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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.

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.

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.

Background and aims Endogenous Cushing's syndrome (CS) is characterized by an unfavorable cardiovascular (CV) and metabolic risk profile, but the potential adverse effects of hypercortisolism on myocardial function are not well known. Myocardial Work analysis is a new echocardiographic method that utilizes left ventricular pressure-strain loops to quantify cardiac performance independent of afterload. Methods and results In a cross-sectional analysis, we compared four groups: patients with overt endogenous CS (n = 31, mean age 47 ± 12 years, 71% women), patients with endogenous CS in long-term remission after medical cure (CS-LTR; n = 49, 53 ± 12 years, 78% women), healthy subjects (n = 439; 49 ± 11 years, 57% women), and individuals with metabolic syndrome (n = 305, 59 ± 10 years, 37% women). Both CS patient groups exhibited a CV risk pattern and metabolic profile worse than healthy subjects but better than individuals with metabolic syndrome. Analyses adjusted for sex and age revealed higher Wasted Work both in overt CS (median; quartiles: 105 mmHg%; 74, 147) and CS-LTR (97 mmHg%; 69, 158), respectively, when compared to healthy individuals (75 mmHg%; 54, 109, p  < 0.01) or individuals with metabolic syndrome (95 mmHg%, 65, 136, p  < 0.05), resulting in compromised Work Efficiency ( p  < 0.05). Conclusion Left ventricular performance is compromised in overt CS beyond alterations found in individuals with metabolic syndrome sharing equal CV risk factors and remains so despite biochemical remission during the LTR period. Myocardial Work analysis is suited to detect the subtle yet clinically relevant differences between different phenotypes of myocardial involvement.

Background The six-minute walk distance (6MWD) is a measure of functional capacity and a frequently used endpoint in clinical trials investigating transthyretin amyloid cardiomyopathy (ATTR-CM). We evaluated the clinical utility of the 6MWD by quantifying the gap between the expected and observed physical performance and estimating its determinants. Methods Outpatients with wild-type (ATTRwt)-CM were investigated. Standardized echocardiographic, laboratory and clinical assessments were performed. A regression formula derived from a healthy local population sample was applied to predict the expected 6MWD. Associations with 6MWD were analyzed by linear regression, adjusted for age and height. Explanatory multivariable models using backward elimination, regularization and clinical reasoning were calculated. Results 100 patients were analyzed. Their mean age was 78.7 (6.3) years and 86% were men. The mean observed 6MWD was 310 (113) m, which corresponded to about 65% of the expected performance. Significant predictors of the 6MWD were (ordered by decreasing explanatory power): high-sensitivity Troponin T, NT-proBNP, NAC disease stage, estimated glomerular filtration rate, atrial fibrillation, hemoglobin, hepatic vein dilation, mitral E-wave maximum velocity, left ventricular ejection fraction, and the tricuspid valve maximal regurgitation pressure gradient. Multivariable models yielded an R² of up to 45.9% with a root mean squared error of 82.9 m. Conclusions Physical performance as measured by the 6MWD in patients with ATTRwt-CM was remarkably compromised. Laboratory and imaging markers indicative of disease severity and congestion predicted the 6MWD in these patients. Cardiovascular markers explained a fair amount of 6MWD variability.

Aims Data on the clinical profiles of patients with transthyretin amyloidosis cardiomyopathy (ATTR‐CM) in the post‐approval era of tafamidis 61 mg are lacking. Study aims were characterization of contemporary ATTR‐CM patients, analysis of potential eligibility for the ‘Transthyretin Amyloidosis Cardiomyopathy Clinical Trial’ (ATTR‐ACT) and identification of factors associated with the decision on tafamidis 61 mg treatment. Methods and results This retrospective study analysed ATTR‐CM patients seen at eight University Hospitals in the first year after approval of tafamidis 61 mg for ATTR‐CM in Germany (April 2020 to March 2021). The cohort comprised 366 patients (median age 79 [74; 82] years, 84% male), with 47% and 45% of the cohort being in National Amyloidosis Centre ATTR stage ≥ II and NYHA class ≥ III, respectively. Sixty‐four per cent of patients met key eligibility criteria of the pivotal ATTR‐ACT. In recently diagnosed patients (58% with diagnosis ≤6 months), the rate of variant ATTR was significantly lower than in patients diagnosed more than 6 months ago (9.3% vs. 19.7%). Of the 293 patients without prior ATTR specific treatment, tafamidis 61 mg was newly initiated in 77%. Patients with tafamidis 61 mg treatment were significantly younger, were more often eligible for ATTR‐ACT, had lower NYHA class and higher serum albumin levels. These variables explained 16% of the variance of treatment decision. Unadjusted survival was higher in patients with than those without treatment (1‐year survival 98.6% vs. 87.3%, P < 0.001). Conclusions Wild‐type ATTR was the primary aetiology amongst contemporary ATTR‐CM patients and almost two‐thirds of patients were in an advanced disease stage. Clinical profiles of 64% of patients in routine care matched those of the ATTR‐ACT. Further effort is needed to detect patients at an earlier disease stage and to validate criteria justifying treatment initiation. The 366 patients diagnosed with transthyretin amyloidosis cardiomyopathy (ATTR‐CM) were analyzed regarding their clinical characteristics in the first year after approval of tafamidis 61 mg for ATTR‐CM in Germany. Nearly two‐thirds of the patients were in an advanced disease stage and 64% met the key criteria of the “Transthyretin Amyloidosis Cardiomyopathy Clinical Trial” (ATTR‐ACT) (6). 58% of the patients were recently diagnosed and the rate of variant ATTR (vATTR) in these patients was significantly lower compared to those with longer‐standing diagnosis. Tafamidis 61 mg was initiated in 77% of the patients (*patients receiving gene silencers, tafamidis meglumine 20 mg approved for PNP or were part of a compassionate use program for tafamdis 61 mg were excluded from this analysis).

Aims Heart failure (HF) impairs skeletal muscle mass and function, which contributes to reduced physical performance. We investigated the prognostic impact of gait speed (GS), handgrip strength (HG) and appendicular skeletal muscle index (ASMI) on cardiovascular outcomes in a prospective HF cohort. Methods This single‐centre prospective cohort study included adults with stable chronic HF with a previous diagnosis of overtly reduced left ventricular ejection fraction (LVEF) <40% and LVEF < 50% at enrolment. GS was measured by the 4 m GS test, maximal HG was measured with a hydraulic dynamometer, and ASMI was measured by dual‐energy X‐ray absorptiometry. The primary combined outcome was cardiovascular death or worsening HF. Fine and Gray regression models were calculated, treating non‐cardiovascular death as the competing event. Results Two hundred five patients (78% male) were analysed. The median age was 66 (quartiles: 58–74) years, 31% had diabetes mellitus, and the median LVEF was 37 (30–43) %. Median GS was 1.0 (0.8–1.0) m/s, median HG was 32 (24–40) kg, and median ASMI was 8.0 (7.2–8.9) kg/m2. During a median follow‐up of 4.7 (4.0–5.3) years, the primary outcome was observed in 52 patients. In models adjusted for key clinical covariates, lower GS predicted a higher risk of cardiovascular death or worsening HF [subdistribution hazard ratio (SHR) per 0.1 m/s increase = 0.81, 95% confidence interval (CI) 0.68–0.95], whereas HG (SHR per 5 kg increase = 0.97, 95% CI 0.84–1.10) and ASMI (SHR per 1 kg/m2 increase = 1.17, 95% CI 0.94–1.44) did not. In the analysis of effect modification, these associations were consistent across key clinical subgroups. Conclusions Higher GS was independently associated with a lower risk of cardiovascular death or worsening HF, whereas HG and ASMI were not. We prospectively confirm GS as a physical performance measure with clear prognostic significance for patients with HF. The prognostic impact of the muscle parameters gait speed, handgrip strength and appendicular skeletal muscle index on cardiovascular outcomes was investigated. We prospectively analyzed a cohort of 205 heart failure patients with a median left ventricular ejection fraction of 37% and a median follow‐up of 4.7 years. Fine and Gray regression modeling identified only gait speed as an independent predictor of the combined outcome of cardiovascular death or worsening heart failure.

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.

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.