Background: There is ambiguity whether frail patients with atrial fibrillation (AF) managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC).Methods... Show moreBackground: There is ambiguity whether frail patients with atrial fibrillation (AF) managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC).Methods: We conducted a pragmatic, multicenter, open-label, randomized controlled superiority trial. Older AF patients living with frailty (age >= 75 years plus a Groningen Frailty Indicator (GFI) score >= 3) were randomized to switch from INR-guided VKA treatment to a NOAC or to continued VKA treatment. Patients with a glomerular filtration rate <30 mLmin(-1)1.73 m(-2) or with valvular AF were excluded. Follow-up was 12 months. The cause-specific hazard ratio (HR) was calculated for occurrence of the primary outcome which was a major or clinically relevant non-major bleeding complication, whichever came first, accounting for death as a competing risk. Analyses followed the intention-to-treat principle. Secondary outcomes included thromboembolic events.Results: Between January 2018 and June 2022, a total of 2,621 patients were screened for eligibility and 1,330 patients were randomized (mean age 83 years, median GFI 4). After randomization 6 patients in the switch to NOAC arm and 1 patient in the continue with VKA arm were excluded due to the presence of exclusion criteria, leaving 662 patients switched from a VKA to a NOAC and 661 patients continued VKAs in the intention-to-treat population. After 163 primary outcome events (101 in the switch arm, 62 in the continue arm), the trial was stopped for futility according to a prespecified futility analysis. The HR for our primary outcome was 1.69 (95% CI 1.23-2.32). The HR for thromboembolic events was 1.26 (95% CI 0.60 to 2.61).Conclusions: Switching INR-guided VKA treatment to a NOAC in frail older patients with AF was associated with more bleeding complications compared to continuing VKA treatment, without an associated reduction in thromboembolic complications. Show less
Supplemental Digital Content is Available in the Text.Background:Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) is a prospective... Show moreSupplemental Digital Content is Available in the Text.Background:Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) is a prospective registry of outcomes from patients with newly diagnosed AF at risk of stroke. In the propensity score (PS)-matched global population of phase 3 GLORIA-AF, at 3 years, dabigatran-treated patients experienced reduced risk for major bleeding, and similar risk for stroke and myocardial infarction, compared with vitamin K antagonist (VKA)-treated patients.Study Question:Do patients in Eastern Europe benefit from treatment with dabigatran versus VKA?Study Design:Descriptive analysis, without PS matching. To contextualize the Eastern Europe results of GLORIA-AF phase 3, we also descriptively analyzed the global population without PS matching. Consecutive patients with newly diagnosed AF and CHA2DS2-VASc-score >= 1 were enrolled until December 2016 in 38 countries (9 in Eastern Europe).Measures and Outcomes:Three-year outcomes with dabigatran and VKA.Results:In Eastern Europe, 1341 patients were eligible (6% of patients globally), and incidence rates (per 100 patient-years) for the following outcomes were numerically lower with dabigatran (N = 498) versus VKA (N = 466): major bleeding (0.26 vs. 0.90), all-cause death (2.04 vs. 3.50), and a composite of stroke, systemic embolism, myocardial infarction, life-threatening bleeding, and vascular death (1.37 vs. 1.92); stroke was comparable (0.51 vs. 0.50). All incidence rates were numerically lower in Eastern Europe versus the global population for both treatments. Chronic concomitant use of high bleeding risk medications (eg, nonsteroidal anti-inflammatories) was lower in Eastern Europe (dabigatran 3.8%, VKA 9.3%) than globally (dabigatran 14.8%, VKA 20.6%) and persistence with dabigatran was higher in Eastern Europe (76%) than globally (64%).Conclusions:Dabigatran was associated with numerically reduced major bleeding, all-cause death, and cardiovascular (CV) composite, with comparable risk of stroke versus VKA, in Eastern Europe. Limitations of this descriptive analysis include few CV events (n = 11 for stroke, in the dabigatran and VKA groups combined) and a lack of statistical analysis and PS matching, which precludes definitive conclusions; however, the CV outcomes in Eastern Europe were consistent with the beneficial impact of dabigatran versus VKA in the statistically analyzed global population with PS matching. Show less
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, progressive in nature, and known to have a negative impact on mortality, morbidity, and quality of life. Patients requiring acute... Show moreAtrial fibrillation (AF) is the most prevalent cardiac arrhythmia, progressive in nature, and known to have a negative impact on mortality, morbidity, and quality of life. Patients requiring acute termination of AF to restore sinus rhythm are subjected to electrical cardioversion, which requires sedation and therefore hospitalization due to pain resulting from the electrical shocks. However, considering the progressive nature of AF and its detrimental effects, there is a clear need for acute out-of-hospital (i.e., ambulatory) cardioversion of AF. In the search for shock-free cardioversion methods to realize such ambulatory therapy, a method referred to as optogenetics has been put forward. Optogenetics enables optical control over the electrical activity of cardiomyocytes by targeted expression of light-activated ion channels or pumps and may therefore serve as a means for cardioversion. First proof-of-principle for such light-induced cardioversion came from in vitro studies, proving optogenetic AF termination to be very effective. Later, these results were confirmed in various rodent models of AF using different transgenes, illumination methods, and protocols, whereas computational studies in the human heart provided additional translational insight. Based on these results and fueled by recent advances in molecular biology, gene therapy, and optoelectronic engineering, a basis is now being formed to explore clinical translations of optoelectronic control of cardiac rhythm. In this review, we discuss the current literature regarding optogenetic cardioversion of AF to restore normal rhythm in a shock-free manner. Moreover, key translational steps will be discussed, both from a biological and technological point of view, to outline a path toward realizing acute shock-free ambulatory termination of AF. Show less
Background: Optogenetics could offer a solution to the current lack of an ambulatory method for the rapid automated cardioversion of atrial fibrillation (AF), but key translational aspects remain... Show moreBackground: Optogenetics could offer a solution to the current lack of an ambulatory method for the rapid automated cardioversion of atrial fibrillation (AF), but key translational aspects remain to be studied. Objective: To investigate whether optogenetic cardioversion of AF is effective in the aged heart and whether sufficient light penetrates the human atrial wall. Methods: Atria of adult and aged rats were optogenetically modified to express light-gated ion channels (i.e., red-activatable channelrhodopsin), followed by AF induction and atrial illumination to determine the effectivity of optogenetic cardioversion. The irradiance level was determined by light transmittance measurements on human atrial tissue. Results: AF could be effectively terminated in the remodeled atria of aged rats (97%, n = 6). Subsequently, ex vivo experiments using human atrial auricles demonstrated that 565-nm light pulses at an intensity of 25 mW/mm(2) achieved the complete penetration of the atrial wall. Applying such irradiation onto the chest of adult rats resulted in transthoracic atrial illumination as evidenced by the optogenetic cardioversion of AF (90%, n = 4). Conclusion: Transthoracic optogenetic cardioversion of AF is effective in the aged rat heart using irradiation levels compatible with human atrial transmural light penetration. Show less
Trinks-Roerdink, E.M.; Geersing, G.J.; Hemels, M.E.W.; Gelder, I.C. van; Klok, F.A.; Smeden, M. van; ... ; Doorn, S. van 2023
Objective Patients with cancer are at increased bleeding risk, and anticoagulants increase this risk even more. Yet, validated bleeding risk models for prediction of bleeding risk in patients with... Show moreObjective Patients with cancer are at increased bleeding risk, and anticoagulants increase this risk even more. Yet, validated bleeding risk models for prediction of bleeding risk in patients with cancer are lacking. The aim of this study is to predict bleeding risk in anticoagulated patients with cancer.Methods We performed a study using the routine healthcare database of the Julius General Practitioners’ Network. Five bleeding risk models were selected for external validation. Patients with a new cancer episode during anticoagulant treatment or those initiating anticoagulation during active cancer were included. The outcome was the composite of major bleeding and clinically relevant non-major (CRNM) bleeding. Next, we internally validated an updated bleeding risk model accounting for the competing risk of death.Results The validation cohort consisted of 1304 patients with cancer, mean age 74.0±10.9 years, 52.2% males. In total 215 (16.5%) patients developed a first major or CRNM bleeding during a mean follow-up of 1.5 years (incidence rate; 11.0 per 100 person-years (95% CI 9.6 to 12.5)). The c-statistics of all selected bleeding risk models were low, around 0.56. Internal validation of an updated model accounting for death as competing risk showed a slightly improved c-statistic of 0.61 (95% CI 0.54 to 0.70). On updating, only age and a history of bleeding appeared to contribute to the prediction of bleeding risk.Conclusions Existing bleeding risk models cannot accurately differentiate bleeding risk between patients. Future studies may use our updated model as a starting point for further development of bleeding risk models in patients with cancer. Show less
BackgroundCancer is suggested to confer thromboembolic and bleeding risk in patients with atrial fibrillation (AF).ObjectivesWe aimed to describe current anticoagulant practice in patients with AF... Show moreBackgroundCancer is suggested to confer thromboembolic and bleeding risk in patients with atrial fibrillation (AF).ObjectivesWe aimed to describe current anticoagulant practice in patients with AF and active cancer, present incidences of thromboembolic and bleeding complications, and evaluate the association between cancer type or anticoagulant management strategy with AF-related complications.MethodsThis retrospective study identified patients with AF and active cancer in 2 hospitals between January 1, 2012, and December 31, 2017. Follow-up lasted for 2 years. Data on cancer and anticoagulant treatment were collected. The outcomes of interest included ischemic stroke or transient ischemic attack (TIA) and clinically relevant nonmajor bleeding (CRNMB/MB). Incidence rates (IRs) per 100 patient-years and subdistribution hazard ratios (SHRs) with corresponding 95% Cis were estimated.ResultsWe identified 878 patients with AF who developed cancer (cohort 1) and 335 patients with cancer who developed AF (cohort 2). IRs for ischemic stroke/TIA and MB/CRNMB were 3.9 (2.8-5.3) and 15.7 (13.3-18.5) for cohort 1 and 4.0 (2.2-6.7) and 16.7 (12.6-21.7) for cohort 2. 14.2% (cohort 1) and 19.1% (cohort 2) of patients with a CHA2DS2-VASc score of ≥2 did not receive anticoagulant treatment. Withholding anticoagulants was associated with thromboembolic complications (SHR: 5.1 [3.20-8.0]). In nonanticoagulated patients with a CHA2DS2-VASc score of <2, IRs for stroke/TIA were 4.5 (0.75-15.0; cohort 1) and 16.0 (5.1-38.7; cohort 2).ConclusionPatients with AF and active cancer experience high rates of thromboembolic and bleeding complications, underlying the complexity of anticoagulant management in these patients. Our data suggest that the presence of cancer is an important factor in determining the indication for anticoagulants in patients with a low CHA2DS2-VASc score. Show less
Meucci, M.C.; Stassen, J.; Tomsic, A.; Palmen, M.; Crea, F.; Bax, J.J.; ... ; Delgado, V. 2022
Objective Left atrial (LA) and left ventricular (LV) mechanics are impaired in patients with atrial functional mitral regurgitation (AFMR), but their prognostic value in this subset of patients... Show moreObjective Left atrial (LA) and left ventricular (LV) mechanics are impaired in patients with atrial functional mitral regurgitation (AFMR), but their prognostic value in this subset of patients remains unknown. The present study aimed to evaluate the association between LA and LV longitudinal strain and clinical outcomes in patients with AFMR. Methods A total of 197 patients (mean age 73 +/- 10 years, 44% men) with at least moderate AFMR were retrospectively identified. LV global longitudinal strain (GLS) and left atrial reservoir strain (LAS) were calculated by two-dimensional speckle tracking echocardiography. All-cause mortality was the primary endpoint of the study. The threshold value of LV GLS (<= 16.3%) to identify impaired LV mechanics was defined based on the risk excess of the primary endpoint described with a spline curve analysis. Results Impaired LV GLS (<= 16.3%) was found in 89 (45%) patients. During a median follow-up of 69 months, 45 (23%) subjects experienced the primary endpoint. Patients with impaired LV GLS (<= 16.3%) had a significantly lower cumulative survival rate at 5 years, as compared with patients with LV GLS (>16.3%) (74% vs 93%, p<0.001). On multivariable Cox regression analysis, LV GLS expressed as continuous variable was independently associated with the occurrence of all-cause mortality (HR 0.856, 95% CI 0.763 to 0.960; p=0.008) after adjustment for age, LAS, pulmonary artery systolic pressure and severe tricuspid regurgitation. Conversely, LAS was not significantly associated with patients' outcome. Conclusions In patients with significant AFMR, the impairment of LV GLS was independently associated with worse outcomes. Show less
Background: Clinical complexity is common in atrial fibrillation (AF) patients. We assessed the impact of clinical complexity on oral anticoagulant (OAC) treatment patterns and major adverse... Show moreBackground: Clinical complexity is common in atrial fibrillation (AF) patients. We assessed the impact of clinical complexity on oral anticoagulant (OAC) treatment patterns and major adverse outcomes in a contemporary cohort of AF patients. Methods: The GLORIA-AF Phase II and III Registry enrolled newly diagnosed AF patients with at least one stroke risk factor. Among patients with CHA(2)DS(2)-VASc score >= 2, we defined four domains of perceived clinical complexity: frail elderly (age >= 75 years and body mass index <23 kg/m(2)), chronic kidney disease (CKD, creatinine clearance <60 mL/min), history of bleeding, and those with >= 2 of the above conditions. We evaluated the associations between clinical complexity domains and antithrombotic treatment prescription, risk of OAC discontinuation, and major adverse outcomes. Results: Among the 29,625 patients included (mean age 69.6 +/- 10.7 years, 44.2% females), 9,504 (32.1%) presented with at least one complexity criterion. Clinical complexity was associated with lower OAC prescription, with stronger associations in frail elderly (odds ratio [OR]: 0.47, 95% confidence interval [CI]: 0.36-0.62) and those with >= 2 complexity domains (OR: 0.50, 95% CI: 0.44-0.57). Risk of OAC discontinuation was higher among frail elderly (hazard ratio [HR]: 1.30, 95% CI: 1.00-1.69), CKD (HR: 1.10, 95% CI: 1.02-1.20), and those with >= 2 complexity domains (HR: 1.39, 95% CI: 1.23-1.57). Clinical complexity was associated with higher risk of the primary outcome of all-cause death, thromboembolism, and major bleeding, with the highest magnitude in those with >= 2 criteria (HR: 1.63, 95% CI: 1.43-1.86). Conclusion: In AF patients, clinical complexity influences OAC treatment management, and increases the risk of poor clinical outcomes. These patients require additional efforts, such as integrated care approach, to improve their management and prognosis. Show less
Fodi, E.; Geest, R.J. van der; Toth, A.; Simor, T. 2022
We present the case of a 58-year-old woman, suffering from high blood pressure, who presented with documented frequently occurring paroxysmal atrial fibrillation attacks. She underwent two prior... Show moreWe present the case of a 58-year-old woman, suffering from high blood pressure, who presented with documented frequently occurring paroxysmal atrial fibrillation attacks. She underwent two prior pulmonary vein isolations, but her palpitations did not cease. We aimed to achieve a long period free of symptoms, and a 3D MRI late enhancement scar map of the left atrium was obtained before the planned third pulmonary vein isolation procedure to visualize the assumed pulmonary vein reconnection sites. First, the endocardial and epicardial contours of the thin left atrial wall were manually determined on the images, then color-coding was added based on the trasmurality of contrast enhancement in the wall. The reconstructed 3D color-coded left atrial surface revealed the localization of left atrial antral wall scars. These images were integrated into the electroanatomical mapping system and ablation was carried out selectively on the spots showing gaps in the antral scar. Isolation was achieved in all four veins without any complications. The patient has become symptom-free for years now. The reconstructed left atrial 3D MRI images gained in an innovative process visualized the gaps in the previous ablation lines and these images were integrated to guide the first gap-closure redo pulmonary vein isolation procedure in Hungary. Show less
Background: Studies on the association of cerebrovascular risk factors to magnetic resonance imaging detected brain infarcts have been inconsistent, partly reflecting limits of assessment to... Show moreBackground: Studies on the association of cerebrovascular risk factors to magnetic resonance imaging detected brain infarcts have been inconsistent, partly reflecting limits of assessment to infarcts anywhere in the brain, as opposed to specific brain regions. We hypothesized that risk-factors may differ depending on where the infarct is located in subcortical-, cortical-, and cerebellar regions. Methods: Participants (n=2662, mean age 74.6 +/- 4.8) from the longitudinal population-based AGES (Age, Gene/Environment Susceptibility)-Reykjavik Study underwent brain magnetic resonance imaging at baseline and on average 5.2 years later. We assessed the number and location of brain infarcts (prevalent versus incident). We estimated the risk-ratios of prevalent (PRR) and incident (IRR) infarcts by baseline cerebrovascular risk-factors using Poisson regression. Results: Thirty-one percent of the study participants had prevalent brain infarcts and 21% developed new infarcts over 5 years. Prevalent subcortical infarcts were associated with hypertension (PRR, 2.7 [95% CI, 1.1-6.8]), systolic blood pressure (PRR, 1.2 [95% CI, 1.1-1.4]), and diabetes (PRR, 2.8 [95% CI, 1.9-4.1]); incident subcortical infarcts were associated with systolic (IRR, 1.2 [95% CI, 1.0-1.4]) and diastolic (IRR, 1.3 [95% CI, 1.0-1.6]) blood pressure. Prevalent and incident cortical infarcts were associated with carotid plaques (PRR, 1.8 [95% CI, 1.3-2.5] and IRR, 1.9 [95% CI, 1.3-2.9], respectively), and atrial fibrillation was significantly associated with prevalent cortical infarcts (PRR, 1.8 [95% CI, 1.2-2.7]). Risk-factors for prevalent cerebellar infarcts included hypertension (PRR, 2.45 [95% CI, 1.5-4.0]), carotid plaques (PRR, 1.45 [95% CI, 1.2-1.8]), and migraine with aura (PRR, 1.6 [95% CI, 1.1-2.2]). Incident cerebellar infarcts were only associated with any migraine (IRR, 1.4 [95% CI, 1.0-2.0]). Conclusions: The risk for subcortical infarcts tends to increase with small vessel disease risk-factors such as hypertension and diabetes. Risk for cortical infarcts tends to increase with atherosclerotic/coronary processes and risk for cerebellar infarcts with a more mixed profile of factors. Assessment of risk-factors by location of asymptomatic infarcts found on magnetic resonance imaging may improve the ability to target and optimize preventive therapeutic approaches to prevent stroke. Show less
BACKGROUND: Effective stroke prevention with oral anticoagulants (OAC) is recommended for some patients with atrial fibrillation (AF). We aimed to describe OAC use by geographical region and type... Show moreBACKGROUND: Effective stroke prevention with oral anticoagulants (OAC) is recommended for some patients with atrial fibrillation (AF). We aimed to describe OAC use by geographical region and type of site in patients with recent-onset AF enrolled in a large global registry. METHODS AND RESULTS: Eligible participants were recruited into GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation), a prospective observational cohort study from 2014 to 2016 in 4 international regions: North America, Europe, Asia, and Latin America. Cumulative incidence functions were generated for direct OACs (DOAC), vitamin K antagonists, and antiplatelet drugs considering competing risks, stratified by region and type of site. Time-to-treatment initiation after AF diagnosis was analyzed with Fine-Gray subdistribution hazard models. A total of 21 237 patients eligible for analysis were identified. By 30 days after AF diagnosis, 40%, 16%, and 8.6% of patients had DOAC, vitamin K antagonists, and antiplatelet drugs initiated, respectively. Earlier initiation of DOACs was observed in Europe, with Asia and Latin America having lower hazard rates of DOAC time-to-treatment initiation than Europe (hazard ratio [HR], 0.66; 95% CI, 0.62-0.70 and HR, 0.79; 95% CI, 0.73-0.85, respectively). DOAC initiation was highest in community hospitals, vitamin K antagonists in outpatient health care centers/anticoagulation clinics, and antiplatelet drugs in primary care clinics. CONCLUSIONS: Important geographic variability exists with the use of OACs for patients with AF. Differences in the time-to-treatment initiation of OAC by type of site suggests suboptimal implementation of guideline recommendations and could result in less benefit and more harm. Optimizing OAC use for patients with AF may improve outcomes and reduce health care costs. Show less
Background Atrial fibrillation (AF) can lead to the loss of microvascular integrity thereby enhancing AF progression. Mechanistically, the pro-coagulant state that drives the risk of stroke in... Show moreBackground Atrial fibrillation (AF) can lead to the loss of microvascular integrity thereby enhancing AF progression. Mechanistically, the pro-coagulant state that drives the risk of stroke in patients with AF may also play a causal role in microvascular loss. Direct oral anticoagulants (DOACs), the preferred anticoagulants for AF, can target factors upstream (factor Xa [FXa]) or downstream (thrombin) in the coagulation cascade and mediate differential vascular effects through interaction with protease-activated receptors (PARs). Objective To investigate the potential effect of different DOACs on vascular integrity. Methods To model the impact of DOACs on vascular integrity, we utilized platelet-free plasma in thrombin generation assays and endothelial barrier assays under identical experimental conditions. These multifactorial systems provide all coagulation factors and their respective natural inhibitors in physiological ratios in combination with the pro-coagulant endothelial surface on which coagulation is initiated. Furthermore, the system provides pro- and anti-barrier factors and monitoring both assays simultaneously permits coupling of thrombin kinetics to endothelial barrier dynamics. Results We provide evidence that the anti-FXa DOAC rivaroxaban and the anti-thrombin DOAC dabigatran are efficient in blocking their target proteases. However, while rivaroxaban could preserve endothelial barrier function, dabigatran failed to protect endothelial integrity over time, which could be prevented in the presence of a custom-made peptide that blocks thrombin's exosite-I. Conclusions Proteolytically inactive thrombin in complex with dabigatran evokes loss of barrier function that can be prevented by a protease-activated receptor-1 mimicking peptide blocking thrombin's exosite-I. Show less
Noseworthy, P.A.; Branda, M.E.; Kunneman, M.; Hargraves, I.G.; Sivly, A.L.; Brito, J.P.; ... ; SDM4AFib Shared Decision-Making At 2022
BACKGROUND Guidelines promote shared decision-making (SDM) for anticoagulation in patients with atrial fibrillation. We recently showed that adding a within-encounter SDM tool to usual care (UC)... Show moreBACKGROUND Guidelines promote shared decision-making (SDM) for anticoagulation in patients with atrial fibrillation. We recently showed that adding a within-encounter SDM tool to usual care (UC) increases patient involvement in decision-making and clinician satisfaction, without affecting encounter length. We aimed to estimate the extent to which use of an SDM tool changed adherence to the decided care plan and clinical safety end points. METHODS AND RESULTS We conducted a multicenter, encounter-level, randomized trial assessing the efficacy of UC with versus without an SDM conversation tool for use during the clinical encounter (Anticoagulation Choice) in patients with nonvalvular atrial fibrillation considering starting or reviewing anticoagulation treatment. We conducted a chart and pharmacy review, blinded to randomization status, at 10 months after enrollment to assess primary adherence (proportion of patients who were prescribed an anticoagulant who filled their first prescription) and secondary adherence (estimated using the proportion of days for which treatment was supplied and filled for direct oral anticoagulant, and as time in therapeutic range for warfarin). We also noted any strokes, transient ischemic attacks, major bleeding, or deaths as safety end points. We enrolled 922 evaluable patient encounters (Anticoagulation Choice=463, and UC=459), of which 814 (88%) had pharmacy and clinical follow-up. We found no differences between arms in either primary adherence (78% of patients in the SDM arm filled their first prescription versus 81% in UC arm) or secondary adherence to anticoagulation (percentage days covered of the direct oral anticoagulant was 74.1% in SDM versus 71.6% in UC; time in therapeutic range for warfarin was 66.6% in SDM versus 64.4% in UC). Safety outcomes, mostly bleeds, occurred in 13% of participants in the SDM arm and 14% in the UC arm. CONCLUSIONS In this large, randomized trial comparing UC with a tool to promote SDM against UC alone, we found no significant differences between arms in primary or secondary adherence to anticoagulation or in clinical safety outcomes. Show less
Background Non-valvular atrial fibrillation (NVAF) patients are advised to switch from a vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) when time in therapeutic range (TTR) is low.... Show moreBackground Non-valvular atrial fibrillation (NVAF) patients are advised to switch from a vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) when time in therapeutic range (TTR) is low. Objective To examine if pre-switch TTR determines persistence patterns in NVAF patients who are switched from a VKA to DOAC. Patients/Methods Adult NVAF patients from three Dutch anticoagulation clinics who were newly switched from a VKA to DOAC between July 1, 2013 and September 30, 2018 were stratified by pre-switch TTR levels. DOAC prescription records were examined to determine persistence patterns according to a 100-day prescription gap. Cumulative incidences of non-persistence to DOAC were estimated using the cumulative incidence competing risk method. The association of pre-switch TTR levels with DOAC non-persistence was evaluated by Cox regression models. Results A total of 3696 NVAF patients were included, of whom 690 (18.7%) had a pre-switch TTR <= 45%. After switching from VKA to DOAC, 14.0% (95% confidence interval [CI] 11.3-17.0%) of the patients with a pre-switch TTR <= 45% became non-persistent to DOAC within 1 year, while 9.8% (95% CI 8.7-11.0%) did in those with a pre-switch TTR > 45%. In a multivariable model, a pre-switch TTR <= 45% was associated with a higher risk of non-persistence to DOAC (adjusted hazard ratio 1.55, 95% CI 1.22-1.97). Results were similar when using other cut-off points (60% or 70%) to define a low TTR. Conclusion NVAF patients switching from VKA to DOAC due to a low pre-switch TTR saw a worse persistence pattern to DOAC after the switch compared to patients with a high pre-switch TTR. Show less
Background Non-valvular atrial fibrillation (NVAF) patients are advised to switch from a vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) when time in therapeutic range (TTR) is low.... Show moreBackground Non-valvular atrial fibrillation (NVAF) patients are advised to switch from a vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) when time in therapeutic range (TTR) is low. Objective To examine if pre-switch TTR determines persistence patterns in NVAF patients who are switched from a VKA to DOAC. Patients/Methods Adult NVAF patients from three Dutch anticoagulation clinics who were newly switched from a VKA to DOAC between July 1, 2013 and September 30, 2018 were stratified by pre-switch TTR levels. DOAC prescription records were examined to determine persistence patterns according to a 100-day prescription gap. Cumulative incidences of non-persistence to DOAC were estimated using the cumulative incidence competing risk method. The association of pre-switch TTR levels with DOAC non-persistence was evaluated by Cox regression models. Results A total of 3696 NVAF patients were included, of whom 690 (18.7%) had a pre-switch TTR <= 45%. After switching from VKA to DOAC, 14.0% (95% confidence interval [CI] 11.3-17.0%) of the patients with a pre-switch TTR <= 45% became non-persistent to DOAC within 1 year, while 9.8% (95% CI 8.7-11.0%) did in those with a pre-switch TTR > 45%. In a multivariable model, a pre-switch TTR <= 45% was associated with a higher risk of non-persistence to DOAC (adjusted hazard ratio 1.55, 95% CI 1.22-1.97). Results were similar when using other cut-off points (60% or 70%) to define a low TTR. Conclusion NVAF patients switching from VKA to DOAC due to a low pre-switch TTR saw a worse persistence pattern to DOAC after the switch compared to patients with a high pre-switch TTR. Show less
Simon, J.; Mahdiui, M. el; Smit, J.M.; Szaraz, L.; Rosendael, A.R. van; Herczeg, S.; ... ; Merkely, B. 2021
Introduction There are no consistently confirmed predictors of atrial fibrillation (AF) recurrence after catheter ablation. Therefore, we aimed to study whether left atrial appendage volume (LAAV)... Show moreIntroduction There are no consistently confirmed predictors of atrial fibrillation (AF) recurrence after catheter ablation. Therefore, we aimed to study whether left atrial appendage volume (LAAV) and function influence the long-term recurrence of AF after catheter ablation, depending on AF type. Methods AF patients who underwent point-by-point radiofrequency catheter ablation after cardiac computed tomography (CT) were included in this analysis. LAAV and LAA orifice area were measured by CT. Uni- and multivariable Cox proportional hazard regression models were performed to determine the predictors of AF recurrence. Results In total, 561 AF patients (61.9 +/- 10.2 years, 34.9% females) were included in the study. Recurrence of AF was detected in 40.8% of the cases (34.6% in patients with paroxysmal and 53.5% in those with persistent AF) with a median recurrence-free time of 22.7 (9.3-43.1) months. Patients with persistent AF had significantly higher body surface area-indexed LAV, LAAV, and LAA orifice area and lower LAA flow velocity, than those with paroxysmal AF. After adjustment left ventricular ejection fraction (LVEF) <50% (HR = 2.17; 95% CI = 1.38-3.43; p < .001) and LAAV (HR = 1.06; 95% CI = 1.01-1.12; p = .029) were independently associated with AF recurrence in persistent AF, while no independent predictors could be identified in paroxysmal AF. Conclusion The current study demonstrates that beyond left ventricular systolic dysfunction, LAA enlargement is associated with higher rate of AF recurrence after catheter ablation in persistent AF, but not in patients with paroxysmal AF. Show less
Sitges, M.; Marsan, N.A.; Cameli, M.; D'Andrea, A.; Carvalho, R.F.; Holte, E.; ... ; Dweck, M.R. 2021
Aims The aim of this study is to analyse how current recommendations on left ventricular (LV) diastolic function assessment have been adopted. Identifying potential discrepancies between... Show moreAims The aim of this study is to analyse how current recommendations on left ventricular (LV) diastolic function assessment have been adopted. Identifying potential discrepancies between recommendations and everyday clinical practice would enable us to better understand and address the remaining challenges in this controversial and complex field.Methods and results A total of 93 centres, mainly from tertiary care settings, responded to the survey. More than three-quarters (77%) of centres follow the 2016 ASE/EACVI recommendations for LV diastolic function evaluation in patients with preserved ejection fraction based upon e, E/e', tricuspid regurgitation velocity, and left atrial (LA) volume. These recommendations were generally preferred to the previous 2009 version. Many centres also consider strain assessments in the LV (48%) and left atrium (53%) as well as diastolic stress echocardiography (33%) to be useful as additional assessments of LV diastolic function. Echocardiographic assessments of LV diastolic function were used frequently to guide therapy in 72% of centres.Conclusion There is widespread adoption of current recommendation on the evaluation of LV diastolic function and these are frequently used to guide patient management. Many centres now also consider LV and LA strain assessments useful in the clinical assessment of diastolic function. These may be considered in future recommendations. Show less
Background Atrial fibrillation (AF) is a major risk factor for mortality. The prevalence, clinical correlates, and prognostic impact of AF in Takotsubo syndrome (TTS) have not yet been investigated... Show moreBackground Atrial fibrillation (AF) is a major risk factor for mortality. The prevalence, clinical correlates, and prognostic impact of AF in Takotsubo syndrome (TTS) have not yet been investigated in a large patient cohort. This study aimed to investigate the prevalence, clinical correlates, and prognostic impact of AF in patients with TTS. Methods and Results Patients with TTS were enrolled from the International Takotsubo Registry, which is a multinational network with 26 participating centers in Europe and the United States. Patients were dichotomized according to the presence or absence of AF at the time of admission. Of 1584 patients with TTS, 112 (7.1%) had AF. The mean age was higher (P<0.001), and there were fewer women (P=0.046) in the AF than in the non-AF group. Left ventricular ejection fraction was significantly lower (P=0.001), and cardiogenic shock was more often observed (P<0.001) in the AF group. Both in-hospital (P<0.001) and long-term mortality (P<0.001) were higher in the AF group. Multivariable Cox regression analysis revealed that AF was independently associated with higher long-term mortality (hazard ratio, 2.31; 95% CI, 1.50-3.55; P<0.001). Among patients with AF on admission, 42% had no known history of AF before the acute TTS event, and such patients had comparable in-hospital and long-term outcomes compared with those with a history of AF. Conclusions In patients presenting with TTS, AF on admission is significantly associated with increased in-hospital and long-term mortality rates. Whether antiarrhythmics and/or cardioversion are beneficial in TTS with AF should thus be tested in a future trial. Registration URL: ; Unique identifier: NCT01947621. Show less
Smit, J.M.; Simon, J.; Mahdiui, M. el; Szaraz, L.; Rosendael, P.J. van; Kolassvary, M.; ... ; Bax, J.J. 2021
Background: The left atrial appendage (LAA) has been regarded as an important source of cardiac thrombus formation and appears important in the contribution to thromboembolism in patients with... Show moreBackground: The left atrial appendage (LAA) has been regarded as an important source of cardiac thrombus formation and appears important in the contribution to thromboembolism in patients with atrial fibrillation (AF). Our aim was to evaluate the relationship between LAA morphology and previous stroke or transient ischemic attack in 2 large and distinct patient cohorts with and without known AF. Methods: The study population consisted of patients with and without drug-refractory AF who underwent computed tomography before transcatheter AF ablation or clinically indicated for suspected coronary artery disease. The computed tomography data were used for volumetric assessment of the left atrium and LAA and to determine LAA morphology. The LAA was classified by 3 readers in consensus as chicken wing, swan, cauliflower, or windsock, based on predefined morphology classification criteria. Results: In total, 1813 patients (mean age 59 +/- 11 years, 42% female) who underwent computed tomography were included in this analysis (908 patients with AF and 905 patients without known AF). Swan LAA morphology was independently associated with prior stroke/transient ischemic attack in the overall study population (odds ratio, 3.40, P<0.001), and in patients with (odds ratio, 2.88, P=0.012) and without known AF (odds ratio, 3.96, P=0.011). Conclusions: Swan morphology of the LAA is independently associated with prior stroke or transient ischemic attack in patients with known AF, as well as in patients not previously diagnosed with AF. Show less
