Antonio Cittadini1,2, Andrea Salzano3, Massimo Iacoviello4, Vincenzo Triggiani5, Giuseppe Rengo1,6, Francesco Cacciatore1, Ciro Maiello7, Giuseppe Limongelli8, Daniele Masarone8, Francesco Perticone9, Antonio Cimellaro9, Pasquale Perrone Filardi10,11, Stefania Paolillo10,11, Antonio Mancini12, Maurizio Volterrani13, Olga Vriz14, Roberto Castello15, Andrea Passantino16, Michela Campo17, Pietro A Modesti18, Alfredo De Giorgi19, Ines P Monte20, Alfonso Puzzo21, Andrea Ballotta22, Roberta D'Assante1,2, Michele Arcopinto1,2, Paola Gargiulo10, Angela Sciacqua9, Dario Bruzzese23, Annamaria Colao24, Raffaele Napoli1, Toru Suzuki25, Kim A Eagle26, Hector O Ventura27, Alberto M Marra1,2,28, Eduardo Bossone2,29. 1. Department of Translational Medical Sciences, Federico II University, Via Sergio Pansini, 5, 80131 Naples, Italy. 2. Italian Clinical Outcome Research and Reporting Program (I-CORRP), Naples, Italy. 3. IRCCS SDN, Diagnostic and Nuclear Research Institute, Naples, Italy. 4. Cardiology Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy. 5. Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari 'A Moro', Bari, Italy. 6. Istituti Clinici Scientifici Maugeri SpA Società Benefit (ICS Maugeri SpA SB), IRCCS, Scientific Institute of Telese Terme, Telese BN, Italy. 7. Heart Transplantation Unit, Monaldi Hospital, Azienda Ospedaliera dei Colli, Naples, Italy. 8. Division of Cardiology, Monaldi Hospital, Azienda Ospedaliera dei Colli, University of Campania Luigi Vanvitelli, Caserta, Italy. 9. Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Catanzaro, Italy. 10. Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy. 11. Mediterranea Cardiocentro, Naples, Italy. 12. Operative Unit of Endocrinology, Catholic University of the Sacred Heart, Rome, Italy. 13. Department of Medical Sciences, IRCCS San Raffaele Pisana, Rome, Italy. 14. Heart Center Department, King Faisal Hospital & Research Center, Riyadh, Kingdom of Saudi Arabia. 15. Division of General Medicine, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. 16. Scientific Clinical Institutes Maugeri, IRCCS, Pavia, Italy. 17. Department of Medical and Surgical Sciences, Unit of Endocrinology and Metabolic Diseases, University of Foggia, Foggia, Italy. 18. Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Florence, Italy. 19. Department of Medical Sciences, School of Medicine, Pharmacy and Prevention, University of Ferrara, Ferrara, Italy. 20. Department of General Surgery and Medical-Surgery Specialties, University of Catania, Catania, Italy. 21. IRCSS Oasi Maria SS, Troina, Enna, Italy. 22. IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy. 23. Department of Public Health, Federico II University, Naples, Italy. 24. Clinical Medicine and Surgery Department, Federico II University, Naples, Italy. 25. Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Glenfield Hospital, Leicester, UK. 26. Michigan Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI, USA. 27. John Ochsner Heart and Vascular Institute, Ochsner Clinical School, The University of Queensland School of Medicine, New Orleans, LA, USA. 28. Center for Pulmonary Hypertension, Thoraxclinic at Heidelberg University Hospital, Heidelberg, Germany. 29. Cardiology Division, A Cardarelli Hospital, Naples, Italy.
Abstract
AIMS: Recent evidence supports the occurrence of multiple hormonal and metabolic deficiency syndrome (MHDS) in chronic heart failure (CHF). However, no large observational study has unequivocally demonstrated its impact on CHF progression and outcome. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Treatment in Heart Failure) Registry has been specifically designed to test the hypothesis that MHDS affects morbidity and mortality in CHF patients. METHODS AND RESULTS: The T.O.S.CA. Registry is a prospective, multicentre, observational study involving 19 Italian centres. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydropianoandrosterone sulfate, insulin resistance, and the presence of diabetes were evaluated. A MHDS was defined as the presence of ≥2 hormone deficiencies (HDs). Primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Four hundred and eighty heart failure patients with ejection fraction ≤45% were enrolled. MHDS or diabetes was diagnosed in 372 patients (77.5%). A total of 271 events (97 deaths and 174 cardiovascular hospitalizations) were recorded, 41% in NO-MHDS and 62% in MHDS (P < 0.001). Median follow-up was of 36 months. MHDS was independently associated with the occurrence of the primary endpoint [hazard ratio 95% (confidence interval), 1.93 (1.37-2.73), P < 0.001] and identified a group of patients with a higher mortality [2.2 (1.28-3.83), P = 0.01], with a graded relation between HDs and cumulative events (P < 0.01). CONCLUSION: MHDS is common in CHF and independently associated with increased all-cause mortality and cardiovascular hospitalization, representing a promising therapeutic target. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT023358017.
AIMS: Recent evidence supports the occurrence of multiple hormonal and metabolic deficiency syndrome (MHDS) in chronic heart failure (CHF). However, no large observational study has unequivocally demonstrated its impact on CHF progression and outcome. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Treatment in Heart Failure) Registry has been specifically designed to test the hypothesis that MHDS affects morbidity and mortality in CHF patients. METHODS AND RESULTS: The T.O.S.CA. Registry is a prospective, multicentre, observational study involving 19 Italian centres. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydropianoandrosterone sulfate, insulin resistance, and the presence of diabetes were evaluated. A MHDS was defined as the presence of ≥2 hormone deficiencies (HDs). Primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Four hundred and eighty heart failure patients with ejection fraction ≤45% were enrolled. MHDS or diabetes was diagnosed in 372 patients (77.5%). A total of 271 events (97 deaths and 174 cardiovascular hospitalizations) were recorded, 41% in NO-MHDS and 62% in MHDS (P < 0.001). Median follow-up was of 36 months. MHDS was independently associated with the occurrence of the primary endpoint [hazard ratio 95% (confidence interval), 1.93 (1.37-2.73), P < 0.001] and identified a group of patients with a higher mortality [2.2 (1.28-3.83), P = 0.01], with a graded relation between HDs and cumulative events (P < 0.01). CONCLUSION: MHDS is common in CHF and independently associated with increased all-cause mortality and cardiovascular hospitalization, representing a promising therapeutic target. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT023358017.
Authors: Andrea Salzano; Roberta D'Assante; Eduardo Bossone; Alberto M Marra; Antonio Cittadini; Massimo Iacoviello; Vincenzo Triggiani; Giuseppe Rengo; Francesco Cacciatore; Ciro Maiello; Giuseppe Limongelli; Daniele Masarone; Angela Sciacqua; Pasquale Perrone Filardi; Antonio Mancini; Maurizio Volterrani; Olga Vriz; Roberto Castello; Andrea Passantino; Michela Campo; Pietro A Modesti; Alfredo De Giorgi; Michele Arcopinto; Paola Gargiulo; Maria Perticone; Annamaria Colao; Salvatore Milano; Agnese Garavaglia; Raffaele Napoli; Toru Suzuki Journal: Cardiovasc Diabetol Date: 2022-06-16 Impact factor: 8.949
Authors: Dominika Klimczak-Tomaniak; Marie de Bakker; Elke Bouwens; K Martijn Akkerhuis; Sara Baart; Dimitris Rizopoulos; Henk Mouthaan; Jan van Ramshorst; Tjeerd Germans; Alina Constantinescu; Olivier Manintveld; Victor Umans; Eric Boersma; Isabella Kardys Journal: Sci Rep Date: 2022-02-18 Impact factor: 4.379
Authors: Alfredo De Giorgi; Alberto Maria Marra; Massimo Iacoviello; Vincenzo Triggiani; Giuseppe Rengo; Francesco Cacciatore; Ciro Maiello; Giuseppe Limongelli; Daniele Masarone; Francesco Perticone; Pasquale Perrone Filardi; Stefania Paolillo; Antonio Mancini; Maurizio Volterrani; Olga Vriz; Roberto Castello; Andrea Passantino; Michela Campo; Pietro Amedeo Modesti; Andrea Salzano; Roberta D'Assante; Michele Arcopinto; Valeria Raparelli; Fabio Fabbian; Angela Sciacqua; Annamaria Colao; Toru Suzuki; Eduardo Bossone; Antonio Cittadini Journal: Intern Emerg Med Date: 2022-04-21 Impact factor: 5.472