By inhibiting sodium/potassium ATP-ase , there is an increase in intracellular sodium, which in turn promotes calcium influx. This leads to:

• Increased contractile force of the myocyte (positive inotropic effect).
• Direct inhibition of AV conduction (negative chronotropic effect).
• Increased vagal tone.

• Slowing of the heart rhythm.
• Enhanced contraction (inotropy) of the myocardium?

Trials: DIG (NEJM, 1997)

• No effect on mortality
• Reduction of hospitalizations for heart failure.
• Reduction of symptoms and better quality of life?

Note: if the DIG trial had used the combined endpoint of mortality and HF hospitalizations (as is common for the large HF trials) of recent years, DIG would have shown positive effects.

Note: The background therapy during the DIG trial was only ACE inhibitors and diuretics and was therefore not comparable to the current way of treating heart failure patients. For this reason, the data from the DIG trials are increasingly being questioned. Two trials with digitalis in heart failure patients treated with current standard therapy are expected in the near future, the DIGIT-HF and DECISION trials. To be continued.

• Chronic heart failure + atrial fibrillation with insufficient rate control (resting heart rate > 90-110/min).
• Refractory severe heart failure – NYHA III-IV independent of underlying rhythm.

• For rate control in atrial fibrillation: digoxin can be charged with, for example, 0.5 mg (intravenous or peroral) and then after 4 hours, if necessary, additional 0.125 or 0.25 mg. Maintenance dose per os further 0.125 or 0.250 mg per day.
• For use in chronic refractory heart failure: 0.125 or 0.250 mg per day.
• During chronic treatment, a daily level must be monitored to avoid toxic effects. See below.
• Caution for toxicity in patients with low weight < 60 kg, renal insufficiency,... Sometimes the necessary maintenance dose is sometimes only 0.125 mg every 2 days or 3 times a week.

• Overgevoeligheid aan digitalis.
• Ernstige nierfunctiebeperking> monitoring spiegels is dan absoluut noodzakelijk.
• Ventrikel fibrillatie.
• Cardiale amyloïdose.

• It is ALWAYS necessary and important to monitor and check the blood concentration of digoxin during blood tests with occasional determination of the digoxin TROUGH LEVEL (in the morning before taking the next dose, or at least 6 hours after the last dose).
  • Target value: 0.5 – 1.0 ng /ml.
  • A higher trough level exponentially increases mortality (due to cardiac arrhythmias)!

• There is an increased risk of a toxic trough level with:
  • Low body weight.
  • Chronic renal insufficiency.
  • Ionic disorders: hypokalemia , hypomagnesemia , hypercalcemia .
  • Take together with P- glycoprotein inhibitors: e.g. amiodarone , verapamil, macrolides, azole fungostatics and cyclosporine.

• Symptoms of intoxication:
  • Often non-specific:
    • Fatigue, lethargy.
    • Confusion.
    • GI symptoms: anorexia, nausea, vomiting, diarrhea and abdominal pain.
    • Rare: visual symptoms – blurred vision, disturbed color vision, halos and scotomas .
  • Hyperkalemia
  • Cardiac arrhythmias, a potential cause of death (even in otherwise asymptomatic patients)!
    • Bradycardia
    • AV block.
    • Ventricular extrasystoles with possible ventricular tachycardia (VT) or ventricular fibrillation (VF) in severe intoxication.

• Therapy for intoxication:
  • Stop digoxin.
  • Admission for, among other things, rhythm monitoring if symptoms or if trough level > 2.0 – 2.5 ng / ml.
  • Correction of hypokalemia and possibly hypomagnesemia .
  • IV Digoxin specific Fab fragments ( DigiFab® ) (40mg/ vial).
    
    Indications:

• • • Life-threatening arrhythmias and conduction disorders.
    • Hyperkalemia (>5.0 mmol /L) in acute intoxication.
    • Increased Digoxin level > 10 ng /ml in adults (measured at least 6 hours after last intake).