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.

Tumor necrosis factor alpha-an underestimated risk predictor in patients undergoing transcatheter aortic valve replacement (TAVR)?

BACKGROUND: Systemic inflammation has been identified as a major cardiovascular risk factor in patients undergoing transcatheter aortic valve replacement (TAVR), yet currently, it is not adequately portrayed in scores for pre-interventional risk assessment. The aim of this study was to investigate the predictive ability of TNF-α in TAVR. METHODS: A total of 431 patients undergoing transfemoral TAVR were enrolled in this study. Blood samples were drawn prior to intervention, 24 h post-intervention, 4, 5, and 7 days post-intervention, and 1, 3, and 6 months post-TAVR. RESULTS: In a univariate Cox proportional hazard analysis, plasma concentrations of TNF-α after 24 h and after 5 days were associated with mortality after 12 months (after 24 h: HR 1.002 (1.000-1.004), p = 0.028; after 5d: HR 1.003 (1.001-1.005), p = 0.013). This association remained significant even after correction for confounders in a multivariate Cox regression analysis. Additionally, cut-offs were calculated. Patients above the cut-off for TNF-α after 5d had a significantly worse 12-month mortality than patients below the cut-off (18.8% vs. 2.8%, p = 0.046). CONCLUSION: Plasma levels of TNF-α after 24 h and 5 days were independently associated with 12-month mortality in patients undergoing TAVR. Thus, TNF-α could represent a novel biomarker for enhanced risk stratification in these patients.

Endothelial receptor proteins in acute venous thrombosis and delayed thrombus resolution in cerebral sinus vein thrombosis.

BACKGROUND AND PURPOSE: Cerebral sinus venous thrombosis (CSVT) is a rare but life-threatening disease and its diagnosis remains challenging. Blood biomarkers, including D-Dimer are currently not recommended in guidelines. Soluble endothelial receptor proteins (sICAM-1, sPECAM-1 and sVCAM-1) have been shown to be promising diagnostic biomarkers in deep vein thrombosis (DVT) and pulmonary embolism (PE). Therefore, we examined endothelial receptor proteins as potential biomarkers for detecting CSVT. METHODS: In this bi-centre, prospective study, we quantified D-Dimer as well as sICAM-1, sPECAM-1 and sVCAM-1 in plasma of patients with clinically suspected CSVT managed in the neurological emergency department (ED) of a tertiary care hospital. All patients underwent cerebral magnetic resonance imaging (MRI) and were followed up after 3, 6 and 12 months to detect thrombus resolution. RESULTS: Twenty-four out of 75 (32%) patients with clinically suspected CSVT presenting with headache to the ED were diagnosed with acute CSVT. These patients had a mean age of 45 ± 16 years and 78% were female. In patients with CSVT, mean baseline D-dimer (p < 0.001) and sPECAM-1 (p < 0.001) were significantly higher compared to patients without CSVT. The combination of D-Dimer and sPECAM-1 yielded the best ROC-AUC (0.994; < 0.001) with a negative predictive value of 95.7% and a positive predictive value of 95.5%. In addition, higher baseline sPECAM-1 levels (> 198 ng/ml) on admission were associated with delayed venous thrombus resolution at 3 months (AUC = 0.83). CONCLUSION: sPECAM-1 in combination with D-Dimer should be used to improve the diagnostic accuracy of acute CSVT and sPECAM-1 may predict long-term outcome of CSVT. Confirmatory results are needed in other settings in order to show their value in the management concept of CSVT patients.

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 < 40 mm (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 measured pulmonary artery to ascending aorta ratio stratified by echocardiographically obtained systolic pulmonary artery pressure values for noninvasive detection of pulmonary hypertension in patients with severe aortic valve stenosis.

BACKGROUND: Transthoracic echocardiography (TTE) offers a measurement method for the determination of pulmonary hypertension (PH) in patients with severe aortic valve stenosis (AS) with determination of maximal tricuspid regurgitation velocity (TRVmax) and systolic pulmonary artery pressure (sPAP). Radiological parameters for noninvasive detection of PH, most importantly computed tomography (CT) based PA/AA-ratio = ratio of pulmonary artery diameter (PA) and ascending aorta diameter (AA), are also included in the latest ESC guidelines. The aim of the present study was to define cut-off values for PA/AA-ratio taking also into account cardiovascular biomarkers to determine criteria for noninvasive diagnosis of PH. METHODS: 194 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR) underwent pre-procedural TTE and CT with measurement of PA/AA-ratio. Additionally, common cardiovascular biomarkers were determined. RESULTS: TAVR patients with an sPAP ≥ 40 mmHg or a TRVmax ≥ 2.9 m/s had a PA/AA-ratio ≥ 0.80 in an AUROC analysis. The cut-off value of ≥ 0.80 resulted in a significantly higher mortality rate (log-rank test: p = 0.034) in these patients in a Kaplan-Meier analysis regarding 1-year survival after TAVR. Significant differences in biomarker expression between patients with a PA/AA-ratio ≥ 0.80 or < 0.80 occurred for BNP (p = 0.001), cTnI (p = 0.032), GDF-15 (p = 0.002) and H-FABP (p = 0.015). CONCLUSION: PA/AA-ratio ≥ 0.80 is a promising radiological parameter that can provide information about mortality in patients with severe AS undergoing TAVR; combined with biomarkers it may contribute to noninvasive detection of PH in patients with severe AS.

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 < 16.6 mm/m2 (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 = <0.001), GDF-15 (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 < 0.001; cut-off 2194.0 pg/mL) showed significant results. Consequently, analyses of combined biomarkers were performed, which yielded IGF-BP2 + BNP (AUC = 0.721; 95%CI = 0.585−0.857; 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 < 16.6 mm/m2 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.

[Transcatheter mitral valve replacement : Indications, options, and techniques as well as important aspects for perioperative care]. / Interventioneller Mitralklappenersatz : Indikationen, Möglichkeiten und Technik sowie wichtige Aspekte für die perioperative Betreuung.

Transcatheter therapy of the mitral valve is more challenging compared to the aortic valve. Interventional therapy with the Mitra-Clip system, mimicking the surgical edge-to-edge repair, was first introduced in 2003 and received the CE mark in 2008. The first implantation of the Tendyne system, which is currently the only commercially available system for mitral valve replacement, was performed in 2014, and routine clinical use was approved in 2020. Several new valve platforms are in clinical development and will expand the treatment portfolio. This article will discuss the clinical indications, technical challenges and specific requirements for perioperative management.

Protocol for the Exercise, Cancer and Cognition - The ECCO-Study: A Randomized Controlled Trial of Simultaneous Exercise During Neo-/Adjuvant Chemotherapy in Breast Cancer Patients and Its Effects on Neurocognition.

Introduction: Epidemiological studies show that increased physical activity is linked to a lower risk of breast cancer and mortality. As a result, physical activity can significantly improve patients' quality of life (QOL) both during and after therapy.Many breast cancer patients demonstrate a decrease in cognitive capacity, referred to as the symptom-complex cancer related cognitive impairment (CRCI). Most frequently reported impairments are mild to moderate deficits in processing speed, attention, memory, and executive functions. Cognitive symptoms persist for months or even years, following medical treatment in roughly 35% of afflicted people, impairing everyday functioning, limiting the ability to return to work, and lowering the overall QOL. Recent studies point toward a key role of inflammatory pathways in the CRCI genesis. Attention to physical activity as a potential supportive care option is therefore increasing. However, evidence for the positive effects of exercise on preventing CRCI is still lacking. Patients and Methods: Against this background, the prospective, two-arm, 1:1 randomized, controlled trial investigates the influence of first line chemotherapy accompanied by exercise training on preventing CRCI in 126 patients with breast cancer at the local University Hospital. The study will evaluate biomarkers and secondary assessments suspected to be involved in the pathogenesis of CRCI in addition to objective (primary outcome) and subjective cognitive function. CRCI is believed to be connected to either functional and/or morphological hippocampal damage due to chemotherapy. Thus, cerebral magnetic resonance imaging (MRI) and hippocampal volume measurements are performed. Furthermore, a specific neuropsychological test battery for breast cancer patients has been developed to detect early signs of cognitive impairments in patients and to be integrated into practice. Discussion: This study will explore how a long-term supervised exercise intervention program might prevent CRCI, enables optimization of supportive care and objectifies limits of psychological and physical resilience in breast cancer patients during and after chemotherapy treatment. Trial Registration: ClinicalTrials.gov: Identifier: NCT04789187. Registered on 09 March 2021.

Main pulmonary artery diameter in combination with cardiovascular biomarkers. New possibilities to identify pulmonary hypertension in patients with severe aortic valve stenosis?

BACKGROUND: Echocardiography is currently the noninvasive method of choice to screen patients with severe aortic valve stenosis (AS) for pulmonary hypertension (PH) by estimating systolic pulmonary artery pressure (sPAP). However, radiological options are also available by determining the main pulmonary artery (MPA) diameter in the setting of CT angiography. The aim of the present study was to compare cardiovascular biomarkers with the MPA diameter to allow other ways of detecting PH in patients with severe AS. METHODS: 194 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR) were included in this study and were divided into two groups based on the CT-angiographically determined MPA diameter. In accordance with ESC guidelines, a cut-off value of 29 mm was determined in this study, with the absence of PH defined by an MPA diameter < 29 mm (n = 79/194) and the presence of PH defined by an MPA diameter ≥ 29 mm (115/194). Immediately before interventional aortic valve replacement, blood samples were drawn from the subjects and relevant cardiovascular biomarkers such as BNP, cTnI, GDF-15, H-FABP, IGF-BP2 and suPAR were assessed. RESULTS: Patients with an MPA diameter ≥ 29 mm had significantly higher BNP (p = 0.004), cTnI (p = 0.039) and HFABP (p = 0.015) plasma levels, whereas GDF-15 (p = 0.140), IGF-BP2 ( p = 0.088) and suPAR (p = 0.140) showed no significant differences. In addition, cut-off values were calculated to predict an MPA diameter ≥ 29 mm. Significant results were shown with 1634.00 pg/ml for BNP (p = 0.004), with 16.50 pg/ml for cTnI (p = 0.039) and with 1.16 ng/ml for H-FABP (p = 0.016). In a combined biomarker analysis, the 2-way combination of BNP and IGF-BP2 (AUC 0.671; 95%CI 0.538 - 0.805; p = 0.023) and the 3-way combination of BNP, H-FABP and IGF-BP2 (AUC 0.685; 95%CI 0.551 - 0.818; p = 0.015) showed the best results. Biomarker follow-up at 3 and 12 months after TAVR did not require additional information gain. Regarding 1-year survival, no significant difference could be detected between patients with an MPA diameter < 29 mm compared to patients with ≥ 29 mm (log-rank test: p = 0.262). CONCLUSIONS: The MPA diameter remains a controversial parameter for the detection of PH in patients with severe AS. Standing on its own, this non-invasive parameter may not be precise enough to detect PH accurately. Combining this parameter with several biomarkers did not provide significant additional information.

Comparability between Computed Tomography Morphological Vascular Parameters and Echocardiography for the Assessment of Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis-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 40−45−50 mmHg) and finally correlation analyses were calculated. Results: The best AUROC and correlation analyses were generally obtained at an sPAP ≥ 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 0.646−0. 836; p < 0.001; YI 0.39; sensitivity 0.87; specificity 0.52) and Spearman's correlation coefficient (r = 0.408; p < 0.001) at an sPAP of ≥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.

CT-Diagnosed Sarcopenia and Cardiovascular Biomarkers in Patients Undergoing Transcatheter Aortic Valve Replacement: Is It Possible to Predict Muscle Loss Based on Laboratory Tests?-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.

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.

Delayed Total Atrioventricular Block After Transcatheter Aortic Valve Replacement Assessed by Implantable Loop Recorders.

OBJECTIVES: The aims of this study were to evaluate the rate and time course of delayed total atrioventricular block (DT-AVB) after transcatheter aortic valve replacement (TAVR) using continuous electrocardiographic monitoring by implantable loop recorders and to identify potential predictors. BACKGROUND: DT-AVB has been defined as onset more than 2 days after TAVR or after hospital discharge and is reported in 10% to 15% of patients at 30-day follow-up. To date, there is no standardized diagnostic and therapeutic algorithm to manage TAVR patients at risk for DT-AVB. METHODS: Consecutive patients undergoing TAVR and simultaneous electrophysiologic testing without persistent or recurrent total atrioventricular block within 48 hours after the procedure underwent loop recorder implantation for full disclosure of atrioventricular conduction during 12-month follow-up. RESULTS: DT-AVB occurred in 7 of 59 patients (11.9%), with onset between 2 days and 3 months after the procedure. Both prolongation of the PQ interval between baseline and day 2 after TAVR (OR: 1.04; 95% CI: 1.01-1.09); P = 0.032) and prolongation of the HV interval during the procedure (OR: 1.07; 95% CI: 1.02-1.14; P = 0.015) significantly predicted the onset of DT-AVB. CONCLUSIONS: TAVR was associated with a considerable rate of DT-AVB of nearly 12% in this series. Prolongation of the PQ interval between baseline and day 2 and intraprocedural prolongation of the HV interval were significant predictors of DT-AVB.

Intraprocedural dynamics of cardiac conduction during transcatheter aortic valve implantation: Assessment by simultaneous electrophysiological testing.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an established treatment for patients with severe aortic stenosis and high to intermediate surgical risk. However, the proximity of the conduction system to the prosthesis landing zone bears the risk of atrioventricular conduction disorders. The underlying pathophysiology is not fully understood. OBJECTIVE: The purpose of this study was to characterize the impact of TAVI on the conduction system as assessed by simultaneous electrophysiological testing. METHODS: AH and HV intervals and QRS duration were measured using a quadripolar His catheter and surface electrocardiogram in 108 patients at baseline (BL), after balloon predilation (timepoint 1 [T1]), after implantation of the valve prosthesis (T2), and after postdilation, if deemed necessary (T3). RESULTS: Between BL and T2, significant increases of HV interval and QRS duration were observed, with a mean delta of +12.4 ms and +32.7 ms, respectively. Both balloon predilation and valve implantation had an impact on infranodal conduction. No significant increase of AH intervals was documented. The increase of QRS duration led to left bundle branch block (LBBB) in 57 patients (52.8%). Implantation depth positively correlated with QRS prolongation (ρ = 0.21, P = .042) but not with changes of AH or HV interval (ρ = -0.03, P = .762; and ρ = 0.15, P = .130, respectively). CONCLUSION: Electrophysiological testing during TAVI shows impairment of infranodal atrioventricular conduction by balloon predilation and valve implantation. This impairment is positively correlated with valve implantation depth and results in an increase of QRS duration with mainly LBBB pattern on surface electrocardiogram.

Changes in renal artery dimensions are associated with clinical response to radiofrequency renal denervation: a series of studies using quantitative angiography and intravascular ultrasound.

OBJECTIVE: Renal denervation (RDN) can cause focal (notches) and global (spasms) changes in renal artery dimensions. We quantified these changes and related them to renal norepinephrin tissue content in animals and to blood pressure (BP) changes in patients. METHODS: We measured renal artery dimensions pre-RDN and post-RDN, utilizing quantitative renal angiography (QRA) in a porcine model and in a retrospective patient cohort, and intravascular ultrasound (IVUS) in a prospective patient cohort. Focal and global measurements were minimum and mean diameter/area/volume with QRA, minimum lumen/vessel/wall area and volume with IVUS. BP was assessed with 24-h ambulatory monitoring, norepinephrin content with liquid chromatography. RESULTS: In 36 pigs treated unilaterally with RDN, norepinephrin content of the treated right kidney was 48.2% of the untreated left kidney. QRA measurements following RDN were associated with norepinephrin content only of the (treated) right kidney. In the human QRA study (n = 43 patients), mean 24-h BP fell by 8/4 and 12/6 mmHg at 1 and 12 months, respectively. More pronounced changes in QRA measurements were associated with a more pronounced BP drop. In multiple regression models, the change in minimum diameter was independently associated with BP changes at 12 months. In the prospective IVUS study (n = 17 patients), a larger decrease in minimum lumen/vessel area and larger increase of wall area/volume were associated with a larger BP drop. CONCLUSION: Focal and global changes in renal arteries following RDN can be quantified, using QRA or IVUS, and may serve as markers of a successful procedure.

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

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. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01278732.

Anti-Inflammatory Effects and Prediction of Blood Pressure Response by Baseline Inflammatory State in Catheter-Based Renal Denervation.

This retrospective analysis aimed to examine off-target effects on inflammatory and renal function parameters in n=78 subsequent patients treated with renal denervation (RDN) for resistant hypertension. Ambulatory and office blood pressure (ABP/OBP), serum creatinine, glomerular filtration rate (GFR), cystatin C, C-reactive protein (CRP), interleukin-6 (IL-6), and white blood cell count (WBC) were assessed before, 6 and 12 months after RDN. ABP was significantly reduced by -8.2/-3.8 mm Hg (P=.002/.021) at 1 year after RDN, while an initial OBP reduction was not sustained during follow-up. IL-6 levels significantly decreased by -0.5 pg/mL (P=.042) and by -1.7 pg/mL (P<.001) at 6 and 12 months, baseline IL-6 levels possibly predicting ABP response to RDN (r=-0.295; P=.020). Concurrently, leukocyte count was reduced by -0.5 × 103 /µL (P=.017) and -0.8 × 103 /µL (P<.001), respectively. Serum creatinine and GFR remained unchanged, but we observed a significant increase in cystatin C by 0.04 mg/L (P=.026) and 0.14 mg/L (P<.001) at 6 and 12 months after the intervention.

Endpoint design for future renal denervation trials - Novel implications for a new definition of treatment response to renal denervation.

BACKGROUND: Defining an adequate endpoint for renal denervation trials represents a major challenge. A high inter-individual and intra-individual variability of blood pressure levels as well as a partial or total non-adherence on antihypertensive drugs hamper treatment evaluations after renal denervation. Blood pressure measurements at a single point in time as used as primary endpoint in most clinical trials on renal denervation, might not be sufficient to discriminate between patients who do or do not respond to renal denervation. METHODS: We compared the traditional responder classification (defined as systolic 24-hour blood pressure reduction of -5mmHg six months after renal denervation) with a novel definition of an ideal respondership (based on a 24h blood pressure reduction at no point in time, one, or all follow-up timepoints). RESULTS: We were able to re-classify almost a quarter of patients. Blood pressure variability was substantial in patients traditionally defined as responders. On the other hand, our novel classification of an ideal respondership seems to be clinically superior in discriminating sustained from pseudo-response to renal denervation. CONCLUSION: Based on our observations, we recommend that the traditional response classification should be reconsidered and possibly strengthened by using a composite endpoint of 24h-BP reductions at different follow-up-visits.

Determinants and covariates of central pressures and wave reflections in systolic heart failure.

BACKGROUND: In general, higher blood pressure levels and increased central pulsatility are indicators for increased cardiovascular risk. However, in systolic heart failure (SHF), this relationship is reversed. Therefore, the aim of this work is to compare pulsatile hemodynamics between patients with SHF and controls and to clarify the relationships between measures of cardiac and arterial function in the two groups. METHODS: We used parameters derived from angiography, echocardiography, as well as from pulse wave analysis (PWA) and wave separation analysis (WSA) based on non-invasively assessed pressure and flow waves to quantify cardiac function, aortic stiffness and arterial wave reflection in 61 patients with highly reduced (rEF) and 122 matched control-patients with normal ejection fraction (nEF). RESULTS: Invasively measured pulse wave velocity was comparable between the groups (8.6/8.05 m/s rEF/nEF, P = 0.24), whereas all measures derived by PWA and WSA were significantly decreased (augmentation index: 18.1/24.8 rEF/nEF, P < 0.01; reflection magnitude: 56.3/62.1 rEF/nEF, P < 0.01). However, these differences could be explained by the shortened ejection duration (ED) in rEF (ED: 269/308 ms rEF/nEF, P < 0.01; AIx: 22.2/22.8 rEF/nEF, P = 0.7; RM: 59.3/60.6 rEF/nEF, P = 0.47 after adjustment for ED). Ventricular function was positively associated with central pulse pressures in SHF in contrast to no or even a slightly negative association in controls. CONCLUSIONS: The results suggest that the decreased measures of pulsatile function may be caused by impaired systolic function and altered interplay of left ventricle and vascular system rather than by a real reduction of wave reflections or aortic stiffness in SHF.