Niels Risum

Aims: The POTCAST trial (n = 1200) showed that targeting high-normal plasma potassium levels reduced ventricular arrhythmias in patients with implantable cardioverter-defibrillators (ICDs). We compared changes in plasma potassium and described outcomes across the three regimens used to increase plasma potassium. Methods: We studied 600 control participants and 572 intervention participants who completed potassium up-titration in POTCAST. Participants in the intervention arm were categorized according to treatment after plasma-potassium up-titration into (i) mineralocorticoid-receptor antagonists (MRAs) monotherapy, (ii) potassium-supplement monotherapy, or (iii) combination therapy with both. The primary endpoint was a composite of sustained ventricular arrhythmia, appropriate ICD therapy, hospitalization for arrhythmia or heart failure, or all-cause mortality. Safety outcomes included death and electrolyte/renal disturbances. Results: After 6 months, plasma potassium increased from 4.12 to 4.27 mmol/L (P = 0.004) with MRA, from 3.99 to 4.24 mmol/L (P < 0.001) with potassium supplements, and from 3.98 to 4.34 mmol/L (P < 0.001) with combination therapy. The primary endpoint occurred in 29% (n = 175) of controls, 22% (n = 16) in the MRA group, 21% (n = 31) in the potassium supplements group, and 22% (n = 72) in the combination therapy group (P = 0.8 between regimens). Hypokalemia occurred in 13% of controls and in 3, 9, and 5% of participants receiving MRA, potassium supplements, and combination therapy, respectively. Hyperkalemia occurred in 0.2% of controls and in 0, 3, and 4% of participants receiving MRA, potassium supplements, and combination therapy (P > 0.1 between regimens). Conclusion: Treatment with MRA, potassium supplements, or both increased potassium levels. All regimens were associated with numerically lower endpoint rates than controls. We detected no statistically significant differences in endpoints or safety between regimens.

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.

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: 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, 1.38–2.87), higher daily heart rate (1.46 bpm; 95% CI, 0.65–2.06), and higher thoracic impedance (0.66 Ω; 95% CI, 0.17–1.15) (all P < .01). S1 amplitude decreased (−0.09 mG; 95% CI, −0.14 to −0.04; P < .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.

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.

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.

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: Patterns in physical behaviour may be associated with an increased risk of ventricular arrhythmia. We examined associations between temporal dynamics in physical behaviour measured through wearable technology and the risk of ventricular arrhythmia Methods and results: The multicentre, prospective SAFEHEART study recruited 303 patients with an implantable cardioverter-defibrillator (ICD) from May 2021 to September 2022. Continuous physical behaviour data were collected over 365 consecutive days and nights using wearable accelerometers. We characterized each 28-day behavioural time series using statistical summary indices and deep representations learned by neural networks. Logistic regression analyses were used to estimate the associations between physical behaviour and the subsequent risk of ventricular arrhythmia as detected by ICD and treated appropriately. Predictive performance was assessed using k-fold cross-validation and quantified by the area under the receiver operating characteristic curve (AUROC). From the SAFEHEART cohort, 277 patients and 56 ventricular arrhythmia were analysed, contributing to a total of 64 995 days of behavioural data. Reduced numbers of daily physical activity bouts and low day-to-day variation in sleep characteristics were associated with an increased risk of an arrhythmic event. Deep representations improved the predictive performance, with an AUROC of 0.74 ± 0.05, compared with statistical summary indices with an AUROC 0.67 ± 0.14 (P = 0.05 for comparison). Conclusion: Our findings suggest that behavioural patterns captured through wearable technology are independently associated with ventricular arrhythmia, particularly when these are characterised by deep representations.