Effect of SGLT-2 inhibitors on the incidence of right ventricular dysfunction in patients with chronic heart failure
G Armentaro, G Severini, C Sinatra, C A Pastura, M R Scarcelli, V Condoleo, S Miceli, C Vitale, G M C Rosano, A SciacquaAbstract
Introduction
Right ventricular dysfunction (RVD) is one of the main complications of left ventricular heart failure (LVHF). Although modulation of the sympathetic nervous system and the renin-angiotensin-aldosterone system has been demonstrated to enhance prognosis in LVHF, it has not exhibited a substantial clinical benefit in reducing the incidence of RVD. However, as of yet, there has been no data regarding the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the incidence of RVD.
Purpose
The aim of this study is to evaluate the possible prognostic impact of SGLT2i use in a cohort of patients with LVHF across the entire spectrum of ejection fraction (EF), and to evaluate other variables associated with the incidence of RVD during long-term follow-up, evaluated as incidence of Tricuspid Annular Plane Systolic Excursion (TAPSE)<17 mm.
Methods
In this retrospective, single-centre observational study a total of 467 outpatients with chronic LVHF, mean age of 78.5±9.7 years, were enrolled and underwent clinical, laboratory and echocardiographic evaluation for a mean follow-up of 4.6±1.0 years. Patients with HF NYHA IV, worsening HF in the last 6 months, TAPSE <17 mm at baseline and eGFR<15 ml/min/1,73m2 were excluded. Variables that correlated significantly with the onset of RVD were included in a multivariate Cox regression model to calculate the hazard ratio (HR) for the incidence of RVD.
Results
The study population was stratified according to SGLT2i use, with 231 receiving SGLT2i therapy and 236 not receiving SGLT2i. The two groups were comparable in terms of gender, major comorbidities, therapies, laboratory and instrumental variables. Patients on SGLT2i therapy were younger than the other group, with a mean age of 75.6±9.3 years compared to 81.3 ± 9.3 years (p<0.0001). Additionally, they exhibited lower EF, with a mean value of 42.5±9.5% compared to 47.1±8.1% (p<0.0001). The incidence of RVD in the entire population was 4.8 events /100 patients-year. Of these, 1.3 events/100 patients-year were observed in the group treated with SGLT2i, while 7.8 events/100 patients-year were reported in the group not treated with SGLT2i (p<0.0001). A multivariate analysis model demonstrated that SGLT2i therapy (HR 0.223; p<0.0001), MRAs (HR 0.604; p<0.026), and an increase of 10 ml/min/1.73 m² in glomerular filtration rate (HR 0.901; p<0.039) were associated with a reduced risk of RVD incidence. In contrast, results indicate that an increase in age of 10 years is associated with an elevated risk of right ventricular dysfunction (RVD) (HR 1.527, p<0.001) in patients with LVHF.
Conclusion
This study confirms the beneficial effect of SGLT2i therapy in elderly patients with LVHF, in reducing the incidence of RVD during 4.6 years follow-up.