General Versus Local Anesthesia With Conscious Sedation in Transcatheter Aortic Valve Implantation: The Randomized SOLVE-TAVI Trial.

BACKGROUND: In clinical practice, local anesthesia with conscious sedation (CS) is performed in roughly 50% of patients undergoing transcatheter aortic valve replacement. However, no randomized data assessing the safety and efficacy of CS versus general anesthesia (GA) are available. METHODS: The SOLVE-TAVI (Comparison of Second-Generation Self-Expandable Versus Balloon-Expandable Valves and General Versus Local Anesthesia in Transcatheter Aortic Valve Implantation) trial is a multicenter, open-label, 2×2 factorial, randomized trial of 447 patients with aortic stenosis undergoing transfemoral transcatheter aortic valve replacement comparing CS versus GA. The primary efficacy end point was powered for equivalence (equivalence margin 10% with significance level 0.05) and consisted of the composite of all-cause mortality, stroke, myocardial infarction, infection requiring antibiotic treatment, and acute kidney injury at 30 days. RESULTS: The primary composite end point occurred in 27.2% of CS and 26.4% of GA patients (rate difference, 0.8 [90% CI, -6.2 to 7.8]; Pequivalence=0.015). Event rates for the individual components were as follows: all-cause mortality, 3.2% versus 2.3% (rate difference, 1.0 [90% CI, -2.9 to 4.8]; Pequivalence<0.001); stroke, 2.4% versus 2.8% (rate difference, -0.4 [90% CI, -3.8 to 3.8]; Pequivalence<0.001); myocardial infarction, 0.5% versus 0.0% (rate difference, 0.5 [90% CI, -3.0 to 3.9]; Pequivalence<0.001), infection requiring antibiotics 21.1% versus 22.0% (rate difference, -0.9 [90% CI, -7.5 to 5.7]; Pequivalence=0.011); acute kidney injury, 9.0% versus 9.2% (rate difference, -0.2 [90% CI, -5.2 to 4.8]; Pequivalence=0.0005). There was a lower need for inotropes or vasopressors with CS (62.8%) versus GA (97.3%; rate difference, -34.4 [90% CI, -41.0 to -27.8]). CONCLUSIONS: Among patients with aortic stenosis undergoing transfemoral transcatheter aortic valve replacement, use of CS compared with GA resulted in similar outcomes for the primary efficacy end point. These findings suggest that CS can be safely applied for transcatheter aortic valve replacement. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02737150.

Comparison of newer generation self-expandable vs. balloon-expandable valves in transcatheter aortic valve implantation: the randomized SOLVE-TAVI trial.

AIMS: Transcatheter aortic valve implantation (TAVI) has emerged as established treatment option in patients with symptomatic aortic stenosis. Technical developments in valve design have addressed previous limitations such as suboptimal deployment, conduction disturbances, and paravalvular leakage. However, there are only limited data available for the comparison of newer generation self-expandable valve (SEV) and balloon-expandable valve (BEV). METHODS AND RESULTS: SOLVE-TAVI is a multicentre, open-label, 2 × 2 factorial, randomized trial of 447 patients with aortic stenosis undergoing transfemoral TAVI comparing SEV (Evolut R, Medtronic Inc., Minneapolis, MN, USA) with BEV (Sapien 3, Edwards Lifesciences, Irvine, CA, USA). The primary efficacy composite endpoint of all-cause mortality, stroke, moderate/severe prosthetic valve regurgitation, and permanent pacemaker implantation at 30 days was powered for equivalence (equivalence margin 10% with significance level 0.05). The primary composite endpoint occurred in 28.4% of SEV patients and 26.1% of BEV patients meeting the prespecified criteria of equivalence [rate difference -2.39 (90% confidence interval, CI -9.45 to 4.66); Pequivalence = 0.04]. Event rates for the individual components were as follows: all-cause mortality 3.2% vs. 2.3% [rate difference -0.93 (90% CI -4.78 to 2.92); Pequivalence < 0.001], stroke 0.5% vs. 4.7% [rate difference 4.20 (90% CI 0.12 to 8.27); Pequivalence = 0.003], moderate/severe paravalvular leak 3.4% vs. 1.5% [rate difference -1.89 (90% CI -5.86 to 2.08); Pequivalence = 0.0001], and permanent pacemaker implantation 23.0% vs. 19.2% [rate difference -3.85 (90% CI -10.41 to 2.72) in SEV vs. BEV patients; Pequivalence = 0.06]. CONCLUSION: In patients with aortic stenosis undergoing transfemoral TAVI, newer generation SEV and BEV are equivalent for the primary valve-related efficacy endpoint. These findings support the safe application of these newer generation percutaneous valves in the majority of patients with some specific preferences based on individual valve anatomy.

OCT-assessment of scaffold resorption: Analysis of strut intensity by a new resorption index for poly-l-lactic acid bioresorbable vascular scaffolds.

BACKGROUND: The aim of this study was to analyze individual differences in resorption of bioresorbable vascular scaffolds (BRS) through optical coherence tomography (OCT) analysis and to identify factors potentially influencing the resorption process. METHODS: Between April 2016 and July 2017 clinically driven invasive coronary angiography and OCT examinations were performed in 36 patients who had previously been treated with a total of 48 BRS (ABSORB BVS, Abbott Vascular, Santa Clara, CA). For each scaffold, a new BRS-RESORB-INDEX (BRI) was calculated. RESULTS: The mean time interval since implantation was 789 ± 321 days. In OCT, BRS struts remained detectable in all 48 BRS. Normalized light intensity as a marker for the resorption of BRS struts increased with time in a linear fashion (Spearman Rho: p < .001, correlation coefficient = .90; R2 [linear] = .91). Multivariable analysis identified diabetes (BRI of patients with diabetes vs. patients without diabetes: 0.34 ± 0.13 vs. 0.58 ± 0.22; p = .002) and presence of Peri-strut low intensity areas (PSLIA, BRI of 10 patients with PSLIA vs. 26 patients without PSLIA: 0.44 ± 0.21 vs. 0.61 ± 18; p = .027) as independent predictors for a prolonged BRS resorption, whereas the resorption rate in ACS patients (STEMI, NSTEMI, and unstable angina; n = 13) was significantly higher as compared to patients without ACS (0.62 ± 0.17 vs. 0.43 ± 0.24; p = .012). CONCLUSION: In humans, BRS resorption rate is significantly influenced by numerous factors. Our data suggest that diabetes and PSLIA are associated with a prolonged resorption process, whereas in ACS patients, BRS resorption appears to be significantly faster.

Barostim Implantation with Ipsilateral Carotid Endarterectomy as a One-Stage Procedure.

Clinical trials have demonstrated significant and lasting reductions in arterial pressure from baroreflex activation therapy (BAT), resulting from electrical stimulation of the carotid sinus in patients with resistant arterial hypertension. Significant carotid atherosclerosis, however, has been a contraindication for ipsilateral implantation due to a potentially increased risk of periprocedural stroke and uncertain antihypertensive efficacy. Here, we describe the first case in which BAT was applied safely and effectively in a patient with distinct cerebral arteriosclerosis after ipsilateral carotid endarterectomy as a one-stage procedure without neurologic complications. BAT resulted in satisfactory blood pressure levels despite distinct cerebral atherosclerosis after an 18-month follow-up period.

Neutrophil gelatinase-associated lipocalin (NGAL) for the early detection of contrast-induced nephropathy after percutaneous coronary intervention.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) occurs in up to 13% of patients undergoing percutaneous coronary intervention (PCI). Neutrophil gelatinase-associated lipocalin (NGAL) is an early biomarker for renal impairment. We investigated whether increased urinary NGAL concentrations were predictive of CI-AKI within 2 days after PCI or of a higher re-hospitalization rate within 9 months. METHODS: Consecutive patients (n = 128), with stable coronary heart disease and eGFR ≥ 30 mL/min/1.73 m(2), undergoing PCI were included. Venous serum samples for measurement of creatinine, blood urea nitrogen, and cystatin C and urine samples for NGAL measurement were collected 4 hours and 1 and 2 days after contrast medium application. Patients were followed over 9 months to determine clinical endpoints. RESULTS: CI-AKI was observed in 14 patients (10.9%) after PCI. NGAL concentrations before PCI were significantly higher in patients with subsequent CI-AKI (19.8 ng/mL [14.4-35.8] vs. 11.6 ng/mL [5.6-28.2]; p = 0.04). There was no significant difference in NGAL concentrations 4 h after PCI between patients with and without CI-AKI. One day after PCI, NGAL concentrations were significant higher in patients developing CI-AKI (100.1 ng/mL [41.5-129.2] vs. 16.6 ng/mL [9.1-28.1]; p < 0.001). Compared to common biomarkers, NGAL best predicted CI-AKI (AUC 0.939 [95% CI 0.89-0.99; p < 0.001]). The re-hospitalization rate due to progressive renal insufficiency within 9 months was higher in the group with CI-AKI than the group without (4 [28.6%] vs. 4 [3.5%], p < 0.01). CONCLUSION: Urinary NGAL is a biomarker for predicting CI-AKI when measured 1 day after PCI.

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).

Impact of implantation depth on outcomes of new-generation balloon-expandable transcatheter heart valves.

BACKGROUND: Little is known about the impact of the ID on outcomes and device success using balloon-expandable devices. This study sought to analyze the impact of implantation depth (ID) on procedural outcomes. METHODS: In consecutive patients (n = 969) undergoing transfemoral TAVR with new-generation balloon-expandable prostheses, the mean ID (IDMean) was determined by aortography and categorized into low, correct, and high device position. Outcomes of interest were device success (VARC-2), paravalvular regurgitation (PVR) ≥ moderate, severe prosthesis-patient mismatch (PPM), permanent pacemaker implantation (PPI), and the composite of the three latter outcome measures (COMPPPP). RESULTS: IDMean was greater among patients with PPI (median 4.0 [interquartile range 2.0; 4.0] vs. 3.5 [1.5; 5.5] mm; p = 0.002), severe PPM (3.5 [1.5; 5.0] vs. 4.0 [2.0; 6.0] mm; p = 0.028), and COMPPPP (4.0 [2.0; 6.0] vs. 3.0 [1.5; 5.5] mm; p < 0.001) when compared with the respective groups without these complications. There was no significant association between IDMean and device success or PVR ≥ moderate. Categorization into low (7.3%), correct (90.7%), and high (2.0%) device position showed significant discrimination with an increase of severe PPM, PPI, and COMPPPP with lower position, whereas device success was not significantly affected by position. Only PVR ≥ moderate showed an asymmetric distribution with highest rates in the high and low position group, which was non-significant. However, among patients without correct position the rate of device success was 45.6%. CONCLUSIONS: A higher device position was associated with improved outcomes. Malpositioning without functional impairment should not be classified as device failure. The odds ratio of IDMean was calculated by univariate logistic regression for each outcome variable, showing that with higher values of IDMean (i.e., low implantation depth), the risk of severe PPM, PPI, and COMPPPP increases. The bar charts under the heading "Position category" denote the frequency of each outcome measure across patients with high, correct, and low device position. The p values are derived from chi-squared test.

Initial experience with a novel, modular, minimalistic approach for transfemoral aortic valve implantation.

OBJECTIVES: We introduce a novel approach that involves a single arterial access and low contrast agent volume (SLIM). BACKGROUND: Transcatheter aortic valve implantation (TAVI) is subject to an ongoing process of refinement and simplification. METHODS: Between January 2019 and November 2020, a total 888 patients with severe aortic stenosis underwent transfemoral TAVI using balloon-expandable or specific self-expanding devices. The study cohort comprised patients with attempted SLIM approach (n = 291). A matched cohort of patients who were treated in a standard fashion served as control group (n = 291). RESULTS: The SLIM approach was successful in 92.4% of attempted cases. In the SLIM group, utilization of contrast agent (23 [19-37] vs. 75 [52-100] ml; p < 0.001), rates of any acute kidney injury (5.5% vs. 12.7%; p = 0.002), complications at the secondary access (0.3% vs. 3.1%; p = 0.011) and length of hospital stay (7 [5-8] vs. 7 [6-9]) days; p = 0.039) were significantly reduced. All other procedural outcomes were similar between groups. CONCLUSIONS: Initial results of this novel, minimalistic approach demonstrate its feasibility and potential beneficial effects without compromising procedural safety. Further refinement of this approach is warranted.

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).

Randomized comparison of multipolar, duty-cycled, bipolar-unipolar radiofrequency versus conventional catheter ablation for treatment of common atrial flutter.

INTRODUCTION: Radiofrequency (RF) catheter ablation has been established as an effective and curative treatment for atrial flutter (AFL). Approved methods include a drag-and-drop method, as well as a point-by-point ablation technique. The aim of this study was to compare the acute efficacy and procedural efficiency of a multipolar linear ablation catheter with simultaneous energy delivery to multiple catheter electrodes against conventional RF for treatment of AFL. METHODS: Patients presenting to our department with symptomatic, typical AFL were enrolled consecutively and randomized to conventional RF ablation with an 8-mm tip catheter (ConvRF) or a duty-cycled, bipolar-unipolar RF generator delivering power to a hexapolar tip-versatile ablation catheter (T-VAC) group. For both groups, the procedural endpoint was bidirectional cavotricuspid isthmus block. RESULTS: Sixty patients were enrolled, 30 patients each assigned to ConvRF and T-VAC groups. Total procedure time (40.2 ± 15.8 min vs 60.5 ± 12.7 min), energy delivery time (8.5 ± 3.7 min vs 14.7 ± 5.2 min), radiation dose (14.5 ± 3.5 cGy/cm² vs 31.7 ± 12.1 cGy/cm²), and the minimum number of RF applications needed to achieve block (4.2 ± 2.4 vs 8.9 ± 7.2) were significantly lower in the T-VAC group. In 7 patients treated with the T-VAC catheter, bidirectional block was achieved with less than 3 RF applications, versus no patients with conventional RF energy delivery. CONCLUSION: The treatment of typical AFL using a hexapolar catheter with a multipolar, duty-cycled, bipolar-unipolar RF generator offers comparable effectiveness relative to conventional RF while providing improved procedural efficiency.

Bauhinia bauhinioides cruzipain inhibitor reduces endothelial proliferation and induces an increase of the intracellular Ca2+ concentration.

Proteinase inhibitors, isolated from different types of Bauhinia, have an effect on apoptosis, angiogenesis and inflammation. The Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a Kunitz-type inhibitor and inactivates the cysteine proteinases cruzipain and cruzain from Trypanosoma cruzi. Cruzipain and tissue kallikrein have similar biochemical properties, e.g. the proteolytic cleavage of the kininogen precursor of lys-bradykinin. Tissue kallikrein stimulation in endothelial cells causes migration and capillary tube formation. The aim of this study was to examine whether the antiproliferative effect of BbCI is dependent on changes of the intracellular calcium concentration and membrane hyperpolarization. Endothelial cells were isolated from human umbilical cord veins (HUVEC). For proliferation experiments, HUVEC were incubated with BbCI (10-100 µmol/L) for 48 h. The proliferation was detected by cell counting with a Neubauer chamber. The effect of BbCI (10-100 µM) on the membrane potential was measured with the fluorescence dye DiBAC4(3) and the effect on [Ca+2]i with the fluorescence probe Fluo-3 AM. The change of the fluorescence intensity was determined with a GENios plate reader (Tecan). The experiments showed that BbCI (10-100 µmol/L) reduces the endothelial cell proliferation significantly in a concentration-dependent manner with a maximum effect at 100 µmol/L (35.1±1.8% as compared to control (p≤0.05; n=45)). As compared to the control, the addition of BbCI (100 µmol/L) caused a significant increase of systolic Ca2+ of 28.4±5.0% after 30 min incubation. HUVEC treatment with BbCI (100 µmol/L) showed a weak but significant decrease of the membrane potential of 9.5±0.9% as compared to control (p≤0.05; n=80). BbCI influenced significantly the endothelial proliferation, the intracellular Ca2+ concentration and the membrane potential.

Bauhinia bauhinioides cruzipain inhibitor reduces endothelial proliferation and induces an increase of the intracellular Ca2+ concentration

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Proteinase inhibitors, isolated from different types of Bauhinia, have an effect on apoptosis, angiogenesis and inflammation. The Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a Kunitz-type inhibitor and inactivates the cysteine proteinases cruzipain and cruzain from Trypanosoma cruzi. Cruzipain and tissue kallikrein have similar biochemical properties, e.g. the proteolytic cleavage of the kininogen precursor of lys-bradykinin. Tissue kallikrein stimulation in endothelial cells causes migration and capillary tube formation. The aim of this study was to examine whether theantiproliferative effect of BbCI is dependent on changes of the intracellular calcium concentration and membrane hyperpolarization. Endothelial cells were isolated from human umbilical cord veins(HUVEC). For proliferation experiments, HUVEC were incubated with (..)(AU)