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. 2021 Aug 17;3(4):522-533.
doi: 10.1016/j.jaccao.2021.05.004. eCollection 2021 Oct.

Two Decades of Cardiac Amyloidosis: A Danish Nationwide Study

Oscar Westin  1 , Jawad H Butt  1 , Finn Gustafsson  1 , Morten Schou  2 , Morten Salomo  3 , Lars Køber  1 , Mathew Maurer  4 , Emil L Fosbøl  1
Affiliations

Two Decades of Cardiac Amyloidosis: A Danish Nationwide Study

Oscar Westin et al. JACC CardioOncol. .

Abstract

Background: Cardiac amyloidosis (CA) has been associated with poor outcomes. Screening studies suggest that CA is overlooked-especially in the elderly. Recent advances in treatment have brought attention to the disease, but data on temporal changes in CA epidemiology are sparse.

Objectives: The aim of this work was to describe all patients with CA in Denmark, examining changes in patient characteristics from 1998 to 2017.

Methods: All patients with any form of amyloidosis diagnosed from 1998 to 2017, as well as their comorbidities and pharmacotherapy, were identified in Danish nationwide registries. CA was defined as any diagnosis code for amyloidosis combined with a diagnosis code for heart failure, cardiomyopathy, or atrial fibrillation or a procedural code for pacemaker implantation, regardless of the order. The index date was defined as the date of meeting those criteria. Patients were divided into 5-year periods by index date. For comparison, we also included control subjects (1:4 ratio) from the general population.

Results: CA criteria were met by 619 patients. Comparing 1998-2002 vs 2013-2017, the median age at baseline increased from 67.4 years (interquartile range [IQR]: 53.9-75.2 years) to 72.3 years (IQR: 66.0-79.3 years). The frequency of male patients increased from 62.1% to 66.2%. The incidence of CA rose from 0.88 to 3.56 per 100,000 person-years in the Danish population aged ≥65 years, and the 2-year mortality decreased from 82.6% (IQR: 69.9%-90.5%) to 50.2% (IQR: 43.1%-56.9%). Compared with control subjects, the mortality among CA patients was significantly higher (log-rank test: P < 0.0001).

Conclusions: CA, as defined in this study, was increasingly diagnosed on a national scale. The increasing frequency of male patients and median age suggest that wild-type transthyretin amyloidosis is driving this increase. Greater recognition of earlier, less advanced cases might explain decreasing mortality.

Keywords: AL, light chain amyloid; ATTR, transthyretin amyloid; CA, cardiac amyloidosis; CTS, carpal tunnel syndrome; cardiac amyloidosis; epidemiology; heart failure; outcomes; temporal changes; wtATTR, wild-type amyloid transthyretin.

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Conflict of interest statement

Dr Westin has received a grant from the Erik og Susanna Olesens Almenvelgørende Fond during the conduct of the study. Dr Westin has received grants from Pfizer, Arvid Nilssons Fond, Højmosegård-legatet, Frimodt-Heineke Fonden, and Hjertecentrets Forskningsudvalg, Rigshospitalet, outside the submitted work. Dr Gustafsson has received personal fees from Abbott, AstraZeneca, Pfizer, Boehringer Ingelheim, Novartis, and Orion Pharma, and other compensation from Corvia, outside the submitted work. Dr Salomo has received consulting income from Takeda, Bristol Myers Squibb, Janssen, and Amgen, outside the submitted work. Dr Køber has received speakers honoraria from Novartis, AstraZeneca, Novo, and Boehringer, outside the submitted work. Dr Maurer has received grant support from National Institutes of Health (R01HL139671, R21AG058348, and K24AG036778); has received consulting income from Pfizer, Eidos, Prothena, Akcea, and Alnylam; and his institution received clinical trial funding from Pfizer, Prothena, Eidos, and Alnylam. Dr Fosbøl has received an independent research grant from Novo Nordisk Foundation, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Flow Chart of Patient Selection All patients with diagnosed amyloidosis from 1998 to 2017 were identified in Danish nationwide registries. Cardiac amyloidosis (CA) was defined using a combination of International Classification of Diseases-10th Revision diagnosis and procedural codes. A total of 1,572 amyloidosis patients were identified, ∼40% of which met criteria for CA. CA, as defined in this study, is increasingly being diagnosed in Denmark.
Figure 2
Figure 2
Temporal Changes in Cardiac Amyloidosis Investigating the changes in incidence of cardiac amyloidosis (CA). The incidence of CA was calculated for each 5-year period of the study, adjusted for population growth per each time period. Between the first and last 5-year period (1998-2002 vs 2013-2017) the incidence of CA increased from 0.88 to 3.56 per 100,000 person-years in the entire Danish population, from 1.21 to 5.19 in men aged ≥65 years and from 1.30 to 7.18 in men aged ≥75 years. The increasing incidence of CA was most pronounced among elderly men, indicating that wild-type transthyretin amyloidosis is driving this rise.
Figure 3
Figure 3
5-Year Mortality in Patients With Cardiac Amyloidosis by Time Period The mortality among patients with cardiac amyloidosis (CA)was described for each 5-year period of the study with the use of cumulative incidence functions. The mortality decreased significantly between the first and last 5-year periods. The improved survival might be explained by increased earlier detection of less severe cases of CA, a greater incidence of new cases of transthyretin amyloidosis vs amyloid light chain amyloidosis, and progress in the treatment of amyloid light chain amyloidosis.
Figure 4
Figure 4
5-Year Mortality in Patients With Cardiac Amyloidosis vs Age- and Sex-Matched Control Subjects From the General Population Comparison of mortality between patients with cardiac amyloidosis (CA) and age- and sex-matched control subjects. The mortality among patients with CA vs age- and sex-matched control subjects from the general population was described with the use of cumulative incidence functions. The mortality among patients with CA was significantly higher than among control subjects. CA is associated with a high mortality after diagnosis.
Central Illustration
Central Illustration
Danish Nationwide Registry Analysis of Cardiac Amyloidosis: Study Design and Main Results
See this image and copyright information in PMC

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