The clinical use of diphenylhydantoin (Dilantin) in the treatment and prevention of cardiac arrhythmias

Role of Angiotensin Receptor Blockers in the Prevention and Treatment of Arrhythmias

Both ventricular and atrial arrhythmias are commonly encountered in patients with ventricular dysfunction. In fact, roughly half of the deaths occurring in patients with ventricular dysfunction are caused by ventricular arrhythmias. Atrial arrhythmias in this patient population compromise left ventricular filling and if uncontrolled can exacerbate (and in some cases cause) the underlying myopathic process. Consequently, the diagnosis and treatment of these complex, and often life-threatening, arrhythmias is a critical component in the management of congestive heart failure (CHF). As the complexity of pharmacologic and nonpharmacologic antiarrhythmic therapy evolves, it has become increasingly important to understand the potential benefits and limitations of the various treatment modalities in the setting of patients with CHF. The management of arrhythmias in patients with CHF includes conventional drug therapies, as well as therapies directed specifically at treating the arrhythmias that are encountered. The treatment of atrial arrhythmias may include anticoagulation, drugs for rate control, rhythm control, or radiofrequency ablation. The treatment of ventricular arrhythmias, conversely, uses the implantable cardioverter-defibrillator to prevent sudden death, with adjuvant drug therapy or ablation for refractory ventricular tachycardia. This article provides an overview of the current state-of-the-art arrhythmia management in patients with CHF.

It has been suggested that protein directly activated by cAMP (Epac), one of the downstream signaling molecules of β-adrenergic receptor (β-AR), may be an effective target for the treatment of arrhythmia. However, there have been no reports on the anti-arrhythmic effects or cardiac side-effects of Epac1 inhibitors in vivo. In this study, the roles of Epac1 in the development of atrial and ventricular arrhythmias are examined. In addition, we examined the usefulness of CE3F4, an Epac1-selective inhibitor, in the treatment of the arrhythmias in mice. In Epac1 knockout (Epac1-KO) mice, the duration of atrial fibrillation (AF) was shorter than in wild-type mice. In calsequestrin2 knockout mice, Epac1 deficiency resulted in a reduction of ventricular arrhythmia. In both atrial and ventricular myocytes, sarcoplasmic reticulum (SR) Ca2+ leak, a major trigger of arrhythmias, and spontaneous SR Ca2+ release (SCR) were attenuated in Epac1-KO mice. Consistently, CE3F4 treatment significantly prevented AF and ventricular arrhythmia in mice. In addition, the SR Ca2+ leak and SCR were significantly inhibited by CE3F4 treatment in both atrial and ventricular myocytes. Importantly, cardiac function was not significantly affected by a dosage of CE3F4 sufficient to exert anti-arrhythmic effects. These findings indicated that Epac1 is involved in the development of atrial and ventricular arrhythmias. CE3F4, an Epac1-selective inhibitor, prevented atrial and ventricular arrhythmias in mice.

To review the electropharmacology, clinical applications, side effects, and hemodynamic profile of intravenous amiodarone. The MEDLINE database was searched for English-language material, including reports of clinical trials and in vivo studies, review articles, and abstracts presented at national symposia, that was published between 1985 and 1996. Bibliographies of textbooks and articles were also examined. Studies that reported on the efficacy, toxicity, and hemodynamic profile of intravenous amiodarone and studies that examined the pharmacologic behavior of intravenous amiodarone in laboratory models were reviewed. Study design and quality and relevant data on efficacy of suppression and treatment of arrhythmias with oral and intravenous amiodarone therapy, the reported mechanisms of antiarrhythmic effect, and hemodynamic changes seen with therapy were analyzed. Amiodarone is a unique antiarrhythmic agent that is now available in oral and intravenous forms in the United States. The use of intravenous amiodarone in the short-term treatment of life-threatening or hemodynamically unstable rhythm disturbances has generated much interest. Amiodarone has many electropharmacologic actions, some of which differ between the oral and intravenous forms. The wide clinical application of amiodarone includes treatment and prevention of supraventricular and ventricular arrhythmias and arrhythmias related to myocardial infarction. Intravenous amiodarone is effective for supraventricular and ventricular arrhythmias that are resistant to other antiarrhythmic agents. The effectiveness of intravenous amiodarone as short-term treatment also suggests that the drug has an important role in protocols of advanced cardiac life support. Intravenous amiodarone seems to have an overall favorable hemodynamic profile and does not produce many of the unwanted long-term side effects associated with oral therapy. Intravenous amiodarone shows much promise for the short-term treatment of unstable arrhythmias. Its favorable hemodynamic effects and minimal short-term side effects make it an attractive option in the management of cardiac arrhythmias.

Beta-blockers for the treatment of arrhythmias: Bisoprolol – a systematic review

Unforeseen consequences: Class III antiarrhythmic amiodarone stimulated increase in prostate-specific antigen

The article analyzes modern methods of diagnosis and treatment of cardiac arrhythmias – atrial fibrillation. The author primarily focuses on the fact that the most important thing for atrial fibrillation is administering an anticoagulant, since failure to follow this recommendation can lead to negative consequences, such as stroke. The article also says on the effectiveness of taking antianrhythmic agents that is proven and recommended. Atrial fibrillation is a kind of pandemic of the 21st century, since, as of 2023, it was found in 43.6 million people worldwide. Particularly, there is a dynamic increase in the frequency of AF after the COVID-19 pandemic. Therefore, updated studies on the follow-up examination and treatment of this arrhythmia are quite relevant.

The rapid growth in computational power, sensor technology, and wearable devices has provided a solid foundation for all aspects of cardiac arrhythmia care. Artificial intelligence (AI) has been instrumental in bringing about significant changes in the prevention, risk assessment, diagnosis, and treatment of arrhythmia. This review examines the current state of AI in the diagnosis and treatment of atrial fibrillation, supraventricular arrhythmia, ventricular arrhythmia, hereditary channelopathies, and cardiac pacing. Furthermore, ChatGPT, which has gained attention recently, is addressed in this paper along with its potential applications in the field of arrhythmia. Additionally, the accuracy of arrhythmia diagnosis can be improved by identifying electrode misplacement or erroneous swapping of electrode position using AI. Remote monitoring has expanded greatly due to the emergence of contactless monitoring technology as wearable devices continue to develop and flourish. Parallel advances in AI computing power, ChatGPT, availability of large data sets, and more have greatly expanded applications in arrhythmia diagnosis, risk assessment, and treatment. More precise algorithms based on big data, personalized risk assessment, telemedicine and mobile health, smart hardware and wearables, and the exploration of rare or complex types of arrhythmia are the future direction.

The Na(+)/Ca(2+) exchanger (NaCaX) plays an important role in calcium handling in myocytes, but in the setting of calcium overload NaCaX can also contribute to the activation of an arrhythmogenic transient inward current (I(ti)). Therefore, approaches to inhibit NaCaX could have potential antiarrhythmic effects in pathophysiological states such as heart failure (HF) or myocardial ischaemia and reperfusion. NaCaX typically functions in a forward (Ca(2+) extrusion) mode but can also function in a reverse (Ca(2+) influx) mode. The determining factors for the directionality of NaCaX ion movement are the electrochemical gradients of calcium and sodium, and membrane potential (E(m)). In HF, upregulated NaCaX plays a dual role: it decreases sarcoplasmic reticulum (SR) calcium load, which leads to contractile dysfunction, and it underlies the I(ti) responsible for delayed after-depolarisations (DADs) and ventricular arrhythmias. In myocardial ischaemia and reperfusion, increases in [Na(+)](i) (as a result of acidosis and activation of the Na(+)/H(+) exchanger [NHE]) lead to calcium overload via the NaCaX and arrhythmogenesis is probably mediated by I(ti) activation due to NaCaX. As such, inhibition of NaCaX could provide a novel therapeutic approach to the prevention and treatment of arrhythmias. Unfortunately, it is difficult to assess the efficacy of such an approach since there are no specific NaCaX inhibitors. Currently available agents are hampered by their nonspecific effects on other ion channels and carriers. The potential utility of specific inhibition of forward or reverse mode NaCaX as an antiarrhythmic approach in the settings of HF and ischaemia/ reperfusion is discussed within the context of current knowledge of myocyte calcium and sodium handling. NaCaX is a challenging and complex therapeutic target because of the delicate balance of SR calcium load (too little contributes to contractile dysfunction and too much leads to calcium overload and arrhythmogenesis). Further understanding of NaCaX function, [Na(+)](i) and [Ca(2+)](i) in HF and ischaemia/reperfusion, combined with the development and assessment of specific NaCaX inhibitors, will ultimately define the potential role of NaCaX inhibition in the prevention and treatment of ventricular arrhythmias.

IN RECENT YEARS there has been an increase in the use of sodium diphenylhydantoin (Dilantin) for the treatment of cardiac arrhythmias. Among the main advantages for the use of diphenylhydantoin are its ready accessibility, relative safety, and the speed with which an effect is noted. Several papers regarding its indications and complications have been published. This report describes a complication not previously recorded of diphenylhydantoin used intravenously in the treatment of cardiac arrhythmias. <h3>Report of a Case</h3> An 85-year-old Negro woman was admitted to the hospital with a one-week history of progressive shortness of breath associated with a cough which produced white sputum. There was no hemoptysis or chest pain. Physical examination revealed a well developed, elderly Negro woman who was semiconscious and who responded poorly to verbal stimuli. She had obvious respiratory distress. Her pulse rate was 104 beats per minute and regular with a blood pressure of 140/80

Improvement of the long‑term survival of patients with Tetralogy of Fallot has been observed in the last few years. Among the late complication arrhythmias are detected most frequently. The aim of this study was to estimate the frequency of atrial and ventricular arrhythmias in the group of 53 adult tetralogy patients. Mean age was 29 years, 21 patients (39,6%) were women. In 4 cases (7,5%) palliative pulmonary‑systemic shunt was performed. Average age of total surgical correction was 6,55 years. Significant ventricular arrhythmias were present in 15 patients (28,3%). 9 (17%) had relevant atrial arrhythmias. Patients with atrial arrhythmia were older (35,4 vs 27,7 years). Older were also patients with ventricular arrhythmias (34,7 vs 26,4 years). Group with atrial arrhythmia used more digoxin (p=0,002) and diuretics (p = 0,021). 3 patients on oral anticoagulants had atrial flutter. Similar data was collected in group with ventricular arrhythmias (diuretics p = 0,0053). There was a high incidence of coexisting ventricular and atrial arrhythmias (p=0,0057). Left ventricular enlargement was present in patients with atrial (p = 0,002) and ventricular (p = 0,027) arrhythmias. Right atrium area and left atrium diameter were greater in group with supraventricular arrhythmias (31,6 vs 21,6 cm2 and 40,4 vs 34,3 mm; respectively). Ventricular arrhythmias were associated with greater right (27,8 vs 21,0 cm2) and left atrium areas (18,5 vs 15,1 cm2). Younger age at the time of corrective surgery is associated with lower frequency of arrhythmias in adults. Arrhythmias however remain one of the most significant problems in this group of patients. Close observation in centers specialized in Grown‑Up Congenital Heart Defects and management of symptoms seems to be the best option in long‑term follow‑up. JRCD 2013; 1 (4): 10–15

Despite advances in catheter ablation techniques and device-based therapies for cardiac arrhythmias, antiarrhythmic drugs remain essential components of any comprehensive therapeutic strategy. Antiarrhythmic drug therapy, however, has been limited by both incomplete efficacy and a substantial potential for cardiac and extracardiac toxicity. As a result, only a few new antiarrhythmic agents have successfully completed clinical development programs and reached routine clinical usage over the past 20 years. Antiarrhythmic drugs may be indicated for ventricular tachycardia, sudden death prevention, or specific types of supraventricular arrhythmia. Implantable cardioverter-defibrillator (ICD) therapy has evolved as the primary treatment for most life-threatening ventricular arrhythmias, and antiarrhythmic drugs for these rhythms are currently mostly used either as acute interventions or as adjuncts to chronic ICD therapy. Although numerous trials have evaluated the effect of antiarrhythmic drugs to decrease ICD shocks or therapies, such data have yet to provide the sole basis for approval for any new agent. At the same time, drug therapy for atrial arrhythmias is often limited by the drug’s simultaneous effects on the ventricles, which has led to efforts to identify ionic channel targets specific to or preferentially located in the atria. The sustained outward K+ current (IKur, encoded by the Kv 1.5 subunit), the acetylcholine-activated outward K+ current (IKAch), and both peak and late atrial Na+ currents have therefore become potential targets for antiarrhythmic drug developers.1–4 Another approach has been to seek agents that synergistically affect multiple channels simultaneously, resulting in a net beneficial effect while minimizing toxicity. Other nontraditional targets for drug therapy that do not directly involve ion channels have also emerged as our understanding of the mechanisms of arrhythmias has improved. As a result, several new compounds are now at or near completion of phase 3 clinical trials, and other promising …

SEUFFERT, GEORGE W. M.D.; HELFANT, RICHARD H. M.D.; DANA, JAMES F. M.D.; URBACH, KARL F. M.D. Author Information

Background/Aim. Numerous trials have shown a high success of radiofrequency ablation (RFA) in the treatment of the patients with cardiac arrhythmias. We aimed to examine the RFA initial success in treatment of different cardiac arrhythmias and the RFA success after 6 months of followup. Second aim was to evaluate influence of all clinical and echocardiography parameters on initial and 6-month success and failure of RFA. Methods. The present study included 320 consecutive patients with atrial and ventricular arrhythmias in which RFA was performed during 2014 in the Institute for Cardiovascular Diseases ?Dedinje?, Belgrade, Serbia. We evaluated the initial RFA success and success of this procedure after 6-month follow-up. We also investigated the prognostic role of clinical and echocardiography parameters on initial and 6-month success and failure of RFA. Results. The RFA initial success for RFA of atrioventriculas (AV) node and AV nodal reentrant tachycardia (AVNRT) was 100%, RFA of pulmonary veins 99%, RFA of atrial flutter 92%, RFA of premature ventricular complexes (PVC) and the Wolf-Parkinson-White (WPW) syndrome 87%, RFA of ventricular tachycardia 85% and RFA of atrial tachycardia 78%. The success of RFA after 6 months of follow-up for RFA of the AV node was 100%, RFA of AVNRT 94%, RFA of atrial flutter 90%, RFA of WPW syndrome 86%, RFA of pulmonary veins 79% (paroxysmal atrial fibrillation 88% and persistent atrial fibrillation 63% with a significant difference p &lt; 0.05), RFA of PVC 78%, RFA of ventricular tachycardia 77% and RFA of atrial tachycardia 67%. Conclusion. This study proved a very high RFA initial success in treatment of cardiac arrhythmias and a satisfactory RFA success after 6 months of follow-up. Only the prognostic value had the type of atrial fibrillation in the group with catheter ablated pulmonary veins: after 6-month follow-up, the patients with paroxysmal atrial fibrillation had a significantly better outcome than those with persistent form.

Guidelines for Potassium Channel Blocker Use.