treatment of ild and pulmonary hypertension
DESCRIPTION
Treatment of ILD and Pulmonary Hypertension. Levent Tabak, M.D. Istanbul Medical Faculty. Pulmon ary H ypertension (PH). DEFINITION Mean pulmonary artery pressure ~14 mmHg) Pulmonary hypertension; During resting > 25 mm Hg During exercise > 30 mm Hg. P H severity. - PowerPoint PPT PresentationTRANSCRIPT
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Treatment of ILD and Pulmonary Hypertension
Levent Tabak, M.D.
Istanbul Medical Faculty
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DEFINITION• Mean pulmonary artery pressure ~14 mmHg)• Pulmonary hypertension;
– During resting > 25 mm Hg
– During exercise > 30 mm Hg
Pulmonary Hypertension(PH)
PH severity
Mild 26 - 35 mmHg Moderate 36 - 45 mmHg Severe > 45 mmHg
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PULMONARY HYPERTENSIONVenice 2003
1.Pulmonary arterial hypertension1.Idıopathic
2.Familial 3.Secondarya)Collagen vascular diseaseb)Congenital systemic to pulmonary shuntc)Portal hypertensiond)HIV infectione)Drugs and toxinsf) Other(Thyroid, glycogen storage disease
splenectomy, nyeloproliferative disor) 4.Venous or capillary involvementa)Pulmonary veno-oclusive diseaseb)Pulmonary capillary hemangiomatozis2. Pulmonary venous hypertension 1.Left sided atrial/ventricular heart dise 2.Left sided valvular heart disease
3.PH associated with hypoxemia 1. COPD 2. Interstitial lung diseases 3. Sleep disorders 4. Alveolar hypoventilation 5. High altitude 6. Developmental abnormalities4.PH due to chronic thrombotic/embolic disease 1.Obstruction of proximal pulmonary arteries 2.Obstruction of distal pulmonary arteries 3.Non-thrombotic pulmonary embolism5.Miscellaneous a)Sarcoidosis b)Histiocytosis XSarkoidoz c)Lymphangiomatosis d)Compression of pulmonary vessels
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• Fatique
• Dyspnea
• Chest pain
• Syncop
• Hemoptysis The interval between disease onset and symptoms
is around 3 years
Clinics
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Diagnosis of PH
PH Detection Chest Radiography ECGTT Echocardiography
PH Class Identification Pulmonary Function TestV/Q scanHRCTSpiral CTPulmonary Angiography
PAH evaluation Blood Tests&ImmunologyHIV testAbdominal USG6 min Walk Test, Max VO2Right Heart
Cath+Vasoreactivity
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• May helpfull only in 30-40% of patients!• Dilated central pulmonary arteries• Reduced peripheral vascularization (Tree in bud)
Chest X-ray
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• Right atrial dilatation• Right ventricular hypertrophy• RBBB (55% sensitivity, 70% specifity)
ECG
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Best non-invasive diagnostic test.
• Right ventricular and atrial
dilation
• Tricuspid/pulmonary valve
regurgitation• Non-invasive measurement of
pulmonary arterial pressure
ECHOCARDIOGRAPHY
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Diagnosis of PH
PH Detection Chest Radiography ECGTT Echocardiography
PH Class Identification Pulmonary Function TestV/Q scanHRCTSpiral CTPulmonary Angiography
PAH evaluation Blood Tests&ImmunologyHIV testAbdominal USG6 min Walk Test, Max VO2Right Heart
Cath+Vasoreactivity
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Pulmonary Function tests & Blood Gases
• PAH patients usually have mild to moderate reduced lung volumes and decreased DLCO
• PaO2 is normal or slightly low and PaCO2 is decreased due to alveolar hyperventilaton
• PaCO2 is increased in COPD as a cause of hypoxic PH together with obstruction
• A decrease in lung volumes and DLCO indicate ILD
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V/Q Lung Scan
• In PAH V/Q scans may be entirely normal
• V/Q scanning showed sensitivity of 90-100% with spesifity of 94-100% for distinguishing between IPAH and CTEPH
• V/Q scans are similar in veno-occlusive disease and CTEPH, HRCT is reguired for differentiation
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Chest CT/MRI
• Right ventricular morphology
• Right atrial morphology
• Pulmonary artery morphology
• Right ventricular function
*The value of serial CT/MRI scans in following
the course of patients is not established
*CT; evaluate the lung parenchyma
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Pulmanary angiography
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Diagnosis of PH
PH Detection Chest Radiography ECGTT Echocardiography
PH Class Identification Pulmonary Function TestV/Q scanHRCTSpiral CTPulmonary Angiography
PAH evaluation Blood Tests&ImmunologyHIV testAbdominal USG6 min Walk Test, Max VO2Right Heart
Cath+Vasoreactivity
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Exercise testing
• A six-minute walk test or a cardiopulmonary exercise test is recommended
• Exercise test best characterise the functional impairment of patients with PPH and their response to therapy
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Right Cath+Vasodilator Testing
• Patients with idiopathic pulmonary arterial hypertension (IPAH) should undergo acute vasoreactivity testing using a short-acting agent such as intravenous (IV) epoprostenol, adenosine, or inhaled nitric oxide (NO).
• Level of evidence: fair; benefit: substantial; grade of recommendation: A.
• Patients with pulmonary arterial hypertension (PAH) associated with underlying processes, such as scleroderma or congenital heart disease, should undergo acute vasoreactivity testing.
• Level of evidence: expert opinion; benefit: small/weak; grade of recommendation: E/C.
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PAH Treatment• General
– Oral anticoagulant– Diuretics-venesection– Oxygen– Digoksin
• VAZODİLATÖR TEDAVİ– Calciun Channel Blockers– Endothelin antagonists
• Bosentan…Sitaxsenten/Ambrisentan– Prostacyclins
• Epoprostenol, Treprostinil, Iloprost, Oral beraprost– PDE-5 inhibitors (c-GMP elevators)
• Sildenafil
• SURGICAL INTERVENTIONS– Atrial septostomY– Lung transplantation
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Anticoagulation
• Microthrombosis of the small vessels is often seen in PPH• Fibrin degradation products have a proliferative effect on the
vessels• Patients treated with coumadin have a better prognosis• Targed INR value in IPAH patients;
– North America 1.5-2.5– Europe; 2-3
*Patients with IPAH should receive anticoagulation with warfarin. Level of evidence: fair; benefit: intermediate; grade of recommendation: B. **In patients with PAH occurring in association with other underlying processes, such as scleroderma or congenital heart disease, anticoagulation should be considered. Level of evidence: expert opinion; benefit: small/weak; recommendation: E/C.
*Patients with IPAH should receive anticoagulation with warfarin. Level of evidence: fair; benefit: intermediate; grade of recommendation: B. **In patients with PAH occurring in association with other underlying processes, such as scleroderma or congenital heart disease, anticoagulation should be considered. Level of evidence: expert opinion; benefit: small/weak; recommendation: E/C.
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Diuretics
• Prevent sodium and water retension
• Great impact on physical capacity and quality of life in many patients with right heart failure
• Drug and dose;……….expertise
• Follow up;……………. Electrolits, renal
function
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Venesection
• Polycytemia increases the viscosity of the blood and therefore increases vascular resistance (HCT>60%)
• Benefial in COPD patients
• Decompensation in Eisenmenger
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Oxygen Therapy
• Oxygen treatment decreases pulmonary artery pressure
• Recommended when PaO2< 65 mmHg, or oxygen saturation < 85%
• It does rarely work in IPAH patients
• O2 therapy is beneficial for right ventricle and respiratory muscles
In patients with PAH, supplemental oxygen should be used as necessaryto maintain oxygen saturations at >90% at all times.Level of evidence: expert opinion; benefit: substantial; recommendation: E/A.
In patients with PAH, supplemental oxygen should be used as necessaryto maintain oxygen saturations at >90% at all times.Level of evidence: expert opinion; benefit: substantial; recommendation: E/A.
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Digitalis&Dobutamine
• Depression of myocardial contractility is the primary event in the progression of right heart failure, inotropic agents have been used.
• Short-term IV administration of digoxin produces increase in cardiac output and a significant reduction in circulating norepinephrine levels
• End stage PAH patients treated with dobutamine in most centres
• Long-term treatment?
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Calcium Channel Blockers Smooth muscle hyperthrophy Vasoconstriction Voltage-dependent potassium channels
• Rich ve ark.NEJM,1992
Only in patients with vasodilator testing (+) Side effects should be followed closely
– Nifedipin (in case of bradicardia)– Diltizem (in case of tachycardia)– ***Verapamil : negative inotropic effects!!! A/F!
Follw-up 1 earl 3 yearl 5 year
Vasodilator testing (-) %68 %47 %38
Vaso-testing(+) & yüksek doz KKB %94 %94 %94
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Calcium Channel Blockers
• Beginning with low doses are recommende;– Nifedipine 30 mg 2x1– Diltiazem 60 mg 3x1
• Doses increased gradually in weeks up to maxium tolerated level;– Nifedipine…> 120-240 mg/day– Diltiazem….-> 240-720 mg/day
*Systemic hypotension and peripheral edema of lower extremities are dose limiting factors.
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NOProstacyclin
C-GMP
EndothelinHypoxia
Pulmonary Arterial Hypertension(New treatments)
Vasoconstruction Vasodilation
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New Agents
• Prostacyclins– Epoprostenol– Treprostinil– Iloprost– Beraprost
• Endothelin Receptor Antagonists– Nonselective Endothelin Receptor Blockade:
(Bosentan)– Specific A-receptor Blockers. (Sitaxentan,
Ambrisentan)• Phosphodiesterase 5 Inhibitors;
– Sildenafil
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PAH and IPF survival
• The median length of survival has been estimated to be between 2.5 and 5 years after the onset of respiratory symptoms or diagnosis
• 1-year survival rate;– 45% in patients with IPF and PAP> 50 mmH– 83% in patients with IPF and PAP< 50 mm Hg
• Therefore, there is often a short window to enable the study of pulmonary hypertension in this population
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Chest X-ray
• Patients with a suggestion of pulmonary hypertension on chest radiography have a poorer prognosis than those without pulmonary artery enlargement
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Echocardiography
• Echocardiography is the most common noninvasive test used to screen for pulmonary hypertension. Unfortunately, in patients with advanced lung disease, the sensitivity and specificity of echo-cardiography are imperfect:
• sensitivity; 85%• specificity; 55%• positive predictive; 52%• Negative predictive; 87%
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V/Q Lung Scan
• In PAH V/Q scans may be entirely normal• V/Q scanning showed sensitivity of 90-100% with
spesifity of 94-100% for distinguishing between IPAH and CTEPH
• V/Q scans are similar in veno-occlusive disease and CTEPH, HRCT is reguired for differentiation
• In parenchymal lung disease the perfusion defects are matched by ventilation defects
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PAH-PFT relationship
• FVC is 50 to 80% of that predicted; – pulmonary hypertension may occur with exercise
• FVC < 50% or DLCO < 45% :– pulmonary hypertension may occur at rest
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ILD-PH Treatment
• Limited data suggest that the treatment of pulmonary hypertension in ILD is beneficial.
• There are some theoretic risks to vasodilation in patients with ILD. – pulmonary artery vasodilation leads to improved blood flow into
areas of fibrotic lung, then worsening of ventilation perfusion mismatch may result
• Patients receiving intravenous prostacyclin experienced decreased arterial oxygen tension, largely because of an increase in shunt fraction. By contrast, inhaled nitric oxide and sildenafil maintained ventilation perfusion matching and decreased pulmonary vascular resistance without a decrease in arterial oxygen tension.– Ghofrani HA, Wiedemann R, Rose F, et al. Sildenafil for treatment of lung
fibrosis and pulmonary hypertension: a randomised controlled trial. Lancet 2002; 360:895-900
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Therapy for PH in ILD
• Pulmonary hypertension is common in advanced ILD and correlates with poor outcome.
• Therapy that targets pulmonary hypertension has been initiated in small clinical trials.
• Larger randomized controlled trials will be needed to establish that therapy of pulmonary hypertension is both efficacious and safe for patients with ILD
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PAH Treatment-summary• General
– Oral anticoagulant– Diuretics-venesection + Physiotherapy– Oxygen Control of infection– Digoksin
• VAZODİLATÖR TEDAVİ– Calciun Channel Blockers– Endothelin antagonists
• Bosentan…Sitaxsenten/Ambrisentan– Prostacyclins
• Epoprostenol, Treprostinil, Iloprost, Oral beraprost– PDE-5 inhibitors (c-GMP elevators)
• Sildenafil
• SURGICAL INTERVENTIONS– Atrial septostomY– Lung transplantation
?
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References
• Medical Therapy For Pulmonary Arterial Hypertension
ACCP Evidence-Based Clinical Practice Guidelines
David B. Badesch, Steve H. Abman, Gregory S. Ahearn, Robyn J. Barst, Douglas C. McCrory, MHSc; Gerald Simonneau,Vallerie V. McLaughlin
Chest 2004;126;35-62• Guidelines on diagnosis and treatment of pulmonary
arterial hypertension Nazzarone Galie, Adam Torbicki, Robyn Barst, Philippe Dartevelle, Shelia Haworth,
Tim Higenbottam, Horst olschewki, Andrew Peacock, Guiseppe Pietra, Lewis J Rubin
European Heart Journal 2004; 25: 2243-2278