Exercise and NO in HFrEF

Prior treatment

• Patients will be sedentary, defined here as no regular physical activity for at least the prior 6 months and current activity level will be documented by an activity questionnaire.
• Women currently taking hormone replacement therapy (HRT) will be excluded from the proposed studies due to the direct vascular effects of HRT Comorbidity Exclusion Criteria: Patients with significant non-cardiac comorbidities, which if present could alter the study results, will be excluded.
  • These include a diagnosis of Dementia
  • Severe chronic obstructive pulmonary disease (COPD)
  • Peripheral Vascular Disease
  • Anemia
  • Sleep-related Breathing Disorder
  • Severe Valvular Heart Disease
  • Diabetes (if on insulin therapy)
  • or End-stage Malignancy

Other illness

• Patients with HF secondary to significant uncorrected primary valvular disease (except mitral regurgitation secondary to left ventricular dysfunction) will also be excluded.

Lab values

• The investigators will also exclude morbidly obese patients (BMI \>40), patients with uncontrolled Hypertension (\>160/100), Anemia (Hgb\<9) and Severe Renal Insufficiency (individuals with creatinine clearance \<30 by the Cockcroft-Gault formula).

Age

• Due to the typical age of patients with HF, all women will be postmenopausal (either natural or surgical) defined as a cessation of menses for at least 2 years, and in women without a uterus, follicle stimulating hormone (FSH) \>40 IU/L.

Other

• Patients with atrial fibrillation or HF believed to be secondary to atrial fibrillation will be excluded.
• Patients must have no orthopedic limitations that would prohibit them from performing knee-extensor exercise.

• General Inclusion/Exclusion Criteria:
• The study group will include subjects with a history of stable cardiomyopathy (ischemic and non-ischemic, \>3 months duration, ages 45-75 yrs) despite a minimum of 6 weeks of optimal treatment.
• Optimal therapy will be according to American Heart Association (AHA) /American College of Cardiology (ACC) and Heart Failure Society of America (HFSA) HF guidelines, including treatment with angiotensin-converting enzyme (ACE) and -blocker therapy (for at least 6 weeks), or have documented reason for variation, including medication intolerance, contraindication, patient preference, or personal physician's judgment.
• Patient enrollment will be limited to those individuals with New York Heart Association (NYHA) class II and III symptoms, left ventricular ejection fraction \<35% (LVEF), with no or minimal smoking history (\<15 pk yrs), and without pacemakers.