Aims:The clinical risk profile of atrial fibrillation (AF) patients is different in men and women. Our aim was to identify sex differences in blood biomarkers in patients with paroxysmal AF.... Show moreAims:The clinical risk profile of atrial fibrillation (AF) patients is different in men and women. Our aim was to identify sex differences in blood biomarkers in patients with paroxysmal AF. Methods and results: Sex differences in 92 blood biomarkers were measured in 364 patients included in our discovery cohort, the identification of a risk profile to guide atrial fibrillation therapy (AF-RISK) study, assessed by multivariable logistic regression and enrichment pathway analysis. Findings were subsequently confirmed in 213 patients included in our validation cohort, the Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) study. In the discovery cohort, mean age was 59 +/- 12 years, 41% were women. CHA(2)DS(2)-VASc-score was 1.6 +/- 1.4. A total of 46% had hypertension, 10% diabetes, and 50% had heart failure, predominantly with preserved ejection fraction (47%). In women, activated leucocyte cell adhesion molecule (ALCAM) and fatty acid binding protein-4 (FABP-4) were higher. In men, matrix metalloproteinase-3 (MMP-3), C-C motif chemokine-16 (CCL-16), and myoglobin were higher. In the validation cohort, four out of five biomarkers could be confirmed: levels of ALCAM (P = 1.73 x 10(-4)) and FABP-4 (P = 2.46 x 10(-7)) and adhesion biological pathways [false discovery rate (FDR) = 1.23 x 10(-8)] were higher in women. In men, levels of MMP-3 (P = 4.31 x 10(-8)) and myoglobin (P = 2.10 x 10(-4)) and markers for extracellular matrix degradation biological pathways (FDR = 3.59 x 10(-9)) were higher. Conclusion: In women with paroxysmal AF, inflammatory biomarkers were more often higher, while in men with paroxysmal AF, biomarkers for vascular remodelling were higher. Our data support the clinical notion that pathophysiological mechanisms in women and men with AF may differ. Show less
Harlaar, N.; Oudeman, M.A.; Trines, S.A.; Ruiter, G.S. de; Mertens, B.J.; Khan, M.; ... ; Brakel, T.J. van 2021
OBJECTIVES: Catheter ablation of long-standing persistent atrial fibrillation (LSPAF) remains challenging, with suboptimal success rates obtained following multiple procedures. Thoracoscopic... Show moreOBJECTIVES: Catheter ablation of long-standing persistent atrial fibrillation (LSPAF) remains challenging, with suboptimal success rates obtained following multiple procedures. Thoracoscopic ablation has shown effective at creating transmural lesions around the pulmonary veins and box; however, long-term rhythm follow-up data are lacking. This study aims, for the first time, to assess the long-term outcomes of thoracoscopic pulmonary vein and box ablation in LSPAF.METHODS: Rhythm follow-up consisted of continuous rhythm monitoring using implanted loop recorders or 24-h Holter recordings. Rhythm status and touch-up interventions were assessed up to 5 years.RESULTS: Seventy-seven patients with symptomatic LSPAF underwent thoracoscopic ablation in 2 centres. Freedom from atrial arrhythmias at 5 years was 50% following a single thoracoscopic procedure and 68% allowing endocardial touch-up procedures (performed in 21% of patients). The mean atrial fibrillation burden in patients with continuous monitoring was reduced from 100% preoperatively to 0.1% at the end of the blanking period and 8.0% during the second year. Antiarrhythmic drug use decreased from 49.4% preoperative to 12.1% and 14.3% at 2 and 5 years, respectively (P < 0.001). Continuous rhythm monitoring resulted in higher recurrence detection rates compared to 24-h Holter monitoring at 2-year follow-up (hazard ratio: 6.5, P= 0.003), with comparable recurrence rates at 5-year follow-up.CONCLUSIONS: Thoracoscopic pulmonary vein and box isolation are effective in long-term restoration of sinus rhythm in LSPAF, especially when complemented by endocardial touch-up procedures, as demonstrated by the 68% freedom rate at 5 years. Continuous rhythm monitoring revealed earlier, but not more numerous documentation of recurrences at 5-year follow-up. Show less
Aims Persistence with direct oral anticoagulants (DOACs) has become a concern in non-valvular atrial fibrillation (NVAF) patients, but whether this affects prognosis is rarely studied. We... Show moreAims Persistence with direct oral anticoagulants (DOACs) has become a concern in non-valvular atrial fibrillation (NVAF) patients, but whether this affects prognosis is rarely studied. We investigated the persistence with oral anticoagulants (OACs) and its association with prognosis among a nationwide cohort of NVAF patients.Methods and results DOAC-naive NVAF patients who started to use DOACs for ischaemic stroke prevention between 2013 and 2018 were included using Dutch national statistics. Persistence with OACs was determined based on the presence of a 100-day gap between the last prescription and the end of study period. In 93 048 patients, 75.7% had a baseline CHA(2)DS(2)-VASc score of >= 2. The cumulative incidence of persistence with OACs was 88.1% [95% confidence interval (CI) 87.9-88.3%], 82.6% (95% CI 82.3-82.9%), 77.7% (95% CI 77.3-78.1%), and 72.0% (95% CI 71.5-72.5%) at 1, 2, 3, and 4 years after receiving DOACs, respectively. Baseline characteristics associated with better persistence with OACs included female sex, age range 65-74 years, permanent atrial fibrillation, previous exposure to vitamin K antagonists, stroke history (including transient ischaemic attack), and a CHA(2)DS(2)-VASc score >= 2. Non-persistence with OACs was associated with an increased risk of the composite outcome of ischaemic stroke and ischaemic stroke-related death [adjusted hazard ratio (aHR) 1.79, 95% CI 1.49-2.15] and ischaemic stroke (aHR 1.58, 95% CI 1.29-1.93) compared with being persistent with OACs.Conclusion At least a quarter of NVAF patients were non-persistent with OACs within 4 years, which was associated with poor efficacy of ischaemic stroke prevention. The identified baseline characteristics may help identify patients at risk of non-persistence. Show less
Aims Persistence with direct oral anticoagulants (DOACs) has become a concern in non-valvular atrial fibrillation (NVAF) patients, but whether this affects prognosis is rarely studied. We... Show moreAims Persistence with direct oral anticoagulants (DOACs) has become a concern in non-valvular atrial fibrillation (NVAF) patients, but whether this affects prognosis is rarely studied. We investigated the persistence with oral anticoagulants (OACs) and its association with prognosis among a nationwide cohort of NVAF patients.Methods and results DOAC-naive NVAF patients who started to use DOACs for ischaemic stroke prevention between 2013 and 2018 were included using Dutch national statistics. Persistence with OACs was determined based on the presence of a 100-day gap between the last prescription and the end of study period. In 93 048 patients, 75.7% had a baseline CHA(2)DS(2)-VASc score of >= 2. The cumulative incidence of persistence with OACs was 88.1% [95% confidence interval (CI) 87.9-88.3%], 82.6% (95% CI 82.3-82.9%), 77.7% (95% CI 77.3-78.1%), and 72.0% (95% CI 71.5-72.5%) at 1, 2, 3, and 4 years after receiving DOACs, respectively. Baseline characteristics associated with better persistence with OACs included female sex, age range 65-74 years, permanent atrial fibrillation, previous exposure to vitamin K antagonists, stroke history (including transient ischaemic attack), and a CHA(2)DS(2)-VASc score >= 2. Non-persistence with OACs was associated with an increased risk of the composite outcome of ischaemic stroke and ischaemic stroke-related death [adjusted hazard ratio (aHR) 1.79, 95% CI 1.49-2.15] and ischaemic stroke (aHR 1.58, 95% CI 1.29-1.93) compared with being persistent with OACs.Conclusion At least a quarter of NVAF patients were non-persistent with OACs within 4 years, which was associated with poor efficacy of ischaemic stroke prevention. The identified baseline characteristics may help identify patients at risk of non-persistence. Show less
Atrial fibrillation (AF) is a major cause of cardiovascular morbidity and mortality. To early detect and to avoid AF-related complications, several cardiac imaging modalities and approaches aim to... Show moreAtrial fibrillation (AF) is a major cause of cardiovascular morbidity and mortality. To early detect and to avoid AF-related complications, several cardiac imaging modalities and approaches aim to quantify the severity of the underlying atrial cardiomyopathy (i.e., the extent of atrial remodeling). However, most established cardiac imaging modalities just incorporate single components of atrial remodeling and do not reflect the complete multifactorial process, which may contribute to their limited predictive value. Echocardiography-derived PA-TDI duration is a sophisticated echocardiographic parameter to assess total atrial conduction time and directly reflects both electrical and structural changes to the atria. Therefore, PA-TDI duration provides a more comprehensive quantification of the extent of atrial remodeling than other imaging modalities. In this article we review the role of PA-TDI duration as a marker of atrial remodeling and summarize the available data on PA-TDI duration to identify patients at risk for AF, as well as to guide AF management. Moreover, we discuss how to assess PA-TDI duration and provide recommendations on the implementation of PA-TDI duration into routine clinical care. Graphic abstract Show less
Background: In patients with active cancer and atrial fibrillation (AF) anticoagulation, thrombotic and bleeding risk still entail uncertainty.Aim: We explored the results of an international... Show moreBackground: In patients with active cancer and atrial fibrillation (AF) anticoagulation, thrombotic and bleeding risk still entail uncertainty.Aim: We explored the results of an international survey examining the knowledge and behaviours of a large group of physicians.Methods and results: A web-based survey was completed by 960 physicians (82.4% cardiologists, 75.5% from Europe). Among the currently available anticoagulants for stroke prevention in patients with active cancer, direct oral anticoagulants (DOACs) were preferred by 62.6%, with lower values for low molecular weight heparin (LMWH) (24.1%) and for warfarin (only 7.3%). About 46% of respondents considered that DOACs should be used in all types of cancers except in non-operable gastrointestinal cancers. The lack of controlled studies on bleeding risk (33.5% of respondents) and the risk of drug interactions (31.5%) were perceived as problematic issues associated with use of anticoagulants in cancer. The decision on anticoagulation involved a cardiologist in 27.8% of cases, a cardiologist and an oncologist in 41.1%, and a team approach in 21.6%. The patient also was involved in decision-making, according to similar to 60% of the respondents. For risk stratification, use of CHA2DS2-VASc and HAS-BLED scores was considered appropriate, although not specifically validated in cancer patients, by 66.7% and 56.4%, respectively.Conclusion: This survey highlights that management of anticoagulation in patients with AF and active cancer is challenging, with substantial heterogeneity in therapeutic choices. Direct oral anticoagulants seems having an emerging role but still the use of LMWH remains substantial, despite the absence of long-term data on thromboprophylaxis in AF. Show less
Background: Data on the epidemiology and treatment of atrial fibrillation in the Africa/Middle East region are limited, and the use of novel oral anticoagulants and their effectiveness in real... Show moreBackground: Data on the epidemiology and treatment of atrial fibrillation in the Africa/Middle East region are limited, and the use of novel oral anticoagulants and their effectiveness in real-world clinical practice has not been evaluated.Methods and Results: This study used prospectively collected data from the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation (GLORIA-AF) to describe anticoagulant use and outcomes in Africa and the Middle East. Baseline characteristics of patients newly diagnosed with nonvalvular atrial fibrillation from Lebanon (242 patients, 40.3%), Saudi Arabia (236 patients, 39.3%), United Arab Emirates (87 patients, 14.5%), and South Africa (35 patients, 5.8%) were described, and clinical outcomes were investigated for all patients in this region who received dabigatran.In newly diagnosed patients (having a diagnosis within the last three months) with nonvalvular atrial fibrillation in Africa and the Middle East, the observed uptake of non-vitamin K oral anticoagulants was high in the first years following their availability; dabigatran was the most commonly used antithrombotic agent (314/600 patients), and only 1.5% of patients did not receive any antithrombotic therapy. Use of dabigatran was associated with a high persistence rate (>88% at 24 months) and low incidence rates of stroke, myocardial infarction, major bleeding, and all-cause mortality after 2 years of follow-up.Conclusions: Data from GLORIA-AF reveal a change in the landscape for stroke prevention in the AME region, and the results were consistent with those observed in the global GLORIA-AF registry, as well as those of randomized clinical trials. (C) 2021 The Authors. Published by Elsevier B.V. Show less
Jong, Y. de; Fu, E.L.; Diepen, M. van; Trevisan, M.; Szummer, K.; Dekker, F.W.; ... ; Ocak, G. 2021
Aims The increasing prevalence of ischaemic stroke (IS) can partly be explained by the likewise growing number of patients with chronic kidney disease (CKD). Risk scores have been developed to... Show moreAims The increasing prevalence of ischaemic stroke (IS) can partly be explained by the likewise growing number of patients with chronic kidney disease (CKD). Risk scores have been developed to identify high-risk patients, allowing for personalized anticoagulation therapy. However, predictive performance in CKD is unclear. The aim of this study is to validate six commonly used risk scores for IS in atrial fibrillation (AF) patients across the spectrum of kidney function.Methods and results Overall, 36 004 subjects with newly diagnosed AF from SCREAM (Stockholm CREAtinine Measurements), a healthcare utilization cohort of Stockholm residents, were included. Predictive performance of the AFI, CHADS(2), Modified CHADS(2), CHA(2)DS(2)-VASc, ATRIA, and GARFIELD-AF risk scores was evaluated across three strata of kidney function: normal kidney function [estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m(2)], mild CKD (eGFR 30-60 mL/min/1.73 m(2)), and advanced CKD (eGFR <30 mL/min/1.73 m(2)). Predictive performance was assessed by discrimination and calibration. During 1.9 years, 3069 (8.5%) patients suffered an IS. Discrimination was dependent on eGFR: the median c-statistic in normal eGFR was 0.75 (range 0.68-0.78), but decreased to 0.68 (0.58-0.73) and 0.68 (0.55-0.74) for mild and advanced CKD, respectively. Calibration was reasonable and largely independent of eGFR. The Modified CHADS(2) score showed good performance across kidney function strata, both for discrimination [c-statistic: 0.78 (95% confidence interval 0.77-0.79), 0.73 (0.71-0.74) and 0.74 (0.69-0.79), respectively] and calibration.Conclusion In the most clinically relevant stages of CKD, predictive performance of the majority of risk scores was poor, increasing the risk of misclassification and thus of over- or undertreatment. The Modified CHADS2 score performed good and consistently across all kidney function strata, and should therefore be preferred for risk estimation in AF patients. Show less
Objective: To investigate the association between body mass index (BMI) and oral anticoagulant (OAC) prescription in atrial fibrillation (AF).Methods: Patients with newly diagnosed non-valvular AF ... Show moreObjective: To investigate the association between body mass index (BMI) and oral anticoagulant (OAC) prescription in atrial fibrillation (AF).Methods: Patients with newly diagnosed non-valvular AF (< 3 months) with >= 1 stroke risk factors enrolled in the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) in Asia, Europe and North America were evaluated.Results: The cohort (n = 13,793) comprised patients from all BMI categories (kg/m(2)): 1.4% were underweight (<18.5), 27.3% had a normal BMI (18.5 to <25), 37.9% were overweight (25 to <30), 19.3% were moderately obese (30 to < 35), and 12.7% were morbidly obese (>= 35). The highest proportion of Asians had a BMI of 18.5 to <25 kg/m(2), while the highest proportion of patients from Europe and North America were overweight and a substantial proportion of North Americans morbidly obese. In the multivariable analysis, the probability ratio of non-prescription of OAC, as compared to normal BMI, decreased for overweight (RR = 0.907), moderately obese (RR = 0.802) and severe very severe obese patients (RR = 0.659). Moreover, the probability ratio of non-prescription of OACs was increased in the Asia or North America regions, as compared with Europe, in patients aged <65 years or female patients, as well as in patients with prior bleeding or vascular disease.Conclusions: The distribution of BMI differed among the continents. An increased BMI was associated with a lower probability of non-prescription of OACs, as compared with a normal BMI. The probability of non-prescription of OACs was increased in the Asia or North America regions, as compared with Europe. Show less
Aims This study aimed to describe baseline characteristics of patients with atrial fibrillation (AF) at risk of stroke with and without history of heart failure (HF) and report 2-year outcomes in... Show moreAims This study aimed to describe baseline characteristics of patients with atrial fibrillation (AF) at risk of stroke with and without history of heart failure (HF) and report 2-year outcomes in the dabigatran-treated subset of a prospective, global, observational study (GLORIA-AF).Methods and results Newly diagnosed patients with AF and CHA(2)DS(2)-VASc score >= 1 were consecutively enrolled. Baseline characteristics were assessed by the presence or absence of HF diagnosis at enrolment. Incidence rates for outcomes in dabigatran-treated patients were estimated with and without standardization by stroke (excluding HF component) and bleeding risk scores. A total of 15 308 eligible patients were enrolled, including 15 154 with known HF status; of these, 3679 (24.0%) had been diagnosed with HF, 11 475 (75.0%) had not. Among 4873 dabigatran-treated patients, 1169 (24.0%) had HF, and 3658 (75.1%) did not; the risk of stroke was high (CHA(2)DS(2)-VASc score >= 2) for 94.3% of patients with HF and 85.8% without, while 6.0% and 7.0%, respectively, had a high bleeding risk (HAS-BLED >= 3). Incidence rates of all-cause death in dabigatran-treated patients with and without HF, standardized for CHA(2)DS(2)-VASc and HAS-BLED scores, were 4.76 vs. 1.80 per 100 patient years (py), with roughly comparable rates of stroke (0.82 vs. 0.60 per 100 py) and major bleeding (1.20 vs. 0.92 per 100 py).Conclusions Patients with AF and history of HF may have greater disease burden at AF diagnosis and increased mortality rates vs. patients without HF. Stroke and major bleeding rates were roughly comparable between groups confirming the long-term safety and effectiveness of dabigatran in patients with HF. Show less
In recent years, as more and more experience has been gained with prescribing direct oral anticoagulants (DOACs), new research initiatives have emerged in the Netherlands to improve the safety and... Show moreIn recent years, as more and more experience has been gained with prescribing direct oral anticoagulants (DOACs), new research initiatives have emerged in the Netherlands to improve the safety and appropriateness of DOAC treatment for stroke prevention in patients with atrial fibrillation (AF). These initiatives address several contemporary unresolved issues, such as inappropriate dosing, non-adherence and the long-term management of DOAC treatment. Dutch initiatives have also contributed to the development and improvement of risk prediction models. Although fewer bleeding complications (notably intracranial bleeding) are in general seen with DOACs in comparison with vitamin K antagonists, to successfully identify patients with high bleeding risk and to tailor anticoagulant treatment accordingly to mitigate this increased bleeding risk, is one of the research aims of recent and future years. This review highlights contributions from the Netherlands that aim to address these unresolved issues regarding the anticoagulant management in AF in daily practice, and provides a narrative overview of contemporary stroke and bleeding risk assessment strategies. Show less
Spencer-Bonilla, G.; Thota, A.; Organick, P.; Ponce, O.J.; Kunneman, M.; Giblon, R.; ... ; Shared Decision Making Atrial Fibr 2020
BackgroundShared decision making (SDM) implementation remains challenging. The factors that promote or hinder implementation of SDM tools for use during the consultation, including contextual... Show moreBackgroundShared decision making (SDM) implementation remains challenging. The factors that promote or hinder implementation of SDM tools for use during the consultation, including contextual factors such as clinician burnout and organizational support, remain unclear. We explored these factors in the context of a practical multicenter randomized trial evaluating the effectiveness of an SDM conversation tool for patients with atrial fibrillation considering anticoagulation therapy.MethodsIn this cross-sectional study, we recruited clinicians who were regularly involved in conversations with patients regarding anticoagulation for atrial fibrillation. Clinicians reported their characteristics and burnout symptoms using the two-item Maslach Burnout Inventory. Clinicians were trained in using the SDM tool, and they recorded their perceptions of the tool's normalization potential using the Normalization MeAsure Development (NoMAD) survey instrument and verbally reflected on their answers to these survey questions. When possible, the training sessions and clinicians' verbal responses to the conversation tool were recorded.ResultsOur study comprised 183 clinicians recruited into the trial (168 with survey responses and 112 with recordings). Overall, clinicians gave high scores to the normalization potential of the intervention; they endorsed all domains of normalization to the same extent, regardless of site, clinician characteristics, or burnout ratings. In interviews, clinicians paid significant attention to making sense of the tool. Tool buy-in seemed to depend heavily on their ability to see the tool as accurate and "evidence-based" and their perceptions of having time in the consultation to use it.ConclusionsWhile time in the consultation remains a barrier, we did not find a significant association between burnout symptoms and normalization of an SDM conversation tool. Possible areas for improving the normalization of SDM conversation tools in clinical practice include enabling collaboration among clinicians to implement the tool and reporting how clinicians elsewhere use the tool. Direct measures of normalization (i.e., observing how often clinicians access the tool in practice outside of the clinical trial) may further elucidate the role that contextual factors, such as clinician burnout, play in the implementation of SDM.Trial registrationClinicalTrials.gov, NCT02905032. Registered on 9 September 2016. Show less
Ng, K.T.; Paassen, J. van; Langan, C.; Sarode, D.P.; Arbous, M.S.; Alston, R.P.; Dekkers, O. 2020
Corticosteroids are often administered prophylactically to attenuate the inflammatory response associated with cardiac surgery using cardiopulmonary bypass (CPB). However, the efficacy and safety... Show moreCorticosteroids are often administered prophylactically to attenuate the inflammatory response associated with cardiac surgery using cardiopulmonary bypass (CPB). However, the efficacy and safety profile of corticosteroids remain uncertain. The primary aim of this systematic review and meta-analysis was to investigate the effect of corticosteroids on mortality in adult cardiac surgery using CPB. Secondary aims were to examine the effect of corticosteroids on myocardial adverse events, pulmonary adverse events, atrial fibrillation, surgical site infection, gastrointestinal bleeding and duration of stay in the intensive care unit and hospital. Randomized controlled trials (RCTs) were systematically searched in electronic databases (MEDLINE, EMBASE, CINAHL, CENTRAL and Web of Science) from their inception until March 2019. Observational studies, case reports, case series and literature reviews were excluded. Sixty-two studies (n = 16 457 patients) were included in this meta-analysis. There was no significant difference in mortality between the corticosteroid and placebo groups [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.81-1.14; P = 0.65, participants = 14 693, studies = 24, evidence of certainty: moderate]. Compared to those receiving a placebo, patients who were given corticosteroids had a significantly higher incidence of myocardial adverse events (OR 1.17, 95% CI 1.03-1.33; P = 0.01, participants = 14 512, studies = 23) and a lower incidence of pulmonary adverse events (OR 0.86, 95% CI 0.75-0.98; P = 0.02, participants = 13 426, studies = 17). The incidences of atrial fibrillation (OR 0.87, 95% CI 0.81-0.94; P < 0.001, participants = 14 148, studies = 24) and surgical site infection (OR 0.81, 95% CI 0.73-0.90; P < 0.001, participants = 13 946; studies = 22) were all lower in patients who were given corticosteroids. In the present meta-analysis of 62 RCTs (16 457 patients), including the 2 major RCTs (SIRS and DECS trials: 12 001 patients), we found that prophylactic corticosteroids in cardiac surgery did not reduce mortality. The clinical significance of an increase in myocardial adverse events remains unclear as the definition of a relevant myocardial end point following cardiac surgery varied greatly between RCTs. Show less
Purpose To study whether polypharmacy or drug-drug interactions have differential effect on safety and efficacy in patients treated with direct oral anticoagulants (DOACs) versus warfarin.Methods... Show morePurpose To study whether polypharmacy or drug-drug interactions have differential effect on safety and efficacy in patients treated with direct oral anticoagulants (DOACs) versus warfarin.Methods We performed a systematic review and meta-analysis of studies that randomized patients with atrial fibrillation to DOACs or warfarin stratified by the number of concomitant drugs. Outcomes included stroke or systemic embolism (SE), all-cause mortality, major bleeding, and intracranial hemorrhage. Risk ratios (RR) were calculated and Mantel-Haenszel random effects were applied.Results Two high-quality studies were eligible, including 32,465 participants who received apixaban, rivaroxaban, or warfarin, with a median follow-up of 1.9 years. Of participants, 29% used < 5 drugs, 55% used 5-9 drugs, and 16% used >= 10 drugs. Drugs interacting with DOACs (P-glycoprotein/CYP3A4) were used by 6460 (20%) of patients. Patients with higher number of drugs (0-4 vs 5-9 vs >= 10) had higher rates of mortality (5.8%, 7.9%, 10.0%) and major bleeding (3.4%, 4.8%, 7.7%). Comparative efficacy or safety of DOACs versus warfarin was not affected by polypharmacy status or P-glycoprotein/CYP3A4 inhibitor use. However, the presence of polypharmacy (p = 0.001) or glycoprotein/CYP3A4-modulating drugs (p = 0.03) was correlated with increased risk of major bleeding when compared with warfarin. Overall, DOAC use was associated with a lower risk of stroke/SE (RR, 0.84; 95%CI, 0.74-0.94), all-cause mortality (RR, 0.91; 95%CI, 0.84-0.98), and intracranial hemorrhage (RR, 0.51; 95%CI, 0.38-0.70) compared with warfarin.Conclusions DOACs were more effective than warfarin, and at least as safe. Polypharmacy was associated with adverse outcomes and attenuated the advantage in risk of major bleeding among rivaroxaban users, particularly in the presence of P-glycoprotein/CYP3A4-modulating drugs. Show less
Chronic kidney disease (CKD) is a worldwide growing epidemic associated with an increased risk of cardiovascular morbidity and mortality. Heart failure is particularly frequent among patients... Show moreChronic kidney disease (CKD) is a worldwide growing epidemic associated with an increased risk of cardiovascular morbidity and mortality. Heart failure is particularly frequent among patients with CKD. Pressure and volume overload and non-hemodynamic factors associated with CKD induce left ventricular (LV) hypertrophy, reduce capillary density and increase myocardial fibrosis that lead to LV diastolic and systolic dysfunction. These processes have been proposed as important determinants of increased mortality in this population. The aim of this thesis was to evaluate cardiac mechanics using two-dimensional (speckle tracking) echocardiography and coronary computed tomography angiography in patients with CKD to define the prevalence and prognostic implications of cardiovascular diseases. In pre-dialysis and dialysis patients with preserved LV ejection fraction (LVEF), assessment of left ventricular global longitudinal strain (LV GLS) helps to identify patients with higher rates of heart failure hospitalization and all-cause mortality. When LVEF has already declined, patients within the lowest quartile of LV GLS showed worse prognosis compared to the other groups. The burden of cardiovascular diseases in patients with CKD is high and thorough assessment of cardiac mechanics with (advanced) echocardiographic techniques and coronary CTA helps in identifying patients with worse prognosis, who would potentially benefit of early treatment. Show less
Aims Pulmonary vein isolation (PVI), the standard for atrial fibrillation (AF) ablation, is most commonly applied with radiofrequency (RF) energy, although cryoballoon technology (CRYO) has gained... Show moreAims Pulmonary vein isolation (PVI), the standard for atrial fibrillation (AF) ablation, is most commonly applied with radiofrequency (RF) energy, although cryoballoon technology (CRYO) has gained widespread use. The aim was to compare the second-generation cryoballoon and the irrigated RF energy regarding outcomes and safety.Methods and results Of 4657 patients undergoing their first AF ablation, 982 with CRYO and 3675 with RF energy were included from the Swedish catheter ablation registry and the Atrial Fibrillation Ablation Long-Term registry of the European Heart Rhythm Association of the European Society of Cardiology. The primary endpoint was repeat AF ablation. The major secondary endpoints included procedural duration, tachyarrhythmia recurrence, and complication rate. The re-ablation rate after 12 months was significantly lower in the CRYO vs. the RF group, 7.8% vs. 11%, P=0.005, while freedom from arrhythmia recurrence (30 s duration) did not differ between the groups, 70.2 % vs. 68.2%, P=0.44. The result was not influenced by AF type and lesion sets applied. In the Cox regression analysis, paroxysmal AF had significantly lower risk for re-ablation with CRYO, hazard ratio 0.56 (P=0.041). Procedural duration was significantly shorter with CRYO than RF, (meanSD) 133.6 +/- 45.2 min vs. 174.6 +/- 58.2 min, P<0.001. Complication rates were similar; 53/982 (5.4%) vs. 191/3675 (5.2%), CRYO vs. RF, P=0.806.Conclusion The lower re-ablation rates and shorter procedure times observed with the cryoballoon as compared to RF ablation may have important clinical implications when choosing AF ablation technique despite recognized limitations with registries. Show less
Atrial fibrillation (AF) is the clinically most prevalent rhythm disorder with large impact on quality of life and increased risk for hospitalizations and mortality in both men and women. In recent... Show moreAtrial fibrillation (AF) is the clinically most prevalent rhythm disorder with large impact on quality of life and increased risk for hospitalizations and mortality in both men and women. In recent years, knowledge regarding epidemiology, risk factors, and patho-physiological mechanisms of AF has greatly increased. Sex differences have been identified in the prevalence, clinical presentation, associated comorbidities, and therapy outcomes of AF. Although it is known that age-related prevalence of AF is lower in women than in men, women have worse and often atypical symptoms and worse quality of life as well as a higher risk for adverse events such as stroke and death associated with AF. In this review, we evaluate what is known about sex differences in AF mechanisms-covering structural, electrophysiological, and hormonal factors-and underscore areas of knowledge gaps for future studies. Increasing our understanding of mechanisms accounting for these sex differences in AF is important both for prognostic purposes and the optimization of (targeted, mechanism-based, and sex-specific) therapeutic approaches. Show less
BACKGROUND The Shockless IMPLant Evaluation (SIMPLE) trial showed that defibrillation testing (DT) at the time of implantable cardioverter-defibrillator (ICD) implant did not improve shock efficacy... Show moreBACKGROUND The Shockless IMPLant Evaluation (SIMPLE) trial showed that defibrillation testing (DT) at the time of implantable cardioverter-defibrillator (ICD) implant did not improve shock efficacy or reduce mortality. There are no data regarding the risk of complications, including stroke, among patients with atrial fibrillation (AF) who undergo DT.OBJECTIVE The purpose of this prospectively planned substudy of SIMPLE was to evaluate the effect of DT vs no DT on clinical outcomes among patients with AF.METHODS We compared efficacy (failed appropriate shock/arrhythmic death) and safety between patients who had AF on their immediate preprocedural ECG to the rest of the study patients. Then among patients with AF we compared these outcomes between patients randomized to DT vs no DT.RESULTS Of the 2500 patients enrolled in SIMPLE, 251 (10%) were in AF immediately before ICD implant. AF patients had an increased risk of failed appropriate shock/arrhythmic death adjusted hazard ratio [HR] 1.64; 95% confidence interval [CI] 1.13-2.39; P = .009) and higher all-cause mortality (adjusted HR 1.58; 95% CI 1.2-2.08; P = .001). Among AF patients, perioperative complications and stroke did not significantly differ between DT vs no-DT groups (9.2% vs 5.4 0 /0; P = .2; and 1.7% vs 1.5%; P >.999, respectively). Failed appropriate shock or arrhythmic death occurred in 35 of 251 AF patients (14%), and the no-DT group proved not inferior to the DT group (HR 0.58; 95 0 /0 CI 0.30-1.15; P-noninferiority = .006).CONCLUSION ICD recipients with AF are at increased risk for adverse outcomes; however, DT does not improve arrhythmic survival or shock efficacy. There is no evidence that DT increased the occurrence of perioperative stroke. Show less
Bijl, P. van der; Vo, N.M.; Leung, M.; Marsan, N.A.; Delgado, V.; Stone, G.W.; Bax, J.J. 2018