Rotational thromboelastometry as a biomarker for mortality - The Maastricht Intensive Care COVID cohort.

BACKGROUND: Patients with severe coronavirus disease 2019 (COVID-19) present with persisting hypercoagulability, hypofibrinolysis and prolonged clot initiation as measured with viscoelastic assays. The objective of this study was to investigate the trajectories of traditional assays of hemostasis, routine and tissue plasminogen activator (tPA) rotational thromboelastometry (ROTEM) in COVID-19 patients and to study their association with mortality. METHODS: Patients enrolled within the Maastricht Intensive Care COVID (MaastrICCht) cohort were included. Traditional assays of hemostasis (prothrombin time; PT, fibrinogen and D-dimer) were measured daily and ROTEM EXTEM, FIBTEM and tPA assays were performed weekly. Trajectories of these biomarkers were analyzed over time for survivors and non-survivors using linear mixed-effects models. Additional Fine and Gray competing risk survival analysis was performed for the first available measurement after intubation. RESULTS: Of the 138 included patients, 57 (41 %) died in the intensive care unit (ICU). Over 450, 400 and 1900 individual measurements were available for analysis of routine, tPA ROTEM and traditional assays of hemostasis, respectively, with a median [IQR] follow-up of 15 [8-24] days. Non-survivors on average had prolonged CT (clotting time) and increased fibrinogen compared to survivors. MCF (maximum clot firmness), LOT (lysis onset time), LT (lysis time) and PT measurements increased more over time in non-survivors compared to survivors. Associations persisted after adjustment for demographics and disease severity. EXTEM and FIBTEM CT at intubation were associated with increased 45-day ICU mortality. CONCLUSIONS: ROTEM measurements demonstrate a further increase of hypercoagulability and (hypo)fibrinolysis parameters in non-survivors throughout ICU admission. Furthermore, prolonged CT at intubation was associated with higher 45-day ICU mortality.

Higher levels of circulating desphospho-uncarboxylated matrix Gla protein over time are associated with worse survival: the prospective Maastricht Intensive Care COVID cohort.

BACKGROUND: Extra-hepatic vitamin K-status, measured by dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), maintains vascular health, with high levels reflecting poor vitamin K status. The occurrence of extra-hepatic vitamin K deficiency throughout the disease of COVID-19 and possible associations with pulmonary embolism (PE), and mortality in intensive care unit (ICU) patients has not been studied. The aim of this study was to investigated the association between dp-ucMGP, at endotracheal intubation (ETI) and both ICU and six months mortality. Furthermore, we studied the associations between serially measured dp-ucMGP and both PE and mortality. METHODS: We included 112 ICU patients with confirmed COVID-19. Over the course of 4 weeks after ETI, dp-ucMGP was measured serially. All patients underwent computed tomography pulmonary angiography (CTPA) to rule out PE. Results were adjusted for patient characteristics, disease severity scores, inflammation, renal function, history of coumarin use, and coronary artery calcification (CAC) scores. RESULTS: Per 100 pmol/L dp-ucMGP, at ETI, the odds ratio (OR) was 1.056 (95% CI: 0.977 to 1.141, p = 0.172) for ICU mortality and 1.059 (95% CI: 0.976 to 1.059, p = 0.170) for six months mortality. After adjustments for age, gender, and APACHE II score, the mean difference in plasma dp-ucMGP over time of ICU admission was 167 pmol/L (95% CI: 4 to 332, p = 0.047). After additional adjustments for c-reactive protein, creatinine, and history of coumarin use, the difference was 199 pmol/L (95% CI: 50 to 346, p = 0.010). After additional adjustment for CAC score the difference was 213 pmol/L (95% CI: 3 to 422, p = 0.051) higher in ICU non-survivors compared to the ICU survivors. The regression slope, indicating changes over time, did not differ. Moreover, dp-ucMGP was not associated with PE. CONCLUSION: ICU mortality in COVID-19 patients was associated with higher dp-ucMGP levels over 4 weeks, independent of age, gender, and APACHE II score, and not explained by inflammation, renal function, history of coumarin use, and CAC score. No association with PE was observed. At ETI, higher levels of dp-ucMGP were associated with higher OR for both ICU and six month mortality in crude and adjusted modes, although not statistically significantly.

Atrial Ablation Lesion Evaluation by Cardiac Magnetic Resonance: Review of Imaging Strategies and Histological Correlations.

Cardiac magnetic resonance (CMR) imaging is a valuable noninvasive tool for evaluating tissue response following catheter ablation of atrial tissue. This review provides an overview of the contemporary CMR strategies to visualize atrial ablation lesions in both the acute and chronic postablation stages, focusing on their strengths and limitations. Moreover, the accuracy of CMR imaging in comparison to atrial lesion histology is discussed. T2-weighted CMR imaging is sensitive to edema and tends to overestimate lesion size in the acute stage after ablation. Noncontrast agent-enhanced T1-weighted CMR imaging has the potential to provide more accurate assessment of lesions in the acute stage but may not be as effective in the chronic stage. Late gadolinium enhancement imaging can be used to detect chronic atrial scarring, which may inform repeat ablation strategies. Moreover, novel imaging strategies are being developed, but their efficacy in characterizing atrial lesions is yet to be determined. Overall, CMR imaging has the potential to provide virtual histology that aids in evaluating the efficacy and safety of catheter ablation and monitoring of postprocedural myocardial changes. However, technical factors, scanning during arrhythmia, and transmurality assessment pose challenges. Therefore, further research is needed to develop CMR strategies to visualize the ablation lesion maturation process more effectively.

Cardiac Magnetic Resonance Imaging-Derived Left Atrial Characteristics in Relation to Atrial Fibrillation Detection in Patients With an Implantable Cardioverter-Defibrillator.

Background Among patients with an implantable cardioverter-defibrillator, a high prevalence of atrial fibrillation (AF) is present. Identification of AF predictors in this patient group is of clinical importance to initiate appropriate preventive therapeutic measures to reduce the risk of AF-related complications. This study assesses whether cardiac magnetic resonance imaging-derived atrial characteristics are associated with AF development in patients with a dual-chamber implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator, as detected by the cardiac implantable electronic device. Methods and Results This single-center retrospective study included 233 patients without documented AF history at the moment of device implantation (dual-chamber implantable cardioverter-defibrillator [63.5%] or cardiac resynchronization therapy defibrillator [36.5%]). All patients underwent cardiac magnetic resonance imaging before device implantation. Cardiac magnetic resonance-derived features of left atrial (LA) remodeling were evaluated in all patients. Detection of AF episodes was based on cardiac implantable electronic device interrogation. During a median follow-up of 6.1 years, a newly diagnosed AF episode was detected in 88 of the 233 (37.8%) patients with an ICD. In these patients, increased LA volumes and impaired LA function (LA emptying fraction and LA strain) were found as compared with patients without AF during follow-up. However, a significant association was only found in patients with dilated cardiomyopathy and not in patients with ischemic cardiomyopathy. Conclusions LA remodeling characteristics were associated with development of AF in patients with dilated cardiomyopathy but not patients with ischemic cardiomyopathy, suggesting different mechanisms of AF development in ischemic cardiomyopathy and dilated cardiomyopathy. Assessment of LA remodeling before device implantation might identify high-risk patients for AF.

Left atrial sphericity in relation to atrial strain and strain rate in atrial fibrillation patients.

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.

Feasibility of CMR Imaging during Biventricular Pacing: Comparison with Invasive Measurement as a Pathway towards a Novel Optimization Strategy.

OBJECTIVES: This prospective pilot study assessed the feasibility of cardiovascular magnetic resonance (CMR) imaging during biventricular (BIV) pacing in patients with a CMR conditional cardiac resynchronization therapy defibrillator (CRT-D) and compared the results with invasive volume measurements. METHODS: Ten CRT-D patients underwent CMR imaging prior to device implantation (baseline) and six weeks after device implantation, including CRT-on and CRT-off modes. Left ventricular (LV) function, volumes, and strain measurements of LV dyssynchrony and dyscoordination were assessed. Invasive pressure-volume measurements were performed, matching the CRT settings used during CMR. RESULTS: Post-implantation imaging enabled reliable cine assessment, but showed artefacts on late gadolinium enhancement images. After six weeks of CRT, significant reverse remodeling was observed, with a 22.7 ± 11% reduction in LV end-systolic volume during intrinsic rhythm (CRT-off). During CRT-on, the LV ejection fraction significantly improved from 27.4 ± 5.9% to 32.2 ± 8.7% (p < 0.01), and the strain assessment showed the abolition of the left bundle branch block contraction pattern. Invasively measured and CMR-assessed LV hemodynamics during BIV pacing were significantly associated. CONCLUSIONS: Post-CRT implantation CMR assessing acute LV pump function is feasible and provides important insights into the effects of BIV pacing on cardiac function and contraction patterns. LV assessment during CMR may constitute a future CRT optimization strategy.

Left atrial strain is associated with arrhythmia recurrence after atrial fibrillation ablation: Cardiac magnetic resonance rapid strain vs. feature tracking strain.

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.

Right atrial function and fibrosis in relation to successful atrial fibrillation ablation.

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.

Applications of rotational thromboelastometry in heparin monitoring in critical COVID-19 disease: Observations in the Maastricht Intensive Care COVID cohort.

Background: Critically ill COVID-19 patients are at risk for venous thromboembolism (VTE). Therefore, they receive thromboprophylaxis and, when appropriate, therapeutic unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). To monitor heparins in COVID-19 disease, whole-blood rotational thromboelastometry (ROTEM) may be a promising alternative to the aPTT and anti-Xa assays. Objective: To evaluate the ROTEM INTEM/HEPTEM ratios in mechanically ventilated COVID-19 patients treated with UFH and therapeutic LMWH. Material and methods: A subcohort of mechanically ventilated COVID-19 patients of the prospective Maastricht Intensive Care Covid (MaastrICCht) cohort was studied. Anti-Xa, aPTT, and ROTEM measurements following treatment with UFH or therapeutic dose of LMWH (nadroparin) were evaluated using uni- and multivariable linear regression analysis and receiver operating characteristics. Results: A total of 98 patients were included, of which 82 were treated with UFH and 16 with therapeutic LMWH. ROTEM-measured INTEM/HEPTEM CT ratio was higher in patients using UFH (1.4 [1.3-1.4]) compared to patients treated with LMWH (1.0 [1.0-1.1], p < 0.001). Both the aPTT and anti-Xa were associated with the CT ratio. However, the ß-regression coefficient (95%CI) was significantly higher in patients on UFH (0.31 (0.001-0.62)) compared to therapeutic LMWH (0.09 (0.05-0.13)) for comparison with the anti-Xa assay. Furthermore, ROC analysis demonstrated an area under the curve for detecting UFH of 0.936(0.849-1.00), 0.851(0.702-1.000), and 0.645(0.465-0.826) for the CT ratio, aPTT, and anti-Xa, respectively. Conclusion: The ROTEM INTEM/HEPTEM CT ratio appears a promising tool to guide anticoagulant therapy in ICU patients with COVID-19 disease, but associations with clinical endpoints are currently lacking.

Serial thrombin generation and exploration of alternative anticoagulants in critically ill COVID-19 patients: Observations from Maastricht Intensive Care COVID Cohort.

Background: COVID-19 associated coagulopathy (CAC) is associated with an increase in thromboembolic events. Current guidelines recommend prophylactic heparins in the management of CAC. However, the efficacy of this strategy in the intensive care population remains uncertain. Objective: We aimed to measure thrombin generation (TG) to assess CAC in intensive care unit (ICU) patients receiving thromboprophylaxis with low molecular weight heparin (LMWH) or unfractionated heparin (UFH). In addition, we performed statistical modeling to link TG parameters to patient characteristics and clinical parameters. Lastly, we studied the potency of different anticoagulants as an alternative to LMWH treatment in ex vivo COVID-19 plasma. Patients/Methods: We included 33 patients with confirmed COVID-19 admitted at the ICU. TG was measured at least twice over the course of 6 weeks after admission. Thrombin generation parameters peak height and endogenous thrombin potential (ETP) were compared to healthy controls. Results were subsequently correlated with a patient characteristics and laboratory measurements. In vitro spiking in TG with rivaroxaban, dabigatran, argatroban and orgaran was performed and compared to LMWH. Results: Anti-Xa levels of all patients remained within the therapeutic range throughout follow-up. At baseline, the mean (SE) endogenous thrombin potential (ETP) was 1,727 (170) nM min and 1,620 (460) nM min for ellagic acid (EA) and tissue factor (TF), respectively. In line with this we found a mean (SE) peak height of 353 (45) nM and 264 (96) nM for EA and TF. Although fluctuating across the weeks of follow-up, TG parameters remained elevated despite thromboprophylaxis. In vitro comparison of LMWHs and direct thrombin inhibitors (e.g., agratroban, dabigatran) revealed a higher efficacy in reducing coagulation potential for direct thrombin inhibition in both ellagic acid (EA) and tissue factor (TF) triggered TG. Conclusion: In a sub-group of mechanically ventilated, critically ill COVID-19 patients, despite apparent adequate anti-coagulation doses evaluated by anti-Xa levels, thrombin generation potential remained high during ICU admission independent of age, sex, body mass index, APACHE II score, cardiovascular disease, and smoking status. These observations could, only partially, be explained by (anti)coagulation and thrombosis, inflammation, and multi-organ failure. Our in vitro data suggested that direct thrombin inhibition compared with LMWH might offer an alternate, more effective anticoagulant strategy in COVID-19.

Pulmonary pathophysiology development of COVID-19 assessed by serial Electrical Impedance Tomography in the MaastrICCht cohort.

Patients with SARS-CoV-2 infection present with different lung compliance and progression of disease differs. Measures of lung mechanics in SARS-CoV-2 patients may unravel different pathophysiologic mechanisms during mechanical ventilation. The objective of this prospective observational study is to describe whether Electrical Impedance Tomography (EIT) guided positive end-expiratory pressure (PEEP) levels unravel changes in EIT-derived parameters over time and whether the changes differ between survivors and non-survivors. Serial EIT-measurements of alveolar overdistension, collapse, and compliance change in ventilated SARS-CoV-2 patients were analysed. In 80 out of 94 patients, we took 283 EIT measurements (93 from day 1-3 after intubation, 66 from day 4-6, and 124 from day 7 and beyond). Fifty-one patients (64%) survived the ICU. At admission mean PaO2/FiO2-ratio was 184.3 (SD 61.4) vs. 151.3 (SD 54.4) mmHg, (p = 0.017) and PEEP was 11.8 (SD 2.8) cmH2O vs. 11.3 (SD 3.4) cmH2O, (p = 0.475), for ICU survivors and non-survivors. At day 1-3, compliance was ~ 55 mL/cmH2O vs. ~ 45 mL/cmH2O in survivors vs. non-survivors. The intersection of overdistension and collapse curves appeared similar at a PEEP of ~ 12-13 cmH2O. At day 4-6 compliance changed to ~ 50 mL/cmH2O vs. ~ 38 mL/cmH2O. At day 7 and beyond, compliance was ~ 38 mL/cmH2O with the intersection at a PEEP of ~ 9 cmH2O vs. ~ 25 mL/cmH2O with overdistension intersecting at collapse curves at a PEEP of ~ 7 cmH2O. Surviving SARS-CoV-2 patients show more favourable EIT-derived parameters and a higher compliance compared to non-survivors over time. This knowledge is valuable for discovering the different groups.

Quantification of left atrial fibrosis by 3D late gadolinium-enhanced cardiac magnetic resonance imaging in patients with atrial fibrillation: impact of different analysis methods.

AIMS: Various methods and post-processing software packages have been developed to quantify left atrial (LA) fibrosis using 3D late gadolinium-enhancement cardiac magnetic resonance (LGE-CMR) images. Currently, it remains unclear how the results of these methods and software packages interrelate. METHODS AND RESULTS: Forty-seven atrial fibrillation (AF) patients underwent 3D-LGE-CMR imaging prior to their AF ablation. LA fibrotic burden was derived from the images using open-source CEMRG software and commercially available ADAS 3D-LA software. Both packages were used to calculate fibrosis based on the image intensity ratio (IIR)-method. Additionally, CEMRG was used to quantify LA fibrosis using three standard deviations (3SD) above the mean blood pool signal intensity. Intraclass correlation coefficients were calculated to compare LA fibrosis quantification methods and different post-processing software outputs. The percentage of LA fibrosis assessed using IIR threshold 1.2 was significantly different from the 3SD-method (29.80 ± 14.15% vs. 8.43 ± 5.42%; P < 0.001). Correlation between the IIR-and SD-method was good (r = 0.85, P < 0.001) although agreement was poor [intraclass correlation coefficient (ICC) = 0.19; P < 0.001]. One-third of the patients were allocated to a different fibrosis category dependent on the used quantification method. Fibrosis assessment using CEMRG and ADAS 3D-LA showed good agreement for the IIR-method (ICC = 0.93; P < 0.001). CONCLUSIONS: Both, the IIR1.2 and 3SD-method quantify atrial fibrotic burden based on atrial wall signal intensity differences. The discrepancy in the amount of LA fibrosis between these methods may have clinical implications when patients are classified according to their fibrotic burden. There was no difference in results between post-processing software packages to quantify LA fibrosis if an identical quantification method including the threshold was used.

Extent of Left Atrial Fibrosis Correlates with Descending Aorta Proximity at 3D Late Gadolinium Enhancement Cardiac MRI in Patients with Atrial Fibrillation.

Purpose: To determine whether the distance between the descending aorta and left atrial (LA) wall correlates with the amount of fibrosis quantified in the posterior left inferior pulmonary vein (LIPV) area of the LA in patients with atrial fibrillation (AF). Materials and Methods: In this retrospective study, patients with AF underwent cardiac MRI in sinus rhythm prior to a pulmonary vein isolation procedure (July 2018 to February 2020). The mean distance (distancemean) and shortest distance (distanceshort) between the descending aorta and the LA wall were measured on three-dimensional (3D) contrast-enhanced MR angiograms; distancemean was defined as the average of five measurements at different levels between the descending aorta and the LA wall. The extent of LA fibrosis, both global fibrosis and regional fibrosis within the LIPV area, was derived from postprocessed, 3D, late gadolinium-enhanced images. Associations between the extent of fibrosis and the proximity of the descending aorta were analyzed by using correlative and multivariable analyses. Results: A total of 47 (mean age, 60 years ± 8 [standard deviation]; 31 men) patients were included for analysis. The extent of fibrosis in the posterior LIPV area was correlated with the distancemean (r s = -0.48; P < .01) and distanceshort (r s = -0.49; P < .01). Patients with a short distance between the descending aorta and LA wall (defined as a distanceshort < 2 mm) had a higher percentage of fibrosis in the posterior LIPV area than patients with a distanceshort greater than 2 mm (38.7% ± 22.7 vs 21.2% ± 17.8; P < .01). Conclusion: The distance between the descending aorta and LA was correlated with the extent of quantified fibrosis within the posterior LIPV area.Keywords: MRI, Cardiac, Left Atrium Supplemental material is available for this article. © RSNA, 2022.

COVID-19 Coagulopathy: From Pathogenesis to Treatment.

Coronavirus disease 2019 (COVID-19) has emerged as a pandemic at the end of 2019 and continues to exert an unfavorable worldwide health impact on a large proportion of the population. A remarkable feature of COVID-19 is the precipitation of a hypercoagulable state, mainly in severe cases, leading to micro- and macrothrombosis, respiratory failure, and death. Despite the implementation of various therapeutic regimes, including anticoagulants, a large number of patients suffer from such serious complications. This review aims to describe the current knowledge on the pathophysiology of the coagulation mechanism in COVID-19. We describe the interplay between three important mediators of the disease and how this may lead to a hyperinflammatory and prothrombotic state that affects outcome, namely, the endothelium, the immune system, and the coagulation system. In line with the hypercoagulability state during COVID-19, we further review on the rare but severe vaccine-induced thrombotic thrombocytopenia. We also summarize and comment on available anticoagulant treatment options and include suggestions for some future treatment considerations for COVID-19 anticoagulation therapy.

Strategies for repeat ablation for atrial fibrillation: A multicentre comparison of nonpulmonary vein versus pulmonary vein target ablation.

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.

Radiofrequency ablation to achieve durable pulmonary vein isolation.

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.

Ablation Index-guided point-by-point ablation versus Grid annotation-guided dragging for pulmonary vein isolation: A randomized controlled trial.

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.

Impaired left atrial reservoir and conduit strain in patients with atrial fibrillation and extensive left atrial fibrosis.

BACKGROUND: Atrial fibrillation (AF) is associated with profound structural and functional changes in the atria. In the present study, we investigated the association between left atrial (LA) phasic function and the extent of LA fibrosis using advanced cardiovascular magnetic resonance (CMR) imaging techniques, including 3-dimensional (3D) late gadolinium enhancement (LGE) and feature tracking. METHODS: Patients with paroxysmal and persistent AF (n = 105) underwent CMR in sinus rhythm. LA global reservoir strain, conduit strain and contractile strain were derived from cine CMR images using CMR feature tracking. The extent of LA fibrosis was assessed from 3D LGE images. Healthy subjects underwent CMR and served as controls (n = 19). RESULTS: Significantly lower LA reservoir strain, conduit strain and contractile strain were found in AF patients, as compared to healthy controls (- 15.9 ± 3.8% vs. - 21.1 ± 3.6% P < 0.001, - 8.7 ± 2.7% vs. - 12.6 ± 2.5% P < 0.001 and - 7.2 ± 2.3% vs. - 8.6 ± 2.2% P = 0.02, respectively). Patients with a high degree of LA fibrosis (dichotomized by the median value) had lower reservoir strain and conduit strain compared to patients with a low degree of LA fibrosis (- 15.0 ± 3.9% vs. - 16.9 ± 3.3%, P = 0.02 and - 7.9 ± 2.7% vs. - 9.5 ± 2.6%, P = 0.01, respectively). In contrast, no difference was found for LA contractile strain (- 7.1 ± 2.4% vs. - 7.4 ± 2.3%, P = 0.55). CONCLUSIONS: Impaired LA reservoir and conduit strain are present in AF patients with extensive atrial fibrosis. Future studies are needed to examine the biologic nature of this association and possible therapeutic implications.

Comparison of the predictive value of ten risk scores for outcomes of atrial fibrillation patients undergoing radiofrequency pulmonary vein isolation.

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.

Serial markers of coagulation and inflammation and the occurrence of clinical pulmonary thromboembolism in mechanically ventilated patients with SARS-CoV-2 infection; the prospective Maastricht intensive care COVID cohort.

BACKGROUND: The incidence of pulmonary thromboembolism is high in SARS-CoV-2 patients admitted to the Intensive Care. Elevated biomarkers of coagulation (fibrinogen and D-dimer) and inflammation (c-reactive protein (CRP) and ferritin) are associated with poor outcome in SARS-CoV-2. Whether the time-course of fibrinogen, D-dimer, CRP and ferritin is associated with the occurrence of pulmonary thromboembolism in SARS-CoV-2 patients is unknown. We hypothesise that patients on mechanical ventilation with SARS-CoV-2 infection and clinical pulmonary thromboembolism have lower concentrations of fibrinogen and higher D-dimer, CRP, and ferritin concentrations over time compared to patients without a clinical pulmonary thromboembolism. METHODS: In a prospective study, fibrinogen, D-dimer, CRP and ferritin were measured daily. Clinical suspected pulmonary thromboembolism was either confirmed or excluded based on computed tomography pulmonary angiography (CTPA) or by transthoracic ultrasound (TTU) (i.e., right-sided cardiac thrombus). In addition, patients who received therapy with recombinant tissue plasminogen activator were included when clinical instability in suspected pulmonary thromboembolism did not allow CTPA. Serial data were analysed using a mixed-effects linear regression model, and models were adjusted for known risk factors (age, sex, APACHE-II score, body mass index), biomarkers of coagulation and inflammation, and anticoagulants. RESULTS: Thirty-one patients were considered to suffer from pulmonary thromboembolism ((positive CTPA (n = 27), TTU positive (n = 1), therapy with recombinant tissue plasminogen activator (n = 3)), and eight patients with negative CTPA were included. After adjustment for known risk factors and anticoagulants, patients with, compared to those without, clinical pulmonary thromboembolism had lower average fibrinogen concentration of - 0.9 g/L (95% CI: - 1.6 - - 0.1) and lower average ferritin concentration of - 1045 µg/L (95% CI: - 1983 - - 106) over time. D-dimer and CRP average concentration did not significantly differ, 561 µg/L (- 6212-7334) and 27 mg/L (- 32-86) respectively. Ferritin lost statistical significance, both in sensitivity analysis and after adjustment for fibrinogen and D-dimer. CONCLUSION: Lower average concentrations of fibrinogen over time were associated with the presence of clinical pulmonary thromboembolism in patients at the Intensive Care, whereas D-dimer, CRP and ferritin were not. Lower concentrations over time may indicate the consumption of fibrinogen related to thrombus formation in the pulmonary vessels.