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WHO-FC
with
•
Exercise testing is measured with the 6-min walking test (6MWT) or with the
IV is
characterized by an inability to perform any physical activity,
evident signs of right ventricular failure.
cardiopulmonary exercise testing (CPET), a non-invasive method used to assess
the performance of heart and lungs at rest and during exercise. CPET offers
several benefits over 6MWT in assessing patients’ exercise capacity but requires
specific technical equipment and must be performed by highly trained medical
personnel.
•
Biomarkers: the most used is brain natriuretic peptide (BNP). BNP precursor is
secreted by heart cells and it is then splitted in the active BNP and a N-terminal
fragment (NT-proBNP). Serum BNP/NT-proBNP levels have been exhibited to
reflect right ventricular dysfunction severity in PAH, correlating with mPAP, PVR,
and right ventricle mass, and inversely correlating with CO and ejection fraction [35].
Echocardiography: many echocardiographic parameters can play a role in the
•
assessment of PAH. One of the most important is pericardial effusion, due to
decreased venous and lymphatic drainage from the myocardium [36]. Another
relevant parameter is TAPSE, a measure of the right ventricular systolic function:
TAPSE<18 mm is associated with right ventricle systolic and diastolic
a
dysfunction.
•
Right heart catheterization (RHC), the gold standard method for diagnosing
Both of these factors have a great link with the prognosis of patients.
PAH: it should be performed at baseline and 3–4 months after the initiation of
therapy, in order to understand if the patient is responding to treatment. Even if
it is considered to be the gold standard, RHC has some disadvantages: it has to be
performed in high expertise center and it is an invasive procedure.
Many scores can help predict survival and assess patient’s risk, such as the REVEAL
2.0
risk score, which takes into consideration 12 variables, such as demographic,
comorbidities,
RHC or the ESC/ESR score.
gram,
3.3.4
Treatment
NYHA class, vital signs, hospitalization, 6MWT, BNP, echocardio-
PAH treatment is based on the severity of disease at diagnosis and on the evalua-
tion
of
how the individual will respond to treatment, using a multiparametric risk
stratification
namic
according
despite
ET1,
NO, and prostacyclin pathways (Figure 2). Therefore, the current progress
observed
approach. Clinical, exercise, right ventricular function, and hemody-
parameters are combined to outline a low-, intermediate- or high-risk status,
to
the expected 1-year mortality. PAH remains a severe clinical condition,
the availability over the past 15 years of multiple drugs interfering with the
in
the medical therapy of PAH is not related to the detection of new pathways, but the development of new strategies of combination therapy and escalation of
treatments
based on clinical response.
The current treatment algorithm provides the most appropriate initial strategy,
including
ment
assessments.
11
monotherapy, or double or triple combination therapy. Additionally, treat-
escalation is required in case low-risk status is not achieved in planned follow-up
Usually, treatment starts with general supportive therapies: these
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Figure 2.
Biological pathways involved in the pathogenesis of PAH. Pre-pro-ET: Pre-pro-endothelin; pro-ET: Proendothelin; ET > 1: Endothelin-1ETA/ETB: ET receptor subtypes A and B; ERA: Endothelin receptor agonist;
sGC: Soluble guanylate cyclase; sGCs: sGCs stimulator; PDE5: Phosphodiesterase type 5; PDE-5-i: PDE5
inhibitors; cGMP: Cyclic guanosine monophosphate (GMP); cAMP: Cyclic adenosine monophosphate; PGI2
analogues: Prostaglandin I2 analogues.
measurements, include oxygen supplementation, supervised physical exercise, respiratory rehabilitation, diuretic therapy, and psychosocial support for the patient and
his family [37]. Moreover, the fundamental milestone of the treatment is the specific
therapy that address the three main specific pathways altered in PAH.
3.3.4.1 Drugs targeting the NO pathway
3.3.4.1.1 Sildenafil
It is a selective inhibitor of type 5 phosphodiesterase (5-PDEi), which specifically
degrades cyclic guanosine monophosphate and its level is increased in pulmonary
arteries. Normally, NO stimulates intracellular soluble guanylate cyclase resulting in
increased levels of cGMP, which then acts to mediate smooth muscle relaxation; in
PAH, there is a decrease in NO production from the endothelium. Therefore, sildenafil
inhibits 5-PDEi, preventing degradation of cGMP and prolonging its effects. The
SUPER-1 trial, a double-blind, and placebo-controlled trial demonstrated a significant
increase in the walked distance of the 6MWT, in the WHO functional class and the
hemodynamic parameters in the sildenafil group [38]. Thence, the SUPER-2 trial
assessed long-term safety and tolerability of sildenafil treatment: it proved that the
drug is generally well tolerated, and, after 3 years, the majority of patients (60%) who
entered the SUPER-1 trial improved or maintained their functional status, and 46%
maintained or improved 6MWT [39]. Common adverse effects of this therapy are
diarrhea, dyspepsia, and flushing.
12
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3.3.4.1.2
Tadalafil
It is an alternative molecule and has a better pharmacokinetic profile than silden-
In
afil.
6MWT
adverse
3.3.4.1.3
the PHIRST-1 trial, tadalafil demonstrated a significant improvement in
and hemodynamic parameters, such as mPAP and PVR [40]. Common
effects of this therapy are myalgia, flushing, and headache.
Riociguat
It is a direct activator of guanylate-cyclase, which synthesizes NO. In the 12-week
PATENT-1
vant
pretreated
assessed
the
long-term treatment of these patients [41].
3.3.4.2
3.3.4.2.1
study, Riociguat was well tolerated and improved several clinically rele-
end-points in patients with PAH who had never received a treatment or had been
with endothelin-receptor antagonists or prostanoids. The PATENT-2 trial
the long-term safety and efficacy of Riociguat, which resulted to be safe in
Drugs targeting the ET1 pathway: endothelin receptor antagonist (ERA)
Bosentan
It is a dual acting ERA, binding to both the ETA and ETB receptors. Two subtypes
ET1 receptor exist: endothelin receptor subtype A (ETA) is mainly found in smooth
of
muscle
smooth
ET1
several
generally
which
and also on fibroblasts, while ET 1 receptor subtype B (ETB) is expressed on
muscle and endothelial cells. Endothelial ETB activation mediates clearance of
and vasodilatation by NO and prostacyclin release. Bosentan has been studied in
clinical PAH trials, such as BREATHE-1, TRUST, and EARLY [42], with
positive results. One of the main problems with Bosentan is hepatotoxicity,
initially presents as a raised levels of alanine aminotransferase and aspartate
aminotransferase.
3.3.4.2.2
Ambrisentan
It is an ERA that only blocks receptor ETA. It has been shown to increase exercise
capacity
to
5-PDEi.
therapy
compared
3.3.4.2.3
and hemodynamics with an acceptable side-effect profile. It has also proven
be
safely used in combination with other PAH-specific medications, especially with
In
the recent randomized trial ambition, it was proven that upfront dual
of
ambrisentan and tadalafil considerably decreases the risk of clinical failure
with monotherapy [43].
Macitentan
It is a dual ERA developed by adjusting the basic structure of bosentan, in order to
increase
the efficacity and safety, and it is approved for the treatment of PAH.
In contrast with bosentan, macitentan also has a longer binding with the ET1
receptor
Macitentan
and a better tissue penetration [44]. One of the most important trials on
was the SERAPHIN trial, a multicenter, double-blind, randomized,
placebo-controlled,
cant
reduction in morbidity and mortality in patients with PAH [45]. Common
adverse
13
effect is anemia.
and event-driven phase 3 trial. This trial demonstrated a signifi-
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3.3.4.3 Drugs targeting the prostacyclin pathway: prostacyclin analogues and prostacyclin
receptor agonist
3.3.4.3.1 Epoprostenol
It is a synthetic prostacyclin, approved by FDA in December 1995 for the treatment of PAH. The pharmacological effects of epoprostenol are due to pulmonary and
systemic arterial vasodilation. The effects on platelet aggregation are directly opposite
to TXA
. Epoprostenol has been demonstrated to be one of the safest treatment pro-
2
tocols for PH. It is also one of the best treatments to reduce the mortality rate in
patients with idiopathic PAH [46]. Due to its short half-life (3–5 min), epoprostenol
must be administered intravenously via continuous infusion pomp and a permanent
tunneled catheter and, in order to maintain its safety-efficacy profile dose-dependent
adjustments are necessary. Major adverse events are headaches, nausea/vomiting,
flushing, myalgias, jaw pain, diarrhea, and upper respiratory tract infections.
3.3.4.3.2 Treprostinil
Treprostinil is an analog of Epoprostenol and can be administered by subcutaneous
injection, intravenous infusion, or inhalation.
The several methods of administration, an extended half-life, and its stability at
room temperature give treprostinil a pro over Epoprostenol, Iloprost, and Selexipag,
the three other FDA-approved drugs targeting the prostacyclin pathway. Moreover, in
clinical trials, treprostinil enhanced exercise capacity measured with 6MWT, quality
of life, WHO functional class, and the clinical status of patients [47].
Usual adverse effects are dizziness, nausea, pain in the jaw and extremities, diarrhea, flushing, and headache.
3.3.4.3.3 Iloprost
It is a stable prostacyclin analog, available as an inhalant and intravenous preparation for PAH. The principal limitation of this inhaled formulation is the need for daily
recurring iloprost inhalations, ranging from 6 to 9, and this can decrease patients’
compliance with pharmacological treatment.
3.3.4.3.4 Selexipag
It is an oral, non-prostacyclin, and IP receptor agonist, approved by FDA in
December 2015. Its molecule is very stable and has a long half-life: its effects are
vasodilation of the pulmonary circulation, inhibition of platelet aggregation, and antiinflammatory effects. In the GRIPHON study, a phase 3 multicenter, randomized,
double-blind, and placebo-controlled trial. 1156 patients with PAH were randomly
assigned to receive either placebo or Selexipag. It resulted that among patients with
PAH, the risk of the primary composite end point of death or complication related to
PAH was significantly lower with Selexipag than with placebo. Instead, there was no
significant difference in mortality between the two study groups [48]. Therefore,
selexipag is indicated for use in patients with World Health Organization functional
class (FC) II or III diseases. Common adverse effects are headache, diarrhea, and
nausea.
14
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Treatment is started with an oral combination therapy of two different types of
then, patients are evaluated after 3–6 months. If patients are at high risk, triple
drugs;
therapy
3.4
can be considered, adding parenteral prostanoids.
Chronic thromboembolic pulmonary hypertension
Chronic thromboembolic PH (CTEPH) is a specific subtype of PH, included within
4. It is
Group
segmental,
incidence
symptoms:
pulmonary
physiology
embolic
characterized by partial obstruction or total occlusion of subsegmental,
or
larger pulmonary arteries by post-embolic fibrotic material. CTEPH
is
uncertain due to difficulties in diagnosing this disease and lack of specific
incidence is estimated to be 4 cases per million [49]. Incidence after acute
embolism is estimated to vary between 0.4% and 9.1% [50]. The patho-
is
peculiar: CTEPH is the result of partial and incomplete resolution of
clots after acute pulmonary embolism, because of impaired fibrinolysis.
The residual intraluminal thrombi phenomena of inflammation, fibrosis, and
organization
highly adherent to the pulmonary vascular wall, containing collagen, elastin, and
clots
inflammatory
mainly
remodeling
to
idiopathic PAH, has been described in small vessels distal to unoccluded arteries.
The
pathogenesis of this micro vasculopathy is not clear: it has been proposed that
pulmonary
leads
in
thelial
lead to development of typical CTEPH lesions characterized by yellow
cells (in contrast to fresh and red clots of acute pulmonary embolism,
consisting of erythrocytes and platelets in a fibrin mesh). In addition, vascular
characterized by intimal fibrosis and fibromuscular proliferation, similar
blood flow redistribution from occluded vessels to non-obstructed areas
the long term to local high-flow pressure and shear stress promoting endo-
dysfunction [51].
Vascular remodeling resulting from incomplete clot resolution and microvas-
culopathy
failure.
such
stages,
Early
leads to increased pulmonary vascular resistance and right ventricular
Patients affected by CTEPH can display many and non-specific symptoms,
as
shortness of breath on exertion in the early stages and at rest in advanced
chest pain, and increased fatigue.
diagnosis remains a challenge and it affects prognosis and survival rate.
The gold standard for diagnosis is RHC, which displays mPAP >20 mmHg, but it
has
to be
associated with ventilation/perfusion (V/Q) scintigraphy that shows at least
large perfusion defect in one segment or two subsegments. CT scan has also
one
an
shown
pathway
CTEPH
excellent diagnostic efficacy, and it is usually included in the diagnostic
of
CTEPH. A correct and early diagnosis is of fundamental importance, as
is
the only PH subtype suitable for a surgical treatment and potentially
curable.
Treatment of choice is pulmonary endarterectomy (PEA): within the use of
circulatory
from
operability
diseases,
(inaccessible
the
accumulation of surgical experience have contributed to the latest surgical
development,
can
be
Balloon
has
been included in the treatment algorithm of CTEPH: it is reserved for patients that
cannot
arrest and hypothermia, it implicates the removal of organized tissue
pulmonary vessels. The milestone of the surgical treatment is to define the
of
patient: this is based on age, comorbidities (diabetes mellitus, lung
hypertension, asthma, and coronary heart disease) and anatomical reasons
or
distal thrombi). Although, the progress in diagnostic pathways and
redefining the distal limits of PEA. Therefore, in expert centers, surgery
performed successfully in patients with thromboembolism of the distal vessels.
pulmonary angioplasty (BPA) is an emerging interventional treatment and
undergo surgical treatment with PEA due to distal thrombi or continuous
15
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symptoms after surgery. It involves the insertion of a balloon catheter into pulmonary
vessels to dilate pulmonary stenosis in order to improve hemodynamics parameters,
clinical symptoms, exercise capacity, and RH compliance, with a low rate of complications [52]. Complications can occur during the procedure (vascular injury, wire
perforation, vascular dissection, balloon over dilatation, and others) or after the
procedure, and include lung injury, contrast-induced kidney injury, and peripheral
access site problems.
Likely between 20% and 40% of patients cannot undergo either of these
treatments or show residual PH after interventional therapy and are amenable to
medical therapy. This includes diuretics, oxygen therapy, and lifelong anticoagulation.
Anticoagulation therapy can be done with either warfarin or direct oral anticoagulants: the choice is up to the doctor, who evaluates bleeding risk, renal impairment,
and decides which therapy suits better for the patient.
Riociguat has been approved for the treatment of CTEPH, it determines vasodilatation and has anti-fibrotic, anti-proliferative, and anti-inflammatory activity.
Other specific drugs are currently tested with positive results in these patients,
such as Macitentan and Treprostinil [53].
4. A look to the future
PH is a complex and multifactorial disease, triggered a nd sustained by m any
pathological alter ations. The three main modified pathways in PAH (NO, ET1, and
PGI2) have been uncovered and targeted with appropriate pharmacological therapy,
leading to an improvement in symptoms, quality of life, and survival of these
patients.
In the next few years, scientists will focus their attention on researching new
molecular targets that can have a role in the pathogenesis of the disease. For example,
there is a trial ongoing on Rho-associated protein kinase (ROCK), which is involved in
many cellular functions, such as smooth muscle cell contraction, cell migration, and
others. It also has been demonstrated to play a role in the pathogenesis of PH. So,
scientists are developing ROCK’s inhibitors [54]. Another target is apelin, an endoge-
nous vasodilator, which levels are decreased in PAH. Therefore, apelin infusion is
being considered and trials are still ongoing [55].
Other drugs target inflammation and immunity: Ubenimex has been tested in a
clinical trial but reported no improvement of symptoms and exercise capacity, tested
with 6MWT [56].
Additionally, cytokines like IL-6 are overexpressed in PH, so drugs that function as
inhibitors of this cytokine can play a role in future pharmacological treatment and are
still going through appropriate development and testing [57].
Also, therapy targeting BMPR2 pathway has been considered: it has been shown
that there is a decreased expression of this gene in heritable PAH and 20% of idiopathic PAH [58].
Moreover, there is evidence that PAH patients usually have low levels of iron.
Actual guidelines suggest that iron supplementations should be considered. Kramer
et al., assessed with a long-term study the use of ferric carboximaltose in PAH patients
with iron deficiency: iron supplementation has demonstrated an improvement in
clinical status, exercise capacity, and a decrease in hospitalization rate [59]. This
resulted in an increase in 6MWT distance and a better WHO-FC and, consequently, a
decreased risk calculated by ESC/ESR risk score.
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References
[1] Boyette LC, Burns B. Physiology,
pulmonary circulation. In: StatPearls
[Internet]. Treasure Island, FL: StatPearls
Publishing; 2021, 2022 PMID: 30085539
[2] Suresh K, Shimoda LA. Lung
Circulation. Comprehensive Physiology.
2016;6(2):897-943. DOI: 10.1002/cphy.
c140049 PMID: 27065170; PMCID:
PMC7432532
[3] Parasuraman S, Walker S,
Loudon BL, Gollop ND, Wilson AM,
Lowery C, et al. Assessment of
pulmonary artery pressure by
echocardiography—A comprehensive
review. International Journal of
Cardiology Heart & vasculature. 2016;
12:45-51. DOI: 10.1016/j.
ijcha.2016.05.011
[4] Simonneau G, Montani D, Celermajer
DS, Denton CP, Gatzoulis MA, Krowka
M, Williams PG, Souza R.
Haemodynamic definitions and updated
clinical classification of pulmonary
hypertension. European Respiratory
Journal. 2019;53(1):1801913. DOI:
10.1183/13993003.01913-2018. PMID:
30545968; PMCID: PMC6351336
world symposium on pulmonary
hypertension: What's old is new.
F1000Research. 2019;8, F1000 Faculty
Rev-:888. DOI: 10.12688/
f1000research.18811.1 (European
Respiratory Journal Jan 2019, 53 (1)
1801913; DOI: 10.1183/13993003.
01913-2018)
[7] Naeije R, Chin K. Differentiating
precapillary from postcapillary
pulmonary hypertension. Circulation.
2019;140(9):712-714. DOI: 10.1161/
CIRCULATIONAHA.119.040295 Epub
26 August 2019. PMID: 31449453
[8] Mehra P, Mehta V, Sukhija R,
Sinha AK, Gupta M, Girish MP, et al.
Pulmonary hypertension in left heart
disease. Archives of Medical Science.
2019;15(1):262-273. DOI: 10.5114/
aoms.2017.68938 Epub 17 July 2017.
PMID: 30697278; PMCID: PMC6348356
[9] Widrich J, Shetty M. Physiology,
pulmonary vascular resistance. In:
StatPearls [Internet]. Treasure Island
(FL): StatPearls Publishing; 2022 19
August 2021. PMID: 32119267
[5] Galiè N, Humbert M, Vachiery J-L,
Gibbs S, Lang I, Torbicki A, et al. ESC/
ERS guidelines for the diagnosis and
treatment of pulmonary hypertension:
The joint task force for the diagnosis and
treatment of pulmonary hypertension of
the European Society of Cardiology
(ESC) and the European Respiratory
Society (ERS): Endorsed by: Association
for European Paediatric and Congenital
Cardiology (AEPC), International
Society for Heart and Lung
Transplantation (ISHLT). European
Heart Journal. 2015, 2016;37(1):67-119
[6] Condon DF, Nickel NP, Anderson R,
Mirza S, de Jesus Perez VA. The 6th
18
[10] Moncada S, Palmer RMJ, Higgs EA.
Nitric oxide: Physiology,
pathophysiology and pharmacology.
Pharmacological Reviews. 1991;43:
109-142
[11] Al-Omary MS, Sugito S, Boyle AJ,
Sverdlov AL, Collins NJ. Pulmonary
hypertension due to left heart disease:
Diagnosis, pathophysiology, and
therapy. Hypertension. 2020;75(6):
1397-1408. DOI: 10.1161/HYPER
TENSIONAHA.119.14330 Epub 27
April 2020. PMID: 32336230
[12] Guazzi M, Ghio S, Adir Y.
Pulmonary hypertension in HFpEF and
Pulmonary
289
https://t.me/medicina_free
DOI:
Hypertension
http://dx.doi.org/10.5772/.107281
HFrEF:
Journal
Cardiology.
DOI:
JACC review topic of the week.
of
the American College of
2020;76(9):1102-1111.
10.1016/j.jacc.2020.06.069 PMID:
32854845
[13]
Moraes DL, Colucci WS,
Givertz
hypertension
The
pathophysiology
Circulation.
DOI:
MM. Secondary pulmonary
in
chronic heart failure:
role of the endothelium in
and management.
2000;102(14):1718-1723.
10.1161/01.cir.102.14.1718 PMID:
11015353
Abramson SV, Burke JF, Kelly JJ Jr,
[14]
et
al. Pulmonary hypertension predicts
mortality
dilated
Internal
[15]
Semigran
ventricular
exercise
advanced
American
and morbidity in patients with
cardiomyopathy. Annals of
Medicine. 1992;116:888-895
Di Salvo TG, Mathier M,
MJ, et al. Preserved right
ejection fraction predicts
capacity and survival in
heart failure. Journal of the
College of Cardiology. 1995;25:
1143-1153
Desai A, Desouza SA. Treatment of
[16]
pulmonary
disease:
Health
hypertension with left heart
A
concise review. Vascular
and Risk Management. 2017;13:
415-420
[17]
Fraser KL, Tullis DE, Sasson Z,
Hyland
Pulmonary
function
hypoxemia.
RH, Thornley KS, Hanly PJ.
hypertension and cardiac
in
adult cystic fibrosis: Role of
Chest. 1999;115(5):
1321-1328
and chronic obstructive pulmonary
disease. American Journal of Respiratory
and Critical Care Medicine. 2005;172:
189-194
[20] Nathan SD, Shlobin OA, Ahmad S,
et al. Serial development of pulmonary
hypertension in patients with idiopathic
pulmonary fibrosis. Respiration. 2008;
76:288-294
[21] Santos S, Peinado VI, Ramirez J,
et al. Characterization of pulmonary
vascular remodeling in smokers and
patients with mild COPD. The European
Respiratory Journal. 2002;19:632-638
[22] Colombat M, Mal H, Groussard O,
et al. Pulmonary vascular lesions in endstage idiopathic pulmonary fibrosis:
Histopathologic study on lung explant
specimens and correlations with
pulmonary hemodynamics. Human
Pathology. 2007;38:60-65
[23] Kim K-H, Maldonado F, Ryu JH,
et al. Iron deposition and increased
alveolar septal capillary density in
nonfibrotic lung tissue are associated
with pulmonary hypertension in
idiopathic pulmonary fibrosis.
Respiratory Research. 2010;11:37
[24] Ruffenach G, Hong J,
Vaillancourt M, Medzikovic L,
Eghbali M. Pulmonary hypertension
secondary to pulmonary fibrosis: Clinical
data, histopathology and molecular
insights. Respiratory Research. 2020;
21(1):303. DOI: 10.1186/s12931-02001570-2
Mirrakhimov AE, Strohl KP. High-
[18]
altitude
update
management.
Medicine
[19]
et
19
pulmonary Hypertension: An
on
disease pathogenesis and
Open Cardiovascular
Journal. 2016;10:19-27
Chaouat A, Bugnet A-S, Kadaoui N,
al. Severe pulmonary hypertension
[25] Mura M, Anraku M, Yun Z, et al.
Gene expression profiling in the lungs of
patients with pulmonary hypertension
associated with pulmonary fibrosis.
Chest. 2012;141:661-673
[26] Patrizio V, Callari A, Martino L,
Stanziola A, Oggionni T, Federica M,
Novel Pathogenesis and Treatments for Cardiovascular Disease
290
https://t.me/medicina_free
et al. SPHERIC-1 (Sildenafil and
Pulmonary HypERtension in COPD):
Intention-to-Treat (ITT) Analysis of
Safety and Efficacy Data. The Journal of
Heart and Lung Transplantation. 2014;
33:S148-S149. DOI: 10.1016/j.
healun.2014.01.398
[27] Waxman A, Restrepo-Jaramillo R,
Thenappan T, et al. Inhaled Treprostinil
in pulmonary hypertension due to
interstitial lung disease. New England
Journal of Medicine. 2021;384(4):
325-334. DOI: 10.1056/NEJMoa2008470
[28] Levine DJ. Pulmonary arterial
hypertension: Updates in epidemiology
and evaluation of patients. The
American Journal of Managed Care.
2021;27(3 Suppl):S35-S41.
DOI: 10.37765/ajmc.2021.88609 PMID:
33710842
[29] Pauwaa S, Machado RF, Desai AA.
Survival in pulmonary arterial
hypertension: A brief review of registry
data. Pulmonary Circulation. 2011;1(3):
430-431. DOI: 10.4103/2045-8932.87314
[30] Farber HW, Miller DP, Poms AD,
Badesch DB, Frost AE, Muros-Le
Rouzic E, et al. Five-year outcomes of
patients enrolled in the REVEAL
registry. Chest. 2015;148(4):1043-1054.
DOI: 10.1378/chest.15-0300 PMID:
26066077
[31] Makino A, Firth AL, Yuan JX.
Endothelial and smooth muscle cell ion
channels in pulmonary vasoconstriction
and vascular remodeling. Comprehensive
Physiology. 2011;1(3):1555-1602
[32] Galie N, Manes A, Branzi A. The
endothelin system in pulmonary arterial
hypertension. Cardiovascular Research.
2004;61:227-237
[33] Tuder RM, Cool CD, Geraci MW,
Wang J, Abman SH, Wright L, et al.
Prostacyclin synthase expression is
decreased in lungs from patients with
severe pulmonary hypertension.
American Journal of Respiratory and
Critical Care Medicine. 1999;159:
1925-1932
[34] Le RJ, Fenstad ER, Maradit-Kremers
H, et al. Syncope in adults with
pulmonary arterial hypertension. Journal
of the American College of Cardiology.
2011;58:863-867
[35] Fijalkowska A, Kurzyna M,
Torbicki A, et al. Serum N-terminal
brain natriuretic peptide as a prognostic
parameter in patients with pulmonary
hypertension. Chest. 2006;129:1312-1321
[36] Raymond RJ, Hinderliter AL,
Willis PW, et al. Echocardiographic
predictors of adverse outcomes in
primary pulmonary hypertension.
Journal of the American College of
Cardiology. 2002;39:1214-1219
[37] Guillevin L, Armstrong I,
Aldrighetti R, Howard LS, Ryftenius H,
Fischer A, et al. Understanding the
impact of pulmonary arterial
hypertension on patients’ and carers’
lives. European Respiratory Review.
2013;22:535-542
[38] Galiè N, Ghofrani HA, Torbicki A,
Barst RJ, Rubin LJ, Badesch D, et al.
Sildenafil use in pulmonary arterial
hypertension (SUPER) study group.
Sildenafil citrate therapy for pulmonary
arterial hypertension. The New England
Journal of Medicine. 2005;353(20):
2148-2157. DOI: 10.1056/NEJMoa050010
Erratum in: N Engl J Med. 2006;354(22):
2400-1. PMID: 16291984
[39] Rubin LJ, Badesch DB, Fleming TR,
Galiè N, Simonneau G, Ghofrani HA,
et al. Long-term treatment with
sildenafil citrate in pulmonary arterial
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