Management and risk of postoperative bleeding in patients with low-dose antiplatelet aspirin medication during endoscopic endonasal surgery for pituitary adenomas.

BACKGROUND: To analyze the risk of postoperative bleeding following endoscopic endonasal transsphenoidal surgery (EETS) for treatment of pituitary adenomas (PA) in patients with short-term discontinuation of low-dose aspirin, if required for prevention of artherothrombotic disease (ATD). METHODS: Patients with preoperative aspirin medication were identified in this single-center retrospective analysis of consecutive patients with PA, who underwent EETS between December 2008 and June 2022. Aspirin was discontinued perioperatively less than 2 days, > 2 and < 4 days, and > 4 and < 7 days according to the assumed risk of perioperative ATD. For those patients, the rate of postoperative bleeding, which required surgery, was compared to patients without aspirin. RESULTS: Forty-five (14.8%) out of 304 patients underwent EETS with short-term perioperative aspirin discontinuation. Thirty-six (80%) patients discontinued aspirin < 2 days, 6 (13.3%) patients > 2 and < 4 days, and 3 patients (6.7%) > 4 but < 7 days. Postoperative bleeding rate was not increased in patients with short-term perioperative aspirin discontinuation. One patient (0.3%) without perioperative aspirin medication underwent revision surgery for treatment of postoperative hemorrhage with suprasellar extension. Eight patients (2.6%) had postoperative epistaxis (1 patient (0.3%) with short-term discontinuation and 7 patients (2.3%) without aspirin). Patients with perioperative aspirin were significantly older (68.3 ± 8.6 vs. 57.9 ± 14.1; p < 0.01) and had a significantly lower rate of hormonally active tumors (11.1% vs. 25.1%; p < 0.05) compared to patients without aspirin. No differences were found for tumor characteristics (tumor extension, tumor volume, largest diameter) between both groups. CONCLUSION: Short-term discontinuation of low-dose aspirin was not associated with increased rate of postoperative bleeding in patients, who underwent EETS for treatment of PA.

Predicted impact of atrial flow regulator on survival in heart failure with reduced and preserved ejection fraction.

AIMS: We aim to assess the theoretical impact of the atrial flow regulator (AFR) on survival in heart failure. METHODS AND RESULTS: The prospective, multicentre, open-label, non-randomised PRELIEVE study (NCT03030274) assessed the safety and efficacy of the Occlutech AFR device in patients with symptomatic heart failure with reduced ejection fraction (HFrEF) (left ventricular ejection fraction (LVEF) ≥ 15% and <40%) or heart failure with preserved ejection fraction (HFpEF) (LVEF ≥40% and <70%) and elevated PCWP (≥15 mmHg at rest or ≥25 mmHg during exercise). In this analysis, after the first 60 patients completed 12 months of follow-up, the theoretical impact of AFR implantation on survival was assessed by comparing the observed mortality rate with the median predicted probability for one-year mortality. Each subject's risk of mortality was predicted from individual baseline data using the Meta-Analysis Global Group in Chronic HF (MAGGIC) prognostic model. A total of 87 patients (46% female, median age 69 years [IQR 62-74]) had undergone successful device implantation for the treatment of HFrEF (53%) and HFpEF (47%). Sixty patients had a complete 12 month follow-up. The median follow-up was 351 days (interquartile range [IQR] 202-370). Six (7%) patients died during follow-up (8.6 deaths per 100 patient-years; 95% confidence interval [CI] 2.7 to 15.5), all of which had HFrEF. The median predicted mortality rate for the overall study population was 12.2 deaths per 100 patient-years (95% CI 10.2 to 14.7). While the observed mortality rate (0 deaths per 100 patient-years) was significantly lower than the median predicted mortality rate (9.3 deaths per 100 patient-years; 95% CI 8.4 to 11.1) in patients with HFpEF (-9.3 deaths per 100 patient-years; 95% CI -11.1 to -8.4), there was no difference in patients with HFrEF (-3.6 deaths per 100 patient-years; 95% CI -9.5 to 3.0). Four deaths were HF-related deaths (5.7 HF-related deaths per 100 patient-years; 95% CI 1.4 to 11.9; 10.8 HF-related deaths per 100 patient-years; 95% CI 2.5 to 23.1 in the HFrEF subgroup). CONCLUSIONS: In patients with HFpEF, the mortality rate following AFR implantation was lower than the predicted mortality rate. Dedicated randomised, controlled trials are needed - and currently ongoing - to investigate whether the AFR improves mortality.

Influence of Culprit Lesion Intervention on Outcomes in Infarct-Related Cardiogenic Shock With Cardiac Arrest.

BACKGROUND: Cardiac arrest (CA) is common in patients with infarct-related cardiogenic shock (CS). OBJECTIVES: The goal of this study was to identify the characteristics and outcomes of culprit lesion percutaneous coronary intervention (PCI) of patients with infarct-related CS stratified according to CA in the CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) randomized trial and registry. METHODS: Patients with CS with and without CA from the CULPRIT-SHOCK study were analyzed. All-cause death or severe renal failure leading to renal replacement therapy within 30 days and 1-year death were assessed. RESULTS: Among 1,015 patients, 550 (54.2%) had CA. Patients with CA were younger, more frequently male, had lower rates of peripheral artery disease, a glomerular filtration rate <30 mL/min, and left main disease, and they presented more often with clinical signs of impaired organ perfusion. The composite of all-cause death or severe renal failure within 30 days occurred in 51.2% of patients with CA vs 48.5% in non-CA patients (P = 0.39) and 1-year death in 53.8% vs 50.4% (P = 0.29), respectively. In a multivariate analysis, CA was an independent predictor of 1-year mortality (HR: 1.27; 95% CI: 1.01-1.59). In the randomized trial, culprit lesion-only PCI was superior to immediate multivessel PCI in patients both with and without CA (P for interaction = 0.6). CONCLUSIONS: More than 50% of patients with infarct-related CS had CA. These patients with CA were younger and had fewer comorbidities, but CA was an independent predictor of 1-year mortality. Culprit lesion-only PCI is the preferred strategy, both in patients with and without CA. (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock [CULPRIT-SHOCK]; NCT01927549).

The first taxonomic and functional characterization of human CAVD-associated microbiota.

Introduction: Calcific aortic valve disease (CAVD) is the most common heart valve disorder, defined by a remodeling multistep process: namely, valve fibrosis with its area narrowing, impaired blood flow, and final calcification phase. Nowadays, the only treatment is the surgical valve replacement. As for other cardiovascular diseases, growing evidence suggest an active role of the immune system in the calcification process that could be modulated by the microbiota. To address this point, we aimed to investigate and characterize, for the first time, the presence of a valve microbiota and associated immune response in human CAVD. Method: Calcified aortic valve (CAV) samples from twenty patients (11 from Germany and 9 from Italy) with diagnosis of severe symptomatic CAVD were used to assess the presence of infiltrating T cells, by cloning approach, and to characterize the valve microbiota, by 16S rRNA gene sequencing (NGS). Results: We documented the presence of infiltrating T lymphocytes, especially the T helper subset, in CAV samples. Moreover, we found a tissue-associated microbiota in freshly collected CAV samples, which was significantly different in Italian and German patients, suggesting potential correlation with other cardiovascular risk factors. Conclusion: The presence of microbiota in inflamed CAV samples represents the right trigger point to explain the valve calcification process, encouraging further studies to explore the potential link between bacteria and adaptive immune response and to define the critical role of local microbiota-immunity axis on CAVD development.

New Cerebral Microbleeds After Catheter-Based Structural Heart Interventions: An Exploratory Analysis.

Background Cerebral microbleeds (CMBs) are increasingly recognized as "covert" brain lesions indicating increased risk of future neurological events. However, data on CMBs in patients undergoing catheter-based structural heart interventions are scarce. Therefore, we assessed occurrence and predictors of new CMBs in patients undergoing catheter-based left atrial appendage closure and percutaneous mitral valve repair using the MitraClip System. Methods and Results We conducted an exploratory analysis using data derived from 2 prospective, observational studies. Eligible patients underwent cerebral magnetic resonance imaging (3 Tesla) examinations and cognitive tests (using the Montreal Cognitive Assessment) before and after catheter-based left atrial appendage closure and percutaneous mitral valve repair. Forty-seven patients (53% men; median age, 77 years) were included. New CMBs occurred in 17 of 47 patients (36%) following catheter-based structural heart interventions. Occurrences of new CMBs did not differ significantly between patients undergoing catheter-based left atrial appendage closure and percutaneous mitral valve repair (7/25 versus 10/22; P=0.348). In univariable analysis, longer procedure time was significantly associated with new CMBs. Adjustment for heparin attenuated this association (adjusted odds ratio [per 30 minutes]: 1.77 [95% CI, 0.92-3.83]; P=0.090). Conclusions New CMBs occur in approximately one-third of patients after catheter-based left atrial appendage closure and percutaneous mitral valve repair using the MitraClip System. Our data suggest that longer duration of the procedure may be a risk factor for new CMBs. Future studies in larger populations are needed to further investigate their clinical relevance. Clinical Trial Registration German Clinical Trials Register: DRKS00010300 (https://drks.de/search/en/trial/DRKS00010300); ClinicalTrials.gov : NCT03104556 (https://clinicaltrials.gov/ct2/show/NCT03104556?term=NCT03104556&draw=2&rank=1).

TAVI With or Without Predilation: Trends From a Large, Propensity-Score Weighted German Aortic Valve Registry (GARY) Population.

BACKGROUND AND AIMS: Currently, it is unclear whether transcatheter aortic valve implantation (TAVI) without predilation (direct TAVI; d-TAVI) or with preimplantation balloon valvuloplasty (b-TAVI) provides similar clinical safety and efficacy. Therefore, we analyzed patients undergoing d-TAVI or b-TAVI for severe aortic stenosis (AS) with either self-expanding or balloon-expandable transcatheter heart valves (THVs) from the German Aortic Valve Registry (GARY). METHODS: Between 2011 and 2017, a total of 44,783 TAVI patients were collected, with 25,717 (57.4%) receiving a balloon-expandable THV and 19,066 (42.6%) receiving a self-expanding THV. A propensity-score weighted model was used to compare d-TAVI vs b-TAVI regarding differences in outcome. RESULTS: B-TAVI was performed in 71% and d-TAVI was performed in 29% of patients. In the investigated time interval, frequency of b-TAVI declined from 88.4% to 58.2%, accompanied by a constant rate of postdilation. After propensity weighting of patients receiving balloon-expandable THV, d-TAVI vs b-TAVI was associated with more frequent postoperative transvalvular mean pressure gradients (mPG) >15 mm Hg (20.7% vs 18.4%; P<.001), similar rates of paravalvular leakage (PVL) ≥ moderate (18.0% vs 16.9%; P=.08), fewer postdilations (13.4% vs 15.5%; P<.001), and fewer complications (permanent pacemaker implantation, 10.2% vs 11.9% [P=.01]; vascular complications, 1.9% vs 2.6% [P<.01]; pericardial tamponade, 0.5% vs 0.9% [P<.01]; and stroke, 0.9% vs 1.3% [P=.02]). In patients receiving self-expanding THVs, d-TAVI vs b-TAVI was associated with more frequent postimplantation mean PG ≥ 15 mm Hg (12.7% vs 10.4%; P<.01), higher rates of PVL ≥ moderate (24.8% vs 16.5%; P<.001), and similar complication rates including permanent pacemaker implantation. CONCLUSIONS: The safety and efficacy of d-TAVI vs b-TAVI depends on the type of THV implanted. For balloon-expandable valves, d-TAVI provides an advantage, while self-expanding valves offer a similar safety profile for d-TAVI compared with b-TAVI. However, increased mPG post intervention with both valve types and more significant PVL in self-expanding THVs emphasize the importance of proper patient selection and evaluation of valve anatomy to identify suitable cases for d-TAVI.

Conundrum of Classifying Subtypes of Pulmonary Hypertension-Introducing a Novel Approach to Classify "Borderline" Patients in a Population with Severe Aortic Stenosis Undergoing TAVI.

Background: Transcatheter aortic valve implantation (TAVI) is an established therapeutic option in patients with severe aortic valve stenosis (AS) and a high surgical risk profile. Pulmonary hypertension (PH)­often co-existing with severe AS­is associated with a limited factor for prognosis and survival. The purpose of this study was to evaluate the prevalence of PH in patients undergoing TAVI, classify these patients based on right heart catheter (RHC) measurements in different PH subtypes, and analyze prognostic values on survival after TAVI. Methods: 284 patients with severe AS underwent an RHC examination for hemodynamic assessment prior to TAVI and were categorized into subtypes of PH according to the 2015 European Society of Cardiology (ESC) guidelines. TAVI patients were followed-up with for one year with regard to 30-days and 1-year mortality as primary endpoints. Results: 74 of 284 participants showed a diastolic pressure gradient (DPG) < 7 mmHg and a pulmonary vascular resistance (PVR) > 3 Wood units (WU) and could not be formally allocated to either isolated post-capillary PH (ipc-PH) or combined pre- and post-capillary PH (cpc-PH). Therefore, a new subgroup called "borderline post-capillary PH" (borderlinepc-PH) was introduced. Compared with TAVI patients with pre-capillary PH (prec-PH), ipc-PH patients suffering from borderlinepc-PH (HR 7.114; 95% CI 2.015−25.119; p = 0.002) or cpc-PH (HR 56.459; 95% CI 7.738−411.924; p < 0.001) showed a significantly increased 1-year mortality. Conclusions: Postcapillary PH was expanded to include the so-called "borderlinepc-PH" variant in addition to the ipc-PH and cpc-PH subtypes. The one-year survival after TAVI was significantly different between the subgroups, with the worst prognosis for borderlinepc-PH and cpc-PH.

Impact of moderate or severe left ventricular outflow tract calcification on clinical outcomes of patients with severe aortic stenosis undergoing transcatheter aortic valve implantation with self- and balloon-expandable valves: a post hoc analysis from the SOLVE-TAVI trial.

BACKGROUND: Left ventricular outflow tract (LVOT) calcification has been associated with worse outcomes in patients undergoing transcatheter aortic valve implantation (TAVI) and may influence the selection of prosthetic valve type. AIMS: We aimed to evaluate the impact of LVOT calcification on outcomes after TAVI with a self-expanding valve (SEV) versus a balloon-expandable valve (BEV). METHODS: Patients of the SOLVE-TAVI trial, randomised to Edwards SAPIEN 3 or Medtronic Evolut R, were divided according to LVOT calcification into no/mild (≤1 calcium nodule extending <5 mm and covering <10% of the LVOT perimeter) and moderate/severe LVOT calcification groups. The primary endpoint was a composite of death, stroke, moderate/severe paravalvular regurgitation, permanent pacemaker implantation and annulus rupture at 30 days. Additional endpoints included all-cause and cardiovascular mortality at 1 year. RESULTS: Out of 416 eligible patients, moderate/severe LVOT calcification was present in 143 (34.4%). Moderate/severe LVOT calcification was associated with significantly longer fluoroscopy time and higher rates of pre- and post-dilation. Regardless of the LVOT calcification group, there was no significant difference in the primary endpoint associated with the valve type (no/mild LVOT calcification group: SEV 25.0% vs BEV 27.0%; hazard ratio [HR] 1.10, 95% confidence interval [95% CI]: 0.68-1.73; p=0.73 and moderate/severe LVOT calcification group: SEV 25.0% vs BEV 19.4%; HR 0.76, 95% CI: 0.38-1.61; p=0.49), no significant interaction between LVOT calcification and valve type (pint=0.29) and no differences between SEV vs BEV within LVOT calcification groups regarding 1-year all-cause and cardiovascular mortality. CONCLUSIONS: Moderate/severe LVOT calcification was associated with longer fluoroscopy time and an increased need for pre- and post-dilation, but not with a higher incidence of early and mid-term adverse clinical outcomes, regardless of valve type. (ClinicalTrials.gov: NCT02737150).

Concomitant mitral regurgitation in patients with low-gradient aortic stenosis: an analysis from the German Aortic Valve Registry.

BACKGROUND: Patients with severe aortic stenosis (AS) frequently presented mitral regurgitation (MR), which may interfere with the standard echocardiographic measurements of mean pressure gradient (MPG), flow velocity, and aortic valve area (AVA). AIMS: Herein we investigated the prevalence and severity of MR in patients with severe AS and its role on the accuracy of the standard echocardiographic parameters of AS quantification. METHODS: Of all patients with severe AS undergoing transcatheter or surgical aortic valve replacement enrolled in the German Aortic Registry from 2011 to 2017, 119,641 were included in this study. The population was divided based on the values of left ventricular ejection fraction ([LVEF] > 50%, LVEF 31-50%, and LVEF ≤ 30%] and AVA (0.80 to ≤ 1.00 cm2, 0.60 to < 0.80 cm2, 0.40 to < 0.60 cm2, and 0.20 to < 0.40 cm2). RESULTS: Overall, 77,890 (65%) patients with mild to-moderate and 4262 (4%) with severe MR were compared with 37,489 (31%) patients without MR. Patients with mild-to-moderate and severe MR presented significantly lower mPG (ΔmPG [95%CI] - 1.694 mmHg [- 2.123 to - 1.265], p < 0.0001 and - 6.954 mmHg [- 7.725 to - 6.183], p < 0.0001, respectively), that increased with LVEF impairment. Conversely, AVA did not differ (severe versus no MR: ΔAVA [95%CI]: - 0.007cm2 [- 0.023 to 0.009], p = 0.973). Increasing MR severity was associated with significant mPG reduction throughout all AVA strata, causing a low-gradient pattern, that manifested since the early stages of severe AS (LVEF > 50%: AVA 0.80 to 1.00 cm2; LVEF 31-50%: AVA 0.60 to 0.80 cm2). CONCLUSIONS: In patients with severe AS, concomitant MR is common, contributes to the onset of a low-gradient AS pattern, and affects the diagnostic accuracy of flow-dependent AVA measurements. In this setting, a multimodality, AVA-centric approach should be implemented. In patients with severe aortic stenosis, concomitant mitral regurgitation contributes to the onset of a low-gradient pattern, warranting a multimodality, and AVA-centric diagnostic approach.

Oesophageal safety in voltage-guided atrial fibrillation ablation using ablation index or contact force only: a prospective comparison.

AIMS: Left atrial ablation using radiofrequency (RF) is associated with endoscopically detected thermal oesophageal lesions (EDELs). The aim of this study was to compare EDEL occurrence after conventional contact force-guided (CFG) RF ablation vs. an ablation index-guided (AIG) approach in clinical routine of voltage-guided ablation (VGA). Predictors of EDEL were also assessed. METHODS AND RESULTS: This study compared CFG (n = 100) with AIG (n = 100) in consecutive atrial fibrillation ablation procedures, in which both pulmonary vein isolation and VGA were performed. In the AIG group, AI targets were ≥500 anteriorly and ≥350-400 posteriorly. Upper endoscopy was performed after ablation.The CFG and AIG groups had comparable baseline characteristics. The EDEL occurred in 6 and 5% (P = 0.86) in the CFG and AIG groups, respectively. Category 2 lesions occurred in 4 and 2% (P = 0.68), respectively. All EDEL healed under proton pump inhibitor therapy. The AI > 520 was the only predictor of EDEL [odds ratio (OR) 3.84; P = 0.039]. The more extensive Category 2 lesions were predicted by: AI max > 520 during posterior ablation (OR 7.05; P = 0.042), application of posterior or roof lines (OR 5.19; P = 0.039), existence of cardiomyopathy (OR 4.93; P = 0.047), and CHA2DS2-VASc score (OR 1.71; P = 0.044). The only Category 2 lesion with AI max < 520 (467) occurred in a patient with low body mass index. CONCLUSIONS: Both methods were comparable with respect to clinical complications and EDEL. In consideration of previous reconnection data and our study results regarding oesophageal safety, optimal AI target range might be between 400 and 450.

Comparison of PCWP and LVEDP Measurements in Patients with Severe Aortic Stenosis Undergoing TAVI-Same Same but Different?

BACKGROUND: Pulmonary capillary wedge pressure (PCWP) and left ventricular end-diastolic pressure (LVEDP) are often used as equivalents for determination of pulmonary hypertension (PH). PH is a comorbidity in patients with severe aortic valve stenosis (AS) and associated with limited prognosis. The aim of the study was to examine the role of differentiated classification basis of PCWP and LVEDP in patients planning for transcatheter aortic valve implantation (TAVI). METHODS: 284 patients with severe AS completed a combined left (LHC) and right heart catheterization (RHC) as part of a TAVI planning procedure. Patients were categorized twice into subtypes of PH according to 2015 European Society of Cardiology (ESC) guidelines-on the one hand with PCWP and on the other hand with LVEDP as classification basis. PCWP-LVEDP relationships were figured out using Kaplan-Meier curves, linear regressions and Bland-Altman analysis. RESULTS: Regarding 1-year mortality, Kaplan-Meier analyses showed similar curves in spite of different classification bases of PH subtypes according to PCWP or LVEDP with exception of pre-capillary PH subtype. PCWP-LVEDP association in the overall cohort was barely present (R = 0.210, R2 = 0.044). When focusing analysis on PH patients only a slightly increased linear regression was noted compared to the overall cohort (R = 0.220, R2 = 0.048). The strongest regression was observed in patients with creatinine ≥ 132 µmol/L (R = 0.357, R2 = 0.127) and in patients with mitral regurgitation ≥ II° (R = 0.326, R2 = 0.106). CONCLUSIONS: In patients with severe AS, there is a weak association between hemodynamic parameters measured by LHC and RHC. RHC measurements alone are not suitable for risk stratification with respect to one-year mortality. If analysis of hemodynamic parameters is necessary in patients with severe AS scheduled for TAVI, measurement results of LHC and RHC should be combined and LVEDP could serve as a helpful indicator for risk assessment.

Gender-Specific Performance of One- Compared to Two-Catheter Concepts in Transradial Coronary Angiography - Insights From the Randomized UDDC-Radial-Trial.

OBJECTIVES: The present sub-analysis from the randomized UDDC-Radial-Trial sought to compare one-catheter concepts (OCC) with two-catheter concepts (TCC) in different patient subgroups, particularly in those depending on gender and age. BACKGROUND: There is an ongoing debate regarding potential performance differences of OCC compared to TCC for transradial coronary angiography in specific patient subgroups. METHODS: The randomized UDDC-Radial-Trial enrolled a total of 300 patients planed for coronary angiography in a 2:1 ratio to either OCC by Tiger II (n = 100) and BLK (n = 100) or TCC by Judkins (n = 100) catheters. Predefined patient subgroups stratified for age, gender and patient constitution were analyzed with regard to the primary outcome measure of time required for a complete coronary angiography. RESULTS: In male patients time for coronary angiography was significantly shorter in the TCC group compared to the OCC group (510 ± 37 s vs. 615 ± 35 s; p = 0.046). No difference between the catheter concepts was observed in the subset of female patients (525 ± 34 s vs. 583 ± 54 s; p = 0.43). TCC was associated with shorter coronary angiography time in patients aged <71 years compared to OCC (462 ± 23 s vs. 570 ± 38 s; p = 0.018). In patients ≥72 years of age no difference was detected (573 ± 41 s vs. 636 ± 45 s; p = 0.31). Other subgroups showed no relevant differences in angiography time among OCC and TCC. CONCLUSIONS: The present subgroup analysis from the UDDC-radial trial demonstrates the use of OCC in transradial diagnostic angiography to be inferior compared to TCC in terms of angiography time in younger and male patients.

Soluble ST2 as a Potential Biomarker for Risk Assessment of Pulmonary Hypertension in Patients Undergoing TAVR?

BACKGROUND: Severe aortic valve stenosis (AS) is associated with pulmonary hypertension (PH) and has been shown to limit patient survival. Soluble suppression of tumorigenicity-2 (sST2) is a cardiovascular biomarker that has proven to be an important prognostic marker for survival in patients undergoing transcatheter aortic valve replacement (TAVR). The aim of this study was to assess the importance of the sST2 biomarker for risk stratification in patients with severe AS in presence or absence of PH. METHODS: In 260 patients with severe AS undergoing TAVR procedure, sST2 serum level concentrations were analyzed. Right heart catheter measurements were performed in 152 patients, with no PH detection in 43 patients and with PH detection in 109 patients. Correlation analyses according to Spearman, AUROC analyses and Kaplan-Meier curves were calculated. RESULTS: Patients with severe AS and PH showed significantly higher serum sST2 concentrations (p = 0.006). The sST2 cut-off value for non-PH patients regarding 1-year survival yielded 5521.15 pg/mL, whereas the cut-off value of PH patients was at a considerably higher level of 10,268.78 pg/mL. A cut-off value of 6990.12 pg/mL was related with a significant probability of PH presence. Survival curves showed that patients with severe AS and PH not only had higher 1-year mortality, but also that increased levels of sST2 plasma concentration were associated with earlier death. CONCLUSION: sST2 definitely has the potential to provide information about the presence of PH in patients with severe AS, in a noninvasive way.

Cerebral embolisation during transcatheter edge-to-edge repair of the mitral valve with the MitraClip system: a prospective, observational study.

BACKGROUND: New ischaemic brain lesions on magnetic resonance imaging (MRI) are reported in up to 86% of patients after transcatheter edge-to-edge repair of the mitral valve (TEER-MV). Knowledge of the exact procedural step(s) that carry the highest risk for cerebral embolisation may help to further improve the procedure. AIMS: The aim of this study was to identify the procedural step(s) that are associated with an increased risk of cerebral embolisation during TEER-MV with the MitraClip system. Furthermore, the risk of overt stroke and silent brain ischaemia after TEER-MV was assessed. METHODS: In this prospective, pre-specified observational study, all patients underwent continuous transcranial Doppler examination during TEER-MV to detect microembolic signals (MES). MES were assigned to specific procedural steps: (1) transseptal puncture and placement of the guide, (2) advancing and adjustment of the clip in the left atrium, (3) device interaction with the MV, and (4) removal of the clip delivery system and the guide. Neurological examination using the National Institutes of Health Stroke Scale (NIHSS) and cerebral MRI were performed before and after TEER-MV. RESULTS: Fifty-four patients were included. The number of MES differed significantly between the procedural steps with the highest numbers observed during device interaction with the MV. Mild neurological deterioration (NIHSS ≤3) occurred in 9/54 patients. New ischaemic lesions were detected in 21/24 patients who underwent MRI. Larger infarct volume was significantly associated with neurological deterioration. CONCLUSIONS: Cerebral embolisation is immanent to TEER-MV and predominantly occurs during device interaction with the MV. Improvements to the procedure may focus on this procedural step.

Caval Valve Implantation.

Transcathetertherapy has expanded the treatment options for patients with heart valve disease. Interventional therapy for aortic, mitral, and pulmonic valve disease is well established; however, catheter-based approaches to tricuspid regurgitation (TR) are still in early stages of development. For some of the interventional concepts to TR, including the edge-to-edge-repair, transcatheter annuloplasty, the tricuspid spacer, and caval valves, procedural feasibility and favorable early clinical outcome have been demonstrated in small compassionate case series. This article reviews the pathophysiological background and current evidence for caval valve implantation and examines the potential role of this approach for the treatment of severe TR.

High-Sensitivity Cardiac Troponin T in Patients with Severe Chronic Kidney Disease and Suspected Acute Coronary Syndrome.

(1) Background: Patients with severe chronic kidney disease (CKD G4-G5) often have chronically elevated high-sensitivity cardiac troponin T (hs-cTnT) values above the 99th percentile of the upper reference limit. In these patients, optimal cutoff levels for diagnosing non-ST-elevation acute coronary syndrome (NSTE-ACS) requiring revascularization remain undefined. (2) Methods: Of 11,912 patients undergoing coronary angiography from 2012 to 2017 for suspected NSTE-ACS, 325 (3%) had severe CKD. Of these, 290 with available serial hs-cTnT measurements were included, and 300 matched patients with normal renal function were selected as a control cohort. (3) Results: In the CKD cohort, 222 patients (76%) had NSTE-ACS with indication for coronary revascularization. Diagnostic performance was high at presentation and similar to that of the control population (AUC, 95% CI: 0.81, 0.75-0.87 versus 0.85, 0.80-0.89, p = 0.68), and the ROC-derived cutoff value was 4 times higher compared to the conventional 99th percentile. Combining the ROC-derived cutoff levels for hs-cTnT at presentation and absolute 3 h changes, sensitivity increased to 98%, and PPV and NPV improved up to 93% and 86%, respectively. (4) Conclusions: In patients with severe CKD and suspected ACS, the diagnostic accuracy of hs-cTnT for the diagnosis of NSTE-ACS requiring revascularization is improved by using higher assay-specific cutoff levels combined with early absolute changes.

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.

In vivo assessment of endothelial permeability of coronary lesions with variable degree of stenosis using an albumin-binding MR probe.

MR imaging with an albumin-binding probe enables the visualization of endothelial permeability and damage in the arterial system. The goal of this study was to compare signal enhancement of lesions with different grades of stenosis segments on molecular CMR in combination with the albumin-binding probe gadofosveset. This prospective clinical study included patients with symptoms suggestive of coronary artery disease (CAD). Patients underwent gadofosveset-enhanced cardiovascular magnetic resonance (CMR) imaging and x-ray angiography (QCA) within 24 h. CMR imaging was performed prior to and 24 h following the administration of gadofosveset. Contrast-to-noise ratios (CNRs) between segments with different grades of stenosis were compared. Overall, n = 203 segments of 26 patients were included. Lesions with more than > 70% stenosis demonstrated significantly higher CNRs compared to lesions < 70% (7.6 ± 8.3 vs. 2.5 ± 4.9; p < 0.001). Post-stenotic segments of lesions > 70% stenosis showed significant higher signal enhancement compared to segments located upstream of these lesions (7.3 ± 8.8 vs. 2.8 ± 2.2; p = 0.02). No difference in signal enhancement between segments proximal and distal of lesions with stenosis greater than 50% was measured (3.3 ± 2.8 vs. 2.4 ± 2.7; p = 0.18). ROC analysis for the detection of lesions ≥ 70% revealed an area under the curve of 0.774 (95% CI 0.681-0.866). This study suggests that relevant coronary stenosis and their down-stream segments are associated with increased signal enhancement on Gadofosveset-enhanced CMR, suggesting a higher endothelial permeability in these lesions. An albumin-binding MR probe could represent a novel in vivo biomarker for the identification and characterization of these vulnerable coronary segments.

Deoxyribonuclease is prognostic in patients undergoing transcatheter aortic valve replacement.

Degenerative aortic valve stenosis is an inflammatory process that resembles atherosclerosis. Neutrophils release their DNA upon activation and form neutrophil extracellular traps (NETs), which are present on degenerated aortic valves. NETs correlate with pressure gradients in severe aortic stenosis. Transcatheter aortic valve replacement (TAVR) is an established treatment option for aortic valve stenosis. Bioprosthetic valve deterioration promoted by inflammatory, fibrotic and thrombotic processes limits outcome. Deoxyribonuclease is a natural counter mechanism to degrade DNA in circulation. In the present observational study, we investigated plasma levels of double-stranded DNA, deoxyribonuclease activity and outcome after TAVR. 345 consecutive patients undergoing TAVR and 100 healthy reference controls were studied. Double-stranded DNA was measured by fluorescence assays in plasma obtained at baseline and after TAVR. Deoxyribonuclease activity was measured at baseline using single radial enzyme diffusion assays. Follow-up was performed at 12 months, and mean aortic pressure gradient and survival were evaluated. Receiver operating characteristic, Kaplan-Meier curves and Cox regression models were calculated. Baseline double-stranded DNA in plasma was significantly higher compared to healthy controls, was increased at 3 and 7 days after TAVR, and declined thereafter. Baseline deoxyribonuclease activity was decreased compared to healthy controls. Interestingly, low deoxyribonuclease activity correlated with higher C-reactive protein and higher mean transaortic gradient after 12 months. Finally, deoxyribonuclease activity was a strong independent predictor of outcome 12 months after TAVR. Deoxyribonuclease activity is a potential biomarker for risk stratification after TAVR. Pathomechanisms of bioprosthetic valve deterioration involving extracellular DNA and deoxyribonuclease merit investigation.

Impact of Anesthesia Strategy and Valve Type on Clinical Outcomes After Transcatheter Aortic Valve Replacement.

BACKGROUND: The randomized SOLVE-TAVI (compariSon of secOnd-generation seLf-expandable vs. balloon-expandable Valves and gEneral vs. local anesthesia in Transcatheter Aortic Valve Implantation) trial compared newer-generation self-expanding valves (SEV) and balloon-expandable valves (BEV) as well as local anesthesia with conscious sedation (CS) and general anesthesia (GA) in patients undergoing transfemoral transcatheter aortic valve replacement (TAVR). Both strategies showed similar outcomes at 30 days. OBJECTIVES: The purpose of this study was to compare clinical outcomes during 1-year follow-up in the randomized SOLVE-TAVI trial. METHODS: Using a 2 × 2 factorial design 447 intermediate- to high-risk patients with severe, symptomatic aortic stenosis were randomly assigned to transfemoral TAVR using either the SEV (Evolut R, Medtronic Inc., Minneapolis, Minnesota) or the BEV (Sapien 3, Edwards Lifesciences, Irvine, California) as well as CS or GA at 7 sites. RESULTS: In the valve-comparison strategy, rates of the combined endpoint of all-cause mortality, stroke, moderate or severe paravalvular leakage, and permanent pacemaker implantation were similar between the BEV and SEV group (n = 84, 38.3% vs. n = 87, 40.4%; hazard ratio: 0.94; 95% confidence interval: 0.70 to 1.26; p = 0.66) at 1 year. Regarding the anesthesia comparison, the combined endpoint of all-cause mortality, stroke, myocardial infarction, and acute kidney injury occurred with similar rates in the GA and CS groups (n = 61, 25.7% vs. n = 54, 23.8%; hazard ratio: 1.09; 95% confidence interval: 0.76 to 1.57; p = 0.63). CONCLUSIONS: In intermediate- to high-risk patients undergoing transfemoral TAVR, newer-generation SEV and BEV as well as CS and GA showed similar clinical outcomes at 1 year using a combined clinical endpoint. (SecOnd-generation seLf-expandable Versus Balloon-expandable Valves and gEneral Versus Local Anesthesia in TAVI [SOLVE-TAVI]; NCT02737150).