This document provides an overview and update on surgical and balloon pulmonary angioplasty (BPA) treatments for chronic thromboembolic pulmonary hypertension (CTEPH). It discusses the history and evolution of pulmonary endarterectomy (PTE) as the gold standard treatment for CTEPH. It then outlines the procedural details and patient selection criteria for BPA, which has grown as an alternative treatment for inoperable CTEPH patients or those with persistent symptoms after PTE. Meta-analyses of BPA studies show improvements in hemodynamics, exercise capacity, and imaging endpoints, though complications like dissection and perforation can occur. BPA is an effective less invasive option for properly selected CTEPH patients but long

1. CTEPH Surgical and BPA
Treatment Update
Richard A. Krasuski, M.D.
Director of the Adult Congenital Heart Disease Center
Director of Hemodynamic Research
Medical Director of CTEPH Program
Duke University Medical Center

2. Disclosures
• Serve a consultant for Actelion/Janssen, Bayer, Gore Medical,
Medtronic and Neptune Medical
• Receive research funding from the Adult Congenital Heart Association
and Actelion/Janssen Pharmaceuticals
• Serve as an investigator for Artivion, Edwards Lifesciences and
Medtronic
I am not a surgeon

3. • CTEPH and the Gold Standard Management (Surgery)
• Evolution of BPA into a major treatment modality
• BPA procedural details
• Patient selection and preparation
• Lesion selection for intervention
• Stopping points – individual sessions and treatment course
• Procedural outcomes data
• Where BPA fits into current CTEPH treatment algorithm
Overview

4. Demographics of CTEPH
• CTEPH develops in 0.5%–4.7% of pulmonary embolism survivors
• ~20,000 new cases per year in the US
• ~50% of patients have no hx of symptomatic VTE or prior confirmed PE
• CTEPH affects ~4% of patients within 2 years following a first
episode of symptomatic PE
• Prevalence (based on Medicaid and
private insurance databases)
• 63 per million <65 years of age
• 1007 per million ≥65 years of age
• Untreated - 90% mortality at 3 years
Klok FA et al. Haematologica 2010;95:970-975.; Humbert M. Eur Respir Rev 2010;19:59-63.;
Pengo V et al. N Engl J Med 2004;350:2257-2264.; Kirson NY et al. Curr Med Res Opin 2011;27:1763-1768.;
Hartopo AB et al. Acta Med Ind 2017;49(2):183-91.
0.04
0.03
0.02
0.01
0.00
0 1 2 3 4 5 6 7 8 9 10 11
Years

5. • Hufnagel and Moser
NEJM 1963
• 42 yo with progressive
DOE 2 yrs after PE
• Sternotomy
• PA clamped, no bypass
utilized
• 30 mo follow-up
History of Pulmonary Thromboendarterectomy

6. • Moor and Sabiston,
Circulation, 1970
• 31yo with 3 yr history of
DOE and hemoptysis
• Left thoracotomy
• CPB (RVOT to femoral
artery)
• 1 yr follow-up
History of Pulmonary Thromboendarterectomy

7. • Moser and Braunwald
• 69 yo man with 16 yr history
of PH
• Right thoracotomy
• CPB (bicaval, femoral artery)
• Bilateral resection
History of Pulmonary Thromboendarterectomy

8. • Stuart Jamieson
• Michael Madani
Modern History of PTE - UCSD
• Standardized PTE
– 1990-2000 1,000 cases
– UCSD experience now >4800
cases

9. • Technically demanding
surgery
• Critical components:
• Circulatory arrest
• Eliminate bronchial
backbleeding and preserve
bloodless field
• Identification of plane
• Bilateral dissection
• Complete endarterectomy
UCSD Model of PTE
Jamieson et al. JCTVS 1993

10. Proposed criteria for an Expert Center
Jenkins D, Madani M, Fadel E, et al. Pulmonary endarterectomy in the management of
chronic thromboembolic pulmonary hypertension. Eur Respir Rev 2017; 26: 160111

11. • Duane Davis 1992-2015 (~20 PTEs/year)
• Jack Haney
• Cardiothoracic fellow 2011-2014
• On faculty 8/2014 – 9/2023
• Adult cardiac, lung transplant, PTE
• 2016-2023 ~35-45 PTEs/year
• Jacob Schroder
• Cardiothoracic fellow 2009-2012
• On faculty 8/2012
• Adult cardiac, heart transplant, PTE
Pulmonary Endarterectomy at Duke

12. • UCSD experience to 2018 (3450 cases)
• Mortality decreased from 17% to 4% over 1000 cases
• Performing ~200/yr with 1% mortality
• Duke experience to 2016-2018 (117 cases)
• 2016 mortality: 16%
• 2017 mortality: 4%
• 2018 mortality: 0%
Surgical Experience Matters

13. • Mean age: 51.7yr
• Mean BMI: 33.9
• Mean PA: 80/31 (48)
• Mean CI: 2.2
• LOS: 12 days
Pulmonary Endarterectomy at Duke

14. Preop Postop
PA Systolic
(mmHg)
80 40
PA Mean
(mmHg)
48 26
• Duke Outcomes
• Circ arrest 40 +/- 18 min
Pulmonary Endarterectomy at Duke
Preop Postop
PA Systolic
(mmHg)
79 45
PA Mean
(mmHg)
46 26
• UCSD Outcomes
– Circ arrest 37 +/- 12 min

15. • Minimally invasive PTE (miPTE)
• Unilateral or bilateral anterior thoracotomy approach, peripheral
cannulation
• may be useful for patients in whom disease is significantly asymmetric or in
whom sternotomy is relatively contraindicated
• May be combined with BPA as a hybrid approach
Innovations at Duke

16. • Continued refinement of technique and improvement in quality
outcomes and mortality
• Provide safe, successful surgery for our region with timely access to care
• Train cardiothoracic surgeons to safely embark on PTE in clinical practice
Surgical Program Goals

17. Why Is BPA Necessary?
• Surgery (PTE) is the most definitive therapy for CTEPH and all patients
need to be properly vetted for possible surgery
• About 1/3 of CTEPH patients are not surgical candidates
• Prohibitive co-morbidities
• Less accessible, distal vascular disease
• 17-31% have persistent or recurrent disease after PTE Surgery
• Medical therapy (Riociguat) is effective, but not THAT effective
• 39 vs. 6 m improvement in 6MWD, 2.8 vs. 0.3 Wu reduction in PVR
• 4 mmHg reduction vs. 1 mmHg increase in mPAP; No  in RA pressure
Mayer E et al. J Thorac Cadiovasc Surg 2011;141:702-10.; Freed DH et al. J Thorac Cardiovasc Surg 2011;141:383-7.;
Hoeper MM et al. 2014;2:573-82.; Ghofrani HA et al. N Engl J Med 2013;369:319-29.

18. • Procedure derived from strategies to manage congenital
peripheral pulmonary artery stenosis
• Recently revisited with newer and “gentler” techniques
• Repeated interventions starting with smaller balloons
• Lesser immediate goals emphasized
• Has grown rapidly in popularity, particularly in regions of world
where surgery is generally less available and less favored
• May be an excellent alternative/adjunct to medical therapy or
after PTE for persistent disease and symptoms
Historical Background of BPA
Serfas JD and Krasuski RA. Cardiology Clinics. 2022;40:103–114.

19. How BPA is Performed

20. Pulmonary
Angiography to Assess
Vascular Anatomy
Review VQ Scan and CT
Perfusion Imaging to Identify
Hypoperfused Territories
- CTEPH Confirmed
- Inoperable or refuses surgery
- ≥ WHO Function Class II
- No contraindications to BPA
Basilar > Upper Lobe Vessels
Webs and Bands >> Pouches
Ease of Access to Lesions
Decide on which segments are
intervenable and in what order; limits
for radiation and contrast exposure
- Patient Discussion Regarding Goals and
Stopping Points
- Planned Interruption of Anticoagulation
- Informed Consent and Medical Rx
- Sedation Plan
- Follow-up Visits and Studies
Multidisciplinary Evaluation to
Ensure That Patient is
Appropriate for BPA
Modified from Serfas JD and Krasuski RA. Advances in PH. 2022;21(3):83-87.
Procedural Preparation Process

21. • Preprocedural imaging is critical
• VQ scanning and CT perfusion imaging to define hypoperfused territories
• Pulmonary angiography to get a good “road map” and develop a plan
• Decide on which segments are intervenable and in which order they should be done
• Determine limits for radiation and contrast exposure
• Decide on the number of planned sessions
• Discuss risks and potential benefits with patient and their family
• Review limited data that is available regarding procedural impact
• Develop realistic goals and how to objectively reassess functional
improvement after each session
BPA: Procedural Planning and Details

22. • Plan for interruption of anticoagulation
• Decide on type of sedation
• Femoral or jugular access
• 8F venous sheath with telescoping smaller sheaths (6F) and guide catheter
• Small bore arterial line for hemodynamic monitoring
• Coronary wires and smaller noncompliant/semicompliant coronary and
peripheral balloons – start small and should never exceed “normal”
surrounding lumen diameter
• Selective hand injections of contrast to assess success and rule out
complications
BPA: Procedural Planning and Details

23. • Meets diagnostic criteria for CTEPH – beware of mimickers
• Considered inoperable or absolutely refuses surgery
• ≧ WHO Function Class II symptoms – consider CPET if “asx”
• No contraindications for transcatheter intervention
• Safe venous access – ideally transfemoral
• Absence of significant/acute renal impairment – prehydrate if necessary
• Ideally no severe coagulopathy or thrombocytopenia
• Patient understanding and ability to provide informed consent
• Initiation of medical therapy prior to intervention
Serfas JD and Krasuski RA. Cardiology Clinics. 2022;40:103-114.
Selecting Appropriate Patients for BPA

24. Selecting Appropriate Lesions for Intervention
• Webs and band/slits > pouches or
tortuous lesions
• Lower lobes > upper lobes
• Territory with documented perfusion
defect
• Region of good ventilation
Serfas JD and Krasuski RA. Cardiology Clinics. 2022;40:103–114.

25. Web
Slit
Sugiyama M et al. Jpn J Radiol 2014;32(7):375-382.; Korn D et al. Am J Pathol 1962;40:129–151.
Images Courtesy of Dr. Takeshi Ogo, National Cerebral and Cardiovascular Center, Osaka, Japan
Lesions Most Amenable to BPA

26. 1
2
3 4
Typical Target Order for BPA
Impact of Ease of Access

27. When to Stop Intervening on a Specific Lesion
• Increase in angiographic diameter to near normal size
• Grade three angiographic pulmonary arterial flow or
visible venous return
• Marked luminal enlargement as seen by OCT or IVUS
• Distal to proximal pressure across lesion ≥ 0.8
• Smaller balloons until mPAP <35 mmHg
Jin Q et al. World J Clin Cases. 2020;8(13):2679-702.;
Serfas JD and Krasuski RA. Cardiology Clinics. 2022;40:103–114.

28. Individual Procedural Limitations
• Radiation administration – 2-3 Gray
• Contrast administration – 200-400 cc – at Duke: 3 x GFR
• Patient/room staff/operator starts to get restless
• Procedural complications
• Wire perforation
• Reperfusion lung injury
• Hemoptysis
• 3-5 segment limits
Serfas JD and Krasuski RA. Cardiology Clinics. 2022;40:103–114.

29. Purported BPA Stopping Points
• “Normalization of hemodynamics” – mPAP <25 or 30 mmHg and O2
saturation >95%
• Resolution of symptoms - NYHA function class I
• Cessation of oxygen administration or advanced PAH therapies
• All reasonable lesions have been approached
• Have reached target or convenience level for patient
Ogawa A and Maysubara H. Circ J 2018;82:1222-30.; Karyofyllis et al. Curr Treat Options Cardio Med 2020;22:7;
Serfas JD and Krasuski RA. Cardiology Clinics. 2022;40:103–114.

30. How Effective is BPA?

31. Meta-analysis of Studies to Assess Efficacy of BPA
• 670 patients
• Median age 62.5 years
• 68% women
• Median 4 sessions of BPA
• Median follow-up 9 (1-51)
months
• Short-term mortality 1.9%
• Long-term mortality 5.7%
Khan MS, Krasuski RA et al. Int J Cardiol 2019;291:134-9.

32. Studies Meeting Inclusion/Exclusion Criteria
Khan MS, Krasuski RA et al. Int J Cardiol 2019;291:134-9.

33. Meta-analysis of BPA: Effect on RA pressure
3 mmHg
reduction
Khan MS, Krasuski RA et al. Int J Cardiol 2019;291:134-9.

34. Meta-analysis of BPA: Effect on PA pressure
14 mmHg
reduction
Khan MS, Krasuski RA et al. Int J Cardiol 2019;291:134-9.

35. Meta-analysis of BPA: Effect on Cardiac Output
0.2 l/min/m2
increase
Khan MS, Krasuski RA et al. Int J Cardiol 2019;291:134-9.

36. Meta-analysis of BPA: Effect on PVR
3.8 Wood unit
reduction
Khan MS, Krasuski RA et al. Int J Cardiol 2019;291:134-9.

37. Meta-analysis of BPA: Effect on 6-Minute Walk
67 meter
increase
Khan MS, Krasuski RA et al. Int J Cardiol 2019;291:134-9.

38. RACE (Riociguat versus BPA in Nonoperable CTEPH) Trial
• Entry criteria: mean PAP 25 mmHg, PCW ≤ 15
mmHg, PVR >4 Wood units
• PVR ↓60% with BPA vs. ↓33% with Rio (p<.0001)
• 6MWD change not significantly different
• FC improved by 1 class in 88% with BPA vs. 49%
with Rio (p<0.001)
• 67% greater BNP reduction with BPA
• Treatment-related serious adverse events (42 vs.
9%) with BPA. No deaths in either group
• Adverse events with BPA lower in patients
pretreated with riociguat (14% vs 42%)
Jais X et al. Lancet Respir Med 2022;10: 961–71.
105
53
52

39. Targeting Imaging Endpoints
• Meta-analysis of CMR (5) and echo studies (5)
• 299 patients – 70% Japanese
• Avg 2.6-6 sessions of BPA
• RVEDVI  by 28.3 ml/m2, RVESVI  by 29.0 ml/m2, RVEF  by 9%
• Basal diameter  and RV fractional area improved but no change in
TAPSE or lateral S’
Li W et al. Eur Radiol 2021;31:3898-3908.

40. Other Endpoints Examined in Studies
• Exercise tolerance – 6MWD and CPET
• Biomarkers – BNP/NTpro-BNP and HS-cTnT and inflammatory
markers
• Renal function – surprising improvements seen – cardiorenal
benefit despite potential for contrast nephropathy

41. What Are the Complications of BPA?

42. • Sub-intimal wire migration – “when it doubt, pull out”
• PA dissection - ?may be the “normal” mechanism
No treatment generally necessary
• Wire perforation – recognize hemoptysis
- minor
- major
• Reperfusion injury – clinical/subclinical, acute/late
• Strongest risk: occlusive lesion morphology
Prolonged balloon occlusion, heparin reversal
Coiling or preferably Gelfoam embolization
Ikeda N et al. Catheter Cardiovasc Intv. 2019;1-8.
BPA Complications

43. Modern Data: Reduced Complication Risk
• 26 studies including 1,714 CTEPH
patients undergoing 7,561 BPA sessions
• Average follow-up 7.3 months after BPA
• Cumulative incidence of hemoptysis/
vascular injury  from 14.1 to 7.7%
(p < 0.01) 2018-2022 vs. 2013-2017
• Lung injury/reperfusion edema  from
11.3% to 1.4% (p < 0.01); invasive
mechanical ventilation  from 0.7% to
0.1% (p < 0.01)
• Mortality  from 2.0% to 0.8% (p < 0.01)
Jain N et al. J Am Coll Cardiol Intv. 2023;16:976-983.

44. Duke BPA Experience
• Program started late in 2018
• 158 cases performed in 47 patients
• No deaths, 3 minor pulmonary hemorrhages, 0 emergent intubations
• 98% discharged within 24 hours; handful discharged same day
0
5
10
15
20
25
30
35
40
45
2019 2020 2021 2022 2023

45. Recent Clinical Case
• 74-year-old gentleman followed by the VA
• Multiple medical issues – diabetes, HTN, high cholesterol, CAD s/p
CABG, COPD, early Parkinson’s, prior stroke, AAA…
• Pulmonary embolism 18 months ago with persistent dyspnea
• VQ scan with bilateral basilar unmatched perfusion defects R>L
• Echo with RVSP 60 mmHg and moderate RV dilatation/mild
dysfunction and CT with RUL apical bleb and otherwise mild
emphysema
• No imaging studies sent over
• Calculated GFR 60 ml/min

46. Procedural Steps and Equipment
• 8 French venous sheath and 4 French arterial sheath
• Balloon wedge catheter (right heart catheterization)
• Exchange length 0.035 in peripheral guidewire (i.e. Advantage Guidewire)
• 6 French long guiding sheath (i.e. Cook Flexor Ansel 90 cm)
• Angled Pigtail catheter (for ventriculography)
• 6 French JR/Multipurpose Guide Catheter
• Tuohy-Borst Adapter System
• 0.014 in workhorse wire (i.e. Terumo Runthrough, Asahi Scion Blue,…)
• Guide Catheter Extensions (i.e. GuideLiner, Telescope, Guidezilla)
• Collection of NC/SC balloons set aside - 2.0-4.5 mm - open when needed

47. Hemodynamics
• RA 10,8 m8
• RV 64/7-10
• PA 64/28 m44
• PCW 9,10 m9
• Cardiac index 2.4 l/min/m2
• PVR 7.8 Wood units

48. Biplane Pulmonary Angiogram

49. Selective Angiography and Workhorse Wire

50. Begin with Small (2.0 mm) Balloon

51. Advancing Wire and Use of Guidewire Extension

52. More Distal Ballooning and Wire Positioning

53. Upsize Balloon and Assess Damage

54. Work on Distal Branches

55. Venous Return is a Great Sign

56. Increase Balloon Size and Touch-up

57. Final Selective Images

58. Primum non nocere
• Remeasure hemodynamics
• Check ACT
• Sew in sheaths or pull if ACT OK
• Overnight observation vs. same
day discharge
• Chest PA and lateral X-Ray
• Arrange for follow-up

59. What is the Current Role of BPA?

60. 0
20
40
60
80
100
120
1990 1995 2000 2005 2010 2015 2020 2025
Yearly "Balloon Pulmonary Angioplasty" Publications
The Literature Has Been Exponentially Growing
PubMed Accessed 10/20/2023

61. Humbert M et al. European Heart Journal. 2022;43:3618–3731.
Latest Guideline-Based Algorithm

62. Humbert M et al. European Heart Journal. 2022;43:3618–3731.
Latest Guideline Updates Regarding BPA

63. Humbert M et al. European Heart Journal. 2022;43:3618–3731.
BPA Fits Into a Complementary Role in CTEPH Management

64. Summary
• CTEPH recognition comes with CTEPH awareness
• First and foremost, CTEPH is a surgical disease – get patient to center
that offers PTE and does it well
• BPA can be performed safely and with excellent hemodynamic, imaging
and symptomatic improvement
• Best candidates are inoperable disease or residual disease after PTE
• BPA complements PTE and medical therapy