BACKGROUND:Glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy is increasingly used, but the physiological effects in patients with heart failure and reduced ejection fraction (HFrEF) remain uncertain. Continuously collected data from implantable cardiac devices may enable evaluation of drug effects in a real-world setting. METHODS:In a nationwide Danish retrospective matched cohort study, GLP-1RA initiators with implantable cardiac devices were matched 1:5 to unexposed device recipients by sex and age. Sensor data were assessed from 30 days before to 30 days after initiation. Primary outcomes were changes in heart rate and thoracic impedance. Analyses were adjusted for baseline sensor value, BMI category, hypertension, and type 2 diabetes. Prespecified subgroup analyses were performed in patients with HFrEF. RESULTS:In 666 patients (111 GLP-1RA initiators, 555 matched controls), semaglutide was used in 95% of initiators. Compared with controls, GLP-1RA initiation was associated with higher night heart rate (adjusted difference 2.12 bpm; 95% CI, 1.38 to 2.87), higher daily heart rate (1.46 bpm; 95% CI, 0.65 to 2.06), and higher thoracic impedance (0.66 Ω; 95% CI, 0.17 to 1.15) (all P<0.01). S1 amplitude decreased (-0.09 mG; 95% CI, -0.14 to -0.04; P<0.01). Heart rate increases followed a stepwise pattern across semaglutide dose levels, with an average increase of 2.5 bpm per dose escalation. Findings were directionally consistent in patients with HFrEF (GLP-1RA n=80), with no evidence of effect modification. CONCLUSION:GLP-1RA initiation was associated with measurable changes in device-derived physiology. Larger studies are needed to evaluate clinical implications, including in HFrEF. TRIAL REGISTRATION:Clinicaltrials.gov (NCT06099158).

BACKGROUND:Cardiac resynchronization therapy (CRT) in patients with symptomatic heart failure and left bundle branch block (LBBB) can be achieved with biventricular pacing (BIV-CRT) or conduction system pacing (CSP-CRT). OBJECTIVES:The present study examined if CSP-CRT was feasible and noninferior to BIV-CRT. METHODS:A total of 150 patients with symptomatic heart failure, left ventricular ejection fraction (LVEF) ≤35%, and LBBB (Strauss criteria) were included. Patients were randomized 1:2 to either BiV-CRT or CSP-CRT (HIS-CRT or LBB-CRT) and followed for 6 months. The primary endpoint was the relative change in left ventricular end-systolic volume (LVESV). Two patients withdrew their consent before implant. RESULTS:At implantation, 15 patients (15 %) crossed over from the CSP-CRT group to the BiV-CRT group and 1 patient crossed over from BiV-CRT to the CSP-CRT group. Accordingly, 85 patients (57 %) were treated with CSP-CRT (26 His-CRT, 59 patients LBB-CRT) and 63 patients (43 %) with BiV-CRT. For the primary endpoint, intention-to-treat 6-month follow-up LVESV decreased by 35% ± 22% with CSP-CRT vs 34% ± 22% with BiV-CRT (between-group differences 0.9%, 95% CI: -6.0% to 7.8%; P < 0.01 for noninferiority, P = 0.80 for superiority). Furthermore, LVEF increased by 14% ± 8% with CSP-CRT vs 14% ± 9% with BiV-CRT (P = NS). QRS duration shortening (-31 ± 22 ms vs -31 ± 21 ms), 6-min walking distance increase (37 ± 53 m vs 24 ± 48 m), Minnesota Living with Heart Failure score reduction (-16 ± 18 vs -13 ± 15), NYHA functional class improvement (-0.6 ± 0.6 vs -0.6 ± 0.7), and N-terminal pro-B-type natriuretic peptide reductions (-72 ± 152 pmol/l vs -110 ± 116 pmol/l) were similar between groups. CONCLUSIONS:In heart failure patients with LBBB, CSP-CRT was noninferior to BiV-CRT in reducing LVESV and both treatment modalities provided similar and excellent improvements in LVEF, QRS duration, heart failure symptoms, and functional capacity.

Small studies suggest that variations in plasma potassium (p-K) levels may affect cardiac contractile function. A substudy to the recently published POTCAST trial demonstrated short-term improvements in myocardial function in patients randomized to potassium-increasing treatment. However, the long-term effects of increasing p-K on cardiac function remain unclear. This study aimed to investigate whether treatment that increases p-K improves diastolic and systolic myocardial function as assessed by echocardiography during long-term follow-up in a Danish implantable cardioverter-defibrillator (ICD) cohort. The POTCAST trial randomized patients with an ICD (1:1) to either usual therapy (control group) or treatment with oral potassium supplements and/or mineralocorticoid receptor antagonists (high-normal potassium group). In this substudy, consecutive patients from both arms of the POTCAST trial were included. Echocardiography was performed at baseline and repeated after > 6 months for the current study to compare changes in left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), global constructive work (GCW), and diastolic parameters (E, e’, and E/e’) between the high-normal potassium and control groups. A total of 289 patients (mean age, 58 ± 13.4 years; 77.5

BACKGROUND AND AIMS:Hypokalaemia and low-normal plasma potassium levels are associated with increased risk of atrial fibrillation. This study examined if potassium-increasing treatment reduces the risk of atrial fibrillation-related clinical events. METHODS:This is a prespecified analysis of the POTCAST trial. Adults with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) and plasma potassium ≤4.3 mmol/L were randomized to potassium-increasing treatment and standard care (high-normal potassium group) or standard care alone (control group). The endpoint was a composite of acute hospitalizations due to atrial fibrillation leading to a change in pharmacological treatment or due to inappropriate shock therapy, hospitalization for electrical cardioversion or ablation of atrial fibrillation, and loading with amiodarone for atrial fibrillation. The endpoint was evaluated in time-to-first-event analyses with death as competing risk. RESULTS:Among 1200 participants [600 in each group, median age 64 years (interquartile range, 56-72), 80.3% male], 390 (32.5%) had a history of atrial fibrillation. Plasma potassium increased by .3 mmol/L after uptitration in the high-normal potassium group compared with the controls. After a median follow-up of 3.3 person-years, the endpoint had occurred in 48 participants in the high-normal potassium group (8.0%, 2.80 events per 100 person-years), when compared with 73 participants in the control group (12.2%, 4.30 events per 100 person-years) (subdistribution hazard ratio, .65; 95% confidence interval, .45-.93, P = .02). The treatment effect appeared similar across subgroups, including those with vs without a history of atrial fibrillation. CONCLUSIONS:In adults with any cardiac disease, treated with an ICD or CRT-D, uptitration of plasma potassium levels within the normal range reduced the risk of atrial fibrillation-related clinical events.

BACKGROUND:Cardiac resynchronization therapy (CRT) using biventricular pacing (BiV-CRT) is an established treatment for patients with symptomatic heart failure, reduced left ventricular ejection fraction, and left bundle branch block (LBBB), leading to improvements in symptoms, ventricular function, exercise capacity and survival. Despite these benefits, up to one third of patients fail to respond optimally with no clinical improvement despite meeting current criteria for implantation. Conduction system pacing (CSP), delivered via His bundle pacing or left bundle branch area pacing, has emerged as an appealing alternative by directly engaging the native His-Purkinje system. However, randomized data directly comparing CSP-based CRT with conventional BiV-CRT remain limited. STUDY DESIGN:His-Alternative II is an investigator-initiated, multicenter, randomized non-inferiority trial designed to evaluate whether CRT delivered via CSP is non-inferior to conventional biventricular pacing with respect to left ventricular reverse remodeling. The study enrolls patients with symptomatic heart failure (New York Heart Association class II to III), left ventricular ejection fraction ≤35%, strict LBBB by electrocardiographic criteria, and optimal medical therapy. A total of 150 patients were randomized with a 1:2 randomization ratio to receive BiV-CRT or CSP-based CRT (His bundle pacing or left bundle branch pacing) and followed for 6 months. The primary endpoint is change in left ventricular end-systolic volume assessed by echocardiography; a surrogate endpoint consistently associated with long-term outcomes in CRT populations. Secondary endpoints include functional capacity, symptomatic status, quality of life, electrical resynchronization, and device-related complications. CONCLUSIONS:His-Alternative II is designed to determine whether CSP-based CRT can achieve left ventricular reverse remodeling comparable to that obtained with conventional BiV-CRT. The study will provide randomized evidence to inform the role of physiologic pacing strategies in contemporary CRT practice. CLINICALTRIALS: GOV IDENTIFIER:NCT04409119.

INTRODUCTION:Patients with heart failure induced by chronic right ventricular (RV) pacing commonly undergo upgrade to cardiac resynchronization therapy (CRT). We aimed to compare the effect size of improvement in cardiac function and functional capacity between patients with RV pacing and intrinsic conduction at baseline. METHODS:We included patients from the ImagingCRT, ElectroCRT and DANISH-CRT trials aged ≥40 years with left ventricular ejection fraction (LVEF) ≤35% and prolonged QRS. The primary endpoint was change in left ventricular end-systolic volume (LVESV) from baseline to 6-month follow-up. Secondary endpoints included change in QRS duration, echocardiographic measures (LVEF, left ventricular end-diastolic volume, left ventricular mass index, and left atrial volume index), N-terminal prohormone of brain natriuretic peptide, six-minute walk test, quality of life, New York Heart Association functional class and loop diuretic use. RESULTS:We included 592 patients [mean age 70.7 ± 9 years; 24.8% women; mean LVEF 27 ± 6%; 97 (16.4%) with RV pacing and 495 (83.6%) with intrinsic conduction at baseline]. We found significant relative reduction in LVESV in patients with RV pacing (-34 ± 25%) and intrinsic conduction (-32 ± 26%) with no difference between the groups [mean difference -2%, 95% CI (-8; 4), P = .469]. Absolute LVEF improvement was 14 ± 9% and 13 ± 10%, respectively. Reduction in QRS duration was larger with RV pacing compared with intrinsic conduction (-38 ± 26 vs -26 ± 24 ms). We found significant improvements in the remaining secondary endpoints, with no difference between the groups. CONCLUSION:Patients with RV paced QRS morphology who are upgraded to CRT derive substantial improvement in cardiac function and functional capacity, comparable to patients with intrinsic conduction undergoing CRT.

BACKGROUND:Left ventricular lead position is a key determinant of optimal biventricular pacing for heart failure. Observational data indicate better outcomes in patients with late myocardial activation at the left ventricular lead site. We aimed to test whether targeting the left ventricular lead at site of latest electrical activation improves outcomes. METHODS:In this national, randomised, controlled, double-blinded, superiority trial we included patients from all five Danish university centres performing device implantation who had heart failure and wide QRS on guideline-directed medication, eligible for biventricular pacing. We randomly assigned (1:1) patients to either the intervention group, with left ventricular lead placement at the latest electrically activated site within the coronary sinus branches, or to control group, with left ventricular lead placement in a posterolateral non-apical branch. Primary outcome was a composite of time to death or first unplanned heart failure hospitalisation. We used block randomisation and masked patients and all study personnel (except operating room personnel) to treatment allocation. The primary outcome was a composite of time to death or first unplanned hospitalisation for heart failure. Analysis followed a modified intention-to-treat approach. Safety was assessed in all correctly assigned patients. The trial is registered at ClinicalTrials.gov (NCT03280862) and is complete. FINDINGS:From March 20, 2018, to June 3, 2024, we included 1001 patients (255 females and 746 males); 499 were randomly assigned to the intervention group and 502 to the control group. One incorrectly enrolled patient was excluded, leaving 1000 patients for the modified intention-to-treat analysis. Electrical activation at left ventricular lead was a mean of 9 milliseconds (95% CI 5-13) later in the intervention group. Follow-up was completed on Feb 27, 2026, after a median 45·8 months (IQR 28·5-65·7). The primary endpoint occurred in 139 (28%) of 499 patients in the intervention group and 128 (26%) of 501 in control group (hazard ratio 1·10 [95% CI 0·86-1·39]; p=0·45). Overall complication risk was similar between groups (71 [14%] patients in the intervention group vs 64 [13%] in the control group), but lead-related complications were more frequent in the intervention group. One procedure-related death occurred in the intervention group. INTERPRETATION:In patients with heart failure and prolonged QRS, targeted left ventricular lead placement at the site of latest electrical activation did not reduce the composite endpoint of death or unplanned hospitalisation for heart failure compared with conventional lead placement in a posterolateral, non-apical position. FUNDING:Novo Nordisk Foundation, Danish Heart Foundation, Danish Pacemaker and ICD Registry, and Independent Research Fund Denmark.

BACKGROUND:The PR interval is a ubiquitous parameter available to all clinicians. Studies on associated risk have been conflicting, often limited by sample sizes and one ECG per individual. The study aimed to investigate the association between the PR interval and its temporal changes with cardiac events in a nationwide cohort. METHODS:Nationwide hospital ECGs were linked with Danish national registries. Associations between index-PR interval and absolute temporal changes in PR interval (ΔPR), and cardiac events were modelled with multivariable cause-specific Cox models. RESULTS:A total of 9 020 051 ECGs (n=2 234 492; 53% female) were available, with 1 213 073 patients having >1 ECG. Median follow-up was 7.1 years. Median index-PR interval was 158 ms. PR interval <120 or >200 ms was found in 2.9% and 7.4%, respectively. Prevalence of prolonged PR interval increased with age. Median ΔPR was 10 ms and highest among the oldest. Cox models between the index-PR interval and events showed the following HR patterns: U-shaped for risk of atrial fibrillation/flutter, heart failure and ventricular arrhythmias (HR 1.03-1.24, 1.04-1.11, 1.08-1.16, respectively, p<0.05); stepwise increase at PR interval ≥170 ms for syncope (HR 1.08-1.36, p<0.001); linear increasing at PR intervals >160 ms (HR 1.07-2.11, p<0.05) for high-degree atrioventricular block/cardiac device implantation; J-shaped with moderate and marginal increases among the shortest (HR 1.44, p<0.001) and longest PR intervals (HR 1.03, p<0.001), respectively, for all-cause mortality. Models on ΔPR showed stepwise increases in HR for all events. CONCLUSION:Prevalence of PR prolongation and temporal PR changes increased with age. Short, long and temporal changes in the PR interval were all associated with increased risk of cardiac events and all-cause mortality.

Background The His-Alternative I (A Randomized Trial of His Pacing Versus Biventricular Pacing in Symptomatic Heart Failure Patients With Left Bundle Branch Block) trial was the first randomized European trial to compare cardiac resynchronization therapy (CRT) delivered by His bundle pacing (His-CRT) vs CRT delivered by conventional biventricular pacing (BiV-CRT). Objectives The goal of this study was to compare long-term lead performance, survival, and echocardiographic response between His-CRT and BiV-CRT. Methods A total of 50 patients with symptomatic heart failure (HF), left ventricular ejection fraction ≤35%, and left bundle branch block were randomized 1:1 to undergo His-CRT or BiV-CRT. Following crossover at implantation, 19 patients received His-CRT and 31 received BiV-CRT. The primary analyses were conducted by these groups, with 5 years of follow-up. Outcomes included the occurrence of reinterventions, an endpoint of all-cause mortality or hospitalization for HF, and echocardiographic response (≥15% reduction in left ventricular end-systolic volume compared with baseline). Results The median follow-up was 5.3 years (Q1-Q3: 4.6-5.7 years). More lead revisions (37% vs 3%; P = 0.003) and generator replacements (47% vs 10%; P = 0.005) occurred in the His-CRT group compared with the BiV-CRT group. However, no statistically significant differences in reinterventions and threshold development over time were observed between the His-CRT patients with implantation thresholds ≤2.5 V/1 millisecond and the BiV-CRT group. The risk of all-cause mortality or hospitalization for HF was similar between groups (HR: 0.32; 95% CI: 0.07-1.49; P = 0.147), and echocardiographic response was comparable between the 2 groups (89% in His-CRT and 90% in BiV-CRT; P = 1.0). Conclusions No statistically significant difference in long-term performance was detected between His-CRT with low implantation thresholds and BiV-CRT, and echocardiographic response was comparable.

BACKGROUND:While preprocedural anxiety is common, evidence regarding state anxiety among patients awaiting Cardiac Implantable Electronic Device procedures (CIEDs) remains limited. OBJECTIVES:To explore levels of preprocedural state anxiety among this population, and to gain an in depth understanding of how these patients with state anxiety experience and make sense of this anxiety in the cardiac catheterization laboratory setting. METHODS:The Pacewise study, at Copenhagen University Hospital is an explanatory sequential mixed methods study of state anxiety in patients awaiting CIED procedures. State anxiety was assessed pre-and post-procedurally using the State-Trait Anxiety Inventory - State scale (STAI-S) with total scores ≤40 indicating no/low state anxiety, 41-45 mild state anxiety, and ≥46 probable state anxiety. A subgroup of five participants underwent individual interviews. RESULTS:Overall, 149 patients (mean age 68 years, 73.2% men) scheduled for CIED procedures participated. Mild state anxiety was reported by 12.1%, and 10.7% met the criteria for probable state anxiety. Somatic manifestations contributed most to the STAI-S* total score, while feelings of insecurity emerged as a salient cognitive-affective component. Younger age (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.93-0.99; p = 0.01) and first-time implantation (OR 2.68; 95% CI 1.20-5.98; p = 0.02) were independently associated with higher odds of preprocedural anxiety. Qualitative findings linked anxiety to a self-reinforcing cycle of bodily tension, lost control, insecurity, and existential fear. CONCLUSION:One-quarter of participants reported preprocedural state anxiety, with prominent somatic manifestations. Younger age and first-time implantation were associated with higher anxiety levels. Systematic assessment of state anxiety may facilitate timely, patient-centered preprocedural care.

Importance:Hypertrophic cardiomyopathy (HCM) is associated with an elevated risk of sudden cardiac death, often preceded by an out-of-hospital cardiac arrest (OHCA). However, population-based estimates of OHCA risk in patients with HCM are limited. Objective:To estimate the risk of OHCA in patients with HCM and identify characteristics associated with OHCA. Design, Setting, and Participants:This cohort study used multiple Danish registers during an observation period ranging from June 1, 2001, to December 31, 2022, and included a nested case-control study. All Danish residents aged 18 to 85 years during the study period constituted the source population. Patients with HCM were identified using codes from the International Statistical Classification of Diseases, Tenth Revision. The cohort included patients with a first-time HCM diagnosis and exposure-matched controls. In the nested case-control study, patients with HCM who experienced OHCA were risk-set matched with controls with HCM and no OHCA at the index time. Analyses were performed between September 1 and November 30, 2025. Exposure:First-time diagnosis of HCM. Main Outcomes and Measures:Time to OHCA from exposure or the matching date was the primary outcome. Risk estimates were determined using the Aalen-Johansen estimator. Association between covariates and OHCA was determined by conditional logistic regression. Results:The cohort included a total of 29 240 individuals: 5901 patients with HCM (median age, 65 [IQR, 54-75] years; 3277 male [55.5%]) and 23 339 matched controls (median age, 65 [IQR, 55-75] years; 12 982 male [55.6%]). In the group aged 61 to 85 years, the 10-year risk of OHCA was 4.3% (95% CI, 3.4%-5.1%) in patients and 3.3% (95% CI, 3.0%-3.7%) in controls. In the group aged 18 to 60 years, the 10-year risk was 2.8% (95% CI, 1.9%-3.7%) in patients and 1.5% (95% CI, 1.2%-1.8%) in controls. The nested case-control study included 250 cases with HCM and OHCA (167 male [66.8%]; median age, 68 [IQR, 59-76] years) and 1000 controls with HCM and no OHCA (668 male [66.8%]; median age, 68 [IQR, 59-76] years). Heart failure, both recent and longer term, was associated with an increased rate of OHCA (hazard ratio, 3.63 [95% CI, 1.55-8.50] and 2.82 [95% CI, 1.88-4.22], respectively). Conclusions and Relevance:The findings of this cohort study suggest that HCM was associated with an increased risk of OHCA in people aged 18 to 85 years. The rate of OHCA was associated with heart failure, underscoring the need for improved risk stratification to optimize primary prevention.

Aims:A typical left bundle branch block (LBBB) contraction pattern prior to cardiac resynchronization therapy (CRT) has been demonstrated to be highly associated with response beyond QRS morphology and duration. This study investigates whether septal deformation type and lateral wall strain amplitude may be of particular importance for long-term outcome after CRT implantation. Methods:From two centres, 208 CRT candidates with LBBB, New York Heart Association functional class II-IV, left ventricular ejection fraction ≤35%, and QRS duration ≥ 120 ms underwent echocardiography before CRT-defibrillator (CRT-D) implantation. Results:Four septal contraction patterns were identified: 36 patients (17%) had double-peaked systolic pattern (LBBB-1), 51 (25%) had early pre-ejection peak shortening followed by systolic stretch (LBBB-2), 43 (21%) had shortening with one systolic peak inside 70% of the ejection phase (LBBB-3), and 78 (38%) had normal septal peak timing outside early 70% of ejection phase (LBBB-4). The primary outcome (freedom from death, implantation of a left ventricular assist device, and heart transplantation) occurred in 48 patients during a median follow-up of 4 years (interquartile range 3.25-4). The most favourable outcome was associated with LBBB-1 and LBBB-2, which had one-seventh the risk of the primary outcome compared to LBBB-4 (HR: 0.14 [95% confidence interval: 0.06-0.34]; P < 0.001). Patients in the lowest tertile of lateral wall strain (>-7.4%) were at high risk of an event compared to the other patients (HR: 2.57 [1.46-4.55]; P = 0.001). Conclusion:The long-term clinical benefit of CRT-D in patients with LBBB pre-implantation varies. Subtypes of septal contraction patterns and, to a lesser degree, lateral function are important determinants of outcome in patients with CRT-D.

Physical activity and sleep behaviors are prognostic for ventricular arrhythmias in ICD patients. However, short-term patterns in these behaviors in the days before ICD therapy remain underexplored. By analyzing accelerometer data in the month before a ventricular arrhythmia, we aim to find actionable predictors of arrhythmias and clinical deterioration in ICD carriers. This study aims to investigate behavioural patterns immediately preceding malignant ventricular arrhythmias in patients with an ICD by analysing day-to-day behavioural data. This is a sub-analysis from a multicenter, prospective study, conducted at two European centres. Patients with an ICD were enrolled between May 2021 and September 2022 and wore wrist-based activity monitors for 12 months. Thirteen metrics of daily activity and sleep were derived from tri-axial accelerometer data. Baseline averages were calculated from the first 30 days of monitoring; deviations from these baselines were analyzed over the last 30 days before the outcome of appropriate ICD therapy (shock or anti-tachycardia pacing). A Cox Proportional Hazards model with time-varying variables averaged over each 30-day period was used to identify risk of outcome based on activity and sleep patterns over time. Patients not wearing the wristband 30 days pre-therapy were excluded. The model was adjusted for age, secondary or primary prevention, ischaemic or nonischaemic cardiomyopathy, device type (ICD or CRT-D), and heart failure diagnosis (reduced or preserved ejection fraction). A total of 277 patients (mean age 63 ± 10 years, 81% male) were included, with 51 (18%) experiencing appropriate ICD therapy during follow-up. Long-term analysis revealed no significant differences in average one-year behavior metrics between patients with and without the outcome. In time-varying analysis, two patterns appeared: higher intensity during the most active six minutes each day (M6) was associated with a lower risk of imminent ICD therapy (HR 0.47, 95% CI 0.24–0.94), while longer exercise duration was linked to higher risk (HR 2.16, 95% CI 1.03–4.59). This inverse association suggests that longer but less intense activity durations can be a sign of disease deterioration. Figure 2 shows four examples of baseline deviations, with no significant differences between baseline and 30 days before ICD therapy. This sub-analysis of a prospective study demonstrated changes in intensity and duration of activity to be associated with imminent ventricular arrhythmia. The findings suggest that both the intensity and duration of daily activity impact arrhythmia risk differently, confirming the role of physical activity in arrhythmia risk and generating further hypotheses for understanding individualized risk assessment and personalized treatment.Forest plot of the hazard ratios Four examples of SDs from baseline

BACKGROUND:Cholecystokinin (CCK) is secreted from the intestines in response to food intake. We previously reported that the CCK gene is also expressed in the mammalian heart, and it has been hypothesized that proCCK could be a novel cardiac biomarker. However, it is not known whether cardiac gene expression leads to secretion in humans. PURPOSE:To investigate myocardial secretion of proCCK in patients with heart failure with reduced ejection fraction (HFrEF) or arrythmias. METHODS:A total of 115 patients undergoing invasive cardiac procedures were included: 55 with HFrEF (67 years [interquartile range (IQR) 60-76], 72.7 % male, LVEF 30 % [IQR 20-35]), and 60 without HFrEF (26 with Wolff-Parkinson-White syndrome (WPW) (30 years [IQR 26-39], 61.5 % male), and 34 with atrial fibrillation (AFIB) (66 years [IQR 60-71], 61.8 % male)). Blood was collected from the coronary sinus (CS) as well as the left atrium or femoral artery (A) to determine the transcardiac concentration gradient (TCproCCK) (CS proCCK concentration - A proCCK concentration). Radioimmunoassays were used for measurements of plasma hormones. RESULTS:TCproCCK across failing hearts was 0.05 pmol/l (IQR: -1.49-2.67) (p = 0.365). In non-failing hearts, TCproCCK was 0.35 pmol/l (IQR: -1.57-1.29) (p = 0.778) for WPW and 0.68 pmol/l (IQR: -1.58-3.28) (p = 0.133) for AFIB. Transcardiac gradients for N-terminal pro B-type natriuretic peptide (NT-proBNP) were observed in all groups. CONCLUSIONS:No evidence of net myocardial secretion of proCCK was found in either failing or structurally normal hearts, questioning its proposed role as a cardiac biomarker.

BACKGROUND:Hypokalemia and even low-normal plasma potassium levels increase the risk of ventricular arrhythmias among patients with cardiovascular disease. An assessment of a strategy of actively increasing plasma potassium levels to the high-normal range is needed. METHODS:In this multicenter, open-label, event-driven, randomized superiority trial conducted in Denmark, we enrolled participants at high risk for ventricular arrhythmias (defined as those with an implantable cardioverter-defibrillator [ICD]) and with a baseline plasma potassium level of 4.3 mmol per liter or lower. Participants were randomly assigned, in a 1:1 ratio, to a treatment regimen aimed at increasing the plasma potassium level to a high-normal level (4.5 to 5.0 mmol per liter) by means of potassium supplementation, a mineralocorticoid receptor antagonist, or both plus dietary guidance and standard care (high-normal potassium group) or to standard care only (standard-care group). The primary end point was a composite of documented sustained ventricular tachycardia or appropriate ICD therapy, unplanned hospitalization (>24 hours) for arrhythmia or heart failure, or death from any cause, assessed in a time-to-first-event analysis. RESULTS:Among the 1200 participants who underwent randomization (600 assigned to each group), the median duration of follow-up was 39.6 months (interquartile range, 26.4 to 49.3). A primary end-point event occurred in 136 participants (22.7%; 7.3 events per 100 person-years) in the high-normal potassium group, as compared with 175 participants (29.2%; 9.6 events per 100 person-years) in the standard-care group (hazard ratio, 0.76; 95% confidence interval, 0.61 to 0.95; P = 0.01). The incidence of hospitalization for hyperkalemia or hypokalemia was similar in the two groups. CONCLUSIONS:Among participants with any cardiovascular disease who had an ICD and were at high risk for ventricular arrhythmias, a treatment-induced increase in plasma potassium levels led to a significantly lower risk of appropriate ICD therapy, unplanned hospitalization for arrhythmia or heart failure, or death from any cause than standard care. (Funded by the Independent Research Fund Denmark and others; POTCAST ClinicalTrials.gov number, NCT03833089.).

The electrocardiographic PR-interval reflects the time from activation of the sinus node to the start of the ventricular depolarization. Studies of the PR-interval and its association with cardiac events have shown inconsistent results, often limited by small cohort sizes and availability of only one electrocardiogram (ECG) per individual. We aimed at investigating the association of the PR-interval – and its temporal changes – with cardiac endpoints and all-cause mortality in a large, nationwide cohort. ECGs from Danish Nationwide Electrogram Cohort (11,952,349 ECGs, n=2,485,981) were linked with national registries and were excluded based on age <18 years, brady- and tachycardia, non-sinus rhythm, pre-excitation syndromes, congenital heart disease, inflammatory cardiomyopathy, preexisting cardiac device, and extreme outliers. The association between the first (index) PR-interval, and absolute changes in PR-interval over time (ΔPR), and cardiac events and all-cause mortality were studied using multivariable Cox proportional hazard models. A total of 9,022,066 ECGs (n= 2,234,660, median age 57 years; 53% female) remained after exclusion, 1,213,095 individuals had >1 ECG available, and the median follow-up was 6.1 years. The median index PR-interval was 158 ms (IQR 142-176); a short PR- (<120 ms) or long (>200 ms) PR-interval was found in 2.9% and 7.4% of the cohort, respectively. Prevalence of PR >200 ms increased with age and was more frequent in men. Cox modelling of the index PR-interval showed a U-shaped association in the hazard ratios (HR) of atrial fibrillation/flutter, heart failure, and ventricular arrhythmias with the highest HR observed in individuals with the shortest (HR range 1.04-1.16, P<0.05) and longest PR-interval (HR range 1.09-1.24, P<0.05) (Figure). In syncope, HR showed a stepwise increase above a PR threshold of ≥170 ms (HR range 1.08-1.36, P<0.001). In high-degree atrioventricular block or implantation of a cardiac device, HR showed a linear association with increasing PR values (HR range 0.8-2.11, P<0.05). The association with all-cause mortality was J-shaped (HR range 0.96-1.44, P<0.05). Cox modelling of temporal changes in the PR interval showed a stepwise increase in HR of all six endpoints with increasing ΔPR values. Short, long, and temporal changes in the PR-interval, are all associated with increased rate of cardiac events and all-cause mortality.

Abstract Aim To investigate whether a compressive dressing after pacemaker or implantable cardioverter defibrillator (ICD) implantation and replacement applied for three hours can prevent bleeding, hematomas and pain. Method The study was a quasi-experimental interventional study including patients scheduled for implantation or replacement of a pacemaker or an ICD. In alternating months patients either received a compressive dressing (intervention group) or no compressive dressing (control group). Patients were followed at the catheterization lab, for three hours on the ward and until the first outpatient control visit (after 1-3 months). Outcomes was: Bleeding graded as bleeding, oozing or pocket-hematomas. Hematomas were measured by degrees and size. Pain was rated in a numerical rank scale (NRS). Results A total of 242 elective patients were included (intervention group n=114, control group n=128). The intervention group did not show any significant difference in development of pocket-hematomas compared to the control (p=0.24). Pain score was low in both groups (intervention NRS=1.41 vs. control NRS 1.32). Furthermore, no significant difference in pocket hematomas at follow-up were observed (p=0.77). Conclusion Using a compressive dressing did not significantly reduce bleeding or pocket hematomas after pacemaker or ICD implantation or replacement. Furthermore, no significant difference related to pain was observed. This study shows that patients who are not considered to be at elevated risk for bleeding or pocket-hematomas do not seem to benefit from a compressive dressing. Keywords Pacemaker, Implantable Cardioverter Defibrillator, Prophylactic compression bandaging, Pocket-hematoma, Device, Compression tool.

Aims:Individuals experiencing a sudden cardiac arrest with ventricular fibrillation and no identifiable cause are diagnosed with idiopathic ventricular fibrillations (IVFs). 2D speckle tracking echocardiography (2DSTE) has been able to detect differences between IVF patients and controls. However, the association between these differences and the risk of ventricular arrhythmias (VAs) remains unknown.This study aimed to investigate whether parameters derived from myocardial deformation analysis using 2DSTE are associated with the recurrence of VA in IVF patients. Methods and results:This single-centre, cross-sectional study enrolled IVF patients treated with an implantable cardioverter defibrillator. IVF patients were compared with healthy sex- and age-matched controls. Furthermore, IVF patients were categorized into two groups (IVF patients with or without recurrent VA) based on the recurrence of VA over a 5-year follow-up period. Left ventricular global longitudinal strain (LVGLS) and left ventricular mechanical dispersion (LVMD) were investigated using 2DSTE and compared across all groups. Fifty-six IVF patients, males 39 (69.9%), age 49 ± 15 years, and 55 controls were included. IVF patients showed significantly increased LVMD (35.78 ± 13.4 ms vs. 31.0 ± 9.8 ms; P = 0.03) and decreased LVGLS (-18.8% ± 3.0% vs. -20.5% ± 2.7%; P < 0.01) compared with controls. IVF patients with recurrent VA had significantly increased LVMD compared with IVF patients without recurrent VA (43.63 ± 13.63 vs. 33.16 ± 12.45; P = 0.02). Conclusion:IVF patients had an increased LVMD and decreased LVGLS compared with healthy controls. Increased LVMD was significantly associated with recurrent VA in IVF patients suggesting a potential clinical value in risk stratification of VA recurrency in IVF patients.