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Coronary bifurcation intervention is common but complex. Progress in this field has been made in recent years with considerable contribution from the Asia Pacific (APAC) region. However, the standard of practice varies across the APAC region due to differences in culture, socioeconomic state and healthcare set-up. Practice may also differ from the rest of the world. Hence, a panel of experts was invited to discuss topics relevant to bifurcation intervention in order to make a concerted effort to achieve consensus that is applicable within the region and in line with available evidence.

Aims: This study aimed to compare the acute expansion behaviour of a polymer-based bioresorbable scaffold and a second-generation metallic DES platform in a realistic coronary artery lesion model. Experimental mechanical data with conventional methods have so far shown little difference between metallic stents and currently available polymer-based bioresorbable scaffolds (BRS). Nevertheless, differences in acute results have been observed in clinical studies comparing BRS directly with metallic DES platforms., Methods and Results: We examined the expansion behaviour of the bioresorbable vascular scaffold (3.0×18 mm Absorb BVS; Abbott Vascular, Santa Clara, CA, USA) and a metallic DES (3.0×18 mm XIENCE Prime; Abbott Vascular) after expansion at 37°C using identical coronary artery stenosis models (in total 12 experiments were performed). Device expansion was compared during balloon inflation and after deflation using microscopy to allow assessment of plaque recoil. Minimal lumen diameter (MLD) and minimal lumen area (MLA) and stent eccentricity were quantified from optical coherence tomography (OCT) imaging at nominal diameter and after post-dilation at 18 atm. The MLA in the models with BVS deployed was 4.92±0.17 mm² while in the metallic DES it was 5.40±0.13 mm2 (p=0.02) at nominal pressure (NP), and 5.41±0.20 and 6.07±0.25 mm2 (p=0.02), respectively, after expansion at 18 atm. Stent eccentricity index at the MLA was 0.71±0.02 in BVS compared to 0.81±0.02 in the metal stent at NP (p=0.004), and 0.73±0.03 compared to 0.75±0.02 at 18 atm (p=0.39)., Conclusions: Results obtained in this in vitro lesion model were comparable to the results in randomised clinical trials comparing BVS and XIENCE stents in vivo. Such models may be useful in future BRS developments to predict their acute response in vivo in eccentric lesions.

Background: Haptoglobin (Hp) is a plasma protein with strong anti‐inflammation and antioxidant activities. Its plasma level is known to be inversely associated with many inflammatory diseases, including cardiovascular diseases. However, the association of HP genetic variants with coronary artery disease (CAD) severity/mortality, and how they interact with common CAD risk factors are largely unknown. Methods: We conducted the analysis in a Singaporean Chinese CAD population with Gensini severity scores (N = 582) and subsequently evaluated the significant findings in an independent cohort with cardiovascular mortality (excluding stroke) as outcome (917 cases and 19,093 controls). CAD risk factors were ascertained from questionnaires, and stenosis information from medical records. Mortality was identified through linkage with the nationwide registry of births and deaths in Singapore. Linear regression analysis between HP genetic variant (rs217181) and disease outcome were performed. Interaction analyses were performed by introducing an interaction term in the same regression models. Results: Although rs217181 was not significantly associated with CAD severity and cardiovascular mortality (excluding stroke) in all subjects, when stratified by hypertension status, hypertensive individuals with the minor T allele have more severe CAD (β = 0.073, SE = 0.030, p = 0.015) and non‐hypertensive individuals with the T allele have lower risk for mortality (odds ratio = 0.771 (0.607–0.980), p = 0.033). Conclusion: HP genetic variant is not associated with CAD severity and mortality in the general population. However, hypertensive individuals with the rs217181 T allele associated with higher Hp levels had more severe CAD while non‐hypertensive individuals with the same allele had lower risk for mortality in the Chinese population. [ABSTRACT FROM AUTHOR]

Androgen dependent tissue factor pathway inhibitor regulating protein (ADTRP) is a novel protein associated with coronary artery disease (CAD) susceptibility, and reduced mRNA expression of ADTRP was shown to be associated with increased CAD risk. This study aimed to determine and compare circulating ADTRP levels between CAD patients and controls, and to test the performance of plasma ADTRP as a biomarker for CAD. We measured plasma ADTRP, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and high sensitivity-C reactive protein (hs-CRP) levels in 362 CAD patients, 150 angiographically negative CAD controls, and 83 healthy adults with no known clinical or medical conditions using commercial ELISA. Statistical analyses were performed using receiver operator characteristic (ROC) curves, quantile regression and logistic regression, with adjustments for age, gender, ethnicity and BMI. CAD patients had significantly lower plasma ADTRP levels 1,545 (1,087–2,408) pg/ml as compared to CAD controls 2,259 (1,533–3,778) pg/ml and healthy adults 3,904 (2,732–5,463) pg/ml. Plasma ADTRP outperformed the other three inflammatory biomarkers (TNF-α, IL-6 and hs-CRP) for CAD (Area under ROC curve: 0.67, Odds ratio (OR): 0.907). Our study has shown for the first time that ADTRP is present in circulation, and that plasma ADTRP may be a novel independent biomarker for CAD. [ABSTRACT FROM AUTHOR]

Background: In 2020 the largest number of patients with coronary artery disease (CAD) will be found in Asia. Published epidemiological and clinical reports are overwhelmingly derived from western (White) cohorts and data from Asia are scant. We compared CAD severity and all-cause mortality among 4 of the world’s most populous ethnicities: Whites, Chinese, Indians and Malays. Methods: The UNIted CORoNary cohort (UNICORN) simultaneously enrolled parallel populations of consecutive patients undergoing coronary angiography or intervention for suspected CAD in the Netherlands and Singapore. Using multivariable ordinal regression, we investigated the independent association of ethnicity with CAD severity and interactions between risk factors and ethnicity on CAD severity. Also, we compared all-cause mortality among the ethnic groups using multivariable Cox regression analysis. Results: We included 1,759 White, 685 Chinese, 201 Indian and 224 Malay patients undergoing coronary angiography. We found distinct inter-ethnic differences in cardiovascular risk factors. Furthermore, the associations of gender and diabetes with severity of CAD were significantly stronger in Chinese than Whites. Chinese (OR 1.3 [1.1–1.7], p = 0.008) and Malay (OR 1.9 [1.4–2.6], p<0.001) ethnicity were independently associated with more severe CAD as compared to White ethnicity. Strikingly, when stratified for diabetes status, we found a significant association of all three Asian ethnic groups as compared to White ethnicity with more severe CAD among diabetics, but not in non-diabetics. Crude all-cause mortality did not differ, but when adjusted for covariates mortality was higher in Malays than the other ethnic groups. Conclusion: In this population of individuals undergoing coronary angiography, ethnicity is independently associated with the severity of CAD and modifies the strength of association between certain risk factors and CAD severity. Furthermore, mortality differs among ethnic groups. Our data provide insight in inter-ethnic differences in CAD risk factors, CAD severity and mortality. [ABSTRACT FROM AUTHOR]

Background: Relationship between obstructive sleep apnoea and atherosclerosis has not been confirmed using coronary angiography. We sought to investigate the relationships between the apnoea-hypopnoea index (AHI) and angiographic coronary disease phenotypes. Methods: SYNTAX score, lesion complexity, and thrombus burden grade were determined in 125 patients presenting with acute myocardial infarction and had undergone a screening sleep study. Severe OSA was defined as AHI ≥ 30. Results: Most of the recruited patients were male (97.6%). Severe obstructive sleep apnoea was diagnosed in 37% of the patients. The severe obstructive sleep apnoea group ( n = 46) was older ( P = 0.039) and more obese ( P = 0.003) than the non-severe group ( n = 79). There was no evidence of difference between the severe and non-severe obstructive sleep apnoea groups with regard to SYNTAX score ( P = 0.871), number of complex lesions (P = 0.241), and thrombus burden grade ( P = 0.433). Multivariate analysis adjusting for difference in age and body mass index did not change the findings. Conclusion: Using the three angiographic scoring systems, we found no association between AHI and angiographic coronary disease phenotypes, suggesting a limited effect of obstructive sleep apnoea on the amount and distribution of coronary plaques in patients presenting with acute myocardial infarction. [ABSTRACT FROM AUTHOR]

Background: Endothelial progenitor cell (EPC) capture stent is designed to promote rapid endothelization and healing and is potentially useful in patients undergoing primary percutaneous coronary intervention ( PCI) for acute myocardial infarction (AMI). We studied the intermediate-term efficacy and safety of EPC stent and compared that with sirolimus-eluting bioabsorbable polymer stent (CURA) and bare metal stent (BMS) in AMI patients. Methodology: Patients presenting with AMI who underwent primary PCI with the respective stents between January 2004 and June 2006 were enrolled in the single-center clinical registry. The study end-points were major adverse cardiac events (MACE) and stent thrombosis. Results: A total of 366 patients (EPC = 95, CURA = 53, BMS 218) were enrolled. Baseline demographics including age, gender, diabetes, renal impairment, predischarge left ventricular ejection fraction, and creatinine kinase level were comparable among the groups. Procedural success rate was 99.5%. Post-procedural thrombolysis in myocardial infarction (TIMI) 3 flow was achieved in EPC 91.6%, CURA 96.2%, and BMS 88.5% (P = 0.209). At 2 years, the MACE rate was EPC 13.7%, CURA 15.1%, and BMS 19.7% (P = 0.383). Target vessel revascularizations (TVR) were EPC 4.2%, CURA 9.4%, and BMS 6.0% (P = 0.439). Nonfatal myocardial infarctions were EPC 1.1%, CURA 3.8%, and BMS 4.1% (P = 0.364). One patient in the EPC group had acute stent thrombosis. There was no late stent thrombosis in the EPC group. Conclusion: EPC stent appeared to be safe and had comparable clinical efficacy with a BMS when used in the AMI setting. At 2-year follow-up, the EPC group showed favorable, single-digit TVR rate and stent thrombosis remained a low-event occurrence. (J Interven Cardiol 2010;23:101-108) [ABSTRACT FROM AUTHOR]

Background: The role of microvascular perfusion in relation to door-to-balloon time and mortality remains unknown. We sought to compare microvascular perfusion in patients who had undergone primary percutaneous coronary intervention with door-to-balloon time ≤90 minute versus >90 minutes. Methods: Using myocardial blush grade (MBG), corrected TIMI frame count (CTFC), and ST-segment resolution, microvascular perfusion was assessed in 297 patients who underwent successful primary percutaneous coronary intervention between January 2007 and April 2008. Results: Door-to-balloon time was ≤90 minutes in 199 (67%) patients and >90 minutes in 98 (33%) patients. Univariate analysis showed that door-to-treatment >90 minutes was associated with MBG 0/1 and CTFC >28. However, it was not associated with ST-segment resolution ≤70%. After adjustment for baseline confounding factors, door-to-balloon time >90 minutes was still associated with MBG 0/1 (adjusted OR 3.20, 95% CI 1.87 to 5.49, P < 0.001) and CTFC >28 (adjusted OR 6.30, 95% CI 3.56 to 11.17, P < 0.001). Thirty-day mortality was higher in patients with longer door-to-balloon time (adjusted OR 2.87, 95% CI 0.94 to 8.77, P = 0.064). Conclusion: We found that door-to-balloon time >90 minutes, compared with ≤90 minutes, was independently associated with MBG 01/2 and CTFC >28, both suggesting microvascular obstruction. However, such association was not found in ST-segment resolution. Patients with door-to-balloon time >90 minutes also had higher 30-day mortality. [ABSTRACT FROM AUTHOR]

Aims: We assessed the use of the endothelial progenitor cell (EPC) capture stent in primary percutaneous intervention in ST-elevation myocardial infarction (STEMI). Methods and Results: One hundred and twenty patients with acute STEMI without cardiogenic shock received 129 EPC capture stents. Procedural success was achieved in 95% of patients. Dual antiplatelet therapy was given for a month and statin therapy started immediately after the procedure. The study end points are major adverse cardiac events inhospital and at 30 days, 6 months, and 1 year. Hypertension was present in 47.5% and diabetes mellitus in 30% of the patients. The left anterior descending artery was the treated artery in 54% of the patients. Mean lesion length was 17.4 +/- 7.15 mm with mean reference vessel diameter of 3.18 +/- 0.6 mm. Platelet glycoprotein IIb/IIIa inhibitor was used in 14% of patients and 58% had thrombosuction before stent implantation. Ninety-five percent of patients achieved Thrombolysis in Myocardial Infarction 3 flow with cumulative major adverse cardiac event rate at 1.6% inhospital, 4.2% at 30 days, 5.8% at 6 months, and 9.2% at 1 year. There was 1 patient each with acute and subacute stent thrombosis but no incidence of late stent thrombosis. Conclusion: Using EPC capture stent during primary percutaneous coronary intervention for STEMI is feasible and safe. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety and efficacy of the X-SIZER thrombectomy device versus the use of abciximab during primary angioplasty for acute ST-elevation myocardial infarction (STEMI). Design: Retrospective analysis of patients undergoing primary angioplasty for STEMI from October 2000 to December 2002 using the X-SIZER thrombectomy device versus abciximab. Setting: National University Hospital, Singapore. Patients: Out of 79 patients, 44 underwent X-SIZER use, while 35 received adjunct abciximab. Both groups were similarly represented with regards to age, gender, risk factors, target vessel site/diameter, cardiogenic shock, and onset of chest pain to procedure time. The infarct-related artery was occluded in 88.6% in both groups. Interventions: A 2-mm X-SIZER was used in 34/44 (77.3%), while a 1.5-mm device was used in the remainder. Final TIMI 3 flow was obtained in 38/44 (86.4%) in the X-SIZER group compared to 26/35 (74.3%) in the abciximab group (P = 0.175). Main Outcome Measures: Coronary TIMI flow rate, electrocardiogram (ECG) resolution, slow flow/no reflow phenomenon, and patient outcome (death, cardiac failure, or repeat revascularization) at 1 month. Results: ECG resolution and slow flow/no reflow were better in the X-SIZER group (77.3% vs 54.3%, P = 0.031; 9.1% vs 25.7%, P = 0.047, respectively). Patient outcome at 1 month was, however, not significantly different (18.2% vs 17.1%, P = 0.904, respectively, for X-SIZER and abciximab). Conclusion: X-SIZER thrombectomy during primary percutaneous coronary intervention for thrombus-laden STEMI is a safe and effective strategy. When compared to patients receiving abciximab, it was associated with improved ECG resolution, less slow flow/no reflow and a trend to better TIMI 3 flow. (J Interven Cardiol 2005;18:267–273) [ABSTRACT FROM AUTHOR]

Background: Occurrence of no reflow phenomenon during percutaneous coronary intervention (PCI) is associated with increased mortality. Although intracoronary medications can improve coronary flow, the effect on mortality is not known. Methods: Patients who had PCI for myocardial infarction (MI) at the Singapore National University Hospital from January 2000 to March 2004 were studied. Our analysis stratified patients into three groups according to the occurrence and persistence of no reflow during PCI. (1) Adequate reflow: without no reflow occurrence; (2) Reversible no reflow: no reflow occurred, but final thrombolysis in myocardial infarction (TIMI) 3 flow restored after intracoronary medications; and (3) Refractory no reflow: no reflow occurred and persisted, final TIMI flow < 3 despite medications. Thirty-day mortality was determined for each group. Results: A total of 1,328 patients (82% male), 703 (53%) underwent primary PCI and 625 (47%) rescue PCI were analyzed. Among the study patients, no reflow (including reversible and refractory) occurred in 135 patients (10.2%). Intracoronary verapamil, adenosine, nitroprusside, or a combination of drugs were used to treat the no reflow in 70.0%, 17.7%, 3.5%, and 8.8% of cases, respectively. Intracoronary medications successfully restored final TIMI 3 in 108 patients (80%, reversible no reflow). The remaining 27 patients (20%) have final TIMI < 3 (refractory no reflow). In comparison with the adequate reflow and reversible no reflow groups, those with refractory no reflow had an increased 30-day mortality (3.7% vs 2.8% vs 32.0%, P < 0.001). Logistic regression analyses showed that patients with refractory no reflow had a significantly higher 30-day mortality compared to patients with adequate reflow (P < 0.001) and reversible no reflow (P = 0.001), but no significant differences in the 30-day mortality between patients with adequate reflow and reversible no reflow (P = 0.157) were detected after adjusting for relevant covariates. Conclusion: Among patients undergoing PCI for MI, reversible no reflow was associated with a significantly lower 30-day mortality compared with the refractory counterpart. (J Interven Cardiol 2005;18:261–266) [ABSTRACT FROM AUTHOR]

Background: Vascular disease is a feature of aging, and coronary vascular events are a major source of morbidity and mortality in rare premature aging syndromes. One such syndrome is caused by mutations in the lamin A/C (LMNA) gene, which also has been implicated in familial insulin resistance. A second gene related to premature aging in man and in murine models is the KLOTHO gene, a hypomorphic variant of which (KL-VS) is significantly more common in the first-degree relatives of patients with premature coronary artery disease (CAD). We evaluated whether common variants at the LMNA or KLOTHO genes are associated with rigorously defined premature CAD. Methods: We identified 295 patients presenting with premature acute coronary syndromes confirmed by angiography. A control group of 145 patients with no evidence of CAD was recruited from outpatient referral clinics. Comprehensive haplotyping of the entire LMNA gene, including the promoter and untranslated regions, was performed using a combination of TaqMan® probes and direct sequencing of 14 haplotype-tagging single nucleotide polymorphisms (SNPs). The KL-VS variant of the KLOTHO gene was typed using restriction digest of a PCR amplicon. Results: Two SNPs that were not in Hardy Weinberg equilibrium were excluded from analysis. We observed no significant differences in allele, genotype or haplotype frequencies at the LMNA or KLOTHO loci between the two groups. In addition, there was no evidence of excess homozygosity at the LMNA locus. Conclusion: Our data do not support the hypothesis that premature CAD is associated with common variants in the progeroid syndrome genes LMNA and KLOTHO. [ABSTRACT FROM AUTHOR]

The association of coronary artery spasm and myocardial bridging is very uncommon and may represent a distinct clinical entity. Three patients are described, presenting with acute coronary syndrome associated with myocardial bridging and coronary artery spasm. The relationship and respective roles of myocardial bridging and spasm, however, remain uncertain and may be consequent to a direct effect on endothelial function from the compressive effect of myocardial bridging. The role of intracoronary nitroglycerin in these patients is unresolved. [ABSTRACT FROM AUTHOR]

Background: Clinical studies have evaluated the safety and efficacy of adjunctive X-sizer (EndiCOR Inc, San Clemente, CA) in percutaneous coronary intervention (PCI). However, patient and lesion subsets were highly selected, and extrapolation of the results to daily practice is problematic. Methods: X-sizer thrombectomy was performed in 200 procedures from August 2000 to July 2005. The indications for the procedures were primary PCI in 71%. Device failure was defined as the occurrence of 1 or more of the following conditions: (a) failure of the X-sizer to reach the target segment, (b) failure to achieve final thrombolysis in myocardial infarction 3 flow, (c) slow flow or no-reflow, (d) distal embolization, and (e) coronary perforation. Results: Device failure occurred in 48 procedures, giving a device failure rate of 24%. Logistic regression analysis showed that ostial lesion was the only independent predictor of device failure (OR 4.89, 95% CI 1.23-19.51, P = .024). A total of 19 patients had developed 22 adverse events, giving a 30-day adverse event rate of 9.5%. Among these, there were 13 deaths, 4 strokes, 2 reinfarctions, 2 repeat PCIs, and 1 coronary artery bypass grafting. Logistic regression analysis showed that X-sizer device failure was independently associated with 30-day adverse events (OR 3.42, 95% CI 1.04-11.25, P = .043). Conclusions: The incidence of device failure of X-sizer thrombectomy was 24%. Ostial lesion was an independent predictor of device failure. Notably, X-sizer device failure was independently associated with 30-day adverse event. These highlight the importance of case selection and the problem with its use in ostial lesions. [Copyright &y& Elsevier]

Background/purpose: Percutaneous coronary intervention (PCI) of diffuse coronary artery disease (CAD) is associated with higher adverse clinical events. This study aimed to compare the clinical outcomes of patients treated with single long 48 mm contemporary drug eluting stents (SL-DES) versus two overlapping contemporary drug eluting stents (OL-DES) for very-long CAD.Methods/materials: We analyzed the clinical outcome of 117 patients with SL-DES and 101 patients with OL-DES who underwent PCI between 1st July 2013 to 31st December 2016. The primary endpoint was target lesion failure (TLF) at two years, defined as a composite of cardiac mortality, target vessel myocardial infarction and target lesion revascularization.Results: Mean age was 60.8 ± 10.5 years for SL-DES group and 60.5 ± 11.9 years in the OL-DES group. SL-DES has longer mean lesion length as compared to OL-DES (43.1 ± 3.7 mm vs. 41.83 ± 2.3 mm p = 0.003). There was no difference in TLF at two years between SL-DES and OL-DES (5.3% vs. 6.4%, adjusted odds ratio 1.43, 95% CI 0.50-4.11). There was one case of probable ST in each group. Contrast volume usage was lower for SL-DES than OL-DES in patients who underwent single vessel PCI.Conclusions: Treatment of very-long CAD showed comparable TLF at two years for SL-DES versus OL-DES. Our results suggest that both strategies are reasonable treatment options for patients with diffuse CAD. [ABSTRACT FROM AUTHOR]

Abstract: Background: Circulating progenitor cells (CPC) especially endothelial progenitor cell (EPC) levels and functions are attenuated in diabetic patients. This may explain the poorer outcome of diabetics undergoing percutaneous coronary intervention (PCI). We aim to study the dynamic changes of these cells in these patients. Methods: Blood of 8 diabetics with stable coronary artery disease who underwent elective PCI, were obtained at baseline, 1, 4 and 24 h after PCI. Fluorescence activated cell sorting (FACS) analysis was performed to quantitate CD34+ and CD34+/ KDR+ cells. Patients with recent acute coronary syndrome were excluded. Results: After PCI, decreases in CPC from baseline were detected in 7 out of the 8 patients. In these 7 patients, mean CD34+ and CD34+/KDR+ cells were 182±99/1×105 and 18±16/1×105 cells respectively. Maximal decrease of CD34+ and CD34+/KDR+ cells were 47.8% and 53.3% at 1 h and 4 h respectively. At 24 h, CPC levels returned to baseline but were not elevated. The only patient with raised cardiac enzymes has instead, 2 to 3 fold increase in CPCs at 1 and 4 h. Conclusions: We found a transient dip in circulating progenitors early during PCI. This suggests incorporation of the cells into the sites of vascular denudation. The absence of subsequent CPC elevation post-PCI in diabetes may be associated with known poorer outcome of these patients. With myocardial injury, more progenitors may be mobilized from the bone marrow into the circulation and abolish the hyperacute reduction in circulating levels. [Copyright &y& Elsevier]

Abstract: Background: There are safety concerns on drug-eluting stents (DESs) using durable polymer. The long-term outcome of next generation DESs using bioabsorbable polymer technology remains unknown. Methods: From March to June, 2005, a novel sirolimus-eluting (170 μg/cm2), bioabsorbable polymer (PLA and PLGA, eroded over 45 days) coated stent was implanted for treatment of acute myocardial infarction (AMI) in 49 patients (male 86%, age 55+10 years, diabetes 31%). All culprits were de novo lesions in the native coronary artery. On discharge, aspirin and clopidogrel for 3 months followed by life-long aspirin were prescribed. Angiographic follow-up was performed at 8 months. Clinical follow-up was performed at 4, 9 and 24 months. Results: Angiographic success rate was 100%. In-hospital adverse events consisted of 1 death (2%). All except one patient (due to aspirin allergy) were compliant to the 3 months dual antiplatelet therapy, and there was no adverse event during this period. One patient developed re-infarction in another coronary territory at 6 months. Twenty-seven patients (56%) underwent 8-month angiographic follow-up (Table 3). At 24 months, 6 patients had 7 major adverse cardiac events (12.2%, 1 death, 2 re-infarctions and 4 target lesion revascularizations). There were no incidences of subacute or late stent thrombosis. Conclusions: The Cura stent, using bioabsorbable polymer technology, appears to be safe at 2 years follow-up. Although the angiographic follow-up parameters were unfavorable, this report paves the way for further studies on DES using bioabsorbable polymer technology. [Copyright &y& Elsevier]