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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., 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.

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., 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.

first_pagesettingsOrder Article Reprints Open AccessArticle Microbiological Etiology in Patients with IE Undergoing Surgery and for Patients with Medical Treatment Only: A Nationwide Study from 2010 to 2020 by Peter Laursen Graversen 1,*ORCID,Lauge Østergaard 1,Marianne Voldstedlund 2ORCID,Malthe Faurschou Wandall-Holm 3ORCID,Morten Holdgaard Smerup 4,Lars Køber 1,5 andEmil Loldrup Fosbøl 1,5 1 Department of Cardiology, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark 2 Department of Data Integration and Analysis, Statens Serum Institut, 2300 Copenhagen, Denmark 3 Danish Multiple Sclerosis Registry, Department of Neurology, University of Copenhagen—Rigshospitalet, 2600 Glostrup, Denmark 4 Department of Cardiothoracic Surgery, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark 5 Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark * Author to whom correspondence should be addressed. Microorganisms 2023, 11(10), 2403; https://doi.org/10.3390/microorganisms11102403 Original submission received: 10 July 2023 / Revised: 21 September 2023 / Accepted: 23 September 2023 / Published: 26 September 2023 (This article belongs to the Special Issue The Infective Endocarditis) Downloadkeyboard_arrow_down Browse Figures Review Reports Versions Notes Abstract 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 mortal, 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.

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.)

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.

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.

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., 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.

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%) 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.

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., 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.

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 = 12.8 x 10(9)/L, admission lactate

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.

BACKGROUND: Infective endocarditis (IE) with involvement of the aortic root is associated with high short-term mortality and morbidity. Long-term data are sparse, and the existing studies with long-term data are restricted by a low number of patients and do not report mortality risks of different age groups. OBJECTIVE: This study examined the all-cause mortality risk postoperatively of patients with first-time IE who underwent aortic root replacement (ARR), according to age at the time of surgery, with one and 10 years follow-up. METHODS: Patients with first-time IE who underwent ARR surgery from 2000-2016 were identified in Danish nationwide administrative registries and divided into age groups: ≤60, 61-74, and ≥75 years. We compared one- and 10-year mortality risk using multivariable Cox regression across the three age groups. RESULTS: We identified 258 patients who underwent ARR (26.0% female, 42.6% with prosthetic valves, median age 64 years (IQR 55-73), of whom 98, 112, and 48 patients were ≤60 years, 61-74 years, and >75 years, respectively. The corresponding in-hospital mortality risk was 10.2%, 22.3%, and 29.2% (P = .01), respectively. The one-year postoperative mortality risk was 17.3%, 28.6%, and 33.3% (P = 0.05), while at 10 years after surgery, it was 31.8%, 62.9%, and 77.1% (P < 0.01), respectively. The adjusted 10-year hazard ratio was higher in the 61-74 and >75-year age groups (HR 1.94 [1.18-3.16] and 2.46 [1.35-4.49]) compared with the ≤60. CONCLUSION: Aortic root replacement in patients with first-time IE was associated with a high in-hospital and one- and 10-year mortality with worse outcomes with age.