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Circulation. 2018;138:e272–e391. DOI: 10.1161/CIR.0000000000000549 September 25, 2018 e321 CLINICAL STATEMENTS AND GUIDELINES

nosis is generally worse. Whether ICDs are effective for primary prevention of SCD is uncertain, but many deaths in patients with cardiac amyloidosis do not appear to be preventable by an ICD.S7.6.1-2

7.7 Heart Failure

7.7.1 HF With Reduced Ejection Fraction

Recommendation for HFrEF References that support the recommendation are summarized in Online Data Supplement 35.

COR LOE Recommendation

IIa B-NR 1. In patients with HFrEF who are awaiting heart transplant and who otherwise would not qualify for an ICD (eg, NYHA class IV and/ or use of inotropes) with a plan to discharge home, an ICD is reasonable.S7.7.1-1–S7.7.1-5

Synopsis

Patients with HFrEF are at an increased risk for VA and SCD. The risk is increased irrespective of HFrEF etiology.S7.7.1-6 SCD makes up a greater proportion of deaths in patients with milder HF symptoms and lesser proportion in those with moderate/severe HF symptoms.S7.7.1-7 The reported incidence of SCD varies depending on the definition used and the population studied. Although many deaths, classified as sudden, are indeed due to lethal VA, others may be due to bradyarrhythmias, pulseless electrical activity, and sudden hemodynamic deterioration.S7.7.1-7–S7.7.1-9 Medical therapy with neurohormonal agents decreases the risk of SCD by reducing both the incidence of VA and disease progression.S7.7.1-7,S7.7.1-10–S7.7.1-12 Despite GDMT for HFrEF, some patients remain at risk for SCD, and an ICD may be helpful. See Sections 7.1 and 7.2 for the indications on ICDs in patients with reduced LVEF. CRT, in appropriate patients, has also been shown to reduce the incidence of SCD.S7.7.1-13 The pathophysiology of SCD in HF is complex, resulting from interactions between both functional and structural changes that occur in patients with HFrEF that result in increased susceptibility to SCD.S7.7.1-14 Although many of the risk factors are shared among HFrEF patients, the reason that SCD strikes a particular individual is usually unknown; however, some individuals may have a genetic susceptibility.S7.7.1-15 Varying degrees of myocardial fibrosis, neurohormonal activation, and increased wall stress alter the electrophysiological properties with changes in cell coupling, ionic currents (electrical remodeling), and calcium handling that likely contribute to the development of lethal VA.S7.7.1-16 Contributing factors extrinsic to the heart include electrolyte abnormalities related to volume shifts and diuretic use, sympathetic activation, hemodynamic stress, and hypoxia. Recommendation-Specific Supportive Text

1.	Many patients with advanced HF listed for heart transplant would not otherwise qualify for ICD given the severity of illness including NYHA class IV status and/or use of inotropic infusion. Although no randomized data  on ICD use in this population exist, data from observational and large registry studies of patients awaiting heart transplant suggest improved survival in  patients with an ICD.S7.7.1-1,S7.7.1-4,S7.7.1-5 One  alternative to ICD in this population is the wearable  cardioverterdefibrillator.S7.7.1-2,S7.7.1-3 The recommendation in this section is relevant to those patients without an ICD where there is a plan to discharge the patient to home to await cardiac transplant and not, for example, to those patients who remain hospitalized with no intention to discharge home until transplant occurs. For those patients with an LVAD, the decision to place an ICD is generally independent of whether they are awaiting heart transplant but rather the indication in those patients is generally based on the need to treat VA.S7.7.1-17

7.7.2 HF With Preserved Ejection Fraction

Nearly half of the patients with HF have a preserved LVEF.S7.7.2-1 These patients tend to be older and have more comorbidities than patients with HFrEF. However, although the rate of SCD is lower in patients with HF with preserved ejection fraction (HFpEF) than in patients with HFrEF,S7.7.2-2 nearly a quarter of all deaths among patients with HFpEF are sudden.S7.7.2-3–S7.7.2-5 The challenge in preventing SCD in patients with HFpEF is identifying which patients are at a high enough risk to benefit from preventive therapies. Studies exploring noninvasive risk factors for SCD in patients with HFpEF do not identify consistent factors with the exception of ischemic heart disease.S7.7.2-2,S7.7.2-6 Consequently, there is no accepted noninvasive test to identify high-risk patients with HFpEF. Invasive risk stratification with an electrophysiological study shows promise in this population.S7.7.2-7,S7.7.2-8 This topic is currently being studied in the PRESERVE-EF (Risk Stratification in Patients With Preserved Ejection Fraction) trial (NCT02124018). Whether to include a recommendation related to an electrophysiological study in patients with HFpEF and ischemic heart disease was carefully considered by the writing committee. However, evidence was deemed insufficient to support a formal recommendation. Still, the pros and cons of an electrophysiological study can reasonably be considered in select patients with HFpEF and ischemic heart disease who are experiencing symptoms suggestive of a VA.

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