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1.
SGLT2 Inhibitors and Their Antiarrhythmic Properties.
Kolesnik, E, Scherr, D, Rohrer, U, Benedikt, M, Manninger, M, Sourij, H, von Lewinski, D
International journal of molecular sciences. 2022;(3)
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are gaining ground as standard therapy for heart failure with a class-I recommendation in the recently updated heart failure guidelines from the European Society of Cardiology. Different gliflozins have shown impressive beneficial effects in patients with and without diabetes mellitus type 2, especially in reducing the rates for hospitalization for heart failure, yet little is known on their antiarrhythmic properties. Atrial and ventricular arrhythmias were reported by clinical outcome trials with SGLT2 inhibitors as adverse events, and SGLT2 inhibitors seemed to reduce the rate of arrhythmias compared to placebo treatment in those trials. Mechanistical links are mainly unrevealed, since hardly any experiments investigated their impact on arrhythmias. Prospective trials are currently ongoing, but no results have been published so far. Arrhythmias are common in the heart failure population, therefore the understanding of possible interactions with SGLT2 inhibitors is crucial. This review summarizes evidence from clinical data as well as the sparse experimental data of SGLT2 inhibitors and their effects on arrhythmias.
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2.
Clinical management of electrical storm: a current overview.
Guarracini, F, Casella, M, Muser, D, Barbato, G, Notarstefano, P, Sgarito, G, Marini, M, Grandinetti, G, Mariani, MV, Boriani, G, et al
Journal of cardiovascular medicine (Hagerstown, Md.). 2021;(9):669-679
Abstract
The number of patients affected by electrical storm has been continuously increasing in emergency departments. Patients are often affected by multiple comorbidities requiring multidisciplinary interventions to achieve a clinical stability. Careful reprogramming of cardiac devices, correction of electrolyte imbalance, knowledge of underlying heart disease and antiarrhythmic drugs in the acute phase play a crucial role. The aim of this review is to provide a comprehensive overview of pharmacological treatment, latest transcatheter ablation techniques and advanced management of patients with electrical storm.
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3.
Could Sodium/Glucose Co-Transporter-2 Inhibitors Have Antiarrhythmic Potential in Atrial Fibrillation? Literature Review and Future Considerations.
Vrachatis, DA, Papathanasiou, KA, Iliodromitis, KE, Giotaki, SG, Kossyvakis, C, Raisakis, K, Kaoukis, A, Lambadiari, V, Avramides, D, Reimers, B, et al
Drugs. 2021;(12):1381-1395
Abstract
The global burden of atrial fibrillation (AF) is constantly increasing, necessitating novel and effective therapeutic options. Sodium glucose co-transporter 2 (SGLT2) inhibitors have been introduced in clinical practice as glucose-lowering medications. However, they have recently gained prominence for their potential to exert substantial cardiorenal protection and are being evaluated in large clinical trials including patients with type 2 diabetes and normoglycemic adults. In this review we present up-to-date available evidence in a pathophysiology-directed manner from cell to bedside. Preclinical and clinical data regarding a conceivable antiarrhythmic effect of SGLT2 inhibitors are beginning to accumulate. Herein we comprehensively present data that explore the potential pathophysiological link between SGLT2 inhibitors and AF. With regard to clinical data, no randomized controlled trials evaluating SGLT2 inhibitors effects on AF as a pre-specified endpoint are available. However, data from randomized controlled trial post-hoc analysis as well as observational studies point to a possible beneficial effect of SGLT2 inhibitors on AF. Meta-analyses addressing this question report inconsistent results and the real magnitude of AF prevention by SGLT2 inhibition remains unclear. Still, while (i) pathophysiologic mechanisms involved in AF might be favorably affected by SGLT2 inhibitors and (ii) emerging, yet inconsistent, clinical data imply that SGLT2 inhibitor-mediated cardiorenal protection could also exert antiarrhythmic effects, the argument of whether these novel drugs will reduce AF burden is unsettled and mandates appropriately designed and adequately sized randomized controlled studies.
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4.
Beyond cardioversion, ablation and pharmacotherapies: Risk factors, lifestyle change and behavioral counseling strategies in the prevention and treatment of atrial fibrillation.
Mehta, NK, Strickling, J, Mark, E, Swinehart, S, Puthumana, J, Lavie, CJ, Haines, DE, Franklin, BA
Progress in cardiovascular diseases. 2021;:2-9
Abstract
IMPORTANCE It has been suggested that atrial fibrillation (AF) is the new cardiovascular disease epidemic of the 21st century. Clinical cardiology has largely focused on AF treatment and associated stroke prevention rather than preventing AF itself. To reduce the global consequences and associated costs of AF, it is critical to now embrace prevention as a priority. Proactively addressing the risk factors for AF and the underlying unhealthy lifestyle habits that contribute to them, using research-based counseling approaches, represents a complementary and adjunctive alternative in combatting this disease burden. OBSERVATIONS Encouraging and sustaining patient involvement to reduce AF incidence and improve outcomes begins with screening to identify risk factors, unhealthy lifestyle habits, and characteristics associated with failed attempts at favorably modifying these causalities. Modulators of and common barriers to achieving risk reduction and lifestyle change include self-efficacy, social support, age, sex, marital and socioeconomic status, education, employment, and psychosocial factors such as depression, isolation, anxiety and chronic life stress. Focused behavioral counseling approaches, including assessing the patient's readiness to change, motivational interviewing and using the 5 A's (assess, advise, agree, assist, arrange), along with employing initial downscaled goals to overcome inertia, are proven methodologies to overcome these common barriers to favorably modifying risk factors and unhealthy lifestyle habits. CONCLUSIONS AND RELEVANCE To complement and enhance the current armamentarium for the medical management of cardiac arrhythmias, there is an urgent need to proactively address the causative factors triggering new-onset, recurrent and persistent AF. Beyond the counseling skills of highly trained professionals (eg, psychiatrists, psychologists), this narrative review highlights the need for and potential impact on lifestyle modification that non-behavioral scientists, including internal medicine, cardiology, and allied health professionals, can have on the patients they serve.
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5.
Ventricular voltage-gated ion channels: Detection, characteristics, mechanisms, and drug safety evaluation.
Chen, L, He, Y, Wang, X, Ge, J, Li, H
Clinical and translational medicine. 2021;(10):e530
Abstract
Cardiac voltage-gated ion channels (VGICs) play critical roles in mediating cardiac electrophysiological signals, such as action potentials, to maintain normal heart excitability and contraction. Inherited or acquired alterations in the structure, expression, or function of VGICs, as well as VGIC-related side effects of pharmaceutical drug delivery can result in abnormal cellular electrophysiological processes that induce life-threatening cardiac arrhythmias or even sudden cardiac death. Hence, to reduce possible heart-related risks, VGICs must be acknowledged as important targets in drug discovery and safety studies related to cardiac disease. In this review, we first summarize the development and application of electrophysiological techniques that are employed in cardiac VGIC studies alone or in combination with other techniques such as cryoelectron microscopy, optical imaging and optogenetics. Subsequently, we describe the characteristics, structure, mechanisms, and functions of various well-studied VGICs in ventricular myocytes and analyze their roles in and contributions to both physiological cardiac excitability and inherited cardiac diseases. Finally, we address the implications of the structure and function of ventricular VGICs for drug safety evaluation. In summary, multidisciplinary studies on VGICs help researchers discover potential targets of VGICs and novel VGICs in heart, enrich their knowledge of the properties and functions, determine the operation mechanisms of pathological VGICs, and introduce groundbreaking trends in drug therapy strategies, and drug safety evaluation.
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6.
Evaluation and Management of Premature Ventricular Complexes.
Marcus, GM
Circulation. 2020;(17):1404-1418
Abstract
Premature ventricular complexes (PVCs) are extremely common, found in the majority of individuals undergoing long-term ambulatory monitoring. Increasing age, a taller height, a higher blood pressure, a history of heart disease, performance of less physical activity, and smoking each predict a greater PVC frequency. Although the fundamental causes of PVCs remain largely unknown, potential mechanisms for any given PVC include triggered activity, automaticity, and reentry. PVCs are commonly asymptomatic but can also result in palpitations, dyspnea, presyncope, and fatigue. The history, physical examination, and 12-lead ECG are each critical to the diagnosis and evaluation of a PVC. An echocardiogram is indicated in the presence of symptoms or particularly frequent PVCs, and cardiac magnetic resonance imaging is helpful when the evaluation suggests the presence of associated structural heart disease. Ambulatory monitoring is required to assess PVC frequency. The prognosis of those with PVCs is variable, with ongoing uncertainty regarding the most informative predictors of adverse outcomes. An increased PVC frequency may be a risk factor for heart failure and death, and the resolution of systolic dysfunction after successful catheter ablation of PVCs demonstrates that a causal relationship can be present. Patients with no or mild symptoms, a low PVC burden, and normal ventricular function may be best served with simple reassurance. Either medical treatment or catheter ablation are considered first-line therapies in most patients with PVCs associated with symptoms or a reduced left ventricular ejection fraction, and patient preference plays a role in determining which to try first. If medical treatment is selected, either β-blockers or nondihydropyridine calcium channel blockers are reasonable drugs in patients with normal ventricular systolic function. Other antiarrhythmic drugs should be considered if those initial drugs fail and ablation has been declined, has been unsuccessful, or has been deemed inappropriate. Catheter ablation is the most efficacious approach to eradicate PVCs but may confer increased upfront risks. Original research remains necessary to identify individuals at risk for PVC-induced cardiomyopathy and to identify preventative and therapeutic approaches targeting the root causes of PVCs to maximize effectiveness while minimizing risk.
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7.
A Compelling Case for Less Aggressive Arrhythmia Management in Patients With Chronic Heart Failure and Long-Standing Atrial Fibrillation.
Packer, M
Journal of cardiac failure. 2020;(1):85-92
Abstract
BACKGROUND AND METHODS Atrial fibrillation (AF) is common in chronic heart failure, and some have advocated intensive rate and/or rhythm control strategies for these patients. However, the loss of atrial systole and irregularity of the ventricular response has not been shown to contribute to the progression of heart failure, and the presence or rate of long-standing AF in patients with chronic heart failure does not have prognostic significance. RESULTS In randomized clinical trials, pharmacological rhythm control has not been shown to be superior to rate-control in influencing long-term outcomes, but the use of membrane-active antiarrhythmic drugs can increase the risk of both pump failure and arrhythmic deaths in patients with heart failure. Additionally, intensive efforts to slow the ventricular rate in AF can potentially cause clinically inapparent bradyarrhythmias, which can trigger rate-dependent lethal rhythm disturbances or hemodynamic abnormalities. In patients with AF, a more stringent approach to rate control (target rate <80/min) is not superior to a more lenient strategy (target rate <110/min) on the risk of major events. Little is known about the effects of catheter ablation of long-standing AF in established heart failure, particularly in patients with a preserved or a meaningfully reduced ejection fraction, but ablation can add to the fibrotic burden of the left atrium and impair its capacitance functions. CONCLUSIONS For all of these reasons, the management of heart failure and long-standing AF should be primarily directed to slowing of the progression of their underlying cardiomyopathic process rather than the treatment of the arrhythmia. In addition, patients should receive long-term oral anticoagulation with non-vitamin K-antagonist oral anticoagulants to reduce the risk of thromboembolic events. The utility of intensive rate and rhythm control interventions for long-standing AF in patients with established heart failure requires further study.
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8.
Thyroid effects of amiodarone: clinical update.
Goundan, PN, Lee, SL
Current opinion in endocrinology, diabetes, and obesity. 2020;(5):329-334
Abstract
PURPOSE OF REVIEW Amiodarone-induced thyroid dysfunction is well established and commonly encountered but is associated with several diagnostic and management challenges. The present review discusses recent evidence published related to the effects of amiodarone on the thyroid gland and thyroid function. RECENT FINDINGS Retrospective studies to evaluate amiodarone-induced thyroid dysfunction in children show the occurrence of potential clinically significant changes within 2 weeks of amiodarone initiation that may not be detected if standard adult guidelines for thyroid hormone monitoring are followed. A small study evaluating beta-glucuronidase activity in amiodarone-induced thyrotoxicosis (AIT) demonstrated higher levels in patients with AIT type 2 compared to type 1. New data have suggested the incidence of agranulocytosis may be higher in patients on thionamides with AIT compared to hyperthyroidism because of other causes. In a small study, investigators demonstrated the use of a combination of intravenous and oral steroids to treat refractory AIT which needs to be evaluated in further controlled trials. Finally, recent data demonstrated a possible mortality benefit of surgery over medical therapy for AIT in patients with moderate to severe reduction in left ventricular ejection fraction. SUMMARY Recent research regarding the prevalence, diagnosis, and management of amiodarone-induced thyroid dysfunction were reviewed.
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9.
Heart Failure and Atrial Fibrillation, Like Fire and Fury.
Carlisle, MA, Fudim, M, DeVore, AD, Piccini, JP
JACC. Heart failure. 2019;(6):447-456
Abstract
Heart failure and atrial fibrillation are 2 common cardiovascular disorders that frequently complicate one another and exert a significant detrimental effect on cardiovascular health and well-being. Both heart failure and atrial fibrillation continue to increase in prevalence as the risk factors underlying each condition become more common. This review encompasses what is currently known about the epidemiology and pathophysiology of these comorbidities along with incorporation of landmark trials that have contributed to current guidelines. The focus is on clinically relevant considerations, including the contribution of inflammation in the pathophysiology of atrial fibrillation and heart failure. We explore the emerging role of catheter ablation relative to medical therapy in the management of heart failure with reduced ejection fraction, along with indications for biventricular pacing modalities in cardiac resynchronization therapy. We discuss current guideline-directed therapies and how practice models and national recommendations will likely change based on the most recent randomized controlled trials.
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10.
Pharmacotherapeutic strategies for atrial fibrillation in pregnancy.
Georgiopoulos, G, Tsiachris, D, Kordalis, A, Kontogiannis, C, Spartalis, M, Pietri, P, Magkas, N, Stefanadis, C
Expert opinion on pharmacotherapy. 2019;(13):1625-1636
Abstract
Introduction: Atrial fibrillation (AF) is rare during pregnancy but its incidence is expected to rise in parallel to increasing age of women in pregnancy and fraction of pregnant women with structural heart disease. Areas covered: The authors provide a review of the contemporary evidence on diagnostic work-up and optimal pharmacotherapeutic management of AF in pregnancy. The authors have performed a systematic search for relevant articles using MEDLINE, the COCHRANE LIBRARY, and ClinicalTrials.gov. Expert opinion: New-onset AF during pregnancy is usually an indication of underlying heart disease and should lead to hospital admission. Patients should be evaluated by an experienced cardiologist or an electrophysiologist. Direct cardioversion is highly effective and safe in pregnant women and should be prioritized over pharmacologic cardioversion with intravenous ibutilide or flecainide. Amiodarone should be avoided if possible. Digoxin and beta-blockers are the rate-control pharmaceutic agents with the widest experience of use. Catheter ablation during pregnancy should be considered in selected cases of atrial flutter refractory to medication and only performed using fluoroless techniques, preferably during the second trimester. Vitamin K antagonists (VKAs) can be used after the first trimester, while low molecular weight heparin should be accompanied by periodic evaluation of anti-Xa factor. Non-VKA oral anticoagulants should be avoided because of limited experience in pregnancy.