A Weakness in the HEART?

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In this month’s Journal Club Recap we take a look at some recently published literature about common heart related complaints in the ED. First, we look at the now nearly ubiquitously used HEART pathway. In a US population, do the benefits of decreased health care utilization sustain themselves to a year out of an index visit? Then we turn our attention to atrial fibrillation with RVR. Does the utility infielder of ED medications, Magnesium, actually help with more rapid rate control? And, should the results of a consensus panel sway us to treat A fib with RVR as an outpatient?

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Stopyra JP, Riley RF, Hiestand BC, et al. The HEART Pathway: Randomized Controlled Trial One‐year Outcomes. Academic Emergency Medicine 2018;174:546–22. 

Background 

Mahler’s group randomized 282 patients presenting to the emergency department with chest pain to either evaluation via the HEART pathway or “usual care.” Inclusion criteria were concern for acute coronary syndrome and the completion of an electrocardiogram and single serum troponin. Primary outcome was the incidence of major adverse cardiac events (MACE), defined as a composite endpoint of myocardial infarction, cardiac mortality, or cardiac intervention (angioplasty, bypass grafting). Secondary endpoints included nonindex cardiac admission and the use of provocative (termed “objective”) testing, such as stress testing or angiography. In the initial study (which evaluated patient outcomes at 30 days) found no MACE in either arm, but found significantly lower use of provocative testing (approximately 12% less) in patients randomized to the HEART pathway.

Methodology 

Preplanned secondary analysis of the same patient population at one year with identical primary and secondary endpoints. 

Results

90.5% of patients from the original study were included in the secondary analysis, with 6 deaths and 23 myocardial infarctions. The incidence of MACE was similar in both arms of the study (9.9% in HEART pathway versus 11.3% in usual care arm, p=0.85). No patients (0/66) identified as low risk per the HEART pathway had MACE at one year. Moreover, both groups had similar rates of nonindex cardiac admissions (14.9 % versus 10.6%) and provocative testing (63.1% versus 71.6%). However, when excluding index provocative testing (i.e., testing done at the time of randomization), patients allocated to the HEART pathway actually had significantly more provocative testing than those in usual care (17.0% versus 8.5%, p=0.049).

Conclusions

The initial reduction in provocative testing amongst patients randomized to the HEART pathway disappeared at one year. No significant difference was observed in the incidence of MACE between the two arms. Patients designated as “low risk” per the HEART pathway had no MACE at one year, with a negative predictive value of 100%. The authors suggest that patients with low risk HEART scores may not require urgent risk stratification or aggressive cardiology follow-up.

Criticisms 

The study was overall small and not powered to assess for differences in the incidence of MACE. The study utilized patient randomization rather than provider randomization, which may have influenced the care of patients assigned to the usual care arm. 

Take away

Patients with low risk HEART scores have overall low incidence of MACE. Non-low risk patients, however, likely warrant further risk stratification.

Bouida W, Beltaief K, Msolli MA, et al. LOw dose MAGnesium sulfate versus HIgh dose in the early management of rapid atrial fibrillation: randomised controlled double blind study. Academic Emergency Medicine 2018;:acem.13522–17. 

The LoMagHI study (Bouida et al., 2018) was a double-blind randomized clinical trial comparing low and high dose magnesium vs placebo when added to routine rate control agents for patients presenting with atrial fibrillation in RVR. This paper adds to an existing body of literature supporting the use of magnesium in atrial fibrillation. Magnesium is believed to function mechanistically by inhibiting L-type calcium channels in cardiac myocytes. Electrophysiology studies have demonstrated that Mg can prolong both atrial and AV nodal refractory times (Rasmusen and Thomsen, 1989). There is an abundant body of literature on the importance of magnesium for afib in cardiac surgery patents; however, few papers have studied the effect of Mg as an adjunct to rate control agents in our ED setting. Chilidakis et al. (2001)compared magnesium head to head with diltiazem and found that magnesium effectively reduced HR. Davey and Teubner (2005)showed increased rate control with the addition of magnesium (5g, in this case) to standard therapies in an ED population. The present study expands on this with a larger enrollment and a comparison of two doses of magnesium.

The PICO model of this study was:


  • P (patients): 450 adults w atrial fibrillation presenting to 3 academic ED’s in Tunisia 2009-2014. Exclusion criteria included hypotension, heart failure (NYHA class 3-4), wide complex tachycardia, renal disease (Cr>~2) and acute MI. 

  • I (intervention): Magnesium sulfate 4.5g or 9g IV, plus physician discretion rate control agent (digoxin ~50%, CCB, BB remaining 50%)

  • C (comparison): placebo plus physician discretion rate control agent

  • O (outcomes): The primary outcome was therapeutic response defined as HR <90 or >20% decrease within 4 hours.

  • Secondary outcomes included time to response, conversion to NSR and adverse events. 

Findings

The study found that rates of therapeutic response at 4 hours were higher in patients receiving magnesium (both high and low dose) compared to placebo. This effect continued to be significant at 24 hours. More adverse events were seen in the magnesium groups, with the most seen with the high dose, The most common reaction was flushing. The low dose mag group also showed an increase in conversion to NSR at 24 hours compared to both the placebo group and the high dose group. There are no differences in conversion to sinus rhythm between placebo and high dose group. 

Strengths

This was a methodologically well-constructed study with a sizable enrollment, and is the largest DBRCT focusing on atrial fibrillation specifically in the ED environment. 

Weaknesses

Digoxin was the most commonly rate control agent, despite being rarely used in our practice as a first line agent (outside of HF pts, who were excluded from the present study). The authors report that the subgroup analyses (pts receiving CCB and BB only) were performed and not significantly different, though these analyses are not included in the manuscript. The difference in combined adverse events was attributable to flushing alone, which the authors comment is likely of minimal clinical concern. Given the relatively low frequency, a much larger cohort would be necessary to detect differences in clinically significant events associated with magnesium. 

Conclusion

Overall, this is a well-designed study that suggests magnesium is an effective addition to our ED armament for controlling RVR. It may not be time to rewrite the guidelines based on this paper alone, but magnesium is a safe, inexpensive, and readily available medication- and something I am likely to reach for the next time I’m managing RVR. 

References

Baugh CW, Clark CL, Wilson JW, et al. Creation and Implementation of an Outpatient Pathway for Atrial Fibrillation in the Emergency Department Setting: Results of an Expert Panel. Academic Emergency Medicine 2018;130(562):A15749–11. 

Baugh and colleagues used a consensus building technique to develop an outpatient protocol for the treatment of atrial fibrillation with rapid ventricular response (RVR).  

Atrial fibrillation with RVR is a common presenting complaint to the ED.  The care of these patients can vary significantly based on practice setting.  Admission rates for these patients are significantly higher in the United States than in Canada and costs associated with admission may exceed $3 billion dollars. Many studies have described safe and effective rapid ED treatment/outpatient treatment for select patients with A fib with RVR, yet these protocols have not seen widespread adoption.

A modified Delphi technique was used to arrive at a consensus guideline for the treatment of A fib with RVR in an outpatient observation setting. The expert panel participating in the consensus building process included Emergency Medicine physicians (academic and community), Cardiologists (Electrophysiology and General Cardiology), Internal Medicine physicians, an Advanced Practice Provider, Pharmacist, Nursing, and Hospital Administration.  The modified Delphi technique was well constructed and conducted.

The panel focused first on agreeing on a process for implementation of an outpatient observation pathway.  The defined process clearly describes the efforts and resources needed to bring a observation protocol into existence as well as maintenance and monitoring for effectiveness.  The panel then developed an example pathway for the outpatient medical management of a patient presenting with A fib with RVR.  The developed protocol is intended to serve as a useful roadmap, able to be adjusted to local resources and needs.  The effectiveness of the protocol was not studied as part of this paper.

What Does the Protocol Look Like?

Patients who have severe renal disease, accompanying co-morbid diagnoses (e.g. decompensated heart failure), hemodynamic instability after attempted cardio version, or significant social barriers to care are EXCLUDED from the pathway.

Patients that have recent onset Atrial fibrillation with RVR (<48 hours) or have been anti-coagulated for 4 weeks have an attempt at cardioversion in the ED.  If cardioversion is successful and patients remain stable for at least 1 hour, they are discharged.  If not, they are admitted to the hospital.

Patients with unclear onset of Atrial fibrillation or inadequate anticoagulation are preferentially rate controlled.  These patients are observed for period of time after adequate rate control to ensure stability and success.  

All patients are evaluated for stroke risk (CHADS2VASc score) and bleeding risk (HAS-BLED score) and given anticoagulation in the form of an Xa inhibitor, direct thrombin inhibitor, or heparin with bridge to warfarin as indicated.

What Do We Make of this Paper?

This paper serves as a useful roadmap for the implementation of an outpatient treatment pathway for atrial fibrillation with RVR.  In hospital and emergency department settings where the resources to conduct robust outpatient treatment pathways exist, we should consider the local development of a protocol to treat these patients.

Authorship

  • Stopyra, et al - Matthew Scanlon, MD, PGY-3 University of Cincinnati Department of Emergency Medicine

  • Bouida, et al. - Aaron Murphy Crews, MD PGY-3 University of Cincinnati Department of Emergency Medicine

  • Baugh et al. - Jeffery Hill, MD MEd

  • Peer Review and Edited - Jeffery Hill, MD MEd