Tom Wade MD

Today, I review, link to, and excerpt from The 2024 ESC Guidelines On Atrial Fibrillation, 5. [C] Comorbidity and risk factor management

All that follows is from the above resource.

5. [C] Comorbidity and risk factor management

A broad array of comorbidities are associated with the recurrence and progression of AF. Managing comorbidities is also central to the success of other aspects of care for patients with AF, with evidence available for hypertension, heart failure, diabetes mellitus, obesity, and sleep apnoea, along with lifestyle changes that improve physical activity and reduce alcohol intake (see Supplementary data online, Additional Evidence Table S4). Identification and treatment of these comorbidities and clusters of risk factors form an important part of effective AF-CARE (Figure 8), with the evidence outlined in the rest of this section highlighting where management can improve patient outcomes or prevent AF recurrence. Many of these factors (and more) are also associated with incident AF (see Section 10).

Figure 8 Management of key comorbidities to reduce AF recurrence.

LVEF, left ventricular ejection fraction; SGLT2, sodium-glucose cotransporter-2.

Recommendation Table 5: Recommendations for comorbidity and risk factor management in AF (see also Evidence Table 5)

5.1. Hypertension

Hypertension in patients with AF is associated with an increased risk of stroke, heart failure, major bleeding, and cardiovascular mortality.^158–161 The target for treated systolic blood pressure (BP) in most adults is 120–129 mmHg. Where BP-lowering treatment is poorly tolerated, clinically significant frailty exists or the patient’s age is 85 years or older, a more lenient target of <140 mmHg is acceptable or ‘as low as reasonably achievable’. On-treatment diastolic BP should ideally be 70–79 mmHg.¹⁶² In an individual participant data meta-analysis of 22 randomized trials reporting baseline AF, a 5 mmHg reduction in systolic BP reduced the risk of major cardiovascular events by 9% (HR, 0.91; 95% CI, 0.83–1.00), with identical effect in patients with AF or sinus rhythm.¹²⁹

In individuals with AF, hypertension often coexists with other modifiable and non-modifiable risk factors that all contribute to recurrence of AF, readmission to hospital, and ongoing symptoms after rhythm control.^163–171 Optimal control of blood pressure should be considered an essential component of treating AF and undertaken within a strategy of comprehensive risk factor management.^126–128 Although the majority of research has focused on clinical outcomes, limited comparative data on hypertension medication suggests that use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) may be superior for prevention of recurrent AF.^172–175

5.2. Heart failure

Heart failure is a key determinant of prognosis in patients with AF, as well as an important factor associated with recurrence and progression of AF.^176,177 During 30 years of follow-up in the Framingham cohort, 57% of those with new heart failure had concomitant AF, and 37% of those with new AF had heart failure.¹⁷⁸ Numerous cardiovascular and non-cardiovascular conditions impact the development of both AF and heart failure, leading to the common pathway of atrial cardiomyopathy.¹⁸ In patients with acute heart failure attending the emergency department, AF is one of the most prevalent triggering factors of the episode.¹⁷⁹ The development of heart failure in patients with AF is associated with a two-fold increase in stroke and thromboembolism,¹⁸⁰ even after anticoagulation,¹⁸¹ and 25% higher all-cause mortality.¹⁷⁸ Prognosis may be affected by left ventricular ejection fraction (LVEF), with the rate of death highest with the combination of AF and heart failure with reduced ejection fraction (HFrEF) (LVEF ≤ 40%), as compared with AF and HFpEF (LVEF ≥ 50%). However, rates of stroke and incident heart failure hospitalization are similar regardless of LVEF.¹⁸² Due to how common concomitant AF and heart failure are in clinical practice, strategies to improve outcomes in these patients are detailed within each component of the AF-CARE pathway. However, it is also critical that heart failure itself is managed appropriately in patients with AF to prevent avoidable adverse events.

Optimization of heart failure management should follow current ESC Guidelines: 2023 Focused Update¹⁸³ of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure.¹³⁷ Achieving euvolaemia with diuretics is an important first step that not only manages the heart failure component, but can also facilitate better control of heart rate in AF. For HFrEF, it should be highlighted that many older guideline-recommended therapies lack specific evidence for benefit in patients with coexisting AF. No trial data are available in this context for ACE inhibitors, there are conflicting data on ARBs,^132,184 and an individual patient-level analysis of RCTs found no difference between beta-blockers and placebo for all-cause mortality in HFrEF with AF.¹³³ However, these drugs have clear proof of safety and there may be other indications for these therapies beyond prognosis, including comorbidity management and symptom improvement. These and other therapies may also have dual functions, for example, beta-blockers or digoxin for rate control of AF, in addition to improving heart failure metrics and reducing hospitalization.^48,185,186 More recent additions to HFrEF management, such as eplerenone, sacubitril-valsartan, and sodium-glucose cotransporter-2 (SGLT2) inhibitors, had substantial numbers of patients with AF enrolled in RCTs, with no evidence that AF status affected their ability to reduce cardiovascular mortality/heart failure hospitalization.^134–136 Cardiac resynchronization therapy (CRT) in the context of HFrEF and AF is discussed in detail in the 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy, with an important focus on ensuring effective biventricular pacing (with a low threshold for considering atrioventricular node ablation).¹⁸⁷ Patients who have heart failure with mildly reduced ejection fraction (HFmrEF) (LVEF 41%–49%) and AF should generally be treated according to guidance for HFrEF,¹³⁷ albeit with limited evidence to date in AF.^188–190 For treatment of HFpEF and AF,¹⁹¹ pre-specified subgroup data on AF from multiple large trials show that the SGLT2 inhibitors dapagliflozin, empaglifozin, and sotagliflozin are effective in improving prognosis.^138–140

Appropriate management of heart failure has the potential to reduce recurrence of AF, e.g. by reducing adverse atrial and ventricular myocardial remodelling, but there are limited data for specific therapies. In the Routine versus Aggressive upstream rhythm Control for prevention of Early AF in heart failure (RACE 3) trial, combined management of mild-to-moderate heart failure with ACE inhibitors/ARBs, mineralocorticoid receptor antagonists, statins, and cardiac rehabilitation increased the maintenance of sinus rhythm on ambulatory monitoring at 12 months.³⁹ This benefit was not preserved at the 5 year follow-up, although this may have been confounded by the lack of ongoing intervention beyond the initial 12 months.¹⁹²

5.3. Type 2 diabetes mellitus

Diabetes mellitus is present in around 25% of patients with AF.^193–195 Patients with both diabetes and AF have a worse prognosis,¹⁹⁶ with increased healthcare utilization and excess mortality and cardiovascular events. The prevalence and incidence of AF and type 2 diabetes are widely increasing, thus making the association of these two conditions a public health challenge.^195,197 Moreover, diabetes is a major factor influencing thromboembolic risk.^198,199 Following catheter ablation of AF, diabetes and higher HbA1c are associated with increased length of stay and a greater recurrence of AF.^200–203

In cohort studies, the management of diabetes mellitus as part of comprehensive risk factor management has been associated with reduced AF symptoms, burden, reversal of the type of AF (from persistent to paroxysmal or no AF), and improved maintenance of sinus rhythm.^126–128 However, robust evidence is limited, and individual glucose-lowering medications have had variable effects on AF.^204–206 There are emerging data of the use of SGLT2 and glucagon-like peptide-1 antagonists in patients with diabetes and AF that may impact on treatment choice in the near future. Importantly, diabetes frequently coexists with multiple risk factors in patients with AF, and a comprehensive approach to management is required. Further details are provided in the 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes.²⁰⁷

5.4. Obesity

Obesity frequently coexists with other risk factors that have been independently associated with the development of AF.^208,209 Obesity (body mass index [BMI] ≥30 kg/m²) and being overweight (BMI >25 kg/m²) are associated with a greater risk of recurrent atrial arrhythmias after AF ablation (13% increase for every 5 kg/m² higher BMI).^210–212 In the setting of comprehensive risk factor management, weight loss of ≥10% in overweight and obese individuals with AF has been associated with reduced AF symptoms and AF burden in an RCT (aiming for BMI <27 kg/m²).¹²⁵ Cohort studies have also shown a graded response to maintenance of sinus rhythm,¹²⁶ improved ablation outcomes,¹²⁸ and reversal of the type of AF¹²⁷ commensurate with the degree of weight loss and risk factor management. However, in the Supervised Obesity Reduction Trial for AF Ablation Patients (SORT-AF) randomized trial in AF ablation patients, a sole weight loss intervention that achieved 4% loss in weight over 12 months did not impact ablation outcomes.²¹³ This is consistent with the findings in LEGACY (Long-Term Effect of Goal directed weight management on Atrial Fibrillation Cohort: a 5 Year follow-up study) that showed that weight loss of ≤3% had no impact on AF recurrence.¹²⁶ Observational studies have raised the possibility of a point of no return in terms of the benefit of weight loss,²¹⁴ but also the possibility that bariatric surgery can improve symptoms and reduce AF recurrence.^215–217

5.5. Obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is a highly prevalent condition, particularly in patients with AF.^157,218 Optimal screening tools in the AF population are still under evaluation, although it may be reasonable to screen for OSA in patients where a rhythm control strategy is being pursued. Polysomnography or home sleep apnoea testing are suggested in preference to screening questionnaires.^{155–157,219} Questionnaires assessing daytime sleepiness are poor predictors of moderate-to-severe OSA.¹⁵⁵ Which parameter should be used to focus on risk of AF in patients with OSA, and to guide OSA treatment in patients with AF, is still unclear.^220,221

Observational studies have suggested that individuals with OSA not treated with continuous positive airway pressure (CPAP) respond poorly to treatments for AF, with an increased risk of recurrence after cardioversion or ablation.²²² Conversely, OSA patients treated with CPAP seem to mitigate their propensity toward developing AF.^{148–153,222–224} A small randomized trial of CPAP vs. no therapy demonstrated reversal of atrial remodelling in individuals with moderate OSA.¹⁵⁴ However, other small RCTs have failed to show a benefit of CPAP therapy on ablation outcomes²²⁵ or post-cardioversion.²²⁶ Data on the cardiovascular mortality benefit of CPAP therapy in OSA are inconclusive.^227–230

5.6. Physical inactivity

Reduced cardiorespiratory fitness frequently coexists with other modifiable risk factors and has been associated with a greater recurrence of AF after catheter ablation.¹⁴¹ Better cardiorespiratory fitness has a demonstrated inverse relationship to AF burden in both middle-aged and elderly people.¹⁴¹ Small RCTs, meta-analyses, and observational cohorts have shown that regular aerobic exercise may also improve AF-related symptoms, quality of life, and exercise capacity.^142,143 Better cardiorespiratory fitness and a gain in cardiorespiratory fitness over time are associated with a greater reduction in AF burden and improved maintenance of sinus rhythm.^141–145

5.7. Alcohol excess

Alcohol consumption can increase the risk of adverse events in patients with AF, such as thromboembolism, death, or AF-related hospitalization.^231,232 Alcohol is associated with an increased risk of ischaemic stroke in patients with newly diagnosed AF, and alcohol abstinence after AF diagnosis can reduce the risk of ischaemic stroke.²³³ In patients receiving OAC, alcohol excess is associated with a greater risk of bleeding,²³⁴ mediated by poor adherence, alcohol–drug interactions, liver disease, and variceal bleeding.

Alcohol consumption is associated with a dose-dependent increase in the recurrence of AF after catheter ablation.^147,235 In an RCT among regular non-binge drinkers with AF, the goal of abstinence led to a significant reduction in AF recurrence and burden; alcohol intake was reduced from 16.8 to 2.1 standard drinks per week (≤30 grams or 3 standard drinks of alcohol) in the intervention arm, with 61% attaining abstinence.¹⁴⁷ In observational data of patients undergoing catheter ablation, reduction of consumption to ≤7 standard drinks (≤70 grams of alcohol) per week was associated with improved maintenance of sinus rhythm.^128,235