Definitions and classification
Atrial fibrillation (AF) is characterized by uncoordinated atrial activation without effective atrial contraction. On the electrocardiogram (ECG), AF is characterized by rapid oscillations or fibrillatory waves that vary in amplitude, shape, and timing; that usually have a cycle length less than 200 ms; and that are associated with an irregular ventricular response. QRS complexes may also be of variable amplitude. Regular R-R intervals are possible in the presence of atrioventricular (AV) block, junctional rhythm, ventricular pacing, or ventricular tachycardia.
Paroxysmal AF is defined as AF that terminates spontaneously or with intervention within 7 days of onset. Episodes typically convert back to sinus rhythm within 48 hours. Up to 8% of patients per year with paroxysmal AF progress to persistent AF.
Persistent AF is continuous AF that is sustained beyond 7 days.
Long-standing persistent AF is AF that has lasted for 1 year or longer.
Permanent AF refers to the situation when the presence of the arrhythmia is accepted by the patient and physician. Hence, rhythm control interventions are, by definition, not pursued in patients with permanent AF. However, the “permanent” label does not preclude the option of rhythm control by catheter ablation.
Lone (idiopathic) AF has been variously defined but generally applies to young individuals (younger than 60 years) without clinical or echocardiographic evidence of cardiopulmonary disease, including hypertension. Increasing knowledge about the pathophysiology of AF suggests that in almost every patient a cause is present.
Nonvalvular AF is defined by the American Heart Association, American College of Cardiology, and Heart Rhythm Society (AHA/ACC/HRS) as AF in the absence of rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair. The European Society of Cardiology (ESC) has defined nonvalvular AF as AF not related to rheumatic valvular disease (predominantly mitral stenosis) or prosthetic heart valves.
AF can be vagally mediated (e.g., nocturnal, postprandial) and also can be associated with sympathetic overactivity. The terms vagal and adrenergic AF are oversimplifications because the balance between sympathetic and parasympathetic influences is as important as absolute tone.
Electrophysiologic mechanisms
Structural remodeling of the atria as a result of heart disease, atrial wall stretch, genetic causes, or other nonidentified mechanisms results in electrical dissociation between muscle bundles and local conduction heterogeneities that facilitate the initiation and perpetuation of AF. Structural atrial abnormalities consist of areas of patchy fibrosis, enhanced connective tissue deposits juxtaposed with normal atrial fibers, inflammatory changes, intracellular substrate accumulation, and disruption of cell coupling at gap junctions with remodeling of connexins (i.e., transmembrane ion channel proteins in the gap junctions). Connexin gene variants are associated with AF, and connexin gene transfer in animal studies has prevented AF. Fibrosis and inflammatory changes, identified by biopsy and delayed enhancement magnetic resonance, have also been documented in patients with lone AF. ,
After the onset of AF, changes of atrial electrophysiologic properties and mechanical function occur within days (>24 hours). Shortening of the atrial effective refractory period results from abbreviation of the atrial action potential duration, which is caused by a decrease in the calcium channel current (I Ca ) and an increase in the potassium channel current (I K1 ) and the constitutively active acetylcholine-sensitive current (I KACh ). Increased diastolic sarcoplasmic reticulum Ca 2+ leak and related delayed after-depolarizations/triggered activity promote cellular arrhythmogenesis. Ryanodine receptor type 2–mediated sarcoplasmic reticulum calcium leak also drives AF progression. Downregulation of the Ca 2+ inward current and impaired release of Ca 2+ from intracellular Ca 2+ stores cause loss of contractility and increased compliance with subsequent atrial dilation. Electrical remodeling of the atria is therefore perpetuated by AF itself in a way that “AF begets AF.” Restoration of sinus rhythm results in recovery of normal atrial refractoriness within a few days. LA structure and function are increasingly abnormal with a greater electrical burden of AF, and LA dysfunction may be present despite normal LA size and sinus rhythm.
The initiation and perpetuation of AF requires both triggers for its onset and a substrate for its maintenance ( Fig. 13.1 ).
Focal electrical activity contributing to the initiation and perhaps perpetuation of AF has been identified at pulmonary vein (PV) ostia. As a result of shorter refractory periods as well as abrupt changes in myocyte fiber orientation, the PV–left atrial junctions have a stronger potential to initiate and perpetuate atrial tachyarrhythmias. Mechanisms of focal activity might involve increased local automaticity, triggered activity, and microreentry. Apart from the PVs, other cardiac veins and certain areas of the posterior left atrial wall may have a profibrillatory role. Fibrillatory conduction and localized anisotropic reentry leading to rotors with a high dominant frequency may also play a role in maintaining AF. Wave fronts emanating from foci and breakthrough sites without reentrant mechanisms have also been demonstrated in persistent AF. Elimination of these rotors and AF nests may be one of the mechanisms for the efficacy of real-time frequency analysis or complex fractionated electrogram-guided ablation.
According to the multiple wavelet hypothesis , proposed by Moe and colleagues, AF is perpetuated by continuous conduction of several independent wavelets propagating through the atrial musculature in a seemingly chaotic manner. Fibrillation wave fronts continuously undergo wave front–wave back interactions, resulting in wave break and the generation of new wave fronts, whereas block, collision, and fusion of wave fronts tend to reduce their number. As long as the number of wave fronts does not decline below a critical level, the multiple wavelets will sustain the arrhythmia.
Areas rich in autonomic innervation may be the source of activity that triggers AF. Ganglionated plexi that can be identified around the circumference of the left atrial–PV junction may also contribute to induction and perpetuation of AF. These plexi are usually located 1 to 2 cm outside the PV ostia, they mediate both sympathetic and parasympathetic activity, and their ablation (autonomic denervation) has been found efficacious when added to antral PV isolation.
These mechanisms are not mutually exclusive and may coexist at various times. Although in most patients with paroxysmal AF localized sources of the arrhythmia can be identified, such attempts are often not successful in patients with persistent or permanent AF. This can be interpreted within the context of the multifactorial etiology of AF. Mechanisms of AF initiation and perpetuation, particularly in patients with persistent AF, are complex and heterogeneous.
Diagnosis
Patients may present with palpitations or otherwise unexplained fatigue or effort intolerance, or the arrhythmia may be an incidental finding. The cause of stroke remains unexplained in 20% to 40% of cases. Among these unexplained strokes, 10% to 30% may be caused by AF that has eluded detection. Discovery of subclinical AF with implantable devices and wearable monitors is common, especially in populations known to have an increased risk of stroke (or recurrent stroke). Opportunistic screening for AF in patients 65 years and older is reasonable, and several methods and devices are now available for screening. Wrist-worn , optically based heart rate monitors are user friendly, but appropriate validation of the device used is imperative. In mechanocardiography, mechanical cardiac activity is recorded with accelerometers and gyroscopes, standard components of modern smartphones . High sensitivity and specificity of this method for AF detection with the use of smartphones has been reported. Smartphone technologies have been developed that can assess heart rate and rhythm using either photoplethysmography or single-lead ECG but usually provide only a brief rhythm assessment without information on AF duration or burden. In a 2019 comparison, an Food and Drug Administration–cleared AF-sensing watch ( Apple Watch with KardiaBand ) that allows a patient to record a 30-second lead I rhythm strip was found highly sensitive for detection of AF and assessment of AF duration in an ambulatory population compared with an insertable cardiac monitor ( Reveal ). In an evaluation of an Apple Watch Application study, the probability of receiving an irregular pulse notification was low. Among participants who received notification of an irregular pulse, 34% had atrial fibrillation on subsequent ECG patch readings and 84% of notifications were concordant with atrial fibrillation.
Frequent atrial ectopy, atrial tachycardia, and atrial flutter may present with rapid irregular RR intervals and mimic AF. Most atrial tachycardias and flutters show longer atrial cycle lengths 200 ms and greater, but patients on antiarrhythmic drugs may have slower atrial cycle lengths during AF. When the ventricular rate is fast, atrioventricular nodal blockade during the Valsalva maneuver, carotid massage, or intravenous adenosine administration can help to unmask atrial activity. Extremely rapid ventricular rates (>200 beats per minute) suggest the presence of an accessory pathway or ventricular tachycardia.
In the absence of a history of the arrhythmia, AF can be detected by ECG monitoring in approximately one-quarter of all patients with acute ischemic stroke by routine monitoring followed by an intensified or prolonged AF search. Patients with ischemic stroke or transient ischemic attack (TIA) should have continuous ECG monitoring after a stroke for at least 72 hours.
Catheter ablation
Rationale
Randomized controlled drug trials have failed to detect significant mortality and cardiovascular morbidity differences between patients with rate (i.e., controlling ventricular response with the patient in AF) versus rhythm (i.e., maintenance of sinus rhythm [SR]) control achieved with antiarrhythmic medication. This is rather surprising in view of the deleterious effects of AF and has been mainly attributed to the proarrhythmic effects of drugs , which may negate any benefits conferred by maintenance of SR. , Assessment of quality of life was also rather inadequate in most trials. In the J-RHYTHM trial, fewer patients requested changes of assigned treatment strategy in the rhythm control versus the rate control group, which was accompanied by improvement in AF-specific quality of life scores. Maintenance of SR also improved quality of life in the SAFE-T trial. Finally, follow-up of most trials was relatively short. However, improved survival with maintenance of sinus rhythm was detected in the CHF-STAT trial (amiodarone in heart failure patients). In an extensive population-based, observational trial, rhythm control therapy was associated with lower rates of stroke/TIA compared to rate control, particularly among patients with moderate and high risk of stroke. In the ATHENA trial, cardiovascular mortality was reduced by dronedarone (3.9% vs 2.7%, P = .003). However, dronedarone has resulted in increased mortality in patients with heart failure, and with permanent AF. In a recent meta-analysis of RCTs comparing drugs for rate vs rhythm control, and drugs vs ablation for rhythm control in patients with AF and heart failure, currently available antiarrhythmic drugs for rhythm control did not offer additional benefit in reducing hard endpoints because of the poor efficacy in restoring sinus rhythm and potential toxic effects. In the EAST-AFNET 4 RCT, early rhythm control with either antiarrhythmic drugs or catheter ablation was associated with a lower risk of adverse cardiovascular outcomes than usual care during adequate rate control therapy among patients with early AF and cardiovascular conditions.
Left atrial catheter ablation offers improved rates of SR maintenance compared with antiarrhythmic therapy, being more beneficial in younger patients and men . Data mainly from registries and observational studies indicate that average success rates after AF (paroxysmal in 70%) ablation are 57% and 71% after a single and multiple procedures, respectively, with an average follow-up of 14 months, compared with 52% with antiarrhythmic drug therapy. In the MANTRA-PAF randomized trial, 85% of ablated patients versus 71% of medically treated patients with paroxysmal atrial fibrillation (PAF) were free of AF in 2 years ( P = .004), but the cumulative burden of AF during that time was not significantly different on an intention-to-treat analysis (36% of patients initially assigned to medication eventually had ablation). However, at 5-year follow-up there was a significantly higher rate of AF-free patients in the ablation group. In the RAAFT-2 randomized clinical trial, 45% of patients with PAF were free of arrhythmia 2 years after ablation, compared with 28% of patients on antiarrhythmic therapy. In the SARA randomized trial on patients with persistent AF, 70% of patients were free of arrhythmia at 1 year after ablation, compared with 44% on patients treated with drugs. However, no symptomatic improvement was detected. The CABANA trial randomly allocated 2204 patients to catheter ablation or drug therapy (87.2% received rhythm control). Of the 2204 patients randomized (42.9% had paroxysmal AF and 57.1% had persistent AF), 89.3% completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8%) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5%) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, catheter ablation did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest that occurred in 8.0% of patients ( n = 89) in the ablation group versus 9.2% of patients ( n = 101) in the drug therapy group (hazard ratio [HR], 0.86 [95% confidence interval, 0.65–1.15]; P = .30). , The main problem in interpreting this trial is the high rate of treatment crossovers. This, together with the lower-than-expected event rates, suggests that in clinical practice a reduction in the composite endpoint of all-cause mortality, stroke, major bleeding, or cardiac arrest by catheter ablation may be seen in patients who meet the CABANA eligibility criteria but not in lower-risk patients. Nevertheless, over 5 years of follow-up, AF recurrence was reduced by approximately 50% in catheter ablation patients compared with drug therapy, regardless of their baseline AF type. Cryoballoon ablation has resulted in a significantly lower rate of AF recurrence than antiarrhythmic drug therapy over a follow-up period of one year in two recent randomized trials (EARLY-AF, and STOP-AF). ,
Atrial kick contributes up to 30% of stroke volume, and in patients with heart failure and AF catheter ablation is associated with improved left ventricular function and reduced hospitalizations and mortality compared to antiarrhythmic therapy in patients with AF and heart failure with reduced ejection fraction. , Restoration of sinus rhythm with catheter ablation, however, has been shown to result in significant improvements in ventricular function (CAMFAT trial), particularly in the absence of ventricular fibrosis on cardiac magnetic resonance (CAMERA-MRI trial). Catheter ablation is also superior to amiodarone in achieving freedom from AF at long-term follow-up and reducing unplanned hospitalization and mortality in patients with heart failure and persistent AF (AATAC trial). In the CASTEL-AF trial, catheter ablation was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure compared with medical therapy. However, in patients with AF and significantly reduced LVEF (≤35%), no benefit of catheter ablation was demonstrated in the AMICA trial. This mainly was due to the fact that at 1 year, LVEF had increased in ablation patients to a similar extent as in medical therapy patients, despite the fact that at any time during follow-up, ablation-group patients more often had SR and a lower AF burden than medical therapy patients.
Both pulmonary vein isolation, and AV nodal modification improve LV function, but PV isolation has been found superior to AV nodal ablation and biventricular pacing in this respect. When the tachycardia itself cannot be ablated, AV nodal modification with biventricular pacing is appropriate. Specific His bundle pacing may offer comparable, or even better results than CRT pacing.
Techniques
Current catheter ablation strategies fall into two broad categories: PV isolation to prevent AF initiation and atrial substrate modification to impede AF perpetuation. Anatomic drawings of the heart relevant to AF ablation are presented in Fig. 13.2 .
PV isolation.
PV isolation is achieved using radiofrequency (RF) energy by circumferential PV antral ablation assisted by circular multielectrode catheters and electroanatomic mapping systems. Bidirectional PV isolation verified with the use of a circular mapping catheter positioned at the PV–LA junction is the established ablation endpoint. Bidirectional PV isolation is defined by the absence of conduction into the PV from the left atrium (LA–PV entry block) and in the opposite direction (PV–LA exit block) and is an established endpoint of PV ablation ( Figs. 13.3 and 13.4 ). However, usually demonstration of entry block also implies exit block.
During circumferential ablation with the aid of an electroanatomic mapping system, electrode–tissue contact force is one of the primary determinants of lesion size, and this function is now provided by modern RF ablation systems ( Figs. 13.5–13.7 ).
PV isolation by cryoablation with a balloon is also feasible and technically easier ( Fig. 13.8 ). Irrigated-tip RF ablation, irrigated-tip catheter using a contact force sensing, and cryoballoon ablation have been reported to yield similar outcomes after AF ablation (FIRE AND ICE and CIRCA-DOSE trials). ,
Novel techniques with the use of radiofrequency balloon, laser balloon, or nonthermal pulsed electric field energy (electroporation) for PV isolation are also under study.
Non-PV triggers.
Non-PV triggers, either in the left or the right atrium may also be sought and ablated, especially in case of recurrence after PV isolation ( Fig. 13.9 ). ,
