Unrecognized HFpEF in a Type 2 DM Patient - Reducing CV and HF Risk

Sara is a 65-year-old woman with long-standing type 2 diabetes mellitus (DM), hypertension, hyperlipidemia, and hypothyroidism. She is morbidly obese and has chronic kidney disease (CKD) with a glomerular filtration rate (GFR) of 65 ml/min/m2. She complains of fatigue but has no chest pain. She is still able to do her activities of daily living, but has become less active, which she attributes to weight gain. She has not been able to walk upstairs for the last year and tends to walk slower than her family at the mall. She has occasional palpitations and wakes up during the night to go to the bathroom. She frequently wakes up with a headache and believes her increased fatigue is due to insomnia.

Physical Exam

  • Blood pressure 146/ 89 mm Hg, pulse 93 bpm
  • Body mass index 43 kg/m2, waist circumference 102 cm
  • Exam: no murmur, short neck, jugular venous distention difficult to assess, S3
  • Mild ankle edema of the left lower extremity, varicose veins, distal pulses palpable 2+


  • Metformin 1000 mg BID and saxagliptin 50 mg
  • Pioglitazone 30 mg
  • Pitavastatin 4 mg and ezetimibe 10 mg (had leg cramps with atorvastatin and rosuvastatin)
  • On amlodipine 10 mg/perindopril 10 mg
  • Levothyroxine 75 µg daily
  • Furosemide 40 mg daily was started recently by her primary care physician for the edema

Basic Investigations

  • Hemoglobin Aa1c (Hb A1C) 7.4%
  • Low-density lipoprotein cholesterol 72 mg/dl, triglycerides 210 mg/dl, non–high-density lipoprotein cholesterol (non–HDL-C) 121 mg/dl, apolipoprotein B 130 mg/dl
  • High-sensitivity C-reactive protein 2.1 mg/L
  • Thyroid-stimulating hormone 2.1 mIU/L
  • Abnormal liver function test (LFT): aspartate aminotransferase 46 U/L and alanine aminotransferase 57 U/L; presumed diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatosis
  • Serum creatinine 1.3 mg/dl, GFR 57 ml/min/1.73 m2, urine albumin-to-creatinine ratio 78 mg/g (CKD stage 3)
  • Electrocardiogram (ECG): left atrial enlargement (LAE) with left ventricular hypertrophy (LVH)

Extended Investigations

  • Referred for sleep apnea evaluation because of uncontrolled hypertension and her symptoms – during sleep study, noted to have both sinus bradycardia and episodes of rapid atrial fibrillation (AF) during apnea episodes
  • Sleep study confirmed moderate to severe obstructive sleep apnea (OSA)
  • Referred to cardiology due to the AF during sleep study
  • N-terminal pro-B-type natriuretic peptide 932 (elevated)
  • ECG repeated: normal sinus rhythm with LVH and LAE
  • Echocardiogram: normal LV ejection fraction (LVEF) 55%, dilated LA (4.1 cm), grade 2 diastolic dysfunction
  • Mild pulmonary hypertension with right ventricular systolic pressure of 42 mm Hg
  • Cannot exercise: 2 minutes on Bruce protocol exercise stress test with hypertensive response and severe dyspnea
  • Coronary computed tomography angiography: mild nonobstructive plaque in left anterior descending (LAD) (40-50% soft plaque in LAD with calcium score 138)
  • Due to morbid obesity and OSA and elevated Hb A1c, the endocrinologist switched her from saxagliptin to glucagon-like peptide-1 receptor agonist (GLP-1 RA) once weekly subcutaneous injectable
  • Icosapent ethyl capsules 2 g twice daily is added for management of residual risk with high triglycerides and non–HDL-C
  • Started on continuous positive airway pressure for OSA
  • Referred for consideration of bariatric surgery

The patient now has an established and confirmed diagnosis of heart failure with preserved EF (HFpEF) in the presence of nonobstructive coronary artery disease (CAD). In addition to the above interventions, which of the following would you recommend next to reduce her cardiovascular (CV) and HF as well as renal risk?

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