ABSTRACT
AIMS: AP30663 is a novel compound under development for pharmacological conversion of atrial fibrillation by targeting the small conductance Ca2+ activated K+ (KCa2) channel. The aim of this extension phase 1 study was to test AP30663 at higher single doses compared to the first-in-human trial. METHODS: Sixteen healthy male volunteers were randomized into 2 cohorts: 6- and 8-mg/kg intravenous single-dose administration of AP30663 vs. placebo. Safety, pharmacokinetic and pharmacodynamic data were collected. RESULTS: AP30663 was associated with mild and transient infusion site reactions with no clustering of other adverse events but with an estimated maximum mean QTcF interval prolongation of 45.2 ms (95% confidence interval 31.5-58.9) in the 6 mg/kg dose level and 50.4 ms (95% confidence interval 36.7-64.0) with 8 mg/kg. Pharmacokinetics was dose proportional with terminal half-life of around 3 h. CONCLUSION: AP30663 in doses up to 8 mg/kg was associated with mild and transient infusion site reactions and an increase of the QTcF interval. Supporting Information support that the QTc effect may be explained by an off-target inhibition of the IKr channel.
Subject(s)
Atrial Fibrillation , Humans , Male , Atrial Fibrillation/chemically induced , Atrial Fibrillation/drug therapy , Dose-Response Relationship, Drug , Double-Blind Method , Electrocardiography , Heart Rate , Injection Site ReactionABSTRACT
AIMS: Substrate assessment of scar-mediated ventricular tachycardia (VT) is frequently performed using late gadolinium enhancement (LGE) images. Although this provides structural information about critical pathways through the scar, assessing the vulnerability of these pathways for sustaining VT is not possible with imaging alone.This study evaluated the performance of a novel automated re-entrant pathway finding algorithm to non-invasively predict VT circuit and inducibility. METHODS: Twenty post-infarct VT-ablation patients were included for retrospective analysis. Commercially available software (ADAS3D left ventricular) was used to generate scar maps from 2D-LGE images using the default 40-60 pixel-signal-intensity (PSI) threshold. In addition, algorithm sensitivity for altered thresholds was explored using PSI 45-55, 35-65, and 30-70. Simulations were performed on the Virtual Induction and Treatment of Arrhythmias (VITA) framework to identify potential sites of block and assess their vulnerability depending on the automatically computed round-trip-time (RTT). Metrics, indicative of substrate complexity, were correlated with VT-recurrence during follow-up. RESULTS: Total VTs (85 ± 43 vs. 42 ± 27) and unique VTs (9 ± 4 vs. 5 ± 4) were significantly higher in patients with- compared to patients without recurrence, and were predictive of recurrence with area under the curve of 0.820 and 0.770, respectively. VITA was robust to scar threshold variations with no significant impact on total and unique VTs, and mean RTT between the four models. Simulation metrics derived from PSI 45-55 model had the highest number of parameters predictive for post-ablation VT-recurrence. CONCLUSION: Advanced computational metrics can non-invasively and robustly assess VT substrate complexity, which may aid personalized clinical planning and decision-making in the treatment of post-infarction VT.
Subject(s)
Cicatrix , Computer Simulation , Tachycardia, Ventricular , Humans , Algorithms , Catheter Ablation , Cicatrix/complications , Myocardial Infarction/complications , Retrospective Studies , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/surgery , Reproducibility of Results , Male , Middle Aged , Aged , Aged, 80 and overABSTRACT
AIMS: Stereotactic arrhythmia radiotherapy (STAR) is suggested as potentially effective and safe treatment for patients with therapy-refractory ventricular tachycardia (VT). However, the current prospective knowledge base and experience with STAR is limited. In this study we aimed to prospectively evaluate the efficacy and safety of STAR. METHODS AND RESULTS: The StereoTactic Arrhythmia Radiotherapy in the Netherlands no.1 was a pre-post intervention study to prospectively evaluate efficacy and safety of STAR. In patients with therapy-refractory VT, the pro-arrhythmic region was treated with a 25 Gy single radiotherapy fraction. The main efficacy measure was a reduction in the number of treated VT-episodes by ≥50%, comparing the 12 months before and after treatment (or end of follow-up, excluding a 6-week blanking period). The study was deemed positive when ≥50% of patients would meet this criterion. Safety evaluation included left ventricular ejection fraction, pulmonary function, and adverse events. Six male patients with an ischaemic cardiomyopathy were enrolled, and median age was 73 years (range 54-83). Median left ventricular ejection fraction was 38% (range 24-52). The median planning target volume was 187 mL (range 93-372). Four (67%) patients completed the 12-month follow-up, and two patients died (not STAR related) during follow-up. The main efficacy measure of ≥50% reduction in treated VT-episodes at the end of follow-up was achieved in four patients (67%). The median number of treated VT-episodes was reduced by 87%. No reduction in left ventricular ejection fraction or pulmonary function was observed. No treatment related serious adverse events occurred. CONCLUSIONS: STAR resulted in a ≥ 50% reduction in treated VT-episodes in 4/6 (67%) patients. No reduction in cardiac and pulmonary function nor treatment-related serious adverse events were observed during follow-up. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register-NL7510.
Subject(s)
Radiosurgery , Tachycardia, Ventricular , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Heart , Radiosurgery/adverse effects , Radiosurgery/methods , Stroke Volume , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/radiotherapy , Treatment Outcome , Ventricular Function, LeftABSTRACT
INTRODUCTION: Radiofrequency (RF) atrial fibrillation (AF) ablation using a catheter dragging technique may shorten procedural duration and improve durability of pulmonary vein isolation (PVI) by creating uninterrupted linear ablation lesions. We compared a novel AF ablation approach guided by Grid annotation allowing for "drag lesions" with a standard point-by-point ablation approach in a single-center randomized study. METHODS: Eighty-eight paroxysmal or persistent AF patients were randomized 1:1 to undergo RF-PVI with either a catheter dragging ablation technique guided by Grid annotation or point-by-point ablation guided by Ablation Index (AI) annotation. In the Grid annotation arm, ablation was visualized using 1 mm³ grid points coloring red after meeting predefined stability and contact force criteria. In the AI annotation arm, ablation lesions were created in a point-by-point fashion with AI target values set at 380 and 500 for posterior/inferior and anterior/roof segments, respectively. Patients were followed up for 12 months after PVI using ECGs, 24-h Holter monitoring and a mobile-based one-lead ECG device. RESULTS: Procedure time was not different between the two randomization arms (Grid annotation 71 ± 19 min, AI annotation 72 ± 26 min, p = .765). RF time was significantly longer in the Grid annotation arm compared with the AI annotation arm (49 ± 8 min vs. 37 ± 8 min, respectively, p < .001). Atrial tachyarrhythmia recurrence was documented in 10 patients (23%) in the Grid annotation arm compared with 19 patients (42%) in the AI annotation arm with time to recurrence not reaching statistical significance (p = .074). CONCLUSIONS: This study shows that a Grid annotation-guided dragging approach provides an alternative to point-by-point RF-PVI using AI annotation.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Catheter Ablation/adverse effects , Catheter Ablation/methods , Humans , Pulmonary Veins/surgery , Recurrence , Treatment OutcomeABSTRACT
INTRODUCTION: Approximately 18% of patients with atrial fibrillation (AF) undergo a repeat ablation within 12 months after their index ablation. Despite the high prevalence, comparative studies on nonpulmonary vein (PV) target strategies in repeat AF ablation are scarce. Here, we describe 12 months efficacy of non-PV and PV target ablations as a repeat ablation strategy. METHODS: A multicentre retrospective, descriptive study was conducted with data of 280 patients who underwent repeat AF ablation. The ablation strategy for repeat ablation was at the operators' discretion. Non-PV target ablation (n = 140) included PV reisolation, posterior wall isolation, mitral line, roofline, and/or complex fractionated atrial electrogram ablation. PV target ablation (n = 140), included reisolation and/or wide atrium circumferential ablation. Patients' demographics and rhythm outcomes during 12 months follow-up were analyzed. RESULTS: At 12 months, more atrial tachyarrhythmias were observed in the non-PV target group (48.6%) compared to the PV target group (29.3%, p = .001). Similarly, a significantly higher AF and atrial tachycardia (AT) recurrence rate was observed after non-PV target ablation compared to PV target ablation (36.4% vs. 22.1% and 22.9% vs. 10.7%). After adjustment, a significantly higher risk of AT recurrence remained in the non-PV target group. Both groups significantly de-escalated antiarrhythmic drug use; de-escalation was more profound after PV target ablation. Patients with isolated PVs during non-PV target ablation had a significantly higher risk for AF recurrence than those with reconnected PVs. CONCLUSION: Compared to PV target ablation, non-PV target repeat ablation did not improve outcomes after 12 months and was independently associated with an increased risk for AT recurrences.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Atrial Fibrillation/diagnosis , Atrial Fibrillation/etiology , Atrial Fibrillation/surgery , Catheter Ablation/adverse effects , Humans , Pulmonary Veins/surgery , Recurrence , Retrospective Studies , Treatment OutcomeABSTRACT
AIMS: Hydroxychloroquine has been suggested as possible treatment for severe acute respiratory syndrome-coronavirus-2. Studies reported an increased risk of QTcF-prolongation after treatment with hydroxychloroquine. The aim of this study was to analyse the concentration-dependent effects of hydroxychloroquine on the ventricular repolarization, including QTcF-duration and T-wave morphology. METHODS: Twenty young (≤30 y) and 20 elderly (65-75 y) healthy male subjects were included. Subjects were randomized to receive either a total dose of 2400 mg hydroxychloroquine over 5 days, or placebo (ratio 1:1). Follow-up duration was 28 days. Electrocardiograms (ECGs) were recorded as triplicate at baseline and 4 postdose single recordings, followed by hydroxychloroquine concentration measurements. ECG intervals (RR, QRS, PR, QTcF, J-Tpc, Tp-Te) and T-wave morphology, measured with the morphology combination score, were analysed with a prespecified linear mixed effects concentration-effect model. RESULTS: There were no significant associations between hydroxychloroquine concentrations and ECG characteristics, including RR-, QRS- and QTcF-interval (P = .09, .34, .25). Mean ΔΔQTcF-interval prolongation did not exceed 5 ms and the upper limit of the 90% confidence interval did not exceed 10 ms at the highest measured concentrations (200 ng/mL). There were no associations between hydroxychloroquine concentration and the T-wave morphology (P = .34 for morphology combination score). There was no significant effect of age group on ECG characteristics. CONCLUSION: In this study, hydroxychloroquine did not affect ventricular repolarization, including the QTcF-interval and T-wave morphology, at plasma concentrations up to 200 ng/mL. Based on this analysis, hydroxychloroquine does not appear to increase the risk of QTcF-induced arrhythmias.
Subject(s)
COVID-19 Drug Treatment , Long QT Syndrome , Aged , Electrocardiography , Heart Rate , Humans , Hydroxychloroquine/adverse effects , Long QT Syndrome/chemically induced , Male , SARS-CoV-2ABSTRACT
Pulmonary vein isolation (PVI) by radiofrequency (RF) ablation is an important alternative to antiarrhythmic drugs in the treatment of symptomatic atrial fibrillation. However, the inability to consistently achieve durable isolation of the pulmonary veins hampers the long-term efficacy of PVI procedures. The large number of factors involved in RF lesion formation and the complex interplay of these factors complicate reliable creation of durable and transmural ablation lesions. Various surrogate markers of ablation lesion formation have been proposed that may provide information on RF lesion completeness. Real-time assessment of these surrogates may aid in the creation of transmural ablation lesions, and therefore, holds potential to decrease the risk of PV reconnection and consequent post-PVI arrhythmia recurrence. Moreover, titration of energy delivery until lesions is transmural may prevent unnecessary ablation and subsequent adverse events. Whereas several surrogate markers of ablation lesion formation have been described over the past decades, a 'gold standard' is currently lacking. This review provides a state-of-the-art overview of ablation strategies that aim to enhance durability of RF-PVI, with special focus on real-time available surrogates of RF lesion formation in light of the biophysical basis of RF ablation.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Anti-Arrhythmia Agents , Atrial Fibrillation/diagnosis , Atrial Fibrillation/etiology , Atrial Fibrillation/surgery , Catheter Ablation/adverse effects , Catheter Ablation/methods , Humans , Pulmonary Veins/surgery , Recurrence , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Previous studies reported that hypo- and hyperthermia are associated with several atrial and ventricular electrocardiographical parameters, including corrected QT (QTc) interval. Enhanced characterization of variations in QTc interval and normothermic body temperature aids in better understanding the underlying mechanism behind drug induced QTc interval effects. The analysis' objective was to investigate associations between body temperature and electrocardiographical parameters in normothermic healthy volunteers. METHODS: Data from 3023 volunteers collected at our center were retrospectively analyzed. Subjects were considered healthy after review of collected data by a physician, including a normal tympanic body temperature (35.5-37.5°C) and in sinus rhythm. A linear multivariate model with body temperature as a continuous was performed. Another multivariate analysis was performed with only the QT subintervals as independent variables and body temperature as dependent variable. RESULTS: Mean age was 33.8 ± 17.5 years and mean body temperature was 36.6 ± 0.4°C. Body temperature was independently associated with age (standardized coefficient [SC] = -0.255, P < .001), female gender (SC = +0.209, P < .001), heart rate (SC = +0.231, P < .001), P-wave axis (SC = -0.051, P < .001), J-point elevation in lead V4 (SC = -0.121, P < .001), and QTcF duration (SC = -0.061, P = .002). In contrast, other atrial and atrioventricular (AV) nodal parameters were not independently associated with body temperature. QT subinterval analysis revealed that only QRS duration (SC = -0.121, P < .001) was independently associated with body temperature. CONCLUSION: Body temperature in normothermic healthy volunteers was associated with heart rate, P-wave axis, J-point amplitude in lead V4, and ventricular conductivity, the latter primarily through prolongation of the QRS duration.
Subject(s)
Body Temperature , Electrocardiography , Healthy Volunteers , Adult , Female , Heart Rate/physiology , Humans , Male , Retrospective StudiesABSTRACT
BACKGROUND: During pulmonary vein isolation (PVI), nonisolation after initial encircling of the pulmonary veins (PVs) may be due to gaps in the initial ablation line, or alternatively, earliest PV activation may occur on the intervenous carina and ablation within the wide-area circumferential ablation (WACA) circle is needed to eliminate residual conduction. This study investigated prognostic implications and predictors of gap-related persistent conduction (gap-RPC) and carina-related persistent conduction (carina-RPC) during PVI. METHODS AND RESULTS: Two hundred fourteen atrial fibrillation (AF) patients (57% paroxysmal, 61% male, mean age 62 ± 9 years) undergoing first contact force-guided radiofrequency PVI were studied. Preprocedural cardiac computed tomography imaging was used to assess left atrial and PV anatomy. PVI was assessed directly after initial WACA circle creation, after a minimum waiting period of 30 minutes, and after adenosine infusion. Persistent conduction was targeted for additional ablation and classified as gap-RPC or carina-RPC, depending on the earliest activation site. The 1-year AF recurrence rate was higher in patients with gap-RPC (47%) compared to patients without gap-RPC (28%; P = .003). No significant difference in 1-year recurrence rate was found between patients with carina-RPC (37%) and patients without carina-RPC (31%; P = .379). Multivariate analyses identified paroxysmal AF and WACA circumference as independent predictors of gap-RPC, whereas carina width and WACA circumference correlated with carina-RPC. CONCLUSIONS: Gap-RPC is associated with increased AF recurrence risk after PVI, whereas carina-RPC does not predict AF recurrence. Moreover, gap-RPC and carina-RPC have different correlates and may thus have different underlying mechanisms.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Aged , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/surgery , Catheter Ablation/adverse effects , Female , Humans , Male , Middle Aged , Prospective Studies , Pulmonary Veins/diagnostic imaging , Pulmonary Veins/surgery , Recurrence , Treatment OutcomeABSTRACT
Purpose: Elevated blood pressure induces electrocardiographic changes and is associated with an increase in cardiovascular disease later in life compared to normal blood pressure levels. The purpose of this study was to evaluate the association between normal to high normal blood pressure values (90-139/50-89 mmHg) and electrocardiographic parameters related to cardiac changes in hypertension in healthy young adults.Methods: Data from 1449 volunteers aged 18-30 years collected at our centre were analyzed. Only subjects considered healthy by a physician after review of collected data with systolic blood pressure values between 90 and 139 mmHg and diastolic blood pressure values between 50 and 89 mmHg were included. Subjects were divided into groups with 10 mmHg systolic blood pressure increment between groups for analysis of electrocardiographic differences. Backward multivariate regression analysis with systolic and diastolic blood pressure as a continuous variable was performed.Results: The mean age was 22.7 ± 3.0 years, 73.7% were male. P-wave area, ventricular activation time, QRS-duration, Sokolow-Lyon voltages, Cornell Product, J-point-T-peak duration corrected for heart rate and maximum T-wave duration were significantly different between systolic blood pressure groups. In the multivariate model with gender, body mass index and cholesterol, ventricular rate (standardized coefficient (SC): +0.182, p < .001), ventricular activation time in lead V6 (SC= +0.065, p = .048), Sokolow-Lyon voltage (SC= +0.135, p < .001), and Cornell product (SC= +0.137, p < .001) were independently associated with systolic blood pressure, while ventricular rate (SC= +0.179, p < .001), P-wave area in lead V1 (SC= +0.079, p = .020), and Cornell product (SC= +0.091, p = .006) were independently associated with diastolic blood pressure.Conclusion: Blood pressure-related electrocardiographic changes were observed incrementally in a healthy young population with blood pressure in the normal range. These changes were an increased ventricular rate, increased atrial surface area, ventricular activation time and increased ventricular hypertrophy indices on a standard 12 lead electrocardiogram.
Subject(s)
Action Potentials , Blood Pressure , Electrocardiography , Heart Rate , Adolescent , Adult , Age Factors , Cross-Sectional Studies , Female , Healthy Volunteers , Humans , Male , Predictive Value of Tests , Retrospective Studies , Time Factors , Young AdultABSTRACT
INTRODUCTION: The present analysis addressed the effect of the number of ECG replicates extracted from a continuous ECG on estimated QT interval prolongation for different QT correction formulas. METHODS: For 100 healthy volunteers, who received a compound prolonging the QT interval, 18 ECG replicates within a 3-minute window were extracted from 12-lead Holter ECGs. Ten QT correction formulas were deployed, and the QTc interval was controlled for baseline and placebo and averaged per dose level. RESULTS: The mean prolongation difference was >4 ms for single and >2 ms for triplicate ECG measurements compared with the 18 ECG replicate mean values. The difference was <0.5 ms after 14 replicates. By contrast, concentration-effect analysis was independent of replicate count and also of the QT correction formula. CONCLUSION: The number of ECG replicates impacted the estimated QT interval prolongation for all deployed QT correction formulas. However, concentration-effect analysis was independent of both the replicate number and correction formula.
Subject(s)
Action Potentials/drug effects , Electrocardiography, Ambulatory , Heart Rate/drug effects , Long QT Syndrome/diagnosis , Adult , Dose-Response Relationship, Drug , Double-Blind Method , Feasibility Studies , Healthy Volunteers , Humans , Long QT Syndrome/chemically induced , Long QT Syndrome/physiopathology , Male , Netherlands , Predictive Value of Tests , Reproducibility of Results , Risk Assessment , Time Factors , Young AdultABSTRACT
INTRODUCTION: During early drug development trials, electrocardiograms (ECGs) in healthy volunteers who are in a fasting state are evaluated to screen for possible adverse cardiac effects. However, the effect of the duration of fasting on electrocardiographic parameters is largely unknown. We compared the effects of fasting on standard 12-lead electrocardiographic recordings. METHODS: Electrocardiograms were available for 432 healthy subjects (mean age 28.5 ± 12.5; 88.9% male) who participated in early drug development studies after 4- and 10-hr fasting. All ECGs were automatically analyzed for conduction intervals and wave amplitudes with the Marquette 12SL algorithm and compared among fasting duration. Mixed model analyses were used to identify confounding variables. RESULTS: After 10 hr of fasting, compared to after 4 hr of fasting, mean P-wave duration and amplitude were reduced by 1.95 ± 1.48 ms and 2.18 ± 2.75 µV, mean R wave and S wave amplitude were decreased by 25.83 ± 31.16 µV and 55.39 ± 78.72 µV, mean QRS duration was decreased by 1.84 ± 6.61 ms, and mean T-wave duration and amplitude were decreased by 2.06 ± 0.72 ms and 9.36 ± 17.21 µV (lead II). The mean PR interval was prolonged by 4.26 ± 17.67 ms, the ventricular rate was reduced by 3.64 ± 8.61 min, and QTcF was reduced by 3.87 ± 14.50 ms. These observations persisted after correction for demographics, electrolytes, blood pressure, heart rate variability, and diurnal variation. CONCLUSION: The present analysis showed that 10-hr fasting compared to 4-hr fasting resulted in changes to the surface ECG, consisting of a reduced wave amplitude and duration and increased isoelectric interval duration.
Subject(s)
Electrocardiography , Fasting , Algorithms , Drug Development , Healthy Volunteers , Heart Rate , Humans , Middle Aged , Netherlands , Time FactorsABSTRACT
BACKGROUND: Implantable cardiac defibrillator (ICD) implantation can protect against sudden cardiac death after myocardial infarction. However, improved risk stratification for device requirement is still needed. OBJECTIVE: The purpose of this study was to improve assessment of postinfarct ventricular electropathology and prediction of appropriate ICD therapy by combining late gadolinium enhancement (LGE) and advanced computational modeling. METHODS: ADAS 3D LV (ADAS LV Medical, Barcelona, Spain) and custom-made software were used to generate 3-dimensional patient-specific ventricular models in a prospective cohort of patients with a myocardial infarction (N = 40) having undergone LGE imaging before ICD implantation. Corridor metrics and 3-dimensional surface features were computed from LGE images. The Virtual Induction and Treatment of Arrhythmias (VITA) framework was applied to patient-specific models to comprehensively probe the vulnerability of the scar substrate to sustaining reentrant circuits. Imaging and VITA metrics, related to the numbers of induced ventricular tachycardias and their corresponding round trip times (RTTs), were compared with ICD therapy during follow-up. RESULTS: Patients with an event (n = 17) had a larger interface between healthy myocardium and scar and higher VITA metrics. Cox regression analysis demonstrated a significant independent association with an event: interface (hazard ratio [HR] 2.79; 95% confidence interval [CI] 1.44-5.44; P < .01), unique ventricular tachycardias (HR 1.67; 95% CI 1.04-2.68; P = .03), mean RTT (HR 2.14; 95% CI 1.11-4.12; P = .02), and maximum RTT (HR 2.13; 95% CI 1.19-3.81; P = .01). CONCLUSION: A detailed quantitative analysis of LGE-based scar maps, combined with advanced computational modeling, can accurately predict ICD therapy and could facilitate the early identification of high-risk patients in addition to left ventricular ejection fraction.
ABSTRACT
AIMS: Bi-atrial remodelling in patients with atrial fibrillation (AF) is rarely assessed and data on the presence of right atrial (RA) fibrosis, the relationship between RA and left atrial (LA) fibrosis, and possible association of RA remodelling with AF recurrence after ablation in patients with AF is limited. METHODS AND RESULTS: A total of 110 patients with AF undergoing initial pulmonary vein isolation (PVI) were included in the present study. All patients were in sinus rhythm during cardiac magnetic resonance (CMR) imaging performed prior to ablation. LA and RA volumes and function (volumetric and feature tracking strain) were derived from cine CMR images. The extent of LA and RA fibrosis was assessed from 3D late gadolinium enhancement images. AF recurrence was followed up for 12 months after PVI using either 12-lead electrocardiograms or Holter monitoring. Arrhythmia recurrence was observed in 39 patients (36%) after the 90-day blanking period, occurring at a median of 181 (interquartile range: 122-286) days. RA remodelling parameters were not significantly different between patients with and without AF recurrence after ablation, whereas LA remodelling parameters were different (volume, emptying fraction, and strain indices). LA fibrosis had a strong correlation with RA fibrosis (r = 0.88, P < 0.001). Both LA and RA fibrosis were not different between patients with and without AF recurrence. CONCLUSIONS: This study shows that RA remodelling parameters were not predictive of AF recurrence after AF ablation. Bi-atrial fibrotic remodelling is present in patients with AF and moreover, the amount of LA fibrosis had a strong correlation with the amount of RA fibrosis.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Humans , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/surgery , Atrial Fibrillation/pathology , Contrast Media , Atrial Function, Right , Gadolinium , Heart Atria , Fibrosis , Catheter Ablation/methods , Recurrence , Treatment OutcomeABSTRACT
PURPOSE: The present study assesses different left atrial (LA) strain approaches in relation to atrial fibrillation (AF) recurrence after ablation and compares LA feature tracking (FT) strain to novel rapid LA strain approaches in AF patients. METHODS: This retrospective single-center study comprised of 110 prospectively recruited AF patients who underwent cardiac magnetic resonance (CMR) imaging in sinus rhythm prior to their first pulmonary vein isolation ablation. LA rapid strain (long axis strain and atrioventricular (AV)-junction strain), LA FT strain, and LA volumes were derived from 2-chamber and 4-chamber cine images. AF recurrence was followed up for 12 months using either 12lead ECGs or rhythm Holter monitoring. RESULTS: Arrhythmia recurrence was observed in 39 patients (36%) after the 90-day blanking period, occurring at a median of 181 (122-286) days. LA long axis strain, AV-junction strain, and FT strain were all more impaired in patients with AF recurrence compared to patients without AF recurrence (long axis strain: P < 0.01; AV-junction strain: P < 0.001; FT strain: P < 0.01, respectively). Area under the curve (AUC) values for LA remodeling parameters in association with AF recurrence were 0.68 for long axis strain, 0.68 for AV-junction strain, 0.66 for FT strain, 0.66 for LA volume index. Phasic FT LA strain demonstrated that contractile strain had the highest AUC (0.70). CONCLUSION: Both LA rapid strain and LA FT strain are associated with arrhythmia recurrence after ablation in AF patients. LA rapid strain can be a convenient and reproducible alternative for LA FT strain to assess LA function in clinical practice.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Humans , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/surgery , Atrial Fibrillation/pathology , Retrospective Studies , Predictive Value of Tests , Heart Atria , Magnetic Resonance Spectroscopy , Catheter Ablation/adverse effects , Catheter Ablation/methods , RecurrenceABSTRACT
PURPOSE: Left atrial (LA) sphericity is a novel, geometry-based parameter that has been used to visualize and quantify LA geometrical remodeling in patients with atrial fibrillation (AF). This study examined the association between LA sphericity, and LA longitudinal strain and strain rate measured by feature-tracking in AF patients. METHODS: 128 AF patients who underwent cardiovascular magnetic resonance (CMR) imaging in sinus rhythm prior to their pulmonary vein isolation (PVI) procedure were retrospectively analyzed. LA sphericity was calculated by segmenting the LA (excluding the pulmonary veins and the LA appendage) on a 3D contrast enhanced MR angiogram and comparing the resulting shape with a perfect sphere. LA global reservoir strain, conduit strain, contractile strain and corresponding strain rates were derived from cine images using feature-tracking. For statistical analysis, Pearson correlations, multivariable logistic regression analysis, and Student t-tests were used. RESULTS: Patients with a spherical LA (dichotomized by the median value) had a lower reservoir strain and conduit strain compared to patients with a non-spherical LA (-15.4 ± 4.2% vs. -17.1 ± 3.5%, P = 0.02 and - 8.2 ± 3.0% vs. -9.5 ± 2.6%, P = 0.01, respectively). LA strain rate during early ventricular diastole was also different between both groups (-0.7 ± 0.3s- 1 vs. -0.9 ± 0.3s- 1, P = 0.001). In contrast, no difference was found for LA contractile strain (-7.2 ± 2.6% vs. -7.6 ± 2.2%, P = 0.30). CONCLUSIONS: LA passive strain is significantly impaired in AF patients with a spherical LA, though this relation was not independent from LA volume.
Subject(s)
Atrial Appendage , Atrial Fibrillation , Atrial Remodeling , Catheter Ablation , Humans , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/surgery , Retrospective Studies , Predictive Value of Tests , Heart Atria , Catheter Ablation/methodsABSTRACT
Background: Stereotactic arrhythmia radioablation (STAR) is a potential new therapy for patients with refractory ventricular tachycardia (VT). The arrhythmogenic substrate (target) is synthesized from clinical and electro-anatomical information. This study was designed to evaluate the baseline interobserver variability in target delineation for STAR. Methods: Delineation software designed for research purposes was used. The study was split into three phases. Firstly, electrophysiologists delineated a well-defined structure in three patients (spinal canal). Secondly, observers delineated the VT-target in three patients based on case descriptions. To evaluate baseline performance, a basic workflow approach was used, no advanced techniques were allowed. Thirdly, observers delineated three predefined segments from the 17-segment model. Interobserver variability was evaluated by assessing volumes, variation in distance to the median volume expressed by the root-mean-square of the standard deviation (RMS-SD) over the target volume, and the Dice-coefficient. Results: Ten electrophysiologists completed the study. For the first phase interobserver variability was low as indicated by low variation in distance to the median volume (RMS-SD range: 0.02-0.02â cm) and high Dice-coefficients (mean: 0.97 ± 0.01). In the second phase distance to the median volume was large (RMS-SD range: 0.52-1.02â cm) and the Dice-coefficients low (mean: 0.40 ± 0.15). In the third phase, similar results were observed (RMS-SD range: 0.51-1.55â cm, Dice-coefficient mean: 0.31 ± 0.21). Conclusions: Interobserver variability is high for manual delineation of the VT-target and ventricular segments. This evaluation of the baseline observer variation shows that there is a need for methods and tools to improve variability and allows for future comparison of interventions aiming to reduce observer variation, for STAR but possibly also for catheter ablation.
ABSTRACT
AIMS: Risk stratification models of sudden cardiac death (SCD) are based on the assumption that risk factors of SCD affect risk to a similar extent in both sexes. The aim of the study is to evaluate differences in clinical outcomes between sexes and evaluate whether risk factors associated with appropriate device therapy (ADT) differ between men and women. METHODS AND RESULTS: We performed a cohort study of implantable cardioverter defibrillator (ICD) patients referred for primary or secondary prevention of SCD between 2009 and 2018. Multivariable Cox regression models for prediction of ADT were constructed for men and women separately. Of 2300 included patients, 571 (25%) were women. Median follow-up was 4.6 (inter-quartile range: 4.4-4.9) years. Time to ADT was shorter for men compared with women [hazard ratio (HR) 1.71, P < 0.001], as was time to mortality (HR 1.37, P = 0.003). In women, only secondary prevention ICD therapy (HR 1.82, P < 0.01) was associated with ADT, whereas higher age (HR 1.20, P < 0.001), absence of left bundle branch block (HR 0.72, P = 0.01), and secondary prevention therapy (HR 1.80, P < 0.001) were independently associated with ADT in men. None of the observed parameters showed a distinctive sex-specific pattern in ADT. CONCLUSIONS: Male ICD patients were at higher risk of ADT and death compared with female ICD patients, irrespective of an ischaemic or non-ischaemic underlying cardiomyopathy. Our study highlights the importance to stratify outcomes of ICD trials by sex, as study results differ between men and women. However, none of the available clinical parameters showed a clear sex-specific relation to ventricular arrhythmias. As a consequence, sex-specific risk stratification models of SCD using commonly available clinical parameters could not be derived.
Subject(s)
Defibrillators, Implantable , Arrhythmias, Cardiac , Cohort Studies , Death, Sudden, Cardiac/epidemiology , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/prevention & control , Female , Humans , Male , Risk AssessmentABSTRACT
BACKGROUND: A significant number of patients experience recurrent atrial fibrillation (AF) after ablation. Various risk scores have been described that may predict outcomes after AF ablation. In this study, we aimed to compare ten previously described risk scores with regard to their predictive value for post-ablation AF recurrence and procedural complications. METHODS: A total of 482 AF patients (63% paroxysmal AF, 66% male, mean age 62 ± 9 years) undergoing initial radiofrequency pulmonary vein isolation (PVI) were included in the present analysis. Prior to ablation, all patients underwent both transthoracic echocardiography (TTE) and either cardiac CT imaging or CMR imaging. The following risk scores were calculated for each patient: APPLE, ATLAS, BASE-AF2, CAAP-AF, CHADS2, CHA2DS2-VASc, DR-FLASH, HATCH, LAGO and MB-LATER. RESULTS: Median follow-up was 16 (12-31) months. AF recurrence after a 90-day blanking period was observed in 199 patients (41%), occurring after a median of 183 (124-360) days. AF recurrence was less frequent in paroxysmal AF patients compared to non-paroxysmal AF patients (34% vs. 54%, p < 0.001). Overall periprocedural complication rate was 6%. All scores, except the HATCH score, demonstrated statistically significant but poor predictive value for recurrent AF after ablation (area under curve [AUC] 0.553-0.669). CHA2DS2-VASc and CAAP-AF were the only risk scores with predictive value for procedural complications (AUC 0.616, p = 0.043; AUC 0.615, p = 0.044; respectively). CONCLUSIONS: Currently available risk scores perform poorly in predicting outcomes after AF ablation. These data suggest that the utility of these scores for clinical decision-making is limited.