The patient initially presented with pulmonary embolism and was treated with anticoagulation and antibiotics for pneumonia, but developed recurrent symptoms of pulmonary hypertension. After pulmonary endarterectomy, the patient still had elevated pulmonary pressures and was started on Riociguat, but had no improvement. Right heart catheterization showed ongoing pulmonary hypertension, so the patient underwent balloon pulmonary angioplasty of lesions in the left lower lobe, followed by initiation of Macitentan.

1. Clinical Case from DUH
Emory Buck, MD
Internal Medicine, PGY-3
November 4th, 2022
Annual North Carolina Research Triangle
Pulmonary Hypertension Symposium

2. • 45-year-old male presented with subacute shortness of breath and chest pain x 2 days
• He described the pain as sharp, located over center of chest, worse with exertion and
relieved by rest.
• He noted associated dyspnea on exertion. The day prior to presentation, he developed
hemoptysis.
• He denied any history of blood clots
• ROS otherwise negative
• PMH: Notable for asthma, uses an albuterol inhaler
• PSH: Negative
• FH: HTN in mother and father, negative for blood clots.
• Social History: The patient worked as truck driver and he had just returned from a long
trip to Baltimore last night. He endorsed occasional marijuana use, but no other illicit
drugs and never smoker.
Case Presentation (Aug. 10th, 2016)

3. Initial Exam
VS: Temp 98.6F, HR 77, BP 121/82, RR 20, and SpO2 89% on room air  5L NC 92%
• GENERAL: Well-developed well-nourished in mild respiratory distress.
• HEENT: Pupils equally round and reactive to light. Anicteric sclera. Moist mucous membranes.
• NECK: Supple no masses. Elevated jugular venous pressure with mild abdominal jugular reflux.
• PULM: Tachypneic. Bilateral chest expansion. Bronchial breath sounds in the right upper lobe. No
other major adventitious breath sounds.
• CV: Tachycardic. Fixed S-2 verses an S3 summation gallop difficult to differentiate. Nondisplaced
PMI.
• ABDOMEN: Distended with good bowel sounds. Overall soft with no masses. Nontender.
• EXTREMITIES: Warm and well perfused. No clubbing cyanosis or edema.
• MSK: No evidence of active synovitis.
• NEURO: Alert and oriented x3. Nonfocal exam.
• SKIN/WOUND: No rash lesions or ulcers.

4. 12.6 (H)
15.9
269
46.4
138
3.9
107
21
14
1.5
113
Troponin I: 0.03
ESR: 10
ANA: Positive, 1:40
ANCA: Negative
RF: Negative
Anti GBM Ab: Negative
AST: 22
ALT: 22
Alkaline phosphatase: 46
T. bilirubin: 1.0
Total Protein: 7.8
Albumin: 4.2
1.2
13.8 27.2
Basic Labs

5. CXR
Impression:
1. Right upper lobe pneumonia. This
process should be followed to
resolution.
2. Possible left perihilar opacity which
could also represent pneumonia
or mass. This finding should be
followed to resolution.

6. CT PE
Impression:
1. Extensive bilateral
pulmonary emboli.
2. Significant areas
of parenchymal
consolidation and
airspace disease
involving both lungs.
Small discrete
nodular densities
also present as
detailed.

7. CT PE
Impression:
1. Extensive bilateral
pulmonary emboli.
2. Significant areas
of parenchymal
consolidation and
airspace disease
involving both lungs.
Small discrete
nodular densities
also present as
detailed.

8. ECHO
Interpretation:
Normal LV function with abnormal
septal motion consistent with volume
and pressure overload
Dilated RV with moderated reduced RV
function
Right atrial enlargement, moderate
Mild tricuspid regurgitation
Pulmonary hypertension (RVSP =
71mmHg)

9. Hospital Course Aug. 10th – Aug. 18th 2016
He was
started on
heparin 
hemoptysis
 concern
for DAH 
additional
A/C was
held
Bronchoscopy
 negative for
DAH 
resumed on
heparin
Treated with
azithromycin
and
Ceftriaxone
for CAP
High oxygen
requirement,
up to 10L NC
Heparin 
transitioned
to
Rivaroxaban
On discharge,
he was able
to be weaned
off oxygen
and
ambulated
well on room
air.

10. NM Perfusion Scan
Conclusions:​ High probability lung
scan for pulmonary embolism.
• He remained having shortness of
breath with moderate to severe
exertion.
ECHO
Normal LV systolic function with mild cLVH.
Mild RV systolic dysfunction
Mild RA enlargement
RVSP = 32mmHg; TAPSE = 1.9cm
Trivial MR, trivial PR, trivial TR
• Endorsed a two-week history of
a cough, but less shortness of
breath with exertional activities
in general.
• Oxygen titration study showed
new O2 requirement: 2 L/min at
rest, up to 6 L when he sleeps at
night and up to 15 L with
exertion.
• He was resumed on Rivaroxaban
and prescribed Augmentin given
cough and elevated WBC and
infiltration on CXR.
The patient stopped taking
rivaroxaban at some point due to
lack of refills
CXR
Impression:
1. New right upper lung opacity.
Differential includes infection or
hemorrhage.
2. Increased prominence of the
pulmonary arteries, suggestive of
pulmonary hypertension.

11. CT PE
Impression:
1. Eccentric soft tissue and bands
within bilateral segmental
and subsegmental pulmonary
arteries compatible with chronic
sequelae of pulmonary embolism.
No acute pulmonary embolism
evident on the current study.
2. Enlarged pulmonary artery
suggests pulmonary
hypertension.
3. Decreased mosaic lung
attenuation suggests differential
perfusion and small vessel
disease related to pulmonary
thromboembolic disease.

12. CT PE
Impression:
1. Eccentric soft tissue and bands
within bilateral segmental
and subsegmental pulmonary
arteries compatible with chronic
sequelae of pulmonary embolism.
No acute pulmonary embolism
evident on the current study.
2. Enlarged pulmonary artery
suggests pulmonary
hypertension.
3. Decreased mosaic lung
attenuation suggests differential
perfusion and small vessel
disease related to pulmonary
thromboembolic disease.

13. Right Heart Catheterization
State: Baseline
RA: 9 mmHg (mean)
RV: 77/ 7 mmHg
PA: 81/ 34 49 mmHg (mean)
PCW: 11 mmHg (mean)
AV O2: 4.7 vol%
Cardiac output: 6.9 L/min
Cardiac index: 2.8 L/min-m2
PVR: 5.5 Wood units
Shunt Ratio: 1.0 (Qp/Qs)
L to R shunt: 0.0 L/min (Qp-Qep)
R to L shunt: 0.0 L/min (Qs-Qep)
+ IVC Filter Placement
Pulmonary Angiogram:
There is relative oligemia in portions of the mid and lower
lung including near complete absence of flow within the RML lateral
segment and RLL anterior basal segment.
There is relative oligemia portions of the left mid and lower lung
including absence of flow within the lingular segments.

14. In a patient with these findings on RHC and PA
angiogram, what should be the next step in
management?

15. PEA Outcomes
• By ESC 2022 guidelines, PEA is the treatment of choice for
accessible lesions since surgery may normalize pulmonary
hemodynamics and functional capacity
• Long term outcomes after PEA surgery are excellent
regarding survival (averaging 90% at 3 years) and quality of
life, even in patients with distal PA obstructions.
• Delcroix et al (2016) prospective trial found that in
operated patients, the preoperative characteristics
increasing mortality included bridging therapy with
PAH drugs
• Quadry et al (2018) found that in patients with
proximal operable disease declining surgery have a
poor long-term outcome, with a 5-year survival of
53% compared with 83% in patients undergoing PEA
6MWD
• 6MWD increased by an average of 95.7 m
after PEA
• (n = 11 studies)
mPAP
• mPAP reduced by an average of 21.42 mm Hg
after PEA
• (n = 23 studies)
PVR
• PVR decreased by an average of
560.3 dyns/cm5 after PEA
• (n= 19 studies)
•RPH
• RPH in 25% of patients
Meta-analysis by Hsieh et al (2018) found that PEA:

16. Back to the Case

17. • He has on multiple CTs with air
space disease that did not fade
away all in between
investigations, could be mosaic
perfusion.
• Planned for PEA
NM Perfusion Scan Post-PEA
Impression:
1. Differential pulmonary perfusion is 29.6% to the left lung and 70.4% to
the right lung.
2. High probability lung scan for pulmonary embolism (PE present), age
indeterminate. Multiple bilateral unmatched perfusion defects are again
demonstrated, with significant interval improvement in perfusion to the
right lower and upper lobes and interval mild, globally reduced perfusion
to the left lung.
ECHO Post-PEA
Normal LV systolic function with
mild LVH
Moderate RV systolic dysfunction
Mild RA enlargement
Trivial MR, trivial PR, mild TR
RVSP = 43mmHg
TAPSE = 1.3cm (was 1.8)

18. • He has had no increasing shortness of
breath or chest pain or tightness, does
not have a cough either.
• He says that he is able now to do
workouts, but not able to walk for
longer distances or tolerate inclines.
• He slowly getting better.
• He was able to return to work
• 6MWT performed off of O2
• Since discharge, he continues to
progress well
• He reports activity level and tolerance
since discharge has been continuing to
improve.

19. Right Heart Catheterization (7/13/2017,
pre-PEA)
State: Baseline
RA: 9 mmHg (mean)
RV: 77/ 7 mmHg
PA: 81/ 34 49 mmHg (mean)
PCW: 11 mmHg (mean)
AV O2: 4.7 vol%
Cardiac output: 6.9 L/min
Cardiac index: 2.8 L/min-m2
PVR: 5.5 Wood units
Shunt Ratio: 1.0 (Qp/Qs)
L to R shunt: 0.0 L/min (Qp-Qep)
R to L shunt: 0.0 L/min (Qs-Qep)
Right Heart Catheterization (post-PEA)
State: Baseline
RA: 1 mmHg (mean)
RV: 71/ 1 mmHg
PA: 71/ 26 40 mmHg (mean)
PCW: 6 mmHg (mean)
AV O2: 5.5 vol%
Cardiac output: 6.1 L/min
Cardiac index: 2.4 L/min-m2
PVR: 5.6 Wood units
NM Perfusion Scan
Conclusions:
1. High probability lung scan for pulmonary
embolism, age indeterminate, which appears
relatively similar to prior with no new perfusion
defects. Findings may be seen in the setting of
chronic thromboembolic pulmonary
hypertension.
2. Scintigraphic findings of mild obstructive airways
disease.
ECHO
Interpretation:
Normal LV systolic function with mild LVH
Moderate RV systolic dysfunction
Trivial MR, trivial PR, mild TR
RVSP = 87mmHg
TAPSE = 1.7cm

20. In a patient with this RHC post-PEA, what
should be the next step in management?

21. Back to the Case

22. Right Heart Catheterization (7/13/2017,
pre-PEA)
State: Baseline
RA: 9 mmHg (mean)
RV: 77/ 7 mmHg
PA: 81/ 34 49 mmHg (mean)
PCW: 11 mmHg (mean)
AV O2: 4.7 vol%
Cardiac output: 6.9 L/min
Cardiac index: 2.8 L/min-m2
PVR: 5.5 Wood units
Shunt Ratio: 1.0 (Qp/Qs)
L to R shunt: 0.0 L/min (Qp-Qep)
R to L shunt: 0.0 L/min (Qs-Qep)
Right Heart Catheterization (post-PEA)
State: Baseline
RA: 1 mmHg (mean)
RV: 71/ 1 mmHg
PA: 71/ 26 40 mmHg (mean)
PCW: 6 mmHg (mean)
AV O2: 5.5 vol%
Cardiac output: 6.1 L/min
Cardiac index: 2.4 L/min-m2
PVR: 5.6 Wood units
NM Perfusion Scan
Conclusions:
1. High probability lung scan for pulmonary
embolism, age indeterminate, which appears
relatively similar to prior with no new perfusion
defects. Findings may be seen in the setting of
chronic thromboembolic pulmonary
hypertension.
2. Scintigraphic findings of mild obstructive airways
disease.
ECHO
Interpretation:
Normal LV systolic function with mild LVH
Moderate RV systolic dysfunction
Trivial MR, trivial PR, mild TR
RVSP = 87mmHg
TAPSE = 1.7cm
Advised to start Riociguat

23. • Has been on Riociguat for ~3
weeks.
• He notes continued shortness of
breath with mild activities and
denies any overall improvement.
• He states that he has been doing okay,
with no worsening but also no
improvement in his shortness of breath or
chest tightness.
• Started Riociguat (had not yet received it)
• Referred for BPA consideration

24. Right Heart Catheterization (pre-BPA)
State: Baseline
RA: 12 mmHg (mean)
RV: 82/ 14 mmHg
PA: 82/ 40 53 mmHg (mean)
PCW: 16 mmHg (mean)
AV O2: 4.3 vol%
Cardiac output: 7.8 L/min
Cardiac index: 3.0 L/min-m2
PVR: 4.7 Wood units
Pulmonary Angiogram:
Selective pulmonary angiography was performed and showed peripheral
CTEPH lesions that predominated in the left lower lobe and lingular lung
segments.

25. Right Heart Catheterization
State: Baseline
RA: 14 mmHg (mean)
RV: 85/ 12 mmHg
PA: 85/ 40 54 mmHg (mean)
PCW: 16 mmHg (mean)
AV O2: 3.7 vol%
Cardiac output: 9.1 L/min
Cardiac index: 3.5 L/min-m2
PVR: 5.9 Wood units
Right Heart Catheterization
State: Post V'plasty
PA: 82/ 38 52 mmHg (mean)
PCW: 17 mmHg (mean)
AV O2: 3.6 vol%
Cardiac output: 9.3 L/min
Cardiac index: 3.6 L/min-m2
PVR: 3.8 Wood units
• Selective pulmonary angiography demonstrated two major lesions to the left lower lung: a mid-to-lower
lesion that was severely stenotic with large distal branches and a totally occluded branch to the left base.
• The superior lesion was dilated multiple times with a 2 mm noncompliant balloon with good result
• The lower lesion was dilated with 2mm balloon  the result looked good but it quickly reoccluded  then
dilated with lesion with a 2.5 mm balloon  finally a 4 mm balloon at nominal inflation
Advised to start Macitentan

26. Overview of Timeline
Initial Presentation Recurrence of PE in
setting of lack of
anticoagulation and
new O2 requirement
PEA Repeat RHC
and initiation
of Riociguat
1st BPA 2nd BPA 3rd BPA
Riociguat
Macitentan

27. • He doesn't have to stop while going for
walk with his wife anymore
• He does get tired and short of breath
after walking few flights of stairs
• He does have significant bendopnea
• Unfortunately, he had a lapse in Riociguat;
restarted but had not titrated up
ECHO
Interpretation:
Normal LV systolic function with
mild LVH
Mild RV systolic dysfunction, mild
enlargement
Normal RA size
Trivial MR, mild PR, mild TR
RVSP = 58mmHg
TAPSE = 1.5cm
NM Perfusion Scan
Conclusions:
Multiple perfusion defects. No new
perfusion defect identified compared to
June 6, 2018 consistent with chronic PE.
• Overall feeling better, able to
walk 2.5 miles
ECHO
Interpretation:
Normal LV systolic function with
mild LVH
Mild RV systolic dysfunction, normal
size
Normal RA size
Trivial MR, trivial PR, mild TR
RVSP = 34mmHg

28. Discussion

29. PEA versus BPA
• No head-to-head comparison of PEA versus BPA
• A systematic review and meta-analysis by Zhang et al in 2021
compared the safety and efficacy of BPA and PEA in the treatment
of CTEPH
• The survival rates at perioperative/in-hospital period, 2 years,
and 3 years were 100%, 99%, and 97%, in BPA group and 93%,
90%, and 88%, respectively, in PEA group.
• The variation of 6-min walk distance was 141.80 m in BPA and
100.73 m in PEA
• At < 1-month, 1–6-month, and > 12-month follow-up, the
changed results of mean pulmonary arterial pressure were −
18.31, − 17.00, and − 12.97 mmHg in BPA group and − 18.93, −
21.21, and − 21.35 mmHg in PEA group.
• At < 1-month and 1–6-month follow-up, the changed values of
pulmonary vascular resistance were − 542.24 and − 599.77
dyne•s•cm−5 in PEA group and − 443.49 and − 280.00
dyne•s•cm−5 in BPA group.
BPA might have higher survival
rate and fewer types of
complications compared with PEA.
The improvement in exercise
capacity in the BPA group might
be more pronounced than in PEA
group.
PEA might be superior in
improvement of hemodynamic
parameters

30. BPA versus Medical Therapy
• A systematic review and meta-analysis
by Wang et al in 2019 compared the
efficacy and safety of BPA with riociguat
therapy in inoperable CTEPH patients.
As compared with Riociguat, BPA was
associated with a greater improvement
in:
• RAP (MD = -3.53 mmHg vs = -1.05
mmHg)
• mPAP (MD = -15.02 mmHg vs MD
= -4.19 mmHg)
• PVR (MD = -1.32 woods vs
standard MD = -0.65 woods)
• NYHA functional class (RR = 6.78 vs
RR = 1.49)
• 6MWD (MD = 71.66 m vs MD =
45.25 m)
Medical Options:
• Riociguat (CHEST-1 Study: improved
6MWD and reduced PVR by 31% compared
with placebo in patients with inoperable
CTEPH or those with persistent/recurrent
PH after PEA)
• Treprostinil SC (CTREPH Study: improved
6MWD at week 24 in patients with
inoperable CTEPH or those with
persistent/recurrent PH after PEA receiving
a high dose compared with a low dose)
• Macitentan (MERIT-1 Study: improved PVR
and 6MWD vs. placebo at 16 and 24 weeks
including only patients with inoperable
CTEPH)

31. Questions?

32. References
1. Ghofrani HA, D’Armini AM, Grimminger F, Hoeper MM, Jansa P, Kim NH, et al. Riociguat for the treatment of chronic
thromboembolic pulmonary hypertension. N Engl J Med 2013;369:319–329.
2. Hsieh WC, Jansa P, Huang WC, Niznansky M, Omara M, Lindner J. Residual pul- monary hypertension after pulmonary
endarterectomy: a meta-analysis. J Thorac Cardiovasc Surg 2018;156:1275–1287.
3. Delcroix M, Lang I, Pepke-Zaba J, Jansa P, D’Armini AM, Snijder R, et al. Long-term outcome of patients with chronic
thromboembolic pulmonary hypertension: re- sults from an international prospective registry. Circulation 2016;133:859–
871.
4. Quadery SR, Swift AJ, Billings CG, Thompson AAR, Elliot CA, Hurdman J, et al. The impact of patient choice on survival in
chronic thromboembolic pulmonary hyper- tension. Eur Respir J 2018;52:1800589.
5. Zhang L, Bai Y, Yan P, He T, Liu B, Wu S, Qian Z, Li C, Cao Y, Zhang M. Balloon pulmonary angioplasty vs. pulmonary
endarterectomy in patients with chronic thromboembolic pulmonary hypertension: a systematic review and meta-analysis.
Heart Fail Rev. 2021 Jul;26(4):897-917. doi: 10.1007/s10741-020-10070-w. Epub 2021 Feb 5. PMID: 33544306.
6. Jaïs X, Brenot P, Bouvaist H, Jevnikar M, Canuet M, Chabanne C, et al. Balloon pul- monary angioplasty versus riociguat for
the treatment of inoperable chronic thromboembolic pulmonary hypertension (RACE): a multicentre, phase 3, open-la- bel,
randomised controlled trial and ancillary follow-up study. Lancet Respir Med 2022. doi:10.1016/S2213-2600(22)00214-4.
7. Wang W, Wen L, Song Z, Shi W, Wang K, Huang W. Balloon pulmonary angioplasty vs riociguat in patients with inoperable
chronic thromboembolic pulmonary hypertension: A systematic review and meta-analysis. Clin Cardiol. 2019 Aug;42(8):741-
752. doi: 10.1002/clc.23212. Epub 2019 Jun 12. Erratum in: Clin Cardiol. 2020 Mar;43(3):315-316. PMID: 31188483; PMCID:
PMC6671827.