Effects of Dapagliflozin on Cardiorespiratory Parameters in Heart Failure

Effects of Dapagliflozin on Exercise Capacity, Respiratory Function, Biomarkers, Sleep Apnoeas and Left Ventricular Remodelling in Heart Failure Patients

Dapagliflozin is a molecule belonging to the class of sodium-glucose transporter type 2 (SGLT2-i) inhibitors. This type of drug, initially used in the treatment of diabetes mellitus, has in recent years demonstrated significant prognostic benefit in patients with heart failure even in the absence of diabetes mellitus. The new international heart failure guidelines have taken up this evidence by suggesting the use of SGLT2-i therapy in patients with heart failure with reduced ejection fraction (HFrEF). Given the drug's recent introduction into clinical routine, the evaluation of "field" experience is important to refine the clinical management of patients treated with SGLT2-i. Moreover, SGLT2-i has currently been shown to be effective in some small preliminary studies in improving ejection fraction and some echocardiographic parameters of ventricular remodelling on top of concomitant optimal medical therapy, although further data are needed in this regard. In particular, the potential benefit of SGLT2-i therapy on exercise capacity, respiratory function parameters, biomarkers and left ventricular remodelling in patients with heart failure has not been extensively studied at present. In this regard, the cardiopulmonary exercise test (CPET) allows the derivation of prognostic functional parameters in patients with chronic heart failure such as peak VO2 and the ventilation/CO2 slope. CPET is a valid, recognised and accurate tool for risk stratification in patients with heart failure. In addition, there are no data available on the effect of SGLT2-i on lung diffusion (DLCO) and specific markers of the alveolar-capillary membrane, such as surfactant binding proteins, as well as on the presence of sleep apnoea, a particularly relevant parameter for the prognosis of decompensated patients.

The aim of the study is to evaluate changes in exercise capacity, spirometry, DLCO, echocardiographic parameters of left ventricular systolic-diastolic function, Nt-proBNP dosage, ST-2, surfactant binding proteins, sleep apnoea, impedance measurement and quality of life in a single-centre cohort of 70 patients with heart failure with stable reduced left ventricular ejection fraction (functional class NYHA II and III) and guideline candidates for treatment with Dapagliflozin.

Patients will undergo, as per regular clinical practice, an initial assessment (baseline) that will include a clinical evaluation, KCCQ questionnaire for quality of life assessment, spirometry, DLCO, impedance measurement, polysomnography, a cardiopulmonary ramp test, blood tests with dosage of Nt-proBNP, ST-2 and surfactant binding protein, and a standard transthoracic echocardiogram. At baseline, the patient will start treatment with Dapagliflozin at the standard dosage of 10mg/day. A similar evaluation with the same study procedures will be performed 6 months after the start of therapy. A re-evaluation of the patient including venous blood sampling is planned between 2 and 4 weeks after the start of Dapagliflozin from clinical practice. In the context of this sampling, the assay of the biomarkers under study will also be repeated.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Sleep Apnea; Heart Failure With Reduced Ejection Fraction; Cardiopulmonary Exercise Test; Left Ventricle Remodeling

• Study Type: Observational
• Enrollment (Anticipated): 70

Contacts and Locations

• Study Contact: Name: Massimo Mapelli, MD; Phone Number: +39 0258002930; Email: massimo.mapelli@ccfm.it

Study Locations

• Italy
  • Milan, Italy, 20138
    • Recruiting
    • Centro Cardiologico Monzino
    • Contact: Massimo Mapelli, MD; Phone Number: +39 0258002930; Email: massimo.mapelli@ccfm.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

patients with heart failure with reduced left ventricular ejection fraction, stable (NYHA functional class II and III) and guideline candidates for treatment with Dapagliflozin

Description

Inclusion Criteria:

• Age >18 years
• stable clinical conditions
• Diagnosis of heart failure according to European guidelines (ESC) with EF≤40%
• New York Heart Association Class (NYHA) II-III, despite optimised treatment for heart failure, candidates for treatment with Dapagliflozin according to current guidelines
• Ability to perform cardiopulmonary testing (CPET)
• Patients who have signed written informed consent

Exclusion Criteria:

• Contraindication for Dapaglilozin prescription
• Moderate-severe obstructive pulmonary disease (COPD)
• Estimated glomerular filtrate (eGFR) <30 mL/min/1.73m2 according to MDRD criteria
• Inability or contraindication to perform a CPET
• Taking an investigational drug within 30 days prior to administration of Dapagliflozin

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
exercise capacity change	Evaluation of the change in patients' exercise capacity by raising oxygen consumption at peak exercise during cardiopulmonary testing	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in FEV1	Change in lung function in terms of forced expiratory volume in 1 s FEV1 (spirometry)	6 months
change in DLCO	Change in lung function in terms of DLCO (lung diffusion capacity for carbon monoxide)	6 months
Change in Nt-proBNP	Change in blood levels of heart failure biomarker Nt-proBNP (amino terminal pro-B-type natriuretic peptide)	6 months
Change in ST-2	Change in blood levels of heart failure biomarker ST-2 (soluble interleukin 1 receptor-like 1)	6 months
Change in surfactant binding protein	Change in blood levels of biomarker surfactant binding protein	6 months
change in LVEF	Chnage in left ventricular ejection fraction (echocardiography)	6 months
change in left ventricular volumes	Change in left ventricular volumes (echocardiography)	6 months
change in central sleep apnoeas	Change in central sleep apnoeas (Nocturnal cardiorespiratory monitoring)	6 months
change in quality of life	Change in patients' quality of life evaluated through Kansas City Cardiomyopathy Questionnaire (KCCQ-12)	6 months
change in hydration index	Change in hydration index HI assessed through Bioimpedance vector analysis (BIVA)	6 months
population stratification according to VO2 peak higher and lower than 15 ml/min/kg	Show any differences in clinical response depending on the severity of heart failure (stratified according to VO2 peak higher and lower than 15 ml/min/kg at CPET)	6 months

Collaborators and Investigators

• Sponsor: Centro Cardiologico Monzino
• Investigators: Principal Investigator: Massimo Mapelli, MD, Centro Cardiologico Monzino

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2022
• Primary Completion (Anticipated): April 1, 2025
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: February 22, 2023
• First Submitted That Met QC Criteria: March 3, 2023
• First Posted (Actual): March 15, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2023
• Last Update Submitted That Met QC Criteria: March 3, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Pathological Conditions, Anatomical; Heart Failure; Sleep Apnea Syndromes; Ventricular Remodeling
• Other Study ID Numbers: CCM 1756

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No