Can digoxin (digitalis glycoside) cause worsening shortness of breath (SOB)?

From the Guidelines

Digoxin can cause worsening shortness of breath (SOB) as a side effect, particularly when it reaches toxic levels in the bloodstream, as evidenced by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. This typically occurs when blood levels exceed the therapeutic range, and patients with kidney dysfunction, the elderly, and those taking certain interacting medications are at higher risk for developing toxicity even at standard doses. Some key points to consider when evaluating the risk of digoxin-induced shortness of breath include:

• The therapeutic range of digoxin is 0.8-2.0 ng/mL, and levels above this range can increase the risk of toxicity 1
• Patients with kidney dysfunction, the elderly, and those taking certain interacting medications (like amiodarone, verapamil, or clarithromycin) are at higher risk for developing toxicity even at standard doses 1
• Regular monitoring of digoxin levels, especially after dose changes or when starting interacting medications, is important to prevent toxicity 1
• The mechanism behind digoxin-induced respiratory symptoms relates to its effects on the cardiovascular system and potential impact on pulmonary function when at toxic levels It is essential to note that the benefit of digoxin in patients with heart failure remains controversial, and its use should be carefully considered, with therapy initiated and maintained at a dose of 0.125 to 0.25 mg daily, and low doses used initially in patients over 70 years old or with impaired renal function 1. If a patient on digoxin experiences new or worsening shortness of breath, they should seek medical attention promptly as this could indicate toxicity requiring dose adjustment or temporary discontinuation.

From the FDA Drug Label

In recent controlled clinical trials, in patients with predominantly mild to moderate heart failure, the incidence of adverse experiences was comparable in patients taking digoxin and in those taking placebo. Cardiac adverse reactions accounted for about one-half, gastrointestinal disturbances for about one-fourth, and CNS and other toxicity for about one-fourth of these adverse reactions. High doses of digoxin may produce a variety of rhythm disturbances, such as first-degree, second-degree (Wenckebach), or third-degree heart block (including asystole); atrial tachycardia with block; AV dissociation; accelerated junctional (nodal) rhythm; unifocal or multiform ventricular premature contractions (especially bigeminy or trigeminy); ventricular tachycardia; and ventricular fibrillation.

Digoxin and Shortness of Breath (SOB)

• The FDA drug label does not directly mention worsening shortness of breath (SOB) as an adverse effect of digoxin.
• However, it does mention that cardiac adverse reactions can occur, which may indirectly affect breathing.
• It is also noted that digoxin can cause heart block and rhythm disturbances, which may lead to decreased cardiac output and potentially worsen shortness of breath in some patients.
• However, without direct evidence, it is unclear if digoxin can cause worsening shortness of breath. 2

From the Research

Digoxin and Shortness of Breath

• The available evidence does not directly address whether digoxin can cause worsening shortness of breath (SOB) 3, 4, 5, 6, 7.
• However, studies suggest that digoxin can reduce hospitalizations due to heart failure (HF) and may also reduce mortality at low serum digoxin concentrations (SDC) 3.
• Digoxin has been shown to increase ejection fraction, augment cardiac output, and reduce pulmonary capillary wedge pressure without causing deleterious increases in heart rate or decreases in blood pressure 4.
• The DECISION trial aims to examine the efficacy and safety of low-dose digoxin in HF patients with reduced or mildly reduced left ventricular ejection fraction (LVEF) 5.
• Some studies have raised concerns about the clinical efficacy and long-term safety of digoxin, but the methodological issues, strengths, and limitations of individual studies need to be considered 6.
• Overall, the relationship between digoxin and shortness of breath is not clearly established in the available literature, and further research is needed to fully understand this potential association.

Mechanism of Action

• Digoxin has positive inotropic and neurohormonal modulation properties, which may contribute to its effects on heart failure symptoms 4, 6.
• The drug increases ejection fraction, augments cardiac output, and reduces pulmonary capillary wedge pressure, which may help alleviate symptoms such as shortness of breath 4.
• However, the exact mechanisms by which digoxin affects shortness of breath are not well understood and require further investigation.

Clinical Evidence

• The Digitalis Investigation Group trial showed that digoxin therapy reduced all-cause and HF-specific hospitalizations but had no effect on survival 4, 7.
• Other studies have reported mixed results regarding the efficacy and safety of digoxin in heart failure patients, highlighting the need for further research 3, 5, 6.