Principle 2: Good HF management is the cornerstone of symptom palliation. Maddox et al. J TABLE 15 Common Cardiovascular and Noncardiovascular Comorbidities Encountered in Patients With HFrEF Comorbidity Association With Heart Failure Outcomes Clinical Trial Evidence for Modulating Comorbidity Suggested Action Cardiovascular Coronary artery disease Strong Strong n Evaluate and revascularize in appropriate patients Atrial brillation/ utter Strong Intermediate n Treat according to the current AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation (158,159) Mitral regurgitation Strong Intermediate n Refer to a structural heart disease expert n Treat according to the current AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease (160,161) and ACC ECDP on the Management of MR (162) n Consider transcatheter intervention in carefully selected patients with symptomatic HF and secondary MR (163) Aortic stenosis Strong Strong n Refer to a structural heart disease expert n Treat according to current AHA/ACC Guidelines for the Management of Patients with Valvular Heart Disease Hypertension Uncertain Strong for prevention n Treat according to current ACC/AHA Guidelines for the Pre- vention, Detection, Evaluation, and Management of High Blood Pressure in Adults (164) Dyslipidemia Uncertain Strong for prevention n Treat according to current AHA/ACC Guidelines on the Man- agement of Blood Cholesterol (165) and the ACC ECDP on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of ASCVD Risk (166) Peripheral vascular disease Moderate None n Treat according to current AHA/ACC Guidelines on the Man- agement of Patients With Lower Extremity Peripheral Artery Cerebrovascular disease Moderate Weak n Treat according to current ASA/AHA Guidelines for the Early Management of Patients with Acute Ischemic Stroke (168) Noncardiovascular Obesity Moderate (inverse association) Weak n Further data needed Chronic lung disease Strong Weak n Smoking cessation n Optimize therapy n Consider pulmonary consultation Diabetes Strong Strong n Optimize therapy n Administer SGLT2 inhibitor n Consider consult with endocrinologist n Treat according to the ACC ECDP on Novel Therapies for CV Risk Reduction in Patients with T2D (31) and ADA Standards of Medical Care in Diabetes (169) Chronic kidney disease Strong Strong n Optimize RAAS inhibitor therapy n Use hydralazine/ISDN if an ARNI/ACEI/ARB cannot be used n Administer SGLT2 inhibitor n Consider nephrology consult Anemia Moderate Weak n Evaluate secondary causes n Consider transfusion in severe cases Iron de ciency Strong Intermediate n Consider intravenous iron replacement for symptom improvement Thyroid disorder (hypo or hyper) Strong Weak n Evaluate and initiate treatment n Consider referral to endocrinologist Sleep disordered breathing Strong Intermediate; note that in patients with symptomatic HFrEF and central sleep apnea, adaptive servo- ventilation is harmful (170) n Refer for sleep study n Treat severe obstructive sleep apnea n Consider referral to sleep medicine specialist Hyperkalemia Uncertain; may limit initiation and titration of GDMT Weak n Recommend dietary modi cations n Consider treating with patiromer (note: data regarding clin- ical outcomes are pending [NCT03888066]) or sodium zir- conium cyclosilicate ACC American College of Cardiology; ACEI angiotensin-converting enzyme inhibitors; ADA American Diabetes Association; AHA American Heart Association; ARB angiotensin receptor blocker; ARNI angiotensin receptor-neprilysin inhibitor; ASCVD atherosclerotic cardiovascular disease; CV cardiovascular; ECDP Expert Consensus Decision Pathway; GDMT guideline-directed medical therapy; HF heart failure; HFrEF heart failure with reduced ejection fraction; HRS Heart Rhythm Society; ISDN iso- sorbide dinitrate; LDL low-density lipoprotein; MR mitral regurgitation; RAAS renin-angiotensin-aldosterone system; SGLT2 sodium-glucose cotransporter-2; T2D type 2 diabetes. 