2020 Asian Pacific Society of Cardiology Consensus Recommendations on the Use of P2Y12 Receptor Antagonists in the Asia-Pacific Region.

The unique characteristics of patients with acute coronary syndrome in the Asia-Pacific region mean that international guidelines on the use of dual antiplatelet therapy (DAPT) cannot be routinely applied to these populations. Newer generation P2Y12 inhibitors (i.e. ticagrelor and prasugrel) have demonstrated improved clinical outcomes compared with clopidogrel. However, low numbers of Asian patients participated in pivotal studies and few regional studies comparing DAPTs have been conducted. This article aims to summarise current evidence on the use of newer generation P2Y12 inhibitors in Asian patients with acute coronary syndrome and provide recommendations to assist clinicians, especially cardiologists, in selecting a DAPT regimen. Guidance is provided on the management of ischaemic and bleeding risks, including duration of therapy, switching strategies and the management of patients with ST-elevation and non-ST-elevation MI or those requiring surgery. In particular, the need for an individualised DAPT regimen and considerations relating to switching, de-escalating, stopping or continuing DAPT beyond 12 months are discussed.

Lipoprotein(a): An underrecognized genetic risk factor for malignant coronary artery disease in young Indians.

Malignant coronary artery disease (CAD) refers to a severe and extensive atherosclerotic process involving multiple coronary arteries in young individuals (aged <45 years in men and <50 years in women) with a low or no burden of established risk factors. Indians, in general, develop acute myocardial infarction (AMI) about 10 years earlier; AMI rates are threefold to fivefold higher in young Indians than in other populations. Although established CAD risk factors have a predictive value, they do not fully account for the excessive burden of CAD in young Indians. Lipoprotein(a) (Lp(a)) is increasingly recognized as the strongest known genetic risk factor for premature CAD, with high levels observed in Indians with malignant CAD. High Lp(a) levels confer a twofold to threefold risk of CAD-a risk similar to that of established risk factors, including diabetes. South Asians have the second highest Lp(a) levels and the highest risk of AMI from the elevated levels, more than double the risk observed in people of European descent. Approximately 25% of Indians and other South Asians have elevated Lp(a) levels (≥50 mg/dl), rendering Lp(a) a risk factor of great importance, similar to or surpassing diabetes. Lp(a) measurement is ready for clinical use and should be an essential part of all CAD research in Indians.

Lipoprotein(a): An independent, genetic, and causal factor for cardiovascular disease and acute myocardial infarction.

Lipoprotein(a) [Lp(a)] is a circulating lipoprotein, and its level is largely determined by variation in the Lp(a) gene (LPA) locus encoding apo(a). Genetic variation in the LPA gene that increases Lp(a) level also increases coronary artery disease (CAD) risk, suggesting that Lp(a) is a causal factor for CAD risk. Lp(a) is the preferential lipoprotein carrier for oxidized phospholipids (OxPL), a proatherogenic and proinflammatory biomarker. Lp(a) adversely affects endothelial function, inflammation, oxidative stress, fibrinolysis, and plaque stability, leading to accelerated atherothrombosis and premature CAD. The INTER-HEART Study has established the usefulness of Lp(a) in assessing the risk of acute myocardial infarction in ethnically diverse populations with South Asians having the highest risk and population attributable risk. The 2018 Cholesterol Clinical Practice Guideline have recognized elevated Lp(a) as an atherosclerotic cardiovascular disease risk enhancer for initiating or intensifying statin therapy.

Three-year clinical and two-year multimodality imaging outcomes of a thin-strut sirolimus-eluting bioresorbable vascular scaffold: MeRes-1 trial.

AIMS: Although the proof of concept of the bioresorbable vascular scaffold (BRS) is well documented, device-related adverse outcomes with first-generation BRS indicate longer-term surveillance. The current study provides insights into the safety and performance of the MeRes100, a novel second-generation sirolimus-eluting BRS, beyond one-year up to three-year follow-up (FU). METHODS AND RESULTS: A total of 108 enrolled patients with de novo coronary artery lesions who underwent implantation of MeRes100 as part of the first-in-human MeRes-1 trial were followed up clinically beyond one year at two and three years and with multiple modality imaging at six months and two years. At three-year FU, the cumulative major adverse cardiac events rate was 1.87%, in the form of two ischaemia-driven target lesion revascularisations. No scaffold thrombosis was reported. Between six months and two years at quantitative coronary angiography, in-segment late lumen loss (LLL) (0.15±0.22 mm vs. 0.23±0.32 mm; p=0.18) and in-scaffold LLL (0.13±0.22 mm vs. 0.24±0.34 mm; p=0.10) changed insignificantly. IVUS subset analysis revealed a non-significant reduction in mean lumen area (6.17±1.28 mm2 vs. 5.47±1.50 mm2; p=0.21) and minimum lumen area (5.14±1.19 mm2 vs. 4.05±1.42 mm2; p=0.10) at two years compared to post-procedural measurements. OCT subset analysis demonstrated 99.24±2.27% neointimal strut coverage. CONCLUSIONS: The extended outcomes of the MeRes-1 trial demonstrated sustained efficacy and safety of the MeRes100 BRS with maintained lumen patency up to two years by multimodality imaging and no very late scaffold thrombosis up to three-year clinical FU.The MeRes-1 trial is registered at the Clinical Trials Registry-India. CTRI Number: CTRI/2015/04/005706.

Correlation of pacing site in right ventricle with paced QRS complex duration.

BACKGROUND: Pacing from RV mid septum and outflow tract septum has been proposed as a more physiological site of pacing and narrower paced QRS complex duration. The paced QRS morphology and duration in different RV pacing sites is under continued discussion. Hence, this study was designed to address the correlation of pacing sites in right ventricle with paced QRS complex duration. METHODS: Two hundred fifty-two consecutive patients who underwent pacemaker implantation were enrolled. Baseline clinical characteristics were recorded for each patient. All patient underwent fluoroscopy, electrocardiogram and echocardiography post pacemaker implantation. Paced QRS duration was calculated from the leads with maximum QRS duration. RESULTS: Mean paced QRS (pQRS) duration was significantly higher in apical septum group with a mean of 148.9 ±â€¯14.8 m s compared to mid septum (139.6 ±â€¯19.9 m s; p-value 0.003) and RVOT septum (139.6 ±â€¯14.8 m s; p-value 0.002) groups, respectively. There was no significant difference between mid-septal and RVOT septal pQRS duration. On multivariate analysis, female gender, baseline QRS duration and RVOT septal pacing were the only predictors for narrow pQRS duration (<150 msec). CONCLUSION: RV mid-septal and RVOT septal pacing were associated with significantly lower pQRS duration as compared with apical pacing. Based on multivariate analysis RVOT septal pacing appears to be preferred and more physiological pacing site.

Prognostic significance of fragmented QRS in patients with ST-elevation myocardial infarction undergoing revascularization.

BACKGROUND & OBJECTIVES: This longitudinal study was carried out to evaluate the prognostic significance of fragmented QRS (fQRS) in patients with acute ST elevation myocardial infarction (STEMI) undergoing revascularization. METHODS: This study included 103 STEMI patients belonging to Killip class I and II who underwent primary revascularization. All patients underwent twelve lead ECG at admission before PCI. Serial ECG were done after PCI at 3 hours, 6 hours, 24 hours, 48 hours and at discharge for detection of fQRS and echocardiography on day 3 post revascularization. Patients developing fQRS within 48 hours and with persistence of fQRS till discharge were included in "persistent fQRS" group. They were followed up after 30 days for major adverse cardiac events (MACE) and assessment of LV function by echocardiography. RESULTS: fQRS was present in 64 patients (61.5%) of study population with 37 patients (57.8%) having persistent fQRS. MACE rates were low (4.8%) and did not differ with respect to fQRS. fQRS significantly correlated with LV dysfunction at 30 days on univariate analysis (p-0.003) but not on multivariate analysis (p -0.10). fQRS was significantly related to impaired myocardial reperfusion as assessed by ΣSTR (percent of total ST segment resolution) (adjusted odds ratio, 95% CI [4.265 (1.034 - 17.58)], p = 0.04). CONCLUSION: In our study, fQRS did not predict MACE and LV dysfunction in acute STEMI patients belonging to Killip class I and II on short term follow-up of 30 days. But, fQRS independently predicted impaired microvascular myocardial reperfusion as assessed by ΣSTR.

Clinical significance of intracoronary thrombus aspirated during primary percutaneous intervention: An immunohistopathological study.

BACKGROUND: Manual thrombus aspiration during primary percutaneous intervention provides us with aspirated thrombus sample, that may contain material from the disrupted plaque. Immunohistopathological analysis of thrombus can yield valuable information about the clinical and cardiovascular outcomes and possible mechanisms of myocardial infarction. MATERIAL AND METHODS: We studied and analysed the immunohistopathological features of coronary thrombus aspirated from patients undergoing primary percutaneous coronary angioplasty. Immunohistological staining included markers namely CD68, SMA and CD34 for macrophages, smooth muscle actin and endothelium, respectively. Major adverse cardiac events, angiographic outcome and infarct size were also noted. RESULTS: Fifty-three patients (Mean age - 51.3±13years; males-47) who underwent primary percutaneous coronary intervention with aspiration thrombectomy were enrolled. Thrombus was successfully aspirated in 40 of 53 patients (75.4%). Patients with successful thrombus aspiration had higher ST-segment resolution (≥50%) as compared to patients with failed thrombus aspiration. Presence of RBC-rich thrombus on microscopy was more commonly associated with post-procedure TIMI flow of <2 as compared to patients with fibrin-rich thrombus and a trend towards lower myocardial blush grade<2 (P=0.10), and a significantly higher final infarct size (37.5±5% vs 25±15%; P=0.04 of myocardium) on nuclear scan. Immunohistology revealed presence of plaque material in 72% (26/36) of the samples. CONCLUSIONS: Immunohistopathological evaluation of intracoronary thrombus may be of prognostic importance. High prevalence of plaque material in the aspirated intracoronary thrombus suggests plaque rupture as a possible etiology for vessel occlusion in these patients. SHORT SUMMARY: Immunohistopathological evaluation of intracoronary thrombus reveals high prevalence of plaque material in the aspirated intracoronary thrombus suggesting plaque rupture as a possible etiology for vessel occlusion in Indian STEMI patients.

First-in-human evaluation of a novel poly-L-lactide based sirolimus-eluting bioresorbable vascular scaffold for the treatment of de novo native coronary artery lesions: MeRes-1 trial.

AIMS: The MeRes-1 trial sought to study the safety and effectiveness of a novel sirolimus-eluting bioresorbable vascular scaffold (MeRes100 BRS) in treating de novo native coronary artery lesions by clinical evaluation and using multiple imaging modalities. METHODS AND RESULTS: The MeRes-1 first-in-human trial was a single-arm, prospective, multicentre study, which enrolled 108 patients with de novo coronary artery lesions (116 scaffolds were deployed to treat 116 lesions in 108 patients). At six months, quantitative coronary angiography revealed in-scaffold late lumen loss of 0.15±0.23 mm with 0% binary restenosis. Optical coherence tomography demonstrated minimum scaffold area (6.86±1.73 mm2) and percentage neointimal strut coverage (99.30%). Quantitative intravascular ultrasound analysis confirmed a 0.14±0.16 mm2 neointimal hyperplasia area. At one year, major adverse cardiac events, a composite of cardiac death, any myocardial infarction and ischaemia-driven target lesion revascularisation, occurred in only one patient (0.93%) and there was no scaffold thrombosis reported. At one year, computed tomography angiography demonstrated that all scaffolds were patent and in-scaffold mean percentage area stenosis was 11.33±26.57%. CONCLUSIONS: The MeRes-1 trial demonstrated the safety and effectiveness of MeRes100 BRS. The favourable clinical outcomes and effective vascular responses have provided the basis for further studies in a larger patient population. The MeRes-1 trial is registered at the Clinical Trials Registry-India.

First-in-human evaluation of a novel poly-L-lactide based sirolimus-eluting bioresorbable vascular scaffold for the treatment of de novo native coronary artery lesions: MeRes-1 trial

AIMS: The MeRes-1 trial sought to study the safety and effectiveness of a novel sirolimus-eluting bioresorbable vascular scaffold (MeRes100 BRS) in treating de novo native coronary artery lesions by clinical evaluation and using multiple imaging modalities. METHODS AND RESULTS: The MeRes-1 first-in-human trial was a single-arm, prospective, multicentre study, which enrolled 108 patients with de novo coronary artery lesions (116 scaffolds were deployed to treat 116 lesions in 108 patients). At six months, quantitative coronary angiography revealed in-scaffold late lumen loss of 0.15±0.23 mm with 0% binary restenosis. Optical coherence tomography demonstrated minimum scaffold area (6.86±1.73 mm2) and percentage neointimal strut coverage (99.30%). Quantitative intravascular ultrasound analysis confirmed a 0.14±0.16 mm2 neointimal hyperplasia area. At one year, major adverse cardiac events, a composite of cardiac death, any myocardial infarction and ischaemia-driven target lesion revascularisation, occurred in only one patient (0.93%) and there was no scaffold thrombosis reported. At one year, computed tomography angiography demonstrated that all scaffolds were patent and in-scaffold mean percentage area stenosis was 11.33±26.57%...

Dual-Source Computed Tomography for Chronic Total Occlusion of Coronary Arteries.

OBJECTIVES: We compared dual-source CT (DSCT) and conventional angiography (CA) in evaluation of chronic total occlusion (CTO) of coronary arteries. BACKGROUND: Percutaneous coronary intervention (PCI) in CTO is technically difficult and has comparatively lower success rate than intervention in non-occluded artery. Accurate assessment of lesion morphology is an important determinant of PCI success in CTO. METHODS: Nineteen symptomatic patients (18 men, age: 58.6 ± 10.6 years) with a CTO on CA were subjected to a DSCT (Definition, Siemens, Germany). Heart rate (HR) control was not performed. Dedicated post-processing software was used for lesion analysis on both modalities. Presence of bridging collaterals, stump morphology, calcification, side branch, proximal tortuosity, occlusion length, distal vessel interpretability, and distal lesions were statistically compared. RESULTS: There were 20 CTOs. HR during DSCT ranged from 53 to 131 bpm. Bridging collaterals were seen in 3/20 (15%) lesions on CA and in none on DSCT. Stump anatomy and side branch were identified equally well. Plaque calcification was identified in 5/20 (25%) lesions on CA and in 12/20 (60%) lesions on DSCT (P = 0.025). Nature and extent of calcification were better visualized on DSCT. No proximal tortuosity was noted. Distal vessel was better interpretable on DSCT (15/20; 75%) compared to CA (9/20; 45%) (P = 0.05). No significant difference in lesion length was noted. CONCLUSION: DSCT performs as well as CA for most features of CTO. Avoidance of need to control HR, ability to better detect and characterize calcium and to interpret distal vessels make it a useful pre-intervention investigation. © 2014 Wiley Periodicals, Inc.

Antistreptokinase antibodies and outcome of fibrinolytic therapy with streptokinase for left-sided prosthetic valve thrombosis.

BACKGROUND: Left-sided prosthetic valve thrombosis (PVT) is a serious complication of valve replacement. In developing countries, fibrinolysis with streptokinase (SK) is often used as the first line of treatment. Anti-streptokinase (anti-SK) antibodies are widely prevalent in the general population, but their effect on the efficacy and outcome of fibrinolysis with SK in patients with PVT is not known. METHODS: Patients with rheumatic heart disease and prosthetic valve replacement presenting with a first episode of left-sided PVT were enrolled. All patients underwent fibrinolysis with SK. An indirect enzyme-linked immunosorbent assay was used to detect anti-SK antibodies before fibrinolysis. Relationship of these antibodies to the outcome of fibrinolysis was evaluated. RESULTS: Forty-four patients treated for left-sided PVT were included. Thrombosis affected 33 mitral and 11 aortic prosthetic valves. On fibrinolysis with SK, 32 (73%) patients achieved complete success, whereas it was unsuccessful in the remaining 12 patients. There were 3 bleeding events, 1 stroke, and 3 deaths. Mean anti-SK antibody levels were not significantly different between patients who had complete success and those who did not (8.81 ± 2.43 vs 7.67 ± 1.26 Au/mL; P = .13) and did not correlate with the outcome after adjustment with other variables. Patients in New York Heart Association class III or IV had a greater chance of failed fibrinolytic therapy, even after adjustment for other prognostic variables (odds ratio 9.0; 95% CI 1.29-63.02; P = .027). CONCLUSION: Anti-SK antibody titers are not associated with success of fibrinolytic therapy using SK in patients with left-sided PVT.

Transient, subclinical atrial fibrillation and risk of systemic embolism in patients with rheumatic mitral stenosis in sinus rhythm.

Stroke and systemic embolism occur frequently in patients with rheumatic mitral stenosis (MS) in sinus rhythm (SR), but the risk and predictors of embolic events in this population are not well studied. The aim of this study was to determine if transient, subclinical atrial fibrillation (AF) increases the risk of systemic embolism in patients with MS in SR. A single-center, prospective observational study of patients with rheumatic MS in SR was performed. The rate of the composite primary outcome of stroke, transient ischemic attack, or non-central nervous system embolism was determined, as well as the predictive value of Holter-detected episodes of transient (<30 seconds), subclinical AF for this outcome. Hazard ratios were derived for subclinical AF, after adjustment for clinical and echocardiographic predictors of systemic embolism, using Cox regression. The sensitivity, specificity, and area under the receiver-operating characteristic curve of subclinical AF were determined for the primary outcome. Among 179 patients (mean follow-up 10.2 months), the rate of the primary outcome was 5.3/100 patient-years (95% confidence interval [CI] 2.6 to 10.5). In univariate analysis, subclinical AF (hazard ratio 4.54, 95% CI 1.08 to 19.0, p = 0.038) and dense spontaneous echocardiographic contrast (hazard ratio 4.32, 95% CI 1.03 to 18.09, p = 0.045) were predictors of the primary outcome. In multivariate analysis, subclinical AF remained the only significant predictor (hazard ratio 5.02, 95% CI 1.15 to 22.0, p = 0.032). Subclinical AF had an area under the receiver-operating characteristic curve of 0.68 and high negative predictive value (97.7%) for the primary outcome. In conclusion, Holter-detected, transient (<30 seconds), subclinical AF is a predictor of stroke and systemic embolism in patients with rheumatic MS in SR. Considering the high risk for embolism, randomized trials of oral anticoagulation are needed in this population.

CYP 450 2C19 polymorphisms in Indian patients with coronary artery disease.

BACKGROUND: Dual antiplatelet therapy is the cornerstone in the management of acute coronary syndromes (ACS) and prevention of stent thrombosis (ST). Genetic polymorphisms in CYP2C19 gene involved in hepatic activation of clopidogrel leads to clopidogrel non-responsiveness and may influence clinical outcomes. These polymorphisms in CYP2C19 gene and their impact on clinical outcome in coronary artery disease (CAD) have not been studied in Indian population. METHODS: We studied 110 consecutive patients (mean age 55.7 ± 10.7 years; 90% male) taking clopidogrel with angiographically proven CAD for various genetic polymorphisms in CYP2C19 gene. Relationship between loss of function mutation and clinical presentation with recurrent ACS including ST was analyzed. RESULTS: Out of 110 patients, 26 (23.64%) had normal genotype, 52 (47.23%) had loss of function mutation *2 and 39 (35.45%) had a gain of function mutation *17, 7 (6.36%) patients were undefined metabolizers (*2/*17) which were excluded from analyses. Final analyses included 103 patients, with 45 (40.90%) having loss of function. Overall 51 patients had ACS, with 27 developing recurrence while on clopidogrel. The prevalence of loss of function mutation was no different between the group with recurrences and those without recurrences (55.6% vs. 50%, p = 0.7). Two patients developed ST while on clopidogrel; both had loss of function mutation. CONCLUSION: CYP2C19 gene polymorphisms are common in Indian population. Loss of function mutation status did not affect the clinical outcomes. A larger study also considering P2Y12 receptor polymorphisms together with platelet activity testing, may be required to establish the role of CYP2C19 gene polymorphisms in clinical practice.

Content of trans fatty acids in human cheek epithelium: comparison with serum and adipose tissue.

Studies pertaining to trans fatty acids (TFA), which have been implicated in development of chronic diseases, are more relevant in developing countries where nutrition transition is changing traditional habits and practices. Measuring TFA is an arduous task because of the need for fat biopsies. This study identifies a tissue, which can be easily accessed for analytical measurement of trans fatty acid. In this cross-sectional study, fatty acid in adipose tissue, cheek epithelium, and blood samples were assessed by gas chromatography. Spearman correlation coefficient was computed to study the correlation of fatty acid distribution among the three tissues. The correlation coefficient of total trans fatty acid between cheek epithelium and serum was 0.30 (P < 0.02) and between cheek epithelium and adipose tissue was 0.33 (P < 0.019). This study is the first to report trans fatty acid profile in cheek epithelium giving scope for utilizing the cheek epithelium as a tissue for objective assessment of trans fatty acid intake.

The paclitaxel-eluting PTCA-balloon in combination with a cobalt-chromium stent in two different sequences to treat de novo coronary artery lesions: an angiographic follow up study.

INTRODUCTION: The paclitaxel-coated balloon catheter (DCB) based on the PACCOCATH(®) technology has yielded angiographic and clinical results superior to drug-eluting stents (DES) in situations like in-stent restenosis (ISR) and a trend towards superior results in small coronary vessels and side branches of coronary bifurcations. Using the DCB followed by cobalt-chromium stent (CoCr) deployment or with a reverse sequence may yield different outcomes in terms of late loss. METHODS: 97 patients with de-novo coronary stenosis (55.6 ± 10.7 years, 79.4% male, ≥70%, length: ≤25 mm, vessel diameter: 2.5-4.0 mm) were randomly treated with the DCB (3 µg/mm²) followed by a CoCr-stent or stent first and DCB later. Six-month angiographic and one-year clinical follow-up intention-to-treat analyses were performed. RESULTS: Angiographic and demographic baseline data was comparable between the two groups. When comparing balloon first versus stent first technique, the primary outcome variables were not statistically different for mean in-segment (0.51 ± 0.56 mm vs. 0.36 ± 0.55 mm, p = 0.23) and in-stent (0.52 ± 0.55 mm vs. 0.46 ± 0.52 mm, p = 0.65) late lumen loss. The lesion related 12-month MACE rates were 5/49 (10.2%) and 2/48 (4.2%) (p = 0.44). Lesion related thrombotic events occurred in three patients in balloon first and in one patient in stent first group, two of which were associated with early discontinuation of continuous dual anti-platelet therapy, two with suboptimal PCI, and one each were performed in a thrombotic lesion and a bifurcation type 1.1.0. CONCLUSION: Drug-coated balloon first followed by cobalt chromium stent deployment versus a reverse sequence is not associated with statistically significantly different 6-month angiographic or 12-month clinical outcomes.