Evaluation of DNAmAge in paired fresh, frozen, and formalin-fixed paraffin-embedded heart tissues.

The continued development in methylome analysis has enabled a more precise assessment of DNA methylation, but treatment of target tissue prior to analysis may affect DNA analysis. Prediction of age based on methylation levels in the genome (DNAmAge) has gained much interest in disease predisposition (biological age estimation), but also in chronological donor age estimation in crime case samples. Various epigenetic clocks were designed to predict the age. However, it remains unknown how the storage of the tissues affects the DNAmAge estimation. In this study, we investigated the storage method impact of DNAmAge by the comparing the DNAmAge of the two commonly used storage methods, freezing and formalin-fixation and paraffin-embedding (FFPE) to DNAmAge of fresh tissue. This was carried out by comparing paired heart tissue samples of fresh tissue, samples stored by freezing and FFPE to chronological age and whole blood samples from the same individuals. Illumina EPIC beadchip array was used for methylation analysis and the DNAmAge was evaluated with the following epigenetic clocks: Horvath, Hannum, Levine, Horvath skin+blood clock (Horvath2), PedBE, Wu, BLUP, EN, and TL. We observed differences in DNAmAge among the storage conditions. FFPE samples showed a lower DNAmAge compared to that of frozen and fresh samples. Additionally, the DNAmAge of the heart tissue was lower than that of the whole blood and the chronological age. This highlights caution when evaluating DNAmAge for FFPE samples as the results were underestimated compared with fresh and frozen tissue samples. Furthermore, the study also emphasizes the need for a DNAmAge model based on heart tissue samples for an accurate age estimation.

Surgery in patients with infective endocarditis and prognostic importance of patient frailty.

PURPOSE: Surgery is required in 20-50% of patients with infective endocarditis (IE). Frailty increases surgical risk; however, the prognostic implications of frailty in patients undergoing IE-related surgery remain poorly understood. We aimed to assess the association between frailty and all-cause mortality or rehospitalization after discharge (≥ 14 days). METHODS: We identified all IE patients who underwent surgery during admission (2010-2020) in Denmark. The Hospital Frailty Risk Score was used to categorize patients into two frailty risk groups, patients with low frailty scores (< 5 points) and frail patients (≥ 5 points). We analyzed time hospitalized after discharge and all-cause mortality from the date of surgery with a one-year follow-up. Statistical analyses utilized the Kaplan-Meier estimator, Aalen-Johansen estimator, and the Cox regression model. RESULTS: We identified 1282 patients who underwent surgery during admission, of whom 967 (75.4%) had low frailty scores, and 315 (24.6%) were frail. Frail patients were characterized by advanced age, a lower proportion of males, and a higher burden of comorbidities. Frail patients were more hospitalized (> 14 days) in the first post-discharge year (19.1% vs.12.3%) compared to patients with low frailty scores. Additionally, frail patients had higher rates of all-cause mortality including in-hospital deaths (27% vs. 15%) and rehospitalizations (43.5% vs 26.1%) compared to patients with low frailty scores. This was also evident in the adjusted analysis (hazard ratio 1.36 [CI 95% 1.09-1.71]). CONCLUSION: Frailty was associated with an ≈40% increased rate of rehospitalization (≥ 14 days) or death. Further studies are needed to assess the effectiveness of surgery with a focus on frailty to improve prognostic outcomes in these patients.

Return to Work After Refractory Out-of-Hospital Cardiac Arrest in Patients Managed With or Without Extracorporeal Cardiopulmonary Resuscitation: A Nationwide Register-Based Study.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used for refractory out-of-hospital cardiac arrest (OHCA). However, survivors managed with ECPR are at risk of poor functional status. The purpose of this study was to investigate return to work (RTW) after refractory OHCA. METHODS AND RESULTS: Of 44 360 patients with OHCA in the period of 2011 to 2020, this nationwide registry-based study included 805 patients with refractory OHCA in the working age (18-65 years) who were employed before OHCA (2% of the total OHCA cohort). Demographics, prehospital characteristics, status at hospital arrival, employment status, and survival were retrieved through the Danish national registries. Sustainable RTW was defined as RTW for ≥6 months without any long sick leave relapses. Median follow-up time was 4.1 years. ECPR and standard advanced cardiovascular life support were applied in 136 and 669 patients, respectively. RTW 1 year after OHCA was similar (39% versus 54%; P=0.2) and sustainable RTW was high in both survivors managed with ECPR and survivors managed with standard advanced cardiovascular life support (83% versus 85%; P>0.9). Younger age and shorter length of hospitalization were associated with RTW in multivariable Cox analysis, whereas ECPR was not. CONCLUSIONS: In refractory OHCA-patients employed prior to OHCA, approximately 1 out of 2 patients were employed after 1 year with no difference between patients treated with ECPR or standard advanced cardiovascular life support. Younger age and shorter length of hospitalization were associated with RTW while ECPR was not.

Computed tomographic-based three-dimensional printing of giant coronary artery fistulas to guide surgical strategy: a case series.

Background: Coronary artery fistulas (CAFs) are abnormal communications between the coronary arteries and the heart chambers, arteries, or veins, potentially leading to significant shunting, myocardial ischaemia and heart failure. Computed tomographic (CT) angiography or conventional invasive angiography is the reference standard for the diagnosis of coronary fistulas. The fistula anatomy can become very complex, which makes surgical or interventional planning challenging. Case summary: We report two cases of hugely dilated and tortuous coronary circumflex artery fistulas draining into the coronary sinus. Both patients were followed up for more than 10 years because of very complex coronary fistula anatomy and mild symptoms. From two-dimensional (2D) sliced CT images alone it, was uncertain whether surgery was feasible. However, since both patients had symptom progression (Patient 1 developed heart failure, and Patient 2 had recurrent pericardial effusions), three-dimensional (3D) heart models were printed for better understanding of the complex fistula anatomy and improved surgical planning. Both patients had successful surgery and symptomatic relief at follow-up. Discussion: The delay in surgery, until clinical deterioration, may partly be a consequence of a general reluctance in performing complex surgery in patients with CAFs. As of now, CT-based 3D printing has primarily been used in isolated cases. However, 3D printing is evolving rapidly and supplementing 2D sliced CT images with a physical 3D heart model may improve the anatomical understanding and pre-surgical planning that could lead to better surgical outcome.

Lactate and lactate clearance as predictors of one-year survival in extracorporeal cardiopulmonary resuscitation - An international, multicentre cohort study.

AIM: Extracorporeal cardiopulmonary resuscitation (ECPR) can be considered in selected patients with refractory cardiac arrest. Given the risk of patient futility and high resource utilisation, identifying ECPR candidates, who would benefit from this therapy, is crucial. Previous ECPR studies investigating lactate as a potential prognostic marker have been small and inconclusive. In this study, it was hypothesised that the lactate level (immediately prior to initiation of ECPR) and lactate clearance (within 24 hours after ECPR initiation) are predictors of one-year survival in a large, multicentre study cohort of ECPR patients. METHODS: Adult patients with refractory cardiac arrest at three German and four Danish tertiary cardiac care centres between 2011 and 2021 were included. Pre-ECPR lactate and 24-hour lactate clearance were divided into three equally sized tertiles. Multivariable logistic regression analyses and Kaplan-Meier analyses were used to analyse survival outcomes. RESULTS: 297 adult patients with refractory cardiac arrest were included in this study, of which 65 (22%) survived within one year. The pre-ECPR lactate level and 24-hour lactate clearance were level-dependently associated with one-year survival: OR 5.40 [95% CI 2.30-13.60] for lowest versus highest pre-ECPR lactate level and OR 0.25 [95% CI 0.09-0.68] for lowest versus highest 24-hour lactate clearance. Results were confirmed in Kaplan-Meier analyses (each p log rank < 0.001) and subgroup analyses. CONCLUSION: Pre-ECPR lactate levels and 24 hour-lactate clearance after ECPR initiation in patients with refractory cardiac arrest were level-dependently associated with one-year survival. Lactate is an easily accessible and quickly available point-of-care measurement which might be considered as an early prognostic marker when considering initiation or continuation of ECPR treatment.

Health-related quality of life and cognitive function after out-of-hospital cardiac arrest; a comparison of prehospital return-of-spontaneous circulation and refractory arrest managed with extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) for selected refractory out-of-hospital cardiac arrest (OHCA) is increasingly used. Detailed knowledge of health-related quality of life (HRQoL) and long-term cognitive function is limited. HRQoL and cognitive function were assessed in ECPR-survivors and OHCA-survivors with prehospital return of spontaneous circulation after standard advanced cardiac life support (sACLS). METHODS: Fifteen ECPR-survivors and 22 age-matched sACLS-survivors agreed to participate in this follow-up study. Participants were examined with echocardiography, 6-minute walk test, and neuropsychological testing, and answered HRQoL (EQ-5D-5L and Short Form 36 (SF-36)), and mental health questionnaires. RESULTS: Most patients were male (73 % and 82 %) and median age at follow-up was similar between groups (55 years and 60 years). Low flow time was significantly longer for ECPR-survivors (86 min vs. 15 min) and lactate levels were significantly higher (14.1 mmol/l vs. 3.9 mmol/l). No between-group difference was found in physical function nor in cognitive function with scores corresponding to the 23rd worst percentile of the general population. SACLS-survivors had HRQoL on level with the Danish general population while ECPR-survivors scored lower in both EQ-5D-5L (index score 0.73 vs. 0.86, p = 0.03, visual analog scale: 70 vs. 84, p = 0.04) and in multiple SF-36 health domains (role physical, bodily pain, general health, and mental health). CONCLUSIONS: Despite substantially longer low flow times with thrice as high lactate levels, ECPR-survivors were similar in cognitive and physical function compared to sACLS-survivors. Nonetheless, ECPR-survivors reported lower HRQoL overall and related to mental health, pain management, and the perception of limitations in physical role.

NatIonal Danish endocarditis stUdieS - Design and objectives of the NIDUS registry.

AIMS: The NatIonal Danish endocarditis stUdieS (NIDUS) registry aims to investigate the mechanisms contributing to the increasing incidence of infective endocarditis (IE) and to discover risk factors associated to the course, treatment and clinical outcomes of the disease. METHODS: The NIDUS registry was created to investigate a nationwide unselected group of patients hospitalized for IE. The National Danish healthcare registries have been queried for validated IE diagnosis codes (International Classification of Disease, 10th edition [ICD-10]: DI33, DI38, and DI398). Subsequently, a team of 28 healthcare professionals, including experts in endocarditis, will systematically review and evaluate all identified patient records using the modified Duke Criteria and the 2015 European Society of Cardiology modified diagnostic criteria. The registry will contain all cases with definite or possible IE found in primary data sources in Denmark between January 1, 2016, and December 31, 2021. We will gather individual patient data, such as clinical, microbiological, and echocardiographic characteristics, treatment regimens, and clinical outcomes. A digital data collection form will be used to the gathering of data. A sample of approximately 4,300 individual patients will be evaluated using primary data sources. CONCLUSIONS AND PERSPECTIVES: The NIDUS registry will be the first comprehensive nationwide IE registry, contributing critical knowledge about the course, treatment, and clinical outcomes of the disease. Additionally, it will significantly aid in identifying areas in which future research is needed.

Pulmonary Valve Replacement in Tetralogy of Fallot: Procedural Volume and Durability of Bioprosthetic Pulmonary Valves.

BACKGROUND: Robust data on changes in pulmonary valve replacement (PVR) procedural volume and predictors of bioprosthetic pulmonary valve (BPV) durability in patients with tetralogy of Fallot (TOF) are scarce. OBJECTIVES: This study sought to assess temporal trends in PVR procedural volume and BPV durability in a nationwide, retrospective TOF cohort. METHODS: Data were obtained from patient records. Robust linear regression was used to assess temporal trends in PVR procedural volume. Piecewise exponential additive mixed models were used to estimate BPV durability, defined as the time from implantation to redo PVR with death as a competing risk, and to assess risk factors for reduced durability. RESULTS: In total, 546 PVR were performed in 384 patients from 1976 to 2021. The annual number of PVR increased from 0.4 to 6.0 per million population (P < 0.001). In the last decade, the transcatheter PVR volume increased by 20% annually (P < 0.001), whereas the surgical PVR volume did not change significantly. The median BPV durability was 17 years (Q1: 10-Q3: 10 years-not applicable). There was no significant difference in the durability of different BPV after adjustment for confounders. Age at PVR (HR: 0.78 per 10 years from <1 year; 95% CI: 0.63-0.96; P = 0.02) and true inner valve diameter (9-17 mm vs 18-22 mm HR: 0.40; 95% CI: 0.22-0.73; P = 0.003 and 18-22 mm vs 23-30 mm HR: 0.59; 95% CI: 0.25-1.39; P = 0.23) were associated with reduced BPV durability in multivariate models. CONCLUSIONS: The PVR procedural volume has increased over time, with a greater increment in transcatheter than surgical PVR during the last decade. Younger patient age at PVR and a smaller true inner valve diameter predicted reduced BPV durability.

Microbiological Etiology in Patients with IE Undergoing Surgery and for Patients with Medical Treatment Only: A Nationwide Study from 2010 to 2020.

Microbiological etiology has been associated with surgery for infective endocarditis (IE) during admission, especially Staphylococcus aureus. We aimed to compare patient characteristics, microbiological characteristics, and outcomes by treatment choice (surgery or not). We identified patients with first-time IE between 2010 and 2020 and examined the microbiological etiology of IE according to treatment choice. To identify factors associated with surgery during initial admission, we used the Aalen-Johansen estimator and an adjusted cause-specific Cox model. One-year mortality stratified by microbiological etiology and treatment choice was assessed using unadjusted Kaplan-Meier estimates and an adjusted Cox proportional hazard model. A total of 6255 patients were included, of which 1276 (20.4%) underwent surgery during admission. Patients who underwent surgery were younger (65 vs. 74 years) and less frequently had cerebrovascular disease, cardiovascular disease, diabetes, and chronic kidney disease. Patients with Staphylococcus aureus IE were less likely to undergo surgery during admission (13.6%) compared to all other microbiological etiologies. One-year mortality according to microbiological etiology in patients who underwent surgery was 7.0%, 5.3%, 5.5%, 9.6%, 13.2, and 11.2% compared with 24.2%, 19.1%, 27,6%, 25.2%, 21%, and 16.9% in patients who received medical therapy for Staphylococcus aureus, Streptococcus spp., Enterococcus spp., coagulase-negative Staphylococci, "other microbiological etiologies", and blood culture-negative infective endocarditis, respectively. Patients with IE who underwent surgery differed in terms of microbiology, more often having Streptococci than those who received medical therapy. Contrary to expectations, Staphylococcus aureus was more common among patients who received medical therapy only.

Fresh and frozen cardiac tissue are comparable in DNA methylation array ß-values, but formalin-fixed, paraffin-embedded tissue may overestimate DNA methylation levels.

Untreated fresh cardiac tissue is the optimal tissue material for investigating DNA methylation patterns of cardiac biology and diseases. However, fresh tissue is difficult to obtain. Therefore, tissue stored as frozen or formalin-fixed, paraffin-embedded (FFPE) is widely used for DNA methylation studies. It is unknown whether storage conditions alter the DNA methylation in cardiac tissue. In this study, we compared the DNA methylation patterns of fresh, frozen, and FFPE cardiac tissue to investigate if the storage method affected the DNA methylation results. We used the Infinium MethylationEPIC assay to obtain genome-wide methylation levels in fresh, frozen, and FFPE tissues from nine individuals. We found that the DNA methylation levels of 21.4% of the examined CpG sites were overestimated in the FFPE samples compared to that of fresh and frozen tissue, whereas 5.7% were underestimated. Duplicate analyses of the DNA methylation patterns showed high reproducibility (precision) for frozen and FFPE tissues. In conclusion, we found that frozen and FFPE tissues gave reproducible DNA methylation results and that frozen and fresh tissues gave similar results.

First-in-Human Implantation of a New Transcatheter Tricuspid Valve Replacement System.

Therapeutic options for patients with isolated severe to torrential tricuspid regurgitation have been limited. Because a surgical option is often not attractive, new catheter-based therapies are emerging. We report the first-in-human percutaneous transcatheter tricuspid valve replacement with the MonarQ system in a 75-year-old female patient with severely symptomatic torrential tricuspid regurgitation. (Level of Difficulty: Advanced.).

Temporal trends in the incidence of infective endocarditis in patients with a prosthetic heart valve.

OBJECTIVE: The incidence of infective endocarditis (IE) is increasing, as is the insertion of prosthetic heart valves. We aimed to examine nationwide temporal trends in the incidence of IE in patients with a prosthetic heart valve in Denmark from 1999 to 2018. METHODS: Using the Danish nationwide registries, we identified patients who underwent heart valve implantation (for other reasons than IE) between 1999 and 2018. Crude incidence rates of IE per 1000 person-years (PY) were computed in 2-year intervals. IE incidences were compared using sex-adjusted and age-adjusted incidence rate ratios (IRR) using Poisson regression across calendar periods (1999-2003, 2004-2008, 2009-2013, and 2014-2018). RESULTS: We identified 26 604 patients with first-time prosthetic valve implantation (median age 71.7 years (IQR 62.7-78.0), 63% males). The median follow-up time was 5.4 years (IQR 2.4-9.6). Patients in the time period 2014-2018 were older (median age of 73.9 years (66.2:80.3)), and with a higher burden of comorbidities compared with the time period 1999-2003 (median age of 67.9 years (58.3:74.5)) at the time of implantation. A total of 1442 (5.4%) patients developed IE. The lowest IE incidence rate was 5.4/1000 PY (95% CI 3.9 to 7.4) in 2001-2002, and the highest incidence rate was 10.0/1000 PY (95% CI 8.8 to 11.1) in 2017-2018 with an unadjusted increase during the study period (p=0.003). We found an adjusted IRR of 1.04 (95% CI 1.02 to 1.06) (p<0.0007) per two calendar-years increments. Age-adjusted IRR for men were 1.04 (95% CI 1.01 to 1.07) (p=0.002) per two calendar years increment, and for women 1.03 (95% CI 0.99 to 1.07) (p=0.12), with p=0.32 for interaction. CONCLUSION: In Denmark, the incidence of IE increased during the last 20 years in patients with prosthetic heart valves.

Comparison of whole transcriptome sequencing of fresh, frozen, and formalin-fixed, paraffin-embedded cardiac tissue.

The use of fresh tissue for molecular studies is preferred but often impossible. Instead, frozen or formalin-fixed, paraffin-embedded (FFPE) tissues are widely used and constitute valuable resources for retrospective studies. We assessed the utility of cardiac tissue stored in different ways for gene expression analyses by whole transcriptome sequencing of paired fresh, frozen, and FFPE tissues. RNA extracted from FFPE was highly degraded. Sequencing of RNA from FFPE tissues yielded higher proportions of intronic and intergenic reads compared to RNA from fresh and frozen tissues. The global gene expression profiles varied with the storage conditions, particularly mitochondrial and long non-coding RNAs. However, we observed high correlations among protein-coding transcripts (ρ > 0.94) with the various storage conditions. We did not observe any significant storage effect on the allele-specific gene expression. However, FFPE had statistically significantly (p < 0.05) more discordant variant calls compared to fresh and frozen tissue. In conclusion, we found that frozen and FFPE tissues can be used for reliable gene expression analyses, provided that proper quality control is performed and caution regarding the technical variability is withheld.

Postoperative free water administration is associated with dysnatremia after congenital heart disease surgery in infants.

Dysnatremia after congenital heart disease (CHD) surgery is common. European guidelines on intraoperative fluid therapy in children recommend isotonic solutions to avoid hyponatremia, but prolonged cardiopulmonary bypass and administration of high sodium-containing solutions (i.e., blood products and sodium bicarbonate) are associated with postoperative hypernatremia. The aim of the study was to describe fluid composition prior to and during the development of postoperative dysnatremia. A retrospective observational, single-center study including infants undergoing CHD surgery. Demographics and clinical characteristics were registered. Highest and lowest plasma sodium values were recorded and associations with perioperative fluid administration, blood products, crystalloids, and colloids were explored in relation to three perioperative periods. Postoperative dysnatremia occurred in nearly 50% of infants within 48 h after surgery. Hypernatremia was mainly associated with administration of blood products (median [IQR]: 50.5 [28.4-95.5] vs. 34.5 [18.5-61.1] mL/kg; p = 0.001), and lower free water load (1.6 [1.1-2.2] mL/kg/h; p = 0.01). Hyponatremia was associated with a higher free water load (2.3 [1.7-3.3] vs. 1.8 [1.4-2.5] mL/kg/h; p = 0.001) and positive fluid balance. On postoperative day 1, hyponatremia was associated with higher volumes of free water (2.0 [1.5-2.8] vs. 1.3 [1.1-1.8] mL/kg/h; p < 0.001) and human albumin, despite a larger diuresis and more negative daily fluid balance. Postoperative hyponatremia occurred in 30% of infants despite restrictive volumes of hypotonic maintenance fluid, whereas hypernatremia was mainly associated with blood product transfusion. Individualized fluid therapy, with continuous reassessment to reduce the occurrence of postoperative dysnatremia is mandatory in pediatric cardiac surgery. Prospective studies to evaluate fluid therapy in pediatric cardiac surgery patients are warranted.

Temporal changes in the surgical management of patients with tetralogy of Fallot in Denmark: a nationwide cohort study.

OBJECTIVES: To assess temporal changes in the surgical management of patients with tetralogy of Fallot including the timing of interventions, surgical techniques, reinterventions and survival in a nationwide cohort. METHODS: Patients with tetralogy of Fallot in Denmark were divided into 3 eras based on their year of birth: early (1977-1991), intermediate (1992-2006) and late (2007-2021). RESULTS: The cohort consisted of 745 patients. Median follow-up was 21.2 years (13.7-30.5). There was a temporal trend towards less shunt palliation (-0.3% per year, 95% CI -0.05 to -0.1). Median age at intracardiac repair was 2.9 years (1.8-5.0), 0.8 years (0.5-1.3) and 0.5 years (0.4-0.7) (P < 0.001) in the early, intermediate and late era, respectively. There was a temporal trend towards less valve-sparing repair (-0.7% per year, 95% CI -0.5 to -1.0) and more repair with transannular patches (0.7% per year, 95% CI 0.5-1.0). Survival at 10 years was 79% (64-76), 90% (87-93) and 95% (92-98) (P < 0.001) and pulmonary valve replacement within the first 10 years after intracardiac repair was performed in 3% (1-6), 12% (8-16) and 21% (13-29) (P < 0.001) in the early, intermediate and late era, respectively. CONCLUSIONS: There was a temporal trend towards less shunt palliation and intracardiac repair at a younger age with more use of transannular patches. While survival throughout childhood and adolescence has improved, more patients undergo pulmonary valve replacement during the first 10 years after intracardiac repair.

Case report of rare highly aggressive cardiac tumour: the intimal sarcoma.

Background: Primary cardiac tumours are rare, and diagnosis may be difficult, as symptoms and cardiac imaging may mimic other cardiac diseases. The intimal sarcoma is the least commonly reported cardiac tumour with only few cases reported worldwide. In this case report, we present a case of an intimal sarcoma with a highly aggressive disease course. Case summary: A 60-year-old male with a history of prior aortoplasty due to congenital aortic stenosis, mechanical aortic valve replacement, and aortic stenting due to aortic dilatation presented with night sweats, malaise, and dyspnoea. Initial imaging (including transthoracic and transoesophageal echocardiography and emergency computed tomography) revealed masses suspected to be thrombi in the left atrium and ventricle. However, a positron emission tomography/computed tomography scan revealed that the masses were suspicious for malignancy. The patient underwent non-radical tumour resection and insertion of biological valve prostheses. Subsequent tissue analysis and pathology assessment revealed an intimal sarcoma. There were no curative treatment options, and the patient succumbed to his illness <3 months after surgery. Discussion: This case report presents a case of a highly aggressive intimal sarcoma. As complete tumour resection is of great importance when it comes to life expectancy in cardiac sarcomas, early diagnosis using non-invasive and invasive imaging modalities is essential to start early treatment and to improve outcomes in this patient group.

Structural abnormalities after aortic root replacement with stentless xenograft.

OBJECTIVE: In complex and high-risk aortic root disease, the porcine Freestyle stentless bioprosthesis (Medtronic Inc, Minneapolis, Minn) is an important surgical treatment option. We aimed to determine prevalence and clinical effect of structural and functional abnormalities after full-root Freestyle implantation. METHODS: Our cross-sectional 2-center study combined with clinical follow-up included 253 patients with full-root Freestyle bioprostheses implanted from 1999 to 2017. Patients underwent transthoracic echocardiography (TTE) and contrast-enhanced, electrocardiogram-gated 4-dimensional cardiac computed tomography (4DCT) at median age 70 (interquartile range, 62-75) years. After 4DCT, clinical follow-up continued throughout 2018. Median follow-up was 3.3 years before 4DCT and 1.4 years after. RESULTS: We identified abnormalities in 46% of patients, including pseudoaneurysms (n = 32; 13%), moderate or severe coronary ostial stenosis (n = 54; 21%), and moderate-severe leaflet thickening or reduced leaflet motion (n = 51; 20%). TTE only identified 1 patient with pseudoaneurysm. After 4DCT, the unadjusted hazard ratio for surgical reintervention among patients with abnormal 4DCT was 4.2 (95% confidence interval, 1.2-15.3), in all, 10% required a reintervention. 4DCT abnormalities were associated with a statistically nonsignificant increased risk of death, stroke, or myocardial infarction (hazard ratio obtained using Cox proportional hazards regression analysis, 2.4; 95% confidence interval, 0.7-7.6). In all, 4.0% died, 3.6% had a myocardial infarction, and 2.0% had a stroke. CONCLUSIONS: Structural and functional abnormalities of the aortic root are frequent after Freestyle implantation and TTE appears to be insufficient for follow-up. Abnormalities might be associated with increased risk of reintervention and potentially adverse clinical outcomes. Longer follow-up and larger study populations are needed to further clarify the clinical implications of abnormalities identified with 4DCT.

Rehospitalisations, repeated aortic surgery, and death in initial survivors of surgery for Stanford type A aortic dissection and the significance of age - a nationwide registry-based cohort study.

AIMS: Describe and compare incidences across age groups of rehospitalization, repeated aortic surgery, and death in patients who survived surgery and hospitalization for type A aortic dissection. METHODS AND RESULTS: From Danish nationwide registries, we identified patients hospitalized with Stanford type A aortic dissections (2006-2018). Survivors of hospitalization and surgery on the ascending aorta and/or aortic arch comprised the study population (n = 606, 36 (38.9%) <60 years old (group I), 194 (32.0%) 60-69 years old (group II), and 176 (29.1%) >69 years old (group III)). During the first year, 62.5% were re-hospitalized and 1.4% underwent repeated aortic surgery with no significant differences across age groups (P = 0.68 and P = 0.39, respectively). Further, 5.9% died (group I: 3.0%, group II: 8.3%, group III: 7.4%, P = 0.04). After 10 years, 8.0% had undergone repeated aortic surgery (group I: 11.5%, group II: 8.5%, group III: 1.6%, P = 0.04) and 10.2% (group I), 17.0% (group II), and 22.2% (group III) had died (P = 0.01). Using multivariable Cox regression analysis, we described long-term outcomes comparing age groups. No age differences were found in one-year outcomes, while age > 69 years compared with age < 60 years was associated with a lower rate of repeated aortic surgery [hazard ratio 0.17, 95% confidence interval (CI) 0.04-0.78] and a higher rate of all-cause mortality (hazard ratio 2.44, 95% CI 1.37-4.34) in the 10-year analyses. CONCLUSION: Rehospitalisations in the first year after discharge were common in all age groups, but survival was high. Repeated aortic surgery was significantly more common among younger than older patients.

Extracorporeal cardiopulmonary resuscitation: a national study on the association between favourable neurological status and biomarkers of hypoperfusion, inflammation, and organ injury.

AIMS: In refractory out-of-hospital cardiac arrest (OHCA) with prolonged whole-body ischaemia, global tissue injury proceeds even after establishment of circulation with extracorporeal cardiopulmonary resuscitation (ECPR). We aimed to investigate the role of biomarkers reflecting hypoperfusion, inflammation, and organ injury in prognostication of patients with refractory OHCA managed with ECPR. METHODS AND RESULTS: This nationwide retrospective study included 226 adults with refractory OHCA managed with ECPR in Denmark (2011-2020). Biomarkers the first days after ECPR-initiation were assessed. Odds ratio of favourable neurological status (Cerebral Performance Category 1-2) at hospital discharge was estimated by logistic regression analyses. Cut-off values were calculated using the Youden's index. Fifty-six patients (25%) survived to hospital discharge, 51 (91%) with a favourable neurological status. Factors independently associated with favourable neurological status were low flow time <81 min, admission leukocytes ≥12.8 × 109/L, admission lactate <13.2 mmol/L, alkaline phosphatase (ALP) < 56 (day1) or <55 U/L (day2), and day 1 creatine kinase MB (CK-MB) < 500 ng/mL. Selected biomarkers (leukocytes, C-reactive protein, and lactate) were significantly better predictors of favourable neurological status than classic OHCA-variables (sex, age, low-flow time, witnessed arrest, shockable rhythm) alone (P = 0.001) after hospital admission. CONCLUSION: Biomarkers of hypoperfusion (lactate), inflammation (leucocytes), and organ injury (ALP and CK-MB) were independently associated with neurological status at hospital discharge. Biomarkers of hypoperfusion and inflammation (at hospital admission) and organ injury (days 1 and 2 after ECPR) may aid in the clinical decision of when to prolong or terminate ECPR in cases of refractory OHCA.

Surgical treatment of patients with infective endocarditis: changes in temporal use, patient characteristics, and mortality-a nationwide study.

BACKGROUND: Valve surgery guidelines for infective endocarditis (IE) are unchanged over decades and nationwide data about the use of valve surgery do not exist. METHODS: We included patients with first-time IE (1999-2018) using Danish nationwide registries. Proportions of valve surgery were reported for calendar periods (1999-2003, 2004-2008, 2009-2013, 2014-2018). Comparing calendar periods in multivariable analyses, we computed likelihoods of valve surgery with logistic regression and rates of 30 day postoperative mortality with Cox regression. RESULTS: We included 8804 patients with first-time IE; 1981 (22.5%) underwent surgery during admission, decreasing by calendar periods (N = 360 [24.4%], N = 483 [24.0%], N = 553 [23.5%], N = 585 [19.7%], P = < 0.001 for trend). For patients undergoing valve surgery, median age increased from 59.7 to 66.9 years (P ≤ 0.001) and the proportion of males increased from 67.8% to 72.6% (P = 0.008) from 1999-2003 to 2014-2018. Compared with 1999-2003, associated likelihoods of valve surgery were: Odds ratio (OR) = 1.14 (95% CI: 0.96-1.35), OR = 1.20 (95% CI: 1.02-1.42), and OR = 1.10 (95% CI: 0.93-1.29) in 2004-2008, 2009-2013, and 2014-2018, respectively. 30 day postoperative mortalities were: 12.7%, 12.8%, 6.9%, and 9.7% by calendar periods. Compared with 1999-2003, associated mortality rates were: Hazard ratio (HR) = 0.96 (95% CI: 0.65-1.41), HR = 0.43 (95% CI: 0.28-0.67), and HR = 0.55 (95% CI 0.37-0.83) in 2004-2008, 2009-2013, and 2014-2018, respectively. CONCLUSIONS: On a nationwide scale, 22.5% of patients with IE underwent valve surgery. Patient characteristics changed considerably and use of valve surgery decreased over time. The adjusted likelihood of valve surgery was similar between calendar periods with a trend towards an increase while rates of 30 day postoperative mortality decreased.