In focus: Heart failure

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Reference: March 2025 | Issue 3 | Vol 11 | Page 18

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Heart Failure (HF) is a global epidemic affecting over 20 million people worldwide.1 It is a clinical syndrome caused by an abnormality of cardiac structure and function which leads to an inability to adequately perfuse body tissues.² The causes of HF are varied.

The most common predisposing conditions are ischaemic heart disease, hypertension, valvular heart disease, and diabetes. It should be noted that in a proportion of cases, multiple conditions may be contributing, and in a significant minority of cases, no clear aetiological cause is defined.

Prevalence

Based on international prevalence rates from countries with similar demographic characteristics, it is likely that approximately 2 per cent of the adult population suffers from HF, predominately older individuals. The prevalence is increasing, reflecting the ageing population, challenges with risk factor management, improved survival in ischaemic heart disease, and indeed HF itself.

With an ageing population, HF is predicted to significantly increase over the next 20 years. It is characterised by persistent signs and symptoms that may be stable or worsen over time.³

In Ireland, there are approximately 6,000 primary HF admissions annually, with an average length of stay of 10.58 days, and a further 15,000 acute admissions where HF is thought to play a significant role. Approximately 30 per cent of patients are readmitted within 90 days. HF is a major public health concern affecting more than 120,000 of the population.⁴

HF trajectory

HF is a chronic and progressive syndrome associated with periods of acute exacerbations requiring hospital admissions. It is not a terminal disease and, like all chronic diseases, the overall aim of care is to delay the onset of symptoms. When present, care focuses on maintaining quality of life and optimisation of guideline treatment to minimise the need for hospital intervention. The HF illness trajectory can be complex, unpredictable, and variable, but it is typically characterised by acute exacerbations of decompensated events and periods of stability.⁵

Phenotypes and pathophysiology

There are three phenotypes of HF described in the European Society of Cardiology (ESC) guidelines.

HF with reduced ejection fraction (HFrEF): Historically known as systolic HF, HFrEF occurs when global left ventricular (LV) systolic dysfunction predominates. The LV contracts poorly and empties inadequately, leading to increased diastolic volume and pressure, and decreased ejection fraction (≤40%). Defective energy utilisation and supply, electrophysiologic function, and contractile element interaction are evident, alongside abnormal intracellular calcium modulation and production of cyclic 3’,5’-adenosine monophosphate (cAMP).⁶

HF with preserved ejection fraction (HFpEF): Historically known as diastolic HF, HFpEF occurs when LV filling is impaired, resulting in increased LV end-diastolic pressure at rest or during exertion and (usually) normal LV end-diastolic volume. Global contractility, and hence ejection fraction, remain normal (≥50%).⁶

HF with mild-reduced ejection fraction (HFmrEF): HFmrEF occurs in patients who have an LV ejection fraction of 41-49 per cent. It is unclear whether this group is a distinct population or consists of a mixture of patients with either HFpEF or HFrEF.^6,13

In HF, the reduction of adequate blood flow to the tissues for metabolic needs, along with cardiac-related elevation of pulmonary or systemic venous pressures, may result in organ congestion. This can result from abnormalities of systolic or diastolic function, or commonly, both. Although a primary abnormality can be a change in cardiomyocyte function, there are also changes in collagen turnover of the extracellular matrix.⁷

Renal responses

Reduced cardiac output results in a decrease in renal blood flow. The filtration fraction and filtered sodium decrease, while tubular resorption increases, leading to sodium and water retention. Therefore, renal venous pressures increase, which results in renal venous congestion and decreased glomerular filtration rate (GFR).

Decreased perfusion activates the renin-angiotensin-aldosterone system (RAAS), which ultimately results in increasing sodium and water retention, as well as renal and peripheral vascular tone, even further.⁸ These effects are amplified by the intense sympathetic activation accompanying HF. The RAAS-vasopressin (antidiuretic hormone) system causes a cascade of potentially damaging long-term effects:

• Angiotensin II worsens heart failure by causing vasoconstriction, including efferent renal vasoconstriction, and by increasing aldosterone production, which enhances sodium reabsorption in the distal nephron and also causes myocardial and vascular collagen deposition and fibrosis.
• Angiotensin II increases norepinephrine release, stimulates release of vasopressin, and triggers apoptosis.
• Angiotensin II may be involved in vascular and myocardial hypertrophy, thus contributing to the remodelling of the heart and peripheral vasculature, potentially worsening HF.
• Aldosterone can be also synthesised in the heart and vasculature, independently of angiotensin II (perhaps mediated by corticotropin, nitric oxide, free radicals, and other stimuli) and may have detrimental effects in these organs.

Neurohumoral responses

In conditions of stress, neurohumoral responses help increase heart function and maintain blood pressure and organ perfusion (fight or flight). However, chronic activation of these responses is damaging to the normal balance between myocardial-stimulating (vasoconstricting) hormones and the myocardial-relaxing (vasodilating) hormones.

The heart contains many neurohumoral receptors (alpha-1, beta-1, beta-2, beta-3, angiotensin II type 1 and 2, muscarinic, endothelin, serotonin, adenosine, cytokine, natriuretic peptides).⁸ In patients with HF, the most common beta-1 receptors are downregulated. This is believed to be in response to intense sympathetic activation, and results in impaired myocyte contractility and increased heart rate.⁸

The increase in sympathetic nerve stimulation increases preload and afterload via the rise in plasma norepinephrine levels and over time can result in direct myocardial damage including apoptosis, reduced renal blood flow, and activation of other neurohumoral systems, such as the RAAS.² Vasopressin is also released in response to a fall in blood pressure, which decreases renal excretion of free water, possibly contributing to hyponatraemia in HF.²

Atrial natriuretic peptide is released in response to increased atrial volume and pressure; brain (B-type) natriuretic peptide (BNP) is released from the ventricle in response to ventricular stretching. These peptides enhance renal excretion of sodium, but in patients with HF, the effect is blunted by decreased renal perfusion pressure, receptor downregulation, and perhaps enhanced enzymatic degradation.

In addition, elevated levels of natriuretic peptides exert a counter-regulatory effect on the RAAS and catecholamine stimulation. Because endothelial dysfunction occurs in HF, fewer endogenous vasodilators (eg, nitric oxide, prostaglandins) are produced, while more endogenous vasoconstrictors (eg, endothelin) are, thus increasing afterload.

The failing heart and other organs produce tumour necrosis factor alpha. This cytokine increases catabolism and is possibly responsible for cardiac cachexia, which may accompany severely symptomatic HF. The heart also undergoes metabolic changes with increased free fatty acid utilisation and decreased glucose utilisation. These changes may, in turn, become therapeutic targets.⁸

Signs and symptoms

Regardless of HF phenotype, the most common specific symptoms include dyspnoea, lower limb oedema, and fatigue.⁹ However, these can be non-specific as many patients with HF suffer from other co-morbidities or conditions.¹⁰

Typical symptoms may be accompanied by clinical signs such as elevated jugular venous pressure, pulmonary crackles, and peripheral oedema, and can occur due to structural and/or functional cardiac abnormality. This may result in a reduced cardiac output and/or elevated intra cardiac pressures at rest or during stress. This reduced cardiac output and subsequent lack of efficient venous return result in the clinical manifestations of HF.

Acute decompensated HF (ADHF) can be categorised into right and left HF.¹¹ Right HF is defined as a venous drainage insufficiency due to increased atrial and vena caval pressure.¹¹ The clinical signs of right HF result in elevated jugular pressure and tachycardia due to cardiac compensation.¹¹

Palpitations are also a common symptom in ADHF as the impaired heart tries to beat faster to accommodate for the lack of blood flow. Left HF – due to the inability of the heart to pump blood – leads to the accumulation of fluid, resulting in clinical manifestations of pulmonary and peripheral oedema.⁹

Dyspnoea occurs due to increased pulmonary capillary oncotic pressure from left-sided backflow, which results in an accumulation of fluid into the pulmonary interstitium, and subsequently reduced pulmonary compliance and increased airway resistance.⁹

Exertional dyspnoea can be due to hypoxaemia, with an increase of pulmonary pressures resulting in a mismatch between ventilation/perfusion and inadequate carbon dioxide clearance.¹² The accumulation of extravascular fluid in the pulmonary system when supine may manifest as orthopnoea and paroxysmal nocturnal dyspnoea – exacerbating dyspnoea, and in some cases, resulting in interstitial pulmonary oedema. Pulmonary congestion can also be associated with coughing and wheezing.¹³

Fatigue is attributable to the inability of the heart to sustain enough cardiac output to meet the body’s metabolic needs, while nausea and lack of appetite may also occur as blood is shifted from the gastrointestinal tract to vital organs, and confusion is due to reduced cerebral blood supply. Lower extremity oedema occurs when the right ventricle is unable to accommodate systemic venous return.¹³

Acute and chronic HF

The first presentation of HF is often with ADHF – known as an index event. This is caused by a decline in pumping capacity of the ventricles, leading to congestion of the systemic and the pulmonary vein. ADHF can predispose the patient to gradual or rapid changes in stability, resulting in HF signs and symptoms, and requiring urgent clinical review and stabilisation.¹³ Timing for treatment initiation is key to reducing further complications and readmissions with HF on its disease trajectory.¹³

Chronic HF patients are deemed stable when the clinical condition remains stable and HF medications are optimised in line with guideline recommendations.¹⁴ Although the ideal timespan of stability is not discussed in the National Institute for Health and Care Excellence guidelines, the ESC guidelines state that a treated patient with unchanged signs and symptoms for a minimum of one month is considered stable.^6,11

DISEASE MANAGEMENT AND TREATMENT

Non-pharmacological

Management of HF should be seen as a shared responsibility between patients, their carers, and healthcare professionals. Therefore, it is critical that patients and their families become actively engaged in prevention, hence improving their health behaviours and self-management.

Current guidelines recommend patients and/or their caregivers understand that worsening symptoms can be indicative of HF deterioration.⁶ Furthermore, it is advocated that each patient should know what symptoms are their accepted baseline, thereby enabling a rapid recognition of warning signs to prompt appropriate action.⁶ The patient and family should be involved in treatment choices, taught the importance of drug adherence, warning signs of an exacerbation, and how to link cause with effect.

Self-care management involves engaging in cognitive process and actions that not only include recognising worsening HF symptoms, but also initiating self-care strategies. Inherent in these processes is the patient’s ability to make decisions as they move through their illness. It is important that patients are given education so that they can develop the skills and confidence needed.

A framework for self-management support for those living with chronic conditions has been developed. Many factors influence patients’ ability to engage in self-care and these must also be considered by healthcare professionals in order to support the patient as they master the ability to engage fully in self-care. These approaches can improve outcomes and reduce hospitalisations.

In general practice under the chronic disease management (CDM) programme, biyearly reviews are arranged for any patient with HF, and a patient-centred, personalised care plan has been agreed as part of the programme.

Fundamental advice for patients with a diagnosis of HF would include:

• Dietary sodium restriction helps limit fluid retention. All patients should eliminate salt in cooking and at the table, and avoid salted foods. Patients with severe disease should limit sodium to <2g/day by consuming only low-sodium foods.⁶
• Monitoring daily morning weight helps detect sodium and water accumulation early. If weight increases >2kg over a few days, patients may be able to adjust their diuretic dose themselves, but if weight gain continues or symptoms occur, patients should be advised to seek medical attention.
• Intensive case management, particularly by monitoring drug adherence and frequency of unscheduled visits to the physician or emergency department and hospitalisations, can identify when intervention is needed. Linking in with secondary care specialists as needed is key and specialist nurses are valuable for education, follow-up, and dosage adjustment according to predefined protocols.
• Patients with atherosclerosis or diabetes should strictly follow a diet appropriate for their disorder. Obesity may cause and aggravate the symptoms of HF; therefore, patients should attain a body mass index ≤30kg/m2 (ideally 21-25kg/m2).
• Regular light activity, tailored to symptoms, is generally encouraged. Activity prevents skeletal muscle deconditioning, which worsens functional status; however, activity does not appear to improve survival or decrease hospitalisations. Rest is appropriate during acute exacerbations. Formal cardiac rehabilitation is useful and programmes such as the Exwell ‘Get active your way’ are useful pathways for suitable patients to mobilise confidently.
• Vaccination adherence should be advocated as influenza can precipitate HF exacerbations, particularly in institutionalised or older patients. Patients should be vaccinated against SARS-CoV-2 and have the pneumococcal vaccine as per current guidelines.

Pharmacological and device therapy

HFrEF: Pharmacotherapy is the cornerstone of treatment for HFrEF and should be implemented before considering device therapy, and alongside non-pharmacological interventions.⁷ There are three major goals of treatment for patients with HFrEF: Reduction in mortality; prevention of recurrent hospitalisations due to worsening HF; and improvement in clinical status, functional capacity, and quality of life.

The four pillars of foundational therapies are:

• Beta-blocker;
• RAAS inhibitor (typically angiotensin receptor-neprilysin inhibitor (ARNI), although an angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) could also used if ARNI is not tolerated);
• Aldosterone antagonist/ mineralocorticoid receptor agonists (MRAs);
• Sodium-glucose co-transporter 2 (SGLT2) inhibitor.

These four drug classes have been studied and have shown benefit for long-term management of HFrEF. Therapy is typically titrated up to maximal tolerated doses and patients are generally given a drug from each class. Addition of a SGLT2 inhibitor has been shown to reduce morbidity and mortality when added to standard care in patients with elevated natriuretic peptide levels. Benefit was similar in patients with and without diabetes.¹⁶

Implantable cardioverter defibrillators (ICDs) are recommended in selected patients with HFrEF of an ischaemic aetiology and should be considered in those with a non-ischaemic aetiology. Cardiac resynchronisation therapy with a defibrillator (CRT-D) is recommended in patients with HFrEF, in sinus rhythm, with a left bundle branch block (LBBB) ≥150ms, and should be considered in those with a LBBB ≥130–149ms or non-LBBB ≥150ms.

HFpEF: The pathophysiology of various HFpEF syndromes differs, and thus they require distinct therapies.⁶ ACE inhibitors, ARBs, or aldosterone antagonists (MRAs) are often used to treat HFpEF and/or associated comorbidities (such as hypertension and renal dysfunction).

However, survival benefit has not been demonstrated in clinical trials and, therefore, these are not considered a standard of care.^6,7,18 The guidelines traditionally recommended treatment that focused more on treating aetiology like atrial fibrillation (AF), obesity, hypertension, and relieving fluid overload with diuretics.

There were no published trials with SGLT2 inhibitors to consider at the time of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic HF. Since then, publication of several randomised controlled trials will likely influence changes to future guideline updates.^13,15,16

In 2023, the taskforce issued a focused update to address changes in recommendations for the treatment of HF because of this new evidence. The two major trials with the SGLT2 inhibitors empagliflozin and dapagliflozin influenced the decision for a class I recommendation of the addition of the SGLT2 inhibitor to standard therapy, which was shown to reduce mortality and hospitalisations for all patients with HF, regardless of ejection fraction.^15,16

HFmrEF: Similarly, for those with HFmrEF with LV ejection fraction between 41-49 per cent, the taskforce previously made weak recommendations. These were based on subgroup analyses of trials that were not specifically designed to focus on HFmrEF, including trials where the overall endpoints were statistically neutral.

In HFmrEF there may also be a specific benefit from ARNIs, MRAs, and beta-blockers; however, these are class IIb recommendation only. In 2021 no recommendations for the use of SGLT2 inhibitors in this cohort was indicated. However, in the focus update in 2023 it was recommended that patients with HFmrEF may benefit from the addition of an SGLT2 inhibitor to standard care.^13,15,16

Adjunct therapy

In addition to oral anticoagulation, a strategy of rhythm control, including catheter ablation, should be considered in patients whose symptoms and/or cardiac dysfunction are associated with AF, according to the ESC. Surgical aortic valve replacement or transcatheter aortic valve implantation, as advised by the heart team, are recommended in patients with symptomatic severe aortic valve stenosis.

Patients should be periodically screened for anaemia and iron deficiency, and intravenous iron supplementation with ferric carboxymaltose should be considered in symptomatic patients with LV ejection fraction <45 per cent and iron deficiency, and in patients recently hospitalised for HF and with LV ejection fraction ≤50 per cent and iron deficiency.

Conclusion

HF involves ventricular dysfunction that ultimately leads to the heart not providing tissues with adequate blood for metabolic needs. HF should be considered in patients with exertional dyspnoea or fatigue, orthopnoea, and/or oedema, particularly in those with a history of myocardial infarction, hypertension, or valvular disorders or murmurs. HF treatment should include education and lifestyle changes, control of underlying disorders or aetiology, and guideline directed therapy as per phenotype. HF can set off renal and neurohumoral cascades of counter regulatory mechanisms. Measurement of BNPs and echocardiography have key roles in the diagnosis of HF. Guideline-targeted treatments are key to reducing hospital readmissions and improving quality of life and the trajectory of this chronic disease.

On a personal note, my vision as an advanced nurse practitioner (ANP) in general practice aims to enhance the efficiency of nursing care for patients with chronic diseases including HF. In my role, I strive to emphasise an integrated primary and secondary care approach, with a focus on keeping affected people out of the hospital setting and well in the community.

This involves opportunistic screening of patients at risk of developing a chronic disease, and coordinating and delivering care for scheduled visits in the chronic disease management programme for patients with a chronic disease or at risk of developing one.

Another element of my role would include assessing and managing the unscheduled visits for acute exacerbations or decompensation, and then linking in with the specialist services as appropriate. The efficiency of having an ANP role in clinic is aimed to develop, increase, and support the capacity of the primary care services, along with reducing delays and enhancing the specialist care offered to patients.

I have a special interest in HF and am in an optimal position to provide proactive care, advising on self-care strategies in managing HF in the community, and being part of the active management of patients with chronic disease.

References

1. Grady KL, Kao A, Spertus JA, et al. Health-related quality of life in older patients with heart failure from before to early after advanced surgical therapies: Findings from the SUSTAIN-IT study. Circ Heart Fail. 2022;15(10):e009579.
2. Greene SJ, Bauersachs J, Brugts JJ, et al. Worsening heart failure: Nomenclature, epidemiology, and future directions: JACC review topic of the week. J Am Coll Cardiol. 2023;81(4):413-424.
3. Hobbs JK, Escutia D, Harrison H, et al. Reducing hospital readmission rates in patients with heart failure. Medsurg Nurs. 2016;25(3):145-152.
4. The Irish Heart Foundation, et al. The cost of heart failure in Ireland – the social, economic, and health implications of heart failure in ireland. 2015. Available at: www.rte.ie/documents/news/cost-of-heart-failure-report-web.pdf.
5. Buck HG, Hupcey J, Watach A. pattern versus change: Community-based dyadic heart failure self-care. Clin Nurs Res. 2018;27(2):148-161.
6. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599-3726.
7. Behnoush AH, Khalaji A, Naderi N, et al. ACC/AHA/HFSA 2022 and ESC 2021 guidelines on heart failure comparison. ESC Heart Fail. 2023;10(3):1531-1544.
8. Jones NR, Roalfe AK, Adoki I, et al. Survival of patients with chronic heart failure in the community: A systematic review and meta-analysis. Eur J Heart Fail. 2019;21(11):1306-1325.
9. Gottdiener JS, Kop WJ. Body and heart: Effects of weight gain and loss on left ventricular size and function. Circ Cardiovasc Imaging. 2017;10(3):e006084.
10. McMurray, J. Lessons from the ESC guidelines of the management of heart failure (TBA). Journal of Cardiac Failure. 2012;18, (10):121-122.
11. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The taskforce for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology. Developed with the special contribution of the Heart Failure Association of the ESC. Eur Heart J. 2016;37(27):2129-2200.
12. Kittleson MM, Panjrath GS, Amancherla K, et al. 2023 ACC expert consensus decision pathway on management of heart failure with preserved ejection fraction: A report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2023;81(18):1835-1878.
13. Savarese G, Stolfo D, Sinagra G, et al. Heart failure with mid-range or mildly reduced ejection fraction. Nat Rev Cardiol 19, 2022;19(2):100-116.
14. National Institute for Health and Care Excellence. Chronic heart failure in adults: Diagnosis and management. NICE; 2018. Available at: www.nice.org.uk/guidance/ng106.
15. Cox ZL, Collins SP, Hernandez GA, et al. Efficacy and safety of dapagliflozin in patients with acute heart failure. J Am Coll Cardiol. 2024;83(14):1295.
16. Voors AA, Angermann CE, Teerlink JR, et al. The SGLT2 inhibitor empagliflozin in patients hospitalised for acute heart failure: A multinational randomised trial. Nat Med. 2022;28(3):568-574.
17. Palazzuoli A, Correale M, Iacoviello M, et al. Does the measurement of ejection fraction still make sense in the HFpEF framework? What recent trials suggest. J Clin Med. 2023;12(2):693.