Hoe moeten bijkomende ziekten, cardiometabole risicofactoren en ongezonde leefstijlfactoren geïdentificeerd en behandeld worden?

Deze uitgangsvraag bevat de volgende deelvragen:

1. Wat is de waarde van leefstijlinterventies gericht op obesitas, alcohol- en cafeïnegebruik en fysieke activiteit bij patiënten met atriumfibrilleren?
2. Hoe moeten de cardiovasculaire risicofactoren hypertensie, hartfalen, coronaire hartziekten, diabetes mellitus en slaapapneu behandeld worden bij patiënten met atriumfibrilleren?

Lifestyle interventions

Obesity and weight loss

Obesity increases the risk for AF progressively according to body mass index (Overvad, 2013; Huxley, 2014; Murphy, 2006; Wanahita, 2008; Wang, 2004; Baek, 2017). It may also increase the risk for ischaemic stroke, thrombo-embolism, and death in AF patients (Overvad, 2013), notwithstanding an obesity paradox in AF patients, especially regarding all cause and cardiovascular death, with an inverse relationship between overweight/obesity and better cardiovascular prognosis in long-term follow-up (Proietti, 2017).

Intense weight reduction with comprehensive management of concomitant cardiovascular risk factors resulted in fewer AF recurrences and symptoms than general advice in obese patients with AF (Pathak, 2014; Abed, 2013; Pathak, 2015). Achieving a healthy weight may reduce blood pressure (BP), dyslipidaemia, and risk of developing type 2 diabetes mellitus, thus improving the cardiovascular risk profile (Piepoli, 2016). Obesity may increase AF recurrence rates after AF catheter ablation (with OSA as a potential confounder) (Wong, 2015; Jongnarangsin, 2008; Winkle, 2017; Cha, 2008). It has also been linked to a higher radiation dose and complication rate during AF ablation (Ector, 2007; Shoemaker, 2013), whereas symptom improvement after AF catheter ablation seems comparable in obese and normal-weight patients (Cha, 2008). Given the potential to reduce AF episodes by weight reduction, AF catheter ablation should be offered to obese patients in conjunction with lifestyle modifications for weight reduction.

Alcohol and caffeine use

Alcohol excess is a risk factor for incident AF (Ettinger, 1978; Conen, 2014; Liang, 2012; Larsson, 2014) and bleeding (Pisters, 2010) in anticoagulated patients (mediated by poor adherence, liver disease, variceal bleeding, and risk of major trauma), and high alcohol intake may be associated with thrombo-embolism or death (Overvad, 2013). In a recent RCT, alcohol abstinence reduced arrhythmia recurrence in regular drinkers with AF (Voskoboinik, 2020).

By contrast, it is unlikely that caffeine consumption causes or contributes to AF (Cheng, 2014). Habitual caffeine consumption might be associated with lower risk of AF, but caffeine intake may increase symptoms of palpitations unrelated to AF.

Physical activity

Many studies have demonstrated beneficial effects of moderate exercise/ physical activity on cardiovascular health (Lavie, 2009; Mont, 2010; Menezes, 2015). Nevertheless, the incidence of AF appears to be increased among elite athletes, and multiple small studies reported a relationship between AF and vigorous physical activity, mainly related to long-term or endurance sport participation (Karjalainen, 1998; Baldesberger,2008; Molina, 2008; Nielsen, 2013). A non-linear relationship between physical activity and AF seems likely. Based on these data, patients should be encouraged to undertake moderate-intensity exercise and remain physically active to prevent AF incidence or recurrence, but maybe avoid chronic excessive endurance exercise (such as marathons and long-distance triathlons, et cetera), especially if aged > 50 years. Owing to few randomized patients and outcomes, the effect of exercise-based cardiac rehabilitation on mortality or serious adverse events is uncertain (Risom, 2017).

Specific cardiovascular risk factors/comorbidities

Hypertension

Hypertension is the most common aetiological factor associated with the development of AF, and patients with hypertension have a 1.7-fold higher risk of developing AF compared with normotensives (Lip, 2017; Dzeshka, 2017).

Hypertension also adds to the complications of AF, particularly stroke, HF, and bleeding risk. AF patients with a longer hypertension duration or uncontrolled systolic BP (SBP) levels should be categorized as ‘high-risk’, and strict BP control in addition to OAC is important to reduce the risk of ischaemic stroke and ICH.

Given the importance of hypertension as a precipitating factor for AF, which should be regarded as a manifestation of hypertension target-organ damage, treatment of hypertension consistent with current BP guidelines (Williams, 2018) is mandatory in AF patients, aiming to achieve BP <130/80 mmHg to reduce adverse outcomes (Kim, 2018; Kim,2019; Lip, 2007). A recent randomized trial in patients with paroxysmal AF and hypertension reported fewer recurrences in patients undergoing renal denervation in addition to PVI compared with patients undergoing PVI only (Steinberg, 2020). Sotalol should not be used in the presence of hypertensive LVH or renal impairment, owing to the risk of proarrhythmia. There is some evidence of angiotensin converting enzyme or angiotensin receptor blocker use to improve outcomes in AF or reduce progression of the arrhythmia (Lip, 2017; Dzeshka, 2017). Other lifestyle changes, including obesity management, alcohol reduction, and attention to OSA, may also help in patients with AF and hypertension.

Coronary artery disease

The interactions between AF and CAD and the optimal management of patients with both AF and CAD are discussed in module 8.2.

Diabetes mellitus

In addition to shared risk factors (e.g., hypertension and obesity) (Wang, 2004; Du, 2009), diabetes is an independent risk factor for AF, especially in young patients (Pallisgaard, 2016). Silent AF episodes are favoured by concurrent autonomic dysfunction (Rizzo, 2015), thus suggesting an opportunity for routine screening for AF in diabetes mellitus patients. The prevalence of AF is at least two-fold higher in patients with diabetes compared with people without diabetes (Movahed, 2005), and AF incidence rises with increasing severity of microvascular complications (retinopathy, renal disease) (Lee, 2016). Both type 1 and type 2 diabetes mellitus are the risk factors for stroke (Fangel, 2018; Mozaffarian, 2015).

Intensive glycaemic control does not affect the rate of new-onset AF (Fatemi, 2014), but metformin and pioglitazone could be associated with lower long-term risk of AF in patients with diabetes (Chang, 2014), while this was not confirmed for rosiglitazone (Zhang, 2017). Currently there is no evidence that glucagon-like peptide-1 agonists, sodium glucose cotransporter-2 inhibitors, and dipeptidyl peptidase-4 inhibitors affect the development of AF (Bell, 2019).

Previous meta-analyses showed no significant interaction between diabetes mellitus and DOAC effects in AF patients (Ruff, 2014; Patti, 2017), but vascular mortality was lower in patients with diabetes treated with DOACs than in those on warfarin (Patti, 2017). Bleeding risk reduction with DOACs was similar in diabetic and non-diabetic patients except for apixaban, where a lower reduction in haemorrhagic complications was reported in the AF patients with diabetes compared with AF patients without diabetes (Hylek, 2014). Regarding potential side-effects of OAC, there is no evidence that bleeding risk is increased in patients with diabetes and retinopathy (Lip, 2015).

Optimal glycaemic control in 12 months before AF catheter ablation was associated with significant reduction in recurrent AF after ablation (Donnellan, 2019).

Sleep apnoea

The most common form of sleep-disordered breathing, OSA, is highly prevalent in patients with AF, HF, and hypertension, and is associated with increased risk of mortality or major cardiovascular events (Linz, 2018). In a prospective analysis, approximately 50% of AF patients had OSA compared with 32% of controls (Gami, 2004). The mechanisms facilitating AF include intermittent nocturnal hypoxemia/hypercapnia, intrathoracic pressure shifts, sympathovagal imbalance, oxidative stress, inflammation, and neurohumoral activation (Goudis, 2017). OSA has been shown to reduce success rates of AADs, electrical cardioversion, and catheter ablation in AF (Goudis, 2017).

Continuous positive airway pressure (CPAP) is the therapy of choice for OSA and may ameliorate OSA effects on AF recurrences (Epstein, 2009; Linz, 2018). Observational studies and meta-analyses showed that appropriate CPAP treatment of OSA may improve rhythm control in AF patients (Naruse, 2013; Li, 2014; Linz, 2018; Fein, 2013; Neilan, 2013; Qureshi, 2015; Shukla, 2015).

It seems reasonable to test for OSA before the initiation of rhythm control therapy in symptomatic AF patients, with the aim to reduce symptomatic AF recurrences. In the ARREST-AF (Aggressive Risk Factor Reduction Study - Implication for AF) and LEGACY (Long-term Effect of Goal-directed weight management on an Atrial fibrillation Cohort: a 5-Year follow-up study) studies, an aggressive risk-factor reduction program focusing on weight management, hyperlipidemia, OSA, hypertension, diabetes, smoking cessation, and alcohol-intake reduction significantly reduced AF burden after PVI (Pathak, 2014; Pathak, 2015). However, it remains unclear how and when to test for OSA and implement OSA management in the standard work-up of AF patients.