1.
Management of patients with chronic
thromboembolic pulmonary hypertension
Anastasia Bykova, NP-Adult, MN
Nurse Practitioner
Marc de Perrot, MD, MSc, FRCSC
Associate Professor of Surgery
Director, Toronto Pulmonary Endarterectomy Program
Division of Thoracic Surgery
Toronto General Hospital

2.
Thromboembolic pulmonary disease
• The incidence of venous thromboembolism is high with about 240
cases per 100,000 person/ year
• The diagnosis and management of patients with acute pulmonary
emboli (PE) is well characterized
• However, the incidence and management of patients with residual
pulmonary hypertension after acute PE is still unclear
• Over the past 10 years, pulmonary endarterectomy has become the
mainstay of therapy for patients with severe pulmonary hypertension
and unresolved PE
• The incidence of CTEPH appears to be about 10x higher than
previously estimated
 Annual incidence of up to 25 cases per million inhabitants
(incidence of idiopathic PAH is 2-3 cases per million
inhabitants)

3.
Definition of chronic thromboembolic pulmonary
hypertension (CTEPH)
• CTEPH is defined by the presence of:
– Precapillary pulmonary hypertension (mean PA
pressure >25 mmHg, PCWP or LVEDP <15
mmHg)
– Combined with the presence of perfusion defects
in the pulmonary arterial tree
– Despite at least 3 months of anticoagulation

4.
Pulmonary hypertension is due to:
• Obstruction of PA bed by thrombo-embolic material
• Vascular remodeling
• in situ thrombosis
• Overflow vasculopathy
• Post-obstructive vasculopathy
Mechanisms leading to pulmonary hypertension
Localized phenomenon
 PH progresses despite adequate anticoagulation!!!

5.
A Closer Look at CTEPH Pathophysiology
• Fibrous obstruction of the pulmonary vascular bed  increase in
PVR.
• Chronic thromboembolic obstruction  small vessel arteriolar
vasculopathy:
 Excessive vascular and inflammatory cell proliferation
 High flow through the pulmonary vasculature induces medial
hypertrophy
 These changes resemble the arteriopathy noted in idiopathic
pulmonary arterial hypertension
 Second process that contributes to elevated PVR and disease
progression in CTEPH
 PH develops because of 1) primary obstruction by embolus
and adjacent remodeling or 2) combination of proximal
obstruction and secondary small vessel vasculopathy

6.
Natural Course of the Disease
Residual pulmonary vascular
obstruction with PH
Thrombus organization in occluded vessels
Increasing shear stress in non-occluded vessels
RV function is compensated
Progression of vascular remodeling
Progressive right ventricle dysfunction
Death
1. VTE/DVT - PE
2. Honey moon period
3. Clinical deterioration

7.
A Closer Look at Natural Course of the Disease with
Focus on RV Failure
Initial stage -
Compensatory
RV pressure overload  RV hypertrophy
*RV is not capable of sustaining a long term
pressure overload *
Later Stage –
Decompensatory
RV dilation with ↑ oxygen demand and ↓
perfusion  vicious circle of compromised
contractility and dilation
RV failure: ↑ filling pressure, diastolic
dysfunction, diminished cardiac output
(CO), hypertrophy
LV diastolic dysfunction through
ventricular interdependence and leftward
septal displacement

8.
Microvascular disease and RV dysfunction directly
impacts on results of pulmonary endarterecomy
• Peri-operative
mortality reduced to
2-3%
• Mortality increases
with RV failure
• Results of PEA are best
during “honey moon” period
– Minimal distal vasculopathy
– Good RV function
 Reduced risk of post-
operative RV failure
 Reduced risk of residual PH
in the long-term

9.
Clinical Presentation of Patients with CTEPH
Clinical Symptoms
Early
• Progressive dyspnea on exertion
Later
• Dyspnea at rest
• Chest tightness, pain
• Syncope
• Hemoptysis
• Early satiety
Caveat: History of acute pulmonary
emboli present in <50% of the
patients
Clinical Signs
Early
• Accentuated pulmonic
component of S2
Later
• Jugular venous distention
• RV heave / lift
• Fixed splitting of S2
• Tricuspid regurgitation
• S3 RV gallop
• Hepatomegaly
• Peripheral edema
• Ascites

10.
Diagnostic Work up
1. Diagnosis
• V/Q scan
2. Evaluation for medical/surgical therapy
• Angio CT scan (64 slices)
• Right heart cath
• Pulmonary angiography
• TTE ECHO
3. Pre-operative evaluation
• Coronary angiogram (>45 years old or risk factors)
• Venous/arterial Doppler
• Pulmonary function tests
• 6 minutes walk test

11.
Diagnostic Algorithm
CTEPH
ruled out
Normal perfusion
scan
Multidisciplinary discussion with
Respirologists/cardiologists, surgeons,
and radiologists
Further imaging with:
CT angiography,
Pulmonary angiogram,
Right heart cath
Indeterminate or multiple
perfusion defects
Ventilation/perfusion scan
Patients with unexplained PH or
with PH and history of PE

12.
Ventilation-perfusion scan
• V/Q scan is the most reliable test
to rule out CTEPH
• V/Q is excellent for diagnosis of
CTEPH, but has no role to
determine feasibility of surgery
• Pulmonary angiogram if
mismatched perfusion defect
presents on V/Q scan

13.
CT pulmonary angiogram
• CT pulmonary angio is
important to assess the
possibility of PEA
• The presence of intra-luminal
webs (*) is pathognomonic of
the disease
• However, a normal CT does
not rule out the diagnosis of
CTEPH
• CTPA complements the
pulmonary angiogram
*

14.
Pulmonary angiogram and right heart cath
• Webs and bands
• Pouches
• Irregularities
• Narrowed and truncated
vessels
• Usually no residual clot is
visible in the lumen

15.
Pulmonary endarterectomy (PEA)
• Therapy of choice for patients with CTEPH
– Major clinical improvement
– Resolution of PH
– Excellent long term survival
– Only treatment is life-long anticoagulation
• The goal of the surgery is curative by:
– Reverse RV compromise caused by high PVR and improve CO
– Complete reperfusion of previously occluded PA and treatment of
dyspnea
– Prevention of progressive RV dysfunction and secondary
vasculopathy in the remaining patent vessel

16.
Indications for pulmonary endarterectomy
• Diagnosis of CTEPH must be established
Importance of adequate imaging
• Surgically accessible disease
• Symptoms related to CTEPH (usually PVR>300
Dynes.sec.cm-5)
• Absence of significant co-morbidities

17.
Pulmonary endarterectomy (PEA)
Thrombectomy
Endarterectomy 

18.
Principles of pulmonary endarterectomy
– Bilateral procedure via median sternotomy
• To achieve complete relief of obstruction
– Intrapericardial surgery
• To avoid pleural adhesions
• To have bilateral access
• To use cardiopulmonary bypass
– Deep hypothermic circulatory arrest (18°-20°C)
• To stop the bronchial back bleeding and obtain good
visualization of the distal vessels
– Video-assistance
• To provide light and visualization of distal vessels

19.
Opitz, de Perrot. Op Technique in Cardiothoracic Surg 2012;17:168-80

20.
Endarterectomy specimen
Right heart cath preop and 3 months postop:
preop: PA 96/14, mean 46 mmHg, CO 6.7 L/min, TPR 549 Dynes.sec.cm-5
postop: PA 28/9, mean 15 mmHg, CO 8.4 L/min, TPR 143 Dynes.sec.cm -5

21.
Mortality after pulmonary endarterectomy
0
2
4
6
8
10
12
Mortality
(%)
Hospital
mortality
1 year
mortality
Overall
1-10 cases /year
11-50 cases /year
>50 cases /year
p=n.s.
Hospital mortality and 1 year mortality tended to be
higher in centers doing 1-10 cases per year
Mayer et al. J Thorac Cardiovasc Surg 2011;141:702-10

22.
Outcomes following PEA
• Improvement of WHO Class from III/IV to I/II
• Immediate and sustained HD improvement with ↑ CI,
significant ↓ in PVR and PAP
• RV remodelling
- Tricuspid valve function and geometry return to normal
- Immediate decrease in right-sided size
- Decreased leftward shift of the interventricular septum
- Increased LV end-diastolic area
 Clinical improvement is related to removal of
pulmonary arterial obstruction and reversal of
pulmonary vascular remodeling.

23.
ICU management of post-op PEA patient
 All patients are transported to the ICU
 Kept fully sedated and ventilated overnight
 POD #1-2 – extubated
POD #2-3 – discharged from the ICU
POD #7-14 – discharged from the hospital
Some complications are similar to other cardiothoracic surgical
procedures: atelectasis, pleural effusion, pericardial effusion,
diaphragmatic dysfunction, and arrhythmias
Unique complications in PEA: reperfusion pulmonary edema (RPA)
and residual PH/RV failure

24.
ICU management of post-op PEA patient
Neuro
Keep fully sedated overnight with
– Propofol 200-300 mg/hr
– Fentanyl 100-200 mcg/hr
Allows for decreased CO and
prevention of pulmonary edema!
Start weaning the sedation on POD#1
with the goal to extubate, if pt tolerates

25.
ICU management of post-op PEA patient
Cardiovascular and Respiratory
Standard postoperative care
• Levophed to target MAP ≥ 75 mmHg (up to 0.3 mcg/kg/min)
• Other HD targets SvO2 ≥ 60%
CI 1.5-2.5 L/min/m² (avoid high CI initially to prevent
RPA)
CVP 8-14 mmHg
• Lines: Cordis and PA catheter, triple lumen CVC, 2 artlines (radial &
femoral), epicardial pacer wires connected to pacemaker
• HD monitoring on an hourly basis via cardiac and continuous SvO2/Swan
Ganz monitors (BP, HR, CI/CO, PAP, CVP). Expect a decrease of PAP
by 25 mmHg from pre-op value, improved RV function and PVR
reduction

26.
ICU management of post-op PEA patient
Review of Basic Hemodynamics
Cardiac Output = Stroke Volume x Heart Rate
Preload Afterload Contractility
Fluid
overload from
RV failure
pre-op 
Lasix to
target 5-15 L
loss/3-5days
Risk for pulmonary
edema from
reduced PVR, CPB
inflammation,
removal of PEEP
with extubation 
keep sedated &
ventilated
overnight with
lower CI/CO
Atrial pacing
at 80-90
beats/min to
help with RV
remodeling
Goal to maintain negative fluid
balance and avoid IV fluid bolus. Keep
pt dry!!!

27.
ICU management of post-op PEA patient
Cardiovascular and Respiratory Cont’d
• Mechanical ventilation overnight to observe for RPA
• 3 CTs to -20 cm H2O (2 large bore CTs - retrosternal and pericardial
above the diaphragm; 1 small bore – mediastinal)
• Monitor CT output for bleeding: output ≥ 50ml/hr
• Target PaCO2 35-45 mmHg
PaO2 ≥ 75 mmHg
• CBC, lytes, extended lytes, creatinine, lactate, LFTs, trop, q4h X 24 hrs
• Ancef 1g q8h IV x 48 hrs
• TED for venous thrombosis prophylaxis, NEVER use SCD
• Anticoagulation Post-op: Hold Heparin IV drip until R/A in 2-3 hours.
When re-started (if no bleeding), UFH level in 6 hours. Dr. de Perrot will
initially manage rate until patient is back on Heparin nomogram.

28.
What to watch for?
PEA-specific complications
Hypoxemia
• Related to atelectasis, postoperative pain, V/Q mismatch d/t loss of
hypoxic vasoconstriction, pulmonary edema
• Vascular “steal” phenomenon in PEA:
Blood flow taking the path of least resistance resulting in relative
“hyperperfusion” of newly endarterectomised lung with “steal” from
previously normal perfused lung region. Low V/Q regions contribute to
hypoxemia. Resolves within several months & O2 is weaned off.

29.
What to watch for?
PEA-specific complications
Reperfusion pulmonary edema
• Occurs in < 5-10% of patients
- 60% immediately post-op
- 30% within the first 48 hours
- 10% later during hospitalization (> 48hours)
• Definition: localized form of high-permeability edema seen as opacity on
CXR in the areas of the lung that have been endarterectomised &
reperfused.
• Associated with ↑ in duration of MV and ICU stay
• Most severe form – severe alveolar hemorrhage with profound
hypoxemia. High morbidity secondary to deconditioning and infections.

30.
What to watch for?
PEA-specific complications
Reperfusion pulmonary edema
Treatment is supportive:
• +++ diuresis to reduce lung water and avoidance of high cardiac
output
• Oxygenation is better in one lateral decubitus position versus the
contralateral
• Inhaled NO may improve oxygenation
• If RV and LV function is preserved, VV ECMO for severe cases is
lifesaving. Natural repair process takes 4-5 days, allowing weaning
from ECMO.

31.
What to watch for?
PEA-specific complications
Residual pulmonary hypertension
• Significant problem in 5% to 35% of patients undergoing PEA
• Most common cause of perioperative mortality
• Etiology: distal chronic thromboembolic disease or superimposed small-
vessel vasculopathy that is not cured by endarterectomy
Treatment of residual PH in immediate post-op period is challenging
1. Inhaled nitric oxide to reduce PVR and does not carry risk for systemic
hypotension
2. Optimization of RV preload
3. Inotropic support (i.e. Milrinone)
 NO systemic vasodilators d/t risk for systemic hypotension

32.
What to watch for?
General complications
Postoperative pericardial effusion
• Suspect with hypoxia and HD compromise (i.e. hypotension)
• Immediate ECHO to confirm the diagnosis
• Significant pericardial effusions should be drained
Atrial arrhythmias
• Atrial flutter / fibrillation are common following PEA secondary to
cardiac manipulation intra-op
• Careful electrolytes management to target Mg ≥ 1.1 & K ≥ 4
• Amiodarone is the drug of choice in CTEPH patients

33.
ICU management of post-op PEA patient
GI/GU
• Keep NPO until extubated then CF
• NG tube – to straight drainage. For medication administration while
intubated and NPO
• Famotidine 20 mg IV BID before and after extubation
• Once oral intake initiated, switch to Pantoloc 40 mg PO OD until
hospital discharge to prevent stress ulcer and GI bleeding
• Foley catheter - aggressive diuresis with target fluid loss of 10 L/2-3
days post-op. Increase Levophed if needed to maintain MAP ≥ 75
mmHg. Avoid fluid boluses.
• Aim at negative 24 hr fluid balance

34.
ICU management of post-op PEA patient
• Extubated POD#1
• PA catheter removed POD#2-3
• 2 out of 3 CTs and epicardial pacer wires removed on POD #3-6.
- Heparin drip held x 4 hours for the procedure
- Bed rest x 1 hr
- Resume Heparin drip 1 hr post CT removal
- CXR 2 hrs post CT removal
• Mediastinal, substernal CT tube removed 24 hrs later to prevent
substernal hematoma
• Ambulate after extubation
• PCA for pain management to promote deep breathing/coughing
and active physiotherapy

35.
Upon discharge from the hospital
• Patients remain on anticoagulation for life with Warfarin and INR
target 2-3
• If residual PH (mean PAP ≥ 35 mmHg) and clinically symptomatic,
consider resuming PAH vasodilators
• Regular outpatient follow up with the CTEPH Team at TGH or PH
Team locally for monitoring
Riociguat (Adempas)
• Member of a new class of medications called soluble guanylate cyclase
stimulators
- Vasorelaxation in the pulmonary arteries
- Antiproliferative and antifibrotic effects
- Results in the increased exercise capacity (↑ 39m on 6MWT) &
improved HD (↓ PVR by 226 dynes.sec.cm-5 )
• The only agent approved for non operable CTEPH patients or for recurrent
PH following PEA

36.
Acknowledgement
• Dr. de Perrot

37.
Thank you for your attention!