Management Strategy

• Initial assessment– H&P (environmental, occupational, family)– PAL CXR– PFT– ECG– CBCD, CMP, Ca, UA, 24 hr urine Ca– +/- ACE level

Management Strategy• Secondary Assessment– Heart• Holter, ECHO with bubble study, PET, MRI, EPS

– Lung• RHC, CPET, ABG, VQ scan

– CNS• MRI, CSF

– Eye• Opthomology eval (slit lamp)

– Skin• +/- Dermatology referral

Management Strategy• 1st year

– Follow up Q 3 months– Optho eval Q 6 months if on hydroxchloroquine

• Otherwise I do yearly– Fasting CMP with CBCD if on steroid sparing alternatives– Dexa scan– Eval for OSA if indicated

• Stable– RTC 6 months-1 year

• Remission/quiescence– Follow yearly x 2 then discharge unless chronic disease with

impairment

Learning Objectives

• Clinical suspicion

• Pathophysiology

• Diagnostic strategies

• Treatment options

• Monitoring your patients response to therapy

PMH

• 75 y/o male presents for follow up with the following problems:– Sarcoidosis– Severe Pulmonary HTN– Right heart failure– Moderate COPD– Home O2 dependent 2 LPM via NC– LVH– CKD

HPI

• Feels at his baseline health– Walks at pace of 1.6 mph on home treadmill (an

accomplishment)– If 2 mph:• tachycardia at 132 bpm• Severe dyspnea resulting in O2 increased to 4 LPM NC

Pertinent Medications

• Bosentan 125 mg PO BID• Combivent QID• Advair 500/50 BID• Furosemide 80 mg BID

• Recently weaned off prednisone 10 mg daily and metolazone 2.5 mg every other day

Pertinent Physical Exam Findings

• BP 137/56, P 84, R 18, SpO2 88% 2LNC at rest• Wt. 128 lbs (16 lbs lost over 1 year)• Chronically ill and cachectic appearing elderly man

with kyphosis• JVD at 10 cm, no LAD• Lungs resonant and CTA b/l• Heart irregular rhythm, S1 wnl, S2 fixed widening, S3

gallop• No hepatosplenomegally• Cyanosis of fingertips and lips, no clubbing or edema

Imaging/Diagnostic Studies

• ECHO– LVEF 55% with septal flattening– RV enlarged with severely reduced systolic

function. Septal flattening with “D-sign”– Right heart pressure estimates:• PASP = 82 mmHg (prior was 110mmHg)• RA pressure = 12 mmHg• TR Doppler gradient = 70 mmHg• PA mean pressure = 54 mmHg• PR early peak gradient = 36 mmHg

– Known PFO

Imaging/Diagnostic Studies

• Right Heart Catheterization

– Flolan stopped after 12 ng/kg/min because of nausea– PA mean pressure at initiation of Flolan gtt was 37 mmHg

Baseline Values Flolan 12 NG/KG/Min

RA Pressure (A/V/M) 7/4/3 mmHgRV Pressure (S/D) 74/5 mmHgPA Pressure (S/D/M) 74/24/41 mmHg 69/22/38 mmHgCO/CI 3.97/2.23 L/minPVR 423 dynes/sec/cm-5

225/025/8/15

155-255

Clinical Suspicion

Prospective observational study246 consecutive Japanese Sarcoidosis patientsPH evaluated by 2D-ECHO (PH + if sPAP > 40 mmHg)192 underwent PFT’s122 underwent HRCT212 successfully evaluated, 12 had PH (5.7%)

Clinical Suspicion

• Patients with PH had following characteristics:– Advanced chest radiographic stage– Decreased oxygen saturation– Predominantly male gender– Decreased VC, FVC, FEV1, FRC, TLC– Decreased TLC independently associated with PH

Incidence of Pulmonary hypertension and its clinical relevance in patients with sarcoidosis.Chest. 129 (5): 1246-52, 2006 May.

Decrease per 10% p < 0.05 (95%CI 0.48--0.99)

Clinical Suspicion

Clinical suspicion

Clinical Suspicion

Retrospective series of 22 sarcoidosis patientsDivided into two groups Presence (15) or absence (7) of pulmonary fibrosis on CXR at time of diagnosis of PHObserved two different phenotypes of sarcoidosis combined with PH

Clinical Suspicion

Clinical Suspicion

Clinical Suspicion

Retrospective survey106 patients with Sarcoidosis classified into two groups by ECHO

1. PH 2. Without PHExamined ECHO’s, CXR’s, PFT’s, and SaO2’s

Clinical Suspicion

Clinical Suspicion

• Spirometry and DlCO lower in group 1 patients

• 60% patients in group 1 had Scadding stage 4 sarcoidosis on CXR

• 40% of patients with PH did not have fibrosis on CXR (Scadding stages 1-3)

Distinctive clinical, radiographic, and functional characteristics of patients with sarcoidosis related pulmonary hypertension. Chest. 128 (3): 1483-9, 2005 Sep.

Clinical Suspicion

Reviewed records of patients with Sarcoidosis for lung transplant in USA 1995-2002PH = mean PA pressure > 25 mmHg and severe PH = mean PA pressure > 40 mmHg363 patients, 73.8% had PHPatients with PH needed more supplemental O2 therapy

The need for O2 had a sensitivity of 91.8% specificity of 32.6%

Accuracy was 68.6%

Pathophysiology

Pathophysiology

• Pathological samples were taken from the lungs of patients who either died or were transplantedOut of 5 transplanted patients, 2 had sarcoidosis granulomas in the arteries

4 had sarcoidosis granulomas in the veins

PathophysiologyTayal, Shalini et Al. Sarcoidosis and pulmonary hypertension. European Journal of Medical Research. 11 (5) : 194-7, 2006 May 5.

43 y/o woman with sarcoidosis and primary pulmonary hypertensionTreated with steroid therapy and prostacyclin infusionTransient improvement in O2 saturations

At autopsy, fibrosis was not present. Granulomas surrounded mediumAnd small-sized pulmonary arteries, but did not destroy the vessel wall.Plexiform lesions identified in pulmonary arteries.

Pathophysiology

Portier, F. Lerebours-Pigeonniere et Al. Sarcoidosis simulating a pulmonary veno-occlusive disease. Revue des Maladies Respiratoires. 8 (1) : 101-2, 1991

43 y/o man with sarcoidosis and pulmonary hypertension.No radiological evidence of fibrosis.Treated with corticosteroids without improvement.

At autopsy the pulmonary veins were obliterated by non-caseating granulomas.Minimal fibrotic parenchymal lesions were observed.

Diagnostic Strategies

• Supplemental O2 therapy > 2 Liters• CXR; Scadding stages• PFT’s, particularly FEV1, FVC, VC, TLC, DlCO• HRCT; fibrosis of bronchovascular bundles• V/Q scan• 2D-ECHO with bubble study• RHC

Treatment Options

Pulmonary Sarcoidosis Scadding stage IIIIncreasing dyspneaPFT’s with TLC 62%, VC 40%, DlCO 46%HRCT with nodular opacities along bronchovascular bundles2D-ECHO with RVSP 78 mmHgRHC confirmed severe PHTx with corticosteroids, CCB, Warfarin, Bosentan 125mg bid

Treatment Options

Treatment options

30 y/o female with increasing dyspneaScadding stage 2 CXRPFT’s demonstrating mild restrictive pattern with DLCO 9mlV/Q with matched defectsRHC with PAP 64/32 and PVR 555

After prednisone x 21 months, dyspnea improvedPFT’s observed for 18 months after therapy discontinued and remained stable

Monitoring Response to Therapy

Prospective, observational study of eight patientsUsed inhaled NO, IV epoprostenol, and/or oral CCB’sFavorable response = > 20% decrease in PVRWith iNO PVR decreased 31 +/- 5% (p=0.006)With epoprostenol PVR decreased 25 +/- 6% (p=0.016)F/U 6 min walks improved in all patients receiving iNO

Monitoring Response to Therapy

Monitoring Response To Therapy

Monitoring Response To Therapy

Monitoring Response To Therapy

Response was a decrease in PVR > 20%

Monitoring Response To Therapy

Monitoring Response To Therapy

Summary for PH in Summary for PH in SarcoidosisSarcoidosis Clinical suspicionClinical suspicion

Advanced stage on CXR (especially stage IV)Advanced stage on CXR (especially stage IV) Increased O2 requirement > 2LIncreased O2 requirement > 2L Male sexMale sex Decreased TLCDecreased TLC Increased NYHA classIncreased NYHA class Significantly decreased DLCO in comparison to FEV1, FEV1/FVCSignificantly decreased DLCO in comparison to FEV1, FEV1/FVC

PathophysiologyPathophysiology Parenchymal involvement leading to fibrosisParenchymal involvement leading to fibrosis Vascular involvement without fibrosisVascular involvement without fibrosis Extrinsic compression of pulmonary arteries by mediastinal lymph nodesExtrinsic compression of pulmonary arteries by mediastinal lymph nodes

Diagnostic strategiesDiagnostic strategies O2 therapy > 2L, CXR, PFT, HRCT, V/Q, 2D-ECHO with bubble study, RHCO2 therapy > 2L, CXR, PFT, HRCT, V/Q, 2D-ECHO with bubble study, RHC

Treatment optionsTreatment options Corticosteroids, Bosentan, iNO/Sildenafil, EpoprostenolCorticosteroids, Bosentan, iNO/Sildenafil, Epoprostenol, CCB, CCB

Monitoring your patients response to therapyMonitoring your patients response to therapy CXR, PFT’s CXR, PFT’s NYHA, 6 minute walkNYHA, 6 minute walk, RHC, RHC

Thank you!!!