Progressive right ventricular dysfunction and exercise impairment in patients with heart failure and diabetes mellitus: insights from the T.O.S.CA. Registry

Andrea Salzano, Roberta D'Assante, 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, Eduardo Bossone, Alberto M Marra, Antonio Cittadini, T.O.S.CA. Investigators, A Cittadini, A M Marra, M Arcopinto, R D'Assante, L Saccà, M G Monti, R Napoli, M Matarazzo, F M Stagnaro, L Piccioli, A Lombardi, V Panicara, M Flora, L Golia, V Faga, A Ruocco, D Della Polla, R Franco, A Schiavo, A Gigante, E Spina, M Sicuranza, F Monaco, M Apicella, C Miele, A G Campanino, L Mazza, R Abete, A Farro, F Luciano, R Polizzi, G Ferrillo, M De Luca, G Crisci, F Giardino, M Barbato, A Salzano, B Ranieri, E Bossone, F Ferrara, V Russo, M Malinconico, R Citro, E Guastalamacchia, M Iacoviello, M Leone, V Triggiani, V A Giagulli, F Cacciatore, C Maiello, C Amarelli, I Mattucci, G Limongelli, D Masarone, P Calabrò, R Calabrò, A D'Andrea, V Maddaloni, G Pacileo, R Scarafile, F Perticone, A Belfiore, A Sciacqua, A Cimellaro, P Perrone Filardi, L Casaretti, S Paolillo, P Gargiulo, A Mancini, A M R Favuzzi, C Di Segni, C Bruno, E Vergani, M Volterrani, R Massaro, O Vriz, F Grimaldi, R Castello, A Frigo, M R Campo, M R Sorrentino, P A Modesti, D Malandrino, R Manfredini, A De Giorgi, F Fabbian, A Puzzo, L Ragusa, L Caliendo, L Carbone, A Frigiola, T Generali, F Giacomazzi, C De Vincentiis, A Ballotta, P Garofalo, G Malizia, S Milano, G Misiano, T Suzuki, M Z Israr, D Bernieh, S Cassambai, Y Yazaki, L M Heaney, K A Eagle, H O Ventura, A Colao, D Bruzzese, Andrea Salzano, Roberta D'Assante, 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, Eduardo Bossone, Alberto M Marra, Antonio Cittadini, T.O.S.CA. Investigators, A Cittadini, A M Marra, M Arcopinto, R D'Assante, L Saccà, M G Monti, R Napoli, M Matarazzo, F M Stagnaro, L Piccioli, A Lombardi, V Panicara, M Flora, L Golia, V Faga, A Ruocco, D Della Polla, R Franco, A Schiavo, A Gigante, E Spina, M Sicuranza, F Monaco, M Apicella, C Miele, A G Campanino, L Mazza, R Abete, A Farro, F Luciano, R Polizzi, G Ferrillo, M De Luca, G Crisci, F Giardino, M Barbato, A Salzano, B Ranieri, E Bossone, F Ferrara, V Russo, M Malinconico, R Citro, E Guastalamacchia, M Iacoviello, M Leone, V Triggiani, V A Giagulli, F Cacciatore, C Maiello, C Amarelli, I Mattucci, G Limongelli, D Masarone, P Calabrò, R Calabrò, A D'Andrea, V Maddaloni, G Pacileo, R Scarafile, F Perticone, A Belfiore, A Sciacqua, A Cimellaro, P Perrone Filardi, L Casaretti, S Paolillo, P Gargiulo, A Mancini, A M R Favuzzi, C Di Segni, C Bruno, E Vergani, M Volterrani, R Massaro, O Vriz, F Grimaldi, R Castello, A Frigo, M R Campo, M R Sorrentino, P A Modesti, D Malandrino, R Manfredini, A De Giorgi, F Fabbian, A Puzzo, L Ragusa, L Caliendo, L Carbone, A Frigiola, T Generali, F Giacomazzi, C De Vincentiis, A Ballotta, P Garofalo, G Malizia, S Milano, G Misiano, T Suzuki, M Z Israr, D Bernieh, S Cassambai, Y Yazaki, L M Heaney, K A Eagle, H O Ventura, A Colao, D Bruzzese

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.

Keywords: Cardiopulmonary exercise test; Chronic heart failure; Diabetes; Insulin resistance; Right ventricle; TOSCA.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Longitudinal changes of Left and Right Ventricular architecture and function (A) and exercise capacity (B) of patients grouped with regard to insulin action impairment. Delta changes of selected variables of left ventricle (LV) and right ventricle (RV) architecture and function from baseline at 36 months (A). Whereas delta changes of LV parameters did not significantly differ between three groups, T2D patients displayed a more prominent progression of RV parameters. This phenomenon is paralleled by a more important impairment in cardiovascular performance, as testified by the delta change of peak VO2 from baseline (B)

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