For years, low magnesium has carried a reputation for worsening outcomes in heart failure, often prompting routine correction in clinic. Yet new data from the large GALACTIC-HF trial turn that assumption on its head, suggesting that high, not low, magnesium is the more potent prognostic signal in HFrEF outpatients.
GALACTIC-HF: Modern HFrEF Cohort with Rigorous Outcomes
GALACTIC-HF was a randomized, double-blind, multicentre, event-driven trial evaluating omecamtiv mecarbil versus placebo in patients with symptomatic heart failure and left ventricular ejection fraction ≤35%. The primary endpoint was a composite of first worsening HF event or cardiovascular death. The results were published in the European Heart Journal.
Among 6147 outpatients with baseline serum magnesium data, 17.6% had hypomagnesaemia (<0.75 mmol/L), 71.7% fell within the normal range, and 10.7% had hypermagnesaemia (>0.95 mmol/L).
Hypermagnesaemia Carries the Highest Event Rates
When event rates were expressed per 100 person-years, patients with high magnesium clearly stood out. The primary composite outcome occurred at a rate of 34.9 (95% CI 31.2–39.0) in those with hypermagnesaemia, compared with 21.5 (95% CI 19.4–23.8) in hypomagnesaemia and 20.9 (95% CI 19.9–22.0) in the normal magnesium group. Similar patterns emerged for the individual components of the primary outcome and for all-cause mortality, consistently pointing to excess risk in the high-magnesium subgroup.
Sudden Death and VT: No Signal Across Magnesium Levels
Contrary to traditional teaching that links magnesium abnormalities to arrhythmia risk, GALACTIC-HF did not show differences in sudden death or ventricular tachyarrhythmia incidence across low, normal, and high magnesium strata. The incidence of these arrhythmic outcomes was similar among all three groups, suggesting that serum magnesium in this range is not a strong discriminator for ventricular arrhythmia risk in a treated HFrEF population.
By contrast, the risk of death from worsening heart failure was highest in those with hypermagnesaemia, aligning magnesium more with disease severity and HF-related outcomes than with fatal arrhythmias.
Practice Implications: Rethinking Routine Magnesium Correction
The authors conclude that 10.7% of outpatients with HFrEF had hypermagnesaemia, and this abnormality was associated with a higher risk of the primary composite outcome compared with normal magnesium concentrations. Abnormal magnesium was not associated with a higher risk of sudden death or ventricular tachyarrhythmias, challenging the reflexive use of magnesium correction as an antiarrhythmic protective measure in this setting.
Most importantly, these findings do not support routine correction of hypomagnesaemia in stable HFrEF outpatients solely for prognostic benefit. Instead, they highlight hypermagnesaemia as a potential marker of higher-risk heart failure, more closely tied to HF progression than to ventricular arrhythmias.