Diagnostic Yield of Genetic Testing in Young Patients With Atrioventricular Block of Unknown Cause.

Background The cause of atrioventricular block (AVB) remains unknown in approximately half of young patients with the diagnosis. Although variants in several genes associated with cardiac conduction diseases have been identified, the contribution of genetic variants in younger patients with AVB is unknown. Methods and Results Using the Danish Pacemaker and Implantable Cardioverter Defibrillator (ICD) Registry, we identified all patients younger than 50 years receiving a pacemaker because of AVB in Denmark in the period from January 1, 1996 to December 31, 2015. From medical records, we identified patients with unknown cause of AVB at time of pacemaker implantation. These patients were invited to a genetic screening using a panel of 102 genes associated with inherited cardiac diseases. We identified 471 living patients with AVB of unknown cause, of whom 226 (48%) accepted participation. Median age at the time of pacemaker implantation was 39 years (interquartile range, 32-45 years), and 123 (54%) were men. We found pathogenic or likely pathogenic variants in genes associated with or possibly associated with AVB in 12 patients (5%). Most variants were found in the LMNA gene (n=5). LMNA variant carriers all had a family history of either AVB and/or sudden cardiac death. Conclusions In young patients with AVB of unknown cause, we found a possible genetic cause in 1 out of 20 participating patients. Variants in the LMNA gene were most common and associated with a family history of AVB and/or sudden cardiac death, suggesting that genetic testing should be a part of the diagnostic workup in these patients to stratify risk and screen family members.

Usefulness of echocardiography for predicting ventricular tachycardia detected by implantable loop recorder in syncope patients.

Ventricular tachycardia (VT) may lead to syncope and sudden cardiac death. Implantable loop recorders (ILR) are recommended in the clinical work-up of patients with unexplained syncope. Our aim was to evaluate if echocardiographic parameters assessed prior to ILR implantation in patients with unexplained syncope may aid in identifying individuals with an increased risk of VT. The present study included 288 ambulatory patients (mean age 58 ± 19 years, 51% women) with syncope (90%) and presyncope (10%) who had an ILR implanted in the diagnostic workup. All patients underwent an echocardiographic examination prior to device implantation (median 3 months [IQR 1 to 6 months]). We examined incident VT, defined as a first-time episode of VT (> 30 s) or non-sustained VT (< 30 s) detected by the ILR. During median follow-up of 2.9 years [IQR 1.3 to 3.5 years] of continuous rhythm monitoring, 36 patients (13%) were diagnosed with incident VT (n = 25 non-sustained VT, n = 11 sustained VT). In unadjusted Cox proportional hazards models, left ventricular (LV) mass index (HR: 1.04 per 1 g/m2 increase [1.00 to 1.08], P = 0.047), mean LV wall thickness (HR: 1.36 per 1 mm increase [1.08 to 1.71], P = 0.009), and global longitudinal strain (HR: 1.15 per 1% decrease [1.05 to 1.25], P = 0.002) were significantly associated with VT. After adjusting for age, sex, implantable loop recorder indication and known heart failure, the above-mentioned parameters remained significantly associated with incident VT. LV mass index, LV wall thickness, and GLS may aid in identifying patients with increased risk of incident VT among patients with syncope. Echocardiography may potentially help select patients who can benefit from ILR.

Sex differences in echocardiographic predictors of bradycardia detected by implantable loop recorder in patients with syncope and palpitations.

OBJECTIVE: Our aim was to investigate whether echocardiography may aid in identifying patients, specifically men, at risk of bradycardia as detected by implantable loop recorders (ILR) in patients evaluated for syncope and palpitations. METHODS: We included ambulatory patients undergoing ILR implantation for syncope (84%), presyncope (9%), and palpitations (8%). Echocardiographic examination was performed prior to implantation (2.9 months [IQR 1.0-6.0 months]). Echocardiograms were analyzed for conventional and speckle tracking parameters. We examined time to first event of bradycardia, defined as (a) heart rate <30 beats/min and (b) ≥4 beats, including sinus arrest, asystole, sinoatrial block, and second- and third-degree atrioventricular nodal block. We applied Cox proportional hazards models. RESULTS: A total of 285 patients we enrolled, and during a median time of 2.7 years [IQR 1.0, 3.3 years] of continuous heart rhythm monitoring, 84 (29%) had bradycardia detected by ILR. Patients with bradycardia were older (61 ± 19 years vs 55 ± 18 years, P = .01) and more frequently men (62% vs 44%, P = .01). Sex modified the association between echocardiographic parameters and bradycardia (P interaction <0.05 for all), such that left ventricular LV mass index (HR: 1.02 per 1g/m2 increase [1.01-1.04], P < .001), LV ejection fraction (HR: 1.04 per 1% decrease [1.01-1.08], P = .02), and global longitudinal strain (HR: 1.09 per 1% decrease [1.01-1.19], P = .03) were associated with bradycardia in men but not women (P > .05 for all in female). After adjusting for baseline clinical characteristics, medical therapy, and loop indication, the abovementioned parameters remained significantly associated with incident bradycardia in men. CONCLUSION: Echocardiographic parameters of LV structure and function may potentially be more useful for predicting bradycardia in men than women, among patients undergoing ILR implantation for syncope, presyncope, and palpations.

Safety of Same-Day Discharge After Percutaneous Coronary Intervention in Selected Patients With Non-ST Elevation Acute Coronary Syndrome.

OBJECTIVES: We aimed to investigate the safety of same-day discharge (SDD) after percutaneous coronary intervention (PCI) for non-ST segment elevation acute coronary syndrome (NSTEACS), and to investigate the reduction in duration of hospitalization achievable by SDD. BACKGROUND: Previous studies have established the safety of SDD after elective PCI, while the safety of SDD after non-elective PCI for acute coronary syndrome has only been sparsely studied. METHODS: A single-center, observational, retrospective study of 923 consecutive procedures in patients with NSTEACS who had PCI was performed. The procedures were divided into 2 groups based on postprocedural management: SDD (n = 195) and non-SDD (n = 728). RESULTS: No differences were seen in the total number of adverse events at 1 month (1.5% SDD vs 1.4% non-SDD; P=.74), 3 months (2.5% SDD vs 2.3% non-SDD; P=.80), and 6 months (3.5% SDD vs 3.3% non-SDD; P=.84) after discharge, and there were no deaths in the SDD group. No difference was found in unplanned rehospitalizations within 6 months (20.5% SDD vs 25.3% non-SDD; P=.17), while unplanned revascularizations were more frequent in non-SDD patients (5.6% SDD vs 13.4% non-SDD; P<.01). Median duration of hospitalization was 1.3 days shorter for SDD patients than for non-elderly, uncomplicated non-SDD patients. CONCLUSIONS: SDD after PCI in a selected group of NSTEACS patients was associated with low rates of adverse events, unplanned rehospitalizations, and revascularizations. SDD was associated with a shorter hospitalization duration.

Risk factors and a 3-month risk score for predicting pacemaker implantation in patients with atrial fibrillations.

Objectives: To identify risk factors and to develop a predictive risk score for pacemaker implantation in patients with atrial fibrillation (AF). Methods: Using Danish nationwide registries, patients with newly diagnosed AF from 2000 to 2014 were identified. Cox proportional-hazards regression computed HRs for risk factors of pacemaker implantation. A logistic regression was used to fit a prediction model for 3-month risk of pacemaker implantation and derived a risk score using 80% of the data and its predictive accuracy estimated using the remaining 20%. Results: Among 155 934 AF patients included, the median age (IQR) was 75 (65-83) and 51.3% were men. During a median follow-up time of 3.4 (1.2-5.0) years, 8348 (5.4%) patients received a pacemaker implantation. Risk factors of pacemaker implantation were (in order of highest risk first) age above 60 years, congenital heart disease, heart failure at age under 60 years, prior syncope, valvular AF, hypertension, ischaemic heart disease, male sex and diabetes mellitus. The derived risk score assigns points ranging from 1 to 14 to each of these risk factors. The 3-month risk of pacemaker implantation increased from 0.4% (95% CI: 0.2 to 0.8) at 1 point to 2.6% (95% CI: 1.9 to 3.6) at 18 points. Area under the receiver operator characteristics curve was 62.9 (95% CI: 60.3 to 65.5). Conclusion: We highlighted risk factors of pacemaker implantation in newly diagnosed AF patients and created a risk score. The clinical utility of the risk score needs further investigation.

Left axis deviation in patients with left bundle branch block is a marker of myocardial disease associated with poor response to cardiac resynchronization therapy.

AIMS: Patients with left axis deviation (LAD) and left bundle branch block (LBBB) show less benefit from cardiac resynchronization therapy (CRT) compared to other LBBB-patients. This study investigates the reasons for this. METHODS: Sixty-eight patients eligible for CRT were included. Patients were divided into groups according to QRS-axis; normal axis (NA), left axis deviation (LAD) and right axis deviation (RAD). Before CRT implantation CMR imaging was performed to evaluate scar tissue. Echocardiography was performed before and after implantation. The electrical substrate was assessed by measuring interlead electrical delays. Response was evaluated after 8 months by left ventricular (LV) remodelling and clinical response. RESULTS: Forty-four (65%) patients were responders in terms of LV remodelling. The presence of LAD was found to be independently associated with a poor LV remodelling non-response OR 0.21 [95% CI 0.06-0.77] (p = 0.02). Patients with axis deviation had more myocardial scar tissue (1.3 ±â€¯0.6 vs. 0.9 ±â€¯0.6, P = 0.04), more severe LV hypertrophy (14 (64%) and 6 (60%) vs. 7 (29%), P = 0.05) and tended to have a shorter interlead electrical delay than patients with NA (79 ±â€¯40 ms vs. 92 ±â€¯48 ms, P = 0.07). A high scar tissue burden was more pronounced in non-responders (1.4 ±â€¯0.6 vs. 1.0 ±â€¯0.5, P = 0.01). CONCLUSIONS: LAD in the presence of LBBB is a predictor of poor outcome after CRT. Patients with LBBB and LAD have more scar tissue, hypertrophy and less activation delay.

GARFIELD-AF model for prediction of stroke and major bleeding in atrial fibrillation: a Danish nationwide validation study.

OBJECTIVES: To externally validate the accuracy of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) model against existing risk scores for stroke and major bleeding risk in patients with non-valvular AF in a population-based cohort. DESIGN: Retrospective cohort study. SETTING: Danish nationwide registries. PARTICIPANTS: 90 693 patients with newly diagnosed non-valvular AF were included between 2010 and 2016, with follow-up censored at 1 year. PRIMARY AND SECONDARY OUTCOME MEASURES: External validation was performed using discrimination and calibration plots. C-statistics were compared with CHA2DS2VASc score for ischaemic stroke/systemic embolism (SE) and HAS-BLED score for major bleeding/haemorrhagic stroke outcomes. RESULTS: Of the 90 693 included, 51 180 patients received oral anticoagulants (OAC). Overall median age (Q1, Q3) were 75 (66-83) years and 48 486 (53.5%) were male. At 1-year follow-up, a total of 2094 (2.3%) strokes/SE, 2642 (2.9%) major bleedings and 10 915 (12.0%) deaths occurred. The GARFIELD-AF model was well calibrated with the predicted risk for stroke/SE and major bleeding. The discriminatory value of GARFIELD-AF risk model was superior to CHA2DS2VASc for predicting stroke in the overall cohort (C-index: 0.71, 95% CI: 0.70 to 0.72 vs C-index: 0.67, 95% CI: 0.66 to 0.68, p<0.001) as well as in low-risk patients (C-index: 0.64, 95% CI: 0.59 to 0.69 vs C-index: 0.57, 95% CI: 0.53 to 0.61, p=0.007). The GARFIELD-AF model was comparable to HAS-BLED in predicting the risk of major bleeding in patients on OAC therapy (C-index: 0.64, 95% CI: 0.63 to 0.66 vs C-index: 0.64, 95% CI: 0.63 to 0.65, p=0.60). CONCLUSION: In a nationwide Danish cohort with non-valvular AF, the GARFIELD-AF model adequately predicted the risk of ischaemic stroke/SE and major bleeding. Our external validation confirms that the GARFIELD-AF model was superior to CHA2DS2VASc in predicting stroke/SE and comparable with HAS-BLED for predicting major bleeding.

Rate or Rhythm Control in Older Atrial Fibrillation Patients: Risk of Fall-Related Injuries and Syncope.

OBJECTIVES: Management of atrial fibrillation (AF) with rate and/or rhythm control could lead to fall-related injuries and syncope, especially in the older AF population. We aimed to determine the association of rate and/or rhythm control with fall-related injuries and syncope in a real-world older AF cohort. DESIGN: A retrospective cohort study. SETTING: Danish nationwide administrative registries from 2000 to 2015. PARTICIPANTS: A total of 100 935 patients with AF aged 65 years or older claiming prescription of rate-lowering drugs (RLDs) and/or anti-arrhythmic drugs (AADs) were included. We compared the use of rate-lowering monotherapy with rate-lowering dual therapy, AAD monotherapy, and AAD combined with rate-lowering therapy. MEASUREMENTS: Outcomes were fall-related injuries and syncope as a composite end point (primary) or separate end point (secondary). RESULTS: In this population, the median age was 78 years (interquartile range [IQR] = 72-84 y), and 53 481 (53.0%) were women. During a median follow-up of 2.1 years (IQR = 1.0-5.1), 17 132 (17.0%) experienced a fall-related injury, 5745 (5.7%) had a syncope, and 21 093 (20.9%) experienced either. Compared with rate-lowering monotherapy, AADs were associated with a higher risk of fall-related injuries and syncope. The incidence rate ratio (IRR) for the composite end point was 1.29 (95% confidence interval [CI]: 1.17-1.43) for AAD monotherapy and 1.46 [95% CI = 1.34-1.58] for AAD combined with rate-lowering therapy. When stratifying by individual drugs, amiodarone significantly increased the risk of fall-related injuries and syncope (IRR = 1.40 [1.26-1.55]). Compared with more than 180 days of rate-lowering monotherapy, a higher risk of all outcomes was seen in the first 90 days of any treatment; however, the greatest risk was in the first 14 days for those treated with AADs. CONCLUSION: In AF patients aged 65 years and older, AAD use was associated with a higher risk of fall-related injuries and syncope, and the risk was highest within the first 14 days for those treated with AADs. Only amiodarone use was associated with a higher risk. J Am Geriatr Soc 67:2023-2030, 2019.

Rate and rhythm therapy in patients with atrial fibrillation and the risk of pacing and bradyarrhythmia.

BACKGROUND: Management of atrial fibrillation (AF) with rate and rhythm therapy can cause bradyarrhythmia. OBJECTIVES: To assess overall risk, temporal risk, and subgroup at risk of bradyarrhythmia-related events by rate and/or rhythm therapy drugs. METHODS: Using Danish nationwide registries, patients with AF between 2000 and 2014 were included if prescribed with rate-lowering drugs (RLDs) or antiarrhythmic drugs (AADs). An adjusted time-dependent Poisson regression model estimated the association between RLDs and AADs with a composite endpoint of pacemaker, temporary pacing, and bradyarrhythmia hospitalization. Secondary outcomes were each individual event. RESULTS: Among 135,017 AF patients, 9196 (6.8%) patients experienced the composite endpoint with a median follow-up of 3.7 (interquartile range [IQR]: 1.6-7.0) years. Median age was 74 (IQR: 65-82) years and 47.6% were women. With rate-lowering monotherapy as the reference, the incidence rate ratios (IRR) (95% confidence interval) for the composite endpoint were 1.36 (1.29-1.43) for rate-lowering dual therapy, 1.62 (1.43-1.84) for antiarrhythmic monotherapy, and 2.49 (2.29-2.71) for AAD combined with RLDs. Similar trend was found for each secondary outcome. Particularly amiodarone increased the risk. This association was strongest within the first 2 weeks of treatment. In those treated with AAD combined with RLDs, high-risk populations were patients ≥70 years (IRR: 3.35 [2.51-4.45] compared to patients <60 years), and women (IRR: 1.35 [1.15-1.57], compared to men). CONCLUSIONS: In real-world AF patients, rate-lowering dual therapy, antiarrhythmic monotherapy, and AADs combined with RLDs were positively associated with bradyarrhythmia-related events. The risk was highest in those treated with amiodarone, in the initial 2 weeks of treatment, in women, and in the elderly.

Interlead electrical delays and scar tissue: Response to cardiac resynchronization therapy in patients with ischemic cardiomyopathy.

BACKGROUND: The importance of interlead electrical delays (IEDs) in the presence of scar tissue for response to cardiac resynchronization therapy (CRT) in patients with ischemic cardiomyopathy is poorly described. METHODS: Sixty-eight CRT patients with ischemic cardiomyopathy and left bundle branch block were included. IEDs, the time between sensing of native impulse at the RV lead and LV lead, were measured at implantation and after 8 months. Magnetic resonance imaging was used for assessment of scar tissue. Echocardiographic response was defined as ≥ 15% decrease in left ventricular end-systolic volume. New York Heart Association (NYHA) class, Minnesota Living with Heart Failure Questionnaire, and 6-minute walk-test were used to assess clinical response. RESULTS: A total of 44 patients (65 %) were responders to CRT. At implantation, IEDs were significantly longer among responders compared to nonresponders (RV-LV-IED: 87 ms ± 33 ms vs 65 ms ± 47 ms, P < 0.05), most evident in patients with QRS < 150 ms. Responders had less myocardial scar tissue than nonresponders (1 ± 0.5 vs 1.4 ± 0.6, P = 0.01). However, in the multivariate model including QRS duration and scar tissue, IEDs were independently associated with LV remodeling after CRT: odds ratio 3.99 [95% confidence interval 1.02-15.7] (P = 0.04). During the course of treatment, no changes were observed in IEDs among echocardiographic responders. CONCLUSION: RV-LV-IED was an independent marker of response in CRT patients with ischemic cardiomyopathy even in the presence of scar tissue and may be particularly useful in patients with QRS < 150 ms. CRT did not influence this measurement over time.

Patients with atrial fibrillation and permanent pacemaker: Temporal changes in patient characteristics and pharmacotherapy.

BACKGROUND: The management of patients with non-valvular atrial fibrillation (NVAF) with rate-lowering or anti-arrhythmic drugs has markedly changed over the last decade, but it is unknown how these changes have affected patients with NVAF with a permanent pacemaker (PPM). METHODS: Through Danish nationwide registries, patients with NVAF and a PPM were identified from 2001 to 2012. Changes in concomitant pharmacotherapy and comorbidities were tested using the Cochran-Armitage trend test and linear regression. Patients with NVAF were identified to calculate the proportional amount of PPM implants. RESULTS: A total of 12,231 NVAF patients with a PPM were included in the study, 55.6% of which were men. Median age was 78 years (interquartile range 70-84). From 2001 to 2012, the number of NVAF patients with a PPM increased from 850 to 1344, while the number of NVAF patients increased from 67,478 to 127,261. Thus, the proportional amount of NVAF patients with a PPM decreased from 1.3% to 1.1% (p = 0.015). Overall 45.9% had atrial fibrillation (AF) duration less than one year and the proportion declined from 55.5% to 42.4% (p <0.001). Diabetes mellitus increased from 7.2% to 16.8% (p <0.001). Heart failure (HF) decreased from 36.7% to 29.3% (p = 0.010) and ischemic heart disease (IHD) decreased from 32.4% to 26.1% (p <0.001). Beta-blocker use increased from 38.1% to 58.0% (p <0.001), while digoxin and anti-arrhythmic drug use decreased over time. CONCLUSION: From 2001 to 2012, the absolute number of NVAF patients with a PPM increased while the proportional amount decreased. The number of NVAF patients receiving a PPM within one year of AF diagnosis decreased. The prevalence of DM increased, while the prevalence of HF and IHD was high but decreasing. The use of beta-blockers increased markedly, while use of digoxin and anti-arrhythmic drugs decreased over time.

Infective endocarditis and risk of death after cardiac implantable electronic device implantation: a nationwide cohort study.

AIMS: To determine the incidence, risk factors, and mortality of infective endocarditis (IE) following implantation of a first-time, permanent, cardiac implantable electronic device (CIED). METHODS AND RESULTS: From Danish nationwide administrative registers (beginning in 1996), we identified all de-novo permanent pacemakers (PMs) and implantable cardioverter defibrillators (ICDs) together with the occurrence of post-implantation IE-events in the period from 2000-2012. Included were 43 048 first-time PM/ICD recipients. Total follow-up time was 168 343 person-years (PYs). The incidence rate (per 1000 PYs) of IE in PM was 2.1 (95% confidence interval [CI]: 1.7-2.6) for single chamber devices and 6.2 (95% CI: 4.5-8.7) for cardiac resynchronization therapy (CRT); similarly, the rate of IE in ICD was 3.7 (95% CI: 2.9-4.7) in single chamber devices and 6.3 (95% CI: 4.4-9.0) in CRT. In multivariable analysis, increased PM complexity served as independent risk factor for IE {dual chamber PM [hazard ratio (HR) 1.39; 95% CI: 1.07-1.80] and CRT [HR: 1.84; 95% CI: 1.20-2.84]}. During follow-up, generator replacement (HR: 2.79; 95% CI: 1.87-4.17) and lead revision (HR: 4.33; 95% CI: 3.25-5.78) in PMs were associated with increased risk. Corresponding estimates in ICDs were 2.49 (95% CI: 1.28-4.86) and 6.58 (95% CI: 4.49-9.63). Risk of death after IE was significantly increased in PM and ICD with HRs of 1.56 (95% CI: 1.33-1.82) and 2.63 (95% CI: 2.00-3.48), respectively. CONCLUSION: The risk of IE increased with increasing PM complexity. Other important risk factors were subsequent generator replacement and lead revision. IE was associated with an increased risk of mortality in the area of CIED.

Thiazolidinediones are associated with a decreased risk of atrial fibrillation compared with other antidiabetic treatment: a nationwide cohort study.

Aim: The aim of this study was to investigate the association between thiazolidinediones (TZDs) vs. other antidiabetic drugs and risk of atrial fibrillation (AF) in diabetic patients. Method and results: Diabetes mellitus (diabetes) increases the risk of AF by approximately 34%. TZD is an insulin sensitizer that also has anti-inflammatory effects, which might decrease the risk of AF compared with other antidiabetic drugs. We used data from the Danish nationwide registries to study 108 624 patients with diabetes and without prior AF who were treated with metformin or sulfonylurea as first-line drugs. The incidence of AF was significantly lower with TZD as the second-line antidiabetic treatment compared with other second-line antidiabetic drugs (P < 0.001). The 10 year cumulative incidence [95% confidence interval (95% CI)] of AF was 6.2% (3.1-9.3%) with TZD vs. 10.2% (9.8-10.6%) with other antidiabetic drugs. The decreased risk of AF remained significant after adjusting for age, sex, and comorbidities with a hazard ratio (95% CI) of 0.76 (0.57-1.00), P = 0.047 associated with TZD treatment compared with other antidiabetic drugs. Conclusion: Use of a TZD to treat diabetes was associated with reduced risk of developing AF compared with other antidiabetic drugs as second-line treatment.

Risk of Ischemic Stroke, Hemorrhagic Stroke, Bleeding, and Death in Patients Switching from Vitamin K Antagonist to Dabigatran after an Ablation.

BACKGROUND: Safety regarding switching from vitamin K antagonist (VKA) to dabigatran therapy in post-ablation patients has never been investigated and safety data for this is urgently needed. The objective of this study was to examine if switch from VKA to dabigatran increased the risk of stroke, bleeding, and death in patients after ablation for atrial fibrillation. METHODS: Through the Danish nationwide registries, patients with non-valvular atrial fibrillation undergoing ablation were identified, in the period between August 22nd 2011 and December 31st 2015. The risk of ischemic stroke, hemorrhagic stroke, bleeding, and death, related to switching from VKA to dabigatran was examined using a multivariable Poisson regression model, where Incidence rate ratios (IRR) were estimated using VKA as reference. RESULTS: In total, 4,236 patients were included in the study cohort. The minority (n = 470, 11%) switched to dabigatran in the follow up period leaving the majority (n = 3,766, 89%) in VKA treatment. The patients in the dabigatran group were older, were more often males, and had higher CHA2DS2-VASc, and HAS-BLED scores. The incident rates of bleeding and death were almost twice as high in the dabigatran group compared with the VKA group. When adjusting for the individual components included in the CHA2DS2-VASc and HAS-BLED scores, the multivariable Poisson analyses yielded a non-significant IRR (95%CI) of 1.64 (0.72-3.75) for bleeding and of 1.41 (0.66-3.00) for death associated with the dabigatran group, compared to the VKA group. A significant increased risk of bleeding was found in the 110mg bid group with an IRR (95%CI) of 4.49(1.40-14.5). CONCLUSION: Shifting from VKA to dabigatran after ablation was associated with twice as high incidence of bleeding compared to the incidence in patients staying in VKA treatment. The only significant increased risk found in the adjusted analyses was for bleeding with 110mg bid dabigatran and not for 150mg bid. Since there was no dose-response for bleeding, the switch from VKA to dabigatran in itself was not a risk factor for bleeding.

Cardioversion and Risk of Adverse Events with Dabigatran versus Warfarin-A Nationwide Cohort Study.

AIM: Cardioversion can rapidly and effectively restore sinus rhythm in patients with persistent atrial fibrillation. Since 2011 dabigatran has been available as an alternative to warfarin to prevent thromboembolic events in patients with non-valvular atrial fibrillation undergoing cardioversion. We studied time to cardioversion, risk of adverse events, and risk of readmission with atrial fibrillation after cardioversion according to anticoagulation therapy. METHODS AND RESULTS: Through the nationwide Danish registries we included 1,230 oral anticoagulation naïve patients with first time non-valvular atrial fibrillation and first time cardioversion from 2011 to 2012; 37% in the dabigatran group (n = 456), and 63% in the warfarin group (n = 774). Median time to cardioversion was 4.0 (interquartile range [IQR] 2.9 to 6.5) and 6.9 (IQR 3.9 to 12.1) weeks in the dabigatran and warfarin groups respectively, and the adjusted odds ratio of cardioversion within the first 4 weeks was 2.3 (95% confidence interval [CI] 1.7 to 3.1) in favor of dabigatran. The cumulative incidence of composite endpoint of stroke, bleeding or death were 2.0% and 1.0% at 30 weeks in the warfarin and dabigatran groups respectively, with an adjusted hazard ratio of 1.33 (95% CI 0.33 to 5.42). Cumulative incidence of readmission with atrial fibrillation after 30 weeks were 9% and 11% in the warfarin and dabigatran groups, respectively, and an adjusted hazard ratio of 0.66 (95% CI 0.41 to 1.08). CONCLUSION: Anticoagulation treatment with dabigatran allows shorter time to cardioversion for atrial fibrillation than warfarin, and appears to be an effective and safe alternative treatment strategy to warfarin.

Management and prognosis of atrial fibrillation in the diabetic patient.

The global burden of atrial fibrillation and diabetes mellitus (diabetes) is considerable, and prevalence rates are increasing. Diabetes is associated with an increased risk of developing atrial fibrillation; however, diabetes also influences the management and prognosis of atrial fibrillation. In the following article, the authors describe the association between diabetes and atrial fibrillation; specifically, the significance of diabetes on the risk of atrial fibrillation, ischemic stroke and bleeding complications associated with anticoagulation. In addition, the authors evaluate the risks and outcomes of heart failure and the success rates of both ablation and cardioversion in atrial fibrillation patients with diabetes. Finally, this article describes the association of HbA1c levels with the management and prognosis of atrial fibrillation patients.

Effects of pharmacological modulation of the ATP-sensitive potassium channels on the development of warm-up angina pectoris.

The aim of this study was to examine the effect of pharmacological modulation of the ATP-sensitive potassium channels in the development of warm-up angina pectoris. Thirty-one patients with stable angina pectoris, a positive exercise test and angiographically documented coronary artery disease underwent three exercise tests 90 min after receiving either glibenclamide 10.5 mg (an ATP-sensitive potassium channel blocker), pinacidil 25 mg (an ATP-sensitive potassium channel opener) or placebo in a blinded fashion. There was a 30-min recovery period between the first and the second test and 60 min between the second and the third test. The rate-pressure product at 1-mm ST-segment depression (ischemic threshold) and the maximum ST-segment depression (STD) adjusted to the highest rate-pressure product common to the three tests were analyzed. In the placebo group, there was a significant increase in the ischemic threshold during the second and third test and a significant decrease in the maximum adjusted STD during the second test which was lost during the third test. This apparent adaptation to exercise-induced ischemia was not seen in the glibenclamide-treated patients. In the pinacidil-treated patients, there was a paradoxical decrease in ischemic threshold during the second test with no change in maximum adjusted STD which tended to be lower than in the placebo-treated patients on each exercise test. This study confirms that the warm-up phenomenon can be induced during repeated exercise testing. The blockade of this phenomenon by glibenclamide suggests that the ATP-sensitive potassium channels may be involved in this potential protective mechanism. At the same time, the paradoxical response in the pinacidil-treated patients flags a warning that drugs acting on the sarcolemmal ATP-sensitive potassium channels may have a direct effect on the ST-segment that may interfere with the interpretation of the electrocardiogram.