N A B E E L H A M Z E H , M D

N A T I O N A L J E W I S H H E A L T H

D E N V E R , C O

Cardiac Sarcoidosis

Disclosures

PI: Celgene Cellular Therapeutics: Phase 1B, Multi-center, Open-label, Dose Escalation Study to Evaluate the Safety of Intravenous Infusion of Human Placenta-Derived Cells (PDA001) for the Treatment of Adults with Stage II or III Pulmonary Sarcoidosis.

Sub-Investigator: Centocor : A phase 2, multicenter, randomized, double-blind, parallel-group, placebo controlled study evaluating the safety and efficacy of treatment with Ustekinumab or Golimumab in subjects with chronic sarcoidosis.

All medications mentioned in the presentation are “off-label” use.

How often is the heart involved?

Clinically detected in 5% of cases.

Autopsy series : 27-40%.

Japan : ~70% of cases.

Second leading cause of death in sarcoidosis

Which parts of the heart can be involved? Basal Septum, LV Free Wall Most

How does heart sarcoidosis present?

Asymptomatic / Detected on screening

Palpitations

Pre-syncope/Syncope episode

Sudden cardiac death

What symptoms should concern me?

Palpitations: Abnormal beats, extra-beats, skipped beats…

Passing out or almost passing out (Presyncope / syncope).

Orthopnea / Paroxysmal Nocturnal Dyspnea (PND): Difficulty breathing when lying down that gets better when sitting up.

Lower extremity swelling.

What to expect for my physician?

Screening :

Signs / Symptoms.

12-lead Electrocardiogram.

Ambulatory monitor.

Echocardiogram.

Workup :

Holter monitor.

Echocardiogram.

Cardiac PET.

Cardiac MRI.

EP study.

Official Recommendations (ATS statement 1999) :

- History and physical exam - 12 lead ECG

Electrocardiographic assessments 12-lead ECG

Sensitivity (rule out) 8% - 61%

Specificity (rule in) 22% - 97%

Ambulatory monitor

Sensitivity (rule out) 50% - 58%

Specificity (rule in) 22% - 97%

Medicine (Baltimore) 2004;83(6):315-34. Chest 1994;106(4):1021-4. Mehta et al Chest 2008

Wide ranges due to different “gold standards” used

What is ambulatory monitoring?

Holter monitor 24/48 hour: Records heart electrical activity for 24-48 hours.

Event monitor: Longer periods of monitoring.

Echocardiogram

Sensitivity (rule out) 25% Specificity (rule in) 95%

Findings suggestive of cardiac sarcoidosis :

- Depressed pump function. - Wall motion abnormalities.

- Abnormal wall thickness. - Pericardial effusion.

Has a role in follow up of patients with confirmed cardiac

sarcoidosis to detect potential complications (LV dysfunction, aneurysms, valvular dysfunction).

HOW DO WE MAKE THE DIAGNOSIS ?

After cardiac involvement is suspected…

Imaging Studies

Cardiac 18-FDG-PET scan:

- 18-FDG: fluror-deoxy-glucose

- PET :Positron Emission Tomography

• Cardiac magnetic resonance imaging (cMRI).

Cardiac 18-FDG-PET scan

Radio-labeled sugar (FDG) is used as a radiotracer.

FDG accumulates at sites of active inflammation and at sites with active metabolism.

The goal is to try to identify areas of granuloma in the heart.

Cardiac FDG-PET

• Special protocols are needed: - Prolonged fasting for 6 hours or more.

- Low carbohydrate diet for about 24 hours.

• Patterns seen : - No uptake.

- Diffuse uptake.

- Patchy uptake.

- Patchy on diffuse uptake.

- Free lateral wall uptake.

Sensitivity (rule out) 87.5%

Specificity (rule in) 38.5%

No uptake Patchy uptake

Patchy on diffuse uptake Diffuse uptake

Shortcomings of Cardiac FDG-PET scan

Radiation exposure.

Normal heart muscle also accumulates radiolabeled sugar.

Exact pre-scan protocols are not standardized.

Cardiac MRI

No radiation involved but has its own contrast material.

Cannot be done if there is metal in the body.

Cardiac MRI

- Sensitivity (rule out) 100% - Specificity (rule in) 78% • Patterns seen : Myocardial wall thickening / thinning. Wall motion changes. Increased T2 weighted signal (edema). Delayed hyperenhancement (scar / fibrosis).

• Also beneficial for assessing pump function. • Limitations : Cannot be used with implantable

devices (pacemakers and AICDs).

How is heart sarcoidosis managed ?

Management

Needs a collaborative effort between:

- Sarcoidosis physician.

- Radiologist.

- Cardiologist.

- Electrophysiologist (EP).

Management (Multi-disciplinary approach)

Immunosuppressive therapy. - Prednisone.

- Methotrexate.

- Mycophenolate Mofetil.

- Azathioprine.

- Anti-TNF agents.

Cardiac management : - Anti-arrhythmics.

- CHF management.

- EP.

EP studies

• Helps in evaluating and managing serious abnormal heart rhythms.

• Determines need for an Automated Implantable Cardiac Device.

• Indications for AICD : - Inducible ventricular tachycardia (VT).

- Spontaneous VT.

- Survival from sudden cardiac death (SCD) event.

Role of Immunosuppressive Therapy

Immunosuppressive therapy

- No difference between high and low dose steroids.

- Immunosuppressive therapy can improve arrhythmias and pump function.

- Pump function (Ejection Fraction, EF) and NYHA activity level predict outcome.

- Retrospective studies, does not answer many other questions.

Questions ?