx 5 mmHg)

European Heart Journal 2004 252253

Screening can be effective in identifying earlier disease

1

24

75

12Pa

tie

nts

(

)

63

0

20

40

60

80

100

I II III IV

100

80

60

40

20

0

n = 8(44) n = 5

(28) n = 2

(11)

II III IV

Pa

tie

nts

39

Hachulla E et al Arthritis Rheum 2005 523698-700 Humbert M et al Am J Respir Crit Care Med 2006 1731023-30

No screening With screening

WHO class WHO class

Survival Daily practice vs screening

Humbert Arthritis Rheum 2011 Nov63(11)3522-30

Screening

PH PresentPeak TRV

(ms)ePASP (mmHg)

Additional Echo Signs of

PHRE

Unlikely lt28 lt35 No I-B

Possiblelt28 lt35 Yes IIa-C

29 ndash 34 36 ndash 50 NoYes IIa-C

Likely gt34 gt50 NoYes I-B

Table 9 Arbitrary Echo Criteria for estimating the presence of PH based on TRV an assumed RAP of 5 mmHg and additional Echo variables suggestive of PH

Galiegrave N et al Eur Heart J and Eur Respir J 2009

increased velocity of pulmonary valve regurgitation short AcT increased dimensions of RH chambers abnormal shape and function of the IVS increased RV wall thickness and dilated main PA

Hoeper et allJacc Vol 62 No 25 Suppl D 2013

Cateterismo cardiaco destro

Permette di misurare quanto descritto nella definizione funzionale della PAH

mPAP gt25 mmHg a riposo o gt30 mmHg in corso di esercizio

Gaine et al Lancet 1998352719

IP all rsquoEcocardiogramma gt PAPs 30-50 mmHg velocitagrave del rigurgito tricuspidalico di 2834 msec (PADx 5 mmHg)

European Heart Journal 2004 252253

Screening can be effective in identifying earlier disease

1

24

75

12Pa

tie

nts

(

)

63

0

20

40

60

80

100

I II III IV

100

80

60

40

20

0

n = 8(44) n = 5

(28) n = 2

(11)

II III IV

Pa

tie

nts

39

Hachulla E et al Arthritis Rheum 2005 523698-700 Humbert M et al Am J Respir Crit Care Med 2006 1731023-30

No screening With screening

WHO class WHO class

Survival Daily practice vs screening

Humbert Arthritis Rheum 2011 Nov63(11)3522-30

Screening

Hoeper et allJacc Vol 62 No 25 Suppl D 2013

Cateterismo cardiaco destro

Permette di misurare quanto descritto nella definizione funzionale della PAH

mPAP gt25 mmHg a riposo o gt30 mmHg in corso di esercizio

Gaine et al Lancet 1998352719

IP all rsquoEcocardiogramma gt PAPs 30-50 mmHg velocitagrave del rigurgito tricuspidalico di 2834 msec (PADx 5 mmHg)

European Heart Journal 2004 252253

Screening can be effective in identifying earlier disease

1

24

75

12Pa

tie

nts

(

)

63

0

20

40

60

80

100

I II III IV

100

80

60

40

20

0

n = 8(44) n = 5

(28) n = 2

(11)

II III IV

Pa

tie

nts

39

Hachulla E et al Arthritis Rheum 2005 523698-700 Humbert M et al Am J Respir Crit Care Med 2006 1731023-30

No screening With screening

WHO class WHO class

Survival Daily practice vs screening

Humbert Arthritis Rheum 2011 Nov63(11)3522-30

Screening

Cateterismo cardiaco destro

Permette di misurare quanto descritto nella definizione funzionale della PAH

mPAP gt25 mmHg a riposo o gt30 mmHg in corso di esercizio

Gaine et al Lancet 1998352719

IP all rsquoEcocardiogramma gt PAPs 30-50 mmHg velocitagrave del rigurgito tricuspidalico di 2834 msec (PADx 5 mmHg)

European Heart Journal 2004 252253

Screening can be effective in identifying earlier disease

1

24

75

12Pa

tie

nts

(

)

63

0

20

40

60

80

100

I II III IV

100

80

60

40

20

0

n = 8(44) n = 5

(28) n = 2

(11)

II III IV

Pa

tie

nts

39

Hachulla E et al Arthritis Rheum 2005 523698-700 Humbert M et al Am J Respir Crit Care Med 2006 1731023-30

No screening With screening

WHO class WHO class

Survival Daily practice vs screening

Humbert Arthritis Rheum 2011 Nov63(11)3522-30

Screening

European Heart Journal 2004 252253

Screening can be effective in identifying earlier disease

1

24

75

12Pa

tie

nts

(

)

63

0

20

40

60

80

100

I II III IV

100

80

60

40

20

0

n = 8(44) n = 5

(28) n = 2

(11)

II III IV

Pa

tie

nts

39

Hachulla E et al Arthritis Rheum 2005 523698-700 Humbert M et al Am J Respir Crit Care Med 2006 1731023-30

No screening With screening

WHO class WHO class

Survival Daily practice vs screening

Humbert Arthritis Rheum 2011 Nov63(11)3522-30

Screening

Screening can be effective in identifying earlier disease

1

24

75

12Pa

tie

nts

(

)

63

0

20

40

60

80

100

I II III IV

100

80

60

40

20

0

n = 8(44) n = 5

(28) n = 2

(11)

II III IV

Pa

tie

nts

39

Hachulla E et al Arthritis Rheum 2005 523698-700 Humbert M et al Am J Respir Crit Care Med 2006 1731023-30

No screening With screening

WHO class WHO class

Survival Daily practice vs screening

Humbert Arthritis Rheum 2011 Nov63(11)3522-30

Screening

Survival Daily practice vs screening

Humbert Arthritis Rheum 2011 Nov63(11)3522-30

Screening

bull Systemic Sclerosis (10-13)

bull SLE (05-14)

bull MCTD (23-53)

bull RA (lt 1)

bull DM (lt 1)

bull Sjogrenrsquos Syndrome (25 )

bull Undifferentiated and Overlap syndromes

bull Antiphospholipid Syndrome

bull Vasculitis

PAH associated to CTD

1 Pulmonary arterial hypertension

bull Associated with CTD

3 PH due to lung diseasehypoxia

bull Interstitial lung disease (fibrosis)

2PH due to left heart disease

bull Systolicdiastolic dysfunction

bull Valvyular disease

PHin

CTD

PH associated with CTD

Pumonary VascularDisease

InterstitialFibrosis

PAHPH associated to SSc

lcSSc dcSSc

50-90 8-50

Raccomandation for PAH associated with connective tissue disease

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Hachulla et al Arthritis Rheum 2005523792

599 patients

29 had known PAH

570 screened for PAH

The ItineacuterAIR-Scleacuterodermie study

18 (54) PAH confirmed

3 pts (9) PH + LVD 12 (36) pts no PH

RHC

45 ECHO False Positive

33 suspected PAH on Echo

Evidence-based detection of pulmonary arterialhypertension in systemic sclerosis the DETECT

study

Coghlan JG Ann Rheum Dis 2013 May 18 [E-pub ahead of print]

1 Pulmonary arterial hypertension

bull Associated with CTD

3 PH due to lung diseasehypoxia

bull Interstitial lung disease (fibrosis)

2PH due to left heart disease

bull Systolicdiastolic dysfunction

bull Valvyular disease

PHin

CTD

PH associated with CTD

Pumonary VascularDisease

InterstitialFibrosis

PAHPH associated to SSc

lcSSc dcSSc

50-90 8-50

Raccomandation for PAH associated with connective tissue disease

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Hachulla et al Arthritis Rheum 2005523792

599 patients

29 had known PAH

570 screened for PAH

The ItineacuterAIR-Scleacuterodermie study

18 (54) PAH confirmed

3 pts (9) PH + LVD 12 (36) pts no PH

RHC

45 ECHO False Positive

33 suspected PAH on Echo

Evidence-based detection of pulmonary arterialhypertension in systemic sclerosis the DETECT

study

Coghlan JG Ann Rheum Dis 2013 May 18 [E-pub ahead of print]

Pumonary VascularDisease

InterstitialFibrosis

PAHPH associated to SSc

lcSSc dcSSc

50-90 8-50

Raccomandation for PAH associated with connective tissue disease

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Hachulla et al Arthritis Rheum 2005523792

599 patients

29 had known PAH

570 screened for PAH

The ItineacuterAIR-Scleacuterodermie study

18 (54) PAH confirmed

3 pts (9) PH + LVD 12 (36) pts no PH

RHC

45 ECHO False Positive

33 suspected PAH on Echo

Evidence-based detection of pulmonary arterialhypertension in systemic sclerosis the DETECT

study

Coghlan JG Ann Rheum Dis 2013 May 18 [E-pub ahead of print]

Raccomandation for PAH associated with connective tissue disease

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Hachulla et al Arthritis Rheum 2005523792

599 patients

29 had known PAH

570 screened for PAH

The ItineacuterAIR-Scleacuterodermie study

18 (54) PAH confirmed

3 pts (9) PH + LVD 12 (36) pts no PH

RHC

45 ECHO False Positive

33 suspected PAH on Echo

Evidence-based detection of pulmonary arterialhypertension in systemic sclerosis the DETECT

study

Coghlan JG Ann Rheum Dis 2013 May 18 [E-pub ahead of print]

Hachulla et al Arthritis Rheum 2005523792

599 patients

29 had known PAH

570 screened for PAH

The ItineacuterAIR-Scleacuterodermie study

18 (54) PAH confirmed

3 pts (9) PH + LVD 12 (36) pts no PH

RHC

45 ECHO False Positive

33 suspected PAH on Echo

Evidence-based detection of pulmonary arterialhypertension in systemic sclerosis the DETECT

study

Coghlan JG Ann Rheum Dis 2013 May 18 [E-pub ahead of print]

Evidence-based detection of pulmonary arterialhypertension in systemic sclerosis the DETECT

study

Coghlan JG Ann Rheum Dis 2013 May 18 [E-pub ahead of print]

Evidence-based detection of pulmonary arterialhypertension in systemic sclerosis the DETECT

study

Coghlan JG Ann Rheum Dis 2013 May 18 [E-pub ahead of print]

Nomograms for practical application of the DETECT algorithm STEP 1

Evidence-based detection of pulmonary arterial

hypertension in systemic sclerosis the DETECT study

Coghlan JG Ann Rheum Dis 2013 May 18 [E-pub ahead of print]

Nomograms for practical application of the DETECT algorithm STEP 2

Evidence-based detection of pulmonary arterial

hypertension in systemic sclerosis the DETECT study

Coghlan JG Ann Rheum Dis 2013 May 18 [E-pub ahead of print]

Missed PAH cases

DETECT algorithm

4

ECHO-based approachESC-ERS guidelines

29

How effective are drugs in connective tissue disease

The PAH-CTD subgroup represents about the 25 of the entire PAH population included in RCTs being the second largest group after IPAH

SPECIFIC EFFECTS OF PAH-TREATMENTS

IN PAH-CTD SUBGROUP

AS REPORTED IN CLINICAL STUDIES

EXERCISE CAPACITY

LOCF Analysis Mean plusmn 95 confidence interval IPAH n=176 PAH-CTD n=91

IPAH

PAH-CTD

Change from Baseline in 6MWD in IPAH and PAH-CTD long-term response

Years

Chan

ge in

6M

WD

(m)

Impr

ovem

ent

-40

-20

0

20

40

60

80

00 05 10 15 20

Pulido T et al American Thoracic Society Annual Meeting 2009 [Abstract]

Meta-analysis of 6MWD in RCTs

Avouac J et al Ann Rheum Dis 200867808ndash14

CTD subset of patients

Whole population of PAH patients

ndash05 0 05 10 15 20

Sildenafil 80 mg TID

Sildenafil 40 mg TID

Sildenafil 20 mg TID

Bosentan 250 mg BID

Bosentan 125 mg BID

Effect size

PACES-1 study improvements in 6MWD

ITT = intention-to-treat LOCF = last observation carried forward 1 Simonneau G et al Ann Intern Med 2008149521ndash30 2 Unpublished data subgroup analysis Burgress G et al

Chan

ge in

6M

WD

(m)

Sildenafil TID +IV epoprostenol (n=27)

Placebo + IV epoprostenol (n=25)

p= ns

0

5

10

15

20

25

30

35

+35

+96

CTD subgroup (LOCF)2

-10

0

10

20

30

40

50

Baseline 4 8 12 16

Study time week

Mea

n ch

ange

from

bas

elin

e (9

5 C

I) m Sildenafil + IV epoprostenol

Placebo + IV epoprostenol

Overall cohort (ITT)1

p lt0001

SPECIFIC EFFECTS OF PAH-TREATMENTS

IN PAH-CTD SUBGROUP

AS REPORTED IN CLINICAL STUDIES

EFFECTS ON OUTCOME

PAH-CREST (n = 18)

0

20

40

60

80

100

0 12 24 36 48 60 72

PPH (n = 36)

(Mois)

P = 00005 test du Log-Rank (Mantel-Cox)

Sur

vie

act u

arie

lle

()

(23)

(6)

(11)

(2)

(9)

(1)

Humbert M et al Eur Respir J 1999 Jun13(6)1351-6

Epoprostenol in PAH-CTD outcome

Time to Clinical Worsening

Time (Wks)

Even

t-Fr

ee s

urvi

val (

)

0

25

50

75

100

0 4 8 12 16 20 24 28

p = 00015

p = 00038

89

63

(n = 144)(n = 69)

(n = 35)(n = 13)

Bosentan

Placebo100

25

50

75

0

Time (Wks)0 4 8 12 16 18

9079

(n = 33)

(n = 14)

B1 ITT Population B1 SSc Subpopulation

Bosentan on PAH-CTD analysis of TCW in Breathe-1 study

Rubin L et al NEJM 2002

p = ns

Even

t-Fr

ee s

urvi

val (

)

Macitentan

Comments on the published data

bull In the RCTs the improvement of 6MWD is consistently lower in patients with CTD-PAH as compared to IPAH

bull Also the outcome of CTD-PAH patients seems to be worse as compared to the outcome in IPAH

CASO CLINICO

bull Donna 53 anni

bull Da circa 10 anni fenomeno di Raynaud

bull Giunge allrsquoosservazione pneumologica per tosse secca e da alcuni anni dispnea per sforzi moderati

bull Agli esami generali Lieve aumento di VES e szlig1 e szlig2 globuline

bull Obiettivitagrave nei limiti

Prove di funzionalitagrave respiratoria

bull Spirometria nel range della normalitagrave

bull Ostruzione piccole vie aeree

bull DLCO lieve riduzione (59)

Visita reumatologica

Nulla di significativo

RX Torace

Non lesioni infilatrative parenchimaliNormale la distribuzione del circolo polmonareLiberi i seni costo-frenici

Cardiologia

Giunge alla nostra osservazione per ecocardiogramma di screening su prescrizione reumatologica

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

The PAH-CTD subgroup represents about the 25 of the entire PAH population included in RCTs being the second largest group after IPAH

SPECIFIC EFFECTS OF PAH-TREATMENTS

IN PAH-CTD SUBGROUP

AS REPORTED IN CLINICAL STUDIES

EXERCISE CAPACITY

LOCF Analysis Mean plusmn 95 confidence interval IPAH n=176 PAH-CTD n=91

IPAH

PAH-CTD

Change from Baseline in 6MWD in IPAH and PAH-CTD long-term response

Years

Chan

ge in

6M

WD

(m)

Impr

ovem

ent

-40

-20

0

20

40

60

80

00 05 10 15 20

Pulido T et al American Thoracic Society Annual Meeting 2009 [Abstract]

Meta-analysis of 6MWD in RCTs

Avouac J et al Ann Rheum Dis 200867808ndash14

CTD subset of patients

Whole population of PAH patients

ndash05 0 05 10 15 20

Sildenafil 80 mg TID

Sildenafil 40 mg TID

Sildenafil 20 mg TID

Bosentan 250 mg BID

Bosentan 125 mg BID

Effect size

PACES-1 study improvements in 6MWD

ITT = intention-to-treat LOCF = last observation carried forward 1 Simonneau G et al Ann Intern Med 2008149521ndash30 2 Unpublished data subgroup analysis Burgress G et al

Chan

ge in

6M

WD

(m)

Sildenafil TID +IV epoprostenol (n=27)

Placebo + IV epoprostenol (n=25)

p= ns

0

5

10

15

20

25

30

35

+35

+96

CTD subgroup (LOCF)2

-10

0

10

20

30

40

50

Baseline 4 8 12 16

Study time week

Mea

n ch

ange

from

bas

elin

e (9

5 C

I) m Sildenafil + IV epoprostenol

Placebo + IV epoprostenol

Overall cohort (ITT)1

p lt0001

SPECIFIC EFFECTS OF PAH-TREATMENTS

IN PAH-CTD SUBGROUP

AS REPORTED IN CLINICAL STUDIES

EFFECTS ON OUTCOME

PAH-CREST (n = 18)

0

20

40

60

80

100

0 12 24 36 48 60 72

PPH (n = 36)

(Mois)

P = 00005 test du Log-Rank (Mantel-Cox)

Sur

vie

act u

arie

lle

()

(23)

(6)

(11)

(2)

(9)

(1)

Humbert M et al Eur Respir J 1999 Jun13(6)1351-6

Epoprostenol in PAH-CTD outcome

Time to Clinical Worsening

Time (Wks)

Even

t-Fr

ee s

urvi

val (

)

0

25

50

75

100

0 4 8 12 16 20 24 28

p = 00015

p = 00038

89

63

(n = 144)(n = 69)

(n = 35)(n = 13)

Bosentan

Placebo100

25

50

75

0

Time (Wks)0 4 8 12 16 18

9079

(n = 33)

(n = 14)

B1 ITT Population B1 SSc Subpopulation

Bosentan on PAH-CTD analysis of TCW in Breathe-1 study

Rubin L et al NEJM 2002

p = ns

Even

t-Fr

ee s

urvi

val (

)

Macitentan

Comments on the published data

bull In the RCTs the improvement of 6MWD is consistently lower in patients with CTD-PAH as compared to IPAH

bull Also the outcome of CTD-PAH patients seems to be worse as compared to the outcome in IPAH

CASO CLINICO

bull Donna 53 anni

bull Da circa 10 anni fenomeno di Raynaud

bull Giunge allrsquoosservazione pneumologica per tosse secca e da alcuni anni dispnea per sforzi moderati

bull Agli esami generali Lieve aumento di VES e szlig1 e szlig2 globuline

bull Obiettivitagrave nei limiti

Prove di funzionalitagrave respiratoria

bull Spirometria nel range della normalitagrave

bull Ostruzione piccole vie aeree

bull DLCO lieve riduzione (59)

Visita reumatologica

Nulla di significativo

RX Torace

Non lesioni infilatrative parenchimaliNormale la distribuzione del circolo polmonareLiberi i seni costo-frenici

Cardiologia

Giunge alla nostra osservazione per ecocardiogramma di screening su prescrizione reumatologica

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

SPECIFIC EFFECTS OF PAH-TREATMENTS

IN PAH-CTD SUBGROUP

AS REPORTED IN CLINICAL STUDIES

EXERCISE CAPACITY

LOCF Analysis Mean plusmn 95 confidence interval IPAH n=176 PAH-CTD n=91

IPAH

PAH-CTD

Change from Baseline in 6MWD in IPAH and PAH-CTD long-term response

Years

Chan

ge in

6M

WD

(m)

Impr

ovem

ent

-40

-20

0

20

40

60

80

00 05 10 15 20

Pulido T et al American Thoracic Society Annual Meeting 2009 [Abstract]

Meta-analysis of 6MWD in RCTs

Avouac J et al Ann Rheum Dis 200867808ndash14

CTD subset of patients

Whole population of PAH patients

ndash05 0 05 10 15 20

Sildenafil 80 mg TID

Sildenafil 40 mg TID

Sildenafil 20 mg TID

Bosentan 250 mg BID

Bosentan 125 mg BID

Effect size

PACES-1 study improvements in 6MWD

ITT = intention-to-treat LOCF = last observation carried forward 1 Simonneau G et al Ann Intern Med 2008149521ndash30 2 Unpublished data subgroup analysis Burgress G et al

Chan

ge in

6M

WD

(m)

Sildenafil TID +IV epoprostenol (n=27)

Placebo + IV epoprostenol (n=25)

p= ns

0

5

10

15

20

25

30

35

+35

+96

CTD subgroup (LOCF)2

-10

0

10

20

30

40

50

Baseline 4 8 12 16

Study time week

Mea

n ch

ange

from

bas

elin

e (9

5 C

I) m Sildenafil + IV epoprostenol

Placebo + IV epoprostenol

Overall cohort (ITT)1

p lt0001

SPECIFIC EFFECTS OF PAH-TREATMENTS

IN PAH-CTD SUBGROUP

AS REPORTED IN CLINICAL STUDIES

EFFECTS ON OUTCOME

PAH-CREST (n = 18)

0

20

40

60

80

100

0 12 24 36 48 60 72

PPH (n = 36)

(Mois)

P = 00005 test du Log-Rank (Mantel-Cox)

Sur

vie

act u

arie

lle

()

(23)

(6)

(11)

(2)

(9)

(1)

Humbert M et al Eur Respir J 1999 Jun13(6)1351-6

Epoprostenol in PAH-CTD outcome

Time to Clinical Worsening

Time (Wks)

Even

t-Fr

ee s

urvi

val (

)

0

25

50

75

100

0 4 8 12 16 20 24 28

p = 00015

p = 00038

89

63

(n = 144)(n = 69)

(n = 35)(n = 13)

Bosentan

Placebo100

25

50

75

0

Time (Wks)0 4 8 12 16 18

9079

(n = 33)

(n = 14)

B1 ITT Population B1 SSc Subpopulation

Bosentan on PAH-CTD analysis of TCW in Breathe-1 study

Rubin L et al NEJM 2002

p = ns

Even

t-Fr

ee s

urvi

val (

)

Macitentan

Comments on the published data

bull In the RCTs the improvement of 6MWD is consistently lower in patients with CTD-PAH as compared to IPAH

bull Also the outcome of CTD-PAH patients seems to be worse as compared to the outcome in IPAH

CASO CLINICO

bull Donna 53 anni

bull Da circa 10 anni fenomeno di Raynaud

bull Giunge allrsquoosservazione pneumologica per tosse secca e da alcuni anni dispnea per sforzi moderati

bull Agli esami generali Lieve aumento di VES e szlig1 e szlig2 globuline

bull Obiettivitagrave nei limiti

Prove di funzionalitagrave respiratoria

bull Spirometria nel range della normalitagrave

bull Ostruzione piccole vie aeree

bull DLCO lieve riduzione (59)

Visita reumatologica

Nulla di significativo

RX Torace

Non lesioni infilatrative parenchimaliNormale la distribuzione del circolo polmonareLiberi i seni costo-frenici

Cardiologia

Giunge alla nostra osservazione per ecocardiogramma di screening su prescrizione reumatologica

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

LOCF Analysis Mean plusmn 95 confidence interval IPAH n=176 PAH-CTD n=91

IPAH

PAH-CTD

Change from Baseline in 6MWD in IPAH and PAH-CTD long-term response

Years

Chan

ge in

6M

WD

(m)

Impr

ovem

ent

-40

-20

0

20

40

60

80

00 05 10 15 20

Pulido T et al American Thoracic Society Annual Meeting 2009 [Abstract]

Meta-analysis of 6MWD in RCTs

Avouac J et al Ann Rheum Dis 200867808ndash14

CTD subset of patients

Whole population of PAH patients

ndash05 0 05 10 15 20

Sildenafil 80 mg TID

Sildenafil 40 mg TID

Sildenafil 20 mg TID

Bosentan 250 mg BID

Bosentan 125 mg BID

Effect size

PACES-1 study improvements in 6MWD

ITT = intention-to-treat LOCF = last observation carried forward 1 Simonneau G et al Ann Intern Med 2008149521ndash30 2 Unpublished data subgroup analysis Burgress G et al

Chan

ge in

6M

WD

(m)

Sildenafil TID +IV epoprostenol (n=27)

Placebo + IV epoprostenol (n=25)

p= ns

0

5

10

15

20

25

30

35

+35

+96

CTD subgroup (LOCF)2

-10

0

10

20

30

40

50

Baseline 4 8 12 16

Study time week

Mea

n ch

ange

from

bas

elin

e (9

5 C

I) m Sildenafil + IV epoprostenol

Placebo + IV epoprostenol

Overall cohort (ITT)1

p lt0001

SPECIFIC EFFECTS OF PAH-TREATMENTS

IN PAH-CTD SUBGROUP

AS REPORTED IN CLINICAL STUDIES

EFFECTS ON OUTCOME

PAH-CREST (n = 18)

0

20

40

60

80

100

0 12 24 36 48 60 72

PPH (n = 36)

(Mois)

P = 00005 test du Log-Rank (Mantel-Cox)

Sur

vie

act u

arie

lle

()

(23)

(6)

(11)

(2)

(9)

(1)

Humbert M et al Eur Respir J 1999 Jun13(6)1351-6

Epoprostenol in PAH-CTD outcome

Time to Clinical Worsening

Time (Wks)

Even

t-Fr

ee s

urvi

val (

)

0

25

50

75

100

0 4 8 12 16 20 24 28

p = 00015

p = 00038

89

63

(n = 144)(n = 69)

(n = 35)(n = 13)

Bosentan

Placebo100

25

50

75

0

Time (Wks)0 4 8 12 16 18

9079

(n = 33)

(n = 14)

B1 ITT Population B1 SSc Subpopulation

Bosentan on PAH-CTD analysis of TCW in Breathe-1 study

Rubin L et al NEJM 2002

p = ns

Even

t-Fr

ee s

urvi

val (

)

Macitentan

Comments on the published data

bull In the RCTs the improvement of 6MWD is consistently lower in patients with CTD-PAH as compared to IPAH

bull Also the outcome of CTD-PAH patients seems to be worse as compared to the outcome in IPAH

CASO CLINICO

bull Donna 53 anni

bull Da circa 10 anni fenomeno di Raynaud

bull Giunge allrsquoosservazione pneumologica per tosse secca e da alcuni anni dispnea per sforzi moderati

bull Agli esami generali Lieve aumento di VES e szlig1 e szlig2 globuline

bull Obiettivitagrave nei limiti

Prove di funzionalitagrave respiratoria

bull Spirometria nel range della normalitagrave

bull Ostruzione piccole vie aeree

bull DLCO lieve riduzione (59)

Visita reumatologica

Nulla di significativo

RX Torace

Non lesioni infilatrative parenchimaliNormale la distribuzione del circolo polmonareLiberi i seni costo-frenici

Cardiologia

Giunge alla nostra osservazione per ecocardiogramma di screening su prescrizione reumatologica

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Meta-analysis of 6MWD in RCTs

Avouac J et al Ann Rheum Dis 200867808ndash14

CTD subset of patients

Whole population of PAH patients

ndash05 0 05 10 15 20

Sildenafil 80 mg TID

Sildenafil 40 mg TID

Sildenafil 20 mg TID

Bosentan 250 mg BID

Bosentan 125 mg BID

Effect size

PACES-1 study improvements in 6MWD

ITT = intention-to-treat LOCF = last observation carried forward 1 Simonneau G et al Ann Intern Med 2008149521ndash30 2 Unpublished data subgroup analysis Burgress G et al

Chan

ge in

6M

WD

(m)

Sildenafil TID +IV epoprostenol (n=27)

Placebo + IV epoprostenol (n=25)

p= ns

0

5

10

15

20

25

30

35

+35

+96

CTD subgroup (LOCF)2

-10

0

10

20

30

40

50

Baseline 4 8 12 16

Study time week

Mea

n ch

ange

from

bas

elin

e (9

5 C

I) m Sildenafil + IV epoprostenol

Placebo + IV epoprostenol

Overall cohort (ITT)1

p lt0001

SPECIFIC EFFECTS OF PAH-TREATMENTS

IN PAH-CTD SUBGROUP

AS REPORTED IN CLINICAL STUDIES

EFFECTS ON OUTCOME

PAH-CREST (n = 18)

0

20

40

60

80

100

0 12 24 36 48 60 72

PPH (n = 36)

(Mois)

P = 00005 test du Log-Rank (Mantel-Cox)

Sur

vie

act u

arie

lle

()

(23)

(6)

(11)

(2)

(9)

(1)

Humbert M et al Eur Respir J 1999 Jun13(6)1351-6

Epoprostenol in PAH-CTD outcome

Time to Clinical Worsening

Time (Wks)

Even

t-Fr

ee s

urvi

val (

)

0

25

50

75

100

0 4 8 12 16 20 24 28

p = 00015

p = 00038

89

63

(n = 144)(n = 69)

(n = 35)(n = 13)

Bosentan

Placebo100

25

50

75

0

Time (Wks)0 4 8 12 16 18

9079

(n = 33)

(n = 14)

B1 ITT Population B1 SSc Subpopulation

Bosentan on PAH-CTD analysis of TCW in Breathe-1 study

Rubin L et al NEJM 2002

p = ns

Even

t-Fr

ee s

urvi

val (

)

Macitentan

Comments on the published data

bull In the RCTs the improvement of 6MWD is consistently lower in patients with CTD-PAH as compared to IPAH

bull Also the outcome of CTD-PAH patients seems to be worse as compared to the outcome in IPAH

CASO CLINICO

bull Donna 53 anni

bull Da circa 10 anni fenomeno di Raynaud

bull Giunge allrsquoosservazione pneumologica per tosse secca e da alcuni anni dispnea per sforzi moderati

bull Agli esami generali Lieve aumento di VES e szlig1 e szlig2 globuline

bull Obiettivitagrave nei limiti

Prove di funzionalitagrave respiratoria

bull Spirometria nel range della normalitagrave

bull Ostruzione piccole vie aeree

bull DLCO lieve riduzione (59)

Visita reumatologica

Nulla di significativo

RX Torace

Non lesioni infilatrative parenchimaliNormale la distribuzione del circolo polmonareLiberi i seni costo-frenici

Cardiologia

Giunge alla nostra osservazione per ecocardiogramma di screening su prescrizione reumatologica

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

PACES-1 study improvements in 6MWD

ITT = intention-to-treat LOCF = last observation carried forward 1 Simonneau G et al Ann Intern Med 2008149521ndash30 2 Unpublished data subgroup analysis Burgress G et al

Chan

ge in

6M

WD

(m)

Sildenafil TID +IV epoprostenol (n=27)

Placebo + IV epoprostenol (n=25)

p= ns

0

5

10

15

20

25

30

35

+35

+96

CTD subgroup (LOCF)2

-10

0

10

20

30

40

50

Baseline 4 8 12 16

Study time week

Mea

n ch

ange

from

bas

elin

e (9

5 C

I) m Sildenafil + IV epoprostenol

Placebo + IV epoprostenol

Overall cohort (ITT)1

p lt0001

SPECIFIC EFFECTS OF PAH-TREATMENTS

IN PAH-CTD SUBGROUP

AS REPORTED IN CLINICAL STUDIES

EFFECTS ON OUTCOME

PAH-CREST (n = 18)

0

20

40

60

80

100

0 12 24 36 48 60 72

PPH (n = 36)

(Mois)

P = 00005 test du Log-Rank (Mantel-Cox)

Sur

vie

act u

arie

lle

()

(23)

(6)

(11)

(2)

(9)

(1)

Humbert M et al Eur Respir J 1999 Jun13(6)1351-6

Epoprostenol in PAH-CTD outcome

Time to Clinical Worsening

Time (Wks)

Even

t-Fr

ee s

urvi

val (

)

0

25

50

75

100

0 4 8 12 16 20 24 28

p = 00015

p = 00038

89

63

(n = 144)(n = 69)

(n = 35)(n = 13)

Bosentan

Placebo100

25

50

75

0

Time (Wks)0 4 8 12 16 18

9079

(n = 33)

(n = 14)

B1 ITT Population B1 SSc Subpopulation

Bosentan on PAH-CTD analysis of TCW in Breathe-1 study

Rubin L et al NEJM 2002

p = ns

Even

t-Fr

ee s

urvi

val (

)

Macitentan

Comments on the published data

bull In the RCTs the improvement of 6MWD is consistently lower in patients with CTD-PAH as compared to IPAH

bull Also the outcome of CTD-PAH patients seems to be worse as compared to the outcome in IPAH

CASO CLINICO

bull Donna 53 anni

bull Da circa 10 anni fenomeno di Raynaud

bull Giunge allrsquoosservazione pneumologica per tosse secca e da alcuni anni dispnea per sforzi moderati

bull Agli esami generali Lieve aumento di VES e szlig1 e szlig2 globuline

bull Obiettivitagrave nei limiti

Prove di funzionalitagrave respiratoria

bull Spirometria nel range della normalitagrave

bull Ostruzione piccole vie aeree

bull DLCO lieve riduzione (59)

Visita reumatologica

Nulla di significativo

RX Torace

Non lesioni infilatrative parenchimaliNormale la distribuzione del circolo polmonareLiberi i seni costo-frenici

Cardiologia

Giunge alla nostra osservazione per ecocardiogramma di screening su prescrizione reumatologica

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

SPECIFIC EFFECTS OF PAH-TREATMENTS

IN PAH-CTD SUBGROUP

AS REPORTED IN CLINICAL STUDIES

EFFECTS ON OUTCOME

PAH-CREST (n = 18)

0

20

40

60

80

100

0 12 24 36 48 60 72

PPH (n = 36)

(Mois)

P = 00005 test du Log-Rank (Mantel-Cox)

Sur

vie

act u

arie

lle

()

(23)

(6)

(11)

(2)

(9)

(1)

Humbert M et al Eur Respir J 1999 Jun13(6)1351-6

Epoprostenol in PAH-CTD outcome

Time to Clinical Worsening

Time (Wks)

Even

t-Fr

ee s

urvi

val (

)

0

25

50

75

100

0 4 8 12 16 20 24 28

p = 00015

p = 00038

89

63

(n = 144)(n = 69)

(n = 35)(n = 13)

Bosentan

Placebo100

25

50

75

0

Time (Wks)0 4 8 12 16 18

9079

(n = 33)

(n = 14)

B1 ITT Population B1 SSc Subpopulation

Bosentan on PAH-CTD analysis of TCW in Breathe-1 study

Rubin L et al NEJM 2002

p = ns

Even

t-Fr

ee s

urvi

val (

)

Macitentan

Comments on the published data

bull In the RCTs the improvement of 6MWD is consistently lower in patients with CTD-PAH as compared to IPAH

bull Also the outcome of CTD-PAH patients seems to be worse as compared to the outcome in IPAH

CASO CLINICO

bull Donna 53 anni

bull Da circa 10 anni fenomeno di Raynaud

bull Giunge allrsquoosservazione pneumologica per tosse secca e da alcuni anni dispnea per sforzi moderati

bull Agli esami generali Lieve aumento di VES e szlig1 e szlig2 globuline

bull Obiettivitagrave nei limiti

Prove di funzionalitagrave respiratoria

bull Spirometria nel range della normalitagrave

bull Ostruzione piccole vie aeree

bull DLCO lieve riduzione (59)

Visita reumatologica

Nulla di significativo

RX Torace

Non lesioni infilatrative parenchimaliNormale la distribuzione del circolo polmonareLiberi i seni costo-frenici

Cardiologia

Giunge alla nostra osservazione per ecocardiogramma di screening su prescrizione reumatologica

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

PAH-CREST (n = 18)

0

20

40

60

80

100

0 12 24 36 48 60 72

PPH (n = 36)

(Mois)

P = 00005 test du Log-Rank (Mantel-Cox)

Sur

vie

act u

arie

lle

()

(23)

(6)

(11)

(2)

(9)

(1)

Humbert M et al Eur Respir J 1999 Jun13(6)1351-6

Epoprostenol in PAH-CTD outcome

Time to Clinical Worsening

Time (Wks)

Even

t-Fr

ee s

urvi

val (

)

0

25

50

75

100

0 4 8 12 16 20 24 28

p = 00015

p = 00038

89

63

(n = 144)(n = 69)

(n = 35)(n = 13)

Bosentan

Placebo100

25

50

75

0

Time (Wks)0 4 8 12 16 18

9079

(n = 33)

(n = 14)

B1 ITT Population B1 SSc Subpopulation

Bosentan on PAH-CTD analysis of TCW in Breathe-1 study

Rubin L et al NEJM 2002

p = ns

Even

t-Fr

ee s

urvi

val (

)

Macitentan

Comments on the published data

bull In the RCTs the improvement of 6MWD is consistently lower in patients with CTD-PAH as compared to IPAH

bull Also the outcome of CTD-PAH patients seems to be worse as compared to the outcome in IPAH

CASO CLINICO

bull Donna 53 anni

bull Da circa 10 anni fenomeno di Raynaud

bull Giunge allrsquoosservazione pneumologica per tosse secca e da alcuni anni dispnea per sforzi moderati

bull Agli esami generali Lieve aumento di VES e szlig1 e szlig2 globuline

bull Obiettivitagrave nei limiti

Prove di funzionalitagrave respiratoria

bull Spirometria nel range della normalitagrave

bull Ostruzione piccole vie aeree

bull DLCO lieve riduzione (59)

Visita reumatologica

Nulla di significativo

RX Torace

Non lesioni infilatrative parenchimaliNormale la distribuzione del circolo polmonareLiberi i seni costo-frenici

Cardiologia

Giunge alla nostra osservazione per ecocardiogramma di screening su prescrizione reumatologica

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Time to Clinical Worsening

Time (Wks)

Even

t-Fr

ee s

urvi

val (

)

0

25

50

75

100

0 4 8 12 16 20 24 28

p = 00015

p = 00038

89

63

(n = 144)(n = 69)

(n = 35)(n = 13)

Bosentan

Placebo100

25

50

75

0

Time (Wks)0 4 8 12 16 18

9079

(n = 33)

(n = 14)

B1 ITT Population B1 SSc Subpopulation

Bosentan on PAH-CTD analysis of TCW in Breathe-1 study

Rubin L et al NEJM 2002

p = ns

Even

t-Fr

ee s

urvi

val (

)

Macitentan

Comments on the published data

bull In the RCTs the improvement of 6MWD is consistently lower in patients with CTD-PAH as compared to IPAH

bull Also the outcome of CTD-PAH patients seems to be worse as compared to the outcome in IPAH

CASO CLINICO

bull Donna 53 anni

bull Da circa 10 anni fenomeno di Raynaud

bull Giunge allrsquoosservazione pneumologica per tosse secca e da alcuni anni dispnea per sforzi moderati

bull Agli esami generali Lieve aumento di VES e szlig1 e szlig2 globuline

bull Obiettivitagrave nei limiti

Prove di funzionalitagrave respiratoria

bull Spirometria nel range della normalitagrave

bull Ostruzione piccole vie aeree

bull DLCO lieve riduzione (59)

Visita reumatologica

Nulla di significativo

RX Torace

Non lesioni infilatrative parenchimaliNormale la distribuzione del circolo polmonareLiberi i seni costo-frenici

Cardiologia

Giunge alla nostra osservazione per ecocardiogramma di screening su prescrizione reumatologica

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Macitentan

Comments on the published data

bull In the RCTs the improvement of 6MWD is consistently lower in patients with CTD-PAH as compared to IPAH

bull Also the outcome of CTD-PAH patients seems to be worse as compared to the outcome in IPAH

CASO CLINICO

bull Donna 53 anni

bull Da circa 10 anni fenomeno di Raynaud

bull Giunge allrsquoosservazione pneumologica per tosse secca e da alcuni anni dispnea per sforzi moderati

bull Agli esami generali Lieve aumento di VES e szlig1 e szlig2 globuline

bull Obiettivitagrave nei limiti

Prove di funzionalitagrave respiratoria

bull Spirometria nel range della normalitagrave

bull Ostruzione piccole vie aeree

bull DLCO lieve riduzione (59)

Visita reumatologica

Nulla di significativo

RX Torace

Non lesioni infilatrative parenchimaliNormale la distribuzione del circolo polmonareLiberi i seni costo-frenici

Cardiologia

Giunge alla nostra osservazione per ecocardiogramma di screening su prescrizione reumatologica

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

CASO CLINICO

bull Donna 53 anni

bull Da circa 10 anni fenomeno di Raynaud

bull Giunge allrsquoosservazione pneumologica per tosse secca e da alcuni anni dispnea per sforzi moderati

bull Agli esami generali Lieve aumento di VES e szlig1 e szlig2 globuline

bull Obiettivitagrave nei limiti

Prove di funzionalitagrave respiratoria

bull Spirometria nel range della normalitagrave

bull Ostruzione piccole vie aeree

bull DLCO lieve riduzione (59)

Visita reumatologica

Nulla di significativo

RX Torace

Non lesioni infilatrative parenchimaliNormale la distribuzione del circolo polmonareLiberi i seni costo-frenici

Cardiologia

Giunge alla nostra osservazione per ecocardiogramma di screening su prescrizione reumatologica

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Prove di funzionalitagrave respiratoria

bull Spirometria nel range della normalitagrave

bull Ostruzione piccole vie aeree

bull DLCO lieve riduzione (59)

Visita reumatologica

Nulla di significativo

RX Torace

Non lesioni infilatrative parenchimaliNormale la distribuzione del circolo polmonareLiberi i seni costo-frenici

Cardiologia

Giunge alla nostra osservazione per ecocardiogramma di screening su prescrizione reumatologica

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Visita reumatologica

Nulla di significativo

RX Torace

Non lesioni infilatrative parenchimaliNormale la distribuzione del circolo polmonareLiberi i seni costo-frenici

Cardiologia

Giunge alla nostra osservazione per ecocardiogramma di screening su prescrizione reumatologica

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Nulla di significativo

RX Torace

Non lesioni infilatrative parenchimaliNormale la distribuzione del circolo polmonareLiberi i seni costo-frenici

Cardiologia

Giunge alla nostra osservazione per ecocardiogramma di screening su prescrizione reumatologica

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

RX Torace

Non lesioni infilatrative parenchimaliNormale la distribuzione del circolo polmonareLiberi i seni costo-frenici

Cardiologia

Giunge alla nostra osservazione per ecocardiogramma di screening su prescrizione reumatologica

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Cardiologia

Giunge alla nostra osservazione per ecocardiogramma di screening su prescrizione reumatologica

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Obiettivitagrave

bull Riferisce dispnea per sforzi moderati

bull Obiettivitagrave op murmure vescicolare diffuso su tutto lrsquoambito polmonare Oc toni ritmici validi Polsi normoisosfigmici

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Elettrocardiogramma

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

ECOCARDIOGRAMMA

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

ECOCARDIOGRAMMA

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

6 Minute Wolking Test

bull distanza percorsa 510 metri senza interruzioni

bull SpO2 inizio test 95 in aa

bull PA inizio test 16080 mmHg

bull fc inizio test 73 bpm

bull SpO2 fine test 90 in aa

bull PA fine test 15080 mmHg

bull fc inizio test 68 bpm

bull Scala di Borg 3

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Pulmonary Arterial Hypertension in France Results from a National Registry

Am J Respir Crit Care Med Vol 173 pp 1023ndash1030 2006

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Cateterismo destroDate

Baseline

HR (bmin) 95

RAP (mmHg) 7

mPAP (mmHg) 32

PWP (mmHg) 10

BP sd (mmHg) 12155

CI (lminm2) 31

PVR (RU) 43

SVR (RU) 127

Art O2 99

PA O2 783

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Galiegrave N et al Eur Heart J and Eur Respir J 2009

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Bosentan dapprima 625 mg x 2 successivamente 125 x 2 sia per lrsquoipertensione polmonare che per le ulcere digitali

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Why is PHPAH-SSc so difficult to treat

bull Older patients

bull Interstitial lung disease

bull Left ventricular diastolic dysfunction

bull Right ventricular diastolic dysfunction

bull More severe structural vasculopathy and poorly known pathobiology

bull Key outcome measures may differ

bull Poor recognition in the community

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Comments

bull Appropriate diagnosis of the type of PH is

required in CTD patients

bull Echo screening for the detection of PH is

recommended in symptomatic patients with CTD

bull RHC is indicated in all cases of suspected PH to

confirm the diagnosis

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Comments

bull In patients with PAH associated with CTD the

same treatment algorithm as in patients with

IPAH is recommended

bull The efficacy of the specific PAH treatment is

less long-lasting in PAH ndash CTD as compared to

IPAH

bull The use of PAH-specific drug therapy is not

recommended in patients with PH due to lung

Diseases or PH due to left heart disease

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

bull Despite progresses PAH-CTD remains a severe condition (worst prognosis among all PAH clinical types)

bull PAH approved drugs are less effective in patients with PAH-CTD and a more aggressive implementation of combination therapy may be required

bull The role of upfront combination therapy and early triple combination therapy in this subset of patients should be explored

bull Listing for lung transplantation should not be delayed in particular in young patients

Final comments

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

Multi-disciplinary team are requested because of

multiple comorbidities

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella

UO Complessa Medicina InternaSS AnnunziataDirettore Dott F SogariServizio di PneumologiaDott G DrsquoAlagniDottssa ScodittiServizio di Ecografia internisticaDott V Le Grazie

Struttura complessadi Radiologia SS AnnunziataDirettore M RestaDottssa MC Resta

Struttura complessa di Medicina NucleareDirettore F LaurieroDott S Di RosaDott P Moda

Ambulatorio ReumatologiaDott A MarsicoDott Semeraro

UO Complessa CardiologiaSS Annunziata Dirett V RussoS LanzoneS GerundaA Fiorella