Sung-Ho Her

Everolimus-Eluting Stent Implantation for Unprotected Left Main Coronary Artery Stenosis: The PRECOMBAT-2 (Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease) Study

OBJECTIVES This study sought to evaluate the safety and efficacy of second-generation drug-eluting stents (DES) for patients with unprotected left main coronary artery (ULMCA) stenosis. BACKGROUND The clinical benefit of second-generation DES for ULMCA stenosis has not been determined. METHODS The authors assessed 334 consecutive patients who received everolimus-eluting stents (EES) for ULMCA stenosis between 2009 and 2010. The 18-month incidence rates of major adverse cardiac or cerebrovascular events (MACCE), including death, myocardial infarction (MI), stroke, or ischemia-driven target vessel revascularization (TVR), were compared with those of a randomized study comparing patients who received sirolimus-eluting stents (SES) (n = 327) or coronary artery bypass grafts (CABG) (n = 272). RESULTS EES (8.9%) showed a comparable incidence of MACCE as SES (10.8%; adjusted hazard ratio [aHR] of EES: 0.84; 95% confidence interval [CI]: 0.51 to 1.40; p = 0.51) and CABG (6.7%, aHR of EES: 1.40; 95% CI: 0.78 to 2.54; p = 0.26). The composite incidence of death, MI, or stroke also did not differ among patients receiving EES (3.3%), SES (3.7%; aHR of EES: 0.63; 95% CI: 0.27 to 1.47; p = 0.29), and CABG (4.8%; aHR of EES: 0.67; 95% CI: 0.29 to 1.54; p = 0.34). However, the incidence of ischemia-driven TVR in the EES group (6.5%) was higher than in the CABG group (2.6%, aHR of EES: 2.77; 95% CI: 1.17 to 6.58; p = 0.02), but comparable to SES (8.2%, aHR of EES: 1.14; 95% CI: 0.64 to 2.06; p = 0.65). Angiographic restenosis rates were similar in the SES and EES groups (13.8% vs. 9.2%, p = 0.16). CONCLUSIONS Second-generation EES had a similar 18-month risk of MACCE for ULMCA stenosis as first-generation SES or CABG.

Long-term outcomes of percutaneous coronary intervention versus coronary artery bypass grafting for unprotected left main coronary bifurcation disease in the drug-eluting stent era

Objectives There are limited data on long-term outcomes (ie, beyond 4 years) for patients with unprotected left main bifurcation disease who underwent percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) in the drug-eluting stent (DES) era. This study therefore compared the treatment effects of PCI and CABG in unprotected left main bifurcation disease. Methods 865 patients with unprotected left main bifurcation disease treated with either PCI using DES (n=556) or CABG (n=309) were evaluated between May 2003 and December 2009. PCI-treated patients were further categorised into simple stenting (n=360) or complex stenting (n=196). Results Median follow-up was 4.2 years (IQR 2.9–5.2 years). After adjusting covariates with multivariate Cox hazard regression model and inverse probability of treatment weighting, the long-term cumulative rates of death (HR 0.95; 95% CI 0.62 to 1.45) or composite of death, Q-wave myocardial infarction, or stroke (HR 0.97, 95% CI 0.64 to 1.48) were not significantly different for patients undergoing PCI or CABG except for target-vessel revascularisation (TVR) (HR 4.42, 95% CI 2.39 to 8.18). The complex stenting group had similar long-term clinical outcomes compared with the simple stenting group except for TVR (HR 1.94, 95% CI 1.22 to 3.10). In further analysis with propensity score matching, overall findings were consistent. Conclusions In patients with unprotected left main bifurcation disease, PCI using DES provides similar long-term (up to 5.2 years) clinical outcomes except for TVR compared with CABG. Complex and simple stenting yielded similar outcomes except for a higher TVR rate in complex stenting.

Benefit of β-blocker treatment for patients with acute myocardial infarction and preserved systolic function after percutaneous coronary intervention

Objective β-blockers are the standard treatment for myocardial infarction (MI) based on evidence from the pre-thrombolytic era. The aim of this study was to examine the effect of β-blocker treatment in patients with acute MI and preserved systolic function in the era of percutaneous coronary intervention (PCI). Methods We analysed a multicentre registry and identified 3019 patients who presented with acute MI between 2004 and 2009. Patients were treated with PCI, had left ventricular EFs ≥50% according to echocardiograms that were performed during the index PCI, and were alive at the time of discharge. The association between β-blocker use after discharge and mortality (all-cause death and cardiac death) within 3 years was examined. Results Patients who were not treated with β-blockers (n=595) showed higher rates of all-cause death and cardiac death compared to patients treated with β-blockers (10.8% vs 5.7%, p<0.001, 7.6% vs 2.6%, p<0001). The multivariate Cox proportional hazards model showed that β-blocker treatment was associated with a significant reduction in all-cause death (adjusted HR 0.633, 95% CI 0.464 to 0.863; p=0.004) and cardiac death (adjusted HR 0.47, 95% CI 0.32 to 0.70; p<0.001). Comparable results were obtained after propensity score matching. Conclusions β-blocker treatment was associated with reduced long term mortality in patients with acute MI and preserved systolic function who received PCI.

Therapeutic potential of human adipose stem cells in a rat myocardial infarction model.

Purpose Stem cell transplantation is expected to have good effects in the treatment of myocardial infarction (MI). We tested the effect of the transplantation of human adipose-derived cells (ASCs) in Sprague-Dawley (SD) rats with myocardial infarctions. Materials and Methods ASCs were isolated from the waste of elective abdominal surgery. The MI model was set up in SD rats by permanent ligation of the left anterior descending coronary artery. One week after MI, either 1 × 106 ASCs or an equal volume of phosphate-buffered saline (PBS) was injected into the infarct zone. Cardiac function was assessed by echocardiography, 1 day, 1 week, 2 weeks, and 4 weeks after treatment. Four weeks after transplantation, immunohistochemistry was performed. Results Left ventricular function, including fractional shortening (FS), and ejection fraction (EF) showed a significant improvement in the ASCs transplantation group compared to the PBS group 4 weeks after treatment (p < 0.05). The anterior wall thickness of the left ventricle was significantly thicker in the ASCs transplantation group compared to the PBS group (p < 0.01). Multiple troponin T staining, and irregular, small amounts of connexin 43 expression also was observed in the ASCs transplantation group. Infarcted myocardium showed higher capillary density in the ASCs transplantation group than in the PBS injected group (p < 0.01). Conclusion This study provides encouraging evidence that transplantation of ASCs can improve cardiac function of infarct myocardium in rat models with a limitation of cardiac remodeling, improved wall thickness, and increased neovascularization.

Metabolically obese status with normal weight is associated with both the prevalence and severity of angiographic coronary artery disease

OBJECTIVE We evaluated prevalence and severity of angiographic coronary artery disease (CAD) according to groups by metabolically obese (MO) and/or weight status. MATERIAL/METHODS Normal weight was defined as body mass index (BMI, kg/m²)<25 and obesity was defined as BMI≥25. The MO was determined using the National Cholesterol Education Program-Adult Treatment Panel III classification with Korean-specific cutoffs for abdominal obesity. Therefore, a total of 856 subjects were categorized as follows: (1) metabolically healthy and normal weight (MHNW); (2) metabolically obese but normal weight (MONW); (3) metabolically healthy but obese (MHO); and (4) metabolically abnormally obese (MAO). The presence of obstructive lesion≥50% of coronary artery was considered as an angiographic CAD and the Gensini scoring system was used for the severity. RESULTS MONW or MO showed a higher prevalence of CAD than MHNW or non-MO after adjustment for age and sex, respectively (MONW, odds ratio [OR]=1.69, 95% confidence interval [CI]: 1.13-2.51 and MO, OR=1.44, 95% CI: 1.09-1.91). In subjects without diabetes mellitus (DM), MONW or MO showed a marginally higher prevalence of CAD (MONW, OR=1.58, 95% CI: 0.96-2.61 and MO, OR=1.41, 95% CI: 0.96-2.08). MONW was independently associated with a higher severity of angiographic CAD than MHNW after age, sex, glomerular filtration rate, smoking status, high sensitive C-reactive protein, and use of anti-platelet and anti-angina drugs (β=0.118, P=0.005). And MO was associated with a higher severity of angiographic CAD than non-MO after adjustment for age and sex (β=0.077, P=0.024). The above associations were also consistent in subjects without DM (MONW, β=0.147, P=0.003 and MO, β=0.129, P=0.005). CONCLUSIONS MONW or MO is associated with both the prevalence and severity of angiographic CAD after adjustment for age and sex and MONW is independently associated with the severity of angiographic CAD irrespective of DM. Therefore, subjects with MO but normal weight (MONW) should be carefully examined for angiographic CAD.

Safety of Dental Extractions in Coronary Drug‐Eluting Stenting Patients Without Stopping Multiple Antiplatelet Agents

The risk of excessive bleeding prompts physicians to stop multiple antiplatelet agents before minor surgery, which puts coronary stenting patients at risk for adverse thrombotic events.

Comparison of Biolimus A9–Eluting (Nobori) and Everolimus-Eluting (Promus Element) Stents in Patients With De Novo Native Long Coronary Artery Lesions A Randomized Long Drug-Eluting Stent V Trial

Background—Procedural and clinical outcomes still remain unfavorable for patients with long coronary lesions who undergo percutaneous coronary intervention. The current study, therefore, evaluated 2 innovative drug-eluting stents for the management of long-lesion coronary artery disease. Methods and Results—This randomized, multicenter, prospective trial, called the Long Drug-Eluting Stent (LONG-DES) V trial, compared the biodegradable polymer–based biolimus A9–eluting stent (BES) and the durable polymer–based platinum chromium everolimus-eluting stent (PtCr-EES) in 500 patients with long (≥25 mm) coronary lesions. The primary end point of the trial was in-segment late luminal loss at the 9-month angiographic follow-up. The BES and PtCr-EES groups had similar baseline characteristics, with a slightly shorter lesion length in the BES group versus the PtCr-EES group (29.24±12.17 versus 32.27±13.84 mm; P=0.016). In-segment late luminal loss was comparable between the 2 groups at the 9-month angiographic follow-up (BES, 0.14±0.38 versus PtCr-EES, 0.11±0.37 mm; difference, 0.031; 95% confidence interval, −0.053 to 0.091; P=0.03 for a noninferiority margin of 0.11, P=0.45 for superiority), as was in-stent late luminal loss (0.20±0.41 versus 0.24±0.38 mm; P=0.29). The incidence of in-segment (6.1% versus 4.9%; P=0.63) and in-stent (3.7% versus 4.9%; P=0.59) binary restenosis was also similar between the groups. There was no significant between-group difference in the rate of composite outcome of death, myocardial infarction, and target vessel revascularization (41, 16.7% in BES versus 42, 16.5% in PtCr-EES; P=0.94). Conclusions—BES and PtCr-EES implantation showed analogous angiographic and clinical outcomes for patients with de novo long coronary lesions. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01186120.

Fractional Flow Reserve and Cardiac Events in Coronary Artery DiseaseClinical Perspective: Data From a Prospective IRIS-FFR Registry (Interventional Cardiology Research Incooperation Society Fractional Flow Reserve)

Background: We evaluated the prognosis of deferred and revascularized coronary stenoses after fractional flow reserve (FFR) measurement to assess its revascularization threshold in clinical practice. Methods: The IRIS-FFR registry (Interventional Cardiology Research In-cooperation Society Fractional Flow Reserve) prospectively enrolled 5846 patients with ≥1coronary lesion with FFR measurement. Revascularization was deferred in 6468 lesions and performed in 2165 lesions after FFR assessment. The primary end point was major adverse cardiac events (cardiac death, myocardial infarction, and repeat revascularization) at a median follow-up of 1.9 years and analyzed on a per-lesion basis. A marginal Cox model accounted for correlated data in patients with multiple lesions, and a model to predict per-lesion outcomes was adjusted for confounding factors. Results: For deferred lesions, the risk of major adverse cardiac events demonstrated a significant, inverse relationship with FFR (adjusted hazard ratio, 1.06; 95% confidence interval, 1.05–1.08; P<0.001). However, this relationship was not observed in revascularized lesions (adjusted hazard ratio, 1.00; 95% confidence interval, 0.98–1.02; P=0.70). For lesions with FFR ≥0.76, the risk of major adverse cardiac events was not significantly different between deferred and revascularized lesions. Conversely, in lesions with FFR ⩽0.75, the risk of major adverse cardiac events was significantly lower in revascularized lesions than in deferred lesions (for FFR 0.71–0.75, adjusted hazard ratio, 0.47; 95% confidence interval, 0.24–0.89; P=0.021; for FFR ⩽0.70, adjusted hazard ratio 0.47; 95% confidence interval, 0.26–0.84; P=0.012). Conclusions: This large, prospective registry showed that the FFR value was linearly associated with the risk of cardiac events in deferred lesions. In addition, revascularization for coronary artery stenosis with a low FFR (⩽0.75) was associated with better outcomes than the deferral, whereas for a stenosis with a high FFR (≥0.76), medical treatment would be a reasonable and safe treatment strategy. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01366404.

Impact of the Stent Length on Long-Term Clinical Outcomes Following Newer-Generation Drug-Eluting Stent Implantation

Stent length has been considered an important predictor of adverse events after percutaneous coronary intervention, even with the first-generation drug-eluting stents (DESs). The introduction of newer-generation DES has further reduced the rates of adverse clinical events such as restenosis, myocardial infarction, and stent thrombosis. The aim of this study was to compare the impact of stent length on the long-term clinical outcomes between first- and newer-generation DESs. The effects of stent length (≥32 vs <32 mm) on the clinical outcomes were evaluated in 8,445 patients who underwent percutaneous coronary intervention using either a first-generation DES (sirolimus- and paclitaxel-eluting stents, n = 6,334) or a newer-generation DES (everolimus- and zotarolimus-eluting stents, n = 2,111) from January 2004 to December 2009. The 3-year adverse outcomes (composite of all-cause death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis) were compared using the inverse probability of treatment-weighted method according to the stent length. After adjustment for differences in the baseline risk factors, a stent length of ≥32 mm was significantly associated with higher cumulative rates of target vessel revascularization and stent thrombosis in the patients treated with a first-generation DES (adjusted hazard ratio 1.875, 95% confidence interval 1.531 to 2.297, p <0.001; adjusted hazard ratio 2.964, 95% confidence interval 1.270 to 6.917, p = 0.012), but it was not associated with the clinical outcomes in patients treated with a newer-generation DES. In conclusion, stent length might not be associated with long-term clinical outcomes in newer-generation DES era, whereas stent length might be associated with long-term clinical outcomes in the first-generation DESs.

Long-term clinical outcomes of overlapping heterogeneous drug-eluting stents compared with homogeneous drug-eluting stents

Objectives To evaluate long-term clinical outcomes of overlapping heterogeneous drug-eluting stents (DES) compared with homogeneous DES. Design and setting The catholic medical centre coronary intervention database is a multicentre database of percutaneous coronary intervention with DES. This database contains data on consecutive patients from eight coronary intervention centres in Korea. Patients Overlapping homogeneous DES were used in 940 patients and overlapping heterogeneous DES in 140 patients between January 2005 and June 2010. Intervention The study enrolled patients with one-vessel disease treated with two overlapping DES in one lesion. Main outcome measures The study end point was the occurrence of major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction (MI) or target lesion revascularisation (TRL). Results The two patient groups had similar baseline clinical and angiographic characteristics. MACE, cardiac death, MI and TRL rates, were not significantly different between the homogeneous and heterogeneous DES groups (9.9% vs 11.4%, p=0.574; 2.7% vs 3.6%, p=0.578; 1.5% vs 1.4%, p=1.000; 5.7% vs 6.4%, p=0.747, respectively). In addition, it was found that overlap with second-generation DES may be safe and effective, and the sirolimus-eluting stent (SES)+SES group had higher rate of MACE-free survival than the paclitaxel-eluting stent (PES)+PES group (p=0.014). Conclusions Overlapping heterogeneous DES and overlapping homogeneous DES had similar long-term safety and efficacy outcomes.