Ticagrelor with or without aspirin following percutaneous coronary intervention in high-risk patients with concomitant peripheral artery disease: A subgroup analysis of the TWILIGHT randomized clinical trial.

BACKGROUND: The optimal antiplatelet regimen after percutaneous coronary intervention (PCI) in patients with peripheral artery disease (PAD) is still debated. This analysis aimed to compare the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients with PAD undergoing PCI. METHODS: In the TWILIGHT trial, patients at high ischemic or bleeding risk that underwent PCI were randomized after 3 months of dual antiplatelet therapy (DAPT) to aspirin or matching placebo in addition to open-label ticagrelor for 12 additional months. In this post-hoc analysis, patient cohorts were examined according to the presence or absence of PAD. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction (MI), or stroke. Endpoints were assessed at 12 months after randomization. RESULTS: Among 7,119 patients, 489 (7%) had PAD and were older, more likely to have comorbidities, and multivessel disease. PAD patients had more bleeding or ischemic complications than no-PAD patients. Ticagrelor monotherapy compared to ticagrelor plus aspirin was associated with less BARC 2, 3, or 5 bleeding in PAD (4.6% vs 8.7%; HR 0.52; 95%CI 0.25-1.07) and no-PAD patients (4.0% vs 7.0%; HR 0.56; 95%CI 0.45-0.69; interaction P-value .830) and a similar risk of death, MI, or stroke in these 2 groups (interaction P-value .446). CONCLUSIONS: Despite their higher ischemic and bleeding risk, patients with PAD undergoing PCI derived a consistent benefit from ticagrelor monotherapy after 3 months of DAPT in terms of bleeding reduction without any relevant increase in ischemic events. CLINICAL TRIAL REGISTRY INFORMATION:: https://www. CLINICALTRIALS: gov/study/NCT02270242.

Redo-TAVI with the ACURATE neo2 and Prime XL for balloon-expandable transcatheter heart valve failure.

BACKGROUND: There are limited data regarding treatment for failed balloon-expandable transcatheter heart valves (THVs) in redo-transcatheter aortic valve implantation (TAVI). AIMS: We aimed to assess THV performance, neoskirt height and expansion when performing redo-TAVI with the ACURATE platform inside a SAPIEN 3 (S3) compared to redo-TAVI with an S3 in an S3. METHODS: Redo-TAVI was performed on the bench using each available size of the S3, the ACURATE neo2 (ACn2) and the next-generation ACURATE Prime XL (AC XL) implanted at 2 different depths within 20 mm/23 mm/26 mm/29 mm S3s serving as the "failed" index THV. Hydrodynamic testing was performed to assess THV function. Multimodality assessment was performed using photography, X-ray, microcomputed tomography (micro-CT), and high-speed videos. RESULTS: The ACURATE in S3 combinations had favourable hydrodynamic performance compared to the S3 in S3 for all size combinations. In the 20 mm S3, redo-TAVI with the ACn2 had lower gradients compared to the S3 (mean gradient 16.3 mmHg for the ACn2 vs 24.7 mmHg for the 20 mm S3 in 20 mm S3). Pinwheeling was less marked for the ACURATE THVs than for the S3s. On micro-CT, the S3s used for redo-TAVI were underexpanded across all sizes. This was also observed for the ACURATE platform, but to a lesser extent. CONCLUSIONS: Redo-TAVI with an ACn2/AC XL within an S3 has favourable hydrodynamic performance and less pinwheeling compared to an S3 in S3. This comes at the price of a taller neoskirt.

Evaluation and management of patients with coronary chronic total occlusions considered for revascularisation. A clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC, the European Association of Cardiovascular Imaging (EACVI) of the ESC, and the ESC Working Group on Cardiovascular Surgery.

Chronic total occlusions (CTOs) of coronary arteries can be found in the context of chronic or acute coronary syndromes; sometimes they are an incidental finding in those apparently healthy individuals undergoing imaging for preoperative risk assessment. Recently, the invasive management of CTOs has made impressive progress due to sophisticated preinterventional assessment, including advanced non-invasive imaging, the availability of novel and dedicated tools for CTO percutaneous coronary intervention (PCI), and experienced interventionalists working in specialised centres. Thus, it is crucial that referring physicians who see patients with CTO be aware of recent developments and of the initial evaluation requirements for such patients. Besides a careful history and clinical examination, electrocardiograms, exercise tests, and non-invasive imaging modalities are important for selecting the patients most suitable for CTO PCI, while others may be referred to coronary artery bypass graft or optimal medical therapy only. While CTO PCI improves angina and reduces the use of antianginal drugs in patients with symptoms and proven ischaemia, hibernation and/or wall motion abnormalities at baseline or during stress, the effect of CTO PCI on major cardiovascular events is still controversial. This clinical consensus statement specifically focuses on referring physicians, providing a comprehensive algorithm for the preinterventional evaluation of patients with CTO and the current evidence for the clinical effectiveness of the procedure. The proposed care track has been developed by members and with the support of the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Association of Cardiovascular Imaging (EACVI), and the European Society of Cardiology (ESC) Working Group on Cardiovascular Surgery.

18F-fluorodeoxyglucose and 18F-sodium fluoride positron emission tomography imaging in assessing early stages of aortic valve degeneration after transcatheter aortic valve implantation.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is a standard treatment for severe aortic stenosis, primarily in elderly patients. With an increasing number of procedures and younger patients, understanding the valve degeneration and its risk factors becomes crucial. OBJECTIVES: We aimed to utilize 18F­sodium fluoride (18F­NaF) and 18F­fluorodeoxyglucose (18F­FDG) positron emission tomography/computed tomography (PET/CT) to evaluate early TAVI valve degeneration. PATIENTS AND METHODS: In this prospective study with a prespecified follow­up protocol, 71 TAVI patients underwent baseline transthoracic and transesophageal echocardiography, and PET/CT with 18F­NaF and 18F­FDG. Of these, 31 patients completed 24­month control examinations, while the others were lost to mortality and the COVID­19 pandemic. We measured PET tracer activity and compared 18F­NaF and 18F­FDG PET/CT uptake at baseline and 24­month follow­up. RESULTS: PET/CT and echocardiography data were analyzed for 31 of the 71 enrolled TAVI patients at a median age of 84 years (interquartile range, 80-86). After TAVI, an improvement in the valve function was observed. During follow­up, the valve function remained stable. PET/CT demonstrated an increase in 18F­FDG maximal uptake in the inner (tissue­to­background ratio, P = 0.009) and outer (P = 0.01) sides of the TAVI valve stent, but no difference in 18F­NaF maximal activity (inner, P = 0.17; outer, P = 0.57). CONCLUSIONS: Twenty­four months post­TAVI, an increase in 18F­FDG uptake, indicative of inflammation, was observed in the valve, while the uptake of the calcification marker (18F­NaF) remained stable. Theseobservations might suggest early stages of TAVI valve degeneration, although further investigation is required to confirm this interpretation.

Feasibility of Coronary Access Following Redo-TAVR for Evolut Failure: A Computed Tomography Simulation Study.

BACKGROUND: Coronary accessibility following redo-transcatheter aortic valve replacement (redo-TAVR) is increasingly important, particularly in younger low-risk patients. This study aimed to predict coronary accessibility after simulated Sapien-3 balloon-expandable valve implantation within an Evolut supra-annular, self-expanding valve using pre-TAVR computed tomography (CT) imaging. METHODS: A total of 219 pre-TAVR CT scans from the Evolut Low-Risk CT substudy were analyzed. Virtual Evolut and Sapien-3 valves were sized using CT-based diameters. Two initial Evolut implant depths were analyzed, 3 and 5 mm. Coronary accessibility was evaluated for 2 Sapien-3 in Evolut implant positions: Sapien-3 outflow at Evolut node 4 and Evolut node 5. RESULTS: With a 3-mm initial Evolut implant depth, suitable coronary access was predicted in 84% of patients with the Sapien-3 outflow at Evolut node 4, and in 31% of cases with the Sapien-3 outflow at Evolut node 5 (P<0.001). Coronary accessibility improved with a 5-mm Evolut implant depth: 97% at node 4 and 65% at node 5 (P<0.001). When comparing 3- to 5-mm Evolut implant depth, sinus sequestration was the lowest with Sapien-3 outflow at Evolut node 4 (13% versus 2%; P<0.001), and the highest at Evolut node 5 (61% versus 32%; P<0.001). CONCLUSIONS: Coronary accessibility after Sapien-3 in Evolut redo-TAVR relates to the initial Evolut implant depth, the Sapien-3 outflow position within the Evolut, and the native annular anatomy. This CT-based quantitative analysis may provide useful information to inform and refine individualized preprocedural CT planning of the initial TAVR and guide lifetime management for future coronary access after redo-TAVR. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02701283.

Dyspnea-Related Ticagrelor Discontinuation After Percutaneous Coronary Intervention.

BACKGROUND: Nearly 20% of patients on ticagrelor experience dyspnea, which may lead to treatment discontinuation in up to one-third of cases. OBJECTIVES: The authors sought to evaluate the incidence, predictors, and outcomes of dyspnea-related ticagrelor discontinuation after percutaneous coronary intervention (PCI). METHODS: In the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. The occurrence of dyspnea associated with ticagrelor discontinuation was evaluated among all patients enrolled in the trial. A landmark analysis was performed at 3 months after PCI, that is, the time of randomization. Predictors of dyspnea-related ticagrelor discontinuation were obtained from multivariable Cox regression with stepwise selection of candidate variables. RESULTS: The incidence of dyspnea-related ticagrelor discontinuation was 6.4% and 9.1% at 3 and 15 months after PCI, respectively. Independent predictors included Asian race (lower risk), smoking, prior PCI, hypercholesterolemia, prior coronary artery bypass, peripheral artery disease, obesity, and older age. Among 179 patients who discontinued ticagrelor because of dyspnea after randomization, ticagrelor monotherapy was not associated with a higher risk of subsequent ischemic events (composite of all-cause death, myocardial infarction, or stroke) compared with ticagrelor plus aspirin (5.0% vs 7.1%; P = 0.566). CONCLUSIONS: In the TWILIGHT trial, dyspnea-related ticagrelor discontinuation occurred in almost 1 in 10 patients and tended to occur earlier rather than late after PCI. Several demographic and clinical conditions predicted its occurrence, and their assessment may help identify subjects at risk for therapy nonadherence.

Clinically Driven Revascularization in High-Risk Patients Treated With Ticagrelor Monotherapy After PCI: Insights from the Randomized TWILIGHT Trial.

Repeat coronary revascularization is a common adverse event after successful percutaneous coronary intervention. This analysis aimed to assess the effects of ticagrelor monotherapy on repeat clinically driven revascularization (CDR). In the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, high-risk patients were maintained on ticagrelor and randomly allocated to aspirin or placebo for 1 year. The primary end point of this analysis was CDR within 12 months after randomization. The key secondary end points were major adverse cardiovascular and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, stroke, or CDR, and net adverse clinical events (NACEs), including the individual components of MACCEs and clinically relevant bleeding. The analysis was performed in the per-protocol population. CDR occurred in 473 of 7,039 patients and was associated with a significantly higher risk of subsequent all-cause death, myocardial infarction, or stroke (adjusted hazard ratios [HRs] 2.92, 95% confidence interval [CI] 1.82 to 4.67). Ticagrelor monotherapy was associated with a similar 12-month risk of CDR (7.1% vs 6.6%; HR 1.09, 95% CI 0.90 to 1.30, p = 0.363) and MACCEs (8.9% vs 8.6%; HR 1.04, 95% CI 0.89 to 1.22, p = 0.619), and a lower risk of NACEs (12.2% vs 14.6%; HR 0.83 95% CI 0.73 to 0.94, p = 0.004) than ticagrelor plus aspirin. In conclusion, among high-risk patients who underwent percutaneous coronary intervention, ticagrelor monotherapy after 3 months of ticagrelor-based dual antiplatelet therapy was associated with a similar risk of CDR and MACCEs and a decrease of NACEs (TWILIGHT: NCT02270242).

Intensive Statin Therapy Versus Upfront Combination Therapy of Statin and Ezetimibe in Patients With Acute Coronary Syndrome: A Propensity Score Matching Analysis Based on the PL-ACS Data.

Background We aimed to compare statin monotherapy and upfront combination therapy of statin and ezetimibe in patients with acute coronary syndromes (ACSs). Methods and Results The study included consecutive patients with ACS included in the PL-ACS (Polish Registry of Acute Coronary Syndromes), which is a national, multicenter, ongoing, prospective observational registry that is mandatory for patients with ACS hospitalized in Poland. Data were matched using the Mahalanobis distance within propensity score matching calipers. Multivariable stepwise logistic regression analysis, including all variables, was next used in propensity score matching analysis. Finally, 38 023 consecutive patients with ACS who were discharged alive were included in the analysis. After propensity score matching, 2 groups were analyzed: statin monotherapy (atorvastatin or rosuvastatin; n=768) and upfront combination therapy of statin and ezetimibe (n=768 patients). The difference in mortality between groups was significant during the follow-up and was present at 1 (5.9% versus 3.5%; P=0.041), 2 (7.8% versus 4.3%; P=0.019), and 3 (10.2% versus 5.5%; P=0.024) years of follow-up in favor of the upfront combination therapy, as well as for the overall period. For the treatment, rosuvastatin significantly improved prognosis compared with atorvastatin (odds ratio [OR], 0.790 [95% CI, 0.732-0.853]). Upfront combination therapy was associated with a significant reduction of all-cause mortality in comparison with statin monotherapy (OR, 0.526 [95% CI, 0.378-0.733]), with absolute risk reduction of 4.7% after 3 years (number needed to treat=21). Conclusions The upfront combination lipid-lowering therapy is superior to statin monotherapy for all-cause mortality in patients with ACS. These results suggest that in high-risk patients, such an approach, rather than a stepwise therapy approach, should be recommended.

Patient-specific commissural alignment for ACURATE neo2 implantation in degenerated surgical bioprostheses.

Valve-in-valve TAVI to treat failing surgical aortic valves (SAVs) is increasingly performed, and commissural alignment is a key technical aspect in such procedures. Surgeons optimize valve alignment, accounting for potential coronary eccentricity and achieving a patient-specific optimized commissural orientation, representing the ideal target for TAVI alignment. Therefore, here we present a dedicated stepwise valve-in-valve implantation technique using the ACURATE neo2. In a specific SAV postoverlap view, isolating one surgical post to the right of the screen representing the target for alignment, rotational orientation of the TAVI commissures, matching the SAV orientation, is achieved and verified before implantation. This technique has been tested in a patient-specific three-dimensionally-printed aortic root anatomy, attached to a pulsatile flow simulator, allowing for native-like simulation of coronary cannulations under fluoroscopy, and enabling detailed assessment with fluoroscopic as well as direct videographic visualization. Furthermore, the technique is exemplified by providing an educational clinical case example.

Complete or Culprit-Only PCI in Older Patients with Myocardial Infarction.

BACKGROUND: The benefit of complete revascularization in older patients (≥75 years of age) with myocardial infarction and multivessel disease remains unclear. METHODS: In this multicenter, randomized trial, we assigned older patients with myocardial infarction and multivessel disease who were undergoing percutaneous coronary intervention (PCI) of the culprit lesion to receive either physiology-guided complete revascularization of nonculprit lesions or to receive no further revascularization. Functionally significant nonculprit lesions were identified either by pressure wire or angiography. The primary outcome was a composite of death, myocardial infarction, stroke, or any revascularization at 1 year. The key secondary outcome was a composite of cardiovascular death or myocardial infarction. Safety was assessed as a composite of contrast-associated acute kidney injury, stroke, or bleeding. RESULTS: A total of 1445 patients underwent randomization (720 to receive complete revascularization and 725 to receive culprit-only revascularization). The median age of the patients was 80 years (interquartile range, 77 to 84); 528 patients (36.5%) were women, and 509 (35.2%) were admitted for ST-segment elevation myocardial infarction. A primary-outcome event occurred in 113 patients (15.7%) in the complete-revascularization group and in 152 patients (21.0%) in the culprit-only group (hazard ratio, 0.73; 95% confidence interval [CI], 0.57 to 0.93; P = 0.01). Cardiovascular death or myocardial infarction occurred in 64 patients (8.9%) in the complete-revascularization group and in 98 patients (13.5%) in the culprit-only group (hazard ratio, 0.64; 95% CI, 0.47 to 0.88). The safety outcome did not appear to differ between the groups (22.5% vs. 20.4%; P = 0.37). CONCLUSIONS: Among patients who were 75 years of age or older with myocardial infarction and multivessel disease, those who underwent physiology-guided complete revascularization had a lower risk of a composite of death, myocardial infarction, stroke, or ischemia-driven revascularization at 1 year than those who received culprit-lesion-only PCI. (Funded by Consorzio Futuro in Ricerca and others; FIRE ClinicalTrials.gov number, NCT03772743.).

Transcatheter interventions for left-sided valvular heart disease complicated by cardiogenic shock: a consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) in collaboration with the Association for Acute Cardiovascular Care (ACVC) and the ESC Working Group on Cardiovascular Surgery.

Valvular heart disease (VHD) is one of the most frequent causes of heart failure (HF) and is associated with poor prognosis, particularly among patients with conservative management. The development and improvement of catheter-based VHD interventions have broadened the indications for transcatheter valve interventions from inoperable/high-risk patients to younger/lower-risk patients. Cardiogenic shock (CS) associated with severe VHD is a clinical condition with a very high risk of mortality for which surgical treatment is often deemed a prohibitive risk. Transcatheter valve interventions might be a promising alternative in this setting given that they are less invasive. However, supportive scientific evidence is scarce and often limited to small case series. Current guidelines on VHD do not contain specific recommendations on how to manage patients with both VHD and CS. The purpose of this clinical consensus statement, developed by a group of international experts invited by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) Scientific Documents and Initiatives Committee, is to perform a review of the available scientific evidence on the management of CS associated with left-sided VHD and to provide a rationale and practical approach for the application of transcatheter valve interventions in this specific clinical setting.

Bleeding and Ischemic Risks of Ticagrelor Monotherapy After Coronary Interventions.

BACKGROUND: In TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention), among high-risk patients undergoing percutaneous coronary intervention (PCI), ticagrelor monotherapy vs continuation of dual antiplatelet therapy (DAPT) with aspirin and ticagrelor after completing a 3-month course of DAPT was associated with reduced bleeding, without an increase in ischemic events. OBJECTIVES: This investigation sought to study the clinical benefit of ticagrelor monotherapy vs DAPT by simultaneously modeling its associated potential bleeding benefits and ischemic harms on an individual patient basis. METHODS: Multivariable Cox regression models for: 1) Bleeding Academic Research Consortium type 2, 3, or 5 (BARC-2/3/5); and 2) cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke (major adverse cardiac and cerebrovascular event [MACCE]) were developed using stepwise forward variable selection. The coefficients in the BARC-2/3/5 and MACCE models were used to calculate bleeding and ischemic risk scores, respectively, for each patient (excluding the coefficient for randomized treatment). RESULTS: In the total study group (N = 7,119), BARC-2/3/5 occurred in 391 (5.5%) patients, and MACCE occurred in 258 (3.6%). There was a consistent reduction in bleeding events associated with ticagrelor monotherapy compared with DAPT across both bleeding and ischemic risk strata (P interaction = 0.54 and 0.11, respectively). Importantly, this benefit associated with ticagrelor monotherapy was not offset by an increase in MACCE at any level of bleeding or ischemic risk. CONCLUSIONS: Three months after PCI, discontinuing aspirin and maintaining ticagrelor monotherapy reduces bleeding in both higher-bleeding risk and lower-bleeding risk patients compared with continued DAPT. This benefit does not appear to be offset by greater ischemic risk. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242).

ACC/AHA and ESC/EACTS Guidelines for the Management of Valvular Heart Diseases: JACC Guideline Comparison.

Valvular heart disease (VHD) is common and poses important challenges from the standpoints of diagnosis and therapeutic management. Clinical practice guidelines have been developed to help health care professionals to overcome these challenges and provide optimal management to patients with VHD. The American College of Cardiology, in collaboration with the American Heart Association, and the European Society of Cardiology, in collaboration with the European Association for Cardio-Thoracic Surgery, recently updated their guidelines on the management of VHD. Although these 2 sets of guidelines are generally concordant, there are some substantial differences between these guidelines, which may have significant implications for clinical practice. This review prepared on behalf of the EuroValve Consortium describes the consistencies and discrepancies between the guidelines and highlights the gaps in these guidelines and the future research perspectives to fill these gaps.

Merging virtual and physical experiences: extended realities in cardiovascular medicine.

Technological advancement and the COVID-19 pandemic have brought virtual learning and working into our daily lives. Extended realities (XR), an umbrella term for all the immersive technologies that merge virtual and physical experiences, will undoubtedly be an indispensable part of future clinical practice. The intuitive and three-dimensional nature of XR has great potential to benefit healthcare providers and empower patients and physicians. In the past decade, the implementation of XR into cardiovascular medicine has flourished such that it is now integrated into medical training, patient education, pre-procedural planning, intra-procedural visualization, and post-procedural care. This review article discussed how XR could provide innovative care and complement traditional practice, as well as addressing its limitations and considering its future perspectives.

Stepwise relationship between delay in percutaneous coronary intervention and long-term mortality in patients with non-ST-segment elevation myocardial infarction.

BACKGROUND: Current guidelines recommend coronary catheterization in patients with non-ST- -segment elevation myocardial infarction (NSTEMI) within 24 hours of hospital admission. However, whether there is a stepwise relationship between the time to percutaneous coronary intervention (PCI) and long-term mortality in patients with NSTEMI treated invasively within 24 hours of admission has not been established yet. AIMS: The study aimed to evaluate the association between door-to-PCI time and all-cause mortality at 12 and 36 months in NSTEMI patients presenting directly to a PCI-capable center who underwent PCI within the first 24 hours of hospitalization. METHODS: We analyzed data of patients hospitalized for NSTEMI between 2007-2019, included in the nationwide registry of acute coronary syndromes. Patients were stratified into twelve groups based on 2-hour intervals of door-to-PCI time. The mortality rates of patients within those groups were adjusted for 33 confounding variables by the propensity score weighting method using overlap weights. RESULTS: A total of 37 589 patients were included in the study. The median age of included patients was 66.7 (interquartile range [IQR], 59.0-75.8) years; 66.7% were male, and the median GRACE (Global Registry of Acute Coronary Events) score was 115 (98-133). There were increased 12-month and 36-month mortality rates in consecutive groups of patients stratified by 2-hour door-to-PCI time intervals. After adjustment for patient characteristics, there was a significant positive correlation between the time to PCI and the mortality rates (rs = 0.61; P = 0.04 and rs = 0.65; P = 0.02 for 12-month and 36-month mortality, respectively). CONCLUSIONS: The longer the door-to-PCI time, the higher were 12-month and 36-month all-cause mortality rates in NSTEMI patients.