The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI)clinical endpoints to make ...them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection.
A recent study confirmed that VARC definitions have already been incorporated into clinical and research practice and represent a new standard for consistency in reporting clinical outcomes of patients with symptomatic severe aortic stenosis (AS) undergoing TAVI. However, as the clinical experience with this technology has matured and expanded, certain definitions have become unsuitable or ambiguous.
Two in-person meetings (held in September 2011 in Washington, DC, USA, and in February 2012 in Rotterdam, the Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and non-interventional cardiologists, imaging specialists, neurologists, geriatric specialists, and clinical trialists), the US Food and Drug Administration (FDA), and industry representatives, provided much of the substantive discussion from which this VARC-2 consensus manuscript was derived. This document provides an overview of risk assessment and patient stratification that need to be considered for accurate patient inclusion in studies. Working groups were assigned to define the following clinical endpoints: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and a miscellaneous category including relevant complications not previously categorized. Furthermore, comprehensive echocardiographic recommendations are provided for the evaluation of prosthetic valve (dys)function. Definitions for the quality of life assessments are also reported. These endpoints formed the basis for several recommended composite endpoints.
This VARC-2 document has provided further standardization of endpoint definitions for studies evaluating the use of TAVI, which will lead to improved comparability and interpretability of the study results, supplying an increasingly growing body of evidence with respect to TAVI and/or surgical aortic valve replacement. This initiative and document can furthermore be used as a model during current endeavours of applying definitions to other transcatheter valve therapies (for example, mitral valve repair).
Contemporary guidelines on valvular heart disease have embraced transcatheter aortic valve replacement (TAVR) as the standard treatment for older patients with symptomatic severe degenerative aortic ...valve stenosis.1,2 It is remarkable that randomised controlled trials comparing TAVR and surgical aortic valve replacement with only 1 or 2 years of clinical follow-up formed the foundation for these recommendations. Extended follow-up to 5 years and longer in these randomised and other trials justified this policy because there has been no signal of accelerated transcatheter valve degeneration or impaired durability.3,4 Regardless, surgical and transcatheter bioprosthetic valves will eventually degenerate. Because of TAVR adoption in younger and patients with lower risk, the individual's lifespan might outlast the bioprosthesis and transcatheter valve failure will become a genuine clinical scenario. ...5-year and 8-year echocardiography follow-up data demonstrated more structural valve degeneration with surgical valves than with self-expanding transcatheter valves.7,8 As far as management of transcatheter valve failure goes, explant surgery is a relatively complex procedure that might require advanced surgical skills including aortic root replacement and enlargement techniques.9 A recent international registry reported a four-times higher 30-day mortality rate after explant surgery as compared with redo-TAVR (13·6% vs 3·4%, p<0·001).10 Makkar and colleagues’ study corroborates redo-TAVR as the preferred treatment strategy for transcatheter valve failure.
Abstract
Aims
The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for ...transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research.
Methods and results
Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs.
Conclusions
Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.
Graphical Abstract
Abstract
Aims
The number of transcatheter aortic valve implantation (TAVI) procedures is rapidly increasing. This has a major impact on health care resource planning. However, the annual numbers of ...TAVI candidates per country are unknown. The aim of this study was to estimate current and future number of annual TAVI candidates in 27 European countries, the USA and Canada.
Methods and results
Systematic literature searches and meta-analyses were performed on aortic stenosis (AS) epidemiology and decision-making in severe symptomatic AS. The incidence rate of severe AS was determined. Findings were combined with population statistics and integrated into a model employing Monte Carlo simulations to predict the annual number of TAVI candidates. Various future scenarios and sensitivity analyses were explored. Data from 37 studies (n = 26 402) informed the model. The calculated incidence rate of severe AS was 4.4‰/year 95% confidence interval (95% CI) 3.0–6.1‰ in patients ≥65 years. AS-related symptoms were present in 68.3% (95% CI 60.8–75.9%) of patients with severe AS. Despite having severe symptomatic AS, 41.6% (95% CI 36.9–46.3%) did not undergo surgical aortic valve replacement. Of the non-operated patients, 61.7% (95% CI 42.0–81.7%) received TAVI. The model predicted 114 757 (95% CI 69 380–172 799) European and 58 556 (95% CI 35 631–87 738) Northern-American TAVI candidates annually.
Conclusion
Currently, approximately 180 000 patients can be considered potential TAVI candidates in the European Union and in Northern-America annually. This number might increase up to 270 000 if indications for TAVI expand to low-risk patients. These findings have major implications for health care resource planning in the 29 individual countries.
Abstract
Ventricular pressure–volume (PV) analysis is the reference method for the study of cardiac mechanics. Advances in calibration algorithms and measuring techniques brought new perspectives for ...its application in different research and clinical settings. Simultaneous PV measurement in the heart chambers offers unique insights into mechanical cardiac efficiency. Beat to beat invasive PV monitoring can be instrumental in the understanding and management of heart failure, valvular heart disease, and mechanical cardiac support. This review focuses on intra cardiac left ventricular PV analysis principles, interpretation of signals, and potential clinical applications.
Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is superior to angiography-guided PCI. The clinical uptake of FFR has been limited, however, by the need to advance a ...wire in the coronary artery, the additional time required and the need for hyperaemic agents which can cause patient discomfort. FFR derived from routine coronary angiography eliminates these issues.
The aim of this study was to assess the diagnostic performance and accuracy of three-dimensional quantitative coronary angiography (3D-QCA)-based vessel FFR (vFFR) compared to pressure wire-based FFR (≤0.80).
The FAST II (Fast Assessment of STenosis severity) study was a prospective observational multicentre study designed to evaluate the diagnostic accuracy of vFFR compared to the reference standard (pressure wire-based FFR ≤0.80). A total of 334 patients from six centres were enrolled. Both site-determined and blinded independent core lab vFFR measurements were compared to FFR.
The core lab vFFR was 0.83±0.09 and pressure wire-based FFR 0.83±0.08. A good correlation was found between core lab vFFR and pressure wire-based FFR (R=0.74; p<0.001; mean bias 0.0029±0.0642). vFFR had an excellent diagnostic accuracy in identifying lesions with an invasive wire-based FFR ≤0.80 (area under the curve AUC 0.93; 95% confidence interval CI: 0.90-0.96; p<0.001). Positive predictive value, negative predictive value, diagnostic accuracy, sensitivity and specificity of vFFR were 90%, 90%, 90%, 81% and 95%, respectively.
3D-QCA-based vFFR has excellent diagnostic performance to detect FFR ≤0.80. The study was registered on clinicaltrials.gov under identifier NCT03791320.
Transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of symptomatic severe aortic valve stenosis. Current guidelines recommend TAVI in patients at increased operative risk ...of death. Advanced imaging planning, new transcatheter valve platforms, procedure streamlining and growing operator experience have improved procedural safety and bioprosthetic valve performance. As a result, TAVI has been explored for other indications. Two randomized trials published in 2019 to assess TAVI in patients with symptomatic severe aortic stenosis at low operative risk have set the stage for a new wave of indications. In younger and low-risk patients, TAVI had an early safety benefit over surgical aortic valve replacement and was associated with faster discharge from hospital and recovery and fewer rehospitalizations. In patients with symptomatic severe aortic stenosis, TAVI has now been explored across the entire spectrum of operative risk, from inoperable to low-risk populations, in properly designed, randomized clinical trials, although data on the long-term durability of these valves are lacking. The use of TAVI in severe bicuspid aortic valve stenosis, asymptomatic severe aortic stenosis, moderate aortic stenosis in combination with heart failure with reduced ejection fraction, and isolated pure aortic regurgitation is now under investigation in clinical trials. In this Review, we provide our perspective on these evolving indications for TAVI, discuss relevant available data from clinical trials, and highlight procedural implications and caveats of new and future indications.
Abstract Objectives The aim of this study was to identify variables associated with tissue fragment embolization during transcatheter aortic valve replacement (TAVR). Background Brain magnetic ...resonance imaging and transcranial Doppler studies have revealed that cerebrovascular embolization occurs frequently during TAVR. Embolized material may be r thrombotic, tissue derived, or catheter (foreign material) fragments. Methods A total of 81 patients underwent TAVR with a dual filter–based embolic protection device (Montage Dual Filter System, Claret Medical, Inc., Santa Rosa, California) deployed in the brachiocephalic trunk and left common carotid artery. Both balloon-expandable and self-expanding transcatheter heart valves (THVs) were used. Filters were retrieved after TAVR and sent for histopathological analysis. Results Overall, debris was captured in 86% of patients. Captured material varied in size from 0.1 to 9.0 mm. Thrombotic material was found in 74% of patients and tissue-derived debris in 63%. Tissue fragments were found more often with balloon-expandable THVs (79% vs. 56%; p = 0.05). The embolized tissue originated from the native aortic valve leaflets, aortic wall, or left ventricular myocardium. On multivariable logistic regression analysis, balloon-expandable THVs (odds ratio: 7.315; 95% confidence interval: 1.398 to 38.289; p = 0.018) and cover index (odds ratio: 1.141; 95% confidence interval: 1.014 to 1.283; p = 0.028) were independent predictors of tissue embolization. Conclusions Debris is captured with filter-based embolic protection in the vast majority of patients undergoing TAVR. Tissue-derived material is found in 63% of cases and is more frequent with the use of balloon-expandable systems and more oversizing.
Background Little is known about the impact of bleeding and red blood cells transfusion (RBC) on the outcome post transcatheter aortic valve implantation (TAVI). Methods Between November 2005 and ...August 2011, 943 consecutive patients underwent TAVI. Bleeding was assessed according to the Valve Academic Research Consortium definitions. Patients receiving RBC were compared to those not requiring transfusion. Results Life-threatening and major bleedings occurred respectively in 13.9% and 20.9% of the patients, significantly more frequently in the RBC cohort. Vascular complications occurred in 23.2% of the patients. Major and minor vascular complications were more frequent in the RBC group: 19.3 vs 5.2%, P < .001; 15.3 vs 9%, P = .003, respectively. Thirty-day all-cause mortality was 7.2%. Of the overall cohort, 38.9% required RBC transfusion; those receiving at least 4 U of RBC had higher 30-day all-cause mortality than those receiving 1 to 4 U of RBC and those not requiring transfusion: 14.4%, vs 6.3% vs 6.3%, respectively, P = .008. By multivariate analysis, transfusion of RBC was associated with an increased 30-day and 1-year mortality. Major stroke and all stages of acute kidney injury were significantly more frequent in the RBC cohort. Conclusions Bleeding is frequent after TAVI, mainly driven by vascular complications. RBC transfusion was associated with increased mortality at 1 year and increased risk of major stroke and acute kidney injury. Specific scores are needed to identify the patients at higher risk for TAVI-related bleeding and RBC transfusion.
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