Liver stiffness as a prognostic parameter and tool for risk stratification in advanced cardiac transthyretin amyloidosis.

BACKGROUND: In light of increasing therapeutic options, risk stratification of advanced cardiac transthyretin amyloidosis (ATTR-CA) is gaining clinical importance to avoid ineffective treatments. Liver stiffness as a marker of hypervolemia and hepatic congestion might predict mortality in advanced ATTR-CA and allow to identify patients at highest risk. METHODS: Proven ATTR-CA patients underwent repeated vibration-controlled transient elastography (VTCE) and standardized serial workup within the local amyloidosis cohort study AmyKoS. Spearman correlation analyses and Cox regressions were performed to evaluate the prognostic value. RESULTS: 41 patients with ATTR-CA were included with median age of 76.6 (55.1-89.1) years, of which 90.2% were male and > 92% wild-type ATTR-CA. In total, 85 VCTE examinations were performed. Median follow-up was 43.7 (2.4-75.6) months; 26.8% of the patients died. At the first clinical evaluation, median left ventricular (LV) absolute global longitudinal strain (GLS) was 11.4 (5.2-19.0) % and median liver stiffness was 6.3 (2.4-22.9) kPa, both significantly correlated with mortality. NT-proBNP possessed statistically significant predictive power in ATTR-CA with more preserved LV function (absolute GLS ≥ 10), whereas stiffness seemed to be more discriminative for ATTR-CA with absolute GLS < 10. The use of alternative congestion surrogates such as liver vein dilation and tricuspid regurgitation peak velocity (tr-vmax) showed congruent results. CONCLUSION: Liver stiffness shows prognostic value regarding all-cause mortality and allows risk stratification in advanced ATTR-CA, particularly in those with markedly impaired longitudinal LV function. These results are transferable to other congestion surrogates.

Incremental prognostic utility of congestion markers in cardiac transthyretin amyloidosis.

BACKGROUND/AIMS: Congestion is prognostically relevant in cardiac transthyretin amyloidosis (ATTR-CA), but whether congestion has an incremental prognostic value beyond the well-established, congestion-sensitive NT-proBNP is unknown. Therefore, we aimed to comparatively evaluate the prognostic utility of several congestion surrogates over NT-proBNP. METHODS: We estimated hazard ratios by Cox proportional hazards regressions with time-varying covariates from a panel data set of the local amyloidosis cohort study AmyKoS. Different models were compared by using chi(χ)2-statistics measuring overall model significance. RESULTS/CONCLUSION: 131 ATTR-CA patients (wild-type 84.0%, hereditary 6.9%, without genetic testing 9.2%; median age 78.7 (quartiles 73.3, 82.1) years; 85.5% male) with 566 observations across a median follow-up of 38.2 (30.6; 48.2) months were analyzed. 83.2% received disease-modifying treatment; 20.6% participated concurrently in placebo-controlled gene silencer trials. Information on congestion improved biomarker-driven risk stratification and identified patients at the highest risk. Echocardiographic congestion markers performed better than clinical findings and daily diuretic use/dosage. Relevant adjusters were daily diuretic dosage, disease-modifying treatment, eGFR, and right atrial volume. NT-proBNP and the tricuspid regurgitation peak velocity (tr-vmax) provided an easy-to-use stratification with overall model performance similar to NAC and Mayo staging systems. Further analyses are necessary for validation and to identify the optimal cut points of the congestion markers.

Sex-related differences in self-efficacy of patients with heart failure: a pooled cross-sectional study of the German Competence Network Heart Failure.

AIM: To assess the level of self-efficacy in patients with heart failure (HF), and identify differences between important subgroups including sex, and to identify the determinants of high self-efficacy. METHODS AND RESULTS: This was a pooled cross-sectional analysis of 2,030 patients from four prospective studies conducted within the German Competence Network Heart Failure. We used the Self-efficacy Subscale and the Overall Summary Score (OSS) of the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) to assess self-efficacy and health-related quality of life. The cut-off of 75 score points was used for the dichotomization into high (≥75) vs low (<75) self-efficacy. Depressive symptoms were measured by the Patient Health Questionnaire (PHQ-9). A total of 1,615 patients with HF provided complete self-efficacy scores: mean age 66.6±12.3 years, 431 (27%) women. Mean self-efficacy was 67.5±24.9, with 907 patients (56.2%) showing high self-efficacy and 708 patients (43.8%) showing low self-efficacy. Men had higher self-efficacy scores than women (68.7±24.5 vs. 64.2±26.0; p=0.001). Multivariable logistic regression identified KCCQ-OSS (OR per 5-point increase 1.08, 95%CI 1.04-1.12), female sex (OR 0.72, 95%CI 0.56-0.94), depressive symptoms (OR per 3-point increase in PHQ-9 0.90, 95%CI 0.83-0.98), and acute HF (0.46, 95% CI 0.34-0.62) as important predictors of high self-efficacy. CONCLUSION: In patients with HF, women seemed to exhibit lower self-efficacy than men. Health-related quality of life and psychological well-being were dominant determinants of self-efficacy. Future studies should investigate the role of self-efficacy as a therapeutic target for tailored and sex-specific nursing interventions.

Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy.

BACKGROUND: Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive, fatal disease. Vutrisiran, a subcutaneously administered RNA interference therapeutic agent, inhibits the production of hepatic transthyretin. METHODS: In this double-blind, randomized trial, we assigned patients with ATTR-CM in a 1:1 ratio to receive vutrisiran (25 mg) or placebo every 12 weeks for up to 36 months. The primary end point was a composite of death from any cause and recurrent cardiovascular events. Secondary end points included death from any cause, the change from baseline in the distance covered on the 6-minute walk test, and the change from baseline in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score. The efficacy end points were assessed in the overall population and in the monotherapy population (the patients who were not receiving tafamidis at baseline) and were tested hierarchically. RESULTS: A total of 655 patients underwent randomization; 326 were assigned to receive vutrisiran and 329 to receive placebo. Vutrisiran treatment led to a lower risk of death from any cause and recurrent cardiovascular events than placebo (hazard ratio in the overall population, 0.72; 95% confidence interval [CI], 0.56 to 0.93; P = 0.01; hazard ratio in the monotherapy population, 0.67; 95% CI, 0.49 to 0.93; P = 0.02) and a lower risk of death from any cause through 42 months (hazard ratio, 0.65; 95% CI, 0.46 to 0.90; P = 0.01). A primary end-point event occurred in 163 patients in the vutrisiran group and in 202 in the placebo group. In the overall population, treatment with vutrisiran resulted in less of a decline in the distance covered on the 6-minute walk test than placebo (least-squares mean difference, 26.5 m; 95% CI, 13.4 to 39.6; P<0.001) and less of a decline in the KCCQ-OS score (least-squares mean difference, 5.8 points; 95% CI, 2.4 to 9.2; P<0.001). Similar benefits were observed in the monotherapy population. The incidence of adverse events was similar in the two groups (99% in the vutrisiran group and 98% in the placebo group); serious adverse events occurred in 62% of the patients in the vutrisiran group and in 67% of those in the placebo group. CONCLUSIONS: Among patients with ATTR-CM, treatment with vutrisiran led to a lower risk of death from any cause and cardiovascular events than placebo and preserved functional capacity and quality of life. (Funded by Alnylam Pharmaceuticals; HELIOS-B ClinicalTrials.gov number, NCT04153149.).

Innate immune memory after brain injury drives inflammatory cardiac dysfunction.

The medical burden of stroke extends beyond the brain injury itself and is largely determined by chronic comorbidities that develop secondarily. We hypothesized that these comorbidities might share a common immunological cause, yet chronic effects post-stroke on systemic immunity are underexplored. Here, we identify myeloid innate immune memory as a cause of remote organ dysfunction after stroke. Single-cell sequencing revealed persistent pro-inflammatory changes in monocytes/macrophages in multiple organs up to 3 months after brain injury, notably in the heart, leading to cardiac fibrosis and dysfunction in both mice and stroke patients. IL-1ß was identified as a key driver of epigenetic changes in innate immune memory. These changes could be transplanted to naive mice, inducing cardiac dysfunction. By neutralizing post-stroke IL-1ß or blocking pro-inflammatory monocyte trafficking with a CCR2/5 inhibitor, we prevented post-stroke cardiac dysfunction. Such immune-targeted therapies could potentially prevent various IL-1ß-mediated comorbidities, offering a framework for secondary prevention immunotherapy.

Association between self-reported and objectively assessed physical functioning in the general population.

Knowledge about a patient's physical fitness can aid in medical decision-making, but objective assessment can be challenging and time-consuming. We aimed to investigate the concordance of self-reported health status and physical functioning with the 6 minute walking distance (6MWD) as objective measure of physical performance. The prospective characteristics and course of heart failure stages A/B and determinants of progression (STAAB) cohort study iteratively follows a representative sample of residents of the city of Würzburg, Germany, aged 30-79 years, without a history of heart failure (HF). The 6MWD was measured in 2752 individuals (aged 58 ± 11 years, 51% women) from a population-based cohort under strictly standardized conditions. Self-reported health status and physical functioning were assessed from items of the short form 36 (SF-36). After the respective classification of self-reported health status and physical functioning into 'good', 'moderate', and 'poor', we determined the association of these categories with 6MWD by applying a generalized linear model adjusted for age and sex. Prevalence of self-reported good/moderate/poor general health and physical functioning was 41/52/7% and 45/48/7%, respectively. Mean 6MWD in the respective categories was 574 ± 70/534 ± 76/510 ± 87 m, and 574 ± 72/534 ± 73/490 ± 82 m, with significant sex-specific differences between all categories (all p < 0.001) as well as significant differences between the respective groups except for the categories 'moderate' and 'poor' health status in men. This cross-sectional analysis revealed a strong association between self-reported health status and physical functioning with the objective assessment of 6MWD, suggesting that physicians can rely on their patients' respective answers. Nevertheless, sex-specific perception and attribution of general health and physical functioning deserve further in-depth investigation. Decision-making based on self-reported health requires prospective evaluation in population-based cohorts as well as adult inpatients.

Long-term cognitive and brain morphologic changes in chronic heart failure: Results of the Cognition.Matters-HF study.

AIMS: Cognitive impairment (CI) is a common, yet frequently unrecognized co-morbidity in chronic heart failure (HF). We quantified trajectories of cognitive performance, brain volume, and related clinical outcome over a time course of 6 years. METHODS AND RESULTS: The Cognition.Matters-HF cohort study recruited patients with stable HF of any aetiology and severity. Beyond cardiological assessment, the workup included cognitive testing and brain magnetic resonance imaging (MRI). Of 148 recruited patients, 70% exhibited CI at baseline. During the median follow-up time of 69 months (quartiles: 68, 70), indicators of HF severity remained essentially unaltered. CI was also stable, with the exception of intensity of attention, where age-adjusted t-scores decreased from 42 (38, 46) to 38 (34, 44; P < 0.001). Complete sets of four serial brain MRI scans were available in 47 patients (32% of total sample). Total brain volume shrank by 0.4% per year, from 1103 (1060, 1143) cm3 to 1078 (1027, 1117) cm3, which was within limits observed in non-diseased ageing individuals. During follow-up, 29 study participants (20%) died, and 26 (18%) were at least once hospitalized due to worsening HF. The presence of CI was not associated with overall (P = 0.290) or hospitalization-free (P = 0.450) survival. CONCLUSIONS: In patients with stable HF patients receiving guideline-directed pharmacologic treatment and regular medical care, the presence of CI did not affect overall and hospitalization-free 6-year survival. The loss of brain parenchyma observed in patients with stable HF did not exceed that of normal ageing.

Improved Interpretation of Pulmonary Artery Wedge Pressures through Left Atrial Volumetry-A Cardiac Magnetic Resonance Imaging Study.

BACKGROUND: The pulmonary artery wedge pressure (PAWP) is regarded as a reliable indicator of left ventricular end-diastolic pressure (LVEDP), but this association is weaker in patients with left-sided heart disease (LHD). We compared morphological differences in cardiac magnetic resonance imaging (CMR) in patients with heart failure (HF) and a reduced left ventricular ejection fraction (LVEF), with or without elevation of PAWP or LVEDP. METHODS: We retrospectively identified 121 patients with LVEF < 50% who had undergone right heart catheterization (RHC) and CMR. LVEDP data were available for 75 patients. RESULTS: The mean age of the study sample was 63 ± 14 years, the mean LVEF was 32 ± 10%, and 72% were men. About 53% of the patients had an elevated PAWP (>15 mmHg). In multivariable logistic regression analysis, NT-proBNP, left atrial ejection fraction (LAEF), and LV end-systolic volume index independently predicted an elevated PAWP. Of the 75 patients with available LVEDP data, 79% had an elevated LVEDP, and 70% had concomitant PAWP elevation. By contrast, all but one patient with elevated PAWP and half of the patients with normal PAWP had concomitant LVEDP elevation. The Bland-Altman plot revealed a systematic bias of +5.0 mmHg between LVEDP and PAWP. Notably, LAEF was the only CMR variable that differed significantly between patients with elevated LVEDP and a PAWP ≤ or >15 mmHg. CONCLUSIONS: In patients with LVEF < 50%, a normal PAWP did not reliably exclude LHD, and an elevated LVEDP was more frequent than an elevated PAWP. LAEF was the most relevant determinant of an increased PAWP, suggesting that a preserved LAEF in LHD may protect against backward failure into the lungs and the subsequent increase in pulmonary pressure.

Prognostic Utility of Pericardial Effusion in the General Population: Findings From the STAAB Cohort Study.

BACKGROUND: The incidental finding of a pericardial effusion (PE) poses a challenge in clinical care. PE is associated with malignant conditions or severe cardiac disease but may also be observed in healthy individuals. This study explored the prevalence, determinants, course, and prognostic relevance of PE in a population-based cohort. METHODS AND RESULTS: The STAAB (Characteristics and Course of Heart Failure Stages A/B and Determinants of Progression) cohort study recruited a representative sample of the population of Würzburg, aged 30 to 79 years. Participants underwent quality-controlled transthoracic echocardiography including the dedicated evaluation of the pericardial space. Of 4965 individuals included at baseline (mean age, 55±12 years; 52% women), 134 (2.7%) exhibited an incidentally diagnosed PE (median diameter, 2.7 mm; quartiles, 2.0-4.1 mm). In multivariable logistic regression, lower body mass index and higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels were associated with PE at baseline, whereas inflammation, malignancy, and rheumatoid disease were not. Among the 3901 participants attending the follow-up examination after a median time of 34 (30-41) months, PE was found in 60 individuals (1.5%; n=18 new PE, n=42 persistent PE). Within the follow-up period, 37 participants died and 93 participants reported a newly diagnosed malignancy. The presence of PE did not predict all-cause death or the development of new malignancy. CONCLUSIONS: Incidental PE was detected in about 3% of individuals, with the vast majority measuring <10 mm and completely resolving. PE was not associated with inflammation markers, death, incident heart failure, or malignancy. Our findings corroborate the view of current guidelines that a small PE in asymptomatic individuals can be considered an innocent phenomenon and does not require extensive short-term monitoring.

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.

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.

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.

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.

[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.

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.

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.