Atrial Fibrillation: Risks, Comorbidities, and Differential Diagnoses - The Cardiology Advisor

Atrial Fibrillation: Risks, Comorbidities, and Differential Diagnoses

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  • AF is a complex condition associated with mechanical, electrical, and structural abnormalities of the atria; thus, many factors can predispose to its development.[6] It is most common in patients aged ≥65 years, affecting 9% of this population.[1] It is also more common in women, those of European descent, those with predisposing comorbidities and lifestyle factors, and after surgery.[1] Comorbidities that increase the risk of AF include obesity, cardiovascular conditions (eg, hypertension, coronary artery disease, structural heart disease), and other chronic conditions (eg, hyperthyroidism, asthma). Heavy alcohol use is known to increase risk of developing AF, but a recently published study indicates that regular consumption of even small amounts of alcohol can lead to atrial enlargement and subsequent AF.[7] In addition, several cases of AF after episodes of heavy binge drinking have been reported in people who normally drink little or no alcohol and have no underlying cardiovascular comorbidities.[8]

    AF Risk Factors

    AF is a complex condition associated with mechanical, electrical, and structural abnormalities of the atria; thus, many factors can predispose to its development.[6] It is most common in patients aged ≥65 years, affecting 9% of this population.[1] It is also more common in women, those of European descent, those with predisposing comorbidities and lifestyle factors, and after surgery.[1] Comorbidities that increase the risk of AF include obesity, cardiovascular conditions (eg, hypertension, coronary artery disease, structural heart disease), and other chronic conditions (eg, hyperthyroidism, asthma). Heavy alcohol use is known to increase risk of developing AF, but a recently published study indicates that regular consumption of even small amounts of alcohol can lead to atrial enlargement and subsequent AF.[7] In addition, several cases of AF after episodes of heavy binge drinking have been reported in people who normally drink little or no alcohol and have no underlying cardiovascular comorbidities.[8]

  • AF treatment hinges on the frequency and severity of symptoms, presence of comorbidities, and whether any underlying causes of AF are identifiable. Treatments include pharmacotherapies, medical or surgical interventions, and lifestyle changes, depending on treatment goals. Most commonly, treatment focuses on controlling heart rate or rhythm while reducing the risk of blood clots.[9] Pharmacotherapies for AF include beta blockers, calcium channel blockers, antiarrhythmics, and anticoagulants. A 2013 AHRQ (Agency for Healthcare Research and Quality) review comparing rate vs rhythm control strategies found comparable efficacy between the 2 in all-cause mortality, cardiovascular mortality, stroke, and bleeding events; however, rate-control strategies were associated with fewer cardiovascular hospitalizations and fewer adverse events.[9] A review from 2015 suggests all patients should receive rate control, with the need for maintenance of sinus rhythm determined on an individual patient basis.[10]

    Managing AF: Rate vs Rhythm Control

    AF treatment hinges on the frequency and severity of symptoms, presence of comorbidities, and whether any underlying causes of AF are identifiable. Treatments include pharmacotherapies, medical or surgical interventions, and lifestyle changes, depending on treatment goals. Most commonly, treatment focuses on controlling heart rate or rhythm while reducing the risk of blood clots.[9] Pharmacotherapies for AF include beta blockers, calcium channel blockers, antiarrhythmics, and anticoagulants. A 2013 AHRQ (Agency for Healthcare Research and Quality) review comparing rate vs rhythm control strategies found comparable efficacy between the 2 in all-cause mortality, cardiovascular mortality, stroke, and bleeding events; however, rate-control strategies were associated with fewer cardiovascular hospitalizations and fewer adverse events.[9] A review from 2015 suggests all patients should receive rate control, with the need for maintenance of sinus rhythm determined on an individual patient basis.[10]

  • Although rate control is the preferred frontline treatment, rhythm control strategies are needed for some patients, such as if symptoms are bothersome or rate control medications fail. Two classes of medication used to restore sinus rhythm include sodium channel blockers and potassium channel blockers; however, these agents’ risk of significant adverse effects [AEs] necessitates careful patient monitoring. Procedural interventions might be preferable to medication in some patients, such as if polypharmacy is a concern, there are intolerable AEs, or antiarrhythmics have failed. These interventions might include electrical cardioversion, catheter ablation, pacemaker implantation, maze procedure, or other interventional procedures. Catheter ablation has shown a high level of success compared with drug treatment, sometimes even providing a cure, leading some researchers to suggest it should be considered a frontline treatment for certain patients, such as those with paroxysmal AF.[11]

    Rhythm Control Strategies

    Although rate control is the preferred frontline treatment, rhythm control strategies are needed for some patients, such as if symptoms are bothersome or rate control medications fail. Two classes of medication used to restore sinus rhythm include sodium channel blockers and potassium channel blockers; however, these agents’ risk of significant adverse effects [AEs] necessitates careful patient monitoring. Procedural interventions might be preferable to medication in some patients, such as if polypharmacy is a concern, there are intolerable AEs, or antiarrhythmics have failed. These interventions might include electrical cardioversion, catheter ablation, pacemaker implantation, maze procedure, or other interventional procedures. Catheter ablation has shown a high level of success compared with drug treatment, sometimes even providing a cure, leading some researchers to suggest it should be considered a frontline treatment for certain patients, such as those with paroxysmal AF.[11]

  • Decisions regarding thromboprophylaxis requires weighing the risk of stroke against the risk of bleeding in each patient.[3,4] Numerous risk assessment tools are available, including CHADS2, CHA2DS2-VASc, and HAS-BLED. American and European guidelines recommend the use of CHA2DS2-VASc, which considers sex, age, and history of congestive HF, hypertension, stroke/transient ischemic attack/thromboembolism, vascular disease, and diabetes mellitus.[3,4] Compared with other stroke risk assessment measures, this tool performed best in identifying patients at low risk of stroke who did not require anticoagulation therapy.[12] Oral anticoagulation is recommended in any patient with a score ≥2 on the CHA2DS2-VASc. In these patients, warfarin or the novel anticoagulants dabigatran, rivaroxaban, apixaban, or edoxaban can be considered, except in the setting of moderate to severe chronic kidney disease, where reduced doses of direct thrombin or factor Xa inhibitors are preferable.[4]

    Anticoagulation in AF

    Decisions regarding thromboprophylaxis requires weighing the risk of stroke against the risk of bleeding in each patient.[3,4] Numerous risk assessment tools are available, including CHADS2, CHA2DS2-VASc, and HAS-BLED. American and European guidelines recommend the use of CHA2DS2-VASc, which considers sex, age, and history of congestive HF, hypertension, stroke/transient ischemic attack/thromboembolism, vascular disease, and diabetes mellitus.[3,4] Compared with other stroke risk assessment measures, this tool performed best in identifying patients at low risk of stroke who did not require anticoagulation therapy.[12] Oral anticoagulation is recommended in any patient with a score ≥2 on the CHA2DS2-VASc. In these patients, warfarin or the novel anticoagulants dabigatran, rivaroxaban, apixaban, or edoxaban can be considered, except in the setting of moderate to severe chronic kidney disease, where reduced doses of direct thrombin or factor Xa inhibitors are preferable.[4]

  • AF is a major risk factor for stroke and has been reported to be an incidental finding in 25% of all stroke admissions.[5] AF is associated with an approximately 2-fold increase in mortality, largely attributable to its association with stroke, which occurs at an annual rate of 5% to 7%.[5] Oral anticoagulation reduces the risk of stroke by more than 60% and all-cause mortality by more than 25% compared with placebo.[13] Historically, warfarin has been the anticoagulant of choice, but novel oral anticoagulants have shown similar efficacy to warfarin with less risk of bleeding and drug interactions.[14] They also require less monitoring and fewer dietary restrictions compared with warfarin. No head-to-head comparisons have been performed between these agents to guide selection, but a 2013 meta-analysis revealed some differences that favored apixaban for most patients, followed by dabigatran and then rivaroxaban; the data for edoxaban were inconclusive because it had not yet been approved by the FDA.[14]

    Stroke in AF

    AF is a major risk factor for stroke and has been reported to be an incidental finding in 25% of all stroke admissions.[5] AF is associated with an approximately 2-fold increase in mortality, largely attributable to its association with stroke, which occurs at an annual rate of 5% to 7%.[5] Oral anticoagulation reduces the risk of stroke by more than 60% and all-cause mortality by more than 25% compared with placebo.[13] Historically, warfarin has been the anticoagulant of choice, but novel oral anticoagulants have shown similar efficacy to warfarin with less risk of bleeding and drug interactions.[14] They also require less monitoring and fewer dietary restrictions compared with warfarin. No head-to-head comparisons have been performed between these agents to guide selection, but a 2013 meta-analysis revealed some differences that favored apixaban for most patients, followed by dabigatran and then rivaroxaban; the data for edoxaban were inconclusive because it had not yet been approved by the FDA.[14]

  • AF is both a cause and consequence of HF.[15] Having one condition significantly increases the risk of the other developing. Patients with AF have a 3-fold increased risk of incident HF and the presence of both significantly increases mortality. [5,15] Preventing AF in HF patients improves outcomes. Use of angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and beta blockers have been reported to reduce the risk of incident and/or new-onset AF.[15] In newly diagnosed concomitant HF, the CAN-TREAT mnemonic can help guide treatment.[15] This approach starts with cardioversion (C), anticoagulation (A), and normalizing (N) fluid balance. It subsequently targets (T) a heart rate <110 beats per minute, modifies the renin-angiotensin-aldosterone (R) system, establishes early (E) rhythm control, considers advanced (A) HF therapies, and treats (T) other cardiovascular diseases.[15]

    Heart Failure in AF

    AF is both a cause and consequence of HF.[15] Having one condition significantly increases the risk of the other developing. Patients with AF have a 3-fold increased risk of incident HF and the presence of both significantly increases mortality. [5,15] Preventing AF in HF patients improves outcomes. Use of angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and beta blockers have been reported to reduce the risk of incident and/or new-onset AF.[15] In newly diagnosed concomitant HF, the CAN-TREAT mnemonic can help guide treatment.[15] This approach starts with cardioversion (C), anticoagulation (A), and normalizing (N) fluid balance. It subsequently targets (T) a heart rate <110 beats per minute, modifies the renin-angiotensin-aldosterone (R) system, establishes early (E) rhythm control, considers advanced (A) HF therapies, and treats (T) other cardiovascular diseases.[15]

  • Examining Other Arrhythmias

    Examining Other Arrhythmias

    Other conditions can mimic AF. Differential diagnoses include atrial flutter, Wolff-Parkinson-White (WPW) syndrome, and atrial tachycardia.[16] A patient’s clinical history and physical examination might not be sufficient to distinguish between these conditions and AF; therefore, any patient presenting with an irregular heart rhythm or symptoms of AF should receive a 12-lead electrocardiogram (ECG) to establish the correct diagnosis. On ECG, an absence of P waves that have been replaced by irregular fibrillatory waves along with irregularly irregular QRS complexes are characteristic of AF.[16] In atrial flutter, the P waves are replaced by a saw-tooth appearance in the inferior limb leads and the QRS complexes are regularly irregular. Patients with atrial tachycardia have P waves with abnormal and variable morphology, whereas those with WPW syndrome have a shortened PR interval and delta wave on the QRS complex.[16]

  • Current AF treatments focus on treating the arrhythmia once it occurs and have been most effective for paroxysmal AF.[17] However, preventive strategies, better identification of AF subtypes, and curative strategies are being actively researched, including pharmacologic, genetic, and procedure-based interventions. In 2015, the FDA approved the Watchman device to prevent strokes in patients with AF unable to take anticoagulants.[17] The device prevents blood clots from leaving the left atrial appendage and entering the bloodstream. Other procedures that have recently become available include FIRM (Focal Impulse and Rotor Modulation) ablation and convergent ablation. Gene therapy is another exciting area of development. Preclinical models have shown gene transfer to control ventricular rate and restore sinus rhythm during AF.[18] As gene transfer methods improve and more gene therapy targets are identified, this approach has the potential to add new dimension to the AF treatment landscape.[18]

    Future Management of AF

    Current AF treatments focus on treating the arrhythmia once it occurs and have been most effective for paroxysmal AF.[17] However, preventive strategies, better identification of AF subtypes, and curative strategies are being actively researched, including pharmacologic, genetic, and procedure-based interventions. In 2015, the FDA approved the Watchman device to prevent strokes in patients with AF unable to take anticoagulants.[17] The device prevents blood clots from leaving the left atrial appendage and entering the bloodstream. Other procedures that have recently become available include FIRM (Focal Impulse and Rotor Modulation) ablation and convergent ablation. Gene therapy is another exciting area of development. Preclinical models have shown gene transfer to control ventricular rate and restore sinus rhythm during AF.[18] As gene transfer methods improve and more gene therapy targets are identified, this approach has the potential to add new dimension to the AF treatment landscape.[18]

  • AF Types and Symptoms

    AF Types and Symptoms

    AF can be classified as paroxysmal, persistent, long-standing persistent, permanent, and nonvalvular.[4] Paroxysmal AF resolves within 7 days, whether spontaneously or following an intervention, though patients can have recurrent episodes. Persistent AF lasts longer than 7 days and long-standing persistent AF lasts for more than 12 months. AF is classified as permanent when the decision is made to stop attempts at restoring or maintaining normal sinus rhythm. Nonvalvular AF occurs in the absence of rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair.[4] AF signs and symptoms can include palpitations, dyspnea, weakness, chest pain, dizziness, fatigue, and confusion.[5] Paroxysmal AF often presents with specific symptoms, while permanent AF is typically associated with less specific symptoms.[5] In some cases, AF is not diagnosed until there is a complication, such as stroke.[5]

Atrial fibrillation (AF) results when the atria do not beat normally, preventing normal blood flow into the ventricles. It is the most common type of arrhythmia, affecting an estimated 2.7 to 6.1 million people in the US.[1] By 2030, these numbers are expected to more than double, totaling ~12 million US residents.[2] Although AF management has improved, it remains a major cause of stroke, heart failure (HF), sudden death, and cardiovascular morbidity.[3] The costs are high, resulting in approximately 750,000 hospitalizations, 130,000 deaths, and $6 billion in healthcare expenses annually.[1] AF’s increasing prevalence, toll on patients and their families, and high economic burden indicate a need to better recognize and manage this condition, particularly in patients with multiple comorbidities.