Giuseppe Limongelli1, Emanuele Monda2, Stefania Tramonte3, Felice Gragnano4, Daniele Masarone3, Giulia Frisso5, Augusto Esposito3, Rita Gravino3, Ernesto Ammendola3, Gemma Salerno3, Marta Rubino3, Martina Caiazza3, Mariagiovanna Russo6, Paolo Calabrò4, Perry Mark Elliott7, Giuseppe Pacileo3. 1. Dipartimento di Scienze Mediche Traslazionali, Università della Campania Luigi Vanvitelli, Napoli, Italy; Unità di Cardiomiopatie e Scompenso Cardiaco - Ospedale Monaldi, AORN Colli, Napoli, Italy; European Reference Network - GUARD HEART, UK; Institute of Cardiovascular Sciences, University College of London and St. Bartholomew's Hospital, London, UK. Electronic address: limongelligiuseppe@libero.it. 2. Dipartimento di Scienze Mediche Traslazionali, Università della Campania Luigi Vanvitelli, Napoli, Italy; Unità di Cardiomiopatie e Scompenso Cardiaco - Ospedale Monaldi, AORN Colli, Napoli, Italy. 3. Unità di Cardiomiopatie e Scompenso Cardiaco - Ospedale Monaldi, AORN Colli, Napoli, Italy. 4. UOC Cardiologia Vanvitelli - Osp. Snat'Anna e San Sebastiano - Caserta, Italy. 5. Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli 'Federico II', Italy; CEINGE-Biotecnologie Avanzate s.c.a r.l, Italy. 6. Dipartimento di Scienze Mediche Traslazionali, Università della Campania Luigi Vanvitelli, Napoli, Italy. 7. Institute of Cardiovascular Sciences, University College of London and St. Bartholomew's Hospital, London, UK.
Abstract
INTRODUCTION: We sought to determine prevalence and predictive accuracy of clinical markers (red flags, RF), known to be associated with specific systemic disease in a consecutive cohort of patients with hypertrophic cardiomyopathy (HCM). METHODS: We studied 129 consecutive patients (23.7 ± 20.9 years, range 0-74 years; male/female 68%/32%). Pre-specified RF were categorized into five domains: family history; signs/symptoms; electrocardiography; imaging; and laboratory. Sensitivity (Se), specificity (Sp), negative predictive value (NPV), positive predictive value (PPV), and predictive accuracy of RF were analyzed in the genotyped population. RESULTS: In the overall cohort of 129 patients, 169 RF were identified in 62 patients (48%). Prevalence of RF was higher in infants (78%) and in adults >55 years old (58%). Following targeted genetic and clinical evaluation, 94 patients (74%) had a definite diagnosis (sarcomeric HCM or specific causes of HCM). We observed 14 RF in 13 patients (21%) with sarcomeric gene disease, 129 RF in 34 patients (97%) with other specific causes of HCM, and 26 RF in 15 patients (45%) with idiopathic HCM (p < 0.0001). Non-sarcomeric causes of HCM were the most prevalent in ages <1yo and > 55yo. Se, Sp, PPV, NPV and PA of RF were 97%, 70%, 55%, 98% and 77%, respectively. Single and clinical combination of RF (clusters) had an high specificity, NPV and predictive accuracy for the specific etiologies (syndromes/metabolic/infiltrative disorders associated with HCM). CONCLUSIONS: An extensive diagnostic work up, focused on analysis of specific diagnostic RF in patients with unexplained LVH facilitates a clinical diagnosis in 74% of patients with HCM.
INTRODUCTION: We sought to determine prevalence and predictive accuracy of clinical markers (red flags, RF), known to be associated with specific systemic disease in a consecutive cohort of patients with hypertrophic cardiomyopathy (HCM). METHODS: We studied 129 consecutive patients (23.7 ± 20.9 years, range 0-74 years; male/female 68%/32%). Pre-specified RF were categorized into five domains: family history; signs/symptoms; electrocardiography; imaging; and laboratory. Sensitivity (Se), specificity (Sp), negative predictive value (NPV), positive predictive value (PPV), and predictive accuracy of RF were analyzed in the genotyped population. RESULTS: In the overall cohort of 129 patients, 169 RF were identified in 62 patients (48%). Prevalence of RF was higher in infants (78%) and in adults >55 years old (58%). Following targeted genetic and clinical evaluation, 94 patients (74%) had a definite diagnosis (sarcomeric HCM or specific causes of HCM). We observed 14 RF in 13 patients (21%) with sarcomeric gene disease, 129 RF in 34 patients (97%) with other specific causes of HCM, and 26 RF in 15 patients (45%) with idiopathic HCM (p < 0.0001). Non-sarcomeric causes of HCM were the most prevalent in ages <1yo and > 55yo. Se, Sp, PPV, NPV and PA of RF were 97%, 70%, 55%, 98% and 77%, respectively. Single and clinical combination of RF (clusters) had an high specificity, NPV and predictive accuracy for the specific etiologies (syndromes/metabolic/infiltrative disorders associated with HCM). CONCLUSIONS: An extensive diagnostic work up, focused on analysis of specific diagnostic RF in patients with unexplained LVH facilitates a clinical diagnosis in 74% of patients with HCM.
Authors: Emanuele Monda; Marta Rubino; Michele Lioncino; Francesco Di Fraia; Roberta Pacileo; Federica Verrillo; Annapaola Cirillo; Martina Caiazza; Adelaide Fusco; Augusto Esposito; Fabio Fimiani; Giuseppe Palmiero; Giuseppe Pacileo; Paolo Calabrò; Maria Giovanna Russo; Giuseppe Limongelli Journal: Front Pediatr Date: 2021-02-25 Impact factor: 3.569
Authors: Cristina Mazzaccara; Bruno Mirra; Ferdinando Barretta; Martina Caiazza; Barbara Lombardo; Olga Scudiero; Nadia Tinto; Giuseppe Limongelli; Giulia Frisso Journal: Int J Mol Sci Date: 2021-05-27 Impact factor: 6.208
Authors: Martina Caiazza; Marta Rubino; Emanuele Monda; Annalisa Passariello; Adelaide Fusco; Annapaola Cirillo; Augusto Esposito; Anna Pierno; Federica De Fazio; Roberta Pacileo; Eloisa Evangelista; Giuseppe Pacileo; Maria Giovanna Russo; Giuseppe Limongelli Journal: Genes (Basel) Date: 2020-08-17 Impact factor: 4.141
Authors: Emanuele Monda; Giuseppe Palmiero; Marta Rubino; Federica Verrillo; Federica Amodio; Francesco Di Fraia; Roberta Pacileo; Fabio Fimiani; Augusto Esposito; Annapaola Cirillo; Adelaide Fusco; Elisabetta Moscarella; Giulia Frisso; Maria Giovanna Russo; Giuseppe Pacileo; Paolo Calabrò; Olga Scudiero; Martina Caiazza; Giuseppe Limongelli Journal: Int J Mol Sci Date: 2020-09-04 Impact factor: 6.208