• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content
Idiopathic pulmonary arterial hypertension by Jayeeta Bhowmick
 

Idiopathic pulmonary arterial hypertension by Jayeeta Bhowmick

on

  • 1,117 views

 

Statistics

Views

Total Views
1,117
Views on SlideShare
1,117
Embed Views
0

Actions

Likes
1
Downloads
37
Comments
0

0 Embeds 0

No embeds

Accessibility

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    Idiopathic pulmonary arterial hypertension by Jayeeta Bhowmick Idiopathic pulmonary arterial hypertension by Jayeeta Bhowmick Presentation Transcript

    • By- Jayeeta Bhowmick Junior Resident & MD studentDept of Medicine, IPGME&R Kolkata
    • DEFINITION & PARAMETER OF PAH • Mean Pulmonary Arterial Pressure > 25 mm Hg at REST > 30 mm Hg with Exercise Normal Left Heart Filling PressureNormal Left Ventricular ED Volume 95 18 mL in Biplane 2D Transthor. Pulmonary Artery Occlusive Pressure < 15 mm Hg
    • PAH IDIOPATHIC
    • PAH For diagnosing IDIOPATHIC PAH Exclude all other Causes
    • Revised Clinical Classification of Pulmonary Hypertension Pulmonary Arterial Hypertension Collagen vascular disease Idiopathic Pulmonary Art. HTN Congenital systemic  pulmonary shunts Portal hypertension Familial Pulmonary Art. HTN HIV infection Associated with Drugs and toxins Other
    • Revised Clinical Classification of Pulmonary Hypertension Pulmonary Arterial Hypertension Collagen vascular disease Idiopathic Pulmonary Art. HTN Congenital systemic  pulmonary shunts Portal hypertension Familial Pulmonary Art. HTNThyroid disorders HIV infectionGlycogen storage diseaseGaucher disease Associated with Drugs and toxinsHereditary hemorrhagic Other telangiectasiaHemoglobinopathiesMyeloproliferative disordersSplenectomy
    • Revised Clinical Classification of Pulmonary Hypertension Pulmonary venoocclusive Pulmonary Arterial Hypertension disease Collagen vascular disease Pulmonary Idiopathic Pulmonary Art. HTN capillary Congenital systemic-to- pulmonary shunts hemangiomatosis Portal hypertension Familial Pulmonary Art. HTN HIV infection Associated with Drugs and toxins Other Associated with significant venous or capillary involvement
    • Revised Clinical Classification of Pulmonary Hypertension Pulmonary Arterial Hypertension Collagen vascular disease Idiopathic Pulmonary Art. HTN Congenital systemic-to- pulmonary shunts Portal hypertension Familial Pulmonary Art. HTN HIV infection Associated with Drugs and toxins Other Associated with significant venous or capillary involvement Persistent pulmonary hypertension of the newborn
    • Revised Clinical Classification of Pulmonary HypertensionPulmonary hypertension with left heart disease Left-sided atrial or ventricular heart disease Left-sided valvular heart diseasePulmonary hypertension associated with lung diseaseand/or hypoxemia Chronic obstructive pulmonary disease Interstitial lung disease Sleep-disordered breathing Alveolar hypoventilation disorders Chronic exposure to high altitude Developmental abnormalities
    • Revised Clinical Classification of Pulmonary Hypertension Pulmonary hypertension caused by chronic thrombotic and/or embolic disease Thromboembolic obstruction of PROXIMAL pulmonary arteries Thromboembolic obstruction of DISTAL pulmonary arteries Nonthrombotic pulmonary embolism (tumor, parasites) Miscellaneous Sarcoidosis Histiocytosis X Lymphangiomatosis Compression of pulmonary vessels (adenopathy, tumor, fibrosing mediastinitis)From Simmoneau G, Galie N, Rubin LJ, et al: Clinical classification of pulmonaryhypertension. J Am Coll Cardiol 43:5S, 2004. (Revision on the WHO classification.)
    • EPIDEMIOLOGY 1-2 cases / million Population Female : Male = 1.7 : 1 Age range 10 – 40 yrs (mean 35.4 yrs) Females predominate after Pubertal age group(Ref: NIH Study)
    • Predisposing Factors1. Dysfunctional Endothelium2. Apoptosis Resistant Cell Line in Vascular intima Uncontrolled Production of NO Smooth muscle Vasoconstrictor proliferation3. Genetic defect in K+ channel4. Plasma Serotonin & activating Mutation in Serotonin receptor5. Sporadic Genetic mutation as in Familial PAH cases.
    • …(contd.) Predisposing Factors1. Dysfunctional Endothelium
    • Predisposing Factors1. Dysfunctional Endothelium2. Apoptosis Resistant Cell Line in Vascular intima3. Genetic defect in K+ channel4. Plasma Serotonin & activating Mutation in Serotonin receptor5. Sporadic Genetic mutation as in Familial PAH cases.
    • …(contd.) Predisposing Factors1.  Mutation in BMPR-2 (25% cases) Dysfunctional Endothelium  Mutation in ALK-1 Autosomal dominant2. Apoptosis Resistant Cell Line in Vascular intima3. with +Incomplete Genetic defect in K channel penetrance4. Plasma Serotonin & activating Mutation in Serotonin receptor5. Sporadic Genetic mutation as in Familial PAH cases.
    • Patients in early stages of PAH may benefit more from antiapoptotic approaches Early PAH is characterized by increased apoptosis in the endothelial layer (PAEC)Late PAH is characterized bysuppressed apoptosis andincreased proliferation inthe intima and media patients presenting in late stages will benefit from proapoptotic strategies
    • Summary of the Neurohumoral Imbalance
    • Schematic Histopathological lesions
    • COMPARATIVE HISTOLOGY INTIMAINTIMA MEDIA MEDIA ADVENTTITIA ADVENTTITIANORMAL PULMONARY VESSEL IN PULMONARY HYPERTENSION
    • Overexpression of Endothelin in Plexiform Lesions of PAH
    • Clinical featuresEarly stage - difficult to recognize Exertional Dyspnœa may be initial complaint Fatigue Syncope Chest pain PalpitationDeath usually due to RVF
    • WHO Functional Classification of Pulmonary HypertensionClass I—Patients with PAH but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnœa or fatigue, chest pain, or syncope.Class II—Pt. with PAH resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnœa or fatigue, chest pain, or syncope.
    • WHO Functional Classification of Pulmonary Hypertension Class III—Pt. with PAH resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnœa or fatigue, chest pain, or syncope. Class IV—Pt with PAH with inability to carry out any physical activity without symptoms. These patients manifest signs of RHF. Dyspnœa and/or fatigue may even be present at rest. Discomfort is increased by any physical activity.
    • On ExaminationProminent Jugular Venous Pulsation –a or v wave Systolic murmur of TR Prominent large ‘a’ waves  High pitched holosystolic murmur of TR
    • …contd. On Examination P 2 Loud with split Left Lower Parasternal impulse Bipedal Oedema
    • …contd. On ExaminationEarly diastolic high pitched Graham-Steell murmur ofPRCaused by dilatation of the PV ring due to PAH S3 S4 gallop
    • Investigations To confirm the presence of PAH To search for the secondary causes To assess prognosis & prerequisites for treatment
    • Chest X Ray
    • ECG
    • Echocardiogram
    • CT Scan Primary pulmonary hypertension in a 32- year-old woman with average systolic pulmonary arterial pressures of 140-150 mm Hg. CT shows enlargement of the central pulmonary arterial system with tapering to the periphery and corkscrew-shaped arteries.
    • For Establishment of Definite diagnosisRight heart catheterization
    • Investigations to exclude the secondary causes PFT : Obstructive Vs Restrictive Lung disease Serology: ANA, HIV LFT and USG Abdomen Polysomnography / Overnight Oximetry
    • History and Physical examination Pulmonary Hypertension suspected ECG ; CXR NonDiagnostic or consistent with PAH unlikely PAH ; PAH still suspected Echocardiography Right Heart Catheterization YES Exclude PAH Diagnose PAH NO Evaluate or treat airway or Parenchymal Likely cause suggested by History, Lung disease, collagen vascular disease, Physical examination, CXR, PFT, neuromuscular disease, or chest wall ABG & Serology restrictive diseaseEvaluate & treat mitral valve dis, Echocardiography suggests causeCongenital Ht Dis, LV Dys? Radionuclide study V/Q scan or Helical CT suggestsEvaluate & treat chronic recurrent high probability for PEthromboembolic disease? Pulmonary angio
    • Treatment Goal To improve symptoms To improve exercise capacities To prevent further functional worsening To improve survival
    • General Measures Rest and Exercise Limitation. Digoxin : C.O. Diuretics: Peripheral Edema RVV overload in presence of TR O2 therapy Anticoagulation: Warfarin in Low doses (maintain INR 2-3)
    • Specific Treatment Options Vasodilators like CCB (for vasoreactive patients)  MOA: 1. Decrease intracellular Ca2+ in vascular smooth muscles. 2. Growth inhibitory property of vascular smooth muscles.  Dosage: High dose Amlodipine 20 - 30 mg daily Nifedipine 180 – 200 mg daily Diltiazem 720 – 960 mg daily
    • Theraputic Responders Fall in mean pulmonary arterial pressure of atleast 10 mm Hg Fall to an absolute mean PAP 35 -40 mm Hg Unchanged or increased C.O.
    • Prostacyclines MOA-potent pulmonary vasodialators Epoprostenil-i.v continuous infusion Treprostenil-S.C Illioprost-aerosol device Beraprost-oral Increased short term survival Antithrombotic effect
    • Phosphodiesterase 5 inhibitors Increased cyclic GMP-vasodilatation Preferential effect on pulmonary circulation Dose -20 mg tds
    • Endothelin receptors & their antagonists
    • Endothelin receptor antagonists Increased exercise capacity Hemodynamic improvement Dose – Bosentan 125 mg BD Only side effect- mild elevation of Hepatic enzymes
    • Surgical management Atrial Septostomy Lung Transplant
    • Factors determining poor prognosis Rapid progression of symptome H/O Syncope Advanced WHO functional class 6 min walking <300 mts Very high & rising BNP levels Pericardial effusion Right atrial pressure <15 mm Hg Decreased C.O
    • Combination Therapy
    • Comparative efficacies of the combination therapy BREATHE 2 study : Epoprostenol + Bosentan more effective compared to Epoprostenol alone. COMBI study: Ilioprost + Bosentan surprisingly caused clinical worsening !!! PACES study: Sildenafil has been found to be more effective than Epoprostenol.
    • Future Aspects No independent activator of cGMP Inhaled VIP Tyrosine kinase inhibitor Rhokinase inhibitor GENE therapy for BMPR2 Endothelin receptor A antagonist- Ambrisentan
    • Take Home Message IPAH is a rare disorder Phenotypic expression of many underlying biological abnormality High index of suspicion is required for diagnosis It is a diagnosis of exclusion There is new horizon for future therapy Though prognosis & survival is still unsatisfactory