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.......... 5.4.6 Recently reported advances from trials in heart failure with reduced ejection fraction Soluble guanylate cyclase stimulator The VICTORIA study assessed the efficacy and safety of the oral soluble guanylate cyclase stimulator, vericiguat, in patients with a reduced EF and recently decompensated CHF. The incidence of the primary endpoint of death from CV causes or hospitalization for HF was lower among those who received vericiguat than among those who received placebo.141 There was no reduction in either all-cause or CV mortality. Thus, vericiguat may be considered, in addition to standard therapy for HFrEF, to reduce the risk of CV mortality and hospitalizations for HF.

Cardiac myosin activator The GALACTIC-HF study assessed the efficacy and safety of the cardiac myosin activator, omecamtiv mecarbil, in HFrEF patients, enrolling patients in both the inpatient and outpatient settings. The primary endpoint of a first HF event or CV death was reduced by 8%. There was no significant reduction in CV mortality. Currently, this drug is not licensed for use in HF. However, in the future it may be able to be considered, in addition to standard therapy for HFrEF to reduce the risk of CV mortality and hospitalization for HF.159

5.5 Strategic phenotypic overview of the

management of heart failure with reduced ejection fraction In addition to the general therapies considered in section 5, other therapies are appropriate to consider in selected patients. These are covered in detail in later sections. Some of the main ones (i.e. those with Class I and IIa Mortality/Hospitalization indications) are depicted in Figure 3. The effect of some interventions on symptoms/QOL are outlined in Supplementary Table 9.

6 Cardiac rhythm management

for heart failure with reduced ejection fraction

This section provides recommendations on the use of implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy (CRT). Other implantable devices will be discussed at the end of this section.

6.1 Implantable cardioverter-

defibrillator A high proportion of deaths among patients with HF, especially in those with milder symptoms, occur suddenly and unexpectedly. Many of these may be due to electrical disturbances, including ventricular arrhythmias, bradycardia, and asystole, although some are due to other acute vascular events. Treatments that improve or delay the progression of CV disease have been shown to reduce the annual rate of sudden death,105,160 but they do not treat arrhythmic events when they occur. ICDs are effective at correcting potentially lethal ventricular arrhythmias, and in the case of transvenous systems, also prevent bradycardia. Some antiarrhythmic drugs might reduce the rate of tachyarrhythmias and sudden death, but they do not reduce overall mortality,161 and may increase it.

Recommendations for an implantable cardioverterdefibrillator in patients with heart failure

Recommendations Classa Levelb

Secondary prevention An ICD is recommended to reduce the risk of sudden death and all-cause mortality in patients who have recovered from a ventricular arrhythmia causing haemodynamic instability, and who are expected to survive for >1 year with good functional status, in the absence of reversible causes or unless the ventricular arrhythmia has occurred <48 h after a MI.162164 I A Primary prevention An ICD is recommended to reduce the risk of sudden death and all-cause mortality in patients with symptomatic HF (NYHA class IIIII) of an ischaemic aetiology (unless they have had a MI in the prior 40 days—see below), and an LVEF <_35% despite >_3 months of OMT, provided they are expected to survive substantially longer than 1 year with good functional status.161,165 I A An ICD should be considered to reduce the risk of sudden death and all-cause mortality in patients with symptomatic HF (NYHA class IIIII) of a non-ischaemic aetiology, and an LVEF <_35% despite >_3 months of OMT, provided they are expected to survive substantially longer than 1 year with good functional status.161,166,167 IIa A Patients should be carefully evaluated by an experienced cardiologist before generator replacement, because management goals, the patient’s needs and clinical status may have changed.168172 IIa B A wearable ICD may be considered for patients with HF who are at risk of sudden cardiac death for a limited period or as a bridge to an implanted device.173176 IIb B ICD implantation is not recommended within 40 days of a MI as implantation at this time does not improve prognosis.177,178 III A ICD therapy is not recommended in patients in NYHA class IV with severe symptoms refractory to pharmacological therapy unless they are candidates for CRT, a VAD, or cardiac transplantation.179183 III C

CRT = cardiac resynchronization therapy; HF = heart failure; ICD = implantable cardioverter-defibrillator; LVEF = left ventricular ejection fraction; MI = myocardial infarction; NYHA = New York Heart Association; OMT = optimal medical therapy; VAD = ventricular assist device. aClass of recommendation. bLevel of evidence. ESC 2021

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