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Background: CYP2C19 genotype-guided de-escalation from ticagrelor or prasugrel to clopidogrel may optimize the balance between ischemic and bleeding risk in patients with acute coronary syndrome (ACS)., Objectives: This study sought to compare bleeding and ischemic event rates in genotyped patients vs standard care., Methods: Since 2015, ACS patients in the multicenter FORCE-ACS (Future Optimal Research and Care Evaluation in Patients with Acute Coronary Syndrome) registry received standard dual antiplatelet therapy (DAPT). Since 2021, genotype-guided P2Y 12 inhibitor de-escalation was recommended at a single center, switching noncarriers of the loss-of-function allele CYP2C19∗3 or CYP2C19∗2 from ticagrelor or prasugrel to clopidogrel, whereas loss-of-function carriers remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction, or stroke, and the primary bleeding endpoint, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, were compared between a genotyped cohort and a cohort treated with standard DAPT after 1 year., Results: Among 5,321 enrolled ACS patients, 406 underwent genotyping compared with 4,915 nongenotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n = 265) were noncarriers, 88.7% (n = 235) of whom were switched to clopidogrel. The primary ischemic endpoint occurred in 5.2% (n = 21) of patients in the genotyped cohort compared to 6.9% (n = 337) in the standard care cohort (adjusted HR: 0.82; 95% CI: 0.53-1.28). The primary bleeding rate was significantly lower in the genotyped cohort compared to the standard care cohort (4.7% vs 9.8%; adjusted HR: 0.47; 95% CI: 0.30-0.76)., Conclusions: The implementation of a CYP2C19 genotype-guided P2Y 12 inhibitor de-escalation strategy in a real-world ACS population resulted in lower bleeding rates without an increase in ischemic events compared to a standard DAPT regimen., Competing Interests: Funding Support and Author Disclosures The FORCE-ACS registry is supported by grants from ZonMw, the St. Antonius Research Fund, and AstraZeneca. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the manuscript, and its final contents. Dr Vlachojannis has received institutional research grants from MicroPort and Ferrer; and has received personal fees from Terumo and AstraZeneca. Dr Appelman has received an institutional research grant from the Dutch Heart Foundation. Dr Henriques has received institutional research grants from Abbott Vascular, AstraZeneca, B. Braun, Getinge, Ferrer, Infraredx, and ZonMw. Dr Kikkert has received an institutional research grant from AstraZeneca. Dr ten Berg has received institutional research grants from AstraZeneca, Daiichi Sankyo, and ZonMw; and has received personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, CeleCor Therapeutics, Daiichi Sankyo, Eli Lilly, Ferrer, and Idorsia. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Complete revascularization of the culprit and all significant nonculprit lesions in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and multivessel disease (MVD) reduces major adverse cardiac events, but optimal timing of revascularization remains unclear., Objectives: This study aims to compare immediate complete revascularization (ICR) and staged complete revascularization (SCR) in patients presenting with NSTE-ACS and MVD., Methods: This prespecified substudy of the BIOVASC (Percutaneous Complete Revascularization Strategies Using Sirolimus Eluting Biodegradable Polymer Coated Stents in Patients Presenting With Acute Coronary Syndrome and Multivessel Disease) trial included patients with NSTE-ACS and MVD. Risk differences of the primary composite outcome of all-cause mortality, myocardial infarction (MI), unplanned ischemia-driven revascularization (UIDR), or cerebrovascular events and its individual components were compared between ICR and SCR at 1 year., Results: The BIOVASC trial enrolled 1,525 patients; 917 patients presented with NSTE-ACS, of whom 459 were allocated to ICR and 458 to SCR. Incidences of the primary composite outcome were similar in the 2 groups (7.9% vs 10.1%; risk difference 2.2%; 95% CI: -1.5 to 6.0; P = 0.15). ICR was associated with a significant reduction of MIs (2.0% vs 5.3%; risk difference 3.3%; 95% CI: 0.9 to 5.7; P = 0.006), which was maintained after exclusion of procedure-related MIs occurring during the index or staged procedure (2.0% vs 4.4%; risk difference 2.4%; 95% CI: 0.1 to 4.7; P = 0.032). UIDRs were also reduced in the ICR group (4.2% vs 7.8%; risk difference 3.5%; 95% CI: 0.4 to 6.6; P = 0.018)., Conclusions: ICR is safe in patients with NSTE-ACS and MVD and was associated with a reduction in MIs and UIDRs at 1 year., Competing Interests: Funding Support and Author Disclosures The BIOVASC trial was funded by the Erasmus University Medical Center, Rotterdam, and Biotronik SE & Co KG, Berlin. Dr Diletti has received institutional research grants from Biotronik, Medtronic, ACIST Medical Systems, and Boston Scientific. Dr den Dekker has received institutional research grants from Biotronik. Dr Van Mieghem has received institutional research grants from Biotronik, Abbott, Medtronic, Edwards Lifesciences, PulseCath, Abiomed, and Daiichi-Sankyo; speaker fees from Abiomed and Amgen; and a travel grant from JenaValve. Dr Bennett has received institutional grants from Biotronik, Abbott Vascular, and Shockwave Medical. Dr Daemen has received institutional grant/research support from Abbott Vascular, Boston Scientific, ACIST Medical Systems, Medtronic, Microport, Pie Medical, and ReCor Medical; and consultancy and speaker fees from Abbott Vascular, Abiomed, ACIST Medical Systems, Boston Scientific, Cardialysis BV, CardiacBooster, Kaminari Medical, ReCor Medical, PulseCath, Pie Medical, Sanofi, Siemens Healthineers, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A new-generation everolimus eluting platinum-chromium stent (EePCS), offering improved radial strength, radiopacity and conformability compared to everolimus-eluting cobalt-chromium stents (EeCCS), was evaluated with regard to safety and efficacy in an all-comer cohort., Methods: A total of 1000 consecutive all-comer patients (including acute coronary syndrome, multivessel disease, calcified lesions) treated with an EePCS (Promus Premier™, Boston Scientific, Natick, Massachusetts) from May 2013 to October 2014 were compared to 1000 consecutive patients treated with an EeCCS (Xience Prime™, Abbott Vascular, Santa Clara, California) from April 2012 to May 2013. Patients were clinically followed for 1year., Results: Mean age was 66±12years with diabetes in 20.7%, previous infarction in 22.7%, and ACS as the indication in 71.2% of patients. The mean number of stents per patient was 1.8±1.13. Total stented length was 35±25mm. Lesion classification was B2/C in 73.9% of patients. At 1year the primary endpoint of major adverse cardiac events (all-cause mortality, myocardial infarction [MI], ischemia-driven target vessel revascularization [TVR]) was reached in 11.7% in the EePCS cohort and 10.9% in the EeCCS cohort (adjusted HR 1.01 [0.77-1.33]; p=0.95). No significant differences were noted in the individual clinical endpoints all-cause mortality (6.8% versus 6.4%), MI (2.2% versus 2.3%), and TVR (4.3% versus 3.7%) in the respective EePCS and EeCCS cohorts. Stent thrombosis occurred in 0.8% and 1.0% respectively., Conclusions: In all-comer patients undergoing percutaneous coronary intervention, the use of EePCS was associated with similar 1-year clinical outcome as compared to EeCCS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Biventricular (BV) electrical wavefront fusion can induce improvement in left ventricular (LV) size and function during cardiac resynchronization therapy (CRT). Changes in BV wave propagation sequence and duration register in the QRS complex on the standard electrocardiogram. We developed a wave interference method for the characterization of BV fusion to predict LV reverse remodeling., Objective: To develop a simple electrocardiographic method for predicting reverse remodeling during CRT., Methods: QRS complexes during left bundle branch block (LBBB) and CRT were analyzed in 375 patients with ejection fraction ≤35% and New York Heart Association class III-IV (Leiden study: n = 226) as well as in patients with ejection fraction ≤40% and New York Heart Association class I-II (REVERSE trial: n = 149) for predictors of ≥10% reduction in left ventricular end-systolic volume at 6 months. CRT-induced changes in ventricular activation (QRS fusion contour), electrical asynchrony (QRS difference = BV-paced QRS - LBBB QRS, in milliseconds), and LBBB substrate (LV activation time and QRS score for LV scar) were quantified., Results: Multivariable predictors of reverse remodeling were as follows: (1) either of 2 BV fusion patterns: QRS normalization in leads V1 and V2 (n = 66 [18%]; odds ratio [OR] 3.71; 95% confidence interval [CI] 1.26-10.94) or a new or an increased R wave in leads V1-V2 (n = 267 [71%]; OR 1.55; 95% CI 0.65-3.65); (2) QRS difference ≤ -25 ms (OR 2.35; 95% CI 1.12-4.91); and (3) good substrate (low to moderate QRS score and LV activation time ≥110 ms; OR 2.94; 95% CI 1.68-5.14). Remodeling rates were 40% for poor substrate and persistent LBBB QRS complex (absent BV fusion; QRS type 3: n = 42 [11%]) and 97% for the best BV QRS fusion pattern and greater reduction in electrical asynchrony (larger QRS difference)., Conclusion: Easily determined QRS complex attributes before and after CRT predict LV reverse remodeling., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Surgical ventricular reconstruction has been proposed as a treatment option in heart failure patients with left ventricular (LV) aneurysm. The feasibility of this procedure has some limitations, and extensive preoperative evaluation is necessary to give the correct indication. For this purpose, magnetic resonance imaging (MRI) is currently considered the gold standard, providing accurate quantification of LV shape, size, and global and regional function together with the assessment of myocardial scar and mitral regurgitation severity. The aim of this study was to evaluate the accuracy of real-time three-dimensional echocardiography (RT3DE) as a potential alternative to MRI for this evaluation., Methods: A total of 52 patients with ischemic cardiomyopathy and LV aneurysm underwent a comprehensive analysis with two-dimensional echocardiography, RT3DE, and MRI., Results: Excellent correlation (r=0.97, p<0.001) and agreement were found between RT3DE and MRI for quantification of LV volumes, ejection fraction, and sphericity index; in a segment-to-segment comparison, RT3DE was shown to be accurate also for the analysis of wall motion abnormalities (k=0.62) and LV regional thickness (k=0.56) as a marker of myocardial scar. In contrast, two-dimensional echocardiography significantly underestimated these variables. Furthermore, mitral regurgitant volume assessed by RT3DE showed excellent correlation (r=0.93) with regurgitant volume measured by MRI, without significant bias (=-0.7 mL/beat)., Conclusions: In the management of heart failure patients with LV aneurysm, RT3DE provides an accurate and comprehensive assessment, including quantification of LV size, shape, global systolic function, regional wall motion, and myocardial scar together with precise evaluation of the severity of mitral regurgitation., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate feasibility and accuracy of real-time 3-dimensional (3D) echocardiography for quantification of mitral regurgitation (MR), in a head-to-head comparison with velocity-encoded cardiac magnetic resonance (VE-CMR)., Background: Accurate grading of MR severity is crucial for appropriate patient management but remains challenging. VE-CMR with 3D three-directional acquisition has been recently proposed as the reference method., Methods: A total of 64 patients with functional MR were included. A VE-CMR acquisition was applied to quantify mitral regurgitant volume (Rvol). Color Doppler 3D echocardiography was applied for direct measurement, in "en face" view, of mitral effective regurgitant orifice area (EROA); Rvol was subsequently calculated as EROA multiplied by the velocity-time integral of the regurgitant jet on the continuous-wave Doppler. To assess the relative potential error of the conventional approach, color Doppler 2-dimensional (2D) echocardiography was performed: vena contracta width was measured in the 4-chamber view and EROA calculated as circular (EROA-4CH); EROA was also calculated as elliptical (EROA-elliptical), measuring vena contracta also in the 2-chamber view. From these 2D measurements of EROA, the Rvols were also calculated., Results: The EROA measured by 3D echocardiography was significantly higher than EROA-4CH (p < 0.001) and EROA-elliptical (p < 0.001), with a significant bias between these measurements (0.10 cm(2) and 0.06 cm(2), respectively). Rvol measured by 3D echocardiography showed excellent correlation with Rvol measured by CMR (r = 0.94), without a significant difference between these techniques (mean difference = -0.08 ml/beat). Conversely, 2D echocardiographic approach from the 4-chamber view significantly underestimated Rvol (p = 0.006) as compared with CMR (mean difference = 2.9 ml/beat). The 2D elliptical approach demonstrated a better agreement with CMR (mean difference = -1.6 ml/beat, p = 0.04)., Conclusions: Quantification of EROA and Rvol of functional MR with 3D echocardiography is feasible and accurate as compared with VE-CMR; the currently recommended 2D echocardiographic approach significantly underestimates both EROA and Rvol.

Background: Data on the occurrence and implications of new-onset atrial fibrillation (AF) following cardiac resynchronization therapy (CRT) are scarce. We studied the incidence of new onset AF in CRT-defibrillator (CRT-D) recipients. The influence of new-onset AF on echocardiographic response to CRT and the rate of adverse events also were evaluated., Objective: The purpose of this study was to assess the incidence and implications of new-onset AF following CRT., Methods: The study population consisted of 223 consecutive patients with no history of AF. New-onset AF was defined as atrial high-rate episodes >180 bpm for more than 10 minutes/day as detected by the device. Echocardiography was performed at baseline and after 6 months of biventricular pacing. Long-term events included implantable cardioverter-defibrillator therapy for ventricular arrhythmias, hospitalization for heart failure, and all-cause mortality., Results: Fifty-five (25%) patients developed new-onset AF during mean follow-up of 32 +/- 16 months. When compared to the patients who maintained sinus rhythm during follow-up, patients who developed AF showed less left ventricular (LV) reverse remodeling (DeltaLV end-systolic volume 37 +/- 53 vs >19 +/- 37 mL, P <.05) and less improvement in LV function (DeltaLV ejection fraction 6.7% +/- 8.9% vs 3.5% +/- 10.3%, P <.05). Importantly, patients who developed AF experienced more appropriate ICD shocks for ventricular arrhythmias, more inappropriate shocks, and more hospitalizations for heart failure., Conclusion: Recipients of CRT-D who develop new-onset AF show less echocardiographic response to CRT and more cardiac adverse events during long-term follow-up.

Background: Real-time 3-dimensional echocardiography (RT3DE) is a novel promising technique for the assessment of left ventricular (LV) dyssynchrony., Objective: This study sought to explore the value of RT3DE to assess LV and left atrium (LA) reverse remodeling and to predict response to cardiac resynchronization therapy (CRT)., Methods: A total of 57 consecutive heart failure patients scheduled for CRT were included, and RT3DE was performed before and 6 months after implantation. LV dyssynchrony was defined as the standard deviation of the time to reach the minimum systolic volume for 16 LV segments, expressed in percentage of cardiac cycle (systolic dyssynchrony index, SDI). Patients were divided into responders or nonresponders, based on a reduction >or=15% in LV end-systolic volume after CRT., Results: Six patients (10%) were excluded from further analysis because of suboptimal images. Of the remaining 51 patients, 34 (67%) were classified as responders. Baseline characteristics were similar between responders and nonresponders, except for the SDI, which was larger in responders (9.7% +/- 3.6% versus 5.1% +/- 1.8%, P <.0001). ROC curve analysis revealed that a cutoff value for SDI of 6.4% yielded a sensitivity of 88% with a specificity of 85% to predict response to CRT. In responders, RT3DE also showed beneficial effects of CRT on LA: (1) significant LA reverse remodeling; (2) significant improvement in LA total emptying fraction and in LA conduit and reservoir function., Conclusion: RT3DE allows assessment of changes in LV and LA volumes and function after CRT, and it is highly predictive for response to CRT.