Valid and Reproducible Quantitative Assessment of Cardiac Volumes by Echocardiography in Patients with Valvular Heart Diseases-Possible or Wishful Thinking?

The analysis of left ventricular function is predominantly based on left ventricular volume assessment. Especially in valvular heart diseases, the quantitative assessment of total and effective stroke volumes as well as regurgitant volumes is necessary for a quantitative approach to determine regurgitant volumes and regurgitant fraction. In the literature, there is an ongoing discussion about differences between cardiac volumes estimated by echocardiography and cardiac magnetic resonance tomography. This viewpoint focuses on the feasibility to assess comparable cardiac volumes with both modalities. The former underestimation of cardiac volumes determined by 2D and 3D echocardiography is presumably explained by methodological and technical limitations. Thus, this viewpoint aims to stimulate an urgent and critical rethinking of the echocardiographic assessment of patients with valvular heart diseases, especially valvular regurgitations, because the actual integrative approach might be too error prone to be continued in this form. It should be replaced or supplemented by a definitive quantitative approach. Valid quantitative assessment by echocardiography is feasible once echocardiography and data analysis are performed with methodological and technical considerations in mind. Unfortunately, implementation of this approach cannot generally be considered for real-world conditions.

Plausible Functional Diagnostics by Rational Echocardiography in the Assessment of Valvular Heart Disease - Role of Quantitative Echocardiography in the Assessment of Mitral Regurgitation.

The echocardiographic assessment of valvular heart diseases is the basic analysis of valvular defects next to clinical investigation and stethoscopy. Severity of mitral regurgitation (MR) is usually estimated by an integrated approach using semi quantitative parameters and is still one of the biggest challenges of echocardiography. Quantitative echocardiographic analysis of MR severity often fails to describe comprehensible hemodynamic conditions. However, comprehensive echocardiography based on standardized image acquisition and proper image quality is required to properly assess hemodynamic parameter comparable to cardiac magnetic resonance tomography. This review focuses on the uncertainty of MR severity assessed by echocardiography in recent trials of interventional MR treatment. In addition, the necessity to provide plausible echocardiographic data for individual decision making is highlighted. In conclusion, plausible functional diagnostics by rational echocardiography is a prerequisite in patients with valvular heart diseases.

Myocardial Work Assessment for the Prediction of Prognosis in Advanced Heart Failure.

Objectives: The aim of this study was to investigate whether echocardiographic assessment of myocardial work is a predictor of outcome in advanced heart failure. Background: Global work index (GWI) and global constructive work (GCW) are calculated by means of speckle tracking, blood pressure measurement, and a normalized reference curve. Their prognostic value in advanced heart failure is unknown. Methods: Cardiopulmonary exercise testing and echocardiography with assessment of GWI and GCW was performed in patients with advanced heart failure caused by ischemic heart disease or dilated cardiomyopathy (n = 105). They were then followed up repeatedly. The combined endpoint was all-cause death, implantation of a left ventricular assist device, or heart transplantation. Results: The median patient age was 54 years (interquartile range [IQR]: 48-59.9). The mean left ventricular ejection fraction was 27.8 ± 8.2%, the median NT-proBNP was 1,210 pg/ml (IQR: 435-3,696). The mean GWI was 603 ± 329 mmHg% and the mean GCW was 742 ± 363 mmHg%. The correlation between peak oxygen uptake and GWI as well as GCW was strongest in patients with ischemic cardiomyopathy (r = 0.56, p = 0.001 and r = 0.53, p = 0.001, respectively). The median follow-up was 16 months (IQR: 12-18.5). Thirty one patients met the combined endpoint: Four patients died, eight underwent transplantation, and 19 underwent implantation of a left ventricular assist device. In the multivariate Cox regression analysis, only NYHA class, NT-proBNP and GWI (hazard ratio [HR] for every 50 mmHg%: 0.85; 95% CI: 0.77-0.94; p = 0.002) as well as GCW (HR for every 50 mmHg%: 0.86; 95% CI: 0.79-0.94; p = 0.001) were identified as independent predictors of the endpoint. The cut-off value for predicting the outcome was 455 mmHg% for GWI (AUC: 0.80; p < 0.0001; sensitivity 77.4%; specificity 71.6%) and 530 mmHg% for GCW (AUC: 0.80; p < 0.0001; sensitivity 74.2%; specificity 78.4%). Conclusions: GWI and GCW are powerful predictors of outcome in patients with advanced heart failure.

Echocardiographic assessment of mitral regurgitation: discussion of practical and methodologic aspects of severity quantification to improve diagnostic conclusiveness.

The echocardiographic assessment of mitral valve regurgitation (MR) by characterizing specific morphological features and grading its severity is still challenging. Analysis of MR etiology is necessary to clarify the underlying pathological mechanism of the valvular defect. Severity of mitral regurgitation is often quantified based on semi-quantitative parameters. However, incongruent findings and/or interpretations of regurgitation severity are frequently observed. This proposal seeks to offer practical support to overcome these obstacles by offering a standardized workflow, an easy means to identify non-severe mitral regurgitation, and by focusing on the quantitative approach with calculation of the individual regurgitant fraction. This work also indicates main methodological problems of semi-quantitative parameters when evaluating MR severity and offers appropriateness criteria for their use. It addresses the diagnostic importance of left-ventricular wall thickness, left-ventricular and left atrial volumes in relation to disease progression, and disease-related complaints to improve interpretation of echocardiographic findings. Finally, it highlights the conditions influencing the MR dynamics during echocardiographic examination. These considerations allow a reproducible, verifiable, and transparent in-depth echocardiographic evaluation of MR patients ensuring consistent haemodynamic plausibility of echocardiographic results.

Validity of visual assessment of aortic valve morphology in patients with aortic stenosis using two-dimensional echocardiography.

The diagnostic value of a visual assessment of aortic valve (AV) morphology for grading aortic stenosis (AS) remains unclear. A visual score (VS) for assessing the AV was developed and its reliability with respect to Doppler measurements and the calcium score (ctCS) derived by multislice computed tomography was evaluated. 99 Patients with AS of various severity and 38 patients without AS were included in the analysis. Echocardiographic studies were evaluated using the new VS which includes echogenicity, thickening, localization of lesions and leaflet mobility, with a total score ranging from 0 to 11. The association of VS with ctCS and the severity of AS was analyzed. There was a significant correlation of VS with AV hemodynamic parameters and with ctCS. The cut-off value for the detection of AS of any grade was a VS of 6 (sensitivity 95%, specificity 85% for women; sensitivity 85%, specificity 88% for men). A VS of 9 for women and of 10 for men was able to predict severe AS with a high specificity (96% in women and 94% in men, AUC 0.8 and 0.86, respectively). The same cut-off values were identified for the detection of ctCS of ≥ 1600 AU and ≥ 3000 AU with a specificity of 77% and 82% (AUC 0.69 and 0.81, respectively). Assessment of aortic valve morphology can serve as an additional diagnostic tool for the detection of AS and an estimation of its severity.

Disproportionate mitral regurgitation: another myth? A critical appraisal of echocardiographic assessment of functional mitral regurgitation.

The contradictory findings of recent prospective randomized controlled trials assessing the impact of percutaneous edge-to-edge repair in patients with functional or secondary mitral regurgitation have triggered a lively discussion about an "integrated" echocardiographic approach for grading severity of mitral regurgitation. In the MITRA-FR trial, the COAPT trial and the REDUCE-FMR trial echocardiographic assessment of the severity of mitral regurgitation was consistent with principles set forth by the current echocardiographic guidelines and analysed in its best settings by expert international leaders in the field of echocardiography. However, serious inconsistencies appeared in the presented echocardiographic assessments regarding cardiac output and regurgitant fraction. A new term "disproportionate functional mitral regurgitation" was introduced describing a situation where the increase of effective regurgitant orifice area exceeds the enlargement of the left ventricular end-diastolic volumes. Further discussion resulted in the idea of a "new conceptional framework" for distinguishing "proportionate" and "disproportionate" functional mitral regurgitation. The aim of this viewpoint is to dispute conclusions based on the term "disproportionate" mitral regurgitation. A "disproportionate" FMR is highly questionable because disproportionateness of flow in communication vessels cannot exist. In addition, a proposal of echocardiographic assessment based on a conventional comprehensive transthoracic echocardiography is given to avoid obvious hemodynamic contradictions.

Limitations in the Assessment of Prosthesis-Patient Mismatch.

BACKGROUND: Prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR) may affect survival but data are conflicting. It is assessed by relating effective orifice area (EOA) to body surface area (EOAi). EOA is patient-specific as the result of flow-velocity times area at the individual patient's outflow tract levels (LVOTA) divided by trans-prosthetic flow velocity. However, some studies use projected EOAs (i.e., valve size associated EOAs from other patient populations) to assess how PPM affects outcome. METHODS: We analyzed 76 studies addressing hemodynamic outcome and/or mortality after bioprosthetic AVR. RESULTS: In 48 studies, projected or measured EOA for calculation of EOAi and PPM assessment was used (of which 25 demonstrated an effect on survival). We identified 28 additional studies providing measured EOA values and the corresponding Bernoulli's pressure gradients after AVR. Despite EOA being a patient-specific parameter, 77% of studies assessing a PPM impact on survival used projected EOAs. The 28 studies are providing measured EOA values and the corresponding Bernoulli's pressure gradients in patients after AVR showed a highly significant, linear relationship between EOA and Bernoulli's gradient. Considering this relationship, it is surprising that relating EOA to body surface area (BSA) (EOAi) is standard but relating pressure gradients to BSA is not. CONCLUSION: We conclude that the majority of studies assessing PPM have used false assumptions because EOA is a patient-specific parameter and cannot be transferred to other patients. In addition, the use of EOAi to assess PPM may not be appropriate and could explain the inconsistent relation between PPM and survival in previous studies.

Expert consensus document on the assessment of the severity of aortic valve stenosis by echocardiography to provide diagnostic conclusiveness by standardized verifiable documentation.

According to recent recommendations on echocardiographic assessment of aortic valve stenosis direct measurement of transvalvular peak jet velocity, calculation of transvalvular mean gradient from the velocities using the Bernoulli equation and calculation of the effective aortic valve area by continuity equation are the appropriate primary key instruments for grading severity of aortic valve stenosis. It is obvious that no gold standard can be declared for grading the severity of aortic stenosis. Thus, conclusions of the exclusive evaluation of aortic stenosis by Doppler echocardiography seem to be questionable due to the susceptibility to errors caused by methodological limitations, mathematical simplifications and inappropriate documentation. The present paper will address practical issues of echocardiographic documentation to satisfy the needs to analyze different scenarios of aortic stenosis due to various flow conditions and pressure gradients. Transesophageal and multidimensional echocardiography should be implemented for reliable measurement of geometric aortic valve area and of cardiac dimensions at an early stage of the diagnostic procedure to avoid misinterpretation due to inconsistent results.

Echocardiographic assessment of functional mitral regurgitation: opening Pandora's box?

Two recent trials of transcatheter mitral-valve repair in patients with functional mitral regurgitation (FMR) presented opposing results for the MitraClip® compared to medical therapy alone. The conflicting results gave rise to intensive discussions about assessment of mitral valve regurgitation (MR). A recent editorial viewpoint provided a potential explanation presenting a new pathophysiologic concept. However, the echocardiographic characterization of both trials' patients is inconsistent and the discussed concepts appear to suffer from plausibility weaknesses. It is well conceivable that limitations in the echocardiographic assessment of the trial patients introduced a bias regarding the selection of patients with severe (or less severe) MR that may be a more plausible explanation for the differences in outcome. We here illustrate our viewpoint regarding the two MitraClip trials and also illustrate the difficulties in assessing functional MR properly. It may indeed be "opening Pandora's box", but we will also make an attempt to provide a solution.

Improvement in the Assessment of Aortic Valve and Aortic Aneurysm Repair by 3-Dimensional Echocardiography.

Reconstructive surgery of the aortic valve is being increasingly used in patients with aortic regurgitation and/or aortic aneurysm. Its success depends on restoring normal aortic valve and root form. Echocardiography is the most reliable and precise imaging technique because it defines abnormal morphology and function, essential for selecting appropriate substrates and guiding the surgical strategy. Despite technical advances in echocardiography, aortic valve and aortic root morphology and function are still assessed mainly using 2-dimensional echocardiography in clinical practice. This review focuses on the need to use 3-dimensional echocardiography to characterize different forms of aortic valve and root abnormalities and attempts to define echocardiographic predictors of successful valve-root complex repair.

The LIFE-Adult-Study: objectives and design of a population-based cohort study with 10,000 deeply phenotyped adults in Germany.

BACKGROUND: The LIFE-Adult-Study is a population-based cohort study, which has recently completed the baseline examination of 10,000 randomly selected participants from Leipzig, a major city with 550,000 inhabitants in the east of Germany. It is the first study of this kind and size in an urban population in the eastern part of Germany. The study is conducted by the Leipzig Research Centre for Civilization Diseases (LIFE). Our objective is to investigate prevalences, early onset markers, genetic predispositions, and the role of lifestyle factors of major civilization diseases, with primary focus on metabolic and vascular diseases, heart function, cognitive impairment, brain function, depression, sleep disorders and vigilance dysregulation, retinal and optic nerve degeneration, and allergies. METHODS/DESIGN: The study covers a main age range from 40-79 years with particular deep phenotyping in elderly participants above the age of 60. The baseline examination was conducted from August 2011 to November 2014. All participants underwent an extensive core assessment programme (5-6 h) including structured interviews, questionnaires, physical examinations, and biospecimen collection. Participants over 60 underwent two additional assessment programmes (3-4 h each) on two separate visits including deeper cognitive testing, brain magnetic resonance imaging, diagnostic interviews for depression, and electroencephalography. DISCUSSION: The participation rate was 33 %. The assessment programme was accepted well and completely passed by almost all participants. Biomarker analyses have already been performed in all participants. Genotype, transcriptome and metabolome analyses have been conducted in subgroups. The first follow-up examination will commence in 2016.

Recommendations for the echocardiographic assessment of native valvular regurgitation: an executive summary from the European Association of Cardiovascular Imaging.

Valvular regurgitation represents an important cause of cardiovascular morbidity and mortality. Echocardiography has become the primary non-invasive imaging method for the evaluation of valvular regurgitation. The echocardiographic assessment of valvular regurgitation should integrate the quantification of the regurgitation, assessment of the valve anatomy and function, as well as the consequences of valvular disease on cardiac chambers. In clinical practice, the management of patients with valvular regurgitation thus largely integrates the results of echocardiography. It is crucial to provide standards that aim at establishing a baseline list of measurements to be performed when assessing regurgitation.

Pill burden in hypertensive patients treated with single-pill combination therapy--an observational study.

INTRODUCTION: Hypertension is a condition which in many cases is treated with more than one drug. Additionally, patients with hypertension often suffer from other concomitant diseases, such as diabetes mellitus or dyslipidemia, which adds to the number of pills that patients need to take (pill burden). The aim of this study was to investigate the impact of this pill burden on patients with hypertension in clinical practice in Germany. METHODS: This prospective, open-label, observational study enrolled adult patients for whom their physician considered treatment with a single-pill combination of amlodipine, valsartan, and hydrochlorothiazide as indicated. At the start of the observation period, physicians and patients filled in a respective questionnaire. RESULTS: The questionnaires of 7,101 patients and 905 physicians were analyzed. The survey among the patients showed that the majority of patients felt burdened by the high number of pills to be taken. This was also seen as a potential reason for medication errors. Approximately half of the patients would be willing to make an out-of-pocket payment for reducing the number of pills to half. The results of the physician questionnaire indicate that the physicians were well aware of the set of problems that is generally associated with the high pill burden and that there is a clear willingness to use combination products in order to reduce the pill burden. CONCLUSION: A high number of pills is considered a burden by the patients. This burden increases with the number of pills taken per day.

European Association of Echocardiography recommendations for the assessment of valvular regurgitation. Part 2: mitral and tricuspid regurgitation (native valve disease).

Mitral and tricuspid are increasingly prevalent. Doppler echocardiography not only detects the presence of regurgitation but also permits to understand mechanisms of regurgitation, quantification of its severity and repercussions. The present document aims to provide standards for the assessment of mitral and tricuspid regurgitation.

European Association of Echocardiography recommendations for the assessment of valvular regurgitation. Part 1: aortic and pulmonary regurgitation (native valve disease).

Valvular regurgitation represents an important cause of cardiovascular morbidity and mortality. Echocardiography has become the primary non-invasive imaging method for the evaluation of valvular regurgitation. The echocardiographic assessment of valvular regurgitation should integrate quantification of the regurgitation, assessment of the valve anatomy, and function as well as the consequences of valvular disease on cardiac chambers. In clinical practice, the management of patients with valvular regurgitation thus largely integrates the results of echocardiography. It is crucial to provide standards that aim at establishing a baseline list of measurements to be performed when assessing regurgitation.