HIPERTENSI

PULMONAL

ALFA ALFIN NURSIDIQ, SP.JP, FIHA

DIVISI PENYAKIT JANTUNG STRUKTURAL
DEPARTEMEN KARDIOLOGI DAN KEDOKTERAN VASKULER
FK UNS-RSDM
 OUTLINE
• Introduction, definition
• Pathophysiology
• Diagnosis
• Laboratory Findings
• Idiopathic Pulmonary Arterial Hypertension
• Natural History
• Treatment
 PENGANTAR
Hipertensi Pulmonal:
 Peningkatan tekanan yang abnormal pada arteri
pulmonalis
 Mengakibatkan gagal jantung kiri, kerusakan
pada sistem vaskular dan parenkim paru,
tromboemboli, atau kombinasi dari hal – hal
tersebut.
 Penyebab dari hipertensi pulmonal harus
ditetapkan sebelum dilakukan pengobatan.
COR PULMONALE
Cor pulmonale :
Pembesaran pada
ventirkel kanan akibat
dari kelainan pada
jantung atau paru –
paru.
Paling sering
disebabkan oleh
hipertensi pulmonal.
Cor pulmonale
tingkat lanjut dapat
menyebabkan
kegagalan pada kerja
ventrikel kanan.
 DEFINISI 
• Hipertensi pulmonal ditentukan
berdasarkan pengukuran pada jantung
kanan melalui metode kateterisasi.
• Hipertensi Pulmonal adalah keadaan
dimana tekanan arteri pulmonal lebih
dari 25 mmHg saat istirahat.
• Nilai normal rata – rata tekanan arteri
pulmonal saat istirahat adalah 8 – 20
mmHg .
Patofisiologi
Dilated RV- Intact pericardium
 RAP

 Intrapericardial pressure
(IPP)

 LV transmural filling
pressure=
LVEDP-IPP
+
Shift of IV septum toward LV

 LV preload and  LV
distensibility

 Systemic Cardiac Output
 PATOFISIOLOGI
• Kemampuan ventrikel kanan untuk beradaptasi
terhadap peningkatan resistensi vaskular dipengaruhi
oleh usia dan progresivitas hipertensi pulmonal.
• Fase akut:  RV afterload,  EDV,  EF, SV of RV
• Fase kronik : Ventirkel kanan yang dilatasi dan
hipertrofi meningkatkan tekanan sistolik secara
progresif, Penurunan fungsi pada Ventrikel kanan
secara gradual.
• Berkurangnya darah balik vena, mempengaruhi
preload ventrikel kanan
• Coexisting hypoxemia dapat mempengaruhi
kemampuan ventrikel untuk mengkompensasi
Pathogenesis of Pulmonary Arterial
Hypertension

NORMAL REVERSIBLE DISEASE IRREVERSIBLE DISEASE

 Gejala Hipertensi
Pulmonal
 Dispnea 60%
 Kelelahan 19%
 Near syncope/syncope 13%
 Nyeri dada 7%
 Palpitasi 5%
 Edema tungkai 3%
PEMERIKSAAN FISIK
• Peningkatan JVP
• P2 mengeras (increases PAP)
• Parasternal kiri terangkat (RV heave=R sided
overload)
• Murmur pada area triskuspid (TR)
• Gallop S3 (RV failure)
• CLEAR lungs
TANDA KEPARAHAN PENYAKIT
• Sesak saat istirahat
• Menurunnya cardiac output
dengan asidosis metabolik
• Hipoksemia
• Tanda gagal jantung kanan (large
V wave on jugularis vein, edema
perifer, hepatomegali)
• Sinkop (prognosis buruk)
• Nyeri dada
 DIAGNOSIS
CXR:Enlarged proximal pulmonary
vessels,”

ECG:RAD, RAE, RVH most common

Echo:Estimate PA pressure
Assess for shunts and valvular
disease; ventricular function
 PENEMUAN PADA EKG

Sering
ditemuka
n RVH
dan RAE
RAE,RVH
 CHEST X-RAY FINDINGS

central Pul arterial and/or RV

enlargement , distal “pruning”
Note the dilated proximal
pulmonary arteries with a
relative lack of pulmonary
vasculature in the periphery.
No cardiomegaly is noted .
Chest roentgenogram from a patient with primary
pulmonary hypertension showing the marked dilation of
the main pulmonary arteries and right ventricular
enlargement.
Pulmonary hypertension.
Chest radiograph in a patient
with secondary pulmonary
hypertension reveals enlarged
pulmonary arteries. This
patient was found to have an
atrial septal defect.
 SEVERE RIGHT CHAMBER DILATION

Estimate PA
pressure
Assess for
shunts
and valvular
disease
 ventricular
function
SECONDARY PULMONARY
HYPERTENSION
SEVERITY OF PULMONARY
HYPERTENSION

Degree of disease Mean PAP (mmHg)

Mild 25 - 40
Moderate 41 - 55
Severe >55
 CATH JANTUNG KANAN

PENTING UNTUK MENEGAKAN

DIAGNOSIS:
Hindari untuk melakukan overdiagnosis!
Vasoreactivity testing
NO, Adenosine—drop in mPAP by 10 mmHg
to value < 40 mmHg
Prediksi respon terhadap CCB
Evaluasi ada tidaknya defek septum
Terangkan masalah disfungsi diastolik
Interpretasi data
 PEMERIKSAAN LABORATORIUM

ANA, RF, ESR

LFTs, hepatitis serologies
HIV antibody
Drugs (cocaine)
ALGORITHM FOR INVESTIGATION OF
SUSPECTED PH
 KOMPLIKASI

• Gagal jantung kanan (cor pulmonale).

• Blood clots.

• Aritmia. Detak jantung yang tidak teratur.

Mengakibatkan palpitasi, pusing dan pingsan.
Dapat berakibat fatal.

• Perdarahan. Hipertensi pulmonal dapat

mengakibatkan perdarahan ke paru – paru dan
hemoptisis.
 CLASSIFICATION
Group 1 "Pulmonary arterial hypertension".
1. Idiopathic (IPAH)
2. Familial (FPAH)
3. Associated with (APAH):
 Collagen vascular disease
 Congenital systemic-to-pulmonary shunts
 Portal hypertension
 HIV infection
 Drugs and toxins
 Other (thyroid disorders, glycogen storage disease, Gaucher
disease, hereditary hemorrhagic telangiectasia,
hemoglobinopathies, myeloproliferative disorders, splenectomy)
4. Associated with significant venous or capillary involvement
Pulmonary veno-occlusive disease (PVOD)
Pulmonary capillary hemangiomatosis (PCH)
5. Persistent pulmonary hypertension of the newborn
CLASSIFICATION
Group 2 : Group 3 PH —
"Pulmonary venous "Pulmonary
hypertension". hypertension
associated with
disorders of the
Examples: respiratory system or
 1. Left-sided atrial or hypoxemia".
ventricular heart disease
 2. Left-sided valvular heart Examples:
disease  1. Chronic obstructive
pulmonary disease
 2. Interstitial lung disease
 3. Sleep-disordered breathing
 4. Alveolar hypoventilation
disorders
 5. Chronic exposure to high
altitude
 6. Development
abnormalities
CLASSIFICATION
• Group 4 PH —
"Pulmonary
hypertension
caused by chronic
thrombotic or
embolic disease".
Examples:
 1. Thromboembolic
obstruction of proximal
pulmonary arteries
 2. Thromboembolic
obstruction of distal
pulmonary arteries
 3. Non-thrombotic
pulmonary embolism (tumor,
parasites, foreign material)
Group 5 PH —
These patients
have PH caused by
inflammation, mechanical
obstruction, or extrinsic
compression of the
pulmonary vasculature
•(eg, sarcoidosis,
histiocytosis X,
lymphangiomatosis,
compression of
pulmonary vessels by
adenopathy, and fibrosing
mediastinitis).
Pulmonary Hypertension: Define Lesion
Post-Capillary PH
(PCWP>15 mmHg; PVR nl)
PAH
Respiratory Atrial Myxoma
Diseases Cor Triatriatum MV Disease
PE

VC RA RV PA PV LA LV
Ao
PC LVEDP
PV Systemic HTN
compression AoV Disease
PVOD
Pre-capillary
PH Myocardial Disea
PCWP<15 mmHg DCM,HCM,ischemic CM
PVR > 3 Wu RCM,Obesity , others
IDIOPATHIC PH
PPH
uncommon,
incidence : 2 cases per million.
female predominance
presenting in the 4th and 5th decades
although the age range is from infancy to >60 years.
Familial PAH :20% of cases of IPAH
autosomal dominant inheritance
 NATURAL HISTORY OF PPH
The natural history of IPAH is uncertain
the disease is typically diagnosed late
Prior to current therapies, a survival of 2–3
years from the time of diagnosis
Functional class remains a strong predictor of
survival,
patients who are in NYHAfunctional class IV
having a mean survival of <6 months.
The cause of death is usually RV failure, which
is manifest by progressive hypoxemia,
tachycardia, hypotension, and edema
MEDIATORS OF PH
Prostacycline
Thromboxane A2
Endothelin-1
Nitric Oxide (NO)
Serotonin
Adrenomedullin
Vasoactive Intestinal Peptide (VIP)
Vascular Endothelial Growth Factor (VEGF)
 PROSTACYCLINE &
THROMBOXANE A2
Prostacycline
 Vasodilator
 Inhibisi aktivasi platelet
 Antiproliferative properties
Thromboxane A2
 Vasokonstriktor
 Platelet agonist
in PH balance shifted to Thromboxane A2
ENDOTHELIN-1

Vasokonstriktor yang poten

Menstimulasi poliferasi otot halus pada PA
Plasma levels increased in PHT
Level inversely proportional to pulmonary blood
flow & CO - ? Direct effect
NO & SEROTONIN

NO
 Vasodilator & inhibitor of platelet activation & vascular SM proliferation
Serotonin
 Vasoconstrictor promoting SM hyperplasia & hypertrophy
 Elevated plasma levels/ reduced platelet levels in PHT
GOALS OF THERAPY

Mengurangi gejala, meningkatkan kemampuan olahraga, meingkatkan

kualitas hidup
Memperbaiki hemodinamik kardiopulmonal, mencegah gagal jantung
kanan
Menunda perburukan
Mengurangi angka kesakitan dan kematian
 Classes of therapy
 Medical
 Diuretik
 Coumadin (IPAH, Anorexigen)
 Oksigen
 Terapi spesifik PAH
 Surgical
 Atrial septostomy
 Transplantasi paru
Mainstay of treatment
PAH THERAPY: MODIFIKASI GAYA
HIDUP
Mengurangi garam
Tidak merokok
Menghindari ketinggian
 <4,000 kaki diatas permukaan laut
Avoid physical exertion in setting of pre-
or frank syncope sx
Hindari kehamilan
 IH
A S
K
A G?
IM SI N
E R U
P SKDI : 1
T UDAH
S
 ANTICOAGULANTS
Warfarin
 Anticoagulant therapy is advocated for all patients with PAH .
 warfarin increases survival of patients with PAH.
 The dose of warfarin is generally titrated to achieve an INR of 2–3 times
control.
 ALGORITHM FOR ASSESSMENT OF
VASOREACTIVITY IN PATIENTS WITH PAH
Right Heart Catheterization With
Acute Vasoreactivity Testing (iNO,
epoprostenol, adenosine)

mPA 10 mmHg

 mPA < 40 mmHg

Non - responder
Responder (<15%) and
candidate for CCB (no
RHF)
Consider p.o. Bosentan
Consider p.o. Sildenafil
Hemodynamically-Monitored
Consider Inhaled Iloprost
Trial of
Consider s.q. Treprostinil
Calcium Channel Blocker
Consider Continuously-
Infused Epoprostenol Therapy
 CALCIUM CHANNEL BLOCKERS
Patients who have substantial reductions in PAP in
response to vasodilators at the time of cardiac
catheterization (a fall of 10 mmHg in mean PAP
and a final mean pressure <40 mmHg) should be
treated with CCB.
dramatic reductions in PAP, PVR,improved
symptoms, regression of RV hypertrophy
improved survival documented to exceed 20 years
patients require high doses (e.g., nifedipine, 240
mg/d, or amlodipine, 20 mg/d).
<20% of patients respond to CCB in the long term.
should not be given to patients who are
unresponsive, as they can result in hypotension,
hypoxemia, tachycardia, and worsening right
heart failure
 ENDOTHELIN RECEPTOR ANTAGONISTS
Bosentan :nonselective endothelin receptor
antagonist
approved treatment of PAH for patients who are
NYHA functional classes III and IV.
bosentan improved symptoms and exercise
tolerance
Therapy is initiated at 62.5 mg bid for 1
month,then increased to 125 mg bid .
Because of the high frequency of abnormal
hepatic function tests associated with drug
use, primarily an increase in transaminases, it
is recommended that liver function be
monitored monthly throughout the duration of
use.
Bosentan is also contraindicated in patients who
are on cyclosporine or glyburide concurrently.
 PHOSPHODIESTERASE INHIBITORS

Sildenafil
 PDE type5 inhibitor
 Reduce metabolism of cGMP
Sildenafil should not be given to patients who are
taking nitrate compounds
lowers pulmonary artery pressure and inhibits
pulmonary vascular growth
sildenafil improves symptoms and exercise
tolerance in PAH
The recommended dose is 20 mg tid. The most
common side effect is headache
 PROSTACYCLINS
1-Iloprost
 IV or Inhaled
 is approved via inhalation for PAH patients who are NYHA functional classes III
and IV.
 improve symptoms and exercise tolerance
 Therapy can be given at either 2.5 or 5 mcg per inhalation treatment.
 inhaler must be given by a dedicated nebulizer
 The most common side effects are flushing and cough
 Because of the very short half-life (<30 min) it is recommended to administer
treatments as often as every 2 h.
Treprostinol
 IV or s/c injection
 No CYP inhibition - ? induction
 t½ 2-4 hours
 PROSTACYCLINS
2-Treprostinol
 is approved for the treatment of PAH patients who are NYHA functional class III or
IV
 improvement in symptoms, exercise tolerance, and survival
 drug is administered iv
 requires placement of a permanent central venous catheter and infusion through
an ambulatory infusion pump system.
 Side effects include flushing, jaw pain, and diarrhea,
SUBCUTANEOUS TREPROSTINIL

(REMODULIN )

•SQ administration
•Longer half-life than
epoprostenol
•Pre-mixed
•Stable at room temperature
IV epoprostenol (flolan)
 PROSTACYCLINS
3- Treprostinil

an analogue of epoprostenol,
 for patients with PAH &NYHA classes II–IV.
 Treprostinil has longer half-life than
epoprostenol (4 h)
 is stable at room temperature,
 may be given iv or sc through a small infusion
pump that was originally developed for insulin.
 improvement in symptoms and exercise
capacity.
 The major problem has been local pain at the
infusion site, which has caused many patients to
discontinue therapy.
 Side effects are similar to those seen with
epoprostenol.
 SURGICAL THERAPY
Transplantation - lung / heart-lung

Lung transplantation is considered for

patients who, while on an intravenous
prostacyclin, continue to manifest right
heart failure.
Acceptable results have been achieved
with heart-lung, bilateral lung, and single-
lung transplant.
 The availability of donor organs often
influences the choice of procedure
FUNCTIONAL CLASSES
Good luck