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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.

Background Prospective longitudinal follow-up of left ventricular ejection fraction (LVEF) trajectories after acute cardiac decompensation of heart failure is lacking. We investigated changes in LVEF and covariates at 6-months' follow-up in patients with a predischarge LVEF ≤40%, and determined predictors and prognostic implications of LVEF changes through 18-months' follow-up. Methods and Results Interdisciplinary Network Heart Failure program participants (n=633) were categorized into subgroups based on LVEF at 6-months' follow-up: normalized LVEF (>50%; heart failure with normalized ejection fraction, n=147); midrange LVEF (41%-50%; heart failure with midrange ejection fraction, n=195), or persistently reduced LVEF (≤40%; heart failure with persistently reduced LVEF , n=291). All received guideline-directed medical therapies. At 6-months' follow-up, compared with patients with heart failure with persistently reduced LVEF, heart failure with normalized LVEF or heart failure with midrange LVEF subgroups showed greater reductions in LV end-diastolic/end-systolic diameters (both P <0.001), and left atrial systolic diameter ( P =0.002), more increased septal/posterior end-diastolic wall-thickness (both P <0.001), and significantly greater improvement in diastolic function, biomarkers, symptoms, and health status. Heart failure duration <1 year, female sex, higher predischarge blood pressure, and baseline LVEF were independent predictors of LVEF improvement. Mortality and event-free survival rates were lower in patients with heart failure with normalized LVEF ( P =0.002). Overall, LVEF increased further at 18-months' follow-up ( P <0.001), while LV end-diastolic diameter decreased ( P =0.048). However, LVEF worsened ( P =0.002) and LV end-diastolic diameter increased ( P =0.047) in patients with heart failure with normalized LVEF hospitalized between 6-months' follow-up and 18-months' follow-up. Conclusions Six-month survivors of acute cardiac decompensation for systolic heart failure showed variable LVEF trajectories, with >50% showing improvements by ≥1 LVEF category. LVEF changes correlated with various parameters, suggesting multilevel reverse remodeling, were predictable from several baseline characteristics, and were associated with clinical outcomes at 18-months' follow-up. Repeat hospitalizations were associated with attenuation of reverse remodeling. Registration URL: https://www.controlled-trials.com; Unique identifier: ISRCTN23325295.

Background: 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., Objectives: 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)., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Caroline Morbach reports a research cooperation with the University of Würzburg and Tomtec Imaging Systems funded by a research grant from the Bavarian Ministry of Economic Affairs, Regional Development and Energy, Germany, speakers honorarium from Amgen, Alnylam and Tomtec, a travel grant from Orion Pharma and Alnylam, and participation in Advisory and Patient Eligibility Boards sponsored by AKCEA, Alnylam, Pfizer and EBR Systems outside the submitted work. Floran Sahiti has nothing to disclose Theresa Tiffe has nothing to disclose. Vladimir Cejka has nothing to disclose. Felizitas Eichner has nothing to disclose Götz Gelbrich reports a research cooperation with the University Hospital Würzburg and TomTec Imaging Systems funded by a research grant from the Bavarian Ministry of Economic Affairs, Regional Development and Energy, Germany, and a grant from the German Research Council (DFG) as the senior biometrician of the FIND-AF II trial outside the submitted work. Peter Heuschmann reports grants from German Ministry of Research and Education, European Union, Charité – Universitätsmedizin Berlin, Berlin Chamber of Physicians, German Parkinson Society, University Hospital Würzburg, Robert Koch Institute, German Heart Foundation, Federal Joint Committee (G-BA) within the Innovationfond, University Hospital Heidelberg (within RASUNOA-prime; RASUNOA-prime is supported by an unrestricted research grant to the University Hospital Heidelberg from Bayer, BMS, Boehringer-Ingelheim, Daiichi Sankyo), grants from Charité – Universitätsmedizin Berlin (within Mondafis; Mondafis is supported by an unrestricted research grant to the Charité from Bayer), from University Göttingen (within FIND-AF randomized; FIND-AF randomized is supported by an unrestricted research grant to the University Göttingen from Boehringer-Ingelheim), outside the submitted work. Stefan Störk reports research grants from the German Ministry of Education and Research, European Union, University Hospital Würzburg; participation in Data Safety Monitoring or Event Adjudication in studies sponsored by Roche, Medtronic; participation in Advisory Boards for Novartis, Bayer, Boehringer Ingelheim, Thermo-Fisher, Boston Scientific; principal investigator in trials (co-) sponsored by Boehringer-Ingelheim, Novartis, Bayer, Lundbeck; speaker honoraria by Boehringer-Ingelheim, Servier, Novartis, Astra-Zeneca, Pfizer, Bayer, Thermo-Fisher, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background:  The interest in information extraction from clinical reports for secondary data use is increasing. But experience with the productive use of information extraction processes over time is scarce. A clinical data warehouse has been in use at our university hospital for several years, which also provides an information extraction of echocardiography reports developed for general use., Objectives:  This study aims to illustrate the difficulties encountered, while using data from a preexisting information extraction process for a large clinical study. To compare the data from the preexisting process with the data obtained from a specially developed process designed to improve the quality and completeness of the study data., Methods:  We extracted the echocardiography variables for 440 patients from the general-use information extraction of the data warehouse (678 reports). Then we developed an information extraction process for the same variables but specifically for this study, with the aim to extract as much information as possible from the text. The extracted data of both processes were compared with a newly created gold standard defined by a cardiologist with long-standing experience in heart failure., Results:  Among 57 echocardiography variables considered relevant for the study, 50 were documented in the routine text reports and could be extracted. Twenty of the required variables were not provided by the general-use extraction process, some others were not provided correctly. The median macro F1-score (precision, recall) across the 30 variables for which values were extracted was 0.81 (0.94, 0.77). Across all 50 variables, as relevant for the study, median macro F1-score was only 0.49 (0.56, 0.46). Employing the study-specific approach considerably improved the quality and completeness of the variables, resulting in F1-scores of 0.97 (0.98, 0.96) across all variables., Conclusion:  Data from information extractions can be used for large clinical studies. However, preexisting information extraction processes should be treated with caution, as the time and effort spent defining each variable in the information extraction process may not be clear., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Aims: We aimed to provide reference values for speckle-tracking derived systolic and diastolic myocardial deformation markers, and to determine their relation with age, sex, and cardiovascular risk factors., Methods and Results: The Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study recruited a representative sample of the population of Würzburg, Germany, aged 30-79 years. In a sample of 1818 participants (52% female, mean age 54±12 years) global longitudinal peak systolic strain (GL-PSS, n = 1218), systolic (GL-SSR, n = 1506), and early (GL-EDSR, n = 1506) and late diastolic strain rates (GL-LDSR, n = 1500) were derived from 2D speckle tracking analysis. From a subgroup of 323 individuals without any cardiovascular risk factor, sex- and age-specific reference values were computed. GL-PSS, GL-SSR, and GL-EDSR were associated with sex, GL-EDSR decreased and GL-LDSR increased with age. In the total sample, dyslipidemia was associated with altered GL-PSS, GL-SSR, and GL-EDSR in women but not in men, whereas obesity was associated with less favorable GL-PSS and GL-EDSR in either sex. Hypertension impacted more adversely on systolic and diastolic myocardial deformation in women compared to men (all p<0.01)., Conclusion: The female myocardium appeared more vulnerable to high blood pressure and dyslipidemia when compared to men, while obesity was associated with adverse myocardial deformation in either sex. The reference values for echocardiographic myocardial deformation provided for a non-diseased population and their here reported associations with cardiovascular risk factors will inform future observational and intervention studies regarding i) effect sizes and power calculation, ii) cross-study comparisons, and iii) categorization of myocardial deformation in specific patient groups., Competing Interests: Caroline Morbach reports a research cooperation with the University of Würzburg and Tomtec Imaging Systems funded by a research grant from the Bavarian Ministry of Economic Affairs, Regional Development and Energy, Germany, speakers honorarium from Amgen and Tomtec, a travel grant from Orion Pharma and Alnylam, and participation in Advisory and Patient Eligibility Boards sponsored by AKCEA, Alnylam, and EBR Systems outside the submitted work. Bettina Walter has nothing to disclose. Margret Breunig has nothing to disclose. Dan Liu has nothing to disclose. Theresa Tiffe has nothing to disclose. Martin Wagner has nothing to disclose. Götz Gelbrich reports a research cooperation with the University Hospital Würzburg and TomTec Imaging Systems funded by a research grant from the Bavarian Ministry of Economic Affairs, Regional Development and Energy, Germany, he receives remuneration as data safety and monitoring board member in the TIM-HF II trial (Charité Berlin), outside the submitted work. Peter Heuschmann reports grants from German Ministry of Research and Education, European Union, Charité – Universitätsmedizin Berlin, Berlin Chamber of Physicians, German Parkinson Society, University Hospital Würzburg, Robert Koch Institute, German Heart Foundation, Federal Joint Committee (G-BA) within the Innovationfond, University Hospital Heidelberg (within RASUNOA-prime; RASUNOA-prime is supported by an unrestricted research grant to the University Hospital Heidelberg from Bayer, BMS, Boehringer-Ingelheim, Daiichi Sankyo), grants from Charité – Universitätsmedizin Berlin (within Mondafis; Mondafis is supported by an unrestricted research grant to the Charité from Bayer), from University Göttingen (within FIND-AF randomized; FIND-AF randomized is supported by an unrestricted research grant to the University Göttingen from Boehringer-Ingelheim), outside the submitted work. Stefan Störk reports research grants from the German Ministry of Education and Research, European Union, University Hospital Würzburg; participation in Data Safety Monitoring and Event Adjudication and Scientific Advisory Boards in studies sponsored by Bayer, Boston Scientific; principal investigator in trials (co-) sponsored by Boehringer, Novartis, Bayer; speaker honoraria by Boehringer, Servier, Novartis, Astra-Zeneca, Pfizer, Bayer, ThermoFisher Scientific, Amgen, Alnylam, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: Cardiac amyloidosis (CA) is a rare cause of heart failure with frequently delayed diagnosis, because specific early signs or symptoms are missing. Recently, direct amyloid imaging using positron emission tomography/computed tomography (PET/CT) has emerged. The aim of this study was to examine the performance of 18 F-florbetaben-PET/CT in detection of CA, and compare it to echocardiography (echo), cardiac MRI (CMR) and scintigraphy. Additionally, the use of 18 F-florbetaben-PET/CT for quantification of amyloid burden and monitoring of treatment response was assessed., Methods: Twenty-two patients with proven (n = 5) or clinical suspicion (n = 17) of CA underwent 18 F-florbetaben-PET/CT for diagnostic work-up. Qualitative and quantitative assessment including calculation of myocardial tracer retention (MTR) was performed, and compared to echo (n = 20), CMR (n = 16), scintigraphy (n = 16) and serologic biomarkers (NT-proBNP, cTnT, free light chains). In four patients, follow-up PET/CT was available (after treatment initiation, n = 3; surveillance, n = 1)., Results: PET demonstrated myocardial 18 F-florbetaben retention consistent with CA in 14/22 patients. Suspicion of CA was subsequently dropped in all eight PET-negative patients. Amyloid subtypes showed characteristic retention patterns (AL > AA > ATTR; all p < 0.005). MTR correlated with morphologic and functional parameters, as measured by CMR and echo (all r| > 0.47|, all p < 0.05), but not with cardiac biomarkers. Changes in MTR from baseline to follow-up corresponded well to treatment response, as assessed by cardiac biomarkers and performance status., Conclusions: Imaging of cardiac amyloidosis (CA) with 18 F-florbetaben-PET/CT is feasible and might be useful in differentiating CA subtypes.

Variability related to image acquisition and interpretation is an important issue of echocardiography in clinical trials. Nevertheless, there is no broadly accepted standard method for quality assessment of echocardiography in clinical research reports. We present analyses based on the echocardiography quality-assurance program of the ongoing STAAB cohort study (characteristics and course of heart failure stages A-B and determinants of progression). In 43 healthy individuals (mean age 50 ± 14 years; 18 females), duplicate echocardiography scans were acquired and mutually interpreted by one of three trained sonographers and an EACVI certified physician, respectively. Acquisition (AcV), interpretation (InV), and inter-observer variability (IOV; i.e., variability between the acquisition-interpretation sequences of two different observers), were determined for selected M-mode, B-mode, and Doppler parameters. We calculated Bland-Altman upper 95% limits of absolute differences, implying that 95% of measurement differences were smaller/equal to the given value: e.g. LV end-diastolic volume (mL): 25.0, 25.0, 27.9; septal e' velocity (cm/s): 3.03, 1.25, 3.58. Further, 90, 85, and 80% upper limits of absolute differences were determined for the respective parameters. Both, acquisition and interpretation, independently and sizably contributed to IOV. As such, separate assessment of AcV and InV is likely to aid in echocardiography training and quality-assurance. Our results further suggest to routinely determine IOV in clinical trials as a comprehensive measure of imaging quality. The derived 95, 90, 85, and 80% upper limits of absolute differences are suggested as reproducibility targets of future studies, thus contributing to the international efforts of standardization in quality-assurance.

Background: Standard echocardiography (SE) is an essential part of the routine diagnostic work-up after ischemic stroke (IS) and also serves for research purposes. However, access to SE is often limited. We aimed to assess feasibility and accuracy of point-of-care (POC) echocardiography in a stroke unit (SU) setting., Methods: IS patients were recruited on the SU of the University Hospital Würzburg, Germany. Two SU team members were trained in POC echocardiography for a three-month period to assess a set of predefined cardiac parameters including left ventricular ejection fraction (LVEF). Diagnostic agreement was assessed by comparing POC with SE executed by an expert sonographer, and intraclass correlation coefficient (ICC) or kappa (κ) with 95% confidence intervals (95% CI) were calculated., Results: In the 78 patients receiving both POC and SE agreement for cardiac parameters was good, with ICC varying from 0.82 (95% CI 0.71-0.89) to 0.93 (95% CI 0.87-0.96), and κ from 0.39 (-95% CI 0.14-0.92) to 0.79 (95% CI 0.67-0.91). Detection of systolic dysfunction with POC echocardiography compared to SE was very good, with an area under the curve of 0.99 (0.96-1.00). Interrater agreement for LVEF measured by POC echocardiography was good with κ 0.63 (95% CI 0.40-0.85)., Conclusions: POC echocardiography in a SU setting is feasible enabling reliable quantification of LVEF and preliminary assessment of selected cardiac parameters that might be used for research purposes. Its potential clinical utility in triaging stroke patients who should undergo or do not necessarily require SE needs to be investigated in larger prospective diagnostic studies.

Background: Right ventricular (RV) dysfunction plays an important role in chronic heart failure (CHF). We evaluated the echocardiographic determinants of 1-year all-cause mortality in CHF patients with clinically relevant functional tricuspid regurgitation (TR)., Methods and Results: A total of 101 consecutive CHF patients (mean age 74 ± 10 years, 53% male) with moderate or severe functional TR were enrolled. Each patient underwent at least 2 echocardiography examinations in an interval of >6 months. Clinical follow-up was made after a median of 305 (interquartile range 164-365) days after the last echocardiography. The primary end point was all-cause mortality. Forty-two patients (42%) died during follow-up. Baseline right atrial (RA) area, TR volume increase and RV enlargement over time were significantly higher in nonsurvivors than survivors (all P < .05). Compared to baseline levels, systolic pulmonary artery pressure (sPAP) was significantly reduced in nonsurvivors during follow-up echocardiography (54 ± 19 vs 49 ± 21 mm Hg; P = .010), but significantly increased in survivors (48 ± 17 vs 54 ± 17 mm Hg; P = .001). Multivariable survival analysis suggested that baseline RA area ≥27 cm 2 (hazard ratio [HR] 2.41, 95% confidence interval [CI] 1.21-4.80; P = .013), follow-up TR proximal isovelocity surface area regurgitant volume increase ≥15 mL (HR 2.27, 95% CI 1.20-4.31; P = .012), RV middle diameter increase ≥10 mm (HR 2.38, 95% CI 1.10-5.11; P = .027), and sPAP reduction ≥10 mm Hg (HR 3.04, 95% CI 1.51-6.13; P = .002) were determinants of 1-year all-cause mortality after the last echocardiography. Patients with 2 or 3 of these determinants were faced with significantly increased 1-year mortality (88% or 100%)., Conclusions: Dynamic RV morphologic and functional changes during serial echocardiography are associated with significantly increased mortality risk in CHF patients with moderate or severe functional TR., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Patients in the early stage of hypertensive heart disease tend to have normal echocardiographic findings. The aim of this study was to investigate whether pathology-specific echocardiographic morphologic and functional parameters can help to detect subclinical hypertensive heart disease. One hundred ten consecutive patients without a history and medication for arterial hypertension (AH) or other cardiac diseases were enrolled. Standard echocardiography and two-dimensional speckle-tracking-imaging analysis were performed. Resting blood pressure (BP) measurement, cycle ergometer test (CET), and 24-hour ambulatory BP monitoring (ABPM) were conducted. Patients were referred to "septal bulge (SB)" group (basal-septal wall thickness ≥ 2 mm thicker than mid-septal wall thickness) or "no-SB" group. Echocardiographic SB was found in 48 (43.6%) of 110 patients. In this SB group, 38 (79.2%) patients showed AH either by CET or ABPM. In contrast, in the no-SB group (n = 62), 59 (95.2%) patients had no positive test for AH by CET or ABPM. When AH was solely defined by resting BP, SB was a reasonable predictive sign for AH (sensitivity 73%, specificity 76%). However, when AH was confirmed by CET or ABPM the echocardiographic SB strongly predicted clinical AH (sensitivity 93%, specificity 86%). In addition, regional myocardial deformation of the basal-septum in SB group was significantly lower than in no-SB group (14 ± 4% vs. 17 ± 4%; P < .001). In conclusion, SB is a morphologic echocardiographic sign for early hypertensive heart disease. Sophisticated BP evaluation including resting BP, ABPM, and CET should be performed in all patients with an accidental finding of a SB in echocardiography., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Information extraction techniques that get structured representations out of unstructured data make a large amount of clinically relevant information about patients accessible for semantic applications. These methods typically rely on standardized terminologies that guide this process. Many languages and clinical domains, however, lack appropriate resources and tools, as well as evaluations of their applications, especially if detailed conceptualizations of the domain are required. For instance, German transthoracic echocardiography reports have not been targeted sufficiently before, despite of their importance for clinical trials. This work therefore aimed at development and evaluation of an information extraction component with a fine-grained terminology that enables to recognize almost all relevant information stated in German transthoracic echocardiography reports at the University Hospital of Würzburg., Methods: A domain expert validated and iteratively refined an automatically inferred base terminology. The terminology was used by an ontology-driven information extraction system that outputs attribute value pairs. The final component has been mapped to the central elements of a standardized terminology, and it has been evaluated according to documents with different layouts., Results: The final system achieved state-of-the-art precision (micro average.996) and recall (micro average.961) on 100 test documents that represent more than 90 % of all reports. In particular, principal aspects as defined in a standardized external terminology were recognized with f 1=.989 (micro average) and f 1=.963 (macro average). As a result of keyword matching and restraint concept extraction, the system obtained high precision also on unstructured or exceptionally short documents, and documents with uncommon layout., Conclusions: The developed terminology and the proposed information extraction system allow to extract fine-grained information from German semi-structured transthoracic echocardiography reports with very high precision and high recall on the majority of documents at the University Hospital of Würzburg. Extracted results populate a clinical data warehouse which supports clinical research.

Diastolic heart failure, also known as heart failure with preserved left ventricular ejection fraction (HF-pEF), is responsible for approximately 50 % of all heart failure cases. According to current guidelines the diagnosis HF-pEF requires three criteria: (1) signs or symptoms of heart failure, (2) presence of a normal left ventricular ejection fraction and (3) evidence of diastolic dysfunction. Echocardiography is the diagnostic modality of choice, especially after ruling out other causes of dyspnea, such as pulmonary diseases, heart rhythm disturbances and volume overload. Important echocardiographic parameters for the assessment of diastolic function are atrial dimensions, myocardial mass, mitral inflow pattern, pulmonary vein flow, propagation velocity of mitral inflow and the tissue Doppler of the mitral annulus. Nevertheless, a complete echocardiographic examination should be performed in every patient with heart failure. In general, diastolic dysfunction is frequently associated with increased atrial diameter and left ventricular hypertrophy. In advanced stages pulmonary hypertension can be present. A robust method for evaluation of systolic function in patients with diastolic dysfunction is crucial. The mitral inflow pattern provides various parameters to describe diastolic function (E/A ratio, deceleration time, isovolumetric relaxation time). In case of difficulties to separate a normal from a pseudonormal mitral inflow pattern the Valsalva maneuver can be used. Another valuable parameter for this differentiation is the duration of the backward flow in the pulmonary veins in contrast to forward flow over the mitral valve. Tachycardia or atrial fibrillation is a major problem for grading of diastolic function; however, in patients with atrial fibrillation E/e' is a well-established parameter. In summary, this review provides a detailed overview and discussion of the established and newer echocardiography techniques for the evaluation of diastolic function and provides an algorithm for the assessment of diastolic dysfunction in everyday routine.

Left ventricular hypertrophy is a non-specific physiological or maladaptive cardiac response to a large array of stimuli mediated by exercise and numerous cardiac and systemic diseases. The precise characterization and quantification of left ventricular hypertrophy may allow a more timely diagnosis of the underlying condition. The clinical reference standard to assess left ventricular hypertrophy is echocardiography, but a comprehensive description of how to approach this frequent finding in clinical practice is lacking. The current review systematically describes the typical echocardiographic patterns of important types of cardiac hypertrophy using both established and advanced imaging modalities. In hypertrophic obstructive cardiomyopathy a markedly reduced regional systolic function is found in the prominent thickened septum, whereas in essential arterial hypertension a typical concentric left ventricular hypertrophy with a less prominent basal septal bulge is present. The echocardiographic characteristics of cardiac amyloidosis are ventricular hypertrophy with sparkling granular myocardial texture and a small epicardial effusion. In addition, the strain rate curve for longitudinal function shows a typically reduced function which reaches maximum already in early systole. The typical feature of Friedreich cardiomyopathy is concentric left ventricular hypertrophy and sparkling granular texture with preserved regional systolic function. In Fabry cardiomyopathy a prominent papillary muscle is presented and a typical strain rate curve can be extracted from the basal lateral wall, indicating replacement fibrosis. Prominent hypertrabecularisation (ratio of non-compacted to compacted myocardium >2) in the apical and mid left ventricular segments is typical for non-compaction cardiomyopathy. Knowledge of these typical echocardiographic features enables the cardiologist to distinguish between the different hypertrophic entities, thus paving the way to early diagnosis.

Fabry disease is often linked with a prominent papillary muscle. It remains unknown whether this sign could be used as a diagnostic marker to screen for Fabry patients. Standard echo was performed in 101 consecutive patients with concentric left ventricular (LV) hypertrophy (28 Fabry, 30 Friedreich, 34 isolated arterial hypertension, 9 amyloidosis) and 50 healthy controls. In addition, the areas of both papillary muscles, as well as the LV endocardial circumference, were manually traced in short axis views. A ratio of papillary muscle size to LV circumference was calculated (PM&#95;LV&#95;ratio). The papillary muscle area was positively correlated to LV wall thickness in this cohort (p < 0.0001; r = 0.58). In all patient subgroups, the absolute papillary muscle area was significantly enlarged and the PM&#95;LV&#95;ratio was significantly higher when compared with controls. However, Fabry patients showed a significantly larger absolute papillary muscle area than Friedreich and amyloidosis patients and a higher PM&#95;LV&#95;ratio than hypertensive and amyloidosis patients. Enlarged absolute papillary muscle area was evidenced in 21 (75%), and increased PM&#95;LV&#95;ratio was found in 22 (78%) of 28 Fabry patients. Combining these two parameters yields a sensitivity of 75% and specificity of 86% for diagnosing Fabry disease with LV hypertrophy. Only 10 of 73 non-Fabry patients (14%) (4 Friedreich, 1 amyloidosis, 5 hypertensive) showed an increased absolute papillary muscle area and PM&#95;LV&#95;ratio. In conclusion, this study confirmed the assumption that the prominent papillary muscle could be an echocardiographic marker for detection of Fabry patients with concentric LV hypertrophy., (Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Left ventricular hypertrophy is a nonspecific physiologic or maladaptive cardiac response to a large array of stimuli mediated by exercise and numerous cardiac and systemic diseases. Hypertrophy, however, is not uniform. Rather, depending on the underlying pathologic mechanism, it may display unique morphologic and functional characteristics. The precise characterization and quantification of left ventricular hypertrophy may therefore allow a more timely diagnosis of the underlying condition. The clinical reference standard to assess left ventricular hypertrophy is echocardiography, but a comprehensive description of how to approach this frequent finding in clinical practice is lacking. The current review systematically describes the typical echocardiographic patterns of important types of cardiac hypertrophy using both established and advanced imaging modalities, thus guiding clinicians' path to early diagnosis., (Copyright 2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

The management of heart failure patients (diagnosis, treatment monitoring, assessment of prognosis) crucially depends on the accuracy of the tools used for patient evaluation. While the diagnostic accuracy of anamnesis, clinical signs and symptoms is poor, "classic" tools like chest X-ray or electrocardiogram show reasonable specificity but poor sensitivity. Transthoracic echocardiography is well suited for the diagnosis of heart failure, but is relatively costly and depends on availability and the skills of the investigator. Over the last 2 decades, numerous biomarkers have emerged that potentially might aid in the complex decisionmaking processes for diagnosis, treatment and monitoring of heart failure. The ideal biomarker would possess a favorable diagnostic test profile and deliver pivotal information. In this respect, the currently best evidence base has been accumulated for the natriuretic peptide family. A large array of other heart failure biomarkers (i.e., markers of inflammation, extracellular matrix remodeling, and myocyte damage and stress) are still in earlier phases of testing. This short review will provide a balanced comparison of those "classic tools" and natriuretic peptides focusing on their diagnostic capacity in various clinical settings, factors influencing test values, cutoff values and their interpretation, and the capacity of these biomarkers to guide the diagnostic and therapeutic decision-making processes in patients with suspected and established heart failure.

Introduction: Left (LVEF) and right ventricular ejection fraction (RVEF) as well as LV regional wall motion at rest are valuable tools to monitor and tailor treatment of congestive heart failure (CHF) patients. Gated blood pool SPECT (GBPS) is under evaluation as an "all-in-one" technique, providing information on LVEF, RVEF, and wall motion derived from a single examination. Aim of the study was to evaluate a commercially available automated GBPS processing software for EF measurements and wall motion analysis in heart failure patients., Methods: Thirty-two patients (12 female; mean age+/-SD: 53+/-13 years), suffering from dilated (63%), ischemic (25%) or hypertrophic (13%) cardiomyopathy, were studied. First-pass radionuclide ventriculography (FP-RNV), planar multigated radionuclide angiography (MUGA), and GBPS were performed at rest after in vivo labeling of red blood cells, and LVEF and RVEF was calculated with each method. Later on the same day LVEF was calculated by echocardiography. LV wall motion (summed motion score and wall motion index) was derived from GBPS and echocardiography using the standard 16-segment model., Results: Mean LVEF measured by GBPS, echocardiography, MUGA and FP-RNV was 33+/-13%, 37+/-15%, 41+/-14% and 45+/-13%, respectively. LVEF values calculated from GBPS showed moderate to good correlation with FP-RNV (r=0.61), MUGA (r=0.65) and ECHO (r=0.74; all p<0.01). Mean RVEF calculated by GBPS, FP-RNV and MUGA was 45+/-14%, 46+/-9% and 38+/-9%, respectively. RVEF values calculated from GBPS showed weak correlation with FP-RNV (r=0.33) and MUGA (r=0.26; all p=n.s.). Assessment of GBPS wall motion was qualitatively possible in all patients. The agreement between GBPS and ECHO was 82% (kappa=0.73). The wall motion index showed good correlation between both methods (r=0.88; p<0.001)., Conclusion: An automated algorithm for LVEF calculation and wall motion analysis using GBPS is feasible for clinical routine diagnostic in CHF patients. The RVEF calculation method needs to be improved before routine clinical application can be recommended.

Heart failure with preserved ejection fraction (HFpEF) is highly prevalent in patients on maintenance haemodialysis (HD) and lacks effective treatment. We investigated the effect of spironolactone on cardiac structure and function with a specific focus on diastolic function parameters. The MiREnDa trial examined the effect of 50 mg spironolactone once daily versus placebo on left ventricular mass index (LVMi) among 97 HD patients during 40 weeks of treatment. In this echocardiographic substudy, diastolic function was assessed using predefined structural and functional parameters including E/e'. Changes in the frequency of HFpEF were analysed using the comprehensive 'HFA-PEFF score'. Complete echocardiographic assessment was available in 65 individuals (59.5 ± 13.0 years, 21.5% female) with preserved left ventricular ejection fraction (LVEF > 50%). At baseline, mean E/e' was 15.2 ± 7.8 and 37 (56.9%) patients fulfilled the criteria of HFpEF according to the HFA-PEFF score. There was no significant difference in mean change of E/e' between the spironolactone group and the placebo group (+ 0.93 ± 5.39 vs. + 1.52 ± 5.94, p = 0.68) or in mean change of left atrial volume index (LAVi) (1.9 ± 12.3 ml/m2 vs. 1.7 ± 14.1 ml/m2, p = 0.89). Furthermore, spironolactone had no significant effect on mean change in LVMi (+ 0.8 ± 14.2 g/m2 vs. + 2.7 ± 15.9 g/m2; p = 0.72) or NT-proBNP (p = 0.96). Treatment with spironolactone did not alter HFA-PEFF score class compared with placebo (p = 0.63). Treatment with 50 mg of spironolactone for 40 weeks had no significant effect on diastolic function parameters in HD patients. The trial has been registered at clinicaltrials.gov (NCT01691053; first posted Sep. 24, 2012). [ABSTRACT FROM AUTHOR]

Background In severe aortic stenosis (AS), brain natriuretic peptide (BNP) and its precursor, the amino-terminal pro-hormone (NT-proBNP) are independent predictors of outcome. Deterioration of cardiac function in AS is currently assessed by symptomatology and echocardiography to determine the optimal time point for surgery. We investigated whether BNP or NT-proBNP may help to estimate the individual risk of patients for subendocardial ischaemia in patients with moderate and severe AS. Design In 71 patients with AS and 24 controls, the association of plasma natriuretic peptides with invasively measured haemodynamic parameters, including the myocardial oxygen supply-to-demand ratio [diastolic pressure time index/systolic pressure time index (DPTI/SPTI)] was cross-sectionally assessed. Results Levels of natriuretic peptides increased with severity of AS. In patients with moderate AS ( n = 30), natriuretic peptides differentiated between symptomatic and asymptomatic status ( P = 0·01). BNP and NT-proBNP values correlated negatively with DPTI/SPTI ( r = −0·58 and −0·51, P < 0·001, respectively) and left ventricular (LV) ejection fraction (EF) ( r = −0·52 and −0·59, P < 0·001, respectively). DPTI/SPTI correlated with aortic valve area ( P < 0·0001) but not with EF. Receiver operating characteristic analysis determined cut-off values of > 450 pg mL−1 for BNP and of > 1800 pg mL−1 for NT-proBNP for those AS patients who were at highest risk for subendocardial ischaemia (i.e. DPTI/SPTI < 0·22) in combination with impaired LV systolic function (i.e. EF < 45%). Conclusions Elevated natriuretic peptides show cardiac deterioration in AS and may help to identify those patients in need for early valve replacement. [ABSTRACT FROM AUTHOR]