HFrEF management

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quadruple therapy — the backbone

All four classes should be initiated in every HFrEF patient unless contraindicated. Start low, go slow — but get all four on board before maximising any single agent.

Class	Agents	Key initiation points	Target dose
ARNI	sacubitril/valsartan	first-line over ACEi/ARB if new dx or symptomatic on ACEi/ARB; 36h ACEi washout required; can start de novo in hospital	97/103 mg BID
beta-blocker	bisoprolol, carvedilol, metoprolol XL	start when euvolaemic and haemodynamically stable; do NOT start in NYHA IV; use only evidence-based agents	bisoprolol 10 mg, carvedilol 25 mg BID, metoprolol XL 200 mg
MRA	spironolactone, eplerenone	monitor K⁺ and Cr within 1 week, then regularly; hold if K⁺ >5.5 or eGFR <30	spironolactone 50 mg, eplerenone 50 mg
SGLT2i	dapagliflozin, empagliflozin	regardless of diabetes status; no dose titration; do not start if eGFR <20	dapa 10 mg, empa 10 mg

Titration strategy:

• titrate every 2–4 weeks
• goal: target doses of all agents by 3–6 months
• tolerability-limiting factors: hypotension (reduce non-HF antihypertensives first), hyperkalaemia (dietary counselling, adjust MRA), bradycardia (reduce BB if HR <50 and symptomatic)

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additional therapies — phenotype-driven

Indication	Therapy	Evidence
sinus rhythm + resting HR >70 despite maximised BB	ivabradine	SHIFT (2010)
recent HF hospitalisation (within 6 months) on GDMT	vericiguat	VICTORIA (2020)
Black patients on optimal GDMT	hydralazine + ISDN (add to, not replace, ARNI/ACEi/ARB)	A-HeFT (2004)
iron deficiency: ferritin <100 or ferritin 100–299 + TSAT <20%	IV iron (ferric carboxymaltose)	AFFIRM-AHF (2020)
congestion	loop diuretics — symptom relief, no mortality benefit	see diuretic therapy in acute heart failure

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drugs to avoid in HFrEF

Drug / Class	Why
non-DHP CCBs (verapamil, diltiazem)	negative inotropy → worsens HF
DHP CCBs other than amlodipine	less safety data; amlodipine OK for HTN/angina
thiazolidinediones (pioglitazone, rosiglitazone)	fluid retention, increased HF hospitalisation
saxagliptin	increased HF hospitalisation — SAVOR-TIMI 53
NSAIDs	Na⁺/water retention, blunt diuretic response, worsen renal function
dronedarone if NYHA III–IV	increased mortality — ANDROMEDA

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device therapy

ICD — primary prevention

Aetiology	LVEF	NYHA	Recommendation
ischaemic	≤35%	II–IV	class I
ischaemic	≤30%	I	class I
non-ischaemic	≤35%	II–III	class I

CRT — strong recommendation

Criteria	All required
rhythm	sinus
symptoms	NYHA II–III (or ambulatory IV)
GDMT	optimised
LVEF	≤35%
ECG	typical LBBB + QRS ≥130 ms

Weaker indications (class IIa/IIb):

• non-LBBB + QRS ≥150 ms
• permanent AF (ensure biventricular pacing >99% — may need AV node ablation)
• patients requiring chronic RV pacing (upgrade to CRT)

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when to refer — “I NEED HELP”

Letter	Criterion
I	IV inotropes needed
N	NYHA IIIB / IV
E	end-organ dysfunction
E	EF ≤35%
D	defibrillator shocks
H	hospitalisations >1 for HF
E	edema despite escalating diuretics
L	low SBP ≤90 mmHg
P	progressive GDMT intolerance