The Case of Marco - European Society of Cardiology...•CV risk factor: smoker (1 pack/day) •Dyspnoea on exercise, WHO FC II •Echocardiogram: RV dilatation •Local hospital admission:

The Case of Marco

Nazzareno Galiè, M.D.

DIMES

Disclosures

• Consulting fees and research support fromActelion Pharmaceuticals Ltd, Bayer HealthCare, Eli Lilly and Co, GlaxoSmithKline and Pfizer Ltd

Clinical history

• 45 YO male

• CV risk factor: smoker (1 pack/day)

• Dyspnoea on exercise, WHO FC II

• Echocardiogram: RV dilatation

Question 1: which further investigation would you require?

1.ECG

2.PFT+DLCO and arterial blood gases

3.Chest radiograph

4.HRCT

5.All the above


1.ECG

2.PFT+DLCO and arterial blood gases

3.Chest radiograph

4.HRCT

5.All the above

www.escardio.org Eur Heart J 2015, Eur Respir J, 2015

Echocardiographic probability of pulmonary hypertension insymptomatic patients with a suspicion of pulmonary hypertension according with PTRV & additional signs

6

Eur Heart J 2015, Eur Respir J, 2015

Diagnostic Algorithmfor Pulmonary Hypertension

7

Speaker

www.escardio.org

Comprehensive clinical classification of pulmonary hypertension

8

Galiè N. et al Eur Heart J 2015, Eur Respir J, 2015

Clinical history

• 45 YO male

• CV risk factor: smoker (1 pack/day)

• Dyspnoea on exercise, WHO FC II

• Echocardiogram: RV dilatation

• Local hospital admission: normal coronaryangiography > discharge

• Persisting dyspnoea, new admission in yourhospital

Clinical Evaluation

• WHO FC III

• Height: 168 cm Weight: 71 kg (BMI = 25)

• JVP < 8 cmH20

• BP = 130/80 mmHg

• HR = 94 b/min

• SaO2 = 90 % in room air

• Left parasternal systolic murmur, increased P2

• 6MWD = 479 m; B 5; Sat. 94% > 74%; HR 86 > 122 bpm

ECG/chest X-ray

Echocardiogram

- PSP = 80 mmHg

- PFO

- Congenital Heart diseases were escluded

Spirometry/arterial blood gases

FVC 85 %

FEV1 91 %

FEV1/FVC 88

FEF25% 125 %

FEF50% 149 %

FEF75% 72 %

DLCO 90 %

pH 7.46

pCO2 27

pO2 64

SatO2 93

HRTC

No parenchymal lung diseases


1.Right heart catheterization

2.Right and left heart catheterization

3.CT pulmonary angiography

4.Cardiac Magnetic Resonance Imaging

5.Perfusion lung scan




3.CT pulmonary angiography


5.Perfusion lung scan


Diagnostic Algorithmfor Pulmonary Hypertension

17

Speaker

Perfusion lung scan

CT Pulmonary Angiography

Moderate dilatation of the main PA (3.8 cm)

Blood tests and immunology

Immunology screening: negative

Thrombophilia screening: negative

Hepatitis serology: negative

HIV test: negative

Thyroid blood tests: normal

BMPR2: negative

Diagnosis: Idiopathic Pulmonary Arterial

Hypertension




3.Right heart catheterization and vasoreactivity


5.3D-Echocardiography




3.Right heart catheterization and vasoreactivity


5.3D-Echocardiography

Treatment Algorithm for PulmonaryArterial Hypertension

23


Right Heart Catheterization

Baseline NO (25 ppm)

HR (b/min) 94 86

RAP (mmHg) 5 3

PAP s/d/m (mmHg) 120/51/77 103/39/63

PAWP (mmHg) 8 7

SAP s/d/m (mmHg) 134/82/102 119/81/98

CO (L/min) 3.7 3.9

CI (L/min/m2) 2.0 2.1

PVR (UR) 18.6 14.4

SVR (UR) 26.2 24.4

SA O2 % 90 96

SP O2 % 58.7 65

Question 4: which is the furthermanagement?

1.Calcium channel blocker therapy

2.Endothelin receptor antagonist (ERA) monotherapy

3.Phosphodiesterase type-5 inhibitors (PDE-5i) monotherapy

4.ERA + PDE-5i initial combination

5.Other

Question 4: which is the furthermanagement?

1.Calcium channel blocker therapy




5.Other


27



Risk assessment in pulmonary arterial hypertension

28

Question 5: which is your initial therapeutic strategy?

1.Prostacyclin analogue monotherapy




5.Other


30


‘90 ‘96 ‘00

EpoprostenolIPAH

‘01 ‘02 ‘03 ‘04 ‘05 ‘06 ‘08 ‘09

Bosentan

Terbogrel

Treprostinil

AIR

BREATHE1

ALPHABET

Beraprost

Sildenafil

BREATHE2

STRIDE1

SUPER

SERAPH

STEP

Sildenafil

STRIDE2

COMBI

BREATHE5ARIES -1/2

EARLY

PACES

PHIRST

EpoprostenolIPAH

EpoprostenolSSc

TRIUMPH

‘10

Time-course of completed RCTs in PAH (39): Therapy Strategy

VARDENAFIL

SELEXIPAG

FREEDOM C1

FREEDOM MFREEDOM C2

IMATINIB PATENT

SERAPHIN

AMBITION

IMPRESIversen

GRIPHON

COMPASS 2

‘11 ‘12 ‘13 ‘14

Modified from Galiè N, et al. Eur Heart J 2010;31(17):2080-6.

RCTs on monotherapy vs placebo or vs monotherapy (21)RCTs on monotherapy and/or sequential combination vs placebo (16)RCTs on initial combination vs monotherapy (2)

8919: PAH patients in RCTs

50/million: PAH prevalence

Current evidence from RCTs in PAH shows that…

• Monotherapy is able to reduce short-term mortality (meta-analysis) and improve long-term outcomes (SERAPHIN and GRIPHON) in incident and prevalent PAH patients

• Sequential combination therapy is able to improve short term (meta-analysis) and long-term (SERAPHIN and GRIPHON) outcomes in prevalent PAH patients

• Initial combination therapy is able to improve long-term outcomes compared with monotherapy (AMBITION) in treatment-naive incident PAH patients. Initial combination issuperior to monotherapy in head – to – head comparison

AMBITION

Galie N et al, et al. New Engl J Med 2015; 379(9):834–44.

AMBITION primary endpoint: Time to Clinical Failure(Death, Hospitalization, Disease Progression, Uns. Clin Resp)

Initial Combination vs pooled Initial Monotherapy

Ambrisentan

+ Tadalafil

Ambrisentan

or Tadalafil

Galie N et al, et al. New Engl J Med 2015; 379(9):834–44.

4/6-month results: % change comparison

AMBITION - BONSAI

Ambrisentan +

Tadalafil

(19)

Joint - INTENTION

Bosentan +

Sildenafil

(23)

BRAND – NEW

Macitentan +

Sildenafil

(12)

RAP (%) -17 - 36 - 16

mPAP (%) -33 - 21 - 29

CI (%) +56 +63 + 54

PVR (%) -61 -60 - 57

PA-SO2 (%) +17 +25 + 14

6MWD (%) +25 + 42 + 34

Question 5: which is your initial therapeutic strategy?

1.Prostacyclin analogue monotherapy




5.Other

Haemodynamics, functional and exercise

capacity

BaselineERA + PDE-5i

6 Mo

ERA + PDE-5i

24 Mo

HR (b/min) 94 73 70

RAP (mmHg) 5 5 5

PAP s/d/m(mmHg)

120/51/77 98/29/56 98/29/45

PWP (mmHg) 8 8 8

BP s/d/m (mmHg) 134/82/102 95/61/75 100/61/75

CI (L/min/m2) 2.0 3.0 3.5

PVR (UR) 18.6 9.6 7.6

SVR (UR) 26.2 13.8 13.5

ART O2 % 90 93 94

PA O2 % 58.7 68 70

6mwd meters 479 573 630

WHO-FC 3 1 1

Key messages

• An appropriate diagnostic strategy allows to clarify the precise clinical diagnosis which iscrucial for the patient management

• In patients with pulmonary arterialhypertension the risk stratification needs to be assessed in order to establish the mostappropriate treatment strategy

• Initial combination with an ERA and a PDE-5i appears to be a suitable strategy in newlydiagnosed, intermediate risk and treatment-naive patients with pulmonary arterialhypertension

Documents

The Case of Marco - European Society of Cardiology...•CV risk factor: smoker (1 pack/day) •Dyspnoea on exercise, WHO FC II •Echocardiogram: RV dilatation •Local hospital admission: