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GDMT Anti-arrhythmic Effects — EECC MCQ

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ModerateHeart FailureGDMT Anti-arrhythmic EffectsEECC

A 55-year-old man with HFrEF and LVEF 22% has recurrent ventricular arrhythmias (NSVT runs on Holter, frequent PVCs). He is on bisoprolol 10 mg, sacubitril/valsartan, eplerenone, and dapagliflozin. Which GDMT component has the most potent anti-arrhythmic effect?

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Correct answer: C — Beta-blockers have the strongest anti-arrhythmic effect in HFrEF — they reduce sympathetic activation, raise the VF threshold, and are the only GDMT component with a primary mechanism of SCD reduction (35-45% SCD reduction in CIBIS-II and MERIT-HF)

All four pillars of GDMT reduce SCD to varying degrees, but beta-blockers have the most potent anti-arrhythmic effect: (1) Beta-blockers: 35-45% SCD reduction (CIBIS-II, MERIT-HF, COPERNICUS — the primary mechanism of their early mortality benefit is SCD prevention through increased VF threshold, reduced sympathetic drive, and anti-ischaemic effects); (2) MRA: ~25-30% SCD reduction (RALES — mechanism includes anti-fibrotic effects reducing arrhythmic substrate and electrolyte stabilisation); (3) ACEi/ARNI: ~15-20% SCD reduction (neurohormonal modulation, anti-remodelling); (4) SGLT2i: emerging data suggest SCD reduction (~10-15% in meta-analyses, possibly through anti-fibrotic and metabolic mechanisms). The combined effect of quadruple therapy on SCD is estimated at 50-60% reduction. Despite this, ICD remains indicated when LVEF is ≤35% on GDMT, as residual SCD risk persists.

Reference: ESC (2023): HF Guidelines; ESC (2022): VA/SCD Guidelines