A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement.

BACKGROUND: Whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear. METHODS: We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns. RESULTS: After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53). CONCLUSIONS: In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.).

Three-year outcomes for transcatheter repair in patients with mitral regurgitation from the CLASP study.

BACKGROUND: Mitral valve transcatheter edge-to-edge repair (M-TEER) is an effective option for treatment of mitral regurgitation (MR). We previously reported favorable 2-year outcomes for the PASCAL transcatheter valve repair system. OBJECTIVES: We report 3-year outcomes from the multinational, prospective, single-arm CLASP study with analysis by functional MR (FMR) and degenerative MR (DMR). METHODS: Patients with core-lab determined MR ≥ 3+ were deemed candidates for M-TEER by the local heart team. Major adverse events were assessed by an independent clinical events committee to 1 year and by sites thereafter. Echocardiographic outcomes were evaluated by the core laboratory to 3 years. RESULTS: The study enrolled 124 patients, 69% FMR; 31% DMR (60% NYHA class III-IVa, 100% MR ≥ 3+). The 3-year Kaplan-Meier estimate for survival was 75% (66% FMR; 92% DMR) and freedom from heart failure hospitalization (HFH) was 73% (64% FMR; 91% DMR), with 85% reduction in annualized HFH rate (81% FMR; 96% DMR) (p < 0.001). MR ≤ 2+ was achieved and maintained in 93% of patients (93% FMR; 94% DMR) and MR ≤ 1+ in 70% of patients (71% FMR; 67% DMR) (p < 0.001). The mean left ventricular end-diastolic volume (181 mL at baseline) decreased progressively by 28 mL [p < 0.001]. NYHA class I/II was achieved in 89% of patients (p < 0.001). CONCLUSIONS: The 3-year results from the CLASP study demonstrated favorable and durable outcomes with the PASCAL transcatheter valve repair system in patients with clinically significant MR. These results add to the growing body of evidence establishing the PASCAL system as a valuable therapy for patients with significant symptomatic MR.

Two-year clinical outcomes after successful transcatheter aortic valve implantation with balloon-expandable versus self-expanding valves: A subanalysis of the GALILEO trial.

BACKGROUND: Midterm data comparing clinical outcomes after successful implantation of self-expanding and balloon-expandable transcatheter heart valves (THV) are limited. We aimed to compare 2-year outcomes after successful transcatheter aortic valve implantation (TAVI) with the Edwards balloon-expandable or the Medtronic self-expanding THV. METHODS: Two-year outcomes were analyzed according to the implanted THV in the GALILEO trial. Major adverse cardiac and cerebrovascular events (MACCE) was a composite of all-cause death or thromboembolic events including stroke, myocardial infarction, symptomatic valve thrombosis, systemic embolism, deep-vein thrombosis, or pulmonary embolism. RESULTS: Among 1644 patients recruited in 136 centers across 16 countries between 2015 and 2018, 499 received a self-expanding and 757 patients received a balloon-expandable THV. Patients treated with a self-expanding THV were more likely to be female, and had higher surgical risk, lower hemoglobin levels, and more frequent valve-in-valve procedures than those with a balloon-expandable THV. After multivariable adjustment, there were no significant differences in major clinical outcomes between self-expanding versus balloon-expandable THV: MACCE (17.0% vs. 13.4%, adjusted-hazard ratios [HR] 1.18, 95% confidence intervals [CI]: 0.82-1.69); all-cause death (11.4% vs. 9.3%, adjusted-HR 1.26; 95% CI: 0.78-2.05); cardiovascular death (8.5% vs. 4.0%, adjusted-HR 1.53; 95% CI: 0.82-2.86), any stroke (5.1% vs. 3.7%, adjusted-HR 0.86; 95% CI: 0.43-1.73); major or life-threatening bleeding (5.9% vs. 6.8%, adjusted-HR 0.93; 95% CI: 0.53-1.63). CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov. NCT02556203. CONCLUSIONS: Two-year follow-up data from the GALILEO trial indicate that successful TAVI either with self-expanding or balloon-expandable THVs according to physician discretion did not show difference in rates of MACCE.

TAVI in Patients with Mitral Annular Calcification and/or Mitral Stenosis.

BACKGROUND: We herein aimed for analysis of influence of mitral annular calcification (MAC) and mitral stenosis (MS) on outcomes in transcatheter aortic valve implantation (TAVI). METHODS: Between 11/2009 and 06/2017, 1,058 patients underwent TAVI in the presence of concomitant MAC or MS at our center. Subgroups were built and multivariate logistic regression, COX regression, Kaplan-Meier survival analyses, and receiver operating characteristics method were performed. RESULTS: Thirty-day mortality was 7.5% (79/1,058) with highest mortality in patients severe MS (MAC: 3.4% vs. mild MS: 5.9% vs. moderate MS: 15.0% vs. severe MS: 72.7%; p < 0.001). Moderate-to-severe MS (odds ratio [OR]: 7.75, confidence interval [CI]: 3.94-16.26, p < 0.001), impaired left ventricular ejection fraction (OR: 1.38, CI: 1.10-1.72, p < 0.01), and coronary artery disease (OR: 1.36, CI: 1.11-1.67, p < 0.01) were predictive of 30-day survival. Left ventricular systolic/end-diastolic pressure drop of <59.5 mm Hg / <19.5 mm Hg was associated with increased mortality. CONCLUSIONS: TAVI in the presence of MAC and mild MS is associated with acceptable acute outcomes but should be considered high-risk procedures in patients with moderate and especially those with severe MS. Our results suggest adverse hemodynamics after TAVI with concomitant MS, which may be caused by underfilling of the left ventricle leading to low-cardiac output.

Mechanical ventilation and mortality among 223 critically ill patients with coronavirus disease 2019: A multicentric study in Germany.

BACKGROUND: There are large uncertainties with regard to the outcome of patients with coronavirus disease 2019 (COVID-19) and mechanical ventilation (MV). High mortality (50-97%) was proposed by some groups, leading to considerable uncertainties with regard to outcomes of critically ill patients with COVID-19. OBJECTIVES: The aim was to investigate the characteristics and outcomes of critically ill patients with COVID-19 requiring intensive care unit (ICU) admission and MV. METHODS: A multicentre retrospective observational cohort study at 15 hospitals in Hamburg, Germany, was performed. Critically ill adult patients with COVID-19 who completed their ICU stay between February and June 2020 were included. Patient demographics, severity of illness, and ICU course were retrospectively evaluated. RESULTS: A total of 223 critically ill patients with COVID-19 were included. The majority, 73% (n = 163), were men; the median age was 69 (interquartile range = 58-77.5) years, with 68% (n = 151) patients having at least one chronic medical condition. Their Sequential Organ Failure Assessment score was a median of 5 (3-9) points on admission. Overall, 167 (75%) patients needed MV. Noninvasive ventilation and high-flow nasal cannula were used in 31 (14%) and 26 (12%) patients, respectively. Subsequent MV, due to noninvasive ventilation/high-flow nasal cannula therapy failure, was necessary in 46 (81%) patients. Renal replacement therapy was initiated in 33% (n = 72) of patients, and owing to severe respiratory failure, extracorporeal membrane oxygenation was necessary in 9% (n = 20) of patients. Experimental antiviral therapy was used in 9% (n = 21) of patients. Complications during the ICU stay were as follows: septic shock (40%, n = 90), heart failure (8%, n = 17), and pulmonary embolism (6%, n = 14). The length of ICU stay was a median of 13 days (5-24), and the duration of MV was 15 days (8-25). The ICU mortality was 35% (n = 78) and 44% (n = 74) among mechanically ventilated patients. CONCLUSION: In this multicentre observational study of 223 critically ill patients with COVID-19, the survival to ICU discharge was 65%, and it was 56% among patients requiring MV. Patients showed high rate of septic complications during their ICU stay.

TAVR for low-flow, low-gradient aortic stenosis: Prognostic impact of aortic valve calcification.

BACKGROUND: Compared to high gradient aortic stenosis (AS), patients with low-flow, low-gradient AS have higher mortality after transcatheter aortic valve replacement (TAVR), but distinct outcome predictors in this patient subset are yet to be determined. The present study investigated the prognostic impact of aortic valve calcification (AVC) in patients with low-flow, low-gradient AS undergoing TAVR. METHODS: This retrospective single-center analysis includes all patients undergoing TAVR for severe low-flow, low-gradient AS (n = 526), ie, low EF low gradient AS (LEF-LG AS; n = 290) and paradoxical low-flow, low-gradient AS (PLF-LG AS; n = 236), in whom AVC was quantified from contrast-enhanced multislice computed tomography images. AVCdensity was defined as calcium volume per annulus area. Patients were trichotomized according to sex-specific AVCdensity tertiles in both subgroups. All-cause mortality was assessed by Kaplan-Meier analyses and independent outcome predictors were determined by multivariable analyses. RESULTS: In both subgroups, patients with high AVCdensity had higher mean transvalvular gradients at baseline and higher rates of PVL after TAVR. High AVCdensity was associated with lowest 1- and 3-year mortality after TAVR in the LEF-LG AS but not in the PLF-LG AS group. According to multivariable analysis AVCdensity was independently associated with better survival in LEF-LG AS patients (HR 0.73 [0.60-0.88], P = .0011), but not in those with PLF-LG AS (HR 0.91 [0.73-1.14], P = .42). CONCLUSIONS: Quantification of AVC may not only be of diagnostic but also of prognostic value, as it facilitates the selection of LEF-LG AS patients with higher probability of beneficial outcome after TAVR.

Clinical outcomes after TAVR with heparin or bivalirudin as periprocedural anticoagulation in patients with and without peripheral arterial disease: Results from the BRAVO-3 randomized trial.

OBJECTIVES: This study sought to investigate the clinical outcomes of patients with and without peripheral artery disease (PAD) in the BRAVO-3 trial with respect to the effect of bivalirudin versus unfractionated heparin (UFH). BACKGROUND: PAD is found frequently in patients undergoing transcatheter aortic valve replacement (TAVR) and is reported to confer an increased risk of adverse events. It is unknown whether patients with and without PAD may demonstrate a differential response to bivalirudin versus UFH. METHODS: BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or cerebrovascular accidents (CVA). Net adverse cardiovascular events (NACE) were a composite of major bleeding or MACE. RESULTS: The total cohort included 119 patients with PAD. Vascular complications occurred significantly more frequently in patients with PAD both in-hospital (25.2 vs. 16.7%; OR 1.68) and at 30 days (29.4 vs. 17.3%; OR 1.99). No significant differences were observed regarding mortality, NACE, MACE, major bleeding or CVA with bivalirudin versus UFH among patients with or without PAD. In patients with PAD, bivalirudin was associated with an increased risk of minor vascular complications at 30 days. CONCLUSIONS: Patients with PAD undergoing transfemoral TAVR did not exhibit an increased risk of any major adverse events, according to the procedural anticoagulant randomization. However, patients treated with Bivalirudin had significantly higher rates of minor vascular complications.

Incidence and outcome of peri-procedural transcatheter heart valve embolization and migration: the TRAVEL registry (TranscatheteR HeArt Valve EmboLization and Migration).

AIMS: Peri-procedural transcatheter valve embolization and migration (TVEM) is a rare but potentially devastating complication of transcatheter aortic valve implantation (TAVI). We sought to assess the incidence, causes, and outcome of TVEM in a large multicentre cohort. METHODS AND RESULTS: We recorded cases of peri-procedural TVEM in patients undergoing TAVI between January 2010 and December 2017 from 26 international sites. Peri-procedural TVEM occurred in 273/29 636 (0.92%) TAVI cases (age 80.8 ± 7.3 years; 53.8% female), of which 217 were to the ascending aorta and 56 to the left ventricle. The use of self-expanding or first-generation prostheses and presence of a bicuspid aortic valve were independent predictors of TVEM. Bail-out measures included repositioning attempts using snares or miscellaneous tools (41.0%), multiple valve implantations (83.2%), and conversion to surgery (19.0%). Using 1:4-propensity matching, we identified a cohort of 235 patients with TVEM (TVEMPS) and 932 patients without TVEM (non-TVEMPS). In the matched cohort, all-cause mortality was higher in TVEMPS than in non-TVEMPS at 30 days (18.6% vs. 4.9%; P < 0.001) and after 1 year (30.5% vs. 16.6%; P < 0.001). Major stroke was more frequent in TVEMPS at 30 days (10.6% vs. 2.8%; P < 0.001), but not at 1 year (4.6% vs. 1.9%; P = 0.17). The need for emergent cardiopulmonary support, major stroke at 30 days, and acute kidney injury Stages 2 and 3 increased the risk of 1-year mortality, whereas a better renal function at baseline was protective. CONCLUSION: Transcatheter valve embolization and migration occurred in approximately 1% and was associated with increased morbidity and mortality.

Impact of percutaneous closure device type on vascular and bleeding complications after TAVR: A post hoc analysis from the BRAVO-3 randomized trial.

BACKGROUND/OBJECTIVE: Prostar XL (PS) and ProGlide (PG) are common vascular closure devices (VCD) used in TAVR via transfemoral vascular approach. The impact of these VCD on vascular and bleeding complications remains unclear. METHODS: The BRAVO-3 trial randomized 802 patients undergoing transfemoral TAVR. We stratified patients according to type of VCD used and examined the 30-day incidence of major or minor vascular complications, major bleeding (BARC ≥3b), AKI and major adverse cardiac and cerebrovascular events (MACCE; death, myocardial infarction or stroke). RESULTS: A total of 746 (93%) patients were treated with either PS (n = 352, 47%) or PG (n = 394, 53%) VCD, without significant differences in successful deployment rate (PS 322 [91.2%] vs. PG 373 [94.2%] respectively, p = .20). PG was associated with a significantly lower incidence of major or minor vascular complications, compared to PS (adjusted OR: 0.54; 95% CI: 0.37-0.80; p < .01). Rates of acute kidney injury were also lower with the PG device. There was no significant difference between bleeding, MACCE, and death. CONCLUSIONS: Compared to PS, the PG VCD was associated with a lower rate of major or minor vascular complications and lower rates of AKI after transfemoral TAVR.

Compassionate use of the PASCAL transcatheter mitral valve repair system for patients with severe mitral regurgitation: a multicentre, prospective, observational, first-in-man study.

BACKGROUND: Severe mitral regurgitation is associated with impaired prognosis if left untreated. Using the devices currently available, transcatheter mitral valve repair (TMVr) remains challenging in complex anatomical situations. We report the procedural and 30-day results of the first-in-man study of the Edwards PASCAL TMVr system. METHODS: In this multicentre, prospective, observational, first-in-man study, we collected data from seven tertiary care hospitals in five countries that had a compassionate use programme in which patients underwent transcatheter mitral valve repair using the Edwards PASCAL TMVr system. Eligible patients were those with symptomatic, severe functional, degenerative, or mixed mitral regurgitation deemed at high risk or inoperable. Safety and efficacy of the procedure were prospectively assessed at device implantation, discharge, and 30 days after device implantation. The key study endpoints were technical success assessed at the end of the procedure and device success 30 days after implantation using the Mitral Valve Academic Research Consortium definitions. FINDINGS: Between Sept 1, 2016, and March 31, 2017, 23 patients (median age 75 years [IQR 61-82]) had treatment for moderate-to-severe (grade 3+) or severe (grade 4+) mitral regurgitation using the Edwards PASCAL TMVr system. At baseline, the median EuroScore II score was 7·1% (IQR 3·6-12·8) and the median Society of Thoracic Surgeons predicted risk of mortality for mitral valve repair was 4·8% (2·1-9·0) and 6·8% (2·9-10·1) for mitral valve replacement. 22 (96%) of 23 patients were New York Heart Association (NYHA) class III or IV at baseline. The implantation of at least one device was successful in all patients, resulting in procedural residual mitral regurgitation of grade 2+ or less in 22 (96%) patients. Six (26%) of 23 patients had two implants. Periprocedural complications occurred in two (9%) of 23 patients (one minor bleeding event and one transient ischaemic attack). Despite the anatomical complexity of mitral regurgitation in the patients in this compassionate use cohort, technical success was achieved in 22 (96%) of 23 patients, and device success at 30 days was achieved in 18 (78%) patients. Three patients (13%) died during the 30 day follow-up. 19 (95%) of 20 patients alive 30 days after implantation were NYHA class I or II. INTERPRETATION: This study establishes feasibility of the Edwards PASCAL TMVr system with a high rate of technical success and reduction of mitral regurgitation severity. Further research is needed on procedural and long-term clinical outcomes. FUNDING: None.

A case of successful Mitraclip implantation in a patient having a large coaptation gap under extracorporeal membrane oxygenation (ECMO).

Mitraclip is an alternative therapeutic option for severe functional mitral regurgitation (MR) with reduced ejection fraction, especially in patients with high surgical risk. Although the Mitraclip was reported as an effective therapy in patients who fulfilled the anatomical criteria of the EVEREST trial, it is still uninvestigated whether the therapy is also feasible and beneficial in patients outside the indication criteria of the EVEREST II trial. Among them, MR with a large coaptation gap is considered as a challenging anatomy, because the gap makes it difficult to grasp both leaflets with a standard Mitraclip procedure. As two techniques to grasp such a large coaptation gap were reported, there was no report concerning the effectiveness of extracorporeal membrane oxygenation (ECMO) during Mitraclip implantation. Here we present a first case of successful Mitraclip implantation in a patient with a large coaptation gap with the support of ECMO. © 2016 Wiley Periodicals, Inc.

Valve-in-valve-in-valve: Balloon expandable transcatheter heart valve in failing self-expandable transcatheter heart valve in deteriorated surgical bioprosthesis.

Valve-in-valve (ViV) procedures for failing bioprostheses carry a certain risk for device malfunction. We herein report a case of a failing Evolut R in a deteriorated Mitroflow, treated with a Sapien 3. An 81 year old female patient received surgical aortic valve replacement and was treated by ViV due to deterioration. Three years later, echocardiography revealed a pressure gradient of peak/mean 105/63 mmHg. Subsequently, a second ViV procedure with initial intentional rupture of the bioprosthetic stent was performed. Immediate stent recoil of the Evolut R prompted implantation of a Sapien 3. In 30-day follow-up, mean pressure gradient of 30 mmHg and nearly complete symptom relief was documented. Fracture of a surgical bioprosthetic stent is feasible in a ViV configuration. Supra-annular placement of a balloon-expandable THV as ViV-in-valve is feasible with suboptimal hemodynamic results in this case. Risk of re-do surgery should be weighted against anticipated hemodynamic and clinical results.

First-in-human implantation of a novel self-expanding supra-annular transcatheter heart valve for transcatheter aortic valve implantation inside a small degenerated aortic surgical bioprosthesis.

With next-generation valves such as the ALLEGRA valve from NewValve Technologies (NVT), Hechingen Germany, there is a very likely treatment expansion for patients with aortic valve disease. Besides treatment of native valvular aortic stenosis with the ALLEGRA valve, the special implant mechanism seems to be an appealing concept for patients with degenerated surgical bioprostheses. We report the first case of a transfemoral implantation in small degenerated surgical bioprosthesis of a 76-year-old woman.

Right Ventricular Index for Risk Stratification of Patients with Pulmonary Arterial Hypertension.

BACKGROUND: Right ventricular (RV) dysfunction is a major prognostic predictor in pulmonary arterial hypertension (PAH). OBJECTIVES: The objective of this study was to assess the prognostic impact of a newly developed index merging haemodynamic parameters into 1 variable. METHODS: We retrospectively assessed 2 cohorts of 248 patients (164 from Hamburg and 84 from Heidelberg) with invasively diagnosed PAH. During a median follow-up time of 3.6 years (3.1 and 4.0 years for Hamburg and Heidelberg, respectively), the composite endpoint of all-cause mortality and lung transplantation occurred in 57 patients (53 and 4 patients for Hamburg and Heidelberg, respectively). The RV index was developed in the Hamburg cohort and validated in the Heidelberg cohort: (right atrial pressure × pulmonary vascular resistance)/mixed venous oxygen saturation. RESULTS: Patients with a high RV index had a higher incidence of the combined endpoint in Kaplan-Meier analyses in the Hamburg and Heidelberg cohort (p = 0.017 and p = 0.034, respectively). The calculated RV index cut-off value was 91 and identified patients with a worse outcome in the Hamburg cohort and showed a trend in the Heidelberg cohort (p < 0.001 and p = 0.089, respectively). The RV index in Cox regression hazard models was an independent predictor of outcomes after adjustment for sex and age in both cohorts (Hamburg: hazard ratio [HR] 1.26 [95% CI 1.08, 1.47], p = 0.0027; Heidelberg: HR 2.27 [95% CI 1.46, 3.51], p < 0.001). A nomogram based on these results allowed risk stratification. CONCLUSION: Merging 3 haemodynamic variables into 1 variable, the RV index increased the prognostic power up to an independent risk factor. The RV index is easy to calculate and allows the construction of a nomogram for an individualized risk assessment.

A case of anomalous left coronary artery obstruction caused by lotus valve implantation.

Trans-catheter aortic valve implantation (TAVI) in patients with high surgical risk is an alternative therapeutic option for severe aortic stenosis. Although second generation TAVI devices are available now, this therapy still cannot overcome all serious complications. Among them, coronary obstruction is a life threatening complication, however, there is no report concerning the complication in patients with anomalous coronary arteries. Here we present a case with coronary obstruction of an anomalous left main coronary that occurred after implantation of the mechanical expanding Lotus valve (Boston Scientific Inc.). © 2016 Wiley Periodicals, Inc.

Baseline anemia and its impact on midterm outcome after transcatheter aortic valve implantation.

BACKGROUND: Anemia is linked to impaired outcome in patients with cardiovascular diseases. We sought to characterize the impact of baseline anemia on mid-term outcome after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: Data of 1201 consecutive TAVI patients were retrospectively analyzed. Baseline anemia was defined according to the WHO (hemoglobin <12g/dl [female], <13g/dl [male]). It was prevalent in 59.0% of patients and associated with a higher preoperative risk (STS-PROM 7.8 ± 5.7 vs. 6.2 ± 4.1%, P < 0.001). Survival was similar at 30 days (90.5 vs. 91.2%, P = 0.626) but NYHA functional capacity was impaired in patients with baseline anemia (classes III/IV: 20.6 vs. 15.6%, P = 0.006). Low baseline hemoglobin (OR 0.85, CI 0.73-0.98, P = 0.025), blood transfusion (OR 2.42, CI 1.38-4.28, P = 0.002), and bleeding complications (OR 2.21, CI 1.27-3.81, P = 0.005) were in addition associated with acute kidney injury after TAVI. Three-year survival was reduced (49.6 vs. 64.9%, P = 0.002) and baseline anemia was linked to increased mid-term mortality (HR 1.43, CI 1.13-1.82, P = 0.003), however its effect was surpassed by the adverse impact of periprocedural complications. CONCLUSIONS: Baseline anemia was associated with increased morbidity and mortality after TAVI. Preprocedural hemoglobin levels need to be assessed for risk stratification and blood conservation management seems essential. As a potentially modifiable target, the role of pretreatment of anemia prior to TAVI remains to be determined. © 2016 Wiley Periodicals, Inc.

Direct percutaneous transaxillary implantation of a novel self-expandable transcatheter heart valve for aortic stenosis.

OBJECTIVES: The aim of this study was to evaluate safety, feasibility, and efficacy of transaxillary TAVI using a novel self-expandable transcatheter heart valve (THV) via a direct percutaneous technique. METHODS: The analysis comprises 12 consecutive patients with severe aortic stenosis treated with the ACURATE Neo™ THV (Symetis) by direct percutaneous transaxillary access. RESULTS: Patients presented with a mean age of 79.9 ± 6.2 years and high calculated surgical risk (logEuroSCORE I: 19.55 ± 15.00%; STS PROM score: 5.42 ± 3.25%). Transaxillary TAVI was performed in 11/12 via the left and in 1/12 via the right-sided axillary artery. Device success was achieved in all patients (12/12). Mortality rate at 30 days was 0% (0/12). No major and one minor access site complication (1/12) occurred. No major or life-threatening access site-related bleeding resulted. None of the patients suffered from postprocedural stroke/transient ischemic attack. There was no need for a permanent pacemaker. Mean effective orifice area post implantation was 2.1 ± 0.29 cm2 and mean aortic gradient 6.2 ± 1.5 mm Hg. In none of the patients, greater than moderate aortic regurgitation or paravalvular leakage was detected at discharge (0/12). CONCLUSIONS: Our study suggests that the implantation of the second-generation self-expandable ACURATE Neo™ via a transaxillary access is technically feasible and safe and yields excellent short-term clinical results. © 2017 Wiley Periodicals, Inc.

Transcatheter Aortic Valve Replacement Using the Portico System: 10 Things to Remember.

The Portico system (St. Jude Medical, Minneapolis, MN, USA) consists of a self-expanding valve prosthesis and a delivery system designed for transcatheter aortic valve replacement (TAVR). We describe this system, its 10-steps implantation procedure, and provide tips and tricks based on our personal experience with this system.

Penetration of topically applied nanocarriers into the hair follicles of dog and rat dorsal skin and porcine ear skin.

BACKGROUND: In humans, topically applied nanocarriers penetrate effectively into the hair follicles where they can be exploited for the localized and targeted treatment of skin disorders. OBJECTIVE: The objective of the present study was to examine the applicability of particle-based systems for follicular drug delivery in companion animals and livestock, which have a large follicular reservoir. ANIMALS: Skin samples from 10 beagle dogs, 14 Wistar rats and four ears from freshly slaughtered cross-bred pigs were used. METHODS: Fluoresceinamine labelled poly (L-lactide-co-glycolide) nanocarriers (256 or 430 nm) were applied on the different skin samples. After penetration, skin biopsies were removed and cryohistological cross sections prepared and investigated with regard to the follicular penetration depths (in µm ± standard deviation) of the nanocarriers using confocal laser scanning microscopy. RESULTS: In canine, rat and porcine hair follicles, the smaller nanoparticles were detected at mean follicular penetration depths of 630.16 ± 135.75 µm, 253.55 ± 47.36 µm and 653.40 ± 94.71 µm, respectively. The larger particles were observed at average follicular depths of 604.79 ± 132.42 µm; 262.87 ± 55.25 µm and 786.81 ± 121.73 µm, respectively, in canine, rat and porcine hair follicles. Statistically significant differences (P < 0.05) in the mean follicular penetration depths of the differently sized nanocarriers could be determined for the canine and porcine skin samples. CONCLUSION: The mean follicular penetration depths of the differently sized nanocarriers were mostly significantly different between the different species, which might be due to different species-specific follicular dimensions. This issue needs to be addressed specifically in further studies.

DEGRO practical guidelines for radiotherapy of non-malignant disorders: Part I: physical principles, radiobiological mechanisms, and radiogenic risk.

PURPOSE: Synopsis of the introductory paragraph of the DEGRO consensus S2e-guideline recommendations for the radiotherapy of benign disorders, including physical principles, radiobiological mechanisms, and radiogenic risk. MATERIALS AND METHODS: This work is based on the S2e-guideline recommendations published November 14, 2013. The basic principles of radiation physics and treatment delivery, evaluation of putative underlying radiobiological mechanisms, and the assessment of genetic and cancer risk following low-dose irradiation will be presented. RESULTS: Radiation therapy of benign diseases is performed according to similar physical principles as those governing treatment of malignant diseases in radiation oncology, using the same techniques and workflows. These methods comprise usage of orthovoltage X-ray units, gamma irradiation facilities, linear accelerators (LINACs), and brachytherapy. Experimental in vitro and in vivo models recently confirmed the clinically observed anti-inflammatory effect of low-dose X-irradiation, and implicated a multitude of radiobiological mechanisms. These include modulation of different immunological pathways, as well as the activities of endothelial cells, mono- and polymorphonuclear leukocytes, and macrophages. The use of effective dose for radiogenic risk assessment and the corresponding tumor incidence rate of 5.5%/Sv are currently controversially discussed. Some authors argue that the risk of radiation-induced cancers should be estimated on the basis of epidemiological data. However, such data are rarely available at present and associated with high variability. CONCLUSION: Current radiobiological studies clearly demonstrate a therapeutic effectiveness of radiation therapy used to treat benign diseases and implicate various molecular mechanisms. Radiogenic risks should be taken into account when applying radiation treatment for benign diseases.