Validation of ERTugliflozin for Inhibiting Cardiac Fibrosis Using Cardiac MRI and Laboratory Parameters in Korean Heart Failure Patients With Nonischemic Cardiomyopathy(VERTICAL)

Inclusion Criteria:

• Patients must agree to the study protocol and provide written informed consent
• Outpatients ≥ 19 years, <75 years of age, male or female
• Non-diabetic or type 2 DM patients with HbA1c 7.0-10.5%
• Patients with nonischemic cardiomyopathy (LVEF ≤40%)
• Exclusion of ischemic origin cardiomyopathy using coronary angiography or CT angiography or SPECT scan (e.g. significant stenosis of proximal LAD or left main & myocardial infarction)
• Dyspnea of NYHA functional class II or III
• NT-proBNP ≥ 400 pg/ml (≥ 900 pg/ml if atrial fibrillation or atrial flutter)
• Titration of HF medications should be completed and patients must take a stable, optimized dose of a β-blocker and an ACE inhibitor (or ARB or ARNI if indicated) for at least 4 weeks prior to study entry

Exclusion Criteria:

• History of hypersensitivity or allergy to the study drug, drugs of similar chemical classes, or SGLT-2 as well as known or suspected contraindications to the study drug
• Current use or prior use of a SGLT-2 inhibitor or combined SGLT-1 and 2 inhibitor
• Known history of angioedema
• Current acute decompensated heart failure or dyspnea of NYHA functional class IV
• Medical history of hospitalization within 6 weeks
• Acute coronary syndrome, stroke, major CV surgery, PCI within 3 months
• Substantial myocardial ischemia requiring coronary revascularization therapy or a plan of coronary revascularization within 6 months
• A plan of heart transplantation or implantation of cardiac resynchronization therapy
• Symptomatic hypotension and/or a SBP < 95 mmHg at screening
• Estimated GFR < 30 mL/min/1.73m2
• History of ketoacidosis
• Symptomatic peripheral artery disease and history of lower limb amputation
• Evidence of hepatic disease as determined by any one of the following: AST or ALT values exceeding 3 x upper limit of normal (ULN) at screening visit (Visit 0), history of hepatic encephalopathy, history of esophageal varices, or history of portacaval shunt.
• History of severe pulmonary disease
• Significant mitral & aortic valve disease (e.g. moderate to severe, severe degree)
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using a barrier method plus a hormonal method
• Pregnant or nursing (lactating) women
• Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the investigator, would preclude safe completion of the study