An increasing number of people suffer from conditions typically associated with aging, including heart failure (HF) and lower urinary tract symptoms (LUTS). HF affects 1–3% of the general population.1 Up to 50% of HF patients suffer from LUTS,2 with urinary frequency, urinary urgency, nocturia, and urinary incontinence as the most common symptoms.2,3 HF and LUTs frequently occur comorbidly, and this comorbidity is associated with poorer functional status in patients with HF.4 An article by Tannenbaum and Johnell4 discusses the pathophysiologic and pharmacologic factors responsible for the comorbidity of HF and LUTS and recommends strategies to manage the competition that often takes place between the pharmacologic regimens used to treat each condition.

Pathophysiological Factors

Patients with HF often experience elevations in brain natriuretic peptide (BNP).4 Elevated BNP levels have been “independently associated with both the presence and the severity of nocturnal voiding and nocturnal polyuria in elderly patients.”5 Additionally, redistribution and elimination of fluid from HF-induced edema further contribute to urinary frequency and excessive diuresis—especially nocturnally, when peripheral edema is resorbed in the supine position.4

The Impact of Pharmacotherapy on the Comorbidity of HF and LUTS

Many of the medications commonly used to treat HF precipitate or worsen urinary incontinence. Conversely, many of the medications used to treat urinary incontinence exacerbate symptoms of HF.

The impact of HF Drugs on LUTS: Diuretics, ACE inhibitors, and beta-blockers are cornerstones of HF treatment, but are associated with exacerbation of LUTS. 

  • Loop diuretics “increase sodium urinary excretion and decrease physical signs of fluid retention, reducing venous pressure, edema, and body weight,” but the increase in sodium excretion and volume of urine lead to urinary frequency, urgency, and incontinence.6
  • ACE inhibitors, which are standard therapy in HF patients with symptomatic left ventricular systolic dysfunction, are frequently associated with persistent dry cough—especially at night.7 The cough can exacerbate stress incontinence by increasing urethral pressure.4
  • Some studies have suggested that beta-blockers may increase bladder contractility and provoke symptoms of urinary urgency. However, these findings are inconsistent and require further investigation.4

The impact of overactive bladder (OAB) medications on HF: OAB presents with symptoms of urinary urgency, frequency, nocturia, and urinary incontinence.4 Two medication classes are typically prescribed for this condition: antimuscarinic agents, and beta 3-adrenergic agonists.

  • Antimuscarinic agents, the “mainstay of treatment” for patients with OAB, block muscarinic (M2 and M3) receptors in the bladder detrusor muscle, thereby reducing frequency and urgency. However, blocking these receptors (particularly M2 subtype) can potentially increase heart rate, prolong the QT interval and induce polymorphic ventricular tachycardia (torsade de pointes).4
  • Beta 3-adrenoceptor agonists enhance the action of the beta 3-adrenoceptor subtype, which is dominant in the detrusor muscle. Mirabegron, a selective beta 3-adrenoceptor agonist, is approved for treatment of OAB but may stimulate beta 3-adrenoreceptors in the heart, raising concerns about the cardiac safety of mirabegron in patients with HF. Although a meta-analysis of three trials (N=2,760) found no obvious treatment-emergent adverse cardiac effects,8 Tannenbaum and Johnell advise caution, stating that further research is warranted to determine the safety of these agents.