The RV needs much less muscle mass

than the LV because it pumps against

lower pressures
The pulmonary circulation is characterized
by high flow (the entire right ventricular
output) and by low pressure and low
resistance
 HYPOXIA.
The effect of oxygen on the pulmonary
vasculature is the most distinctive
characteristic by which it differs from the
systemic vasculature.
Alveolar hypoxia results in local vasoconstriction
 NITRIC OXIDE.
The biological action of nitric oxide (NO) is
similar to that of prostacyclin in the way in
which it relaxes vascular smooth muscle
inhibits platelet activation
 ENDOTHEL
.
IN .
vasoconstriction and cellular proliferation
by increasing intracellular calcium

ET-1 has vasoconstrictive and mitogenic

effects, stimulates the production of growth
factors such as fibroblast,
 Altitude
Life at high altitudes is associated with
pulmonary hypertension of variable
severity, reflecting the pulmonary
vasoconstrictive effect of chronic hypoxia.
plexiform lesion, which was first
considered characteristic (but not
pathognomonic) of PPH, but is now
known to occur in many forms of PH
TX de la HAP siempre dependiendo de la
causa subyacente
Cual tipo de HAP es el mas frecuente;

A) tipo 1
B) tipo 2
C) tipo 3
D) tipo 4
E) tipo 5
Hemodinámicamente se diferencia hap.
1 de causas cardiacas o tipo 2;
PRIMARY PULMONARY HYPERTENSION

is a mean pulmonary artery pressure

greater than 25 mm Hg at rest
disease of young women. between 20 and 45
years of age
PATHOGENESIS AND ETIOLOGY
,
An imbalance between prostacyclin and
thromboxane

a defect in the vasodilatory,

antiproliferative molecule nitric oxide

An excess in endothelin-1
treatment strategies aimed at replacing the
deficient (nitric oxide, prostacyclin) and
blocking the overproduced (endothelin-1)
 Connective Tissue Disease
they may be considerably more common than primary
pulmonary hypertension itself and share many features
with it.
Patients with the scleroderma spectrum of diseases, most
notably limited scleroderma (previously known as CREST
syndrome) have been reported to have pulmonary
hypertension in up to 40% of cases. Pulmonary vascular
involvement is associated with worse survival in
scleroderma.
Other connective tissue diseases albeit less commonly,
include systemic lupus erythematosus mixed connective
tissue diseas and rheumatoid arthritis.
 Intracardiac
Shunts
Congenital heart disease is a well-recognized
"risk factor" for development of pulmonary
arterial hypertension
Eisenmenger complex to describe pulmonary
hypertension at the systemic level due to high
pulmonary vascular resistance, with reversed
shunting through a large ventricular septal
defect. Subsequently the term has been used to
describe pulmonary hypertension with cyanosis
and any systemic-to-pulmonary circulatory
shunt..
 Liver
PortalDisease
hypertension
The mechanism of pulmonary hypertension development in portal
hypertension is not known. One hypothesis is that portosystemic
shunting allows vasoactive substances, normally cleared in the liver
 Drugs
aminorex, an appetite suppressant
resembling epinephrine and amphetamine
fenfluramine and dexfenfluramine
Illicit drug
 EPOC
Pulmonary airway disease (e.g., chronic
bronchitis and emphysema)
Respiratory function tests (FVC/FEV1,
chest x-ray)
 El TX pilar del tipo
EPOC es tipo 3
Dado que el mecanismo es hiopoxia el
tratamiento es a base de
oxigeno
cuanto tiempo de oxigeno?
18 horas
Los vasodilatadores dado que producen
redistribución a zonas de hipoxemia, No son
parte fundamental del Tx como
sildenafil o calcio antagonistas
 SYMPTOMS
Dyspnea is the cardinal symptom of primary
pulmonary hypertension, occurring in more than
95% (tambien se puede describir como fatiga en el
examen)
The most likely cause for the dyspnea of pulmonary
hypertension is the inadequacy of cardiac output
relative to metabolic requirements
Closely related to dyspnea are fatigue and weakness,
reported by a majority. They presumably reflect
impaired tissue oxygenation resulting from the
depressed cardiac output
 Histor
With the onset of right ventricular failure, lower
extremity edema.
y
Angina is also a common symptom, generally
representing more advanced disease. It likely
represents reduced coronary blood flow to a
markedly hypertrophied right ventricle
syncope or near-syncope
coughing.
Hemoptysis presumably stems from
microvascular aneurysms that rupture under
the high pulmonary artery pressure. with
advanced mitral stenosis also present with
hemoptysis
hoarseness may result from pressure of the enlarged main
pulmonary artery on the recurrent laryngeal nerve
Paroxysmal nocturnal dyspnea is strongly
suggestive of pulmonary venous
hypertension
 Physical Examination
large a wave in the jugular venous pulse
,
loud pulmonic component,
holosystolic murmur of tricuspid
regurgitation
signs of right ventricular failure (e.g.,
hepatomegaly, peripheral edema, and ascites)
Cyanosis is a late finding and usually
attributable to a markedly reduced cardiac
output, with systemic vasoconstriction and
ventilation-perfusion mismatch in the lung.
 jugular venous pulse
Visualization
The patient is positioned
under 45°, and the
filling level of the
jugular vein determined. In
healthy people, it is
maximum several (3-4)
centimetres above the sternal
angle. A pen-light can
aid in discerning the
jugular filling level by
providing tangential
light.
 Tipo 4; por TEP cronica
El DX del tipo 4 es con;
A) gasometría que muestre hipoxemia
B) Ecocardiograma
C) gammagrafía ventilatoria perfusoria
D) angiotac de tórax
E) electrocardiograma con S1,Q3,T3
LA tep aguda se DX con;
Angiotac

Pero al TEP crónica es mas difícil ver el

trombo en las arterias pulmonares.
Se observa mejor las consecuencias de la
tep crónica en la gamagrafía ventilatoria
perfusoria por tanto es el DX de elección
en TEP cronica tipo 4
Braunwald 2014
El Tx de eleccion en la HAP por TEP
cronica o tipo 4 es;
A) antiagregantes plaquetarios
B) anticoagulantes
C) sildenafil
D) cirugía con endarterectomia
E) Epoprostenol
Braunwald 2014
El Tx de eleccion en la HAP por TEP
cronica o tipo 4 es;
A) antiagregantes plaquetarios
B)anticoagulantes como warfarina o
acenocumarina hasta tener un INR entre
2y3
C) sildenafil
D) calcio antagonistas
E) Epoprostenol
El Tratamiento de la TEP crónica con
HAP o tipo IV

Endarterectomia

Anticoagulantes
 Ingurgitacion
yugular
Hepatomegalia
Edema M. Inf.
 estudios
echocardiogram will be indicated in most
cases
 laboratorio
If chronic arterial oxygen desaturation exists,
polycythemia should be present.
Brain natriuretic peptide (BNP) levels are
elevated in patients with pulmonary
hypertension and correlate positively with the
pulmonary artery pressure.
BNP is secreted predominantly from cardiac
ventricles through a constitutive pathway and is
affected by the degree of myocardial stretch,
damage, and ischemia in the ventricle
 Radiography
reveals protrusion
of the main
pulmonary artery,
increased width of
the descending
branch of the right
pulmonary artery,
peripheral
oligemia, and an
increase in the
cardiothoracic
ratio.
 Electrocardiography
R-to-S ratio in lead V1 that is greater than 1, and
an R-to-S ratio in lead V6 that is less than 1.
right atrial enlargement with a symmetrical and
peaked P wave in lead II that is greater than
2.5 mm in amplitude;
ST segment depression and T wave inversion
may be seen in the anterior chest leads
(sobrecarga sistolica)
This electrocardiogram was recorded from a
patient with repeated pulmonary emboli
TREATMENT AND PROGNOSIS
Buen o mal px?

Primary PH (PPH), has a median survival of

2.8 years if left untreated
establish the underlying etiology and
should be focused on treating the
underlying cause
Ej. Oxygen administration in patients
with COPD and hypoxemia has been
shown to improve long-term survival
TREATMENT AND PROGNOSIS
.
oxygen should be given to hypoxemic patients, and
cigarette smoking should be avoided
 Warfarin
the value of anticoagulation has yet to be
established in a prospective randomized
trial
Four agents or classes of agents have been
employed:
calcium channel antagonists,
intravenous epoprostenol (prostaglandin
I2),
prostacyclin analogues,
and endothelin receptor antagonists
El medicamento que ha demostrado aumento en
la sobrevida en HAP 1 o idiopatoca es;

A) calcio antagonistas
B) sildenafil
C) Epoprostenol
D) Bosentan
E) Iloprost
F) Macitentan
 Calcium
antagonist
Recent data suggest that no more than 6%
of patients will sustain a long-term benefit
from calcium channel antagonists.
Nifedipine, diltiazem, and amlodipine.
Moreover, calcium channel antagonist
therapy may cause significant morbidity
and even mortality in "nonresponders,"
given their effects on systemic blood
pressure and negative inotropy.
Tx base de la HAP tipo 1
 Prostacyclin Analogues
IV prostacyclin (epoprostenol) is a short half-life drug
indicated for patients in NYHA or WHO functional class III-IV.
It is expensive and requires a continuous IV infusion via an
external pump and central line. It is the only therapy shown to
decrease PPH mortality in a randomized, controlled trial
Subcutaneous prostacyclin (treprostinil) It is expensive and
requires a continuous subcutaneous infusion delivered by a
small pump and catheter-related infections are rare.
Inhaled prostacyclin (iloprost) has been approved in Europe
for patients with functional class III-IV PPH. It improves
exercise tolerance, but it requires 6-9 inhalations a day
Oral prostacyclin (beraprost) has been approved in Japan
and is currently under evaluation in Europe
 Endothelin-Receptor Antagonists
Bosentan is a nonselective oral ETA and ETB
antagonist

. Frequent monitoring of liver function tests

is indicated.Sitaxsentan and ambrisentan are
two ETA-selective antagonists. The
mechanism of action is similar to Bosentan,
but both have more ETA selectivity.
 Phosphodiesteras
e Inhibitors
Sildenafil, a potent and highly specific PDE-5
inhibitor, was demonstrated to improve
exercise capacity, FC, and hemodynamics in
PAH in the Sildenafil Use in Pulmonary
Hypertension (SUPER) trial
Sildenafil was approved for the treatment of
PAH by the FDA at a dose of 20 mg 3 times
per day in 2005
causing the release of nitric oxide
Braunwald 2014: inhibidores de
fosdodiesterasas; cuantos son?
La combinacion de medicamentos es
mejor que uno solo??
 Anticoagulation

PPH patients have been documented to

have thrombosis in situ.
Also, RV failure and venous stasis likely
increase the risk for PTE.
Improved survival in nonrandomized
trials has been reported when
anticoagulation is used in patients with
PPH. The target INR is 1.5-2.5
PPH has been associated with all of the
following, except:
A. Mutations in the BMPR-II.
B. Male gender.
C. Infection with the HHV-8.
D. Increased levels of endothelin-1.
E. Young age.
 intravenous infusions of prostacyclin
Continuous intravenous infusions of
prostacyclin (prostaglandin I2,
epoprostenol) Follow-up studies have
confirmed the significant effect of chronic
epoprostenol on survival compared to
historical controls,

numerous side effects, including jaw

claudication, leg and foot pain, diarrhea,
rash, weight loss,

Infecciones
treprostini treprostinil
l
A prostacyclin analogue,
treprostinil, is available as a
continuous subcutaneous
infusion. This agent has been
shown to improve exercise
tolerance and pulmonary
hemodynamics, albeit to a lesser
degree than with epoprostenol.[
191] The major challenge to
treprostinil therapy is the
sometimes debilitating pain
that occurs at the site of infusion
in many patients.
Iloprost, an analogue of
prostacyclin, has been approved for
use via inhalation
prostacyclin ,
prostacyclin (prostaglandin I2
(prostaglandin I2,
epoprostenol epoprostenol)
Treprostinil
Treprostinil
Iloprost
Iloprost
only significant adverse effect of bosentan is
elevation in hepatic enzymes, which occurs in
bosentan
approximately 5% to 10% of patients. These abnormalities appear to
be completely reversible following dose reduction or cessation
 Otros Tx
Digoxin;

DIURETICS:
symptom relief venous congestion
Oxigen:
maintain their arterial oxygen saturation
above 90 percent
 Refractario a tratamiento?
Lung transplantation is the only therapy
available for patients failing medical
treatment. Successful lung transplantation,
even of a single lung
Survival of patients with untreated primary
pulmonary hypertension is generally poor,
with a median survival in the U.S. registry
of 2.8 years.
La combinacion de medicamentos es
mejor que uno solo??
Macitentan
Macitentan; Dr. Pulido
Endothelin-receptor antagonists, phosphodiesterase
type 5 inhibitors, and prostacyclin and its analogues
have been approved for the treatment of pulmonary
arterial hypertension and adopted clinically on the
basis of short-term trials (12 to 16 weeks) that have
shown improvements in exercise capacity
current guidelines suggest that the primary end point
in phase 3 trials of new treatments for pulmonary
arterial hypertension should be morbidity and
mortality
 Metodos
idiopathic or heritable pulmonary arterial
hypertension or pulmonary arterial
hypertension related to connective-tissue
disease, repaired congenital systemic-to-
pulmonary shunts, human immunodeficiency
virus infection, or drug use or toxin exposure
were eligible for inclusion in the trial. (que
tipo de HAP es?)
Confirmation of pulmonary arterial
hypertension with the use of right heart
catheterization was required.
FDA aprobo Macitentan?Dr. Pulido INC
Se vende en México, Macitentan?
Cuanto cuesta macitentan ?
Riociguat has a dual mode of
action, acting in synergy with
endogenous nitric oxide and also
directly stimulating soluble
guanylate cyclase independently
of nitric oxide availability
Como riociguat libera oxido nitrico,
con quien no hay que usarlo?
Inotropicos en quienes?
REFRACTARIOS A
TRATAMIENTO MÉDICO ?
Refractarios a tratamiento médico
Guias Europeas 2015
Estudios
Tratamiento; Tx de falla cardiaca izquierda como
Iecas, BB, ant de aldosterona, ivabradina ??
Calcio Antagonistas
 HAP tipo 2 o por causas cardiacasSe puede
usar macitentan, sildenafil o epoprostenol?
HAP tipo 3 o por causas pulmonares