Cerebral Embolic Protection during Transcatheter Aortic-Valve Replacement.

BACKGROUND: Transcatheter aortic-valve replacement (TAVR) for the treatment of aortic stenosis can lead to embolization of debris. Capture of debris by devices that provide cerebral embolic protection (CEP) may reduce the risk of stroke. METHODS: We randomly assigned patients with aortic stenosis in a 1:1 ratio to undergo transfemoral TAVR with CEP (CEP group) or without CEP (control group). The primary end point was stroke within 72 hours after TAVR or before discharge (whichever came first) in the intention-to-treat population. Disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the CEP access site, and acute kidney injury were also assessed. A neurology professional examined all the patients at baseline and after TAVR. RESULTS: A total of 3000 patients across North America, Europe, and Australia underwent randomization; 1501 were assigned to the CEP group and 1499 to the control group. A CEP device was successfully deployed in 1406 of the 1489 patients (94.4%) in whom an attempt was made. The incidence of stroke within 72 hours after TAVR or before discharge did not differ significantly between the CEP group and the control group (2.3% vs. 2.9%; difference, -0.6 percentage points; 95% confidence interval, -1.7 to 0.5; P = 0.30). Disabling stroke occurred in 0.5% of the patients in the CEP group and in 1.3% of those in the control group. There were no substantial differences between the CEP group and the control group in the percentage of patients who died (0.5% vs. 0.3%); had a stroke, a transient ischemic attack, or delirium (3.1% vs. 3.7%); or had acute kidney injury (0.5% vs. 0.5%). One patient (0.1%) had a vascular complication at the CEP access site. CONCLUSIONS: Among patients with aortic stenosis undergoing transfemoral TAVR, the use of CEP did not have a significant effect on the incidence of periprocedural stroke, but on the basis of the 95% confidence interval around this outcome, the results may not rule out a benefit of CEP during TAVR. (Funded by Boston Scientific; PROTECTED TAVR ClinicalTrials.gov number, NCT04149535.).

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.).

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.

Predictors of left ventricular reverse remodeling after percutaneous therapy for mitral regurgitation with the MitraClip system.

OBJECTIVES: To investigate the predictors and clinical impact of left ventricular reverse remodeling (LVRR) after MitraClip (MC) therapy for degenerative (DMR) and functional mitral regurgitation (FMR). BACKGROUND: MC therapy induces LVRR in patients with mitral regurgitation (MR) at high-risk for surgery. However, specific data on predictors of LVRR therapy are limited. METHODS: This study included 164 patients treated by MC implantation with complete clinical and echocardiographic evaluation at baseline, 6 months, and 12 months. LVRR was defined as a decrease of ≥10% of the left ventricular end-diastolic diameter after 12 months and was found in 49% of the patients. RESULTS: LVRR was associated with significantly reduced event rate 2 years after MC procedure. In the total cohort, multivariate regression analysis determined severe recurrent/residual MR after 12 months (p = .010, odds ratio [OR] = 0.26), male gender (p = .050, OR = 0.49) and left ventricular ejection fraction (LVEF) <20% (p = .046, OR = 0.24) as predictors of absence of LVRR. In the subgroup analysis according to etiology of MR, multivariate regression analysis revealed severe recurrent/residual MR after 12 months (p = .04, OR = 0.184) to inversely predict LVRR only in the DMR subgroup. In FMR, residual severe tricuspid regurgitation (TR) inversely predicts LVRR (p = .032, OR = 0.361). CONCLUSIONS: LVRR occurs in half of the patients after MC and is associated with reduced MACCE rates at follow-up. Combined information on residual/recurrent MR, baseline LVEF and gender predict LVRR after MC procedure. While residual/recurrent MR is the independent predictor for the absence of LVRR in DMR, in FMR only severe residual TR independently predict LVRR.

Insights on Embolic Protection, Repositioning, and Stroke: A Subanalysis of the RESPOND Study.

RESPOND is a prospective, single-arm study enrolling 1014 transcatheter aortic valve replacement (TAVR) patients. The objective of this analysis is to assess the impact of cerebral embolic protection (CEP) devices and prosthetic valve repositioning on the risk of neurologic complications in patients treated with the fully repositionable Lotus Valve in the RESPOND postmarket study. Valve repositioning and CEP use were at the operators' discretion. Stroke events were adjudicated by an independent medical reviewer. This analysis assessed the baseline differences among patients according to CEP use and valve repositioning and evaluated the neurological complications at 72 hours after TAVR, hospital discharge, and 30-day follow-up. A multivariate analysis was performed to identify the potential predictors of stroke. Of the 996 patients implanted with the Lotus Valve (mean age: 80.8 years, 50.8% female, STS score 6.0 ± 6.9), 92 cases (9.2%) used CEP. The overall rate of acute stroke/transient ischemic attack (TIA) was 3.0% at 72 hours after TAVR. The 72-hour stroke/TIA rate was 1.1% in patients who had CEP and 3.2% in those who did not. Use of CEP was associated with a 2.1% absolute reduction in the risk of acute neurological events (relative risk reduction: 65.6%), although the difference was not statistically significant (p=0.51). Repositioning of the Lotus Valve occurred in 313/996 procedures (31.4%). The 72-hour rate of stroke/TIA was similar in patients who had valve repositioning (2.9%) compared with those who did not (3.1%; p=0.86). The selective use of a CEP device in the RESPOND study was associated with a nonsignificantly lower risk for stroke within 72 hours. The use of the repositioning feature of the Lotus Valve did not increase the stroke risk.

Rate of peri-procedural stroke observed with cerebral embolic protection during transcatheter aortic valve replacement: a patient-level propensity-matched analysis.

AIMS: The role of cerebral embolic protection (CEP) in transcatheter aortic valve replacement (TAVR) remains controversial. Randomized trials have not been powered to demonstrate a reduction in stroke rates. The aim of this patient level pooled analysis was to validate the impact of the dual-filter CEP device (Claret Medical Inc., CA, USA) on peri-procedural stroke in a large number of TAVR patients. METHODS AND RESULTS: Patients from the SENTINEL US IDE trial were combined with the CLEAN-TAVI and SENTINEL-Ulm study in a patient level pooled analysis (N = 1306). Propensity score matching was performed to adjust for possible confounders. The primary endpoint was procedural stroke within 72 h post-TAVR according to Valve Academic Research Consortium-2 criteria. The secondary endpoint was the combination of all-cause mortality or all-stroke within 72 h after TAVR. In the propensity-matched population, 533 patients underwent TAVR without CEP and 533 patients underwent TAVR with CEP. TAVR patients without vs. with CEP were similar with respect to baseline characteristics, procedural approach, or valve type. In patients undergoing TAVR with dual-filter CEP, procedural all-stroke was significantly lower compared with unprotected procedures [1.88% vs. 5.44%, odds ratio 0.35, 95% confidence interval (CI) 0.17-0.72, relative risk reduction 65%, P = 0.0028]. In addition, all-cause mortality and all-stroke were significantly lower (2.06% vs. 6.00%, odds ratio 0.34, 95% CI 0.17-0.68, relative risk reduction 66%, P = 0.0013). CONCLUSION: Our findings suggest that TAVR with the dual-filter CEP device is associated with a significant lower rate of peri-procedural stroke compared with unprotected procedures. However, randomized trials are still needed to clarify this issue.

Long-term clinical outcome of persistent left bundle branch block after transfemoral aortic valve implantation.

OBJECTIVE: The impact of persistent left bundle-branch block (pLBBB) on long-term clinical outcome remains to be determined. BACKGROUND: New-onset of pLBBB occurs frequently after transfemoral aortic valve implantation (TAVI). METHODS: Seven hundred and seven consecutive patients who underwent TAVI were analyzed for baseline and procedural characteristics and clinical outcome in an up to 2-year follow-up. Patients were divided into either a group with pLBBB until hospital discharge or a group without LBBB. We performed propensity-score matching and analyzed baseline characteristics, procedural data and clinical outcome of both groups. Patients received balloon-expandable valves in 56.4%, mechanically expandable valves in 37.5%, and self-expandable valves in 6.3%. RESULTS: A new-onset, pLBBB was observed in 47.5% of patients after TAVI. The implantation of a mechanically expandable valve was associated with higher rate of pLBBB (54.2% vs. 20.8%, P < 0.001), whereas implantation of a balloon-expandable valve was associated with lower incidence of pLBBB (39.8% vs. 73.1%, P < 0.001). Deeper ventricular implantation at left-coronary side led to higher rates of pLBBB (7.5 ± 2.5 vs. 6.7 ± 2.6 mm, P < 0.001). The occurrence of pLBBB was associated with higher rates of permanent pacemaker implantation (40.9% vs. 15.9%, P < 0.001). By multivariate analysis, implantation of a mechanically expandable valve (Boston Scientific Lotus valve) was identified as independent predictor of occurrence of pLBBB (odds ratio 4.7, confidence interval 3.2-7.0, P < 0.001). In the 2-year follow-up, there were no significant differences between "pLBBB" and "no LBBB"-groups regarding mortality and rehospitalization due to heart failure. CONCLUSIONS: The occurrence of pLBBB is associated with the choice of valve type and implantation depth and requires significantly higher rates of permanent pacemaker implantations. Importantly, there are no differences in the 2-year follow-up regarding mortality and rehospitalization due to heart failure.

Clinical results of bioresorbable drug-eluting scaffolds in short and long coronary artery lesions using the PSP technique.

BACKGROUND: Data on bioresorbable vascular scaffolds (BVS) for the treatment of long lesions are limited. We studied the use of BVS-Absorb in routine clinical practice and compared the outcome of long lesions with short lesions. Implantation of drug-eluting scaffolds without PSP-technique (predilation, proper sizing and postdilation) is associated with an increased thrombotic risk. We compared the long-term outcome up to 36 months of patients with short (< 20 mm) and long (≥20 mm) coronary artery lesions after implantation of bioresorbable vascular scaffolds (BVS) via PSP-technique. METHODS: Three hundred twenty-six patients with 424 lesions were enrolled in this prospective study and underwent percutaneous coronary intervention with the Absorb BVS. Clinical follow-up was scheduled after 12, 24 and 36 months. In all lesions the PSP-technique was used. The device oriented composite endpoint (DOCE) was defined as cardiac death, myocardial infarction (MI) not clearly related to a non-target vessel and target lesion revascularization (TLR). RESULTS: Kaplan-Meier estimates for DOCE after 12 months were 2.63% for short lesions and 8.09% for long lesions (p = 0.0131), 5.51% vs. 11.35% (p = 0.0503) after 24 months and 8.00% vs. 18.00% (p = 0.0264) after 36 months of clinical follow-up. Kaplan-Meier estimates for TLR after 12 months were 1.46% for short and 7.69% for long lesions (p = 0.0012), 2.06% vs. 8.75% after 24 months (p = 0.0027) and 4.96% vs. 9.59% after 36 months of follow-up (p = 0.0109). Scaffold thrombosis rates were low. CONCLUSIONS: In long lesions compared to short ones the bioresorbable scaffold Absorb implanted with the proper PSP technique Absorb has significant higher rates of DOCE. THE LEVEL OF EVIDENCE: Is 3 (non-random sample).

Intra-aortic balloon counterpulsation pump in heart failure patients during MitraClip implantation-A propensity-score matched analysis.

OBJECTIVES: To analyze 30-day and 6-month results after percutaneous mitral valve repair using an IABP as circulatory support. BACKGROUND: The use of intra-aortic balloon counterpulsation pump extended the spectrum of cardiovascular interventions. METHODS: Since 2014, 17 patients of 365 patients (4.7%) at our center received an IABP during MitraClip implantation procedure. We compare the periprocedural results to a control group of 17 patients treated with MitraClip without an IABP support. To adjust for differences of baseline characteristics a propensity-score matching for age, baseline blood pressure, preoperative EuroSCORE II and left ventricular ejection fraction was performed. The decision for prophylactic implantation of an IABP was at the discretion of the interventionalist. For both groups, clinical results up to 6 months were evaluated. RESULTS: The IABP group had higher NT-pro BNP levels at baseline and increased left ventricular diameters. The procedure was more often categorized as "urgent" due to refractory heart failure in the IABP group. All procedures were carried out successfully, thereby achieving a sufficient MR reduction in both groups. Length of hospital stay was significantly longer in the IABP group 11.7 ± 14 days (compared to 6.5 ± 2.9 days in the No IABP group, P < 0.01). All patients in both groups had an event-free 30-day follow-up. MACCE rate was higher in the IABP group compared to the No IABP group (47.1% vs. 23.5%, P = 0.14). CONCLUSION: Insertion of an IABP during MitraClip procedure might be a feasible option to achieve comparable results and may provide additional safety and procedural hemodynamic stability in the setting of high-risk percutaneous mitral valve repair.

Predictors of permanent pacemaker implantation after transfemoral aortic valve implantation with the Lotus valve.

BACKGROUND: Permanent pacemaker implantation (PPMI) after transcatheter aortic valve implantation is of high clinical relevance, but PPMI rates differ widely between valve types. Although the Lotus valve can be repositioned, reported rates for PPMI are high. The predictors of PPMI after Lotus valve implantation have not been defined yet. METHODS: We analyzed the impact of preexisting conduction disturbances, depth of implantation, oversizing, and amount of calcification on PPMI in 216 patients with severe symptomatic aortic stenosis underdoing Lotus valve implantation. RESULTS: PPMI was required in 39.8% of patients. Patients with need for PPMI compared with patients without need for PPMI had more often the following criteria: male gender (P=.035); preprocedural right bundle-branch block (RBBB) (16.3% vs 0, P<.001); atrioventricular (AV) block first degree (26.7% vs 10.1%, P=.004); higher calcium volume of the left coronary cusp (63.1±87.5 mm3 vs 42.8±49.3 mm3, P=.05); and deeper valve implantation at right coronary (P=.011), noncoronary (P=.026), and left coronary (P=.012) position. Oversizing in relation to annulus and left ventricular outflow tract did not have an impact on need for PPMI. By multiple regression analysis, preprocedural AV block first degree (P=.005), RBBB (P<.001), and depth of implantation (P=.006) were independent risk factors for need of PPMI. CONCLUSIONS: In patients with severe aortic stenosis receiving transfemoral Lotus valve, preexisting AV block first degree, RBBB, and implantation depth are independent predictors of PPMI, highlighting the importance of careful valve positioning.

Transfemoral valve-in-valve implantation for degenerated bioprosthetic aortic valves using the new balloon-expandable Edwards Sapien 3 valve.

BACKGROUND: Surgical aortic bioprosthetic valves deteriorate 10 to 20 years after operation. Valve-in-valve implantation with first generation transcatheter aortic valve implantation (TAVI) devices has shown to be feasible. We report a first case series with the new Edwards Sapien 3 valve for transfemoral aortic valve-in-valve implantation. METHODS AND RESULTS: Nine patients underwent valve-in-valve-TAVI with the Edward Sapien 3 valve. Seven patients presented with severe aortic stenosis and two patients with severe aortic insufficiency of surgical aortic bioprosthesis. Procedures were performed in local anaesthesia under fluoroscopic guidance with pre-procedural 256 multislice computed tomography for procedural planning. In all patients the Edwards Sapien 3 was successfully implanted decreasing the mean echocardiographic gradient from 42 ± 22mmHg to 18 ± 7mmHg (p < 0.01). Device success according to VARC 2 criteria was achieved in 8 out of 9 patients. There was no death, coronary obstruction, use of second valve or need for post-dilation. Furthermore there were no access-site complications, no minor or major bleedings or vascular injury. Two patients required pacemaker implantation within the first 7 days after valve-in-valve TAVI. Post-procedural echocardiography demonstrated no or trace aortic regurgitation. Early safety events within 30 days according to VARC-2 definition occurred in 1 patient. CONCLUSIONS: The Edwards Sapien 3 valve for treatment of failed surgical bioprostheses is feasible and is associated with no relevant post-procedural aortic regurgitation and a low risk of access site complications. © 2016 Wiley Periodicals, Inc.

Impact of Insulin-Treated Compared to Non-Insulin-Treated Diabetes Mellitus on Outcome of Percutaneous Coronary Intervention with Drug-Coated Balloons versus Drug-Eluting Stents in De Novo Coronary Artery Disease: The Randomized BASKET-SMALL 2 Trial.

BACKGROUND: We evaluated the outcome of PCI of de novo stenosis with drug-coated balloons (DCB) versus drug-eluting stents (DES) in patients with insulin-treated diabetes mellitus (ITDM) versus non-insulin-treated diabetes mellitus (NITDM). METHODS: Patients were randomized in the BASKET-SMALL 2 trial to DCB or DES and followed over 3 years for MACE (cardiac death, non-fatal myocardial infarction [MI], and target vessel revascularization [TVR]). Outcome in the diabetic subgroup (n = 252) was analyzed with respect to ITDM or NITDM. RESULTS: In NITDM patients (n = 157), rates of MACE (16.7% vs. 21.9%, hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.29-1.58, p = 0.37), death, non-fatal MI, and TVR (8.4% vs. 14.5%, HR 0.30, 95% CI 0.09-1.03, p = 0.057) were similar between DCB and DES. In ITDM patients (n = 95), rates of MACE (DCB 23.4% vs. DES 22.7%, HR 1.12, 95% CI 0.46-2.74, p = 0.81), death, non-fatal MI, and TVR (10.1% vs. 15.7%, HR 0.64, 95% CI 0.18-2.27, p = 0.49) were similar between DCB and DES. TVR was significantly lower with DCB versus DES in all diabetic patients (HR 0.41, 95% CI 0.18-0.95, p = 0.038). CONCLUSIONS: DCB compared to DES for treatment of de novo coronary lesions in diabetic patients was associated with similar rates of MACE and numerically lower need for TVR both for ITDM and NITDM patients.

Sex Differences Among Patients Receiving Edoxaban vs Vitamin K Antagonist for Atrial Fibrillation After TAVR.

Background: In the ENVISAGE-TAVI AF (Edoxaban vs Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation-Atrial Fibrillation) trial, edoxaban was noninferior to vitamin K antagonists (VKA) for a composite outcome of ischemic and bleeding complications but increased major bleeding in patients with atrial fibrillation after successful transcatheter aortic valve replacement. Women are at higher risk of bleeding and stroke than men after transcatheter aortic valve replacement. It is unclear whether the effect of edoxaban on these complications varies in relation to sex. Objectives: This study was to assess the effect of edoxaban vs VKA according to sex in the ENVISAGE-TAVI AF trial. Methods: The primary outcomes were net adverse cardiovascular events (NACE) and major bleeding, assessed considering the effective time on study medication (safety analysis). Results: Out of 1,377 patients, 658 (47.8%) were women. Risks for ischemic and major bleeding outcomes were similar between women and men. Edoxaban compared to VKA was associated with a similar risk of NACE in women (HR: 1.16; 95% CI: 0.81-1.65) and men (HR: 1.08; 95% CI: 0.76-1.53; P for interaction = 0.820) and a higher risk of major bleeding in both sexes (P for interaction = 0.170). The risk increase of major bleeding was attenuated in women (HR: 1.11; 95% CI: 0.69-1.79) as compared to men (HR: 1.75; 95% CI: 1.07-2.85). There were no treatment-related differences for ischemic complications in both sexes. Conclusions: Edoxaban compared to VKA was associated with a similar risk of NACE and higher risk of major bleeding in both sexes. The increase in bleeding complications with edoxaban was attenuated in women.

Efficacy and Safety of ELOM-080 as Add-On Therapy in COVID-19 Patients with Acute Respiratory Insufficiency: Exploratory Data from the Prospective Placebo-Controlled COVARI Trial.

INTRODUCTION: Enhancement of mucociliary clearance (MCC) might be a potential target in treating COVID-19. The phytomedicine ELOM-080 is an MCC enhancer that is used to treat inflammatory respiratory diseases. PATIENTS/METHODS: This randomised, double-blind exploratory study (EudraCT number 2020-003779-17) evaluated 14 days' add-on therapy with ELOM-080 versus placebo in patients with COVID-19 hospitalised with acute respiratory insufficiency. RESULTS: The trial was terminated early after enrolment of 47 patients as a result of poor recruitment. Twelve patients discontinued prematurely, leaving 35 in the per-protocol set (PPS). Treatment with ELOM-080 had no significant effect on overall clinical status versus placebo (p = 0.49). However, compared with the placebo group, patients treated with ELOM-080 had less dyspnoea in the second week of hospitalisation (p = 0.0035), required less supplemental oxygen (p = 0.0229), and were more often without dyspnoea when climbing stairs at home (p < 0.0001). CONCLUSION: These exploratory data suggest the potential for ELOM-080 to improve respiratory status during and after hospitalisation in patients with COVID-19.

Outcomes After Transcatheter Aortic Valve Implantation in Men Versus Women.

Gender-based differences in outcomes after successful transcatheter aortic valve implantation (TAVI) in patients without an indication for oral anticoagulation have not been well studied. We aim to evaluate gender-based differences in clinical outcomes after TAVI. In the present analysis of the GALILEO (Global study comparing a rivaroxaban-based antithrombotic strategy to an antiplatelet-based strategy after transcatheter aortic valve replacement to optimize clinical outcomes) trial, patients with symptomatic severe aortic stenosis and who underwent successful TAVI were stratified by gender. The primary outcome was major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause mortality or thromboembolic events (including any stroke, myocardial infarction, symptomatic valve thrombosis, systemic embolism, deep-vein thrombosis, or pulmonary embolism). Major bleeding was defined as a composite of major, life-threatening, or disabling Valve Academic Research Consortium-2 bleeding. Of 1,644 patients, 813 were female, and 831 were male. At baseline, female patients were older and at higher surgical risk (Society of Thoracic Surgeons risk score: 4.7 ± 3.6 versus 3.6 ± 3.0, p <0.0001) than male patients. After adjustment for differences in baseline clinical and procedural parameters, female patients had lower rates of MACCE (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.49 to 0.96), all-cause mortality (HR 0.54, 95% CI 0.34 to 0.87), and noncardiovascular mortality (HR 0.33, 95% CI 0.15 to 0.75) at a median of 17 months of follow-up. By landmark analyses, these differences appeared to emerge with a longer follow-up time. No significant differences in major, life-threatening, or disabling bleeding, cardiovascular mortality, and stroke were noted. In conclusion, compared with male patients, female patients with severe symptomatic aortic stenosis had a lower risk of MACCE and mortality but a similar risk of bleeding events after TAVI.

Impact of Diabetes on Outcome With Drug-Coated Balloons Versus Drug-Eluting Stents: The BASKET-SMALL 2 Trial.

OBJECTIVES: The study sought to evaluate the impact of diabetes mellitus on 3-year clinical outcome in patients undergoing drug-coated balloon (DCB) or drug-eluting stent (DES) treatment for de novo lesions. BACKGROUND: For treatment of de novo coronary small vessel disease, DCBs are noninferior to DES. METHODS: In this prespecified analysis of a multicenter, randomized, noninferiority trial, including 758 patients with de novo lesions in coronary vessels <3 mm who were randomized 1:1 to DCB or DES and followed over 3 years for major adverse cardiac events (MACE) (cardiac death, nonfatal myocardial infarction [MI], and target vessel revascularization [TVR]), outcome was analyzed regarding the presence or absence of diabetes mellitus. RESULTS: In nondiabetic patients (n = 506), rates of MACE (DCB 13.0% vs DES 11.5%; hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 0.73-2.09; P = 0.43), cardiac death (2.8% vs 2.9%; HR: 0.97; 95% CI: 0.32-2.92; P = 0.96), nonfatal MI (5.1% vs 4.8%; HR: 1.00; 95% CI: 0.44-2.28; P = 0.99), and TVR (8.8% vs 6.1%; HR: 1.64; 95% CI: 0.83-3.25; P = 0.16) were similar. In diabetic patients (n = 252), rates of MACE (19.3% vs 22.2%; HR: 0.82; 95% CI: 0.45-1.48; P = 0.51), cardiac death (8.8% vs 5.9%; HR: 2.01; 95% CI: 0.76-5.31; P = 0.16), and nonfatal MI (7.1% vs 9.8%; HR: 0.55; 95% CI: 0.21-1.49; P = 0.24) were similar in DCB and DES. TVR was significantly lower with DCBs vs DES (9.1% vs 15.0%; HR: 0.40; 95% CI: 0.17-0.94; P = 0.036; P = 0.011 for interaction). CONCLUSIONS: The rates of MACE are similar in DCBs and DES in de novo coronary lesions of diabetic and nondiabetic patients. In diabetic patients, need for TVR was significantly lower with DCB versus DES. (Basel Stent Kosten Effektivitäts Trial Drug Eluting Balloons vs Drug Eluting Stents in Small Vessel Interventions [BASKET-SMALL2]; NCT01574534).

Ticagrelor or Prasugrel in Patients With Acute Coronary Syndrome in Relation to Estimated Glomerular Filtration Rate.

OBJECTIVES: The aim of this study was to assess the safety and efficacy of ticagrelor versus prasugrel for patients with acute coronary syndrome (ACS) according to their estimated glomerular filtration rates (eGFRs). BACKGROUND: The outcomes of ticagrelor versus prasugrel in patients with ACS according to eGFR have not been defined. METHODS: Patients (n = 4,012) were categorized into 3 groups: low eGFR (<60 mL/min/1.73 m2), intermediate eGFR (≥60 and <90 mL/min/1.73 m2), and high eGFR (≥90 mL/min/1.73 m2). The primary endpoint was a composite of all-cause death, myocardial infarction, and stroke; the secondary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding, both at 1 year. RESULTS: Patients with low eGFRs had a higher risk for the primary endpoint compared with patients with intermediate eGFRs (adjusted HR: 1.89; 95% CI: 1.46-2.46]) and those with high eGFRs (adjusted HR: 2.33; 95% CI: 1.57-3.46). A risk excess for low eGFR was also observed for bleeding (adjusted HR: 1.55 [95% CI: 1.12-2.13] vs intermediate eGFR; adjusted HR: 1.59 [95% CI: 1.01-2.50] vs high eGFR). However, eGFR did not affect the relative efficacy and safety of ticagrelor versus prasugrel. In patients with low eGFR, the primary endpoint occurred in 20.5% with ticagrelor and in 14.7% with prasugrel (HR: 1.47; 95% CI: 1.04-2.08; P = 0.029); there was no significant difference in bleeding. CONCLUSIONS: These results show that among patients with ACS, reduction of eGFR is associated with increased risk for ischemic and bleeding events but has no significant impact on the relative efficacy and safety of ticagrelor versus prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800).

Apixaban: An Update of the Evidence for Its Place in the Prevention of Stroke in Patients with Atrial Fibrillation.

Oral anticoagulant therapy for stroke prevention in atrial fibrillation patients has been remarkably changed by the introduction of non-vitamin k oral anticoagulants (NOAC). Apixaban was the third NOAC introduced to clinical practice. Aim was to outline the current evidence for Apixaban in stroke prevention in atrial fibrillation patients in the randomized trials and real-world data. Apixaban has been shown to be superior to warfarin in preventing stroke and systemic embolism and causes significantly less major bleeding based on large randomized trials. These data are confirmed in real-world studies. Apixaban has been shown to be safe and effective in atrial fibrillation patients in acute coronary syndrome or undergoing PCI in combination with a P2Y12 inhibitor. Regarding expanded use of apixaban also in valvular heart disease patients, there is still missing knowledge in relation to the safety and efficacy of apixaban which is being addressed by ongoing randomized clinical trials.

A hierarchical algorithm for multicentric matched cohort study designs.

OBJECTIVE: Lack of structural equality is a major issue to be addressed in observational studies. Their major disadvantage of these studies compared to randomized controlled trials is the vulnerability towards confounding, but they often better mirror real world patients and, therefore, entail an increased external validity. Numerous approaches have been developed to account for confounding in observational research, including multiple regression, subgroup analysis and matched cohort designs. The latter has been often described as a useful tool if large control data sets are available. METHODS: In this paper we present a hierarchical matching algorithm entailing two stages which enables a multicentric matched cohort study to be conducted. In particular, the algorithm defines the matching strategy as a combination of exact matching and a subsequent consideration of further matching variables to be controlled using a distance measure (e.g. the propensity score). RESULTS: The algorithm is applied to a study in interventional cardiology and demonstrates high flexibility and usefulness with regard to the aim of finding comparable cases of exposed and non-exposed patients from observational data. The algorithm increased structural equality by balancing the most important covariates which might be of different importance for the matching process. CONCLUSION: The implementation of the algorithm in the statistical software SAS offers high flexibility regarding an application to various data analysis projects. Specifically, it provides a broader range of features (e.g. diverse distance measures) when compared to other existing solutions for conducting matched cohort analyses.

Long-Term Outcome After Percutaneous Closure of Patent Foramen Ovale for Cryptogenic Ischemic Events.

BACKGROUND: Randomized trials for percutaneous closure of patent foramen ovale (PFO) have demonstrated a lower rate of recurrent ischemic events compared with medical therapy. The aim of this long-term follow-up analysis was to validate the impact of PFO closure on recurrent ischemic events. METHODS AND RESULTS: A total of 570 patients were enrolled. Patients were followed for recurrent ischemic events for a median of 7.2 years. Mean age at the time of procedure was 49.3 ± 13.1 years. PFO closure was performed with the Amplatzer occluder in 44.9% of patients and with BioStar, Cardia or Premere occluders in 55.1% of patients. Within 10 years of follow-up, recurrent ischemic stroke occurred in 5.1% of patients in the Amplatzer group vs 7.6% with the other occluders (log rank P=.61). There was no difference in the rate of recurrent transient ischemic attack (1.86% vs 1.51%; log rank P=.52) or all-cause mortality (2.9% vs 3.8%; log rank P=.84) between the two groups, in patients with or without an atrial septal aneurysm or with respect to grade of preprocedural shunt. Recurrent stroke was lower in patients <45 years old at the time of occluder implantation (hazard ratio, 4.14; 95% confidence interval, 0.94-18.8; log rank P=.05). CONCLUSION: In this long-term follow-up after PFO closure, the rate of recurrent stroke was low. There were no significant differences in event rates between different occluder devices, the existence of an atrial septal aneurysm, or grade of preprocedural shunt at baseline. Patients <45 years old had lower rates of recurrent ischemic stroke.