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Heart failure

Treatment and management

Management of heart failure1

The objectives of the treatment of patients with heart failure are mainly focused on the improvement of symptoms and the quality and duration of life. In addition, another goal is the prevention of hospitalization associated with heart failure, as the need for frequent hospital admission indicates the progression of disease and an increased risk of death1.

Management of HFrEF1,2

Treatment algorithm from 2021 ESC guideline

The management of patients with HFrEF is often multifactorial and can include pharmacological therapies, the implantation of medical devices and cardiac transplantation1. Figure 1 shows management options with Class I and IIa recommendations. Green for Class of recommendation I; yellow for Class of recommendation IIa (Figure 1)2.

Treatment_and_management_Fig1

Figure 1. 2021 ESC guideline. Strategic phenotypic overview of the management of HFrEF2

Treatment algorithm from 2021 ACC guideline3

In a patient with new-onset stage C HFrEF, the writing committee recommends that either an ARNI/ACEI/ARB or β-blocker should be started (Figure 2). SGLT2 inhibitors are added in as part of the therapy for patients with chronic HFrEF who are already receiving β-blockers, an ARNI/ACEI/ARB, and aldosterone antagonists, if not contraindicated.3

Treatment_and_management_Fig2

Figure 2. 2021 ACC guideline. Treatment algorithm for guideline-directed medical therapy including novel therapies3

Goals of pharmacotherapy for patients with HFrEF2

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

(i) reduction in mortality,

(ii) prevention of recurrent hospitalizations due to worsening HF, and

(iii) improvement in clinical status, functional capacity, and QOL.

Figure 2 depicts the algorithm for the treatment strategy, including drugs and devices in patients with HFrEF, for Class I indications for the reduction of mortality (either all-cause or CV).2 (Figure 3)

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Figure 3. 2021 ESC guideline. Therapeutic algorithm of Class I Therapy Indications for a patient with heart failure with reduced ejection fraction2

General principles of pharmacotherapy for HFrEF2

Modulation of the renin-angiotensin-aldosterone (RAAS) and sympathetic nervous systems with angiotensin-converting enzyme inhibitors (ACE-I) or an angiotensin receptor-neprilysin inhibitor (ARNI), β-blockers, and mineralocorticoid receptor antagonists (MRA) has been shown to improve survival, reduce the risk of HF hospitalizations, and reduce symptoms in patients with HFrEF. The sodium-glucose co-transporter 2 (SGLT2) inhibitors dapagliflozin and empagliflozin added to therapy with ACE-I/ARNI/β-blocker/MRA reduced the risk of CV death and worsening HF in patients with HFrEF2.

Angiotensin-converting enzyme inhibitors (ACE-Is)2

ACE-Is were the first class of drugs shown to reduce mortality and morbidity in patients with HFrEF. They have also been shown to improve symptoms. They are recommended in all patients unless contraindicated or not tolerated. They should be up titrated to the maximum tolerated recommended doses.

β-blockers2

β-blockers have been shown to reduce mortality and morbidity in patients with HFrEF, in addition to treatment with an ACE-I and diuretic. They also improve symptoms. There is consensus that ACE-I and beta-blockers can be commenced together as soon as the diagnosis of symptomatic HFrEF is established.2

Mineralocorticoid receptor antagonists (MRAs)2

MRAs (spironolactone or eplerenone) are recommended, in addition to an ACE-I and a beta-blocker, in all patients with HFrEF to reduce mortality and the risk of HF hospitalization.2

Angiotensin receptor-neprilysin inhibitor (ARNI)2

In the PARADIGM-HF trial, sacubitril/valsartan, an ARNI, was shown to be superior to enalapril in reducing hospitalizations for worsening HF, CV mortality, and all-cause mortality in patients with ambulatory HFrEF with LVEF ≤40% (changed to ≤35% during the study).2

Sodium-glucose cotransporter 2 (SGLT-2)2

The EMPEROR-Reduced trial found that empagliflozin reduced the combined primary endpoint of CV death or HF hospitalization by 25% in patients with NYHA class II–IV symptoms, and an LVEF ≤40% despite OMT. This trial included patients with an eGFR >20 mL/min/1.73 m2 and there was also a reduction in the decline in eGFR in individuals receiving empagliflozin. It was also associated with an improvement in QOL.2

Therefore, dapagliflozin or empagliflozin are recommended, in addition to OMT with an ACE-I/ARNI, a β-blocker and an MRA, for patients with HFrEF regardless of diabetes status. The diuretic/natriuretic properties of SGLT2 inhibitors may offer additional benefits in reducing congestion and may allow a reduction in loop diuretic requirement.2

Treatment of advanced chronic HFrEF4

Patients with advanced chronic HFrEF remain severely symptomatic and have severe cardiac dysfunction despite optimal treatment with drugs and devices. These patients are candidates for heart transplantation when not contraindicated by age or major comorbidities.

Treatment of heart failure with preserved ejection fraction (HFpEF)2

To date, no treatment has been shown to convincingly reduce mortality and morbidity in patients with HFpEF, although improvements have been seen for some specific phenotypes of patients within the overall HFpEF umbrella. However, none of the large RCTs conducted in HFpEF have achieved their primary endpoints.

Footnotes:

  • ACC, American College of Cardiology; ACCF, Anterior cervical corpectomy and fusion; ACEi, angiotensin-converting enzyme inhibitor; AHA, American Heart Association; ARB, 
    angiotensin receptor blocker; ARNI, angiotensin II receptor–neprilysin inhibitor; AT1, angiotensin II receptor type 1; BB, beta-blocker; BP, blood pressure; b.p.m, beats per 
    minute; BTC, bridge to candidacy; BTT, bridge to transplantation; CABG, coronary artery bypass graft; COR, class of recommendation; CrCl, creatinine clearance; CRT, cardiac 
    resynchronization therapy; CRT-D, CRT defibrillator; CRT-P, cardiac resynchronization therapy with pacemaker; DT, destination therapy; ESC, European Society of Cardiology; 
    GDMT, guideline-determined medical therapy; HbA1c, glycated hemoglobin; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HFpEF, heart failure with 
    preserved ejection fraction; HFSA, Heart Failure Society of America; HF, heart rate; HYD-ISDN, hydralazine/isosorbide dinitrate; ICD, implantable cardioverter defibrillator; 
    ISDN, isosorbide dinitrate; LVAD, left ventricular assist device; LBBB, left bundle branch block; LVEF, left ventricular ejection fraction; MCS, mechanical circulatory support; 
    MR, mineralocorticoid receptor; MRAs, mineralocorticoid receptor antagonists; MV, mitral valve; NSR, normal sinus rhythm; NYHA, New York Heart Association; OMT, optimal 
    medical therapy; PVI, pulmonary vein isolation; QOL, quality of life; QRS, Q, R, and S waves (on a 12-lead electrocardiogram); RAAS, renin-angiotensin-aldosterone system; 
    SAVR, surgical aortic valve replacement; SGLT-2, sodium-glucose cotransporter 2; SR, sinus rhythm; TAVI, transcatheter aortic valve replacement; TEE, transcatheter edge to 
    edge; VF, ventricular fibrillation; VT, ventricular tachycardia.

References:

  1. Bloom MW, et al. Nat Rev Dis Primers. 2017;3:17058.

  2. McDonagh TA, et al. Eur Heart J. 2021;ehab368.

  3. Maddox TM, et al. J Am Coll Cardiol 2021;77:772–810.

  4. Metra M, Teerlink JR. Lancet. 2017;390(10106):1981-1995.

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