Abstract Disclosure: M. Marino: None. L.S. Phillips: Advisory Board Member; Self; Diasyst, Inc.. Research Investigator; Self; Abbvie, Research Support, Jansen Pharmaceuticals, Research Support, Novo Nordisk, Research Support, Abbott Laboratories, Research Support, GlaxoSmithKline, Research Support, Sanofi-Aventis, Research Support, Pfizer, Inc.. Background: HFpEF is a major public health problem, since contributors include age, hypertension, hyperglycemia, and inactivity - and the US population is aging, hypertension and hyperglycemia are often inadequately treated, and inactivity is common. Moreover, management is difficult, since few medications have improved outcomes, and there is little long-term experience with sodium-glucose co-transporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and mineralocorticoid receptor antagonists. Clinical Case: In October 2010, a 69-year-old male with a history of lung adenocarcinoma with left lower lobe segmentectomy, prostate cancer post prostatectomy, and well-managed hypertension and hyperglycemia experienced severe shortness of breath while running on a track as part of his routine exercise. A left heart catheterization was performed to determine if the symptoms reflected inadequate perfusion, revealing only 30% stenosis in the left anterior descending coronary artery, ruling out coronary disease as the primary etiology. However, the left ventricular end diastolic pressure (LVEDP) was elevated (25 mmHg vs. normal <12), indicating heart failure. A transthoracic echocardiogram (TTE) in December 2010 revealed a normal left ventricular ejection fraction (EF 65%), a severely dilated left atrium [left atrial volume index (LAVI) 57 mL/m2 vs. normal <34], and diastolic dysfunction [flow velocity across the mitral valve (E/A ratio 1.61 and E/e’ 7.26). The patient was given pioglitazone 30mg daily before and nebivolol 2.5mg BID after the TTE, but in March 2011, a TTE showed an EF of 57% with persistent left atrial dilation (LAVI 50 mL/m2). A dipeptidyl peptidase-4 (DPP-4) inhibitor (sitagliptin 100mg daily) was begun August 2011, changed to liraglutide 1.8mg daily in December 2011, and eplerenone 75mg daily was begun February 2012. In June 2012, the LAVI was markedly improved (39 mL/m2). The nebivolol was switched to irbesartan 225mg daily in August 2012, and canagliflozin 300mg daily was added September 2013. A repeat TTE in March 2014 found an EF of 60%, and showed that the LAVI had returned to normal (34 mL/m2). During this period, mean blood pressure was 111/67 mmHg, LDL cholesterol 57 mg/dL, and HbA1c 5.4%, indicating that inadequate risk factor management was unlikely to be contributing to the diastolic dysfunction. Presently, the patient takes semaglutide, pioglitazone, telmisartan, empagliflozin, and eplerenone, continues to exercise vigorously, and a recent TTE showed an EF of 62% with mild left atrial dilation (LAVI 36.6). Conclusion: Left atrial dilation was improved after addition of a GLP-1 receptor agonist and a mineralocorticoid receptor antagonist, prior to use of an SGLT-2 inhibitor. Future investigations are needed to further understand the cardiovascular utility of these medications - beyond glycemic control and electrolyte balance. Presentation: 6/3/2024
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