Survival After Invasive or Conservative Management of Stable Coronary Disease.

BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing. METHODS: ISCHEMIA participants were randomized to an initial invasive strategy added to guideline-directed medical therapy or a conservative strategy. Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and noncardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models, and Bayesian methods. Undetermined deaths were classified as cardiovascular as prespecified in the trial protocol. RESULTS: Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23% women, 16% Hispanic, 4% Black, 42% with diabetes, and median ejection fraction 0.60. A total of 557 deaths accrued during a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 noncardiovascular deaths, and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 [95% CI, 0.85-1.18]). There was a lower 7-year rate cardiovascular mortality (6.4% versus 8.6%; adjusted hazard ratio, 0.78 [95% CI, 0.63-0.96]) with an initial invasive strategy but a higher 7-year rate of noncardiovascular mortality (5.6% versus 4.4%; adjusted hazard ratio, 1.44 [95% CI, 1.08-1.91]) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease. CONCLUSIONS: There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of noncardiovascular mortality with an initial invasive strategy during a median follow-up of 5.7 years. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04894877.

Strategy to optimize PeriproCeduraL AnticOagulation in structural transseptal interventions: Design and rationale of the STOP CLOT trial.

BACKGROUND: Both transcatheter edge-to-edge repair (TEER) of mitral regurgitation or left atrial appendage closure (LAAC) require periprocedural anticoagulation with unfractionated heparin (UFH) that is administered either before or immediately after transseptal puncture (TSP). The optimal timing of UFH administration (before or after TSP) is unknown. The Strategy To Optimize PeriproCeduraL AnticOagulation in Structural Transseptal Interventions trial (STOP CLOT Trial) was designed to determine if early anticoagulation is effective in reducing ischemic complications without increasing the risk of periprocedural bleeding. METHODS: The STOP CLOT trial is a multicenter, prospective, double-blind, placebo-controlled, randomized trial. A total of 410 patients scheduled for TEER or LAAC will be randomized 1:1 either early UFH administration (iv. bolus of 100 units/kg UFH or placebo, given after obtaining femoral vein access and at least 5 minutes prior to the start of the TSP) or late UFH administration (iv. bolus of 100 units/kg UFH or placebo given immediately after TSP). Prespecified preliminary statistical analysis will be performed after complete follow-up of the first 196 randomized subjects. To ensure blinding, a study nurse responsible for randomization and UFH/placebo preparation is not involved in the care of the patients enrolled into the study. The primary study endpoint is a composite of (1) major adverse cardiac and cerebrovascular events (death, stroke, TIA, myocardial infarction, or peripheral embolization) within 30 days post-procedure, (2) intraprocedural fresh thrombus formation in the right or left atrium as assessed with periprocedural transesophageal echocardiography, or (3) occurrence of new ischemic lesions (diameter ≥4 mm) on brain magnetic resonance imaging performed 2 to 5 days after the procedure. The safety endpoint is the occurrence of moderate or severe bleeding complications during the index hospitalization. CONCLUSIONS: Protocols of periprocedural anticoagulation administration during structural interventions have never been tested in a randomized clinical trial. The Stop Clot trial may help reach consensus on the optimal timing of initiation of periprocedural anticoagulation. CLINICAL TRIALS REGISTRATION NUMBER: The study protocol is registered at ClinicalTrials.gov, identifier NCT05305612.

Management of Coronary Disease in Patients with Advanced Kidney Disease.

BACKGROUND: Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS: We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS: At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P = 0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P = 0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P = 0.03). CONCLUSIONS: Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).

Imaging risk features for device related pulmonary artery injury after left atrial appendage closure with Amplatzer™ Amulet™ device.

OBJECTIVES: This study aimed to find imaging risk features for device related-pulmonary artery (PA) injury (DR-PAI) in patients after left atrial appendage closure (LAAC). BACKGROUND: Cardiac tamponade resulting from DR-PAI is a rare but life-threatening complication of LAAC. METHODS: In vitro analysis of Amplatzer™ Amulet™ (Abbott, MN) device was done. Measurements of the distance between PA and Amplatzer lobe at its middle part, distal part, and along the stabilizing wires' trajectory (wires-to-PA distance) were taken in 100 consecutive patients on post-LAAC computed tomography (CT) studies. Clinical outcomes were collected. RESULTS: In vitro analysis indicated that both middle and distal lobe had to be in close PA proximity (<1.5 mm) for the stabilizing wires to cause risk for DR-PAI, configuration called ''cuddling lobe orientation''. On CT measurements middle lobe-PA distance was 4.7 mm (IQR = 2.7-9.5), with close proximity in 4 (4%) patients, and distal lobe-PA distance was 3.2 mm (IQR = 1.8-7.2 mm), with close proximity in 17 (17%) patients. Stabilizing wires were pointing toward PA in 47 patients (47%) with median wire-to-PA distance 5.7 mm (IQR = 3.6-8.5 mm). ''Cuddling'' was found in 2 (2%) patients and resulted in shorter wires-to-PA distance vs no ''cuddling'' group (2.3 vs 5.8 mm p <.01). At 2.9 ± 1.0 yrs of follow-up, the two patients with ''cuddling lobe orientation'' on post-LAAC CT scan developed late cardiac tamponades (p <.001). One of those required surgery, which confirmed DR-PAI. CONCLUSIONS: ''Cuddling lobe orientation'' of Amulet device with the PA was associated with short wires-to-PA distance and late pericardial effusions, including DR-PAI. Hence, such device-to-PA configuration should be avoided.

A randomized comparison of modified subcutaneous "Z"-stitch versus manual compression to achieve hemostasis after large caliber femoral venous sheath removal.

OBJECTIVES: To compare subcutaneous "Z"-stitch versus manual compression in attaining hemostasis after large bore femoral venous access, and to assess its impact on venous patency. BACKGROUND: Structural interventions increasingly require large caliber venous access, for which convenient, safe, and effective method of postprocedural hemostasis is needed. "Z"-stitch has been introduced for this purpose in some centers but systematic data on its performance is limited. METHODS: This single center study randomized consecutive patients with femoral venous access sites requiring ≥10F sheaths to the "Z"-stitch or manual compression for hemostasis in a 2:1 fashion. There were three co-primary endpoints: time to hemostasis, time to ambulation, and a composite safety endpoint comprising vascular access site complications. Groin Doppler-Duplex was performed with the stitch in place and after its removal. RESULTS: 86 consecutive patients with 90 access sites were randomized. Mean age was 61.7 ± 19.1 years, 33.3% were men. Median sheath size was 14 F (range 10-22 F). Patients randomized to "Z"-stitch achieved hemostasis quicker [<1 min vs. 12.0 (IQR 10.0-15.0) min, P < 0.001] and ambulated sooner [7.0 (IQR 4.0-12.0) vs. 16.0 (IQR 11.8-20.3) hr post procedure, P < 0.001] when compared with manual compression alone. The "Z"-stitch reduced rates of access site complications (OR = 0.27, 95%CI 0.09-0.76, P = 0.01). All imaged veins were patent before and after stitch removal. CONCLUSIONS: The "Z"-stitch is a safe and effective method of achieving hemostasis after large bore femoral venous sheath removal and results in faster hemostasis, early patient ambulation and less access site complications, without compromising vein patency when compared with manual compression alone. © 2017 Wiley Periodicals, Inc.

Patterns of Coronary Calcification and Their Impact on the Diagnostic Accuracy of Computed Tomography Coronary Angiography.

OBJECTIVE: Despite coronary calcifications being a major factor affecting the diagnostic accuracy of coronary computed tomography angiography (CTA), there is a lack of established criteria for categorizing calcifications. We aimed to evaluate patterns of coronary calcification based on quantitative radiodensity and size parameters to provide coronary calcium categories and assess their impact on the accuracy of coronary CTA. METHODS AND RESULTS: We analyzed length, maximum thickness, volume, mean density, and maximum density of coronary calcium and divided each of these parameters into tertiles. Subsequently, we summarized the tertiles for each individual calcification and divided them into 3 equal groups of: mild, moderate, and severe calcification. The accuracy of coronary CTA was defined as the difference between the measurements obtained on coronary CTA versus the reference of intravascular ultrasound (IVUS). We evaluated 252 coronary calcifications within 97 arteries of 60 patients. There was an expected increase in size and density values for mild versus moderate versus severe calcifications, but there was no difference in IVUS measured minimum lumen area among the 3 groups. Of note, coronary CTA significantly underestimated IVUS minimum lumen area measurement by 1.2 ± 1.6 mm (14.6 ± 23.1%, P < 0.001) for severe calcifications and by 0.5 ± 2.0 mm (3.7 ± 32.1%, P = 0.021) for moderate calcifications. Within mild calcifications, the difference was not significant. CONCLUSION: Based on their dimensional and radiodensity characteristics, our analysis revealed patterns of individual coronary artery calcifications that affected the accuracy of coronary CTA measurements; coronary CTA inaccuracy was associated with the presence of moderate or severe calcifications, but not mild calcifications.

Use of troponin assay 99th percentile as the decision level for myocardial infarction diagnosis.

BACKGROUND: The Universal Definition of Myocardial Infarction recommends the 99th percentile concentration of cardiac troponin in a normal reference population as part of the decision threshold to diagnose type 1 spontaneous myocardial infarction. Adoption of this recommendation in contemporary worldwide practice is not well known. METHODS: We performed a cohort study of 276 hospital laboratories in 31 countries participating in the National Heart, Lung, and Blood Institute-sponsored International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial. Each hospital laboratory's troponin assay manufacturer and model, the recommended assay's 99th percentile upper reference limit (URL) from the manufacturer's package insert, and the troponin concentration used locally as the decision level to diagnose myocardial infarction were ascertained. RESULTS: Twenty-one unique troponin assays from 9 manufacturers were used by the surveyed hospital laboratories. The ratio of the troponin concentration used locally to diagnose myocardial infarction to the assay manufacturer-determined 99th percentile URL was <1 at 19 (6.6%) laboratories, equal to 1 at 91 (31.6%) laboratories, >1 to ≤5 at 101 (35.1%) laboratories, >5 to ≤10 at 34 (11.8%) laboratories, and >10 at 43 (14.9%) laboratories. The variability in troponin decision level for myocardial infarction relative to the assay 99th percentile URL was present for laboratories in and outside of the United States, as well as for high- and standard-sensitivity assays. CONCLUSIONS: There is substantial hospital-level variation in the troponin threshold used to diagnose myocardial infarction; only one-third of hospital laboratories currently follow the Universal Definition of Myocardial Infarction consensus recommendation for use of troponin concentration at the 99th percentile of a normal reference population as the decision level to diagnose myocardial infarction. This variability across laboratories has important implications for both the diagnosis of myocardial infarction in clinical practice as well as adjudication of myocardial infarction in clinical trials.

Comparison of conventional and high-sensitivity troponin in patients with chest pain: a collaborative meta-analysis.

BACKGROUND: Multiple studies have evaluated the diagnostic and prognostic performance of conventional troponin (cTn) and high-sensitivity troponin (hs-cTn). We performed a collaborative meta-analysis comparing cTn and hs-cTn for diagnosis of acute myocardial infarction (AMI) and assessment of prognosis in patients with chest pain. METHODS: MEDLINE/PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing both cTn and hs-cTn in patients with chest pain. Study authors were contacted and many provided previously unpublished data. RESULTS: From 17 included studies, there were 8,644 patients. Compared with baseline cTn, baseline hs-cTn had significantly greater sensitivity (0.884 vs 0.749, P < .001) and negative predictive value (NPV; 0.964 vs 0.935, P < .001), whereas specificity (0.816 vs 0.938, P < .001) and positive predictive value (0.558 vs 0.759, P < .001) were significantly reduced. Based on summary receiver operating characteristic curves, test performance for the diagnosis of AMI was not significantly different between baseline cTn and hs-cTn (0.90 [95% CI 0.85-0.95] vs 0.92 [95% CI 0.90-0.94]). In a subanalysis of 6 studies that alternatively defined AMI based on hs-cTn, cTn had lower sensitivity (0.666, P < .001) and NPV (0.906, P < .001). Elevation of baseline hs-cTn, but negative baseline cTn, was associated with increased risk of death or nonfatal myocardial infarction during follow-up (P < .001) compared with both negative. CONCLUSION: High-sensitivity troponin has significantly greater early sensitivity and NPV for the diagnosis of AMI at the cost of specificity and positive predictive value, which may enable early rule in/out of AMI in patients with chest pain. Baseline hs-cTn elevation in the setting of negative cTn is also associated with increased nonfatal myocardial infarction or death during follow-up.

International Variation in Health Status Benefits in Patients Undergoing Initial Invasive Versus Conservative Management for Chronic Coronary Disease: Insights From the ISCHEMIA Trial.

BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) demonstrated greater health status benefits with an initial invasive strategy, as compared with a conservative one, for patients with chronic coronary disease and moderate or severe ischemia. Whether these benefits vary globally is important to understand to support global adoption of the results. METHODS: We analyzed participants' disease-specific health status using the validated 7-item Seattle Angina Questionnaire (SAQ: >5-point differences are clinically important) at baseline and over 1-year follow-up across 37 countries in 6 international regions. The average effect of initial invasive versus conservative strategies on 1-year SAQ scores was estimated using Bayesian proportional odds regression and compared across regions. RESULTS: Considerable regional variation in baseline health status was observed among 4617 participants (mean age=64.4±9.5 years, 24% women), with the mean SAQ summary scores of 67.4±19.5 in Eastern Europe participants (17% of the total), 71.4±15.4 in Asia-Pacific (18%), 74.9±16.7 in Central and South America (10%), 75.5±19.5 in Western Europe (26%), and 78.6±19.2 in North America (28%). One-year improvements in SAQ scores were greater in regions with lower baseline scores with initial invasive management (17.7±20.9 in Eastern Europe and 11.4±19.3 in North America), but similar in the conservative arm. Adjusting for baseline SAQ scores, similar health status benefits of an initial invasive strategy on 1-year SAQ scores were observed (ranging from 2.38 points [95% CI, 0.04-4.50] in North America to 4.66 points [95% CI, 2.46-6.94] in Eastern Europe), with an 88.3% probability that the difference in benefit across regions was <5 points. CONCLUSIONS: In patients with chronic coronary disease and moderate or severe ischemia, initial invasive management was associated with a consistent health status benefit across regions, with modest regional variability, supporting the international generalizability of health status benefits from invasive management of chronic coronary disease. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial.

BACKGROUND: ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease. METHODS: Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use. RESULTS: Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14-2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78-12.86] and 2.63 [95% CI, 1.51-4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23-3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34-2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46-0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography. CONCLUSIONS: Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Performance of balloon-expandable transcatheter bioprostheses in inoperable patients with pure aortic regurgitation of a native valve: The BE-PANTHEON international project.

BACKGROUND: The off-label utilization of transcatheter heart valve (THV) devices for the treatment of inoperable or high-surgical risk patients with pure native aortic valve regurgitation (NAVR) has demonstrated suboptimal outcomes, both with self- and balloon-expandable (BE) devices. The aim of this study is to compare the use of different BE scaffolds in treating pure NAVR. METHODS: Consecutive patients with pure severe NAVR who were deemed to be at high-risk and were treated with last-generation BE-THVs among seventeen Centers in Europe and US. Technical and device success rates were the primary objectives. RESULTS: Between February 2018 and July 2023, among 144 patients, 41 (28 %) received a MyVal device and 103 (72 %) were treated with a Sapien THV. Patients treated with a MyVal THV had an extra-large annulus more frequently compared to the Sapien group (49%vs.20 %, p < 0.001). Technical and device success rates were 90 % and 81 %, respectively, p > 0.1. The rate of THV migration/embolization (MyVal 4.9%vs. Sapien 11 %, p = 0.4) and second valve needed (4.9%vs.7.8 %, p = 0.7) were numerically lower in the MyVal group, whereas the rate of at least moderate paravalvular leak (15%vs.7.8 %, p = 0.2) and permanent pacemaker implantation (25%vs.18 %, p = 0.16) were numerically higher in the Myval group. CONCLUSIONS: Off-label use of BE devices for pure NAVR represents a potential alternative in high-risk patients in the absence of dedicated devices. However, BE in NAVR is associated with suboptimal outcomes. The availability of larger THV sizes may introduce transcatheter aortic valve replacement as an effective treatment for patients traditionally deemed unsuitable. NON-STANDARD ABBREVIATIONS AND ACRONYMS: AR = aortic regurgitation, BE = balloon-expandable, NAVR = native aortic valve regurgitation, PM = pacemaker, TAVR = transcatheter aortic valve replacement, THV = transcatheter heart valve, TVEM = transcatheter valve embolization and migration, VARC-3 = Valve Academic Research Consortium 3.

Left Atrial Appendage Occlusion vs Standard of Care After Ischemic Stroke Despite Anticoagulation.

Importance: Patients with atrial fibrillation (AF) who have ischemic stroke despite taking oral anticoagulation therapy (OAT) have a very high risk of recurrence. Left atrial appendage occlusion (LAAO) is a mechanical stroke prevention strategy that may provide additional protection in patients with thromboembolic events under OAT. Objective: To compare percutaneous LAAO with continuing OAT alone regarding stroke prevention in patients with AF who had a thromboembolic event despite taking OAT. Design, Setting, and Participants: This cohort study was a propensity score-matched comparison of the STR-OAC LAAO cohort, an international collaboration of 21 sites combining patients from multiple prospective registries of patients who underwent LAAO between 2010 and 2022. STR-OAC LAAO cohort patients who had follow-up longer than 3 months were propensity score-matched to a previously published control cohort comprising patients from an established international collaboration of investigator-initiated prospective studies. This control cohort included patients with nonvalvular AF, recent ischemic stroke or transient ischemic attack, and follow-up longer than 3 months who were taking OAT before the index event. Analyses were adjusted for imbalances in gender, age, hypertension, diabetes, and CHA2 DS2-VASc score. Exposure: Left atrial appendage occlusion vs continuation of oral anticoagulation therapy alone (control group). Main Outcomes and Measures: The primary outcome was time to first ischemic stroke. Results: Four hundred thirty-three patients from the STR-OAC LAAO cohort (mean [SD] age, 72 [9] years; 171 [39%] females and 262 [61%] males; mean [SD] CHA2 DS2-VASc score, 5.0 [1.6]) were matched to 433 of 1140 patients (38%) from the control group. During 2-year follow-up, 50 patients experienced ischemic stroke: an annualized event rate of 2.8% per patient-year in the STR-OAC LAAO group vs 8.9% per patient-year in the control group. Left atrial appendage occlusion was associated with a lower risk of ischemic stroke (hazard ratio, 0.33; 95% CI, 0.19-0.58; P < .001) compared with the control group. After LAAO, OAT was discontinued in 290 patients (67%), and the remaining 143 patients (33%) continued OAT after LAAO as an adjunctive therapy. Conclusions and Relevance: In patients with nonvalvular AF and a prior thromboembolic event despite taking OAT, LAAO was associated with a lower risk of ischemic stroke compared with continued OAT alone. Randomized clinical trial data are needed to confirm that LAAO may be a promising treatment option for this population with a very high risk of stroke.

Left Atrial Appendage Occlusion in Patients With Anticoagulation Failure vs Anticoagulation Contraindication.

BACKGROUND: Left atrial appendage occlusion (LAAO) provides mechanical cardioembolic protection for atrial fibrillation (AF) patients who cannot use oral anticoagulation therapy (OAT). Patients with a thrombotic event despite OAT are at high risk for recurrence and may also benefit from LAAO. OBJECTIVES: This study sought to investigate the efficacy of LAAO in AF patients with a thrombotic event on OAT compared to: 1) LAAO in AF patients with a contraindication for OAT; and 2) historical data. METHODS: The international LAAO after stroke despite oral anticoagulation (STR-OAC LAAO) collaboration included patients who underwent LAAO because of thrombotic events on OAT. This cohort underwent propensity score matching and was compared to the EWOLUTION (Evaluating Real-Life Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology) registry, which represents patients who underwent LAAO because of OAT contraindications. The primary outcome was ischemic stroke. Event rates were compared between cohorts and with historical data without OAT, yielding relative risk reductions based on risk scores. RESULTS: Analysis of 438 matched pairs revealed no significant difference in the ischemic stroke rate between the STR-OAC LAAO and EWOLUTION cohorts (2.5% vs 1.9%; HR: 1.37; 95% CI: 0.72-2.61). STR-OAC LAAO patients exhibited a higher thromboembolic risk (HR: 1.71; 95% CI: 1.04-2.83) but lower bleeding risk (HR: 0.39; 95% CI: 0.18-0.88) compared to EWOLUTION patients. The mortality rate was slightly higher in EWOLUTION (4.3% vs 6.9%; log-rank P = 0.028). Relative risk reductions for ischemic stroke were 70% and 78% in STR-OAC LAAO and EWOLUTION, respectively, compared to historical data without OAT. CONCLUSIONS: LAAO in patients with a thrombotic event on OAT demonstrated comparable stroke rates to the OAT contraindicated population in EWOLUTION. The thromboembolic event rate was higher and the bleeding rate lower, reflecting the intrinsically different risk profile of both populations. Until randomized trials are available, LAAO may be considered in patients with an ischemic event on OAT.

Midterm Outcomes in Patients With Aortic Stenosis Treated With Contemporary Balloon-Expandable and Self-Expanding Valves: Does Valve Size Have an Impact on Outcome?

Background No data currently exist comparing the contemporary iterations of balloon-expandable (BE) Edwards SAPIEN 3/Ultra and the self-expanding (SE) Medtronic Evolut PRO/R34 valves. The aim of the study was the comparison of these transcatheter heart valves with emphasis on patients with small aortic annulus. Methods and Results In this retrospective registry, periprocedural outcomes and midterm all-cause mortality were analyzed. A total of 1673 patients (917 SE versus 756 BE) were followed up for a median of 15 months. A total of 194 patients died (11.6%) during follow-up. SE and BE groups showed similar survival at 1 (92.6% versus 90.6%) and 3 (80.3% versus 85.2%) years (Plog-rank=0.136). Compared with the BE group, patients treated with the SE device had lower peak (16.3±8 mm Hg SE versus 21.9±8 mm Hg BE) and mean (8.8±5 mm Hg SE versus 11.5±5 mm Hg BE) gradients at discharge. Conversely, the BE group demonstrated lower rates of at least moderate paravalvular regurgitation postoperatively (5.6% versus 0.7% for SE and BE valves, respectively; P<0.001). In patients treated with small transcatheter heart valves (≤26 mm for SE and ≤23 mm for BE; N=284 for SE and N=260 for BE), survival was higher among patients treated with SE valves at both 1 (96.7% SE versus 92.1% BE) and 3 (91.8% SE versus 82.2% BE) years (Plog-rank=0.042). In propensity-matched patients treated with small transcatheter heart valve, there remained a trend for higher survival among the SE group at both 1 (97% SE versus 92.3% BE) and 3 years (91.8% SE versus 78.7% BE), Plog-rank=0.096). Conclusions Real-world comparison of the latest-generation SE and BE devices demonstrated similar survival up to 3 years' follow-up. In patients with small transcatheter heart valves, there may be a trend for improved survival among those treated with SE valves.

Persistent and Recurrent Device-Related Thrombus After Left Atrial Appendage Closure: Incidence, Predictors, and Outcomes.

BACKGROUND: Scarce data exist on the evolution of device-related thrombus (DRT) after left atrial appendage closure (LAAC). OBJECTIVES: This study sought to assess the incidence, predictors, and clinical impact of persistent and recurrent DRT in LAAC recipients. METHODS: Data were obtained from an international multicenter registry including 237 patients diagnosed with DRT after LAAC. Of these, 214 patients with a subsequent imaging examination after the initial diagnosis of DRT were included. Unfavorable evolution of DRT was defined as either persisting or recurrent DRT. RESULTS: DRT resolved in 153 (71.5%) cases and persisted in 61 (28.5%) cases. Larger DRT size (OR per 1-mm increase: 1.08; 95% CI: 1.02-1.15; P = 0.009) and female (OR: 2.44; 95% CI: 1.12-5.26; P = 0.02) were independently associated with persistent DRT. After DRT resolution, 82 (53.6%) of 153 patients had repeated device imaging, with 14 (17.1%) cases diagnosed with recurrent DRT. Overall, 75 (35.0%) patients had unfavorable evolution of DRT, and the sole predictor was average thrombus size at initial diagnosis (OR per 1-mm increase: 1.09; 95% CI: 1.03-1.16; P = 0.003), with an optimal cutoff size of 7 mm (OR: 2.51; 95% CI: 1.39-4.52; P = 0.002). Unfavorable evolution of DRT was associated with a higher rate of thromboembolic events compared with resolved DRT (26.7% vs 15.1%; HR: 2.13; 95% CI: 1.15-3.94; P = 0.02). CONCLUSIONS: About one-third of DRT events had an unfavorable evolution (either persisting or recurring), with a larger initial thrombus size (particularly >7 mm) portending an increased risk. Unfavorable evolution of DRT was associated with a 2-fold higher risk of thromboembolic events compared with resolved DRT.

Incidence and Predictors of Clinically Significant Bleedings after Transcatheter Left Atrial Appendage Closure.

BACKGROUND: Transcatheter left atrial appendage closure (LAAC) is performed in patients unsuitable for long-term anticoagulation, predominantly due to prior bleeding events. The study aimed to investigate the incidence and predictors of clinically significant bleeding (CSB) post-LAAC. METHODS: Consecutive patients after LAAC with an Amplatzer or WATCHMAN device were analyzed (05.2014-11.2019). Bleeding was classified as CSB when associated with at least one of the following: death, ≥2 g/dL hemoglobin drop, ≥2 blood units transfusion, critical anatomic site, or hospitalization/invasive procedure. RESULTS: Among 195 patients (age 74 (68-80), 43.1% females, HAS-BLED score 2.0 (2.0-3.0)), during median follow-up of 370 (IQR, 358-392) days, there were 15 nonprocedural CSBs in 14 (7.2%) patients. Of those, 9 (60.0%) occurred during postprocedural dual antiplatelet therapy (DAPT) (median 46 (IQR: 16-60) days post-LAAC) vs. 6 (40%) after DAPT discontinuation (median 124 (81-210) days post-LAAC), translating into annualized CSB rates of 14.0% (per patient-year on DAPT) vs. 4.6% (per patient-year without DAPT). In 92.9% (13/14) of patients, the post-LAAC nonprocedural CSB was a recurrence from the same site as bleeding pre-LAAC. In the multivariable model, admission systolic blood pressure (SBP) > 127 mmHg (HR = 10.73, 1.37-84.26, p = 0.024), epistaxis history (HR = 5.84, 1.32-25.89, p = 0.020), permanent atrial fibrillation (AF) (HR = 4.55, 1.20-17.20, p = 0.025), and prior gastrointestinal bleeding (HR = 3.35, 1.01-11.08, p = 0.048) predicted post-LAAC CSB. CONCLUSIONS: Nonprocedural CSBs after LAAC, with a similar origin as the pre-LAAC bleedings, were observed predominantly during postprocedural DAPT and predicted by elevated admission SBP, prior epistaxis, permanent AF, and gastrointestinal bleeding history. Whether a more reserved post-LAAC antiplatelet regimen and stringent blood pressure control may improve LAAC outcomes remains to be studied.

Residual stroke risk after left atrial appendage closure in patients with prior oral anticoagulation failure.

BACKGROUND: Patients with atrial fibrillation (AF) and oral anticoagulation (OAC) failure may benefit from left atrial appendage closure (LAAC), however, the evidence is scarce. We report outcomes of LAAC in patients with OAC failure compared to those with classic indications of OAC contraindications. METHODS: Prospective registry of LAAC with Amplatzer or WATCHMAN device followed by dual antiplatelet therapy (DAPT) was analyzed (05.2014-11.2019). The study group included patients with OAC failure defined as stroke/TIA/PE/LAA thrombus (n = 39) during OAC, whereas the control group consisted of patients with OAC contraindications (n = 156). Structured follow-up at 3, 6, and 12 months was done. RESULTS: The study group compared to controls was younger [73 (IQR, 62-77) vs 74 (IQR, 68-81) years, P = 0.046], with higher CHA2DS2-VASc [5.0 (IQR, 3.0-6.0) vs 4.0 (IQR, 3.0-5.0), P = 0.001)], lower HAS-BLED [2.0 (IQR, 1.0-3.0) vs 3.0 (IQR, 2.0-3.0), P = 0.006] and similar proportion of WATCHMAN implantations (43.6% vs 44.2%, P = 1.000). The reduction from CHA2DS2-VASc predicted to observed annual stroke/TIA/PE rate was markedly smaller in the study vs control group (14% vs 77%) with 10.3% vs 1.9% stroke/TIA/PE respectively (P = 0.031). The reduction from HAS-BLED predicted to observed annual major nonprocedural bleeding rate was higher (100% vs 7.4%) with 0.0% vs 5.1% major bleedings respectively (P = 0.361). The device-related thrombosis remained similar (13.2% vs 11.3%, P = 0.778). CONCLUSIONS: Patients after LAAC for OAC failure and unremarkable prior bleeding history presented with high residual stroke and low bleeding risks. Therefore concomitant long-term OAC or prolonged DAPT should strongly be considered in this population.

Cardiovascular and Renal Implications of Myocardial Infarction in the ISCHEMIA-CKD Trial.

BACKGROUND: ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) reported an initial invasive treatment strategy did not reduce the risk of death or nonfatal myocardial infarction (MI) compared with a conservative treatment strategy in patients with advanced chronic kidney disease, stable coronary disease, and moderate or severe myocardial ischemia. The cumulative frequency of different MI type after randomization and subsequent prognosis have not been reported. METHODS: MI classification was based on the Third Universal Definition for MI. For procedural MI, the primary MI definition used creatine kinase-MB as the preferred biomarker, whereas the secondary MI definition used cTn (cardiac troponin); both definitions included elevated biomarker-only events with higher thresholds than nonprocedural MIs. The cumulative frequency of MI type according to treatment strategy was determined. The association of MI with subsequent all-cause death and new dialysis initiation was assessed by treating MI as a time-dependent covariate. RESULTS: The 3-year incidence of type 1 or 2 MI with the primary MI definition was 11.2% in invasive treatment strategy and 13.6% in conservative treatment strategy (hazard ratio [HR], 0.66 [95% CI, 0.42-1.02]). Procedural MIs were more frequent in invasive treatment strategy and accounted for 9.8% and 28.3% of all MIs with the primary and secondary MI definitions, respectively. Patients had an increased risk of all-cause death after type 1 MI (adjusted HR, 4.35 [95% CI, 2.73-6.93]) and after procedural MI with the primary (adjusted HR, 2.75 [95% CI, 0.99-7.60]) and secondary MI definitions (adjusted HR, 2.91 [95% CI, 1.73-4.88]). Dialysis initiation was increased after a type 1 MI (HR, 6.45 [95% CI, 2.59-16.08]) compared with patients without an MI. CONCLUSIONS: In ISCHEMIA-CKD, the invasive treatment strategy had higher rates of procedural MIs, particularly with the secondary MI definition, and lower rates of type 1 and 2 MIs. Procedural MIs, type 1 MIs, and type 2 MIs were associated with increased risk of subsequent death. Type 1 MI increased the risk of dialysis initiation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01985360.

Management and outcomes of patients with left atrial appendage thrombus prior to percutaneous closure.

OBJECTIVE: Left atrial appendage (LAA) thrombus has heretofore been considered a contraindication to percutaneous LAA closure (LAAC). Data regarding its management are very limited. The aim of this study was to analyse the medical and invasive treatment of patients referred for LAAC in the presence of LAA thrombus. METHODS: This multicentre observational registry included 126 consecutive patients referred for LAAC with LAA thrombus on preprocedural imaging. Treatment strategies included intensification of antithrombotic therapy (IAT) or direct LAAC. The primary and secondary endpoints were a composite of bleeding, stroke and death at 18 months, and procedural success, respectively. RESULTS: IAT was the preferred strategy in 57.9% of patients, with total thrombus resolution observed in 60.3% and 75.3% after initial and subsequent IAT, respectively. Bleeding complications and stroke during IAT occurred in 9.6% and 2.9%, respectively, compared with 3.8% bleeding and no embolic events in the direct LAAC group before the procedure. Procedural success was 90.5% (96.2% vs 86.3% in direct LAAC and IAT group, respectively, p=0.072), without cases of in-hospital thromboembolic complications. The primary endpoint occurred in 29.3% and device-related thrombosis was found in 12.8%, without significant difference according to treatment strategy. Bleeding complications at 18 months occurred in 22.5% vs 10.5% in the IAT and direct LAAC group, respectively (p=0.102). CONCLUSION: In the presence of LAA thrombus, IAT was the initial management strategy in half of our cohort, with initial thrombus resolution in 60% of these, but with a relatively high bleeding rate (~10%). Direct LAAC was feasible, with high procedural success and absence of periprocedural embolic complications. However, a high rate of device-related thrombosis was detected during follow-up.

Aspiration coronary thrombectomy for acute myocardial infarction increases myocardial salvage: single center randomized study.

OBJECTIVES: The aim of the study was to assess if aspiration thrombectomy in high risk patients with STEMI and angiographic evidence of thrombus may improve myocardial salvage. BACKGROUND: It is unclear if thrombus aspiration before percutaneous intervention (PCI) improves myocardial salvage. METHODS: The trial was a prospective randomized study. The inclusion criteria were: first STEMI within 12 hr from symptoms onset, culprit lesion in left anterior descending or right coronary artery, culprit artery TIMI flow ≤ 2 and angiographic evidence of thrombus. The primary endpoint was myocardial salvage index (MSI) as assessed by (99m) Tc-sestamibi SPECT imaging. RESULTS: We randomized 137 patients (98 male, mean age 64.1 ± 12.5 years) either to aspiration thrombectomy followed by standard PCI with stent implantation (n = 67) or to standard primary PCI (n = 70). Index perfusion defect was similar in both study groups: 34.2% ± 13.1% in thrombectomy group versus 37.1% ± 12.0% in primary PCI group (P = 0.2). MSI was larger in aspiration thrombectomy group than in control patients [25.4% (IQR 13.5-44) vs. 18.5% (IQR 7.7-30.3) respectively, P = 0.02]. The final infarct size was smaller in patients treated with aspiration thrombectomy (23.1% ± 13.3% vs. 28.9% ± 10.2% in the control group, P = 0.002). CONCLUSIONS: Aspiration thrombectomy improves myocardial salvage in high risk STEMI patients with angiographic evidence of thrombus.