RESUMO

Importance: Previous studies investigated atherosclerotic changes induced by lipid-lowering therapy in extensive coronary segments irrespective of baseline disease burden (a vessel-level approach). Objective: To investigate the effects of lipid-lowering therapy on coronary lesions with advanced atherosclerotic plaque features and presumably higher risk for future events. Design, Setting, and Participants: The PACMAN-AMI randomized clinical trial (enrollment: May 2017 to October 2020; final follow-up: October 2021) randomized patients with acute myocardial infarction to receive alirocumab or placebo in addition to high-intensity statin therapy. In this post hoc lesion-level analysis, nonculprit lesions were identified as segments with plaque burden 40% or greater defined by intravascular ultrasound (IVUS). IVUS, near-infrared spectroscopy, and optical coherence tomography images at baseline and the 52-week follow-up were manually matched by readers blinded to treatment allocation. Data for this study were analyzed from October 2022 to November 2023. Interventions: Alirocumab or placebo in addition to high-intensity statin therapy. Main Outcomes and Measures: Lesion-level imaging outcome measures, including high-risk plaque characteristics and phenotypes. Results: Of the 245 patients in whom lesions were found, 118 were in the alirocumab group (mean [SD] age, 58.2 [10.0] years; 101 [85.6%] male and 17 [14.4%] female) and 127 in the placebo group (mean [SD] age, 57.7 [8.8] years; 104 [81.9%] male and 23 [18.1%] female). Overall, 591 lesions were included: 287 lesions (118 patients, 214 vessels) in the alirocumab group and 304 lesions (127 patients, 239 vessels) in the placebo group. Lesion-level mean change in percent atheroma volume (PAV) was -4.86% with alirocumab vs -2.78% with placebo (difference, -2.02; 95% CI, -3.00 to -1.05; P < .001). At the minimum lumen area (MLA) site, mean change in PAV was -10.14% with alirocumab vs -6.70% with placebo (difference, -3.36; 95% CI, -4.98 to -1.75; P < .001). MLA increased by 0.15 mm2 with alirocumab and decreased by 0.07 mm2 with placebo (difference, 0.21; 95% CI, 0.01 to 0.41; P = .04). Among 122 lipid-rich lesions, 34 of 55 (61.8%) in the alirocumab arm and 27 of 67 (41.8%) in the placebo arm showed a less lipid-rich plaque phenotype at follow-up (P = .03). Among 63 lesions with thin-cap fibroatheroma at baseline, 8 of 26 (30.8%) in the alirocumab arm and 3 of 37 (8.1%) in the placebo arm showed a fibrous/fibrocalcific plaque phenotype at follow-up (P = .02). Conclusions and Relevance: At the lesion level, very intensive lipid-lowering therapy induced substantially greater PAV regression than described in previous vessel-level analyses. Compared with statin therapy alone, alirocumab treatment was associated with greater enlargement of the lesion MLA and more frequent transition of presumably high-risk plaque phenotypes into more stable, less lipid-rich plaque phenotypes. Trial Registration: ClinicalTrials.gov Identifier: NCT03067844.

RESUMO

Adverse events (AEs) experienced by children and adults with congenital heart disease (CHD) on ventricular assist devices (VADs) are sometimes unique to these populations. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and the Academic Research Consortium (ARC) aimed to harmonize definitions of pediatric and CHD AEs for use in clinical trials, registries, and regulatory evaluation. Data from the ACTION registry and adjudication committee were used to adapt general mechanical circulatory support ARC definitions. This ACTION-ARC international expert panel of trialists, clinicians, patients, families, statisticians, biomedical engineers, device developers, and regulatory agencies drafted and iterated definitions harmonized to ACTION data and existing literature during sessions conducted between December 2022 and May 2023, followed by dissemination across clinical/research audiences and professional organizations and further revision. Both email-linked, internet-based surveys and in-person discussions were used as a modified Delphi process. Nineteen AE types were identified and defined, including seven new event types and six event types that were deleted and will no longer be collected, achieving consensus. ACTION-ARC paired rigorous development with methodical stakeholder involvement and dissemination to define pediatric VAD AEs to facilitate assimilation of data across future clinical trials and evaluation of devices for VAD-supported children and adults with CHD.

RESUMO

AIMS: There is a paucity of data on the performance of angiography-derived vessel fractional flow reserve (vFFR) in coronary artery lesions of patients presenting with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Optical coherence tomography (OCT) allows for visualization of lumen dimensions and plaque integrity with high resolution. The aim of the present study was to define the association between vFFR and OCT findings in intermediate coronary artery lesions in patients presenting with NSTE-ACS. METHODS AND RESULTS: The FAST OCT study was a prospective, multicenter, single-arm study. Patients presenting with NSTE-ACS with intermediate to severe coronary artery stenosis in one or multiple vessels with TIMI 3 flow suitable for OCT imaging were eligible. Complete pre-procedural vFFR and OCT data were available in 226 vessels (in 188 patients). A significant association between vFFR and minimal lumen area (MLA) was observed, showing an average decrease of 20.4% (95% CI -23.9% - -16.7%) in MLA per 0.10 decrease in vFFR (adjusted p<0.001). vFFR≤0.80 showed a sensitivity of 56.7% and specificity of 92.5% to detect MLA≤2.5 mm². Conversely, vFFR had a poor to moderate discriminative ability to detect plaque instability (sensitivity, 46.9% specificity 71.6%). CONCLUSIONS: In patients with NSTE-ACS, vFFR is significantly associated with OCT-detected MLA and a vFFR≤0.80 is highly predictive for the presence of significant disease based on OCT. Conversely, the sensitivity of vFFR≤0.80 to detect OCT-assessed significant disease was low, indicating that the presence of significant OCT findings cannot be ruled out based on a negative vFFR. CLINICALTRIALS.GOV ID: NCT04683133.

RESUMO

Inter-echocardiography core laboratory (ECL) harmonization is pivotal to consider data from different ECLs interchangeable. On the basis of the experience of the first trans-Atlantic harmonization of 2 established ECLs in the field of transcatheter aortic valve replacement (TAVR) trials, this review describes the harmonized ECL methodology in analyzing and adjudicating the post-TAVR echocardiographic endpoints according to Valve Academic Research Consortium 3 definitions. This review presents the feasibility and intra- and inter-ECL reproducibility, explains the root cause of potential important inter-ECL variability, and formulates ECL recommendations for optimal post-TAVR echocardiographic image acquisition. The implementation of inter-ECL harmonization may further define the best practice of ECLs and have logistic and regulatory implications for the realization of future TAVR trials.

RESUMO

The identification and management of patients at high bleeding risk (HBR) undergoing transcatheter aortic valve implantation (TAVI) are of major importance, but the lack of standardised definitions is challenging for trial design, data interpretation, and clinical decision-making. The Valve Academic Research Consortium for High Bleeding Risk (VARC-HBR) is a collaboration among leading research organisations, regulatory authorities, and physician-scientists from Europe, the USA, and Asia, with a major focus on TAVI-related bleeding. VARC-HBR is an initiative of the CERC (Cardiovascular European Research Center), aiming to develop a consensus definition of TAVI patients at HBR, based on a systematic review of the available evidence, to provide consistency for future clinical trials, clinical decision-making, and regulatory review. This document represents the first pragmatic approach to a consistent definition of HBR evaluating the safety and effectiveness of procedures, devices and drug regimens for patients undergoing TAVI..

Assuntos

Assuntos

RESUMO

BACKGROUND: Significant unprotected left main coronary artery (ULMCA) disease is encountered in approximately 5 % of patients undergoing diagnostic coronary angiography. Intravascular ultrasound (IVUS) overcomes many of the known limitations of angiography and improves outcomes of patients undergoing percutaneous coronary interventions (PCI) in stable or complex coronary artery disease. The aim of this systematic review is to evaluate the evidence on IVUS-guidance versus angiography-guidance in ULMCA PCI, highlighting the chronological frequencies of event rates in line with the maturation of PCI technique and devices over time. METHODS: A comprehensive systematic search in Medline was performed to identify all studies that had assessed the effect of IVUS-guided versus angiography-guided ULMCA PCI on various primary and secondary endpoints. RESULTS: Seventeen studies (2 randomized, 10 non-randomized and 5 meta-analyses) were included in this systematic review. CONCLUSIONS: This systematic review on IVUS-guided versus angiography-guided PCI in patients with significant ULMCA disease strongly supports the hypothesis that IVUS-guided PCI is associated with a significant reduction in major adverse cardiac events composites, all-cause death, cardiac death, myocardial infarction and stent thrombosis. Ongoing, adequately powered trials will contribute significantly to the level of evidence.

Assuntos

RESUMO

The Shock Academic Research Consortium is a multi-stakeholder group, including representatives from the US Food and Drug Administration and other government agencies, industry, and payers, convened to develop pragmatic consensus definitions useful for the evaluation of clinical trials enrolling patients with cardiogenic shock, including trials evaluating mechanical circulatory support devices. Several in-person and virtual meetings were convened between 2020 and 2022 to discuss the need for developing the standardized definitions required for evaluation of mechanical circulatory support devices in clinical trials for cardiogenic shock patients. The expert panel identified key concepts and topics by performing literature reviews, including previous clinical trials, while recognizing current challenges and the need to advance evidence-based practice and statistical analysis to support future clinical trials. For each category, a lead (primary) author was assigned to perform a literature search and draft a proposed definition, which was presented to the subgroup. These definitions were further modified after feedback from the expert panel meetings until a consensus was reached. This manuscript summarizes the expert panel recommendations focused on outcome definitions, including efficacy and safety.

Assuntos

RESUMO

Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.

Assuntos

RESUMO

Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.

Assuntos

RESUMO

Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.

Assuntos

RESUMO

BACKGROUND: Global longitudinal strain (GLS) is an accurate and reproducible parameter of left ventricular (LV) systolic function which has shown meaningful prognostic value. Fast, user-friendly, and accurate tools are required for its widespread implementation. We aim to compare a novel web-based tool with two established algorithms for strain analysis and test its reproducibility. METHODS: Thirty echocardiographic datasets with focused LV acquisitions were analyzed using three different semi-automated endocardial GLS algorithms by two readers. Analyses were repeated by one reader for the purpose of intra-observer variability. CAAS Qardia (Pie Medical Imaging) was compared with 2DCPA and AutoLV (TomTec). RESULTS: Mean GLS values were -15.0 ± 3.5% from Qardia, -15.3 ± 4.0% from 2DCPA, and -15.2 ± 3.8% from AutoLV. Mean GLS between Qardia and 2DCPA were not statistically different (p = 0.359), with a bias of -0.3%, limits of agreement (LOA) of 3.7%, and an intra-class correlation coefficient (ICC) of 0.88. Mean GLS between Qardia and AutoLV were not statistically different (p = 0.637), with a bias of -0.2%, LOA of 3.4%, and an ICC of 0.89. The coefficient of variation (CV) for intra-observer variability was 4.4% for Qardia, 8.4% 2DCPA, and 7.7% AutoLV. The CV for inter-observer variability was 4.5%, 8.1%, and 8.0%, respectively. CONCLUSIONS: In echocardiographic datasets of good image quality analyzed at an independent core laboratory using a standardized annotation method, a novel web-based tool for GLS analysis showed consistent results when compared with two algorithms of an established platform. Moreover, inter- and intra-observer reproducibility results were excellent.

RESUMO

BACKGROUND: Physiological assessment of intermediate coronary lesions to guide coronary revascularization is currently recommended by international guidelines. Vessel fractional flow reserve (vFFR) has emerged as a new approach to derive fractional flow reserve (FFR) from 3D-quantitative coronary angiography (3D-QCA) without the need for hyperemic agents or pressure wires. STUDY DESIGN AND OBJECTIVES: The FAST III is an investigator-initiated, open label, multicenter randomized trial comparing vFFR guided versus FFR guided coronary revascularization in approximately 2228 patients with intermediate coronary lesions (defined as 30%-80% stenosis by visual assessment or QCA). Intermediate lesions are physiologically assessed using on-line vFFR or FFR and treated if vFFR or FFR ≤0.80. The primary end point is a composite of all-cause death, any myocardial infarction, or any revascularization at 1-year post-randomization. Secondary end points include the individual components of the primary end point and cost-effectiveness will be investigated. CONCLUSIONS: FAST III is the first randomized trial to explore whether a vFFR guided revascularization strategy is non-inferior to an FFR guided strategy in terms of clinical outcomes at 1-year follow-up in patients with intermediate coronary artery lesions.

Assuntos

RESUMO

OBJECTIVES: To validate a simplified core laboratory intravascular ultrasound (IVUS) analysis method based on frames with visually determined minimal lumen areas (MLAs) as compared with a comprehensive (per frame) analysis method. BACKGROUND: IVUS-guided percutaneous coronary intervention has proven to be superior to angiography-guided stenting. In clinical practice, cross-sections with visually determined MLA are measured to determine lesion severity or minimal stent area (MSA), however, its accuracy has not been compared with a comprehensive per frame analysis method. METHODS: A total of 50 stented coronary segments of anonymized core lab datasets were analyzed using a comprehensive analysis method and reanalyzed by two core lab analysts using the simplified method including a maximum of seven frames to be analyzed (the visually determined MSA, the first and last frame, and the MLA of each reference segment). The main parameters of interest were MSA, MLA in the reference segments, and plaque burden. RESULTS: The simplified method showed moderate agreement for measurement of the proximal MLA (7.51 ± 2.52 vs. 6.32 ± 1.88 mm2 , intraclass correlation coefficient [ICC] = 0.73), good agreement for the distal MLA (5.41 ± 1.85 vs. 5.11 ± 1.38 mm2 , ICC = 0.84) and plaque burden proximal (0.49 ± 0.12 vs. 0.50 ± 0.11, ICC = 0.88), and excellent agreement for the MSA (5.35 ± 1.05 vs. 5.32 ± 0.99 mm2 , ICC = 0.94) and plaque burden distal (0.47 ± 0.14 vs. 0.47 ± 0.12, ICC = 0.92), when compared with the comprehensive analysis method. Inter- and intraobserver analysis revealed good-to-excellent agreement for all parameters. CONCLUSIONS: Measuring poststenting IVUS cross-sections with visually determined MLAs by experienced core lab analysts is an accurate and reproducible method to identify MLAs.

Assuntos

Assuntos

RESUMO

BACKGROUND: Vessel fractional flow reserve (vFFR) has a high diagnostic accuracy in assessing functional lesion significance compared with FFR. Nonhyperemic pressure ratios (NHPRs) were noninferior to FFR to guide revascularization of intermediate lesions. Therefore, the diagnostic performance of vFFR compared with NHPR warrants interest. AIM: To evaluate the diagnostic performance of vFFR with a generic diastolic pressure ratio (dPR) as a reference. METHODS: The study population was derived from the FAST EXTEND and FAST II studies. Between January 2016 and September 2020, a total of 475 patients were enrolled. RESULTS: Median dPR was 0.92 (interquartile range [IQR], 0.87-0.95), median vFFR was 0.86 (IQR, 0.80-0.90). The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of vFFR ≤0.80 for dPR ≤0.89 were 66%, 92%, 79%, 85%, and 84%, respectively. Vessel FFR showed a good agreement with dPR (r=0.68), consistent among specific clinical lesion subsets and a high diagnostic accuracy for dPR ≤0.89 (area under the curve=0.89). Discordance between vFFR and dPR was observed in 78/492 cases (15.6%) and logistic regression analysis did not reveal any clinical, angiographic, or hemodynamic variables associated with vFFR and dPR discordance. CONCLUSION: Vessel FFR shows a good agreement with dPR and a high diagnostic accuracy for dPR ≤0.89.

Assuntos

RESUMO

BACKGROUND: Randomized clinical trials are the gold standard to assess the causal relationship between an intervention and subsequent outcomes, also known as clinical endpoints. In order to limit bias, central clinical events committees (CEC) are established to ensure consistent event reporting across participating centers, as well as complete and accurate ascertainment of endpoints. However, defining independence is challenging. METHODS: This consensus statement was generated by teleconferences and electronic communications among clinical research organizations from the United States, Europe and Australia. This document does not constitute regulatory guidance. RESULTS: An independent CEC is defined when the adjudicators are not primarily involved in designing, funding, sponsoring, organizing, conducting, analyzing or regulating the clinical trial for which they serve as an adjudicator, beyond their role as CEC member. Moreover, independence requires absence of conflicts of interest with the steering committee, sponsor, grant giver, manufacturer, coordinating center, other independent committees, core laboratories, medical monitor, safety physician, participating clinical sites, statistician or data manager, regulatory agencies or authorities, which could influence (or be perceived to influence) a member's objectivity in evaluating trial data. Such conflicts of interest include financial benefits, directing or advisory role (paid or unpaid), decision-making position, as well as being a direct relative. An independent adjudicator has no other role within a clinical trial. CONCLUSIONS: This consensus statement presents a standardized definition of an independent CEC to be considered by clinical research organizations, manufacturers, and investigators. In addition, it provides recommendations on best practices for implementation of an independent CEC.

Assuntos

RESUMO

The clinical implications of hypertension in addition to a high prevalence of both uncontrolled blood pressure and medication nonadherence promote interest in developing device-based approaches to hypertension treatment. The expansion of device-based therapies and ongoing clinical trials underscores the need for consistency in trial design, conduct, and definitions of clinical study elements to permit trial comparability and data poolability. Standardizing methods of blood pressure assessment, effectiveness measures beyond blood pressure alone, and safety outcomes are paramount. The Hypertension Academic Research Consortium (HARC) document represents an integration of evolving evidence and consensus opinion among leading experts in cardiovascular medicine and hypertension research with regulatory perspectives on clinical trial design and methodology. The HARC document integrates the collective information among device-based therapies for hypertension to better address existing challenges and identify unmet needs for technologies proposed to treat the world's leading cause of death and disability. Consistent with the Academic Research Consortium charter, this document proposes pragmatic consensus clinical design principles and outcomes definitions for studies aimed at evaluating device-based hypertension therapies.

Assuntos