12 research outputs found
Rhythm monitoring, success definition, recurrence, and anticoagulation after atrial fibrillation ablation: results from an EHRA survey
Atrial fibrillation (AF) is a major challenge for the healthcare field. Pulmonary vein isolation is the most effective treatment for the maintenance of sinus rhythm. However, clinical endpoints for the procedure vary significantly among studies. There is no consensus on the definition of recurrence and no clear roadmap on how to deal with recurrences after a failed ablation. The purpose of this study was to perform a survey in order to show how clinicians currently approach this knowledge gap. An online survey, supported by the European Heart Rhythm Association (EHRA) Scientific Initiatives Committee, was conducted between 1 April 2022 and 8 May 2022. An anonymous questionnaire was disseminated via social media and EHRA newsletters, for clinicians to complete. This consisted of 18 multiple-choice questions regarding rhythm monitoring, definitions of a successful ablation, clinical practices after a failed AF ablation, and the continuance of anticoagulation. A total of 107 replies were collected across Europe. Most respondents (82%) perform routine monitoring for AF recurrences after ablation, with 51% of them preferring a long-term monitoring strategy. Cost was reported to have an impact on the choice of monitoring strategy. Self-screening was recommended by most (71%) of the respondents. The combination of absence of symptoms and recorded AF was the definition of success for most (83%) of the respondents. Cessation of anticoagulation after ablation was an option mostly for patients with paroxysmal AF and a low CHA2DS2-VASc score. The majority of physicians perform routine monitoring after AF ablation. For most physicians, the combination of the absence of symptoms and electrocardiographic endpoints defines a successful result after AF ablation
Myocardial Protection and Current Cancer Therapy: Two Opposite Targets with Inevitable Cost
Myocardial protection against ischemia/reperfusion injury (IRI) is mediated by various ligands, activating different cellular signaling cascades. These include classical cytosolic mediators such as cyclic-GMP (c-GMP), various kinases such as Phosphatydilinositol-3- (PI3K), Protein Kinase B (Akt), Mitogen-Activated-Protein- (MAPK) and AMP-activated (AMPK) kinases, transcription factors such as signal transducer and activator of transcription 3 (STAT3) and bioactive molecules such as vascular endothelial growth factor (VEGF). Most of the aforementioned signaling molecules constitute targets of anticancer therapy; as they are also involved in carcinogenesis, most of the current anti-neoplastic drugs lead to concomitant weakening or even complete abrogation of myocardial cell tolerance to ischemic or oxidative stress. Furthermore, many anti-neoplastic drugs may directly induce cardiotoxicity via their pharmacological effects, or indirectly via their cardiovascular side effects. The combination of direct drug cardiotoxicity, indirect cardiovascular side effects and neutralization of the cardioprotective defense mechanisms of the heart by prolonged cancer treatment may induce long-term ventricular dysfunction, or even clinically manifested heart failure. We present a narrative review of three therapeutic interventions, namely VEGF, proteasome and Immune Checkpoint inhibitors, having opposing effects on the same intracellular signal cascades thereby affecting the heart. Moreover, we herein comment on the current guidelines for managing cardiotoxicity in the clinical setting and on the role of cardiovascular confounders in cardiotoxicity
Molecular Insights in Atrial Fibrillation Pathogenesis and Therapeutics: A Narrative Review
The prevalence of atrial fibrillation (AF) is bound to increase globally in the following years, affecting the quality of life of millions of people, increasing mortality and morbidity, and beleaguering health care systems. Increasingly effective therapeutic options against AF are the constantly evolving electroanatomic substrate mapping systems of the left atrium (LA) and ablation catheter technologies. Yet, a prerequisite for better long-term success rates is the understanding of AF pathogenesis and maintenance. LA electrical and anatomical remodeling remains in the epicenter of current research for novel diagnostic and treatment modalities. On a molecular level, electrical remodeling lies on impaired calcium handling, enhanced inwardly rectifying potassium currents, and gap junction perturbations. In addition, a wide array of profibrotic stimuli activates fibroblast to an increased extracellular matrix turnover via various intermediaries. Concomitant dysregulation of the autonomic nervous system and the humoral function of increased epicardial adipose tissue (EAT) are established mediators in the pathophysiology of AF. Local atrial lymphomononuclear cells infiltrate and increased inflammasome activity accelerate and perpetuate arrhythmia substrate. Finally, impaired intracellular protein metabolism, excessive oxidative stress, and mitochondrial dysfunction deplete atrial cardiomyocyte ATP and promote arrhythmogenesis. These overlapping cellular and molecular alterations hinder us from distinguishing the cause from the effect in AF pathogenesis. Yet, a plethora of therapeutic modalities target these molecular perturbations and hold promise in combating the AF burden. Namely, atrial selective ion channel inhibitors, AF gene therapy, anti-fibrotic agents, AF drug repurposing, immunomodulators, and indirect cardiac neuromodulation are discussed here
Molecular Insights in Atrial Fibrillation Pathogenesis and Therapeutics: A Narrative Review
The prevalence of atrial fibrillation (AF) is bound to increase globally
in the following years, affecting the quality of life of millions of
people, increasing mortality and morbidity, and beleaguering health care
systems. Increasingly effective therapeutic options against AF are the
constantly evolving electroanatomic substrate mapping systems of the
left atrium (LA) and ablation catheter technologies. Yet, a prerequisite
for better long-term success rates is the understanding of AF
pathogenesis and maintenance. LA electrical and anatomical remodeling
remains in the epicenter of current research for novel diagnostic and
treatment modalities. On a molecular level, electrical remodeling lies
on impaired calcium handling, enhanced inwardly rectifying potassium
currents, and gap junction perturbations. In addition, a wide array of
profibrotic stimuli activates fibroblast to an increased extracellular
matrix turnover via various intermediaries. Concomitant dysregulation of
the autonomic nervous system and the humoral function of increased
epicardial adipose tissue (EAT) are established mediators in the
pathophysiology of AF. Local atrial lymphomononuclear cells infiltrate
and increased inflammasome activity accelerate and perpetuate arrhythmia
substrate. Finally, impaired intracellular protein metabolism, excessive
oxidative stress, and mitochondrial dysfunction deplete atrial
cardiomyocyte ATP and promote arrhythmogenesis. These overlapping
cellular and molecular alterations hinder us from distinguishing the
cause from the effect in AF pathogenesis. Yet, a plethora of therapeutic
modalities target these molecular perturbations and hold promise in
combating the AF burden. Namely, atrial selective ion channel
inhibitors, AF gene therapy, anti-fibrotic agents, AF drug repurposing,
immunomodulators, and indirect cardiac neuromodulation are discussed
here
Could Sodium/Glucose Co-Transporter-2 Inhibitors Have Antiarrhythmic Potential in Atrial Fibrillation? Literature Review and Future Considerations
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
Immunologic Dysregulation and Hypercoagulability as a Pathophysiologic Background in COVID-19 Infection and the Immunomodulating Role of Colchicine
In 2020, SARS-COV-2 put health systems under unprecedented resource and
manpower pressure leading to significant number of deaths. Expectedly,
researchers sought to shed light on the pathophysiologic background of
this novel disease (COVID-19) as well as to facilitate the design of
effective therapeutic modalities. Indeed, early enough the pivotal role
of inflammatory and thrombotic pathways in SARS-COV-2 infection has been
illustrated. The purpose of this article is to briefly present the
epidemiologic and clinical features of COVID-19, analyze the
pathophysiologic importance of immunologic dysregulation and
hypercoagulability in developing disease complications and finally to
present an up-to-date systematic review of colchicine's immunomodulating
capacity in view of hindering coronavirus complications
P6469Catheter ablation during sinus rhythm is associated with acute loss of left atrial contractile function in paroxysmal atrial fibrillation: a strain study
Background: Catheter ablation is the recommended treatment in patients with paroxysmal atrial fibrillation (AF). However, the data on acute effects of catheter ablation on left atrial (LA) contractile function are scarce. Therefore, the purpose of the study was twofold:Purpose: Firstly, to describe acute effects of catheter ablation on LA contractile function in patients with paroxysmal AF and in sinus rhythm at the time of ablation. Secondly, to assess potential value of different indices of LA morphology and function.Background: Catheter ablation is the recommended treatment in patients with paroxysmal atrial fibrillation (AF). However, the data on acute effects of catheter ablation on left atrial (LA) contractile function are scarce. Therefore, the purpose of the study was twofold:Purpose: Firstly, to describe acute effects of catheter ablation on LA contractile function in patients with paroxysmal AF and in sinus rhythm at the time of ablation. Secondly, to assess potential value of different indices of LA morphology and function.status: Published onlin
Efficacy, Safety and Feasibility of Superior Vena Cava Isolation in Patients Undergoing Atrial Fibrillation Catheter Ablation: An Up-to-Date Review
Pulmonary vein isolation (PVI) is the cornerstone in atrial fibrillation (AF) ablation; yet, the role of arrhythmogenic superior vena cava (SVC) is increasingly recognized and different ablation strategies have been employed in this context. SVC can act as a trigger or perpetuator of AF, and its significance might be more pronounced in patients undergoing repeated ablation. Several cohorts have examined efficacy, safety and feasibility of SVC isolation (SVCI) among AF patients. The majority of these studies explored as-needed SVCI during index PVI, and only a minority of them included repeated ablation subjects and non-radiofrequency energy sources. Studies of heterogeneous design and intent have explored both empiric and as-needed SVCI on top of PVI and reported inconclusive results. These studies have largely failed to demonstrate any clinical benefit in terms of arrhythmia recurrence, although safety and feasibility are undisputable. Mixed population demographics, small number of enrollees and short follow-up are the main limitations. Procedural and safety data are comparable between empiric SVCI and as-needed SVCI, and some studies suggested that empiric SVCI might be associated with reduced AF recurrences in paroxysmal AF patients. Currently, no study has compared different ablation energy sources in the setting of SVCI, and no randomized study has addressed as-needed SVCI on top of PVI. Furthermore, data regarding cryoablation are still in their infancy, and regarding SVCI in patients with cardiac devices more safety and feasibility data are needed. PVI non-responders, patients undergoing repeated ablation and patients with long SVC sleeves could be potential candidates for SVCI, especially via an empiric approach. Although many technical aspects remain unsettled, the major question to answer is which clinical phenotype of AF patients might benefit from SVCI