Continued non-vitamin K antagonist oral anticoagulants versus vitamin K antagonists during transcatheter aortic valve implantation.

BACKGROUND: One-third of patients undergoing transcatheter aortic valve implantation (TAVI) have an indication for long-term oral anticoagulation (OAC). AIMS: We aimed to investigate whether continued non-vitamin K antagonist oral anticoagulant (NOAC) therapy compared with continued vitamin K antagonist (VKA) therapy during TAVI is equally safe and effective.  Methods: Consecutive patients on OAC with either NOAC or VKA undergoing transfemoral TAVI at five European centres were enrolled. The primary outcome measure was a composite of major/life-threatening bleeding, stroke, and all-cause mortality at 30 days. RESULTS: In total, 584 patients underwent TAVI under continued OAC with 294 (50.3%) patients receiving VKA and 290 (49.7%) patients receiving NOAC. At 30 days, the composite primary outcome had occurred in 51 (17.3%) versus 36 (12.4%) patients with continued VKA and with continued NOAC, respectively (odds ratio [OR] 0.68, 95% confidence interval [CI]: 0.43-1.07; p=0.092). Rates of major/life-threatening bleeding (OR 0.87, 95% CI: 0.52-1.47; p=0.606) and stroke (OR 1.02, 95% CI: 0.29-3.59; p=0.974) were not different between groups. In a multivariate Cox regression analysis, continued NOAC, compared with continued VKA, was associated with a lower risk for all-cause 1-year mortality (hazard ratio [HR] 0.61, 95% CI: 0.37-0.98; p=0.043). The analysis of the propensity score-matched cohort revealed similar results. CONCLUSIONS: Continued NOAC compared with continued VKA during TAVI led to comparable outcomes with regard to the composite outcome measure indicating that continued OAC with both drugs is feasible. These hypothesis-generating results need to be confirmed by a dedicated randomised controlled trial.

Left atrial appendage closure versus medical therapy in patients with atrial fibrillation: the APPLY study.

AIMS: Left atrial appendage closure (LAAC) with AMPLATZER occluders is used for stroke prevention in atrial fibrillation (AF). Net clinical benefit compared to medical therapy has not been tested. The aim of this study was to test whether long-term clinical outcome after LAAC with AMPLATZER occluders may be similar to medical therapy. METHODS AND RESULTS: Five hundred consecutive patients who underwent LAAC with AMPLATZER occluders were compared to 500 patients with medical therapy by propensity score matching. The primary efficacy endpoint was a composite of stroke, systemic embolism and cardiovascular/unexplained death. The primary safety endpoint consisted of major procedural adverse events and major bleedings. For assessment of net clinical benefit, all of the above-mentioned hazards were combined. After 2,645 patient-years at a mean follow-up of 2.7±1.5 years, the primary efficacy endpoint was reached by 75/1,342, 5.6% in the LAAC group versus 102/1,303, 7.8% per 100 patient-years (hazard ratio [HR] 0.70, 95% confidence interval [CI]: 0.53-0.95, p=0.026). The primary safety endpoint occurred in 48/1,342, 3.6% versus 60/1,303, 4.6% per 100 patient-years (HR 0.80, 95% CI: 0.55-1.18, p=0.21), and the combined hazard endpoint in 109/1,342, 8.1% versus 142/1,303, 10.9% per 100 patient-years (HR 0.76, 95% CI: 0.60-0.97, p=0.018). Patients receiving LAAC demonstrated lower rates of both all-cause and cardiovascular mortality (111/1,342, 8.3% vs 151/1,303, 11.6% per 100 patient-years [HR 0.72, 95% CI: 0.56-0.92, p=0.005] and 54/1,342, 4.0% vs 84/1,303, 6.5% per 100 patient-years [HR 0.64, 95% CI: 0.46-0.89, p=0.007]). CONCLUSIONS: LAAC with AMPLATZER devices showed a net clinical benefit over medical therapy by superior efficacy, similar safety and a benefit in all-cause and cardiovascular mortality.

Left atrial appendage closure for prevention of death, stroke, and bleeding in patients with nonvalvular atrial fibrillation.

Nonvalvular atrial fibrillation (AF) is the most frequent arrhythmia with a prevalence of 1%-2% in the general population. Its prevalence increases with age and its diagnosis benefits of improvement and simplification of technologies for its detection. Today, AF affects approximately 7% of individuals age>65years and 15%-20% of octogenarians. Due to stasis and activation of coagulation in a fibrillating atrium, patients are at increased risk of thromboembolism, in particular ischemic stroke, with an overall stroke risk of 5% per year. Since the left atrium itself is round and smooth-walled, thrombi typically do not form there, but almost exclusively in the left atrial appendage (LAA), a blind sac-like heterogeneous structure trabeculated by pectinate muscles. In the past five decades, oral anticoagulation (OAC) with vitamin K antagonists (VKA) has been the state-of-the art treatment to prevent stroke and systemic embolism from thrombi in AF. In the last decade, nonvitamin K dependant oral anticoagulants (NOAC) have been shown to be overall superior to VKA with respect to efficacy and safety in large trials and registries. Given the safety issues of indefinite OAC with either VKA or NOAC, it is plausible to consider left atrial appendage closure (LAAC) as an alternative strategy for prevention of all three catastrophes for patients with AF on anticoagulation: death, stroke or other systemic embolization, and bleeding. In the past years, LAAC has been compared to VKA in prospective randomized trials, yielding superior results regarding efficacy and non-inferiority regarding safety in the mid-term. Today, the decision to provide the most appropriate treatment for a patient with AF (OAC, NOAC, or LAAC) is complex and needs to be individualized. This review provides a comprehensive update on the current state of LAAC in the field of prevention of death, stroke and bleedings in patients suffering from nonvalvular AF. We describe the pathophysiology of the LAA with regard to stroke, elucidate the evidence and limitations of anticoagulation as the classical treatment paradigm, and review devices and techniques for LAAC. Most importantly, the current clinical evidence on efficacy and safety is outlined and finally, contemporary recommendations for patient selection are provided.

Infective endocarditis following transcatheter aortic valve replacement: comparison of balloon- versus self-expandable valves

BACKGROUND: No data exist about the characteristics of infective endocarditis (IE) post-transcatheter aortic valve replacement (TAVR) according to transcatheter valve type. We aimed to determine the incidence, clinical characteristics, and outcomes of patients with IE post-TAVR treated with balloon-expandable valve (BEV) versus self-expanding valve (SEV) systems. METHODS: Data from the multicenter Infectious Endocarditis After TAVR International Registry was used to compare IE patients with BEV versus SEV. RESULTS: A total of 245 patients with IE post-TAVR were included (SEV, 47%; BEV, 53%). The timing between TAVR and IE was similar between groups (SEV, 5.5 [1.2-15] months versus BEV, 5.3 [1.7-11.4] months; P=0.89). Enterococcal IE was more frequent in the SEV group (36.5% versus 15.4%; P<0.01), and vegetation location differed according to valve type (stent frame, SEV, 18.6%; BEV, 6.9%; P=0.01; valve leaflet, SEV, 23.9%; BEV, 38.5%; P=0.01). BEV recipients had a higher rate of stroke/systemic embolism (20.0% versus 8.7%, adjusted OR: 2.46, 95% CI: 1.04-5.82, P=0.04). Surgical explant of the transcatheter valve (SEV, 8.7%; BEV, 13.8%; P=0.21), and in-hospital death at the time of IE episode (SEV, 35.6%; BEV, 37.7%; P=0.74) were similar between groups. After a mean follow-up of 13±12 months, 59.1% and 54.6% of the SEV and BEV recipients, respectively, had died (P=0.66). CONCLUSIONS: The characteristics of IE post-TAVR, including microorganism type, vegetation location, and embolic complications but not early or late mortality, differed according to valve type. These results may help to guide the diagnosis and management of IE and inform future research studies in the field. (AU)

The Learning Curve and Annual Procedure Volume Standards for Optimum Outcomes of Transcatheter Aortic Valve Replacement: Findings From an International Registry

OBJECTIVES: The authors aimed to determine the procedural learning curve and minimum annual institutional volumes associated with optimum clinical outcomes for transcatheter aortic valve replacement (TAVR).BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a complex procedure requiring significant training and experience for successful outcome. Despite increasing use of TAVR across institutions, limited information is available for its learning curve characteristics and minimum annual volumes required to optimize clinical outcomes. METHODS: The study collected data for patients at 16 centers participating in the international TAVR registry since initiation of the respective TAVR program. All cases were chronologically ordered into initial (1 to 75), early (76 to 150), intermediate (151 to 225), high (226 to 300), and very high (>300) experience operators for TAVR learning curve characterization. In addition, participating institutions were stratified by annual TAVR case volume into low-volume (<50), moderate-volume (50 to 100), and high-volume (>100) groups for comparative analysis. Procedural and 30-day clinical outcomes were collected and multivariate regression analysis performed for 30-day mortality and the early safety endpoint. RESULTS: A total of 3,403 patients comprised the study population. On multivariate analysis, all-cause mortality was significantly higher for initial (odds ratio [OR]: 3.83; 95% confidence interval [CI]: 1.93 to 7.60), early (OR: 2.41; 95%CI: 1.51 to 5.03), and intermediate (OR: 2.53; 95% CI: 1.19 to 5.40) experience groups compared with the very high experience operators. In addition, the early safety endpoint was significantly worse for all experience groups compared with the very high experience operators. Low annual volume (<50) TAVR institutions had significantly higher all-cause30-day mortality (OR: 2.70; 95% CI: 1.44 to 5.07) and worse early safety endpoint (OR: 1.60; 95% CI: 1.17 to 2.17) compared with the moderate- and high-volume groups. There was no difference in patient outcomes between intermediate and high annual volume groups. CONCLUSIONS: TAVR procedures display important learning curve characteristics with both greater procedural safety and a lower mortality when performed by experienced operators. In addition, TAVR performed at low annual volume (<50 procedures) institutions is associated with decreased procedural safety and higher patient mortality. These findings have important implications for operator training and patient care at centers performing TAVR.

Impact of Preexisting Left Bundle Branch Block in Transcatheter Aortic Valve Replacement Recipients

BACKGROUND: The impact of preexisting left bundle branch block (LBBB) in transcatheter aortic valve replacement (TAVR) recipients is unknown. The aim of this study was to determine the impact of preexisting LBBB on clinical outcomes after TAVR. METHODS AND RESULTS: This multicenter study evaluated 3404 TAVR candidates according to the presence or absence of LBBB on baseline ECG. TAVR complications and causes of death were defined according to Valve Academic Research Consortium-2 definitions. Follow-up outpatient visits or telephone interviews were conducted at 30 days, 12 months, and yearly thereafter. Echocardiography examinations were performed at baseline, at hospital discharge, and at 1-year follow-up. Preexisting LBBB was present in 398 patients (11.7%) and was associated with an increased risk of permanent pacemaker implantation (PPI; 21.1% versus 14.8%; adjusted odds ratio, 1.51; 95% CI, 1.12­2.04) but not death (7.3% versus 5.5%; adjusted odds ratio, 1.33; 95% CI, 0.84­2.12) at 30 days. At a mean follow-up of 22±21 months, there were no differences between patients with and without preexisting LBBB in overall mortality (adjusted hazard ratio, 0.94; 95% CI, 0.75­1.18) and cardiovascular mortality (adjusted hazard ratio, 0.90; 95% CI, 0.68­1.21). In a subanalysis of 2421 patients without PPI at 30 days and with complete follow-up about the PPI, preexisting LBBB was not associated with an increased risk of PPI or sudden cardiac death. Patients with preexisting LBBB had a lower left ventricular ejection fraction (LVEF) at baseline and at 1-year follow-up (P <0.001 for both), but those with low LVEF exhibited a similar increase in LVEF over time after TAVR compared with patients with no preexisting LBBB (P=0.327). CONCLUSIONS: Preexisting LBBB significantly increased the risk of early (but not late) PPI after TAVR, without any significant effect on overall mortality or cardiovascular mortality. Preexisting LBBB was associated with lower LVEF pre-TAVR but did not prevent an increase in LVEF post-TAVR similar to patients without LBBB.

Clinical impact of baseline right bundle branch block in patients undergoing transcatheter aortic valve replacement

This study sought to assess the influence of baseline right bundle branch block (RBBB) on all-cause and cardiovascular mortality as well as sudden cardiac death (SCD) among patients undergoing transcatheter aortic valve replacement (TAVR). Few data exist regarding the late clinical impact of pre-existing RBBB in TAVR recipients. A total of 3,527 patients (mean age 82 8 years, 50.1% men) were evaluated according to the presence of RBBB on baseline electrocardiography. Intraventricular conduction abnormalities were classified according to the American Heart Association, American College of Cardiology Foundation, and Heart Rhythm Society recommendations for standardization and interpretation of the electrocardiogram. TAVR complications and causes of death were defined according to Valve Academic Research Consortium 2 definitions. RBBB was present on baseline electrocardiography in 362 patients (10.3%) and associated with higher 30-day rates of permanent pacemaker implantation (PPI) (40.1% vs. 13.5%; p < 0.001) and death (10.2% vs. 6.9%; p » 0.024). At a mean follow-up of 20 18 months, pre-existing RBBB was independently associated with all-cause mortality (hazard ratio [HR]: 1.31; 95% confidence interval [CI]: 1.06 to 1.63; p » 0.014) and cardiovascular mortality (HR: 1.45; 95% CI: 1.11 to 1.89; p » 0.006) but not with SCD (HR: 0.71; 95% CI: 0.22 to 2.32; p » 0.57). Patients with pre-existing RBBB and without PPI at discharge from the index hospitalization had the highest 2-year risk for cardiovascular death (27.8%; 95% CI: 20.9% to 36.1%; log-rank p » 0.007). In a subanalysis of 1,245 patients without PPI at discharge from the index hospitalization and with complete follow-up regarding the need for PPI, pre-existing RBBB was independently associated with the composite of SCD and PPI (HR: 2.68; 95% CI: 1.16 to 6.17; p » 0.023)

Association between transcatheter aortic valve replacement and subsequent infective endocarditis and in-hospital death

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...

Late cardiac death in patients undergoing transcatheter aortic valve replacement

BACKGROUND Little evidence exists of the burden and predictors of cardiac death after transcatheter aortic valvereplacement (TAVR).OBJECTIVES The purpose of this study was to assess the incidence and predictors of cardiac death from advancedheart failure (HF) and sudden cardiac death (SCD) in a large patient cohort undergoing TAVR.METHODS The study included a total of 3,726 patients who underwent TAVR using balloon (57%) or self-expandable(43%) valves. Causes of death were defined according to the Valve Academic Research Consortium–2.RESULTS At a mean follow-up of 22 18 months, 155 patients had died due to advanced HF (15.2% of total deaths,46.1% of deaths from cardiac causes) and 57 had died due to SCD (5.6% of deaths, 16.9% of cardiac deaths). Baselinecomorbidities (chronic obstructive pulmonary disease, atrial fibrillation, left ventricular ejection fraction #40%, lowermean transaortic gradient, pulmonary artery systolic pressure >60 mm Hg; p 160 ms had a greater SCD risk (HR: 4.78, 95% CI: 1.56 to 14.63; p » 0.006).CONCLUSIONS Advanced HF and SCD accounted for two-thirds of cardiac deaths in patients after TAVR.Potentially modifiable or treatable factors leading to increased risk of mortality for HF and SCD were identified. Future.