Biomarkers to improve functional outcome prediction after ischemic stroke: Results from the SICFAIL, STRAWINSKI, and PREDICT studies.

BACKGROUND AND AIMS: Acute ischemic stroke (AIS) outcome prognostication remains challenging despite available prognostic models. We investigated whether a biomarker panel improves the predictive performance of established prognostic scores. METHODS: We investigated the improvement in discrimination, calibration, and overall performance by adding five biomarkers (procalcitonin, copeptin, cortisol, mid-regional pro-atrial natriuretic peptide (MR-proANP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP)) to the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) and age/NIHSS scores using data from two prospective cohort studies (SICFAIL, PREDICT) and one clinical trial (STRAWINSKI). Poor outcome was defined as mRS > 2 at 12 (SICFAIL, derivation dataset) or 3 months (PREDICT/STRAWINSKI, pooled external validation dataset). RESULTS: Among 412 SICFAIL participants (median age 70 years, quartiles 59-78; 63% male; median NIHSS score 3, quartiles 1-5), 29% had a poor outcome. Area under the curve of the ASTRAL and age/NIHSS were 0.76 (95% CI 0.71-0.81) and 0.77 (95% CI 0.73-0.82), respectively. Copeptin (0.79, 95% CI 0.74-0.84), NT-proBNP (0.80, 95% CI 0.76-0.84), and MR-proANP (0.79, 95% CI 0.75-0.84) significantly improved ASTRAL score's discrimination, calibration, and overall performance. Copeptin improved age/NIHSS model's discrimination, copeptin, MR-proANP, and NT-proBNP improved its calibration and overall performance. In the validation dataset (450 patients, median age 73 years, quartiles 66-81; 54% men; median NIHSS score 8, quartiles 3-14), copeptin was independently associated with various definitions of poor outcome and also mortality. Copeptin did not increase model's discrimination but it did improve calibration and overall model performance. DISCUSSION: Copeptin, NT-proBNP, and MR-proANP improved modest but consistently the predictive performance of established prognostic scores in patients with mild AIS. Copeptin was most consistently associated with poor outcome in patients with moderate to severe AIS, although its added prognostic value was less obvious.

Medical Care as Flea Market Bargaining? An International Interdisciplinary Study of Varieties of Shared Decision Making in Physician-Patient Interactions.

Phenomenon: Shared decision making (SDM) is a core ideal in the interaction between healthcare providers and patients, but the implementation of the SDM ideal in clinical routines has been a relatively slow process. Approach: In a sociological study, 71 interactions between physicians and simulated patients enacting chronic heart failure were video-recorded in China, Germany, the Netherlands, and Turkey as part of a quasi-experimental research design. Participating physicians varied in specialty and level of experience. The secondary analysis presented in this article used content analysis to study core components of SDM in all of the 71 interactions and a grounded theory approach to observe how physicians responded actively to patients even though they did not actively employ the SDM ideal. Findings: Full realization of the SDM ideal remains an exception, but various aspects of SDM in physician-patient interaction were observed in all four locations. Analyses of longer interactions show dynamic processes of interaction that sometimes surprised both patient and physician. We observed varieties of SDM that differ from the SDM ideal but arguably achieve what the SDM ideal is intended to achieve. Our analysis suggests a need to revisit the SDM ideal-to consider whether varieties of SDM may be acceptable, even valuable, in their own right. Insights: The gap between the SDM ideal and SDM as implemented in clinical practice may in part be explained by the tendency of medicine to define and teach SDM through a narrow lens of checklist evaluations. The authors support the argument that SDM defies a checklist approach. SDM is not uniform, but nuanced, dependent on circumstances and setting. As SDM is co-produced by patients and physicians in a dynamic process of interaction, medical researchers should consider and medical learners should be exposed to varieties of SDM-related practice rather than a single idealized model. Observing and discussing worked examples contributes to the physician's development of realistic expectations and personal professional growth.

Cardio-Hepatic Interaction in Cardiac Amyloidosis.

Background: Congestion is associated with poor prognosis in cardiac amyloidosis (CA). The cardio-hepatic interaction and the prognostic impact of secondary liver affection by cardiac congestion in CA are poorly understood and require further characterisation. Methods: Participants of the amyloidosis cohort study AmyKoS at the Interdisciplinary Amyloidosis Centre of Northern Bavaria with proven transthyretin (ATTR-CA) and light chain CA (AL-CA) underwent serial work-up including laboratory tests, echocardiography, and in-depth hepatic assessment by vibration-controlled transient elastography (VCTE) and 13C-methacetin breath test. Results: In total, 74 patients with AL-CA (n = 17), ATTR-CA (n = 26) and the controls (n = 31) were analysed. ATTR-CA patients showed decreased microsomal liver function expressed by maximal percentage of dose rate (PDRpeak) related to hepatic congestion. Reduced PDRpeak in AL-CA could result from altered pharmacokinetics due to changed hepatic blood flow. Liver stiffness as a combined surrogate of chronic liver damage and congestion was identified as a predictor of all-cause mortality. Statistical modelling of the cardio-hepatic interaction revealed septum thickness, NT-proBNP and PDRpeak as predictors of liver stiffness in both CA subtypes; dilatation of liver veins and the fibrosis score FIB-4 were only significant for ATTR-CA. Conclusions: Non-invasive methods allow us to characterise CA-associated hepatic pathophysiology. Liver stiffness might be promising for risk stratification in CA.

Activated rate-response is associated with increased mortality risk in cardiac device carriers with acute heart failure.

AIMS: This study investigated whether an activated R-mode in patients carrying a cardiac implantable electronic device (CIED) is associated with worse prognosis during and after an episode of acutely decompensated heart failure (AHF). METHODS: Six hundred and twenty-three patients participating in an ongoing prospective cohort study that phenotypes and follows patients admitted for AHF were studied. We compared CIED carriers with activated R-mode stimulation (CIED-R) to CIED carriers not in R-mode (CIED-0) and patients without CIEDs (no-CIED). The independent impact of R-mode activation on 12-month all-cause death was examined using uni- and multivariable Cox proportional hazards regression taking into account potential confounders, and hazard ratios (HR) with their 95% confidence intervals (CI) were reported. RESULTS: Mean heart rate on admission was lower in CIED-R (n = 37, 16% women) vs. CIED-0 (n = 64, 23% women) or no-CIED (n = 511, 43% women): 70 bpm vs. 80 bpm or 82 bpm; both p<0.001. In-hospital mortality was similar across groups, but age- and sex-adjusted all-cause 12-month mortality risk was differentially affected by R-mode activation; CIED-R vs. CIED-0: HR 2.44, 95%CI 1.25-4.74; CIED-R vs. no-CIED: HR 2.61, 95%CI 1.59-4.29. These effects persisted after multivariable adjustment for potential confounders. Within CIED-R, mortality risk was similar in patients with pacemakers vs. ICDs and in subgroups with left ventricular ejection fraction (LVEF) <50% vs. ≥50%. CONCLUSION: In patients admitted with AHF, R-mode stimulation was associated with a significantly increased 12-month mortality risk. Our findings shed new light on "admission heart rate" as a potentially treatable target in AHF. Our data are compatible with the concept that chronotropic incompetence contributes to an adverse outcome in these patients and may not be adequately treated through accelerometer-based R-mode stimulation.

Predictors of non-recovery from fatigue and cognitive deficits after COVID-19: a prospective, longitudinal, population-based study.

Background: Despite the high prevalence and major disability associated with fatigue and cognitive deficits after SARS-CoV-2 infection, little is known about long-term trajectories of these sequelae. We aimed to assess long-term trajectories of these conditions and to identify risk factors for non-recovery. Methods: We analyzed longitudinal data from the population-based COVIDOM/NAPKON-POP cohort in Germany. Participants with confirmed SARS-CoV-2 infection were assessed at least 6 months (baseline) and again at least 18 months (follow-up) after infection using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale (cutoff ≤ 30) and the Montreal Cognitive Assessment (MoCA, cutoff ≤ 25). Predictors of recovery from fatigue or cognitive deficits between assessments were identified through univariate and multivariable logistic regression models. The COVIDOM study is registered at the German registry for clinical studies (DRKS00023742) and at ClinicalTrials.gov (NCT04679584). Findings: Between 15 November 2020 and 9 May 2023, a total of 3038 participants were assessed at baseline (median 9 months after infection) and 83% responded to invitations for follow-up (median 26 months after infection). At baseline, 21% (95% confidence interval (CI) [20%, 23%]) had fatigue and 23% (95% CI [22%, 25%]) had cognitive deficits according to cutoff scores on the FACIT-Fatigue or MoCA. Participants with clinically relevant fatigue (at baseline) showed significant improvement in fatigue scores at follow-up (Hedges' g [95% CI] = 0.73 [0.60, 0.87]) and 46% (95% CI [41%, 50%]) had recovered from fatigue. Participants with cognitive deficits showed a significant improvement in cognitive scores (g [95% CI] = 1.12 [0.90, 1.33]) and 57% (95% CI [50%, 64%]) had recovered from cognitive deficits. Patients with fatigue exhibiting a higher depressive symptom burden and/or headache at baseline were significantly less likely to recover. Significant risk factors for cognitive non-recovery were male sex, older age and <12 years of school education. Importantly, SARS-CoV-2 reinfection had no significant impact on recovery from fatigue or cognitive deficits. Interpretation: Fatigue and cognitive deficits are common sequelae after SARS-CoV-2 infection. These syndromes improved over time and about half of the patients recovered within two years. The identified risk factors for non-recovery from fatigue and cognitive deficits could play an important role in shaping targeted strategies for treatment and prevention. Funding: Funded by the German Federal Ministry of Education and Research (BMBF; grant number 01KX2121) and German Research Foundation (DFG) Excellence Cluster "Position Medicine in Information".

[Update: Heart Failure with Preserved Ejection Fraction]. / Update: Herzinsuffizienz mit erhaltener Pumpfunktion.

Heart failure with a preserved ejection fraction (HFpEF) is a multifaceted disease entity. Confirming the diagnosis as well as tailoring the most appropriate therapy remains an ongoing challenge. The 2021 heart failure guidelines of the European Society of Cardiology (ESC) suggested a simplified diagnostic approach, and the guideline update provided in 2023 gave recommendations regarding pharmacotherapy based on recent evidence. Further, the Heart Failure Association (HFA) and the European Heart Rhythm Association of the ESC jointly proposed a scheme how to classify HFpEF patients into phenogroups of distinct pathophysiology that may benefit from individually targeted treatment. Regarding HFpEF originating from secondary causes, e.g. M. Fabry, amyloidosis or hypertrophic cardiomyopathy, there are emerging therapeutic options with the potential to substantially improve the physical capacity, quality of life and prognosis in these patients. The here presented update gives an overview on the recent advances in the area of HFpEF.

Safety and Tolerability of SGLT2 Inhibitors in Cardiac Amyloidosis-A Clinical Feasibility Study.

Sodium-glucose transport protein 2 inhibitors (SGLT2i) slow the progression of renal dysfunction and improve the prognosis of patients with heart failure. Amyloidosis constitutes an important subgroup for which evidence is lacking. Amyloidotic fibrils originating from misfolded transthyretin and light chains are the causal agents in ATTR and AL amyloidosis. In these most frequent subtypes, cardiac involvement is the most common organ manifestation. Because cardiac and renal function frequently deteriorate over time, even under best available treatment, SGLT2i emerge as a promising treatment option due to their reno- and cardioprotective properties. We retrospectively analyzed patients with cardiac amyloidosis, who received either dapagliflozin or empagliflozin. Out of 79 patients, 5.1% had urinary tract infections; 2 stopped SGLT2i therapy; and 2.5% died unrelated to the intake of SGLT2i. No genital mycotic infections were observed. As expected, a slight drop in the glomerular filtration rate was noted, while the NYHA functional status, cardiac and hepatic function, as well as the 6 min walk distance remained stable over time. These data provide a rationale for the use of SGLT2i in patients with amyloidosis and concomitant cardiac or renal dysfunction. Prospective randomized data are desired to confirm safety and to prove efficacy in this increasingly important group of patients.

Determinants and reference values of the 6-min walk distance in the general population-results of the population-based STAAB cohort study.

AIMS: The 6-min walk test is an inexpensive, safe, and easy tool to assess functional capacity in patients with cardiopulmonary diseases including heart failure (HF). There is a lack of reference values, which are a prerequisite for the interpretation of test results in patients. Furthermore, determinants independent of the respective disease need to be considered when interpreting the 6-min walk distance (6MWD). METHODS: The prospective Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study investigates a representative sample of residents of the City of Würzburg, Germany, aged 30 to 79 years, without a history of HF. Participants underwent detailed clinical and echocardiographic phenotyping as well as a standardized assessment of the 6MWD using a 15-m hallway. RESULTS: In a sample of 2762 participants (51% women, mean age 58 ± 11 years), we identified age and height, but not sex, as determinants of the 6MWD. While a worse metabolic profile showed a negative association with the 6MWD, a better systolic and diastolic function showed a positive association with 6MWD. From a subgroup of 681 individuals without any cardiovascular risk factors (60% women, mean age 52 ± 10 years), we computed age- and height-specific reference percentiles. CONCLUSION: In a representative sample of the general population free from HF, we identified determinants of the 6MWD implying objective physical fitness associated with metabolic health as well as with cardiac structure and function. Furthermore, we derived reference percentiles applicable when using a 15-m hallway.

[Current therapy of heart failure with mildly reduced or preserved left ventricular ejection fraction]. / Aktuelle Therapie der Herzinsuffizienz mit mäßiggradig reduzierter und erhaltener Pumpfunktion.

Based on the results of recent clinical trials investigating patients with heart failure and a mildly reduced (HFmrEF) or preserved (HFpEF) left ventricular ejection fraction, an update of the ESC guidelines on acute and chronic heart failure as well as the German `Nationale Versorgungsleitlinie Herzinsuffizienz' has been released. Consistently, they now recommend the use of SGLT2 inhibitors also in these patients' groups. Further, patients with diabetes mellitus and chronic renal failure should receive the non-steroidal mineralocorticoid antagonist finerenone to reduce the risk of heart failure related hospitalization. In patients with HFmrEF, intravenous application of iron can be considered to improve quality of life in iron-depleted patients. Patients experiencing a heart failure related hospitalization shall receive the foundational guideline-directed pharmacotherapy already while in hospital and undergo a timely post discharge visit to further optimize treatment.

Population data-based federated machine learning improves automated echocardiographic quantification of cardiac structure and function: the Automatisierte Vermessung der Echokardiographie project.

Aims: Machine-learning (ML)-based automated measurement of echocardiography images emerges as an option to reduce observer variability. The objective of the study is to improve the accuracy of a pre-existing automated reading tool ('original detector') by federated ML-based re-training. Methods and results: Automatisierte Vermessung der Echokardiographie was based on the echocardiography images of n = 4965 participants of the population-based Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression Cohort Study. We implemented federated ML: echocardiography images were read by the Academic Core Lab Ultrasound-based Cardiovascular Imaging at the University Hospital Würzburg (UKW). A random algorithm selected 3226 participants for re-training of the original detector. According to data protection rules, the generation of ground truth and ML training cycles took place within the UKW network. Only non-personal training weights were exchanged with the external cooperation partner for the refinement of ML algorithms. Both the original detectors as the re-trained detector were then applied to the echocardiograms of n = 563 participants not used for training. With regard to the human referent, the re-trained detector revealed (i) superior accuracy when contrasted with the original detector's performance as it arrived at significantly smaller mean differences in all but one parameter, and a (ii) smaller absolute difference between measurements when compared with a group of different human observers. Conclusion: Population data-based ML in a federated ML set-up was feasible. The re-trained detector exhibited a much lower measurement variability than human readers. This gain in accuracy and precision strengthens the confidence in automated echocardiographic readings, which carries large potential for applications in various settings.

Non-invasive estimation of left ventricular systolic peak pressure: a prerequisite to calculate myocardial work in hypertrophic obstructive cardiomyopathy.

AIMS: Myocardial work (MyW) is an echocardiographically derived parameter to estimate myocardial performance. The calculation of MyW utilizes pressure strain loops from global longitudinal strain and brachial blood pressure (BP) as a surrogate of left ventricular systolic pressure (LVSP). Since LVSP cannot be equated with BP in hypertrophic obstructive cardiomyopathy (HOCM), we explored whether LVSP can be derived non-invasively by combining Doppler gradients and BP. METHODS AND RESULTS: We studied 20 consecutive patients (8 women, 12 men; mean age 57.0 ± 13.9 years; NYHA 2.1 ± 0.8; maximal septal thickness 24.7 ± 6.3 mm) with indication for first alcohol septal ablation. All measurements were performed simultaneously in the catheterization laboratory (CathLab)-invasively: ascending aortic and LV pressures; non-invasively: BP, maximal (CWmax) and mean (CWmean) Doppler gradients.LVSP was 188.9 ± 38.5 mmHg. Mean gradients of both methods were comparable (CathLab 34.3 ± 13.4 mmHg vs. CW 31.0 ± 13.7 mmHg). Maximal gradient was higher in echocardiography (64.5 ± 28.8 mmHg) compared with CathLab (54.8 ± 24.0 mmHg; P < 0.05). Adding BP (143.1 ± 20.6 mmHg) to CWmax resulted in higher (207.7 ± 38.0 mmHg; P < 0.001), whereas adding BP to CWmean in lower (174.1 ± 26.1 mmHg; P < 0.01) derived LVSP compared with measured LVSP. However, adding BP to averaged CWmax and CWmean resulted in comparable results for measured and derived LVSP (190.9 ± 31.6 mmHg) yielding a favourable correlation (r = 0.87, P < 0.001) and a good level of agreement in the Bland-Altman plot. CONCLUSION: Non-invasive estimation of LVSP in HOCM is feasible by combining conventional BP and averaged CWmean and CWmax gradients. Hereby, a more reliable estimation of MyW in HOCM may be feasible.

Accuracy of VO2 estimation according to the widely used Krakau formula for the prediction of cardiac output.

BACKGROUND: Invasive cardiac output (CO) is measured with the thermodilution (TD) or the indirect Fick method (iFM) in right heart catheterization (RHC). The iFM estimates CO using approximation formulas for oxygen consumption ([Formula: see text]O2), but there are significant discrepancies (> 20%) between both methods. Although regularly applied, the formula proposed by Krakau has not been validated. We compared the CO discrepancies between the Krakau formula with the reference (TD) and three established formulas and investigated whether alterations assessed in cardiac magnetic resonance imaging (CMR) determined the extent of the deviations. METHODS: This retrospective study included 188 patients aged 63 ± 14 years (30% women) receiving both CMR and RHC. The CO was measured with TD or with the iFM using the formulas by Krakau, LaFarge, Dehmer, and Bergstra for [Formula: see text]O2 estimation (iFM-K/-L/-D/-B). Percentage errors were calculated as twice the standard deviation of the difference between two CO methods divided by their means; a cut-off of < 30% was regarded as acceptable. The iFM and TD-derived CO ratio was built, and deviations > 20% were counted. Logistic regression analyses were performed to identify determinants of a deviation of > 20%. RESULTS: The TD-derived CO (5.5 ± 1.7 L/min) was significantly different from all iFM (K: 4.8 ± 1.6, L: 4.3 ± 1.6; D: 4.8 ± 1.5 L/min; B: 5.4 ± 1.8 L/min all p < 0.05). The iFM-K-CO differed from all methods (p < 0.001) except iFM­D (p = 0.19). Percentage errors between TD-CO and iFM-K/-L/-D/-B were all beyond the acceptance limit (44/45/44/43%), while percentage errors between iFM­K and other iFM were all < 16%. None of the parameters measured in CMR was predictive of a discrepancy of > 20% between both methods. CONCLUSION: The Krakau formula was comparable to other iFM in estimating CO levels, but none showed satisfactory agreement with the TD method. Improved derivation cohorts for [Formula: see text]O2 estimation are needed that better reflect today's patients undergoing RHC.

Diagnosing post-capillary hypertension in patients with left heart disease: impact of new guidelines.

BACKGROUND: In 2022, the definition of pulmonary hypertension (PH) in the presence of left heart disease was updated according to the new joint guidelines of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). The impact of the new ESC/ERS definition on the prevalence of post-capillary PH (pc-PH) and its subgroups of isolated post-capillary (Ipc-PH) and combined pre- and post-capillary PH (Cpc-PH) in patients with left heart disease is unclear. METHODS: We retrospectively identified N = 242 patients with left heart disease with available data on right heart catheterisation (RHC) and cardiac magnetic resonance imaging (CMR). The proportion of pc-PH and its subgroups was calculated according to the old and new ESC/ERS PH definition. As the old definition did not allow the exact allocation of all patients with pc-PH into a respective subgroup, unclassifiable patients (Upc-PH) were regarded separately. RESULTS: Seventy-six out of 242 patients had pc-PH according to the new ESC/ERS definitions, with 72 of these patients also meeting the criteria of the old definition. Using the old definition, 50 patients were diagnosed with Ipc-PH, 4 with Cpc-PH, and 18 with Upc-PH. Applying the new definition, Ipc-PH was diagnosed in 35 patients (4 newly), and Cpc-PH in 41 patients. No CMR parameter allowed differentiating between Ipc-PH and Cpc-PH, regardless of which guideline version was used. CONCLUSION: Applying the new ESC/ERS 2022 guideline definitions mildly increased the proportion of patients diagnosed with pc-PH (+ 5.5%) but markedly increased Cpc-PH diagnoses. This effect was driven by the allocation of patients with formerly unclassifiable forms of post-capillary PH to the Cpc-PH subgroup and a significant shift of patients from the Ipc-PH to the Cpc-PH subgroup. Distribution of post-capillary pulmonary hypertension (pc-PH) subgroups according to the European Society of Cardiology/European Respiratory Society (ESC/ERS) PH guidelines from 2015 and 2022 in N = 242 patients with left heart disease.

Prevalence of anti-beta-1 antibody 6 months after hospitalization for acute heart failure predicts adverse outcome.

AIMS: Agonistic antibodies against neurohumoral receptors can induce cardio-noxious effects by altering the baseline receptor activity. To estimate the prevalence of autoantibodies directed against the beta-1 receptor (b1-AAB) in patients admitted to the hospital for acute heart failure (HF) at (i) baseline and (ii) after 6 months of follow-up (F6) and (iii) after another 12 months of follow-up (i.e. 18 months after index hospitalization), to estimate their prognostic impact on clinical outcome (death or first hospitalization for HF). METHODS AND RESULTS: In 47 patients, b1-AAB were serially determined in serum samples collected at index hospitalization and at 6 months of follow-up (F6) with a flow cytometry-based assay: median age 71 years (quartiles 60, 80), 23 (49%) women, 24 (51%) HF with preserved ejection fraction. Beta1-AAB were detected in three subjects at index hospitalization (6%), and in eight subjects at F6 (17%). There were no differences apparent between patients with and without b1-AAB at F6 with regard to age, sex, type, duration, or main cause of HF. During the 12 month period following F6 (i.e. up to month 18), eight events occurred. Event-free survival was associated with prevalence of b1-AAB at F6. Compared with patients without b1-AAB at F6, age-adjusted Cox regression indicated a higher event risk in patients harbouring b1-AAB, with a hazard ratio of 8.96 (95% confidence interval 1.81-44.50, P = 0.007). CONCLUSIONS: Our results suggest a possible adverse prognostic relevance of b1-AAB in patients with acute HF, but this observation needs to be confirmed in larger patient collectives.

Internal carotid artery blood flow and pulsatility index in cognitively impaired people with chronic heart failure.

AIMS: Mild cognitive impairment and dementia are common and serious co-morbidities in people with chronic heart failure (HF) as they increase hospitalization rates, mortality and health care costs. Upon other factors, dysregulated cerebral perfusion might contribute to brain pathology. We aimed to evaluate the association of non-invasively measured blood flow (BF) and pulsatility index (PI) of the internal carotid artery (ICA) with (i) chronic HF parameters, (ii) brain morphologic measures and (iii) cognitive impairment. METHODS AND RESULTS: This post-hoc analysis of the observational, prospective Cognition.Matters-HF study included 107 chronic HF patients without atrial fibrillation or carotid artery stenosis (aged 63 ± 10 years; 19% women). Using extracranial sonography, we measured ICA-BF and ICA-PI 1.5 cm distal of the carotid bifurcation. Brain magnetic resonance imaging was performed on a 3-Tesla scanner to quantify cerebral atrophy, hippocampal atrophy and white matter hyperintensities. Extensive neuropsychological testing tested the cognitive domains intensity of attention, visual/verbal memory and executive function (including its subdomains selectivity of attention, visual/verbal fluency and working memory) using a comprehensive test battery. (i) Neither ICA-BF (median 630 (quartiles 570, 700) mL/min) nor ICA-PI (1.05 (0.96. 1.23)) related to left ventricular ejection fraction, left atrial volume index or NT-proBNP. (ii) Higher ICA-PI (r = 0.25; P = 0.011), but not ICA-BF (r = 0.08; P = 0.409), associated with increased volume of white matter hyperintensities beyond ageing, while neither ICA-PI nor ICA-BF related to cerebral or hippocampal atrophy indices. (iii) ICA-BF, but not ICA-PI, positively correlated with age-adjusted T-scores of executive function (r = 0.38; P < 0.001) and its subdomains working memory (r = 0.32; P < 0.001) and visual/verbal fluency (r = 0.32; P < 0.001). In a multivariate linear model of executive function, only ICA-BF (T = 3.79; P < 0.001), but not HF or magnetic resonance imaging parameters, remained a significant correlate of executive function. CONCLUSIONS: ICA-BF and ICA-PI, measured in broadly available extracranial sonography, independently related to measures of functional and structural brain changes in people with chronic HF, respectively. Due to limitations of this cross-sectional approach without a healthy control group, larger controlled longitudinal studies are needed to further elucidate the role of ICA-BF dysregulation and its implication for clinical care in this vulnerable cohort.

Effect of bariatric surgery on cardio-psycho-metabolic outcomes in severe obesity: A randomized controlled trial.

OBJECTIVE: Randomized evidence comparing the cardiovascular effects of surgical and conservative weight management is lacking. PATIENTS & METHODS: In this single-center, open-label randomized trial, obese patients with indication for Roux-en-Y gastric bypass (RYGB) and able to perform treadmill cardiopulmonary exercise testing (CPET) were included. After a 6-12 month run-in phase of multimodal anti-obesity treatment, patients were randomized to RYGB or psychotherapy-enhanced lifestyle intervention (PELI) and co-primary endpoints were assessed 12 months later. Thereafter, PELI patients could opt for surgery and patients were reassessed 24 months after randomization. Co-primary endpoints were mean change (95 % confidence intervals) in peak VO2 (ml/min/kg body weight) in CPET and the physical functioning scale (PFS) of the Short Form health survey (SF-36). RESULTS: Of 93 patients entering the study, 60 were randomized. Among these (median age 38 years; 88 % women; mean BMI 48·2 kg/m2), 46 (RYGB: 22 and PELI: 24) were evaluated after 12 months. Total weight loss was 34·3 % after RYGB vs. 1·2 % with PELI, while peak VO2 increased by +4·3 ml/min/kg (2·7, 5·9) vs +1·1 ml/min/kg (-0·2, 2·3); p < 0·0001. Respective improvement in PFS score was +40 (30, 49) vs +10 (1, 15); p < 0·0001. 6-minute walking distance also favored the RYGB group: +44 m (17, 72) vs +6 m (-14, 26); p < 0·0001. Left ventricular mass decreased after RYGB, but not with PELI: -32 g (-46, -17) vs 0 g (-13,13); p < 0·0001. In the non-randomized follow-up, 34 patients were assessed. Favorable changes were sustained in the RYGB group and were repeated in the 15 evaluated patients that opted for surgery after PELI. CONCLUSIONS: Among adults with severe obesity, RYGB in comparison to PELI resulted in improved cardiopulmonary capacity and quality of life. The observed effect sizes suggest that these changes are clinically relevant.

Increased circulating fibronectin, depletion of natural IgM and heightened EBV, HSV-1 reactivation in ME/CFS and long COVID.

Myalgic Encephalomyelitis/ Chronic Fatigue syndrome (ME/CFS) is a complex, debilitating, long-term illness without a diagnostic biomarker. ME/CFS patients share overlapping symptoms with long COVID patients, an observation which has strengthened the infectious origin hypothesis of ME/CFS. However, the exact sequence of events leading to disease development is largely unknown for both clinical conditions. Here we show antibody response to herpesvirus dUTPases, particularly to that of Epstein-Barr virus (EBV) and HSV-1, increased circulating fibronectin (FN1) levels in serum and depletion of natural IgM against fibronectin ((n)IgM-FN1) are common factors for both severe ME/CFS and long COVID. We provide evidence for herpesvirus dUTPases-mediated alterations in host cell cytoskeleton, mitochondrial dysfunction and OXPHOS. Our data show altered active immune complexes, immunoglobulin-mediated mitochondrial fragmentation as well as adaptive IgM production in ME/CFS patients. Our findings provide mechanistic insight into both ME/CFS and long COVID development. Finding of increased circulating FN1 and depletion of (n)IgM-FN1 as a biomarker for the severity of both ME/CFS and long COVID has an immediate implication in diagnostics and development of treatment modalities.

Moving toward gender equity in the cardiology and cardiovascular research workforce in Germany: a report from the German Cardiac Society.

Aims: Although the share of women in cardiology in Germany is growing steadily, this does not translate into leadership positions. Medical societies play a crucial role in shaping the national and international medical and scientific environment. The German Cardiac Society (DGK) aims to serve the public discourse on gender-equity by systematic analysis of data on gender representation within the society and in Germany. Methods and results: We present gender disaggregated data collection of members, official organs, working groups, scientific meetings, as well as awards of the DGK based on anonymized exports from the DGK office as well as on data gathered from the DGK web page. From 2000 to 2020, the overall number of DGK members as well as the share of women increased (12.5% to 25.3%). In 2021, the share of women ranged from 40% to 50% in earlier career stages but was substantially lower at senior levels (23.9% of consulting/attending physicians, 7.1% of physicians-in-chief, 3.4% of directors). The share of women serving in DGK working groups had gained overall proportionality, but nuclei and speaker positions were largely held by men. Boards and project groups were predominantly represented by men as well. At the DGK-led scientific meetings, women contributed more often in junior relative to (invited) senior roles. Conclusion: Increasing numbers of women in cardiology and in the DGK over the past 20 years did not translate into the respective increase in representation of women in leadership positions. There is an urgent need to identify and, more importantly, to overcome barriers towards gender equity. Transparent presentation of society-related data is the first step for future targeted actions in this regard.

Hearts in their hands-Physicians' gestures embodying shared professional knowledge around the world.

The biomedical approach to medical knowledge is widely accepted around the world. This article considers whether the incorporated aspects of physician-patient interaction have become similarly common across the globe by comparing the gestures that physicians use in their interactions with patients. Up to this point, there has been little research on physicians' use of gestures in health-care settings. We explore how-in four university hospitals in Turkey, the People's Republic of China, The Netherlands and Germany-physicians use gesture in their discussions with simulated patients about the condition of heart failure. Our analysis confirms the importance of gestures for organising both the personal interaction and the knowledge transfer between physician and patient. From the perspective of global comparison, it is notable that physicians in all four hospitals used similar gestures. This demonstrates the globality of biomedical knowledge in an embodied mode. Physicians used gestures for a range of purposes, including to convey the idea of an 'anatomical map' and for constructing visual models of (patho-)physiological processes. Since biomedical language is rife with metaphor, it was not surprising that we also identified an accompanying metaphorical gesture which has a similar form in the various locations that were part of the study.