Clinical Therapeutics/Volume 36, Number 9, 2014
Editor-in-Chief’s Note Some Observations About Atrial Fibrillation As I walked out of the theater one evening, an elderly man next to me slumped to the ground. I spotted and called over a nearby usher, and together we eased him into a chair. White haired and probably in his 70s, he said he had suddenly felt faint but was otherwise okay. I checked his pulse, and it was rapid, weak, and irregularly irregular. It seemed likely that he was experiencing an episode of atrial fibrillation (AFib). His wife, who was behind others when this happened, came rushing over. I asked her if he was known to have AFib. She replied that it was diagnosed a year before but that he was ignoring his physician’s advice to be further evaluated and treated because he only rarely felt palpitations. His age and sex are classic risk factors for AFib. Given the availability of databases derived from large population studies, many characteristics (in addition to being male and elderly) are Richard I. Shader, MD now recognized as AFib risk factors. Table I, created from the cited references, lists some of the risk factors that appear to have valid associations with AFib. They are not listed in any specific order of magnitude because studies and populations are not comparable.1–10 Several people I know who have AFib have been told to avoid coffee and other caffeinated drinks. The idea of caffeine intake as a risk factor seemed to me to make common sense because of increases in heart rate via caffeine’s inhibitory effect on adenosine. However, this concern should only apply to caffeine-naive individuals because long-term ingestion is associated with tolerance to caffeine’s cardiovascular effects. Coffee drinkers who have AFib will be heartened by a recent article proclaiming the relative neutrality and even possible benefits of coffee consumption in many forms of heart disease (including arrhythmias) and stroke.11 Early recognition and treatment to improve any underlying or predisposing causes are essential. Once a diagnosis is established, agents to lower heart rate (eg, β-adrenergic receptor antagonists, popularly called βblockers) or to reestablish sinus rhythm (eg, sotalol) are typically used. These therapies may be combined, when indicated and safe, with proper anticoagulation. Thus, a regimen that involves rate and rhythm control and anticoagulation is usually central to the prevention of strokes and to reduce the likelihood of falls and their
Table I. Risk factors for atrial fibrillation. Advanced Age Male Coronary artery disease Left ventricular dysfunction (by echocardiography) Wolff-Parkinson-White syndrome Physical stress or exertion
September 2014
Hyperthyroidism Hypertension Congestive heart failure Congenital heart disease
Obstructive Sleep Apnea Diabetes mellitus Valvular heart disease Hypertrophic cardiomyopathy
Obesity or Dyslipidemia or metabolic syndrome Emotional distress
Excessive use of alcohol Various genetic factors
1127
Clinical Therapeutics
Table II. Agents for the prevention of thromboembolic complications from atrial fibrillation. Generic Name
Trade Name
Warfarin sodium Apixaban Dabigatran Rivaroxaban
Coumadin Eliquis Pradaxa Xarelto
Mechanism of Action Vitamin K–dependent clotting factors inhibitor Factor Xa inhibitor Direct thrombin inhibitor Factor Xa inhibitor
complications, particularly in vulnerable elderly people. However, it is also clear that not all patients require anticoagulation. Amiodarone is often recommended for the prevention of AFib in patients undergoing cardiac or pulmonary surgery.12,13 Another option for patients who are already fibrillating is direct current cardioversion. This strategy is particularly useful for patients who are hemodynamically unstable and already receiving anticoagulant therapy.14 Very symptomatic patients can undergo catheter radiofrequency ablation or surgical ablation (when having an otherwise needed heart surgery). Low-dose aspirin is still used by some clinicians for its antithrombotic properties, but the newest (2014) guidelines from England’s National Institute for Health and Care Excellence clearly state that aspirin should not be used.15 Currently available anticoagulants are listed in Table II. Unwanted bleeding can occur with all these agents. Warfarin is the only one of these 4 agents that has an antidote, vitamin K, which is typically given orally. Before the use of any anticoagulant, patients need to be carefully assessed for bleeding tendencies. Another caution is that only warfarin is approved for patients with mechanical prosthetic heart valves.16 Professor Peter Thompson, our Topic Editor for Cardiology, Preventive Medicine, and Primary Care, has chosen to focus on AFib in this issue. He has invited a series of useful and informative contributions to examine aspects of AFib.17–23 As more experience is gained with newly available agents, we plan to continue our coverage of this troublesome disorder. I encourage readers who have comments regarding AFib to submit them to us. In June of this year, the New England Journal of Medicine featured 2 articles that examined cohorts of patients with cryptogenic strokes or transient ischemic attacks.24,25 A cryptogenic stroke was defined as one whose cause could not be determined by standard testing, including 24-hour electrocardiography. In one study, the experimental intervention was the use of 30 days of event-triggered monitoring.24 In the other study, the intervention involved the use of an insertable cardiac monitor that transmitted data to the investigators.25 The conclusions from both studies were comparable: more intensive monitoring revealed underlying AFib 5 to 6 times more frequently than was detected by conventional testing. Carefully diagnosing and treating AFib have been facilitated by new treatments and new diagnostic strategies. Patients will benefit when their treating clinicians become better informed about these changes—lives will be saved and morbidity will be reduced. In a recent issue, I included a poem of mine. Several readers have told me they enjoyed it as a change of pace from the usual editorial content. This month’s topic inspired another poem. When AFib is Not a Lie Lub dub, lub dub, lub dub Normal sounds from the heart First the blood swirls about Then the valves move apart The lub is the soft one It’s longer than dub The dub is much louder And briefer than lub
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Volume 36 Number 9
Editor-in-Chief’s Note But if yours are chaotic, irregular, unplanned Like this stanza is when it’s scanned If you’re not a faker or a consummate liar And your lub dubs speed up and you easily tire If you think this poem too silly or glib You could easily be in, not telling, AFib Richard I. Shader, MD Editor-in-Chief
REFERENCES 1. Kannel WB, Abbott RD, Savage DD, et al. Coronary heart disease and atrial fibrillation: the Framingham study. 1983;106:389–396. 2. Benjamin EJ, Levy D, Vaziri SM, et al. Independent risk factors for atrial fibrillation in a population-based cohort: the Framingham Heart Study. JAMA. 1994;271:840–844. 3. Furberg CD, Pstay BM, Manolo TA, et al. Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Am J Cardiol. 1994;74:236–241. 4. Krahn AD, Manfreda Jut-e, Tate RB, et al. The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba follow-up study. Am J Med. 1995;98:476–488. 5. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults. JAMA. 2001;285:2370–2375. 6. McCabe PJ. Psychological distress in patients diagnosed with atrial fibrillation. J Cardiovasc Nurs. 2010;25:40–51. 7. Digby GC, Baranchuk A. Sleep apnea and atrial fibrillation: 2012 update. Curr Cardiol Rev. 2012;8:265–272. 8. Hansson A, Madsen-Hardig B, Olsson SB. Arrhythmia-provoking factors and symptoms at the onset of paroxysmal atrial fibrillation: a study based on interviews with 100 patients seeking hospital assistance. BMC Cardiovasc Disord. 2004;4:13. 9. Menezes AR, Lavie CJ, DiNicolantonio JJ, et al. Atrial fibrillation in the 21st century: a current understanding of risk factor and primary prevention strategies. Mayo Clin Proc. 2013;88:394–409. 10. Wyss DG, Van Gelder IC, Ellinor PT, et al. Lone atrial fibrillation does it exist? J Am Coll Cardiol. 2014;63:1715–1723. 11. O’Keefe JH, Bhatti SK, Patil HR, et al. Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality. J Am Col Cardiol. 2013;62:1043–1051. 12. Arsenault KA, Yusuf AM, Crystal E, et al. Prophylactic amiodarone for prevention of atrial fibrillation after cardiac surgery: a meta-analysis. Ann Thorac Surg. 2006;82:1927–1937. 13. Bagshaw SM, Galbraith PD, Mitchell LB, et al. Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery. Cochrane Database Syst Rev. 2013;1:CD003611. 14. Gorenek B. Cardioversion in atrial fibrillation described. http://www.escardio.org/communities/councils/ccp/e-journal/ volume11/Pages/cardioversiony-atrial-fibrillation-Bulent-Gorenek.aspx#.U7K8pfldXOE. Accessed July 15, 2014. 15. National Institute for Health and Care Excellence. Atrial fibrillation: the management of atrial fibrillation. CG180 atrial fibrillation (update) guidelines. 18 June 2014. http://www.nice.org.uk/guidance/cg180/resources/cg180-atrial-fibrillation-up date-full-guideline2. Accessed July 15, 2014. 16. Baber U, van der Zee S, Fuster V. Anticoagulation for mechanical heart valves in patients with and without atrial fibrillation. Curr Cardiol Rep. 2010;12:133–139. doi:http://dx.doi.org/10.1007/s11886-010-0085-x. 17. Thompson PL. Atrial fibrillation: risk is still not well controlled, let alone ablated. Clin Ther. 2014;36:1132–1134. 18. Agarwal M, Apostolakis S, Lane DA, Lip GYH. The impact of heart failure in predicting stroke, thromboembolism and mortality in atrial fibrillation patients: a systematic review. Clin Ther. 2014;36:1135–1144. 19. Weerasooriya R, Shah AJ, Hocini M, et al. Contemporary challenges of catheter ablation for atrial fibrillation. Clin Ther. 2014;36:1145–1150. 20. Lau DH, Kalman JM, Sanders P. Management of recent onset sustained atrial fibrillation: pharmacological and nonpharmacological strategies. Clin Ther. 2014;36:1151–1159. 21. Cotté F-E, Benhaddi H, Duprat-Lomon I, et al. Vitamin K antagonist treatment in patients with atrial fibrillation and time in therapeutic range in four European countries. Clin Ther. 2014;36:1160–1168. 22. Chun KJ, Byeon K, Im SI, et al. Efficacy of dronedarone versus propafenone for the maintenance of sinus rhythm in patients with atrial fibrillation after electrical cardioversion. Clin Ther. 2014;36:1169–1175.
September 2014
1129
Clinical Therapeutics 23. Thompson PL, Verheugt FWA. Managing antithrombotic therapy in patients with both atrial fibrillation and coronary heart disease. Clin Ther. 2014;36:1176–1181. 24. Gladstone DJ, Spring M, Dorian P, et al. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014;370: 2467–2477. 25. Sanna T, Diener H-C, Passman RS, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014;370: 2478–2486.
http://dx.doi.org/10.1016/j.clinthera.2014.08.008
1130
Volume 36 Number 9
Editor-in-Chief’s Note Some Observations About Atrial Fibrillation As I walked out of the theater one evening, an elderly man next to me slumped to the ground. I spotted and called over a nearby usher, and together we eased him into a chair. White haired and probably in his 70s, he said he had suddenly felt faint but was otherwise okay. I checked his pulse, and it was rapid, weak, and irregularly irregular. It seemed likely that he was experiencing an episode of atrial fibrillation (AFib). His wife, who was behind others when this happened, came rushing over. I asked her if he was known to have AFib. She replied that it was diagnosed a year before but that he was ignoring his physician’s advice to be further evaluated and treated because he only rarely felt palpitations. His age and sex are classic risk factors for AFib. Given the availability of databases derived from large population studies, many characteristics (in addition to being male and elderly) are Richard I. Shader, MD now recognized as AFib risk factors. Table I, created from the cited references, lists some of the risk factors that appear to have valid associations with AFib. They are not listed in any specific order of magnitude because studies and populations are not comparable.1–10 Several people I know who have AFib have been told to avoid coffee and other caffeinated drinks. The idea of caffeine intake as a risk factor seemed to me to make common sense because of increases in heart rate via caffeine’s inhibitory effect on adenosine. However, this concern should only apply to caffeine-naive individuals because long-term ingestion is associated with tolerance to caffeine’s cardiovascular effects. Coffee drinkers who have AFib will be heartened by a recent article proclaiming the relative neutrality and even possible benefits of coffee consumption in many forms of heart disease (including arrhythmias) and stroke.11 Early recognition and treatment to improve any underlying or predisposing causes are essential. Once a diagnosis is established, agents to lower heart rate (eg, β-adrenergic receptor antagonists, popularly called βblockers) or to reestablish sinus rhythm (eg, sotalol) are typically used. These therapies may be combined, when indicated and safe, with proper anticoagulation. Thus, a regimen that involves rate and rhythm control and anticoagulation is usually central to the prevention of strokes and to reduce the likelihood of falls and their
Table I. Risk factors for atrial fibrillation. Advanced Age Male Coronary artery disease Left ventricular dysfunction (by echocardiography) Wolff-Parkinson-White syndrome Physical stress or exertion
September 2014
Hyperthyroidism Hypertension Congestive heart failure Congenital heart disease
Obstructive Sleep Apnea Diabetes mellitus Valvular heart disease Hypertrophic cardiomyopathy
Obesity or Dyslipidemia or metabolic syndrome Emotional distress
Excessive use of alcohol Various genetic factors
1127
Clinical Therapeutics
Table II. Agents for the prevention of thromboembolic complications from atrial fibrillation. Generic Name
Trade Name
Warfarin sodium Apixaban Dabigatran Rivaroxaban
Coumadin Eliquis Pradaxa Xarelto
Mechanism of Action Vitamin K–dependent clotting factors inhibitor Factor Xa inhibitor Direct thrombin inhibitor Factor Xa inhibitor
complications, particularly in vulnerable elderly people. However, it is also clear that not all patients require anticoagulation. Amiodarone is often recommended for the prevention of AFib in patients undergoing cardiac or pulmonary surgery.12,13 Another option for patients who are already fibrillating is direct current cardioversion. This strategy is particularly useful for patients who are hemodynamically unstable and already receiving anticoagulant therapy.14 Very symptomatic patients can undergo catheter radiofrequency ablation or surgical ablation (when having an otherwise needed heart surgery). Low-dose aspirin is still used by some clinicians for its antithrombotic properties, but the newest (2014) guidelines from England’s National Institute for Health and Care Excellence clearly state that aspirin should not be used.15 Currently available anticoagulants are listed in Table II. Unwanted bleeding can occur with all these agents. Warfarin is the only one of these 4 agents that has an antidote, vitamin K, which is typically given orally. Before the use of any anticoagulant, patients need to be carefully assessed for bleeding tendencies. Another caution is that only warfarin is approved for patients with mechanical prosthetic heart valves.16 Professor Peter Thompson, our Topic Editor for Cardiology, Preventive Medicine, and Primary Care, has chosen to focus on AFib in this issue. He has invited a series of useful and informative contributions to examine aspects of AFib.17–23 As more experience is gained with newly available agents, we plan to continue our coverage of this troublesome disorder. I encourage readers who have comments regarding AFib to submit them to us. In June of this year, the New England Journal of Medicine featured 2 articles that examined cohorts of patients with cryptogenic strokes or transient ischemic attacks.24,25 A cryptogenic stroke was defined as one whose cause could not be determined by standard testing, including 24-hour electrocardiography. In one study, the experimental intervention was the use of 30 days of event-triggered monitoring.24 In the other study, the intervention involved the use of an insertable cardiac monitor that transmitted data to the investigators.25 The conclusions from both studies were comparable: more intensive monitoring revealed underlying AFib 5 to 6 times more frequently than was detected by conventional testing. Carefully diagnosing and treating AFib have been facilitated by new treatments and new diagnostic strategies. Patients will benefit when their treating clinicians become better informed about these changes—lives will be saved and morbidity will be reduced. In a recent issue, I included a poem of mine. Several readers have told me they enjoyed it as a change of pace from the usual editorial content. This month’s topic inspired another poem. When AFib is Not a Lie Lub dub, lub dub, lub dub Normal sounds from the heart First the blood swirls about Then the valves move apart The lub is the soft one It’s longer than dub The dub is much louder And briefer than lub
1128
Volume 36 Number 9
Editor-in-Chief’s Note But if yours are chaotic, irregular, unplanned Like this stanza is when it’s scanned If you’re not a faker or a consummate liar And your lub dubs speed up and you easily tire If you think this poem too silly or glib You could easily be in, not telling, AFib Richard I. Shader, MD Editor-in-Chief
REFERENCES 1. Kannel WB, Abbott RD, Savage DD, et al. Coronary heart disease and atrial fibrillation: the Framingham study. 1983;106:389–396. 2. Benjamin EJ, Levy D, Vaziri SM, et al. Independent risk factors for atrial fibrillation in a population-based cohort: the Framingham Heart Study. JAMA. 1994;271:840–844. 3. Furberg CD, Pstay BM, Manolo TA, et al. Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Am J Cardiol. 1994;74:236–241. 4. Krahn AD, Manfreda Jut-e, Tate RB, et al. The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba follow-up study. Am J Med. 1995;98:476–488. 5. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults. JAMA. 2001;285:2370–2375. 6. McCabe PJ. Psychological distress in patients diagnosed with atrial fibrillation. J Cardiovasc Nurs. 2010;25:40–51. 7. Digby GC, Baranchuk A. Sleep apnea and atrial fibrillation: 2012 update. Curr Cardiol Rev. 2012;8:265–272. 8. Hansson A, Madsen-Hardig B, Olsson SB. Arrhythmia-provoking factors and symptoms at the onset of paroxysmal atrial fibrillation: a study based on interviews with 100 patients seeking hospital assistance. BMC Cardiovasc Disord. 2004;4:13. 9. Menezes AR, Lavie CJ, DiNicolantonio JJ, et al. Atrial fibrillation in the 21st century: a current understanding of risk factor and primary prevention strategies. Mayo Clin Proc. 2013;88:394–409. 10. Wyss DG, Van Gelder IC, Ellinor PT, et al. Lone atrial fibrillation does it exist? J Am Coll Cardiol. 2014;63:1715–1723. 11. O’Keefe JH, Bhatti SK, Patil HR, et al. Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality. J Am Col Cardiol. 2013;62:1043–1051. 12. Arsenault KA, Yusuf AM, Crystal E, et al. Prophylactic amiodarone for prevention of atrial fibrillation after cardiac surgery: a meta-analysis. Ann Thorac Surg. 2006;82:1927–1937. 13. Bagshaw SM, Galbraith PD, Mitchell LB, et al. Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery. Cochrane Database Syst Rev. 2013;1:CD003611. 14. Gorenek B. Cardioversion in atrial fibrillation described. http://www.escardio.org/communities/councils/ccp/e-journal/ volume11/Pages/cardioversiony-atrial-fibrillation-Bulent-Gorenek.aspx#.U7K8pfldXOE. Accessed July 15, 2014. 15. National Institute for Health and Care Excellence. Atrial fibrillation: the management of atrial fibrillation. CG180 atrial fibrillation (update) guidelines. 18 June 2014. http://www.nice.org.uk/guidance/cg180/resources/cg180-atrial-fibrillation-up date-full-guideline2. Accessed July 15, 2014. 16. Baber U, van der Zee S, Fuster V. Anticoagulation for mechanical heart valves in patients with and without atrial fibrillation. Curr Cardiol Rep. 2010;12:133–139. doi:http://dx.doi.org/10.1007/s11886-010-0085-x. 17. Thompson PL. Atrial fibrillation: risk is still not well controlled, let alone ablated. Clin Ther. 2014;36:1132–1134. 18. Agarwal M, Apostolakis S, Lane DA, Lip GYH. The impact of heart failure in predicting stroke, thromboembolism and mortality in atrial fibrillation patients: a systematic review. Clin Ther. 2014;36:1135–1144. 19. Weerasooriya R, Shah AJ, Hocini M, et al. Contemporary challenges of catheter ablation for atrial fibrillation. Clin Ther. 2014;36:1145–1150. 20. Lau DH, Kalman JM, Sanders P. Management of recent onset sustained atrial fibrillation: pharmacological and nonpharmacological strategies. Clin Ther. 2014;36:1151–1159. 21. Cotté F-E, Benhaddi H, Duprat-Lomon I, et al. Vitamin K antagonist treatment in patients with atrial fibrillation and time in therapeutic range in four European countries. Clin Ther. 2014;36:1160–1168. 22. Chun KJ, Byeon K, Im SI, et al. Efficacy of dronedarone versus propafenone for the maintenance of sinus rhythm in patients with atrial fibrillation after electrical cardioversion. Clin Ther. 2014;36:1169–1175.
September 2014
1129
Clinical Therapeutics 23. Thompson PL, Verheugt FWA. Managing antithrombotic therapy in patients with both atrial fibrillation and coronary heart disease. Clin Ther. 2014;36:1176–1181. 24. Gladstone DJ, Spring M, Dorian P, et al. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014;370: 2467–2477. 25. Sanna T, Diener H-C, Passman RS, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014;370: 2478–2486.
http://dx.doi.org/10.1016/j.clinthera.2014.08.008
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Volume 36 Number 9
