HFrEF — structured viva

Stem

Practice scenario. You are the consultant reviewing a 61-year-old woman with new symptomatic heart failure, NYHA II, and an LVEF of 45%. She already takes ramipril for hypertension. She has had no ventricular arrhythmia and has no pacing indication. Your registrar questions both the diagnosis and the plan to start four drug classes together.^[1]

Branch A — Is this HFrEF?

Examiner: An LVEF of 45%. HFrEF or not?^[1]

Strong answer: Under the 2026 ESC guideline, yes. HFrEF needs current or prior symptoms and/or signs of HF with an LVEF below 50%, and HFmrEF has been removed.^[1] Among the reasons ESC gives, HFmrEF has a similar aetiology to HFrEF, and its pathophysiology (reduced contractility) is more similar to HFrEF than to HFpEF. Its medical treatment efficacy is more similar to HFrEF than HFpEF, and many patients at 41–49% may experience a deterioration in LVEF.^[1] AHA/ACC/HFSA 2022 keeps HFrEF at 40% or less and would call her HFmrEF, provided there is evidence of spontaneous or provokable raised LV filling pressures, such as an elevated natriuretic peptide.^[2] I would be candid that no large prospective RCT has been performed exclusively at LVEF 41–49%; these patients appear to respond to FMT like those below 40%.^[1]

Branch B — Why four drugs, and why now?

Examiner: Justify each class and defend starting them together.^[1]

Strong answer: FMT for HFrEF is a beta-blocker, an ACE-I or ARNI (an ARB if neither is tolerated), an MRA and an SGLT2 inhibitor, each Class I, level A in ESC 2026 for symptomatic HFrEF (the beta-blocker in stable patients).^[1] The trials behind them enrolled lower LVEF: PARADIGM-HF, DAPA-HF, EMPEROR-Reduced and MERIT-HF 40% or less; CIBIS-II, RALES and EMPHASIS-HF 35% or less.^{[4][5][6][9][10][12][13][2]} PARADIGM-HF: sacubitril–valsartan versus enalapril, HR 0.80.^[4][2] MERIT-HF and CIBIS-II: beta-blocker mortality RR 0.66 and HR 0.66.^[9][10] RALES: spironolactone mortality RR 0.70; EMPHASIS-HF: eplerenone in NYHA II, primary outcome HR 0.63 (death HR 0.76).^[12][13][2] DAPA-HF HR 0.74 and EMPEROR-Reduced HR 0.75.^[5][6] No sequence is favoured, so by consensus FMT can be commenced together, with individual variations based on clinical assessment, as soon as HFrEF is diagnosed. Uptitration at least every 1–2 weeks towards trial target doses, guided by symptoms, vital signs and laboratory findings, is Class I, level C.^[1]

Examiner follow-up: Why do these drugs work at all?^[24]

Strong answer: Falling cardiac output activates the sympathetic system and RAAS. Chronic activation causes haemodynamic stress and is one of the main mechanisms of progression, which is why neurohormonal antagonism is the cornerstone of treatment.^[24] Beta-blockers reverse the neurohumoral effects of the sympathetic nervous system.^[27]

Branch C — The ARNI switch

Examiner: She is on ramipril. Convert her.^[1]

Strong answer: Switching from ACE-I or ARB to ARNI in symptomatic HFrEF is Class I, level B1.^[1] Stop ramipril and wait at least 36 h before sacubitril–valsartan to minimise angio-oedema; AHA/ACC/HFSA 2022 sets the same minimum of at least 36 hours.^[1][2] Table 11 start is 49/51 mg b.i.d. with a target of 97/103 mg b.i.d. A 24/26 mg start is an option with a history of symptomatic hypotension, in ACE-I-naive patients or with eGFR 30–60.^[1]

Branch D — Devices

Examiner: When does she see the device team?^[1]

Strong answer: Not now. At LVEF 45% she meets neither the primary-prevention ICD criteria nor the QRS-based CRT criteria, which need LVEF 35% or less; she has no ventricular arrhythmia and no pacing indication.^[1] If LVEF falls to 35% or less despite at least 3 months of optimal FMT, an ICD becomes relevant for symptomatic NYHA II/III patients expected to survive more than 1 year with good functional status. It should be considered for non-ischaemic aetiology (Class IIa, level B1) and is recommended for ischaemic aetiology outside 40 days of MI (Class I, level B1).^[1] SCD-HeFT (NYHA II–III, LVEF 35% or less) showed a 23% mortality reduction with ICD versus placebo, and no survival benefit from amiodarone.^[14][1][2] CRT is Class I, level A for symptomatic HFrEF with LVEF 35% or less despite optimal FMT, in sinus rhythm with LBBB and QRS 150 ms or more. With QRS below 130 ms and no indication for pacing due to high-degree AV block it is Class III, level A.^[1]

Branch E — Kidney function and potassium

Examiner: After uptitration her creatinine rises 25%, eGFR is 52 mL/min/1.73 m², and potassium reaches 5.7 mmol/L. Stop the MRA?^[1]

Strong answer: The creatinine rise is considered acceptable: under 50% with eGFR above 15 mL/min/1.73 m².^[1] For potassium above 5.5 mEq/L on an MRA, I recheck first; dose reduction or a temporary pause may follow, and the MRA is restarted once hyperkalaemia resolves. ESC adds that severe hyperkalaemia (above 5.5 or above 6 mmol/L) should lead to temporary down-titration or discontinuation of MRAs and/or ARNI/ACE-I/ARB.^[1] Misreading kidney function is a leading cause of under-dosing.^[1]

Branch F — Her LVEF falls

Examiner: A year later, despite FMT, her LVEF has fallen to 30%. On bisoprolol 5 mg she is in sinus rhythm at 76 beats/min and still symptomatic. Ivabradine?^[1]

Strong answer: Not yet. Beta-blockers go to target first; bisoprolol's target is 10 mg daily.^[1] ESC notes that only 25% of SHIFT patients were on optimal beta-blocker doses.^[1][17] Ivabradine is Class IIa, level B1 for symptomatic HFrEF with LVEF 35% or less, sinus rhythm and resting heart rate above 70 b.p.m. on the highest tolerated ACE-I/ARNI, MRA, SGLT2-I and beta-blocker.^[1] In SHIFT (symptomatic HF, LVEF 35% or lower, sinus rhythm at 70 beats/min or more, HF admission within the previous year), ivabradine reduced its composite of cardiovascular death or admission for worsening HF (HR 0.82), mainly through fewer admissions.^[17] At LVEF 30% the device questions from Branch D now apply.^[1]

Branch G — Her LVEF improves

Examiner: Two years on, her LVEF is 55%, she is asymptomatic, and she wants to stop.^[1]

Strong answer: I advise continuing FMT at the highest tolerated doses (Class I, level C); ESC 2026 states there is no solid evidence that such improvement reflects actual recovery rather than remission.^[1] In TRED-HF, which enrolled HFrEF with DCM whose LVEF had improved, LV volume had normalised and NT-proBNP was below 250 ng/L, withdrawal led to relapse in 40% within 6 months. The small open-label CATHEDRAL-HF pilot (60 patients, carvedilol continued) found no higher relapse rate with phased withdrawal.^[1] Gradual discontinuation, under frequent clinical, laboratory and imaging surveillance, is only a Class IIb, level C option, to accommodate patient preference, in highly selected asymptomatic patients with complete normalisation of LV function, volume and natriuretic peptides after specific treatment of a reversible cause.^[1]