Flowreversal in the left internal jugular vein due to a prominent brachiocephalic trunk: A case report.

Reversal of blood flow has only been reported in the left internal jugular vein following interventions such as central venous catheter, dialysis shunt placement, or external compression from a tumor. We describe a rare case of chronic headache and hearing loss due to flow reversal in the left internal jugular vein and compensatory massive dilation of the right internal jugular vein. Flow reversal was caused by a prominent brachiocephalic trunk with subseqent compression of the vena brachiocephalica sinistra. Vascular anomalies and associated venous bypass circulation may be considered as a rare cause of non-specific malaise. Restoration of the physiological direction of blood flow should be discussed on an interdisciplinary basis given the unpredictable haemodynamic consequences.

Lipoprotein(a) as a risk factor for atherosclerotic cardiovascular disease in patients in non-metropolitan areas of Brandenburg, Germany.

Background and aims: In the non-metropolitan region of Brandenburg (Germany), which is characterized by high rates of cardiovascular diseases and underserved medical care, there is a lack of awareness regarding lipoprotein(a) [Lp(a)] as a risk factor. In addition, data from patients with atherosclerotic cardiovascular disease (ASCVD) in diverse regional backgrounds, including the understudied Brandenburg cohort, and various healthcare statuses remain insufficient. Methods: In this WalkByLab study, Lp(a) levels were monitored in a non-metropolitan cohort (n = 850) in Brandenburg, Germany, comprising 533 patients at high cardiovascular risk and 317 healthy controls. Patients underwent a comprehensive angiological screening, which included blood serum analysis, assessment of medical and family history, cardiovascular risk, and disease status, and evaluation of lifestyle and quality of life. All parameters were evaluated with regard to two groups based on Lp(a) levels: low (<50 mg/dl) and high (≥50 mg/dl). Results: Brandenburg patients with cardiovascular diseases showed higher Lp(a) levels than healthy controls (24.2% vs. 14.8%, p = 0.001). Logistic regression analysis with different characteristics revealed that Lp(a) was an independent risk factor significantly associated with ASCVD (OR 2.26, 95% CI 1.32-3.95, p = 0.003). The high-Lp(a) group showed a higher proportion of patients with coronary artery disease, peripheral artery disease, or cerebrovascular disease compared to the low-Lp(a) group (50% vs. 36.8%; 57.7% vs. 45.8%; 17.6% vs. 9.2%; p = 0.004); also, a higher percentage of patients in the high-Lp(a) group had heart failure (72.8% vs. 53.2%, p = 0.014) and myocardial infarction (24.7% vs. 13.9%, p = 0.001). The high-Lp(a) group exhibited higher rates of statins (63.1% vs. 50.4%, p = 0.003), ezetimibe (14.8% vs. 5.5.%, p = 0.001), and beta-blockers (55.7% vs. 40.7%, p = 0.001) use. Lp(a) levels were found to be independent of physical activity or smoking behavior and did not change over time (12 months). Conclusions: Our study highlights the significance of elevated Lp(a) levels in Brandenburg cardiovascular patients and identifies them as an independent risk factor for ASCVD, which has implications for addressing cardiovascular health of non-metropolitan populations.

Coronary microthrombi in the failing human heart: the role of von Willebrand factor and PECAM-1.

The recognition of microthrombi in the heart microcirculation has recently emerged from studies in COVID-19 decedents. The present study investigated the ultrastructure of coronary microthrombi in heart failure (HF) due to cardiomyopathies that are unrelated to COVID-19 infection. In addition, we have investigated the role of von Willebrand factor (VWF) and PECAM-1 in microthrombus formation. We used electron microscopy to investigate the occurrence of microthrombi in patients with HF due to dilated (DCM, n = 7), inflammatory (MYO, n = 6) and ischemic (ICM, n = 7) cardiomyopathy and 4 control patients. VWF and PECAM-1 was studied by quantitative immunohistochemistry and Western blot. In comparison to control, the number of microthrombi was increased 7-9 times in HF. This was associated with a 3.5-fold increase in the number of Weibel-Palade bodies (WPb) in DCM and MYO compared to control. A fivefold increase in WPb in ICM was significantly different from control, DCM and MYO. In Western blot, VWF was increased twofold in DCM and MYO, and more than threefold in ICM. The difference between ICM and DCM and MYO was statistically significant. These results were confirmed by quantitative immunohistochemistry. Compared to control, PECAM-1 was by approximatively threefold increased in all groups of patients. This is the first study to demonstrate the occurrence of microthrombi in the failing human heart. The occurrence of microthrombi is associated with increased expression of VWF and the number of WPb, being more pronounced in ICM. These changes are likely not compensated by increases in PECAM-1 expression.

Atrial fibrillation in human patients is associated with increased collagen type V and TGFbeta1.

Background and aim: Atrial fibrosis is an important factor in initiating and maintaining atrial fibrillation (AF). Collagen V belongs to fibrillar collagens. There are, however no data on collagen V in AF. The aim of this work was to study the quantity of collagen V and its relationship with the number of fibroblasts and TGF- b 1 expression in patients in sinus rhythm (SR) and in patients with atrial fibrillation (AF). Methods: We used quantitative immuhistochemistry to study collagen V in right and left atrial biopsies obtained from 35 patients in SR, 35 patients with paroxysmal AF (pAF) and 27 patients with chronic, long-standing persistent AF (cAF). In addition, we have quantified the number of vimentin-positive fibroblasts and expression levels of TGF-ß1. Results: Compared to patients in SR, collagen V was increased 1.8- and 3.1-fold in patients with pAF and cAF, respectively. In comparison with SR patients, the number of vimentin-positive cells increased significantly 1.46- and 1.8-fold in pAF and cAF patients, respectively.Compared to SR patients, expression levels of TGF-ß1, expressed as fluorescence units per tissue area, was significantly increased by 77 % and 300 % in patients with pAF and cAF, respectively. Similar to intensity measurements, the number of TGFß1-positive cells per 1 mm2 atrial tissue increased significantly from 35.5 ± 5.5 cells in SR patients to 61.9 ± 12.4 cells in pAF and 131.5 ± 23.5 cells in cAF. In both types of measurements, there was a statistically significant difference between pAF and cAF groups. Conclusions: This is the first study to show that AF is associated with increased expression levels of collagen V and TGF-ß1indicating its role in the pathogenesis of atrial fibrosis. In addition, increases in collagen V correlate with increased number of fibroblasts and TGF-ß1 and are more pronounced in cAF patients than those in pAF patients.

Adherence to guidelines for management of acute kidney injury.

BACKGROUND AND AIM: Acute kidney injury (AKI) affects a significant number of patients and the prognosis for this condition remains poor. The aim of this study was to assess adherence to KDIGO clinical practice guidelines and identify areas for improvement. METHODS: For this retrospective study, data were extracted from the medical database of the University Hospital Brandenburg, for patients who had been diagnosed with AKI from January to March 2021. Implementation rates of eight KDIGO AKI therapeutic measures were analyzed in relation to several AKI severity/risk categories. RESULTS: Data from 200 patients were included in the study. Three specific measures were commonly implemented: hyperglycemia control (100%), volume therapy (82%), and fluid balance management (65%). Nephrotoxic medications were discontinued in 51% patients, while iodinated contrast media was used in 35% patients. Patients with an increased risk of complications, such as those requiring ICU therapy or with sepsis, received these measures more frequently. CONCLUSIONS: While some 2012 KDIGO recommended measures were implemented for a substantial number of affected individuals, others were not. Our study highlights the need for improvement in the quality of care for patients with AKI.

Multiple blood gas variables predict AKI survival in an independent manner.

BACKGROUND AND AIM: Acute kidney injury (AKI) is becoming increasingly prevalent among hospitalized patients and carries a poor prognosis. While new biomarkers show promise in identifying early stages of AKI, accurately predicting severe outcomes such as the need for kidney replacement therapy (KRT) or death remains a challenge. However, blood gas analyses (BGA) can be used to diagnose life-threatening complications associated with AKI. The objective of this study was to assess the role of BGA as a biomarker panel in both emerging and established cases of AKI. METHODS: Retrospective observational study examining subjects with newly developed acute kidney injury (AKI). The study will document venous and arterial pH, pCO2, and actual bicarbonate levels upon hospital admission and at the onset of AKI. The primary endpoints include in-hospital mortality, the need for kidney replacement therapy (KRT), and the recovery of kidney function (ROKF). RESULTS: A total of 202 individuals were included in the study. Three variables were found to be independent predictors of in-hospital survival: admission arterial pH, arterial pH at acute kidney injury (AKI) onset, and arterial pCO2 at AKI onset. Additionally, venous pCO2 at AKI onset was identified as an independent predictor for the need of kidney replacement therapy (KRT). CONCLUSIONS: Our study suggests that blood gas analysis may have a potential role in predicting severe outcome variables in acute kidney injury (AKI). The associated costs are minimal.

Oxidized high-density lipoprotein associates with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common heart arrhythmia and considered to be a progressive chronic disease associated with increased morbidity and mortality. Recent data suggest a link between inflammation, oxidative stress, and AF, although the underlying mechanisms are not fully understood. Because oxidized lipoproteins cause structural damage and electrophysiologic changes in cardiomyocytes, it is feasible that the transformation of atheroprotective high-density lipoprotein (HDL) into dysfunctional HDL contributes to the development of AF. OBJECTIVE: The purpose of this study was to determine whether a reduced antioxidant function of HDL is associated with the presence of AF. METHODS: In this multicenter cross-sectional cohort study, we assessed HDL function in sera of 1206 participants. Patients were divided into groups according to the presence of AF (n = 233) or no AF (n = 973). A validated cell-free biochemical assay was used to determine reduced HDL antioxidant function as assessed by increased normalized HDL lipid peroxide content (nHDLox). RESULTS: Participants with AF had a 9% higher mean relative nHDLox compared to persons without AF (P = .025). nHDLox was strongly associated with AF in all models of logistic regression, including the analysis adjusted for age, sex, and risk factors for AF (all P ≤.01). CONCLUSION: Reduced antioxidant HDL function is associated with the presence of AF, which supports growing evidence that impaired lipoprotein function is linked to electrophysiological changes in cardiomyocytes. nHDLox is one of several contributors to the initiation and perpetuation of AF.

New Insights into Mortality-Related Risk Factors in Infective Endocarditis: Results from the Brandenburg State Endocarditis Register.

OBJECTIVE: Endocarditis as a potentially life-threatening disease with high complication and mortality rates. In recent years, an increase in the incident of endocarditis has been reported throughout Europe. In the aging society, successful treatment is complex and challenging owing to the high rate of multimorbidity. METHODS: We initiated a statewide prospective multicenter endocarditis registry in 2020. Perioperative risk factors, comorbidities, microbiological, laboratory and imaging diagnostics, complications, and mortality including 1-year follow-up were collected. The present midterm analysis includes factors influencing mortality in the first 313 patients. RESULT: In-hospital mortality and 1-year mortality were 28.4 and 40.9%, respectively. Preoperative risk factors include age (p < 0.001), EuroSCORE II (p < 0.001), coronary artery disease (p = 0.022), pacemaker probe infection (p = 0.033), preoperative left ventricular ejection fraction (LVEF), systemic inflammatory response syndrome (SIRS), pulmonary edema, heart failure, septic emboli, acute renal failure, impaired coagulation, hypalbuminemia (p < 0.001), and N-terminal prohormone of brain natriuretic peptide (NTproBNP) (p = 0.001). The presence of peri-annular abscess, perforation, and shunt were associated with increased mortality (p = 0.004, 0.001, and 0.004, respectively). In addition, cardiopulmonary bypass time influenced mortality (p = 0.002). The main postoperative causes of death were multi-organ failure, renal failure, vasoplegia, and low-output syndrome (p < 0.001). Previous endocarditis was 7.7%, while 35.5% were prosthetic valve recipients and 33.6% were redo surgeries. CONCLUSION: Our first registry data show the complexity of endocarditis patients and the challenging treatment. Some risk factors can be treated preoperatively. For instance, hypalbuminemia and the duration of the procedure can be controlled with adequate albumin substitution and carefully planned procedures restricted to the essential requirements, that is, hybrid approaches with consecutive interventions.

Impact of Access Site on Periprocedural Bleeding and Cerebral and Coronary Events in High-Bleeding-Risk Percutaneous Coronary Intervention: Findings from the RIVA-PCI Trial.

INTRODUCTION: The preference for using transradial access (TRA) over transfemoral access (TFA) in patients requiring percutaneous coronary intervention (PCI) is based on evidence suggesting that TRA is associated with less bleeding and fewer vascular complications, shorter hospital stays, improved quality of life, and a potential beneficial effect on mortality. We have limited study data comparing the two access routes in a patient population with atrial fibrillation (AF) undergoing PCI, who have a particular increased risk of bleeding, while AF itself is associated with an increased risk of thromboembolism. METHODS: Using data from the RIVA-PCI registry, which includes patients with AF undergoing PCI, we analyzed a high-bleeding-risk (HBR) cohort. These patients were predominantly on oral anticoagulants (OAC) for AF, and the PCI was performed via radial or femoral access. Endpoints examined were in-hospital bleeding (BARC 2-5), cerebral events (TIA, hemorrhagic or ischemic stroke) and coronary events (stent thrombosis and myocardial infarction). RESULTS: Out of 1636 patients, 854 (52.2%) underwent TFA, while 782 (47.8%) underwent the procedure via TRA, including nine patients with brachial artery puncture. The mean age was 75.5 years. Groups were similar in terms of age, sex distribution, AF type, cardiovascular history, risk factors, and comorbidities, except for a higher incidence of previous bypass surgeries, heart failure, hyperlipidemia, and chronic kidney disease (CKD) with a glomerular filtration rate (GFR) < 60 ml/min in the TFA group. No clinically relevant differences in antithrombotic therapy and combinations were present at the time of PCI. However, upon discharge, transradial PCI patients had a higher rate of triple therapy, while dual therapy was preferred after transfemoral procedures. Radial access was more frequently chosen for non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina pectoris (UAP) cases (NSTEMI 26.6% vs. 17.0%, p < 0.0001; UAP 21.5% vs. 14.5%, p < 0.001), while femoral access was more common for elective PCI (60.3% vs. 44.1%, p < 0.0001). No differences were observed for ST-segment elevation myocardial infarction (STEMI). Both groups had similar rates of cerebral events (TFA 0.2% vs. TRA 0.3%, p = 0.93), but the TFA group had a higher incidence of bleeding (BARC 2-5) (4.2% vs. 1.5%, p < 0.01), mainly driven by BARC 3 bleeding (1.5% vs. 0.4%, p < 0.05). No significant differences were found for stent thrombosis and myocardial infarction (TFA 0.2% vs. TRA 0.3%, p = 0.93; TFA 0.4% vs. TRA 0.1%, p = 0.36). CONCLUSIONS: In HBR patients with AF undergoing PCI for acute or chronic coronary syndrome, the use of TRA might be associated with a decrease in in-hospital bleeding, while not increasing the risk of embolic or ischemic events compared to femoral access. Further studies are required to confirm these preliminary findings.

Hypernatremia: Epidemiology and Predictive Role in Emerging and Established Acute Kidney Injury.

Hypernatremia (plasma sodium > 145 mmol/L) reflects impaired water balance, and affected patients can suffer from severe neurologic symptoms. Hyponatremia, on the other hand, is the most frequent electrolyte disorder in hospitals. It may be diagnosed in acute kidney injury (AKI), but hyponatremia prior to the diagnosis of AKI has also predictive or prognostic value in the short term. Aim of the article was to summarize data on both, epidemiology and outcomes of in-hospital acquired hypernatremia ("In-hospital acquired" refers to the diagnosis of either hypo- or hypernatremia in patients, who did not exhibit any of these electrolyte imbalances upon admission to the hospital). It also aimed to discuss its predictive role in patients with emerging or established AKI. Five databases were searched for references: PubMed, Medline, Google Scholar, Scopus, and Cochrane Library. Studies published between 2000 and 2023 were screened. The following keywords were used: "hypernatremia", "mortality", "pathophysiology", "acute kidney injury", "AKI", "risk prediction", "kidney replacement therapy", "KRT", "renal replacement therapy", "RRT", "hyponatremia", and "heart failure". A total of 16 studies were deemed eligible for inclusion. Among these, 13 studies had a retrospective design, two investigations were published as secondary analyses from prospective trial cohorts, and one study was prospective in nature. Out of the 16 studies, 11 focused on the epidemiology and outcomes of hypernatremia, while five investigations were related to AKI and/or AKI-associated endpoints. The prevalence of hypernatremia diagnosed during hospitalization varied from 1.9% to 6.8%, with one exception where it was 30.8%. All studies demonstrated associations between hypernatremia and mortality, even over extended periods after discharge. In AKI patients, hypernatremia shows potential for predicting in-hospital death. In conclusion, hypernatremic individuals are at higher risk of death during in-hospital therapy. Also, the electrolyte disorder potentially qualifies as a future biomarker for AKI onset and AKI-associated mortality.

Electronic Acute Kidney Injury Alert at the Brandenburg Medical School: Implementation and Follow-Up.

INTRODUCTION: Acute kidney injury (AKI) substantially worsens the prognosis of hospitalized patients worldwide. In order to optimize early AKI recognition and therapeutic intervention, AKI alert systems have been implemented and evaluated in the past. Herein, we aimed to analyze outcome variables of AKI patients under the conditions of a de novo-established AKI alert system at the Brandenburg Hospital of the Brandenburg Medical School. METHODS: Automated e-mail messages were generated and sent to the nephrologist with responsibility based on an electronic algorithm. The message was exclusively generated if one of the two first KDIGO criteria was fulfilled. During period 1, all alerts were ignored. During the second period, every alert was followed up, coupled with therapeutic management of respective individuals according to an AKI care bundle. Endpoints were in-hospital death, need for dialysis, and renal recovery. RESULTS: In periods 1 and 2, 200 and 112 patients were included. In period 1, 150 out of 200 AKI alerts were identified as correct (75%); in the second period, 93 out of 112 AKI alerts were accepted as correct (83%) (p = 0.16). Kidney replacement therapy was initiated in 21 (14%) of all period 1 patients and in 32 (34.4%) of the period 2 patients (p = 0.017). In-hospital mortality of affected patients was 24 (16%) in period 1 and 21 (22.5%) in period 2 (p = 0.4). Restoration of kidney function was 69 (46%) in period 1 and 45 (48.3%) in period 2 (p = 0.71). CONCLUSIONS: We finally conclude that an AKI alert system, as implemented and followed-up in our study, did not significantly improve clinically relevant endpoints in AKI patients. Potential weaknesses were the lack of documentation of the time between receiving the alert and patient contact, and physicians in responsibility were not particularly informed about the alert system.

Metabolomics in Acute Kidney Injury: The Experimental Perspective.

Acute kidney injury (AKI) affects increasing numbers of in-hospital patients in Central Europe and the USA, the prognosis remains poor. Although substantial progress has been achieved in the identification of molecular/cellular processes that induce and perpetuate AKI, more integrated pathophysiological perspectives are missing. Metabolomics enables the identification of low-molecular-weight (< 1.5 kD) substances from biological specimens such as certain types of fluid or tissue. The aim of the article was to review the literature on metabolic profiling in experimental AKI and to answer the question if metabolomics allows the integration of distinct pathophysiological events such as tubulopathy and microvasculopathy in ischemic and toxic AKI. The following databases were searched for references: PubMed, Web of Science, Cochrane Library, Scopus. The period lasted from 1940 until 2022. The following terms were utilized: "acute kidney injury" OR "acute renal failure" OR "AKI" AND "metabolomics" OR "metabolic profiling" OR "omics" AND "ischemic" OR "toxic" OR "drug-induced" OR "sepsis" OR "LPS" OR "cisplatin" OR "cardiorenal" OR "CRS" AND "mouse" OR "mice" OR "murine" OR "rats" OR "rat". Additional search terms were "cardiac surgery", "cardiopulmonary bypass", "pig", "dog", and "swine". In total, 13 studies were identified. Five studies were related to ischemic, seven studies to toxic (lipopolysaccharide (LPS), cisplatin), and one study to heat shock-associated AKI. Only one study, related to cisplatin-induced AKI, was performed as a targeted analysis. The majority of the studies identified multiple metabolic deteriorations upon ischemia/the administration of LPS or cisplatin (e.g., amino acid, glucose, lipid metabolism). Particularly, abnormalities in the lipid homeostasis were shown under almost all experimental conditions. LPS-induced AKI most likely depends on the alterations in the tryptophan metabolism. Metabolomics studies provide a deeper understanding of pathophysiological links between distinct processes that are responsible for functional impairment/structural damage in ischemic or toxic or other types of AKI.

Measuring context that matters: validation of the modular Tele-QoL patient-reported outcome and experience measure.

PURPOSE: A setting-sensitive instrument for assessing Quality of Life (QoL) in Telemedicine (TM) was unavailable. To close this gap, a content-valid "add-on" measure was developed. In parallel, a brief index was derived featuring six items that summarise the main content of the multidimensional assessment. After pre- and pilot-testing, the psychometric performance of the final measures was investigated in an independent validation study. METHODS: The questionnaires were applied along with other standardised instruments of similar concepts as well as associated, yet disparate concepts for validation purposes. The sample consisted of patients with depression or heart failure, with or without TM (n = 200). Data analyses were aimed at calculating descriptive statistics and testing the psychometric performance on item, scale, and instrument level, including different types of validity and reliability. RESULTS: The proposed factor structure of the multidimensional Tele-QoL measure has been confirmed. Reliability coefficients for internal consistency, split-half, and test-retest reliability of the subscales and index reached sufficient values. The Tele-QoL subscales and the index demonstrated Rasch scalability. Validity of both instruments can be assumed. Evidence for discriminant construct validity was provided. Known-groups validity was indicated by respective score differences for various classes of disease severity. CONCLUSION: Both measures show convincing psychometric properties. The final multidimensional Tele-QoL assessment consists of six outcome scales and two impact scales assessing (un-)intended effects of TM on QoL. In addition, the Tele-QoL index provides a short alternative for outcome assessment. The Tele-QoL measures can be used as complementary modules to existing QoL instruments capturing healthcare-related aspects of QoL from the patients' perspective.

[Access to cardiological care infrastructure in the federal state of Brandenburg considering the local care needs]. / Erreichbarkeit der kardiologischen Versorgungsinfrastruktur im Bundesland Brandenburg in Abhängigkeit des lokalen Versorgungsbedarfs.

AIM OF THE STUDY: In a nationwide comparison, the state of Brandenburg has one of the highest morbidity and mortality rates of ischemic heart disease. Access to medical care infrastructure is considered to be one possible explanation for regional health inequalities. Accordingly, the study aims to calculate the distances to different types of cardiology care at the community level and to consider these in the context of local care needs. METHODOLOGY: Preventive sports facilities, general practitioners, outpatient specialist care, hospitals with cardiac catheterization laboratory and outpatient rehabilitation were chosen and mapped as essential facilities for cardiological care. Thereafter, the distances across the road network from the center of each Brandenburg community to the nearest location of each care facility was calculated and divided into quintiles. Medians and interquartile ranges of the German Index of Socioeconomic Deprivation and the proportion of the population over 65 were used as measures of the need for care. They were then related to the distance quintiles per type of care facility. RESULTS: For 60% of Brandenburg's municipalities, general practitioners were found to be within 2.5 km, preventive sports facilities within 19.6 km, cardiology practices within 18.3 km, hospitals with cardiac catheterization laboratories within 22.7 km, and outpatient rehabilitation facilities within 14.7 km. The median of the German Index of Socioeconomic Deprivation rose with increasing distance for all types of care facilities. The median of the proportion of over 65-year-olds showed no significant variation between distance quintiles. CONCLUSIONS: The results show that a high proportion of the population lives far away from cardiology care services, while a high proportion seems to be able to reach a general practitioner. In Brandenburg, a regional and locally oriented cross-sectoral care seems to be necessary.

Defibrillator exchange in the elderly.

Background: Implantable cardioverter-defibrillator (ICD) therapy in elderly patients is controversial because survival benefits might be attenuated by nonarrhythmic causes of death. Objective: The purpose of this study was to investigate the outcome of septuagenarians and octogenarians after ICD generator exchange (GE). Methods: A total of 506 patients undergoing elective GE were analyzed to determine the incidence of ICD shocks and/or survival after GE. Patients were divided into a septuagenarian group (age 70-79 years) and an octogenarian group (age ≥80 years). The primary endpoint was death from any cause. Secondary endpoints were survival after appropriate ICD shock and death without experiencing ICD shocks after GE ("prior death"). Results: The association of the ICD with all-cause mortality and arrhythmic death was determined for septuagenarians and octogenarians. Comparing both groups, similar left ventricular ejection fraction (35.6% ± 11.2% vs 32.4% ± 8.9%) and baseline prevalence of New York Heart Association functional class III or IV heart failure (17.1% vs 14.7%) were found. During the entire follow-up period of the study, 42.5% of patients in the septuagenarian group died compared to 79% in the octogenarian group (P <.01). Prior death was significantly more frequent in both age groups than were appropriate ICD shocks. Predictors of mortality were common in both groups and included advanced heart failure, peripheral arterial disease, and renal failure. Conclusion: In clinical practice, decision-making for ICD GE among the elderly should be considered carefully for individual patients.

Metabolomics in Acute Kidney Injury: The Clinical Perspective.

BACKGROUND: Acute kidney injury (AKI) affects increasing numbers of hospitalized patients worldwide. The diagnosis of AKI is made too late in most individuals since it is still based on dynamic changes in serum creatinine. In recent years, new AKI biomarkers have been identified; however, none of these can reliably replace serum creatinine yet. Metabolomic profiling (metabolomics) allows the concomitant detection and quantification of large numbers of metabolites from biological specimens. The current article aims to summarize clinical studies on metabolomics in AKI diagnosis and risk prediction. METHODS: The following databases were searched for references: PubMed, Web of Science, Cochrane Library, and Scopus, and the period lasted from 1940 until 2022. The following terms were utilized: 'AKI' OR 'Acute Kidney Injury' OR 'Acute Renal Failure' AND 'metabolomics' OR 'metabolic profiling' OR 'omics' AND 'risk' OR 'death' OR 'survival' OR 'dialysis' OR 'KRT' OR 'kidney replacement therapy' OR 'RRT' OR 'renal replacement therapy' OR 'recovery of kidney function' OR 'renal recovery' OR 'kidney recovery' OR 'outcome'. Studies on AKI risk prediction were only selected if metabolomic profiling allowed differentiation between subjects that fulfilled a risk category (death or KRT or recovery of kidney function) and those who did not. Experimental (animal-based) studies were not included. RESULTS: In total, eight studies were identified. Six studies were related to the diagnosis of AKI; two studies were performed on metabolic analysis in AKI risk (death) prediction. Metabolomics studies in AKI already helped to identify new biomarkers for AKI diagnosis. The data on metabolomics for AKI risk prediction (death, KRT, recovery of kidney function), however, are very limited. CONCLUSIONS: Both the heterogenous etiology and the high degree of pathogenetic complexity of AKI most likely require integrated approaches such as metabolomics and/or additional types of '-omics' studies to improve clinical outcomes in AKI.

Leukocyte telomere length and mitochondrial DNA copy number associate with endothelial function in aging-related cardiovascular disease.

Background: We investigated the association between leukocyte telomere length, mitochondrial DNA copy number, and endothelial function in patients with aging-related cardiovascular disease (CVD). Methods: In total 430 patients with CVD and healthy persons were enrolled in the current study. Peripheral blood was drawn by routine venipuncture procedure. Plasma and peripheral blood mononuclear cells (PBMCs) were collected. Cell-free genomic DNA (cfDNA) and leukocytic genomic DNA (leuDNA) were extracted from plasma and PBMCs, respectively. Relative telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) were analyzed using quantitative polymerase chain reaction. Endothelial function was evaluated by measuring flow-mediated dilation (FMD). The correlation between TL of cfDNA (cf-TL), mtDNA-CN of cfDNA (cf-mtDNA), TL of leuDNA (leu-TL), mtDNA-CN of leuDNA (leu-mtDNA), age, and FMD were analyzed based on Spearman's rank correlation. The association between cf-TL, cf-mtDNA, leu-TL, leu-mtDNA, age, gender, and FMD were explored using multiple linear regression analysis. Results: cf-TL positively correlated with cf-mtDNA (r = 0.1834, P = 0.0273), and leu-TL positively correlated with leu-mtDNA (r = 0.1244, P = 0.0109). In addition, both leu-TL (r = 0.1489, P = 0.0022) and leu-mtDNA (r = 0.1929, P < 0.0001) positively correlated with FMD. In a multiple linear regression analysis model, both leu-TL (ß = 0.229, P = 0.002) and leu-mtDNA (ß = 0.198, P = 0.008) were positively associated with FMD. In contrast, age was inversely associated with FMD (ß = -0.426, P < 0.0001). Conclusion: TL positively correlates mtDNA-CN in both cfDNA and leuDNA. leu-TL and leu-mtDNA can be regarded as novel biomarkers of endothelial dysfunction.

Autophagy-related genes analysis reveals potential biomarkers for prediction of the impaired walking capacity of peripheral arterial disease.

BACKGROUND: The role of autophagy and autophagy-related genes in peripheral arterial disease (PAD) remains unknown and may be of diagnostic and prognostic value. The aim of this study is to investigate the relationship between autophagy and PAD, and identify potential diagnostic or prognostic biomarkers for medical practice. METHODS: Differentially expressed autophagy-related genes in PAD were explored from GSE57691 and validated in our WalkByLab registry participants by quantitative real-time polymerase chain reaction (qRT-PCR). The level of autophagy in peripheral blood mononuclear cells (PBMCs) of WalkByLab participants was assessed by analyzing autophagic marker proteins (beclin-1, P62, LC3B). Single sample gene set enrichment analysis (ssGSEA) was used to evaluate the immune microenvironment within the artery wall of PAD patients and healthy persons. Chemokine antibody array and enzyme-linked immunosorbent assay were used to assess the chemokines in participants' plasma. Treadmill testing with Gardner protocol was used to evaluate participants' walking capacity. Pain-free walking distance, maximum walking distance, and walking time were recorded. Finally, a nomogram model based on logistic regression was built to predict impaired walking performance. RESULTS: A total of 20 relevant autophagy-related genes were identified, and these genes were confirmed to be expressed at low levels in our PAD participants. Western blotting demonstrated that the expression of autophagic marker proteins beclin-1 and LC3BII were significantly reduced in PAD patients' PBMCs. ssGSEA revealed that most of the autophagy-related genes were strongly correlated with immune function, with the largest number of associated genes showing interaction between cytokine-and-cytokine receptors (CCR). In this context, the chemokines growth-related oncogene (GRO) and neutrophil activating protein2 (NAP2) are highly expressed in the plasma of WalkByLab PAD patients and were significantly negatively correlated with the walking distance assessed by Gardner treadmill testing. Finally, the plasma NAP2 level (AUC: 0.743) and derived nomogram model (AUC: 0.860) has a strong predictive potential to identify a poor walking capacity. CONCLUSIONS: Overall, these data highlight both the important role of autophagy and autophagy-related genes in PAD and link them to vascular inflammation (expression of chemokines). In particular, chemokine NAP2 emerged as a novel biomarker that can be used to predict the impaired walking capacity in PAD patients.

Association of plasma propionate concentration with coronary artery disease in a large cross-sectional study.

Background: Microbiome has been linked to the pathogenesis of coronary artery disease (CAD) but data providing direct evidence for an association of short-chain fatty acids (SCFA) with CAD are lacking. This study aimed to evaluate the role of propionate, the most important SCFA in patients with CAD. Methods: We performed a cross-sectional study enrolling patients admitted for invasive coronary angiography in two university hospitals in Germany. Patients with known or suspected CAD and risk factors for cardiovascular disease were prospectively recruited. Blood sampling was performed after overnight fasting and before invasive procedures. Measurement of propionate was performed by liquid chromatography. Results: The study included 1,253 patients (median [IQR], 67 [58-76] years; 799 men [64%]). A total of 739 had invasively confirmed CAD with at least one coronary artery stenosis ≥50% and 514 had exclusion of CAD. CAD patients had significant lower levels of propionate (median 5.75 µM, IQR, 4.1-7.6) compared to the non-CAD groups 6.53 µM (4.6-8.6, p < 0.001). Multivariate linear regression analysis revealed an odds ratio of 0.94 (CI 0.90-0.98, p = 0.002) for propionate as predictor of CAD. The odds ratio was further decreased to 0.45 (CI 0.31-0.65, p < 0.001) when comparing patients in the lowest quartile of propionate with those with higher levels of propionate. Conclusion: The study provides large-scale in vivo data for the association of propionate to manifest coronary artery disease, independent of other traditional cardiovascular risk factors.