Atrial fibrillation with slow-ventricular response (AF-SVR): A literature review

Abstract

Atrial fibrillation is a common cardiac arrhythmia affecting over 33 million individuals globally; however, atrial fibrillation with slow-ventricular response (AF-SVR) remains an underexplored subset. AF-SVR is characterized by an irregular ventricular rate of less than 60 beats per minute without the influence of atrioventricular (AV) blocking agents. This review aims to consolidate current knowledge on AF-SVR, focusing on the epidemiology, pathophysiology, clinical manifestations, complications, diagnosis, and management strategies. AF-SVR is more prevalent in older adults, often attributed to age-related degeneration of the cardiac conduction system. Conditions such as AV nodal block, sick sinus syndrome (SSS), and the effects of certain medications are significant contributors to the development of AF-SVR. The pathophysiology involves complex electrical and structural remodeling of the atria, which can lead to bradycardia and symptomatic conduction delays. Clinically, AF-SVR presents similarly to other forms of bradycardia, with symptoms including fatigue, dizziness, and syncope. Diagnosis is primarily based on electrocardiogram (ECG) findings of AF with a slow-ventricular rate, supplemented by ambulatory ECG monitoring and exercise tolerance testing. Transthoracic echocardiography (TTE) is crucial for identification of underlying structural heart disease. Management of AF-SVR involves first addressing reversible causes such as medication effects, electrolyte imbalances, and underlying ischemia. Pharmacological options including the use of anticholinergic medications such as theophylline and hyoscyamine, which have shown efficacy in reversing bradycardia. Persistent or severe cases often require permanent pacemaker implantation to maintain adequate heart rates and prevent complications. This review highlights the need for further research on AF-SVR, particularly regarding non-invasive treatment options and the long-term outcomes of different management strategies. Understanding the unique challenges of AF-SVR is essential for optimizing patient care and improving clinical outcomes. Future studies should focus on establishing comprehensive guidelines for the diagnosis and management of AF-SVR.

Introduction

Atrial fibrillation (AF) is the most frequently encountered form of cardiac arrhythmia in healthcare settings and has a global impact. ¹ It affects over 33 million individuals worldwide and more than 3 million people in the United States alone. ²

In the 1990s, the pathogenesis and clinical significance of AF became more apparent due to epidemiological research such as the Framingham Heart Study. ³ Over the past 30 years, there has been significant growth in research on AF, resulting in advances in its clinical management. These developments are crucial as AF is becoming more widespread.

AF is uncommon in individuals under 50 years old, and its prevalence increases with age. ² There are numerous associated medical and cardiac conditions, including hypertension, coronary artery disease, heart failure (HF), valvular heart disease, obesity, and sleep apnea syndrome. ⁴

The exact mechanism behind the electrical activity in AF is not entirely clear, but it may involve complex re-entrant mechanisms, focal discharges, and micro re-entry. ⁵ The presence of both ectopic electrical impulses and underlying structural changes are essential for the initiation and maintenance of AF. Paroxysmal AF always precedes persistent AF, which is consistent with the idea that the atrial remodeling induced by AF contributes to its further progression. These are the result of various inherited and acquired pathophysiological processes, with significant variability in their contributions to individual cases. ⁶

The clinical manifestations of AF with a rapid ventricular response (RVR) have been the primary focus of studies and guidelines. AF with slow-ventricular response (AF-SVR) is this topic that is less commonly examined. There is some debate regarding its definition, but it is generally defined as having a resting ventricular rate of less than 60 beats per minute (bpm) without concomitant use of atrioventricular (AV) blocking agents. The prevalence of AF-SVR in the general population is not well established, and there are no large clinical trials investigating its treatment strategies. AF-SVR more likely represents a subset of patients that have both inherent conduction system disease and AF, which is not uncommon in clinical practice. Even when patients with AF have a normal or high heart rate (HR), the presence of underlying risk factors for conduction disease may still result in the deterioration to AF-SVR. With increased rates, the strain on the conduction system increases the likelihood to deteriorate due to pathologic remodeling of both the myocardium and the conduction system, known as tachycardia-induced cardiomyopathy. This risk can be further increased by introducing certain medications for other concomitant heart conditions, valvular heart diseases like aortic stenosis, and progressive conduction disease that develop with age. Due to the location of the conduction system within the myocardium, any process that changes the morphology of the native heart can cause conduction delay, with AF being a common cause.

There should be specific approaches to the diagnosis, investigation, and management of patients with AF and an HR that falls into the bradycardic range. There are multiple potential predisposing mechanisms, many of which have important implications for clinical practice. This review will highlight current practices and identify essential studies that can inform a deeper understanding of AF-SVR and its associated risks, as well as propose an approach for clinical practice.

Causes of AF-SVR and considerations

Epidemiology and demographics

Bradycardia and conduction abnormalities are frequently found in elderly individuals above 65 due to the natural aging process and disease progression. ⁷ These abnormalities can be caused by issues with various parts of the heart, such as the sinus node, atrial tissue, atrioventricular nodal (AVN) tissue, and specialized conduction system. They can lead to slower HRs, discordant timing of atrial and ventricular depolarization, and abnormal ventricular depolarization. There are no direct epidemiological studies documenting the incidence of AF with a concurrent cause of bradycardia or conduction abnormality, although AF has been found to be a common co-existing issue in those requiring pacemaker implantation for AVN disease. ⁸

Atrial ventricular nodal block

AV block occurs when the conduction system is anatomically or functionally impaired, leading to a delay or interruption in the transmission of an electrical impulse through the AV node, interfering with normal conduction from the atria to the ventricles.

Fibrosis of the conduction system and ischemic heart disease are the most common causes of AV block, accounting for approximately 50% and 40% of cases, respectively. AV block can also be caused by cardiomyopathies, congenital heart disease, and medications such as beta-blockers, non-dihydropyridine calcium channel blockers, and digitalis. Various heart procedures, including open heart surgery, transcatheter aortic valve implantation, catheter ablation of arrhythmias, transcatheter closure of a ventricular septal defect, and alcohol septal ablation, can also lead to AV block. ⁹

Few studies investigate the degree of AV block required to cause clinically significant bradycardia in those with AF. However, there are numerous case reports documenting complete heart block (CHB) in patients with AF. ¹⁰ There can be a diagnostic challenge in identifying AV nodal disease or block in patients with AF due to a lack of p-waves, although CHB will be easier to discern on electrocardiogram (ECG). Regardless, AV conduction delay, with its diverse range of etiologies, should be considered a potential cause of any presentation of AF-SVR.

Medications

Medications causing AV nodal conduction delay will be easier to identify as a potential culprit in AF-SVR. It is likely that patients with AV block taking medications that can affect conduction have an underlying conduction system disease to some degree. However, medication toxicity may also occur due to intentional or unintentional overdose or if the patient has renal or hepatic dysfunction, leading to decreased medication clearance. The most frequently implicated medications are beta-blockers and non-dihydropyridine calcium channel blockers (CCBs). Other common medications include digoxin, adenosine, and antiarrhythmic drugs (AADs) such as amiodarone. ¹¹ In patients with AF, discerning the exact mechanism underlying a slow-ventricular rate with these medications remains difficult. However, it is well-known that they can cause clinically significant bradycardia.

Monotherapy treatment with beta-blockers or a CCB for AF is less likely to lead to a slow-ventricular rate in the absence of underlying AVN disease and medication toxicity. A recent study indicated that rate-lowering dual therapy, antiarrhythmic monotherapy, and a combination of AADs and rate-lowering drugs were associated with an increased risk of permanent pacing, temporary pacing, and bradyarrhythmia compared to rate-lowering monotherapy. The association was particularly strong during the first 2 weeks of treatment. ¹² In general, overly strict control of HR instead of a more lenient and non-inferior target of 110 beats per minute, as demonstrated by the Rate Control Efficacy in Permanent Atrial Fibrillation: a Comparison between Lenient versus Strict Rate Control II (RACE II) trial, can increase the risk of symptomatic bradycardia and pacemaker implantation. ¹³

SSS with AF

SSS is a group of diseases characterized by abnormal cardiac pacing, leading to various cardiac arrhythmias, particularly bradycardia. Bradycardia–tachycardia syndrome is a form of SSS that involves a slow-ventricular rhythm (sinus bradycardia or sinus pause) coupled with secondary atrial tachyarrhythmias, with AF being the most prevalent arrhythmia. ¹⁴ Age-related interstitial fibrosis is believed to be the shared underlying pathophysiological mechanism between sinus node dysfunction and AF. It is difficult to distinguish between patients with AF related to SSS and those with AF and normal sinus function. Although periods of sinus bradycardia in those with SSS with AF should not be classified as AF-SVR, it is nevertheless an essential clinical entity to appreciate. It should be suspected in patients with known AF and episodes of syncope or light-headedness and is confirmed by sinus pauses following conversion from AF or episodes of sinus bradycardia, not further explained by medications. More common cardioactive drugs, such as digoxin, quinidine, and procainamide, as well as hyperkalemia, can cause periodic sinus arrest or sinoatrial exit block. ¹⁵

Diagnosis and definition of AF-SVR

Defining parameters

AF-SVR can be defined on ECG as a rhythm consistent with AF and a ventricular rate of less than 60 beats per minute in the absence of medication that slows AV conduction, with an ECG example demonstrated in Figure 1. The initial diagnosis of AF-SVR should be confirmed with ECG if suspected from a patient’s history and examination findings.

Figure 1.

ECG depicting atrial fibrillation with slow-ventricular response of 25 bpm. ¹⁶

When approaching AF-SVR, it is essential to consider the underlying pathophysiology of the slow-ventricular response. Symptoms of AF-SVR will not be distinguishable from another presentation of symptomatic bradycardia. Fatigue, weakness, and shortness of breath can be caused by reduced cardiac output due to a slow HR, while sinus pauses following conversion to sinus rhythm may cause neurological symptoms like light-headedness or fainting. In a patient with known AF, a thorough medication history can yield important information, including asking about recent medication changes and overdoses. The examination typically reveals an irregular pulse at a bradycardic rate, with an ECG tracing resembling Figure 2.

Figure 2.

Atrial fibrillation with slow-ventricular response. ¹⁷

Incidental findings of AF-SVR on ECG without symptoms and evidence of high-grade AV block should be considered benign. Symptoms of bradycardia and atrial tachyarrhythmias with RVR often overlap. Without evidence of bradycardia on initial presentation, AF-SVR is unlikely a strong consideration unless correlated with symptoms on ambulatory ECG monitoring or telemetry.

Thorough assessments, including obtaining the patient’s medical history, conducting a physical examination, performing an ECG, 24-h Holter monitoring or prolonged monitoring, transthoracic echocardiography (TTE), and exercise tolerance testing, should be carried out to assess chronotropic competence and will guide further treatments including rate or rhythm control, pacemaker insertion, and cardiac ablation.

ECG findings

Various findings on ECG may be suggestive of a cause of AF-SVR, but the absence of p-waves can mask expected findings in a patient without AF. This is particularly the case for second-degree AV block in AF-SVR.

In cases of third-degree block, no atrial impulses are conducted, causing a lower pacemaker to take over. This results in an escape from the His–Purkinje system or ventricular myocardium. On ECG, this is recognized by regular QRS intervals that can be narrow or wide depending on the origin of the escape rhythm.

A strong indicator of digoxin toxicity is when an accelerated lower pacemaker, possibly caused by triggered activity resulting in an accelerated junctional rhythm, leads to regular R-R intervals. It is important to note that this regularity is in contrast to the irregular R-R intervals seen in AF, which can be seen in Figure 3. ¹⁸ In such cases, simply palpating the peripheral pulse may lead to an incorrect assumption that the patient has converted to sinus rhythm; however, the ECG will still show fibrillatory waves.

Figure 3.

Another example of atrial fibrillation with SVR. ¹⁹

Exercise tolerance testing

Exercise tolerance testing (ETT) is a standard method for evaluating the AV conduction response by measuring the HR during periods of increased demand. During exercise, the HR escalates in a linear fashion with workload and oxygen demand, with an expected increase of about 10 beats per minute per metabolic equivalent of task (MET) achieved. It can be considered a sign of chronotropic incompetence if the HR fails to increase sufficiently to match the metabolic demands during exercise, commonly described in individuals with underlying sinus node dysfunction and conduction abnormalities. ²⁰

In previous studies of patients undergoing ETT to assess the need for rate-responsive pacing before primary pacemaker implantation or pacemaker replacement, there is a relatively high incidence of chronotropic incompetence in individuals with chronic AF and bradycardia. ²¹

There is a role for ETT in the assessment of AF-SVR in those with clear reversible causes, such as medications, similar to the approach for any patient with symptomatic bradycardia. It has been shown to be safe to perform in patients with AF. ²¹ Although other modalities of testing are more routinely recommended for assessment of ischemic disease, it should be considered in AF-SVR patients with symptoms transiently related to exercise, asymptomatic second-degree AV block, or suspected chronotropic incompetence.

Role of echocardiography

TTE as part of the initial workup in AF-SVR can help detect various structural cardiac abnormalities that may be responsible for bradycardia or conduction disturbances. These abnormalities include various forms of cardiomyopathy, valvular heart disease, infections, or infiltrative processes. A TTE is particularly vital in patients at high risk for myocardial ischemia in order to appreciate new regional wall motion abnormalities and acutely depressed cardiac function.

According to the 2018 Bradycardia Guidelines, patients with new left bundle-branch block, Mobitz type II AV block, high-grade AV block, or complete AV block are recommended to undergo transthoracic echocardiogram with a class I recommendation. ²²

Advanced imaging modalities such as cardiac computed tomography (CT), cardiac magnetic resonance imaging (MRI), nuclear imaging, or transesophageal echocardiography, may be appropriate for certain patients based on clinical suspicion for specific disease processes.

Role of an electrophysiology study

An electrophysiology study (EPS) can help identify the presence of abnormal sinus node function or AV conduction and the anatomic location of any conduction disorder. In the current American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, an EPS can be utilized in the event of inconclusive non-invasive cardiac evaluations for bradycardia, especially in the event of unexplained syncope.

However, in most cases, establishing the etiology of symptomatic bradycardia can be accomplished with non-invasive evaluation. In patients with AF-SVR, it can be used as an adjunctive tool when the cause of bradycardia is unclear, especially with no evidence of medication effect, ECG abnormalities at rest and exercise, or new structural heart defects.

There are no studies to our knowledge documenting routine use of EPS specifically with AF-SVR at present, but given the potential difficulty of elucidating an underlying cause of AF-SVR, its utility should be considered, especially when considering more advanced therapies, including cardiac ablation.

Complications of AF-SVR

Recognition of AF-SVR is crucial as it poses significant consequences and complications due to the combined risks of AF and bradycardia, requiring a distinct approach from that of conventional AF or bradycardia alone.

Physicians are highly concerned about three aspects while treating patients with AF, which can have serious consequences, even in the absence of symptoms. These include preventing thromboembolic risk, managing symptoms, and preventing or treating cardiomyopathy. In the case of AF-SVR, multiple factors determine the urgency and significance of a bradycardic HR, including the presence of symptoms and the underlying cause of the bradycardia.

Thromboembolic risk

In patients with AF, an ischemic stroke can occur as the initial manifestation of AF or even with appropriate antithrombotic prophylaxis. The most common cause of ischemic stroke in these patients is a cardiac embolus, typically a thrombus originating from the left atrial appendage (LAA). ²² Stroke risk in patients with asymptomatic AF has been shown to be similar to those with symptomatic AF. ²³

Cardiomyopathy

AF is associated with cardiomyopathy, which can be caused either as a function of tachycardia or remodeling associated with AF itself, wholly or partially. The term tachycardia-induced cardiomyopathy (T-CM) describes the existence of reversible left ventricular (LV) dysfunction that results solely from an increase in ventricular rates, regardless of the underlying cause of the tachycardia. One of the significant characteristics of T-CM is its ability to be reversed once the underlying tachycardia is resolved. Therefore, the primary approach to treating T-CM involves suppressing the tachycardia causing the condition. HF symptoms will appear earlier at higher rates of tachycardia, irrespective of the type of tachyarrhythmia. ²⁴

In addition, AF-mediated cardiomyopathy (AMC) is an important reversible cause of HF. ²⁵ AMC can cause irreversible remodeling of the ventricles and atria—therefore, it is crucial to promptly diagnose and intervene to achieve the best possible clinical outcome. Studies have indicated that a higher ventricular rate may be linked to a greater likelihood of developing AMC. ²⁶ Addressing the RVR or restoring sinus rhythm can significantly enhance or normalize the left ventricular ejection fraction (LVEF) in some patients, demonstrating that rapid AF is the primary contributor to LV dysfunction. Currently, it is uncertain if there is a specific threshold of ventricular rate that can cause AMC. Patients with AF who have achieved proper rate control may still develop AMC. ²⁷

There is insufficient research on the impact of AF-SVR on the development of cardiomyopathy. However, it is plausible that maintaining a lower HR could potentially delay the onset of cardiomyopathy based on the physiological changes that occur at higher HRs. Approximately 20%–30% of the cardiac output results from atrial contraction; as a result, patients with AF may experience significant symptoms due to the loss of atrial contraction. Therefore, restoring atrial rhythm may offer benefits to AF-SVR patients. According to Hwang et al. ²⁸ ’s study, patients with HF and reduced ejection fraction with AF-SVR showed similar reverse remodeling as those with sinus rhythm.

Symptoms

Symptoms of bradycardia can negatively impact a patient’s quality of life and pose serious health risks. Syncope is a frequent presenting symptom, and patients may experience a reduced ability to perform daily activities. In addition, comorbid cardiovascular conditions such as myocardial ischemia with anginal symptoms and HF with dyspnea may be compounded due to bradycardia. Symptomatic AF-SVR must be clinically evaluated, given the possibility for the need of pacemaker implantation in this population.

Treatment of AF-SVR

Approach to symptomatic bradycardia

The approach of AF-SVR should begin with assessing whether the patient has symptoms that are attributed to a slow-ventricular rate. If this is the case, the patient must be evaluated for unstable bradycardia. Concerning signs and symptoms include evidence of end-organ ischemia such as hypotension, HF, ischemic chest pain, and altered mental status. In this situation, the patient should be treated according to the Advanced Cardiovascular Life Support (ACLS) guidelines. Generally, a trial of medications may be appropriate, with a low threshold for transcutaneous or transvenous pacing as a bridge to permanent pacemaker placement.

Atropine is commonly used for treating AV block and bradycardia due to its simple administration and low adverse reactions profile. However, it is usually used temporarily as a bridge to longer-lasting therapies. Aminophylline and glucagon may also have a role in treating AV block in certain circumstances, such as during acute myocardial infarction or beta-blocker toxicity, but there are limited data on their effectiveness. It is unclear whether atropine is appropriate for cases of AF-SVR. It will likely depend on the etiology of AF-SVR, especially if there is evidence of CHB or a high-grade AV block.

Addressing reversible causes

In patients presenting with new AF-SVR, transient or reversible causes should be elucidated by medical valuation, and the treatment approach should center around these causes. Permanent pacing is often times unnecessary. Electrolyte abnormalities, ischemia, and medications remain the leading reversible causes.

Medications that can slow down or impede the conduction of electrical impulses in the heart’s AV node are frequently prescribed for patients with AF, as well as other arrhythmias and co-existing heart conditions. Examples include beta-blockers, non-dihydropyridine CCBs, and class I and III AADs. Consequently, patients taking one or more of these medications may experience AV block. However, these medications may be necessary and should not be immediately discontinued without further evaluation in a patient with stable AF-SVR. Although stopping the medication may occasionally reverse AV block, several case studies suggest that it is uncommon for this to occur, even when used at therapeutic doses. Furthermore, if the AV block does reverse, it often requires the later implantation of a pacemaker. ²⁹

Digoxin toxicity is another increasingly common cause of AV block reversible with drug washout or treatment. Other reversible causes include Lyme carditis in endemic areas, hypothyroidism, and cardiac sarcoidosis.

Role of cardioversion and rhythm control

The effectiveness of cardioversion for patients with AF-SVR has yielded inconsistent long-term results. Various case studies and reports have demonstrated that cardioversion in the context of AF-SVR can result in harmful effects on patients, such as junctional escape rhythm, tachycardia–bradycardia syndrome, prolonged pauses, and even cardiac arrest. ³⁰

The potential risk of potential arrhythmia secondary to rhythm control in patients with AF and bradyarrhythmia has been a concern for some time. AADs can potentially induce or aggravate bradycardia due to abnormal AV conduction or sinus node dysfunction. A history of syncope, sinus bradycardia, bundle-branch block, or PR interval prolongation raises concerns regarding the risk of bradyarrhythmia during AAD therapy. As a result, current guidelines advise against using pharmacological cardioversion in patients with sinus node dysfunction or AV conduction issues.

However, current guidelines lack recommendations for electrical cardioversion in patients with AF-SVR, and the efficacy of rhythm control for this subgroup has yet to be characterized. In addition, evaluating the level of dysfunction of the sinoatrial or AV node in patients without a previous history of conduction dysfunction prior to cardioversion can be challenging.

Role of medications

Anticholinergic medications such as theophylline, glycopyrrolate, and hyoscyamine, among others, block receptors found in smooth and cardiac muscle, the sinoatrial and AV nodes, and the exocrine glands. Anticholinergic drug therapy has been shown in case reports to be effective in patients with AF-SVR who would otherwise require a pacemaker. Administration of intravenous glycopyrrolate to assess for a chronotropic effect, followed by frequent doses of hyoscyamine, can be effective in reversing stable AF-SVR. ³⁰ There are also data supporting use of oral theophylline in patients with AF-SVR and a narrow-complex QRS over pacemaker implantation in certain groups. ³¹ Electrophysiologic investigations showed that theophylline enhances AV nodal conduction; it shortens both the interval and cycle length of the fastest 1:1 AV conduction.

Pacemaker implantation

For patients with symptomatic bradycardia, especially with an HR that consistently falls below 40 bpm, pacemaker implantation is an established treatment option.

Patients who have AV node disease represent a subset of individuals with a higher risk of recurrent symptoms, necessitating more careful monitoring during follow-up. Even after the first symptomatic presentation, evaluation should be considered for possible permanent pacemaker (PPM) implantation. ³² If there is no reversible cause of AV block, permanent pacemaker placement is typically necessary. Regardless of symptoms, many advanced degrees of conduction system disease indicate permanent pacing. Placement of a PPM has been shown to improve survival in patients with high-grade AV block (greater than 2:1), complete AV block, or Mobitz type II second-degree AV block. ³³

Implantation of a pacemaker should be considered in those with AF-SVR and AV block or SSS who require pharmacologic antiarrhythmic therapy. ³⁴ For patients with chronotropic incompetence, selection of pacemaker type should address response to exercise and provide a rate-responsive system (VVIR). ³⁵

Cardiac resynchronization therapy and cardiac ablation

Due to AF, AV synchrony is near unattainable in AF patients with cardiac resynchronization therapy (CRT). This can lead to further cardiomyopathy and dyssynchrony in this cohort of patients. Thus, AV node ablation (AVNA) may be warranted in patients with AF, which allows a higher biventricular pacing percentage. ³⁵ Furthermore, the atrioventricular junction ablation and biventricular pacing for atrial fibrillation and heart failure (APAF-CRT) trial demonstrated that patients with permanent AF and narrow QRS and at least one HF hospitalization in the previous year who had AVNA and CRT device implantation had superior mortality outcomes to patients with pharmacologic regulation of atrial rhythm and CRT implantation. ³⁶

AV node ablation may be an effective treatment option for patients with AF and RVR due to tachycardia. Controlling inappropriate tachycardia with cardiac CRT and AVN ablation may be one of the mechanisms contributing to the effectiveness of CRT in patients with AF-SVR, similar to those with sinus rhythm. There are currently no studies demonstrating a benefit for ablation in AF-SVR, but given that a possible underlying AV conduction block could be present, it may not be necessary nor safe.

CRT has demonstrated benefits for patients with AF-SVR and those with SR, by correcting electrical desynchrony and increasing the rate of biventricular pacing. These benefits include narrowing of the QRS, symptomatic improvement, reverse ventricular remodeling, and improvement of long-term clinical outcomes. ³⁵ All of the patients in the study had the following characteristics: LVEF ⩽35% on transthoracic echocardiogram, QRS duration more than 120 ms on 12-lead ECG, and drug-refractory systolic HF with the New York Heart Association (NYHA) class III or ambulatory IV symptoms. When evaluating for pacemaker implantation for AF-SVR, many patient factors should be considered including the projected burden of ventricular pacing and the LVEF. Additional research to assess the effects of CRT on AF-SVR patients with a narrow QRS and LVEF greater than 35% would be beneficial.

Vagal ablation

Vagal ablation is a specialized procedure that targets the vagus nerve to increase HR, but its use in treating AF-SVR is so far limited. It may be considered in specific circumstances, for example, when there is evidence of an excessive vagal influence. Patient cohorts have typically included patients with vagal AF, usually younger individuals with well-established association with athletic training.^36,37 The decision to pursue vagal ablation in AF-SVR should be made after careful evaluation by a cardiac electrophysiologist and tailored to the patient’s specific clinical circumstances.

Future directions

AF-SVR deserves recognition as a distinct clinical entity because its diagnosis and management involve a unique approach that differs from that used for patients with bradycardia or AF alone.

It is important to prioritize the search for reversible causes and recognize the challenges in interpreting ECG changes in patients with concurrent AF rhythm and AV conduction disease. Seeking the input of a cardiologist is often critical, especially for patients taking AV nodal blocking agents. To identify any potential sources of conduction disease, especially in cases of suspected myocardial ischemia, structural imaging is crucial.

When developing strategies for managing AF-SVR, it is important to consider that AV block is likely to be a significant factor in many cases. Simply discontinuing medications may not be enough to address the underlying, potentially progressive disease process.

More research and studies are needed to explore temporizing measures and non-pacemaker implantation methods for managing AF-SVR, with a specific emphasis on anticholinergic medications like theophylline and hyoscyamine. These drugs have shown promise in various clinical reports and warrant further investigation. Generally, however, it is advisable to have a low threshold for PPM implantation. Based on recent case reports, rhythm control measures such as pharmacological and electrical cardioversion do not appear to be suitable for this subset of patients. It is important to determine the most appropriate PPM for these individuals, particularly in light of new trials that demonstrate the comparable efficacy of CRT in AF-SVR patients with HF as compared to those in sinus rhythm. Cardiac ablation does not appear to be a viable option for AF-SVR patients, but more studies are needed in this area.

Conclusion

AF-SVR is a distinct but underrecognized clinical entity with significant diagnostic and management implications. While it shares features with both AF and bradycardia, AF-SVR often arises due to intrinsic conduction system disease, medication effects, or underlying structural heart abnormalities. Proper evaluation requires a comprehensive approach, including ECG, ambulatory monitoring, echocardiography, and, in select cases, electrophysiologic studies. Treatment strategies should prioritize identifying reversible causes while addressing symptomatic bradycardia through pharmacologic or device-based interventions. The role of pacemaker implantation remains crucial for patients with persistent symptoms or high-grade AV block. However, emerging therapies, including selective anticholinergic agents, warrant further investigation. Despite its clinical significance, AF-SVR remains poorly studied, and future research should aim to establish evidence-based guidelines to optimize patient outcomes. Recognizing and appropriately managing AF-SVR is essential to improving quality of life and reducing the risk of adverse cardiovascular events.