Progressive right ventricular dysfunction and exercise impairment in patients with heart failure and diabetes mellitus: insights from the T.O.S.CA. Registry
Authors: Salzano Andrea , D’Assante Roberta , Iacoviello Massimo , Triggiani Vincenzo , Rengo Giuseppe , Cacciatore Francesco , Maiello Ciro , Limongelli Giuseppe , Masarone Daniele , Sciacqua Angela , Filardi Pasquale Perrone , Mancini Antonio , Volterrani Maurizio , Vriz Olga , Castello Roberto , Passantino Andrea , Campo Michela , Modesti Pietro A. , De Giorgi Alfredo , Arcopinto Michele , Gargiulo Paola , Perticone Maria , Colao Annamaria , Milano Salvatore , Garavaglia Agnese , Napoli Raffaele , Suzuki Toru , Bossone Eduardo , Marra Alberto M. , Cittadini Antonio ,   T.O.S.CA. Investigators, Cittadini A. , Marra A. M. , Arcopinto M. , D’Assante R. , Saccà L. , Monti M. G. , Napoli R. , Matarazzo M. , Stagnaro F. M. , Piccioli L. , Lombardi A. , Panicara V. , Flora M. , Golia L. , Faga V. , Ruocco A. , Della Polla D. , Franco R. , Schiavo A. , Gigante A. , Spina E. , Sicuranza M. , Monaco F. , Apicella M. , Miele C. , Campanino A. G. , Mazza L. , Abete R. , Farro A. , Luciano F. , Polizzi R. , Ferrillo G. , De Luca M. , Crisci G. , Giardino F. , Barbato M. , Salzano A. , Ranieri B. , Bossone E. , Ferrara F. , Russo V. , Malinconico M. , Citro R. , Guastalamacchia E. , Iacoviello M. , Leone M. , Triggiani V. , Giagulli V. A. , Cacciatore F. , Maiello C. , Amarelli C. , Mattucci I. , Limongelli G. , Masarone D. , Calabrò P. , Calabrò R. , D’Andrea A. , Maddaloni V. , Pacileo G. , Scarafile R. , Perticone F. , Belfiore A. , Sciacqua A. , Cimellaro A. , Perrone Filardi P. , Casaretti L. , Paolillo S. , Gargiulo P. , Mancini A. , Favuzzi A. M. R. , Di Segni C. , Bruno C. , Vergani E. , Volterrani M. , Massaro R. , Vriz O. , Grimaldi F. , Castello R. , Frigo A. , Campo M. R. , Sorrentino M. R. , Modesti P. A. , Malandrino D. , Manfredini R. , De Giorgi A. , Fabbian F. , Puzzo A. , Ragusa L. , Caliendo L. , Carbone L. , Frigiola A. , Generali T. , Giacomazzi F. , De Vincentiis C. , Ballotta A. , Garofalo P. , Malizia G. , Milano S. , Misiano G. , Suzuki T. , Israr M. Z. , Bernieh D. , Cassambai S. , Yazaki Y. , Heaney L. M. , Eagle K. A. , Ventura H. O. , Colao A. , Bruzzese D. 
Published: June 2022

Abstract
Background
Findings from the T.O.S.CA. Registry recently reported that patients with concomitant chronic heart failure (CHF) and impairment of insulin axis (either insulin resistance—IR or diabetes mellitus—T2D) display increased morbidity and mortality. However, little information is available on the relative impact of IR and T2D on cardiac structure and function, cardiopulmonary performance, and their longitudinal changes in CHF.

Methods
Patients enrolled in the T.O.S.CA. Registry performed echocardiography and cardiopulmonary exercise test at baseline and at a patient-average follow-up of 36 months. Patients were divided into three groups based on the degree of insulin impairment: euglycemic without IR (EU), euglycemic with IR (IR), and T2D.

Results
Compared with EU and IR, T2D was associated with increased filling pressures (E/e′ratio: 15.9 ± 8.9, 12.0 ± 6.5, and 14.5 ± 8.1 respectively, p < 0.01) and worse right ventricular(RV)-arterial uncoupling (RVAUC) (TAPSE/PASP ratio 0.52 ± 0.2, 0.6 ± 0.3, and 0.6 ± 0.3 in T2D, EU and IR, respectively, p < 0.05). Likewise, impairment in peak oxygen consumption (peak VO2) in TD2 vs EU and IR patients was recorded (respectively, 15.8 ± 3.8 ml/Kg/min, 18.4 ± 4.3 ml/Kg/min and 16.5 ± 4.3 ml/Kg/min, p < 0.003). Longitudinal data demonstrated higher deterioration of RVAUC, RV dimension, and peak VO2 in the T2D group (+ 13% increase in RV dimension, − 21% decline in TAPSE/PAPS ratio and − 20% decrease in peak VO2).

Conclusion
The higher risk of death and CV hospitalizations exhibited by HF-T2D patients in the T.O.S.CA. Registry is associated with progressive RV ventricular dysfunction and exercise impairment when compared to euglycemic CHF patients, supporting the pivotal importance of hyperglycaemia and right chambers in HF prognosis.
Trial registration ClinicalTrials.gov identifier: NCT023358017