SGLT2 Inhibitors in Transthyretin Amyloid Cardiomyopathy

Inclusion Criteria:

• Every participant must meet all of the following inclusion criteria to be eligiblefor enrollment in this study:

1. Age ≥ 18 years old

2. Diagnosis of TTR cardiac amyloidosis (wild type or variant), confirmed by thepresence of amyloid deposits on analysis of biopsy specimens obtained fromcardiac and noncardiac sites (e.g. fat aspirate, gastrointestinal sites,salivary glands, or bone marrow), technetium-99m pyrophosphate cardiacscintigraphy, or mass spectrometry

3. Normal serum free light chain ratio and the absence of abnormal monoclonal bandon serum and urine immunofixation

4. Subjects will have at least 1 of the indications below for an SGLT2i, and meetpackage-insert criteria for drug initiation: non-insulin dependent diabetesmellitus with hemoglobin A1c ranging from 6.5-9.9 OR chronic kidney disease (defined as an estimated glomerular filtration rate of 25-75 ml/minute/1.73 m2of body-surface area)

5. On stable oral diuretics (defined as no more than a 50% increase from baselinediuretic dose established during a sustained 2 week period) within 2 weeksbefore enrollment

6. Able to understand and sign the informed consent document after the nature ofthe study has been fully explained

Exclusion Criteria:

• The presence of any of the following excludes eligibility for enrollment in thisstudy:

1. Prior liver or heart transplantation

2. Active malignancy or non-amyloid disease with expected survival of less than 1year

3. Heart failure, in the opinion of the investigator, primarily caused by severeleft-sided valve disease. Note: if valve was repaired, subject may beconsidered as no longer with severe valve disease

4. Heart failure, in the opinion of the investigator, primarily caused by ischemicheart disease

5. Ventricular assist device or anticipated within the next 6 months

6. Pacemaker or implantable cardioverter defibrillator incompatible with magneticresonance technology

7. Absolute contraindication for quantitative magnetic resonance (e.g. aneurysmalclips, metal objects)

8. Impairment from stroke, injury or other medical disorder that precludesparticipation in the study

9. Myocardial infarction, cardiovascular surgery, stroke or transient ischemicattack within the prior 90 days

10. Disabling dementia or other mental or behavioral disease

11. Enrollment in a clinical trial not approved for co-enrollment

12. Expected use of continuous intravenous inotropic therapy in the next 6 months

13. High risk for non-adherence as determined by screening evaluation

14. Inability or unwillingness to comply with the study requirements

15. Chronic kidney disease with estimated glomerular filtration rate (eGFR) <15mL/min/1.73 m2 or end-stage renal disease

16. Current or prior SGLT2i use

17. Type 1 diabetes mellitus or insulin-dependent diabetes mellitus

18. N-terminal (NT)-pro hormone BNP (NT-proBNP) < 300 pg/mL or < 900 pg/mL ifconcomitant diagnosis of atrial fibrillation

19. History of ketoacidosis

20. History of complex urinary tract or genital infections

21. History of kidney stone

22. Systolic blood pressure < 90 mmHg and symptomatic hypotension

23. Systolic blood pressure ≥ 180 mmg Hg

24. Chronic obstructive pulmonary disease

25. Major surgery in the 90 days before or after screening

26. Chronic alcohol or drug abuse

27. Nursing home resident

28. Other reason that would make the subject inappropriate for entry into thisstudy