Expert proposal to analyze the combination of aortic and mitral regurgitation in multiple valvular heart disease by comprehensive echocardiography.

The assessment of valvular pathologies in multiple valvular heart disease by echocardiography remains challenging. Data on echocardiographic assessment-especially in patients with combined aortic and mitral regurgitation-are rare in the literature. The proposed integrative approach using semi-quantitative parameters to grade the severity of regurgitation often yields inconsistent findings and results in misinterpretation. Therefore, this proposal aims to focus on a practical systematic echocardiographic analysis to understand the pathophysiology and hemodynamics in patients with combined aortic and mitral regurgitation. The quantitative approach of grading the regurgitant severity of each compound might be helpful in elucidating the scenario in combined aortic and mitral regurgitation. To this end, both the individual regurgitant fraction of each valve and the total regurgitant fraction of both valves must be determined. This work also outlines the methodological issues and limitations of the quantitative approach by echocardiography. Finally, we present a proposal that enables verifiable assessment of regurgitant fractions. The overall interpretation of echocardiographic results includes the symptomatology of patients with combined aortic and mitral regurgitation and the individual treatment options with respect to their individual risk. In summary, a reproducible, verifiable, and transparent in-depth echocardiographic investigation might ensure consistent hemodynamic plausibility of the quantitative results in patients with combined aortic and mitral regurgitation.

Intratumoral heterogeneity after targeted therapy in murine cancer models with differing degrees of malignancy.

INTRODUCTION: Conventional morphologic and volumetric assessment of treatment response is not suitable for adequately assessing responses to targeted cancer therapy. The aim of this study was to evaluate changes in tumor composition after targeted therapy in murine models of breast cancer with differing degrees of malignancy via non-invasive magnetic resonance imaging (MRI). MATERIALS AND METHODS: Mice bearing highly malignant 4T1 tumors or low malignant 67NR tumors were treated with either a combination of two immune checkpoint inhibitors (ICI, anti-PD1 and anti-CTLA-4) or the multi-tyrosine kinase inhibitor sorafenib, following experiments with macrophage-depleting clodronate-loaded liposomes and vessel-stabilizing angiopoietin-1. Mice were imaged on a 9.4 T small animal MRI system with a multiparametric (mp) protocol, comprising T1 and T2 mapping and diffusion-weighted imaging. Tumors were analyzed ex vivo with histology. RESULTS AND DISCUSSIONS: All treatments led to an increase in non-viable areas, but therapy-induced intratumoral changes differed between the two tumor models and the different targeted treatments. While ICI treatment led to intratumoral hemorrhage, sorafenib treatment mainly induced intratumoral necrosis. Treated 4T1 tumors showed increasing and extensive areas of necrosis, in comparison to 67NR tumors with only small, but also increasing, necrotic areas. After either of the applied treatments, intratumoral heterogeneity, was increased in both tumor models, and confirmed ex vivo by histology. Apparent diffusion coefficient with subsequent histogram analysis proved to be the most sensitive MRI sequence. In conclusion, mp MRI enables to assess dedicated therapy-related intratumoral changes and may serve as a biomarker for treatment response assessment.

Expert proposal to characterize cardiac diseases with normal or preserved left ventricular ejection fraction and symptoms of heart failure by comprehensive echocardiography.

Currently, the term "heart failure with preserved left ventricular ejection fraction (HFpEF)" is based on echocardiographic parameters and clinical symptoms combined with elevated or normal levels of natriuretic peptides. Thus, "HFpEF" as a diagnosis subsumes multiple pathophysiological entities making a uniform management plan for "HFpEF" impossible. Therefore, a more specific characterization of the underlying cardiac pathologies in patients with preserved ejection fraction and symptoms of heart failure is mandatory. The present proposal seeks to offer practical support by a standardized echocardiographic workflow to characterize specific diagnostic entities associated with "HFpEF". It focuses on morphological and functional cardiac phenotypes characterized by echocardiography in patients with normal or preserved left ventricular ejection fraction (LVEF). The proposal discusses methodological issues to clarify why and when echocardiography is helpful to improve the diagnosis. Thus, the proposal addresses a systematic echocardiographic approach using a feasible algorithm with weighting criteria for interpretation of echocardiographic parameters related to patients with preserved ejection fraction and symptoms of heart failure. The authors consciously do not use the diagnosis "HFpEF" to avoid misunderstandings. Central illustration: Scheme illustrating the characteristic echocardiographic phenotypes and their combinations in patients with "HFpEF" symptoms with respect to the respective cardiac pathology and pathophysiology as well as the underlying typical disease.

[Diagnostic value of right thoracic ECG recording in detection of pulmonary hypertension in chronic obstructive respiratory disease]. / Diagnostischer Wert rechtsthorakaler EKG-Ableitungen in der Erkennung der pulmonalen Hypertonie bei der chronisch obstruktiven Atemwegserkrankung.

There are many electrocardiographic criteria of pulmonary hypertension and cor pulmonale. These criteria are generally highly specific but not sensitive. Therefore many patients with pulmonary hypertension remain undetected. The aim of this study was to delineate a sensitive as well as a specific ECG parameter for noninvasive prediction of pulmonary hypertension under special consideration of the right thoracic leads. 75 patients were included in this study, 62 male and 13 female, mean age 62.7 +/- 9.5 years. All presented with chronic obstructive lung disease known since 12.1 +/- 9.7 years. The underlying disease had been confirmed clinically and by body plethysmography. Laboratory and lung function data showed a high air way resistance with a mean value of 6.8 +/- 3.3 cm H2O/l/s and a high intrathoracic gas volume of 149.1% of the expected value. The severity of hypoxemia was variable but generally moderate with a PaO2 of 65.3 +/- 11.6 mm Hg on average. All patients applied aerosols with ipratropiumbromid, fenoterol and glucocorticoids. 92% additionally received aminophylline and 87.0% oral glucocorticoids. Diuretics and glycosides were prescribed in 50.0% and 34.8% respectively. The four right thoracic ECG leads Vr3 to Vr6 were recorded in addition to the common twelve leads I to III, a VR, aVL, aVF and V1 to V6. A modified Sokolow-Lyon-Index (SIm) as a sum of amplitudes of R in lead Vr3 and S in lead V6 and the combination of SIm with PaO2 (SIm-PaO2, n = 44) according to the formula SIm + 0.02 (100--PaO2%) were established. Additionally a right heart catherization by Swan-Ganz technique was performed. The mean values of hemodynamic data demonstrated a constellation of precapillary pulmonary hypertension with high PAPm and pulmonary resistance and low pulmonary capillary wedge pressure (26.4 +/- 12.9 mm Hg, 396.0 +/- 294.0 dyn.s./cm5 and 8.7 +/- 4.2 mm Hg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)