Niccolò Maurizi1, Valeria Rella2, Carlo Fumagalli3, Sabrina Salerno2, Silvia Castelletti4, Federica Dagradi4, Margherita Torchio5, Azzurra Marceca6, Martino Meda6, Massimo Gasparini7, Beatrice Boschi3, Francesca Girolami8, Gianfranco Parati6, Iacopo Olivotto3, Lia Crotti9, Franco Cecchi10. 1. Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy. Electronic address: niccolo.maurizi@gmail.com. 2. IRCCS, Istituto Auxologico Italiano, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy. 3. Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy. 4. IRCCS, Istituto Auxologico Italiano, Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy. 5. IRCCS, Istituto Auxologico Italiano, Laboratory of Cardiovascular Genetics, Milan, Italy. 6. IRCCS, Istituto Auxologico Italiano, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy. 7. Department of Nuclear Medicine, IRCCS MultiMedica Sesto San Giovanni, Milan, Italy. 8. Cardiology Unit, Meyer Children Hospital, Florence, Italy. 9. IRCCS, Istituto Auxologico Italiano, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy; IRCCS, Istituto Auxologico Italiano, Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy; IRCCS, Istituto Auxologico Italiano, Laboratory of Cardiovascular Genetics, Milan, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy. 10. Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy; IRCCS, Istituto Auxologico Italiano, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy.
Abstract
BACKGROUND: Differential diagnosis of genetic causes of left ventricular hypertrophy (LVH) is crucial for disease-specific therapy. We aim to describe the prevalence of Cardiac Amyloidosis (CA) among patients ≥40 years with an initial diagnosis of HCM referred for second opinion to national cardiomyopathy centres. METHODS: Consecutive patients aged ≥40 years referred with a tentative HCM diagnosis in the period 2014-2017 underwent clinical evaluation and genetic testing for HCM (including trans-thyretin-TTR). Patients with at least one red flag for CA underwent blood/urine tests, abdominal fat biopsy and/or bone-scintigraphy tracing and eventually ApoAI sequencing. RESULTS: Out of 343 patients (age 60 ± 13 years), 251 (73%) carried a likely/pathogenic gene variant, including 12 (3.5%) in the CA-associated genes TTR (n = 11) and ApoAI (n = 1). Furthermore, 6 (2%) patients had a mutation in GLA. Among the remaining, mutation-negative patients, 26 with ≥1 CA red-flag were investigated further: 3 AL-CA and 17 wild-type-TTR-CA were identified. Ultimately, 32(9%) patients were diagnosed with CA. Prevalence of CA increased with age: 1/75 (1%) at age 40-49, 2/86 (2%) at age 50-59, 8/84 (9%) at age 60-69, 13/61 (21%) at age 70-79, 8/31 (26%) at age ≥80 (p for trend <0.01). CONCLUSIONS: Among patients referred with and initial diagnosis of HCM, CA was the most common unrecognized mimic (9% prevalence) and increased with age (from 1% at ages 40-49 years to 26% >80 years). Age at diagnosis should be considered one of the most relevant red flags for CA in patients with HCM phenotypes; however, there is no clear age cut-off mandating scintigraphy and other second level investigations in the absence of other features suggestive of CA.
BACKGROUND: Differential diagnosis of genetic causes of left ventricular hypertrophy (LVH) is crucial for disease-specific therapy. We aim to describe the prevalence of Cardiac Amyloidosis (CA) among patients ≥40 years with an initial diagnosis of HCM referred for second opinion to national cardiomyopathy centres. METHODS: Consecutive patients aged ≥40 years referred with a tentative HCM diagnosis in the period 2014-2017 underwent clinical evaluation and genetic testing for HCM (including trans-thyretin-TTR). Patients with at least one red flag for CA underwent blood/urine tests, abdominal fat biopsy and/or bone-scintigraphy tracing and eventually ApoAI sequencing. RESULTS: Out of 343 patients (age 60 ± 13 years), 251 (73%) carried a likely/pathogenic gene variant, including 12 (3.5%) in the CA-associated genes TTR (n = 11) and ApoAI (n = 1). Furthermore, 6 (2%) patients had a mutation in GLA. Among the remaining, mutation-negative patients, 26 with ≥1 CA red-flag were investigated further: 3 AL-CA and 17 wild-type-TTR-CA were identified. Ultimately, 32(9%) patients were diagnosed with CA. Prevalence of CA increased with age: 1/75 (1%) at age 40-49, 2/86 (2%) at age 50-59, 8/84 (9%) at age 60-69, 13/61 (21%) at age 70-79, 8/31 (26%) at age ≥80 (p for trend <0.01). CONCLUSIONS: Among patients referred with and initial diagnosis of HCM, CA was the most common unrecognized mimic (9% prevalence) and increased with age (from 1% at ages 40-49 years to 26% >80 years). Age at diagnosis should be considered one of the most relevant red flags for CA in patients with HCM phenotypes; however, there is no clear age cut-off mandating scintigraphy and other second level investigations in the absence of other features suggestive of CA.
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