Washington University Emergency Medicine Journal Club- March 2024
Vignette
You are working in TCC one morning when you encounter Mrs. D, a 64-year-old woman with a past medical history of paroxysmal atrial fibrillation, hypertension, and heart failure with reduced ejection fraction. Her last ECHO a few months prior revealed an EF of 40%. She presents with 3 days of weakness, shortness of breath, and palpitations. Her vital signs are:
BP 130/70 HR 155 SpO2 96% (on room air) RR 18 T 36.8
Her ECG shows atrial fibrillation with a ventricular rate of 155 and her chest x-ray shows mild pulmonary edema. BNPeptide is 6000 (previously 2000) and high-sensitivity troponin is 28. Her renal function, electrolytes, and blood counts are all stable.
You plan are planning to rate control the patient and give a dose of diuretics, but remember being told not to use calcium channel blockers (i.e. diltiazem) patients with heart failure with reduced ejection fraction (see ACC/AHA guidelines). You instead discuss giving beta-blockers or amiodarone with your attending, but wonder if there is any solid evidence that calcium channel blockers are harmful in such patients, and decide to search the literature…
PICO Question
Population: Adults patients presenting to the ED with AF with rapid ventricular rate
(RVR) and a known congestive heart failure (CHF)
Intervention: IV diltiazem for rate control
Comparison: IV beta blockers (e.g. metoprolol), amiodarone, or electrical
cardioversion
Outcome: Successful rate control, rhythm control, hypotension, bradycardia,
worsening congestive heart failure symptoms (shortness of breath, increase oxygen
requirement), MI, mortality, hospital/ICU length of stay
Search Strategy
PubMed was searched using the terms ”diltiazem AND atrial fibrillation AND heart
failure,” resulting in 85 citations (https://tinyurl.com/2cwddbpj). The four most
relevant articles were chosen.
Article 1: Goldenberg IF, Lewis WR, Dias VC, Heywood JT, Pedersen WR. Intravenous diltiazem for the treatment of patients with atrial fibrillation or flutter and moderate to severe congestive heart failure. Am J Cardiol. 1994 Nov 1;74(9):884-9. doi: 10.1016/0002-9149(94)90580-0. PMID: 7977118. Answer Key.
Article 2: Compagner CT, Wysocki CR, Reich EK, Zimmerman LH, Holzhausen JM. Intravenous metoprolol versus diltiazem for atrial fibrillation with concomitant heart failure. Am J Emerg Med. 2022 Dec;62:49-54. doi: 10.1016/j.ajem.2022.10.001. Epub 2022 Oct 8. PMID: 36252310. Answer Key.
Article 3: Niforatos JD, Ehmann MR, Balhara KS, Hinson JS, Ramcharran L, Lobner K, Weygandt PL. Management of atrial flutter and atrial fibrillation with rapid ventricular response in patients with acute decompensated heart failure: A systematic review. Acad Emerg Med. 2023 Feb;30(2):124-132. doi: 10.1111/acem.14618. Epub 2022 Dec 5. PMID: 36326565. Answer Key.
Article 4: Hasbrouck M, Nguyen TT. Acute management of atrial fibrillation in congestive heart failure with reduced ejection fraction in the emergency department. Am J Emerg Med. 2022 Aug;58:39-42. doi: 10.1016/j.ajem.2022.03.058. Epub 2022 Apr 6. PMID: 35623182. Answer Key.
Bottom Line:
Guideline the management of AF with RVR in patients with CHF vary widely. The 2016 European Society of Cardiology (ECS) guidelines specifically recommend avoiding nondihydropyridine calcium channel blockers (CCBs) (i.e. diltiazem and verapamil) for rate control in such patients in favor of beta blockers and digoxin due to the potential for negative inotropy. By contrast, the 2014 AHA/ACC/HRS guidelines suggest avoiding both beta blockers and CCBs for patients with AF with RVR and decompensated heart failure. These recommendations are based on low levels of evidence, however, which we sought to review here.
One of the earliest articles addressing the use of diltiazem for rate control in AF in patients with heart failure was a multi-center randomized controlled trial comparing diltiazem with placebo (Goldenberg 1995). With only 37 patients enrolled, of whom 22 were randomized to receive diltiazem and 15 to receive placebo, the authors found—not surprisingly—that diltiazem was more likely to result in a reduction in ventricular rate within 15 minutes (less than 100 beats per minute or ≥ 20% from baseline) or conversion to sinus rhythm than placebo (82% vs. 0%, p < 0.001). Of 4 patients in the diltiazem group who did not respond, one was inadvertently not given any additional study drug; the other 3 responded to a 2nd dose of IV diltiazem. After 30 minutes, all 15 placebo group patients received IV diltiazem, with 13 designated as responsive to this treatment; the remaining 2 patients responded to a 2nd dose of IV diltiazem. Hypotension occurred in 2 patients in the diltiazem group (9%) and was symptomatic in one patient, while no patient in the placebo group had an adverse event. There was no difference in the incidence of hypotension between those with an EF < 25% and those with an EF > 25%. While this study suffered from the lack of a comparison to an alternate, viable treatment, it does suggest that the use of diltiazem in this patient population was safe and effective.
More recently, a retrospective, observational study conducted in the EDs of an 8-hospital health system in Michigan compared IV push metoprolol and IV push diltiazem in patients with AF with RVR with documented heart failure on echocardiogram (Compagner 2022). With 193 patients included, of whom 59 received metoprolol and 134 received diltiazem, successful rate control at 30 minutes occurred more frequently in the diltiazem group, but this did not achieve statistical significance (55% vs. 41%; RR 1.35, 95% CI 0.96 to 1.91). Although diltiazem was associated with a higher frequency of bradycardia (6% vs. 0%) and hypotension (22% vs. 14%) compared with metoprolol, these differences did not achieve statistical significance (p = 0.109 and 0.155, respectively). Interestingly, in the subgroup of patients with HFpEF there was a higher frequency of hypotension in the diltiazem group compared to metoprolol (28% vs. 7%, p = 0.005), but no other differences in safety outcomes were seen in either subgroup (HFpEF/HFrEF).
Another recent single-center, retrospective study conducted in the ED of Virginia Commonwealth Medical Center compared IV diltiazem and metoprolol in patients with AF with RVR and known HFrEF with an EF ≤ 40% (Hasbrouch 2022). With 125 patients identified (57 receiving diltiazem and 68 receiving metoprolol), there was no statistically significant difference in the groups with respect to the primary composite of adverse events (32% vs. 21%, p = 0.217). This composite outcome included hypotension (SBP < 90 mmHg requiring a fluid bolus or vasopressors) or bradycardia (HR < 60 bpm) within 60 minutes of ED intervention, or worsening heart failure symptoms (increase in O2 requirement by at least 2 liters or requirement of an inotrope) within 48 hours of ED intervention. There was, however, a statistically significant increased risk of worsening CHF symptoms in the diltiazem group (33% vs. 15%, p = 0.019). Rate control was achieved in similar proportions in the two groups.
A systematic review of pharmacological and nonpharmacological treatment options for AF with RVR in patients with acute decompensated heart failure identified five relevant articles, two of which (Goldenberg and Hasbrouck) have already been reviewed here (Niforatos 2023). The remaining three articles were retrospective, observational studies. In Krothapelli et al (published as an abstract only), 52 hospitalized patients with AF with RVR and systolic heart failure received a CCB (10 patients), a beta blocker (42 patients), digoxin (22 patients), or AV nodal ablation (2 patients). Rates of survival to hospital discharge were significantly higher in patients administered BBs (80.9%) and digoxin (90.9%) compared to patients receiving CCB (56.8%) or AV nodal ablation (74%). There was no significant difference in groups with regards to worsening heart failure symptoms. The remaining two articles compared either rate control versus rhythm control (Scheuermeyer 2015) or management with AV nodal ablation (Volle 2021), and were not relevant to this discussion.
As demonstrated here, while diltiazem is an effective rate control agent for AF with RVR in patients with heart failure, the evidence surrounding the potential harm associated with its use in this patient population of is very limited. Care should be taken when managing this special population in the ED to avoid worsening heart failure or hypotension.