Clinical Presentation and Multi-Parametric Screening Surrogates of Ischemic Stroke Patients Suffering from Infective Endocarditis.

BACKGROUND: Infective endocarditis (IE) represents a life-threatening condition due to complications like cardiac failure and thromboembolism. In ischemic stroke, IE formally excludes patients from approaches addressing the recanalization of occluded vessels, challenging decision-making in the early phase of hospitalization. This study aimed at the rate and clinical course of stroke patients with IE and explored clinical, imaging-based and serum parameters, which would allow early identification. METHODS: A hospital-based registry containing 1,531 ischemic stroke patients was screened for IE identified by echocardiography. In addition to clinical parameters, patterns of cerebral manifestation as well as a variety of inflammatory serum and myocardial markers were analyzed concerning their predictive impact for identifying affected patients. RESULTS: IE was found in 26 patients (1.7%) and was associated with an increased body temperature and cardiac murmurs. Patients suffering from IE demonstrated a more severe clinical affection at hospital discharge and an impaired symptom decline during hospitalization, further deteriorated by the use of systemic thrombolysis. Distribution of cerebral infarction patterns did not differ between the groups. C-reactive protein (CRP) and leukocyte count as well as troponin and myoglobin, taken at hospital admission, were found to be significantly associated with IE. CONCLUSIONS: IE in stroke patients is associated with worse clinical outcome, complicated by intravenously applied thrombolysis, and therefore needs to be screened during the early phase of hospitalization. Increased serum levels of CRP and leukocyte count in combination with an increased body temperature or abnormal cardiac murmurs should entail rapid initiation of further diagnostics, that is, transoesophageal echocardiography.

Echocardiographic monitoring of myocardial function in a female patient with right heart Loeffler endocarditis at thrombotic stage after Epstein-Barr-virus infection.

BACKGROUND: Transthoracic echocardiography is usually the first non-invasive imaging modality for the detection of Loeffler endocarditis at thrombotic stage. In the recent decade 3D echocardiography and deformation imaging already proved as a helpful tool for the monitoring of left and right ventricular heart disease. CASE PRESENTATION: The present case illustrates the diagnostic role of 3D echocardiography and deformation imaging in the acute stage of right sided Loeffler endocarditis in a 70-year-old Western European (German) woman. This case proves that myocardial involvement due to inflammation can be detected at subclinical stages by speckle tracking echocardiography. Acute deterioration of left and right ventricular function and the early response to prednisolone therapy can objectively be monitored. In addition, alterations of effective stroke volume can quantitatively be assessed by 3D right ventricular volumetry with exclusion of thrombus formation in the volume measurements. CONCLUSION: This case underlines the importance of 3D echocardiography and deformation imaging as a helpful diagnostic tool in disease management in the acute phase of Loeffler endocarditis at thrombotic stage.

Detection of direct oral anticoagulants with the diluted Russel's viper venom time.

INTRODUCTION: The activity of direct oral anticoagulants (DOAC) is important in acute clinical situations. Recent studies have suggested a strong influence of DOAC on the diluted Russel's Viper Venom Time (dRVVT). Therefore, it may be a suitable screening parameter for antithrombotic plasma activity of different DOAC. This prospective study aims to evaluate the sensitivity and specificity of dRVVT to detect residual DOAC activity at recommended plasma level thresholds. METHODS: A total of 80 patients were recruited, with 20 each treated with one of the four approved DOAC (apixaban, edoxaban, rivaroxaban or dabigatran), respectively. Blood plasma was collected before (baseline), at plasma peak time, and 6 and 12 h after DOAC. DRVVT was measured using the screen (LA1) and confirm (LA2) assay for lupus anticoagulant and compared with DOAC plasma levels. A reference range was calculated based on the dRVVT values of 61 healthy blood donors. RESULTS: All DOAC significantly prolonged the dRVVT especially at higher DOAC plasma levels. The LA1 time ≥41 s had a sensitivity ≥98% to detect edoxaban, dabigatran and rivaroxaban plasma levels ≥30 ng/mL but it was only 87% for apixaban. Sensitivity was ≥98% for all DOAC with the LA2 assay ≥36 s. The negative predictive value of a DOAC plasma level <30 ng/mL and dRVVT LA2 <36 s was 99%. CONCLUSIONS: The dRVVT confirm assay (LA2) reliably detects residual DOAC plasma levels ≥30 ng/mL and could be useful to rapidly rule out relevant DOAC activity in emergency situations and to guide treatment decisions.

Echocardiographic assessment of left ventricular volumes: a comparison of different methods in athletes.

BACKGROUND: Cardiac magnetic resonance imaging (cMRI) is considered the gold standard for the assessment of left ventricular (LV) systolic function. However, discrepancies have been reported in the literature between LV volumes assessed by transthoracic echocardiography (TTE) and cMRI. The objective of this study was to analyze the differences in LV volumes between different echocardiographic techniques and cMRI. METHODS AND RESULTS: In 64 male athletes (21.1 ± 4.9 years), LV volumes were measured by TTE using the following methods: Doppler echocardiography, anatomical M-Mode, biplane/triplane planimetry and 3D volumetry. In addition, LV end-diastolic (LVEDV), end-systolic (LVESV), and stroke volumes (LVSV) were assessed in 11 athletes by both TTE and cMRI. There was no significant difference between LVEDV and LVESV determined by biplane/triplane planimetry and 3D volumetry. LVEDV and LVESV measured by M-Mode were significantly lower compared to 3D volumetry. LVSV determined by Doppler with 3D planimetry of LV outflow tract was significantly higher than 2D planimetry and 3D volumetry, whereas none of the planimetric or volumetric methods for determining LVSV differed significantly. There were no significant differences for LVEDV, LVESV, LVSV and LVEF between cMRI and TTE determined by biplane planimetry in the subgroup of 11 athletes. CONCLUSION: The choice of echocardiographic method used has an impact on LVSV in athletes, so the LVSV should always be checked for plausibility. The same echocardiographic method should be used to assess LVSV at follow-ups to ensure good comparability. The data suggest that biplane LV planimetry by TTE is not inferior to cMRI.

[Echocardiography in cardiac arrhythmias]. / Echokardiographie in der Rhythmologie.

Echocardiography plays a key role in planning and guidance of electrophysiological procedures. After exclusion of structural heart disease, echocardiography provides insight into the extent of left atrial remodeling by determining left atrial metrics. This "biomarker" is associated with the risk of new-onset atrial fibrillation and predictive of atrial fibrillation recurrence after ablation. Transesophageal echocardiography is necessary to exclude left atrial thrombi and is able to guide a transseptal puncture. In case of a rare but life-threatening cardiac tamponade, an echocardiographic-guided pericardiocentesis ensures quick and effective treatment. Left ventricular ejection fraction and deformation analysis determined by echocardiography are established methods for risk stratification in patients with systolic dysfunction and used to guide pharmacological and device therapy.

Impact of Aortic Valve Regurgitation on Doppler Echocardiographic Parameters in Patients with Severe Aortic Valve Stenosis.

BACKGROUND: Diagnosing severe aortic stenosis (AS) depends on flow and pressure conditions. It is suspected that concomitant aortic regurgitation (AR) has an impact on the assessment of AS severity. The aim of this study was to analyze the impact of concomitant AR on Doppler-derived guideline criteria. We hypothesized that both transvalvular flow velocity (maxVAV) and the mean pressure gradient (mPGAV) will be affected by AR, whereas the effective orifice area (EOA) and the ratio between maximum velocity of the left ventricular outflow tract and transvalvular flow velocity (maxVLVOT/maxVAV) will not. Furthermore, we hypothesized that EOA (by continuity equation), and the geometric orifice area (GOA) (by planimetry using 3D transesophageal echocardiography, TEE), will not be affected by AR. METHODS AND RESULTS: In this retrospective study, 335 patients (mean age 75.9 ± 9.8 years, 44% male) with severe AS (defined by EOA < 1.0 cm2) who underwent a transthoracic and transesophageal echocardiography were analyzed. Patients with a reduced left ventricular ejection fraction (LVEF < 53%) were excluded (n = 97). The remaining 238 patients were divided into four subgroups depending on AR severity, and they were assessed using pressure half time (PHT) method: no, trace, mild (PHT 500-750 ms), and moderate AR (PHT 250-500 ms). maxVAV, mPGAV and maxVLVOT/maxVAV were assessed in all subgroups. Among the four subgroups (no (n = 101), trace (n = 49), mild (n = 61) and moderate AR (n = 27)), no differences were obtained for EOA (no AR: 0.75 cm2 ± 0.15; trace AR: 0.74 cm2 ± 0.14; mild AR: 0.75 cm2 ± 0.14; moderate AR: 0.75 cm2 ± 0.15, p = 0.998) and GOA (no AR: 0.78 cm2 ± 0.20; trace AR: 0.79 cm2 ± 0.15; mild AR: 0.82 cm2 ± 0.19; moderate AR: 0.83 cm2 ± 0.14, p = 0.424). In severe AS with moderate AR, compared with patients without AR, maxVAV (p = 0.005) and mPGAV (p = 0.022) were higher, whereas EOA (p = 0.998) and maxVLVOT/maxVAV (p = 0.243) did not differ. The EOA was smaller than the GOA in AS patients with trace (0.74 cm2 ± 0.14 vs. 0.79 cm2 ± 0.15, p = 0.024), mild (0.75 cm2 ± 0.14 vs. 0.82 cm2 ± 0.19, p = 0.021), and moderate AR (0.75 cm2 ± 0.15 vs. 0.83 cm2 ± 0.14, p = 0.024). In 40 (17%) patients with severe AS, according to an EOA < 1.0 cm2, the GOA was ≥ 1.0 cm2. CONCLUSION: In severe AS with moderate AR, the maxVAV and mPGAV are significantly affected by AR, whereas the EOA and maxVLVOT/maxVAV are not. These results highlight the potential risk of overestimating AS severity in combined aortic valve disease by only assessing transvalvular flow velocity and the mean pressure gradient. Furthermore, in cases of borderline EOA, of approximately 1.0 cm2, AS severity should be verified by determining the GOA.

Prognostic Relevance of Global Myocardial Work Index in Patients with Moderate Aortic Valve Stenosis.

BACKGROUND: A reduced global myocardial work index (GWI) ≤ 1951 mmHg% is associated with increased mortality in patients with severe aortic valve stenosis (AS). However, parameters predicting the outcome in patients with moderate AS are limited. Therefore, the aim of this study was to evaluate the prognostic value of the GWI in patients with moderate AS. METHODS AND RESULTS: In this prospective study, 103 patients with moderate AS (mean age 72 ± 10 years; male: 69%) underwent standardized transthoracic echocardiography. The primary endpoint was survival without an aortic valve replacement (AVR). After a median follow-up of 30 ± 5 months, 37 patients (36%) were referred for an AVR. Survival without an AVR was 96% at 12 months and 80% at 30 months (>1951 mmHg%) versus 96% and 68% (≤1951 mmHg%). A GWI ≤ 1951 mmHg% did not predict the need for an AVR (hazard ratio 1.31 (95% CI, 0.63-2.72), p = 0.49). Furthermore, there was no significant correlation between the mean GWI (1644 ± 448 mmHg%) and mean aortic valve pressure gradient (24.2 mmHg ± 6.2, p = 0.615) or effective aortic orifice area (1.24 cm2 ± 0.11, p = 0.678). There was no difference between the AVR and non-AVR groups in the occurrence of clinical symptoms. CONCLUSION: In contrast to patients with severe AS, a GWI ≤ 1951 mmHg% did not predict the need for an AVR. Further research is needed to improve the risk stratification in patients with moderate AS.

First case report of the use of two stents following coronary artery obstruction during indirect mitral annuloplasty.

The case of a 71-year-old male with end stage heart failure and severe mitral regurgitation is presented, where percutaneous indirect mitral annuloplasty was performed. During device implantation in the coronary sinus the circumflex artery was compromised at two anatomic locations, while the mitral regurgitation was efficiently reduced. After weighing risks and alternative therapeutic options, stent implantation was chosen as bailout strategy to leave the device in place and retain the efficient MR reduction. The anatomical proximity of Cx and coronary sinus in the mitral valve plane bears the risk of circumflex artery damage during surgical and interventional mitral repair. Usually, a device exchange solves the problem of arterial flow limitation in most cases. While stent implantation remains off label use in this setting and should not be performed without critical evaluation, it has been performed successfully in similar clinical settings as well (e.g. artery stenosis by surgical suture).

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.

Comparison of left ventricular deformation abnormalities by echocardiography with cardiac magnetic resonance imaging in patients with acute myocarditis and preserved left ventricular ejection fraction.

Purpose: Cardiac magnetic resonance imaging (cMRI) represents the gold standard to detect myocarditis. Left ventricular (LV) deformation imaging provides additional diagnostic options presumably exceeding conventional transthoracic echocardiography (TTE). The present study aimed to analyze the feasibility to detect myocarditis in patients (pts) with preserved LV ejection fraction (LVEF) by TTE compared to cMRI. It has been hypothesized that the number of pathological findings by deformation imaging correspond to findings in cMRI. Methods and results: Between January 2018 and February 2020 102 pts with acute myocarditis according to the modified Lake Louise criteria and early gadolinium enhancement (EGE) by cMRI were identified at the department of cardiology at the University Hospital Leipzig. Twenty-six pts were included in this retrospective comparative study based on specific selection criteria. Twelve pts with normal cMRI served as a control group. LV deformation was analyzed by global and regional longitudinal strain (GLS, rLS), global and regional circumferential and radial strain (GCS, rCS, GRS, rRS), and LV rotation (including layer strain analysis). All parameters were compared to findings of edema, inflammation, and fibrosis by cMRI according to Lake Louise criteria. All pts with acute myocarditis diagnosed by cMRI showed pathological findings in TTE. Especially rCS and LV rotation analyzed by regional layer strain exhibit a high concordance with pathological findings in cMRI. In controls no LV deformation abnormalities were documented. Mean values of GLS, GRS, and GCS were not significantly different between pts with acute myocarditis and controls. Conclusion: This retrospective analysis documents the feasibility of detecting regional deformation abnormalities by echocardiography in patients with acute myocarditis confirmed by cMRI. The detection of pathological findings due to myocarditis requires the determination of regional deformation parameters, particularly rCS and LV rotation. The assessment of global strain values does not appear to be of critical value.

Native T1 mapping for the diagnosis of cardiac amyloidosis in patients with left ventricular hypertrophy.

BACKGROUND: Cardiac magnetic resonance (CMR) with parametric mapping can improve the characterization of myocardial tissue. We studied the diagnostic value of native T1 mapping to detect cardiac amyloidosis in patients with left ventricular (LV) hypertrophy. METHODS: One hundred twenty-five patients with increased LV wall thickness (≥ 12 mm end-diastole) who received clinical CMR in a 3 T scanner between 2017 and 2020 were included. 31 subjects without structural heart disease served as controls. Native T1 was measured as global mean value from 3 LV short axis slices. The study was registered at German clinical trial registry (DRKS00022048). RESULTS: Mean age of the patients was 66 ± 14 years, 83% were males. CA was present in 24 patients, 21 patients had hypertrophic cardiomyopathy (HCM), 80 patients suffered from hypertensive heart disease (HHD). Native T1 times were higher in patients with CA (1409 ± 59 ms, p < 0.0001) compared to healthy controls (1225 ± 21 ms), HCM (1266 ± 44 ms) and HHD (1257 ± 41 ms). HCM and HHD patients did not differ in their native T1 times but were increased compared to control (p < 0.01). ROC analysis of native T1 demonstrated an area under the curve for the detection of CA vs. HCM and HHD of 0.9938 (p < 0.0001), which was higher than that of extracellular volume (0.9876) or quantitative late gadolinium enhancement (0.9406; both p < 0.0001). The optimal cut-off value of native T1 to diagnose CA was 1341 ms (sensitivity 100%, specificity 97%). CONCLUSION: Non-contrast CMR imaging with native T1 mapping provides high diagnostic accuracy to diagnose cardiac amyloidosis in patients with left ventricular hypertrophy.

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.

[Functional Diagnostics by Rational Echocardiography]. / Rationale echokardiografische Funktionsdiagnostik.

Functional diagnostics by rational echocardiography are the base of a verifiable and reliable analysis of ventricular and valvular function. The most important functional parameters in echocardiography are cardiac volumes - especially total and effective left ventricular stroke volume -, global longitudinal strain, effective orifica areas in valvular stenoses and effective regurgitant volumes, regurgitant fraction and regurgitant orifice areas in valvular regurgitations. Standardized documentation and correct measurements are the prerequisites for accurate echocardiographic estimations. In addition, optimization of image quality supports the correctness of measurements to ensure plausibility of hemodynamics in each individual patient. However, measurements of cardiac volumes by planimetry are error-prone. In addition, calculation of the effective orifice areas using the continuity equation needs methodological accuracy and standardization. Finally, assessment of regurgitant volumes, regurgitant fraction, and regurgitant orifice is often inconsistent with stable hemodynamic conditions - especially by functional assessment the 2D-PISA method. Thus, functional diagnostics by echocardiography in valvular heart diseases should focus on a plausible hemodynamic assessment.

[Clinical exam of the unconscious patient]. / Notfallmedizinische Untersuchung bei bewusstlosen Patienten ­ Schritt für Schritt.

In the setting of emergency medicine, the unconscious patient requires a special approach of clinical examination. The patient is mostly unable to communicate and cannot express any complaints. The early identification of life-threatening conditions is of utmost importance. Following the well established ABCDE scheme, we present a short algorithm, which allows the emergency physician to identify the most conditions within a few minutes.

Left ventricular hypertrophy, diastolic dysfunction and right ventricular load predict outcome in moderate aortic stenosis.

Aims: Predictors of progression of moderate aortic valve stenosis (AS) are incompletely understood. The objective of this study was to evaluate the prognostic value of left ventricular hypertrophy (LVH), diastolic dysfunction, and right ventricular (RV) load in moderate AS. Methods and results: Moderate AS was defined by aortic valve area (AVA), peak transvalvular velocity (Vmax) or mean pressure gradient (PGmean). A total of 131 Patients were divided into two groups according to the number of pathophysiological changes (LVH, diastolic dysfunction with increased LV filling pressures and/or RV load): <2 (group 1); ≥2 (group 2). The primary outcome was survival without aortic valve replacement (AVR). After follow-up of 30 months, the reduction of AVA (-0.06 ± 0.16 vs. -0.24 ± 0.19 cm2, P < 0.001), the increase of PGmean (2.89 ± 6.35 vs 6.29 ± 7.13 mmHg, P < 0.001) and the decrease of the global longitudinal strain (0.8 ± 2.56 vs. 1.57 ± 3.42%, P < 0.001) from baseline to follow-up were significantly more pronounced in group 2. Survival without AVR was 82% (group 1) and 56% (group 2) [HR 3.94 (1.74-8.94), P < 0.001]. Survival without AVR or progression of AS was 77% (group 1) and 46% (group 2) [HR 3.80 (1.84-7.86), P < 0.001]. The presence of ≥2 pathophysiological changes predicted outcome whereas age, comorbidities, LDL-cholesterol did not. Conclusion: The presence of ≥2 pathophysiological changes is a strong predictor of outcome in moderate AS and may be useful for risk stratification, particularly for scheduling follow-up time intervals and deciding the timing of AVR.

Global longitudinal strain differentiates physiological hypertrophy from maladaptive remodeling.

Aims: Differentiation of left ventricular (LV) hypertrophy in healthy athletes from pathological LV hypertrophy in heart disease is often difficult. We explored whether extended echocardiographic measurements such as E/e' and global longitudinal strain (GLS) distinguish physiologic from maladaptive hypertrophy in hypertrophic cardiomyopathy, excessively trained athletes' hearts and normal hearts. Methods: Seventy-eight professional athletes (cyclists n = 37, soccer players n = 29, handball players n = 21) were compared with patients (n = 88) with pathological LV hypertrophy (hypertrophic obstructive cardiomyopathy (HOCM, n = 17), hypertensive heart disease (HHD, n = 36), severe aortic valve stenosis (AVS, n = 35) and with sedentary healthy individuals as controls (n = 37). Results: LV ejection fraction (LVEF) was ≥50% in all patients, athletes (median age 26 years, all male) and the controls (97% male, median age 32 years). LV mass index (LVMI) and septal wall thickness was in normal range in controls, but elevated in cyclists and patients with pathological hypertrophy (p < 0.001 for both). E/e' was elevated in all patients with maladaptive hypertrophy but normal in controls and athletes (p < 0.001 vs. pathological hypertrophy). Furthermore GLS was reduced in patients with pathological hypertrophy compared with athletes and controls (for both p < 0.001). In subjects with septal wall thickness >11 mm, GLS (≥-18%) has a specificity of 79% to distinguish between physiological and pathological hypertrophy. Conclusion: GLS and E/e' are reliable parameters unlike left ventricular mass or LV ejection fraction to distinguish pathological and physiological hypertrophy.

Dynamics in myocardial deformation as an indirect marker of myocardial involvement in acute myocarditis due to HIV infection: a case report.

BACKGROUND: The diagnosis of acute myocarditis (AM) is often challenging and mainly performed by cardiac magnetic resonance (CMR). CASE SUMMARY: The present case describes echocardiographic findings of a 38-year-old male patient with exertional dyspnoea probably due to myocardial involvement of previously undiagnosed acute human immunodeficiency virus (HIV) infection. Myocardial deformation imaging might be helpful to detect early stages of myocardial dysfunction in patients with AM and/or systemic infectious diseases by documentation of patchy abnormalities of longitudinal, circumferential and rotational left ventricular (LV) deformation. DISCUSSION: CMR still represents the gold standard to diagnose AM, which has been confirmed by myocardial oedema and hyperaemia in the present case. However, speckle tracking echocardiography seems to be useful to detect myocardial involvement in HIV infection by dynamic alterations of different components of LV deformation. This was documented by comparing echocardiographic findings at the acute stage of HIV infection to findings at follow-ups during antiviral treatment. The diagnostic option to detect myocardial involvement by deformation imaging in a patient with HIV infection is described for the first time.

Long-term clinical and haemodynamic results after transcatheter annuloplasty for secondary mitral regurgitation.

AIMS: The study sought to investigate the long-term outcome after transcatheter mitral valve annuloplasty for secondary mitral regurgitation (MR). METHODS AND RESULTS: Consecutive patients with symptomatic secondary MR undergoing transcatheter mitral valve annuloplasty with the Carillon device at Leipzig University Hospital between 2012 and 2018 were studied prospectively. Left ventricular (LV) function and MR severity were quantified by standardized echocardiography. 33 patients were included. Mean age was 75 ± 10 years, and 20 patients were women. A Society of Thoracic Surgeons score of 8.1 ± 7.2% indicated high-risk status. In 24 patients, MR resulted from LV remodelling and dysfunction, eight suffered from left atrial dilatation, and one patient had MR due to combined primary and secondary aetiology. LV ejection fraction at baseline was (median) 38% [inter-quartile range (IQR) 30-49%]. During the mean follow-up time of 45 ± 20 months, 17 patients died, two patients withdraw consent, and four patients were lost. Of the remaining patients, four were hospitalized for decompensated heart failure. Two of these patients underwent additional transcatheter edge-to-edge mitral valve repair. At follow-up, New York Heart Association (NYHA) functional class improved from 95% in Class III/IV at baseline to 70% in Class I/II with no patients in NYHA Class IV (P < 0.0001). Mitral regurgitant volume was reduced from 27 mL (IQR 25-42 mL) to 8 mL (IQR 3-17 mL) (P = 0.018) and regurgitant fraction from 42% (IQR 34-54%) to 11% (IQR 8-24%) (P = 0.014). LV end-diastolic volume index [92 mL/m2 (IQR 74-107 mL/m2 ) vs. 67 mL/m2 (IQR 46-101 mL/m2 ), P = 0.065] and end-systolic volume index [50 mL/m2 (IQR 44-69 mL/m2 ) vs. 32 mL/m2 (IQR 20-53 mL/m2 ), P = 0.037] decreased. Total stroke volume remained unchanged [38 mL/m2 (IQR 33-43 mL/m2 ) vs. 33 mL/m2 (IQR 26-44 mL/m2 ), P = 0.695], while LV ejection fraction increased [43% (IQR 35-49%) vs. 54% (IQR 46-57%), P = 0.014]. Forward stroke volume, heart rate, and forward cardiac output were not significantly altered. CONCLUSIONS: Among high-risk patients undergoing transcatheter mitral valve annuloplasty for symptomatic secondary MR, mortality was ~50% at 4 years. In the surviving patients, reduced MR severity was associated with reduced NYHA functional class, reverse LV remodelling, and improved LV function.

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.

Plasma levels do not predict thrombin generation in patients taking direct oral anticoagulants.

BACKGROUND: The antithrombotic effect of direct oral anticoagulants (DOAC) in specific clinical scenarios is difficult to assess. OBJECTIVE: This study aimed to evaluate the effect of DOAC on thrombin generation (TG) in relation to their plasma level. METHODS: Eighty patients newly started on anticoagulation were included, 20 patients for each DOAC-apixaban, edoxaban, rivaroxaban, and dabigatran. Plasma was sampled before DOAC (baseline), at plasma peak time, 6 and 12 hours after starting DOAC for quantification of drug levels and TG. RESULTS: The baseline TG before DOAC intake showed inter-individual variability. All DOACs significantly prolonged lag time (LT) and time to peak (TTP), but did not change endogenous thrombin potential (ETP). Anti-Xa inhibitors but not dabigatran reduced thrombin peak, but the effect of apixaban at plasma peak was less pronounced (factor 1.6). LT and TTP prolongation of dabigatran was lower compared to anti-Xa inhibitors. All DOACs showed a nonlinear dose-response relationship, with the greatest antithrombotic effect at lower DOAC plasma levels. The inhibition of TG parameters between baseline and peak was parallel between individual patients but the coefficient of variation of TG was lower compared to drug levels. CONCLUSION: The antithrombotic effect at DOAC peak plasma level measured by TG depends on the patient-specific baseline TG level and the drug-specific inhibition by the particular DOAC. Although peak plasma levels have a high variability, the variation of TG is lower compared to drug levels. Therefore, TG assays may be superior to plasma levels in the assessment of the intensity of anticoagulation.