Arrhythmias in Cardiac Sarcoidosis Bench to Bedside: A Case-Based Review

Abstract

Cardiac sarcoidosis is a component of an often multiorgan granulomatous disease of still uncertain cause. It is being recognized with increasing frequency, mainly as the result of heightened awareness and new diagnostic tests, specifically cardiac magnetic resonance imaging and ¹⁸F-fluorodeoxyglucose positron emission tomography scans. The purpose of this case-based review is to highlight the potentially life-saving importance of making the early diagnosis of cardiac sarcoidosis using these new tools and to provide a framework for the optimal care of patients with this disease. We will review disease mechanisms as currently understood, associated arrhythmias including conduction abnormalities, and atrial and ventricular tachyarrhythmias, guideline-directed diagnostic criteria, screening of patients with extracardiac sarcoidosis, and the use of pacemakers and defibrillators in this setting. Treatment options, including those related to heart failure, and those which may help clarify disease mechanisms are included.

Keywords: atrial fibrillation; bradycardia; defibrillator; heart failure; sarcoidosis; tachycardia.

Figure 1:

Key events in pulmonary sarcoid pathogenesis. 1) Antigen (Ag) exposure in regional lymph nodes leads to internalization, degradation to peptides and presentation on the surface of antigen presenting cells (APCs), such as dendritic cells in peptide-major histocompatibility complexes (MHC); 2) Recognition by CD4+ T cells that have T cell receptors (TCRs) that recognize the peptide-MHC complex, leads to clonal amplification and activation of these CD4+ T cells and proliferation with Th1 polarization (the detection of clonal amplification of CD4+ T cells support the existence of a pathogenic antigen that is recognized by these cells); 3) Activated circulating CD4+ T cells home via chemokines (e.g. CCL2) to tissue sites with antigen, activating macrophages to organize into granulomas, which consist of multinuclear giant cells and fused highly differentiated macrophages and also include Th1 cells; 4) Resolution of the inflammatory process with remission vs. progression to fibrosis with ongoing chronic inflammation.

Figure 2:

(Panels A-B) Echocardiogram demonstrating a left ventricular basal anteroseptal aneurysm complicated by ventricular septal rupture (denoted by asterisk) with left-to-right shunt seen by color flow. (Panels C-D) Left ventricular basal anteroseptal thickening thought to be due to inflammation, shown in both diastole and systole, that mimics hypertrophic obstructive cardiomyopathy with systolic anterior motion of the mitral valve (MV).

Figure 3:

Panel A: CMR with areas of subtle hypoperfusion seen in Gradient Echo Perfusion Imaging (GRE) as areas of decreased signal intensity in endo and mid-myocardium of the LV (yellow arrows). Panel B: Areas of corresponding LGE seen in the anterior (endo/midmyocardial) and inferior (near transmural) wall of the LV (yellow arrows).

Figure 4:

Rest 82-Rubidium perfusion images from Case 2 show perfusion defects in the basal septum, basal anterior and anterolateral segments, as well as apical inferior, apical lateral, and mid inferolateral segments suggesting areas of scar (A). ¹⁸F-FDG PET imaging shows a mismatch pattern with increased uptake in these segments, increased uptake in adjacent basal and mid inferior as well as mid anterolateral segments (A), and increased RV uptake (B) consistent with active inflammation in these areas. The combination of perfusion defects (scar) and ¹⁸F-FDG uptake (inflammation) allows a more complete understanding of the patient’s burden of disease, prognosis, and pathology. Whole body imaging (C), shows increased ¹⁸F-FDG uptake in hilar and mediastinal lymph nodes.

Figure 5:

ECG showing sinus tachycardia with high degree heart block and an escape rhythm with a RBBB, complete and incomplete, and alternating normal and left axis.

Figure 6:

ICD interrogation showing rapid ventricular tachycardia (FS), meeting criteria for the “ventricular fibrillation” (VF) zone, terminated by burst pacing (TP) prior to device charging. AR/Ab=markers of atrial activity, VS=Ventricular sensed event.

Figure 7:

Panels A and B: Pathology of explanted heart of a patient with cardiac sarcoidosis. Giant cells and focal granulomata are seen.