Highlights
- •Prevalence of cardiac amyloidosis (CA) was low with 1.87 hospitalizations per 100,000 German population.
- •While CA prevalence increased (4.0-fold) 2005–2018, in hospital-mortality decreased.
- •Highest number of CA hospitalizations was seen in the 8th decade of life.
- •HF patients of other aetiologies had unfavourable cardiovascular profile, while mortality was comparable to CA.
- •CA was associated with in-hospital mortality in the 5th to 8th decade, but was influenced by cancer.
- •amyloidosis was an independent risk factor for adverse in-hospital events.
Abstract
Background
Amyloidosis is a multi-systemic disease potentially leading to failure of affected
organs. We aimed to investigate prevalence and prognostic implications of cardiac
amyloidosis of any etiology on outcomes of hospitalized patients with heart failure
(HF) in Germany.
Methods
We analyzed data of the German nationwide inpatient sample (2005–2018) of patients
hospitalized for HF (including myocarditis with HF and heart transplantation with
HF). HF patients with amyloidosis (defined as cardiac amyloidosis [CA]) were compared
with those HF patients without amyloidosis and impact of CA on outcomes was assessed.
Results
During this fourteen-year observational period 5,478,835 hospitalizations for HF were
analyzed. Amyloidosis was coded in 5,407 HF patients (0.1%). CA prevalence was 1.87
hospitalizations per 100,000 German population. CA patients were younger (75.0[IQR
67.0–80.0]vs.79.0[72.0–85.0]years, p < 0.001), predominantly male (68.9%) and had a higher prevalence of cancer (14.8%
vs. 3.6%, p < 0.001). Adverse in-hospital events including necessity of transfusions of blood
constituents (7.1% vs. 5.4%, p < 0.001) and cardio-pulmonary resuscitation (CPR, 2.7% vs. 1.4%; p < 0.001) were more frequent in CA. CA was independently associated with acute kidney
failure (OR 1.40 [95%CI 1.28–1.52], p < 0.001), CPR (OR 1.58 [95%CI 1.34–1.86], p < 0.001), intracerebral bleeding (OR 3.13 [95%CI 1.68–5.83], p < 0.001) and in-hospital mortality between the 5 and 8th decade of life, but in-hospital
mortality was strongly influenced by cancer.
Conclusions
CA was identified as an independent risk factor for complications and in-hospital
mortality in HF patients, whereby it has to be mentioned that amyloidosis subtypes
could not differentiated in the present study. Physicians should be aware of this
issue concerning treatments and monitoring of CA-patients.
Graphical abstract
Graphical Abstract
Keywords
Abbreviation:
AL (Amyloid light chain), ATTR (Amyloid transthyretin), ATTRh (Hereditary amyloid transthyretin), ATTRwt (Wild type amyloid transthyretin), CA (Cardiac amyloidosis), DRG (Diagnosis Related Groups), GM (German Modification), HF (Heart failure), HfpEF (Heart failure with preserved ejection fraction), HFmrEF (Heart failure with mid-range ejection fraction), HfrEF (Heart failure with reduced ejection fraction), ICD (International Classification of Diseases and Related Health Problems), IQR (Inter-quartile range), OR (Odds ratio), RDC (Research Data Center), AKF (Acute kidney failure), CPR (Cardio-pulmonary resuscitation)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of Internal MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Amyloidosis and the heart: a comprehensive review.Arch Intern Med. 2006; 166: 1805-1813
- Patterns of isolated atrial amyloid: a study of 100 hearts on autopsy.Cardiovasc Pathol. 2006; 15: 287-290
- High prevalence of amyloid in 150 surgically removed heart valves–a comparison of histological and clinical data reveals a correlation to atheroinflammatory conditions.Cardiovasc Pathol. 2010; 19: 228-235
- Systemic amyloidosis.Lancet. 2016; 387 (10038): 2641-2654
- Genotype and phenotype of transthyretin cardiac amyloidosis: THAOS (transthyretin amyloid outcome survey).J Am Coll Cardiol. 2016; 68: 161-172
- Transthyretin cardiac amyloidosis in continental Western Europe: an insight through the transthyretin amyloidosis outcomes survey (THAOS).Eur Heart J. 2019; 43: 391-400https://doi.org/10.1093/eurheartj/ehz173
- Light-chain) cardiac amyloidosis: a review of diagnosis and therapy.J Am Coll Cardiol. 2016; 68: 1323-1341
- Endomyocardial biopsy characterization of heart failure with preserved ejection fraction and prevalence of cardiac amyloidosis.JACC Heart Fail. 2020; 8: 712-724
- Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction.Eur Heart J. 2015; 36: 2585-2594
- Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death.Blood. 2017; 129: 2111-2119
- Diagnosis and treatment of cardiac amyloidosis: position statement of the German cardiac society (DGK).Clin Res Cardiol. 2021; 110: 479-506
- Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy.N Engl J Med. 2018; 379: 1007-1016
- Light chain amyloidosis: patient experience survey from the amyloidosis research consortium.Adv Ther. 2015; 32: 920-928
- Seven factors predict a delayed diagnosis of cardiac amyloidosis.Amyloid. 2018; 25: 174-179
- Natural history, quality of life, and outcome in cardiac transthyretin amyloidosis.Circulation. 2019; 140: 16-26
- A European collaborative study of cyclophosphamide, bortezomib, and dexamethasone in upfront treatment of systemic AL amyloidosis.Blood. 2015; 126: 612-615
- Epidemiology of cardiac amyloidosis-associated heart failure hospitalizations among fee-for-service medicare beneficiaries in the United States.Circ Heart Fail. 2019; 12e005407
- Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans.N Engl J Med. 1997; 336: 466-473
Internet Page of the InEK GmbH, Institut für das Entgeltsystem im Krankenhaus vanO. Deutsche kodierrichtlinien 2018 druckversion A4 (PDF). https://www.g-drg.de/inek_site_de/layout/set/standard/Media/Files/G-DRG-System/G-DRG-System_2018/Deutsche_Kodierrichtlinien_2018_Druckversion_A4_PDF 2018 (assessed 10th April 2019).
- A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.J Chronic Dis. 1987; 40: 373-383
- Amyloid cardiomyopathy: disease on the rise.Circ Res. 2017; 120: 1865-1867
- Expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis.Circ Heart Fail. 2019; 12e006075
- Cardiac amyloidosis: evolving diagnosis and management: a scientific statement from the American heart association.Circulation. 2020; 142: e7-e22
- Pilot study for left ventricular imaging phenotype of patients over 65 years old with heart failure and preserved ejection fraction: the high prevalence of amyloid cardiomyopathy.Int J Cardiovasc Imaging. 2016; 32: 1403-1413
- Prevalence and outcomes of concomitant aortic stenosis and cardiac amyloidosis.J Am Coll Cardiol. 2021; 77: 128-139
- Prevalence of cardiac amyloidosis in patients referred for transcatheter aortic valve replacement.J Am Coll Cardiol. 2018; 71: 463-464
- Incidence of AL amyloidosis in Olmsted county, Minnesota, 1990 through 2015.Mayo Clin Proc. 2019; 94: 465-471
- Epidemiology of AL amyloidosis: a real-world study using US claims data.Blood Adv. 2018; 2: 1046-1053
- Geographic disparities in reported US amyloidosis mortality from 1979 to 2015: potential underdetection of cardiac amyloidosis.JAMA Cardiol. 2018; 3: 865-870
- Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification international society of amyloidosis 2016 nomenclature guidelines.Amyloid. 2016; 23: 209-213
- Nonbiopsy diagnosis of cardiac transthyretin amyloidosis.Circulation. 2016; 133: 2404-2412
- Diagnosis, prognosis, and therapy of transthyretin amyloidosis.J Am Coll Cardiol. 2015; 66: 2451-2466
- Cancer risk in amyloidosis patients in Sweden with novel findings on non-Hodgkin lymphoma and skin cancer.Ann Oncol. 2014; 25: 511-518
- Management of AL amyloidosis in 2020.Blood. 2020; 136: 2620-2627
- Comprehensive review of AL amyloidosis: some practical recommendations.Blood Cancer J. 2021; 11: 97
- Current chemotherapy and immune therapy treatment strategies: JACC: cardiooncology state-of-the-art review.JACC CardioOncol. 2021; 3: 467-487
- Cardiac amyloidosis: overlooked, underappreciated, and treatable.Annu Rev Med. 2020; 71: 203-219
- Transthyretin amyloidosis and the kidney.Clin J Am Soc Nephrol. 2012; 7: 1337-1346
- Tenosynovial and cardiac amyloidosis in patients undergoing carpal tunnel release.J Am Coll Cardiol. 2018; 72: 2040-2050
- Carpal tunnel syndrome: a common initial symptom of systemic wild-type ATTR (ATTRwt) amyloidosis.Amyloid. 2016; 23: 58-63
- Factor X deficiency in primary amyloidosis: resolution after splenectomy.N Engl J Med. 1979; 301: 1050-1051
- Acquired factor X deficiency in patients with amyloid light-chain amyloidosis: incidence, bleeding manifestations, and response to high-dose chemotherapy.Blood. 2001; 97: 1885-1887
- Amyloid heart disease.Prog Cardiovasc Dis. 2010; 52: 347-361
- Prevalence and prognostic value of conduction disturbances at the time of diagnosis of cardiac AL amyloidosis.Ann Noninvasive Electrocardiol. 2013; 18: 327-335
- Electrocardiographic findings in primary systemic amyloidosis and biopsy-proven cardiac involvement.Am J Cardiol. 2005; 95: 535-537
- Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types.Circulation. 2009; 120: 1203-1212
- Temporal trends and predictors of inhospital death in patients hospitalised for heart failure in Germany.Eur J Prev Cardiol. 2021; 28: 990-997https://doi.org/10.1177/2047487320936020
- Standard heart failure medication in cardiac transthyretin amyloidosis: useful or harmful?.Amyloid. 2017; 24: 132-133
- Effect of combined systolic and diastolic functional parameter assessment for differentiation of cardiac amyloidosis from other causes of concentric left ventricular hypertrophy.Circ Cardiovasc Imaging. 2013; 6: 1066-1072
- Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis.Heart. 2012; 98: 1442-1448
- Cardiovascular magnetic resonance in clinically suspected cardiac amyloidosis: noninvasive imaging compared to endomyocardial biopsy.J Am Coll Cardiol. 2008; 51: 1022-1030
- Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis.J Clin Oncol. 2004; 22: 3751-3757
- Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements.J Clin Oncol. 2012; 30: 989-995
Article info
Publication history
Published online: May 16, 2022
Accepted:
May 2,
2022
Received in revised form:
April 27,
2022
Received:
December 22,
2021
Identification
Copyright
© 2022 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
