Faculty Bibliography

Systemic amyloidosis is a rare multisystem disease caused by incorrectly folded proteins that deposit pathologically in different tissues and organs of the human body. It has a very wide spectrum of clinical presentations according to the affected organ(s), and its diagnosis is commonly delayed. Cardiac involvement is the leading cause of morbidity and mortality and carries a poor prognosis, especially in primary light chain amyloidosis. Therefore any delay in the diagnosis can result in devastating outcomes for the patient. We report the case of a 65-year-old man who presented with dizziness and lightheadedness. He was found to have orthostatic hypotension and further investigations revealed the diagnosis of amyloid cardiomyopathy complicating a plasma cell dyscrasia. What is worth noting, in this case, is that the patient had cardiac amyloidosis presenting primarily as autonomic dysfunction and orthostatic hypotension, without any cardiac-specific symptoms such as heart failure or angina. This is a very unusual presentation of advanced-stage cardiac amyloidosis. This article highlights the variety of clinical presentations of cardiac amyloidosis, and focuses on the recent progress such as novel diagnostic and surveillance approaches using imaging, biomarkers, and new histological typing techniques. Current and future promising treatment options are also discussed, including methods directly targeting the amyloid deposits.

INTRODUCTION/BACKGROUND:Anti-arrhythmic medications (AAMs) are known to increase cardiac mortality significantly due to their pro-arrhythmic effects. However, the effect of AAMs on non-cardiac mortality has not been evaluated. METHODS:Trials published in English language journals from 1990 to 2015 were thoroughly retrieved by searching websites such as PubMed, Medline, Cochrane Library, and Google Scholar. Randomized controlled trials reporting non-cardiac deaths as primary or secondary outcomes were used to compare AAMs to non-arrhythmic therapy (AV nodal blocking agents, implantable cardiovascular defibrillation (ICD), or placebo). Information regarding the sample size, treatment type, baseline characteristics, and outcomes was obtained by using a standardized protocol. The fixed effect model was used to perform meta-analysis, and results were expressed in terms of odds ratio (OR) with confidence interval (CI) of 95%, inter study heterogeneity was assessed using I (2). Intention to treat principle was applied to extract data. RESULTS:Total of 18,728 patients were enrolled in 15 trials; 9359 patients received AAMs and 9369 received non-arrhythmic therapy. AAMs were associated with an increased risk of non-cardiac mortality (OR=1.30, [95% CI: 1.12, 1.50], p=0.0005, I (2) index=24%) and all-cause mortality (OR=1.09, [95% CI: 1.01, 1.18], p=0.04, I (2)=54%) as compared to non-arrhythmic therapy. There was no difference in the cardiac mortality (OR=1.01, [95% CI: 0.92, 1.11], p=0.82, I (2)=53%) or arrhythmic mortality (OR=1.00, [95% CI: 0.89, 1.13], p=0.94, I (2)=64%) between the two groups. CONCLUSION/CONCLUSIONS:AAMs are associated with an increased risk of non-cardiac and all-cause mortality. The effect of AAMs, especially amiodarone, on non-cardiac mortality requires further evaluation.