Elsevier

International Journal of Cardiology

Volume 222, 1 November 2016, Pages 562-568
International Journal of Cardiology

Outcome and incidence of appropriate implantable cardioverter-defibrillator therapy in patients with cardiac amyloidosis

https://doi.org/10.1016/j.ijcard.2016.07.254Get rights and content

Highlights

  • Appropriate ICD therapies in CA patients are common (27% of the patients), regardless of CA and prevention types

  • Conventional selection criteria for ICD implantation in primary prevention (e.g. LVEF) are not suitable for CA patients.

  • Patients with an advanced form of CA, particularly the AL-CA type, had a very poor outcome despite ICD placement.

  • TTR-CA with early cardiac involvement and AL-CA awaiting cardiac transplant should be patients considered for an ICD.

  • Prospective studies are warranted to further investigate whether prophylactic ICD implantation would reduce mortality in CA.

Abstract

Background

Cardiac amyloidosis (CA) is associated with a poor prognosis with the proposed mechanism of sudden cardiac death in the majority of patients being pulseless electrical activity. However, the incidence of ventricular arrhythmias (VA) and implantable cardioverter-defibrillator (ICD) indications in CA patients are unclear.

We performed a detailed evaluation of our CA population undergoing ICD implantation and assessed appropriate ICD therapy and survival predictors.

Methods

We included consecutive patients from June 2008 to November 2014 in five centers. ICDs were systematically interrogated and clinical data recorded during follow-up.

Results

Forty-five patients (35 males, mean age 66 ± 12 years) with CA who underwent ICD implantation (84.4% primary prevention) were included. CA types were hereditary transthyretin in 27 patients (60%), light chain (AL) in 12 (27%) and senile in 6 (13%). After a mean follow-up of 17 ± 14 months, 12 patients (27%) had at least 1 appropriate ICD therapy occurring after 4.7 ± 6.6 months. Patients with or without ICD therapy had no significant differences in baseline characteristics, amyloidosis type, LVEF, and type of prevention although there was a trend towards a better 2D global longitudinal strain in patients with ICD therapy (P = 0.08). Over the follow-up, 12 patients died (27%) and 6 underwent cardiac transplantation (13%). From multivariate analysis a worse prognosis was associated with higher NT-proBNP level (> 6800 pg/mL, HR = 5.5[1.7–17.8]) and AL type (HR = 4.9[1.5–16.3]).

Conclusions

Appropriate ICD therapies are common (27%) in CA patients. No specific strong VA predictor could be identified. However, patients with advanced heart disease, especially with AL-CA, display a poorer outcome.

Introduction

Amyloidosis is a severe systemic disease. Cardiac amyloidosis (CA) may occur in the three main types of amyloidosis and markedly impacts upon prognosis, with a median survival of < 1 year after the onset of heart failure symptoms until quite recently. The mechanism of death has been traditionally attributed to pulseless electrical activity (PEA) and therefore implantable cardioverter-defibrillator (ICD) implantation has not been considered to be a beneficial therapeutic option.

Recent advances in amyloid specific therapy for light chain (AL) [1] or hereditary amyloidosis transthyretin related (ATTR) amyloidosis, as well as earlier diagnosis at the preclinical stage based on cardiac biomarkers [2] or more sensitive imaging technics [3], [4], [5], have contributed to a significant improvement in CA prognosis. Furthermore, many studies have shown that sustained ventricular arrhythmias (VA) on ECG-holter monitoring [6] or successful termination of VAs with appropriate ICD therapies [7], [8] are not uncommon. However, no robust predictors for malignant VA have been identified. In addition, it has been recently suggested that non-sustained ventricular tachycardia (NSVT) can predict subsequent ICD therapy and should be a risk factor for prophylactic ICD implantation [8]. However, NSVT does not appear to correlate with sudden cardiac death (SCD) or survival in non-implanted CA patients [6].

Cardiac biomarkers seem to predict adverse outcome in AL patients [2], [3], [9], but there is no data to suggest that these biomarkers would predict further VA occurrence [10]. Finally, whether echocardiographic parameters (e.g. strain) associated with worse outcomes [3], [11] would predict malignant VA in CA remain unclear. As a result, the consensus statement from the European Society of Cardiology is that there is insufficient data to provide recommendations on prophylactic ICD implantation in CA patients [12].

We aimed to assess the usefulness of ICD implantation in CA patients with analysis of: i) the occurrence of VA with appropriate ICD therapy and ii) predictors of a combined survival endpoint including death and cardiac transplant.

Section snippets

Patient characteristics

This study was approved by the local institutional review boards, and all patients provided informed consent to participate. All consecutive CA patients undergoing ICD implantation in our centers (5 centers in Paris) were included within this study.

Diagnosis of CA was determined by the presence of a positive endomyocardial biopsy or by a confirmed extra-cardiac histological diagnosis, in addition with thickened cardiac septum (≥ 12 mm by echocardiography with no other cardiac cause of

Patient characteristics

From June 2008 to November 2014, 45 consecutive CA patients (12 AL, 27 ATTR and 6 SSA) met the inclusion criteria and were enrolled in our study. Clinical characteristics are summarized in Table 1. The main indication for ICD placement was primary prevention (84.4%) and 12 patients (26.7%) received a bi-ventricular ICD. LVEF was decreased (< 50%) in 68.9% of cases and ≤ 35% in one third of our population. All but 2 patients had a NT-proBNP > 332 ng/L and interventricular septal wall thickness > 15 mm

Discussion

The main findings of our study were:

  • (1)

    Appropriate ICD therapies are common (26.7% over 17 months of follow-up) in CA patients while 84% were implanted for primary prevention. Time to first event was short (4.7 months) and all but one patient (92%) experienced the first therapy within the first year post ICD implantation.

  • (2)

    No specific clinical, echocardiographic or biological criteria could predict ICD therapy but patients with milder heart failure were more likely to experience VA.

  • (3)

    Mortality from

Conclusion

Malignant VA with subsequent appropriate ICD therapies were frequent (27%) in patients with CA, implanted predominately for primary prevention. No strong predictor was found to predict future appropriate ICD therapies within this population and patients with a more advanced heart failure, especially associated with AL type had a poorer prognosis. Further multicenter prospective studies are clearly necessary to refine ICD indications in CA. Recent advance in amyloidosis therapies might change

Funding sources

This work was supported by the Federation Française de Cardiologie to D. Hamon and V·Algalarrondo and AREMCAR to D. Hamon.

Disclosures

V. Algalarrondo received scholarship funding by St. Jude Medical, Biotronik, Medtronic, Sorin and Boston Scientific.

Acknowledgments

We thank Kamila Djouadi, Karima Ayad and Mounira Kharoubi for helping collecting data and Dr. Tarvinder S. Dhanjal for providing language assistance.

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    All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

    1

    Both authors contributed equally to this work.

    2

    Present address: UCLA Cardiac Arrhythmia Center, David Geffen School of Medicine, University of California – Los Angeles, Los Angeles, CA, USA. Fax: + 1-310-825-2092.

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