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Circulation. 2022;145:e895–e1032. DOI: 10.1161/CIR.0000000000001063 May 3, 2022 e921 CLINICAL STATEMENTS AND GUIDELINES

or diastolic) with or without newly diagnosed HF.22 Similarly, in another small, single-center RCT, 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.23 5.	 Incident HF may be predicted from different models, including those derived from diverse populations (Table 9). The PCP-HF (Pooled Cohort equations to Prevent HF) model provides race- and sexspecific 10-year risk equations from 7 communitybased cohorts with at least 12 years of follow-up.29 Predictors of HF included in the race- and sex-specific models were age, blood pressure (treated or untreated), fasting glucose (treated or untreated), body mass index, cholesterol, smoking status, and QRS duration. Models can be applied to the clinical setting of interest, with clinical trial models potentially less generalizable to registry- or population-based models. In addition, predictive models provide the average estimate of risk derived from a population, and individual risk may vary.36 The integration of risk scores into clinical practice have shown improved outcomes. As data generation increases from electronic health records and digital sources, advanced methods with machine learning are expected to proliferate the development of risk prediction models. Machine learning models are often not externally validated, and their performance may vary based on the population and clinical setting.37 Patient populations change over time, and models may need to be recalibrated periodically.

6 STAGE B (PATIENTS WITH PRE-HF)

6.1 Management of Stage B: Preventing the

Syndrome of Clinical HF in Patients With Pre-HF Recommendations for Management of Stage B: Preventing the Syndrome of Clinical HF in Patients With Pre-HF Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1 A 1.	 In patients with LVEF ≤40%, ACEi should be used to prevent symptomatic HF and reduce mortality.1–4 1 A 2.	 In patients with a recent or remote history of MI or ACS, statins should be used to prevent symptomatic HF and adverse cardiovascular events.5–9

1 B-R 3.	 In patients with a recent MI and LVEF ≤40% who are intolerant to ACEi, ARB should be used to prevent symptomatic HF and reduce mortality.10

1 B-R 4.	 In patients with a recent or remote history of MI or acute coronary syndrome (ACS) and LVEF ≤40%, evidence-based beta blockers should be used to reduce mortality.11–13

1 B-R 5.	 In patients who are at least 40 days post-MI with LVEF ≤30% and NYHA class I symptoms while receiving GDMT and have reasonable expectation of meaningful survival for >1 year, an ICD is recommended for primary prevention of sudden cardiac death (SCD) to reduce total mortality.14

1 C-LD 6.	 In patients with LVEF ≤40%, beta blockers should be used to prevent symptomatic HF.12,13

3: Harm B-R 7.	 In patients with LVEF <50%, thiazolidinediones should not be used because they increase the risk of HF, including hospitalizations.15

3: Harm C-LD 8.	 In patients with LVEF <50%, nondihydropyridine calcium channel blockers with negative inotropic effects may be harmful.16,17

Synopsis In general, all recommendations for patients with stage A HF also apply to those with stage B HF. Stage B (pre- HF) represents a phase of clinically asymptomatic structural and functional cardiac abnormalities that increases the risk for symptomatic HF.18–21 Identifying individuals with stage B HF provides an opportunity to initiate lifestyle modification and pharmacological therapy that may prevent or delay the transition to symptomatic HF (stage C/D). Several ACC/AHA clinical practice guidelines address appropriate management of patients with stage B HF (Table 10). Although multiple studies highlight the increased HF risk associated with asymptomatic LV systolic19,20,22–26 and diastolic dysfunction identified by noninvasive imaging,19,26–30 beneficial pharmacotherapy for asymptomatic LV systolic dysfunction, such as inhibitors of the renin-angiotensin system and beta blockers, have been predominantly observed in individuals with depressed LVEF (LVEF <35%–40%).1–4,11–13 Studies of specific treatments to alter the onset of HF in the setting of asymptomatic cardiac dysfunction with preserved LVEF (eg, abnormalities of myocardial deformation or diastolic dysfunction) have been limited. Several comorbid conditions, including diabetes, obesity, and hypertension, have been associated with asymptomatic LV dysfunction27,28,30,31 and with progression of asymptomatic LV dysfunction to symptomatic HF.27 Accordingly, these comorbidities are controlled according to current clinical

Table 9.  Selected Multivariable Risk Scores to Predict Development of Incident HF Risk Score Reference Year Published Framingham Heart Failure Risk Score 24 1999 Health ABC Heart Failure Score 25 2008 ARIC Risk Score 26 2012 PCP-HF 29 2019 ARIC indicates Atherosclerosis Risk in Communities; HF, heart failure; and PCP-HF, Pooled Cohort Equations to Prevent HF. Recommendations for Management of Stage B: Preventing the Syndrome of Clinical HF in Patients With Pre-HF (Continued)

COR LOE Recommendations

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