Background: Left atrial appendage occlusion (LAAO) provides an alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). In patients with a long... Show moreBackground: Left atrial appendage occlusion (LAAO) provides an alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). In patients with a long-term or permanent contraindication for OAC ran-domized controlled trial (RCT) data is lacking. Study objectives: To assess the efficacy and safety of LAAO in AF patients who are ineligible to use OAC. The co-primary efficacy endpoint is (1) time to first occurrence of stroke (ischemic, hemorrhagic, or undetermined) and (2) time to first occurrence of the composite of stroke, transient ischemic attack (TIA), and systemic embolism (SE). The primary safety endpoint is the 30-day rate of peri-procedural complications. Study design: This is a multicenter, investigator-initiated, open-label, blinded endpoint (PROBE), superiority-driven RCT. Patients with AF, a CHA 2DS 2 -VASc score >= 2 for men and >= 3 for women and a long-term or permanent contraindica-tion for OAC will be randomized in a 2:1 fashion to the device- or control arm. Patients in the device arm will undergo percutaneous LAAO and will receive post-procedural dual antiplatelet therapy (DAPT) per protocol, while those in the control arm will continue their current treatment consisting of no antithrombotic therapy or (D)APT as deemed appropriate by the primary responsible physician. In this endpoint-driven trial design, assuming a 50% lower stroke risk of LAAO compared to conservative treatment, 609 patients will be followed for a minimum of 1 and a maximum of 5 years. Cost-effectiveness and budget impact analyses will be performed to allow decision-making on reimbursement of LAAO for the target population in the Netherlands. Summary: The COMPARE LAAO trial will investigate the clinical superiority in preventing thromboembolic events and cost-effectiveness of LAAO in AF patients with a high thromboembolic risk and a contraindication for OAC use. Show less
Nguyen, B.O.; Weberndorfer, V.; Crijns, H.J.G.M.; Geelhoed, B.; Cate, H. ten; Spronk, H.; ... ; Rienstra, M. 2022
Objective Atrial fibrillation (AF) often progresses from paroxysmal AF (PAF) to more permanent forms. To improve personalised medicine, we aim to develop a new AF progression risk prediction model... Show moreObjective Atrial fibrillation (AF) often progresses from paroxysmal AF (PAF) to more permanent forms. To improve personalised medicine, we aim to develop a new AF progression risk prediction model in patients with PAF.Methods In this interim-analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF study, patients with PAF undergoing extensive phenotyping at baseline and continuous rhythm monitoring during follow-up of >= 1 year were analysed. AF progression was defined as (1) progression to persistent or permanent AF or (2) progression of PAF with >3% burden increase. Multivariable analysis was done to identify predictors of AF progression.Results Mean age was 65 (58-71) years, 179 (43%) were female. Follow-up was 2.2 (1.6-2.8) years, 51 of 417 patients (5.5%/year) showed AF progression. Multivariable analysis identified, PR interval, impaired left atrial function, mitral valve regurgitation and waist circumference to be associated with AF progression. Adding blood biomarkers improved the model (C-statistic from 0.709 to 0.830) and showed male sex, lower levels of factor XIIa:C1-esterase inhibitor and tissue factor pathway inhibitor, and higher levels of N-terminal pro-brain natriuretic peptide, proprotein convertase subtilisin/kexin type 9 and peptidoglycan recognition protein 1 were associated with AF progression.Conclusion In patients with PAF, AF progression occurred in 5.5%/year. Predictors for progression included markers for atrial remodelling, sex, mitral valve regurgitation, waist circumference and biomarkers associated with coagulation, inflammation, cardiomyocyte stretch and atherosclerosis. These prediction models may help to determine risk of AF progression and treatment targets, but validation is needed. Show less
Aims: Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been... Show moreAims: Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular (CV) disease in association with COVID-19. Methods and results: A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, which was reported previously, focused on the epidemiology, pathophysiology, and diagnosis of CV conditions that may be manifest in patients with COVID-19. This second part addresses the topics of: care pathways and triage systems and management and treatment pathways, both of the most commonly encountered CV conditions and of COVID-19; and information that may be considered useful to help patients with CV disease (CVD) to avoid exposure to COVID-19. Conclusion: This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities. Show less
Aims: Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been... Show moreAims: Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two-part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular disease (CVD) in association with COVID-19. Methods and results: A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, reported here, focuses on the epidemiology, pathophysiology, and diagnosis of cardiovascular (CV) conditions that may be manifest in patients with COVID-19. The second part, which will follow in a later edition of the journal, addresses the topics of care pathways, treatment, and follow-up of CV conditions in patients with COVID-19. Conclusion: This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities. Show less
Aims: Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been... Show moreAims: Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two-part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular disease (CVD) in association with COVID-19. Methods and results: A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, reported here, focuses on the epidemiology, pathophysiology, and diagnosis of cardiovascular (CV) conditions that may be manifest in patients with COVID-19. The second part, which will follow in a later edition of the journal, addresses the topics of care pathways, treatment, and follow-up of CV conditions in patients with COVID-19. Conclusion: This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities. Show less
Aims: Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been... Show moreAims: Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular (CV) disease in association with COVID-19. Methods and results: A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, which was reported previously, focused on the epidemiology, pathophysiology, and diagnosis of CV conditions that may be manifest in patients with COVID-19. This second part addresses the topics of: care pathways and triage systems and management and treatment pathways, both of the most commonly encountered CV conditions and of COVID-19; and information that may be considered useful to help patients with CV disease (CVD) to avoid exposure to COVID-19. Conclusion: This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities. Show less
Fienieg, B.; Hassing, G.J.; Wall, H.E.C. van der; Westen, G.J.P. van; Kemme, M.J.B.; Adiyaman, A.; ... ; Gal, P. 2020
Background Previous studies reported that hypo- and hyperthermia are associated with several atrial and ventricular electrocardiographical parameters, including corrected QT (QTc) interval.... Show moreBackground Previous studies reported that hypo- and hyperthermia are associated with several atrial and ventricular electrocardiographical parameters, including corrected QT (QTc) interval. Enhanced characterization of variations in QTc interval and normothermic body temperature aids in better understanding the underlying mechanism behind drug induced QTc interval effects. The analysis' objective was to investigate associations between body temperature and electrocardiographical parameters in normothermic healthy volunteers.Methods Data from 3023 volunteers collected at our center were retrospectively analyzed. Subjects were considered healthy after review of collected data by a physician, including a normal tympanic body temperature (35.5-37.5 degrees C) and in sinus rhythm. A linear multivariate model with body temperature as a continuous was performed. Another multivariate analysis was performed with only the QT subintervals as independent variables and body temperature as dependent variable.Results Mean age was 33.8 +/- 17.5 years and mean body temperature was 36.6 +/- 0.4 degrees C. Body temperature was independently associated with age (standardized coefficient [SC] = -0.255, P < .001), female gender (SC = +0.209, P < .001), heart rate (SC = +0.231, P < .001), P-wave axis (SC = -0.051, P < .001), J-point elevation in lead V4 (SC = -0.121, P < .001), and QTcF duration (SC = -0.061, P = .002). In contrast, other atrial and atrioventricular (AV) nodal parameters were not independently associated with body temperature. QT subinterval analysis revealed that only QRS duration (SC = -0.121, P < .001) was independently associated with body temperature.Conclusion Body temperature in normothermic healthy volunteers was associated with heart rate, P-wave axis, J-point amplitude in lead V4, and ventricular conductivity, the latter primarily through prolongation of the QRS duration. Show less
Fienieg, B.; Hassing, G.J.; Wall, H.E.C. van der; Westen, G.J.P. van; Kemme, M.J.B.; Adiyaman, A.; ... ; Gal, P. 2020
BACKGROUNDPrevious studies reported that hypo- and hyperthermia are associated with several atrial and ventricular electrocardiographical parameters, including corrected QT (QTc) interval. Enhanced... Show moreBACKGROUNDPrevious studies reported that hypo- and hyperthermia are associated with several atrial and ventricular electrocardiographical parameters, including corrected QT (QTc) interval. Enhanced characterization of variations in QTc interval and normothermic body temperature aids in better understanding the underlying mechanism behind drug induced QTc interval effects. The analysis' objective was to investigate associations between body temperature and electrocardiographical parameters in normothermic healthy volunteers.METHODSData from 3023 volunteers collected at our center were retrospectively analyzed. Subjects were considered healthy after review of collected data by a physician, including a normal tympanic body temperature (35.5-37.5°C) and in sinus rhythm. A linear multivariate model with body temperature as a continuous was performed. Another multivariate analysis was performed with only the QT subintervals as independent variables and body temperature as dependent variable.RESULTSMean age was 33.8 ± 17.5 years and mean body temperature was 36.6 ± 0.4°C. Body temperature was independently associated with age (standardized coefficient [SC] = -0.255, P < .001), female gender (SC = +0.209, P < .001), heart rate (SC = +0.231, P < .001), P-wave axis (SC = -0.051, P < .001), J-point elevation in lead V4 (SC = -0.121, P < .001), and QTcF duration (SC = -0.061, P = .002). In contrast, other atrial and atrioventricular (AV) nodal parameters were not independently associated with body temperature. QT subinterval analysis revealed that only QRS duration (SC = -0.121, P < .001) was independently associated with body temperature.CONCLUSIONBody temperature in normothermic healthy volunteers was associated with heart rate, P-wave axis, J-point amplitude in lead V4, and ventricular conductivity, the latter primarily through prolongation of the QRS duration. Show less
Chu, G.; Seelig, J.; Trinks-Roerdink, E.M.; Alem, A.P. van; Alings, M.; Bemt, B. van den; ... ; Huisman, M.V. 2020
Introduction Anticoagulation therapy is pivotal in the management of stroke prevention in atrial fibrillation (AF). Prospective registries, containing longitudinal data are lacking with detailed... Show moreIntroduction Anticoagulation therapy is pivotal in the management of stroke prevention in atrial fibrillation (AF). Prospective registries, containing longitudinal data are lacking with detailed information on anticoagulant therapy, treatment adherence and AF-related adverse events in practice-based patient cohorts, in particular for non-vitamin K oral anticoagulants (NOAC). With the creation of DUTCH-AF, a nationwide longitudinal AF registry, we aim to provide clinical data and answer questions on the (anticoagulant) management over time and of the clinical course of patients with newly diagnosed AF in routine clinical care. Within DUTCH-AF, our current aim is to assess the effect of non-adherence and non-persistence of anticoagulation therapy on clinical adverse events (eg, bleeding and stroke), to determine predictors for such inadequate anticoagulant treatment, and to validate and refine bleeding prediction models. With DUTCH-AF, we provide the basis for a continuing nationwide AF registry, which will facilitate subsequent research, including future registry-based clinical trials.Methods and analysis The DUTCH-AF registry is a nationwide, prospective registry of patients with newly diagnosed 'non-valvular' AF. Patients will be enrolled from primary, secondary and tertiary care practices across the Netherlands. A target of 6000 patients for this initial cohort will be followed for at least 2 years. Data on thromboembolic and bleeding events, changes in antithrombotic therapy and hospital admissions will be registered. Pharmacy-dispensing data will be obtained to calculate parameters of adherence and persistence to anticoagulant treatment, which will be linked to AF-related outcomes such as ischaemic stroke and major bleeding. In a subset of patients, anticoagulation adherence and beliefs about drugs will be assessed by questionnaire.Ethics and dissemination This study protocol was approved as exempt for formal review according to Dutch law by the Medical Ethics Committee of the Leiden University Medical Centre, Leiden, the Netherlands. Results will be disseminated by publications in peer-reviewed journals and presentations at scientific congresses. Show less
Hassing, G.J.; Wall, H.E.C. van der; Westen, G.J.P. van; Kemme, M.J.B.; Adiyaman, A.; Elvan, A.; ... ; Gal, P. 2019
Elevated blood pressure induces electrocardiographic changes and is associated with an increase in cardiovascular disease later in life compared to normal blood pressure levels. The purpose of this... Show moreElevated blood pressure induces electrocardiographic changes and is associated with an increase in cardiovascular disease later in life compared to normal blood pressure levels. The purpose of this study was to evaluate the association between normal to high normal blood pressure values (90–139/50–89 mmHg) and electrocardiographic parameters related to cardiac changes in hypertension in healthy young adults.Data from 1449 volunteers aged 18–30 years collected at our centre were analyzed. Only subjects considered healthy by a physician after review of collected data with systolic blood pressure values between 90 and 139 mmHg and diastolic blood pressure values between 50 and 89 mmHg were included. Subjects were divided into groups with 10 mmHg systolic blood pressure increment between groups for analysis of electrocardiographic differences. Backward multivariate regression analysis with systolic and diastolic blood pressure as a continuous variable was performed.The mean age was 22.7 ± 3.0 years, 73.7% were male. P-wave area, ventricular activation time, QRS-duration, Sokolow–Lyon voltages, Cornell Product, J-point–T-peak duration corrected for heart rate and maximum T-wave duration were significantly different between systolic blood pressure groups. In the multivariate model with gender, body mass index and cholesterol, ventricular rate (standardized coefficient (SC): +0.182, p < .001), ventricular activation time in lead V6 (SC= +0.065, p = .048), Sokolow–Lyon voltage (SC= +0.135, p < .001), and Cornell product (SC= +0.137, p < .001) were independently associated with systolic blood pressure, while ventricular rate (SC= +0.179, p < .001), P-wave area in lead V1 (SC= +0.079, p = .020), and Cornell product (SC= +0.091, p = .006) were independently associated with diastolic blood pressure.Blood pressure-related electrocardiographic changes were observed incrementally in a healthy young population with blood pressure in the normal range. These changes were an increased ventricular rate, increased atrial surface area, ventricular activation time and increased ventricular hypertrophy indices on a standard 12 lead electrocardiogram. Show less
Hassing, G.J.; Wall, H.E.C. van der; Westen, G.J.P. van; Kemme, M.J.B.; Adiyaman, A.; Elvan, A.; ... ; Gal, P. 2019
IntroductionAn increased body mass index (BMI) (>25 kg/m2) is associated with a wide range of electrocardiographic changes. However, the association between electrocardiographic changes and BMI in... Show moreIntroductionAn increased body mass index (BMI) (>25 kg/m2) is associated with a wide range of electrocardiographic changes. However, the association between electrocardiographic changes and BMI in healthy young individuals with a normal BMI (18.5–25 kg/m2) is unknown. The aim of this study was to evaluate the association between BMI and electrocardiographic parameters.MethodsData from 1,290 volunteers aged 18 to 30 years collected at our centre were analysed. Only subjects considered healthy by a physician after review of collected data with a normal BMI and in sinus rhythm were included in the analysis. Subjects with a normal BMI (18.5–25 kg/m2) were divided into BMI quartiles analysis and a backward multivariate regression analysis with a normal BMI as a continuous variable was performed.ResultsMean age was 22.7 ± 3.0 years, mean BMI was 22.0, and 73.4% were male. There were significant differences between the BMI quartiles in terms of maximum P-wave duration, P-wave balance, total P-wave area in lead V1, PR-interval duration, and heart axis. In the multivariate model maximum P-wave duration (standardised coefficient (SC) = +0.112, P < 0.001), P-wave balance in lead V1 (SC = +0.072, P < 0.001), heart axis (SC = −0.164, P < 0.001), and Sokolow-Lyon voltage (SC = −0.097, P < 0.001) were independently associated with BMI.ConclusionIncreased BMI was related with discrete electrocardiographic alterations including an increased P-wave duration, increased P-wave balance, a leftward shift of the heart axis, and decreased Sokolow-Lyon voltage on a standard twelve lead electrocardiogram in healthy young individuals with a normal BMI. Show less
Huisman, M.V.; Rothman, K.J.; Paquette, M.; Teutsch, C.; Diener, H.C.; Dubner, S.J.; ... ; Frappe, T 2017
Pressure-Volume Loop Analyses during CRT Implants. Introduction: cardiac resynchronization therapy (CRT) may improve prognosis in patients with chronic right ventricular (RV) pacing, and optimal... Show morePressure-Volume Loop Analyses during CRT Implants. Introduction: cardiac resynchronization therapy (CRT) may improve prognosis in patients with chronic right ventricular (RV) pacing, and optimal lead position can decrease nonresponders. We evaluated the clinical and echocardiographic response to CRT in patients with previous chronic RV pacing, using pressure-volume loop analyses to determine the optimal left ventricular (LV) lead position during implantation. Methods and Results: In this single-blinded, randomized, controlled crossover study, 40 patients with chronic RV apical pacing and symptoms of heart failure, decreased LV ejection fraction (LVEF) or dyssynchrony were included. During implantation, stroke work (SW), LVEF, cardiac output, and LV dP/dt(max) were assessed by a conductance catheter. Clinical and echocardiographic response was studied during a 3-month period of RV pacing (RV period, LV lead inactive) and a 3-month period of biventricular pacing (CRT period). At the optimal LV lead position, SW (37 ± 41%), LVEF (16 ± 13%), cardiac output (29 ± 16%), and LV dP/dt(max) increased (11 ± 11%) significantly during biventricular pacing compared to baseline. Additional benefit could be achieved by pressure-volume loop guided selection of the best left-sided pacing location. RV outflow tract pacing did not improve hemodynamics. During follow-up, symptoms improved during CRT, VO(2,max) increased 10% and significant improvements in LVEF, LV volumes, and mitral regurgitation were observed as compared to the RV period. Conclusions: CRT in patients with chronic RV pacing causes significant improvement of both LV function as measured by pressure-volume loops during implantation and clinical and echocardiographic improvement during follow-up. Pressure-volume loops during implantation may facilitate selection of the most optimal pacing site. (J Cardiovasc Electrophysiol, Vol. pp. 1-7). Show less
