Elsevier

Heart Rhythm

Volume 5, Issue 2, February 2008, Pages 235-240
Heart Rhythm

Original-clinical
Prophylactic implantation of cardioverter-defibrillator in patients with severe cardiac amyloidosis and high risk for sudden cardiac death

https://doi.org/10.1016/j.hrthm.2007.10.016Get rights and content

Background

Cardiac light-chain amyloidosis carries a high risk for death predominantly from progressive cardiomyopathy or sudden death (SCD). Independent risk factors for SCD are syncope and complex nonsustained ventricular arrhythmias.

Objective

The purpose of this study was to test whether prophylactic placement of an implantable cardioverter-defibrillator (ICD) reduces SCD in patients with cardiac amyloidosis.

Methods

Nineteen patients with histologically proven cardiac amyloidosis and a history of syncope and/or ventricular extra beats (Lown grade IVa or higher) received an ICD.

Results

During a mean follow-up of 811 ± 151 days, two patients with sustained ventricular tachyarrhythmias were successfully treated by the ICD. Two patients underwent heart transplantation, and seven patients died due to electromechanical dissociation (n = 6) or glioblastoma (n = 1). Nonsurvivors more often showed progression of left ventricular wall thickness, low-voltage pattern, ventricular arrhythmias (Lown grade IVa or higher), and higher N-terminal pro-brain natriuretic peptide levels than did survivors. Bradycardias requiring ventricular pacing (VVI 40/min <1%, DDD 60/min 6% ± 1%) occurred only rarely.

Conclusion

Patients with cardiac amyloidosis predominantly die as a result of electromechanical dissociation and other diagnoses not amenable to ICD therapy. Selected patients with cardiac amyloidosis may benefit from ICD placement. Better predictors of arrhythmia-associated SCD and randomized trials are required to elucidate the impact of ICD placement in high-risk patients with cardiac amyloidosis.

Introduction

Amyloidosis is a rare disorder of protein conformation and metabolism that results in tissue deposition of insoluble fibrils. Increased amyloid tissue deposition causes organ dysfunction and finally death. Usually, systemic amyloid deposits are formed by immunoglobulin light-chains (light-chain amyloidosis) and may involve various organs.1 Cardiac involvement occurs in approximately 60% of patients with light-chain amyloidosis2 and is by far the most relevant factor for the poor prognosis of patients. High-dose melphalan chemotherapy and autologous stem cell transplantation represent a potentially curative treatment of light-chain amyloidosis, resulting in complete remission in approximately 60% of patients.3, 4 However, treatment-related mortality is exceptionally high in patients with advanced cardiac involvement.5, 6, 7, 8 Without therapy, patient survival is approximately 6 months.9

Approximately two thirds of patients with cardiac amyloidosis die of “sudden” types of death.10 In patients with light-chain amyloidosis, ventricular rhythm disturbances (ventricular extra beats Lown grade IVa or higher) are common and prognostically relevant.11 Syncope is an independent risk factor for sudden cardiac death (SCD).12

Implantable cardioverter-defibrillator (ICD) therapy theoretically could be a treatment option for high-risk patients with light-chain amyloidosis because ICD placement has been proved to be the treatment of choice in patients with ischemic and dilated cardiomyopathies.13, 14, 15 To date, only anecdotal reports of ICD therapy in patients with cardiac amyloidosis are available.16, 17

The aim of the present study was to evaluate the impact of ICD treatment on the prognosis of selected patients with histologically proven cardiac light-chain amyloidosis and at least one risk factor for SCD.11, 12, 18

Section snippets

Study population

Nineteen patients with light-chain amyloidosis and histologically proven cardiac involvement diagnosed at a university tertiary referral center between March 2003 and December 2006 received an ICD because of potentially high risk for SCD.

Diagnosis of amyloidosis was made by Congo red staining of any biopsy. The type of light-chain amyloidosis was confirmed by immunohistochemical staining.19 Further organ involvement was defined according to the guidelines of amyloidosis diagnostics.20 All

Results

At the time of ICD placement, 4 (21%) patients had a history of syncope, 10 (53%) had ventricular extra beats (Lown grade IVa or higher), and 5 (26%) had both risk factors for SCD. Also present were low-voltage pattern (n = 12 [63%]), interventricular septum ≥15 mm (n = 17 [89%]), markedly impaired left ventricular ejection fraction ≤45% (n = 5 [26%]), cardiac troponin T level ≥0.03 μg/L (n = 9 [47%]), N-terminal pro-brain natriuretic peptide (NT-proBNP) level ≥3,500 ng/L (n = 12 [63%]), and

Discussion

The present study attempted to elucidate the impact of ICD placement on mortality in patients with cardiac amyloidosis. The data indicate that (1) mortality in patients with cardiac light-chain amyloidosis is mainly due to electromechanical dissociation that is not amenable to ICD treatment, (2) ICD treatment successfully terminated sustained ventricular arrhythmias in individual patients, (3) the percentage of ventricular pacing was very low, and (4) patients who died due to electromechanical

Conclusion

Cardiac light-chain amyloidosis carries a critical prognosis, with infrequent occurrence of sustained ventricular arrhythmias amenable to ICD treatment. Based on the results of this study with small sample size, prophylactic ICD placement cannot be generally recommended. Nevertheless, select patients might benefit from ICD therapy; therefore, larger randomized studies are needed to further elucidate the impact of prophylactic ICD placement in patients with cardiac amyloidosis. Novel selection

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