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.

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.

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.

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.

Postoperative dysnatremia in infants after open-heart surgery occurs frequently and is associated with prolonged intensive care length of stay.

BACKGROUND: Dysnatremia after surgery for congenital heart disease (CHD) is well known and has been associated with prolonged pediatric intensive care unit length of stay (PICU-LOS). Fluctuations in plasma sodium levels occur perioperatively. The primary aim of the study was to evaluate the occurrence of dysnatremia during the first 48 h after surgery and whether it was associated with PICU-LOS. The secondary aim was to evaluate if the degree of sodium fluctuations was associated with PICU-LOS. METHODS: A retrospective observational, single-center study including infants undergoing surgery for CHD. The highest and lowest plasma sodium value was registered for the prespecified time periods. PICU-LOS was analyzed in relation to the occurrence of dysnatremia and the degree of plasma sodium fluctuations. The occurrence of dysnatremia was evaluated in relation to surgical procedure and fluid administration. RESULTS: Two hundred and thirty infants who underwent 249 surgical procedures were included. Dysnatremia developed in more than 60% within 48 h after surgery. Infants with normonatremia had a 40%-50% shorter PICU-LOS among children in RACHS-1 category 3-6, compared with infants developing either hypo- or hyper-/hyponatremia within 48 h after surgery (p = .006). Infants who had a decline of plasma sodium >11 mmol/L had almost double the PICU-LOS compared to those with a decline of <8 mmol/L. CONCLUSION: Dysnatremias were common after surgery for CHD and associated with prolonged PICU-LOS. The degree of decline in plasma sodium was significantly associated with PICU-LOS. Fluid administration both in terms of volume and components (blood products and crystalloids) as well as diuresis were related to the occurrence of dysnatremias.

Long-Term Mortality in Different Age Groups of Patients with Infective Endocarditis Who Undergo Aortic Root Replacement: A Nationwide Study.

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.

Differences in mortality in patients undergoing surgery for infective endocarditis according to age and valvular surgery.

BACKGROUND: Infective endocarditis (IE) is associated with high mortality. Surgery may improve survival and reduce complications, but the balance between benefit and harm is difficult and may be closely related to age and type of surgical intervention. We aimed to examine how age and type of left-sided surgical intervention modified mortality in patients undergoing surgery for IE. METHODS: By crosslinking nationwide Danish registries we identified patients with first-time IE undergoing surgical treatment 2000-2017. Patients were grouped by age < 60 years, 60-75 years, and ≥ 75 years. Multivariable adjusted Cox proportional hazard analysis was used to examine factors associated with 90-day mortality. RESULTS: We included 1767 patients with IE undergoing surgery, 735 patients < 60 years (24.1% female), 766 patients 60-75 years (25.8% female), and 266 patients ≥75 years (36.1% female). The proportions of patients undergoing surgery were 35.3, 26.9, and 9.1% for patients < 60 years, 60-75 years, and > 75 years, respectively. Mortality at 90 days were 7.5, 13.9, and 22.3% (p < 0.001) for three age groups. In adjusted analyses, patients 60-75 years and patients ≥75 years were associated with a higher mortality, HR = 1.84 (95% CI: 1.48-2.29) and HR = 2.47 (95% CI: 1.88-3.24) as compared with patients < 60 years. Factors associated with 90-day mortality were: mitral valve surgery, a combination of mitral and aortic valve surgery as compared with isolated aortic valve surgery, age, diabetes, and prosthetic heart valve implantation prior to IE admission. CONCLUSIONS: In patients undergoing surgery for IE, mortality increased significantly with age and 1 in 5 died above age 75 years. Mitral valve surgery as well as multiple valve interventions augmented mortality further.

Resolving the natural myocardial remodelling brought upon by cardiac contraction; a porcine ex-vivo cardiovascular magnetic resonance study of the left and right ventricle.

BACKGROUND: The three-dimensional rearrangement of the right ventricular (RV) myocardium during cardiac deformation is unknown. Previous in-vivo studies have shown that myocardial left ventricular (LV) deformation is driven by rearrangement of aggregations of cardiomyocytes that can be characterised by changes in the so-called E3-angle. Ex-vivo imaging offers superior spatial resolution compared with in-vivo measurements, and can thus provide novel insight into the deformation of the myocardial microstructure in both ventricles. This study sought to describe the dynamic changes of the orientations of the cardiomyocytes in both ventricles brought upon by cardiac contraction, with particular interest in the thin-walled RV, which has not previously been described in terms of its micro-architecture. METHODS: The hearts of 14 healthy 20 kg swine were excised and preserved in either a relaxed state or a contracted state. Myocardial architecture was assessed and compared between the two contractional states by quantification of the helical, transmural and E3-angles of the cardiomyocytes using high-resolution diffusion tensor imaging. RESULTS: The differences between the two states of contraction were most pronounced in the endocardium where the E3-angle decreased from 78.6° to 24.8° in the LV and from 82.6° to 68.6° in the RV. No significant change in neither the helical nor the transmural angle was found in the cardiomyocytes of the RV. In the endocardium of the LV, however, the helical angle increased from 35.4° to 47.8° and the transmural angle increased from 3.1° to 10.4°. CONCLUSION: The entire myocardium rearranges through the cardiac cycle with the change in the orientation of the aggregations of cardiomyocytes being the predominant mediator of myocardial wall thickening. Interestingly, differences also exist between the RV and LV, which helps in the explanation of the different physiological capabilities of the ventricles.

Incidence and factors associated with infective endocarditis in patients undergoing left-sided heart valve replacement.

Aims: Patients with left-sided heart valve replacement are considered at high-risk of infective endocarditis (IE). However, data on the incidence and risk factors associated with IE are sparse. Methods and results: Through Danish administrative registries, we identified patients who underwent left-sided heart valve replacement from January 1996 to December 2015. Patients were categorized in mitral and aortic valve replacement (MVR and AVR) and followed until: 12 years after valve surgery, end of study, death, emigration, or hospitalization due to IE, whichever came first. Multivariable adjusted Cox proportional hazard analysis was used to investigate which baseline characteristics were associated with IE. A total of 18 041 patients were included. The cumulative IE risk at 10 years follow-up was 5.2% in both MVR and AVR patients. In patients with MVR, male sex [hazard ratio (HR) = 1.68, 95% confidence interval (95% CI) 1.06-2.68], bioprosthetic valve (HR = 1.91, 95% CI 1.08-3.37), and heart failure (HR = 1.69, 95% CI 1.06-2.68) were among factors associated with an increased risk of IE. In AVR patients, male sex (HR = 1.59, 95% CI 1.33-1.89), bioprosthetic valve (HR = 1.70, 95% CI 1.35-2.15), and cardiac implantable electronic device (CIED) (HR = 1.57, 95% CI 1.19-2.06) were among factors associated with an increased risk of IE. Conclusion: Infective endocarditis after left-sided heart valve replacement is not uncommon and occurs in about 1/20 over 10 years. Male, bioprosthetic valve, and heart failure were among factors associated with IE in MVR patients while male, bioprosthetic valve, and CIED were among factors associated with IE in AVR patients.

Changes in overall ventricular myocardial architecture in the setting of a porcine animal model of right ventricular dilation.

BACKGROUND: Chronic pulmonary regurgitation often leads to myocardial dysfunction and heart failure. It is not fully known why secondary hypertrophy cannot fully protect against the increase in wall stress brought about by the increased end-diastolic volume in ventricular dilation. It has been assumed that mural architecture is not deranged in this situation, but we hypothesised that there might be a change in the pattern of orientation of the aggregations of cardiomyocytes, which would contribute to contractile impairment. METHODS: We created pulmonary valvular regurgitation by open chest, surgical suturing of its leaflets in seven piglets, performing sham operations in seven control animals. Using cardiovascular magnetic resonance imaging after 12 weeks of recovery, we demonstrated significantly increased right ventricular volumes in the test group. After sacrifice, diffusion tensor imaging of their hearts permitted measurement of the orientation of the cardiomyocytes. RESULTS: The helical angles in the right ventricle approached a more circumferential orientation in the setting of right ventricular RV dilation (p = 0.007), with an increased proportion of surface-parallel cardiomyocytes. In contrast, this proportion decreased in the left ventricle. Also in the left ventricle a higher proportion of E3 angles with a value around zero was found, and conversely a lower proportion of angles was found with a numerical higher value. In the dilated right ventricle the proportion of E3 angles around -90° is increased, while the proportion around 90° is decreased. CONCLUSION: Contrary to traditional views, there is a change in the orientation of both the left ventricular and right ventricular cardiomyocytes subsequent to right ventricular dilation. This will change their direction of contraction and hinder the achievement of normalisation of cardiomyocytic strain, affecting overall contractility. We suggest that the aetiology of the cardiac failure induced by right vetricular dilation may be partly explained by morphological changes in the myocardium itself.

The thick left ventricular wall of the giraffe heart normalises wall tension, but limits stroke volume and cardiac output.

Giraffes--the tallest extant animals on Earth--are renowned for their high central arterial blood pressure, which is necessary to secure brain perfusion. Arterial pressure may exceed 300 mmHg and has historically been attributed to an exceptionally large heart. Recently, this has been refuted by several studies demonstrating that the mass of giraffe heart is similar to that of other mammals when expressed relative to body mass. It thus remains unexplained how the normal-sized giraffe heart generates such massive arterial pressures. We hypothesized that giraffe hearts have a small intraventricular cavity and a relatively thick ventricular wall, allowing for generation of high arterial pressures at normal left ventricular wall tension. In nine anaesthetized giraffes (495±38 kg), we determined in vivo ventricular dimensions using echocardiography along with intraventricular and aortic pressures to calculate left ventricular wall stress. Cardiac output was also determined by inert gas rebreathing to provide an additional and independent estimate of stroke volume. Echocardiography and inert gas-rebreathing yielded similar cardiac outputs of 16.1±2.5 and 16.4±1.4 l min(-1), respectively. End-diastolic and end-systolic volumes were 521±61 ml and 228±42 ml, respectively, yielding an ejection fraction of 56±4% and a stroke volume of 0.59 ml kg(-1). Left ventricular circumferential wall stress was 7.83±1.76 kPa. We conclude that, relative to body mass, a small left ventricular cavity and a low stroke volume characterizes the giraffe heart. The adaptations result in typical mammalian left ventricular wall tensions, but produce a lowered cardiac output.

The myocardial architecture changes in persistent pulmonary hypertension of the newborn in an ovine animal model.

BACKGROUND: Persistent pulmonary hypertension in the newborn remains a syndrome with high mortality. Knowledge of changes in myocardial architecture in the setting of heart failure in persistent pulmonary hypertension is lacking, and could aid in the explanation of the prevailing high mortality. METHODS: Persistent pulmonary hypertension was induced by antenatal ligation of the arterial duct in six ovine fetuses. The hearts were compared ex vivo with five matched control hearts, using diffusion tensor imaging to provide the overall anatomical arrangement, and assessment of the angulations and course of the cardiomyocytes. Fibrosis was assessed with histology. RESULTS: We found an overall increase in heart size in pulmonary hypertension, with myocardial thickening confined to the interventricular septum. An increase of 3.5° in angulation of myocyte aggregations was found in hypertensive hearts. In addition, we observed a 2.2% increase in collagen content in the right ventricular free wall. Finally, we found a previously undescribed subepicardial layer of strictly longitudinally oriented cardiomyocytes confined to the right ventricle in all hearts. CONCLUSION: Myocardial fibrosis and possibly changes in angulations of myocytes seem to play a part in the etiology of persistent pulmonary hypertension. Moreover, a new anatomical arrangement of right ventricular mural architecture is described.

The functional architecture of skeletal compared to cardiac musculature: Myocyte orientation, lamellar unit morphology, and the helical ventricular myocardial band.

How the cardiomyocytes are aggregated within the heart walls remains contentious. We still do not fully understand how the end-to-end longitudinal myocytic chains are arranged, nor the true extent and shape of the lamellar units they aggregate to form. In this article, we show that an understanding of the complex arrangement of cardiac musculature requires knowledge of three-dimensional myocyte orientation (helical and intrusion angle), and appreciation of myocyte packing within the connective tissue matrix. We show how visualization and segmentation of high-resolution three-dimensional image data can accurately identify the morphology and orientation of the myocytic chains, and the lamellar units. Some maintain that the ventricles can be unwrapped in the form of a "helical ventricular myocardial band," that is, as a compartmentalized band with selective regional innervation and deformation, and a defined origin and insertion like most skeletal muscles. In contrast to the simpler interpretation of the helical ventricular myocardial band, we provide insight as to how the complex myocytic chains, the heterogeneous lamellar units, and connective tissue matrix form an interconnected meshwork, which facilitates the complex internal deformations of the ventricular wall. We highlight the dangers of disregarding the intruding cardiomyocytes. Preparation of the band destroys intruding myocytic chains, and thus disregards the functional implications of the antagonistic auxotonic forces they produce. We conclude that the ventricular myocardium is not analogous to skeletal muscle, but is a complex three-dimensional meshwork, with a heterogeneous branching lamellar architecture.

Optimal preservation of porcine cardiac tissue prior to diffusion tensor magnetic resonance imaging.

The effects of ex vivo preservation techniques on the quality of diffusion tensor magnetic resonance imaging in hearts are poorly understood, and the optimal handling procedure prior to investigation remains to be determined. Therefore, 24 porcine hearts were examined in six groups treated with different preservation techniques, including chemical fixation and freezing. Diffusion properties of each heart were assessed with diffusion tensor imaging in terms of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da) and radial diffusivity (Dr). Tractography was performed to visualize the course of the cardiomyocytes, assuming greater diffusivity in the longitudinal than the transverse axis of individual cardiomyocytes. Significant differences in MD, Da and Dr were found, as well as in FA between groups (P < 0.001). Freezing of specimens resulted in the lowest mean FA of 0.21 (0.06) and highest Dr of 8.92 (1.5) mm2 s(-1) . The highest mean FA was found to be 0.43 (0.11) in hearts perfusion-fixed with formalin. Calculated tractographies were indistinguishable among groups except in frozen specimens, where no fibres could be tracked. Perfusion fixation with formalin provided the best tractography, but immersion fixation yielded diffusion data most similar to fresh hearts. These findings suggest that parameters derived from diffusion tensor imaging in ex vivo hearts are sensitive to fixation and storage methods. In particular, freezing of specimens should be avoided prior to diffusion tensor imaging investigation due to significant changes in diffusion parameters and subsequent image deteriorations.

Development of left ventricular hypertrophy in a novel porcine model of mitral regurgitation.

OBJECTIVES: We aimed to develop a porcine model for chronic nonischemic mitral regurgitation (MR) to investigate left ventricular (LV) enlargement and eccentric hypertrophy. DESIGN: Nonischemic MR was induced in 30 pigs by open-chest immobilization of the posterior mitral leaflet by transannular traction sutures that where applied in transmyocardial fashion. A sham operated control group (n = 13) was included. Echocardiographic LV size and heart weight assessed at euthanasia were used to evaluate the development of LV enlargement and eccentric hypertrophy after 8 weeks follow-up. RESULTS: Eight pigs died and seven were excluded due to mediastinal infection (n = 2) or failure to produce MR (n = 5). Thus, 28 pigs were included and were divided into three groups: controls (n = 12), mild MR (mMR; n = 10), and moderate to severe MR (sMR; n = 6). The change in LV internal diameter in diastole (LVIDd) from baseline to follow-up was significantly higher in the sMR group compared to that of the control group (P = 0.0017). Furthermore, LV weight was significantly increased in the mMR (P = 0.047) and the sMR (P = 0.0087) groups compared to that of the control group. CONCLUSIONS: A new model for chronic moderate to severe nonischemic MR with development of LV enlargement and eccentric hypertrophy within 8 weeks has been established in pigs.

Prognostic Impact of Anemia in Patients Undergoing Aortic Valve Replacement: A Nationwide Study.

BACKGROUND: Patients undergoing aortic valve replacement (AVR) have high readmission rates. Several risk factors have been proposed as potential modifiable targets, including anemia. We examined the association between anemia at discharge and subsequent outcomes in these patients. METHODS: Using Danish nationwide registries, we identified all patients who underwent AVR between 2015-2021, were alive at discharge (index date), and had an available hemoglobin (Hb) measurement taken between procedure and discharge. Patients were categorized as having i) moderate/severe anemia (Hb<6.2 mmol/L) or ii) no/mild anemia (Hb≥6.2 mmol). The one-year rates of all-cause mortality, all-cause hospital admission, heart failure (HF) admission, and atrial fibrillation (AF) admission were compared using multivariable Cox regression models. RESULTS: 8,614 patients were identified; 2,847 (33.1%) had moderate/severe anemia (60.2% male, median age 74) and 5,767 (66.9%) had no/mild anemia (68.0% male, median age 76). For these two groups, respectively, the cumulative one-year incidences of the outcomes were: i) all-cause mortality: 5.1% vs. 4.3%; ii) all-cause admission: 53.8% vs. 47.5%; iii) AF admission: 14.0% vs. 11.6%); iv) HF admission: 6.8% vs. 6.2%. In adjusted analysis, moderate/severe anemia, compared with no/mild anemia, was associated with higher rates of all-cause mortality (hazard ratio (HR) 1.27 [95%CI 1.02-1.58]), all-cause admission (HR 1.22 [95%CI 1.14-1.30]), and AF admission (HR 1.23 [95%CI 1.08-1.40]), but not HF admission (HR 1.09 [95%CI 0.91-1.31]). CONCLUSION: In patients undergoing AVR, moderate/severe anemia at discharge, compared with no/mild anemia, was associated with increased all-cause mortality, all-cause hospital admission, and AF admission, but not HF admission, at one-year post-discharge.

Early surgery to prevent embolic events in patients with infective endocarditis: a comprehensive review.

BACKGROUND: Infective endocarditis (IE) is a dangerous and lethal illness with high mortality rates. One of the main indications for surgery according to the guidelines is prevention of embolic events. However, uncertainty remains concerning the timing of surgery and the effect of early surgery in combination with antibiotic therapy versus antibiotic therapy alone in IE patients with a vegetation size > 10 mm. METHODS: We conducted a comprehensive review by searching the PubMed, MEDLINE, and EMbase databases. Titles and abstracts were screened, and studies of interest were selected for full-text assessment. Studies were selected for review if they met the criteria of comparing surgical treatment + antibiotic therapy to antibiotic therapy alone in patients with vegetations > 10 mm. RESULTS: We found 1,503 studies through our database search; nine of these were eligible for review, with a total number of 3,565 patients. Median age was 66 years (range: 17-80) and the median percentage of male patients was 65.6% (range: 61.8 - 71.4%). There was one randomised controlled trial, one prospective study, and seven retrospective studies. Seven studies found surgery + antibiotic therapy to be associated with better outcomes in patients with IE and vegetations > 10 mm, one of them being the randomised trial [hazard ratio = 0.10; 95% confidence interval 0.01-0.82]. Two studies found surgery + antibiotic therapy was associated with poorer outcomes compared with antibiotic therapy alone. CONCLUSION: Overall, data vary in quality due to low numbers and selection bias. Evidence is conflicting, yet suggest that surgery + antibiotic therapy is associated with better outcomes in patients with IE and vegetations > 10 mm for prevention of emboli. Properly powered randomised trials are warranted.

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.

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.

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.