Lauge Østergaard

Background: Mitral regurgitation (MR) is a common complication of mitral valve prolapse (MVP) and increases left ventricular (LV) preload, promotes LV remodeling and hypertrophy, but its impact on myocardial perfusion and coronary microvascular dysfunction remains unclear. Objectives: To assess myocardial perfusion using, for the first time, quantitative cardiac magnetic resonance (CMR) perfusion mapping in patients with significant MR due to MVP. Methods: Patients with significant primary MR, without coronary artery disease were prospectively enrolled and compared to age- and sex-matched controls without MR. All underwent 1.5T CMR including cine imaging, adenosine stress perfusion, native T1, native T2, extracellular volume (ECV) mapping and late gadolinium enhancement (LGE). Myocardial perfusion reserve (MPR) was calculated as the ratio of stress to rest myocardial perfusion. Results: In total 33 patients and 33 controls were included (age 56±13 vs. 58±12 years, 46% women in both groups). Patients with MR had increased LV mass and volumes, higher native T1 and ECV and a higher prevalence of LGE (36% vs 0%). No differences were observed in global myocardial perfusion at rest (0.88±0.27 vs. 0.85±0.30, p=0.52), at stress (2.6±0.56 vs. 2.8±0.73 ml/min/g, p=0.29) or for MPR (3.1±0.75 vs. 3.4±1.0, p=0.24). In age- and sex-adjusted linear regression, higher NYHA class was associated with lower MPR (β =–0.60, p=0.04). Conclusion: In patients with significant MR due to MVP, myocardial perfusion appears preserved despite LV volume overload. However, lower MPR in symptomatic patients suggests that microvascular dysfunction may emerge in a more advanced disease stage.

Purpose: Antimicrobial therapy of Enterococcus faecalis endocarditis treatment is challenged by high intrinsic resistance and relapse rates. Knowledge on practice patterns is warranted. We aimed to describe early-phase monotherapy and combination therapy use in E. faecalis endocarditis treatment. Methods: This retrospective, nationwide cohort study was conducted in Denmark between 2016 and 2021. All patients with left-sided E. faecalis endocarditis were derived from the NatIonal Danish endocarditis stUdieS registry (NIDUS). Antimicrobial therapy during the first 10 days was compared between monotherapy and combination therapy. The groups were compared by in-hospital mortality, acute kidney injury and surgery with logistic regression and 6-month relapse and recurrence rate and 6-month mortality rate with Kaplan-Meier estimates and multivariable cox regression. Results: We included 392 patients, 59(15.1%) received monotherapy and 333 (84.9%) combination therapy. Patients in monotherapy were older (median 79.3 versus 76.0 years) and had more comorbidities. Monotherapy comprised ampicillin (74.6%), vancomycin (16.9%) and penicillin (6.8%). Among combination regimens the most frequent were ampicillin +gentamicin (65.4%), ampicillin + linezolid (6.6%) and ampicillin + ceftriaxone (5.1%). Surgical rates were comparable. Acute kidney injury during admission occurred in 20.7% versus 16.6% patients. No significant difference in relapse (5.9% versus 8.5%) or recurrence rates (5.4% versus 6.8%) was found. Similar in-hospital mortality (13.8% vs. 11.9%) and 6-month mortality rates were seen in the monotherapy and combination therapy groups. Conclusion: The most common treatment of E. faecalis endocarditis was combination therapy, however certain selected patients were treated with monotherapy with similar outcomes. Use of monotherapy remains controversial and would need testing in a controlled randomized setting.

Background: Mitral valve prolapse (MVP) causes mitral regurgitation (MR), leading to volume overload and maladaptive left ventricular (LV) remodelling. Objective: To comprehensively characterize markers of maladaptive LV remodelling across MR severity grades in MVP using cardiovascular magnetic resonance (CMR), and their association with functional status. Methods: Patients with MVP undergoing 1.5T CMR (2016–2025) were stratified by MR fraction: mild<20%, moderate 20–39%, and severe ≥40%. Exclusion criteria were significant coronary artery disease, rheumatic valve disease, mitral stenosis, previous mitral valve procedures, endocarditis or signs of primary cardiomyopathy. Global native T1, T2, extracellular volume (ECV), indexed ECV (iECV), indexed intracellular volume (iICV), and late gadolinium enhancement (LGE) were quantified. Indexed LV end-diastolic volume (EDVI) and the EDV-to-LV mass ratio (EDV/LVM-ratio) were also calculated as indices of LV remodelling and adaptive hypertrophy. Functional status was assessed by NYHA class. Results: Among 112 MVP patients (23 mild, 48 moderate, 41 severe MR) and 20 controls, LGE prevalence (17% vs. 46% vs. 51% vs. 0%) and the proportion with LV dilatation (46% vs. 67% vs. 88% vs 15%) rose progressively with MR severity. Increased EDVI, prevalence of LGE, higher EDV/LVM-ratio, global native T1 and iECV showed the strongest associations with more severe MR, whereas EDV/LVM-ratio, iECV and global native T1 were independently related to NYHA class≥II. Conclusions: CMR markers of maladaptive LV remodelling were abnormal across all MR grades and increased markedly with MR severity. Global native T1, iECV and EDV/LVM-ratio correlated most strongly with symptom burden, rather than MR severity per se. Clinical Trial Registration: NCT06255457 Abstract Figure:

Aims: According to the European Society of Cardiology (ESC) guidelines, patients with a cardiac implantable electronic device (CIED) are considered at moderate risk of infective endocarditis (IE), irrespective of CIED type. However, comparative data across CIED types and IE risk groups are limited. We examined IE rates according to CIED type compared with moderate- and high-risk groups. Methods and results: Danish nationwide registries were used to identify patients with first-time CIED implantation and reference populations at moderate and high risk of IE (2000–2022), based on the ESC guidelines. The high-risk group included patients with a left-sided prosthetic valve. Patients with prior IE or left-sided prosthetic valve were excluded from the CIED group. The primary outcome was incident IE within 10 years. The study included 84 171 CIED recipients, 127 966 moderate-risk patients, and 23 505 high-risk patients. Pacemakers were the most common CIED type (74.9%), followed by implantable cardioverter-defibrillator (16.6%), cardiac resynchronization therapy device with defibrillator (CRT-D) (4.6%), and cardiac resynchronization therapy device without defibrillator (3.9%). Pacemaker recipients were the oldest (median 78.2 years) and most frail. The 10-year cumulative incidence of IE was lowest in pacemaker recipients (1.0% [95% confidence interval (CI): 0.9–1.1]) and highest in CRT-D recipients (2.2% [95% CI: 1.7–2.9]). In adjusted analyses, all CIED types were associated with higher IE rates than the moderate-risk group but lower than the high-risk group. Conclusion: In this nationwide cohort, IE risk differed across CIED types, highest in CRT-D and lowest in pacemaker recipients. All CIED types were associated with higher risk than moderate-risk patients but lower risk than high-risk patients, supporting the ESC classification. Cardiac resynchronization therapy device with defibrillator recipients may warrant further evaluation of preventive strategies.

Background: Loop diuretic use (LDU) may provide complementary information on post-operative heart failure (HF) burden after mitral valve surgery (MVS). Aims: We investigated changes in LDU before and after MVS for mitral regurgitation (MR) and assessed post-operative HF admission according to age. Methods and results: Using Danish nationwide registries, we identified patients aged ≥18 years discharged after first-time MVS for MR between 1996 and 2022. LDU was assessed from redeemed prescriptions before surgery and at post-operative landmarks. HF admission within 5 years was estimated with death as a competing risk. Among 6840 patients, LDU was 46.2% before surgery and declined among survivors to 27.0% at 12–15 months and 23.7% at 36–39 months. Pre-operative use was more frequent with increasing age, ranging from 27.9% in patients aged 18–49 years to 64.3% in those aged ≥80 years. Postoperatively, LDU remained common, ranging from 13.5% to 41.6% at 12–15 months and from 11.9% to 35.4% at 36–39 months across age groups. The 5-year cumulative incidence of HF admission was 20.9% (95% CI: 20.0–22.0%) overall and increased across age groups, from 13.9% to 27.4%. Pre-operative LDU was associated with higher 5-year mortality irrespective of recorded HF status. Conclusions: LDU declined after MVS for MR but remained common, particularly among older patients, and showed an age-related pattern consistent with hospital admission for HF.

Aim: Amiodarone increases the risk of thyroid dysfunction, but the prognostic significance of this complication in patients with heart failure (HF) is uncertain. This study investigates the association between amiodarone‐related thyroid dysfunction and risk of HF hospitalization or death in a nationwide cohort. Methods: Cases and controls were identified from a source population of all HF patients who initiated treatment with amiodarone from 1996 to 2021. Patients diagnosed with and/or treated for thyroid dysfunction within 3 years of starting amiodarone were classified as cases and comprised the study population together with controls matched 1:2 based on age, sex, calendar year, and HF duration. The primary outcome was a composite of HF hospitalization and death within 1 year from onset of thyroid dysfunction, analyzed using Kaplan–Meier curves and Cox regression models adjusted for comorbidities. Results: Of 21,947 HF patients who initiated amiodarone, 2972 (14%) developed thyroid dysfunction. After matching, the study population consisted of 2953 cases and 5857 controls, mean age 70 years, and 65% men. At 1‐year follow‐up the primary outcome occurred in 1154 (39%) cases and 1826 (31%) matched controls, yielding an adjusted hazard ratio (HR) of 1.30 (95% CI 1.21–1.40). This increased risk was observed for both HF hospitalization (30% vs. 23%, HR 1.35 [1.24–1.47]) and all‐cause death (19% vs. 15%, HR 1.21 [1.08–1.34]). Conclusions: In this nested case–control study derived from a nationwide cohort of amiodarone‐treated HF patients, new‐onset thyroid dysfunction was associated with a 30% higher risk of a composite of HF hospitalization and death within 1 year.

Structured Background and Aims: Cardiac implantable electronic device (CIED)-related infective endocarditis (IE) presents distinct diagnostic and therapeutic challenges due to its unique characteristics and limited evidence supporting guidelines compared with left-sided valvular IE. We aimed to examine clinical characteristics, treatment, and mortality in patients with CIED-related IE versus left-sided valvular IE. Methods: We included patients with first-time IE using nationwide data from the NatIonal Danish endocarditis StUdieS (NIDUS) registry (2016-2021) and categorised them into isolated CIED-related IE without concomitant valvular IE and left-sided valvular IE. Results: A total of 340 patients with isolated CIED-related IE and 2,510 patients with left-sided IE were included. Patients with CIED-related IE vs. left-sided IE were older (76.1 vs. 73.2 years), and a higher proportion were males (78.5% vs. 65.9%), had diabetes (32.9% vs. 21.9%), heart failure (46.2% vs. 11.7%), Staphylococcus aureus (37.1% vs. 30.7%), coagulase-negative staphylococci (11.2% vs. 6.4%), and culture-negative IE (12.1% vs. 7.8%). However, fever at admission was lower in CIED-related IE (55.4% vs. 61.5%). CIED removal was performed in 78.2% of patients with CIED-related IE. The six-month cumulative incidence of mortality was 20.4% (95% CI:16.2-24.9%) in CIED-related IE and 26.8% (95% CI:25.1-28.6%) in left-sided IE (P=0.009). In a multivariable Cox regression model, CIED-related IE was associated with lower six-month mortality compared with left-sided IE (adjusted HR:0.52 [95% CI:0.40–0.68], P<0.001). Conclusion: In this nationwide study, patients with CIED-related IE were distinctly different from those with left-sided IE. Staphylococci were more prevalent, and despite higher age and differences in comorbidities, mortality was lower.

Background and Aims: Aortic root abscess is a severe and diagnostically challenging complication of infective endocarditis (IE). This study aimed to examine differences between IE patients with and without aortic root abscesses in patient characteristics, treatment strategies, and clinical outcomes. Methods: We conducted nationwide, unselected, registry-based cohort study using National Danish Endocarditis Studies registry. All patients with aortic valve endocarditis in Denmark from 2016 to 2021 were included. Clinical and microbiological characteristics, treatment, and mortality were compared according to status of aortic root abscess. Mortality was adjusted for clinically relevant covariates. Results: The study population included 1902 patients with aortic endocarditis, of whom 316 (17%) had an aortic root abscess. Patients with an abscess versus those without were significantly younger (median 71.5 vs 75.1 years, P-value ≤.001), more often male (76.3% vs. 69.7%, P-value = .02), prosthetic valve (50.0% vs. 30.4%, P-value ≤.001), AV-block (10% vs 1.7%, P-value ≤.001), coagulase-negative staphylococci and streptococci in their blood cultures, and were surgically treated (59.5% vs 16.1%). In multivariable Cox regression, patients with abscesses had significantly higher 1-year mortality rate compared with those without (HR 1.41, 95% CI: 1.13–1.76). When stratifying for surgery, non-operated patients with an abscess had the highest 1-year mortality 55.4%, alongside a high pre-operative risk (median age 79, 38% not self-reliant, more comorbidities including 12% active cancer). Conclusions: Aortic root abscess was present in 17% of patients with aortic valve endocarditis and was associated with distinct clinical and microbiological characteristics, a higher frequency of complications, greater prevalence of surgery albeit a higher mortality rate compared with those without an abscess.