The following are key points to remember from this JACC State-of-the-Art Review on exercise intolerance in patients with heart failure (HF):

1. Exercise intolerance is a cardinal symptom of HF and is associated with a poor quality of life and increased mortality.
2. While impaired cardiac reserve is considered to be central in HF, reduced exercise and functional capacity are also the result of key patient characteristics and multisystem dysfunction, including aging, impaired pulmonary reserve, as well as peripheral and respiratory skeletal muscle dysfunction.
3. Most patients with HF display several comorbidities (i.e., diabetes mellitus, obesity, chronic kidney disease, obstructive and/or restrictive lung disease, psychiatric disorders) that may promote, confound, and influence the presentation of the syndrome and the assessment of exercise and functional capacity, and are independently associated with an increased risk of hospitalization, higher health care costs, and poorer exercise and functional capacity.
4. Cardiopulmonary exercise testing (CPX) is the accepted gold-standard assessment for exercise capacity and cardiorespiratory function in HF and allows for a refined, noninvasive assessment of the mechanisms limiting exercise capacity, of which there are several in the patient with HF.
5. Of note, when paired with cardiac imaging or with invasive hemodynamics to also simultaneously monitor stroke volume and pulmonary artery wedge pressure, the ability of the CPX to detect cardiac abnormalities is significantly improved and allows measurement of peripheral tissue oxygen extraction.
6. At this time, pharmacological and nonpharmacological treatments for HF with proven beneficial effects on clinical outcomes have variable effects on exercise and functional capacity.
7. Exercise training results in improved exercise and functional capacity in both HF with reduced ejection fraction (HFrEF) and HF with preserved EF (HFpEF), and appears to reduce HF-related hospitalizations.
8. Current guidelines for individuals with cardiovascular diseases wishing to participate in outpatient exercise programs recommend moderate-intensity (40-60% heart rate reserve), supervised, aerobic exercise for 20-60 minutes on 3 or more days/week.
9. Identifying the mechanisms responsible for reduced functional and exercise capacity is an important clinical priority in patients with HF with therapeutic and prognostic implications.
10. Improved understanding of the pathophysiology of exercise intolerance may allow for the development of tailored/individualized therapeutic strategies to improve exercise and functional capacity and thereby improve quality of life.

Keywords: Comorbidity, Diabetes Mellitus, Diagnostic Imaging, Exercise, Exercise Test, Exercise Therapy, Geriatrics, Health Care Costs, Heart Failure, Hemodynamics, Lung Diseases, Mental Disorders, Muscle, Skeletal, Obesity, Primary Prevention, Quality of Life, Renal Insufficiency, Chronic, Stroke Volume

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