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Clinical Cardiology Feb 2024To investigate the effect of ablation compared to medical therapy on clinical outcomes of patients with atrial fibrillation (AF). PubMed, Scopus, Embase, and Web of... (Meta-Analysis)
Meta-Analysis Review
To investigate the effect of ablation compared to medical therapy on clinical outcomes of patients with atrial fibrillation (AF). PubMed, Scopus, Embase, and Web of Science databases were searched using ablation, medical treatment, AF, and related words. The effect of ablation and medical therapy was sought to be gathered on stroke or transitional ischemic attack, mortality, hospitalization, recurrence of AF, progression of AF, and left ventricular ejection fraction. Analyses were performed using R software. 31 studies (the results of 27 randomized controlled trials), compromising an overall 6965 patients (Ablation, n = 3643; Medical treatment, n = 3322) were reviewed in our study, revealed that catheter ablation would result in substantial benefits for patients with AF without significant difference in serious adverse events compared to medical management (Risk Ratio: 0.92, [95% Confidence Interval (CI), 0.64-1.33]). Catheter ablation in patients with AF significantly resulted in a 29% reduction in all-cause mortality (RR: 0.71, [95% CI, 0.57-0.88]), a 57% reduction in hospitalization (RR: 0.43, [95% CI, 0.27-0.67]), a 53% reduction in AF recurrence (RR: 0.47, [95% CI, 0.36-0.61]), and a dramatic reduction, 89%, in progression of paroxysmal to persistent AF (RR: 0.11, [95% CI, 0.02-0.65]); also associated with a remarkable improvement in their left ventricular ejection fraction (LVEF) (Mean Difference, MD: 6.84%, [95% CI, 3.27-10.42]) compared to medical therapy. Our study showed that ablation may be superior to medical therapy in patients with AF regarding AF recurrence, mortality, LVEF improvement, hospitalization, and AF progression outcomes.
Topics: Humans; Atrial Fibrillation; Stroke Volume; Ventricular Function, Left; Anti-Arrhythmia Agents; Stroke; Catheter Ablation; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37937825
DOI: 10.1002/clc.24184 -
Journal of Personalized Medicine Dec 2023Although substantial progress has been made to prevent sudden cardiac death in repaired tetralogy of Fallot patients, ventricular arrhythmia and sudden death continue to... (Review)
Review
Although substantial progress has been made to prevent sudden cardiac death in repaired tetralogy of Fallot patients, ventricular arrhythmia and sudden death continue to be major causes of morbidity and mortality in these patients. Greater survival in contemporary cohorts has been attributed to enhanced surgical techniques, more effective management of heart failure, and increased efforts in risk stratification and management of ventricular arrhythmias. More recently, our understanding of predictive risk factors has evolved into personalized risk prediction tools that rely on comprehensive demographic, imaging, functional, and electrophysiological data. However, the universal applicability of these different scoring systems is limited due to differences between study cohorts, types of anatomic repair, imaging modalities, and disease complexity. Noninvasive risk stratification is critical to identify those who may derive benefit from catheter ablation or cardioverter defibrillator implantation for primary prevention. Ultimately, assessment and risk stratification by a multidisciplinary team is crucial to analyze the various complex factors for every individual patient and discuss further options with patients and their families.
PubMed: 38138942
DOI: 10.3390/jpm13121715 -
Europace : European Pacing,... Dec 2023The electrocardiographic and electrophysiological characteristics of ventricular arrhythmia (VA) arising from the intramural basal inferior septum (BIS) have not been...
AIMS
The electrocardiographic and electrophysiological characteristics of ventricular arrhythmia (VA) arising from the intramural basal inferior septum (BIS) have not been specifically addressed to date. The aim of the current study was to characterize intramural BIS-VA and distinguish it from those with endocardial origins besides clarifying the anatomical configurations of the pyramidal space.
METHODS AND RESULTS
Fifty-five consecutive patients undergoing catheter ablation of VAs from BIS were identified and divided into three groups: the left ventricular (LV)-BIS group (n = 28), right ventricular (RV)-BIS group (n = 8), and intramural group (Intra, n = 19). Compared with the LV-BIS and RV-BIS groups, patients in the Intra group presented with no adequate earliest activation time at the two-sided BIS and epicardial coronary system [right: 7.79 ± 2.38 vs. left: 7.16 ± 2.59 vs. the middle cardiac vein (MCV): 6.26 ± 1.73 ms, P = 0.173] and poor-matched pacing-produced QRS at each site. Under the intracardiac echocardiography view, the pyramidal base was the broadest part of the septum and served as the division of the two-sided BIS. Focal ablation yielded promising acute-term and long-term procedural success in the LV-BIS and RV-BIS groups. But for the Intra group, VAs disappeared only after stepwise ablation successively targeted early preferential exit. After follow-up, three patients in the Intra group had recurrent VA, and all of them were treated well by a redo procedure or drug therapy.
CONCLUSION
Intramural VAs were relatively common in the BIS region in our series. Intra-procedural mapping was important to distinguish the intramural VAs from other VAs by comparing the local activation time and pacing mapping. Procedural success could be achieved by stepwise ablation on the counterpart sides of the BIS and within the MCV.
Topics: Humans; Treatment Outcome; Arrhythmias, Cardiac; Heart Ventricles; Electrocardiography; Ventricular Septum; Catheter Ablation; Tachycardia, Ventricular
PubMed: 38180948
DOI: 10.1093/europace/euae001 -
Frontiers in Cardiovascular Medicine 2023In the past 20 years, genetic variants in encoding the cardiac voltage-gated sodium channel Na1.5 have been linked to a range of inherited cardiac arrhythmias: variants... (Review)
Review
In the past 20 years, genetic variants in encoding the cardiac voltage-gated sodium channel Na1.5 have been linked to a range of inherited cardiac arrhythmias: variants resulting in loss-of-function of Na1.5 have been linked to sick sinus syndrome, atrial stand still, atrial fibrillation (AF) impaired pulse generation, progressive and non-progressive conduction defects, the Brugada Syndrome (BrS), and sudden cardiac death. variants causing increased sodium current during the plateau phase of the cardiac action potential is associated with Long QT Syndrome type 3 (LQTS3), ventricular tachycardia and SCD. Recently, gain-of-function variants have been linked to complex electrical phenotypes, such as the Multifocal Ectopic Purkinje-related Premature Contractions (MEPPC) syndrome. MEPPC is a rare condition characterized by a high burden of premature atrial contractions (PACs) and/or premature ventricular contractions (PVCs) often accompanied by dilated cardiomyopathy (DCM). MEPPC is inherited in an autosomal dominant fashion with an almost complete penetrance. The onset is often in childhood. The link between variants, MEPPC and DCM is currently not well understood, but amino acid substitutions resulting in gain-of-function of Na1.5 or introduction of gating pore currents potentially play an important role. DCM patients with a MEPPC phenotype respond relatively poorly to standard heart failure medical therapy and catheter ablation as the PVCs originate from all parts of the fascicular Purkinje fiber network. Class 1c sodium channel inhibitors, notably flecainide, have a remarkable positive effect on the ectopic burden and the associated cardiomyopathy. This highlights the importance of genetic screening of DCM patients to identify patients with variants associated with MEPPC. Here we review the MEPPC phenotype, MEPPC- associated variants, and pathogenesis as well as treatment options.
PubMed: 37600057
DOI: 10.3389/fcvm.2023.1179018 -
Strahlentherapie Und Onkologie : Organ... Jul 2023Single-session cardiac stereotactic radiation therapy (SBRT) has demonstrated promising results for patients with refractory ventricular tachycardia (VT). However, the...
BACKGROUND
Single-session cardiac stereotactic radiation therapy (SBRT) has demonstrated promising results for patients with refractory ventricular tachycardia (VT). However, the full safety profile of this novel treatment remains unknown and very limited data from prospective clinical multicenter trials are available.
METHODS
The prospective multicenter multiplatform RAVENTA (radiosurgery for ventricular tachycardia) study assesses high-precision image-guided cardiac SBRT with 25 Gy delivered to the VT substrate determined by high-definition endocardial and/or epicardial electrophysiological mapping in patients with refractory VT ineligible for catheter ablation and an implanted cardioverter defibrillator (ICD). Primary endpoint is the feasibility of full-dose application and procedural safety (defined as an incidence of serious [grade ≥ 3] treatment-related complications ≤ 5% within 30 days after therapy). Secondary endpoints comprise VT burden, ICD interventions, treatment-related toxicity, and quality of life. We present the results of a protocol-defined interim analysis.
RESULTS
Between 10/2019 and 12/2021, a total of five patients were included at three university medical centers. In all cases, the treatment was carried out without complications. There were no serious potentially treatment-related adverse events and no deterioration of left ventricular ejection fraction upon echocardiography. Three patients had a decrease in VT episodes during follow-up. One patient underwent subsequent catheter ablation for a new VT with different morphology. One patient with local VT recurrence died 6 weeks after treatment in cardiogenic shock.
CONCLUSION
The interim analysis of the RAVENTA trial demonstrates early initial feasibility of this new treatment without serious complications within 30 days after treatment in five patients. Recruitment will continue as planned and the study has been expanded to further university medical centers.
TRIAL REGISTRATION NUMBER
NCT03867747 (clinicaltrials.gov). Registered March 8, 2019. Study start: October 1, 2019.
Topics: Humans; Radiosurgery; Stroke Volume; Prospective Studies; Quality of Life; Feasibility Studies; Ventricular Function, Left; Tachycardia, Ventricular; Treatment Outcome
PubMed: 37285038
DOI: 10.1007/s00066-023-02091-9 -
Journal of Clinical Medicine Nov 2023Although implantable cardioverter defibrillators offer the best protection against sudden cardiac death, catheter ablation for ventricular arrhythmias (VAs) can modify... (Review)
Review
Although implantable cardioverter defibrillators offer the best protection against sudden cardiac death, catheter ablation for ventricular arrhythmias (VAs) can modify or prevent this event from occurring. In order to achieve a successful ablation, the correct identification of the underlying arrhythmogenic substrate is mandatory to tailor the pre-procedural planning of an ablative procedure as appropriately as possible. We propose that several of the imaging modalities currently used could be merged, including echocardiography (also intracardiac), cardiac magnetic resonance, cardiac computed tomography, nuclear techniques, and electroanatomic mapping. The aim of this state-of-the-art review is to present the value of each modality, that is, its benefits and limitations, in the assessment of arrhythmogenic substrate. Moreover, VAs can be also idiopathic, and in this paper we will underline the role of these techniques in facilitating the ablative procedure. Finally, a hands-on workflow for approaching such a VA and future perspectives will be presented.
PubMed: 38068472
DOI: 10.3390/jcm12237420 -
Circulation Research Jan 2024Brugada syndrome is associated with loss-of-function variants, yet these account for only ≈20% of cases. A recent genome-wide association study identified a novel...
BACKGROUND
Brugada syndrome is associated with loss-of-function variants, yet these account for only ≈20% of cases. A recent genome-wide association study identified a novel locus within , which encodes EB2 (microtubule end-binding protein 2), implicating microtubule involvement in Brugada syndrome.
METHODS
A knockout zebrafish model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated protein 9) and validated by Western blot. Larval hearts at 5 days post-fertilization were isolated for voltage mapping and immunocytochemistry. Adult fish hearts were used for ECG, patch clamping, and immunocytochemistry. Morpholinos were injected into embryos at 1-cell stage for knockdown experiments. A transgenic zebrafish line with tandem fluorescent timer was used to study adherens junctions. Microtubule plus-end tracking and patch clamping were performed in human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) with knockdown and knockout, respectively.
RESULTS
Voltage mapping of knockout hearts showed a decrease in ventricular maximum upstroke velocity of the action potential and conduction velocity, suggesting loss of cardiac voltage-gated sodium channel function. ECG showed QRS prolongation in adult knockout fish, and patch clamping showed decreased sodium current density in knockout ventricular myocytes and arrhythmias in knockout iPSC-CMs. Confocal imaging showed disorganized adherens junctions and mislocalization of mature Ncad (N-cadherin) with loss of function, associated with a decrease of detyrosinated tubulin. knockdown in iPSC-CMs led to an increase in microtubule growth velocity and distance, indicating changes in microtubule dynamics. Finally, knockdown of encoding tubulin tyrosine ligase in knockout larvae rescued tubulin detyrosination and ventricular maximum upstroke velocity of the action potential.
CONCLUSIONS
Genetic ablation of led to a decrease in voltage-gated sodium channel function, a hallmark of Brugada syndrome, associated with disruption of adherens junctions, decrease of detyrosinated tubulin as a marker of microtubule stability, and changes in microtubule dynamics. Restoration of the detyrosinated tubulin fraction with knockdown led to rescue of voltage-gated sodium channel-related functional parameters in knockout hearts. Taken together, our study implicates microtubule dynamics in the modulation of ventricular conduction.
Topics: Animals; Humans; Action Potentials; Brugada Syndrome; Genome-Wide Association Study; Induced Pluripotent Stem Cells; Microtubule-Associated Proteins; Microtubules; Myocytes, Cardiac; NAV1.5 Voltage-Gated Sodium Channel; Tubulin; Voltage-Gated Sodium Channels; Zebrafish
PubMed: 38095085
DOI: 10.1161/CIRCRESAHA.123.323231 -
Herzschrittmachertherapie &... Mar 2024This article focuses on ventricular arrythmias without evidence for structural heart disease. There are many different reasons for this type of arrythmia and there is... (Review)
Review
This article focuses on ventricular arrythmias without evidence for structural heart disease. There are many different reasons for this type of arrythmia and there is still a gap of knowledge. Starting with the first description of this disease, we present the diagnosis and management with medication, and finally catheter ablation procedures from the beginning to how it is currently treated and how it possibly will be treated in the near future.
Topics: Humans; Tachycardia, Ventricular; Arrhythmias, Cardiac; Heart Diseases; Catheter Ablation
PubMed: 38407580
DOI: 10.1007/s00399-024-01007-z -
Annals of Noninvasive Electrocardiology... Sep 2023The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past two decades. Data have demonstrated reduced LVAD efficacy, worse clinical outcome, and higher mortality for patients who experience significant ventricular tachyarrhythmia (VTA). We hypothesize that a novel prophylactic intra-operative VTA ablation protocol at the time of LVAD implantation may reduce the recurrent VTA and adverse events postimplant.
METHODS
We designed a prospective, multicenter, open-label, randomized-controlled clinical trial enrolling 100 patients who are LVAD candidates with a history of VTA in the previous 5 years. Enrolled patients will be randomized in a 1:1 fashion to intra-operative VTA ablation (n = 50) versus conventional medical management (n = 50) with LVAD implant. Arrhythmia outcomes data will be captured by an implantable cardioverter defibrillator (ICD) to monitor VTA events, with a uniform ICD programming protocol. Patients will be followed prospectively over a mean of 18 months (with a minimum of 9 months) after LVAD implantation to evaluate recurrent VTA, adverse events, and procedural outcomes. Secondary endpoints include right heart function/hemodynamics, healthcare utilization, and quality of life.
CONCLUSION
The primary aim of this first-ever randomized trial is to assess the efficacy of intra-operative ablation during LVAD surgery in reducing VTA recurrence and improving clinical outcomes for patients with a history of VTA.
Topics: Humans; Heart-Assist Devices; Prospective Studies; Quality of Life; Risk Factors; Electrocardiography; Arrhythmias, Cardiac; Tachycardia, Ventricular; Heart Failure; Defibrillators, Implantable; Treatment Outcome
PubMed: 37515396
DOI: 10.1111/anec.13073 -
Nature Communications Jul 2023Heart failure is a leading cause of mortality in developed countries. Cell death is a key player in the development of heart failure. Calcium-independent phospholipase...
Heart failure is a leading cause of mortality in developed countries. Cell death is a key player in the development of heart failure. Calcium-independent phospholipase Aβ (iPLAβ) produces lipid mediators by catalyzing lipids and induces nuclear shrinkage in caspase-independent cell death. Here, we show that lysophosphatidylserine generated by iPLAβ induces necrotic cardiomyocyte death, as well as contractile dysfunction mediated through its receptor, G protein-coupled receptor 34 (GPR34). Cardiomyocyte-specific iPLAβ-deficient male mice were subjected to pressure overload. While control mice showed left ventricular systolic dysfunction with necrotic cardiomyocyte death, iPLAβ-deficient mice preserved cardiac function. Lipidomic analysis revealed a reduction of 18:0 lysophosphatidylserine in iPLAβ-deficient hearts. Knockdown of Gpr34 attenuated 18:0 lysophosphatidylserine-induced necrosis in neonatal male rat cardiomyocytes, while the ablation of Gpr34 in male mice reduced the development of pressure overload-induced cardiac remodeling. Thus, the iPLAβ-lysophosphatidylserine-GPR34-necrosis signaling axis plays a detrimental role in the heart in response to pressure overload.
Topics: Rats; Mice; Male; Animals; Myocytes, Cardiac; Heart Failure; Necrosis; Receptors, G-Protein-Coupled; Ventricular Remodeling; Mice, Knockout
PubMed: 37524709
DOI: 10.1038/s41467-023-40201-4