CPD: Preventing sudden death in patient with heart failure

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Preventing sudden death in patient with heart failure

Sudden cardiac death is the main cause of mortality in 30% to 50% of patients with heart failure with reduced ejection fraction (HFrEF).1 Healthcare professionals are often unaware of the risk of sudden cardiac death in patients with HFrEF and assume that those with mild-to-moderate symptoms do not require intensive therapy. As a result, interventions that can prevent sudden death in HFrEF are underutilised.1

The prevalence of HF has been steadily increasing over the last few years and currently affect between 1% and 2% of adults globally.1 More than 50% of HF patients are women, however, women have higher survival rates, despite receiving suboptimal treatment.2

HF is defined as a clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion.3

HF symptoms include dyspnoea, fatigue, and fluid retention that may be accompanied by signs (elevated jugular venous pressure, pulmonary crackles, and peripheral oedema.2

The symptoms of HF are due to myocardial dysfunction: either systolic, diastolic or both. Other factors that play a role include pathology of the valves, pericardium and endocardium, and abnormalities of heart rhythm and conduction.2

HF is associated with a five-year mortality rate of between 20% and 67%. The two most common types of HF are:2

» HFrEF: HF with left ventricular ejection fraction =40%. About 50% of patients have HFrEF, and will therefore be the focus of this article2,3

» HF with preserved ejection fraction: HF with LVEF 50%. About 50% of patients have HFpEF/HF with mildly reduced ejection fracture.2,3

The 2021 European Society of Cardiology for the diagnosis and treatment of acute and chronic HF guideline, recommends the following to diagnose HF:2

» Electrocardiogram (ECG). A normal ECG makes the diagnosis of HF unlikely. The ECG may reveal abnormalities such as atrial fibrillation, Q waves, left ventricular hypertrophy (LVH), and a widened QRS complex

» Measurement of natriuretic peptides (NPs) are recommended, if available. A plasma concentration of B-type NP (BNP) <35pg/ mL, N-terminal pro-B-type NP <125pg/mL, or mid-regional pro-atrial natriuretic peptide <40pmol/L make a diagnosis of HF unlikely

» Basic investigations such as serum urea and electrolytes, creatinine, full blood count, liver and thyroid function tests are recommended to differentiate HF from other conditions, to provide prognostic information, and to guide potential therapy

» Echocardiography is recommended as the key investigation for the assessment of cardiac function. As well as the determination of the LVEF, echocardiography also provides information on other parameters such as chamber size, eccentric or concentric left ventricular hypertrophy, regional wall motion abnormalities (that may suggest underlying coronary artery syndrome, Takotsubo syndrome or myocarditis), right ventricular function, pulmonary hypertension, valvular function, and markers of diastolic function.

» A chest X-ray is recommended to investigate other potential causes of breathlessness e.g., pulmonary disease). It may also provide supportive evidence of HF (e.g., pulmonary congestion or cardiomegaly).

Optimising treatment to prevent sudden cardiac death

There are three major goals of treatment for patients with HFrEF: 2

1. Reduction in mortality

2. Prevention of recurrent hospitalisations due to worsening HF

3. Improvement in clinical status, functional capacity, and quality of life.

Recommended first-line treatment2

Modulation of the renin-angiotensinaldosterone and sympathetic nervous systems with angiotensin-converting enzyme inhibitors (ACE-I) or an angiotensin receptorneprilysin inhibitor (ARNI), beta-blockers, and mineralocorticoid receptor antagonists (MRA) have been shown to improve survival, reduce the risk of HF hospitalisations, and reduce symptoms in patients with HFrEF. These drugs serve as the foundations of pharmacotherapy for patients with HFrEF.

They should be up titrated to the doses used in the clinical trials (or to maximally tolerated doses if that is not possible). This guideline still recommends the use of ARNI as a replacement for ACE-I in suitable patients who remain symptomatic on ACE-I, beta-blocker, and MRA therapies.

However, an ARNI may be considered as a first-line therapy instead of an ACE-I. It should be noted that in South Africa, ARNI’s are indicated as second-line treatment for HFrEF.

Angiotensin-receptor blockers (ARBs) still have a role in those who are intolerant to ACE-I or ARNI. The sodium-glucose cotransporter 2 (SGLT2) inhibitors dapagliflozin and empagliflozin added to therapy with ACE-I/ ARNI/beta-blocker/ MRA reduced the risk of CV death and worsening HF in patients with HFrEF.

Unless contraindicated or not tolerated, dapagliflozin or empagliflozin are recommended for all patients with HFrEF already treated with an ACE-I/ARNI, a betablocker, and an MRA, regardless of whether they have diabetes or not.

Recommended second-line treatment1

» Diuretics are recommended in patients with HFrEF with signs and/or symptoms of congestion to alleviate HF symptoms, improve exercise capacity and reduce HF hospitalisations

» An ARB is recommended to reduce the risk of HF hospitalisation and CV death in symptomatic patients unable to tolerate an ACE-I or ARNI (patients should also receive a beta-blocker and an MRA)

» Ivabradine should be considered in symptomatic patients with LVEF ≤35%, in SR and a resting heart rate ≥70 beats per minute despite treatment with an evidencebased dose of beta-blocker (or maximum tolerated dose below that), ACE-I/(or ARNI), and an MRA, to reduce the risk of HF hospitalisation and CV death

» A soluble guanylate cyclase receptor stimulator may be considered in patients in NYHA class II-IV who have had worsening HF despite treatment with an ACE-I (or ARNI), a beta-blocker and an MRA to reduce the risk of CV mortality or HF hospitalisation

» Hydralazine and isosorbide dinitrate should be considered in self-identified black patients with LVEF ≤35% or with an LVEF <45% combined with a dilated left ventricle in NYHA class III-IV despite treatment with an ACE-I (or ARNI), a beta-blocker and an MRA to reduce the risk of HF hospitalisation and death. Hydralazine and isosorbide dinitrate may be considered in patients with symptomatic HFrEF who cannot tolerate any of an ACE-I, an ARB, or ARNI (or they are contraindicated) to reduce the risk of death

» Digoxin may be considered in patients with symptomatic HFrEF in sinus rhythm despite treatment with an ACE-I (or ARNI), a betablocker and an MRA, to reduce the risk of hospitalisation.

Cardiac rhythm management

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.2

Treatments that improve or delay the progression of CV disease have been shown to reduce the annual rate of sudden death, but they do not treat arrhythmic events when they occur.2

An implantable cardioverter-defibrillator (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 more than a year with good functional status, in the absence of reversible causes or unless the ventricular arrhythmia has occurred <48 hours after a myocardial infarction (MI).2

The ESC guideline recommends:2

» An ICD is recommended to reduce the risk of sudden death and all-cause mortality in patients with symptomatic HF (NYHA class II-III) of an ischaemic aetiology (unless they have had a MI in the prior 40 days), and an LVEF ≤35% despite ≥3 months of optimal medical therapy, provided they are expected to survive substantially longer than one year with good functional status

» An ICD should be considered to reduce the risk of sudden death and all-cause mortality in patients with symptomatic HF (NYHA class II-III) of a non-ischaemic aetiology, and an LVEF ≤35% despite ≥3 months of optimal medical therapy, provided they are expected to survive substantially longer than a year with good functional status

» 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

» 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

» ICD implantation is not recommended within 40 days of a MI as implantation at this time does not improve prognosis

» ICD therapy is not recommended in patients in NYHA class IV with severe symptoms refractory to pharmacological therapy unless they are candidates for cardiac resynchronisation therapy (CRT), a ventricular assist device, or cardiac transplantation.

Appropriate patient selection for CRT

In appropriately selected patients, CRT reduces morbidity and mortality. Furthermore, CRT improves cardiac function, and enhances QOL. To reduce morbidity and mortality, the ESC guideline recommends:2

» CRT in symptomatic patients with a QRS duration ≥150ms and left bundle branch block (LBBB) QRS morphology and with LVEF ≤35% despite OMT in order to improve symptoms and reduce morbidity and mortality

» CRT rather than RV pacing is recommended for patients with HFrEF regardless of NYHA class or QRS width who have an indication for ventricular pacing for high degree atrioventricular block in order to reduce morbidity. This includes patients with atrial fibrillation

» CRT should be considered for symptomatic patients with HF in SR with a QRS duration ≥150ms and non-LBBB QRS morphology and with LVEF ≤35% despite optimal medical therapy in order to improve symptoms and reduce morbidity and mortality

» CRT should be considered for symptomatic patients with HF in SR with a QRS duration of 130-149ms and LBBB QRS morphology and with LVEF ≤35% despite OMT in order to improve symptoms and reduce morbidity and mortality

» Patients with an LVEF ≤35% who have received a conventional pacemaker or an ICD and subsequently develop worsening HF despite OMT and who have a significant proportion of RV pacing should be considered for ‘upgrade’ to CRT.

References

1. Packer M. What causes sudden death in patients with chronic heart failure and a reduced ejection fraction? European Heart Journal, 2020.

2. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal, 2021.

3. Kozkurt B, Coats AJS, Tsutsui H, et al. Universal definition, and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association. European Journal of Heart Failure, 2021. SF

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