HF comorbidities: iron deficiency, CKD, gout and cachexia

This page covers comorbidities that the heart failure (HF) guidelines ask clinicians to look for and treat: iron deficiency and anaemia, diabetes, chronic kidney disease (CKD) and potassium, sleep-disordered breathing, wasting and frailty, depression and gout.^[1][2] Atrial fibrillation (AF) is covered only as pointers to the HF-specific rows.

• Related topic: Heart failure with reduced ejection fraction.
• Related topic: HFmrEF and HFpEF.
• Related topic: Acute heart failure.
• Related topic: Atrial fibrillation.

Why comorbidities matter in heart failure

Most patients with HF carry several other diagnoses.^[2] AHA/ACC/HFSA 2022 says multimorbidity is common in HF, with over 85% of patients having two or more additional chronic conditions.^[2] It lists hypertension, ischaemic heart disease, diabetes, anaemia, CKD, morbid obesity, frailty and malnutrition among the most common comorbid conditions in HF.^[2]

^[2]

Those percentages come from US Medicare administrative claims data for 2011, so they describe Medicare beneficiaries in one year.^[2] The ESC 2026 key messages give the practical instruction: patients should be routinely screened and treated for non-cardiovascular comorbidities (such as diabetes, CKD, obesity, iron deficiency, anxiety and depression) and for frailty.^[1]

Screening starts as soon as HF is suspected.^[1] In suspected HF, ESC 2026 recommends a full blood count, kidney function (eGFR and urine albumin-to-creatinine ratio), electrolytes, liver function, thyroid function, HbA1c, lipids and iron status (TSAT and ferritin) when screening for comorbidities (Class I, Level C).^[1]

Iron deficiency

Why it matters

ESC 2026 says iron deficiency and anaemia are common in HF and are associated with reduced functional capacity and worse quality of life (QoL) and prognosis, independently of each other.^[1] Iron deficiency is slightly more prevalent in HFpEF than in HFrEF.^[1] AHA/ACC/HFSA 2022 adds that iron deficiency appears to be uniquely associated with reduced exercise capacity.^[2]

Definition: the ferritin rule and the TSAT rule

One rule has defined iron deficiency in HF trials.^[1] ESC 2026 states it as ferritin <100 ng/mL, or ferritin 100–299 ng/mL with TSAT <20% (TSAT: transferrin saturation).^[1] It was adopted by the 2021 ESC guideline and its 2023 focused update, and used in almost all recent trials of intravenous iron in HF.^[1]

ESC 2026 now questions that rule.^[1] It says the rule does not reliably identify absolute or functional iron deficiency in HF.^[1] It may include patients with TSAT ≥20% and serum ferritin in the normal range, who are probably not iron deficient, have a better prognosis and might not respond to intravenous iron.^[1] Serum ferritin is also highly sensitive to inflammation and oxidative stress.^[1]

The alternative is TSAT <20% alone, proposed mainly on evidence from explorative analyses and meta-analyses of randomised trials.^[1] ESC 2026 says TSAT <20% has higher sensitivity and specificity than the previous definition and is associated with higher mortality, independently of HF phenotype.^[1] Some meta-analyses of large trials reported that lower TSAT values better identify patients who will respond favourably to intravenous iron.^[1] The Task Force supports this newer definition and recognises the need for new trials of intravenous iron in patients with iron deficiency defined by TSAT <20%.^[1]

Definitions of iron deficiency by guideline

^{[1] [2] [5]}

The 2018 Australian guideline explains why two ferritin ranges were used.^[5] Ferritin is an acute phase reactant and may rise with inflammation, and a TSAT below 20% indicates functional iron deficiency, with insufficient circulating iron to supply metabolising cells (NHFA/CSANZ 2018).^[5]

^{[1] [2]}

Intravenous iron: the recommendation rows

Intravenous iron rows in heart failure

^{[1] [2] [5]}

Remember the phenotype boundaries: the ESC rows use the 2026 HFrEF definition (LVEF <50%), and the AHA/ACC/HFSA row uses LVEF ≤40%.^[1][2]

The symptom row is the stronger of the two ESC rows.^[1] ESC 2026 reports that trials including AFFIRM-AHF, CONFIRM-HF, FAIR-HF, EFFECT-HF and IRONMAN, which defined iron deficiency by the ferritin rule, showed that intravenous ferric carboxymaltose is safe and effective in improving symptoms and QoL in HF with LVEF <40%–45%.^[1] It adds that data in HFpEF are scarce.^[1]

The hospitalisation benefit is less certain.^[1] Given conflicting results of major trials, the ESC 2026 Task Force says the evidence on strong endpoints is not conclusive.^[1] It says this is primarily due to three factors: the old definition was used for enrolment in almost all trials, the trials differed in populations and in iron doses and timing, and some major trials were affected by the COVID-19 pandemic.^[1] It therefore says ferric carboxymaltose or ferric derisomaltose should be considered in symptomatic HFrEF with iron deficiency to reduce the risk of HF hospitalisation, taking into account that patients with TSAT <20% might benefit most.^[1] Further trials using TSAT <20%, or other criteria that do not rely on ferritin, are warranted.^[1]

AHA/ACC/HFSA 2022 says intravenous repletion of iron has been shown to improve exercise capacity and QoL.^[2] It notes that those trials were underpowered for hard clinical endpoints, while two meta-analyses suggested intravenous iron is associated with a reduction in cardiovascular death and hospitalisations.^[2] It reports that AFFIRM-AHF, a multicentre trial of 1132 patients with EF <50% hospitalised for HF, showed fewer HF hospitalisations with intravenous ferric carboxymaltose than with placebo (RR 0.74; 95% CI 0.58–0.94) but no reduction in cardiovascular death.^[2]

Why not oral iron?

AHA/ACC/HFSA 2022 reports that the IRONOUT HF trial showed no improvement of the kind seen with intravenous iron (exercise capacity and QoL) with oral iron supplementation.^[2] It attributes this to poor absorption of oral iron and its inadequacy to replete iron stores in HF, and concludes that oral iron is not adequate to treat iron deficiency anaemia in HF.^[2] The 2018 Australian guideline says oral iron alters iron stores minimally and did not improve exercise capacity in HFrEF with iron deficiency compared with placebo, probably because of reduced absorption and reduced uptake secondary to the effects of hepcidin.^[5]

Practical points from the 2018 Australian guideline (dated)

• Look for a cause: if iron deficiency is diagnosed, consider investigation for gastrointestinal pathology, including peptic ulcer and malignancy, especially if also anaemic (NHFA/CSANZ 2018).^[5]
• Dose used in trials: intravenous ferric carboxymaltose was evaluated in most randomised studies, usually as one to two doses between 500 and 1000 mg (NHFA/CSANZ 2018).^[5]
• Recheck: intravenous iron should be considered in HFrEF with iron deficiency with or without anaemia; recheck iron studies after 4 months (NHFA/CSANZ 2018).^[5]
• Congested patients: monitor fluid status and favour a lower-volume infusion; long-term effects are uncertain (NHFA/CSANZ 2018).^[5]

^{[1] [2] [5]}

Anaemia

AHA/ACC/HFSA 2022 says routine baseline assessment of every patient with HF includes an evaluation for anaemia.^[2] Anaemia is independently associated with HF disease severity and mortality.^[2]

The 2018 Australian guideline uses the World Health Organization definition: Hb <120 g/L in females and <130 g/L in males.^[5] It says anaemia is present in about one-third of patients with chronic HF.^[5] Iron deficiency is the most common cause, but vitamin B12 and folate deficiency and CKD can contribute, and reversible causes such as blood loss and iron, vitamin B12 or folic acid deficiency should be treated (NHFA/CSANZ 2018).^[5]

Erythropoietin-stimulating agents

Correcting haemoglobin with an erythropoietin-stimulating agent did not help.^[1][2] ESC 2026 reports that in RED-HF, in HFrEF with mild to moderate anaemia, darbepoetin alfa failed to reduce all-cause death or HF hospitalisation and showed an increased risk of thromboembolic events.^[1] AHA/ACC/HFSA 2022 describes a high-quality randomised trial of darbepoetin alfa in 2278 patients that showed no benefit and an increase in thrombotic events, including stroke.^[2]

Erythropoietin-stimulating agents in HF with anaemia

^{[1] [2] [5]}

Diabetes and SGLT2 inhibitors

ESC 2026 says patients with HF and type 2 diabetes (T2DM) have a poorer prognosis than those without it.^[1] The diagnostic process and HF treatment are the same as without T2DM, and there is no evidence that diabetes alters the efficacy of foundational medical therapy (FMT).^[1]

ESC 2026 says SGLT2 inhibitors are recommended in all patients with HF and T2DM, independently of HbA1c or other glucose-lowering agents (text; no class or level given).^[1] The formal ESC row does not depend on diabetes at all: an SGLT2 inhibitor (dapagliflozin or empagliflozin) is recommended in symptomatic HF independent of LVEF to reduce the risk of HF hospitalisation or CV death (Recommendation Table 5, Class I, Level A).^[1]

SGLT2 inhibitor rows for HF with diabetes

^{[1] [2] [3]}

The 2026 cardiovascular-kidney-metabolic (CKM) guideline defines CKM stage 4 as clinical cardiovascular disease, including HF, in people with excess or dysfunctional adiposity, other metabolic risk factors or CKD.^[3] Its row, for CKM stage 4 with T2D and HF, points the same way as the 2022 row for HF with type 2 diabetes, with the same COR 1, LOE A.^[3][2] The 2022 row recommends SGLT2i for the management of hyperglycaemia and to reduce HF-related morbidity and mortality; the CKM row says SGLT2i should be prioritised as the first-line cardioprotective glucose-lowering medications to reduce cardiovascular death and HF hospitalisation.^[2][3]

Safety of SGLT2 inhibitors

ESC 2026 says SGLT2 inhibitors are generally well tolerated but may cause urinary infections and genital fungal infections, such as vulvovaginitis and balanitis, in up to 6.9% of women and 4.8% of men.^[1] They are not indicated in type 1 diabetes because of the risk of diabetic ketoacidosis (reported incidence 2%–3%).^[1] AHA/ACC/HFSA 2022 asks for close monitoring for potential risks, including severe genitourinary infections and, less commonly, diabetic ketoacidosis.^[2]

Other glucose-lowering drugs

• Metformin: no dedicated cardiovascular outcome trials; observational studies reported lower risk of death or HF hospitalisation than with insulin and sulphonylureas; not recommended with eGFR <30 mL/min/1.73 m² or hepatic impairment because of the risk of lactic acidosis (ESC 2026).^[1]
• Metformin (CKM 2026): in T2D with stable HF, eGFR ≥30 mL/min/1.73 m² and HbA1c above the individualised goal, adding metformin to an SGLT2 inhibitor can be beneficial to help achieve glycaemic targets (COR 2a, LOE B-NR); metformin is contraindicated in decompensated HF.^[3]
• Insulin: associated with poorer outcomes in HF in post-hoc trial analyses and registries; if insulin is needed, monitor for worsening HF after starting it (ESC 2026).^[1]
• Saxagliptin and thiazolidinediones: associated with an approximately 30% increased risk of HF hospitalisation, and so contraindicated in HF (ESC 2026).^[1]
• Sulphonylureas: no consistent data in HF (ESC 2026).^[1]
• Semaglutide or tirzepatide: should be added, if not contraindicated, in HFpEF with T2DM, especially if the patient is also obese (ESC 2026 text; no class or level given).^[1]
• Semaglutide or tirzepatide in obesity (ESC 2026 Recommendation Table 18): should be considered in symptomatic HF with LVEF ≥45% and BMI ≥30 kg/m², regardless of diabetes status, to reduce body weight and improve exercise capacity and QoL (Class IIa, Level B1).^[1]
• GLP-1–based therapy (CKM 2026): in T2D, HFpEF and other CKM risk factors, adding GLP-1–based therapy with proven cardiovascular benefit to foundational SGLT2 inhibitor therapy can be beneficial to improve HF symptoms and reduce CKM-related adverse outcomes (COR 2a, LOE B-R).^[3]

On glycaemic targets, the CKM 2026 guideline says an HbA1c between 7% and 8% is felt to be appropriate in T2D with HF.^[3] The 2018 Australian guideline gave a similar band, around 7.1%–8.0%, with gradual glucose lowering.^[5]

Chronic kidney disease

^[1]

ESC 2026 calls CKD a major independent determinant of mortality and morbidity in HF.^[1] CKD might affect optimisation of FMT and is often cited as a reason for its under-use.^[1] Yet in trials, patients with HF and CKD were at higher risk of events while subgroup analyses showed no interaction between drug effects and kidney function.^[1] ESC 2026 therefore says that even in most patients with CKD, starting beta-blockers, ACE-I/ARNI/ARB, SGLT2 inhibitors and MRAs is recommended (text; no class or level given).^[1]

The gap is severe CKD.^[1] ESC 2026 notes that these patients were generally excluded from trials.^[1] AHA/ACC/HFSA 2022 likewise called the effectiveness of guideline-directed therapy in HF with kidney disease uncertain because outcome data are sparse.^[2]

A rising creatinine after starting therapy

ESC 2026 says worsening kidney function in chronic HF is not necessarily associated with worse outcomes.^[1] After starting ACE-I/ARNI/ARB, MRA or SGLT2 inhibitor, a fall in glomerular filtration pressure may lower GFR and raise creatinine; these changes are generally transient, occur despite better outcomes and may delay long-term decline in kidney function.^[1] A transient decrease should not prompt interruption, and a creatinine rise of <50% above baseline is considered acceptable as long as eGFR remains >15 mL/min/1.73 m².^[1]

The CKM 2026 guideline says renin–angiotensin system inhibitors may be associated with a modest acute fall in kidney function, usually due to haemodynamic changes, which is not indicative of harm and may be associated with better long-term outcomes.^[3] In a participant-level pooled analysis of DAPA-HF and DELIVER, ESC 2026 reports that patients whose eGFR fell below 25 mL/min/1.73 m² were at higher risk of later CV events, and continuing dapagliflozin was associated with lower rates of the primary composite outcome.^[1]

^{[1] [5]}

In decompensated HF, ESC 2026 says adverse CV outcomes are observed in patients with worsening kidney function and a poor diuretic response, but not in those with a good diuretic response.^[1]

CKD-specific rows in the 2026 CKM guideline

AHA/ACC/ADA/ASN CKM 2026: CKM stage 4 with CKD and HF

^[3]

The same guideline says further evidence is needed for starting an SGLT2 inhibitor at eGFR <20 mL/min/1.73 m².^[3] It also says dual therapy with more than one renin–angiotensin system inhibitor (ACEi/ARB/ARNI) should be avoided, because it can worsen kidney function and cause angioedema, hyperkalaemia and hypotension (no COR or LOE given).^[3]

ESC 2026 refers readers to the 2026 ESC guideline on cardiovascular disease and CKD for further detail.^[1] That guideline is not held as text for this topic, so none of its rows are used here.

^{[1] [5] [3] [2]}

Hyperkalaemia and potassium binders

ESC 2026 says hyperkalaemia is common in HF, often from comorbidities such as diabetes and CKD, from renin–angiotensin–aldosterone system inhibitors (ACE-I/ARNI/ARB and MRAs), and from HF itself.^[1] It may increase the risk of arrhythmias and death.^[1] Hyperkalaemia, and the fear of inducing it, often results in under-use, dose reduction or discontinuation of these drugs, compromising their cardio-kidney benefit in HF.^[1]

Patiromer and sodium zirconium cyclosilicate remove potassium by exchanging cations, which increases faecal excretion (ESC 2026).^[1] Both have shown favourable results in treating or preventing hyperkalaemia in patients on ACE-I/ARNI/ARB and MRAs, so facilitating continuation or uptitration of those drugs.^[1] Whether binders improve clinical outcomes is still unclear; in REALIZE-K there was a signal towards more HF deterioration with sodium zirconium cyclosilicate than placebo, although the trial was not powered for clinical outcomes.^[1] Potential adverse effects include gastrointestinal symptoms (nausea, constipation, diarrhoea), hypomagnesaemia with patiromer and oedema with sodium zirconium cyclosilicate.^[1]

Potassium binders by guideline

^{[1] [2] [3] [5]}

Read the two North American rows by population.^[2][3] The 2022 row covers patients with HF who experience hyperkalaemia (potassium ≥5.5 mEq/L) while taking a RAASi, and calls the effectiveness of binders to improve outcomes by facilitating continuation of RAASi therapy uncertain.^[2] For adults with CKD, HFrEF and eGFR >30 mL/min/1.73 m², the 2026 CKM row says novel oral potassium-binding agents may be reasonable to reduce risk of hyperkalaemia and allow use of RAAS inhibition; unlike the 2022 row, it sets no potassium threshold.^[3][2] The CKM guideline adds that few patients with eGFR <30 mL/min/1.73 m² and HF were included in the binder trials.^[3] It also says sodium zirconium cyclosilicate may increase the risk of HF events, and current data do not show whether that risk is greater than with patiromer.^[3]

AHA/ACC/HFSA 2022 lists hypomagnesaemia with patiromer and oedema with sodium zirconium cyclosilicate as adverse effects.^[2] In the 2018 Australian guideline, renin–angiotensin–aldosterone inhibitors should be temporarily stopped when acute hyperkalaemia occurs (K >6.0 mmol/L) and carefully reintroduced once potassium normalises.^[5] That guideline also cites a nationwide registry in which a serum potassium of 4.2–4.7 mmol/L was associated with the lowest mortality in chronic HF.^[5]

Sleep-disordered breathing

ESC 2026 says sleep-disordered breathing is found in over one-third of patients with HF and is even more prevalent in decompensated HF.^[1] It includes obstructive sleep apnoea (OSA), central sleep apnoea (CSA) and mixed disease, and it worsens disease progression and prognosis.^[1] The 2018 Australian guideline gave a higher figure, 50%–75% of patients with HF.^[5]

AHA/ACC/HFSA 2022 says daytime sleepiness, typically a feature of OSA, may not reflect the degree of sleep-disordered breathing in HF.^[2] Because OSA and CSA are treated differently and can co-occur, sleep studies can inform decisions.^[2] ESC 2026 says patients with suspected sleep-disordered breathing should be referred for overnight polysomnography to make the diagnosis and document the predominant type, central or obstructive.^[1] Treatment includes correcting underlying causes when identified (ESC 2026).^[1]

Sleep-disordered breathing rows in HF

^{[1] [2] [5]}

The two adaptive servo-ventilation trials

The type of apnoea decides which ESC row applies.^[1] ESC 2026 bases its Class III row on SERVE-HF, which showed an increase in both all-cause and CV death in chronic HF with LVEF ≤45% and sleep-disordered breathing with predominant CSA.^[1] AHA/ACC/HFSA 2022 says adaptive servo-ventilation was associated with increased mortality in two randomised trials in HFrEF with CSA, and that the weight of evidence does not support its use for CSA in HFrEF.^[2]

ADVENT-HF randomised 731 patients with HF, LVEF ≤45% and sleep-disordered breathing, mostly OSA (73%), to standard optimal treatment with or without adaptive servo-ventilation (1:1).^[1] Over a mean 3.6 years, adaptive servo-ventilation had a neutral effect on the primary composite of all-cause death, first CV hospitalisation, new AF or flutter and appropriate ICD shock.^[1] It did improve sleep quality and structure, health-related QoL and symptoms, which is the basis of the ESC Class IIb row for predominant OSA.^[1]

In predominant OSA, ESC 2026 says nocturnal hypoxaemia can be treated with nocturnal oxygen, continuous positive airway pressure (CPAP), bilevel positive airway pressure or adaptive servo-ventilation.^[1] When sleep-disordered breathing is caused by CSA, implantable phrenic nerve stimulation was found to be safe and effective in reducing the apnoea–hypopnoea index in a small randomised trial (ESC 2026).^[1] The 2018 Australian guideline says the primary aim in predominant CSA should be to treat the HF.^[5]

^{[1] [2]}

Malnutrition, cachexia, sarcopenia and frailty

ESC 2026 separates three wasting states in its supplementary data (Table S17).^[1] For cachexia, Table S17 gives an 18-month mortality of 50%, against 17% in HF patients without cachexia.^[1]

Malnutrition, cardiac cachexia and sarcopenia (ESC 2026, supplementary Table S17)

^[1]

AHA/ACC/HFSA 2022 says patients with advanced HF have the greatest risk of developing cachexia or malnutrition, although nutritional counselling in HF typically focuses on restricting sodium and fluid.^[2] It lists cardiac cachexia among the clinical indicators of advanced HF in its Table 18.^[2] The 2018 Australian guideline says referral to a dietitian may be beneficial, particularly with reduced appetite or cardiac cachexia.^[5]

^[1]

Frailty

ESC 2026 defines frailty as a multidimensional, dynamic and potentially reversible state, related to but independent of age, that makes people more vulnerable to stressors and at higher risk of poor outcomes.^[1] A frailty score including four domains (clinical, functional, psychocognitive and social) has recently been proposed.^[1]

Frailty might affect disease management and is associated with higher rates of death and hospitalisation and reduced health-related QoL, whichever tool was used to assess it (ESC 2026).^[1] It is particularly prevalent in older adults with HF, and when it is suspected or identified a multidisciplinary approach to individualised management is warranted.^[1] AHA/ACC/HFSA 2022 cites a meta-analysis of 29 cohort studies in which frailty was associated with an increased risk of all-cause mortality and hospitalisation.^[2] The 2018 Australian guideline estimated its prevalence in HF at 40%–50%, with no consensus on which frailty instrument to use or when.^[5]

Depression, anxiety and cognitive impairment

ESC 2026 says anxiety and depression are common in chronic disabling conditions such as HF and need to be identified promptly.^[1] Depression affects 20% of patients with HF, may affect adherence to FMT, is more prevalent in women, and is associated with worse clinical status and poorer prognosis.^[1] AHA/ACC/HFSA 2022 calls depression a risk factor for poor self-care, rehospitalisation and all-cause mortality in HF.^[2]

Diagnosis is harder than it looks.^[1] ESC 2026 says it typically relies on standardised questionnaires and clinical interviews, and that symptom overlap can complicate diagnosis, as both HF and depression may present with cognitive issues, such as difficulty concentrating, and physical symptoms, such as fatigue.^[1] The 2018 Australian guideline says screening for depression should be undertaken with a validated questionnaire, such as the Patient Health Questionnaire-9 (PHQ-9); alternatively, the PHQ-2 can be used as an initial screen, and if either question is positive, one may proceed to the PHQ-9.^[5]

Assessment and screening rows for depression and frailty

^{[1] [6] [2]}

The two ESC rows sit side by side.^[1][6] The HF guideline row covers anxiety, depression and frailty in HF at Class IIa; the cardiac rehabilitation row covers psychological screening for depression and anxiety in patients with heart disease at Class I.^[1][6]

Treatment

• Cognitive behavioural therapy: significant favourable long-term (4–9 months) reduction of anxiety and depression and better QoL than in untreated patients (ESC 2026 HF guideline).^[1]
• Psychological interventions and cognitive behaviour therapy (ESC 2026 cardiac rehabilitation): psychological interventions are recommended in CAD and HF to improve mental functioning (reduce anxiety and depressive symptoms) and HRQoL (Class I, Level B1); cognitive behaviour therapy is recommended in CAD, HF and after ICD implantation to improve mental functioning (depression, anxiety, HRQoL) and reduce cardiovascular risk (Class I, Level B1).^[6]
• Telemonitoring and digital psychosocial education (ESC 2026 cardiac rehabilitation): telemonitoring systems and computer or cell phone-based psychosocial education and training should be considered in CAD and HF to reduce anxiety and depression symptoms (Class IIa, Level B1).^[6]
• Sertraline and escitalopram: safety demonstrated, but without a significant reduction in depression compared with placebo (ESC 2026).^[1]
• No agreed best therapy: ESC 2026 says there is still no consensus on the best therapy for HF with depression, and cognitive impairment has also been reported in these patients.^[1]
• Tricyclic antidepressants: should be avoided for depression in HF because they may cause hypotension, worsening HF and arrhythmias (ESC 2026).^[1]
• Australian practice advice (2018): SSRIs are the safest choice if drugs are used; avoid tricyclic antidepressants; citalopram and mirtazapine can prolong the QTc and cause torsades de pointes (NHFA/CSANZ 2018).^[5]

Gout, hyperuricaemia and NSAIDs

ESC 2026 says hyperuricaemia and gout attacks can be frequent in HF, mainly caused or precipitated by diuretic treatment.^[1] Allopurinol is recommended as the first choice to lower uric acid chronically, whereas colchicine can be used for acute attacks (ESC 2026 text; no class or level given).^[1] The 2018 Australian guideline put hyperuricaemia at 37%–54% of patients with HF.^[5]

The common trap is the anti-inflammatory drug.^[1] ESC 2026 says NSAIDs and COX-2 inhibitors are not recommended in HF because they increase the risk of HF worsening and HF hospitalisation (Recommendation Table 22, Class III, Level B2).^[1] Its text adds that they may precipitate decompensation and worsen kidney function.^[1]

• Acute gout (NHFA/CSANZ 2018): treat with colchicine or a short course of oral prednisolone; avoid or minimise NSAIDs and COX-2 inhibitors.^[5]
• Prevention (NHFA/CSANZ 2018): use allopurinol after an acute episode has completely resolved, aiming for serum urate below 0.36 mmol/L (6 mg/dL), or 0.30 mmol/L (5 mg/dL) if tophi are present.^[5]
• Asymptomatic hyperuricaemia (NHFA/CSANZ 2018): does not require treatment.^[5]

Atrial fibrillation in heart failure: pointers

ESC 2026 says HF and AF frequently coexist: AF occurs in more than half of patients with HF, and HF in more than one-third of patients with AF.^[1] Their coexistence is associated with a high risk of death, HF hospitalisation and stroke regardless of LVEF.^[1] Management includes identifying triggers, preventing embolic events, managing HF, and rate or rhythm control.^[1]

Several triggers are comorbidities on this page.^[1] ESC 2026 lists precipitating factors such as hyperthyroidism, alcohol and other toxic agents, valve disease, infection, diabetes, uncontrolled hypertension, obesity, sleep disorders and volume overload, which should be routinely identified and appropriately managed.^[1] All patients with HF and AF should receive optimal HF therapy regardless of AF, and there is insufficient evidence to favour rhythm control over rate control.^[1]

ESC 2026: AF in patients with HF (selected rows)

^[1]

ACC/AHA/ACCP/HRS 2023 AF guideline: management of AF in patients with HF (selected rows)

^[4]

• Related topic: Atrial fibrillation.

Evidence, guidelines and regional differences

The ESC 2026 HF guideline and the 2022 AHA/ACC/HFSA HF guideline are the two core sources on this page.^[1][2] For diabetes and CKD in HF, the 2026 AHA/ACC/ADA/ASN CKM guideline is the newer North American source checked, and for AF in HF the 2023 ACC/AHA/ACCP/HRS AF guideline.^[3][4]

^{[1] [2] [3] [5]}

ANZ practice

The Australian HF guideline from the National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand (NHFA/CSANZ) dates from 2018.^[5] In 2018 it reported that trials of SGLT2 inhibitors in HF, with or without diabetes, were still ongoing, so its diabetes advice predates the SGLT2 rows above.^[5]

• In HFrEF with persistent symptoms despite optimised therapy, iron studies should be performed and, if the patient is iron deficient, intravenous iron should be considered, to improve symptoms and quality of life (strong recommendation for; moderate quality of evidence).^[5]
• Erythropoietin should not be used routinely for anaemia in HF because of an increased risk of thromboembolic adverse events (strong recommendation against; moderate quality of evidence).^[5]
• Thiazolidinediones are not recommended in HF because of the risk of worsening HF (weak recommendation against; moderate quality of evidence).^[5]
• Adaptive servoventilation is not recommended in HFrEF with predominant central sleep apnoea because of increased all-cause and cardiovascular mortality (strong recommendation against; moderate quality of evidence).^[5]
• If sleep apnoea is suspected, referral to a sleep physician is indicated; predominant OSA with nocturnal hypoxaemia and an apnoea/hypopnoea index over 30 per hour may be treated with nocturnal oxygen, CPAP, BiPAP or adaptive servo-ventilation to improve quality of life and decrease sleepiness (practice advice).^[5]

Guidelines checked

A row called the current one is so among the guidelines checked for this topic:

• Sources of the rows and statements used: ESC heart failure (2026, with its supplementary data); ESC cardiac rehabilitation (2026, psychosocial rows only); AHA/ACC/HFSA heart failure (2022); AHA/ACC/ADA/ASN cardiovascular-kidney-metabolic syndrome (2026); ACC/AHA/ACCP/HRS atrial fibrillation (2023); NHFA/CSANZ heart failure (2018).^{[1][6][2][3][4][5]}
• The 2026 ESC guideline on cardiovascular disease and chronic kidney disease is not held as text for this topic; its rows were not checked.

Exam pearls

• Iron deficiency: ferritin <100 ng/mL, or 100–299 ng/mL with TSAT <20% (the trial definition); ESC 2026 supports TSAT <20% alone.^[1]
• ESC 2026 intravenous iron in symptomatic HFrEF with iron deficiency: Class I, Level B1 for symptoms and QoL; Class IIa, Level B1 for HF hospitalisation, with ferric carboxymaltose or ferric derisomaltose.^[1]
• Oral iron: IRONOUT HF showed no improvement of the kind seen with intravenous iron (exercise capacity and QoL) with oral iron supplementation (AHA/ACC/HFSA 2022).^[2]
• Adaptive servo-ventilation in HFrEF: not recommended with predominant CSA because of an increased risk of CV and all-cause death (ESC 2026, Class III, Level A; SERVE-HF); may be considered with predominant OSA to improve sleep quality, QoL and symptoms (Class IIb, Level C; ADVENT-HF).^[1]
• Saxagliptin and thiazolidinediones are contraindicated in HF (ESC 2026); NSAIDs and COX-2 inhibitors are not recommended because they increase the risk of HF worsening and HF hospitalisation (Class III, Level B2).^[1]
• Cachexia can be defined as weight loss >7.5% in the absence of oedema; 50% 18-month mortality vs 17% in non-cachectic HF (ESC 2026, Table S17).^[1]
• Depression affects 20% of patients with HF; sertraline and escitalopram were safe but did not significantly reduce depression versus placebo (ESC 2026).^[1]

References6ShowHide

1. [1]Køber L, et al. 2026 ESC Guidelines for the management of heart failure. Eur Heart J, 2026.PMID 42661420
2. [2]Heidenreich PA, 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.PMID 35363499
3. [3]Ndumele CE, et al. 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol, 2026.PMID 42265997
4. [4]Joglar JA, et al. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation, 2024.PMID 38033089
5. [5]Atherton JJ, et al. National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Guidelines for the Prevention, Detection, and Management of Heart Failure in Australia 2018. Heart Lung Circ, 2018.PMID 30077227
6. [6]Bäck M, et al. 2026 ESC Guidelines on cardiac rehabilitation. Eur Heart J, 2026.PMID 42661418