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Evaluation and Management of Patients with Suspected Cardiac Sarcoidosis

2016 UCSF/Queen’s Hospital Innovative Procedures, Devices, and State of the Art Care for Arrhythmias, Heart Failure, and Structural Heart Disease

Vasanth Vedantham MD, PhD Assistant Professor

Division of Cardiology Cardiac Electrophysiology

Outline

• 1. Basics of Cardiac Sarcoidosis
• 2. Diagnosis of Cardiac Sarcoidosis
• 3. Management of Cardiac Sarcoidosis
• 4. Ventricular Arrhythmia in Cardiac Sarccoidosis

Systemic Sarcoidosis

Granulomatous Disease of Unknown Etiology Prevalence ~ 10-20 per 100,000 Presents between 10 and 40 years of age Half noted incidentally on CXR Lung most commonly affected organ

Patterns of Myocardial Involvement

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Histology

Favora et. al. Am J Cardiol 2009;104:571–577 EARLY – Lymphocytic Infiltrate GRANULOMA PHASE LATE - SCAR

Diagnosis

Diagnosis of Cardiac Sarcoidosis

2014 HRS Expert Consensus Document on CS

Case 1.

39 year old man developed mild chronic cough. A CXR showed hilar adenopathy. Biopsy of adenopathy showed noncaseating granuloma consistent with sarcoidosis. ECG showed RBBB with T wave inversions. A TTE was normal. An ETT showed excellent exercise tolerance. Should this patient receive further testing for cardiac sarcoidosis?

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Who should be evaluated?

Frequently Silent 5% of patients with sarcoidosis have clinically apparent cardiac involvement Variable numbers from autopsy studies 20-70% of patients with sarcoidosis have subclinical cardiac involvement. Cardiac involvement is the most common cause of death in patients with sarcoidosis. All patients with systemic sarcoidosis should be screened for CS

Cardiac Sarcoidosis

2014 HRS Expert Consensus Document on CS

Screening for cardiac involvement

2014 HRS Expert Consensus Document on CS

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ECG/Holter

Infra-His Conduction System Disease Repolarization Abnormalities QRS Fragmentation Abnormal SAECG with Late Potentials Pseudoinfarction Frequent PVCs Findings can mimic ARVC.

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EKG

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TTE

Can be normal Common Findings: WMA or Anneurysm Basal LV septal HK or thinning Global HK Valvular Regurgitation (with Pap Muscle Involvement) Right ventricular dilation/dysfunction pHTN (lung involvement or LHF)

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MRI

Utility in Cardiac Sarcoidosis ~25% of ECS have positive MRI findings LGE as a single test performs better than most

• ther clinical criteria in detection of disease

Patterns can mimic CAD or other myopathies Severity of MRI findings predict adverse events. Challenges Distinguishing scar from active disease ICDs and pacemaker dependent patients

Imaging

RV PET

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Case 2.

42 year old woman well until November 2010, when she developed episodes of sudden-onset anxiety accompanied by coughing and shortness

• f breath. A Holter was done and was interpreted

as normal. She was told to lose weight, then was given antibiotics which did not improve the cough. She then complained of heart pounding and

• ccasional palpitations, and was diagnosed with

anxiety and depression and started on SSRIs.

Case 2.

In March 2011, she had an episode of syncope with no prodrome. She was taken to the ED, where she was diagnosed with complete heart block and a dual chamber pacemaker was implanted. PVCs and polymorphic NSVT were noted during the

• implant. TTE showed normal function. Over the

next year, she had occasional palpitations and 2 episodes of NSVT were recorded on her

• pacemaker. Coronary angiography was normal,

and she was referred with the questions: Is this cardiac sarcoidosis?

Who Should be Evaluated?

Complete Heart Block < 60 years of age 2 recent retrospective case series: 11/32 with unexplained CHB < 60 had CS 18/72 with unexplained CHB has CS 25-35% of young and middle-aged patients with unexplained CHB have cardiac sarcoidosis.

Nery et al. (2014) J Cardiovasc Electrophysiol, 25(8): 875-881 Kandolin et al. (2011) Circ Arrhythm Electrophysiol, 4(3):303-9

Workup for Unexplained AV Block

2014 HRS Expert Consensus Document on CS

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Nuclear Imaging

F-18 FDG PET Sensitivity comparable or superior to MRI Technique and adherence to pre-imaging diet are critical and can prevent over- or under-diagnosis Can be used to follow disease activity Can identify extra-cardiac sites amenable to bx

F18-FDG-PET Case 3.

A 45 year old man with no significant PMH presented with sudden-onset syncope while at work as a physical therapist. He regained consciousness but HR was 200 so taken to ED, where he was in a WCT and ultimately required

• cardioversion. Underlying ECG showed RBBB.

TTE showed mild RV enlargement with normal biventricular function. Referred to UCSF for EPS/ablation. Cardiac MRI showed extensive

• LGE. Chest CT with no adenopathy or pulmonary

dz. Could this be isolated cardiac sarcoidosis?

Case 3: EKG

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Case 3: PET Cardiac Sarcoid Who Should be Evaluated?

Unexplained MMVT (not outflow tract) 2 case series: 4/14 unexplained MMVT had CS 18/103 unexplained VT had CS ~15-30% of patients with unexplained VT have cardiac sarcoidosis.

Nery et al. (2014) Pacing Clin Electrophysiol, 37(3): 364-374 Tung et al (2015) Heart Rhythm, Aug 10, S1547-527

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Endomyocardial Biopsy

Low sensitivity because disease is patchy Try to biopsy area of abnormality Can do EPS and voltage map to guide

Liang et al. (2014) JACC Heart Fail. 2(5):466-73 See also: Nery et al. (2013) Can J Cardiol. 29(8):1015

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Voltage-Guided Biopsy

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Voltage-Guided Biopsy

Management

Immunosuppression.

No consensus on optimal approach Standard of care is corticosteroids ?role for adjunctive steroid-sparing therapy

• methotrexate
• TNF blockers

Immunosuppression: UCSF Approach

3 weeks of high dose prednisone, followed by taper over 10 weeks Methotrexate Follow-up with PET scan in 6 months TNF Blocker if persistent disease activity

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Case 4.

A 32 year old woman complained of lightheadedness to her PCP . She wore a Holter monitor which showed episodes of 2:1 heart block. She underwent pacemaker implantation and subsequently developed complete heart block with 100% ventricular pacing. She was referred to UCSF, where chest CT showed hilar adenopathy and cardiac MRI and PET were consistent with active cardiac sarcoidosis. The patient was asymptomatic with normal LV function and no ventricular arrhythmia. Should this patient receive immunosuppression?

Immunosuppression – Why Treat?

No Randomized Data! Observational Data:

• 1. Prevent Scarring/Heart Failure
• 2. Prevent Arrhythmias
• 3. Reverse AV Block
• 4. Prolong Life?

Case 4: Before Treatment

Complete Heart Block, 100% V-pacing

Case 4: 1 week into treatment

AV Conduction Present, prolonged PR, QRS 145, 30% V-pacing

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Case 4: 1 month into treatment

PR normal, QRS 135, 1% ventricular pacing

Recovery of AV Block in CS

Risk Stratification and ICDs

Who Should Receive an ICD.

History of Sustained VT or VF Impaired LV Function Imaging Findings (Scar Size) Inducible VT at EPS (controversial) Needs Pacing ?Anyone with bona fide cardiac sarcoidosis

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Who Should Receive an ICD.

Penn Data: 38% Received Appropriate Therapies 15%/year Rate of Appropriate Therapies Colorado Data 33% Appropriate Therapies 12%/yr Rate in Primary Prevention Main Predictor was impaired LVEF. Many primary prevention patients received therapies.

Who Should Receive an ICD.

Management of VT

VT in Sarcoid

Commonly Pleiomorphic or Multiple Morphologies Immunosuppression and Antiarrhythmics for Active Disease Catheter Ablation for VT in Quiescent CS or for refractory VT

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Example of VT in a Quiescent CS Pt Outcomes of VT ablation in CS

Kumar et al 2015 and Muser et al 2016. Circ AEP . Complex Confluent Biventricular Scar; Multiple VT Morphologies; 86% Recurrence Rate after 1 procedure; Overall effectiveness at 2 years ~50% inclusive of multiple procedures

Natural History of CS: Cardiac Sarcoidosis Consortium Active Research Questions in CS

2014 HRS Expert Consensus Document on CS

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Conclusions

• Patients with systemic sarcoidosis, unexplained

CHB or VT should be screened for CS

• Although ECG and TTE can be suggestive or

diagnostic, advanced imaging or guided endomyocardial biopsy is frequently required to make the diagnosis

• No randomized data, but Immunosuppression for

active disease can prevent deterioration in EF, improve ventricular arrhythmias, and reverse complete heart block

• ICDs are usually indicated for primary or secondary
• prevention. Role of catheter ablation for VT

remains to be fully defined, but is probably best used in quiescent disease

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Thank You