Hoe kunnen we ritme bij patiënten met atriumfibrilleren reguleren?

Deze uitgangsvraag bevat de volgende deelvragen:

1. Wat zijn de indicaties voor ritmecontrole?
2. Hoe kan sinusritme worden hersteld? Welke therapieën zijn er om sinusritme te bereiken en te behouden?
3. Wanneer dient elektrische cardioversie en wanneer dient farmacologische cardioversie te worden overwogen?

The ‘rhythm control strategy’ refers to attempts to restore and maintain sinus rhythm, and may engage a combination of treatment approaches, including cardioversion (Ecker, 2018; Gilbert, 2015), antiarrhythmic medication (Singh, 2005; Shiga, 2017; Capucci, 2016), and catheter ablation (Shi, 2015; Siontis, 2016; Kim, 2016), along with an adequate rate control, anticoagulation therapy (see module 6.6) and comprehensive cardiovascular prophylactic therapy (upstream therapy, including lifestyle and sleep apnoea management) (Figure 1).

Figure 1 Rhythm control strategy

AAD = antiarrhythmic drug; AF = atrial fibrillation; CMP = cardiomyopathy; CV = cardioversion; LAVI = left atrial volume index; PAF = paroxysmal atrial fibrillation; PVI = pulmonary vein isolation; QoL = quality of life; SR = sinus rhythm. ^aConsider cardioversion to confirm that the absence of symptoms is not due to unconscious adaptation to reduced physical and/or mental capacity.

Adapted from Hindricks (2020)

Indications for rhythm control

Based on the currently available evidence from RCTs, the primary indication for rhythm control is to reduce AF-related symptoms and improve QoL (Figure 1). In case of uncertainty, an attempt to restore sinus rhythm in order to evaluate the response to therapy may be a rational first step. Factors that may favour an attempt at rhythm control should be considered (Bayes de Luna, 2012; Jadidi, 2018) (Figure 1).

As AF progression is associated with a decrease in QoL (Dudink, 2018) and, with time, becomes irreversible or less amenable to treatment (De Vos, 2010), rhythm control may be a relevant choice, although currently there is no substantial evidence that this may result in a different outcome. Reportedly, rates of AF progression were significantly lower with rhythm control than rate control (Zhang, 2013). Older age, persistent AF, and previous stroke/TIA independently predicted AF progression (Zhang, 2013), which may be considered when deciding the treatment strategy. For many patients, an early intervention to prevent AF progression may be worth considering (Bunch, 2013), including optimal risk-factor management (rienstra, 2018). Ongoing trials in patients with newly diagnosed symptomatic AF will assess whether early rhythm control interventions such as AF catheter ablation offer an opportunity to halt the progressive patho-anatomical changes associated with AF (Andrade, 2018). However, there is evidence that, at least in some patients, a successful rhythm control strategy with AF catheter ablation may not affect atrial substrate development (The, 2012). Important evidence regarding the effect of early rhythm control therapy on clinical outcomes are expected in 2020 from the ongoing EAST (Early treatment of Atrial fibrillation for Stoke prevention Trial) trial (Aliot, 2015).

General recommendations regarding active informed patient involvement in shared decision making (module 4) also apply for rhythm control strategies. The same principles should be applied in female and male AF patients when considering rhythm control therapy (Michelena, 2010).

Cardioversion

Immediate cardioversion/elective cardioversion

Acute rhythm control can be performed as an emergency cardioversion in a haemodynamically unstable AF patient or in a non-emergency situation. Synchronized direct current electrical cardioversion is the preferred choice in haemodynamically compromised AF patients as it is more effective than pharmacological cardioversion and results in immediate restoration of sinus rhythm (Kirchhof, 2005; Kirchhof, 2002). In stable patients, either pharmacological cardioversion or electrical cardioversion can be attempted; pharmacological cardioversion is less effective but does not require sedation. Of note, pre-treatment with AADs can improve the efficacy of elective electrical cardioversion (Um, 2019). A RCT showed maximum fixed-energy electrical cardioversion was more effective than an energy-escalation strategy (Schmidt, 2020).

In a RCT, a wait-and-watch approach with rate control medication only and cardioversion when needed within 48 h of symptom onset was as safe as and non-inferior to immediate cardioversion of paroxysmal AF, which often resolves spontaneously within 24 h (Pluymaekers, 2019).

Elective cardioversion refers to the situation when cardioversion can be planned beyond the nearest hours. Observational data (Pokorney, 2017) showed that cardioversion did not result in improved AF-related QoL or halted AF progression, but many of these patients did not receive adjunctive rhythm control therapies (Pokorney, 2017). Other studies reported significant QoL improvement in patients who maintain sinus rhythm after electrical cardioversion and the only variable independently associated with a moderate to large effect size was sinus rhythm at 3 months (Sandhu, 2017).

Factors associated with an increased risk for AF recurrence after elective cardioversion include older age, female sex, previous cardioversion, chronic obstructive pulmonary disease (COPD), renal impairment, structural heart disease, larger LA volume index, and HF (Ecker, 2018; Baranchuk, 2018; Toufan, 2017). Treatment of potentially modifiable conditions should be considered before cardioversion to facilitate maintenance of sinus rhythm (Figure 1) (Rienstra, 2018). In case of AF recurrence after cardioversion in patients with persistent AF, an early re-cardioversion may prolong subsequent duration of sinus rhythm (Voskoboinik, 2019).

Non-emergency cardioversion is contraindicated in the presence of known LA thrombus. Peri-procedural thrombo-embolic risk should be evaluated and peri-procedural and long-term OAC use considered irrespective of cardioversion mode (i.e., pharmacological cardioversion or electrical cardioversion) (module 6.6). A flowchart for decision making on cardioversion is shown in Figure 2.

Figure 2 Flowchart for decision making on cardioversion of AF depending on clinical presentation, AF onset, oral anticoagulation intake, and risk factors for stroke

AF = atrial fibrillation; CHA2DS2-VASc = Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes mellitus, Stroke, Vascular disease, Age 65 to 74 years, Sex category (female); cardioversion = cardioversion; ECV = electrical cardioversion; h = hour; LA = left atrium; LAA = left atrial appendage; LMWH = low-molecular-weight heparin; NOAC = non-vitamin K antagonist oral anticoagulant (referred to as DOAC in this guideline); OAC = oral anticoagulant; TE = thromboembolism; TOE = transoesophageal echocardiography; UFH = unfractionated heparin; VKA = vitamin K antagonist.

Adapted from Hindricks (2020)

Electrical cardioversion

Electrical cardioversion can be performed safely in sedated patients treated with i.v. midazolam and/or propofol or etomidate (Furniss, 2015). BP monitoring and oximetry during the procedure should be used routinely. Skin burns may occasionally be observed. Intravenous atropine or isoproterenol, or temporary transcutaneous pacing, should be available in case of post-cardioversion bradycardia. Biphasic defibrillators are standard because of their superior efficacy compared with monophasic defibrillators (Mittal, 2000; Inacio, 2016). Anterior-posterior electrode positions restore sinus rhythm more effectively (Kirchhof, 2005; Kirchhof, 2002), while other reports suggest that specific electrical pad positioning is not critically important for successful cardioversion (Kirkland, 2014).

Pharmacological cardioversion (including ‘pill in the pocket’)

Pharmacological cardioversion to sinus rhythm is an elective procedure indicated in haemodynamically stable patients. Its true efficacy is biased by the spontaneous restoration of sinus rhythm within 48 h of hospitalization in 76-83% of patients with recent onset AF (10 to 18% within first 3 h, 55 to 66% within 24 h, and 69% within 48 h) (Boriani, 2004; Danias, 1998; Dan, 2018). Therefore, a ‘wait-and-watch’ strategy (usually for < 24 h) may be considered in patients with recent-onset AF as a non-inferior alternative to early cardioversion (Pluymaekers, 2019).

The choice of a specific drug is based on the type and severity of associated heart disease (See Farmacotherapeutisch kompas) and pharmacological cardioversion is more effective in recent onset AF. Flecainide (and other class Ic agents), indicated in patients without significant LV hypertrophy (LVH), LV systolic dysfunction, or ischaemic heart disease, results in prompt (3 to 5 h) and safe (Markey, 2018) restoration of sinus rhythm in > 50% of patients (Chevalier, 2003; Capucci, 1992; Donovan, 1992; Reisinger, 2004; Khan, 2003), while i.v. amiodarone, mainly indicated in HF patients, has a limited and delayed effect but can slow heart rate within 12 h (Chevalier, 2003; Galve, 1996; Vardas, 2000; Letelier, 2003). Intravenous vernakalant is the most rapidly cardioverting drug, including patients with mild HF and ischaemic heart disease, and is more effective than amiodarone (Bash, 2012; Camm, 2011; Akel, 2018; Beatch, 2016; Roy; 2008; Kowey, 2009) or flecainide (Pohjantahti-Maaroos, 2019). Dofetilide is not used in Europe and is rarely used outside Europe. Ibutilide is effective to convert atrial flutter (AFL) to sinus rhythm (Vos, 1998).

In selected outpatients with rare paroxysmal AF episodes, a self-administered oral dose of flecainide or propafenone is slightly less effective than in-hospital pharmacological cardioversion but may be preferred (permitting an earlier conversion), provided that the drug safety and efficacy has previously been established in the hospital setting (Alboni, 2004). An atrioventricular node-blocking drug should be instituted in patients treated with class Ic AADs (especially flecainide) to avoid transformation to AFL with 1:1 conduction (Brembilla-Perrot, 2001).

Follow-up after cardioversion

The goals of follow-up after cardioversion are shown in Table 1. When assessing the efficacy of a rhythm control strategy, it is important to balance symptoms and AAD side-effects. Patients should be reviewed after cardioversion to detect whether an alternative rhythm control strategy including AF catheter ablation, or a rate control approach is needed instead of current treatment.

Table 1 Goals of follow-up after cardioversion of AF

AAD = antiarrhythmic drug; AF = atrial fibrillation; BP = blood pressure; ECG = electrocardiogram; HF = heart failure; LV = left ventricular; PR = PR interval; QoL = quality of life; QRS = QRS interval; QTc = corrected QT interval. Adapted from Hindricks (2020)