Cardiac Sarcoidosis (Or How I Learned to Stop Worrying and Love Managing the Disease)

Cardiac Sarcoidosis (or How I Learned to Stop Worrying and Love Managing the Disease)

Ronald Wieles, MD Sarcoid: Overview

Can involve essenally any organ • Pulmonary involvement = most common • Mortality most commonly from cardiac or pulmonary causes

Cardiac clinical features

Sarcoid: Overview

Can involve essenally any organ • Pulmonary involvement = most common • Mortality most commonly from cardiac or pulmonary causes

Cardiac clinical features • Heart block • VT • LV dysfuncon – oen segmental • Lack of signiﬁcantly elevated troponin • EKG voltages are variable

Sarcoid: Overview

Can involve essenally any organ • Pulmonary involvement = most common • Mortality most commonly from cardiac or pulmonary causes

Cardiac clinical features • Heart block • VT • LV dysfuncon – oen segmental • Lack of signiﬁcantly elevated troponin • EKG voltages are variable

So when should you be suspicious?

Sarcoid: Overview

Can involve essenally any organ • Pulmonary involvement = most common • Mortality most commonly from cardiac or pulmonary causes

Cardiac clinical features • Heart block • VT • LV dysfuncon – oen segmental • Lack of signiﬁcantly elevated troponin • EKG voltages are variable

So when should you be suspicious? • Any of the above ﬁndings in a paent with known extra-cardiac sarcoid • Clustering of the above ﬁndings without a good alternave explanaon

Sarcoid: Overview

Can involve essenally any organ • Pulmonary involvement = most common • Mortality most commonly from cardiac or pulmonary causes

Cardiac clinical features • Heart block • VT • LV dysfuncon – oen segmental • Lack of signiﬁcantly elevated troponin • EKG voltages are variable

So when should you be suspicious? • Any of the above ﬁndings in a paent with known extra-cardiac sarcoid • Clustering of the above ﬁndings without a good alternave explanaon

Diagnosis • Role (or lack thereof) of endomyocardial biopsy • So how do you make the diagnosis?

Sarcoid: Imaging Opons

TTE: Can see segmental dysfuncon, but nothing speciﬁc for sarcoid

MRI: Besides accurate morphologic picture à abnormal delayed gadolinium enhancement in noncoronary distribuon • Does not well-differenate from other infiltrave disease • Does not differenate acve disease from scar • Many/most paents cannot get due to PPM/ICD

This is where we were not too long ago… making this disease very challenging to manage! • Frequently unsure of diagnosis • Constantly worried about overtreang disease (wrong diagnosis, treang inacve disease) or undertreang disease • I used to be referred these paents – but wished I wasn’t! • What changed?

FDG-PET Imaging

Myocardial metabolism overview

FDG-PET Imaging

Myocardial metabolism overview • Main energy sources: Glucose & fay acids • Glucose: More ATP generaon per O2 molecule used • Fay acids: More ATP generaon per substrate molecule • Heart: Omnivore à Will switch back/forth based on substrate availability, insulin sensivity, myocardial stress

FDG-PET Imaging

Concept in viability imaging

FDG-PET Imaging

Concept in viability imaging • Try to drive myocardium to use glucose • Remember: Always done along with perfusion scan (e.g. SPECT Myoview) • Raonale: Myocardium is alive if takes up perfusion agent or takes up FDG • Healthiest myocardium: FDG may be negave (because using fay acids) but then should take up perfusion agent • Insulin can be given to drive metabolism à glucose.

FDG-PET Imaging

Concept in sarcoid imaging • Want to drive metabolism à fay acids, so only areas taking up glucose are areas of acve inﬂammaon • Achieve with dietary intervenons (Carbohydrate free meals day prior à overnight fast)

FDG-PET Imaging

Advantages of FDG-PET imaging • Diﬀerenates acve disease from burnt out disease • Helpful for both diagnosis & disease monitoring! • No issues re: PPM/ICD • Gives full-body scan, not just heart • If classic uptake in other areas of body à diagnosis much more likely • Provides other potenal sites for biopsy • Can use disease response in rest of body as sanity-check for disease response in heart

Potenal pialls of FDG-PET imaging • Not specific for sarcoid; really just saying acve inflammaon (but do we care?) • If diet not meculously followed à largely worthless test • Findings can be obvious... Or subtle. • Focal sites of cardiac uptake à most convincingly posive • No significant cardiac uptake à convincingly negave • What to do with diffuse uptake? • Is the disease super-acve, or was it just a bad prep? • Always look at these scans yourself (great variaon in reads)

Sarcoid: Treatment

Queson 1: To treat or not to treat? • Always a balance of overtreatment vs. undertreatment • Only want to treat acve disease, not inacve/burnt out disease • General goal: Suppress acve disease with minimum dose of long-term steroids as possible (including dose of 0)

Queson 2: I’ve decided to treat, what should I use? (**Evidence-free zone**) • Steroids: Most effecve, typically use up front for acve cardiac disease • Inial dose: Usually prednisone 40-60 mg, unless very mild disease • Methotrexate: Well-tolerated, good safety profile • Goal: Suppress disease with MTX, use to minimize steroid dose • My protocol on next slide… • Other agents: TNF inhibitors, azathioprine, leflunomide, chloroquine…

What about arrhythmias? • Low threshold for ICD placement

Sarcoid Treatment: My Usual Protocol Iniaon: • Prednisone 40 mg qd • Methotrexate 10 mg po qweek, increase by 2.5 mg/week every 2 weeks unl maximum of 25 mg qweek. • Monitor CBC/LFTs at baseline, monthly during uptraon, then q3 months • Cauon if signiﬁcant renal insuﬃciency • Usually also give folate 1 mg qd.

Weaning: • Guided by signs of disease acvity (clinical/imaging) • Aim for MTX 25 mg qweek as long as tolerang & no laboratory evidence of toxicity à maintain indeﬁnitely • Repeat PET based on clinical signs as well as periodically as wean prednisone (e.g. at 20 mg, 10 mg, oﬀ) • Once at a stable & low prednisone dose (including 0), only repeat PET if clinical suspicion of change in disease acvity (e.g. change in arrhythmias, clinical heart failure, worsening LVEF)

Don’t forget about: • PCP prophylaxis (if on >20 mg qd of prednisone, parcularly in combinaon with another agent) • Osteoporosis screening/treatment, eye exams, glucose control Other Cardiac Therapy Rhythm management: • Anarrhythmics • VT ablaon • Can be helpful, but usually only turn to if sll having large VT burden despite appropriate immunosuppression

Device placement: • Many paents need PPM for AV block • Low threshold for ICD placement

Standard HF therapy (?) if LV dysfuncon • Seems like a good idea, but we don’t really know… • Cauon with beta-blockers if no pacer/ICD Case Examples Case #1

53 y.o. man:

Summer 2012: GI discomfort /palpitaons à MD à Holter à 332 runs of NSVT.

ETT à No ST changes, exercise tolerance okay, +NSVT at peak exercise

Cath à No CAD. LVG = Inferior akinesis

What next?

MRI Results MRI Results

Interpretaon: “Transmural DE of basal-mid inferoseptal/inferior LV & adjacent septal/inferior RV myocardium extending to basal-mid anteroseptal/inferolateral, most c/w RCA infarct. If no RCA infarct by history, consider myocardis.” LVEF 48%, AK basal inf-septum Clinical Course

VT ablaon 12/12 à Mulple sites of inducible VT. Ablaon performed. Postop VT.

Referred to sarcoid clinic 1/13. Suspicious for sarcoid on basis of scar (which didn’t appear to be truly vascular distribuon on review), VT.

PET ordered…

PET 2/13 PET 2/13

Interpretaon: Defect in inferior wall/septum on SPECT with associated increased metabolism c/w cardiac sarcoid. Nodular hypermetabolism seen in spleen/liver & mulple osseous foci of uptake, suggesve of diﬀuse sarcoid vs. malignancy. Clinical Course

Paent did not want to start empiric treatment.

3/13: Liver biopsy à Non-caseang granuloma

Started on prednisone 40 mg qd & methotrexate. ICD recommended à came for placement à in sustained VT à admied, treated with lidocaine with resoluon à ICD placed.

TTE: LVEF down to 35%, area of basal-mid anteroseptal wall/inferior septum/posterior wall now frankly aneurysmal.

PET 4/13 (on therapy) PET 4/13 (on therapy)

Interpretaon: Near complete resoluon of acvity in spleen, liver, spine. Markedly decreased acvity in LV. Minimal residual acvity. Clinical Course

Sll had very high VT burden à Repeat VT ablaon à decreased VT, but sll 1 shock.

TTE: Unchanged.

Plan: 1) Connue methotrexate/prednisone, repeat PET, plan for prednisone downtraon as possible. 2) Paent’s local rheumatologist did quick downtraon of prednisone to 15 mg qd (faster than I would have done).

PET 8/13 PET 8/13

Interpretaon: “Near complete resoluon of abnormal acvity in the LV. No abnormal uptake elsewhere in the body.” Clinical Course

Connued prednisone downtraon to 10 mg à VT ﬂurry requiring frequent ATP.

On sotalol & mexiline for anarrhythmics.

Paent very reluctant to increase prednisone à agreed to 12.5 mg qd, and further MTX uptraon (had stopped at 15 mg q week) to goal 25 mg/week dose, repeat PET. (Paent self lowered prednisone to 10 qd shortly thereaer.)

PET 12/13: No abnormal acvity à connued steroid wean to 5 mg.

PET 5/14: Mild diﬀuse acvity in LV, ongoing slow VT episodes (not more or less) à connued current therapy.

PET 11/14: Unchanged from 5/14. Ongoing stable VT burden, TTE unchanged. Connued current therapy.

Current clinical update: Remains on stable immunosuppression, stable burden of slow VT. Connuing current treatment & immunosuppression

Case #2

74 y.o. man with longstanding asthma:

2000: MI à PCI to LAD

2003: Respiratory symptoms à abnormal CXR à biopsy à sarcoid

2005: PCI to LAD

2012: Complete heart block

11/3/12: MRI ordered

MRI Results MRI Results

Interpretaon: “Nonspeciﬁc subtle mesocardial delayed enhancement of the mid-basal LV septum at the inferior inseron site of the RV. Sarcoid involvement at this locaon remains a possibility.” Mediasnal lymphadenopathy also noted. MRI Results

ICD placed in hospital • Normal LVEF but placed in seng of need for PPM & presumpve cardiac sarcoid • Diﬃcult decision (though did later have signiﬁcant NSVT burden on device)

Referred to sarcoid cardiac clinic 8/13 • Not on any immunosuppressives other than inhaled steroids for asthma

What would you do?

Management

ICD placed in hospital • Normal LVEF but placed in seng of need for PPM & presumpve cardiac sarcoid • Diﬃcult decision (though did later have signiﬁcant NSVT burden on device)

Referred to sarcoid cardiac clinic 8/13 • Not on any immunosuppressives other than inhaled steroids for asthma

What would you do?

What we did: • Methotrexate iniaon, no steroids • PET imaging

PET Results PET Results

Interpretaon: PET+ nodes (parcularly paratracheal) PET+ LLL node (stable from old CT) No signiﬁcant cardiac uptake Management

Tolerated methotrexate well à connued indeﬁnitely

No systemic steroids (not otherwise indicated)

Monitored clinically • No signs of progression via symptoms/arrhythmia ﬂares/EF drop as of now

Case #3

58 y.o. man, previously healthy

2011: Screening calcium score CT done (50th %ile)

3/13: Exercise tolerance when riding bike dropped oﬀ à realized HR had abruptly dropped & developed DOE. Went to PAMF urgent care à interiment high-grade heart block à PPM placed

Postop CXR performed…

CXR CXR

“A cluster of pulmonary nodules, largest 9 mm, are seen in the RUL. Recommend clinical correlaon. If clinically indicated a repeat 2-view CXR in 6 weeks can be taken to demonstrate resoluon.” Clinical Course

Referred to PAMF Pulmonary

Reviewed past calcium-score CT from 2011 à had actually had some small pulmonary nodules seen then.

New CT 3/13: Mildly enlarged mediasnal LN, mulple RUL nodules, 1 small RLL nodule, either stable or slightly enlarged from 2011

F/U CT 7/13: Lesions slightly larger, sll largest = 9 mm. Rec’d f/u imaging.

F/U CT 3/14: Some nodules stable, mulple new nodules, largest = 12 x 7 mm RLL nodule & noted that some smaller lesions had peribronchovascular distribuon suggesve of sarcoidosis.

6/14: PET performed… PET Results PET Results

Interpretaon: Hypermetabolic nodal disease above/below the diaphragm with FDG-avid pulmonary nodules, likely represenng acve sarcoid. Increased FDG uptake in anteroseptal wall without perfusion defect. EF 45% Treatment Plan

Prednisone 40 per day

Methotrexate as per usual uptraon protocol PET aer 2 months of Prednisone 60 & MTX PET aer 2 months of Prednisone 60 & MTX

Interpretaon: Diﬀuse low-grade uptake throughout myocardium, ? Poor prep. Focal areas of uptake in anterior apex/septum have decreased uptake à favorable response. Markedly decreased uptake in mediasnal/hilar/portocaval nodes/lung nodules. Treatment Plan

Connue current prednisone

Connue uptraon of MTX to goal

Plan to repeat PET aer that… 3 Months Later… 3 Months Later…

Interpretaon: Diﬀuse LV uptake. Given lack of other abnormal uptake elsewhere, suggesve of poor prep elsewhere. Supraspinatus muscle uptake (golf injury) Clinical Course

Device interrogaon à Increasing VT burden TTE: Stable LVEF 46% (global) Queson: Does he have acve cardiac sarcoid or not?

Plan: ICD upgrade (CRT-D placed) BB uptraon (ulmately also started on sotalol) & losartan Inﬂixamab added to regimen Plan for repeat PET 3-4 months

3 Months Post-Inﬂiximab Addion… 3 Months Post-Inﬂiximab Addion…

Interpretaon: Interval development of a mild FDG avid GGO in RLL. Focal FDG uptake in anteroseptal/anterolateral wall, suggesve of acve sarcoid. Ongoing supraspinatus uptake (golf injury) Clinical Course

Was sll going to try steroid downtraon but…

Device interrogaon à more ﬂurries of VT.

Plan: Sotalol uptraon, connue triple-immunosuppression, plan repeat PET, TTE, device check in 2-3 months.

3 Months later: - Sll having episodes of VT, though less - TTE with stable EF 48% - Repeat PET…

3 Months Later…

Interpretaon: Interval increase in LV uptake Decreased uptake of pulmonary nodule Resolved supraspinatus uptake So Now What?

Illustrates challenge which sll exists in managing cardiac sarcoid paents.

Could reasonably make a case for uptraon, downtraon, or no change.

My take: - Noncardiac acve disease has disappeared (by PET) - Arrhythmia burden connues but is beer, and ? If from acve disease or scar - Unlikely to have very acve cardiac disease over this meframe without drop in LVEF - High need to get him oﬀ some of the immunosuppression if at all possible.

Acon: - Dropping prednisone 40 à 30 à 20 (watching arrhythmias) - F/U PET, TTE, device check at that me - Crossing of ﬁngers/prayer Summary

1) Think about cardiac sarcoid if either: a) Heart block, VT, or low EF in paent with extracardiac sarcoid, or b) Clustering of 2 of the above in any paent without a good explanaon.

2) PET imaging: a) Most useful diagnosc tool these days for cardiac sarcoid b) Can be helpful in making the diagnosis & in monitoring

3) Cardiac management besides immunosuppression: a) Rhythm management b) Low threshold for ICD c) Standard HF therapy if LV dysfuncon (?), cauously

4) Immunosuppression: a) Goal: Suppress disease acvity with lowest possible dose of chronic prednisone b) My tacc: Use steroid-sparing agent (usually MTX) in everyone c) Remember: Monitoring of appropriate labs, osteoporosis/eye/glucose screening, PCP prophylaxis