Katrin Leadley

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.)

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.

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.

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

OBJECTIVES This study was designed to compare contemporary surgical revascularization (coronary artery bypass graft surgery [CABG]) versus TAXUS Express (Boston Scientific, Natick, Massachusetts) paclitaxel-eluting stents (PES) in diabetic and nondiabetic patients with left main and/or 3-vessel disease. BACKGROUND Although the prevalence of diabetes mellitus is increasing, the optimal coronary revascularization strategy in diabetic patients with complex multivessel disease remains controversial. METHODS The SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) study randomly assigned 1,800 patients (452 with medically treated diabetes) to receive PES or CABG. RESULTS The overall 1-year major adverse cardiac and cerebrovascular event rate was higher among diabetic patients treated with PES compared with CABG, but the revascularization method did not impact the death/stroke/myocardial infarction rate for nondiabetic patients (6.8% CABG vs. 6.8% PES, p = 0.97) or for diabetic patients (10.3% CABG vs. 10.1% PES, p = 0.96). The presence of diabetes was associated with significantly increased mortality after either revascularization treatment. The incidence of stroke was higher among nondiabetic patients after CABG (2.2% vs. PES 0.5%, p = 0.006). Compared with CABG, mortality was higher after PES use for diabetic patients with highly complex lesions (4.1% vs. 13.5%, p = 0.04). Revascularization with PES resulted in higher repeat revascularization for nondiabetic patients (5.7% vs. 11.1%, p < 0.001) and diabetic patients (6.4% vs. 20.3%, p < 0.001). CONCLUSIONS Subgroup analyses suggest that the 1-year major adverse cardiac and cerebrovascular event rate is higher among diabetic patients with left main and/or 3-vessel disease treated with PES compared with CABG, driven by an increase in repeat revascularization. However, the composite safety end point (death/stroke/myocardial infarction) is comparable between the 2 treatment options for diabetic and nondiabetic patients. Although further study is needed, these exploratory results may extend the evidence for PES use in selected patients with less complex left main and/or 3-vessel lesions. (SYNergy Between PCI With TAXus and Cardiac Surgery [SYNTAX]; NCT00114972).

Quality of Life after PCI with Drug-Eluting Stents or Coronary-Artery Bypass Surgery

BACKGROUND Previous studies have shown that among patients undergoing multivessel revascularization, coronary-artery bypass grafting (CABG), as compared with percutaneous coronary intervention (PCI) either by means of balloon angioplasty or with the use of bare-metal stents, results in greater relief from angina and improved quality of life. The effect of PCI with the use of drug-eluting stents on these outcomes is unknown. METHODS In a large, randomized trial, we assigned 1800 patients with three-vessel or left main coronary artery disease to undergo either CABG (897 patients) or PCI with paclitaxel-eluting stents (903 patients). Health-related quality of life was assessed at baseline and at 1, 6, and 12 months with the use of the Seattle Angina Questionnaire (SAQ) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The primary end point was the score on the angina-frequency subscale of the SAQ (on which scores range from 0 to 100, with higher scores indicating better health status). RESULTS The scores on each of the SAQ and SF-36 subscales were significantly higher at 6 and 12 months than at baseline in both groups. The score on the angina-frequency subscale of the SAQ increased to a greater extent with CABG than with PCI at both 6 and 12 months (P=0.04 and P=0.03, respectively), but the between-group differences were small (mean treatment effect of 1.7 points at both time points). The proportion of patients who were free from angina was similar in the two groups at 1 month and 6 months and was higher in the CABG group than in the PCI group at 12 months (76.3% vs. 71.6%, P=0.05). Scores on all the other SAQ and SF-36 subscales were either higher in the PCI group (mainly at 1 month) or were similar in the two groups throughout the follow-up period. CONCLUSIONS Among patients with three-vessel or left main coronary artery disease, there was greater relief from angina after CABG than after PCI at 6 and 12 months, although the extent of the benefit was small. (Funded by Boston Scientific; ClinicalTrials.gov number, NCT00114972.).

Intrapericardial Left Ventricular Assist Device for Advanced Heart Failure.

Background Mechanical circulatory support with a left ventricular assist device (LVAD) is an established treatment for patients with advanced heart failure. We compared a newer LVAD design (a small intrapericardial centrifugal‐flow device) against existing technology (a commercially available axial‐flow device) in patients with advanced heart failure who were ineligible for heart transplantation. Methods We conducted a multicenter randomized trial involving 446 patients who were assigned, in a 2:1 ratio, to the study (centrifugal‐flow) device or the control (axial‐flow) device. Adults who met contemporary criteria for LVAD implantation for permanent use were eligible to participate in the trial. The primary end point was survival at 2 years free from disabling stroke or device removal for malfunction or failure. The trial was powered to show noninferiority with a margin of 15 percentage points. Results The intention‐to treat‐population included 297 participants assigned to the study device and 148 participants assigned to the control device. The primary end point was achieved in 164 patients in the study group and 85 patients in the control group. The analysis of the primary end point showed noninferiority of the study device relative to the control device (estimated success rates, 55.4% and 59.1%, respectively, calculated by the Weibull model; absolute difference, 3.7 percentage points; 95% upper confidence limit, 12.56 percentage points; P=0.01 for noninferiority). More patients in the control group than in the study group had device malfunction or device failure requiring replacement (16.2% vs. 8.8%), and more patients in the study group had strokes (29.7% vs. 12.1%). Quality of life and functional capacity improved to a similar degree in the two groups. Conclusions In this trial involving patients with advanced heart failure who were ineligible for heart transplantation, a small, intrapericardial, centrifugal‐flow LVAD was found to be noninferior to an axial‐flow LVAD with respect to survival free from disabling stroke or device removal for malfunction or failure. (Funded by HeartWare; ENDURANCE ClinicalTrials.gov number, NCT01166347.)

Complex coronary anatomy in coronary artery bypass graft surgery: Impact of complex coronary anatomy in modern bypass surgery? Lessons learned from the SYNTAX trial after two years

OBJECTIVE SYNTAX study compares outcomes of coronary artery bypass grafting with percutaneous coronary intervention in patients with 3-vessel and/or left main disease. Complexity of coronary artery disease was quantified by the SYNTAX score, which combines anatomic characteristics of each significant lesion. This study aims to clarify whether SYNTAX score affects the outcome of bypass grafting as defined by major adverse cerebrovascular and cardiac events (MACCE) and its components over a 2-year follow-up period. METHODS Of the 3075 patients enrolled in SYNTAX, 1541 underwent coronary artery bypass grafting (897 randomized controlled trial patients, and 644 registry patients). All patients undergoing bypass grafting were stratified according to their SYNTAX score into 3 tertiles: low (0-22), intermediate (22-32), and high (≥33) complexity. Clinical outcomes up to 2 years after allocation were determined for each group and further risk factor analysis was performed. RESULTS Registry patients had more complex disease than those in the randomized controlled trial (SYNTAX score: registry 37.8 ± 13.3 vs randomized 29.1 ± 11.4; P < .001). At 30 days, overall coronary bypass mortality was 0.9% (registry 0.6% vs randomized 1.2%). MACCE rate at 30 days was 4.4% (registry 3.4% vs randomized 5.2%). SYNTAX score did not significantly affect overall 2-year MACCE rate of 15.6% for low, 14.3% for medium, and 15.4% for high SYNTAX scores. Compared with randomized patients, registry patients had a lower rate of overall MACCE rate (registry 13.0% vs randomized 16.7%; P = .046) and repeat revascularization (4.7% vs 8.6%; P = .003), whereas other event rates were comparable. Risk factor analysis revealed left main disease (P = .049) and incomplete revascularization (P = .005) as predictive for adverse 2-year outcomes. CONCLUSIONS The outcome of coronary artery bypass grafting was excellent and independent from the SYNTAX score. Incomplete revascularization rather than degree of coronary complexity adversely affects late outcomes of coronary bypass.

Bypass versus drug-eluting stents at three years in SYNTAX patients with diabetes mellitus or metabolic syndrome.

BACKGROUND Diabetes mellitus increases adverse outcomes after coronary revascularization; however, the impact of metabolic syndrome is unclear. We examined the impact of diabetes and metabolic syndrome on coronary artery bypass graft surgery (CABG) and stenting outcomes to determine the optimal revascularization option for the treatment of complex coronary artery disease. METHODS Patients (n = 1,800) with left main or three-vessel disease or both were randomly allocated to treatment with a TAXUS Express(2) paclitaxel-eluting stent (PES) or CABG, and were included in predefined nondiabetic (n = 1,348) or diabetic subgroups (n = 452); 258 patients with diabetes also had metabolic syndrome. RESULTS Among diabetic patients, the 3-year major adverse cardiac and cerebrovascular event (MACCE) rate (22.9% CABG, 37.0% PES; p = 0.002) and revascularization rate (12.9% CABG, 28.0% PES; p < 0.001) were higher after PES treatment. Diabetes increased MACCE rates among PES-treated patients, but had little impact on results after CABG. Compared with CABG, PES treatment yielded comparable MACCE in diabetic patients (30.5% versus 29.8%, p =0.98) and nondiabetic patients (20.2% versus 20.3%, p =0.99) with low Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) study scores of 22 or less. For patients with SYNTAX Scores of 33 or greater, MACCE rates were lower with CABG (18.5% versus 45.9%, p < 0.001 diabetic; 19.8% versus 30.0%, p = 0.01 nondiabetic). Metabolic syndrome did not significantly predict MACCE or repeat revascularization. CONCLUSIONS These exploratory analyses suggest that among diabetic patients with complex left main or three-vessel disease, or both, 3-year MACCE is higher after PES compared with CABG. Although PES 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. Metabolic syndrome had little impact on 3-year outcomes.

Identification and Management of Pump Thrombus in the HeartWare Left Ventricular Assist Device System: A Novel Approach Using Log File Analysis.

OBJECTIVES The study sought to characterize patterns in the HeartWare (HeartWare Inc., Framingham, Massachusetts) ventricular assist device (HVAD) log files associated with successful medical treatment of device thrombosis. BACKGROUND Device thrombosis is a serious adverse event for mechanical circulatory support devices and is often preceded by increased power consumption. Log files of the pump power are easily accessible on the bedside monitor of HVAD patients and may allow early diagnosis of device thrombosis. Furthermore, analysis of the log files may be able to predict the success rate of thrombolysis or the need for pump exchange. METHODS The log files of 15 ADVANCE trial patients (algorithm derivation cohort) with 16 pump thrombus events treated with tissue plasminogen activator (tPA) were assessed for changes in the absolute and rate of increase in power consumption. Successful thrombolysis was defined as a clinical resolution of pump thrombus including normalization of power consumption and improvement in biochemical markers of hemolysis. Significant differences in log file patterns between successful and unsuccessful thrombolysis treatments were verified in 43 patients with 53 pump thrombus events implanted outside of clinical trials (validation cohort). RESULTS The overall success rate of tPA therapy was 57%. Successful treatments had significantly lower measures of percent of expected power (130.9% vs. 196.1%, p = 0.016) and rate of increase in power (0.61 vs. 2.87, p < 0.0001). Medical therapy was successful in 77.7% of the algorithm development cohort and 81.3% of the validation cohort when the rate of power increase and percent of expected power values were <1.25% and 200%, respectively. CONCLUSIONS Log file parameters can potentially predict the likelihood of successful tPA treatments and if validated prospectively, could substantially alter the approach to thrombus management.

Patients awaiting heart transplantation on HVAD support for greater than 2 years

Advanced heart failure patients who are classified as bridge to transplant (BTT) often remain on mechanical circulatory support (MCS) for long durations because of the limited supply of donor organs. Here, we present the outcomes of patients who have been supported by the HeartWare ventricular assist device system for more than 2 years. In the HeartWare BTT and continued access protocol trial, 74 of the 382 total patients (19.4%) had more than 2 years of MCS with a mean time of 1,045 days on device. The long-term group was more frequently female, was nonwhite, and had Interagency Registry for Mechanically Assisted Circulatory Support profiles 4–7. Postimplant adverse event rates including bleeding, cardiac arrhythmia, infection, stroke, renal dysfunction, and right heart failure were less frequent in the long-term cohort. In addition, the long-term cohort displayed significant improvements in Kansas City Cardiomyopathy Questionnaire Overall Summary Score, EuroQOL-5D Overall Health State Score, and 6 minute walk scores from baseline values. The rate of heart transplantation was lower for the long-term cohort, which may have been a result of their sex and blood type. However, most of these patients are still listed for cardiac transplantation and maintained their quality of life profiles through 3 years of support.