Scleroderma Associated Pulmonary HTN August 13 th /03 Wael Batobara

History 69 y female Ex smoker 8y {30 pack y} 69 y female Ex smoker 8y {30 pack y} NIDDM Microalbuminuria & PVD NIDDM Microalbuminuria & PVD HTN,Dyslipidemia HTN,Dyslipidemia Admitted under Vascular Sx 15 th July/03 Admitted under Vascular Sx 15 th July/03 Rt Femoral – Popliteal Bypass June/03 Rt Femoral – Popliteal Bypass June/03 Worsening Ischemic toe Worsening Ischemic toe  planed amputation  planed amputation

History Chest Medicine consult : Chest Medicine consult : preoperative evaluation preoperative evaluation Exertional SOB & LL swelling 1/12 Exertional SOB & LL swelling 1/12 SR: -ve orthopnea,PND, Chest Pain SR: -ve orthopnea,PND, Chest Pain,Cough,sputum, Wheeze,Cough,sputum, Wheeze,Hemoptysis, Fever,Wt loss,Hemoptysis, Fever,Wt loss PMH: -ve IHD normal MIBI June/03 PMH: -ve IHD normal MIBI June/03 -ve Valvular disease -ve Valvular disease -ve VTE,Recurrent Pneumonias -ve VTE,Recurrent Pneumonias

History Medications Medications At Home Glyburide, Metformin At Home Glyburide, Metformin Lisinopril,Nifidipine,Pravastatin Lisinopril,Nifidipine,Pravastatin In Hospital Lasix, ASA In Hospital Lasix, ASA No H/O Travel,Pets No H/O Travel,Pets,Occupational exposure,Occupational exposure FH : unremarkable FH : unremarkable

Examinations No respiratory distress, Cyanosis No respiratory distress, Cyanosis RR 16 Sat 90-92% at rest 74% walking RR 16 Sat 90-92% at rest 74% walking BP 130/80 HR 75 Afebrile BP 130/80 HR 75 Afebrile JVP 7 cm ASA with normal carotids JVP 7 cm ASA with normal carotids

Examinations Lt parasternal lift apex 6 th ICS MCL Lt parasternal lift apex 6 th ICS MCL S1+S2+S3+S4 Loud S2 S1+S2+S3+S4 Loud S2 3/6 PSM Lt sternal border 3/6 PSM Lt sternal border increased with inspiration increased with inspiration Chest : -ve clubbing Chest : -ve clubbing Good B/S Clear Good B/S Clear

Examinations Abdomen Hepatosplenomegaly Abdomen Hepatosplenomegaly ? Ascites ? Ascites LL : Bilateral pitting edema LL : Bilateral pitting edema -ve DVT signs -ve DVT signs No Connective tissue diseases signs No Connective tissue diseases signs

Investigations CBC N CBC N BUN,Creatinine & Electrolytes N BUN,Creatinine & Electrolytes N U/A N U/A N LFT, CK & TnT N LFT, CK & TnT N EKG Lt Axis,Poor R wave progression EKG Lt Axis,Poor R wave progression

Investigations CXR & PFT CXR & PFT ABG PH 7.48 PCO2 43 Sat 86% ABG PH 7.48 PCO2 43 Sat 86% PO2 49 HCO3 31 On room air PO2 49 HCO3 31 On room air 2DE: LVH EF N 2DE: LVH EF N Mild Diastolic Dysfunction Mild Diastolic Dysfunction pulmonary HTN  RV SP 75 pulmonary HTN  RV SP 75 Moderate TR Dilated RV & RA Moderate TR Dilated RV & RA

Working Dx Pulmonary HTN  Rt HF Pulmonary HTN  Rt HF Etiology ? Secondary Vs Primary Etiology ? Secondary Vs Primary What Possible secondary causes? What Possible secondary causes?

Something Unexpected Anti-centromere Abs +ve 1 : 5120 Anti-centromere Abs +ve 1 : 5120 Other ENA –VE Other ENA –VE 2 nd Rheumatologic exam 2 nd Rheumatologic exam {By Rheumatology Team }  -ve {By Rheumatology Team }  -ve Rx  O2, Diuretics Rx  O2, Diuretics Referral to Pulmonary HTN Clinic Referral to Pulmonary HTN Clinic

Few Question That Needs Answers How sensitive is Anticetromere Ab ? How sensitive is Anticetromere Ab ? Is any clinical predictors of worse outcome? Patient Characteristics Is any clinical predictors of worse outcome? Patient Characteristics Physical exam Physical exam Laboratory tests Laboratory tests

Sensitivity & Specificity Of ACA Retrospective Study Retrospective Study 397 Clinical Dx Systemic Sclerosis 397 Clinical Dx Systemic Sclerosis 26% +ve Anti Scl70 Vs 22% +ve ACA 26% +ve Anti Scl70 Vs 22% +ve ACA Clinical Correlations & Prognosis Based on serum Abs in SS Arthritis-Rheum Feb 1988 Arthritis-Rheum Feb 1988

Sensitivity & Specificity Of ACA 96% of +ve ACA were in Limited Scler. 96% of +ve ACA were in Limited Scler. BUT BUT only 43% of Limited Scler. Had +ve ACA only 43% of Limited Scler. Had +ve ACA ACA +ve more Calcinosis & Telangectasias ACA +ve more Calcinosis & Telangectasias Equal Pulmonary HTN Equal Pulmonary HTN

Sensitivity & Specificity Of Anti Scl70 66% of +ve Anti Scl70 were Diffuse Scler. 66% of +ve Anti Scl70 were Diffuse Scler. BUT Only BUT Only 33% of Diffuse Scler. Had +ve Anti Scl70 33% of Diffuse Scler. Had +ve Anti Scl70 Anti Scl70  more Raynauds & IPF Anti Scl70  more Raynauds & IPF Equal renal & cardiac events Equal renal & cardiac events

Patient Characteristics Retrospective study Retrospective study 189 female patients with normal initial CXR & 2DE 189 female patients with normal initial CXR & 2DE 63/189 developed Pulmonary HTN 63/189 developed Pulmonary HTN Annals Of NY Academy Of Science Annals Of NY Academy Of Science June 2002 June 2002

Patient Characteristics What Clinical & Biological markers was predictive? What Clinical & Biological markers was predictive? Postmenopausal Status RR 5.2 CREST RR 2.8 HLA B35 RR 2.8

Physical Examination Prospective Study Prospective Study Quantitative Nail fold Capillaroscopy in Quantitative Nail fold Capillaroscopy in 10 Controls Vs 20 Limited SS 10 Controls Vs 20 Limited SS 18/20 +ve ACA & 8/20 Pulmonary HTN 18/20 +ve ACA & 8/20 Pulmonary HTN Pulmonary HTN has significant decrease in capillary density > 2 groups ( p 2 groups ( p < 0.01) Asian Pacific Journal Of Allergy & Immunology Asian Pacific Journal Of Allergy & Immunology June 1998 June 1998

Laboratory Investigations Soluble Thrombomodulin Levels Soluble Thrombomodulin Levels In 34 Scleroderma with Pulm.HTN In 34 Scleroderma with Pulm.HTN & 38 Scleroderma without Pulm.HTN & 38 Scleroderma without Pulm.HTN & 2o Controls & 2o Controls Significant Elevations In SS with Pulm HTN Significant Elevations In SS with Pulm HTN No Difference between SS without HTN & Controls No Difference between SS without HTN & Controls NO further elevation with worsening HTN NO further elevation with worsening HTN Annals Of Rheum Dis Annals Of Rheum Dis Feb 2000 Feb 2000

Laboratory Investigations Prospective Study Prospective Study Survival in Patients with Pulmonary HTN Survival in Patients with Pulmonary HTN 40 Patients 40 Patients 24/40 Cyanotic heart disease 24/40 Cyanotic heart disease 11/40 Primary Pulm.HTN 11/40 Primary Pulm.HTN 3/40 Schitosomiasis 2/40 CTD 3/40 Schitosomiasis 2/40 CTD Plasma vWF levels Plasma vWF levels Chest Chest November 1998 November 1998

Laboratory Investigations 7/11 Primary HTN died over 1 year 7/11 Primary HTN died over 1 year 4/29 Secondary died over 1 year 4/29 Secondary died over 1 year Plasma vWF > 240% was Plasma vWF > 240% was 54% sensitive & 93% specific 54% sensitive & 93% specific for predicting who is unlikely to survive for predicting who is unlikely to survive