1. This proposed double-blind placebo controlled randomized controlled trial incorporates recent advances in management of heart failure and portal hypertension using the SGLT-2 inhibitor i.e. EMPAGLIFLOZIN. The drug has been found to be useful in large trials on heart failure with preserved ejection fraction in the general population with improvement in MASLD progression, with improvement in body weight and hepatic steatosis but no change in liver fibrosis. 2. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce the development and progression of heart failure in patients with type 2 diabetes and in those with heart failure and a reduced and preserved ejection fraction. In patients with cirrhosis safety of empagliflozin in a dose of 10 mg has been demonstrated. 3. Prevention of decompensation related events in cirrhosis is the key endpoint of any liver-directed therapy as the median survival in the compensated state exceeds 10 years but median survival in the decompensated state approximates 1.5 years. Previous data has demonstrated the risk of hepatic decompensation acute kidney injury and poor survival in patients with cirrhosis and heart failure with preserved ejection fraction (HFpEF) i.e. LVDD a large subset of whom meet criteria for CCM.
Age range of 18-65 years
Cirrhosis as diagnosed by histology or clinical laboratory and USG findings
LVDD (with EF>50%) on 2D echocardiography with TDI
Written informed consent.
Age >65 years
Serum Creatinine>2 mg/dl
History of urinary tract /genital infections in last 3 months
Patient on treatment with statin (one month before the study)
Parallel
Empagliflozin + Carvedilol
DrugPatient Recruitment: The study participants are all cirrhosis patients receiving treatment at PGIMER Chandigarh. Eligible participants meeting LVDD criteria per the CCM Consortium 2020 consensus. Carvedilol Dosing protocol in this study Patients will be given carvedilol in a starting dose of 3.125 mg twice daily. The dose will be titrated weekly to achieve a target heart rate of 50-60/ min taking care that side effects such as hypotension bronchospasm excessive bradycardia are not seen. The maximum dosage allowed as per prior trial data is 25 mg per day. Empagliflozin Dosing protocol in this Study: • All patients will receive a standard dose of Empagliflozin fixed dose of 10 mg per day in patients with or without diabetes.
Carvedilol
Drug* Carvedilol: Starting dose of 3.125 mg twice daily targeted upwards q 7 days to achieve target heart rate 10 mg placebo pill * Standard Medical Therapy
Composite end point of decompensation event and/or death
The primary outcome measure is defined as a composite end point of acute decompensation event (acute variceal bleeding new ascites or recurrence of previously controlled ascites episode of hepatic encephalopathy or acute kidney injury) OR all-cause death in patients with cirrhosis and LVDD
Improvement in Cardiac Diastolic Function
Improvement in CCM parameters (left ventricular diastolic function) in either arm based on Echocardiography and Cardiac Imaging Septal E/e' ratio
Improvement in Cardiac Diastolic Function
Improvement in CCM parameters (left ventricular diastolic function) in either arm based on Echocardiography and Cardiac Imaging Septal e' velocity
Improvement in Cardiac Diastolic Function
Improvement in CCM parameters (left ventricular diastolic function) in either arm based on Echocardiography and Cardiac Imaging Left atrial volume index
Improvement in Cardiac Diastolic Function
Improvement in CCM parameters (left ventricular diastolic function) in either arm based on Echocardiography and Cardiac Imaging Tricuspid regurgitant Velocity
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