Heart failure with preserved ejection fraction: implications for anaesthesia

Learning objectivesBy reading this article, you should be able to:•Describe the epidemiology and pathophysiology of heart failure with preserved ejection fraction (HFpEF).•Discuss the diagnostic work-up of patients in whom a diagnosis of HFpEF is suspected.•Outline the pharmacological and non-pharmacological management of HFpEF.•Summarise the perioperative considerations in patients with HFpEF undergoing major surgery.•Safely manage patients taking sodium-glucose cotransporter type 2 (SGLT2) inhibitors in the perioperative period.Key points•The numbers of patients with HFpEF presenting for surgery are likely to increase.•Diagnosing HFpEF relies on the presence of clinical signs and symptoms, and echocardiographic evidence of preserved left ventricular (LV) systolic function and increased LV filling pressures.•First-line management of HFpEF includes sodium-glucose cotransporter type 2 (SGLT2) inhibitors, diuretics and treatment of coexisting comorbidities such as hypertension and diabetes. Atrial fibrillation should be managed aggressively.•SGLT2 inhibitors should be stopped 2–3 days before elective surgery to minimise the risk of developing euglycaemic diabetic ketoacidosis in the perioperative period. By reading this article, you should be able to:•Describe the epidemiology and pathophysiology of heart failure with preserved ejection fraction (HFpEF).•Discuss the diagnostic work-up of patients in whom a diagnosis of HFpEF is suspected.•Outline the pharmacological and non-pharmacological management of HFpEF.•Summarise the perioperative considerations in patients with HFpEF undergoing major surgery.•Safely manage patients taking sodium-glucose cotransporter type 2 (SGLT2) inhibitors in the perioperative period. •The numbers of patients with HFpEF presenting for surgery are likely to increase.•Diagnosing HFpEF relies on the presence of clinical signs and symptoms, and echocardiographic evidence of preserved left ventricular (LV) systolic function and increased LV filling pressures.•First-line management of HFpEF includes sodium-glucose cotransporter type 2 (SGLT2) inhibitors, diuretics and treatment of coexisting comorbidities such as hypertension and diabetes. Atrial fibrillation should be managed aggressively.•SGLT2 inhibitors should be stopped 2–3 days before elective surgery to minimise the risk of developing euglycaemic diabetic ketoacidosis in the perioperative period. Globally, >60 million people are estimated to have heart failure (HF), of which heart failure with preserved ejection fraction (HFpEF) accounts for 50% of cases.1Savarese G. Becher P.M. Lund L.H. et al.Global burden of heart failure: a comprehensive and updated review of epidemiology.Cardiovasc Res. 2023; 118: 3272-3287Google Scholar The prevalence of HFpEF is steadily increasing because of improved recognition, an ageing population and reduction in death from comorbidities that can lead to HFpEF. This review provides an update on the epidemiology, pathophysiology, diagnosis and management and perioperative considerations for patients with HFpEF. Previous definitions of HF were largely arbitrary and lacked standardisation. In 2021, various cardiology societies developed a universal definition and classification system for HF (Fig. 1) designed to be clinically relevant with prognostic and therapeutic validity, applicable globally and allow standardisation of endpoints in research.2Bozkurt B. Coats A.J.S. 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.Eur J Heart Fail. 2021; 23: 352-380Google Scholar The definition describes HF as a clinical syndrome with current or prior:(i)Symptoms, signs, or both caused by a structural or functional cardiac abnormality(ii)Corroborated by at least one of the following: (a) increased natriuretic peptide concentrations, (b) objective evidence of cardiogenic pulmonary or systemic congestion through imaging (echocardiography) or haemodynamic measurement (e.g. right heart catheterisation) at rest or exercise. Other syndromes may also fulfil this definition of HF. Examples include right HF (the commonest cause of which is left HF), cardiogenic shock, acute coronary syndrome, congenital heart disease, valvular heart disease, high-output failure and hypertensive crises. Management should be guided towards treating the underlying cause and treating the symptoms of HF. Current global patterns demonstrate that whilst the incidence of HF has stabilised and is possibly declining in industrialised nations, the prevalence is increasing because of an ageing population and improvements in medical care.1Savarese G. Becher P.M. Lund L.H. et al.Global burden of heart failure: a comprehensive and updated review of epidemiology.Cardiovasc Res. 2023; 118: 3272-3287Google Scholar In a UK population-based study of 4 million individuals between 2002 and 2014, the incidence of HF decreased by 7% (from 358 to 332 per 100,000 person-years) but the absolute number of people diagnosed with HF increased by 12%.3Conrad N. Judge A. Tran J. et al.Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals.Lancet. 2018; 391: 572-580Google Scholar The prevalence remained stable between 1.5% and 1.6% but the absolute number increased by 23%. Socioeconomically deprived people were more likely to develop HF compared with affluent people and did so earlier in life.3Conrad N. Judge A. Tran J. et al.Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals.Lancet. 2018; 391: 572-580Google Scholar These data are consistent with a meta-analysis of >6 million individuals which found that low socioeconomic status was associated with an increased risk of incident HF ranging between 43% and 87%.4Potter E.L. Hopper I. Sen J. et al.Impact of socioeconomic status on incident heart failure and left ventricular dysfunction: systematic review and meta-analysis.Eur Heart J Qual Care Clin Outcomes. 2019; 5: 169-179Google Scholar Heart failure with preserved ejection fraction now accounts for 50% of cases of HF.5Redfield M.M. Borlaug B.A. Heart failure with preserved ejection fraction: a review.JAMA. 2023; 329: 827-838Google Scholar One large, multicohort study demonstrated an increase in the incidence of HFpEF from 4.7 to 6.8 per 1000 person-years over two decades.6Tsao C.W. Lyass A. Enserro D. et al.Temporal trends in the incidence of and mortality associated with heart failure with preserved and reduced ejection fraction.JACC Heart Fail. 2018; 6: 678-685Google Scholar Risk factors for developing HFpEF include increasing age, hypertension, obesity, diabetes and previous myocardial infarction.7Ho J.E. Enserro D. Brouwers F.P. et al.Predicting heart failure with preserved and reduced ejection fraction: the International Collaboration on Heart Failure Subtypes.Circ Heart Fail. 2016; 9e003116Google Scholar Several pathophysiological pathways have been proposed, and a detailed review can be found elsewhere.8Gevaert A.B. Boen J.R.A. Segers V.F. et al.Heart failure with preserved ejection fraction: a review of cardiac and noncardiac pathophysiology.Front Physiol. 2019; 10: 638Google Scholar,9Shah S.J. Borlaug B.A. Kitzman D.W. et al.Research priorities for heart failure with preserved ejection fraction: national Heart, Lung, and Blood Institute working group summary.Circulation. 2020; 141: 1001-1026Google Scholar The historical model is one of hypertension with a hypertensive heart developing diastolic dysfunction (DD) with systolic dysfunction then developing over time. Treatment of hypertension has been shown to reduce incidence of HFpEF by 40% over 2–8 yrs.10Sciarretta S. Palano F. Tocci G. et al.Antihypertensive treatment and development of heart failure in hypertension: a Bayesian network meta-analysis of studies in patients with hypertension and high cardiovascular risk.Arch Intern Med. 2011; 171: 384-394Google Scholar Differences exists in the pathophysiology of left ventricular (LV) function between HFpEF and HF with reduced ejection fraction (HFrEF). Heart failure with preserved ejection fraction is associated with impaired ventricular relaxation, increased stiffness and increased filling pressures with pressure overload, whereas in HFrEF, the left ventricle undergoes eccentric remodelling resulting in chamber dilatation with volume overload.5Redfield M.M. Borlaug B.A. Heart failure with preserved ejection fraction: a review.JAMA. 2023; 329: 827-838Google Scholar,8Gevaert A.B. Boen J.R.A. Segers V.F. et al.Heart failure with preserved ejection fraction: a review of cardiac and noncardiac pathophysiology.Front Physiol. 2019; 10: 638Google Scholar Recent data suggest a proinflammatory state induced by comorbidities such as obesity, diabetes, chronic obstructive pulmonary disease (COPD) and chronic kidney disease which cause systemic microvascular endothelial inflammation with downstream myocardial inflammation, increased oxidative stress and deregulation of nitric oxide signalling, fibrosis and hypertrophy.5Redfield M.M. Borlaug B.A. Heart failure with preserved ejection fraction: a review.JAMA. 2023; 329: 827-838Google Scholar,11Paulus W.J. Zile M.R. From systemic inflammation to myocardial fibrosis: the heart failure with preserved ejection fraction paradigm revisited.Circ Res. 2021; 128: 1451-1467Google Scholar Interleukin (IL)-6 concentrations are commonly increased in HFpEF and are associated with greater symptom severity, poor exercise capacity and increased upper body fat composition.12Alogna A. Koepp K.E. Sabbah M. et al.Interleukin-6 in patients with heart failure and preserved ejection fraction.JACC Heart Fail. 2023; 11: 1549-1561Google Scholar Current European Society of Cardiology guidelines recommend a simplified, pragmatic approach which should include the following:13McDonagh T.A. 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.Eur Heart J. 2021; 42: 3599-3726Google Scholar(i)The presence of symptoms and signs of HF(ii)LV ejection fraction (LVEF) ≥50%(iii)Exclusion of other pathologies that can mimic HFpEF(iv)Evidence of increased LV filling pressures/DD/increased left atrial volume and raised natriuretic peptides Approximately two thirds of patients with HFpEF present with dyspnoea and clinical signs of congestion such as peripheral oedema, raised jugular venous pressure and ascites.5Redfield M.M. Borlaug B.A. Heart failure with preserved ejection fraction: a review.JAMA. 2023; 329: 827-838Google Scholar Those with unexplained dyspnoea without evidence of congestion require further diagnostic testing. As outlined above, patients diagnosed with HFpEF often have other comorbidities such as pulmonary disease, anaemia and atrial fibrillation which should be investigated and managed accordingly.14Forsyth F. Brimicombe J. Cheriyan J. et al.Characteristics of patients with heart failure with preserved ejection fraction in primary care: a cross-sectional analysis.BJGP Open. 2021; 5 (BJGPO.2021.0094)Google Scholar,15Mohammed S.F. Borlaug B.A. Roger V.L. et al.Comorbidity and ventricular and vascular structure and function in heart failure with preserved ejection fraction: a community-based study.Circ Heart Fail. 2012; 5: 710-719Google Scholar Differential diagnoses of cardiac origin can be split into those affecting the myocardium and those that affect loading conditions. Conditions affecting the myocardium include coronary artery disease, either epicardial or microvascular. Infiltrative cardiomyopathies include amyloidosis, sarcoidosis, hypertrophic and storage diseases such as haemochromatosis. Loading conditions include hypertensive disease, left-sided valvular disease, pericardial disease, arrhythmias and conditions leading to a high-output state. Differential diagnoses for HFpEF include hypertrophic cardiomyopathy, amyloid cardiomyopathy, pulmonary hypertension, constrictive pericarditis and coronary artery disease.5Redfield M.M. Borlaug B.A. Heart failure with preserved ejection fraction: a review.JAMA. 2023; 329: 827-838Google Scholar In cases of diagnostic uncertainty or unexplained dyspnoea, various algorithms have been proposed. Pieske and colleagues propose a stepwise HFA-PEFF algorithm which uses four steps (Fig. 2).16Pieske B. Tschope C. de Boer R.A. et al.How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).Eur J Heart Fail. 2020; 22: 391-412Google Scholar The H2PEF score is also recommended by guidelines to estimate likelihood of HFpEF in unexplained dyspnoea (Table 1).17Reddy Y.N.V. Carter R.E. Obokata M. et al.A simple, evidence-based approach to help guide diagnosis of heart failure with preserved ejection fraction.Circulation. 2018; 138: 861-870Google Scholar,18Heidenreich P.A. Bozkurt B. Aguilar D. et al.2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American college of cardiology/American heart association joint committee on clinical practice guidelines.Circulation. 2022; 145: e895-e1032Google Scholar In areas of high disease prevalence, a score of ≥6 is associated with >95% probability of HFpEF whereas a score of 0–1 was associated with <25% probability of having HFpEF.17Reddy Y.N.V. Carter R.E. Obokata M. et al.A simple, evidence-based approach to help guide diagnosis of heart failure with preserved ejection fraction.Circulation. 2018; 138: 861-870Google ScholarTable 1H2PEF score to assess risk of HFpEF in unexplained dyspnoea.Clinical variablePointsHeavy (BMI >30 kg m−2)2Hypertensive (>2 antihypertensive medications)1Fibrillation, atrial (any history)3Pulmonary hypertension (rest RVSP >35 mmHg)1Elderly (age >60 yrs)1Filling pressure (E/e’>9)1Score0–1HFpEF ruled out2–5Consider rest/stress RHC or stress echo6–9HFpEF ruled inBMI, body mass of diastolic to right heart right ventricular systolic in a body mass of diastolic to right heart right ventricular systolic natriuretic peptide and of the are by of the a in is by high LV which is to studies have demonstrated that concentrations have a high for HF in acute or and or T.A. 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.Eur Heart J. 2021; 42: 3599-3726Google Scholar in can stress and natriuretic peptide concentrations can be to of patients with HFpEF diagnosed by have concentrations the diagnostic B. Tschope C. de Boer R.A. et al.How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).Eur J Heart Fail. 2020; 22: 391-412Google Scholar associated with concentrations in patients with HFpEF are age, obesity, presence of or both and is in peptides to HFpEF in M.M. Borlaug B.A. Heart failure with preserved ejection fraction: a review.JAMA. 2023; 329: 827-838Google et clinical and associated with natriuretic peptide concentrations in heart failure with preserved ejection J 2012; Scholar dysfunction is an of HFpEF but for the of should be that diastolic function as a of ventricular to a of ventricular and an increase in chamber Risk factors for developing include hypertension, coronary artery disease, increasing age, and dysfunction in and 2016; Scholar As can of stress myocardial function is (e.g. overload, hypertension, atrial signs and symptoms include those of on is from the American Society of S.F. et for the of left ventricular diastolic function by an update from the American Society of and the European Association of 2016; Scholar clinical considerations for are heart and pressure and The echocardiographic should be in to LV and ejection of left atrial volume and function should also be The that are to are in the and include the at the of the at the and Other include left atrial volume and and the of a The presence or of is on the four and or volume dysfunction is present more of the are management of HFpEF includes sodium-glucose cotransporter type 2 (SGLT2) inhibitors, diuretics for and treatment of other cardiovascular and are or both that a is or from the updated ESC T.A. 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