Stuart J. Head

2014 ESC/EACTS Guidelines on myocardial revascularization The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI)

Authors/Task Force members: Stephan Windecker* (ESC Chairperson) (Switzerland), Philippe Kolh* (EACTS Chairperson) (Belgium), Fernando Alfonso (Spain), Jean-Philippe Collet (France), Jochen Cremer (Germany), Volkmar Falk (Switzerland), Gerasimos Filippatos (Greece), Christian Hamm (Germany), Stuart J. Head (The Netherlands), Peter Jüni (Switzerland), A. Pieter Kappetein (The Netherlands), Adnan Kastrati (Germany), Juhani Knuuti (Finland), Ulf Landmesser (Switzerland), Günther Laufer (Austria), Franz-Josef Neumann (Germany), Dimitrios J. Richter (Greece), Patrick Schauerte (Germany), Miguel Sousa Uva (Portugal), Giulio G. Stefanini (Switzerland), David Paul Taggart (UK), Lucia Torracca (Italy), Marco Valgimigli (Italy), William Wijns (Belgium), and Adam Witkowski (Poland).

Updated standardized endpoint definitions for transcatheter aortic valve implantation: The Valve Academic Research Consortium-2 consensus document

OBJECTIVES 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. BACKGROUND 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. METHODS AND RESULTS Two in-person meetings (held in September 2011 in Washington, DC, and in February 2012 in Rotterdam, The Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and noninterventional 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. CONCLUSIONS 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 endeavors of applying definitions to other transcatheter valve therapies (for example, mitral valve repair).

Updated Standardized Endpoint Definitions for Transcatheter Aortic Valve Implantation

OBJECTIVES 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. BACKGROUND 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. METHODS AND RESULTS 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 echocardiography 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. CONCLUSIONS 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 endeavors of applying definitions to other transcatheter valve therapies (for example, mitral valve repair).

2014 ESC/EACTS Guidelines on myocardial revascularization

Acute coronary syndromes Bare-metal stents Coronary artery bypass grafting Coronary artery disease Drug-eluting stents EuroSCORE Guidelines Heart Team Myocardial infarction Myocardial ischaemia Myocardial revascularization Medical therapy Percutaneous coronary intervention Recommendation Revascularisation Risk stratification Stents Stable angina Stable coronary artery disease ST-segment elevation myocardial infarction SYNTAX score

Clinical Outcomes After Transcatheter Aortic Valve Replacement Using Valve Academic Research Consortium Definitions A Weighted Meta-Analysis of 3,519 Patients From 16 Studies

OBJECTIVES This study sought to perform a weighted meta-analysis to determine the rates of major outcomes after transcatheter aortic valve replacement (TAVR) using Valve Academic Research Consortium (VARC) definitions and to evaluate their current use in the literature. BACKGROUND Recently, the published VARC definitions have helped to add uniformity to reporting outcomes after TAVR. METHODS A comprehensive search of multiple electronic databases from January 1, 2011, through October 12, 2011, was conducted using predefined criteria. We included studies reporting at least 1 outcome using VARC definitions. RESULTS A total of 16 studies including 3,519 patients met inclusion criteria and were included in the analysis. The pooled estimate rates of outcomes were determined according to VARCs definitions: device success, 92.1% (95% confidence interval [CI]: 88.7% to 95.5%); all-cause 30-day mortality, 7.8% (95% CI: 5.5% to 11.1%); myocardial infarction, 1.1% (95% CI: 0.2% to 2.0%); acute kidney injury stage II/III, 7.5% (95% CI: 5.1% to 11.4%); life-threatening bleeding, 15.6% (95% CI: 11.7% to 20.7%); major vascular complications, 11.9% (95% CI: 8.6% to 16.4%); major stroke, 3.2% (95% CI: 2.1% to 4.8%); and new permanent pacemaker implantation, 13.9% (95% CI: 10.6% to 18.9%). Medtronic CoreValve prosthesis use was associated with a significant higher rate of new permanent pacemaker implantation compared with the Edwards prosthesis (28.9% [95% CI: 23.0% to 36.0%] vs. 4.9% [95% CI: 3.9% to 6.2%], p < 0.0001). The 30-day safety composite endpoint rate was 32.7% (95% CI: 27.5% to 38.8%) and the 1-year total mortality rate was 22.1% (95% CI: 17.9% to 26.9%). CONCLUSIONS VARC definitions have already been used by the TAVR clinical research community, establishing a new standard for reporting clinical outcomes. Future revisions of the VARC definitions are needed based on evolving TAVR clinical experiences.

Clinical ResearchInterventional CardiologyClinical Outcomes After Transcatheter Aortic Valve Replacement Using Valve Academic Research Consortium Definitions: A Weighted Meta-Analysis of 3,519 Patients From 16 Studies

OBJECTIVES This study sought to perform a weighted meta-analysis to determine the rates of major outcomes after transcatheter aortic valve replacement (TAVR) using Valve Academic Research Consortium (VARC) definitions and to evaluate their current use in the literature. BACKGROUND Recently, the published VARC definitions have helped to add uniformity to reporting outcomes after TAVR. METHODS A comprehensive search of multiple electronic databases from January 1, 2011, through October 12, 2011, was conducted using predefined criteria. We included studies reporting at least 1 outcome using VARC definitions. RESULTS A total of 16 studies including 3,519 patients met inclusion criteria and were included in the analysis. The pooled estimate rates of outcomes were determined according to VARCs definitions: device success, 92.1% (95% confidence interval [CI]: 88.7% to 95.5%); all-cause 30-day mortality, 7.8% (95% CI: 5.5% to 11.1%); myocardial infarction, 1.1% (95% CI: 0.2% to 2.0%); acute kidney injury stage II/III, 7.5% (95% CI: 5.1% to 11.4%); life-threatening bleeding, 15.6% (95% CI: 11.7% to 20.7%); major vascular complications, 11.9% (95% CI: 8.6% to 16.4%); major stroke, 3.2% (95% CI: 2.1% to 4.8%); and new permanent pacemaker implantation, 13.9% (95% CI: 10.6% to 18.9%). Medtronic CoreValve prosthesis use was associated with a significant higher rate of new permanent pacemaker implantation compared with the Edwards prosthesis (28.9% [95% CI: 23.0% to 36.0%] vs. 4.9% [95% CI: 3.9% to 6.2%], p < 0.0001). The 30-day safety composite endpoint rate was 32.7% (95% CI: 27.5% to 38.8%) and the 1-year total mortality rate was 22.1% (95% CI: 17.9% to 26.9%). CONCLUSIONS VARC definitions have already been used by the TAVR clinical research community, establishing a new standard for reporting clinical outcomes. Future revisions of the VARC definitions are needed based on evolving TAVR clinical experiences.

Aortic Stenosis in the Elderly: Disease Prevalence and Number of Candidates for Transcatheter Aortic Valve Replacement: A Meta-Analysis and Modeling Study

OBJECTIVES The purpose of this study was to evaluate the prevalence of aortic stenosis (AS) in the elderly and to estimate the current and future number of candidates for transcatheter aortic valve replacement (TAVR). BACKGROUND Severe AS is a major cause of morbidity and mortality in the elderly. A proportion of these patients is at high or prohibitive risk for surgical aortic valve replacement, and is now considered for TAVR. METHODS A systematic search was conducted in multiple databases, and prevalence rates of patients (>75 years) were pooled. A model was based on a second systematic literature search of studies on decision making in AS. Monte Carlo simulations were performed to estimate the number of TAVR candidates in 19 European countries and North America. RESULTS Data from 7 studies (n = 9,723 subjects) were used. The pooled prevalence of all AS in the elderly was 12.4% (95% confidence interval [CI]: 6.6% to 18.2%), and the prevalence of severe AS was 3.4% (95% CI: 1.1% to 5.7%). Among elderly patients with severe AS, 75.6% (95% CI: 65.8% to 85.4%) were symptomatic, and 40.5% (95% CI: 35.8% to 45.1%) of these patients were not treated surgically. Of those, 40.3% (95% CI: 33.8% to 46.7%) received TAVR. Of the high-risk patients, 5.2% were TAVR candidates. Projections showed that there are approximately 189,836 (95% CI: 80,281 to 347,372) TAVR candidates in the European countries and 102,558 (95% CI: 43,612 to 187,002) in North America. Annually, there are 17,712 (95% CI: 7,590 to 32,691) new TAVR candidates in the European countries and 9,189 (95% CI: 3,898 to 16,682) in North America. CONCLUSIONS With a pooled prevalence of 3.4%, the burden of disease among the elderly due to severe AS is substantial. Under the current indications, approximately 290,000 elderly patients with severe AS are TAVR candidates. Nearly 27,000 patients become eligible for TAVR annually.

Paravalvular leak after transcatheter aortic valve replacement: The new achilles' heel? A comprehensive review of the literature

Paravalvular leak (PVL) is a frequent complication of transcatheter aortic valve replacement (TAVR) and is seen at a much higher rate after TAVR than after conventional surgical aortic valve replacement. Recent reports indicating that PVL may be correlated with increased late mortality have raised concerns. However, the heterogeneity of methods for assessing and quantifying PVL, and lack of consistency in the timing of such assessments, is a hindrance to understanding its true prevalence, severity, and effect. This literature review is an effort to consolidate current knowledge in this area to better understand the prevalence, progression, and impact of post-TAVR PVL and to help direct future efforts regarding the assessment, prevention, and treatment of this troublesome complication.

Treatment of complex coronary artery disease in patients with diabetes: 5-year results comparing outcomes of bypass surgery and percutaneous coronary intervention in the SYNTAX trial

OBJECTIVES This prespecified subgroup analysis examined the effect of diabetes on left main coronary disease (LM) and/or three-vessel disease (3VD) in patients treated with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in the SYNTAX trial. METHODS Patients (n = 1800) with LM and/or 3VD were randomized to receive either PCI with TAXUS Express paclitaxel-eluting stents or CABG. Five-year outcomes in subgroups with (n = 452) or without (n = 1348) diabetes were examined: major adverse cardiac or cerebrovascular events (MACCE), the composite safety end-point of all-cause death/stroke/myocardial infarction (MI) and individual MACCE components death, stroke, MI and repeat revascularization. Event rates were estimated with Kaplan-Meier analyses. RESULTS In diabetic patients, 5-year rates were significantly higher for PCI vs CABG for MACCE (PCI: 46.5% vs CABG: 29.0%; P < 0.001) and repeat revascularization (PCI: 35.3% vs CABG: 14.6%; P < 0.001). There was no difference in the composite of all-cause death/stroke/MI (PCI: 23.9% vs CABG: 19.1%; P = 0.26) or individual components all-cause death (PCI: 19.5% vs CABG: 12.9%; P = 0.065), stroke (PCI: 3.0% vs CABG: 4.7%; P = 0.34) or MI (PCI: 9.0% vs CABG: 5.4%; P = 0.20). In non-diabetic patients, rates with PCI were also higher for MACCE (PCI: 34.1% vs CABG: 26.3%; P = 0.002) and repeat revascularization (PCI: 22.8% vs CABG: 13.4%; P < 0.001), but not for the composite end-point of all-cause death/stroke/MI (PCI: 19.8% vs CABG: 15.9%; P = 0.069). There were no differences in all-cause death (PCI: 12.0% vs CABG: 10.9%; P = 0.48) or stroke (PCI: 2.2% vs CABG: 3.5%; P = 0.15), but rates of MI (PCI: 9.9% vs CABG: 3.4%; P < 0.001) were significantly increased in the PCI arm in non-diabetic patients. CONCLUSIONS In both diabetic and non-diabetic patients, PCI resulted in higher rates of MACCE and repeat revascularization at 5 years. Although PCI is a potential treatment option in patients with less-complex lesions, CABG should be the revascularization option of choice for patients with more-complex anatomic disease, especially with concurrent diabetes.

The impact of prosthesis–patient mismatch on long-term survival after aortic valve replacement: a systematic review and meta-analysis of 34 observational studies comprising 27 186 patients with 133 141 patient-years

AIMS Numerous studies have linked prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR) to adverse outcomes. Its correlation with long-term survival has been described but with contradicting results. This systematic review and meta-analysis of observational studies aims to determine the hazard of PPM after AVR. METHODS AND RESULTS The Medline and EMBase databases were searched for English-language original publications. Two researchers independently screened studies and extracted data. Pooled estimates were obtained by random effects model. Subgroup analyses were performed to detect sources of heterogeneity. The search yielded 348 potentially relevant studies; 34 were included comprising 27 186 patients and 133 141 patient-years. Defined by the universally accredited indexed effective orifice area <0.85 cm(2)/m(2), 44.2% of patients were categorized as having PPM. In 34.2 and 9.8% of patients moderate (0.65-0.85 cm(2)/m(2)) and severe (<0.65 cm(2)/m(2)) PPM was present, respectively. Prosthesis-patient mismatch was associated with a statistically significant increase in all-cause mortality (HR = 1.34, 95% CI: 1.18-1.51), but only a trend to an increase in cardiac-related mortality (HR = 1.51, 95% CI: 0.88-2.60) was recognized. Analysis by severity of PPM demonstrated that both moderate and severe PPM increased all-cause mortality (HR = 1.19, 95% CI: 1.07-1.33 and HR = 1.84, 95% CI: 1.38-2.45) and cardiac-related mortality (HR = 1.32, 95% CI: 1.02-1.71 and HR = 6.46, 95% CI: 2.79-14.97). Further analyses showed a consistent effect over separate time intervals during follow-up. CONCLUSION Prosthesis-patient mismatch is associated with an increase in all-cause and cardiac-related mortality over long-term follow-up. We recommend that current efforts to prevent PPM should receive more emphasis and a widespread acceptance to improve long-term survival after AVR.