Pulsed field ablation – new perspective in atrial fibrillation therapy

2021 ◽  
Vol 1 (58) ◽  
pp. 4-7
Author(s):  
Adam Wojtaszczyk ◽  
Paweł Ptaszyński ◽  
Krzysztof Kaczmarek
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
High Voltage ◽  
Gold Standard ◽  
Thermal Ablation ◽  
Irreversible Electroporation ◽  
Preclinical Studies ◽  
High Efficacy ◽  
New Perspective

Atrial fibrillation (AF) is one of the most important problems in cardiology. Thermal ablation therapies are “gold standard” to treat symptomatic patients. Despite the improvements, both success rate and safety are limited by their thermal nature. Pulsed filed ablation is a new non-thermal ablation method. It is based on the phenomenon of unrecoverable permeabilization of cell membranes caused by pulses of high voltage (irreversible electroporation). Several preclinical studies suggest its safety. Clinical trials published so far have showed high efficacy. Further studies especially with longer follow-up period are needed.

P2846Focal impulse and rotor modulation ablation versus pulmonary vein isolation for the treatment of paroxysmal atrial fibrillation (FIRMAP AF study)

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R Tilz ◽  
C L Lenz ◽  
P S Sommer ◽  
N Sawan ◽  
R Meyer-Saraei ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Pulmonary Vein ◽  
Pulmonary Vein Isolation ◽  
Paroxysmal Atrial Fibrillation ◽  
Gold Standard ◽  
Artery Aneurysm ◽  
Rf Ablation ◽  
Af Ablation ◽  
Number Of Patients

Abstract Background Based on the assumption of trigger elimination, pulmonary vein isolation (PVI) currently presents the gold standard of atrial fibrillation (AF) ablation. Recently, rapidly spinning rotors or focal impulse formation has been raised as a crucial sustaining mechanism of AF. Ablation of these rotors may potentially obviate the need for trigger elimination with PVI. Purpose This study sought to compare the safety and effectiveness of Focal Impulse and Rotor Modulation (FIRM) guided catheter ablation only with the gold standard of pulmonary vein isolation (PVI) in patients with paroxysmal AF. Methods This was a post-market, prospective, single-blinded, randomized, multi-center trial. Patients were enrolled at three centers and equally (1:1) randomized between those undergoing conventional RF ablation with PVI (PVI group) vs. those treated with FIRM-guided RF ablation without PVI (FIRM group). Data was collected at enrollment, procedure, and at 7-day, 3-month, 6-month, and 12-month follow-up visits. The study was closed early by the sponsor. At the time of study closure, any pending follow-up visits were waived. Results From February 2016 until February 2018, a total of 51 (out of a planned 170) patients (mean age 63±10.6 years, 57% male) were enrolled and randomized. Four patients withdrew from the study prior to treatment, resulting in 23 patients allocated to the FIRM group and 24 in the PVI group. Only 13 patients in the FIRM group and 11 patients in the PVI group completed the 12-month follow-up. Statistical analysis was not completed given the small number of patients. Single-procedure effectiveness (freedom from AF/atrial tachycardia recurrence after blanking period) was 52.9% (9/17) in the FIRM group and 85.7% (12/14) in the PVI group at 6 months; and 31.3% (5/16) in the FIRM group and 80% (8/10) in the PVI group at 12 months. Repeat procedures were performed in 45.8% (11/24) patients in the FIRM group and 7.4% (2/27) in the PVI group. The acute safety endpoint [freedom from procedure-related serious adverse events (SAE)] was achieved in 87% (20/23) of FIRM group patients and 100% (24/24) of PVI group patients. Procedure related SAEs occurred in three patients in the FIRM group: 1 femoral artery aneurysm and 2 injection site hematomas. No additional procedure-related SAEs were reported >7 days post-procedure. Conclusions These partial study effectiveness results reinforce the importance of PVI in paroxysmal atrial fibrillation patients and suggest that FIRM-guided ablation alone (without PVI) is not an effective strategy for treatment of paroxysmal AF in most patients. Further study is needed to understand the effectiveness of adding FIRM-guided ablation as an adjunct to PVI in this patient group. Acknowledgement/Funding Abbot

scholarly journals MP100-13 IRREVERSIBLE ELECTROPORATION FOR RENAL MASSES NOT AMENABLE TO THERMAL ABLATION IN NON-SURGICAL CANDIDATES: MID-TERM CLINICAL FOLLOW-UP

2017 ◽  
Vol 197 (4S) ◽  
Author(s):  
Robert Medairos ◽  
Wei Phin Tan ◽  
Kelsey Gallo ◽  
Kalyan Latchamsetty ◽  
Jordan Tasse ◽  
...  
Keyword(s):  
Thermal Ablation ◽  
Irreversible Electroporation ◽  
Renal Masses

scholarly journals Should deep-sequenced amplicons become the new gold-standard for analysing malaria drug clinical trials?

2021 ◽  
Author(s):  
Sam Jones ◽  
Katherine Kay ◽  
Eva Maria Hodel ◽  
Maria Gruenberg ◽  
Anita Lerch ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Malaria Transmission ◽  
Gold Standard ◽  
Low Density ◽  
Recurrent Infections ◽  
Routine Surveillance ◽  
Potential Impact ◽  
The Impact ◽  
Statistical Criteria

Background. Regulatory clinical trials are required to ensure the continued supply and deployment of effective antimalarial drugs. Patient follow-up in such trials typically lasts several weeks as the drugs have long half-lives and new infections often occur during this period. “Molecular correction” is therefore used to distinguish drug failures from new infections. The current WHO-recommend method for molecular correction uses length-polymorphic alleles at highly diverse loci but is inherently poor at detecting low density clones in polyclonal infections. This likely leads to substantial underestimates of failure rates, delaying the replacement of failing drugs with potentially lethal consequences. Deep sequenced amplicons (AmpSeq) substantially increase the detectability of low-density clones and may offer a new “gold standard” for molecular correction. Methods. Pharmacological simulation of clinical trials was used to evaluate the suitability of AmpSeq for molecular correction. We investigated the impact of factors such as the number of amplicon loci analysed, the informatics criteria used to distinguish genotyping ‘noise’ from real low density signals, the local epidemiology of malaria transmission, and the potential impact of genetic signals from gametocytes. Results. AmpSeq greatly improved molecular correction and provided accurate drug failure rate estimates. The use of 3 to 5 amplicons was sufficient, and simple, non-statistical, criteria could be used to classify recurrent infections as drug failures or new infections. Conclusions. These results suggest AmpSeq is strongly placed to become the new standard for molecular correction in regulatory trials, with its potential extension into routine surveillance once the requisite technical support becomes established.

Abstract 17109: Real World Assessment of Atrial Fibrillation and Other Arrhythmias After Cryptogenic Stroke

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Naga Venkata K Pothineni ◽  
Uyanga Batnyam ◽  
Jeffrey Arkles ◽  
John Bullinga ◽  
Brett L CUCCHIARA ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Real World ◽  
Cryptogenic Stroke ◽  
Premature Ventricular Contractions ◽  
Entire Cohort ◽  
Detection Algorithms ◽  
Term Monitoring

Introduction: Long-term monitoring for atrial fibrillation (AF) is recommended in patients, who have experienced a cryptogenic stroke (CS). Clinical trials have identified AF in ~30% of patients after 3 years of continuous monitoring with insertable cardiac monitors (ICMs). Hypothesis: In a real-world analysis from a large academic healthcare system, we sought to evaluate a CS population with ICMs and a) determine the yield of AF and subsequent initiation of anticoagulation; and b) identify the presence of other arrhythmias. Methods: We evaluated all CS patients who had received an ICM between October 2014 and April 2020. We manually reviewed all stored electrocardiograms that were automatically labeled as AF by the ICM and adjudicated them as either a) AF or b) other cardiac arrhythmia including premature atrial contractions (PAC), premature ventricular contractions (PVC), supraventricular tachycardia (SVT), or nonsustained ventricular tachycardia (NSVT). Results: A total of 84 CS patients with ICMs were included: 51% men, mean age 63 years, and mean CHA 2 DS 2 -VASc 4.1. Over a median follow-up duration of 15.7 months, there were 34 patients (40% of the cohort) who did not have any AF alerts. In the remaining 50 patients, there were 960 stored electrograms that were adjudicated. Only 154 recordings from 16 patients (19% of the entire cohort) were adjudicated as AF. Oral anticoagulation was initiated in all these patients with adjudicated AF. The remaining tracings, which had been automatically categorized by the ICM as AF alerts, represented 34 patients (40% of the cohort). These patients had other arrhythmias including frequent PACs or PVCs, SVT, or NSVT. Conclusions: Compared to clinical trials, our real-world assessment suggests that the yield of AF following CS is lower - approximately 20%. Our findings highlight the importance for reviewing device tracings given the high rates of false positive for AF. Further research to refine AF detection algorithms in ICMs is needed.

scholarly journals Survival analysis for AdVerse events with VarYing follow-up times (SAVVY)—estimation of adverse event risks

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Regina Stegherr ◽  
Claudia Schmoor ◽  
Jan Beyersmann ◽  
Kaspar Rufibach ◽  
Valentine Jehl ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Gold Standard ◽  
Incidence Density ◽  
Incidence Proportion ◽  
Kaplan Meier ◽  
Meta Regression ◽  
Definition Of ◽  
Non Parametric

Abstract Background The SAVVY project aims to improve the analyses of adverse events (AEs), whether prespecified or emerging, in clinical trials through the use of survival techniques appropriately dealing with varying follow-up times and competing events (CEs). Although statistical methodologies have advanced, in AE analyses, often the incidence proportion, the incidence density, or a non-parametric Kaplan-Meier estimator are used, which ignore either censoring or CEs. In an empirical study including randomized clinical trials from several sponsor organizations, these potential sources of bias are investigated. The main purpose is to compare the estimators that are typically used to quantify AE risk within trial arms to the non-parametric Aalen-Johansen estimator as the gold-standard for estimating cumulative AE probabilities. A follow-up paper will consider consequences when comparing safety between treatment groups. Methods Estimators are compared with descriptive statistics, graphical displays, and a more formal assessment using a random effects meta-analysis. The influence of different factors on the size of deviations from the gold-standard is investigated in a meta-regression. Comparisons are conducted at the maximum follow-up time and at earlier evaluation times. CEs definition does not only include death before AE but also end of follow-up for AEs due to events related to the disease course or safety of the treatment. Results Ten sponsor organizations provided 17 clinical trials including 186 types of investigated AEs. The one minus Kaplan-Meier estimator was on average about 1.2-fold larger than the Aalen-Johansen estimator and the probability transform of the incidence density ignoring CEs was even 2-fold larger. The average bias using the incidence proportion was less than 5%. Assuming constant hazards using incidence densities was hardly an issue provided that CEs were accounted for. The meta-regression showed that the bias depended mainly on the amount of censoring and on the amount of CEs. Conclusions The choice of the estimator of the cumulative AE probability and the definition of CEs are crucial. We recommend using the Aalen-Johansen estimator with an appropriate definition of CEs whenever the risk for AEs is to be quantified and to change the guidelines accordingly.

scholarly journals Should deep-sequenced amplicons become the new gold-standard for analysing malaria drug clinical trials?

2021 ◽  
Author(s):  
Sam Jones ◽  
Katherine Kay ◽  
Eva Maria Hodel ◽  
Maria Gruenberg ◽  
Anita Lerch ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Malaria Transmission ◽  
Gold Standard ◽  
Low Density ◽  
Recurrent Infections ◽  
Routine Surveillance ◽  
Potential Impact ◽  
The Impact ◽  
Statistical Criteria

Background. Regulatory clinical trials are required to ensure the continued supply and deployment of effective antimalarial drugs. Patient follow-up in such trials typically lasts several weeks as the drugs have long half-lives and new infections often occur during this period. Molecular correction is therefore used to distinguish drug failures from new infections. The current WHO-recommend method for molecular correction uses length-polymorphic alleles at highly diverse loci but is inherently poor at detecting low density clones in polyclonal infections. This likely leads to substantial underestimates of failure rates, delaying the replacement of failing drugs with potentially lethal consequences. Deep sequenced amplicons (AmpSeq) substantially increase the detectability of low-density clones and may offer a new gold standard for molecular correction. Methods. Pharmacological simulation of clinical trials was used to evaluate the suitability of AmpSeq for molecular correction. We investigated the impact of factors such as the number of amplicon loci analysed, the informatics criteria used to distinguish genotyping noise from real low density signals, the local epidemiology of malaria transmission, and the potential impact of genetic signals from gametocytes. Results. AmpSeq greatly improved molecular correction and provided accurate drug failure rate estimates. The use of 3 to 5 amplicons was sufficient, and simple, non-statistical, criteria could be used to classify recurrent infections as drug failures or new infections. Conclusions. These results strongly endorse the deployment of AmpSeq as the standard for molecular correction in regulatory trials, with its potential extension into routine surveillance once the requisite technical support becomes established.

scholarly journals Digoxin treatment and long-term mortality depending on left ventricular ejection fraction and atrial fibrillation: a propensity score matched analysis

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M.R Grubler ◽  
N.D Verheyen ◽  
A Meinitzer ◽  
L Fiedler ◽  
M Tscharre ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Coronary Angiography ◽  
Propensity Score ◽  
Ejection Fraction ◽  
Propensity Score Matching ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Background/Introduction Atrial fibrillation (AF) is a common heart rhythm disturbance, associated with an increased risk of stroke, hospital admissions and mortality, especially in patients with reduced ejection fraction. Among the oldest medications used for heart-rate control is digitalis, but largely due to observational studies showing an increased risk of death it has fallen out of favour. Recently newer clinical trials reported that the treatment with digitalis in permanent AF might be superior to beta blocker therapy in regard to functional status and symptom burden. Given this diverging results we attempt to analysis a large cohort of patients facilitating a propensity score matching algorithm. Purpose To assess the associations of digitalis treatment with mortality in patients with increased cardiovascular risk. Methods Patients were derived from a large cohort study including participants from a tertiary care centre who were referred to coronary angiography. The propensity score matching is based on a predefined list of variables, with digitalis as treatment. Matching strategy is nearest neighbour matching and to prove consistency, radius matching (radius = 0.1). For survival analysis we used a Cox proportional hazard regression comparing patients with and without digitalis for all-cause mortality. The analysis is conducted using STATA 13 MP. All patients provided written informed consent and the study was approved by the ethics committee. Results A total of 2457 patients (median age: 63.5 [IQR = 56.3–70.6] years, 30.1% women) referred to coronary angiography, with a median follow up of 9.9 (IQR = 8.5–10.7) years were included. The matching process and the resulting propensity score fulfilled all statistical assumptions and resulted in a balanced cohort. The risk for all-cause mortality was higher among propensity score matched participants not treated with digitalis compared to patients on treatment (n=514) HR 3.03 (95% CI 2.5 to 3.7). Total mortality in patients with AF on digitalis after a median follow-up of 9.9 years was 27.6%. At baseline, only 42.4% of patients with AF were on oral anticoagulation. Conclusions In the present cohort treatment with digitalis was associated with a lower risk of all-cause mortality after long-term follow-up. The patient population has a clinically significant 10-year mortality risk. The results may not apply to other cohorts but may help inform future clinical trials. FUNDunding Acknowledgement Type of funding sources: None.

Sign in / Sign up

Export Citation Format

Share Document