Characterization of Von Willebrand Factor Multimer Structure in Patients With Severe Aortic Stenosis

Acquired von Willebrand syndrome (AVWS) associated with severe aortic stenosis (AS) has been frequently subclassified into a subtype 2A based on the deficiency of high-molecular-weight (HMW) multimers as it is seen in inherited von Willebrand disease (VWD) type 2A. However, the multimeric phenotype of VWD type 2A does not only include an HMW deficiency but also a decrease in intermediate-molecular-weight (IMW) multimers and an abnormal inner triplet band pattern. These additional characteristics have not been evaluated in AVWS associated with severe AS. Therefore, we recruited N = 31 consecutive patients with severe AS and performed a high-resolution Western blot with densitometrical band quantification to characterize the von Willebrand factor (VWF) multimeric structure and reevaluate the AVWS subtype classification. Study patients showed an isolated HMW VWF multimer deficiency without additional abnormalities of the IMW portions and the inner triplet structure in 65%. In conclusion, the multimeric pattern of AVWS associated with severe AS does neither resemble that seen in AVWS type 2A nor that seen in inherited VWD type 2A. Therefore, a subclassification into a type 2A should not be used

Transapical mitral valve implantation for treatment of symptomatic mitral valve disease: a real-world multicentre experience.

AIMS Transcatheter mitral valve implantation (TMVI) is a new treatment option for patients with symptomatic mitral valve (MV) disease. Real-world data have not yet been reported. This study aimed to assess procedural and 30-day outcomes of TMVI in a real-world patient cohort. METHOD AND RESULTS All consecutive patients undergoing implantation of a transapically delivered self-expanding valve at 26 European centres from January 2020 to April 2021 were included in this retrospective observational registry. Among 108 surgical high-risk patients included (43% female, mean age 75 ± 7 years, mean STS-PROM 7.2 ± 5.3%), 25% was treated for an off-label indication (e.g. previous MV intervention or surgery, mitral stenosis, mitral annular calcification). Patients were highly symptomatic (New York Heart Association [NYHA] functional class III/IV in 86%) and mitral regurgitation (MR) was graded 3+/4+ in 95% (38% primary, 37% secondary, and 25% mixed aetiology). Technical success rate was 96%, and MR reduction to ≤1+ was achieved in all patients with successful implantation. There were two procedural deaths and 30-day all-cause mortality was 12%. At early clinical follow-up, MR reduction was sustained and there were significant reductions of pulmonary pressure (systolic pulmonary artery pressure 52 vs. 42 mmHg, p < 0.001), and tricuspid regurgitation severity (p = 0.013). Heart failure symptoms improved significantly (73% in NYHA class I/II, p < 0.001). Procedural success rate according to MVARC criteria was 80% and was not different in patients treated for an off-label indication (74% vs. 81% for off- vs. on-label, p = 0.41). CONCLUSION In a real-world patient population, TMVI has a high technical and procedural success rate with efficient and durable MR reduction and symptomatic improvement

A Story of PA/BSA and Biomarkers to Diagnose Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis—The Rise of IGF-BP2 and GDF-15

(1) Background: Currently, echocardiography is the primary non-invasive diagnostic method used to screen patients with severe aortic valve stenosis (AS) for pulmonary hypertension (PH) by estimating systolic pulmonary artery pressure (sPAP). Other radiological methods have been a focus of research in the past couple of years, as it was shown that by determining the pulmonary artery (PA) diameter, prognostic statements concerning overall mortality could be made in these patients. This study compared established and novel cardiovascular biomarkers with the PA/BSA value to detect PH in patients with severe AS. (2) Methods: The study cohort comprised 188 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), who were then divided into two groups based on PA/BSA values obtained through CT-angiography. The presence of PH was defined as a PA/BSA ≥ 16.6 mm/m2 (n = 81), and absence as a PA/BSA 2 (n = 107). Blood samples were taken before TAVR to assess cardiovascular biomarkers used in this study, namely brain natriuretic peptide (BNP), cardiac troponin I (cTnI), high-sensitive troponin (hsTN), soluble suppression of tumorigenesis-2 (sST2), growth/differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2), and soluble urokinase-type plasminogen activator receptor (suPAR). (3) Results: Patients with a PA/BSA ≥ 16.6 mm/m2 showed significantly higher levels of BNP (p = p = 0.040), and H-FABP (p = 0.007). The other investigated cardiovascular biomarkers did not significantly differ between the two groups. To predict a PA/BSA ≥ 16.6 mm/m2, cut-off values for the biomarkers were calculated. Here, GDF-15 (p = 0.029; cut-off 1172.0 pg/mL) and BNP (p p = 0.004) as the best result of the two-way analyses and GDF-15 + IGF-BP2 + BNP (AUC = 0.727; 95%CI = 0.590–0.864; p = 0.004) as the best result of the three-way analyses. No significant difference regarding the 1-year survival between patients with PA/BSA 2 and patients with PA/BSA ≥ 16.6 mm/m2 was found (log-rank test: p = 0.452). (4) Conclusions: Although PA/BSA aims to reduce the bias of the PA value caused by different body compositions and sizes, it is still a controversial parameter for diagnosing PH. Combining the parameter with different cardiovascular biomarkers did not lead to a significant increase in the diagnostic precision for detecting PH in patients with severe AS

The Presence of Ascending Aortic Dilatation in Patients Undergoing Transcatheter Aortic Valve Replacement Is Negatively Correlated with the Presence of Diabetes Mellitus and Does Not Impair Post-Procedural Outcomes

Both relevant aortic valve stenosis (AS) and aortic valve insufficiency significantly contribute to structural changes in the ascending aorta (AA) and thus to its dilatation. In patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), survival data regarding aortic changes and laboratory biomarker analyses are scarce. Methods: A total of 179 patients with severe AS and an available computed tomography were included in this retrospective study. AA was measured, and dilatation was defined as a diameter ≥ 40 mm. Thirty-two patients had dilatation of the AA. A further 32 patients from the present population with a normal AA were matched to the aortic dilatation group with respect to gender, age, body mass index and body surface area, and the resulting study groups were compared with each other. In addition to echocardiographic and clinical characteristics, the expression of cardiovascular biomarkers such as brain natriuretic peptide (BNP), soluble suppression of tumorigenicity-2 (sST2), growth/differentiation of factor-15 (GDF-15), heart-type fatty-acid binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2) and soluble urokinase-type plasminogen activator receptor (suPAR) was analyzed. Kaplan–Meier curves for short- and long-term survival were obtained, and Pearson’s and Spearman’s correlations were calculated to identify the predictors between the diameter of the AA and clinical parameters. Results: A total of 19% of the total cohort had dilatation of the AA. The study group with an AA diameter ≥ 40 mm showed a significantly low comorbidity with respect to diabetes mellitus in contrast to the comparison cohort with an AA diameter p = 0.010). This result continued in the correlation analyses performed, as the presence of diabetes mellitus correlated negatively not only with the diameter of the AA (r = −0.404; p = 0.001) but also with the presence of aortic dilatation (r = −0.320; p = 0.010). In addition, the presence of AA dilatation after TAVR was shown to have no differences in terms of patient survival at 1, 3 and 5 years. There were no relevant differences in the cardiovascular biomarkers studied between the patients with dilated and normal AAs. Conclusion: The presence of AA dilatation before successful TAVR was not associated with a survival disadvantage at the respective follow-up intervals of 1, 3 and 5 years. Diabetes mellitus in general seemed to have a protective effect against the development of AA dilatation or aneurysm in patients with severe AS

CT-Diagnosed Sarcopenia and Cardiovascular Biomarkers in Patients Undergoing Transcatheter Aortic Valve Replacement: Is It Possible to Predict Muscle Loss Based on Laboratory Tests?&mdash;A Multicentric Retrospective Analysis

Background: Patients with severe aortic valve stenosis (AS) often present with heart failure and sarcopenia. Sarcopenia, described as progressive degradation of skeletal muscle mass, has frequently been implicated as a cause of increased mortality, prolonged hospitalization and generalized poor outcome after transcatheter aortic valve replacement (TAVR). At present, sarcopenia is defined by the European Working Group on Sarcopenia in Older People (EWGSOP) based on clinical examination criteria and radiological imaging. The aim of the present study was to compare patients with Computed Tomography (CT)-diagnosed sarcopenia with regard to the expression of cardiovascular biomarkers in order to obtain additional, laboratory-chemical information. Methods: A total of 179 patients with severe AS were included in this retrospective study. Sarcopenia was determined via CT by measurement of the psoas muscle area (PMA), which was indexed to body surface area (PMAi). According to previous studies, the lowest tertile was defined as sarcopenic. Patients with (59/179) and without sarcopenia (120/179) in the overall cohort were compared by gender-specific cut-offs with regard to the expression of cardiovascular biomarkers such as brain natriuretic peptide (BNP), soluble suppression of tumorigenicity-2 (sST2), growth/differentiation of factor-15 (GDF-15), heart-type fatty-acid binding protein (H-FABP), insulin like growth factor binding protein 2 (IGF-BP2) and soluble urokinase-type plasminogen activator receptor (suPAR). Additionally, binary logistic regression analyses were calculated to detect possible predictors of the presence of sarcopenia. Results: No statistical differences regarding one-year survival could be detected between sarcopenic and non-sarcopenic patients in survival curves (log rank test p = 0.179). In the entire cohort, only BNP and hemoglobin (HB) showed a statistically significant difference, with only HB emerging as a relevant predictor for the presence of sarcopenia after binary logistic regression analysis (p = 0.015). No relevant difference in biomarker expression could be found in the male cohort. Regarding the female cohort, statistically significant differences were found in BNP, HB and hematocrit (HK). In binary logistic regression, however, none of the investigated criteria could be related to sarcopenia. Conclusion: Regardless of gender, patients with imaging-based muscle degradation did not demonstrate significantly different cardiovascular biomarker expression compared to those without it

Systolic Pulmonary Artery Pressure and Cardiovascular Biomarkers—New Non-Invasive Ways to Detect Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis Undergoing TAVR?

Background: Patients with severe aortic valve stenosis (AS) frequently present with pulmonary hypertension (PH). The gold standard for detection of pulmonary hypertension is right heart catheterization, which is not routinely performed as a preoperative standard in cardiology centers today, neither before surgical valve replacement nor before transcatheter aortic valve replacement (TAVR) procedure. Echocardiographic determination of systolic pulmonary artery pressure (sPAP) provides an opportunity to assess the presence or absence of PH. The aim of the present study was to investigate the extent to which plasma levels of common cardiovascular biomarkers behave in patients with severe AS and an sPAP <40 mmHg in comparison to patients with an sPAP ≥40 mmHg. Methods: 179 patients with echocardiographic evidence of severe AS before TAVR procedure were divided into 2 groups based on sPAP. An sPAP of 40 mmHg was considered the cut-off value, with absence of PH defined by an sPAP <40 mmHg (n = 82) and presence of PH defined by an sPAP ≥40 mmHg (n = 97). Directly before TAVR, a blood sample was drawn from each patient, and plasma concentrations of the cardiovascular biomarkers Soluble Suppression of Tumorigenicity-2 (sST2), Growth/Differentiation of Factor-15 (GDF-15), Heart-Type Fatty-Acid Binding Protein (H-FABP), Insulin Like Growth Factor Binding Protein 2 (IGF-BP2), Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR), Brain Natriuretic Peptide (BNP) and Cardiac Troponin I (cTnI) were determined. Results: Patients with an sPAP ≥40 mmHg had significantly higher sST2 (p = 0.010), GDF-15 (p = 0.005), IGF-BP2 (p = 0.029), suPAR (p = 0.018), BNP (p < 0.001) and cTnI (p = 0.039) plasma levels. Only for H-FABP (p = 0.069), no significant differences were discernible between the two groups. In addition, cut-off values were calculated to predict an sPAP ≥40 mmHg. Significant results were shown with 16045.84 pg/mL for sST2 (p = 0.010), with 1117.54 pg/mL for GDF-15 (p = 0.005), with 107028.43 pg/mL for IGF-BP2 (p = 0.029), with 3782.84 pg/mL for suPAR (p = 0.018), with 2248.00 pg/mL for BNP (p < 0.001) and with 20.50 pg/mL for cTnI (p = 0.002). Conclusions: sPAP as an echocardiographic parameter in combination with supplementary use of cardiovascular biomarkers presented here have the potential to provide more detailed information about the presence or absence of PH in a non-invasive way

Comparability between Computed Tomography Morphological Vascular Parameters and Echocardiography for the Assessment of Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis&mdash;Results of a Multi-Center Study

Background: Computed tomography (CT) of the aorta and cardiac vessels, which is performed in patients with severe aortic valve stenosis (AS) before transcatheter aortic valve replacement (TAVR), offers the possibility of non-invasive detection of pulmonary hypertension (PH), for example, by determining the diameter of the main pulmonary artery (PA), the right pulmonary artery (RPA) or the left pulmonary artery (LPA). An improvement of the significance of these radiological parameters is often achieved by indexing to the body surface area (BSA). The aim of this study was to compare different echocardiographic systolic pulmonary artery pressure (sPAP) values with radiological data in order to define potential clinical cut-off values for the presence or absence of PH. Methods: A total of 138 patients with severe AS undergoing TAVR underwent pre-interventional transthoracic echocardiography with determination of sPAP values and performance of CT angiography (CTA) of the aorta and femoral arteries. Radiologically, the PA, RPA, LPA, and ascending aorta (AA) diameters were obtained. Vascular diameters were not only indexed to BSA but also ratios were created with AA diameter (for example PA/AA-ratio). From these CT-derived vascular parameters, AUROC curves were obtained regarding the prediction of different sPAP values (sPAP 40&ndash;45&ndash;50 mmHg) and finally correlation analyses were calculated. Results: The best AUROC and correlation analyses were generally obtained at an sPAP &ge; 40 mmHg. When considering diameters alone, the PA diameter was superior to the RPA and LPA. Indexing to BSA generally increased the diagnostic quality of the parameters, and finally, in a synopsis of all results, PA/BSA had the best AUC 0.741 (95% CI 0.646&ndash;0. 836; p &lt; 0.001; YI 0.39; sensitivity 0.87; specificity 0.52) and Spearman&rsquo;s correlation coefficient (r = 0.408; p &lt; 0.001) at an sPAP of &ge;40 mmHg. Conclusions: Features related to pulmonary hypertension are fast and easily measurable on pre-TAVR CT and offer great potential regarding non-invasive detection of pulmonary hypertension in patients with severe AS and can support the echocardiographic diagnosis. In this study, the diameter of the main pulmonary artery with the additionally determined ratios were superior to the values of the right and left pulmonary artery. Additional indexing to body surface area and thus further individualization of the parameters with respect to height and weight can further improve the diagnostic quality

Relationship Between 24-Hour Ambulatory Central Systolic Blood Pressure and Left Ventricular Mass: A Prospective Multicenter Study

Abstract—We investigated the relationship between left ventricular mass and brachial office as well as brachial and central ambulatory systolic blood pressure in 7 European centers. Central systolic pressure was measured with a validated oscillometric device, using a transfer function, and mean/diastolic pressure calibration. M-mode images were obtained by echocardiography, and left ventricular mass was determined by one single reader blinded to blood pressure. We studied 289 participants (137 women) free from antihypertensive drugs (mean age: 50.8 years). Mean office blood pressure was 145/88 mm Hg and mean brachial and central ambulatory systolic pressures were 127 and 128 mm Hg, respectively. Mean left ventricular mass was 93.3 kg/m2, and 25.6% had left ventricular hypertrophy. The correlation coefficient between left ventricular mass and brachial office, brachial ambulatory, and central ambulatory systolic pressure was 0.29, 0.41, and 0.47, respectively (P=0.003 for comparison between brachial office and central ambulatory systolic pressure and 0.32 for comparison between brachial and central ambulatory systolic pressure). The results were consistent for men and women, and young and old participants. The areas under the curve for prediction of left ventricular hypertrophy were 0.618, 0.635, and 0.666 for brachial office, brachial, and central ambulatory systolic pressure, respectively (P=0.03 for comparison between brachial and central ambulatory systolic pressure). In younger participants, central ambulatory systolic pressure was superior to both other measurements. Central ambulatory systolic pressure, measured with an oscillometric cuff, shows a strong trend toward a closer association with left ventricular mass and hypertrophy than brachial office/ambulatory systolic pressure