How your ears can tell what is hidden in your heart: wild-type transthyretin amyloidosis as potential cause of sensorineural hearing loss inelderly-AmyloDEAFNESS pilot study.
TL;DR: These findings suggest that amyloid deposits could infiltrate the various anatomical structures of the inner ear and could help for early identification of patients who may be at high risk of ATTRwt amyloidsosis as specific treatments are available.
Abstract: Background: Wild-type transthyretin amyloidosis (ATTRwt) is an age-related life-threatening condition. Prognosis is mainly dependent on cardiac involvement. Other organs and tissues may be affected...
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TL;DR: Given the high surgical risk of patients with AS and concomitant CA, transcatheter aortic valve replacement may be preferred to surgery in these patients and recently developed pharmacological treatment dedicated to transthyretin amyloidosis is preferred.
158 citations
Mélanie Bézard, Mounira Kharoubi, Arnault Galat, Elsa Poullot, Soulef Guendouz, Pascale Fanen, Benoît Funalot, Anissa Moktefi, Jean-Pascal Lefaucheur1, Mukedaisi Abulizi, Jean-François Deux, Thierry Gendre, Vincent Audard, Khalil El Karoui2, Florence Canoui-Poitrine, Amira Zaroui, Emmanuel Itti, Emmanuel Teiger, Violaine Planté-Bordeneuve, Silvia Oghina, Thibaud Damy •
TL;DR: The clinical characteristics of ATTR amyloidosis in a real‐life population in comparison to the population included in the ATTR‐ACT trial were assessed and the impact of tafamidis treatment on major cardiovascular outcome (MCO)‐free survival time without cardiac decompensation, heart transplant, or death was assessed.
Abstract: AIMS Hereditary (ATTRv) and wild-type (ATTRwt) transthyretin amyloidosis are severe and fatal systemic diseases, characterised by amyloid fibrillar accumulation principally in the heart or peripheral nerves (or both). Since 2012, tafamidis has been used in France to treat patients with ATTRv with neuropathy (alone or combined with cardiomyopathy). Recently, the Phase III ATTR-ACT trial showed that tafamidis decreased the relative risk of mortality in ATTR amyloidosis with cardiomyopathy. The aims of this study were to assess the clinical characteristics of ATTR amyloidosis in a real-life population in comparison to the population included in the ATTR-ACT trial and to assess the impact of tafamidis treatment on major cardiovascular outcome (MCO)-free survival time without cardiac decompensation, heart transplant, or death. METHODS AND RESULTS From June 2008 to November 2018, 648 patients with ATTR amyloidosis (423 ATTRwt and 225 ATTRv) consecutively referred to the French Referral Center for cardiac amyloidosis were included. A total of 467 (72%) patients matched the inclusion criteria of the ATTR-ACT trial. For the 631 patients with cardiomyopathy, tafamidis treatment was associated with a longer median MCO-free survival time (n = 98): 1565 (1010-2400) days vs. 771 (686-895) days without treatment (log-rank P < 0.001). This association was confirmed after considering confounding factors (age at inclusion, N-terminal pro-B-type natriuretic peptide and amyloidosis type) with a propensity score (hazard ratio 0.546; P = 0.0132). CONCLUSION In a large cohort of ATTRwt and ATTRv patients, representative of the inclusion criteria of the ATTR-ACT trial, the present results show an association between tafamidis treatment and a lower occurrence of cardiovascular outcomes in a real-life population.
30 citations
TL;DR: La ATTR es una enfermedad mas frecuente of lo tradicionalmente considerado y que es particularmente relevante en pacientes mayores de 65 anos con insuficiencia cardiaca o con estenosis aortica, y se hace necesario que los clinicos esten familiarizados with el proceso diagnostico and el tratamiento oficial.
Abstract: Resumen La amiloidosis cardiaca por transtiretina (TTR) es una enfermedad infiltrativa, grave y progresiva, que se produce por el deposito de TTR en el corazon. Puede deberse a una alteracion genetica en su forma hereditaria (ATTRv) o a consecuencia de un proceso degenerativo asociado a la edad (ATTRwt). Gracias a los avances en tecnicas de imagen y a la posibilidad de realizar un diagnostico no invasivo hoy conocemos que la ATTR es una enfermedad mas frecuente de lo tradicionalmente considerado y que es particularmente relevante en pacientes mayores de 65 anos con insuficiencia cardiaca o con estenosis aortica. Con la aparicion de opciones de tratamiento capaces de modificar la historia natural de la ATTR se hace necesario que los clinicos esten familiarizados con el proceso diagnostico y el tratamiento de esta enfermedad. En esta revision se repasara el espectro clinico de presentacion de la ATTR, su diagnostico y su tratamiento.
19 citations
TL;DR: This prospective study suggests, for the first time, that amyloid associated with CA could infiltrate the various anatomical structures of the pharyngo-larynx, responsible for functional impairment and potential nutritional depletion and poor quality of life.
Abstract: Background: Systemic amyloidosis with cardiac involvement (CA) is a severe disease caused by the aggregation of misfolded proteins infiltrating organs and tissues and leading to their dysfunction. ...
11 citations
Cites background from "How your ears can tell what is hidd..."
...In a recent study, we reported potential infiltration of the auditory system in patients with ATTRwt amyloidosis [8]....
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TL;DR: In this article, the prevalence of autonomic neuropathy in patients with hereditary transthyretin wild-type cardiac amyloidosis (ATTRwt-CA) was determined using Sudoscan, a non-invasive method used to provide evidence of AN in clinical practice and based on measurement of electrochemical skin conductance at the hands and feet.
Abstract: AIMS The prevalence of autonomic neuropathy (AN) is high in patients with hereditary transthyretin amyloidosis but remains unknown in transthyretin wild-type cardiac amyloidosis (ATTRwt-CA). This study aimed to determine the prevalence of AN in patients with ATTRwt-CA using Sudoscan®, a non-invasive method used to provide evidence of AN in clinical practice and based on measurement of electrochemical skin conductance at the hands and feet (fESC). METHODS AND RESULTS A series of 62 non-diabetic patients with ATTRwt-CA was prospectively included over 2 years and compared with healthy elderly subjects, matched by age, gender, and body mass index. The presence of AN was defined as electrochemical skin conductance at the hands <60 μS and/or fESC <70 μS, and conductances were analysed according to clinical, biological, and echocardiographic data. Mean fESC was significantly lower in patients with ATTRwt-CA compared with elderly controls: 68.3 (64.1-72.5) vs. 76.9 (75.6-78.1) μS (P < 0.0001), respectively. Prevalence of fESC <70 μS was higher in ATTRwt-CA patients than in controls: 48.4% vs. 19.9%, P < 0.05. Univariate analysis showed that fESC, N-terminal pro-B-type natriuretic peptide, creatinine plasma levels, and echocardiographic global longitudinal strain were associated with decompensated cardiac failure and death. Multivariate analysis revealed that fESC was an independent prognostic factor, and Kaplan-Meier estimator evidenced a greater occurrence of cardiac decompensation and death in patients with fESC <70 μS, P = 0.046. CONCLUSIONS Reduced fESC was observed in almost 50% of patients with ATTRwt-CA and was associated with a worse prognosis. Sudoscan® could easily be used to screen ATTRwt-CA patients for the presence of AN and identify patients at higher risk for a poor outcome.
9 citations
References
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Julian D. Gillmore1, Mathew S. Maurer2, Rodney H. Falk3, Giampaolo Merlini4, Thibaud Damy, Angela Dispenzieri5, Ashutosh D. Wechalekar1, John L. Berk6, John L. Berk7, Candida Cristina Quarta1, Martha Grogan5, Helen J. Lachmann1, Sabahat Bokhari2, Adam Castano2, Sharmila Dorbala3, Geoff B. Johnson5, Andor W. J. M. Glaudemans, Tamer Rezk1, Marianna Fontana1, Giovanni Palladini4, Paolo Milani4, P.L Guidalotti8, Katarina Flatman1, Thirusha Lane1, Frederick W. Vonberg1, Carol J. Whelan1, James C. Moon1, Frederick L. Ruberg7, Frederick L. Ruberg6, Edward J. Miller9, David F. Hutt1, Bouke P. C. Hazenberg, Claudio Rapezzi8, Philip N. Hawkins1 •
TL;DR: Bone scintigraphy enables the diagnosis of cardiac ATTR amyloidosis to be made reliably without the need for histology in patients who do not have a monoclonal gammopathy, and proposes noninvasive diagnostic criteria that are applicable to the majority of patients with this disease.
Abstract: Background—Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal cardiomyopathy for which several promising therapies are in development. The diagnosis is frequently delayed or missed...
1,185 citations
"How your ears can tell what is hidd..." refers methods in this paper
...When an extracardiac biopsy was negative and an endomyocardial biopsy was deemed ethically unacceptable due to advanced age, the diagnosis was based on bisphosphonate scintigraphy [11] as well as the medical history, findings from the ECG, transthoracic echocardiography and cardiac MRI [12]....
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TL;DR: The mean heart weight, frequency of atrial fibrillation, percentage of patients with heart failure, and frequency of myocardial infarction were increased in patients with cardiac amyloid, but these differences failed to reach statistical significance.
398 citations
"How your ears can tell what is hidd..." refers background in this paper
...autopsy findings reported decades ago with a prevalence of 25% in subjects older than 80 [3]....
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TL;DR: A broad overview of the scientific findings related to ARHI is given, focusing mainly on environmental and genetic data in humans and in animal models, and methods for the identification of contributing genetic factors as well as possible future therapeutic strategies are discussed.
Abstract: Age-related hearing impairment (ARHI) is the most common sensory impairment seen in the elderly. It is a complex disorder, with both environmental as well as genetic factors contributing to the impairment. The involvement of several environmental factors has been partially elucidated. A first step towards the identification of the genetic factors has been made, which will result in the identification of susceptibility genes, and will provide possible targets for the future treatment and/or prevention of ARHI. This paper aims to give a broad overview of the scientific findings related to ARHI, focusing mainly on environmental and genetic data in humans and in animal models. In addition, methods for the identification of contributing genetic factors as well as possible future therapeutic strategies are discussed.
250 citations
TL;DR: The results suggest the possibility of systemic ATTRwt amyloidosis diagnosis at an early stage by carefully examining patients with CTS and investigate clinical findings of a series of patients diagnosed with antemortem diagnosis.
Abstract: Background: Systemic wild-type ATTR (ATTRwt) amyloidosis is a prevalent aging-related disorder. However, a limited number of systemic ATTRwt amyloidosis patients have been diagnosed antemortem, and therefore, the prevalence of ATTRwt is underestimated. Here, we investigated clinical findings of a series of systemic ATTRwt amyloidosis patients with antemortem diagnosis.Methods: Thirty-one consecutive patients diagnosed with systemic ATTRwt amyloidosis at Shinshu University Hospital were included in this study. Systemic ATTRwt amyloidosis was diagnosed based on proven ATTR amyloid deposition in biopsy specimens and confirmation of wild-type TTR genotype.Results: The systemic ATTRwt amyloidosis patients consisted of 24 men and seven women, and mean age of onset was 69.8 ± 9.0 years. The most common initial symptom was carpal tunnel syndrome (CTS, 17 patients), followed by heart failure symptoms (14 patients). The mean age at diagnosis was 74.5 ± 8.3 years and the duration of illness from onset to dia...
142 citations
"How your ears can tell what is hidd..." refers background in this paper
...Recently, carpal tunnel syndrome due to synovial infiltration has been reported to occur in 68% of the patients with TTRwt cardiac amyloidosis (CA) and seems to be an initial symptom of ATTRwt amyloidosis [5]....
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TL;DR: It is concluded that lumbar spinal stenosis quite frequently may be a consequence of SSA and that further studies are warranted.
Abstract: Background.Senile systemic amyloidosis (SSA) derived from wild-type transthyretin is a fairly common condition of old individuals, particularly men. The main presentation is by cardiac involvement, ...
120 citations
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