Cardiac Sarcoidosis 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 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

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 : Workup : Signs / Symptoms. 12-lead Electrocardiogram. Ambulatory monitor. Echocardiogram. 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% Wide ranges due to different gold standards used Medicine (Baltimore) 2004;83(6):315-34. Chest 1994;106(4):1021-4. Mehta et al Chest 2008

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).

After cardiac involvement is suspected HOW DO WE MAKE THE DIAGNOSIS?

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 Diffuse uptake Patchy on 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?