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Review | DOI: https://doi.org/10.31579/2690-4861/855
1Department of Cardiology CHU UCL Namur-Godinne 1, avenue Docteur G. Thérasse 5530 Yvoir, Belgium.
2Department of Cardiology Cliniques Universitaires Saint-Luc 10, avenue Hippocrate 1200 Brussels, Belgium.
*Corresponding Author: Benoit Martin, Department of Cardiology CHU UCL Namur-Godinne 1, avenue Docteur G. Thérasse 5530 Yvoir, Belgium.
Citation: Benoit Martin, Robaye Benoît, Higny Julien, Xhaet Olivier, Henry J. Philippe, et al, (2025), Flecainide-induced Failure to Capture: A Narrative Review, International Journal of Clinical Case Reports and Reviews, 30(2); DOI:10.31579/2690-4861/855
Copyright: © 2025, Benoit Martin. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 02 September 2025 | Accepted: 15 September 2025 | Published: 26 September 2025
Keywords: flecainide; pacemaker; dysfunction
Postoperative abdominal and visceral pain is a common complication in patients following appendectomy, especially when associated with peritonitis. The diaphragm, as the primary respiratory muscle innervated by the phrenic nerve (C3–C5), has extensive anatomical and functional relationships with thoracoabdominal and pelvic structures. Fascial restrictions or dysfunction in diaphragmatic movement may contribute to increased intra-abdominal tension and altered visceral mobility, thereby intensifying pain in the abdominal and pelvic regions. This case report presents a 45-year-old female patient who developed persistent abdominal and right thigh pain following an appendectomy complicated by peritonitis. The patient also suffered from right shoulder pain and was referred to physiotherapy for treatment of shoulder pain. In addition to standard physiotherapy, six sessions of diaphragmatic myofascial release were administered.
Outcomes measure were Pain that assessed using the Visual Analog Scale (VAS), chest expansion by tape measure, the Shoulder Pain and Disability Index by SPADI, and the satisfaction by SF-12 quality of life questionnaire. After six sessions treatment consists of diaphragmatic release besides of conventional treatment on shoulder, the patient reported a 90% reduction in visceral pain in the abdominal and inguinal areas. Chest expansion increased from 1.6 cm to 3.5 cm, and the SPADI score improved from 40 to 25. These findings suggest that restoring diaphragmatic mobility through myofascial release can significantly alleviate postoperative abdominal and referred pain, likely by reducing fascial tension and improving neurovisceral dynamics.
Flecainide is one of the most commonly used anti-arrhythmic drugs that can be prescribed to effectively treat supraventricular and ventricular arrhythmias. Many patients receive antiarrhythmic drugs while implanted with a Pacemaker. The Vaughan-Williams class Ic sodium-channel blocking agent, first synthetized in 1977, is used to convert and prevent episodes of AF with stable hemodynamics AV nodal reentry tachycardia and Wolff-Parkinson-White syndrome. The drug may also be indicated in the treatment of recurrence of dysrhythmias (e.g. idopathic ventricular tachycardias). It is contra-indicated in presence of ischemic heart disease, heart failure or LV dysfunction, left bundle branch block, bifascicular block or 2nd and 3rd degree AV block and sinus dysfunction. Clinical and electrocardiographic monitoring is required [1].
The antiarrhythmic effect of the drug is mediated by a rate-dependent slowing of the rapid sodium inward channel (NaV1.5) current (INa). This results in reduction of action potential duration (APD) by slowing the phase 0 of the AP in all cardiac tissues, but particularly the ventricular myocardium. Flecainide increasing atrial APD to a greater extent at faster rates may be due to sodium channel blockade resulting in decreased sodium loading and reduced Na+, K(+)-ATP'ase stimulation during tachycardia [2]. Flecainide has also been reported to reduce cardiac ryanodine receptor (RyR2)-mediated sarcoplasmic reticulum (SR) Ca2+ release. Effects of flecainide on RyR2 is complex, with different binding sites, mostly inhibiting calcium, thus modulating excitability. These caracteristics of flecainide are clinically useful in catecholaminergic polymorphic ventricular tachycardia (CPVT), associated with gain-of-function RyR2 mutations, but could contribute to occasional proarrhythmic phenomena [3].
The delay of electrical conduction in atria and ventricle, manifest on the ECG by a prolongation of the PR interval and QRS duration. QT interval prolongation is predominantly linked to QRS prolongation, while JT interval is usually unchanged. Flecainide increases the AH interval (about 20%) and the HV interval (25%-50%), thus slightly slowing both intra-atrial and atrioventricular nodal conduction. Widening by 25% or more of the QRS interval as compared to the baseline value should lead to drug dosage decrease, as discontinuation is required in case of atrioventricular block, permanent complete bundle branch block, or sino-atrial block [4]. In some patients, high dose flecainide or class-Ic –AAD can trigger Brugada-like ECG patterns, so that it is used by electro-physiologists as diagnostic tool [5].
The described proarrhythmic effect of flecainide is explained by promoting re - entry in ventricular tissue. Recently, the description of paradoxical influence or activation on ryanodine receptor 2 under low activity conditions raised new potential explanations for pro-arythmic effect [6].
Normal functioning of a pacemaker depends on its ability to depolarize the myocardium leading to its contraction. The minimal energy required to induce myocardial depolarization and contraction is determined during a threshold measure. These depolarization thresholds are dynamic, depending of internal and external factors. Lead instability or micro-dislodgement, interface tissue oedema, inflammation, ischemia or hypoxia but also metabolic disorders as severe acidosis, ionic imbalances (hyperkalaemia) are known to raise stimulation thresholds. Chronic thresholds vary under physiological states. While sympathetic modulation like exercise and orthostatic posture can decrease stimulation threshold, vagal tone can increase threshold up to 30-40 % during digestion or sleep [7].
Certain drugs have been reported for decreasing stimulation thresholds such as sympathomimetic agents (epinephrine, ephedrine and isoproterenol) and corticosteroids [8]. These steroid’s properties have been successfully used in now widely-spread steroid-eluting pacemaker leads to prevent usual inflammation-mediated threshold rise in early permanent lead implantation [9].
A number of drugs have been reported to raise stimulation thresholds. Beta-blockers or calcium-channel blockers have been suggested to raise capture thresholds, but clinical data have not confirmed significant variation [10].
If amiodarone can raise defibrillation threshold, the clinical influence on pacing threshold is not convincing [11].
While Class IA agents such a quinidine and procainamide may raise thresholds (but not defibrillation thresholds) at toxic levels or intravenously, Class IB agents (lidocaine, mexiletine) do not seem to have clinical effect on pacing threshold but on defibrillation thresholds at therapeutic levels. Cardiac glycoside digoxin, on the other hand, has been shown reducing pacing thresholds. Class-Ic-AAD are the anti-arrhythmic drugs that raise ventricular capture threshold the most at their upper therapeutic dose range [12].
In fact, more than encainide or propafenone, oral and intravenous flecainide have been shown to rise stimulation thresholds to up 520 % (160-200 % in average increase at chronic oral maximal dose of 400 mg per day), potentially leading to exit block and failure to capture ventricular myocardium, as demonstrated by Hellestrand. Ventricular escape rhythm depression in patients with atrio-ventricular block was also demonstrated [13].
Atrial thresholds were significantly elevated with propafenone potentially leading to atrial lead dysfunction [14].
Threshold increase is correlated to QRS-duration so that no threatening threshold rise (> 100% increase) is expected at less than 25 % QRS lengthening with propafenone treatment [15].
Furthermore, it has also been demonstrated that flecainide substantially raises defibrillation thresholds in open-chested pentobarbital anesthetized dogs [16].
The figures 1 and 2 display an intermittent failure to capture with activation delay and significantly major widened paced- QRS complexes in a case of subacute flecainide overdosis. Ventricular capture threshold increase is well known but still ECG displaying intermittent failure to capture is a rare finding [17-19].
Figure 1: intermittent failure to capture with activation delay and significantly major widened paced- QRS complexes in a case of subacute flecainide overdosis
Figure 2: intermittent failure to capture: unipolar mode
Heart failure can be related to severe bradycardia and the drugs negative inotropic effect by reducing intracellular calcium concentration and interaction with Ryanodine-receptors [20].
Extreme caution should be taken in pacemaker-dependent patients, who do not have any intrinsic rhythm or whose intrinsic rhythm is suppressed by flecainide, as pacemaker dysfunction can lead to loss of consciousness, extreme bradycardia, heart failure and sudden death. Output adjustment and generous safety margins as well as automatic output regulation should be considered without neglecting medical monitoring in these patients.
In case of pacemaker dysfunction, a technical pacemaker issue such as lead displacement or rupture should be assessed by chest X-ray. First-line intervention consists of increasing the stimulation output of the device to assure persistent ventricular capture during drug clearance.
Flecainide clearance pathways are hepatic metabolization by cytochrome CYP 2D6 (to m-O- dealkylated flecainide, keeping 20 % of flecainide’s initial antiarrhythmic effect, and other inactive metabolites), renal excretion of the molecule (up to 50 %) and its metabolites, while faecal excretion is marginal (5 %). Elimination half-life varies from 12 to 27 h in healthy individuals [21].
Simultaneous use of inducing drugs (antidepressants, neuroleptics, propranolol) or inhibitors (phenytoin, phenobarbital) of this iso-enzyme may respectively increase or decrease the plasma concentrations of flecainide. As the drugs clearance is globally moderately correlated to creatinine clearance, there is an important individual variability in serum drug levels due to hepatic oxidation enzyme polymorphism (sparteine/debrisoquin phenotype) so that renal function insufficiently predicts the drug’s clearance [22-24]. EHRA guidelines recommend caution and dose reduction if GFR is below 50 mL/min/1.73 m2, while discontinuation is recommended below 35 mL/min/1.73 m2.
Nevertheless, the toxic effect of flecainide is transient and no remanent effect has been described. Flecainide can be administered orally or intravenously. In recent years, oral flecainide solution inhalation has been introduced for acute cardioversion of new-onset atrial fibrillation [25].
Drug overdose may occur in acute (suicide attempts) or chronic settings and may also include noncardiac manifestations, such as nausea, vomiting, dizziness, blurred vision and seizures [26]. The overall mortality with class 1c agents’ overdoses has been reported to be as high as 22% [27]. This should underline the importance of diagnosis and intensive treatment.
Gastric lavage and activated charcoal administration should be undertaken in the early phase of large ingestion. Hypertonic sodium bicarbonate infusion in case flecainide toxicity is as well described first-line treatment (initial 50–100 mEq bolus with subsequent therapy targeting pH 7.5 and sodium concentration 150 mEq/L). Even if mechanisms aren’t fully understood it has been shown that alkalization and sodium concentration increase reverse flecainide effects in animals, probably by decreasing Na-channel-receptor affinity to the molecule [28,29].
Calcium chloride or gluconate, amiodarone and lidocaine are to be considered in refractory arrythmias linked to flecainide intoxication but understanding of underlying mechanism and experience remain limited [30-32]. If transvenous pacing might be required in severe bradycardia, overdrive pacing may be ineffective in severe intoxications because of the rate-dependent properties of the molecule. Isoproterenol infusion has also been suggested for antiarrhythmic drug induced arrythmias and pacing capture failure [33]. Hyponatremia with normal flecainide serum level has been reported with similar pacemaker malfunction, as hyponatremia is thought to enhance the drugs toxicity [34].
Its lipophilic properties and high distribution volume make conventional dialysis or hemofiltration ineffective for clinically significant drug extraction but lipid-emulsion infusion [35] and hemo-adsorption technique (CytoSorb®) have been reported as therapies in severe flecainide intoxications.
Hemodynamic support by administration of beta-sympathomimetic agents may be needed and extra-corporeal life support (ECMO) might be required and in refractory shock or arrythmias [36,37].
This review underscores the importance of recognising a particular pattern of pacemaker malfunction and the necessity of ECG and threshold monitoring with electrolyte control in patients treated with IC anti-arrhythmic drugs, especially those with advanced age and impaired renal function, including patients requiring stimulation devices and particularly the pacemaker-dependent patient.
The authors Declare no conflict of interest.
In terms of illustration, the Patient’s consent was obtained prior to writing.
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Dear Jessica, and the super professional team of the ‘Clinical Cardiology and Cardiovascular Interventions’ I am sincerely grateful to the coordinated work of the journal team for the no problem with the submission of my manuscript: “Cardiometabolic Disorders in A Pregnant Woman with Severe Preeclampsia on the Background of Morbid Obesity (Case Report).” The review process by 5 experts was fast, and the comments were professional, which made it more specific and academic, and the process of publication and presentation of the article was excellent. I recommend that my colleagues publish articles in this journal, and I am interested in further scientific cooperation. Sincerely and best wishes, Dr. Oleg Golyanovskiy.
Dear Ashley Rosa, Editorial Coordinator of the journal - Psychology and Mental Health Care. " The process of obtaining publication of my article in the Psychology and Mental Health Journal was positive in all areas. The peer review process resulted in a number of valuable comments, the editorial process was collaborative and timely, and the quality of this journal has been quickly noticed, resulting in alternative journals contacting me to publish with them." Warm regards, Susan Anne Smith, PhD. Australian Breastfeeding Association.
Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. I appreciate the journal (JCCI) editorial office support, the entire team leads were always ready to help, not only on technical front but also on thorough process. Also, I should thank dear reviewers’ attention to detail and creative approach to teach me and bring new insights by their comments. Surely, more discussions and introduction of other hemodynamic devices would provide better prevention and management of shock states. Your efforts and dedication in presenting educational materials in this journal are commendable. Best wishes from, Farahnaz Fallahian.
Dear Maria Emerson, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. I am delighted to have published our manuscript, "Acute Colonic Pseudo-Obstruction (ACPO): A rare but serious complication following caesarean section." I want to thank the editorial team, especially Maria Emerson, for their prompt review of the manuscript, quick responses to queries, and overall support. Yours sincerely Dr. Victor Olagundoye.
Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews. Many thanks for publishing this manuscript after I lost confidence the editors were most helpful, more than other journals Best wishes from, Susan Anne Smith, PhD. Australian Breastfeeding Association.
Dear Agrippa Hilda, Editorial Coordinator, Journal of Neuroscience and Neurological Surgery. The entire process including article submission, review, revision, and publication was extremely easy. The journal editor was prompt and helpful, and the reviewers contributed to the quality of the paper. Thank you so much! Eric Nussbaum, MD
Dr Hala Al Shaikh This is to acknowledge that the peer review process for the article ’ A Novel Gnrh1 Gene Mutation in Four Omani Male Siblings, Presentation and Management ’ sent to the International Journal of Clinical Case Reports and Reviews was quick and smooth. The editorial office was prompt with easy communication.
Dear Erin Aust, Editorial Coordinator, Journal of General Medicine and Clinical Practice. We are pleased to share our experience with the “Journal of General Medicine and Clinical Practice”, following the successful publication of our article. The peer review process was thorough and constructive, helping to improve the clarity and quality of the manuscript. We are especially thankful to Ms. Erin Aust, the Editorial Coordinator, for her prompt communication and continuous support throughout the process. Her professionalism ensured a smooth and efficient publication experience. The journal upholds high editorial standards, and we highly recommend it to fellow researchers seeking a credible platform for their work. Best wishes By, Dr. Rakhi Mishra.
Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. The peer review process of the journal of Clinical Cardiology and Cardiovascular Interventions was excellent and fast, as was the support of the editorial office and the quality of the journal. Kind regards Walter F. Riesen Prof. Dr. Dr. h.c. Walter F. Riesen.
Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. Thank you for publishing our article, Exploring Clozapine's Efficacy in Managing Aggression: A Multiple Single-Case Study in Forensic Psychiatry in the international journal of clinical case reports and reviews. We found the peer review process very professional and efficient. The comments were constructive, and the whole process was efficient. On behalf of the co-authors, I would like to thank you for publishing this article. With regards, Dr. Jelle R. Lettinga.
Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, I would like to express my deep admiration for the exceptional professionalism demonstrated by your journal. I am thoroughly impressed by the speed of the editorial process, the substantive and insightful reviews, and the meticulous preparation of the manuscript for publication. Additionally, I greatly appreciate the courteous and immediate responses from your editorial office to all my inquiries. Best Regards, Dariusz Ziora
Dear Chrystine Mejia, Editorial Coordinator, Journal of Neurodegeneration and Neurorehabilitation, Auctores Publishing LLC, We would like to thank the editorial team for the smooth and high-quality communication leading up to the publication of our article in the Journal of Neurodegeneration and Neurorehabilitation. The reviewers have extensive knowledge in the field, and their relevant questions helped to add value to our publication. Kind regards, Dr. Ravi Shrivastava.
Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, Auctores Publishing LLC, USA Office: +1-(302)-520-2644. I would like to express my sincere appreciation for the efficient and professional handling of my case report by the ‘Journal of Clinical Case Reports and Studies’. The peer review process was not only fast but also highly constructive—the reviewers’ comments were clear, relevant, and greatly helped me improve the quality and clarity of my manuscript. I also received excellent support from the editorial office throughout the process. Communication was smooth and timely, and I felt well guided at every stage, from submission to publication. The overall quality and rigor of the journal are truly commendable. I am pleased to have published my work with Journal of Clinical Case Reports and Studies, and I look forward to future opportunities for collaboration. Sincerely, Aline Tollet, UCLouvain.
Dear Ms. Mayra Duenas, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews. “The International Journal of Clinical Case Reports and Reviews represented the “ideal house” to share with the research community a first experience with the use of the Simeox device for speech rehabilitation. High scientific reputation and attractive website communication were first determinants for the selection of this Journal, and the following submission process exceeded expectations: fast but highly professional peer review, great support by the editorial office, elegant graphic layout. Exactly what a dynamic research team - also composed by allied professionals - needs!" From, Chiara Beccaluva, PT - Italy.
Dear Maria Emerson, Editorial Coordinator, we have deeply appreciated the professionalism demonstrated by the International Journal of Clinical Case Reports and Reviews. The reviewers have extensive knowledge of our field and have been very efficient and fast in supporting the process. I am really looking forward to further collaboration. Thanks. Best regards, Dr. Claudio Ligresti
Dear Chrystine Mejia, Editorial Coordinator, Journal of Neurodegeneration and Neurorehabilitation. “The peer review process was efficient and constructive, and the editorial office provided excellent communication and support throughout. The journal ensures scientific rigor and high editorial standards, while also offering a smooth and timely publication process. We sincerely appreciate the work of the editorial team in facilitating the dissemination of innovative approaches such as the Bonori Method.” Best regards, Dr. Matteo Bonori.
I recommend without hesitation submitting relevant papers on medical decision making to the International Journal of Clinical Case Reports and Reviews. I am very grateful to the editorial staff. Maria Emerson was a pleasure to communicate with. The time from submission to publication was an extremely short 3 weeks. The editorial staff submitted the paper to three reviewers. Two of the reviewers commented positively on the value of publishing the paper. The editorial staff quickly recognized the third reviewer’s comments as an unjust attempt to reject the paper. I revised the paper as recommended by the first two reviewers.
Dear Maria Emerson, Editorial Coordinator, Journal of Clinical Research and Reports. Thank you for publishing our case report: "Clinical Case of Effective Fetal Stem Cells Treatment in a Patient with Autism Spectrum Disorder" within the "Journal of Clinical Research and Reports" being submitted by the team of EmCell doctors from Kyiv, Ukraine. We much appreciate a professional and transparent peer-review process from Auctores. All research Doctors are so grateful to your Editorial Office and Auctores Publishing support! I amiably wish our article publication maintained a top quality of your International Scientific Journal. My best wishes for a prosperity of the Journal of Clinical Research and Reports. Hope our scientific relationship and cooperation will remain long lasting. Thank you very much indeed. Kind regards, Dr. Andriy Sinelnyk Cell Therapy Center EmCell
