Hemodynamic classification of pulmonary hypertension Three categories of PH: pre-capillary (Pre-PH), combined pre-and-post capillary (Cpc-PH), and isolated post-capillary (Ipc-PH).unexplained dyspnea or signs/symptoms suggesting PH .3 different drug classes Nitric Oxide Pathway( PDE-5is and sGCs ).PAH (without cardiopulmonary comorbidities and non-vasoresponders Endothelin Pathway( ERA ) Prostacyclin Pathway( PCA & PRA )Comprehensive risk assessment in PAH

1. Magdy El-Masry
Prof. of Cardiology
Tanta University

2. “Diagnostic and management
dilemmas in PH”

3. Definition Hemodynamic characteristics
PH mPAP> 20 mmHg
Precapillary
PH
mPAP> 20 mmHg
PAWP ≤ 15 mmHg : normal
↑PVR> 2 WU
Isolated
postcapillary
PH
mPAP> 20 mmHg
↑PAWP> 15 mmHg
PVR ≤ 2 WU : normal
Combined post-
and precapillary
PH
mPAP> 20 mmHg
↑PAWP> 15 mmHg
↑PVR> 2 WU
Exercise
PH
mPAP/CO slope between rest and
exercise> 3 mmHg/L/min
 mPAP , mean pulmonary arterial pressure(mmHg)
 PAWP , pulmonary arterial wedge pressure(mmHg)
 PVR , pulmonary vascular resistance(WU, Wood units)
Hemodynamic classification of pulmonary hypertension
Three categories of PH:
pre-capillary (Pre-PH),
combined pre-and-post capillary (Cpc-PH),
and isolated post-capillary (Ipc-PH)

4. Pre- capillary component (↑PVR )
Post-capillary component (↑PAWP)
Pulmonary Hypertension and the Right Ventricle : Forgotten No More
PH is not a rare condition
as it affects 1% of the
global population.

5. 1.1 Idiopathic PAH
1.1.1 Nonresponders at vasoreactivity testing
1.1.1 Acute responders at vasoreactivity testing
1.2 Heritable PAH
1.3 Drug- and toxin-induced PAH
1.4 PAH associated with:
1.4.1 Connective tissue disease
1.4.2 HIV infection
1.4.3 Portal hypertension
1.4.4 Congenital heart diseases
1.4.5 Schistosomiasis
1.5 PAH with overt features of venous/capillary (PVOD/PCH) involvement
1.6 Persistent PH of the newborn syndrome
2.1 PH due to HF
2.1.1 With preserved LVEF
2.1.2 Due to HF with reduced LVEF
2.2 Valvular heart disease
2.3 Congenital/acquired cardiovascular conditions
leading to postcapillary PH
1. Pulmonary Arterial Hypertension
2. PH Associated With Left Heart Disease
3. PH Associated With Lung Diseases and/or Hypoxia
4. PH Associated With Pulmonary Artery Obstructions
5. PH With Unclear and/or Multifactorial Mechanisms
3.1 Obstructive lung disease
3.2 Restrictive lung disease
3.3 Lung disease with mixed restrictive/obstructive pattern
3.4 Hypoventilation syndromes
3.5 Hypoxia without lung disease (eg, high altitude)
3.6 Developmental lung disorders
4.1 Chronic thromboembolic PH
4.2 Other pulmonary artery obstructions
5.1 Hematological disorders
5.2 Systemic disorders
5.3 Metabolic disorders
5.4 Chronic kidney failure (+/-hemodialysis)
5.5 Pulmonary tumor thrombotic microangiopathy
5.4 Fibrosing mediastinitis
Recent ESC/ERS Updates to 6th World Symposium on PH Classification
Humbert. Eur Heart J. 2022;43:3618. Humbert. Eur Resp J. 2023;61:2200879. Simonneau. Eur Resp J. 2019;53:1801913.

6. IpcPH= isolated post-
capillary PH
CpcPH= combined post-
and pre-capillary PH
Pre-capillary PH Pre-capillary PH Pre- (or post-)
capillary PH
---------

8. PEA= pulmonary endarterectomy
BPA=pulmonary balloon angioplasty

9. Guidelines recognize that focusing on multiple pathways
is an effective treatment strategy : 3 different drug classes
 Nitric Oxide Pathway( PDE-5is and sGCs )
 Endothelin Pathway( ERA )
 Prostacyclin Pathway( PCA & PRA )
Pathway Class Drug
Endothelin
ERA, endothelin receptor
antagonist
Ambrisentan:oral
Bosentan:oral
Macitentan:oral
Nitric Oxide
PDE5i, phosphodiesterase
5 inhibitor
Sildenafil:oral
Tadalafil:oral
sGCs, soluble guanylate
cyclase stimulator
Riociguat:oral
Prostcyclin
PCA, prostacyclin
analogue
Epoprostenol:iv infusion
Iloprost:inhaled
Treprostinil:iv,sc,oral,inhaled
Beraprost:oral
PRA, prostacyclin receptor
agonist
Selexipag:oral
Too Much Endothelin-1
Too Little Nitric Oxide
Too Little Prostacyclin
The balance between
vasodilators and vasoconstrictors,
is disturbed in PAH
PAH Drugs

10. Demand affordable prices for PH medications

11. Ten Points to Remember

12. (1) First, how did the 2022 ESC/ERS update change from the
2018 WSPH Guidelines?
6th World Symposium
on PH 2018
2022
ESC/ERS
In the new guideline, there are minor changes in the
haemodynamic definition of PH, for example:
#The threshold of PH was lowered to a mean pulmonary
arterial pressure (mPAP) >20 mmHg*
#The threshold of pre-capillary PH was lowered to a
pulmonary vascular resistance (PVR) >2 Woods units (WU)
#The threshold of isolated post-capillary PH was lowered to a
PVR ≤2 WU
#The threshold of combined post- and pre-capillary PH was
lowered to a PVR >2 WU.
*Lowering the diagnostic threshold captures more at-risk individuals,
but it should be noted that an mPAP >20 mm Hg alone is not pathognomonic for PH.

13. (2) The clinical classification of PH distinguishes five main groups:
(i) Pulmonary arterial hypertension (PAH)
(ii) PH associated with left heart disease
(iii) PH associated with lung diseases and/or hypoxia
(iv) PH associated with pulmonary artery obstructions (mainly CTEPH)
(v) PH with unclear and/or multi-factorial mechanisms
The differential diagnosis is crucial, because the therapeutic
strategies for each of these five groups are fundamentally different.
Update of PH classification
The main changes in the classification of PH include the addition of
the subgroups ‘‘nonresponders at vasoreactivity testing’’ and ‘‘acute
responders at vasoreactivity testing’’ to the group of idiopathic PAH.

14. (3) New diagnostic algorithm aims at earlier detection & early referral
The proposed diagnostic algorithm should be considered
in patients with unexplained dyspnea or signs/symptoms suggesting PH
and includes 3 steps:
Step 1. Suspicion. Initial evaluation (first-line physicians)
Step 2: Detection. Includes noninvasive lung and cardiac testing.
Step 3. Confirmation. Patients should be referred to a PH center.
At any time, a fast-track
referral to a PH center
in case of warning signs or
when PAH and CTEPH are
suspected is recommended.
Rapidly evolving or severe
symptoms (WHO-FC III/IV),
clinical signs of RV failure,
syncope, signs of low CO
,poorly tolerated arrhythmias,
and hemodynamic instability.
#Based on the TR velocity and other echo
signs of PH, including the TAPSE/sPAP ratio
(<0.55 mm/mmHg is suggestive of PH)
#

15. (4) Initial Treatment Strategies: In patients with PAH (without cardiopulmonary
comorbidities and non-vasoresponders), risk assessment utilizing a three-strata
approach is recommended at the time of diagnosis.
For patients presenting with low or intermediate risk, initial combination therapy
with a phosphodiesterase type 5 inhibitor (PDE5i) and an endothelin receptor
antagonist (ERA) is recommended.
In patients at high risk, initial combination therapy with a PDE5i, an ERA, and
s.c./i.v. prostacyclin analogues (PCA) should be considered.
Acute vasoreactivity testing
PAH :I/H/D-PAH only
Acute
responders
CCB therapy
Amlodipine/Diltiazem/Felodipine
Non-
responders
Risk (3 strata)
Dual Triple

16. Comprehensive risk
assessment in PAH
(3-strata model)
6MWD, 6-minute walking distance; BNP,
brain natriuretic peptide; CI, cardiac
index; cMRI, cardiac magnetic resonance
imaging; CPET, cardiopulmonary exercise
testing; HF, heart failure;NT-proBNP, N-
terminal pro-brain natriuretic peptide;
PAH, pulmonary arterial hypertension;
pred., predicted; RA, right atrium; RAP,
right atrial pressure; sPAP, systolic
pulmonary arterial pressure; SvO2, mixed
venous oxygen saturation; RVESVI, right
ventricular end-systolic volume index;
RVEF, right ventricular ejection fraction;
SVI, stroke volume index;TAPSE, tricuspid
annular plane systolic excursion;
VE/VCO2, ventilatory equivalents for
carbon dioxide; VO2, oxygen uptake;
WHO-FC, World Health Organization
functional class
.aOccasional syncope during heavy
exercise or occasional orthostatic syncope
in a stable patient.
bRepeated episodes of syncope even with
little or regular physical activity.
cObserve that 6MWD is dependent upon
age, height, and burden of comorbidities.
dTo harmonize with the four-strata model
shown in Table 18, the BNP and NT-
proBNP cut-off levels have been updated
from the 2015 version based on data from
the REVEAL registry,acknowledging that
the European validation studies have used
the original cut-off
levels.274,292,293,295,296,302
ecMRI parameters adapted from Section
6.2.2.2.

17. (5) Risk assessment and treatment goals in follow-up
During follow-up, PAH patients should be re-assessed using the refined four-
strata risk assessment model.
In patients at intermediate-low-risk, therapy should be intensified by adding
a prostacyclin receptor agonist (PRA), or by switching from PDE5i to a soluble
guanylate cyclase stimulator (sGCs).
For patients at intermediate- high or high risk, addition of s.c./i.v.
prostacyclin analogues(PCA) and evaluation for lung transplantation should be
considered.
F/U: Assessment Tool

19. (6) In patients with ‘PAH with comorbidities’, initial monotherapy
with a PDE5i or an ERA should be considered.
For patients presenting at intermediate or high risk during follow-up,
additional PAH medications may be considered on an individual basis.
Cardiopulmonary comorbidities : These are found predominantly in elderly patients and include
risk factors such as obesity, DM,CAD, systemic HTN (left heart phenotype) or a history of chronic
smoking and low diffusing capacity =DLCO (cardiopulmonary phenotype).
These patients respond worse to PAH medication, are less likely to reach low-risk status, have a higher mortality risk
and are more likely to discontinue this medication due to efficacy failure or low tolerance.

20. (7) PH associated with left heart disease is sub-categorized into
isolated post-capillary PH (PVR ≤2 WU), and combined post- and
pre-capillary PH (PVR >2 WU).
No PH IpcPH, isolated post-capillary PH
PVR ≤ 2 WU : normal
CpcPH, combined post- and pre-capillary PH
↑PVR> 2 WU
Finally, although drugs approved for PAH are not recommended in patients with PH-left heart disease, the
guidelines do not provide any recommendation for or against using PDE5i in patients with HFpEF and
combined post- and precapillary PH. In contrast, there is clear recommendation against the use of PDE5i in
patients with HFpEF who have isolated postcapillary PH.
In patients with a severe pre- capillary component (PVR >5 WU),
an individualized approach to treatment is recommended.

21. (8) For PH associated with lung diseases and/or hypoxia, ‘severe PH’ is
defined by a PVR >5 WU.
In such patients, an individualized approach to treatment is recommended.
Inhaled treprostinil may be considered in patients with PH associated with
interstitial lung disease(ILD).
 COPD= Chronic obstructive pulmonary disease
 CPFE = Combined pulmonary fibrosis and emphysema
 ILD =Interstitial lung disease
Hypoxemia at rest and/or during exercise

22. (9) For patients with CTEPH, a multi-modality approach to treatment is
recommended, considering pulmonary endarterectomy(PEA), balloon
pulmonary angioplasty(BPA), and medical therapy.
Overlap in treatments/multimodality approaches in chronic CTEPH

23. Collaborative team approach for the diagnosis & management of patients with PH.
(10) It is recommended for PH centres to provide care by
a multi- disciplinary team, which collaborates with patient associations, and is
involved in research, teaching, and education.
Editorial/Rev Esp Cardiol.
2023;76(5):294–300

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