Do benzodiazepines (BZDs) have any effects on the heart?

Cardiac Effects of Benzodiazepines

Benzodiazepines have modest but clinically favorable hemodynamic effects on the heart, causing minimal reductions in blood pressure and preload through direct vasodilation while maintaining cardiac contractility and coronary blood flow—making them the preferred sedative choice in patients with acute heart failure and cardiogenic shock. 1

Hemodynamic Profile

Benzodiazepines produce a "nitroglycerin-like effect" with specific cardiovascular actions 1:

• Preload: Decreased 1
• Afterload: Decreased 1
• Heart Rate: Neutral or slightly decreased 1
• Cardiac Contractility: Maintained (no clinically significant negative inotropic effects) 1
• Cardiac Output: Maintained 1
• Coronary Blood Flow: Maintained or increased 1
• Myocardial Oxygen Consumption: Decreased 1

Mechanisms of Action

The cardiovascular effects occur through several pathways 1:

• Direct vasodilation causing minimal blood pressure reductions 1
• Autonomic nervous system modulation 1
• Suppression of arterial baroreceptors 1
• Reduction in cardiac filling pressures without compromising coronary perfusion 1

While in vitro and in vivo studies incorporating the autonomic system suggest direct negative inotropic effects, these effects are clinically insignificant in practice 1.

Clinical Context: Heart Failure and Cardiogenic Shock

In patients with failing hearts, benzodiazepines provide the safest hemodynamic profile among sedative agents 1. The European Heart Journal guidelines specifically recommend benzodiazepines as the preferred adjunctive sedative in:

• Acute heart failure 1
• Cardiogenic shock 1
• Compensated but severely depressed left ventricular function 1

This recommendation is based on their superior hemodynamic safety compared to propofol (which causes 20% reduction in cardiac output and significant hypotension) and dexmedetomidine (which causes bradycardia, hypotension, and reduced cardiac output) 1.

Vagal Tone and Heart Rate Effects

Benzodiazepines may act as vagolytics through enhancement of GABAergic inhibition of cardiac vagal preganglionic neurons 2:

• Can increase heart rate by suppressing cardiac vagal activity 2
• This effect is blocked by the benzodiazepine antagonist flumazenil 2
• No consensus exists on their chronotropic effects in clinical practice 1

Important caveat: This vagolytic property should be considered in post-myocardial infarction patients, where vagal tone may be protective against fatal ventricular arrhythmias 2.

Arrhythmia Risk

The evidence on arrhythmia risk is mixed:

• Benzodiazepines may increase the ventricular tachycardia threshold (potentially protective) 1
• No changes in QT duration have been reported in clinical use 1
• However, recent large-scale data shows concerning associations: A 2024 study found benzodiazepine initiation associated with a 101% increased risk of sudden cardiac arrest in patients with cardiovascular disease (adjusted HR: 2.01,95% CI: 1.42-2.83) 3
• The risk appears dose-dependent: HR 1.43 for ≤1 defined daily dose and HR 2.58 for >1 defined daily dose 3

Heart Failure Prognosis

A 2020 study demonstrated that benzodiazepines are associated with worse outcomes in heart failure patients with insomnia 4:

• Higher rehospitalization rates for heart failure compared to Z-drugs (HR: 1.530,95% CI: 1.025-2.284) 4
• Higher cardiac death rates (though less robust association) 4
• This remained significant after propensity score matching 4

Critical Trade-offs

The hemodynamic advantages of benzodiazepines must be weighed against their detrimental effects 1:

• Prolonged mechanical ventilation 1
• Increased ICU length of stay 1
• Increased delirium risk 1
• Increased all-cause mortality risk in severe COPD 1
• Increased fall risk, especially in elderly patients 5

FDA-Labeled Cardiovascular Effects

The FDA labels for benzodiazepines list hypotension as a known cardiovascular adverse effect 5. In overdose situations, markedly abnormal blood pressure and heart rate can occur, particularly when combined with other CNS depressants 5.

Clinical Algorithm for Use

For critically ill cardiovascular patients requiring sedation 1:

1. First-line approach: Sedative-less strategy using fentanyl for pain control and antipsychotics for delirium management 1

2. If adjunctive sedative needed:

   • Acute heart failure/cardiogenic shock/severely depressed LV: Benzodiazepines are preferred 1
   • Compensated mild-moderate LV dysfunction: No evidence to contraindicate non-benzodiazepine sedatives 1
   • Ischemic heart disease: No specific contraindication, but consider vagolytic effects post-MI 2

3. Use only for persistent agitation, not routinely 1

Important Caveats

• Benzodiazepines should be avoided or used with extreme caution when combined with opioids, alcohol, or other CNS depressants due to risk of respiratory depression, coma, and death 6, 5
• The long-term prognostic data (increased sudden cardiac arrest risk and heart failure rehospitalization) suggests caution with chronic use in cardiovascular patients 3, 4
• Despite favorable acute hemodynamic effects, the association with worse long-term outcomes in heart failure patients requires careful risk-benefit assessment 4