Who Benefits Most? Patient Selection for Atrial Fibrillation Catheter Ablation in Heart Failure

AF and heart failure (HF) are two prevalent cardiovascular conditions that frequently coexist, sharing common risk factors such as hypertension, diabetes and advanced age. The coexistence of AF and HF is associated with increased morbidity and mortality, leading to a compounded risk profile for affected patients.¹ The pathophysiological interplay between AF and HF is complex and bidirectional. AF can exacerbate HF by promoting rapid ventricular rates and irregular rhythm, resulting in reduced cardiac output and potential development of tachycardia-induced cardiomyopathy. Conversely, HF can facilitate the onset and maintenance of AF through structural and electrical remodelling of the atria, including atrial dilation and fibrosis.²

Management of AF in the context of HF poses significant clinical challenges. While rate control strategies are commonly employed, they may not adequately address the haemodynamic compromise associated with AF in HF patients. Rhythm control, particularly through catheter ablation, has emerged as a therapeutic option aimed at restoring sinus rhythm, improving symptoms and potentially enhancing long-term outcomes.³

Recent randomised controlled trials (RCTs) have explored the efficacy of catheter ablation in patients with coexisting HF and AF (Table 1 ). In CASTLE-AF, patients with symptomatic AF and left ventricular ejection fraction (LVEF) ≤35% (approximately 70% with persistent AF) randomised to catheter ablation experienced a significant reduction in the composite endpoint of all-cause mortality and HF hospitalisation compared with medical therapy. Over a median follow-up of nearly 4 years, ablation was associated with a 38% RR reduction in the primary outcome, along with an absolute improvement in LVEF of approximately 8% among patients maintaining sinus rhythm.⁴ However, data on catheter ablation in HF with preserved ejection fraction (HFpEF) remain limited and are primarily derived from observational studies and subgroup analyses, highlighting an important area for ongoing research.

Given the evolving landscape of AF management in HF patients, this review provides a narrative synthesis of contemporary evidence with a focus on clinical decision-making and patient selection for AF ablation in HF.

Pathophysiological Rationale for Catheter Ablation in Heart Failure

AF and HF share a complex pathophysiological relationship that forms the rationale for catheter ablation as a therapeutic strategy. AF can precipitate or worsen HF by promoting rapid and irregular ventricular rates, which reduce diastolic filling time and consequently cardiac output. These effects are particularly detrimental in patients with pre-existing left ventricular dysfunction or significant diastolic dysfunction, where a loss of atrial contribution and increased myocardial oxygen demand can exacerbate symptoms and progression of HF.^1,5

Catheter ablation aims to restore and maintain sinus rhythm, offering several potential benefits for HF patients, potentially halting or even reversing maladaptive changes. Restoration of atrial systole improves diastolic filling and cardiac output, while regularisation of ventricular rate enhances haemodynamic stability. Additionally, ablation may mitigate or reverse tachycardia-induced cardiomyopathy, a reversible form of systolic dysfunction resulting from persistently elevated heart rates.⁶ Beyond haemodynamics, ablation may promote structural and electrical reverse remodelling. Studies have shown that successful ablation is associated with reductions in left atrial (LA) size and fibrosis, improved ventricular function and decreased neurohormonal activation, including suppression of natriuretic peptides and sympathetic tone.^3,4 These effects collectively improve exercise capacity, quality of life (QoL) and potentially long-term prognosis.

Translational studies support the role of ablation in modulating AF and HF pathophysiology, which involves autonomic dysfunction, calcium mishandling and profibrotic signalling. Ablation targeting the intrinsic cardiac ganglionated plexi may reduce autonomic triggers and improve rhythm stability in select patients; however, elimination of vagal inputs is also associated with a sustained increase in resting heart rate, often on the order of 10 BPM. In patients with HF, this autonomic shift may be undesirable and could offset haemodynamic benefit in some cases.⁷ Neurohormonal activation, including sympathetic overactivity and renin–angiotensin–aldosterone system signalling, drives atrial stretch, oxidative stress and fibrosis.⁸ Calcium dysregulation and Ca²⁺ calmodulin-dependent protein kinase II activation disrupt excitation–contraction coupling and promote fibroblast-driven collagen deposition, while transforming growth factor-β signalling further mediates fibrosis and conduction remodelling.^9,10 Ablation that addresses autonomic and fibrotic pathways may interrupt these maladaptive processes and promote structural and electrical recovery in selected patients.

While rate control remains a cornerstone of AF management in HF, it may not adequately address the pathophysiological consequences of AF, especially in symptomatic patients or those with advanced HF. Rhythm control through catheter ablation offers a more definitive approach to interrupting the deleterious AF–HF interaction. However, the degree of benefit varies based on several factors. While AF pattern and duration influence rhythm outcomes, emerging data suggest that underlying myocardial substrate and extent of structural remodelling are more powerful determinants of ventricular recovery than AF classification alone. A recent systematic review identified several structural and functional predictors of left ventricular systolic function improvement after AF ablation, including lower left ventricular end-systolic volume index, smaller left ventricular end-diastolic diameter, higher early diastolic mitral annular velocity (e′) and absence of advanced atrial or ventricular fibrosis. These findings support the concept that a subset of patients with HF have a reversible AF-mediated or tachycardia-induced component of cardiomyopathy, in whom catheter ablation can facilitate meaningful reverse remodelling, whereas extensive myocardial fibrosis may limit recovery potential.¹¹ Additionally, patients with significant atrial fibrosis or dilation may exhibit limited recovery of atrial function despite rhythm restoration, and the likelihood of maintaining sinus rhythm post-ablation is reduced in these populations.¹² Thus, understanding the pathophysiological interplay between AF and HF, and identifying patients with reversible remodelling potential, forms the foundation for appropriate patient selection.

Evidence Base for Catheter Ablation in Heart Failure with Reduced Ejection Fraction

The efficacy and safety of catheter ablation for AF in patients with HF with reduced ejection fraction have been evaluated in several RCTs, subgroup analyses and meta-analyses, providing a growing body of evidence supporting its use.

The landmark CASTLE-AF trial was pivotal in demonstrating the benefits of catheter ablation in HF with reduced ejection fraction (HFrEF). This multicentre RCT enrolled patients with symptomatic AF and an LVEF ≤35%, randomised to catheter ablation or conventional medical therapy. Over a median follow-up of nearly 4 years, ablation was associated with a significant reduction in the composite endpoint of all-cause mortality and HF hospitalisations (HR 0.62; 95% CI [0.43–0.87]; p=0.007). Improvements were also noted in LVEF, QoL and exercise capacity.⁴ This trial established ablation as a mortality- and morbidity-modifying therapy in select HFrEF patients.

Subgroup analyses of broader AF ablation trials such as CABANA have provided additional insights. The CABANA trial included a large population with AF, with a subgroup of patients having reduced LVEF (≤50%). In this subgroup, catheter ablation was associated with a trend towards a decreased composite outcome of death, disabling stroke, serious bleeding, or cardiac arrest compared with drug therapy, although these results did not reach statistical significance, possibly due to lower statistical power. Complication rates in the reduced LVEF subgroup were similar to those observed in the overall trial population, suggesting that catheter ablation carries a comparable risk profile in patients with reduced EF.¹³ Nonetheless, the direction of benefit aligns with CASTLE-AF findings.

A 2023 meta-analysis including CASTLE-AF, CABANA and other RCTs (such as AMICA and CAMERA-MRI) concluded that catheter ablation in HFrEF significantly improves LVEF (+6.8%), reduces HF hospitalisations (RR 0.58) and may decrease all-cause mortality (RR 0.63), though heterogeneity among trials was noted.¹⁴

Variability in left ventricular recovery observed across randomised trials increasingly reflects differences in baseline myocardial substrate rather than procedural efficacy alone. In a recent systematic synthesis, predictors of favourable LVEF response following AF ablation included lower left ventricular end-systolic volume index, smaller ventricular dimensions, preserved diastolic relaxation and absence of low-voltage zones on electroanatomic mapping. Conversely, the presence of myocardial fibrosis on cardiac MRI and prolonged QRS duration were associated with attenuated response. Collectively, these data reinforce that catheter ablation yields the greatest ventricular benefit when AF is a primary driver of cardiomyopathy rather than a marker of advanced myocardial disease.¹¹

Limitations do persist. Many trials included highly selected populations with fewer comorbidities, relatively preserved functional status and smaller left atria. Generalisability to real-world patients is less certain. Additionally, most trials compared ablation to rate control or amiodarone-based rhythm control, raising questions about relative efficacy in the era of newer antiarrhythmics and HF therapies. Nevertheless, for appropriately selected HFrEF patients, catheter ablation provides durable rhythm control with substantial clinical benefit.

Evidence and Unmet Needs in Heart Failure with Reduced Ejection Fraction

HFpEF represents a growing proportion of HF cases and poses unique challenges in the management of comorbid AF. While rhythm control has demonstrated clear benefits in HFrEF, the evidence base for catheter ablation in HFpEF remains less robust. HFpEF is characterised by impaired ventricular relaxation, increased LA pressure and high sensitivity to atrial mechanical dysfunction and rhythm irregularity. Consequently, restoring atrial systole and rhythm stability may confer substantial physiological benefit in HFpEF.¹⁵

Despite the clear rationale for rhythm control in HFpEF, high-quality evidence supporting catheter ablation remains limited. Most RCTs have focused on HFrEF, leaving HFpEF patients underrepresented. To date, most data on AF ablation in HFpEF are derived from observational studies.¹⁶ A recent observational study using the Swedish Heart Failure Registry evaluated catheter ablation for HF patients across the EF spectrum, with lower risk of primary outcome (all-cause mortality/first HF hospitalisation) in both HFrEF and HFpEF patients.¹⁷ However, these findings may be confounded by selection bias, as patients undergoing ablation were generally younger and healthier.

A recent contemporary review focusing on AF ablation in HFpEF highlights that despite limited randomised outcome data, catheter ablation is consistently associated with improvements in symptoms, exercise capacity and QoL. Importantly, the magnitude of benefit appears highly dependent on underlying atrial and ventricular substrate, with patients exhibiting less atrial fibrosis, smaller LA volumes and earlier-stage HFpEF phenotypes deriving greater benefit. Conversely, advanced atrial myopathy and heavy comorbidity burden may attenuate response, emphasising the heterogeneity of HFpEF populations.¹⁶

The RAFT-AF trial included patients across the HF spectrum (including HFpEF) and randomised them to early catheter ablation versus rate control, with a primary composite outcome of mortality and HF events. This trial enrolled 411 patients with HF (mixed HFrEF and HFpEF), New York Heart Association class II–III symptoms, elevated N-terminal pro b-type natriuretic peptide and either high burden paroxysmal AF or persistent AF. The primary endpoint was composite of all-cause mortality and HF events, occurring in 23.4% in the ablation group versus 32.5% in the medical therapy group (HR 0.71, 95% CI [0.49–1.03]; p=0.066). While the trial did not demonstrate a statistically significant difference in the primary outcome between the two groups, it provided valuable insight into rhythm control in contemporary HF populations. RAFT-AF did include HFpEF patients and reported subgroup analyses, but the results for HFpEF should be interpreted with caution due to limited sample size and statistical power.¹⁸

Observational studies and meta-analyses have provided mixed results. Some suggest that patients with preserved or mid-range EF derive symptomatic and QoL benefit from ablation, but effects on hard outcomes like mortality remain uncertain.¹⁹ The heterogeneity of HFpEF, driven by variable atrial myopathy, fibrosis and comorbid burden, makes universal conclusions difficult. Patients with less atrial remodelling, smaller LA volumes and earlier AF onset may benefit most. More granular risk stratification tools are needed to guide decision-making in this complex population. While catheter ablation offers a promising rhythm control option for patients with HFpEF and AF, the evidence base is currently insufficient to draw definitive conclusions.

Advanced Heart Failure and Borderline Populations

Managing AF in patients with advanced HF or borderline clinical profiles poses significant challenges, as the potential benefits of catheter ablation must be weighed against increased procedural risks and uncertain outcomes.

The CASTLE-HTx trial extended the exploration of AF ablation into patients with end-stage HF listed for heart transplantation. Although the trial faced scepticism due to small sample size and complex patient selection, it suggested that catheter ablation may confer meaningful benefits, including reduced AF burden and possibly improved post-transplant outcomes.²⁰ Recently published 3-year follow-up data from CASTLE-HTx further support the feasibility of catheter ablation in carefully selected patients with end-stage HF listed for transplantation. Extended follow-up demonstrated sustained reductions in AF burden and signals toward improved clinical stability during the pre-transplant period, although outcomes remained closely linked to baseline frailty and comorbidity burden.²¹ This represents an important signal that ablation should not be categorically excluded in advanced HF, provided patient-specific factors are carefully considered.

Procedural risk in this population is heightened by factors such as haemodynamic instability, frailty and the presence of devices like left ventricular assist devices or cardiac resynchronisation therapy. Ablation in left ventricular assist device patients is complicated by altered atrial anatomy, increased fibrosis and potential thromboembolic risk, while cardiac resynchronisation therapy recipients may experience variable responses due to ongoing ventricular dyssynchrony and atrial arrhythmia burden.²²

Considerations in this population include procedural risk, likelihood of reverse remodelling and alignment with overall goals of care. For some, ablation may represent a bridge-to-therapy strategy; for others, especially with extensive atrial disease or frailty, conservative rhythm or rate control may be preferable.

Timing and Rhythm Control Strategy: What Do EAST-AFNET 4 and Other Trials Teach Us?

The timing of rhythm control initiation in patients with AF and HF significantly influences outcomes. Early intervention to maintain sinus rhythm may prevent adverse remodelling and haemodynamic deterioration, yet the optimal timing remains debated.

The EAST-AFNET 4 trial randomised over 2,700 patients with recently diagnosed AF (≤12 months) to early rhythm control (using antiarrhythmic drugs or ablation) versus usual care. In prespecified subgroup analyses, patients with HF (approximately 28%) experienced similar relative benefits, with reduced composite cardiovascular outcomes including stroke, HF hospitalisation and CV death.²³ While not focused solely on HF patients, EAST-AFNET 4 suggests that early rhythm control may attenuate progression of both AF and HF by limiting remodelling and recurrent decompensation.

Conversely, earlier trials such as AF-CHF, AMIOVIRT and DIAMOND-CHF have provided mixed results on rhythm control benefits in HF, often using antiarrhythmic drugs rather than ablation. AF-CHF, for example, found no mortality benefit with rhythm control over rate control but did not include catheter ablation as a primary strategy.²⁴ However, these studies predate current ablation techniques and guideline-directed medical therapy for HF, limiting their relevance to contemporary practice.²⁵

The ‘earlier is better’ hypothesis is gaining traction, particularly when AF is treated within 12 months of initial diagnosis. These observations align with data demonstrating diminished response to ablation once advanced myocardial fibrosis is established, underscoring the importance of timing rhythm control interventions before irreversible structural remodelling occurs.¹¹ However, patient heterogeneity necessitates individualised risk–benefit assessments, considering factors such as symptom burden, comorbidities and HF severity.

Procedural Considerations and Evolving Techniques

Catheter ablation in HF patients is increasingly recognised as a highly effective strategy for rhythm control, offering substantial clinical benefit when patients are appropriately selected. Periprocedural risks in HF patients, such as haemodynamic instability, thromboembolism and complications like cardiac tamponade, warrant careful attention. However, with thorough patient optimisation and guideline-based management, including anticoagulation and fluid balance, these risks can be effectively minimised. Contemporary data demonstrate that in experienced centres, complication rates are comparable to those in the general AF population, highlighting that ablation is a safe option for HF patients when performed with modern techniques and imaging guidance.^26,27

Pulmonary vein isolation remains the cornerstone of ablation, providing robust efficacy in restoring sinus rhythm. Adjunctive strategies, including posterior wall isolation, non-pulmonary vein trigger ablation, or substrate modification, may offer additional benefit for patients with persistent AF or structural remodelling. These approaches should be tailored to the individual patient, balancing the potential for improved outcomes with procedural complexity. Both cryoablation and radio frequency have proven safe and effective in HF populations. Emerging technologies, such as pulsed field ablation, hold promise for enhancing safety, particularly for oesophageal and phrenic nerve protection, even though HF-specific data are still evolving.²⁸

Arrhythmia recurrence may necessitate repeat procedures, particularly in advanced HF and persistent AF. A proactive approach with early reintervention can further optimise long-term rhythm control and clinical outcomes. With these advancements and tailored strategies, catheter ablation is not only increasingly safe in HF patients but also offers meaningful improvements in rhythm, symptoms and potentially prognosis, supporting its role as a preferred therapy when patients are suitable candidates.

Patient Selection: A Practical Framework

Given the heterogeneous responses to catheter ablation among patients with AF and HF, careful patient selection is paramount. Several clinical factors consistently predict better outcomes.

Favourable factors for ablation:

• Younger age and fewer comorbidities: Patients with less advanced atrial remodelling tolerate procedural risks better and experience more sustained benefits.
• Symptom burden: Those with persistent symptoms like dyspnoea or reduced exercise tolerance often see marked QoL improvements post-ablation.
• AF type: Paroxysmal or recent-onset AF typically responds better to ablation than longstanding persistent AF, mainly due to lesser atrial fibrosis.
• ‘Reversible’ HF: Patients with HFrEF who demonstrate potential for reverse remodelling (e.g. nonischaemic, LVEF <35% but viable myocardium) have shown marked benefits, as seen in CASTLE-AF.

Red flags that may diminish benefit:

• Severe frailty or comorbidities: Increased procedural risk and limited recovery potential; risk–benefit ratio must be carefully considered.
• Extreme atrial remodelling: LA diameter >55 mm or dense atrial fibrosis suggests substrate likely to resist rhythm control.
• Shared decision-making is essential. Clinicians should incorporate patient preferences, procedural expectations and competing health priorities when discussing rhythm control strategies. Decision aids, multidisciplinary input and transparent discussion of risks and benefits can support individualised care.

Future Directions and Ongoing Trials

Despite growing evidence supporting catheter ablation in patients with AF and HF, significant gaps remain, particularly for those with preserved ejection fraction, advanced HF or atypical atrial substrates. Ongoing trials and emerging technologies aim to address these knowledge deficits and further refine patient selection, procedural approach and long-term outcomes.

DECAAF II examined fibrosis-guided ablation using MRI to target atrial substrate.²⁹ While not focused exclusively on HF, this trial may inform patient stratification by identifying those with significant atrial myopathy who may respond poorly to traditional ablation approaches.

Future strategies will likely emphasise team-based approaches that combine the expertise of electrophysiologists, HF specialists, cardiac imaging and, when appropriate, palliative care. Personalised treatment algorithms incorporating patient values, disease trajectory and comorbidities will be essential to optimise outcomes and resource use.

The advent of pulsed field ablation, with its potential to minimise collateral injury and procedural risk, may open the door to treating more complex HF patients. Early-phase studies suggest promising safety profiles, but randomised data in HF populations are needed.²⁸

Conclusion

AF and HF frequently coexist, forming a pathophysiological and clinical intersection that demands nuanced management. Catheter ablation has emerged as a compelling rhythm control strategy, particularly for patients with HFrEF, demonstrating improvements in mortality, HF hospitalisations and QoL in select populations. However, the optimal selection of patients remains a challenge. Evidence for HFpEF, advanced HF and device-supported populations is still evolving. Clinical trial data, including from CASTLE-AF, CABANA subgroup analyses and observational cohorts, underscore the importance of timing, atrial substrate and individual patient characteristics in determining the potential benefit of ablation. The role of early rhythm control, particularly in less remodelled atria, may represent a paradigm shift, but must be weighed against procedural risks and patient-specific goals. Moving forward, a tailored approach, anchored in multidisciplinary collaboration, informed by emerging trial data and guided by evolving imaging and biomarker tools, will be essential. In this rapidly advancing landscape, thoughtful patient selection remains the cornerstone of effective, safe and durable rhythm control in the HF population.