Optimizing Heart Rate and Controlling Symptoms in Atrial Fibrillation

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Abstract

Atrial fibrillation (AF) is the most common arrhythmia noted in clinical practice and its incidence and prevalence are on the rise. The single most important intervention is the evaluation and treatment of stroke risk. Once the risk for stroke has been minimized, controlling the ventricular rate and treating symptoms become relevant. In this review article, we emphasize the importance of confirming and treating the appropriate arrhythmia and correlating symptoms with rhythm changes. Furthermore, we evaluate some of the risk factors for AF that independently result in symptoms, underlining the need to treat these risk factors as part of symptom control. We then discuss existing and novel approaches to rate control in AF and briefly cover rhythm control methods.

Disclosure
The authors have no conflicts of interest to declare.
Correspondence
KL Venkatachalam, Department of Cardiology, Mayo Clinic Florida, 4500 San Pablo Road, Davis 7, Jacksonville, FL 32224, USA. E: Venkat.KL@mayo.edu
Received date
06 January 2016
Accepted date
03 February 2016
DOI
https://doi.org/10.15420/usc.2016.10.1.26

Atrial fibrillation (AF) is the most common pathologic clinical arrhythmia lasting more than 30 seconds, and its incidence and prevalence continue to increase. It has been estimated that 5.9 % of patients aged >65 years suffer from AF.1 In the Rotterdam study, 17.8 % of patients over 85 had AF.2 The lifetime risk for developing AF in both men and women above age 40 is one in four.3 This arrhythmia, with its attendant comorbidities, poses a substantial physical, psychologic, and financial burden on the populace and is a significant public health concern. Evaluating and managing AF appropriately at the primary care level (by minimizing risk factors) and recognizing and treating the arrhythmia immediately will play important roles in containing this epidemic. This review article addresses the recognition of AF and the importance of distinguishing it from other arrhythmias with an irregular pulse. It discusses the available options for stroke reduction and examines the correlation between symptoms and rhythms. It then reviews existing and potentially novel approaches to rate and rhythm control and their role in controlling symptoms in patients with AF.

Types of Atrial Fibrillation

The type of AF determines treatment, and we will use the definitions from the most recent American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines on AF from 2014.4 Paroxysmal AF (PAF) terminates spontaneously or with intervention within 7 days of onset. Persistent AF lasts >7 days and often requires pharmacologic or electrical cardioversion. Long-standing persistent AF lasts >12 months. This is an important change to the definition since cardioversion and ablation success rates diminish substantially in patients with long-standing persistent AF. Permanent AF describes the situation where the patient and physician have decided to stop pursuing a rhythm control strategy.

Confirming the Arrhythmia

The most common clue for suspecting that a patient may be in AF is the irregularity of the pulse. As medical students, we are all taught to associate an “irregularly irregular” pulse with AF. However, there are several arrhythmias that can produce irregularly irregular pulses and a few that produce regularly irregular pulses, which can also feel irregularly irregular if they have not been assessed for an adequate period of time. Irregularly irregular pulses are present in AF, atrial flutter with variable atrioventricular (AV) conduction, wandering atrial pacemaker, multifocal atrial tachycardia, and frequent premature atrial and ventricular complexes. Regularly irregular pulses may be noted in patients with sinoatrial exit block as well as second degree AV block. If the pulse is not monitored for an adequate interval the pattern of irregularity may not be perceived, and a wrong conclusion may be drawn.

An electrical rhythm strip is still the only reliable way to identify these arrhythmias. Patients now have access to home blood pressure (BP) monitors, pulse oximeters, and single lead rhythm monitors, which indicate the presence of irregularity.5,6 This does not constitute proof of AF. Even computer-based ECG diagnostics frequently get the above arrhythmias confused, and simply reading the verbal report of an ECG without looking at the rhythm strips for oneself will result in an erroneous diagnosis (see Figure 1). Implanted pacemaker and defibrillator diagnostics can also confuse supraventricular tachycardia with AF or atrial flutter and simply using the presence of atrial high rate (AHR) episodes from a pacemaker check as proof of AF is not appropriate. The stored electrograms need to be evaluated to confirm the arrhythmia before treatment can be suggested.

Based on present knowledge, only AF and atrial flutter pose a significant stroke risk and require risk-factor-based anticoagulation. Also, the treatment for typical atrial flutter (counterclockwise isthmus dependent flutter) is significantly different from the treatment of AF since typical atrial flutter can be ablated relatively easily with excellent success rates (90 %). The clinician is obliged to offer patients the appropriate treatment choices based on risk and efficacy, and identifying the correct arrhythmia is the first step.

Evaluating and Treating Stroke Risk

Once AF has been confirmed, estimating a patient’s stroke risk in AF is paramount, as an embolic stroke due to inadequately treated AF is the surest way to negatively impact quality of life (QoL) in these patients. Several algorithms have been developed over the past 25 years and the CHA2DS2-VaSc scoring system has been most recently validated.7–9 With nonvalvular AF and a CHA2DS2-VASc score of 0 (i.e., aged <65 years with lone AF), both the US and European guidelines agree that it is reasonable to omit antithrombotic therapy. However, the two guidelines differ in their recommendations for patients with a CHA2DS2-VaSc score of 1. The US guidelines allow for antiplatelet therapy, anticoagulation, or neither, based upon an assessment of the risk for bleeding complications and patient preferences; whereas the European guidelines recommend anticoagulation as the only option. Both guidelines agree that at a CHA2DS2-VaSc score of ≥2 anticoagulation should be instituted.4,10 Warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban have been approved for this use. Patients who are intolerant, or have a contraindication, to the use of anticoagulants would be candidates for a left atrial appendage occlusion, whose efficacy has been validated recently.11

Symptoms Related to Atrial Fibrillation

Patients may present with a variety of symptoms related to AF. The most common symptoms include palpitations, dyspnea, and fatigue. Additionally, chest pain, lightheadedness, presyncope, and syncope may be also reported. More than half of patients with AF experience a decrease in exercise tolerance defined by lowered New York Heart Association functional class. In addition to simple awareness of having an irregular rhythm, there are multiple potential mechanisms for these symptoms, including loss of atrial contraction, loss of AV synchrony, bradycardia, tachycardia, or even tachycardia-mediated cardiomyopathy. Understanding the type of symptom and the mechanism behind it are important steps in determining the optimal treatment strategy for patients with AF.

Figure 1: Electrocardiogram Rhythm Strips Showing a) Atrial Fibrillation; b) Atrial Flutter with Variable Atrioventricular Block; c) Multifocal Atrial Tachycardia; and d) Sinus Rhythm with Frequent Premature Atrial Complexes

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Figure 2: An Example of the Lack of Symptom–Arrhythmia Correlation on Event Monitoring

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Correlating Symptoms with Rhythm

While patients may present with a variety of symptoms in AF, these may also be noted in a host of other conditions including pulmonary disease, poorly controlled hypertension (or due to the BP medications themselves), obstructive sleep apnea, obesity, or deconditioning.12–14 Therefore, it is important to confirm that the patient’s symptoms are, in fact, related to AF before beginning treatment. This is typically achieved with prolonged rhythm monitoring, ranging from 1 to 30 days depending on the frequency of symptoms. This approach can identify symptomatic bradycardia, prolonged pauses, tachycardia, or simply awareness of conversion into or out of AF. However, it is important to correlate the patient’s symptoms temporally with an episode of AF, as noted in Figure 2. Having episodes of paroxysmal AF on a particular day should not result in symptoms on another day, and concluding that AF produced these symptoms will result in needless testing and therapy. Additionally, an exercise electrogram can be utilized to identify poor rate control or chronotropic incompetence as potential causes for dyspnea on exertion or exercise intolerance. Once the AF and symptoms have been correlated, appropriate therapy can be instituted.15 Anxiety in the presence of palpitations is common; allaying a patient’s fears regarding the arrhythmia and using a systematic approach to treating the risk factors and controlling AF will go a long way toward improving QoL in these patients.16

Figure 3: Rate Control Recommendations from the 2014 American Heart Association/American College of Cardiology/ Heart Rhythm Society Guideline for Atrial Fibrillation Management

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Figure 4: Drug Selection for Rhythm Control in Atrial Fibrillation from the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society guideline for Atrial Fibrillation Management.

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Lifestyle Modification

In addition to considering pharmacologic or procedural treatment options for AF management, it is important to address modifiable risk factors. Obesity, obstructive sleep apnea, hypertension, type 2 diabetes, and alcohol consumption have all been identified as independent risk factors for the development of AF. Properly evaluating and treating these risk factors may help minimize episodes of AF and also tackle the symptoms.17–21 Caffeine intake has also often been discouraged for patients with AF. However multiple studies have demonstrated no association between caffeine exposure and risk for AF, and there is even evidence to suggest that caffeine consumption in moderate amounts may actually decrease the occurrence of AF.22 Finally, exercise can improve symptoms throughout the spectrum of AF. In fact, multiple studies have demonstrated that exercise training in adults with permanent AF significantly improves rate control (at rest and with exertion), functional capacity, muscle strength, activities of daily living, and QoL.23

Approaches to Rate Control in Atrial Fibrillation

Controlling heart rate (ventricular response) is a well-established approach to treating patients with minimally symptomatic AF. Beta blockers, calcium channel blockers, and digitalis (see Figure 3) are commonly used to accomplish this goal.24,25 The Atrial Fibrillation Follow- up Investigation of Rhythm Management (AFFIRM) trial used 80 beats/ min as a reasonable resting heart rate in AF. More recently, the Rate Control Efficacy in Permanent Atrial Fibrillation II (RACE-II) trial compared strict versus lenient rate control and demonstrated that a lenient rate control strategy does not increase morbidity. The criticism levelled against this study is that most patients in the control and treatment groups had heart rates below 90 beats/min and the results were really based on an intention-to-treat analysis.26,27

In active individuals, digitalis is not as helpful for rate control since sympathetic drive during activity can overwhelm the vagotonic action of digitalis. However, it can be useful in conjunction with a beta blocker or calcium channel blocker since it can control ventricular rate without reducing BP. Anti-arrhythmic drugs (AADs), even if they fail to maintain sinus rhythm, can provide rate control without lowering BP. Amiodarone has strong AV nodal blocking activity and may be effective in this application. There is mounting evidence that the hyperpolarization- activated cyclic nucleotide-gated (HCN) channels, responsible for funny current (If) modulation, are also present in the AV node and could be targeted to achieve rate control. The prototypical drug to modulate If in the sinus node is ivabradine.28 Recent case reports highlight the rate- controlling effect of ivabradine in AF through its additional action on the AV node, and this may turn out to be a very useful drug for this purpose, though presently this would be an off-label use of this medication.29–31

The extreme approach in the continuum of rate control is AV node ablation, with pacemaker implantation. This technique has fallen out of favor over the past 20 years due to the rapid incorporation of AF ablation into clinical practice. Nevertheless, AV node ablation with pacemaker implantation remains a very effective technique to control symptoms and improve QoL, particularly in the elderly population, often intolerant of rate-controlling medications.32–33

Managing Rhythm Control in Atrial Fibrillation

In patients who are symptomatic from AF, despite good control of heart rate, a rhythm-control strategy should be implemented. Success at maintaining sinus rhythm long-term is highest with good control of underlying risk factors (hypertension, sleep apnea, and obesity). Cardioversion as a means of establishing that AF is responsible for symptoms is a very reasonable first step, even if the long-term success of this approach is only 30–35 %. Once the symptom-rhythm correlation has been established and risk factors have been controlled, AADs may be attempted. The 2014 ACC/AHA/HRS AF guidelines provide a systematic approach to trying AADs (see Figure 4), based on the patient’s co-morbidities.4 Ranolazine in conjunction with dronedarone or ivabradine may also play an important role in effective rate control of AF.30,34 Intolerance of AADs or breakthrough AF while on AADs should prompt consideration of an invasive approach. The specific technique (radiofrequency ablation, cryoablation, focal impulse and rotor modulation, laser ablation, or a surgical maze procedure in patients undergoing cardiac surgery) is not as important as the decision to attempt the intervention, and the risks and benefits of this approach need to be discussed with patients in detail. The success rate for all ablative methods for paroxysmal AF has been reported between 66–89 % at 1 year. In long-standing persistent AF, multiple ablation procedures may often be required.35,36

Conclusion

AF should be considered a chronic condition, and like other chronic conditions, such as hypertension and diabetes, should be treated with risk factor control and symptom management. Since the morbidity associated with this condition and with the available treatment options is considerable, exhaustive attempts to confirm the diagnosis of AF must be made early. Symptom-rhythm correlation is an important part of this evaluation. Advances in heart rate control, rhythm management, and stroke prevention over the next decade will aid in reducing the burden of AF.

References
  1. Feinberg WM, Blackshear JL, Laupacis A, et al. Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Arch Intern Med 1995;155:469–73.
    Crossref | PubMed
  2. Heeringa J, van der Kuip DA, Hofman A, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J 2006;27:949–53.
    Crossref | PubMed
  3. Lloyd-Jones DM, Wang TJ, Leip EP, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 2004;110:1042–6.
    Crossref | PubMed
  4. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014;64:e1–76.
    Crossref | PubMed
  5. Lamb TS, Thakrar A, Ghosh M, et al. Comparison of two oscillometric blood pressure monitors in subjects with atrial fibrillation. Clin Invest Med 2010;33:E54–62.
    PubMed
  6. Scully CG, Lee J, Meyer J, et al. Physiological parameter monitoring from optical recordings with a mobile phone. IEEE Trans Biomed Eng 2012;59:303–6.
    Crossref | PubMed
  7. Lip GY. Stroke in atrial fibrillation: epidemiology and thromboprophylaxis. J Thromb Haemost 2011;9(Suppl 1):344–51.
    Crossref | PubMed
  8. Olesen JB, Lip GY, Hansen ML, et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ 2011;342:d124.
    Crossref | PubMed
  9. Van Staa TP, Setakis E, Di Tanna GL, et al. A comparison of risk stratification schemes for stroke in 79,884 atrial fibrillation patients in general practice. J Thromb Haemost 2011;9:39–48.
    Crossref | PubMed
  10. Camm AJ, Lip GY, De Caterian R, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation–developed with the special contribution of the European Heart Rhythm Association. Europace 2012;14:1385–413.
    Crossref | PubMed
  11. Holmes DR Jr, Kar S, Price MJ, et al. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol 2014;64:1–12.
    Crossref | PubMed
  12. Garimella RS, Chung EH, Mounsey JP, et al. Accuracy of patient perception of their prevailing rhythm: a comparative analysis of monitor data and questionnaire responses in patients with atrial fibrillation. Heart Rhythm 2015;12:658–65.
    Crossref | PubMed
  13. Rienstra M, Lubitz SA, Mahida S, et al. Symptoms and functional status of patients with atrial fibrillation: state of the art and future research opportunities. Circulation 2012;125:2933–43.
    Crossref | PubMed
  14. Vermond RA, Crijns HJGM, Tijssen JGP, et al. Symptom severity is associated with cardiovascular outcome in patients with permanent atrial fibrillation in the RACE II study. Europace 2014;16:1417–25.
    Crossref | PubMed
  15. Patel N, Chung EH, Mounsey JP, et al. Effectiveness of atrial fibrillation monitor characteristics to predict severity of symptoms of atrial fibrillation. Am J Cardiol 2014;113:1674–8.
    Crossref | PubMed
  16. Kochhäuser S, Joza J, Essebag V, et al. The impact of duration of atrial fibrillation recurrences on measures of health related quality of life and symptoms. Pacing Clin Electrophysiol 2015: epub ahead of print.
    Crossref | PubMed
  17. Pathak RK, Middeldorp ME, Meredith M, et al. Long-Term Effect of Goal-Directed Weight Management in an Atrial Fibrillation Cohort: A Long-Term Follow-Up Study (LEGACY). J Am Coll Cardiol 2015;65:2159–69.
    Crossref | PubMed
  18. Nalliah CJ, Sanders P, Kottkamp H, Kalman JM. The role of obesity in atrial fibrillation. Eur Heart J 2015; epub ahead of press.
    Crossref | PubMed
  19. Chung MK, Foldvary-Schaefer N, Somers VK, et al. Atrial fibrillation, sleep apnea and obesity. Nat Clin Pract Cardiovasc Med 2004;1:56–9.
    PubMed
  20. Kanagala R, Murali NS, Friedman PA, et al. Obstructive sleep apnea and the recurrence of atrial fibrillation. Circulation 2003;107:2589–94.
    Crossref | PubMed
  21. Gami AS, Hodge DO, Herges RM, et al. Obstructive sleep apnea, obesity, and the risk of incident atrial fibrillation. J Am Coll Cardiol 2007;49:565–71.
    Crossref | PubMed
  22. Menezes AR, Lavie CJ, De Schutter A, et al. Lifestyle modification in the prevention and treatment of atrial fibrillation. Prog Cardiovasc Dis 2015;58:117–25.
    Crossref | PubMed
  23. Reed JL, Mark AE, Reid RD, Pipe AL. The effects of chronic exercise training in individuals with permanent atrial fibrillation: a systematic review. Can J Cardiol 2013;29:1721–8.
    Crossref | PubMed
  24. Costea AI, Platonov PG. Rate modulation drugs in atrial fibrillation: what is the clinical impact? J Cardiovasc Electrophysiol 2015;26:142–4.
    Crossref | PubMed
  25. Waldo AL. Rate control versus rhythm control in atrial fibrillation: lessons learned from clinical trials of atrial fibrillation. Prog Cardiovasc Dis 2015;58:168–76.
    Crossref | PubMed
  26. Van Gelder IC, Groenveld HF, Crijns HJ, et al. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med 2010;362:1363–73.
    Crossref | PubMed
  27. Steinberg BA, Kim S, Thomas L, et al. Increased heart rate is associated with higher mortality in patients with atrial fibrillation (AF): Results from the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF). JAMA 2015;4:e002031.
    Crossref | PubMed
  28. Giuseppe C, Chiara F, Giuseppe R, Maurizio V. Addition of ivabradine to betablockers in patients with atrial fibrillation: Effects on heart rate and exercise tolerance. Int J Cardiol 2016;202:73–4.
    Crossref | PubMed
  29. Moubarak G, Logeart D, Cazeau S, Cohen Solal A. Might ivabradine be useful in permanent atrial fibrillation? Int J Cardiol 2014;175:187–8.
    Crossref | PubMed
  30. Verrier RL, Silva AF, Bonatti R, et al. Combined actions of ivabradine and ranolazine reduce ventricular rate during atrial fibrillation. J Cardiovasc Electrophysiol 2015;26:329–35.
    Crossref | PubMed
  31. Kosiuk J, Oebel S, John S, et al. Ivabradine for rate control in atrial fibrillation. Int J Cardiol 2015;179:27–8.
    Crossref | PubMed
  32. Dong K, Shen K-W, Powell BD. et al. Atrioventricular nodal ablation predicts survival benefit in patients with atrial fibrillation receiving cardiac resynchronization therapy. Heart Rhythm 2010;7:1240–5.
    Crossref | PubMed
  33. Vlacho K, Letsas KP, Korantzopoulos P, et al. A review on atrioventricular junction ablation and pacing for heart rate control of atrial fibrillation. J Geriatr Cardiol 2015;12:547–54.
    Crossref | PubMed
  34. Reiffel JA, Camm AJ, Belardinelli L, et al. The HARMONY Trial: Combined Ranolazine and Dronedarone in the Management of Paroxysmal Atrial Fibrillation: Mechanistic and Therapeutic Synergism. Circ Arrhythm Electrophysiol 2015;8:1048–56.
    Crossref | PubMed
  35. Packer DL, Kowal RC, Wheelan KR, et al. Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the North American Arctic Front (STOP AF) pivotal trial. J Am Coll Cardiol 2013;61:1713–23.
    Crossref | PubMed
  36. Calkins H, Kuck KH, Cappato R, et al. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society. Heart Rhythm 2012;9:632–696 e21.
    Crossref | PubMed