Management of refractory heart failure

Definition. Refractory (advanced or stage D) heart failure is persistent severe symptoms at rest or on minimal exertion (NYHA class III–IV) despite optimal guideline-directed medical and device therapy, with objective severe cardiac dysfunction, recurrent hospitalisation or need for intravenous inotropes, and severely impaired exercise capacity. Prognosis is poor — one-year mortality approaches 50%.

Step 1 — confirm it is truly refractory. Before labelling refractory failure, verify the diagnosis and the ejection fraction, and exclude a reversible or under-treated cause: myocardial ischaemia, severe valve disease (especially aortic stenosis and mitral regurgitation), uncontrolled atrial fibrillation or other arrhythmia, anaemia and iron deficiency, thyroid dysfunction, infection, cardiac amyloidosis, sleep apnoea, chronic kidney disease and non-adherence. Review the drug chart and stop the aggravating drugs — NSAIDs, corticosteroids, thiazolidinediones, verapamil/diltiazem, class I antiarrhythmics and excessive negative inotropes.

Optimise and re-sequence medical therapy. Ensure the patient is on maximally tolerated four-pillar therapy. If blood pressure limits uptitration, reduce or stop non-prognostic vasodilators (nitrates, alpha-blockers, calcium channel blockers) first. Add digoxin for symptom control and reduced hospitalisation, and ivabradine if the sinus rate remains ≥ 70/min. Consider hydralazine plus isosorbide dinitrate where ACE inhibitors or ARNIs are not tolerated. Correct iron deficiency with intravenous ferric carboxymaltose, which improves symptoms and reduces hospitalisation.

Manage diuretic resistance. This is the central practical problem. Steps: restrict sodium and fluid; switch oral to intravenous loop diuretic (bioavailability is unpredictable in gut oedema) as bolus or infusion; double the dose rather than increase the frequency (there is a threshold effect); add sequential nephron blockade with a thiazide-type diuretic (metolazone or a thiazide) given 30 minutes before the loop diuretic; add or continue an MRA; and consider acetazolamide or an SGLT2 inhibitor for additional natriuresis. Monitor daily weight, strict fluid balance, renal function and electrolytes; a modest rise in creatinine during effective decongestion is acceptable and should not automatically stop treatment. Ultrafiltration is reserved for genuinely diuretic-resistant congestion.

Advanced therapies and referral. Refer to a specialist heart failure service to consider: cardiac resynchronisation therapy if the QRS is broad; revascularisation or valve intervention (including TAVI or transcatheter edge-to-edge mitral repair) where indicated; continuous intravenous inotropes (dobutamine, milrinone, levosimendan) as a bridge or for palliation — these improve symptoms but increase arrhythmia and mortality; left ventricular assist devices, which have been used in older patients as destination therapy in carefully selected cases; and cardiac transplantation, which is essentially precluded by advanced age. In the very old, the decision hinges on frailty, cognition, comorbidity and patient goals rather than on age alone.

Palliative care and end-of-life planning. This is the highest-yield section for a geriatric examination. Recognise the terminal phase — repeated admissions, cachexia, hypotension limiting therapy, worsening renal function, refractory symptoms. Provide opioids (low-dose morphine) for refractory breathlessness, oxygen if hypoxaemic, treatment of anxiety and depression, and management of pain, nausea and constipation. Undertake advance care planning, agree a ceiling of treatment and resuscitation status, and discuss ICD deactivation explicitly. Simplify the drug regimen, deprescribe drugs whose time-to-benefit exceeds life expectancy (statins, some prognostic agents), continue diuretics for symptom relief, and support the family and caregivers, whose physical and emotional health should be assessed as an outcome in their own right.

Decongestion strategy has been sharpened by two randomised trials now embedded in the 2023 ESC focused update. ADVOR showed that adding intravenous acetazolamide 500 mg daily to loop diuretics significantly increased successful decongestion and reduced length of stay in acute decompensated heart failure, and CLOROTIC showed that adding hydrochlorothiazide to a loop diuretic improved weight loss and diuretic response. Combined with the STRONG-HF strategy of rapid post-discharge uptitration with close follow-up (which reduced death and readmission), the modern approach to refractory congestion is early combination diuretic therapy plus intensive early follow-up, rather than escalating a loop diuretic alone.