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Background: Data about the impact of left-atrial appendage thrombosis (LAAT) on early safety and mortality in patients undergoing transfemoral transcatheter aortic valve implantation (TF-TAVI) are scarce. We aimed to investigate the prevalence and predictors of LAAT and the outcome associated with this condition in patients treated by TF-TAVI., Methods: Retrospective data analysis was derived from a prospective single-centre registry comparing patients with and without LAAT regarding early safety at 30 days, according to Valve Academic Research Consortium-2 (VARC-2) and 2-year mortality., Results: LAAT was found in 7.6% of the whole cohort (n = 2527) and in 16.6% in those patients with known pre-existing atrial fibrillation (AF cohort, n = 1099). Compared with controls, patients with LAAT were sicker, indicated by a higher Society of Thoracic Surgeons (STS) score and burden of comorbidities. Neither VARC-2-defined early safety at 30 days nor the rate of stroke was different between LAAT and controls in both the whole (early safety: 29.2% vs 24.2%, P = 0.123; stroke: 5.9% vs 4.7%, P = 0.495) and AF cohort (early safety: 29.1% vs 22.9%, P = 0.072; stroke: 5.6% vs 3.3%, P = 0.142). Evaluating the whole cohort in a univariate analysis, the 2-year mortality was significantly higher in LAAT compared with controls (hazard ratio, 1.41; 95% confidence interval, 1.07-1.86; P = 0.014). However, multivariate analysis of the whole cohort and the AF cohort revealed no association between LAAT and 2-year mortality., Conclusions: LAAT was frequent in patients undergoing TF-TAVI- in particular, in patients with histories of AF-but it was not associated with an increase in periprocedural complications and did not predict 2-year mortality., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve replacement (TAVR) has become the standard of care in the majority of patients with symptomatic severe aortic stenosis. Data on long-term mortality and durability of transcatheter heart valves (THVs) beyond 5 years are limited. Our study aimed to assess elderly and high-risk patients' long-term outcomes treated with TAVR in a prospective single-centre registry focusing on the durability of THVs., Methods: We included 795 patients with severe calcific aortic stenosis treated by transfemoral TAVR between 2006 and 2011. Echocardiography was performed at baseline; discharge; 1 year; and afterward, annually, until the longest available follow-up. Mortality rates were estimated for 1, 5, 6, 7, and 8 years. The rates of structural valve deterioration (SVD) and bioprosthetic valve failure (BVF) were assessed in accordance with consensus definitions. Outcome measures were adjudicated according to Valve Academic Research Consortium-2 (VARC-2)., Results: Median (interquartile range) follow-up time was 1345 (316; 2015) days. One-year, 5-year, 6-year, 7-year, and 8-year overall mortality was 25.4%, 59.0%, 64.6%, 67.9%, and 69.2%, respectively. At 8 years, no significant differences in mortality were found comparing self-expanding vs balloon-expandable valves (69.5% vs 68.0%, P  = 0.709) and postdilatation (PD) vs no-PD (69.4% vs 69.2%, P  = 0.363). SVD was detected in 26 patients (3.3%), and 19 (2.4%) of the 795 patients had evidence of BVF during follow-up., Conclusions: Our study demonstrates good long-term results for high-risk patients who were alive up to 8 years after TAVR., (© 2021 The Authors.)

Objectives: This study investigated whether transcatheter aortic valve replacement (TAVR) with peri-procedural continuation of oral anticoagulation is equally safe and efficacious as TAVR with peri-procedural interruption of anticoagulation., Background: A significant proportion of patients undergoing TAVR have an indication for long-term oral anticoagulation. The optimal peri-procedural management of such patients is unknown., Methods: Consecutive patients on oral anticoagulation who underwent transfemoral TAVR at 5 European centers were enrolled. Oral anticoagulation was either stopped 2 to 4 days before TAVR or continued throughout the procedure. Primary safety outcome was major bleeding. Secondary efficacy endpoints included vascular complications, stroke, and mortality., Results: Of 4,459 patients, 584 patients were treated with continuation of anticoagulation and 733 with interruption of anticoagulation. At 30 days, major or life-threatening bleedings occurred in 66 (11.3%) versus 105 (14.3%; odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.61 to 1.21; p = 0.39) and major vascular complications in 64 (11.0%) versus 90 (12.3%; OR: 0.89; CI: 0.62 to 1.27; p = 0.52) of patients with continuation and with interruption of anticoagulation, respectively. Transfusion of packed red blood cells was less often required in patients with continuation of anticoagulation (80 [13.7%] vs. 130 [17.7%]; OR: 0.59; 95% CI: 0.42 to 0.81; p = 0.001). Kaplan-Meier estimates of survival at 12 months were 85.3% in patients with continuation of anticoagulation and 84.0% in patients with interruption of anticoagulation (hazard ratio: 0.90; 95% CI: 0.73 to 1.12; p = 0.36)., Conclusions: Continuation of oral anticoagulation throughout TAVR did not increase bleeding or vascular complication rates. Moreover, packed red blood cell transfusions were less often required in patients with continuation of oral anticoagulation., Competing Interests: Author Disclosures Dr. Mangner has received speaker honoraria from Edwards Lifesciences, Medtronic, Novartis, Sanofi Genzyme, and AstraZeneca; and has received consultant honoraria from Biotronik, outside the submitted work. Dr. Kobza has received institutional grants from Abbott Vascular, Boston Scientific, Biosense Webster, Biotronik, Medtronic, and Sis-Medical. Dr. Linke has received institutional grants from Novartis; and has received personal fees from Medtronic, Abbott Vascular, Edwards Lifesciences, Boston Scientific, AstraZeneca, Novartis, and Pfizer. Dr. Stortecky has received institutional research grants from Edwards Lifesciences, Medtronic, and Boston Scientific; and has been a consultant for Boston Scientific, BTG, and Teleflex. Dr. Nietlispach has been a consultant for Edwards Lifesciences and Abbott Vascular. Dr. Pilgrim has received institutional research grants from Edwards Lifesciences, Biotronik, and Boston Scientific; and has received personal fees from Biotronik and Boston Scientific. Dr. Toggweiler has been a proctor for Boston Scientific, Medtronic, Biosensors/New Valve Technology, and Abbott Vascular; has been a consultant for Carag, Medira, Boston Scientific, Medtronic, Biosensors/New Valve Technology, and Abbott Vascular; has received institutional research grants from Boston Scientific and Fumedica; and holds equity in Hi-D Imaging. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In the treatment of de-novo coronary small vessel disease, drug-coated balloons (DCBs) are non-inferior to drug-eluting stents (DESs) regarding clinical outcome up to 12 months, but data beyond 1 year is sparse. We aimed to test the long-term efficacy and safety of DCBs regarding clinical endpoints in an all-comer population undergoing percutaneous coronary intervention., Methods: In this prespecified long-term follow-up of a multicentre, randomised, open-label, non-inferiority trial, patients from 14 clinical sites in Germany, Switzerland, and Austria with de-novo lesions in coronary vessels <3 mm and an indication for percutaneous coronary intervention were randomly assigned 1:1 to DCB or second-generation DES and followed over 3 years for major adverse cardiac events (ie, cardiac death, non-fatal myocardial infarction, and target-vessel revascularisation [TVR]), all-cause death, probable or definite stent thrombosis, and major bleeding (Bleeding Academic Research Consortium bleeding type 3-5). Analyses were performed on the full analysis set according to the modified intention-to-treat principle. Dual antiplatelet therapy was recommended for 1 month after DCB and 6 months after DES with stable symptoms, but 12 months with acute coronary syndromes. The study is registered with ClinicalTrials.gov, NCT01574534 and is ongoing., Findings: Between April 10, 2012, and Feb 1, 2017, of 883 patients assessed, 758 (86%) patients were randomly assigned to the DCB group (n=382) or the DES group (n=376). The Kaplan-Meier estimate of the rate of major adverse cardiac events was 15% in both the DCB and DES groups (hazard ratio [HR] 0·99, 95% CI 0·68-1·45; p=0·95). The two groups were also very similar concerning the single components of adverse cardiac events: cardiac death (Kaplan-Meier estimate 5% vs 4%, HR 1·29, 95% CI 0·63-2·66; p=0·49), non-fatal myocardial infarction (both Kaplan-Meier estimate 6%, HR 0·82, 95% CI 0·45-1·51; p=0·52), and TVR (both Kaplan-Meier estimate 9%, HR 0·95, 95% CI 0·58-1·56; p=0·83). Rates of all-cause death were very similar in DCB versus DES patients (both Kaplan-Meier estimate 8%, HR 1·05, 95% CI 0·62-1·77; p=0·87). Rates of probable or definite stent thrombosis (Kaplan-Meier estimate 1% vs 2%; HR 0·33, 95% CI 0·07-1·64; p=0·18) and major bleeding (Kaplan-Meier estimate 2% vs 4%, HR 0·43, 95% CI 0·17-1·13; p=0·088) were numerically lower in DCB versus DES, however without reaching significance., Interpretation: There is maintained efficacy and safety of DCB versus DES in the treatment of de-novo coronary small vessel disease up to 3 years., Funding: Swiss National Science Foundation, Basel Cardiovascular Research Foundation, and B Braun Medical., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background Efficacy data on drug-eluting stents (DES) versus bare-metal stents (BMS) in saphenous vein grafts are controversial. We aimed to compare DES with BMS among patients undergoing saphenous vein grafts intervention regarding long-term outcome. Methods and Results In this multinational trial, patients were randomized to paclitaxel-eluting or BMS. The primary end point was major adverse cardiac events (cardiac death, nonfatal myocardial infarction, and target-vessel revascularization at 1 year. Secondary end points included major adverse cardiac events and its individual components at 5-year follow-up. One hundred seventy-three patients were included in the trial (89 DES versus 84 BMS). One-year major adverse cardiac event rates were lower in DES compared with BMS (2.2% versus 16.0%, hazard ratio, 0.14; 95% CI, 0.03-0.64, P =0.01), which was mainly driven by a reduction of subsequent myocardial infarctions and need for target-vessel revascularization. Five-year major adverse cardiac event rates remained lower in the DES compared with the BMS arm (35.5% versus 56.1%, hazard ratio, 0.40; 95% CI, 0.23-0.68, P <0.001). A landmark-analysis from 1 to 5 years revealed a persistent benefit of DES over BMS (hazard ratio, 0.33; 95% CI, 0.13-0.74, P =0.007) in terms of target-vessel revascularization. More patients in the BMS group underwent multiple target-vessel revascularization procedures throughout the study period compared with the DES group (DES 1.1% [n=1] versus BMS 9.5% [n=8], P =0.013). Enrollment was stopped before the target sample size of 240 patients was reached. Conclusions In this randomized controlled trial with prospective long-term follow-up of up to 5 years, DES showed a better efficacy than BMS with sustained benefits over time. DES may be the preferred strategy in this patient population. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00595647.

Background: The randomized BASKET-SMALL 2 trial showed non-inferiority for treatment with drug-coated balloon (DCB) compared with drug-eluting stents (DES) in patients undergoing percutaneous coronary intervention (PCI) for de novo lesions in small coronary arteries regarding clinical endpoints at 1 year. In this predefined substudy, we investigated the angiographic findings in patients undergoing a clinically indicated follow-up angiography during the study phase., Methods: Eight-hundred and eighty-three patients underwent PCI with either DES or DCB in a culprit vessel < 3 mm in diameter for stable coronary artery disease or acute coronary syndrome. Event-driven re-angiographies and the corresponding images at baseline were analyzed for angiographic endpoints., Results: One-hundred and eleven patients (117 lesions, 66 DES versus 51 DCB) presented for an unscheduled re-angiography at median 5.7 months after the index procedure. At baseline, mean reference vessel diameter was 2.05 mm and the residual in-segment stenosis after the index procedure was less in DES compared to DCB (23.7% vs 33.8%, p = 0.001). At follow-up angiography, diameter stenosis in the DES group (29.0%) was still somewhat smaller than after DCB angioplasty (35.8%) when adjusting for time since PCI (p = 0.047), whereas lumen loss (LL) did not differ between the two treatment arms (LL-DES 0.06 mm vs LL-DCB 0.10 mm, p = 0.20). Eight patients following DES implantation presented with a complete occlusion of the target lesion compared to no occlusion in the DCB group (p = 0.009)., Conclusions: The clinically indicated follow-up angiography within 1 year showed no difference in LL. Complete thrombotic vessel occlusions were found only in the DES group., Clinical Trial Registration: www.clinicaltrials.gov ; number, NCT01574534.

Objectives: To evaluate the impact of previous coronary artery bypass grafting (CABG) on early safety at 30 days and 1-year mortality in patients receiving transcatheter aortic valve replacement (TAVR)., Background: The use of TAVR in patients with previous CABG suffering from severe aortic stenosis has increased in the last years., Methods: Consecutive TAVR patients were stratified according to previous CABG versus no previous cardiac surgery (control). All-cause 1-year mortality and early safety at 30 days were evaluated., Results: In the unmatched cohort and compared to control (n = 2,364), CABG (n = 260) were younger, more often male and suffered more often from comorbidities leading to an increased STS-score (p < .001). The rate of early safety events at 30 days was comparable between CABG and control (21.2% vs. 24.6%, p = .22) with a higher mortality in CABG (9.6% vs. 5.3%, p = .005). All-cause 1-year mortality was higher in CABG compared to controls (HR 1.51 [95%-CI 1.15-1.97], p = .003). Applying Cox regression analysis, both 30-day (HR 1.57 [95%-CI 0.97-2.53], p = .067) and all-cause 1-year mortality (HR 1.24 [95%-CI 0.91-1.70], p = .174) were not significantly different between groups. After propensity-score matching, the rate of early safety events at 30 days was lower in CABG compared to controls (21.6% vs. 31.7%, p = .02). Thirty-day (9.1% vs. 7.7%, p = .596) and all-cause 1-year mortality (24.0% vs. 23.1%, p = .520, HR 1.14 [95%-CI 0.77-1.69], p = .520) were not different between groups., Conclusion: In patients receiving TAVR, previous CABG was not associated with an increase in periprocedural complications and all-cause 1-year mortality when adjusted for other comorbidities., (© 2019 Wiley Periodicals, Inc.)

Background As transcatheter aortic valve replacement (TAVR) is expected to progress into younger patient populations, valve-in-TAVR (ViTAVR) may become a frequent consideration. Data on ViTAVR, however, are limited. This study investigated the outcome of ViTAVR in comparison to valve in surgical aortic valve replacement (ViSAVR), because ViSAVR is an established procedure for higher-risk patients requiring repeated aortic valve intervention. Methods and Results Clinical and procedural data of patients who underwent ViTAVR at 3 sites in the United States and Germany were retrospectively compared with data of patients who underwent ViSAVR at Cedars-Sinai Medical Center, according to Valve Academic Research Consortium-2 criteria. A total of 99 consecutive patients, 52.5% women, with a median Society of Thoracic Surgeons score of 7.2 were identified. Seventy-four patients (74.7%) underwent ViSAVR, and 25 patients (25.3%) underwent ViTAVR. Balloon-expandable devices were used in 72.7%. ViSAVR patients presented with smaller index devices (21.0 versus 26.0 mm median true internal diameter; P <0.001). Significantly better postprocedural hemodynamics (median prosthesis mean gradient, 12.5 [interquartile range, 8.8-16.2] versus 16.0 [interquartile range, 13.0-20.5] mm Hg; P =0.045) were observed for ViTAVR compared with the ViSAVR. Device success, however, was not different (79.2% and 66.2% for ViTAVR and ViSAVR, respectively; P =0.35), as were rates of permanent pacemaker implantation (16.7% versus 5.4%; P =0.1). One-year-mortality was 9.4% and 13.4% for ViTAVR and ViSAVR, respectively (log-rank P =0.38). Conclusions Compared with ViSAVR, ViTAVR provides acceptable outcomes, with slightly better hemodynamics, similar device success rates, and similar 1-year mortality.

The presence of a left ventricular (LV) thrombus is considered an absolute contraindication to transcatheter aortic valve implantation (TAVI) because of the very high embolic risk. We report a case of TAVI under complete protection of the cerebral arteries in a patient with a large LV thrombus, severely impaired LV function, and no surgical options. ( Level of Difficulty: Beginner. )., (© 2020 The Authors.)

Purpose of Review: Stroke remains a devastating complication of cardiovascular interventions. This review is going to discuss stroke rates and outcomes in different cardiovascular procedures with a highlight on the current evidence for the use of cerebral protection devices (CPD)., Recent Findings: Depending on the quality of neurological assessment, stroke occurs in up to 9.1% after TAVI, 3.9% after mitral clipping, 3.1% in LAAO patients, 0.4% after PCIs, and 1.8% after catheter ablation. CPDs are available for routine use. They are easy to use in most anatomies, feasible, and safe. Data on clinical impact and stroke reduction from RCTs are still missing. Most evidence for the routine use of CPDs exists in TAVI patients, who are at the highest risk. The PROTECTED TAVI RCT will shed more light on the clinical impact of CPD-use in TAVI patients. In other cardiovascular procedures like mitral clipping, PCIs, and ablation, the current data do not support the routine use of CPDs in these patients.

Purpose: This study aimed to investigate baseline, exercise testing, and exercise training-mediated predictors of change in peak oxygen uptake (V˙O2peak) from baseline to 12-wk follow-up (ΔV˙O2peak) in a post hoc analysis from the SMARTEX Heart Failure trial., Methods: We studied 215 patients with heart failure with left ventricular ejection fraction (LVEF) ≤35%, and New York Heart Association (NYHA) classes II-III who were randomized to either supervised high-intensity interval training with exercise target intensity of 90%-95% of peak heart rate (HRpeak) or supervised moderate continuous training (MCT) with target intensity of 60%-70% of HRpeak, or who received a recommendation of regular exercise on their own. Predictors of ΔV˙O2peak were assessed in two models: a logistic regression model comparing highest and lowest tertiles (baseline parameters) and a multivariate linear regression model (test/training/clinical parameters)., Results: The change in V˙O2peak in response to the interventions (ΔV˙O2peak) varied substantially, from -8.50 to +11.30 mL·kg·min. Baseline NYHA (class II gave higher odds vs III; odds ratio (OR), 7.1 (2.0-24.9); P = 0.002), LVEF (OR per percent, 1.1 (1.0-1.2); P = 0.005), and age (OR per 10 yr, 0.5 (0.3-0.8); P = 0.003) were associated with ΔV˙O2peak.In the multivariate linear regression, 34% of the variability in ΔV˙O2peak was explained by the increase in exercise training workload, ΔHRpeak between baseline and 12-wk posttesting, age, and ever having smoked., Conclusion: Exercise training response (ΔV˙O2peak) correlated negatively with age, LVEF, and NYHA class. The ability to increase workload during the training period and increased ΔHRpeak between baseline and the 12-wk test were associated with a positive outcome.

Aims: The efficacy of a telephone support program in chronic heart failure has been questioned particularly when considering short-term follow-up. This study is aimed to assess the impact of the HeartNetCare telephone support program in chronic heart failure within 18 months of observation and to verify a possible effect of a learning-to-care curve on outcome., Methods: We retrospectively compared a cohort of 269 chronic heart failure patients included in HeartNetCare program with 200 patients receiving usual care as a control group. All-cause death and hospitalization for heart failure or implantation of left ventricular assist device were the primary composite outcome. Secondary endpoints were the changes in left ventricular ejection fraction and in New York Heart Association (NYHA) functional class. Outcome data were also analyzed in relation to the time of enrollment from program initiation., Results: At baseline, HeartNetCare group showed lower ejection fraction and higher NYHA class. At the follow-up, 59 HeartNetCare patients (21.9%) and 49 usual care patients (24.5%) reached the primary endpoint (P = 0.51). After 18 months of follow-up, HeartNetCare patients improved ejection fraction and NYHA class compared with the usual care patients (P < 0.001). We also observed that the HeartNetCare patients enrolled after 12 months from the initiation of the program had a more favorable outcome in primary endpoint compared with controls., Conclusion: These results indicate that the long-term impact of a structured telephone support program might be able to positively influence symptoms and reduce events in chronic heart failure. These appreciable effects where more evident after an initial period essential for completing the learning-to-care curve.

Background: The use of bioprostheses for surgical aortic valve replacement increased substantially within the last years. In case of prosthesis failure, re-SAVR is standard of care, whereas valve-in-valve deployment of a transfemoral transcatheter aortic valve prosthesis (VinV-TFAVI) has recently emerged as an alternative. We sought to evaluate early safety, clinical efficacy, and all-cause 1-year-mortality of VinV-TFAVI and redo surgery for failing aortic bioprostheses (re-SAVR)., Methods and Results: Patients receiving either VinV-TFAVI (n = 147) or re-SAVR (n = 111) for a degenerated aortic bioprosthesis between 01/2006 and 05/2017 were included in this analysis. All-cause 1-year mortality was the primary outcome measure. Early safety and clinical efficacy according to VARC-2 endpoint definitions were evaluated at 30 days. Baseline characteristics differed significantly between both groups including age, STS-PROM, and incidence of relevant comorbidities. Re-stenosis was the predominant mode of failure in 45.9% of re-SAVR and 63.1% of VinV-TFAVI patients. The rate of "early safety" endpoints was lower with VinV-TFAVI (17.7% vs. 64.9%, p < 0.01), the rate of "clinical efficacy" endpoints was lower, e.g. better with re-SAVR (53.1% vs. 32.4%, p < 0.01). All-cause 1-year-mortality (VinV-TFAVI 8.8% vs re-SAVR 9.9%, p = 0.84) was not different. Treatment strategy was not associated with 1-year-mortality in a Cox regression analysis. The incidence of prosthesis-patient-mismatch was higher in VinV-TFAVI compared to re-SAVR., Conclusion: VinV-TFAVI represents a viable alternative for treatment of degenerated aortic bioprostheses in patients at increased surgical risk. However, in patients at low risk for reoperation, a better clinical efficacy and acceptable safety may favour re-SAVR., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Chronic heart failure (CHF) leads to diaphragm myopathy that significantly impairs quality of life and worsens prognosis. In this study, we aimed to assess the efficacy of a recently discovered small-molecule inhibitor of MuRF1 in treating CHF-induced diaphragm myopathy and loss of contractile function., Methods: Myocardial infarction was induced in mice by ligation of the left anterior descending coronary artery. Sham-operated animals (sham) served as controls. One week post-left anterior descending coronary artery ligation animals were randomized into two groups-one group was fed control rodent chow, whereas the other group was fed a diet containing 0.1% of the compound ID#704946-a recently described MuRF1-interfering small molecule. Echocardiography confirmed development of CHF after 10 weeks. Functional and molecular analysis of the diaphragm was subsequently performed., Results: Chronic heart failure induced diaphragm fibre atrophy and contractile dysfunction by ~20%, as well as decreased activity of enzymes involved in mitochondrial energy production (P < 0.05). Treatment with compound ID#704946 in CHF mice had beneficial effects on the diaphragm: contractile function was protected, while mitochondrial enzyme activity and up-regulation of the MuRF1 and MuRF2 was attenuated after infarct., Conclusions: Our murine CHF model presented with diaphragm fibre atrophy, impaired contractile function, and reduced mitochondrial enzyme activities. Compound ID#704946 rescued from this partially, possibly by targeting MuRF1/MuRF2. However, at this stage of our study, we refrain to claim specific mechanism(s) and targets of compound ID#704946, because the nature of changes after 12 weeks of feeding is likely to be complex and is not necessarily caused by direct mechanistic effects., (© 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: The ACURATE neo prosthesis is commonly implanted using introducer sheaths with inner diameters of up to 20 French. The use of only the expandable mesh component of the transGlide introducer system (Mesh only ) would substantially decrease the inner diameter to 13 French. We sought to assess the feasibility and safety of using Mesh only for femoral access of the ACURATE neo device and to compare outcomes with patients in whom standard sheaths were used., Methods and Results: We retrospectively analyzed a total of 551 patients with severe aortic stenosis from 4 high volume centers in Germany and Switzerland undergoing transfemoral TAVI between February 2016 and February 2018 with implantation of the ACURATE neo device. The median age was 81.7 [78.3-85.2], 67.0% were female, the STS score was 4.2% [2.8-6.5]. The use of the Mesh only was feasible in all attempted cases (n = 272); in all other patients, a standard sheath was used. Major vascular complications at the main access-site (VARC-2) were less frequent in the Mesh only group than in the standard sheath group (1.5% vs. 7.9%; p < 0.001). In the multivariable analysis, the use of Mesh only was independently associated with less major vascular complications (odds ratio 0.10 [95% CI 0.02-0.48]; p = 0.004)., Conclusions: Transfemoral implantation of the ACURATE neo device using the Mesh only was associated with a lower rate of major access-related complications when compared to the standard of care., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The role of continued versus interrupted oral anticoagulation (OAC) in patients with atrial fibrillation (AF) who underwent transfemoral transcatheter aortic valve implantation (TF-TAVI) for severe aortic stenosis is uncertain. The aim of this retrospective investigation was to evaluate the impact (1) of continued versus interrupted OAC on early safety and (2) of postoperative anticoagulant management on the 1-year mortality in patients with AF who underwent TF-TAVI. Consecutive patients with AF and on OAC at admission (n = 598) were stratified according to interrupted (iVKA) versus continued vitamin K antagonist (cVKA) versus continued direct oral anticoagulants (DOAC) at the time of TF-TAVI. Valve Academic Research Consortium-2 early safety was the primary outcome measure. Patients with iVKA (n = 299), cVKA (n = 117), and DOAC (n = 182) had comparable baseline characteristics including age (p = 0.25), gender (p = 0.33), and STS-Score (p = 0.072). The proportion of patients having a CHA 2 DS 2 -VASc-Score ≥3 (p = 0.791) and HAS-BLED-Score ≥3 (p = 0.185) was not different between groups. The rate of early safety events (with lower values indicating superior safety) was lowest in DOAC (13.2%) and not increased in cVKA (19.7%) compared to iVKA (23.1%) (p = 0.029). Valve Academic Research Consortium-2 defined stroke (p = 0.527) and bleeding (p = 0.097) did not differ between groups. Renal failure occurred more often in iVKA compared to cVKA and DOAC (p = 0.02). All-cause 1-year mortality was 20.1% in iVKA, 13.7% in cVKA, and 8.8% in DOAC (p = 0.015). Multivariate analysis revealed DOAC to be associated with reduced all-cause 1-year mortality (HR 0.56 (95%-CI 0.32 to 0.99), p = 0.047) whereas cVKA was comparable to iVKA (HR 0.75 (95%-CI 0.43 to 1.31), p = 0.307). In conclusion, cVKA did not increase the rate for the composite end point of early safety at 30 days in this cohort of patients. Treatment with a DOAC was associated with a significantly reduced rate of early safety end points at 30 days and lower 1-year mortality., (Copyright © 2019. Published by Elsevier Inc.)

Background: Experimental trials suggest improved outcome by mild therapeutic hypothermia for cardiogenic shock after acute myocardial infarction. The objective of this study was to investigate the hemodynamic effects of mild therapeutic hypothermia in patients with cardiogenic shock complicating acute myocardial infarction., Methods: Patients (n=40) with cardiogenic shock undergoing primary percutaneous coronary intervention without classic indications for mild therapeutic hypothermia underwent randomization in a 1:1 fashion to mild therapeutic hypothermia for 24 hours or control. The primary end point was cardiac power index at 24 hours; secondary end points included other hemodynamic parameters and serial measurements of arterial lactate., Results: No relevant differences were observed for the primary end point of cardiac power index at 24 hours (mild therapeutic hypothermia versus control: 0.41 [interquartile range, 0.31-0.52] versus 0.36 [interquartile range, 0.31-0.48] W/m 2 ; P=0.50; median difference, -0.025 W/m 2 ; 95% CI, -0.12 to 0.06). Similarly, all other hemodynamic measurements were not statistically different. Arterial lactate levels at 6, 8, and 10 hours were significantly higher in patients in the mild therapeutic hypothermia group with a slower decline ( P for interaction=0.03). There were no differences in 30-day mortality (60% versus 50%; hazard ratio, 1.27; 95% CI, 0.55-2.94; P=0.55)., Conclusions: In this randomized trial, mild therapeutic hypothermia failed to show a substantial beneficial effect on cardiac power index at 24 hours in patients with cardiogenic shock after acute myocardial infarction., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01890317.

Background: Diabetes mellitus (DM) is a risk factor for cardiovascular disease. However, its effect on procedural and follow-up performance after transcatheter aortic valve replacement (TAVR) remains controversial., Methods and Results: We performed an observational study of all consecutive patients treated with a transfemoral TAVR in a single-center cohort (n = 1818). All patients were stratified by diabetes status and gender. All-cause 3-year mortality was the primary endpoint. Male patients with DM were identified to have substantially increased 3-year mortality [125/314 (39.8%)] compared to males without DM [142/478 (29.7%), p < 0.01]. Male patients with DM had significantly higher 3-year mortality in comparison to female patients with (p < 0.01) or without DM (p < 0.01). There was no difference in 3-year mortality for female patients with [135/465 (29.0%)] and without DM [151/554 (27.3%); p = 0.70]. This increase in mortality in male DM patients was triggered by both cardiovascular and non-cardiovascular mortality. Furthermore, DM served as an independent predictor of 3-year mortality after TAVR selectively only in men. The interaction between male gender and diabetes mellitus was identified as an independent predictor of 3-year mortality [HR 1.88 (1.25; 2.82); p < 0.01]. DM did not affect 30-day mortality for the overall cohort and for males., Conclusion: Males with DM are a high-risk subgroup of patients after TAVR and require close medical attention including aggressive therapy of modifiable risk factors. Intensified diabetes management may improve long-term survival after TAVR.

In the recent years, ischemic brain injury related to embolization after transcatheter aortic valve replacement (TAVR) has received increased attention as new embolic protection strategies emerged to protect the brain. Diverse cerebral protection devices have been developed to reduce cerebral embolization during TAVR. These devices work through various mechanisms and are in different stages of clinical translation. This review provides the evidence-based review of peri-procedural stroke prevention during TAVR and summarizes currently available cerebral embolic protection devices., (© 2018 Wiley Periodicals, Inc.)

Background: Drug-coated balloons (DCB) are a novel therapeutic strategy for small native coronary artery disease. However, their safety and efficacy is poorly defined in comparison with drug-eluting stents (DES)., Methods: BASKET-SMALL 2 was a multicentre, open-label, randomised non-inferiority trial. 758 patients with de-novo lesions (<3 mm in diameter) in coronary vessels and an indication for percutaneous coronary intervention were randomly allocated (1:1) to receive angioplasty with DCB versus implantation of a second-generation DES after successful predilatation via an interactive internet-based response system. Dual antiplatelet therapy was given according to current guidelines. The primary objective was to show non-inferiority of DCB versus DES regarding major adverse cardiac events (MACE; ie, cardiac death, non-fatal myocardial infarction, and target-vessel revascularisation) after 12 months. The non-inferiority margin was an absolute difference of 4% in MACE. This trial is registered with ClinicalTrials.gov, number NCT01574534., Findings: Between April 10, 2012, and February 1, 2017, 382 patients were randomly assigned to the DCB group and 376 to DES group. Non-inferiority of DCB versus DES was shown because the 95% CI of the absolute difference in MACE in the per-protocol population was below the predefined margin (-3·83 to 3·93%, p=0·0217). After 12 months, the proportions of MACE were similar in both groups of the full-analysis population (MACE was 7·5% for the DCB group vs 7·3% for the DES group; hazard ratio [HR] 0·97 [95% CI 0·58-1·64], p=0·9180). There were five (1·3%) cardiac-related deaths in the DES group and 12 (3·1%) in the DCB group (full analysis population). Probable or definite stent thrombosis (three [0·8%] in the DCB group vs four [1·1%] in the DES group; HR 0·73 [0·16-3·26]) and major bleeding (four [1·1%] in the DCB group vs nine [2·4%] in the DES group; HR 0·45 [0·14-1·46]) were the most common adverse events., Interpretation: In small native coronary artery disease, DCB was non-inferior to DES regarding MACE up to 12 months, with similar event rates for both treatment groups., Funding: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Basel Cardiovascular Research Foundation, and B Braun Medical AG., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background Infective endocarditis ( IE ) after transcatheter aortic valve replacement is a devastating complication associated with a high mortality. Our objective was to determine the impact of cardiac surgery (CS) and antibiotics ( IE - CS ) compared with medical treatment with antibiotics only ( IE - AB x) on 1-year mortality in patients developing IE after transcatheter aortic valve replacement. Methods and Results Patients developing IE after transcatheter aortic valve replacement were included in this retrospective analysis. All-cause 1-year mortality was the primary end point. A total of 20 patients underwent IE - CS compared with 44 patients treated by IE - AB x. In this unmatched cohort, patients treated by IE - AB x were older ( P=0.006), had a higher Society of Thoracic Surgeons score ( P=0.029), and more often had severe chronic kidney disease ( P=0.037). One-year mortality was not different between groups ( IE -CS versus IE-ABx, 65% versus 68.2%; P=0.802). The rate of any complication during treatment was higher in the IE - CS group ( P=0.024). In a matched cohort, baseline characteristics were not significantly different. All-cause 1-year mortality was not different between groups ( IE -CS versus IE-ABx, 65% versus 75%; P=0.490). A Cox regression analysis revealed any indication for surgery (hazard ratio, 6.20; 95% confidence interval, 1.80-21.41; P=0.004), sepsis on admission (hazard ratio, 4.03; 95% confidence interval, 1.97-8.24; P<0.001), and mitral regurgitation ≥2 (hazard ratio, 2.91; 95% confidence interval, 1.33-6.37) as factors associated with 1-year mortality. Conclusions In patients developing IE after transcatheter aortic valve replacement, mortality was predicted by the severity of IE and concomitant mitral regurgitation. In this small, and therefore statistically limited, but high-risk patient cohort, CS provided no significant mortality benefit compared with medical therapy. Individual decision making by a "heart and endocarditis team" is necessary to offer those patients the most reasonable treatment option.

The treatment of coronary small vessel disease (SVD) remains an unresolved issue. Drug-eluting stents (DES) have limited efficacy due to increased rates of instent-restenosis, mainly caused by late lumen loss. Drug-coated balloons (DCB) are a promising technique because native vessels remain structurally unchanged. Basel Stent Kosten-Effektivitäts Trial: Drug-Coated Balloons vs. Drug-Eluting Stents in Small Vessel Interventions (BASKET-SMALL 2) is a multicenter, randomized, controlled, noninferiority trial of DCB vs DES in native SVD for clinical endpoints. Seven hundred fifty-eight patients with de novo lesions in vessels <3 mm in diameter and an indication for percutaneous coronary intervention such as stable angina pectoris, silent ischemia, or acute coronary syndromes are randomized 1:1 to angioplasty with DCB vs implantation of a DES after successful initial balloon angioplasty. The primary endpoint is the combination of cardiac death, nonfatal myocardial infarction, and target-vessel revascularization up to 1 year. Secondary endpoints include stent thrombosis, Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding, and long-term outcome up to 3 years. Based on clinical endpoints after 1 year, we plan to assess the noninferiority of DCB compared to DES in patients undergoing primary percutaneous coronary intervention for SVD. Results will be available in the second half of 2018. This study will compare DCB and DES regarding long-term safety and efficacy for the treatment of SVD in a large all-comer population., (© 2018 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Background: Impaired left ventricular (LV) ejection fraction is a common finding in patients with aortic stenosis and serves as a predictor of morbidity and mortality after transcatheter aortic valve replacement. However, conflicting data on the most accurate measure for LV function exist. We wanted to examine the impact of LV ejection fraction, mean pressure gradient, and stroke volume index on the outcome of patients treated by transcatheter aortic valve replacement., Methods and Results: Patients treated by transcatheter aortic valve replacement were primarily separated into normal flow (NF; stroke volume index >35 mL/m 2 ) and low flow (LF; stroke volume index ≤35 mL/m 2 ). Afterwards, patients were divided into 5 groups: "NF-high gradient," "NF-low gradient" (NF-LG), "LF-high gradient," "paradoxical LF-LG," and "classic LF-LG." The 3-year mortality was the primary end point. Of 1600 patients, 789 (49.3%) were diagnosed as having LF, which was characterized by a higher 30-day ( P =0.041) and 3-year ( P <0.001) mortality. LF was an independent predictor of all-cause (hazard ratio, 1.29; 95% confidence interval, 1.03-1.62; P =0.03) and cardiovascular (hazard ratio, 1.37; 95% confidence interval, 1.06-1.77; P =0.016) mortality. Neither mean pressure gradient nor LV ejection fraction was an independent predictor of mortality. Patients with paradoxical LF-LG (35.0%), classic LF-LG (35.1%) and LF-high gradient (38.1%) had higher all-cause mortality at 3 years compared with NF-high gradient (24.8%) and NF-LG (27.9%) ( P =0.001). However, surviving patients showed a similar improvement in symptoms regardless of aortic stenosis entity., Conclusions: LF is a common finding within the aortic stenosis population and, in contrast to LV ejection fraction or mean pressure gradient, an independent predictor of all-cause and cardiovascular mortality. Despite increased long-term mortality, high procedural success and excellent functional improvement support transcatheter aortic valve replacement in patients with LF severe aortic stenosis., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Patients undergoing transcatheter aortic valve replacement (TAVR) are often characterized by risk factors not reflected in conventional risk scores. In this context, little is known about the outcome of patients suffering from an active cancer disease (ACD). The objective was to determine the prevalence, clinical characteristics, perioperative outcomes, and mortality of patients with ACD undergoing TAVR compared to those with a history of cancer (HCD) and controls without known tumor disease., Methods: TAVR patients between 02/2006 and 09/2014 were stratified according to the presence of ACD, HCD, and control. All-cause-mortality at 1-year was the primary end point. All end point definitions were subject to the Valve Academic Research Consortium II definitions., Results: Overall, 1821 patients were included: 99 patients (5.4%) suffered from ACD and 251 patients (13.8%) had HCD. ACD was related to a solid organ or hematological source in 72.7% and 27.3%, respectively. Patients with ACD were more often male (P = 0.004) and had a lower logisticEuroScore I (P = 0.033). Overall rates of VARC-II defined periprocedural myocardial infarction, stroke, bleeding, access-site complications, and acute kidney injury were not different between groups. Thirty-day mortality did not differ between patients with ACD, HCD, and controls (6.1% vs 4.4% vs 7.6%, P = 0.176). All-cause 1-year mortality was higher in patients with ACD compared HCD and controls (37.4% vs 16.4% vs 20.8%, P < 0.001). ACD was an independent predictor of all-cause 1-year mortality (HR 2.10, 95%-CI 1.41-3.13, P < 0.001)., Conclusion: The presence of ACD in patients undergoing TAVR is associated with significantly higher 1-year mortality., (© 2017, Wiley Periodicals, Inc.)

Valve-in-valve implantation is an alternative to reoperation for patients with degenerated bioprostheses. This case report presents a 75-year-old woman presenting with worsening dyspnoea according New York Heart Association (NYHA) Class III after she had received a Sorin Perceval® S sutureless valve due to severe aortic valve stenosis 5 years ago. Echocardiography revealed a degenerated Perceval valve with severe valvular aortic regurgitation and stenosis. After exclusion of acute infective endocarditis, an Edwards SAPIEN 3 was implanted leading to an immediate haemodynamic improvement. A cerebral protection device caught a big embolized piece of material in the left carotid artery filter. The case demonstrates that not only suture-based stented and stentless bioprostheses can be treated by a valve-in-valve strategy, but it is also feasible to treat a failed sutureless Sorin Perceval using a balloon-expandable SAPIEN 3., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Muscle ring finger 1 (MuRF1) is a muscle-specific ubiquitin E3 ligase activated during clinical conditions associated with skeletal muscle wasting. Yet, there remains a paucity of therapeutic interventions that directly inhibit MuRF1 function, particularly in vivo. The current study, therefore, developed a novel compound targeting the central coiled coil domain of MuRF1 to inhibit muscle wasting in cardiac cachexia., Methods: We identified small molecules that interfere with the MuRF1-titin interaction from a 130 000 compound screen based on Alpha Technology. A subset of nine prioritized compounds were synthesized and administrated during conditions of muscle wasting, that is, to C2C12 muscle cells treated with dexamethasone and to mice treated with monocrotaline to induce cardiac cachexia., Results: The nine selected compounds inhibited MuRF1-titin complexation with IC 50 values <25 μM, of which three were found to also inhibit MuRF1 E3 ligase activity, with one further showing low toxicity on cultured myotubes. This last compound, EMBL chemical core ID#704946, also prevented atrophy in myotubes induced by dexamethasone and attenuated fibre atrophy and contractile dysfunction in mice during cardiac cachexia. Proteomic and western blot analyses showed that stress pathways were attenuated by ID#704946 treatment, including down-regulation of MuRF1 and normalization of proteins associated with apoptosis (BAX) and protein synthesis (elF2B-delta). Furthermore, actin ubiquitinylation and proteasome activity was attenuated., Conclusions: We identified a novel compound directed to MuRF1's central myofibrillar protein recognition domain. This compound attenuated in vivo muscle wasting and contractile dysfunction in cardiac cachexia by protecting de novo protein synthesis and by down-regulating apoptosis and ubiquitin-proteasome-dependent proteolysis., (© 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Transcatheter mitral valve implantation (TMVI) is still in its infancy and is mainly limited to valve-in-valve or valve-in-ring implantations. We present the early experience with TMVI for severe calcified native MV stenosis., Methods: Between January 2014 and June 2015, 6 of 11 patients screened (mean age, 77.4 ± 6.3 years; 66% men) with severe native mitral valve (MV) stenosis (mean gradient [Pmean], 11.1 ± 2.1 mm Hg; mean effective orifice area [EOA], 0.9 ± 0.12 cm 2 ) underwent transcatheter MV replacement at our institution as a bailout procedure. Conventional surgical procedures were denied in all patients because of severe annular calcification and extensive comorbidities (mean logistic EuroScore, 31.4% ± 8.3%). The Edwards SAPIEN 3 (29 mm) (Edwards Lifesciences, Irvine, CA) was used in all cases. Procedural access was transapical in 5 cases and concomitant to aortic valve replacement through the left atrium through a sternotomy in 1 case., Results: Initial implantation was successful in 100% of the cases. Because of early migration, 1 patient needed a valve-in-valve procedure. Postoperative echocardiography showed no residual mitral regurgitation in 4 cases (66%) and mild regurgitation in 2 cases (34%). Mean gradients were reduced to 4.2 ± 0.6 mm Hg (mean EOA, 2.8 ± 0.4 cm 2) . No patient had a stroke during hospitalization, and 30-day mortality was seen in 1 patient (17%) resulting from pneumonia., Conclusions: TMV implantation using the SAPIEN 3 aortic prosthesis in patients with heavy annular calcification is feasible and represents a reasonable bailout option for inoperable patients. However, several limitations need to be considered in this special patient population., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to assess characteristics including endomyocardial biopsy and outcome of patients with methamphetamine (MA)-associated cardiomyopathy in a series of patients treated in Germany., Background: MA abuse is an increasing problem worldwide., Methods: The cases of 30 consecutive MA-abusing patients with a left ventricular (LV) ejection fraction of <40% and endomyocardial biopsy performed at initial diagnosis were analyzed. Baseline characteristics were collected retrospectively, whereas follow-up was prospective. The primary endpoint was a composite of death, nonfatal stroke, and rehospitalization for heart failure., Results: Patients were 30.3 ± 1.9 years of age, predominantly male (93.3%), and highly symptomatic; 83.3% had New York Heart Association functional class III or IV dyspnea. Echocardiography revealed marked LV dilatation (mean LV end-diastolic diameter 67.1 ± 7.4 mm) and impaired LV ejection fraction (mean 19 ± 6%). One-third of the patients had intraventricular thrombi. Endomyocardial biopsy revealed markers of inflammation and fibrosis; the fibrosis correlated with the duration of MA abuse. At follow-up, discontinuation of MA abuse together with medical therapy partially improved cardiac function (LV ejection fraction, 19 ± 6 vs. 43 ± 13; p < 0.001) and symptoms (p = 0.056), whereas patients with continued abuse did not show any improvement. The improvement in cardiac function was independently associated with the extent of fibrosis. The primary endpoint occurred more often in patients with continued MA abuse (57.1% vs. 13.0%; p = 0.037)., Conclusions: MA-associated cardiomyopathy is characterized by severe heart failure and depressed cardiac function. The extent of myocardial fibrosis seems to predict the recoverability of LV function. Cessation of MA abuse is associated with improvement in cardiac function and symptoms, whereas continued MA abuse leads to ongoing heart failure and worse outcome., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to assess silent and clinically apparent cerebral embolic events in patients undergoing transcatheter left atrial appendage closure., Methods and Results: In this prospective single-centre study, 28 patients underwent percutaneous closure of the left atrial appendage. In all patients, a diffusion-weighted magnetic resonance imaging (DW-MRI) study was performed before, the day after the procedure, and during routine follow-up after 45 days. All patients underwent neurological assessment at the time of DW-MRI. Additionally, transcranial Doppler ultrasound monitoring (TCD) for the detection of microembolic material during the procedure was performed. The procedure was successfully completed in all patients. New embolic lesions were detected in nine patients (32%) after the procedure, of which three (33%) were detectable as gliotic lesions at follow-up. One (3.6%) new lesion was observed at 45-day follow-up. Neurological assessment showed no neurological deficits. We observed no relationship between the numbers of microembolic signals on TCD monitoring and the occurrence of cerebral infarctions on DW-MRI., Conclusions: New cerebral embolic events occur after transcatheter closure of the left atrial appendage. However, most of the lesions demonstrate no gliotic transformation at follow-up. In all patients, the cerebral lesions were clinically unapparent.

Background: Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE)., Methods: Two hundred sixty-one patients with left ventricular ejection fraction ≤35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE. Thereafter, patients were encouraged to continue exercising on their own. Clinical assessments were performed at baseline, after the intervention, and at follow-up after 52 weeks. Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks., Results: Groups did not differ in age (median, 60 years), sex (19% women), ischemic pathogenesis (59%), or medication. Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT ( P =0.45); left ventricular end-diastolic diameter changes compared with RRE were -2.8 mm (-5.2 to -0.4 mm; P =0.02) in HIIT and -1.2 mm (-3.6 to 1.2 mm; P =0.34) in MCT. There was also no difference between HIIT and MCT in peak oxygen uptake ( P =0.70), but both were superior to RRE. However, none of these changes was maintained at follow-up after 52 weeks. Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks (HIIT, 39%; MCT, 25%; RRE, 34%; P =0.16). Training records showed that 51% of patients exercised below prescribed target during supervised HIIT and 80% above target in MCT., Conclusions: HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity, and its feasibility remains unresolved in patients with heart failure., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046., (© 2017 The Authors.)

Background: Neurological complications after transcatheter aortic valve replacement (TAVR) may be reduced with transcatheter cerebral embolic protection (TCEP)., Objectives: This study evaluated the safety and efficacy of TCEP during TAVR., Methods: Nineteen centers randomized 363 patients undergoing TAVR to a safety arm (n = 123), device imaging (n = 121), and control imaging (n = 119). The primary safety endpoint consisted of major adverse cardiac and cerebrovascular events (MACCE) at 30 days, and the primary efficacy endpoint was reduction in new lesion volume in protected brain territories on magnetic resonance imaging scans at 2 to 7 days. Patients underwent neurocognitive assessments, and the debris captured was analyzed., Results: The rate of MACCE (7.3%) was noninferior to the performance goal (18.3%, p noninferior  < 0.001) and not statistically different from that of the control group (9.9%; p = 0.41). New lesion volume was 178.0 mm 3 in control subjects and 102.8 mm 3 in the device arm (p = 0.33). A post hoc multivariable analysis identified pre-existing lesion volume and valve type as predictors of new lesion volume. Strokes at 30 days were 9.1% in control subjects and 5.6% in patients with devices (p = 0.25) Neurocognitive function was similar in control subjects and patients with devices, but there was a correlation between lesion volume and neurocognitive decline (p = 0.0022). Debris found within filters in 99% of patients included thrombus, calcification, valve tissue, artery wall, and foreign material., Conclusions: TCEP was safe, captured embolic debris in 99% of patients, and did not change neurocognitive function. Reduction in new lesion volume on magnetic resonance scans was not statistically significant. (Cerebral Protection in Transcatheter Aortic Valve Replacement [SENTINEL]; NCT02214277)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Hypertension is a key risk factor for heart failure, with the latter characterized by diaphragm muscle weakness that is mediated in part by increased oxidative stress. In the present study, we used a deoxycorticosterone acetate (DOCA)-salt mouse model to determine whether hypertension could independently induce diaphragm dysfunction and further investigated the effects of high-intensity interval training (HIIT). Sham-treated (n = 11), DOCA-salt-treated (n = 11), and DOCA-salt+HIIT-treated (n = 15) mice were studied over 4 wk. Diaphragm contractile function, protein expression, enzyme activity, and fiber cross-sectional area and type were subsequently determined. Elevated blood pressure confirmed hypertension in DOCA-salt mice independent of HIIT (P < 0.05). Diaphragm forces were impaired by ∼15-20% in DOCA-salt vs. sham-treated mice (P < 0.05), but this effect was prevented after HIIT. Myosin heavy chain (MyHC) protein expression tended to decrease (∼30%; P = 0.06) in DOCA-salt vs. sham- and DOCA-salt+HIIT mice, whereas oxidative stress increased (P < 0.05). Enzyme activity of NADPH oxidase was higher, but superoxide dismutase was lower, with MyHC oxidation elevated by ∼50%. HIIT further prevented direct oxidant-mediated diaphragm contractile dysfunction (P < 0.05) after a 30 min exposure to H 2 O- 2 (1 mM). Our data suggest that hypertension induces diaphragm contractile dysfunction via an oxidant-mediated mechanism that is prevented by HIIT.-Bowen, T. S., Eisenkolb, S., Drobner, J., Fischer, T., Werner, S., Linke, A., Mangner, N., Schuler, G., Adams, V. High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice., (© FASEB.)

Purpose: Patient studies have demonstrated the efficacy of exercise training in attenuating respiratory muscle weakness in chronic heart failure (HF), yet direct assessment of muscle fiber contractile function together with data on the underlying intracellular mechanisms remains elusive. The present study, therefore, used a mouse model of HF to assess whether exercise training could prevent diaphragm contractile fiber dysfunction by potentially mediating the complex interplay between intracellular oxidative stress and proteolysis., Methods: Mice underwent sham operation (n = 10) or a ligation of the left coronary artery and were randomized to sedentary HF (n = 10) or HF with aerobic exercise training (HF + AET; n = 10). Ten weeks later, echocardiography and histological analyses confirmed HF., Results: In vitro diaphragm fiber bundles demonstrated contractile dysfunction in sedentary HF compared with sham mice that was prevented by AET, with maximal force 21.0 ± 0.7 versus 26.7 ± 1.4 and 25.4 ± 1.4 N·cm, respectively (P < 0.05). Xanthine oxidase enzyme activity and MuRF1 protein expression, markers of oxidative stress and protein degradation, were ~20% and ~70% higher in sedentary HF compared with sham mice (P < 0.05) but were not different when compared with the HF + AET group. Oxidative modifications to numerous contractile proteins (i.e., actin and creatine kinase) and markers of proteolysis (i.e., proteasome and calpain activity) were elevated in sedentary HF compared with HF + AET mice (P < 0.05); however, these indices were not significantly different between sedentary HF and sham mice. Antioxidative enzyme activities were also not different between groups., Conclusion: Our findings demonstrate that AET can protect against diaphragm contractile fiber dysfunction induced by HF, but it remains unclear whether alterations in oxidative stress and/or protein degradation are primarily responsible.

Objective: Surgical femoral cutdown for decannulation after veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is considered standard practice. However, access-site complications with this technique are not rare. The objective of this study is to evaluate feasibility, safety, and efficacy of a complete percutaneous decannulation procedure after VA-ECMO compared with the conventional surgical cutdown approach., Methods: In 35 patients who were successfully weaned from VA-ECMO support, femoral artery and vein access sites were closed using a completely percutaneous approach in 15 patients, whereas 20 patients had conventional surgical cutdown for access-site closure. Data concerning all 35 patients were collected retrospectively and analyzed regarding immediate vascular closure success, associated complications, and clinical outcomes., Results: Technical deployment success of the percutaneous vascular closure devices was achieved in all patients. Immediate success of closure was achieved more frequently in the surgical group (29% vs 100%; P<.05). Severe wound complications requiring surgery occurred only in the surgical group (0% vs 35%; P=NS). Surgical cutdown was associated with a significantly greater need for transfusion of packed red blood cells (1.6 ± 1.4 vs 2.2 ± 1.2; P<.05). Mean hospital stay was shorter in the percutaneous group (32 ± 18 days vs 36 ± 12 days; P=NS). One patient in the surgical group complained about sustained paresthesia after discharge., Conclusions: Complete percutaneous closure of the femoral access site after VA-ECMO is feasible, effective, and safe when compared with conventional surgical closure and performed by experienced operators.

Importance: Limited data exist on clinical characteristics and outcomes of patients who had infective endocarditis after undergoing transcatheter aortic valve replacement (TAVR)., Objective: To determine the associated factors, clinical characteristics, and outcomes of patients who had infective endocarditis after TAVR., Design, Setting, and Participants: The Infectious Endocarditis after TAVR International Registry included patients with definite infective endocarditis after TAVR from 47 centers from Europe, North America, and South America between June 2005 and October 2015., Exposure: Transcatheter aortic valve replacement for incidence of infective endocarditis and infective endocarditis for in-hospital mortality., Main Outcomes and Measures: Infective endocarditis and in-hospital mortality after infective endocarditis., Results: A total of 250 cases of infective endocarditis occurred in 20 006 patients after TAVR (incidence, 1.1% per person-year; 95% CI, 1.1%-1.4%; median age, 80 years; 64% men). Median time from TAVR to infective endocarditis was 5.3 months (interquartile range [IQR], 1.5-13.4 months). The characteristics associated with higher risk of progressing to infective endocarditis after TAVR was younger age (78.9 years vs 81.8 years; hazard ratio [HR], 0.97 per year; 95% CI, 0.94-0.99), male sex (62.0% vs 49.7%; HR, 1.69; 95% CI, 1.13-2.52), diabetes mellitus (41.7% vs 30.0%; HR, 1.52; 95% CI, 1.02-2.29), and moderate to severe aortic regurgitation (22.4% vs 14.7%; HR, 2.05; 95% CI, 1.28-3.28). Health care-associated infective endocarditis was present in 52.8% (95% CI, 46.6%-59.0%) of patients. Enterococci species and Staphylococcus aureus were the most frequently isolated microorganisms (24.6%; 95% CI, 19.1%-30.1% and 23.3%; 95% CI, 17.9%-28.7%, respectively). The in-hospital mortality rate was 36% (95% CI, 30.0%-41.9%; 90 deaths; 160 survivors), and surgery was performed in 14.8% (95% CI, 10.4%-19.2%) of patients during the infective endocarditis episode. In-hospital mortality was associated with a higher logistic EuroSCORE (23.1% vs 18.6%; odds ratio [OR], 1.03 per 1% increase; 95% CI, 1.00-1.05), heart failure (59.3% vs 23.7%; OR, 3.36; 95% CI, 1.74-6.45), and acute kidney injury (67.4% vs 31.6%; OR, 2.70; 95% CI, 1.42-5.11). The 2-year mortality rate was 66.7% (95% CI, 59.0%-74.2%; 132 deaths; 115 survivors)., Conclusions and Relevance: Among patients undergoing TAVR, younger age, male sex, history of diabetes mellitus, and moderate to severe residual aortic regurgitation were significantly associated with an increased risk of infective endocarditis. Patients who developed endocarditis had high rates of in-hospital mortality and 2-year mortality.

Background: A greater understanding of the different underlying mechanisms between patients with heart failure with reduced (HFrEF) and with preserved (HFpEF) ejection fraction is urgently needed to better direct future treatment. However, although skeletal muscle impairments, potentially mediated by inflammatory cytokines, are common in both HFrEF and HFpEF, the underlying cellular and molecular alterations that exist between groups are yet to be systematically evaluated. The present study, therefore, used established animal models to compare whether alterations in skeletal muscle (limb and respiratory) were different between HFrEF and HFpEF, while further characterizing inflammatory cytokines., Methods and Results: Rats were assigned to (1) HFrEF (ligation of the left coronary artery; n=8); (2) HFpEF (high-salt diet; n=10); (3) control (con: no intervention; n=7). Heart failure was confirmed by echocardiography and invasive measures. Soleus tissue in HFrEF, but not in HFpEF, showed a significant increase in markers of (1) muscle atrophy (ie, MuRF1, calpain, and ubiquitin proteasome); (2) oxidative stress (ie, higher nicotinamide adenine dinucleotide phosphate oxidase but lower antioxidative enzyme activities); (3) mitochondrial impairments (ie, a lower succinate dehydrogenase/lactate dehydrogenase ratio and peroxisome proliferator-activated receptor-γ coactivator-1α expression). The diaphragm remained largely unaffected between groups. Plasma concentrations of circulating cytokines were significantly increased in HFrEF for tumor necrosis factor-α, whereas interleukin-1β and interleukin-12 were higher in HFpEF., Conclusions: Our findings suggest, for the first time, that skeletal muscle alterations are exacerbated in HFrEF compared with HFpEF, which predominantly reside in limb, rather than in respiratory, muscle. This disparity may be mediated, in part, by the different circulating inflammatory cytokines that were elevated between HFpEF and HFrEF., (© 2016 American Heart Association, Inc.)

Importance: Stroke remains a major predictor of mortality after transcatheter aortic valve implantation (TAVI). Cerebral protection devices might reduce brain injury as determined by diffusion-weighted magnetic resonance imaging (DWMRI)., Objective: To determine the effect of a cerebral protection device on the number and volume of cerebral lesions in patients undergoing TAVI., Design, Setting, and Participants: Investigator-initiated, single center, blinded, randomized clinical trial in higher-risk patients with severe aortic stenosis undergoing TAVI at the University of Leipzig Heart Center. Brain MRI was performed at baseline, 2 days, and 7 days after TAVI. Between April 2013 and June 2014, patients were randomly assigned to undergo TAVI with a cerebral protection device (filter group) or without a cerebral protection device (control group). The last 1-month follow-up occurred in July 2014., Interventions: TAVI with or without a cerebral protection device (filter system)., Main Outcomes and Measures: The primary end point was the numerical difference in new positive postprocedure DWMRI brain lesions at 2 days after TAVI in potentially protected territories. The first hierarchical secondary outcome was the difference in volume of new lesions after TAVI in potentially protected territories., Results: Among the 100 enrolled patients, mean (SD) age was 80.0 (5.1) years in the filter group (n = 50) and 79.1 (4.1) years in the control group (n = 50), and the mean (SD) procedural risk scores (logistic EuroScores) were 16.4% (10.0%) in the filter group and 14.5% (8.7%) in the control group. For the primary end point, the number of new lesions was lower in the filter group, 4.00 (interquartile range [IQR], 3.00-7.25) vs 10.00 (IQR, 6.75-17.00) in the control group (difference, 5.00 [IQR, 2.00-8.00]; P < .001). For the first hierarchical secondary end point, new lesion volume after TAVI was lower in the filter group (242 mm3 [95% CI, 159-353]) vs in the control group (527 mm3 [95% CI, 364-830]) (difference, 234 mm3 [95% CI, 91-406]; P = .001). Considering adverse events, 1 patient in the control group died prior to the 30-day visit. Life-threatening hemorrhages occurred in 1 patient in the filter group and 1 in the control group. Major vascular complications occurred in 5 patients in the filter group and 6 patients in the control group. One patient in the filter group and 5 in the control group had acute kidney injury, and 3 patients in the filter group had a thoracotomy., Conclusions and Relevance: Among patients with severe aortic stenosis undergoing TAVI, the use of a cerebral protection device reduced the frequency of ischemic cerebral lesions in potentially protected regions. Larger studies are needed to assess the effect of cerebral protection device use on neurological and cognitive function after TAVI and to devise methods that will provide more complete coverage of the brain to prevent new lesions., Trial Registration: clinicaltrials.gov Identifier: NCT01833052.

Background: Scoring balloons produce excellent acute results in the treatment of in-stent restenosis (ISR), fibro-calcific and bifurcation lesions but have not been shown to affect the restenosis rate. A novel paclitaxel-coated scoring balloon (SB) was developed and tested to overcome this limitation., Methods and Results: SB were coated with paclitaxel admixed with a specific excipient. Patients at four clinical sites in Germany and one in Brazil with ISR of coronary bare metal stent (BMS) were randomized 1:1 to treatment with either a drug-coated or uncoated SB. Baseline and 6-month follow-up quantitative coronary angiography was performed by an independent blinded core lab and all patients will be evaluated clinically for up to one year. The primary endpoint was angiographic in-segment late lumen loss (LLL). Secondary endpoints included the rate of clinically driven target lesion revascularization (TLR), composite of major adverse cardiovascular events (MACE), stent thrombosis and other variables. Sixty-one patients were randomized (28 uncoated and 33 drug-coated SB); mean age 65 years, males 72%, and presence of diabetes 39%. At 6-month angiography, in-segment LLL was 0.48 ± 0.51 mm in the uncoated SB group versus 0.17 ± 0.40 mm in the drug-coated SB group (P = 0.01; ITT analysis). The rate of binary restenosis was 41% in the uncoated SB group versus 7% in the drug-coated SB group (P = 0.004). The MACE rate was 32% with the uncoated SB vs. 6% in the drug-coated SB group (P = 0.016). This difference was primarily due to the reduced need for clinically driven TLR in the coated SB group (3% vs. 32% P = 0.004)., Conclusions: A novel paclitaxel-coated coronary SB has been developed and successfully used in a first-in-human randomized controlled trial [ClinicalTrials.gov Identifier: NCT01495533]. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Objectives: Assessment of aortic regurgitation (AR) immediately after transcatheter aortic valve replacement (TAVR) is essential to guide further intervention in cases of relevant AR. It was the aim of this study to identify a simple and reproducible hemodynamic parameter for the assessment of AR., Background: Relevant AR after TAVR is present in up to 21% of cases and might be associated with adverse long-term outcomes., Methods: Three hundred sixty-two consecutive patients who were treated with TAVR for symptomatic aortic valve stenosis were analyzed. AR was assessed by aortic root angiography according to the Sellers classification. For hemodynamic evaluation, the diastolic pressure-time (DPT) index was calculated after TAVR: the area between the aortic and left ventricular pressure-time curves was measured during diastole and divided by the duration of diastole to calculate the DPT index. The DPT index was finally adjusted for the respective systolic blood pressure: DPT indexadj = (DPT index/systolic blood pressure) × 100., Results: Patients with angiographically nonrelevant AR (grade <2) had higher DPT indexadj (30.7 ± 6.8) compared with those with relevant AR (grade ≥2) (26.2 ± 5.8) (p < 0.05). Patients with DPT indexadj ≤27.9 had significantly higher 1-year mortality risk in comparison with those with DPT indexadj >27.9: 41.4% versus 13.5% (hazard ratio: 3.8; 95% confidence interval: 2.4 to 5.9; p [log rank-test] < 0.001). In multivariate regression analysis, DPT indexadj ≤27.9 was the strongest independent predictor of 1-year mortality (hazard ratio: 2.5; 95% confidence interval: 1.8 to 3.7; p < 0.001)., Conclusions: DPT indexadj is a simple, investigator-independent parameter that should be considered to differentiate between relevant and nonrelevant AR after TAVR., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: A well-developed coronary collateral circulation provides a potential source of blood supply in coronary artery disease. However, the prognostic importance and functional relevance of coronary collaterals is controversial with the association between exercise training and collateral growth still unclear., Methods and Results: This prospective, open-label study randomly assigned 60 patients with significant coronary artery disease (fractional flow reserve ≤0.75) to high-intensity exercise (group A, 20 patients) or moderate-intensity exercise (group B, 20 patients) for 4 weeks or to a control group (group C, 20 patients). The primary end point was the change of the coronary collateral flow index (CFI) after 4 weeks. Analysis was based on the intention to treat. After 4 weeks, baseline CFI increased significantly by 39.4% in group A (from 0.142±0.07 at beginning to 0.198±0.09 at 4 weeks) in comparison with 41.3% in group B (from 0.143±0.06 to 0.202±0.09), whereas CFI in the control group remained unchanged (0.7%, from 0.149±0.09 to 0.150±0.08). High-intensity exercise did not lead to a greater CFI than moderate-intensity training. After 4 weeks, exercise capacity, Vo2 peak and ischemic threshold increased significantly in group A and group B in comparison with group C with no difference between group A and group B., Conclusions: A significant improvement in CFI was demonstrated in response to moderate- and high-intensity exercise performed for 10 hours per week., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01209637., (© 2016 American Heart Association, Inc.)

Purpose: In moderately impaired, stable chronic heart failure (CHF) patients, exercise training (ET) enhances exercise capacity. In contrast, the therapeutic benefits of regular ET in patients with advanced CHF, especially in the long-term, are limited or conflicting. Therefore, the aim of the present investigation was to elucidate whether ET performed over 12 months would improve left ventricular performance and exercise capacity in patients with advanced CHF., Methods: Thirty-seven patients with CHF and New York Heart Association (NYHA) class IIIb were randomized to a sedentary lifestyle or daily ET on a cycle ergometer (in-hospital and home-based at 50%-60% of maximal exercise capacity). Cardiopulmonary exercise testing and echocardiography were performed at baseline, 3, 6, and 12 months., Results: Exercise training resulted in continuous decreases in left ventricular end-diastolic diameter at 3, 6, and 12 months versus baseline (all P < .05). This was accompanied by a significant increase in resting left ventricular ejection fraction from 24.1% ± 1.2% at baseline to 38.4% ± 2.0% at 12-month followup (P < .05). Moreover, ET patients increased exercise capacity measured by maximal oxygen uptake (Equation is included in full-text article.)O2max at 3, 6, and 12 months compared with baseline: 15.3 ± 0.8 mL/min/kg, 17.8 ± 0.8 mL/min/kg, 19.0 ± 0.7 mL/min/kg, and 19.5 ± 0.9 mL/min/kg, respectively (all P < .05 vs baseline). This was associated with a reduced NYHA classification., Conclusions: Exercise training over 12 months resulted in an improvement in exercise capacity and reversing of left ventricular remodeling in patients with advanced CHF (NYHA IIIb). These beneficial adaptations continued to improve up to 6 months and remained stable thereafter.

Background: A reduction in number and function of endothelial progenitor cells (EPCs) occurs in both physiologic aging and chronic heart failure (CHF). We assessed whether disease and aging have additive effects on EPCs or whether beneficial effects of exercise training are diminished in old age., Methods: We randomized 60 patients with stable CHF and 60 referent controls to a training or a control group. To detect possible aging effects we included subjects below 55 (young) and above 65 years (older). Subjects in the training group exercised four times daily at 60% to 70% of VO2max for four weeks under supervision. At baseline and after the intervention the number and function of EPCs were assessed., Results: As compared with young referent controls, older referent controls showed at baseline a reduced EPC number (young: 190 ± 37 CD34/KDR positive cells/ml blood; older: 131 ± 26 CD34/KDR positive cells/ml blood; p < 0.05) and function (young: 230 ± 41 migrated cells/1000 plated cells; older: 185 ± 28 cells/1000 plated cells; p < 0.05). In young and older CHF patients EPC-number (young: 85 ± 21 CD34/KDR positive cells/ml blood; older: 78 ± 20 CD34/KDR positive cells/ml blood) and EPC-function (young: 113 ± 26 cells/1000 plated cells; older: 120 ± 27 cells/1000 plated cells) were impaired. As a result of exercise training, EPC function improved by 24% in older referent controls (p < 0.05), while it remained unchanged in young training referent controls and controls respectively. In young and older patients with CHF four weeks of exercise training resulted in a significant improvement in EPC numbers and EPC function (young: number +66% function +43%; p < 0.05; older: number +69% function +36%; p < 0.05). These results were accompanied by a significant increase in flow mediated dilatation in the training groups of young/older CHF patients and in older referent controls., Conclusions: Four weeks of exercise training are effective in improving EPC number and EPC function in CHF patients. These training effects were not impaired among older patients, emphasizing the potentials of rehabilitation interventions in a patient group where CHF has a high prevalence., (© The European Society of Cardiology 2015.)