HOME LEARNING CPD ARTICLE Novartis provided financial support in the production of this content. Clinical Pharmacistretains sole editorial responsibility. Cardiovascular disease Pathophysiology and management of heart failure Clinical Pharmacist6 DEC 2018By Paul Wright , Martin Thomas Ensuring patients are optimised on maximum tolerated doses of medicines to treat heart failure with reduced ejection fraction is essential in minimising the burden of the condition. Fluorescent micrograph of heart failure Source: Sciencephotolibrary Around 550,000 people in the UK are recorded as having heart failure (HF), which equates to a prevalence of 0.8%[1]. The true number (including those with unrecorded/undiagnosed HF) is likely to be much higher and estimated to be 920,000 in the UK[2]. Depending on the definition applied, it is estimated that the prevalence of HF is around 1–2% of the adult population, increasing to over 10% in people aged over 70 years[3]. Males are affected slightly more than females, with an estimated lifetime risk of HF at the age of 55 years being 33% for men compared with 28% for women[4]. Data from the 2015–2016 National Heart Failure Audit, which is carried out each year by the National Institute for Cardiovascular Outcomes Research, highlights that patient prognosis remains poor; mortality in patients admitted with HF is 8.9% during hospital admission, with a third of those discharged dying within the following year. Following admission to hospital for HF, survival rates are similar to those of colon cancer, and worse than those of breast or prostate cancer. HF is the cause of, or complicates, around 5% of all emergency admissions in adults and consumes up to 2% of total NHS expenditure[5]. Unfortunately, it is predicted that hospital admissions resulting from HF will continue to rise, mainly driven by an ageing population[2] This article describes what happens to the heart during HF and how to treat it, as well as how to determine ejection fraction (EF). Definition HF is a complex clinical syndrome whereby the heart is unable to meet the metabolic demands of the body. Reasons for this mismatch can be multifactorial, and various underlying pathological conditions make the management and treatment complex. Initially, patients may tolerate small declines in output as various compensatory measures are activated to redress the balance. Over time, however, these compensatory measures become deleterious to heart function and lead to worsening cardiac output, resulting in further activation and additional stress on a failing heart. Given the multitude of causes of HF, it is difficult to give a precise classification and definition compared with other common cardiac diseases, such as atrial fibrillation (AF), ischaemic heart disease (IHD) or hypertension, where a diagnosis is relatively straightforward. However, the European Society of Cardiology defines HF as a clinical syndrome characterised by symptoms such as shortness of breath, persistent coughing or wheezing, ankle swelling and fatigue, which may be accompanied by the following signs: elevated jugular venous pressure; pulmonary crackles; increased heart rate; and peripheral oedema[3]. In addition, patients with HF often have several pathologies that may potentiate HF progression and symptoms. Diagnosis relies on clinical judgement based on a combination of patient history, physical examination and appropriate investigations to determine the likely underlying pathophysiology. Identification of the cause of HF is essential in the diagnostic workup, as this may offer specific therapeutic opportunities (i.e. if HF results from valvular causes, surgery may be curative). Symptom classification HF is a clinical syndrome characterised by a number of typical symptoms, such as breathlessness, oedema and fatigue. HF can be categorised in a number of different ways, although the underlying aetiologies are numerous. It is common practice in the UK to use the New York Heart Association (NYHA) functional classification to document and assess severity of symptoms and physical activity (see Table 1). It is also common to differentiate between left and right-sided HF, although the failure of one side often leads to failure of the other (biventricular failure). This is because the circulatory system works on a double pump with blood from the left ventricle being pumped systemically, returning to the right side where it is pumped towards the lungs for oxygenation; blood then returns to the left side for distribution round the systemic circulation again. If there is a failing on one side, given they are linked, failure on the other side will often follow. Table 1: New York Heart Association functional classification Class I No limitation of physical activity. Ordinary physical activity does not cause undue breathlessness, fatigue or palpitations Class II Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in undue breathlessness, fatigue or palpitations Class III Marked limitation of physical activity. Comfortable at rest, but less than ordinary physical activity results in undue breathlessness, fatigue or palpitations Class IV Unable to carry out any physical activity without discomfort. Symptoms at rest can be present. If any physical activity is undertaken, discomfort is increased Source: Reproduced with permission from the American Heart Association. Classes of heart failure. 2017. Available at: http://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure/classes-of-heart-failure (accessed December 2018) A further differentiation can be made on whether there is dysfunction with the active pumping action in the ventricle (systolic dysfunction), or whether there is a problem with the relaxation or filling of the ventricle (diastolic dysfunction). Diagnosis Determining ejection fraction The ‘gold standard’ tool for the assessment and diagnosis of HF is a transthoracic echocardiogram (TTE). This test allows a thorough assessment of chamber dimensions, valvular function and various estimates of heart function, including an estimation of EF (the proportion of blood ejected from the heart during a heartbeat). EF, which is typically between 55% and 70%, can be calculated using the following equation: Ejection fraction = end diastolic volume – end systolic volume/end diastolic volume HF is often classified based on the EF. HF with reduced ejection fraction (HFrEF) is identified where the EF is less than 40%. HF with preserved ejection fraction (HFpEF) can be harder to diagnose, and is defined as EF >50% with other markers of heart failure (e.g. diastolic dysfunction or structural heart disease). This important as underlying pathologies are distinct, with treatment in people with HFrEF having a strong evidence base in reducing mortality and morbidity. This is not replicated in patients with HFpEF, although patients typically exhibit similar clinical symptoms. Compared with HFrEF, patients with HFpEF are often older, more often female, and more commonly have a history of hypertension and valvular disease, while people with HFrEF tend to have a medical history that includes IHD[5]. Table 2 represents the aetiology and comorbidity of patients with HF admitted to hospital in the UK. Table 2: Aetiology and comorbidities of patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) Medical history HFrEF (%) HFpEF (%) Ischaemic heart disease 48.4 37.9 Atrial fibrillation 49.1 40.0 Myocardial infarction 30.7 18.1 Valve disease 23.9 31.4 Hypertension 52.1 59.9 Diabetes 33.3 33.5 Asthma 8.4 9.4 Chronic obstructive pulmonary disease 16.7 18.9 HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction Source: Reproduced with permission from the British Society for Heart Failure. National Heart Failure Audit, April 2015 to March 2016. Available at: http://www.ucl.ac.uk/nicor/audits/heartfailure/documents/annualreports/annual-report-2015-6-v8.pdf (accessed December 2018) To understand the differences and similarities in patients with HFrEF and HFpEF, it is important to understand another measure of heart function — cardiac output. Cardiac output can be defined as: Cardiac output = stroke volume (amount of blood ejected in a heartbeat)x heart rate (beats per minute [bpm]) Generally, this is 70mL x 70bpm, which gives a cardiac output of 4.9L/min and the end diastolic volume is 110mL. Therefore, the EF will be 64% (110mL – 70mL / 110mL; see Figure 1A). In a patient with HFrEF, stroke volume is typically reduced, which will therefore reduce cardiac output. For example, the patient’s stroke volume reduces to 44mL. This would result in an EF of 40% (44mL / 110mL) and a new cardiac output of 44mL x 70bpm = 3L/min (see Figure 1B). In a patient with HFpEF, although the EF is normal, diastolic dysfunction is often present, lowering the end diastolic volume (either through ventricular hypertrophy, which reduces the cavity size, or through ventricular stiffening, where blood is not allowed to fill the ventricle). In either case, stroke volume ejected will be less because the initial volume is lower, which again leads to a reduction in stroke volume and a decline in cardiac output. For example, the patient’s end diastolic volume reduces to 70mL. As in the first case, the stroke volume is reduced to 44mL but the EF remains ‘normal’. This would result in an EF of 63% (44mL / 70mL) and a cardiac output of 3L/min (44mL x 70bpm; see Figure 1C).
