Ten-year Durability, Hemodynamic Performance, and Clinical Outcomes after Transcatheter Aortic Valve Implantation Using a Self-expanding Device.

INTRODUCTION: The expansion of transcatheter aortic valve implantation (TAVI) to low-risk and younger patients has increased the relevance of the long-term durability of transcatheter heart valves (THV). The present study aims to assess the 10-year durability, hemodynamic performance, and clinical outcomes after TAVI using the CoreValve system. METHODS: An analysis from a prospective registry with predefined clinical and echocardiographic follow-up included 302 patients who underwent TAVI with the CoreValve system between 2007 and 2015. Bioprosthetic valve failure (BVF) was defined as any bioprosthetic valve dysfunction-related death, re-intervention, or severe hemodynamic valve deterioration. RESULTS: At the time of TAVI, the mean age was 80.41 ± 7.01 years, and the Society of Thoracic Surgeons (STS) score was 6.13 ± 5.23%. At latest follow-up (median [IQR]: 5 [2-7] years), cumulative all-cause mortality rates at 3, 5, 7, and 10 years was 23.7%, 40%, 65.8%, and 89.8%, respectively. Mean aortic valve area and transvalvular gradient post-TAVI and at 5, 7, and 10 years were 1.94, 1.87, 1.69, and 1.98 cm2 (p = 0.236) and 8.3, 9.0, 8.2, and 10.1 mmHg (p = 0.796), respectively. Overall, 11 patients had BVF, of whom six had structural valve deterioration (SVD). The 10-year actual and actuarial freedom from BVF was 96.1% and 78.8%, and from SVD was 97.9% and 80.9%, respectively. Three patients developed significant non-SVD due to severe paravalvular leakage, and two patients were diagnosed with infective endocarditis. CONCLUSION: Using an early-generation self-expanding bioprosthesis, we documented durable hemodynamic performance and low rates of BVF and SVD up to 10 years after TAVI.

Lower revascularization rates after high-speed rotational atherectomy compared to modified balloons in calcified coronary lesions: 5-year outcomes of the randomized PREPARE-CALC trial.

BACKGROUND: In the PREPARE-CALC trial, severely calcified lesion preparation with rotational atherectomy (RA) before biodegradable polymer sirolimus-eluting stent (SES) implantation demonstrated higher procedural success and comparable rates of acute lumen gain and late lumen loss compared to modified balloons (MB) (scoring/cutting). We aimed to analyze the 5-year outcomes of both lesion preparation strategies. METHODS: PREPARE-CALC randomly assigned 200 patients 1:1 to MB or RA, followed by SES implantation. The principal endpoint of the current analysis was target vessel failure (TVF) at 5 years. RESULTS: At 5 years, MB had comparable rates of TVF to RA (19% vs. 21%, HR 1.14, 95% CI 0.60-2.16, p = 0.687). Subgroup analysis showed a lesion length treatment interaction, favoring MB for short lesions and RA for long ones (p for interaction = 0.042). Target lesion revascularization (TLR) was significantly less common with RA (12 vs. 3%, HR 0.28, 95% CI 0.08-0.98, p = 0.048). In a multivariate analysis, RA was independently protective against TLR (adj. HR 0.17, 95% CI 0.04-0.78, p = 0.022), while ostial lesions were associated with higher TLR independent of treatment strategy (adj. HR 11.3, 95% CI 2.98-42.6, p < 0.001). CONCLUSION: In patients with severely calcified coronary lesions, using MB or RA for lesion preparation followed by biodegradable polymer SES implantation was associated with comparable rates of TVF at 5 years. However, a significant reduction of TLR was observed after RA. PREPARE-CALC is the first randomized trial showing potential clinical advantages of RA over MB during long-term follow-up. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov . Unique identifier: NCT02502851.

LAA occlusion is effective and safe in very high-risk atrial fibrillation patients with prior stroke: results from the multicentre German LAARGE registry.

BACKGROUND: Interventional left atrial appendage occlusion (LAAO) mitigates the risk of thromboembolic events in nonvalvular atrial fibrillation (AF) patients with contraindication for long-term oral anticoagulation (OAC). Patients with prior stroke have a relevantly increased risk of recurrent stroke, so the effectiveness of LAAO could be reduced in this specific very high-risk patient group. AIM: This sub-study of the LAARGE registry investigates the effectiveness and safety of LAAO for secondary prevention in nonvalvular AF patients with a history of stroke. METHODS: LAARGE is a prospective, non-randomised registry on the clinical reality of LAAO. The current sub-study employs data from index procedure and 1-year follow-up. Effectiveness and safety were assessed by documentation of all-cause mortality, non-fatal thromboembolism, procedure-related complications, and bleeding events. RESULTS: A total of 638 patients were consecutively included from 38 hospitals in Germany and divided into two groups: 137 patients with a history of stroke (21.5%) and 501 patients without. Successful implantation was consistent between both groups (98.5% vs. 97.4%, p = NS), while peri-procedural MACCE and other complications were rare (0% vs. 0.6% and 4.4% vs. 4.0%, respectively; each p = NS). Kaplan-Meier estimate showed no significant difference in primary effectiveness outcome measure (freedom from all-cause death or non-fatal stroke) between both groups at follow-up (87.8% vs. 87.7%, p = NS). The incidence of transient ischemic attack or systemic embolism at follow-up was low (0% vs. 0.5% and 0.9% vs. 0%, respectively; each p = NS). Severe bleeding events after hospital discharge were rare (0% vs. 0.7%, p = NS). CONCLUSIONS: Patients with prior stroke demonstrated similar effectiveness and safety profile for LAAO as compared to patients without prior stroke. LAAO could serve as a feasible alternative to OAC for secondary stroke prevention in this selected group of nonvalvular AF patients. GOV IDENTIFIER: NCT02230748.

Predictors of long-term adverse outcomes after successful chronic total occlusion intervention: physiology or morphology?

BACKGROUND: Quantitative flow ratio (QFR) and target-vessel SYNTAX score (tvSS) are novel indices used to assess lesion physiology and morphology in percutaneous coronary intervention (PCI). Their prognostic implication after successful recanalization of coronary chronic total occlusion (CTO) is unknown. OBJECTIVES: To investigate the prognostic value of QFR measured immediately after successful CTO-recanalization in predicting vessel-oriented adverse events, and to compare it with the pre-procedural morphological tvSS. METHODS: QFR was measured offline after successful CTO-PCIs in a single center. We grouped the patients according to a cut-off value of post-PCI QFR (0.91). The primary outcome was target-vessel failure (TVF) at 2 years. RESULTS: Among 470 CTO lesions performed during the study period, 324 were eligible for QFR analysis (258 with QFR ≥ 0.91 and 66 with QFR < 0.91). The mean age of the study population was 68.3 ± 10.7 years. The low QFR group had a lower left ventricular ejection fraction (45.8 ± 13.9% vs. 49.8 ± 12.4%, p = 0.025) and a higher rate of atrial fibrillation (19.7% vs. 11.2%, p = 0.020). The mean tvSS was 12.8 ± 4.8, and it showed no significant difference in both groups (13.6 ± 5.1 vs. 12.6 ± 4.6, p = 0.122). Patients with low post-CTO QFR had a trend to develop more TVF at 2 years (21.2% vs. 12.4%, HR 1.74; 95% CI 0.93-3.25, p = 0.086). Low post-CTO QFR failed to predict 2-year TVF (aHR 1.67; 95% CI 0.85-3.29, p = 0.136), while pre-procedural tvSS was an independent predictor for 2-year TVF (aHR 1.06; 95% CI 1.01-1.13, p = 0.030). CONCLUSION: We found a limited prognostic value of immediate physiological assessment using QFR after successful CTO intervention. Pre-procedure morphological characteristics of CTO lesions using tvSS can play a role in predicting long-term adverse events.

Sex-specific Inequalities in the Treatment of Severely Calcified Coronary Lesions: A Sub-analysis of the PREPARE-CALC Trial.

Background: Coronary vessels in women may have anatomical and histological particularities. The aim of this study was to investigate sex-specific characteristics and outcomes of patients with calcified coronary arteries in the Prepare-CALC (Comparison of Strategies to Prepare Severely Calcified Coronary Lesions) trial. Methods: The Prepare-CALC trial randomised patients with severe coronary calcification to coronary lesion preparation either using modified balloons (MB; cutting or scoring) or rotational atherectomy (RA). Results: Of 200 randomised patients, 24% were women. Strategy success in general was similar between women (93.8%) and men (88.2%; p=0.27). For men, strategy success was significantly more common with an RA-based strategy than an MB-based strategy (98.7% in the RA group versus 77.3% in the MB group, p<0.001), whereas for women there was no evidence of a significant difference in strategy success between RA and MB (95.7% in the RA group versus 92% in the MB group, p>0.99, p for interaction between sex and treatment strategy=0.03). Overall, significant complications such as death, MI, stent thrombosis, bypass operation and perforations were rare and did not differ significantly by gender or treatment strategy. Plaque rupture and disrupted calcified nodules were more common in women. Conclusion: In a well-defined patient population with severely calcified coronary arteries, lesion preparation with an RA-strategy was superior to an MB-strategy in men. For women, both RA and MB strategies appear to have a similar success rate, although definitive conclusions are limited due to the small number of women in the trial.

Association of atrial myopathy in mitral valve disease on safety outcomes in left atrial appendage closure.

BACKGROUND: Patients undergoing left atrial appendage (LAA) occlusion (LAAO) are multi-morbid, including mitral valve disease (MVD) which is associated with anatomic changes of the left atrium (LA). This study aims to identify how atrial myopathy in MVD influences outcomes in LAAO. METHODS: Atrial myopathy in MVD was defined as LA diameter > 45 mm (♀) and > 48 mm (♂) and existing MVD or history of surgical/interventional treatment. Patients were compared with controls from the prospective, multicentre LAArge registry of LAAO. RESULTS: A total of 528 patients (52 MVD, 476 no-MVD) were included. The MVD group was significantly more likely to be older (78.2 years vs 75.9 years, p = 0.036) and female (59.6% vs 37.8%, p = 0.002). Altered LA anatomy was observed in MVD with significantly larger LA diameter (53 mm vs. 48 mm, p < 0.001) and LAA Ostia [at 135° 23.0 mm (20.5, 26.0) vs 20.0 mm (18.0, 23.0), p = 0.002]. Implant success was high with 96.2% and 97.9%, respectively, without differences in severe complications (7.7% vs 4.6%, p = 0.31). One-year mortality (17.8% vs 11.5%, p = 0.19) and a combined outcome of death, stroke, and systemic embolism (20.3% vs 12.4%, p = 0.13) were not different. Independent predictors of the combined outcome were peripheral artery disease (HR 2.41, 95% CI 1.46-3.98, p < 0.001) and chronic kidney disease (HR 3.46, 95% CI 2.02-5.93, p < 0.001) but not MVD and atrial myopathy. CONCLUSION: Patients with MVD present with altered LA anatomy with increased LA and LAA diameter. However, procedural success and safety in LAAO are not compromised. One-year mortality is numerically higher in patients with MVD but driven by comorbidities.

Combined rotational atherectomy and cutting balloon angioplasty prior to drug-eluting stent implantation in severely calcified coronary lesions: The PREPARE-CALC-COMBO study.

OBJECTIVES: To evaluate the safety and efficacy of lesion preparation using rotational atherectomy (RA) with consecutive cutting balloon angioplasty (Rota-Cut). BACKGROUND: Whether the Rota-Cut combination improves stent performance in severely calcified coronary lesions is unknown. METHODS: PREPARE-CALC-COMBO is a single-arm prospective trial in which 110 patients were treated with a Rota-Cut strategy before implantation of sirolimus-eluting stents and compared with patients treated with modified balloon (MB, scoring or cutting) or RA from a historical cohort (the randomized PREPARE-CALC trial). The study had two primary endpoints: in-stent acute lumen gain (ALG) by quantitative angiographic analysis and stent expansion (SE) on optical coherence tomography. RESULTS: In-stent ALG was significantly higher with Rota-Cut compared to RA or MB alone (1.92 ± 0.45 mm vs. 1.74 ± 0.45 mm with MB vs. 1.70 ± 0.42 mm with RA; p = 0.001 and p < 0.001, respectively). SE was comparable between groups (75.1 ± 13.8% vs. 73.5 ± 13.3 with MB vs. 73.1 ± 12.2 with RA; p = 0.19 and p = 0.39, respectively). The Rota-Cut combination resulted in higher minimal stent area (MSA) (7.1 ± 2.2mm2 vs. 6.1 ± 1.7mm2  with MB vs. 6.2 ± 1.9mm2 with RA; p = 0.003 and p = 0.004, respectively). In-hospital death occurred in one patient. Target vessel failure at 9 months was low and comparable between groups (8.2% vs. 8% with MB vs. 6% with RA; p = 1 and p = 0.79, respectively). CONCLUSION: Rota-Cut combination resulted in higher ALG and larger MSA compared with historical control of RA or MB alone, but was not associated with higher SE. Despite extensive lesion preparation, this strategy is safe, feasible, and associated with favorable clinical outcome at 9 months.

Adverse events and stroke prevention by interventional left atrial appendage occlusion in patients with low CHA2 DS2 -VASc score-results from the multicenter German LAARGE registry.

BACKGROUND: Interventional left atrial appendage occlusion (LAAO) is routinely performed in patients with nonvalvular atrial fibrillation and contraindications to standard anticoagulation. AIMS: We investigated its role in patients at low stroke risk, and compared the effectiveness and safety in patients with low versus high risk. METHODS: LAARGE is a prospective registry depicting the clinical reality of LAAO. LAAO was conducted with different standard commercial devices, and follow-up period was 1 year. Patients with started procedure and documented CHA2 DS2 -VASc score were selected from the whole database. RESULTS: A total of 638 patients from 38 centers were divided into CHA2 DS2 -VASc score ≤2, i.e., low-risk group (10.2%), and >2, i.e., high-risk group (89.8%). The latter had a pronounced cardiovascular risk profile and preceding strokes (0% vs. 23.9%; p < 0.001). Implantation success was consistently high (97.6%), frequencies of intrahospital major adverse cardiac and cerebrovascular events (0% vs. 0.5%) and other major complications (4.6% vs. 4.0%) were low (each p = not significant [NS]). Numerous moderate complications were also observed in the low-risk patients (12.3% vs. 9.4%; p = NS). Frequencies of nonfatal strokes (0% vs. 0.7%) and severe bleedings (0% vs. 0.7%) were low (each p = NS). In a specific analysis, patients at very high risk of stroke (i.e., CHA2 DS2 -VASc score >4) did not have increased rates of complications or nonfatal strokes in the first year after the procedure. CONCLUSIONS: Low-risk patients had no nonfatal strokes and major bleedings within 1 year after hospital discharge but had unexpectedly high rates of moderate procedural complications. The indication in these patients should be strictly defined based on an individual benefit-risk assessment.

Angiographic predictors of unplanned rotational atherectomy in complex calcified coronary artery disease: a pooled analysis from the randomised ROTAXUS and PREPARE-CALC trials.

BACKGROUND: Calcified coronary lesions present therapeutic challenges for the interventional cardiologist, often requiring rotational atherectomy (RA). AIMS: This study aimed to develop an angiographic scoring tool to predict the need for a priori RA. METHODS: A pooled analysis of the randomised ROTAXUS and PREPARE-CALC studies was carried out, (N=220 patients, N=313 lesions), by virtue of the fact that both studies made provision for crossover to RA (from balloon dilatation or modified balloon dilatation, respectively). Logistical regression techniques were employed to assess for the presence of patient- or lesion-specific factors leading to a necessity for RA. External validation was performed though retrospective calculation of the score for 192 patients who underwent bail-out RA in a single centre. RESULTS: Lesion length (odds ratio [OR] 1.02, 95% confidence interval [CI]: 1.00-1.04 per mm, p=0.04), bifurcation lesion (OR 2.60, 95% CI: 1.27-5.30, p=0.009), vessel tortuosity >45° (OR 3.49, 95% CI: 1.73-7.03, p<0.001) and severe vessel calcification (OR 11.60, 95% CI: 3.40-39.64, p<0.001) were predictive of the need for RA in multivariate analysis. Based on the regression coefficients, a scoring system was devised. The greater the score, the more likely a lesion required RA. The scoring system performed well in the external validation cohort, with 78% of patients crossing over having a score of greater than the proposed cut-off of 3. CONCLUSIONS: We provide an angiographic scoring tool to support the expeditious use of time and resources, allowing assessment of the likelihood of success of a balloon-based strategy, or the necessity for RA.

Interventional occlusion of left atrial appendage in patients with atrial fibrillation. Gender-related outcomes in the German LAARGE Registry.

INTRODUCTION: Gender-based differences in atrial fibrillation have been identified, but limited data exist for patients undergoing left atrial appendage occluder (LAAO) implantation. This study reports gender-related periprocedural and 1-year outcomes of the prospective, multicenter German left atrial appendage occlusion registry (LAARGE). METHODS: LAARGE enrolled 641 patients who were scheduled for LAAO implantation from July 2014 to January 2016 in 38 hospitals in Germany. The data collected included demographics, clinical characteristics, details of implantation, and outcome. Efficacy and safety at 1-year follow-up were assessed by the occurrence of thrombembolic and bleeding events, as well as mortality. RESULTS: Of 638 patients undergoing LAAO implantation 38.9% were female and 61.1% male. Females were older (76.4 ± 8.2 [females] vs. 75.6 ± 7.7 [males], p = .042) and had a higher stroke risk (CHA2 DS2 -VASc score: 4.9 ± 1.5 vs. 4.3 ± 1.5, p < .001). In contrast, males suffered more often from coronary artery (33.1% vs. 53.8%, p < .001) and vascular disease (18.5% vs. 31.0%, p < .001). Technical success was high and similar for both genders (98.4% vs. 97.2%, p = .33). Severe periprocedural complications (6.9% vs. 3.1%, p = .032) occurred more often in females. At 1-year follow-up the rates of all-cause stroke (0.5% vs. 1.3%, p = .65) and severe bleeding (0.0% and 1.0%, p = .29) were low and comparable between the genders. Also, one-year all-cause mortality (9.2% vs. 13.1%, p = .14) did not differ significantly. CONCLUSION: LAARGE documented in this elderly patient population undergoing LAAO implantation a higher rate of severe periprocedural complications in females. At 1-year follow-up similar efficacy and safety outcomes were observed for both genders.

Impact of Lesion Preparation Technique on Side Branch Compromise in Calcified Coronary Bifurcations: A Subgroup Analysis of the PREPARE-CALC Trial.

OBJECTIVES: To analyze the impact of different techniques of lesion preparation of severely calcified coronary bifurcation lesions. BACKGROUND: The impact of different techniques of lesion preparation of severely calcified coronary bifurcation lesions is poorly investigated. METHODS: We performed an as-treated analysis on 47 calcified bifurcation lesions treated with scoring/cutting balloons (SCB) and 68 lesions treated with rotational atherectomy (RA) in the PREPARE-CALC trial. Compromised side branch (SB) as assessed in the final angiogram was the primary outcome measure and was defined as any significant stenosis, dissection, or thrombolysis in myocardial infarction flow <3. RESULTS: True bifurcation lesions were present in 49% vs. 43% of cases in the SCB and RA groups, respectively. After stent implantation, SB balloon dilatation was necessary in around one-third of cases (36% vs. 38%; p = 0.82), and a two-stent technique was performed in 21.3% vs. 25% (p = 0.75). At the end of the procedure, the SB remained compromised in 15 lesions (32%) in the SCB group and 5 lesions (7%) in the RA group (p = 0.001). Large coronary dissections were more frequently observed in the SCB group (13% vs. 2%; p = 0.02). Postprocedural levels of cardiac biomarkers were significantly higher in patients with a compromised SB at the end of the procedure. CONCLUSIONS: In the PREPARE-CALC trial, side branch compromise was more frequently observed after lesion preparation with SCB as compared with RA. Consequently, in calcified bifurcation lesions, an upfront debulking with an RA-based strategy might optimize the result in the side branch.

WATCHMAN versus ACP or Amulet devices for left atrial appendage occlusion: a sub-analysis of the multicentre LAARGE registry.

AIMS: Several left atrial appendage (LAA) closure systems are available. Due to differences in device design, the results of specific occluders derived from trials cannot simply be generalised to all devices. The present analysis sought to assess two contemporary LAA closure devices in clinical practice. METHODS AND RESULTS: The work represents a non-randomised sub-analysis of the prospective, multicentre, Left-Atrium-Appendage Occluder Register - GErmany (LAARGE) registry. The WATCHMAN (group 1) and the AMPLATZER Cardiac Plug (ACP) or Amulet occluder (group 2) were assessed. A total of 641 patients at 38 centres were enrolled. Of these, 278 (43%) and 340 (53%) patients received the WATCHMAN and ACP/Amulet occluder, respectively. High technical success was achieved with a slight difference between the groups (96% in group 1 vs 99% in group 2; p=0.007). Procedural safety did not differ (98% in group 1 vs 97% in group 2; p=0.55). The Kaplan-Meier estimated one-year composite of death or stroke was 12.0% and 12.9%, respectively (p=0.79). CONCLUSIONS: Both the WATCHMAN and the ACP/Amulet occluder provide excellent procedural results with comparable implantation success and no differences with respect to procedural safety and long-term effectiveness.

Left atrial appendage closure in patients with a reduced left ventricular ejection fraction: results from the multicenter German LAARGE registry.

BACKGROUND: Interventional left atrial appendage closure (LAAC) effectively prevents thromboembolic events in atrial fibrillation patients. Impaired left ventricular ejection fraction (LVEF) increases not only the thromboembolic risk but also the complication rates of cardiac interventions. The LAAC procedure's benefit in patients with an impaired LVEF, therefore, has yet to be investigated. METHODS: LAARGE is a prospective, non-randomized registry depicting the clinical reality of LAAC in Germany. Procedure was conducted with different standard commercial devices, and follow-up period was one year. In the sense of an as-treated analysis, patients with started procedure and documented LVEF were selected from the whole database. RESULTS: 619 patients from 37 centers were categorized into one of three groups: LVEF > 55% (56%), 36-55% (36%), and ≤ 35% (8%). Prevalence of cardiovascular comorbidity increased with LVEF reduction (p < 0.001 for trend). CHA2DS2-VASc score was 4.3, 4.8, and 5.1 (p < 0.001), and HAS-BLED score was 3.7, 4.1, and 4.2 (p < 0.001). Implantation success was consistently high (97.9%), rates of intra-hospital MACCE (0.5%), and other major complications (4.2%) were low (each p = NS). Kaplan-Meier estimation showed a decrease in survival free of stroke with LVEF reduction during one-year follow-up (89.3 vs. 87.0 vs. 79.8%; p = 0.067), a trend which was no longer evident after adjustment for relevant confounding factors. Rates of non-fatal strokes (0.4 vs. 1.1 vs. 0%) and severe bleedings (0.7 vs. 0.0 vs. 3.1%) were consistently low across all groups (each p = NS). CONCLUSIONS: LVEF reduction neither influenced the procedural success nor the effectiveness and safety of stroke prevention by LAAC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02230748.

Interventional occlusion of left atrial appendage in patients with atrial fibrillation. Acute and long-term outcome of occluder implantation in the LAARGE Registry.

BACKGROUND: Left atrial appendage occluder (LAAO) implantation is an alternative method for stroke prevention in atrial fibrillation (AF) patients who are not eligible for long-term oral anticoagulation. The present paper describes the acute and 1-year follow-up outcome data of the prospective, multicenter German left atrial appendage occlusion registry (LAARGE). METHODS: LAARGE enrolled 641 patients who were scheduled for LAAO implantation. The data collected included demographics, clinical characteristics, procedure indication, details of implantation, and outcome; patients were followed at 1-year post-implant. Efficacy and safety during follow-up are assessed by the occurrence of thrombembolic and bleeding events, respectively. RESULTS: A total of 641 consecutive patients (mean age: 75.9 ± 8.0) were enrolled from July 2014 to January 2016 in 38 hospitals in Germany. Patient demographics represent a critically-ill population with a calculated mean CHA2DS2-VASc score and HASBLED score of 4.5 and 3.9, respectively, with bleeding events as the main indication for LAAO implantation (79.4%). One-year all-cause mortality post-procedure was 11.5% with a non-fatal stroke/TIA rate of 1.3% (8 patients) and a rate of major bleeding of 1.6% (10 patients). The anticoagulation regimen after 1 year consisted of oral anticoagulation in 5.5% of patients and an antiplatelet therapy (APT) rate of 84.1% (majority single APT with ASS (74.5%), dual APT in 6.7%). CONCLUSIONS: LAARGE, a prospective multicenter real-world and all-comer registry, is unique in its concept, as it is non-manufacturer sponsored and includes all commercially available devices. LAAO implantation is mainly performed in elderly, critically-ill patients with a history of bleeding. LAARGE demonstrates a favorable outcome at 1-year follow-up in terms of stroke/TIA (1.3%) and major bleeding (1.6%) while using a single APT in the vast majority of patients.

High-Speed Rotational Atherectomy Versus Modified Balloons Prior to Drug-Eluting Stent Implantation in Severely Calcified Coronary Lesions.

BACKGROUND: Balloon dilatation or debulking seems to be essential to allow successful stent implantation in calcified coronary lesions. Compared with standard balloon predilatation, debulking using high-speed rotational atherectomy (RA) is associated with higher initial procedural success albeit with higher in-stent late lumen loss at intermediate-term follow-up. Whether modified (scoring or cutting) balloons (MB) could achieve similar procedural success compared with RA is not known. In addition, whether new-generation drug-eluting stents could counterbalance the excessive neointimal proliferation triggered by RA remains to be determined. METHODS AND RESULTS: We randomly assigned patients with documented myocardial ischemia and severely calcified native coronary lesions undergoing percutaneous coronary intervention to a strategy of lesion preparation using MB or RA followed by drug-eluting stent implantation. Stenting was performed using a third-generation sirolimus-eluting stent with a bioabsorbable polymer. The trial had 2 primary end points: strategy success (defined as successful stent delivery and expansion with attainment of <20% in-stent residual stenosis in the presence of TIMI [Thrombolysis in Myocardial Infarction] 3 flow without crossover or stent failure; powered for superiority) and in-stent late lumen loss at 9 months (powered for noninferiority). Two hundred patients were enrolled at 2 centers in Germany (n=100 in each treatment group). The mean age of the study population was 74.9±7.0 years; 76% were men, and 33.5% had diabetes mellitus. Strategy success was significantly more common in the RA group (81% versus 98%; relative risk of failure with an MB- versus RA-based strategy, 9.5; 95% CI, 2.3-39.7; P=0.0001), but mean fluoroscopy time was longer (19.6±13.4 versus 23.9±12.2 minutes; P=0.03). At 9 months, mean in-stent late lumen loss was 0.16±0.39 mm in the MB group and 0.22±0.40 mm in the RA group ( P=0.21, P=0.02 for noninferiority). Target lesion revascularization (7% versus 2%; P=0.17), definite or probable stent thrombosis (0% versus 0%; P=1.00), and target vessel failure (8% versus 6%; P=0.78) were low and not significantly different between the MB and RA groups. CONCLUSIONS: Lesion preparation with upfront RA before drug-eluting stent implantation is feasible in nearly all patients with severely calcified coronary lesions, is more commonly successful as a primary strategy compared with MB, and is not associated with excessive late lumen loss. A strategy of provisional MB remains feasible, safe, and effective as long as bailout RA is readily available and may offer the advantages of compatibility with smaller sized catheters and less irradiation. Both strategies are associated with excellent clinical outcome at 9 months. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02502851.

12-Month Results From the First-in-Human Randomized Study of the Ranger Paclitaxel-Coated Balloon for Femoropopliteal Treatment.

OBJECTIVES: The authors sought to evaluate the performance of the Ranger paclitaxel-coated balloon versus uncoated balloon angioplasty for femoropopliteal lesions at 12 months. BACKGROUND: Drug-coated balloons (DCBs) are a promising endovascular treatment option for peripheral artery disease of the femoropopliteal segment, and each unique device requires dedicated clinical study. METHODS: The prospective, randomized RANGER SFA (Comparison of the Ranger™ Paclitaxel-Coated PTA Balloon Catheter and Uncoated PTA Balloons in Femoropopliteal Arteries) study (NCT02013193) enrolled 105 patients with symptomatic lower limb ischemia (Rutherford category 2 to 4) and stenotic lesions in the nonstented femoropopliteal segment at 10 European centers. Seventy-one patients (mean age 68 ± 8 years, n = 53 men) were enrolled in the Ranger DCB arm, and 34 patients (mean age 67 ± 9 years, n = 23 men) were assigned to the control group. Twelve-month analysis included patency, safety, and clinical outcomes and quality-of-life assessments. RESULTS: The DCB group had a greater primary patency rate at 12 months (Kaplan-Meier estimate 86.4% vs. 56.5%), with a significantly longer time to patency failure (log-rank p < 0.001). The estimated freedom from target lesion revascularization rate was 91.2% in the DCB group and 69.9% in the control group at 12 months, with a significantly longer time to reintervention (p = 0.010). No target limb amputations or device-related deaths occurred in either group. CONCLUSIONS: Twelve-month results show that patency was maintained longer after Ranger DCB treatment than after conventional balloon angioplasty, and this result was associated with a low revascularization rate and good clinical outcomes.

Impact of left atrial appendage morphology on indication and procedural outcome after interventional occlusion: results from the prospective multicentre German LAARGE registry.

AIMS: Interventional left atrial appendage closure (LAAC) is an emerging alternative to oral anticoagulation (OAC) for stroke prevention in atrial fibrillation (AF) in concomitance with a contraindication for standard OAC. This sub-analysis of the LAARGE registry aimed to investigate differences between different LAA morphologies in a real-world setting. METHODS AND RESULTS: This prospective, multicentre, observational registry included 562 patients from 37 centres with ineligibility for long-term OAC between April 2014 and January 2016. Baseline characteristics, indications, procedural data and complications were registered according to each LAA morphology (i.e., chicken wing, cauliflower, windsock, cactus and atypical morphologies). Implantation success was high across the four typical anatomies (≥97.5%, p=n.s.); only atypical anatomies exhibited a lower success rate (94%). The cactus-shaped LAA was linked to a trend indicating a shorter fluoroscopy time, while the atypical LAA was linked to a significantly prolonged fluoroscopy time (p=0.089 and p=0.025 versus the overall mean, respectively). Periprocedural and intra-hospital complications were generally rare, with no differences among the different morphologies (p=n.s.). CONCLUSIONS: Procedural success as well as the complication rates of LAAC were not different among the four typical LAA morphologies. A lower implantation success rate was only obvious in patients with atypical LAA morphologies.

Left atrial appendage occlusion with the AMPLATZER Amulet device: periprocedural and early clinical/echocardiographic data from a global prospective observational study.

AIMS: The global, prospective AMPLATZER Amulet observational study documents real-world periprocedural, transoesophageal echocardiographic (TEE) and clinical outcomes from left atrial appendage occlusion (LAAO) using the AMPLATZER Amulet device. The aim of this report is to describe the periprocedural and early clinical/TEE results from this study. METHODS AND RESULTS: This multicentre prospective real-world registry included 1,088 patients (75±8.5 years, 64.5% male, CHA2DS2-VASc: 4.2±1.6, HAS-BLED: 3.3±1.1) with non-valvular atrial fibrillation; 82.8% of patients were considered to have an absolute or relative contraindication to long-term anticoagulation and 72.4% had had a previous major bleeding. Periprocedural results, clinical outcomes up to the first three months and the available TEE results from the first scheduled follow-up (one to three months post implant) are reported. Successful device implantation was achieved in 99.0% of patients. During the procedure and index hospitalisation, major adverse events occurred in 3.2% of patients. Patients were discharged on a single antiplatelet agent (23.0%), dual antiplatelets (54.3%) or an oral anticoagulant (18.9%). TEE follow-up 67±23 days post procedure in 673 patients showed adequate (<3 mm jet) occlusion of the appendage in 98.2% of patients and device thrombus in 10 patients (1.5%), as evaluated by core laboratory analysis. CONCLUSIONS: This large real-world prospective registry of catheter-based LAAO using the AMPLATZER Amulet device reports a high implant success rate and a low periprocedural complication rate in a population with a high risk of stroke and bleeding. Transoesophageal echo data confirm good closure rates during follow-up and low rates of device-associated thrombus.

Six-Month Results From the Initial Randomized Study of the Ranger Paclitaxel-Coated Balloon in the Femoropopliteal Segment.

PURPOSE: To evaluate the performance of the Ranger paclitaxel-coated balloon vs uncoated balloon angioplasty for femoropopliteal lesions. METHODS: Between January 2014 and October 2015, the prospective, randomized RANGER SFA study ( ClinicalTrials.gov identifier NCT02013193) enrolled 105 patients with symptomatic lower limb ischemia (Rutherford category 2-4) and stenotic lesions in the nonstented femoropopliteal segment at 10 European centers. Seventy-one patients (mean age 68±8 years; 53 men) were enrolled in the Ranger drug-coated balloon (DCB) arm and 34 patients (mean age 67±9 years; 23 men) were assigned to the control group. Six-month analysis included angiographic late lumen loss and safety and clinical outcomes assessments. RESULTS: Baseline characteristics of the DCB and control groups were similar, as were lesion lengths (68±46 vs 60±48 mm; p=0.731), severity of calcification (p=0.236), and the prevalence of occlusions (34% vs 34%; p>0.999). At 6 months, late lumen loss was significantly less for the DCB group vs controls (-0.16±0.99 vs 0.76±1.4; p=0.002). The DCB group had significantly greater freedom from binary restenosis (92% vs 64%; p=0.005) and primary patency rates (87% vs 60%; p=0.014). Target lesion revascularization rates were 5.6% in the DCB group and 12% in the control group (p=0.475). No target limb amputations or device-related deaths occurred in either group. CONCLUSION: Six-month results suggest that Ranger DCB treatment effectively inhibited restenosis in symptomatic femoropopliteal disease, resulting in improved vessel patency and a low revascularization rate in the short term compared with uncoated balloon angioplasty.