CTEPH and CTED. Diseases that hide in plain sight to the eye, the mind, philosophically

Transcription

1 CTEPH and CTED Diseases that hide in plain sight to the eye, the mind, philosophically Paul R. Forfia, MD Associate Professor of Medicine Direct, PH, RHF and PTE Program Fran Rogers, CRNP Nurse Practitioner Program Coordinator Temple University Hospital

2 Disclosures Paul Forfia Participant discloses the following financial or non-financial relationships: Bayer: consulting United Therapeutics: Consulting Actelion: consulting Fran Rogers Participant has no financial or non-financial arrangements or affiliations to disclose. This continuing education activity is managed and accredited by Professional Education Services Group in cooperation with the Pulmonary Hypertension Association. Neither PESG, nor PHA, nor any accrediting organization support or endorse any product or service mentioned in the is activity. PESG and PHA staff has no financial interest to disclose. Commercial Support was not received for this activity.

3 Learning Objectives Discuss the pathophysiology of CTEPH and CTED Identify proper application of cardiac and lung imaging diagnostics Describe the importance of rest and exercise gas exchange testing to uncover more subtle forms of the CTEPH and CTED Participate in identification of CTEPH vs CTED through case presentations

4 Classification* Pulmonary Hypertension Clinical Classification Group 1: PAH-idiopathic (primary) and associated conditions (CTD, anorexigen, portopulmonary, left-right shunt, HIV etc) Group 2: Pulmonary venous hypertension (due to left heart disease) Group 3: Pulmonary hypertension associated with hypoxemia (due to lung disease) Group 4: Pulmonary hypertension due to chronic thrombotic/embolic disease Group 5: Miscellaneous 1. Farber H W, Loscalzo J. N Engl J Med. 2004;351;

5 Pulmonary Arterial Hypertension vs Chronic Thromboembolic Pulmonary Hypertension Group 1: PAH Remodeling, occlusion, constriction of small pulmonary arteries mpap > 25 mmhg PAWP < 15 PVR > 3 WU Group 4: CTEPH Incomplete resolution of initial or recurrent pulmonary embolism (PE) Thrombosis of main, lobar, or segmental pulmonary arteries High pulmonary vascular resistance (PVR) Remodeling of pulmonary blood vessels Haythe J. Prog Cardiovasc Dis 2012;55: Humbert M. Eur Respir Rev 2010;19(115):59 63 Moser KM et al. Circulation 1990;81:

6 CTEPH Epidemiology CTEPH may develop in 4-5% of PE survivors ~19,000 cases per year in the US Up to 50% of patients have no history of symptomatic VTE or confirmed PE First PE-4-5% incidence CTEPH Prior PE-35-40% incidence CTEPH 1. Klok FA et al. Haematologica 2010; 95: Humbert M. Eur Respir Rev 2010; 19 (115): Kirson NY. Curr Med Res Opin Sep; 27 (9): Korkmaz A et al. Clin Appl Thromb Hemost 2012; 18: 281

7 Natural and Pathologic History of Normal: Pulmonary Embolism Natural resolution in weeks CTEPH: Incomplete resolution of the initial pulmonary embolism Embolic material becomes attached to the pulmonary arterial wall Embolic material progresses and becomes connective and elastic tissues Humbert M. Eur Respir Rev 2010;19(115):59 63

8 Pathologic Progression of CTEPH DVT Acute PE Incomplete resolution and organization of thrombus Vascular occlusion/obliteration High pressure/sheer stress in open areas Progressive increase in pulmonary vascular resistance CTEPH Humbert M. Eur Respir Rev 2010;19(115):59 63.

9 . Risk Factors for Symptomatic CTEPH Previous PE (OR = 19.0) Younger age (OR = 1.79 per decade) Larger perfusion defect (OR = 2.22 per decile in perfusion) Idiopathic PE at presentation (OR= 5.70) Presence of a ventriculo-atrial shunt or infected pacemaker (OR=76) Splenectomy (OR=18) Chronic inflammation (osteomyelitis, inflammatory bowel disease) Antiphospholipid antibodies Auger et al. Clin Chest Med 31 (2010) Bonderman D et al. Thromb Haemost 2005;93: Humbert M. Eur Respir Rev 2010; 19: 115, Pengo V et al. New Engl J Med 2004;350:

10 Clinical Presentation of CTEPH Early nonspecific clinical symptoms Unexplained exertional dyspnea Atypical chest pain Episodic hemoptysis Non-productive cough Palpitations Fatigue Palpitations Presentation can be initially subtle, but can progress to similar manifestations as PAH Auger WR et al. Clin Chest Med 2010;31: Auger WR et al. Pulmonary Circ 2012;2:

11 Clinical Presentation of CTEPH (cont) Evidence of Right Ventricular dysfunction Peripheral edema Severe exercise limitation Chest discomfort/pain Exertional dizziness or syncopal episodes Auger WR et al. Pulmonary Circ 2012;2:

12 Chronic Thromboembolic Disease CTEPH but without the PH CTED (?) Partial or complete obstruction of pulmonary vascular segments does NOT always mean you will have PH. PV obstruction in areas of normal ventilation will lead to dead space ventilation (V/Q>>1) which contributes to dyspnea, hypoxia. Examples: modest total degree PV obstruction (symptoms at higher workload) single lung occlusion cases with normal contralateral lung circulation

13 ARS Question 1 Which patient is more short of breath in the setting of large segmental perfusion defects In the right lung? A. PAP 70/30, PVR 8, CI 2.2 B. PAP 50/25, PVR 5, CI 2.6 C. PAP 30/12, PVR 2.5, CI 2.4 D. You cannot tell

14 A practical approach to CTEPH: Step 1: look at the heart -echo-doppler exam Step 2: look to the lungs -hemodynamics -VQ scan -CTA -PA gram Step 3: When you need it.add exercise physiology

15 Which of these patients has CTEPH and which has PAH?

16 CTEPH vs. PAH? YOU CAN T TELL

17 The RV responds to afterload regardless of origin of the load. Unlike the LV, the RV is thin walled and distensible Thus, the RV is subject to size, shape, functional changes early in the context of pulmonary vascular disease. RV BEARS WITNESS to increased PVR High PVR FLOW RV LV

18 The VAST MAJORITY (like everyone or just about) of CTEPH patients will have evidence of 1 or more of the following: RV dilation (Size) RV dysfunction (Squeeze) 3 S s systolic septal flattening (Smush) RVOT Doppler notching

19 A practical approach to CTEPH: Step 1: look at the heart -echo-doppler exam Step 2: look to the lungs -hemodynamics -VQ scan -CTA -PA gram Step 3: When you need it.add exercise physiology

20 A practical approach to CTEPH: Step 1: look at the heart -echo-doppler exam Step 2: look to the lungs -hemodynamics -VQ scan -CTA -PA gram Step 3: When you need it.add exercise physiology

21 Hemodynamics of CTEPH Generally, similar to PAH in terms of mpap > 25, wedge < 15, PVR > 3 WU However, the extent, site of vascular obstruction, and obstruction distance from the heart often dictates important differences in the hemodynamics.

22 Case 1 RAP 4 mpap 27 PAWP 5 PA 50/15 CO 5 PVR FPP=PAPP/mPAP 1.3 PTE-maybe. Depends We ll revisit this case.

23 Case 2 RAP 12 mpap 42 PAWP 5 PA 85/20 CO 5 PVR 7 65 FPP=PAPP/mPAP Yoshi PTE!!

24 Case 3 RAP 20 mpap 54 PAWP 5 PA 85/38 CO 3.6 PVR FPP=PAPP/mPAP 0.87 PTE-caution!!!!!!!!!! -never? Or -bridge to transition physiology

25 VQ scan: the gatekeeper of chronic PE imaging A true negative VQ scan essentially rules out CTEPH CTA and PA gram imaging should stem from results of VQ scan

26 With this VQ CTEPH diagnosis I m thinking not

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28 ACUTE CHRONIC

29 ARS Question 2 Which modality of lung imaging gives you the best information for diagnosing CTEPH? A. VQ scan B. CT angiogram C. Invasive pulmonary angiogram D. Integration of all 3 imaging modalities

30 VQ scan CTA PA Gram

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32 Case 1-CTEPH hiding, to the eye 51 yo woman, history of morbid obesity. Remote history of pulmonary embolism. Known, severe PH. Transferred to TUH with 50+ lbs volume overload, hypoxia. ON IV Remodulin, 28 ng/kg/min diuresed lbs, PH meds adjusted. PH workup performed Outside hospital CTA reviewed First OP office visit: 6MWD 165 meters. SpO2 78% on room air. 90% on 3 liters.

33 CTA sensitivity it depends on who is reading it! Initial read: LAN compressing left LLL PA No filling defects Clues: look to RLL also Typical distribution of chronic clot Fear not as we have other ways to look at the lung

34 The VQ scan (same patient) Basically poor perfusion to both lungs in all lobes

35 The PA Gram (same patient)

36 PRE PTE 5 DAYS POST PTE

37 PTE on August 21 st, 2013 Marked improvements in PH, PVR Initial hemos: PVR 11, CI 1.4 Post PTE PVR 5 WU, CI 2.3 Marked overall functional improvements. -off IV prostacyclin -Adempas 2.5 mg TID -no supplemental oxygen 6MWD 165 to 380 meters. SpO2 94% on room air. Lost 50 lbs of flesh weight. Back to work full time

38 Case 2-CTEPH hiding, to the mind 58 yo man, Family Medicine Physician. Competetive cyclist mile rides on the weekends. Reports difficulty in keeping up with the pack on rides In the last 2 weeks, near syncope while cycling Exam: 116/82, HR 74, lbs. Muscular build. SpO2 96% RA. JVP 10, AJR 1+ edema ETCO2 22 6MWD 493 meters 98% SpO2 at end of walk on RA HR 72 86

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40 Normal RVOT Doppler

41 Healthy, fit cyclist. How bad could it be? R H C RHC data: PA 74/29 (44) RA 10 PCWP 8 CI 1.65 PVR 10.0 WU

42 Let s make a collage (spelling?)

43 Case 2b-CTED hiding, to the mind 19 yo woman. College student. Picture of health. Progressive dyspnea. Echo shows normal RV size, function. No PH. History of PE 18 months prior. Prior history of OC use.

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45 No notch but, look at the shape again. Still not normal

46 RHC data: PA 35/13 (21) RA 6 WP 11 CI 2.3 PVR 2.2 This may be CTED Let s exercise

47 REST EXERCISE RA 6 PA 35/13 (21) PAWP 8 CO 5 CI 2.3 PVR 2.2 RA 10 PA 60/25 (37) PAWP 8 CO 8 CI 4.0 PVR 3.6

48 Gas exchange testing the key is ventilatory inefficiency. Look for the dead space! +/- Blunted rise in O2 pulse ***High VE/VCO2 Lack of fall in VD/Vt Desaturation

49 Not all exercise is the same, or informs in a similar way 6 MWD 558 meters SpO2 BP HR 100% rest, 100% with exercise 125/60 rest, 153/75 with exercise 85 rest, 101 with exertion Ramped cycle ergometer protocol (during cath) with CPET 5 Watt/minute ramp Exercised to near maximal SVO2 down to 35% VO2 15 ml O2/kg/min (55% max) *****VE/VCO2 50 (marked ventilatory inefficiency)

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51 Case 3-CTEPH hiding, by philosophy Echo report: LV mild to moderately dilated Anteroseptal, apical akinesis LVEF 25% Grade 2 diastolic dysfunction Mild septal flattening RV moderately dilated Moderate RV dysfunction + mid-systolic notch RVOT Doppler RHC data: PA 80/29 (49) RA 18 WP 21 CI 1.9 PVR 7

52 Philosophies of problem solving Occam s razor (circa 1300)-fewest assumptions should be made to problem solving. diagnostic parsimony Hickam s dictum (Duke U. 1950)-counter to the above. Diagnoses should not be excluded for violating Occam s razor. Applied to medicine=a patient may have as many diseases as they damn well please

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54 PTE centers are all beautiful ARS Question 3 Which picture below is an image of North Philadelphia? A. Image A B. Image B C. The images look too similar. You can t tell the difference. A B

55 Summary CTEPH and CTED are chronic diseases of pulmonary vascular obstruction. Pulmonary vascular obstruction may, or may not cause PH Pulmonary vascular obstruction will always, or nearly always produce symptoms of dyspnea, Exercise intolerance, and at times, hypoxia. Dead space ventilation is a key part of the pathophysiology of CTEPH and CTED Cardiac imaging (echo-doppler) is a key part of the initial screening for CTED and CTEPH -the 3 S s and the NOTCH Lung imaging requires use of all 3 lung imaging modalities VQ first CTA next PA gram last When in doubt we are happy to help you sort it out! Rest and exercise gas exchange testing can be very helpful in revealing the underlying diagnosis. Don t let CTED or CTEPH hide to the eye (get the VQ and have CTA read by an expert) Don t let CTED or CTEPH hide to the mind (you must consider these diagnoses in any dyspneic patient) Don t let CTED or CTEPH hide by philosophy or convention (patients can have > 1 disease!)

56 THANKS-PTE Team, TUH Paul R. Forfia, M.D. Yoshiya Toyoda, M.D. Sheila Weaver, D.O. Chandra Dass, MD Riyaz Bashir, MD Fran Rogers, CRNP Sandra Swain Sia Carter, RN BSN Parag Desai, MD Marshall Lee, MD Kathy Tyson, MD T. Sloane Guy, MD Akira Shiose, MD

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