Heart Failure
Conditions
Keywords
Heart failure, Cardiac imaging, SGLT2, Biomarkers
Brief summary
This is a 26-week, open label, single-arm prospective evaluation of the effects of sodium glucose cotransporter 2 (SGLT2) inhibition on cardiac biomarkers, myocardial remodeling and patient reported outcomes in heart failure with both impaired and preserved left ventricular fraction.
Detailed description
The primary aims of this study are to evaluate whether SGLT2 inhibition in patients with heart failure effects changes in novel cardiac biomarkers. This is an exploratory evaluation of novel cardiac pathways which may serve to establish, as of yet unknown, therapeutic mechanisms of action of SGLT2 inhibition in heart failure. Secondary aims include evaluation of changes in standard of care biomarkers following SGLT2 inhibition and changes in markers of cardiac remodeling as identified on echocardiography. Further exploratory analysis will seek to correlate changes in quantitative and qualitative heart failure outcomes with changes in both novel and standard of care cardiac biomarkers.
Interventions
Patients identified with heart failure (both reduced ejection fraction and preserved) who are on optimal standard therapy and are candidates for treatment with SGLT2 inhibition will be identified from local heart failure databases, and local heart failure clinics. Following signed, informed consent and screening, patients will be allocated a first appointment where baseline clinical assessment and biomarker analysis will be obtained along with commencement on a SGLT2 inhibitor. Repeat assessment will be performed following a minimum period of 26 weeks.
Sponsors
Belfast Health and Social Care Trust
Queen's University, Belfast
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
40 Years to 90 Years
Inclusion criteria
1. Provision of signed informed consent prior to any study specific procedures. 2. Male or female, between 40 and 90 years of age. 3. LVEF \<50% on echocardiography or if \>50%, co-existing structural markers of diastolic dysfunction must be present; * LA width (diameter) ≥3.8 cm or LA length ≥5.0 cm, or LA area ≥20 cm, or LA volume ≥55 mL or LA volume index ≥29 mL/m. * Left ventricular hypertrophy. * Markers of diastolic dysfunction as assessed by pulsed wave doppler echocardiography. * N-terminal pro-B-type natriuretic peptide (NT-proBNP) of at least 125pg per millilitre (or ≥365pg per millilitre if co-existing atrial fibrillation). 4. New York Heart Association (NYHA) class II, III, or IV symptoms. 5. On optimal tolerated evidence-based HF medications. 6. Patients may be ambulatory or recently hospitalized; however, must be \>6 weeks post-discharge on stable diuretic therapy.
Exclusion criteria
1. Receiving therapy with an SGLT2 inhibitor \> 6 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor. 2. Severe (eGFR \<20 mL/min/1.73m2), unstable or rapidly progressing renal disease at the time of recruitment. 3. Type 1 diabetes mellitus 4. Recent hospitalisation \< 1 month. 5. Symptomatic hypotension or systolic BP \<95 mmHg at 2 out of 3 measurements 6. Symptomatic bradycardia or second or third-degree heart block without a pacemaker. 7. Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or implantation expected after recruitment. 8. Cardiomyopathy secondary to uncorrected primary valvular disease, infiltrative, arrhythmogenic or right ventricular dysplasia. 9. Significant comorbidity including; pulmonary lung disease requiring home oxygen or non-invasive ventilation, CTEPH or primary pulmonary hypertension.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate whether SGLT2 inhibition in heart failure produces changes in novel cardiac biomarkers. | 26 weeks | Assessment of changes in levels of novel biomarkers associated with heart failure, cardiac remodeling, or response to SGLT2i, including; KIM-1, IGFBP7, TNFR, IL-6, collagen IV, MMP7, FN1, sST2, LRG1, Tetranectin, collagen XIV (Olink and ELISA based analysis). Additional novel biomarkers may be added to this investigatory panel as the trial continues. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate if SGLT2 inhibition produces changes in markers of cardiac remodeling as assessed by echocardiography. | 26 weeks | Changes in global longitudinal strain (GLS) (%) and left ventricular systolic function \[LVEF (%)\] as assessed on strain echocardiography. |
| To evaluate if SGLT2 inhibition produces changes in markers of cardiac remodeling as assessed by diastolic parameters on echocardiography. | 26 weeks | Change in left ventricular lateral e' (cm/s), septal e' (cm/s) and E/e' ratio obtained from echocardiography. |
| To evaluate changes in quantitative markers of heart failure outcomes following initiation of SGLT2 inhibition in heart failure. | 26 weeks | Changes in standard care cardiac biomarkers following SGLT2 inhibition including, N-terminal prohormone of brain natriuretic peptide \[NT-proBNP (ng/L)\] and high sensitivity troponin \[hs-TnT (ng/L)\]. |
| To evaluate changes in qualitative markers of heart failure outcomes. | 26 weeks. | Change in New York Heart Association (NYHA) score, classified on a scale I to IV, with a higher number indicating a worse outcome. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory evaluation of correlation of effect of SGLT2 inhibition on novel cardiac biomarkers with markers of cardiac remodeling. | 26 weeks. | Correlation of log transformed delta change in novel cardiac biomarkers with global longitudinal strain \[GLS (%)\] and left ventricular ejection fraction \[LVEF (%)\]. |
| Exploratory evaluation of correlation of effect of SGLT2 inhibition on novel cardiac biomarkers with qualitive markers of heart failure outcomes. | 26 weeks. | Correlation of log transformed delta change in novel cardiac biomarkers with change in Kansas-City Cardiomyopathy Questionnaire (KCCQ). |
Countries
United Kingdom
Contacts
Primary ContactPatrick Savage, MB BChBAO Bsc
Backup ContactChris Watson, PhD
Outcome results
None listed