Arrhythmogenic Inflammatory Cardiomyopathy in Autoimmune Rheumatic Diseases: A Challenge for Cardio-Rheumatology

Abstract

Ventricular arrhythmia (VA) in autoimmune rheumatic diseases (ARD) is an expression of autoimmune inflammatory cardiomyopathy (AIC), caused by structural, electrical, or inflammatory heart disease, and has a serious impact on a patient’s outcome. Myocardial scar of ischemic or nonischemic origin through a re-entry mechanism facilitates the development of VA. Additionally, autoimmune myocardial inflammation, either isolated or as a part of the generalized inflammatory process, also facilitates the development of VA through arrhythmogenic autoantibodies and inflammatory channelopathies. The clinical presentation of AIC varies from oligo-asymptomatic presentation to severe VA and sudden cardiac death (SCD). Both positron emission tomography (PET) and cardiovascular magnetic resonance (CMR) can diagnose AIC early and be useful tools for the assessment of therapies during follow-ups. The AIC treatment should be focused on the following: (1) early initiation of cardiac medication, including ACE-inhibitors, b-blockers, and aldosterone antagonists; (2) early initiation of antirheumatic medication, depending on the underlying disease; and (3) potentially implantable cardioverter–defibrillator (ICD) and/or ablation therapy in patients who are at high risk for SCD.

Molecular Basis of Inflammation in the Pathogenesis of Cardiomyopathies

“…In particular, compared to controls, ACM patients showed higher plasma levels of the inflammatory cytokines IL-1β, IL-6 and TNF-α and a higher myocardial 67 Ga uptake [ 32 ]. There is evidence that these inflammatory cytokines can modulate the expression and function of ion channels, both by directly acting on cardiomyocytes and/or by inducing a systemic effect [ 33 ]. These changes may be involved in disease progression, heart failure development and ventricular arrhythmias.…”

Organ Manifestation and Systematic Organ Screening at the Onset of Inflammatory Rheumatic Diseases

“…So far, there are no data for such a combined screening approach, but it is well-known that cTnI is an appropriate biomarker of primary cardiac involvement in IRD [ 48 , 49 , 50 ], and cardiac MRI is able to detect myocardial inflammation, subendocardial vasculitis, and fibrosis in early and established IRD, even in the absence of echocardiogram abnormalities [ 51 , 52 , 53 , 54 ]. Furthermore, arrhythmia (especially ventricular arrhythmia) in IRD is associated with cardiac inflammation, which can be accurately detected by cardiac MRI [ 55 , 56 ]. A high level of experience is required to evaluate a cardiac MRI [ 53 ].…”

Ventricular Tachycardia Has Mainly Non-Ischaemic Substrates in Patients with Autoimmune Rheumatic Diseases and a Preserved Ejection Fraction

“…Furthermore, myocytes within areas of interstitial fibrosis may spontaneously depolarise during diastole, resulting in abnormal automaticity and arrhythmia [ 31 ]. More recently, a plethora of additional interweaving mechanisms, such as immune cell infiltration of the myocardium and pro-arrhythmogenic effects of cytokines and antibodies, have been recognised as additional facets of the underlying multifactorial pathophysiology of arrhythmogenicity in NIHD [ 1 ]. In these patients, there is often mid-wall or subepicardial fibrosis, making ablation of arrhythmogenic loci challenging and potentially explaining why outcomes of ablation for control of arrhythmogenicity in NIHD are worse compared with IHD [ 32 ].…”

“…In patients with autoimmune rheumatic diseases (ARDs), development of arrhythmogenic inflammatory cardiomyopathy can lead to out-of-hospital cardiac arrest (OHCA) and can also potentially cause sudden cardiac death (SCD) [ 1 , 2 ]. An important challenge in the context of OHCA is that the majority of patients experience it as a first presentation, often without previous symptoms or a diagnosed cardiac condition [ 3 ].…”

“…This arrhythmogenicity was traditionally attributed to ventricular scarring leading to re-entrant VT/VF [ 10 ]. However, a complex interplay between the immune system and the heart may lead to arrhythmogenicity via other routes in patients with ARDs, namely microvascular coronary artery disease, myocardial oedema, immune cell infiltration and direct effects of cytokines and immunoglobulins on cardiac ion channels [ 1 ]. These factors may adversely affect the conductive properties of the myocardium, thus causing pathological alterations in excitability and subsequent arrhythmogenicity.…”