Louis Bonnefous1, Mounira Kharoubi2, Mélanie Bézard2, Silvia Oghina2, Fabien Le Bras3, Elsa Poullot4, Valérie Molinier-Frenkel5, Pascale Fanen6, Jean-François Deux7, Vincent Audard8, Emmanuel Itti9, Thibaud Damy10, Etienne Audureau11. 1. AP-HP (Assistance Publique-Hôpitaux de Paris), Public Health Department, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France. 2. AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Cardiology Department, Henri Mondor University Hospital, Créteil, France. 3. AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Hematology Department, Henri Mondor University Hospital, Créteil, France. 4. AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Biology-Pathology Department, Henri Mondor University Hospital, Créteil, France. 5. AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Biology-Pathology Department, Henri Mondor University Hospital, Créteil, France. 6. AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Genetics Department, Henri Mondor University Hospital, Créteil, France. 7. AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Radiology Department, Henri Mondor University Hospital, Créteil, France. 8. AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Nephrology Department, Henri Mondor University Hospital, Créteil, France. 9. AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Nuclear Medicine Department, Henri Mondor University Hospital, Créteil, France. 10. AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Cardiology Department, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Clinical Investigation Center 1430, Henri Mondor University Hospital, Créteil, France. 11. AP-HP (Assistance Publique-Hôpitaux de Paris), Public Health Department, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France. Electronic address: etienne.audureau@aphp.fr.
Abstract
BACKGROUND: Cardiac amyloidosis (CA) is a set of amyloid diseases with usually predominant cardiac symptoms, including light-chain amyloidosis (AL), hereditary variant transthyretin amyloidosis (ATTRv), and wild-type transthyretin amyloidosis (ATTRwt). CA are characterized by high heterogeneity in phenotypes leading to diagnosis delay and worsened outcomes. OBJECTIVES: The authors used clustering analysis to identify typical clinical profiles in a large population of patients with suspected CA. METHODS: Data were collected from the French Referral Center for Cardiac Amyloidosis database (Hôpital Henri Mondor, Créteil), including 1,394 patients with suspected CA between 2010 and 2018: 345 (25%) had a diagnosis of AL, 263 (19%) ATTRv, 402 (29%) ATTRwt, and 384 (28%) no amyloidosis. Based on comprehensive clinicobiological phenotyping, unsupervised clustering analyses were performed by artificial neural network-based self-organizing maps to identify patient profiles (clusters) with similar characteristics, independent of the final diagnosis and prognosis. RESULTS: Mean age and left ventricular ejection fraction were 72 ± 13 years and 52% ± 13%, respectively. The authors identified 7 clusters of patients with contrasting profiles and prognosis. AL patients were distinctively located within a typical cluster; ATTRv patients were distributed across 4 clusters with varying clinical presentations, 1 of which overlapped with patients without amyloidosis; interestingly, ATTRwt patients spread across 3 distinct clusters with contrasting risk factors, biological profiles, and prognosis. CONCLUSIONS: Clustering analysis identified 7 clinical profiles with varying characteristics, prognosis, and associations with diagnosis. Especially in patients with ATTRwt, these results suggest key areas to improve amyloidosis diagnosis and stratify prognosis depending on associated risk factors.
BACKGROUND: Cardiac amyloidosis (CA) is a set of amyloid diseases with usually predominant cardiac symptoms, including light-chain amyloidosis (AL), hereditary variant transthyretin amyloidosis (ATTRv), and wild-type transthyretin amyloidosis (ATTRwt). CA are characterized by high heterogeneity in phenotypes leading to diagnosis delay and worsened outcomes. OBJECTIVES: The authors used clustering analysis to identify typical clinical profiles in a large population of patients with suspected CA. METHODS: Data were collected from the French Referral Center for Cardiac Amyloidosis database (Hôpital Henri Mondor, Créteil), including 1,394 patients with suspected CA between 2010 and 2018: 345 (25%) had a diagnosis of AL, 263 (19%) ATTRv, 402 (29%) ATTRwt, and 384 (28%) no amyloidosis. Based on comprehensive clinicobiological phenotyping, unsupervised clustering analyses were performed by artificial neural network-based self-organizing maps to identify patient profiles (clusters) with similar characteristics, independent of the final diagnosis and prognosis. RESULTS: Mean age and left ventricular ejection fraction were 72 ± 13 years and 52% ± 13%, respectively. The authors identified 7 clusters of patients with contrasting profiles and prognosis. AL patients were distinctively located within a typical cluster; ATTRv patients were distributed across 4 clusters with varying clinical presentations, 1 of which overlapped with patients without amyloidosis; interestingly, ATTRwt patients spread across 3 distinct clusters with contrasting risk factors, biological profiles, and prognosis. CONCLUSIONS: Clustering analysis identified 7 clinical profiles with varying characteristics, prognosis, and associations with diagnosis. Especially in patients with ATTRwt, these results suggest key areas to improve amyloidosis diagnosis and stratify prognosis depending on associated risk factors.