Cardiac Amyloid Buildup Correlates with Risk of Atrial Fibrillation

Amyloids are misfolded proteins that become insoluble in their incorrect configuration, forming structures that encourage other molecules of the same protein to also misfold in the same way. These structures spread, grow, and clump together into solid deposits in and around cells. Only a handful of proteins can form amyloid, and many are associated with age-related disease. Consider the amyloid-β characteristic of Alzheimer's disease, for example. The better understood forms of amyloid are known to be accompanied by a surrounding halo of toxic biochemistry that harms cells and cell function.

Setting aside genetic diseases in which proteins are created in a damaged form, more prone to amyloid formation, there are a couple of forms of amyloid that tend to show up in heart tissue with age, light chain amyloid and transthyretin amyloid. The present consensus is that light chain amyloidosis is more common to heart disease in comparison to the presence of transthyretin amyloid, but this may or may not in fact be the case, given (a) the comparatively lack of rigorous data for the subclinical, early stage of amyloidosis, and (b) work of recent years showing a greater prevalence of transthyretin amyloid in patients than previously suspected.

Everyone accumulates transthyretin amyloid as aging progresses, transthyretin amyloidosis is the major cause of death of supercentenarians, but it is far from clear as to how much harm is being done - relative to other issues - in earlier old age. Consider that aging is an accumulation of damage, and amyloids are a form of damage that degrades tissue function, but the clinical community tends to only declare a diagnosis of amyloidosis somewhere well past the point at which meaningful long-term harm is probably resulting.

The study here is an attempt to gain data on just how much damage might be taking pace to heart function in older individuals as a result of subclinical levels of amyloid in the heart. The authors do not distinguish between types of amyloid, but I think that this sort of effort is useful. You might compare it to a paper from recent years in which researchers discovered a significant presence of transthyretin amyloid in a minority of heart failure cases. The more evidence that is obtained, the more support there will be for development programs that can clear transthyretin amyloid, not just slow down its accumulation, such as that undertaken at Covalent Bioscience.

Atrial Fibrillation in the Elderly: The Role of Sub-Clinical Isolated Cardiac Amyloidosis

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and is associated with considerable morbidity and mortality. The prevalence of AF increases with increasing age and is related to the increasing prevalence of comorbidities and structural remodelling of the atria that is believed to occur with aging. Increasing atrial fibrosis is known to be associated with more frequent paroxysms of AF, persistent AF, and refractoriness to medical therapy.

Recently, a considerable proportion of elderly patients with heart failure with preserved ejection fraction (HFpEF) have been found to have isolated amyloid deposits in the heart. Further, a proportion of patients with valvular heart disease have been found to have clinically undetected amyloid deposits on atrial biopsies obtained during cardiac surgery and such deposits have been shown to be associated with an increased risk of AF. The role of such clinically undetected atrial amyloid deposits in the aetiopathogenesis of AF occurring in the absence of valvular heart disease has not been previously evaluated.

In this study, we sought to assess the prevalence of AF in patients with clinically undetected isolated cardiac amyloidosis (ICA) detected at autopsy and identify electrocardiographic (EKG) markers of such amyloid deposits. A total of 1083 patients were included in the study and 3.1% of patients were found to have asymptomatic ICA. Patients with ICA were older and had a higher odds of AF independent of age and CHA2DS2VASc score. Amongst patients with AF, those with ICA were more likely to have persistent forms of AF and had a lower sinus rhythm P-wave amplitude. Further studies are required to further define this entity, identify imaging modalities to aid in antemortem diagnosis of ICA and to establish the optimal management strategies in these patients.

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