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Recently, myocardial work analysis as an echocardiographic tool to non-invasively determine LV work has been introduced and validated against invasive measurements. Based on systolic blood pressure and speckle-tracking derived longitudinal strain (GLS) during systole and isovolumic relaxation, it is considered less load-dependent than LV ejection fraction (LVEF) or GLS and to integrate information on LV active systolic and diastolic work. We aimed to establish reference values for global constructive (GCW) and global wasted work (GWW) as well as of global work index (GWI) and global work efficiency (GWE) across a wide age range and to assess the association with standard echocardiography parameters to estimate the potential additional information provided by myocardial work (MyW). The Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study carefully characterized a representative sample of the population of the City of Würzburg, Germany, aged 30-79 years. We performed myocardial work analysis using the standardized, quality-controlled transthoracic echocardiograms of all individuals lacking any cardiovascular risk factor. Out of 4965 participants, 779 (49±10 years, 59% women) were eligible for the present analysis. Levels of GCW, GWW, and GWE were independent of sex and body mass index, and were stable until the age of 45 years. Thereafter, we observed an upward shift to further stable values of GCW and a linear increase of GWW with advancing age, resulting in lower GWE. Age-adjusted percentiles for GCW, GWW, GWI, and GWE were derived. Higher levels of blood pressure or LV mass were associated with higher GCW, GWI, and GWW, resulting in lower GWE; higher LVEF correlated with higher GCW and GWI, but lower GWW. Higher E/e' correlated with higher GWW, higher e' with lower GWW. Derived from a large sample of apparently healthy individuals from a population based-cohort, we provide age-adjusted reference values for myocardial work indices, applicable for either sex. Weak correlations with common echocardiographic parameters suggest MyW indices to potentially provide additional information, which has to be evaluated in diseased patient cohorts.

BackgroundValvular heart disease (VHD) is described in American guidelines as a progressive disease continuum: stage A (at-risk), stage B (progressive), stage C/D (severe). We aimed to identify frequency and course of VHD stages as well as determinants of VHD progression in the general population.MethodsThe STAAB cohort study (Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression) recruited a prestratified, population-based sample of residents (30–79 years) from Würzburg, Germany, without self-reported heart failure. Participants underwent baseline transthoracic echocardiography (2013–2017) with follow-up after 3 years (2017–2021). VHD progression was defined as an increase in stage or valve intervention.ResultsOf 4943 participants (mean age 55 years, 53% women) VHD stages were: 24% no VHD, 54% stage A, 21% stage B and 0.3% stage C/D. Prevalence of VHD increased with advancing age. Among 3833 participants who were followed for a median of 34 months, 10% in stage A and 1.3% in stage B progressed. Progression rates were highest in participants aged 60–69 and 70–79 years, at rates of 15% and 25% for stage A and 1.6% and 2.6% for stage B, respectively. In multivariable age-adjusted models, elevated E/e’ predicted progression from stage A, while elevated N‐terminal pro‐brain natriuretic peptide (NT-proBNP) predicted progression from stage B. Continuous analysis of aortic stenosis progression showed associations with older age, higher body mass index, diabetes and baseline peak velocity.ConclusionIn a large community cohort, VHD was common, especially at older ages, and about 11% of individuals progressed within 3 years. Echocardiographic indices (E/e’) and the biomarker NT-proBNP emerged as stage-specific predictors, supporting their potential role, along with age and metabolic factors, in identifying individuals at higher risk for progression.

Purpose Amyloidosis represents an increasingly recognized but still frequently missed cause of heart failure. In the light of many effective therapies for light chain (AL) amyloidosis and promising new treatment options for transthyretin (ATTR) amyloidosis, awareness among caregivers needs to be raised to screen for amyloidosis as an important and potentially treatable differential diagnosis. This review outlines the diversity of cardiac amyloidosis, its relation to heart failure, the diagnostic algorithm, and therapeutic considerations that should be applied depending on the underlying type of amyloidosis. Recent Findings Non-biopsy diagnosis is feasible in ATTR amyloidosis in the absence of a monoclonal component resulting in higher detection rates of cardiac ATTR amyloidosis. Biomarker-guided staging systems have been updated to facilitate risk stratification according to currently available biomarkers independent of regional differences, but have not yet prospectively been tested. Novel therapies for hereditary and wild-type ATTR amyloidosis are increasingly available. The complex treatment options for AL amyloidosis are improving continuously, resulting in better survival and quality of life. Mortality in advanced cardiac amyloidosis remains high, underlining the importance of early diagnosis and treatment initiation. Summary Cardiac amyloidosis is characterized by etiologic and clinical heterogeneity resulting in a frequently delayed diagnosis and an inappropriately high mortality risk. New treatment options for this hitherto partially untreatable condition have become and will become available, but raise challenges regarding their implementation. Referral to specialized centers providing access to extensive and targeted diagnostic investigations and treatment initiation may help to face these challenges.

Myocardial work is a new echocardiography-based diagnostic tool, which allows to quantify left ventricular performance based on pressure–strain loops, and has been validated against invasively derived pressure–volume measurements. Myocardial work is described by its components (global constructive work [GCW], global wasted work [GWW]) and indices (global work index [GWI], global work efficiency [GWE]). Applying this innovative concept, we characterized the prevalence and severity of subclinical left ventricular compromise in the general population and estimated its association with cardiovascular (CV) risk factors. Within the Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study we comprehensively phenotyped a representative sample of the population of Würzburg, Germany, aged 30–79 years. Indices of myocardial work were determined in 1929 individuals (49.3% female, mean age 54 ± 12 years). In multivariable analysis, hypertension was associated with a mild increase in GCW, but a profound increase in GWW, resulting in higher GWI and lower GWE. All other CV risk factors were associated with lower GCW and GWI, but not with GWW. The association of hypertension and obesity with GWI was stronger in women. We conclude that traditional CV risk factors impact selectively and gender-specifically on left ventricular myocardial performance, independent of systolic blood pressure. Quantifying active systolic and diastolic compromise by derivation of myocardial work advances our understanding of pathophysiological processes in health and cardiac disease.

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.

To date, there is no validated telephone version of the Kansas City Cardiomyopathy Questionnaire (KCCQ) available to collect data about health-related quality of life among patients with heart failure (HF). We assessed the reliability of the German KCCQ administered via telephone in comparison to the self-administered version. Patients with HF admitted to the outpatient clinic of the University Hospital Würzburg were consecutively identified and recruited. Patients completed (a) the self-administered version of the KCCQ, and (b) the telephone-based interview performed by trained raters. The sequence of both approaches was randomized. For the between-method agreement, the intraclass correlation coefficient (ICC) was calculated using a non-parametric, rank-based approach. We analysed data from sixty-one HF patients. The median KCCQ overall summary score was 84.8 (interquartile range (IQR) 71.6–76.9). The test-retest reliability between the self-administered and the telephone interview showed good agreement for the total symptom score, the clinical score and the overall summary core: ICC 0.75, 95 % confidence interval (CI) 0.72–0.79; ICC 0.80, CI 0.77–0.84; ICC 0.83, CI 0.80–0.86, respectively. The German KCCQ administered via telephone showed good test-retest reliability, indicating its applicability to collect data about health status among HF patients over the phone.

Communicating cardiovascular risk based on individual vascular age (VA) is a well acknowledged concept in patient education and disease prevention. VA may be derived functionally, e.g. by measurement of pulse wave velocity (PWV), or morphologically, e.g. by assessment of carotid intima-media thickness (cIMT). The purpose of this study was to investigate whether both approaches produce similar results. Within the context of the German subset of the EUROASPIRE IV survey, 501 patients with coronary heart disease underwent (a) oscillometric PWV measurement at the aortic, carotid-femoral and brachial-ankle site (PWVao, PWVcf, PWVba) and derivation of the aortic augmentation index (AIao); (b) bilateral cIMT assessment by high-resolution ultrasound at three sites (common, bulb, internal). Respective VA was calculated using published equations. According to VA derived from PWV, most patients exhibited values below chronological age indicating a counterintuitive healthier-than-anticipated vascular status: for VA PWVao in 68% of patients; for VA AIao in 52% of patients. By contrast, VA derived from cIMT delivered opposite results: e.g. according to VA total-cIMT accelerated vascular aging in 75% of patients. To strengthen the concept of VA, further efforts are needed to better standardise the current approaches to estimate VA and, thereby, to improve comparability and clinical utility.

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). 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. 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%. 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.

Left ventricular (LV) rotational function parameters provide in-depth information about LV mechanical function as well as prognostic information. Using three-dimensional (3D) echocardiography, we identified determinants of LV “twist” and “torsion”, and established reference values using a large population-based cohort. 3D echocardiography images were recorded in n = 2803 subjects within the prospective STAAB cohort study investigating a representative age- and sex-stratified sample of residents of the city of Würzburg, aged 30–79 years, without history of heart failure. Valid 3D image analysis was performed in n = 1831 (65.3%) subjects (mean age 57 ± 11 years, 49.3% women). Using general linear models, we identified determinants of LV twist and torsion: there was a positive association between LV rotational parameters and age, female sex, and blood pressure but a negative association with body weight. From a subset of 479 apparently healthy individuals exhibiting no cardiovascular (CV) risk factors or CV disease (mean age 52 ± 10 years, 56.4% women), we derived reference percentiles for twist and torsion. LV rotation is determined by a complex interplay of sub-endocardial and sub-epicardial fibers which might be affected differentially by potential risk factors. We found a differential association with respective determinants as LV rotational parameters increased with age and with higher blood pressure but decreased with higher body weight. Further research is needed to elucidate these associations in more detail and to determine the additional information contributed by twist and torsion. To facilitate respective attempts and to set an individual’s results in relation to a population-based reference, we derived normal values for twist and torsion from a sub-collective of healthy individuals.

Adaptive immune responses, particularly the production of anti-myocardial antibodies, have been implicated as critical mediators in myocardial healing and remodeling following myocardial infarction (MI), acute myocarditis (Myo), and heart failure (HF). However, current methods for detecting heart-reactive antibodies in patients are insufficient, as most rely on heart tissue slices from primates or other species. These approaches pose technical, logistical, and ethical challenges, including the risk of false negative results due to lack of inter-species cross-reactivity. To address these limitations, we developed a human cell-based assay to screen for patient-derived serum or plasma reactivity against human cardiomyocytes differentiated from induced pluripotent stem cells (iPSC-CMs). This human-on-human test system can detect cardiomyocyte-specific immunoglobulins present in patient plasma by applying indirect immunofluorescence staining, followed by convenient visualization through either confocal microscopy or standard widefield systems available in clinical laboratories. Overall, this approach provides a physiologically relevant and ethically responsible model for rapid, accurate testing of anti-myocardial antibodies across various clinical settings, thus offering accessible tools to stratify patients with myocardial disease according to their adaptive immune response status.