Rediscovering digitalis in heart failure with reduced ejection fraction: Current evidence and expert survey on...

Digitalis glycosides are among the oldest therapies for heart failure (HF) with reduced ejection fraction, yet their contemporary role remains debated. Clinical data now indicate that the predominant clinical benefits of digitalis appear to derive from autonomic and neurohormonal modulation (enhanced vagal activity, attenuation of sympathetic drive, and suppression of renin-angiotensin-aldosterone activation) rather than from classical positive inotropy. At low serum concentrations, these effects translate into improved rate control, reduced congestion, and fewer decompensations with a lower risk of toxicity, whereas higher "inotropic" levels are associated with proarrhythmia and excess mortality. This review summarises the mechanistic and pharmacokinetic differences between digoxin and digitoxin, appraises evidence from PROVED, RADIANCE and DIG, and integrates emerging outcome data from DIGIT-HF, which showed that low-dose digitoxin added to contemporary guideline-directed therapy reduces the composite of death or HF hospitalisation. Finally, this review also provides valuable insights from a 2025 survey of Portuguese HF specialists into real-world clinical practice regarding digitalis use. With 55 experts responding, the survey highlights a predominant, selective application of digitalis glycosides, primarily after optimization of foundational HF therapies, consistent with guideline recommendations. Perceived benefits focus on rate control and symptom relief, while concerns about toxicity, the need for monitoring, and gaps in modern trial evidence continue to restrict broader adoption. Together, current data support a repositioning of digitalis as a low-dose, concentration-guided, neurohormonal modulator and rate-control agent for carefully selected patients with HF with reduced ejection fraction, an approach that ongoing and future trials should further refine.