Commentary: ART: Let it rest in peace
2020; Elsevier BV; Volume: 163; Issue: 3 Linguagem: Inglês
10.1016/j.jtcvs.2020.03.100
ISSN1097-685X
Autores Tópico(s)Surgical Simulation and Training
ResumoCentral MessageTotal arterial revascularization may improve outcomes in selected low-risk patients, but further studies are needed.See Article page 1002. Total arterial revascularization may improve outcomes in selected low-risk patients, but further studies are needed. See Article page 1002. The Arterial Revascularization Trial (ART) was a multicenter, prospective trial consisting of 3102 patients who underwent coronary artery bypass graft (CABG) randomized to receive either bilateral internal thoracic artery (BITA) or single internal thoracic artery (SITA) grafts along with guideline-directed medical therapy (GDMT).1Taggart D.P. Bennedetto U. Garry S. Altman D.G. Gray A.M. Lees B. et al.Arterial revascularization trial investigators: bilateral versus single internal thoracic artery grafts at ten years.N Engl J Med. 2019; 380: 437-446Crossref PubMed Scopus (289) Google Scholar Both groups received saphenous vein grafts (SVGs), and 21.8% of the SITA and 19.4% of the BITA patients also received a radial artery (RA) graft. After 10 years, there was no significant difference between the groups in mortality from any cause, or the composite endpoint of death, myocardial infarction (MI), stroke, or the need for a repeat revascularization. There was, however, a significant increase in the incidence of sternal wound complications in patients who received BITA (3.5% BITA vs 1.9% SITA; P = .005) and the need for sternal wound reconstruction (2.0% BITA vs 0.6% SITA; P < .02). The ART investigators proposed several explanations to explain the lack of superiority of BITA over SITA grafting:•The crossover rate was high; 14% of patients assigned to the BITA group actually received a SITA graft.•The incidence of off-pump CABG (OPCAB) was 40.6%. In a recent study from the New York State (NYS) database, improved survival in patients receiving multiple arterial grafts (MAGs) was not observed in a subpopulation of MAG patients undergoing OPCAB procedures.2Samadashvili Z. Sundt T.M. Weschler A. Chikwe J. Adams D.H. Smith C.R. et al.Multiple versus single arterial coronary bypass graft surgery for multivessel disease.J Am Coll Cardiol. 2019; 74: 1275-1285Crossref PubMed Scopus (49) Google Scholar It is possible that the high incidence of OPCAB in ART may have contributed to decreased long-term graft patency.•Adherence to GDMT was extremely high in ART. Noncompliance with GDMT following CABG has been shown to decrease long-term survival, freedom from MIs, and the need for repeat coronary revascularization procedures.3Pinho-Gomes A.C. Azevedo L. Aha -J.-M. Park S.-J. Hamza T.H. Farkousch M.E. Compliance with guideline direct medical therapy in contemporary coronary revascularization trials.J Am Coll Cardiol. 2018; 71: 591-602Crossref PubMed Scopus (82) Google Scholar The long-term survival of SITA patients in ART was greater than in other trials that had decreased compliance with GDMT, and this may have negated the superiority of BITA grafting.•Since 21.8% of patients in the SITA group also received RA grafts, in essence, they actually were MAG patients. The RA has been shown to have superior patency compared with SVGs and could have contributed to improved long-term survival in SITA patients.4Gaudino M. Benedetto U. Fremes S. Radial artery or saphenous vein graft in coronary artery bypass surgery.N Engl J Med. 2018; 378: 2069-2077Crossref PubMed Scopus (353) Google Scholar In this edition of the Journal, Taggart and his ART co-investigators report the result of a post-hoc analysis of ART to determine the effect of MAG, total arterial grafting (TAG), and single arterial grafting (SAG) on 10-year survival and the composite outcome of death, MI, stroke, and repeat revascularization.5Taggart D.P. Gaudino M.F. Gerry S. Gray A. Lees B. Dimagli A. et al.Effect of total arterial grafting in the Arterial Revascularization Trial.J Thorac Cardiovasc Surg. 2022; 163: 1002-1009.e6Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar As opposed to ART, in this analysis, patients were assigned to SAG, MAG, and TAG based on the number and types of grafts that they actually received. Only those patients who received 3 or more grafts were included in this analysis, thereby potentially excluding those patients who might have received an incomplete revascularization, which has been shown to decrease long-term survival following CABG despite the use of BITA and MAG.6Schwann T.A. Yammine M.B. El-Hage-Sleiman A.K.M. Engoren M.C. Bonnell M.R. Habib R.H. The effect of completeness of revascularization during coronary artery bypass grafting with single versus multiple arterial grafts.J Card Surg. 2018; 33: 620-628Crossref PubMed Scopus (14) Google Scholar Patients in the TAG group were 2 years younger, were less likely to have concomitant right coronary artery disease, and had worse New York Heart Association functional class but were more likely to have a left ventricular ejection fraction 70 years. However, in the entire patient cohort, there was a significant trend toward a reduction in 10-year mortality with MAG and TAG compared with SAG. The greatest benefit was seen in the TAG group, which showed the lowest risk of 10-year mortality (P = .03) and a significant reduction in the composite endpoint of death, MI, stroke, and repeat revascularization; P = .02. In patients with insulin-dependent diabetes; MAG and TAG were associated with a lower incidence of the composite endpoint, whereas TAG was associated with the lowest incidence of mortality. As noted by the authors, there were several limitations with this post-hoc analysis of ART. This was a nonrandomized comparison of relatively low-risk patients who received CABG and the outcomes may not be comparable with a current cohort of patients who tend to be older, with more comorbidities, and who present with a greater incidence of unstable symptoms. The relatively small numbers of patients with chronic obstructive pulmonary disease, end-stage renal disease, and peripheral vascular disease did not permit conclusions to be made regarding the benefits of MAG and TAG in these high-risk patients. Perhaps the most important limitation is the lack of follow-up angiograms to determine graft patency among the 3 groups. This is crucial to determine the mechanism for the potential benefits of MAG and TAG in CABG patients. No data are provided as to whether the re-revascularization procedures were performed in grafted versus nongrafted vessels, or whether it involved a vessel previously grafted by either an arterial or SVG conduit. Therefore, it is unclear as to whether the need for a repeat revascularization was due to an initial incomplete revascularization, primary graft failure, or the progression of atherosclerotic disease distal to the grafted vessel. It has been postulated that arterial grafts have enhanced patency due to the secretion of substances that preserve endothelial function and prevent atherosclerotic disease in both the arterial conduit and the distal vessel it supplies.7Dimitrova K.R. Hoffman D.M. Geller C.M. Arterial grafts protect the native coronary vessels from atherosclerotic disease progression.Ann Thorac Surg. 2012; 94: 475-481Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar Therefore, follow-up angiograms would be expected to show both enhanced arterial conduit patency and freedom from atherosclerotic disease in the distal native vessel. The role of MAG and TAG in CABG remains undefined. However, we do know those groups of patients who may not benefit from multiple arterial conduits:•Age: In both the post-hoc analysis of ART and the NYS database, there was no benefit of MAG and SAG in patients >70 years. Lytle and colleagues8Lytle B.W. Blackstone E.H. Sabik J.F. Sabik J.K. Houghtaling P. Loop F.D. et al.The effect of bilateral internal thoracic artery grafting on survival during 20 postoperative years.Ann Thorac Surg. 2004; 78: 2005-2012Abstract Full Text Full Text PDF PubMed Scopus (416) Google Scholar showed that improved survival following BITA grafting was seen only after 10 years. In the NYS study, the survival curves for MAG versus SAG began to diverge only after 7 years.2Samadashvili Z. Sundt T.M. Weschler A. Chikwe J. Adams D.H. Smith C.R. et al.Multiple versus single arterial coronary bypass graft surgery for multivessel disease.J Am Coll Cardiol. 2019; 74: 1275-1285Crossref PubMed Scopus (49) Google Scholar Therefore, to see a long-term survival advantage, patients undergoing MAG or TAG should have a life expectancy of at least 7 to 10 years.•Comorbidities: Patients with comorbidities that will limit life expectancy, such as end-stage renal disease, active smokers with chronic obstructive pulmonary disease, peripheral vascular disease, underlying malignancies, and those with poorly controlled diabetes who already have evidence of end-organ dysfunction, will also not benefit from MAG.•Completeness of revascularization: Patients in whom complete revascularization is not possible due to irreversibly damaged myocardium, and those with small and diffusely diseased target vessels, will also not benefit from the use of BITA and MAG.6Schwann T.A. Yammine M.B. El-Hage-Sleiman A.K.M. Engoren M.C. Bonnell M.R. Habib R.H. The effect of completeness of revascularization during coronary artery bypass grafting with single versus multiple arterial grafts.J Card Surg. 2018; 33: 620-628Crossref PubMed Scopus (14) Google Scholar•Sternal issues: Patients at risk for sternal complications, such as obese, insulin-dependent females, frail patients with osteoporosis, patients on chronic steroids, and heavy smokers with COPD are all at risk for sternal complications and in whom MAG with BITA grafting should be avoided.•Degree of target vessel stenosis: Arterial conduit patency is more sensitive to the degree of target vessel stenosis. Internal thoracic artery grafting should be avoided in patients with a <70% stenosis, and RA graft patency has been shown to be decreased in target vessels < 80% stenosis.4Gaudino M. Benedetto U. Fremes S. Radial artery or saphenous vein graft in coronary artery bypass surgery.N Engl J Med. 2018; 378: 2069-2077Crossref PubMed Scopus (353) Google Scholar There are multiple reasons why surgeons continue to be reluctant to perform MAG and TAG. These include the increased time needed to harvest multiple arterial grafts, especially in urgent and emergent cases, and the concern for the increased incidence of sternal wound infections with its increased morbidity and mortality, in an age of open reporting of CABG outcomes. Perhaps the most important factor is the lack of data to support the role of MAG and TAG. The majority of studies are retrospective, underpowered, and nonrandomized, with no data regarding graft patency, the quality of distal vessel targets, and compliance with GDMT. It is hoped that the ongoing Randomized comparison of the clinical Outcome of single versus Multiple Arterial grafts (ROMA) trial, comparing SAG vs MAG, will address these concerns.9Gaudino M. Alexander J.H. Bakaeen F.G. Ballman K. Barili F. Calafiore A.M. et al.Randomized comparison of the clinical outcome of single versus multiple arterial grafts: the ROMA trial—rationale and study protocol.Eur J Cardiothorac Surg. 2017; 52: 1031-1040Crossref PubMed Google Scholar The ART investigators are to be congratulated for attempting to determine why this trial failed to show a superiority for BITA over SITA grafting after 10 years. In doing so, they have helped us to understand the limitations of existing CABG trials and to identify which groups of patients may benefit the most from MAG and TAG. ART should not be viewed as a “failed” study but rather as a “landmark” trial. It showed that when RA grafting is combined with SITA and compliance with GDMT, the results can be equivalent to BITA grafting without the increased risk of sternal wound complications. It is now time to let ART rest in peace and move on to newer, prospectively randomized, adequately powered trials developed to avoid the pitfalls of ART, such as the ongoing ROMA trial, to provide the data needed to determine the role of MAG and TAG in the current practice of CABG surgery. Effect of total arterial grafting in the Arterial Revascularization TrialThe Journal of Thoracic and Cardiovascular SurgeryVol. 163Issue 3PreviewThe Arterial Revascularization Trial (ART) was designed to compare 10-year survival in bilateral versus single internal thoracic artery grafts. The intention-to-treat analysis has showed comparable outcomes between the 2 groups but an explanatory analysis suggested that those receiving 2 or more arterial grafts had better survival. Whether the exclusive use of arterial grafts provide further benefit is unclear. Full-Text PDF
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