- Email: [email protected]
Conversion of recent onset atrial fibrillation: which drug is faster?
American Journal of Emergency Medicine 31 (2013) 1410–1417
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Correspondence Epinephrine-induced myocardial infarction in severe anaphylaxis: is β-blocker a bad actor or bystander?☆,☆☆
Narendra Nath Jena MBBS Department of Emergency Medicine Meenakshi Mission Hospital & Research Centre Madurai, India
To the Editor, It was interesting to review the recent case report by Cunnington et al [1]. The authors had linked the prior use of nonselective β-blocker as a predisposing factor for the myocardial ischemia that occurred after epinephrine administration. Although no epidemiological studies point out that anaphylaxis occurs more frequently in patients taking β-blockers [2], it is more likely that, in this patient, coronary vasoconstriction would have occurred due to repeated boluses of epinephrine. Interestingly, Alam et al [3] from the Cleveland clinic have reported that the fatality rate of anaphylaxis patients on β-blockers and those who were not was 3%, and 8.5%, respectively. They also found no significant difference between the 2 groups for surviving resuscitation, length of hospital stay, and 1-month survival. Another point of curiosity is that was there any hard evidence of myocardial necrosis or dysfunction because it is well known that elevated troponin could be due to a myriad of etiological factors [4]. The decision to withhold or discontinue β-blockers must be considered carefully from the perspective of risk vs benefit for each individual. Furthermore, in this case, advice of an autoinjector needs to be relooked at because this patient developed drug-induced anaphylaxis and because the authors incriminate epinephrine to be the culprit for myocardial ischemia. Therapeutically, intravenous injection of glucagon may be beneficial in these cases, as glucagon has inotropic, chronotropic, and vasoactive properties independent of β-receptors. In addition, it stimulates endogenous catecholamine release by activating adenyl cyclase. Thus, glucagon overcomes myocardial ischemia as well as overrides the paradoxical response to epinephrine [5]. From the point of education and training, all those involved in the treatment of anaphylaxis shall be taught and trained to consider adverse effects, nonresponsiveness and paradoxical response of epinephrine, and the alternatives under such circumstances.
Subramanian Senthilkumaran MD Department of Emergency & Critical Care Medicine Sri Gokulam Hospitals & Research Institute Salem, Tamil Nadu, India E-mail address: [email protected] Suresh S. David Department of Emergency Medicine Christian Medical College and Hospital, Vellore, India
☆ Financial support: Nil. ☆☆ Conflict of interest: Nil. 0735-6757/$ – see front matter © 2013 Elsevier Inc. All rights reserved.
Ponniah Thirumalaikolundusubramanian MD Department of Internal medicine Chennai Medical College and Research Center Irungalur, Trichy, India http://dx.doi.org/10.1016/j.ajem.2013.04.027 References [1] Cunnington C, McDonald JE, Singh RK. Epinephrine-induced myocardial infarction in severe anaphylaxis: is nonselective β-blockade a contributory factor? Am J Emerg Med 2013;31:759.e1–2. [2] Miller MM. Beta-blockers and anaphylaxis: are the risks overstated? J Allergy Clin Immunol 2005;116:933–4. [3] Alam MM, Alvarezdel Real G,Hsieh FH.Cardiopulmonaryresuscitation (CPR) inpatients with acute anaphylaxis taking beta-blockers. J Allergy Clin Immunol 2005;115:40. [4] Blich M, Sebbag A, Attias J, Aronson D, Markiewicz W. Cardiac troponin elevation in hospitalized patients without acute coronary syndromes. Am J Cardiol 2008;101: 1384–8. [5] Thomas M, Crawford I. Best evidence topic report. Glucagon infusion in refractory anaphylactic shock in patients on beta blockers. Emerg Med J 2005;22:272–3.
Conversion of recent onset atrial fibrillation: which drug is faster?☆ To the Editor, Atrial fibrillation (AF) is the most common arrhythmia in medical practice. Recent onset AF is a frequent cause for presentation to the emergency department. Conversion of recent onset AF to sinus rhythm with antiarrhythmic drugs reduces the risk of hemodynamic instability, hospitalizations, and atrial remodeling seen with persistent AF. Boriani et al [1] compared oral loading dose of propafenone 600 mg with intravenous propafenone and placebo. At 8 hours, either intravenous or oral propafenone was effective in almost two-thirds of the patients with a statistical difference vs placebo. Conde et al showed that intravenous vernakalant is faster than oral propafenone [2]. A single dose of flecainide 300 mg showed that it has the same time to conversion to sinus rhythm as intravenous flecainide, but vernakalant was faster than oral flecainide [3]. Vernakalant has proved to be more rapid in converting recent onset AF to sinus rhythm compared with placebo and amiodarone [4]. Up to the present time, there is not a study that has compared these 4 drugs.
☆ Conflict of interest: None.
Correspondence / American Journal of Emergency Medicine 31 (2013) 1410–1417
The goal of my study was to compare the time taken for conversion of recent onset AF in hemodynamically stable patients without structural heart disease treated with these 4 drugs in a cardiovascular emergency care section. I included 75 patients, hemodynamically stable with symptomatic recent onset AF (lasting b 48 hours) without structural heart. I compared 4 groups: oral loading dose of propafenone 600 mg (n = 20), a single dose of flecainide 300 mg (n = 20), intravenous vernakalant (n = 20), and intravenous amiodarone (n = 15). The median time to conversion to sinus rhythm was 159 minutes in the propafenone group, 161 minutes in the flecainide group, 10 minutes in vernakalant group, and 350 minutes in amiodarone group. There was not statistical different between propafenone and flecainide groups (P = 1). Propafenone and flecainide groups were faster than amiodarone (P b .01). In addition, vernakalant group was faster than propafenone and flecainide groups (P b .01). I concluded that vernakalant is the faster drug for conversion of recent onset AF because the median time to conversion to sinus rhythm was significantly shorter in the vernakalant group compared with the other 3 groups. Diego Conde MD Instituto Cardiovascular de Buenos Aires Blanco Encalada 1543 1428 Buenos Aires, Argentina E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2013.05.039 References
atypical T-wave morphologies, as in case 2, and/or when a T-wave slurs into a U wave or P wave, as in case 1 [3]. Were the automated electrocardiographic QTc reads for cases 1 and 2 similar to the QTc values reported in the article (563 and 538 milliseconds, respectively)? Did the original interpreters of the ECGs perform manual QT measurement and QTc calculation? If not, do you believe that the arrhythmia risk was underappreciated because of reliance on automated electrocardiographic interpretation? Manual assessment of repolarization may provide additional prognostic insight. The QTc indicates total repolarization duration, but this may not be the sole determinant of arrhythmia risk. Increased QT duration seen on the surface ECG may be caused by uniform myocardial repolarization delay; therefore, the conditions required for reentry—multiple pathways, relative conduction delay in 1 limb, and functional unidirectional block—may not be present. This would give the false impression of increased arrhythmia risk if risk is assessed with the QTc alone. It may be helpful to measure the terminal portion of the QT interval, defined as the duration from the peak of the T-wave to the end of the T-wave (Tpeak-Tend, or TpTe), which reflects repolarization heterogeneity within the myocardium [4]. Tpeak-Tend measurements have demonstrated superior discriminatory characteristics when compared with QTc for predicting adverse arrhythmic events in diverse patient populations [5-7]. Although the use of TpTe for risk stratification of emergency department patients with syncope has not been investigated, a TpTe greater than 117 milliseconds was associated with an increased risk of torsades de pointes in patients with congenital bradyarrhythmias [8]. It would be interesting to compare the TpTe values of the 2 patients who developed arrhythmias (cases 1 and 2) with that of the patient who did not (case 3).
[1] Boriani G, Capucci A, Lenzi T, et al. Propafenone for conversion of recent-onset atrial fibrillation. A controlled comparison between oral loading dose and intravenous administration. Chest 1995;108:355–8. [2] Conde D, Costabel JP, Aragon M, et al. Flecainide or propafenone vs vernakalant for conversion of recent-onset atrial fibrillation. Can J Cardiol 2013. [3] Conde D, Costabel JP, Caro M, et al. Flecainide versus vernakalant for conversion of recent-onset atrial fibrillation. Int J Cardiol 2013. [4] Camm AJ, Capucci A, Hohnloser SH, et al. A randomized active-controlled study comparing the efficacy and safety of vernakalant to amiodarone in recent-onset atrial fibrillation. J Am Coll Cardiol 2011;57:313–21.
Manual corrected QT and Tpeak-Tend calculations may assist emergency physicians risk stratify patients for arrhythmia☆,☆☆
To the Editor, We applaud Dr Moskovitz and his colleagues [1] for drawing attention to the often-neglected evidence of abnormal repolarization on the electrocardiogram (ECG) of emergency department patients. As emergency physicians and medical toxicologists, we agree that abnormalities of ventricular repolarization are often underappreciated, which can lead to disastrous consequences, particularly in the context of acute drug overdose. We would like to add a few points to the discussion and ask some questions. Assessing the prognostic value of corrected QT (QTc) prolongation is challenging because QTc interval prolongations are fairly common in acutely ill patients, whereas torsades de pointes is rare [2]. In addition, electrocardiograph manufacturers use proprietary computer algorithms to measure the QT interval and to calculate the QTc. These QTc calculations may be inaccurate in the presence of
☆ Sources of support: None. ☆☆ This information has not been previously presented.
1411
John J. Devlin MD Mohan Punja MD Ziad Kazzi MD Georgia Poison Center Atlanta, GA Department of Emergency Medicine Emory University School of Medicine Atlanta, GA E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2013.05.041
References [1] Moskovitz JB, Hayes BD, Martinez JP, Mattu A, Brady W. Electrocardiographic implications of the prolonged QT interval. Am J Emerg Med 2013 http://dx.doi.org/ 10.1016/j.ajem.2012.12.013. [2] Pinkham D, Helfenbein E, Shinn JA, Chan G, Funk M, Weinacker A, et al. High prevalence of corrected QT interval prolongation in acutely ill patients is associated with mortality: results of the QT in Practice (QTIP) study. Crit Care Med 2012;40(2): 394–9. [3] Guglin ME, Thatai D. Common errors in computer electrocardiogram interpretation. Int J Cardiol 2006;106(2):232–7. [4] Antzelevitch C. Ionic, molecular, and cellular basis of QT-interval prolongation and torsades de pointes. Europace 2007;9(Suppl. 4):iv4–iv15. [5] Barbhaiya C, Ricardo J, Hanon S, Schweitzer P. Tpeak-Tend and Tpeak-Tend/QT ratio as markers of ventricular arrhythmia risk in cardiac resynchronization therapy patients. Pacing Clin Electrophysiol 2013;36(1):103–8. [6] Lestas KP, Weber R, Astheimer K, Kalusche D, Arentz T. Tpeak-Tend interval and TpeakTend/QT ratio as markers of ventricular tachycardia inducibility in subjects with Brugada ECG phenotype. Europace 2010;12(2):271–4. [7] Shimizu M, Ino H, Okeie K, Yamaguchi M, Nagata M, et al. Tpeak-Tend interval may be a better predictor of high-risk patients with hypertrophic cardiomyopathy associated with a cardiac troponin I mutation than QT dispersion. Clin Cardiol 2002;25(7):335–9. [8] Topliski I, Rogowski O, Rosso R, Justo D, Copperman Y, et al. The morphology of the QT interval predicts torsades de pointes during acquired bradyarrhythmias. J Am Coll Card 2007;49(3):320–8.
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Correspondence Epinephrine-induced myocardial infarction in severe anaphylaxis: is β-blocker a bad actor or bystander?☆,☆☆
Narendra Nath Jena MBBS Department of Emergency Medicine Meenakshi Mission Hospital & Research Centre Madurai, India
To the Editor, It was interesting to review the recent case report by Cunnington et al [1]. The authors had linked the prior use of nonselective β-blocker as a predisposing factor for the myocardial ischemia that occurred after epinephrine administration. Although no epidemiological studies point out that anaphylaxis occurs more frequently in patients taking β-blockers [2], it is more likely that, in this patient, coronary vasoconstriction would have occurred due to repeated boluses of epinephrine. Interestingly, Alam et al [3] from the Cleveland clinic have reported that the fatality rate of anaphylaxis patients on β-blockers and those who were not was 3%, and 8.5%, respectively. They also found no significant difference between the 2 groups for surviving resuscitation, length of hospital stay, and 1-month survival. Another point of curiosity is that was there any hard evidence of myocardial necrosis or dysfunction because it is well known that elevated troponin could be due to a myriad of etiological factors [4]. The decision to withhold or discontinue β-blockers must be considered carefully from the perspective of risk vs benefit for each individual. Furthermore, in this case, advice of an autoinjector needs to be relooked at because this patient developed drug-induced anaphylaxis and because the authors incriminate epinephrine to be the culprit for myocardial ischemia. Therapeutically, intravenous injection of glucagon may be beneficial in these cases, as glucagon has inotropic, chronotropic, and vasoactive properties independent of β-receptors. In addition, it stimulates endogenous catecholamine release by activating adenyl cyclase. Thus, glucagon overcomes myocardial ischemia as well as overrides the paradoxical response to epinephrine [5]. From the point of education and training, all those involved in the treatment of anaphylaxis shall be taught and trained to consider adverse effects, nonresponsiveness and paradoxical response of epinephrine, and the alternatives under such circumstances.
Subramanian Senthilkumaran MD Department of Emergency & Critical Care Medicine Sri Gokulam Hospitals & Research Institute Salem, Tamil Nadu, India E-mail address: [email protected] Suresh S. David Department of Emergency Medicine Christian Medical College and Hospital, Vellore, India
☆ Financial support: Nil. ☆☆ Conflict of interest: Nil. 0735-6757/$ – see front matter © 2013 Elsevier Inc. All rights reserved.
Ponniah Thirumalaikolundusubramanian MD Department of Internal medicine Chennai Medical College and Research Center Irungalur, Trichy, India http://dx.doi.org/10.1016/j.ajem.2013.04.027 References [1] Cunnington C, McDonald JE, Singh RK. Epinephrine-induced myocardial infarction in severe anaphylaxis: is nonselective β-blockade a contributory factor? Am J Emerg Med 2013;31:759.e1–2. [2] Miller MM. Beta-blockers and anaphylaxis: are the risks overstated? J Allergy Clin Immunol 2005;116:933–4. [3] Alam MM, Alvarezdel Real G,Hsieh FH.Cardiopulmonaryresuscitation (CPR) inpatients with acute anaphylaxis taking beta-blockers. J Allergy Clin Immunol 2005;115:40. [4] Blich M, Sebbag A, Attias J, Aronson D, Markiewicz W. Cardiac troponin elevation in hospitalized patients without acute coronary syndromes. Am J Cardiol 2008;101: 1384–8. [5] Thomas M, Crawford I. Best evidence topic report. Glucagon infusion in refractory anaphylactic shock in patients on beta blockers. Emerg Med J 2005;22:272–3.
Conversion of recent onset atrial fibrillation: which drug is faster?☆ To the Editor, Atrial fibrillation (AF) is the most common arrhythmia in medical practice. Recent onset AF is a frequent cause for presentation to the emergency department. Conversion of recent onset AF to sinus rhythm with antiarrhythmic drugs reduces the risk of hemodynamic instability, hospitalizations, and atrial remodeling seen with persistent AF. Boriani et al [1] compared oral loading dose of propafenone 600 mg with intravenous propafenone and placebo. At 8 hours, either intravenous or oral propafenone was effective in almost two-thirds of the patients with a statistical difference vs placebo. Conde et al showed that intravenous vernakalant is faster than oral propafenone [2]. A single dose of flecainide 300 mg showed that it has the same time to conversion to sinus rhythm as intravenous flecainide, but vernakalant was faster than oral flecainide [3]. Vernakalant has proved to be more rapid in converting recent onset AF to sinus rhythm compared with placebo and amiodarone [4]. Up to the present time, there is not a study that has compared these 4 drugs.
☆ Conflict of interest: None.
Correspondence / American Journal of Emergency Medicine 31 (2013) 1410–1417
The goal of my study was to compare the time taken for conversion of recent onset AF in hemodynamically stable patients without structural heart disease treated with these 4 drugs in a cardiovascular emergency care section. I included 75 patients, hemodynamically stable with symptomatic recent onset AF (lasting b 48 hours) without structural heart. I compared 4 groups: oral loading dose of propafenone 600 mg (n = 20), a single dose of flecainide 300 mg (n = 20), intravenous vernakalant (n = 20), and intravenous amiodarone (n = 15). The median time to conversion to sinus rhythm was 159 minutes in the propafenone group, 161 minutes in the flecainide group, 10 minutes in vernakalant group, and 350 minutes in amiodarone group. There was not statistical different between propafenone and flecainide groups (P = 1). Propafenone and flecainide groups were faster than amiodarone (P b .01). In addition, vernakalant group was faster than propafenone and flecainide groups (P b .01). I concluded that vernakalant is the faster drug for conversion of recent onset AF because the median time to conversion to sinus rhythm was significantly shorter in the vernakalant group compared with the other 3 groups. Diego Conde MD Instituto Cardiovascular de Buenos Aires Blanco Encalada 1543 1428 Buenos Aires, Argentina E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2013.05.039 References
atypical T-wave morphologies, as in case 2, and/or when a T-wave slurs into a U wave or P wave, as in case 1 [3]. Were the automated electrocardiographic QTc reads for cases 1 and 2 similar to the QTc values reported in the article (563 and 538 milliseconds, respectively)? Did the original interpreters of the ECGs perform manual QT measurement and QTc calculation? If not, do you believe that the arrhythmia risk was underappreciated because of reliance on automated electrocardiographic interpretation? Manual assessment of repolarization may provide additional prognostic insight. The QTc indicates total repolarization duration, but this may not be the sole determinant of arrhythmia risk. Increased QT duration seen on the surface ECG may be caused by uniform myocardial repolarization delay; therefore, the conditions required for reentry—multiple pathways, relative conduction delay in 1 limb, and functional unidirectional block—may not be present. This would give the false impression of increased arrhythmia risk if risk is assessed with the QTc alone. It may be helpful to measure the terminal portion of the QT interval, defined as the duration from the peak of the T-wave to the end of the T-wave (Tpeak-Tend, or TpTe), which reflects repolarization heterogeneity within the myocardium [4]. Tpeak-Tend measurements have demonstrated superior discriminatory characteristics when compared with QTc for predicting adverse arrhythmic events in diverse patient populations [5-7]. Although the use of TpTe for risk stratification of emergency department patients with syncope has not been investigated, a TpTe greater than 117 milliseconds was associated with an increased risk of torsades de pointes in patients with congenital bradyarrhythmias [8]. It would be interesting to compare the TpTe values of the 2 patients who developed arrhythmias (cases 1 and 2) with that of the patient who did not (case 3).
[1] Boriani G, Capucci A, Lenzi T, et al. Propafenone for conversion of recent-onset atrial fibrillation. A controlled comparison between oral loading dose and intravenous administration. Chest 1995;108:355–8. [2] Conde D, Costabel JP, Aragon M, et al. Flecainide or propafenone vs vernakalant for conversion of recent-onset atrial fibrillation. Can J Cardiol 2013. [3] Conde D, Costabel JP, Caro M, et al. Flecainide versus vernakalant for conversion of recent-onset atrial fibrillation. Int J Cardiol 2013. [4] Camm AJ, Capucci A, Hohnloser SH, et al. A randomized active-controlled study comparing the efficacy and safety of vernakalant to amiodarone in recent-onset atrial fibrillation. J Am Coll Cardiol 2011;57:313–21.
Manual corrected QT and Tpeak-Tend calculations may assist emergency physicians risk stratify patients for arrhythmia☆,☆☆
To the Editor, We applaud Dr Moskovitz and his colleagues [1] for drawing attention to the often-neglected evidence of abnormal repolarization on the electrocardiogram (ECG) of emergency department patients. As emergency physicians and medical toxicologists, we agree that abnormalities of ventricular repolarization are often underappreciated, which can lead to disastrous consequences, particularly in the context of acute drug overdose. We would like to add a few points to the discussion and ask some questions. Assessing the prognostic value of corrected QT (QTc) prolongation is challenging because QTc interval prolongations are fairly common in acutely ill patients, whereas torsades de pointes is rare [2]. In addition, electrocardiograph manufacturers use proprietary computer algorithms to measure the QT interval and to calculate the QTc. These QTc calculations may be inaccurate in the presence of
☆ Sources of support: None. ☆☆ This information has not been previously presented.
1411
John J. Devlin MD Mohan Punja MD Ziad Kazzi MD Georgia Poison Center Atlanta, GA Department of Emergency Medicine Emory University School of Medicine Atlanta, GA E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2013.05.041
References [1] Moskovitz JB, Hayes BD, Martinez JP, Mattu A, Brady W. Electrocardiographic implications of the prolonged QT interval. Am J Emerg Med 2013 http://dx.doi.org/ 10.1016/j.ajem.2012.12.013. [2] Pinkham D, Helfenbein E, Shinn JA, Chan G, Funk M, Weinacker A, et al. High prevalence of corrected QT interval prolongation in acutely ill patients is associated with mortality: results of the QT in Practice (QTIP) study. Crit Care Med 2012;40(2): 394–9. [3] Guglin ME, Thatai D. Common errors in computer electrocardiogram interpretation. Int J Cardiol 2006;106(2):232–7. [4] Antzelevitch C. Ionic, molecular, and cellular basis of QT-interval prolongation and torsades de pointes. Europace 2007;9(Suppl. 4):iv4–iv15. [5] Barbhaiya C, Ricardo J, Hanon S, Schweitzer P. Tpeak-Tend and Tpeak-Tend/QT ratio as markers of ventricular arrhythmia risk in cardiac resynchronization therapy patients. Pacing Clin Electrophysiol 2013;36(1):103–8. [6] Lestas KP, Weber R, Astheimer K, Kalusche D, Arentz T. Tpeak-Tend interval and TpeakTend/QT ratio as markers of ventricular tachycardia inducibility in subjects with Brugada ECG phenotype. Europace 2010;12(2):271–4. [7] Shimizu M, Ino H, Okeie K, Yamaguchi M, Nagata M, et al. Tpeak-Tend interval may be a better predictor of high-risk patients with hypertrophic cardiomyopathy associated with a cardiac troponin I mutation than QT dispersion. Clin Cardiol 2002;25(7):335–9. [8] Topliski I, Rogowski O, Rosso R, Justo D, Copperman Y, et al. The morphology of the QT interval predicts torsades de pointes during acquired bradyarrhythmias. J Am Coll Card 2007;49(3):320–8.