HIPERTENSI

PULMONAL

A L F A A L F I N N U R S I D I Q , S P. J P, F I H A
DI VI SI P EN YAKI T JAN T U N G ST RU KT U RAL
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

IRREVERSIBLE
NORMAL REVERSIBLE DISEASE 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
ditemukan
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 : "Pulmonary Group 3 PH — "Pulmonary
venous hypertension". hypertension associated
Examples: with disorders of the
 1. Left-sided atrial or ventricular
respiratory system or
heart disease hypoxemia".
 2. Left-sided valvular heart
disease Examples:
 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 — Group 5 PH —
These patients have PH
"Pulmonary caused by inflammation,
hypertension caused mechanical obstruction, or
extrinsic compression of the
by chronic thrombotic pulmonary vasculature
or embolic disease". •(eg, sarcoidosis, histiocytosis X,
lymphangiomatosis, compression
of pulmonary vessels by
Examples: adenopathy, and fibrosing
mediastinitis).
 1. Thromboembolic
obstruction of proximal
pulmonary arteries
 2. Thromboembolic
obstruction of distal
pulmonary arteries
 3. Non-thrombotic pulmonary
embolism (tumor, parasites,
foreign material)
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
SKDI : 1
 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
Consider p.o. Bosentan RHF)
Consider p.o. Sildenafil
Consider Inhaled Iloprost Hemodynamically-Monitored
Consider s.q. Treprostinil Trial of
Consider Continuously- Calcium Channel Blocker
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