Serruys, Patrick W.

Abstract Background Periprocedural myocardial infarction (PMI) occurs frequently after both percutaneous coronary intervention (PCI) and bypass grafting surgery (CABG) in patients with complex coronary artery disease (CAD), and PMI has been shown to have a detrimental impact on mortality. On the other hand, long-term impact of PMI on mortality has not been fully evaluated. Purpose This study aimed to assess the impact of PMI according to SCAI definition on 10-year all-cause death in patients with complex CAD. Methods The SYNTAX Extended Survival (SYNTAXES) study evaluated vital status up to 10 years in 1800 patients with de novo three-vessel disease and/or left main coronary artery disease randomized to treatment with CABG or PCI in the SYNTAX trial. Blood was sampled for creatine kinase (CK) pre- and post-revascularisation, and the cardiac specific MB iso-enzyme (CK-MB) was determined only if the CK ratio ≥2 x the upper limit of normal (ULN). If the CK ratio <2 ULN, CK-MB assessment was not mandated. In this analysis, patients with at least one blood sampling within 48 hours of the procedure were included. PMI was defined as follows; peak CK-MB measured within 48 hours of the procedure ≥10 x ULN, or ≥5 x ULN with new Q-waves in 2 contiguous leads or new persistent left bundle branch block. Results Of 1800 patients, 1679 (93.2%) patients were included. Of 877 patients treated with PCI, PMI occurred in 26 patients (3.0%), whereas 14 (1.7%) PMIs were observed in 802 patients treated with CABG. Compared with patients without PMI, patients with PMI presented with unstable angina more frequently (45.0% vs. 28.7, p=0.033), and had a higher rate of bifurcation lesion (87.5% vs. 72.5, p=0.046). PMI was associated with a higher all-cause mortality at 10 years compared with no PMI (55.3% vs. 25.4%; Log-rank p<0.001, Figure), which was mainly driven by a high mortality rate within 1 year. In patients undergoing PCI, the mortality rates were significantly higher in patients with PMI not only within 1 year (Log-rank p<0.001) but also beyond one year (Log-rank p=0.016), compare to patients without PMI (Figure). On the other hand, in patients undergoing CABG, a higher mortality rate in patients with PMI was observed until 1 year (Log-rank p<0.001), but the impact of PMI on mortality beyond one year after CABG subsided (Log-rank p=0.308) (Figure 1). Conclusion PMI was associated with a poor prognosis at 10 years. The impact of PMI on mortality was strong within one year. Of note, the impact of PMI on mortality persisted beyond 1 year only in patients undergoing PCI. Patients who were treated with PCI and suffered PMI need careful follow-up beyond one year after revascularization. Figure 1 Funding Acknowledgement Type of funding source: None

Abstract Despite advanced understanding of the biology of atherosclerosis, coronary heart disease remains the leading cause of death worldwide. Progress has been challenging as half of the individuals who suffer sudden cardiac death do not experience premonitory symptoms. Furthermore, it is well-recognized that also a plaque that does not cause a haemodynamically significant stenosis can trigger a sudden cardiac event, yet the majority of ruptured or eroded plaques remain clinically silent. In the past 30 years since the term ‘vulnerable plaque’ was introduced, there have been major advances in the understanding of plaque pathogenesis and pathophysiology, shifting from pursuing features of ‘vulnerability’ of a specific lesion to the more comprehensive goal of identifying patient ‘cardiovascular vulnerability’. It has been also recognized that aside a thin-capped, lipid-rich plaque associated with plaque rupture, acute coronary syndromes (ACS) are also caused by plaque erosion underlying between 25% and 60% of ACS nowadays, by calcified nodule or by functional coronary alterations. While there have been advances in preventive strategies and in pharmacotherapy, with improved agents to reduce cholesterol, thrombosis, and inflammation, events continue to occur in patients receiving optimal medical treatment. Although at present the positive predictive value of imaging precursors of the culprit plaques remains too low for clinical relevance, improving coronary plaque imaging may be instrumental in guiding pharmacotherapy intensity and could facilitate optimal allocation of novel, more aggressive, and costly treatment strategies. Recent technical and diagnostic advances justify continuation of interdisciplinary research efforts to improve cardiovascular prognosis by both systemic and ‘local’ diagnostics and therapies. The present state-of-the-art document aims to present and critically appraise the latest evidence, developments, and future perspectives in detection, prevention, and treatment of ‘high-risk’ plaques occurring in ‘vulnerable’ patients.

Background: Elevated B-type natriuretic peptide (BNP) is reflective of impaired cardiac function and is associated with worse prognosis among patients with coronary artery disease (CAD). We sought to assess the association between baseline BNP, adverse outcomes, and the relative efficacy of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with left main CAD. Methods: The EXCEL trial (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) randomized patients with left main CAD and low or intermediate SYNTAX scores (Synergy Between PCI With TAXUS and Cardiac Surgery) to PCI with everolimus-eluting stents versus CABG. The primary end point was the composite of all-cause death, myocardial infarction, or stroke. We used multivariable Cox proportional hazards regression to assess the associations between normal versus elevated BNP (≥100 pg/mL), randomized treatment, and the 3-year risk of adverse events. Results: BNP at baseline was elevated in 410 of 1037 (39.5%) patients enrolled in EXCEL. Patients with elevated BNP levels were older and more frequently had additional cardiovascular risk factors and lower left ventricular ejection fraction than those with normal BNP, but had similar SYNTAX scores. Patients with elevated BNP had significantly higher 3-year rates of the primary end point (18.6% versus 11.7%; adjusted hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.16–2.28; P =0.005) and higher mortality (11.5% versus 3.9%; adjusted HR, 2.49; 95% CI, 1.48–4.19; P =0.0006), both from cardiovascular and noncardiovascular causes. In contrast, there were no significant differences in the risks of myocardial infarction, stroke, ischemia-driven revascularization, stent thrombosis, graft occlusion, or major bleeding. A significant interaction ( P interaction =0.03) was present between elevated versus normal BNP and treatment with PCI versus CABG for the adjusted risk of the primary composite end point at 3 years among patients with elevated BNP (adjusted HR for PCI versus CABG, 1.54; 95% CI, 0.96–2.47) versus normal BNP (adjusted HR, 0.74; 95% CI, 0.46–1.20). This interaction was stronger when log(BNP) was modeled as a continuous variable ( P interaction =0.002). Conclusions: In the EXCEL trial, elevated baseline BNP levels in patients with left main CAD undergoing revascularization were independently associated with long-term mortality but not nonfatal adverse ischemic or bleeding events. The relative long-term outcomes after PCI versus CABG for revascularization of left main CAD may be conditioned by the baseline BNP level. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01205776.

Background— There is a paucity of data on the use of optimal medical therapy (OMT) in patients with complex coronary artery disease undergoing revascularization with percutaneous coronary intervention or coronary artery bypass grafting (CABG) and its long-term prognostic significance. Methods and Results— The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial is a multicenter, randomized, clinical trial of patients (n=1800) with complex coronary disease randomized to revascularization with percutaneous coronary intervention or CABG. Detailed drug history was collected for all patients at discharge and at the 1-month, 6-month, 1-year, 3-year, and 5-year follow-ups. OMT was defined as the combination of at least 1 antiplatelet drug, statin, β-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Five-year clinical outcomes were stratified by OMT and non-OMT. OMT was underused in patients treated with coronary revascularization, especially CABG. OMT was an independent predictor of survival. OMT was associated with a significant reduction in mortality (hazard ratio, 0.64; 95% confidence interval, 0.48–0.85; P =0.002) and composite end point of death/myocardial infarction/stroke (hazard ratio, 0.73; 95% confidence interval, 0.58–0.92; P =0.007) at the 5-year follow-up. The treatment effect with OMT (36% relative reduction in mortality over 5 years) was greater than the treatment effect of revascularization strategy (26% relative reduction in mortality with CABG versus percutaneous coronary intervention over 5 years). On stratified analysis, all the components of OMT were important for reducing adverse outcomes regardless of revascularization strategy. Conclusions— The use of OMT remains low in patients with complex coronary disease requiring coronary intervention with percutaneous coronary intervention and even lower in patients treated with CABG. Lack of OMT is associated with adverse clinical outcomes. Targeted strategies to improve OMT use in postrevascularization patients are warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00114972.

ObjectivesTo investigate the prognostic implications of the presence of severe lesion calcification in patients undergoing coronary artery bypass graft (CABG) operation.BackgroundThere is robust evidence that lesion calcification is a predictor of worse prognosis in patients undergoing percutaneous coronary intervention; however, there is limited data about the prognostic implication of lesion calcium in patients treated with CABG.MethodsWe retrospectively analyzed data from 1,545 patients who underwent CABG and were recruited in the SYNTAX study and CABG registry. Two experts reviewed the angiographic data and classified patients in two groups: those with severely calcified coronary arteries and those without severe lesion calcification. Clinical outcomes at 5‐year follow‐up were collected and compared in the two groups.ResultsOne out of three patients exhibited severe lesion calcification (n = 588). Patients with calcified coronaries had an increased mortality at 5‐year follow‐up (17.1% vs. 9.9%, P < 0.001) and a higher event rate of death‐myocardial infarction (MI) compared with those without (19.4% vs. 13.2%, P = 0.003), but there was no statistical significant difference between the two groups for major adverse cardiovascular events (MACE, 26.8% vs. 21.8%, P = 0.057). In multivariate Cox regression analysis severe lesion calcification was an independent predictor of an increased all‐cause mortality (hazard ratio: 1.39, 95% confidence interval: 1.02–1.89; P = 0.037) but it was not an independent predictor of the combined end‐points death‐MI or MACE.ConclusionsSevere lesion calcification is associated with an increased mortality in patients undergoing CABG, but it is not an independent predictor of death‐MI or MACE. This paradox can be attributed to the fact that CABG allows perfusion of the healthy coronaries bypassing the diseased arteries and thus it minimizes the risk of coronary events due to progressive atherosclerosis. © 2014 Wiley Periodicals, Inc.

Background— Current guidelines recommend coronary artery bypass graft surgery (CABG) when treating significant de novo left main coronary artery (LM) stenosis; however, percutaneous coronary intervention (PCI) has a class IIa indication for unprotected LM disease in selected patients. This analysis compares 5-year clinical outcomes in PCI- and CABG-treated LM patients in the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) trial, the largest trial in this group to date. Methods and Results— The SYNTAX trial randomly assigned 1800 patients with LM or 3-vessel disease to receive either PCI (with TAXUS Express paclitaxel-eluting stents) or CABG. The unprotected LM cohort (N=705) was predefined and powered. Major adverse cardiac and cerebrovascular event rates at 5 years was 36.9% in PCI patients and 31.0% in CABG patients (hazard ratio, 1.23 [95% confidence interval, 0.95–1.59]; P =0.12). Mortality rate was 12.8% and 14.6% in PCI and CABG patients, respectively (hazard ratio, 0.88 [95% confidence interval, 0.58–1.32]; P =0.53). Stroke was significantly increased in the CABG group (PCI 1.5% versus CABG 4.3%; hazard ratio, 0.33 [95% confidence interval, 0.12–0.92]; P =0.03) and repeat revascularization in the PCI arm (26.7% versus 15.5%; hazard ratio, 1.82 [95% confidence interval, 1.28–2.57]; P <0.01). Major adverse cardiac and cerebrovascular events were similar between arms in patients with low/intermediate SYNTAX scores but significantly increased in PCI patients with high scores (≥33). Conclusions— At 5 years, no difference in overall major adverse cardiac and cerebrovascular events was found between treatment groups. PCI-treated patients had a lower stroke but a higher revascularization rate versus CABG. These results suggest that both treatments are valid options for LM patients. The extent of disease should accounted for when choosing between surgery and PCI, because patients with high SYNTAX scores seem to benefit more from surgery compared with those in the lower tertiles. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00114972.

Background— The residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) Score is an objective measure of the degree and complexity of residual stenosis after percutaneous coronary intervention (PCI). Methods and Results— In the randomized PCI cohort of the SYNTAX Trial (n=903), the baseline and residual SYNTAX Scores were calculated. Subjects with a residual SYNTAX Score of 0 were defined as having undergone complete revascularization (CR), and a residual SYNTAX Score >0 as incomplete revascularization (ICR). Five-year clinical outcomes were stratified by CR and ICR (tertiles of the residual SYNTAX Score: >0–4, >4–8, and >8). In the PCI cohort, the mean baseline and residual SYNTAX Scores were 28.4±11.5 and 4.5±6.9, respectively. The mean Δ SYNTAX Score (representative of the burden of disease removed by PCI) was 23.8±10.9. The residual SYNTAX Score was distributed as follows: CR, 0 (n=386, 42.7%); ICR, >0 to 4 (n=184, 20.4%), >4 to 8 (n=167, 18.5%), >8 (n=153, 16.9%). A progressively higher residual SYNTAX Score was shown to be a surrogate marker of increasing clinical comorbidity and anatomic complexity. Subjects with CR or residual SYNTAX Scores ≤8 had comparable 5-year mortality (CR, 8.5%; residual SYNTAX Score >0–4, 8.7%; >4–8, 11.4%; P =0.60). A residual SYNTAX Score >8 was associated with 35.3% all-cause mortality at 5-years ( P <0.001). Stratified analyses in the predefined medical treated diabetic and left main subgroups yielded similar results. Conclusions— The residual SYNTAX Score was shown to be a powerful indicator of 5-year mortality in the SYNTAX Trial. The residual SYNTAX Score may aid in determining a reasonable level of revascularization. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00114972.