奥斯陆大学医院，乌勒瓦尔

Abstract Background Registry-based randomised clinical trials are increasingly dependent on registry-derived outcomes, providing advantages in feasibility and data capture. However, registry data may introduce bias through misclassification or incomplete information. In the BETAMI-DANBLOCK trial, we compared registry-based cardiovascular events with and without adjudication, using information from national registries, electronic health records, and patient reports. Purpose To investigate whether registry-based endpoints can substitute adjudicated endpoints without materially altering trial results. Methods BETAMI-DANBLOCK enrolled 5,574 patients with myocardial infarction (MI) and a left ventricular ejection fraction ≥40% from 2018 through 2024. Patients were randomised to beta-blocker therapy or no beta-blocker therapy. The primary endpoint events (death, MI, ischemic stroke, heart failure, unplanned coronary revascularisation, and ventricular arrhythmias) were identified from the Danish and Norwegian national patient registries, self-reported questionnaires, and medical records. All registry-identified events, except death, underwent blinded adjudication. We compared events with and without adjudication by calculating incidence rates and hazard ratios (HRs) for beta-blocker treatment versus controls. Results National registries had almost complete capture of events when compared to site-reporting. In total, 75% of the primary endpoint events identified through the registries were confirmed by adjudication. The confirmation rate was lower during the first six months and varied by event type (from 92% for ischemic stroke to 45% for unplanned coronary revascularisations). The incidence rate of the primary endpoint was 6.23 per 100 person-years using registry data without adjudication and 4.43 with adjudication. Estimated treatment effects were consistent for the primary endpoint (0.88, 95% confidence interval (CI): 0.78-0.98 without adjudication and 0.85, 95% CI: 0.75-0.98 with adjudication), with no apparent differences across event types. Conclusion Registry data provide treatment effect estimates comparable to those obtained from adjudicated data in BETAMI-DANBLOCK. However, adjudication substantially reduced the total number of endpoint events and event-specific misclassification was a limitation, particularly during the first months after the index event.Cumulative incidence of primary endpointFor image description, please refer to the figure legend and surrounding text. Forest plot of hazard ratiosFor image description, please refer to the figure legend and surrounding text.

Abstract Background Elderly myocardial infarction (MI) survivors face a high risk of developing heart failure (HF), but diagnosis is challenging due comorbidities and inactivity after discharge masking symptoms. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a robust cardiac stress marker and a defining feature of HF. Aims To evaluate NT-proBNP concentrations in elderly post-MI patients without clinically diagnosed HF and assess their association with cardiovascular event risk. Methods The OMEMI trial, a randomized controlled study across four Norwegian academic hospitals, included 1014 elderly (range 70-82 years) patients with a recent MI between 2012 and 2020. Participants were randomized to omega-3 fatty acids or placebo for two years and monitored for cardiovascular events. The overall trial was neutral. NT-proBNP was analyzed at baseline (2-8 weeks post-MI) using the Roche Elecsys assay. The age-adjusted NT-proBNP threshold of 500 ng/L for HF rule-in was applied (ref). Patients with pre-existing HF (n=65) or new-onset HF between MI and baseline (n=22) were excluded. Cox proportional hazards regression was used to analyze time to event data for HF hospitalization and mortality, with adjustment for age, sex, BMI, hypertension, diabetes, previous MI, atrial fibrillation, eGFR, and NYHA-class at baseline, in addition to index MI peak troponin T concentration and ST-elevation MI (STEMI). Results Among 937 patients without HF diagnosis, median NT-proBNP was 494 (224-1159) ng/L. NT-proBNP ≥500 ng/L was present in 49.7% (n=466), and associated with older age, lower BMI, and more atrial fibrillation. The index MI being STEMI and higher peak troponin T during the MI (r=0.51) also predicted higher NT-proBNP at the baseline visit 2-8 weeks later. At baseline, patients with NT-proBNP ≥500 ng/L showed significantly higher rates of NYHA class ≥2 (41.8%) and peripheral edema (34.7%). During two-year follow-up, this group accounted for 81.0% of deaths (30/37) and 92.8% of HF hospitalizations (26/28). After multivariable adjustment, NT-proBNP ≥500 ng/L remained associated with increased risk of death (HR 3.16, 95%CI 1.28-7.84, p=0.013); HF hospitalization (HR 6.34, 95%CI 1.88-21.35, p=0.003) and a composite of the two outcomes (HR 4.21, 95%CI 2.03-8.90, p<0.001). The risk of HF hospitalization or death increased significantly and progressively across ascending quartiles of NT-proBNP levels (log-rank p<0.001; Figure) Conclusion Half of the elderly post-MI patients without clinical HF diagnosis had NT-proBNP levels above the HF rule-in threshold, exhibiting HF signs/symptoms and significantly increased risk of HF hospitalization or death. These findings support NT-proBNP screening for HF in elderly patients in the months following MI, especially in patients with large troponin elevations during the MI.Baseline characteristicsFor image description, please refer to the figure legend and surrounding text.Nelson-Aalen plotFor image description, please refer to the figure legend and surrounding text.

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with adverse cardiovascular outcomes. Elective electrical cardioversion (ECV) is a standard therapeutic strategy to restore sinus rhythm in patients with persistent AF. However, its impact on right ventricular (RV) physiology—particularly right ventricular free wall strain (RV-FWS)—remains poorly understood. This study aimed to evaluate changes in RV-FWS before and after elective ECV in patients with AF. We conducted a prospective cohort study involving 46 patients with symptomatic persistent AF scheduled for elective ECV. RV-FWS was assessed using speckle-tracking echocardiography both prior to and 10 days after ECV, allowing time for post-procedural myocardial stunning to resolve. Strain measurements were compared pre- and post-procedure, and changes were analyzed for associations with baseline clinical variables, including heart rate, right and left atrial dimensions, and right and left ventricular size. RV strain measurement before and after ECV was feasible in 44 of the 46 patients (95.6%). Mean RV-FWS significantly improved post-ECV (−13.0 ± 4.2% vs. −18.1 ± 5.1%, p < 0.001). Similarly, RV global strain (11.1 ± 3.0% vs. 15.9 ± 4.6%, p < 0.001) and tricuspid annular plane systolic excursion (TAPSE) (1.5 ± 0.42 cm vs. 1.9 ± 0.49 cm, p < 0.001) increased significantly. No significant changes were observed in right atrial area, RV basal diameter, left atrial volume, LV volume, or the degree of tricuspid regurgitation. The change in RV-FWS was not significantly associated with changes in heart rate (p = 0.197). Elective electrical cardioversion in patients with atrial fibrillation is associated with significant improvements in right ventricular free wall strain, global strain, and TAPSE. These findings suggest that restoration of sinus rhythm may probably have a beneficial effect on right ventricular function. Further studies are warranted to investigate the clinical implications of these changes, particularly regarding long-term cardiovascular outcomes.Figure 1

Elective cardioversion (ECV) frequently restores sinus rhythm in patients with atrial fibrillation (AF); however, recurrence rates remain high, and reliable predictors of sustained rhythm control are limited. This study evaluated whether recovery of myocardial strain following ECV correlates with early AF recurrence and long-term AF burden, using continuous rhythm monitoring. In this prospective cohort study, echocardiographic assessment—including left atrial reservoir strain (LA reservoir strain), left ventricular global longitudinal strain (LV-GLS), and right ventricular free wall strain (RV-FWS)—was performed prior to and within 3 weeks after ECV. Continuous rhythm data were collected over 12 months using implantable loop recorders. AF burden, defined as the percentage of time spent in AF, was categorized into five groups: 0%, >0–1%, 1.1–10%, >10–50%, and >50%. Early recurrence was defined as AF reappearance within 30 days post-ECV. Group comparisons were conducted using one-way ANOVA. A total of 46 patients were included. Significant post-ECV improvements in strain were observed in all chambers (mean ΔLA reservoir strain: +6.68 ± 7.71%, p<0.001; ΔLV-GLS: –3.98 ± 3.26%, p<0.001; ΔRV-FWS: –5.14 ± 5.22%, p<0.001). Improvements in LV-GLS and RV-FWS were significantly associated inversely with long-term AF burden (ΔLV-GLS: p = 0.004; ΔRV-FWS: p = 0.028). LA reservoir strain changes did not differ significantly across burden categories (p = 0.147). Patients with >50% AF burden exhibited minimal or no improvement in ventricular strain (ΔLV-GLS: –0.4%; ΔRV-FWS: +1.14%). Additionally, early AF recurrence (<30 days) was significantly associated with smaller improvements in all three strain parameters (ΔLV-GLS: p < 0.001; ΔRV-FWS: p < 0.001; ΔLA reservoir strain: p = 0.011). Functional recovery of both the left and right ventricles following cardioversion was strongly associated with long-term rhythm stability. Although LA reservoir strain improved across all groups, it did not distinguish between AF burden outcomes. These findings suggest that ventricular strain recovery may serve as a marker of myocardial resilience and a predictor of cardioversion success.

Abstract Background Mineralocorticoid receptor antagonists (MRA) are cornerstones of heart failure (HF) therapy, but increase serum potassium levels, potentially resulting in hyperkalemia. Whether hyperkalemia during MRA treatment confers different prognostic implications compared to hyperkalemia from other causes remains unknown. Purpose To evaluate prevalence, predictors, and prognostic significance of hyperkalemia in real-world HF patients, and to test the hypothesis that the prognostic impact of hyperkalemia differs between MRA users and non-users. Methods We analysed data from the Norwegian HF Registry (2013-2025), capturing nearly all patients attending HF outpatient clinics during guideline-directed medical therapy (GDMT) optimization. Mortality data were obtained from the Norwegian Cause of Death Registry. Missing data were handled using multiple imputation. Predictors and prognostic associations were assessed using logistic and Cox regression with restricted cubic splines, adjusting for variables in the Table. Effect modification by MRA on the association between hyperkalemia and mortality was evaluated through interaction analyses. Results Among 23,658 patients, 7.4% had hyperkalemia at the final follow-up visit, including 6.5% with mild (5.1–5.5 mmol/L), 0.9% with moderate (5.6–6.0 mmol/L), and 0.1% with severe (>6.0 mmol/L) hyperkalemia. Compared to normokalemic (3.6–5.0 mmol/L) patients, those with hyperkalemia were older, more often male, had lower eGFR, and more comorbidities (Table). Independent predictors of hyperkalemia included reduced eGFR (OR 0.75 per 10 ml/min/1.73m², 95% CI 0.73–0.78), diabetes (OR 1.45 [1.30–1.63]), current smoking (OR 1.34 [1.17–1.54]), COPD/asthma (OR 1.26 [1.12–1.43]), and male sex (OR 1.38 [1.22–1.56]). MRA use was not associated with hyperkalemia (OR 1.02 [0.91–1.14]). During median follow-up of 1061 (526–1935) days, 24.4% of patients died, including 27.8% with hyperkalemia and 23.8% with normokalemia, p<0.001. Restricted cubic spline analysis demonstrated a U-shaped association between potassium and mortality (p-for-nonlinearity<0.001), with lowest risk at 4.5 mmol/L (Figure). In unadjusted analyses, MRA users had lower mortality across all potassium levels (Figure panel A). However, after multivariable adjustment, the curves overlapped with no significant interaction between hyperkalemia and MRA use on mortality (p-interaction=0.75, Figure panel B). Conclusions In this large real-world HF cohort, moderate and severe hyperkalemia after GDMT optimization was uncommon and associated with only a modest increase in mortality risk. Although MRA users had lower mortality across all potassium levels in unadjusted analyses, this association was attenuated after adjustment for baseline characteristics. These findings suggest that hyperkalemia can be avoided through careful titration of GDMT in HF clinics and that hyperkalemia carries similar prognostic implications regardless of MRA treatment status.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.