Friedrich W. Mohr

Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease

BACKGROUND Percutaneous coronary intervention (PCI) involving drug-eluting stents is increasingly used to treat complex coronary artery disease, although coronary-artery bypass grafting (CABG) has been the treatment of choice historically. Our trial compared PCI and CABG for treating patients with previously untreated three-vessel or left main coronary artery disease (or both). METHODS We randomly assigned 1800 patients with three-vessel or left main coronary artery disease to undergo CABG or PCI (in a 1:1 ratio). For all these patients, the local cardiac surgeon and interventional cardiologist determined that equivalent anatomical revascularization could be achieved with either treatment. A noninferiority comparison of the two groups was performed for the primary end point--a major adverse cardiac or cerebrovascular event (i.e., death from any cause, stroke, myocardial infarction, or repeat revascularization) during the 12-month period after randomization. Patients for whom only one of the two treatment options would be beneficial, because of anatomical features or clinical conditions, were entered into a parallel, nested CABG or PCI registry. RESULTS Most of the preoperative characteristics were similar in the two groups. Rates of major adverse cardiac or cerebrovascular events at 12 months were significantly higher in the PCI group (17.8%, vs. 12.4% for CABG; P=0.002), in large part because of an increased rate of repeat revascularization (13.5% vs. 5.9%, P<0.001); as a result, the criterion for noninferiority was not met. At 12 months, the rates of death and myocardial infarction were similar between the two groups; stroke was significantly more likely to occur with CABG (2.2%, vs. 0.6% with PCI; P=0.003). CONCLUSIONS CABG remains the standard of care for patients with three-vessel or left main coronary artery disease, since the use of CABG, as compared with PCI, resulted in lower rates of the combined end point of major adverse cardiac or cerebrovascular events at 1 year. (ClinicalTrials.gov number, NCT00114972.)

Transapical Minimally Invasive Aortic Valve Implantation: Multicenter Experience

Background— To evaluate initial multicenter results with minimally invasive transapical aortic valve implantation (TAP-AVI) for high risk patients with aortic stenosis. Methods and Results— TAP-AVI was performed via a small anterolateral minithoracotomy with or without femoro-femoral extracorporeal circulation (ECC) on the beating heart. A pericardial xenograft fixed within a stainless steel, balloon expandable stent (Edwards SAPIEN THV, Edwards Lifesciences) was used. Fifty-nine consecutive patients (81±6 years, 44 female) were operated on from 02/06 until 10/06 at 4 centers using fluoroscopic and echocardiographic visualization. Average EuroSCORE predicted risk for mortality was 27±14%. TAP valve positioning was performed successfully in 53 patients, 4 required early conversion to sternotomy. Implantation (23-mm valves in 19 and 26-mm valves in 40 patients) was performed on the beating heart during brief periods of rapid ventricular pacing. Thirty-one patients were operated on without cardiopulmonary bypass. Neither coronary artery obstruction nor migration of the prosthesis was observed, and all valves had good hemodynamic function. Echocardiography revealed minor paravalvular leakage in 26 patients (trace in 11, mild in 12, and severe in 3). Eight patients died in-hospital (13.6%) without any valve dysfunction. Actuarial survival was 75.7±5.9% at a follow-up interval of 110±77 days (range 1 to 255 days). Conclusions— TAP-AVI can be performed safely with good early results in high risk patients. Long-term valve performance as well as broader based applications of this promising approach will need to be studied.

Outcomes in Patients With De Novo Left Main Disease Treated With Either Percutaneous Coronary Intervention Using Paclitaxel-Eluting Stents or Coronary Artery Bypass Graft Treatment in the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) Trial

Background— The prospective, multinational, randomized Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial was designed to assess the optimal revascularization strategy between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), for patients with left main (LM) and/or 3-vessel coronary disease. Methods and Results— This observational hypothesis-generating analysis reports the results of a prespecified powered subgroup of 705 randomized patients who had LM disease among the 1800 patients with de novo 3-vessel disease and/or LM disease randomized to PCI with paclitaxel-eluting stents or CABG in the SYNTAX trial. Major adverse cardiac and cerebrovascular event rates at 1 year in LM patients were similar for CABG and PCI (13.7% versus 15.8%; &Dgr;2.1% [95% confidence interval −3.2% to 7.4%]; P=0.44). At 1 year, stroke was significantly higher in the CABG arm (2.7% versus 0.3%; &Dgr;−2.4% [95% confidence interval −4.2% to −0.1%]; P=0.009]), whereas repeat revascularization was significantly higher in the PCI arm (6.5% versus 11.8%; &Dgr;5.3% [ 95% confidence interval 1.0% to 9.6%]; P=0.02); there was no observed difference between groups for other end points. When patients were scored for anatomic complexity, those with higher baseline SYNTAX scores had significantly worse outcomes with PCI than did patients with low or intermediate SYNTAX scores; outcomes for patients with CABG did not correlate with baseline SYNTAX score, but baseline EuroSCORE significantly predicted outcomes for both treatments. Conclusions— Patients with LM disease who had revascularization with PCI had safety and efficacy outcomes comparable to CABG at 1 year; longer follow-up is required to determine whether these 2 revascularization strategies offer comparable medium-term outcomes in this group of complex patients. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT00114972.

Comparison of coronary bypass surgery with drug-eluting stenting for the treatment of left main and/or three-vessel disease: 3-year follow-up of the SYNTAX trial

AIMS Long-term randomized comparisons of percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG) in left main coronary (LM) disease and/or three-vessel disease (3VD) patients have been limited. This analysis compares 3-year outcomes in LM and/or 3VD patients treated with CABG or PCI with TAXUS Express stents. METHODS AND RESULTS SYNTAX is an 85-centre randomized clinical trial (n= 1800). Prospectively screened, consecutive LM and/or 3VD patients were randomized if amenable to equivalent revascularization using either technique; if not, they were entered into a registry. Patients in the randomized cohort will continue to be followed for 5 years. At 3 years, major adverse cardiac and cerebrovascular events [MACCE: death, stroke, myocardial infarction (MI), and repeat revascularization; CABG 20.2% vs. PCI 28.0%, P< 0.001], repeat revascularization (10.7 vs. 19.7%, P< 0.001), and MI (3.6 vs. 7.1%, P= 0.002) were elevated in the PCI arm. Rates of the composite safety endpoint (death/stroke/MI 12.0 vs. 14.1%, P= 0.21) and stroke alone (3.4 vs. 2.0%, P= 0.07) were not significantly different between treatment groups. Major adverse cardiac and cerebrovascular event rates were not significantly different between arms in the LM subgroup (22.3 vs. 26.8%, P= 0.20) but were higher with PCI in the 3VD subgroup (18.8 vs. 28.8%, P< 0.001). CONCLUSIONS At 3 years, MACCE was significantly higher in PCI- compared with CABG-treated patients. In patients with less complex disease (low SYNTAX scores for 3VD or low/intermediate terciles for LM patients), PCI is an acceptable revascularization, although longer follow-up is needed to evaluate these two revascularization strategies.

Stroke after cardiac surgery: a risk factor analysis of 16,184 consecutive adult patients.

BACKGROUND Stroke remains a devastating complication after cardiac surgical procedures despite advances in perioperative monitoring and management. The purpose of this study was to determine the predictors of stroke in a large, contemporary cardiac surgery population. METHODS Prospective data on 16,184 consecutive patients undergoing cardiac surgery (coronary artery bypass grafting [CABG], n = 8,917; beating heart CABG, n = 1,842; aortic valve surgery, n = 1,830; mitral valve surgery, n = 708; double or triple valve surgery, n = 381; CABG and valve surgery, n = 2,506) between April 1996 and August 2001 were subjected to univariate and multivariate analysis. Stroke was defined as any new permanent (manifest stroke) or temporary neurologic deficit or deterioration (transient ischemic attack or prolonged reversible ischemic neurologic deficit) and was confirmed by computed tomography or magnetic resonance imaging whenever possible. RESULTS Overall incidence of stroke was 4.6% and varied between surgical procedures (CABG 3.8%; beating-heart CABG 1.9%; aortic valve surgery 4.8%; mitral valve surgery 8.8%; double or triple valve surgery 9.7%; CABG and valve surgery 7.4%). Of 63 patient-specific and treatment variables, 54 were found to have a significant univariate association with postoperative stroke. Multivariable analysis revealed 10 variables that were independent predictors of stroke: history of cerebrovascular disease, peripheral vascular disease, diabetes, hypertension, previous cardiac surgery, preoperative infection, urgent operation, CPB time more than 2 hours, need for intraoperative hemofiltration, and high transfusion requirement. Beating heart CABG was associated with a lower incidence of stroke in this multivariable analysis. CONCLUSIONS Identification of predictors for stroke is important for understanding the pathogenesis of this devastating complication as well as for developing preventative strategies. Although retrospective analyses can be subject to selection bias we believe beating heart CABG is associated with a lower incidence of stroke and may therefore improve patient outcomes.

Neuromonitoring and neurocognitive outcome in off-pump versus conventional coronary bypass operation☆

BACKGROUND Cardiopulmonary bypass seems to be a major cause for both intraoperative microemboli and cerebral hypoperfusion. This study investigates high intensive transient signals (HITS) in transcranial Doppler ultrasound (TCD) and serum levels of the neurobiochemical marker protein S-100 in patients who underwent coronary artery bypass operation without cardiopulmonary bypass (off-pump CABG) in comparison with the conventional procedure using cardiopulmonary bypass (CPB). The results are related to the neuropsychologic outcome in both surgical groups. METHODS Forty patients were randomized in 2 groups (20 conventional and 20 off-pump CABG). Neurocognitive status was assessed preoperatively and postoperatively. Venous serum levels of S-100 protein were measured before and after coronary operation, HITS were measured in the middle cerebral artery during the operation. RESULTS The median value of HITS was 394.5 (0 to 2217) in the conventional versus 11 (0 to 50) in the off-pump group, p less than 0.0001. Postoperative S-100 serum levels were: 3.76 (0.13 to 11.2) microg/L (conventional) versus 0.13 (0.04 to 1.01) microg/L (off-pump), p less than 0.0001. Postoperative cognitive testing showed significantly different results with a postoperative impairment of 90% of the patients in the conventional group versus no impairment in the off-pump group. CONCLUSIONS Cognitive impairment seems to be strongly associated to CPB and the occurrence of micro-emboli. The off-pump technique appears to be promising in order to eliminate the source of these neuropyschologic impairments following CABG operation.

Assessment of the SYNTAX score in the Syntax study

AIMS The SYNTAX score has been designed to better anticipate the risks of percutaneous or surgical revascularisation, taking into account the functional impact of the coronary circulation with all its anatomic components including the presence of bifurcations, total occlusions, thrombus, calcification, and small vessels. The purpose of this paper is to describe the baseline assessment of the SYNTAX score in the Syntax randomised trial, the corelab reproducibility, the potential difference in score assessment between the investigator and the corelab, and to ascertain the impact on one-year outcome after either percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) in patients with complex coronary artery disease. METHODS AND RESULTS To assess the reliability of Syntax scoring, 100 diagnostic angiograms from the Syntax trial were randomly selected and assessed independently by two observers. Intra-observer variability was assessed by analysing 91 sets of angiograms after an interval of at least eight weeks by one of the observers. Clinical outcomes in the randomised cohort of the Syntax trial up to one year are presented with stratification by tertile group of the SYNTAX score. The weighted kappa value for the inter-observer reproducibility on the global score was 0.45, while the intra-observer weighted kappa value was 0.59. The SYNTAX score as calculated by investigators consistently underscored the corelab score by 3.4 points. When the Syntax randomised cohort was stratified by tertiles of the SYNTAX score, there were similar or non-significantly different MACCE rates in those with low or intermediate scores; however in the top tertile the MACCE rate was greater in those receiving PCI compared to CABG. CONCLUSIONS The SYNTAX score is a visual coronary score with an acceptable corelab reproducibility that has an impact on the one-year outcome of those having PCI, whereas it has no effect on the one-year outcome following surgical revascularisation. The SYNTAX score tool is likely to be useful in a wide range of patients with complex coronary disease.

Anatomical and clinical characteristics to guide decision making between coronary artery bypass surgery and percutaneous coronary intervention for individual patients: development and validation of SYNTAX score II

BACKGROUND The anatomical SYNTAX score is advocated in European and US guidelines as an instrument to help clinicians decide the optimum revascularisation method in patients with complex coronary artery disease. The absence of an individualised approach and of clinical variables to guide decision making between coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) are limitations of the SYNTAX score. SYNTAX score II aimed to overcome these limitations. METHODS SYNTAX score II was developed by applying a Cox proportional hazards model to results of the randomised all comers SYNTAX trial (n=1800). Baseline features with strong associations to 4-year mortality in either the CABG or the PCI settings (interactions), or in both (predictive accuracy), were added to the anatomical SYNTAX score. Comparisons of 4-year mortality predictions between CABG and PCI were made for each patient. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. External validation was done in the multinational all comers DELTA registry (n=2891), a heterogeneous population that included patients with three-vessel disease (26%) or complex coronary artery disease (anatomical SYNTAX score ≥33, 30%) who underwent CABG or PCI. The SYNTAX trial is registered with ClinicalTrials.gov, number NCT00114972. FINDINGS SYNTAX score II contained eight predictors: anatomical SYNTAX score, age, creatinine clearance, left ventricular ejection fraction (LVEF), presence of unprotected left main coronary artery (ULMCA) disease, peripheral vascular disease, female sex, and chronic obstructive pulmonary disease (COPD). SYNTAX score II significantly predicted a difference in 4-year mortality between patients undergoing CABG and those undergoing PCI (p(interaction) 0·0037). To achieve similar 4-year mortality after CABG or PCI, younger patients, women, and patients with reduced LVEF required lower anatomical SYNTAX scores, whereas older patients, patients with ULMCA disease, and those with COPD, required higher anatomical SYNTAX scores. Presence of diabetes was not important for decision making between CABG and PCI (p(interaction) 0·67). SYNTAX score II discriminated well in all patients who underwent CABG or PCI, with concordance indices for internal (SYNTAX trial) validation of 0·725 and for external (DELTA registry) validation of 0·716, which were substantially higher than for the anatomical SYNTAX score alone (concordance indices of 0·567 and 0·612, respectively). A nomogram was constructed that allowed for an accurate individualised prediction of 4-year mortality in patients proposing to undergo CABG or PCI. INTERPRETATION Long-term (4-year) mortality in patients with complex coronary artery disease can be well predicted by a combination of anatomical and clinical factors in SYNTAX score II. SYNTAX score II can better guide decision making between CABG and PCI than the original anatomical SYNTAX score. FUNDING Boston Scientific Corporation.

Clinical and economic impact of diabetes mellitus on percutaneous and surgical treatment of multivessel coronary disease patients: insights from the Arterial Revascularization Therapy Study (ARTS) trial.

Background—Our aims were to compare coronary artery bypass grafting (CABG) and stenting for the treatment of diabetic patients with multivessel coronary disease enrolled in the Arterial Revascularization Therapy Study (ARTS) trial and to determine the costs of these 2 treatment strategies. Methods and Results—Patients (n=1205) were randomly assigned to stent implantation (n=600; diabetic, 112) or CABG (n=605; diabetic, 96). Costs per patient were calculated as the product of each patient’s use of resources and the corresponding unit costs. Baseline characteristics were similar between the groups. At 1 year, diabetic patients treated with stenting had the lowest event-free survival rate (63.4%) because of a higher incidence of repeat revascularization compared with both diabetic patients treated with CABG (84.4%, P <0.001) and nondiabetic patients treated with stents (76.2%, P =0.04). Conversely, diabetic and nondiabetic patients experienced similar 1-year event-free survival rates when treated with CABG (84.4% and 88.4%). The total 1-year costs for stenting and CABG in diabetic patients were

Diabetic and Nondiabetic Patients With Left Main and/or 3-Vessel Coronary Artery Disease: Comparison of Outcomes With Cardiac Surgery and Paclitaxel-Eluting Stents

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