2022 AHA_ACC_HFSA Guideline for the Management of -WT_Summaries.docx

2022 AHA\_ACC\_HFSA Guideline for the Management of Heart Failure\_ A Report of the American College of Cardiology\_American Heart Association Joint Committee on Clinical Practice Guidelines.pdf Made by Wordtune \| [Open](https://app.wordtune.com/editor/read/37c85036-e8af-5c50-9f0e-c3b7de6fcfd0) P...

2022 AHA\_ACC\_HFSA Guideline for the Management of Heart Failure\_ A Report of the American College of Cardiology\_American Heart Association Joint Committee on Clinical Practice Guidelines.pdf Made by Wordtune \| [Open](https://app.wordtune.com/editor/read/37c85036-e8af-5c50-9f0e-c3b7de6fcfd0) Page 2 The authors describe the methodology and evidence review, the writing committee, the scope of the guideline, the class of recommendation and level of evidence, the abbreviations, the definition of HF, the stages of HF, the classification of HF by Left Ventricular Ejection Fraction, and the diagnostic algorithm for HF. Initial and serial evaluation, clinical assessment, risk scoring, patients at risk for HF, patients with pre-HF, management of stage B, self-care support, dietary sodium restriction, stage C, HF. Management of stage C HF includes activity, exercise prescription, and cardiac rehabilitation. Pharmacological treatment includes renin-angiotensin system inhibition with ACEi, ARB, or ARNi, beta blockers, mineralocorticoid receptor antagonists, sodium-glucose cotransporter 2 inhibitors, hydralazine, and isosorbide dinitrate. Devices and Interventional Therapies for Heart Failure with Mildly Reduced Ejection Fraction (HFrEF) and Improved Ejection Fraction (HFimpHF) are discussed. Page 3 Acute decompensated HF patients require management of comorbidities, management of HF in pregnancy, palliative and supportive care, shared decision-making, and end-of-life, as well as a referral to a specialist for advanced HF. This text recommends that patient-reported outcomes be used to guide future research, and lists evidence gaps and future research directions. TOP 10 TAKE-HOME MESSAGES Guideline-directed medical therapy for heart failure with reduced ejection fraction now includes sodium-glucose cotransporter-2 inhibitors (SGLT2i), ARNi, ACEi, ARB, MRA, and beta blockers, and weaker recommendations are made for HFmrEF and HFpEF. Patients with previous HFrEF who now have an LVEF \>40% should continue their HFrEF treatment. Patients with advanced HF who wish to prolong survival should be referred to a team specializing in HF. Page 4 PREAMBLE The American College of Cardiology and American Heart Association develop clinical practice guidelines based on systematic methods to evaluate and classify evidence. These guidelines are official policy of the ACC and AHA. Intended Use Clinical practice guidelines are intended to improve quality of care for patients with or at risk of developing cardiovascular disease. Methodology and Modernization The ACC/AHA Joint Committee on Clinical Practice Guidelines continuously reviews, updates, and modifies guideline methodology, and presents guidelines in a modular, \"knowledge chunk\" format to facilitate quick access and review. The ACC/AHA will review new data and update guidelines dynamically after publication and timely peer review of potentially practice-changing science. Selection of Writing Committee Members The Joint Committee selects experts from a spectrum of backgrounds to ensure that the guideline writing committee is representative of the broader cardiovascular community. Relationships With Industry and Other Entities The ACC and AHA have strict policies to ensure that their documents are developed without bias or improper influence. Evidence Review and Evidence Review Committees Page 5 Independent evidence review committees are commissioned when a question about a drug, device, or treatment strategy is deemed of utmost clinical importance. They conduct a formal systematic review and make recommendations to the guideline writing committee. Guideline-Directed Medical Therapy The term guideline-directed medical therapy encompasses clinical evaluation, diagnostic testing, and both pharmacological and procedural treatments. 1.1. Methodology and Evidence Review This guideline recommends treatments for heart failure based on the best available evidence. It was reviewed in several databases and included key words such as beta blockers, cardiac failure, chronic heart failure, and cardiogenic shock. During the guideline writing process, additional relevant studies were considered and added to the evidence tables. The final evidence tables are included in the Online Data Supplement. 1.2. Organization of the Writing Committee The writing committee consisted of cardiologists, heart failure specialists, internists, interventionalists, an electrophysiologist, surgeons, a pharmacist, an advanced nurse practitioner, and 2 lay/patient representatives. 1.3. Document Review and Approval This document was reviewed by 32 people and was approved by the governing bodies of the ACC, AHA, and HFSA. Page 6 The 2019 ACC/AHA primary prevention of cardiovascular disease guideline3 and the 2021 valvular heart disease guideline4 include recommendations relevant to HF. In stage C HF, there are several treatment strategies, including sodium-glucose cotransporter-2 inhibitors (SGLT2i) and angiotensin receptor-neprilysin inhibitors (ARNi), ablation of atrial fibrillation, and MV transcatheter edge-to-edge repair. This document is intended for clinicians who are involved in the care of patients with HF. It provides the most up-to-date evidence to inform the clinician during shared decision-making with the patient. 1.5. Class of Recommendation and Level of Evidence The Class of Recommendation indicates the strength of the recommendation, and the Level of Evidence indicates the quality of the scientific evidence. Page 7 HF Description HF is a clinical syndrome that results from structural or functional impairment of ventricular filling or ejection of blood. Asymptomatic stages are not covered under the above definition. 2.1. Stages of HF The ACC/AHA stages of heart failure emphasize the development and progression of disease, and advanced stages are associated with reduced survival. Therapeutic interventions aim to modify risk factors, treat risk and structural heart disease, and reduce symptoms, morbidity, and mortality. New York Heart Association (NYHA) Classification The NYHA classification is used to characterize symptoms and functional capacity of patients with symptomatic or advanced heart failure. It is a subjective assessment by a clinician and can change over time. 2.2. Classification of HF by Left Ventricular Ejection Fraction (LVEF) LVEF is important in the classification of patients with HF because of differing prognosis and response to treatments. HF with preserved EF is defined as LVEF \>40% and represents at least 50% of the population with HF. Page 9 Patients with HF and an LVEF between the HFrEF and HFpEF range are classified as HF with mildly reduced EF (HFmrEF). The trajectory of LVEF over time and the cause are important to evaluate. The diagnosis of HFmrEF and HFpEF can be challenging. The writing committee proposes to add evidence of spontaneous or provokable increased LV filling pressures to the classifications of HFm-rEF and HFpEF. Page 10 The \"2013 ACCF/AHA Guideline for the Management of Heart Failure\" has used the HFpEF-improved terminology for patients whose EF improved from a lower level to EF \>40% under the subgrouping of patients with HFpEF. However, EF can decrease after withdrawal of pharmacological treatment in many patients. Page 11 2.3. Diagnostic Algorithm for Classification of HF According to LVEF The diagnosis of HFmrEF and HFpEF is supported by increased LV filling pressures at rest, exercise, or other provocations, as well as evidence of structural heart disease. Exercise stress testing with echocardiographic evaluation of diastolic parameters can be helpful if the diagnosis remains uncertain. A clinical composite score to diagnose HFpEF was created based on obesity, atrial fibrillation, age \>60 years, treatment with 2 antihypertensive medications, echocardiographic E/e′ ratio \>9, and echocardiographic PA systolic pressure \>35 mm Hg. A score between 2 and 5 may require further evaluation of hemodynamics. Page 12 The European Society of Cardiology developed a diagnostic algorithm that involves a pretest, typical clinical demographics, laboratory tests, ECG, and echocardiography, and a points score for functional, morphological, and biomarker domains. Trends in Mortality and Hospitalization for HF HF is a growing health and economic burden for the United States, in large part because of the aging popula- tion. From 2013 to 2017, there was an increase in HF hospitalizations and number of patients hospitalized with HF. Page 13 Although the absolute number of patients with HF has partly grown as a result of the increasing number of older adults, the incidence of HF has decreased. Racial and Ethnic Disparities in Mortality and Hospitalization for HF Racial and ethnic disparities in death resulting from heart failure persist, with non-Hispanic Black patients having the highest death rate per capita. Asian/Pacific Islander patients with heart failure have a similar rate of hospitalization but a lower rate of death compared with non-Hispanic White patients. 3.2. Cause of HF In the US, approximately 115 million people have hypertension, 100 million have obesity, 92 million have prediabetes, 26 million have diabetes, and 125 million have atherosclerotic CVD, which puts them at risk for developing heart failure. There are many causes of heart failure, including ischemic heart disease and myocardial infarction. Page 14 Synopsis The history and physical examination are critical in the assessment of patients with HF. They provide information about the cause of an underlying cardiomyopathy, reasons why a previously stable patient developed acutely decompensated HF, and clinical clues that suggest advanced HF. Clinical congestion can be assessed by various methods, including jugular venous distention, orthopnea, bendopnea, a square-wave response to the Valsalva maneuver, and leg edema. It is an important adverse risk factor in patients with heart failure. Some patients with HF progress to an advanced state, which can be treated with specialized interventions such as mechanical circulatory support (MCS) or cardiac transplantation. These patients should be identified early and referred to an advanced HF center. Familial cardiomyopathy is recognized as a more accurate diagnosis in some patients previously classified as having an idiopathic dilated cardiomyopathy. A detailed family history may provide the first clue of a genetic basis, and periodic updating of the family history may lead to a diagnosis of familial cardiomyopathy. Certain conditions that cause HF require disease-specific therapies. The history and physical examination can help to identify the cause of a clinical deterioration, including concurrent illness, initiation of a medication potentially detrimental in the setting of HF, nonadherence to a medication or dietary regimen, and ongoing substance abuse. Page 16 Synopsis Laboratory evaluation includes complete blood count, urinalysis, serum electrolytes, blood urea nitrogen, serum creatinine, glucose, fasting lipid profile, liver function tests, iron studies, and thyroid-stimulating hormone level. Recommendation-Specific Supportive Text 1\. Identifying the cause of HF is important, because conditions that cause HF may require disease-specific therapies in addition to or beyond GDMT. A complete blood count, urinalysis, serum electrolytes, blood urea nitrogen, serum creatinine, glucose, fasting lipid profile, liver function tests, iron studies, and thyroid-stimulating hormone levels are performed on initial evaluation of patients with HF. Electrocardiography is performed when necessary. Page 17 Synopsis BNP and NT-proBNP are frequently used to establish the presence and severity of heart failure. Although a reduction in BNP and NT-proBNP levels has been associated with better outcomes, the evidence for treatment guidance using serial BNP or NT-proBNP measurements remains insufficient. Measurement of BNP and NT-proBNP levels in patients with suspected cardiac causes of dyspnea provides incremental diagnostic value to clinical judgment, and may be more useful for ruling out than ruling in heart failure. Higher levels are associated with a greater risk for adverse short- and long-term outcomes in patients with heart failure. The STOP-HF study, a large single-center trial, found that screening with BNP testing reduced incident asymptomatic LV dysfunction with or without newly diagnosed HF, and that accelerated uptitration of RAAS antagonists and beta blockers reduced cardiac events in patients with diabetes and elevated NT-proBNP levels but without cardiac disease at baseline. Predischarge BNP and NT-proBNP levels are strong predictors of death or hospital readmission for HF. However, targeting a certain threshold, value, or relative change in these biomarkers during hospitalization has not been shown to be consistently effective in improving outcomes. Page 18 Synopsis In patients with suspected genetic cardiomyopathy, a family history should be performed, including at least 3 generations and ideally diagrammed as a family tree pedigree. Genetic testing may be useful for risk stratification and treatment decisions, including defibrillators for primary prevention of sudden death and exercise limitation for hypertrophic cardiomyopathy. Page 19 Recommendation-Specific Supportive Text Inherited dilated, restrictive, and hypertrophic cardiomyopathies have been identified, and pathogenic variants in titin, lamin A/C, filamin-C, and desmosomal protein variants have been associated with increased risk of sudden death, HF, and ventricular arrhythmias. Synopsis Cardiac imaging is used in the initial evaluation of individuals with suspected HF and in the serial assessment of patients with HF. A comprehensive TTE is the most useful initial diagnostic test given the vast amount of diagnostic and prognostic information provided. Page 20 Recommendation-Specific Supportive Text The chest x-ray is a useful initial diagnostic test for the evaluation of patients presenting with signs and symptoms of heart failure. It can reveal alternative causes, cardiopulmonary or otherwise, of the patient\'s symptoms. TTE provides information regarding cardiac structure and function, and identifies abnormalities of myocardium, heart valves, and pericardium. Echocardiography reveals structural and functional information that predicts subsequent risk of developing HF or recurrent HF hospitalizations. Echocardiography is the preferred initial imaging modality for evaluation of patients with suspected HF, and point-of-care cardiac ultrasound is an evolving tool for assessment of cardiac function and assessment of volume status and pulmonary congestion. Serial echocardiograms are useful in various situations, including monitoring for worsening ventricular or valvular function. Additional noninvasive imaging modalities are available if TTE is unable to accurately evaluate cardiac structure and function. CMR provides accurate assessment of cardiac volumes, mass, and EF, and is recommended in known or suspected congenital heart diseases. It also provides noninvasive characterization of the myocardium that may provide insights into HF cause. CMR findings can suggest specific infiltrative and inflammatory cardiomyopathies, such as myocarditis, sarcoidosis, Fabry disease, Chagas disease, noncompaction, iron overload, and amyloidosis. The presence of delayed hyperenhancement has been associated with worse outcomes and can provide risk stratification. HF is often caused by coronary atherosclerosis, and noninvasive testing can help determine the presence of significant coronary artery disease. Invasive or computed tomography coronary angiography can detect and characterize extent of CAD. Multiple nonrandomized, observational studies have reported improved survival with revascularization in patients with viable but dysfunctional myocardium, but randomized controlled trials have not shown that viability imaging improves guidance of revascularization to a reduction of adverse cardiovascular outcomes. Page 21 Synopsis Invasive evaluation of patients with heart failure may provide important clinical information to determine the cause of heart failure and treatment options. Routine right heart catheterization does not provide sufficient information to guide treatment decisions. Recommendation-Specific Supportive Text Endomyocardial biopsy may be useful in patients with rapidly progressive clinical HF or worsening ventricular dysfunction that persists despite appropriate medical treatment, or in patients suspected of having acute cardiac rejection status after heart transplantation or having myocardial infiltrative processes. Page 22 The ESCAPE trial found that routine use of PA catheter monitoring for patients with HF did not provide benefit, but invasive hemodynamic evaluation or monitoring can be useful to guide management in carefully selected patients with acute HF who have persistent symptoms despite treatment. Synopsis HF is a chronic condition punctuated by periods of instability. A recent trial testing an implantable PA pressure sensor did not meet its primary endpoint, and previous studies do not support the use of alternative remote monitoring strategies. Recommendation-Specific Supportive Text The CHAMPION trial reported that an implanted PA pressure monitor reduced HF-related hospitalizations by 28% after 6 months, but the GUIDE-HF study found that hemodynamic-guided management of patients with NYHA class II to IV heart failure did not significantly reduce mortality and total HF events. The cost-effectiveness of noninvasive telemonitoring or remote monitoring of physiological parameters via implanted electrical devices (ICDs or CRT-Ds) to improve clinical outcomes remains uncertain. Additional data regarding clinical outcomes following CardioMEMS implantation will improve estimates of its economic value. Page 23 Synopsis Functional impairment and exercise intolerance are common in HF. The NYHA functional classification can be used to grade severity of functional limitation. NYHA functional classification is an ordinal, categorical variable (I-IV) used to document functional limitation in patients with cardiac disease, including heart failure. It has been widely used in clinical practice, clinical trials, and clinical practice guidelines. Many CPET variables have been associated with prognosis in patients with HF. Peak exercise oxygen consumption/oxygen uptake (VO 2 ) is often used to risk stratify patients and make decisions about timing of advanced HF therapies, including heart transplantation and LVAD. Exercise capacity can be measured objectively with CPET, but it requires special equipment and trained personnel and is not well tolerated by some patients. The 6-minute walk test is a widely available and well tolerated alternative way to measure exercise capacity in patients with HF. Patients who cannot walk \>490 m are associated with worse 3-year survival free of heart transplant. Dyspnea is a complex symptom that can reflect abnormalities in a number of different systems. CPET can help distinguish respiratory versus cardiac etiologies of dyspnea, and can be used to assess metabolic abnormalities and deconditioning. Page 24 Synopsis Clinicians should routinely assess a patient\'s risk for an adverse outcome to guide discussions on prognosis, goals of care, and treatment decisions. Several methods objectively assess risk, including biomarker testing, as well as various multivariable clinical risk scores, and some that include machine learning. Page 25 Recommendation-Specific Supportive Text For HF, several clinical models may be used to predict survival. These models include the Seattle Heart Failure Model, the Heart Failure Survival score, and the MAGGIC score. Synopsis Healthy lifestyle habits such as physical activity, normal weight, blood pressure, and blood glucose levels, healthy dietary patterns, and not smoking reduce the risk of developing HF. Patients at risk for HF should be screened with BNP or NT-proBNP and treated if elevated. Recommendation-Specific Supportive Text Elevated systolic and diastolic blood pressure are major risk factors for the development of symptomatic HF. Effective hypertension treatment reduces the risk of HF events. SGLT2i prevent heart failure hospitalizations in patients with type 2 diabetes and at risk for, or with established CVD or at high risk for CVD. The mechanisms for this improvement are not clear, but may be independent of glucose lowering. Healthful lifestyle habits, such as regular physical activity, avoiding obesity, maintaining normal blood pressure and blood glucose, not smoking, and healthy dietary patterns, are associated with a lower lifetime risk of HF. Page 26 A large scale unblinded single center study found that screening with BNP testing and then intervening on patients with levels of 50 pg/mL reduced the composite endpoint of asymptomatic LV dysfunction with or without newly diagnosed HF. Incident HF may be predicted from different models, including those derived from diverse populations. These models can be applied to the clinical setting of interest, with clinical trial models potentially less generalizable to registry- or population-based models. Page 27 Synopsis All recommendations for patients with stage A HF also apply to those with stage B HF. Several ACC/AHA clinical practice guidelines address appropriate management of patients with stage B HF, including lifestyle modification and pharmacological therapy that may prevent or delay the transition to symptomatic HF. Page 28 ARNi have not been well studied in stage B HF. The PARADISE-MI study will compare sacubitril/valsartan with ramipril. Recommendation-Specific Supportive Text ACE inhibitors and statins have been shown to reduce the risk of HF and cardiovascular events in patients with acute MI and ACS. These studies have also shown that ACEi and statins can prevent HF hospitalizations and progression to severe HF. Two major trials compared ARB with ACEi after MI, but losartan did not meet the noninferiority criteria for mortality compared with captopril. No clinical trials have specifically evaluated ARB in patients with asymptomatic reduced LVEF in the absence of previous MI. Current evidence supports the use of beta blockers to improve adverse cardiac remodeling and outcomes in patients with asymptomatic reduced LVEF after MI. Page 29 The Framingham studies showed that patients with asymptomatic low LVEF had a 60% increased risk of death compared to those with normal LVEF, and that 31% of patients received a prophylactic ICD compared to standard of care. Beta blockers have been shown to improve outcomes in patients with symptomatic HFrEF and in patients with reduced LVEF after MI, but few data exist regarding the use of beta blockers in asymptomatic patients with depressed LVEF without a history of MI. Thiazolidinediones have been associated with fluid retention and increased rates of HF in patients with type 2 diabetes. In patients with more mild symptoms but depressed LVEF, rosiglitazone has been associated with more fluid-related events. Nondihydropiridine calcium channel blockers may be harmful in patients with low LVEF, although they have no impact on mortality in patients with nonischemic cardiomyopathy. Synopsis HF care is ideally provided by multidisciplinary teams that include cardiologists, nurses, pharmacists, dieticians, mental health clinicians, social workers, primary care clinicians, and additional specialists. Patients with HF need time and support to gain skills and overcome barriers to effective self-care. Interventions reduced hospital admission and all-cause mortality. Specialized multidisciplinary team follow-up and multidisciplinary interventions that included a pharmacist reduced HF hospitalizations and all-cause hospitalizations. Meta-analyses of RCTs have shown that interventions focused on improving self-care in patients with HF reduce the risk of HF-related hospitalization, all-cause hospitalization, all-cause mortality, and improve QOL. Mobile health - delivered educational interventions may improve self-care in patients with HF. In propensity-adjusted models, influenza vaccination was associated with a significant reduction in all-cause mortality among participants in PARADIGM-HF, and was associated with significant reductions in all-cause mortality, cardiovascular mortality, and cardiovascular hospitalizations in another registry study. Many health and social factors are associated with poor HF self-care, including depression, frailty, social isolation, poor social support, marginal health literacy, and low literacy. Interventions that focus on improving HF self-care are effective among patients with moderate/ severe depression and reduce hospitalization and mortality risk. Page 31 Synopsis Sodium restriction is a common nonpharmacological treatment for patients with HF symptomatic with congestion, but there are no trials to support this level of restriction in patients with HF. The DASH diet is rich in antioxidants and potassium and may be associated with reduced hospitalizations for HF. Recommendation-Specific Supportive Text A registered dietitian- or nurse-coached intervention with 2 to 3 g/d sodium restriction improved NYHA functional class and leg edema in patients with HFrEF. Page 32 HF indicates heart failure. Recent pilot RCTs have shown that providing 1.5 g/d sodium meals can reduce urinary sodium and improve QOL, but not improve clinical outcomes in patients with HF. Page 33 Synopsis Exercise training in patients with heart failure is safe and has numerous benefits, including improved functional capacity, exercise duration, and health-related QOL. Recommendation-Specific Supportive Text Exercise training improves functional status, exercise performance, and QOL in patients with HFrEF and HFpEF. Exercise training has been associated with improved endothelial function, blunted catecholamine spillover, increased peripheral oxygen extraction, and improved peak oxygen consumption. In older patients hospitalized for acute decompensated HF, early, transitional, tailored, progressive rehabilitation improved physical function more than usual care. Synopsis Bumetanide, furosemide, and torsemide inhibit reabsorption of sodium and chloride at the loop of Henle, whereas thiazide and thiazide-like diuretics act in the distal convoluting tubule and potassium-sparing diuretics in the collecting duct. Loop diuretics are the preferred diuretic agents for use in most patients with HF. Page 34 Recommendation-Specific Supportive Text Diuretics increase urinary sodium excretion, decrease physical signs of fluid retention, improve symptoms, QOL, and exercise tolerance in patients with heart failure. In outpatients with HF, furosemide is the most commonly used loop diuretic, but some patients respond more favorably to other agents in this category. Patients may become unresponsive to high doses of diuretics if they consume large amounts of dietary sodium, are taking agents that can block the effects of diuretics, or have significant impairment of renal function or perfusion. Synopsis Inhibition of the renin-angiotensin system is recommended to reduce morbidity and mortality in patients with HFrEF, and an ARNi, ACEi, or ARB are recommended as first-line therapy. An ARNi may be used as de novo treatment in patients with symptomatic chronic HFrEF to simplify management. Page 35 Recommendation-Specific Supportive Text An ARNi, composed of an ARB and an inhibitor of neprilysin, reduces cardiovascular death and HF hospitalization in patients with symptomatic HFrEF tolerating an adequate dose of either ACEi or ARB. Trial data showed that ARNi reduced NT-proBNP levels in patients hospitalized for acute decompensated HF without increased rates of adverse events, and that ARNi may be initiated de novo in patients with chronic symptomatic HFrEF to simplify management. The PARADISE-MI trial will provide information on whether sacubitril-valsartan will reduce cardiovascular death, heart failure hospitalization or outpatient HF requiring treatment in patients after acute MI, compared with ACEi ramipril, and whether the safety and tolerability was comparable to ramipril. ACEi reduce morbidity and mortality in patients with HFrEF. ACEi should be started at low doses and titrated upward to doses shown to reduce the risk of cardiovascular events in clinical trials. ARB reduce mortality and hospitalizations in patients with HFrEF in large RCTs, and produce hemodynamic, neurohormonal, and clinical effects consistent with interference with the renin-angiotensin system. ARB are an alternative to ACEi for patients who are intolerant to ACEi because of cough or angioedema. Several cost-effectiveness analyses found that ACEi therapy provides high value for patients with chronic HF. A model-based analysis found ACEi therapy was high value, and previous analyses found ACEi therapy was high value despite previously higher ACEi costs. Patients with chronic stable HFrEF who tolerate ACEi and ARB should be switched to ARNi. Multiple model-based analyses showed that ARNi was cost-effective compared to ACEi therapy, and that ARNi would need to maintain effectiveness beyond the PARADIGM-HF study period to be considered high value. Neprilysin inhibitors, used in combination with ACE inhibitors, can cause angioedema. The drug omapatrilat was studied in hypertension and HF, but its development was terminated because of an unacceptable incidence of angioedema. Omapatrilat, a neprilysin inhibitor, was associated with a higher frequency of angioedema than enalapril in an RCT of patients with HFrEF. In a very large RCT of hypertensive patients, omapatrilat was associated with a 3-fold increased risk of angioedema compared with enalapril. Page 37 Synopsis Beta blockers reduce the risk of death and the combined risk of death or hospitalization in patients with HFrEF, improve LVEF, and improve clinical status. These benefits were observed in patients with or without CAD, diabetes, older patients, women, and across racial and ethnic groups. Recommendation-Specific Supportive Text Three beta blockers have been shown to reduce the risk of death in patients with HFrEF. Even when asymptomatic or mild symptoms improve with other therapies, beta-blocker therapy is important and should not be delayed until symptoms return or disease progression is documented. A model-based analysis found that beta-blocker therapy was high value among HF patients. Synopsis Aldosterone antagonists improve all-cause mortality, heart failure hospitalizations, and SCD in patients with HFrEF. Patients at risk for renal dysfunction or hyperkalemia require close monitoring. Page 38 Recommendation-Specific Supportive Text The clinical trials taken on MRA together suggest a benefit of MRA across the spectrum of HFrEF, including a wide range of etiologies and disease severities. Initiation in the ambulatory or hospital setting is appropriate, and dosing should be increased to 50 mg daily orally after a month. A model-based analysis found that MRA therapy was high value, with a cost per QALY of under \$1000.4 Spironolactone and eplerenone decrease renal potassium excretion, raising the risk of hyperkalemia, particularly when administered at serum potassium 5.0 mEq/L and continued 5.5 mEq/L. However, the incidence of clinically significant hyperkalemia events was 1% in EPHESUS and EMPHASIS-HF, without a significant difference between eplerenone and placebo. When diarrhea causes dehydration or loop diuretic therapy interruption, the MRA should be temporarily held. Potassium binders may improve outcomes by facilitating continuation of MRA. Synopsis Several trials have shown that SGLT2i prevent heart failure hospitalizations compared with placebo in patients with type 2 diabetes and either established CVD or high risk for CVD. The benefit appears independent of the glucose-lowering effects. Page 39 Recommendation-Specific Supportive Text In the DAPA-HF and EMPEROR-Reduced trials, dapagliflozin and empagliflozin reduced cardiovascular death and HF hospitalization by approximately 25% and 30%, respectively, compared with placebo. Furthermore, serious renal outcomes were less frequent and the rate of decline in eGFR was slower in patients treated with SGLT2i. SGLT2i increased risk for genital infections, but were otherwise well tolerated in the trials. Dapagliflozin had a cost per QALY between \$60 000 and \$90 000, which is consistent with intermediate value according to the benchmarks adopted for the current guideline. Synopsis Two RCTs, V-HeFT I and A-HeFT, established benefit of hydralazine-isosorbide dinitrate in self-identified African Americans with heart failure. However, uptake of this regimen has been modest because of the complexity of the medical regimen and the array of drug-related adverse effects. Page 40 Recommendation-Specific Supportive Text A large-scale trial found that hydralazine and isosorbide dinitrate reduced mortality in patients with HF treated with digoxin and diuretics, but an ACEi or beta blocker produced more favorable effects on survival. A smaller trial found that hydralazine and isosorbide dinitrate increased survival and reduced health care costs. Although there is little data with the combined use of hydralazine and isosorbide dinitrate in patients who are intolerant of ACEi or ARB, the use of hydralazine and isosorbide dinitrate in patients with HF might be considered as a therapeutic option. Synopsis Omega-3 PUFA supplementation can reduce cardiovascular events in patients with HF, and two newer gastrointestinal potassium-binding agents can lower potassium levels and enable treatment with a RAASi. Recommendation-Specific Supportive Text Supplementation with omega-3 PUFA has been evaluated as an adjunctive therapy for CVD and H F. The GISSI-HF trial showed that 1 g of omega-3 PUFA reduced death among post-MI patients and that death or admission to hospital for a cardiovascular event was also significantly reduced. Omega-3 PUFA therapy has been well tolerated, but there may be a dose-related risk of AF in patients with cardiovascular risk treated with omega-3 fatty acid. Hyperkalemia is common in HF, and two newer gastrointestinal potassium binders, patiromer and sodium zirconium cyclosilicate, have been FDA approved for treatment of hyperkalemia. In several retrospective analyses, patients with HF taking warfarin did not have a lower risk of thromboembolic events than patients not taking antithrombotic drugs. Warfarin was associated with a reduction in major cardiovascular events and death in some studies but not in others. Page 41 Synopsis Although there is strong evidence for benefit with selected medications for heart failure with reduced ejection fraction, there remain several classes of medications that have either unproven value or potential for harm. Page 42 Second-generation dihydropyridine calcium channel blockers, including amlodipine and felodipine, have less myocardial depressant activity than first-generation calcium channel blockers and may be used for treatment of hypertension in patients with elevated blood pressure despite optimization of GDMT. Many nutritional supplements and hormonal therapies have been proposed for the treatment of heart failure, but most studies are limited by small sample sizes, surrogate endpoints, or nonrandomized design. In addition, adverse effects and drug-nutraceutical interactions remain unresolved. Hormonal therapies have been proposed for the treatment of HF, but trials have shown that they have a neutral effect. Nondihydropyridine calcium channel blockers are generally not well tolerated in HF. Patients with HFrEF and asymptomatic ventricular arrhythmias post-MI who took the class IC antiarrhythmics encainide or flecainide had increased mortality. Patients with HFrEF who took the class III antiarrhythmics dronedarone or sotalol had increased mortality. Thiazolidinediones increase insulin sensitivity by activating nuclear peroxisome proliferator-activated receptor gamma (PPAR-), and DPP-4 inhibitors affect glucose regulation through multiple mechanisms, including enhancement of glucose-dependent insulin secretion, slowed gastric emptying, and reduction of postprandial glucagon and of food intake. Page 43 Several observational cohort studies have revealed increased morbidity and mortality in patients with heart failure using either nonselective or selective NSAIDs, and whether the risk of worsening HF is a class effect of DPP-4 inhibitors is unclear. Synopsis Clinical trials of ACEi, ARB, ARNi, beta blockers, and most other HFrEF medications started patients at low dose and increased the dose over time to a specified target dose, unless not well tolerated. The highest tolerated dose is recommended if the target dose cannot be achieved. Page 45 Recommendation-Specific Supportive Text The use of these specific medications for HFrEF involves initiation at low-starting doses, uptitration at specified intervals as tolerated, and achieving-maintaining the target doses shown to be effective in major clinical trials. In patients with HFrEF, beta blockers provide dose-dependent improvements in LVEF, reduction in HF hospitalizations, and reduction in all-cause mortality. ACEi and ARBs reduce cardiovascular death and HF hospitalization with similar safety and tolerability. Synopsis Heart rate is a strong predictor of cardiovascular outcomes in patients with CVD, including HF. The SHIFT trial demonstrated that reducing heart rate improves cardiovascular outcomes. Page 46 Recommendation-Specific Supportive Text SHIFT included patients with heart failure and a resting heart rate of 70 bpm. The greatest benefit was a reduction in heart failure hospitalization, but only 25% of patients were on optimal doses of beta-blocker therapy. Synopsis To date, there has been only 1 large-scale, RCT of digoxin in patients with HF.1 The trial showed no effect on mortality but modestly reduced the combined risk of death and hospitalization.2 Digoxin has also shown improvement in symptoms and exercise tolerance in mild to moderate HF. Recommendation-Specific Supportive Text Digoxin is typically initiated at a low dose and maintained at a dose of 0.125 to 0.25 mg daily in patients with HF. Higher doses are rarely required in the management of HF and are potentially detrimental. Page 47 Synopsis In patients with progression of HFrEF despite GDMT, oral soluble guanylyl cyclase stimulators may be useful. These agents increase cGMP production, which may have several beneficial effects in patients with HF. Recommendation-Specific Supportive Text In the VICTORIA trial, patients with HFrEF who were on GDMT, had elevated natriuretic peptides, and recent HF worsening were treated with vericiguat versus placebo. The relative risk reduction of 10% in the primary outcome was lower than expected, even in a higher risk population. Page 48 Synopsis RCTs have informed decisions regarding cardiac implantable devices over the past 20 years, but subgroup analyses of these trials should be interpreted with caution. ICDs were first assessed in patients who had been resuscitated from a cardiac arrest. Other patient populations that were at perceived risk of SCD also showed benefit from ICDs, including patients with previous MI, LVEF 35% with nonsustained VT, and those with no arrhythmia qualifier but with previous MIs and LVEF 30%. In the DANISH trial, patients with nonischemic cardiomyopathy and LVEF 35% received an ICD or standard care, but there was no reduction in total mortality. In 3 RCTs, 1 observational study, and 3 simulation models, ICD implantation for primary prevention of SCD was associated with increased survival and life expectancy and higher lifetime costs of medical care than without an ICD. The incremental cost-effectiveness ratios were generally \$60 000 per year of life added. Most relevant data for the guidelines of CRT in HF come from seminal trials published from 2002 to 2010. These trials included the MIRACLE (Multicenter InSync Randomized Clinical Evaluation) trial and the COMPANION (Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure) trial. Patients with NYHA class I to II HF and LVEF 40% were randomized to CRT-D on for 1 year and CRT-D off for 1 year or vice versa. CRT-D reduced the risk of death or HF hospitalization. Page 50 The economic value of CRT has been evaluated by 3 RCTs, 2 model-based analyses, and 1 observational study. It is likely that CRT provides at least intermediate value for patients with other guideline-indicated recommendations in which CRT is expected to reduce mortality. The most benefit was gained with wider QRS durations and with LBBB, and a prolonged PR predicted benefit in MADIT-CRT but not in REVERSE. The benefit of CRT has been seen in patients with LVEF between 35% and 50%, in patients with atrioventricular block, and in patients with atrial fibrillation. CRT may be used to reduce mortality, reduce hospitalizations, and improve symptoms and QOL. Identification of specific arrhythmogenic genetic variants may lead to earlier implantation of ICDs in patients with LVEF \>35% or 3 months of GDMT. The MADIT-CRT trial included patients with ischemic heart disease, LVEF \ 30%, and QRS duration \> 130 ms. Patients with nonischemic cardiomyopathy were enrolled if they had NYHA class II HF. Page 51 The RETHINQ, ECHO-CRT, and LESSER-EARTH trials, which included patients with narrow QRS and severe LV dysfunction, showed no benefit from cardiac resynchronization therapy. The NARROW-CRT trial showed a benefit in a clinical composite score for patients with an indication for an ICD and narrow QRS. 7.4.2. Other Implantable Electrical Interventions Autonomic nervous system modulation is intriguing as a treatment for HFrEF because of the heightened sympathetic response and decreased parasympathetic response in HF. However, the most recent trial did not show a reduction in mortality and HF hospitalizations. Cardiac contractility modulation (CCM) is a device-based therapy that has been associated with augmentation of LV contractile performance in patients with class III CHF. Synopsis CAD is commonly associated with HF, necessitating revascularization in selected patients with angina or HF symptoms. CABG surgery plus GDMT did not reduce all-cause mortality at 56 months, but resulted in significant reductions in all-cause mortality, cardiovascular mortality, and death from any cause or cardiovascular hospitalization at 10 years. CABG has been shown to improve outcomes in patients with left main or left main equivalent disease and HF, including a reduction in all-cause, cardiovascular, and HF hospitalizations and in all-cause and cardiovascular mortality. CABG also improves QOL compared with GDMT alone. Page 52 Mitral Regurgitation Patients with persistent severe secondary MR despite GDMT may benefit from either surgical or transcatheter repair, depending on clinical scenario. GDMT, CRT, TEER, and MV surgery may be indicated in patients with disproportionate MR relative to LV remodeling. Aortic Stenosis Patients with symptomatic aortic stenosis can benefit from transcatheter and surgical aortic valve repair, but the choice of GDMT versus surgical aortic valve replacement is based on shared decision-making, indications, and assessment of the risk-benefit profile. Recommendation-Specific Supportive Text Management of VHD in patients with HF should be performed by a multidisciplinary team with expertise in HF and VHD, in accordance with the VHD guidelines. Cardiologists are integral to the multidisciplinary team and to guiding the optimization of GDMT. Patients with HFrEF and secondary MR who are on optimal GDMT, including RAAS inhibition, beta blockers, and biventricular pacing, have a mortality benefit with TEER, and a cardiologist with expertise in the management of HF should guide optimization of GDMT. Page 54 Synopsis There are no prospective RCTs for patients with HFmrEF. Patients with LVEF 41% to 49% respond to medical therapies similarly to patients with HFrEF, and repeat evaluation of LVEF should be performed to determine the trajectory of their disease process. Recommendation-Specific Supportive Text Empagliflozin, a SGLT2i, showed a significant benefit in patients with symptomatic HF, with LVEF \>40% and elevated natriuretic peptides. It also showed a significant reduction in total HF hospitalizations, decrease in the slope of the eGFR decline, and modest improvement in QOL at 52 weeks. In a meta-analysis of 11 trials, beta blockers reduced the primary outcome of all-cause and cardiovascular mortality in patients with LVEF 40% to 49% in sinus rhythm. In a subgroup analysis, sacubitril-valsartan versus valsartan alone was associated with a favorable outcome. Page 55 Patients with heart failure and preserved ejection fraction (HFmrEF) should have repeat evaluation of LVEF to determine the trajectory of their disease process, and should undergo testing as clinically indicated to diagnose conditions warranting disease-specific therapy (eg, CAD, sarcoidosis, amyloidosis). Synopsis Although GDMT can improve symptoms, functional capacity, LVEF, and reverse remodeling in patients with HFrEF, symptoms and biomarker abnormalities may persist or reoccur. In those patients who do not improve, GDMT should be continued and optimized. Recommendation-Specific Supportive Text Phased withdrawal of HF medications in patients with previous DCM who were now asymptomatic, had improved LVEF and LVEDV, and had an NT-proBNP concentration 250 ng/L resulted in relapse of cardiomyopathy and HF in 40% of the patients within 6 months. Page 56 Synopsis HFpEF is a heterogenous disorder that is associated with significant morbidity and mortality. Currently, recommended management is that used for HF in general with use of diuretics to reduce congestion and improve symptoms, and identification and treatment of specific causes such as cardiac amyloidosis. Recommendation-Specific Supportive Text Blood pressure control is well established for the prevention of HF and other cardiovascular outcomes in patients with high cardiovascular risk. Recent clinical practice guidelines for hypertension recommend RAAS antagonists, ACEi, ARB, MRA, and possibly ARNi, for patients with HFpEF. Beta blockers may be used in patients with a history of MI, symptomatic CAD, or AF with rapid ventricular response. The SGLT2i empagliflozin showed a significant benefit in patients with chronic heart failure with preserved ejection fraction and elevated natriuretic peptides, reducing time to HF hospitalization or cardiovascular death by 21%, with no benefit on all-cause mortality. Large, randomized clinical trial data are unavailable to specifically guide therapy in patients with HFpEF and AF. However, a recent smaller open-label trial compared the use of the beta blocker, bisoprolol, to digoxin in elderly patients with AF and symptoms of HF. Spironolactone may improve diastolic function in patients with HFpEF, but the effectiveness was not statistically significant. Careful monitoring of potassium, renal function, and diuretic dosing at initiation and follow-up are key to minimizing the risk of hyperkalemia and worsening renal function. Although RAAS inhibition strategies have been successful in the treatment of HFrEF, clinical trials with RAAS inhibition have not shown much benefit in patients with HFpEF. The CHARM-Preserved trial showed that improvement in outcomes with candesartan was greater at the lower end the LVEF spectrum. In a meta-analysis of 4 trials evaluating ARB, sacubitril-valsartan did not achieve a significant reduction in cardiovascular death or total mortality in patients with heart failure and preserved ejection fraction, but it did result in a lower level of NT-proBNP and a higher incidence of hypotension and angioedema. In prespecified subgroup analyses, sacubitril-valsartan compared with valsartan was beneficial in patients with LVEF below the median, and in women with HFrEF. However, the NEAT-HFpEF trial found no beneficial effects on activity levels, QOL, exercise tolerance, or NT-proBNP levels. Phosphodiesterase-5 inhibition augments the nitric oxide system by upregulating cGMP activity. The RELAX trial13 did not show improvement in oxygen consumption or exercise tolerance. Page 58 Synopsis Cardiac amyloidosis can be caused by pathogenic variants in the transthyretin gene TTR or wild-type transthyretin. Recommendation-Specific Supportive Text ATTR-CM is diagnosed by LV thickening, fatigue, dyspnea, or edema, and by discordance between wall thickness on echocardiogram and QRS voltage on ECG. ATTR-CM is prevalent in severe aortic stenosis, HFpEF, carpal tunnel syndrome, lumbar spinal stenosis, and autonomic or sensory polyneuropathy, but a bone scintigraphy scan alone cannot distinguish ATTR-CM from AL amyloidosis. A 99mTc-PYP scan is diagnostic of ATTR-CM in the absence of a monoclonal protein in serum or urine, if there is grade 2/3 cardiac uptake or an H/CL ratio of \>1.5. Genetic sequencing of the TTR gene determines if the patient has a pathological variant (ATTRv) or wild-type disease. Page 60 Synopsis Patients with ATTR-CM and EF \ 40% may be poorly tolerated for GDMT, ARNi, ACEi, and ARB, and beta blockers may worsen HF symptoms. TTR silencers, TTR stabilizers, and TTR disruptors may be useful in patients with ATTR-CM and HFrEF, but the impact of these agents on cardiovascular morbidity and mortality has not been assessed. Tafamidis, a drug that binds to the thyroxin-binding site of TTR, has been shown to reduce all-cause mortality and cardiovascular-related hospitalization in patients with ATTR-CM. Tafamidis is best used in patients with NYHA class I to III symptoms. One model-based analysis used the results of the ATTR-ACT study1 to evaluate the cost-effectiveness of chronic tafamidis compared with no amyloidosis-specific therapy among patients with wild-type or variant transthyretin amyloidosis and NYHA class I to III HF. Intracardiac thrombosis occurs in approximately one-third of patients with cardiac amyloidosis, regardless of CHA 2 DS 2 -VASc score, and anticoagulation may reduce the risk of intra- versus warfarin has not been studied in patients with ATTR. Page 61 Synopsis Patients with chronic HF who continue to develop persistently severe symptoms despite maximum GDMT are described as having advanced HF. The INTERMACS has developed 7 profiles that further stratify patients with advanced HF. Determining that HF and not a concomitant pulmonary disorder is the basis of dyspnea is important. Patients should be stabilized and evaluated for nonadherence to medications. Recommendation-Specific Supportive Text Clinical indicators of advanced HF include end-organ dysfunction, persistently elevated natriuretic peptides, NYHA class IIIB to IV, hospitalizations \>1, low systolic BP 90, high heart rate, progressive intolerance or down-titration of GDMT, and I-Need-Help. Timely referral for review and consideration of advanced therapies is crucial to achieve optimal patient outcomes. Page 62 Synopsis Hyponatremia and diuretic-refractory congestion are common in advanced HF and are associated with poor clinical and patient-reported outcomes. Although fluid restriction is commonly prescribed for patients with hyponatremia, it improves hyponatremia modestly and has limited effect on clinical outcomes. Recommendation-Specific Supportive Text Fluid restriction improved NYHA functional classification and leg edema in patients with HFrEF but did not reduce hospitalization or mortality rates, thirst, intravenous diuretic use, serum creatinine, or serum sodium levels. Page 63 Synopsis Despite improving hemodynamic compromise, positive inotropic agents have not shown improved survival in patients with heart failure in either the hospital or the outpatient setting. Parenteral inotropes remain an option for patients who are refractory to other therapies and are suffering consequences from end-organ hypoperfusion. Page 64 Recommendation-Specific Supportive Text Inotropes may be used to reduce pulmonary hypertension and maintain end-organ perfusion in patients awaiting heart transplantation or mechanical circulatory support, but carry risks for arrhythmias and catheter-related infections. Patients may elect to have their shocking devices deactivated if they receive numerous shocks. Synopsis MCS is a therapeutic option for patients with advanced HFrEF to prolong life and improve functional capacity. It can be effective for short-term support (hours to days) and long-term management (months to years). Page 65 Recommendation-Specific Supportive Text A durable left ventricular assist device (LVAD) should be considered in selected patients with advanced NYHA class IV symptoms who are deemed dependent on IV inotropes or temporary MCS. The device offers impressive functional improvement and QOL improvement, although patients remain tethered to external electrical power supplies. Patients with NHYA class IV symptoms despite optimal medical therapy or those deemed dependent on IV inotropes should consider durable MCS. There is no clear 1-risk model to assess patient risk for complications, but factors such as elevated central venous pressure, pulmonary hypertension, and coagulopathy have been linked to poorer outcomes. Multiple studies have evaluated the cost-effectiveness of ventricular assist device implantation for advanced heart failure between 2012 and 2017, and have consistently found device implantation to be of low economic value. However, recent data suggest improved health care costs and intermediate economic value with LVAD therapy. Temporary MCS can help stabilize patients in cardiogenic shock that cannot be managed solely with IV inotropes, and allow time for decision-making about durable MCS or transplantation. Page 66 Synopsis Heart transplantation provides a mortality and morbidity benefit to selected patients with stage D HF (refractory, advanced). The median survival of adult transplant recipients is now \>12 years, and the risk of death becomes greater than survival between 3 and 4 years on an LVAD. Recommendation-Specific Supportive Text Cardiac transplantation is the established treatment for eligible patients with stage D HF refractory to GDMT, device, and surgical optimization. It improves functional status and health-related QOL and can be used to treat patients with systemic conditions complicated by HF. Synopsis Initial triage includes clinical assessment of hemodynamic profile for severity of congestion and adequacy of perfusion. Patients with ACS and conduction block or ventricular arrhythmias should be evaluated for urgent revascularization, and patients with pulmonary edema and severe hypertension require urgent treatment to reduce blood pressure. Page 67 Recommendation-Specific Supportive Text Most patients admitted with HF have clinical evidence of congestion without apparent hypoperfusion. Disproportionate elevation of right- and left-sided filling pressures, particularly with TR, hinders effective decongestion, and elevated natriuretic peptides can help identify HF in the urgent care setting. HF hospitalization is a sentinel event that signals worse prognosis and the need to restore hemodynamic compensation. The approach to management should include assessment and management of precipitating factors, comorbidities, and previous limitations to ongoing disease management related to social determinants of health. Page 68 Synopsis Hospitalization for HFrEF is a critical opportunity to continue, initiate, and further optimize GDMT. However, only 73% of eligible patients with HFrEF are prescribed ACEi-ARB-ARNi, beta blockers, and MRA therapy, respectively, and 42% of patients are not prescribed any GDMT within 30 days postindex hospitalization. Recommendation-Specific Supportive Text In OPTIMIZE-HF, discontinuation of beta blockers was associated with a higher risk for mortality, short-term mortality, and combined endpoint of short-term rehospitalization or mortality. Withholding or reducing beta-blocker therapy in patients with marked volume overload or marginal low cardiac output was associated with higher rates of postdischarge mortality and readmission. However, oral GDMT should not be withheld for mild or transient reductions in blood pressure or mild deteriorations in renal function. Patients with HF and SBP 110 mm Hg received very few target doses of beta blockers, ACEi-ARBs, or ARNi, and patients with lower SBP had the same tolerance and relative benefit over enalapril compared with patients with higher SBP. In patients with HF on oral GDMT, small to moderate worsening of renal function was not associated with AKI. Moreover, spironolactone and beta blockers might be protective in patients with HF and worsening renal function. In GWTG-HF, ACEi-ARB was associated with reduced 30-day and 1-year mortality, while MRA therapy was associated with improved HF readmission but not mortality or cardiovascular readmission among older adults hospitalized with HFrEF. In COACH, spironolactone therapy was associated with reduced 30-day mortality and HF rehospitalization. In CHAMP-HF, initiation or dose increases of beta blockers, ACEi-ARB-ARNi, and MRA occur in 10% of patients within 1 year of hospitalization, but less than 1% are on target doses of these drugs within 12 months of an index hospitalization. Page 69 Synopsis Intravenous loop diuretic therapy provides rapid and effective treatment for signs and symptoms of congestion leading to hospitalization for heart failure. Recommendation-Specific Supportive Text Diuretic therapy was the cornerstone of HF therapy for \>20 years before construction of the modern bases of evidence for HF therapies. The pivotal RCTs showing benefit in ambulatory HFrEF have been conducted on the background of diuretic therapy. Monitoring of HF treatment includes careful measurement of fluid intake and output, vital signs, standing body weight at the same time each day, and clinical signs and symptoms of congestion and hypoperfusion. Daily laboratory tests during active medication adjustment include serum electrolytes, urea nitrogen, and creatinine concentrations. After discharge, patients with recent HF hospitalization require continued use of diuretics to prevent recurrent fluid retention and hospitalization. Increases in diuretic doses are frequently required early after discharge even in patients on all other currently recommended therapies. Titration of diuretics has been described in multiple recent trials of patients hospitalized with HF, often initiated with at least 2 times the daily home diuretic dose administered intravenously. MRAs have mild diuretics properties and can help with diuresis in addition to significant cardiovascular benefits in patients with HF. Bedside ultrafiltration increased fluid loss and decreased rehospitalizations when compared with diuretics without systematic escalation, but was also associated with adverse events. Page 70 Synopsis Vasodilators can be used in acute HF to relieve symptoms of pulmonary congestion, but they have not been shown to have durable effects for either rehospitalization or mortality benefit. Page 71 Recommendation-Specific Supportive Text Acute decompensated HF patients may be suitable for intravenous nitroglycerin, but tachyphylaxis may develop within 24 hours and up to 20% of those with HF may develop resistance to even high doses. Nitroprusside is potentially of value in severely congested patients with hypertension or severe MV regurgitation complicating LV dysfunction. Synopsis When patients with HF are hospitalized, they are at increased risk for venous thromboembolic disease. This risk may extend for up to 2 years after hospitalization. Studies using available antithrombotic drugs often included patients with acute illnesses, severe respiratory diseases, or simply a broad spectrum of hospitalized medical patients. The studies showed decreased development of venous thrombosis but were associated with increased bleeding events and overall do not appear to provide additional benefit. Synopsis Cardiogenic shock is a clinical challenge with a high mortality that can be caused by acute decompensations of chronic HF, acute myocardial dysfunction without precedent HF, and survivors of cardiac arrest. The approach to cardiogenic shock should include early recognition, invasive hemodynamic assessment, and appropriate pharmacological and MCS. Page 73 Intravenous inotropic support can increase cardiac output and improve hemodynamics in patients presenting with cardiogenic shock. There are few prospective data and a paucity of randomized trials to guide the use of inotropic agents, but clinicians should consider the risks and benefits of using different devices. Team-based cardiogenic shock management provides the opportunity for various clinicians to provide their perspective and input to the patient\'s management. This approach has been associated with improved 30-day all-cause mortality and reduced in-hospital mortality. If time allows, invasively obtained hemodynamic data should be used to guide escalation to MCS, and transfer to centers capable of providing such support should be considered early in the assessment of a patient with cardiogenic shock and a trajectory of worsening end-organ malperfusion. Synopsis For patients with HF transitioning from inpatient to outpatient care, a multidisciplinary system of care that promotes improved communication between health care professionals, systematic use and monitoring of GDMT, medication reconciliation, and consistent documentation is essential to reduce avoidable readmissions. Page 74 Recommendation-Specific Supportive Text HF disease management programs may include education, self-management, medication optimization, device management, weight monitoring, exercise and dietary advice, facilitated access to care during episodes of decompensation, and social and psychological support. Although hospitalizations for worsening HF are often characterized by rapid changes in medical, surgical, and device therapy, the patient\'s journey with achieving optimal HF care continues beyond hospital discharge. Thorough discharge planning is associated with improved patient outcomes. Systems of care designed to support patients with HF as they move through the continuum of care can improve outcomes. Real-time feedback on performance measure benchmarks, quality improvement programs, and transparent health care analytics platforms may be helpful. Early outpatient follow-up is important for transitional care, but varies significantly across US hospitals. A structured contact with the patient within 7 days of hospital discharge is a desired goal, but telemedicine is being increasingly used for chronic management. Page 75 Synopsis Multimorbidity is common in patients with HF, and many of these conditions complicate the management of HF and have a significant impact on the prognosis. Although there is evolving evidence for specific treatment strategies in HF, these strategies are not addressed as specific recommendations. Page 76 Anemia Routine baseline assessment of all patients with HF includes an evaluation for anemia. Iron deficiency is independently associated with HF disease severity and mortality, and iron repletion improves exercise capacity and QOL. Page 77 The 6-minute walk test, and QOL of 459 outpatients with chronic HF who received weekly intravenous ferric carboxymaltose until iron repletion improved, and this improvement was independent of the presence of anemia. Oral iron was not adequate to treat iron deficiency anemia in patients with HF. Although small studies have shown a trend toward improvement in functional capacity and reduction in hospitalization, a high-quality randomized trial of darbepoetin alpha in 2278 patients showed no benefit and an increase in thrombotic events, including stroke. Clinical trials assessing the impact of goal blood pressure reduction on outcomes in patients with HFrEF and concomitant hypertension are lacking. However, low blood pressure has been associated with poor outcomes in patients with HFrEF. In patients with HF and sleep-disordered breathing, daytime sleepiness may not reflect the degree of underlying sleep-disordered breathing. Sleep studies can inform clinical decision-making, and continuous positive airway pressure is associated with better sleep quality and nocturnal oxygenation, but has not been shown to affect survival. The American Diabetes Association recommends the use of SGLT2i as first-line agent for the treatment of hyperglycemia in patients with diabetes and HF or at high risk of HF. SGLT2i are associated with a reduction in major adverse cardiovascular events, including hospitalization for HF and cardiovascular death. Page 78 Synopsis The interplay between AF and HF is complex, but data from randomized trials support the use of anticoagulation among those with HF and AF, but not in patients with HF without AF. Patients with HF and difficult to control rates may benefit from atrioventricular nodal ablation and implantation of a permanent pacemaker. Recommendation-Specific Supportive Text Long-term warfarin therapy for the prevention of stroke is well established in patients with atrial fibrillation. The CHA 2 DS 2 -VASc score is recommended to assess patient risk for adverse outcomes before initiating anticoagulation therapy. Several DOAC are available, including factor Xa inhibitors apixaban, rivaroxaban, edoxaban, and the direct thrombin inhibitor dabigatran. These drugs do not need routine anticoagulation monitoring or dose adjustment, but may simplify patient management. In patients with paroxysmal or persistent atrial flutter and HF, DOAC reduced the rate of stroke, major bleeding, and intracranial bleeding, and had no treatment heterogeneity by HF status. Atrioventricular nodal ablation with implantation of a CRT device can be considered as a treatment option. Ablate and pace is an old strategy for difficult to rate control AF. However, recent trials have shown that cardiac resynchronization therapy (CRT) produces more benefit than RV pacing, especially in patients with reduced LVEFs. HF is a hypercoagulable state and serves as an independent risk factor for stroke, systemic embolism, and mortality in the setting of AF. Anticoagulation should be used in most patients with HF and concomitant AF, barring contraindications. Page 79 Synopsis There are important differences in HF incidence, risk factors, clinical care needs, and outcomes between specific patient populations. It is essential that HF clinicians be aware of these differences, and that they remove implicit biases through implicit bias training, recruiting a diverse workforce, and promoting broad access to HF care. Recommendation-Specific Supportive Text Black patients are more likely to have hypertension and diabetes than White patients, and low income, social isolation, and lack of caregiver support are more likely to have poor HF outcomes. Case management and social work services are essential to the comprehensive multidisciplinary HF team approach. Health care system factors may be a source of disparate HF care delivery and outcomes. Women are less likely to receive discharge instructions for HF, less likely to be referred to specialty care, and less likely to receive a heart transplantation compared with men. Page 81 Synopsis Cancer therapy - related cardiomyopathy is a heterogeneous disease with a wide range of presentations and drug-dependent pathophysiologic mechanisms that are often poorly understood. A unified framework for the management of cancer therapy - related cardiomyopathy is necessary to mitigate the cardiovascular risks of established novel therapies. HF secondary to cancer therapy - related cardiomyopathy is associated with significantly worse outcomes. Patients who develop HF while receiving potentially cardiotoxic therapies should have these therapies discontinued while a diagnostic workup is undertaken to ascertain the cause of HF and initiate GDMT. In patients with cancer therapy - related cardiomyopathy, beta blockers and ACEi are effective in improving LV dysfunction. Echocardiography is recommended as the first-line modality for LVEF assessment, and is a strong predictor of major adverse cardiovascular events in patients receiving potentially cardiotoxic therapies. Page 83 Patients with cancer and preexisting cardiovascular risk factors are at significantly higher risk of cancer therapy - related cardiomyopathy. Serial monitoring of LVEF is recommended. LVEF monitoring has been implemented in patients receiving anthracyclines, trastuzumab, or both, but the clinical significance of an asymptomatic decrease in LVEF is less clear. The preemptive use of ACEi-ARB, spironolactone, or selected beta blockers may be effective in reducing the risk of cancer therapy - related cardiomyopathy. There have been a number of small clinic trials investigating the use of enalapril to prevent cardiomyopathy in patients receiving high-dose chemotherapy. However, the studies have shown conflicting findings, and none have assessed whether preemptive use of HF therapies improves clinical outcomes. Cardiovascular biomarkers, notably troponin, have been studied for cardiovascular risk stratification in patients undergoing potentially cardiotoxic therapies. Some studies have found no advantage in measuring troponin or natriuretic peptides pretherapy, but serial biomarkers may be more useful in risk stratification. Page 84 Synopsis HF may complicate pregnancy either secondary to an existing prepregnancy cardiomyopathy, or as a result of peripartum cardiomyopathy. Treatment includes GDMT adjusted for pregnancy or breast-feeding status and anticoagulation consideration, and early institution of mechanical support for shock. Recommendation-Specific Supportive Text Pregnancy is generally well-tolerated in women with cardiomyopathy and NYHA class I prepregnancy, but clinical deterioration can occur. Pregnancy counseling and shared decision-making are essential, and the ROPAC study validated the modified WHO risk classification. Previous peripartum cardiomyopathy is associated with further decreases in LV function, maternal death, and adverse fetal outcomes in subsequent pregnancies. Pregnancy is a hypercoagulable state, and women with severe acute HF caused by peripartum cardiomyopathy and LVEF 35% should receive at least prophylactic-dosed anticoagulation. However, the efficacy and safety of bromocriptine for acute peripartum cardiomyopathy treatment currently remains uncertain. Page 86 The FDA adopted the Pregnancy and Lactation Labeling Rule in 2015, which assigned a descriptive risk summary to aid medication counseling for pregnant and breastfeeding women. ACE inhibitors and ARBs are strictly contraindicated, and ARNi, ivabradine, spironolactone, and eplerenone are considered acceptable during pregnancy. Synopsis The ACC/AHA Task Force on Performance Measures distinguishes between quality measures and performance measures. Performance measures are selected from the most important ACC/AHA clinical practice guideline recommendations with the strongest evidence. Recommendation-Specific Supportive Text The current ACC/AHA performance and quality measures are displayed in Table 31.8. Observational data suggest that hospitals that receive feedback on their HF care improve over time, but a randomized trial did not clearly show improvement in care. Page 87 Synopsis Palliative care is patient-centered care that optimizes health-related QOL by anticipating, preventing, and treating suffering. It includes high-quality communication, estimation of prognosis, anticipatory guidance, addressing uncertainty, shared decision-making about medically reasonable treatment options, advance care planning, attention to physical, emotional, spiritual, and psychological distress, relief of suffering, and inclusion of family caregivers. Page 88 Recommendation-Specific Supportive Text All health care professionals should incorporate palliative and supportive care considerations into the care of patients with HF. As illness progresses, major decisions are increasingly made regarding the initiation, continued use, and discontinuation of potentially life-sustaining therapies. Patients have a right to decline or withdraw care at any time. Although many clinicians caring for patients with heart failure are able to manage many palliative care needs, formal palliative care consultation may be particularly helpful for patients with refractory symptoms, major medical decisions, and multimorbidity, frailty, or cognitive impairment. Page 89 Advance care planning involves discussing patients\' values, documenting plans for medical treatments, designating a surrogate decision maker, and revisiting this process over time. Few patients with HF have formally defined their care goals and designated a surrogate decision maker, and hospice use has been low among patients dying with HF. Page 92 Synopsis Health status can be assessed using standardized questionnaires, such as the Kansas City Cardiomyopathy Questionnaire, and is an independent predictor of hospitalization and mortality. Increasing the patient\'s voice in clinical assessment and decision-making is important in its own right. Recommendation-Specific Supportive Text Standardized patient-reported health status questionnaires provide reliable measures of health status correlated to other functional status measures and independently associated with clinical outcomes. Although some clinics have successfully implemented patient-reported health status in clinical practice, there are minimal data regarding the impact of such efforts. Page 93 American College of Cardiology Nancy Brown, Mariell Jessup, Radhika Rajgopal Singh, Paul St. Laurent, Jody Hundley are the chief executives and science and medicine advisors for the Office of Science and Medicine.