Can we sustain

change for patients

with inoperable or

persistent/recurrent

CTEPH? Irene M Lang

Medical University of Vienna, Austria

Nick H Kim

University of California, San Diego,

CA, USA

ERS International

Congress 2015

Monday, 28 September

L.NL.MA.09.2015.0072

Disclosures (1)

Irene Lang has received research grants and speaker’s honoraria

from Abbott, Actelion, AOP Orphan Pharmaceuticals, Astra Zeneca,

Bayer HealthCare, Biotronik, Cordis, Daiichi-Sankyo, Euromed,

GSK, Medtronic, Novartis, Pfizer, Terumo, and United Therapeutics,

and is a board member of CTEPH.com and the International

CTEPH Association

Nick Kim has served as a consultant/speaker for Actelion and

Bayer HealthCare (steering committee member for the MERIT and

CHEST studies), and is a board member of CTEPH.com and the

International CTEPH Association

L.NL.MA.09.2015.0072

Disclosures (2)

This presentation includes discussion of riociguat in combination

with BPA in patients with CTEPH

To date, there have been no formal clinical trials of riociguat in

combination with BPA, nor is it approved for use in combination with

BPA

BPA, balloon pulmonary angioplasty.

L.NL.MA.09.2015.0072

Treatment algorithm for CTEPH

BPA, balloon pulmonary angioplasty.

Galiè N et al. Eur Heart J 2015:doi:10.1093/eurheart/ehv317.

aTechnically operable patients with non-acceptable risk/benefit ratio can be considered also for BPA. bIn some centers medical therapy and BPA are initiated concurrently.

Diagnosis confirmed by

CTEPH expert center

Lifelong anticoagulation

Operability assessment by a

multidisciplinary CTEPH team

Technically operable Technically non-operable

Targeted medical

therapy

Consider BPA in

expert centerb

Persistent severe

symptomatic PH

Consider lung

transplantation

Persistent

symptomatic PH

Non-acceptable

risk:benefit ratioa

Acceptable

risk:benefit ratio

Pulmonary

endarterectomy

Copyright protected content.

Please view original content in the following reference:

Galiè N et al. Eur Heart J 2015:doi:10.1093/eurheart/ehv317

L.NL.MA.09.2015.0072

Pulmonary endarterectomy

The treatment of choice for CTEPH in eligible patients: potentially

curative1

Technically demanding procedure, requiring specialist training and

intensive postoperative care1,2

– Bilateral endarterectomy through the medial layer of the pulmonary

arteries

– Performed under deep hypothermic circulatory arrest

Effective and highly successful

– Substantial relief of symptoms; near normalization of hemodynamic

parameters1

– Low mortality in experienced centers1

– Cognitive function postsurgery not impaired3

1. Jenkins D. Eur Respir Rev 2015;24:263–71. 2. Jamieson SW et al. Ann Thorac Surg 2003;76:1457–64.

3. Vuylsteke A et al. Lancet 2011;378:1379–87.

L.NL.MA.09.2015.0072

The “operable” vs “non operable” patient

Lang IM and Madani M. Circulation 2014;130:508–18.

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Please view original content in the following reference:

Lang IM and Madani M. Circulation 2014;130:508–18.

L.NL.MA.09.2015.0072

Treatment algorithm for CTEPH

BPA, balloon pulmonary angioplasty.

Galiè N et al. Eur Heart J 2015:doi:10.1093/eurheart/ehv317.

aTechnically operable patients with non-acceptable risk/benefit ratio can be considered also for BPA. bIn some centers medical therapy and BPA are initiated concurrently.

Diagnosis confirmed by

CTEPH expert center

Lifelong anticoagulation

Operability assessment by a

multidisciplinary CTEPH team

Technically operable Technically non-operable

Targeted medical

therapy

Consider BPA in

expert centerb

Persistent severe

symptomatic PH

Consider lung

transplantation

Persistent

symptomatic PH

Non-acceptable

risk:benefit ratioa

Acceptable

risk:benefit ratio

Pulmonary

endarterectomy

Copyright protected content.

Please view original content in the following reference:

Galiè N et al. Eur Heart J 2015:doi:10.1093/eurheart/ehv317

L.NL.MA.09.2015.0072

Riociguat as targeted medical therapy for

CTEPH

First evidence-based, medical therapy approved for patients in

WHO FC II to III with inoperable CTEPH, or persistent or recurrent

CTEPH after surgical treatment, to improve exercise capacity1

– Clinical evidence from CHEST: robust long-term (2 year) efficacy and safety

data2

– Reinforced by real-world data from the riociguat Early Access Study3

Highest recommendation (IB) in the 2015 ESC/ERS guidelines for

treatment strategies other than PEA4

WHO FC, World Health Organization functional class.

1. Bayer HealthCare. Adempas® EU Summary of Product Characteristics. July 2015. 2. Simonneau G et al. Eur Respir J 2014;44(Suppl.58):

1802; 3. McLaughlin V et al. Am J Respir Crit Care Med 2015;191:A4840. 4. Galiè N et al. Eur Heart J 2015:doi:10.1093/eurheart/ehv317.

Case study 1 Recurrent CTEPH

post-PEA

Nick H Kim

L.NL.MA.09.2015.0072

Case history prior to referral to UCSD

29-year-old woman

History Previously healthy, no prior medical history, shortness

of breath for 1.5 years; no PAH risk factors

WHO FC IV

O2 saturation 87%

Heart rate 107 to 134 bpm during walk

6MWD 161 m

Hypercoaguability

assessment

No DVT or PE history; negative thrombophilia work-

up; CT pulmonary angiogram negative for PE (early

2014)

Treatment ERA + PDE5i; later added inhaled PGI2;

no subjective benefit from any of these therapies

6MWD, 6-minute walking distance; bpm, beats per minute; CT, computed tomography; DVT, deep vein thrombosis; ERA, endothelin receptor antagonist; O2,

oxygen; PDE5i; phosphodiesterase type 5 inhibitor; PE, pulmonary embolism; PGI2, prostacyclin; UCSD, University of California, San Diego; WHO FC, World

Health Organization functional class.

CASE

STUDY 1

L.NL.MA.09.2015.0072

Case history prior to referral to UCSD

CO, cardiac output; PA, pulmonary artery; PAWP, pulmonary arterial wedge pressure; PVR, pulmonary vascular resistance; RA, right atrium;

UCSD, University of California, San Diego; WU, Wood units.

Transferred to UCSD for further evaluation

and management

CASE

STUDY 1

RHC April 2014

RA (mmHg) 13

PA (mmHg) 97/41 (mean 61)

PAWP (mmHg) 10

CO (L/min) 2.22

PVR 22.93 WU (1,838 dyn·sec·cm-5)

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Referral to UCSD: assessment

Arrives at our center, late 2014

On arrival c/o episodic chest pain; distress with any activity

Vital signs BP 110/70 mmHg, HR 113 bpm,

SpO2 96% on 3 L/min O2; 44 kg

Exam +JVD sitting upright, regular rhythm, + right S3 gallop,

+ hepatomegaly 3 FB below the costal margin,

lungs clear, no pulmonary bruit, no ascites or edema,

no clubbing

Laboratory tests Hgb 12, Plts 325k, Cr 0.8, NT-proBNP 2983 pg/mL

Echo

Severe RA/RV enlargement with depressed function;

+ small pericardial effusion

BP, blood pressure; bpm, beats per minute; c/o, complains of; Cr, creatinine; ECG, electrocardiography; echo, echocardiography; FB, finger breadths; Hgb,

hemoglobin; HR, heart rate; JVD, jugular vein distention; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; Plts, platelets; RA, right atrium; RV,

right ventricle; SpO2, peripheral capillary oxygen saturation; UCSD, University of California, San Diego.

CASE

STUDY 1

13

CASE

STUDY 1

14

CASE

STUDY 1

15

CASE

STUDY 1

16

RA 16 mmHg, PA 82/35 (53) mmHg, PAWP 7 mmHg

CO 2.6 L/min, CI 1.9 L/min/m2, PVR 1415 dyn·sec·cm-5 (17.69 WU)

CASE

STUDY 1

L.NL.MA.09.2015.0072

CTEPH operability assessment

Late 2014

Assessment Deemed inoperable; severe right heart failure

Therapy Transitioned from inhaled prostanoid to i.v. epoprostenol

(15 ng/kg/min) + ERA/PDE5i (triple combination therapy)

RHC

(2 months after

therapy change)

RA 13 mmHg

PA 79/34 (mean 47) mmHg

PAWP 7 mmHg

CI 1.9 L/min/m2

PVR 1055 dyn·sec·cm-5 (13.19 WU)

WHO FC IV

CI, cardiac index; ERA, endothelin receptor antagonist; i.v., intravenous; PA, pulmonary artery; PAWP, pulmonary arterial wedge pressure; PDE5i;

phosphodiesterase type 5 inhibitor; PVR, pulmonary vascular resistance; RA, right atrium; RHC, right heart catheterization; WHO FC, World Health

Organization functional class; WU, Wood units.

CASE

STUDY 1

L.NL.MA.09.2015.0072

What would you recommend now?

1. Lung transplantation

2. Transition to other medications

3. PEA

4. Hospice referral

PEA, pulmonary endarterectomy.

CASE

STUDY 1

VOTE NOW!

CASE

STUDY 1

20

RA 12 mmHg

PA 67/20 (36) mmHg

PAWP 12 mmHg

CO 4.4 L/min

CI 3.3 L/min/m2

PVR 436

dyn.sec.cm-5

(5.45 WU)

CASE

STUDY 1

2 weeks post-PEA

hemodynamics:

L.NL.MA.09.2015.0072

Follow-up at 2 months after PEA

Off all meds except warfarin, spironolactone, and prednisone taper

(transient lung injury)

WHO FC II; oxygen 2 L/min with exertion

SBP 110s, HR 90s; No JVD, accentuated P2, no S3, wound healed,

lungs clear, no hepatomegaly, no edema

Shortness of breath with activity, chest pain

Started riociguat for persistent symptomatic CTEPH after PEA

HR, heart rate; JVD, jugular vein distension; PEA, pulmonary endarterectomy; SBP, systolic blood pressure; WHO FC,World Health Organization functional

class. 21

CASE

STUDY 1

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Longer term follow-up after PEA

On riociguat TID: early subjective benefit

4 month visit: off oxygen, WHO FC I

No limitations; cleared to return home after

securing riociguat

Now back home, over 6 months after PEA

and 4 months on riociguat: WHO FC I

PEA, pulmonary endarterectomy; TID, three times daily; WHO FC, World Health Organization functional class. 22

CASE

STUDY 1

Sustained, improved activities of daily living with

riociguat for persistent CTEPH post-PEA

Case study 2 Inoperable CTEPH

Irene M Lang

L.NL.MA.09.2015.0072

Case study

38-year-old woman

History Dyspnea on exertion since 2013, arterial

hypertension, pulmonary embolism July 2013 and

June 2014

CASE

STUDY 2

November 2014: referred to Medical University of

Vienna for evaluation of PH

Confidential patient information: slides not shown

L.NL.MA.09.2015.0072

Unresolved issues in CTEPH

Optimal path toward timely and accurate diagnosis of CTEPH

L.NL.MA.09.2015.0072

Do you have resources to follow the current

guidelines for CTEPH?

1. Yes: we have access to V/Q scan, pulmonary angiography (either

catheter, CT, or MRI), and a CTEPH team for operability

assessment

2. No: we do not have access to V/Q scan or pulmonary angiography

3. No: we do not have access to a CTEPH team for operability

assessment

4. We use our own guidelines (disagree with what’s published!)

CT, computed tomography; V/Q, ventilation/perfusion; MRI, magnetic resonance imaging.

VOTE NOW!

L.NL.MA.09.2015.0072

Unresolved issues in CTEPH

Optimal path toward timely and accurate diagnosis of CTEPH

Operability versus opinion?

Role of medical therapy (bridge) in operable CTEPH

Place for BPA in the treatment of CTEPH

BPA, balloon pulmonary angioplasty.

L.NL.MA.09.2015.0072

What is your top priority of interest in

CTEPH?

1. Access or establishment of a PEA program

2. Further exploring/expanding medical therapy for CTEPH

3. Establishing BPA in your center

4. Receiving more CTEPH referrals (we don’t see enough)

VOTE NOW!

BPA, balloon pulmonary angioplasty; PEA, pulmonary endartectomy.

L.NL.MA.09.2015.0072

Summary

CTEPH patients should be evaluated for surgical eligibility by a

multidisciplinary team of experts using high-quality imaging

technologies

Riociguat is an alternative for patients who are inoperable or have

persistent CTEPH after PEA, which can improve exercise capacity,

hemodynamics, functional class, and RV function

Whilst there are clear guidelines for the management of CTEPH,

there is still much work ahead to address the unanswered questions

that remain

PEA, pulmonary endartectomy; RV, right ventricle.

Thank you