Key Information
Source
Year
2024
summary/abstract
Cardiac amyloidosis is the most frequent infiltrative disease caused by the deposition of misfolded proteins in the cardiac tissue, leading to heart failure, brady- and tachyarrhythmia and death. Conduction disorders, atrial fibrillation (AF) and ventricular arrhythmia (VA) significantly impact patient outcomes and demand recognition. However, several issues remain unresolved regarding early diagnosis and optimal management. Extreme bradycardia is the most common cause of arrhythmic death, while fast and sustained VAs can be found even in the early phases of the disease. Risk stratification and the prevention of sudden cardiac death are therefore to be considered in these patients, although the time for defibrillator implantation is still a subject of debate. Moreover, atrial impairment due to amyloid fibrils is associated with an increased risk of AF resistant to antiarrhythmic therapy, as well as recurrent thromboembolic events despite adequate anticoagulation. In the last few years, the aging of the population and progressive improvements in imaging methods have led to increases in the diagnosis of cardiac amyloidosis. Novel therapies have been developed to improve patients’ functional status, quality of life and mortality, without data regarding their effect on arrhythmia prevention. In this review, we consider the latest evidence regarding the arrhythmic risk stratification of cardiac amyloidosis, as well as the available therapeutic strategies.
1. Introduction
Cardiac amyloidosis (CA) is the most frequent infiltrative cardiomyopathy worldwide [1external link, opens in a new tab]. In the last few years, its growing prevalence has been recorded due to the aging population, advances in diagnosis and therapeutic methods and finally the increased awareness of the medical population [2external link, opens in a new tab]. Indeed, from 2000 to 2012, there was a significant increase in prevalence (8 to 17 per 100,000 person-years) and incidence (18 to 55 per 100,000 person-years) [3external link, opens in a new tab,4external link, opens in a new tab].
Amyloidosis is caused by the deposition of misfolded and non-degradable proteins in the extracellular space of different tissue types; to date, more than 30 different proteins have been identified as responsible for amyloid formation due to genetic or acquired modifications, but only 10 proteins are known to be stored in the myocardium. Among them, immunoglobulins, light chains and transthyretin (TTR) [1external link, opens in a new tab] represent more than 98% of all cardiac amyloid precursors, with TTR being the most frequent type. The progressive accumulation of amyloids in the heart leads to hypertrophic remodeling and increased stiffness, resulting in diastolic dysfunction in the early stages [5external link, opens in a new tab]. Heart failure with preserved ejection fraction (HFpEF) is the earliest and most frequent presentation at the time of diagnosis [6external link, opens in a new tab,7external link, opens in a new tab]; systolic impairment follows, and it is characterized at the beginning by a reduction in left ventricle global longitudinal strain, associated traditionally with “apical sparing” [8external link, opens in a new tab,9external link, opens in a new tab]. Atrial wall dysfunction [10external link, opens in a new tab,11external link, opens in a new tab] and valve defects, like significant mitral regurgitation and aortic stenosis, due to direct amyloid deposition are also distinguishing features of CA [12external link, opens in a new tab]. Indeed, in patients over 65 years old, affected by severe aortic stenosis, cardiac amyloidosis is frequently encountered and needs to be excluded. Moreover, palpitations, syncope and sudden cardiac death (SCD) characterize the natural history of this disease, with atrial fibrillation (AF), ventricular arrhythmia (VA) and conduction disorders as the most frequently underlined findings. The arrhythmia prevalence is up to 60% according to studies [13external link, opens in a new tab], being associated with an increased rate of hospitalization and length of stay and a reduction in survival rates [14external link, opens in a new tab,15external link, opens in a new tab]. Table 1external link, opens in a new tab and Figure 1external link, opens in a new tab provide an overview of the prevalence, etiopathogenesis, prognosis and treatment of arrythmias in cardiac amyloidosis (CA).