Multiple hormonal and metabolic deficiency syndrome in chronic heart failure: rationale, design, and demographic characteristics of the T.O.S.CA. Registry
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Recent evidence supports the concept that progression of chronic heart failure (CHF) depends upon an imbalance of catabolic forces over the anabolic drive. In this regard, multiple hormonal deficiency syndrome (MHDS) significantly has impacts upon CHF progression, and is associated with a worse clinical status and increased mortality. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Therapy in Heart Failure) Registry (clinicaltrial.gov = NCT02335801) tests the hypothesis that anabolic deficiencies reduce survival in a large population of mild-to-moderate CHF patients. The T.O.S.CA. Registry is a prospective multicenter observational study coordinated by “Federico II” University of Naples, and involves 19 centers situated throughout Italy. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydroepiandrosterone , and insulin are measured at baseline and every year for a patient-average follow-up of 3 years. Subjects with CHF are divided into two groups: patients with one or no anabolic deficiency, and patients with two or more anabolic deficiencies at baseline. The primary endpoint is the composite of all-cause mortality and cardiovascular hospitalization. Secondary endpoints include the composite of all-cause mortality and hospitalization, the composite of cardiovascular mortality and cardiovascular hospitalization, and change of VO2 peak. Patient enrollment started in April 2013, and was completed in July 2017. Demographics and main clinical characteristics of enrolled patients are provided in this article. Detailed cross-sectional results will be available in late 2018. The T.O.S.CA. Registry represents the most robust prospective observational trial on MHDS in the field of CHF. The study findings will advance our knowledge with regard to the intimate mechanisms of CHF progression and hopefully pave the way for future randomized clinical trials of single or multiple hormonal replacement therapies in CHF.
KeywordsChronic heart failure Anabolic deficiency Multiple hormonal deficiency syndrome Registry Heart failure metabolism
We are especially grateful to the patients and nurses who have participated in this study. The TOSCA investigators also include: Cittadini A, Arcopinto M, Salzano A, Saccà L, Monti MG, Napoli R, Matarazzo M, Stagnaro FM, Schiavo A, Valente P (Department of Translational Medical Sciences, Federico II University, Naples, Italy); D’Assante R, Marra AM (IRCCS S.D.N., Naples, Italy); Bossone E, Ferrara F, Russo V, Malinconico M, Citro R (Heart Department, Cardiology Division, “Cava de’ Tirreni and Amalfi Coast” Hospital, University of Salerno, Salerno, Italy); Guastalamacchia E, Iacoviello M, Leone M, (University of Bari “Aldo Moro”, Bari, Italy); Triggiani V (Interdisciplinary Department of Medicine-Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases. University of Bari “A. Moro”, Bari, Italy) Cacciatore F, Maiello C, Amarelli C, Mattucci I (Heart Transplantation Unit, Monaldi Hospital, Azienda Ospedaliera dei Colli, Naples, Italy); Limongelli G, Masarone D, Calabrò P, Calabrò R, D’Andrea A, Maddaloni V, Pacileo G, Scarafile R (Cardiology SUN, Monaldi Hospital, Azienda Ospedaliera dei Colli, Second University of Naples, Naples, Italy); Perticone F, Belfiore A, Sciacqua A, Cimellaro A (University Magna Graecia of Catanzaro, Catanzaro, Italy); Perrone Filardi P, Casaretti L, Paolillo S, Gargiulo P (Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy); Mancini A, Favuzzi AMR, Di Segni C, Bruno C, Vergani E (Operative Unit of Endocrinology, Catholic University of the Sacred Heart, Rome); Volterrani M, Massaro R (IRCCS S. Raffaele Pisana, Roma, Italy); Vriz O (Heart Center Department, King Faisal Hospital & Research Center Riyadh, Kingdom of Saudi Arabia), Grimaldi F (Azienda Ospedaliero-Universitaria “Santa Maria della Misericordia” San Daniele del Friuli, Udine, Italy); Castello R, Frigo A (Azienda Ospedaliera Universitaria Integrata di Verona, Italy); Campo M, Sorrentino MR (Ospedali Riuniti di Foggia, Italy); Modesti PA, Malandrino D (Università di Firenze, Italy); Manfredini R, De Giorgi A, Fabbian F (Azienda Ospedaliera-Universitaria S. Anna, Ferrara, Italy); Puzzo A, Ragusa L (I.R.C.S.S. Oasi Maria SS, Troina, Italy.); Caliendo L, Carbone L (Ospedale Santa Maria della Pietà, Nola, Napoli, Italy); Frigiola A, Generali T, Giacomazzi F, De Vincentiis C, Ballotta A (IRCCS San Donato Milanese, Milano, Italy); Garofalo P, Malizia G (Ospedali Riuniti “Villa Sofia—Cervello”, Palermo, Italy); Milano S, Misiano G (Policlinico P. Giaccone, Palermo, Italy); Suzuki T, Heaney LM (Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Glenfield Hospital, Leicester, UK). Bruzzese D, Statistical Management (Department of Public Health, University Federico II of Naples, Naples, Italy). Dr. Salzano receives research grant support from Cardiopath. The T.O.S.CA. Registry is an Investigator initiated trial with external funding being provided mainly by unrestricted grants from MerckSerono.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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