Preventive percutaneous coronary intervention versus optimal medical therapy alone for the treatment of vulnerable atherosclerotic coronary plaques (PREVENT): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Acute coronary syndrome and sudden cardiac death are often caused by rupture and thrombosis of lipid-rich atherosclerotic coronary plaques (known as vulnerable plaques), many of which are non-flow-limiting. The safety and effectiveness of focal preventive therapy with percutaneous coronary intervention of vulnerable plaques in reducing adverse cardiac events are unknown. We aimed to assess whether preventive percutaneous coronary intervention of non-flow-limiting vulnerable plaques improves clinical outcomes compared with optimal medical therapy alone. METHODS: PREVENT was a multicentre, open-label, randomised controlled trial done at 15 research hospitals in four countries (South Korea, Japan, Taiwan, and New Zealand). Patients aged 18 years or older with non-flow-limiting (fractional flow reserve >0·80) vulnerable coronary plaques identified by intracoronary imaging were randomly assigned (1:1) to either percutaneous coronary intervention plus optimal medical therapy or optimal medical therapy alone, in block sizes of 4 or 6, stratified by diabetes status and the performance of percutaneous coronary intervention in a non-study target vessel. Follow-up continued annually in all enrolled patients until the last enrolled patient reached 2 years after randomisation. The primary outcome was a composite of death from cardiac causes, target-vessel myocardial infarction, ischaemia-driven target-vessel revascularisation, or hospitalisation for unstable or progressive angina, assessed in the intention-to-treat population at 2 years. Time-to-first-event estimates were calculated with the Kaplan-Meier method and were compared with the log-rank test. This report is the principal analysis from the trial and includes all long-term analysed data. The trial is registered at ClinicalTrials.gov, NCT02316886, and is complete. FINDINGS: Between Sept 23, 2015, and Sept 29, 2021, 5627 patients were screened for eligibility, 1606 of whom were enrolled and randomly assigned to percutaneous coronary intervention (n=803) or optimal medical therapy alone (n=803). 1177 (73%) patients were men and 429 (27%) were women. 2-year follow-up for the primary outcome assessment was completed in 1556 (97%) patients (percutaneous coronary intervention group n=780; optimal medical therapy group n=776). At 2 years, the primary outcome occurred in three (0·4%) patients in the percutaneous coronary intervention group and in 27 (3·4%) patients in the medical therapy group (absolute difference -3·0 percentage points [95% CI -4·4 to -1·8]; p=0·0003). The effect of preventive percutaneous coronary intervention was directionally consistent for each component of the primary composite outcome. Serious clinical or adverse events did not differ between the percutaneous coronary intervention group and the medical therapy group: at 2 years, four (0·5%) versus ten (1·3%) patients died (absolute difference -0·8 percentage points [95% CI -1·7 to 0·2]) and nine (1·1%) versus 13 (1·7%) patients had myocardial infarction (absolute difference -0·5 percentage points [-1·7 to 0·6]). INTERPRETATION: In patients with non-flow-limiting vulnerable coronary plaques, preventive percutaneous coronary intervention reduced major adverse cardiac events arising from high-risk vulnerable plaques, compared with optimal medical therapy alone. Given that PREVENT is the first large trial to show the potential effect of the focal treatment for vulnerable plaques, these findings support consideration to expand indications for percutaneous coronary intervention to include non-flow-limiting, high-risk vulnerable plaques. FUNDING: The CardioVascular Research Foundation, Abbott, Yuhan Corp, CAH-Cordis, Philips, and Infraredx, a Nipro company.

Preventive PCI or medical therapy alone for vulnerable atherosclerotic coronary plaque: Rationale and design of the randomized, controlled PREVENT trial.

BACKGROUND: Acute coronary syndromes are commonly caused by the rupture of vulnerable plaque, which often appear angiographically not severe. Although pharmacologic management is considered standard therapy for stabilizing plaque vulnerability, the potential role of preventive local treatment for vulnerable plaque has not yet been determined. The PREVENT trial was designed to compare preventive percutaneous coronary intervention (PCI) plus optimal medical therapy (OMT) with OMT alone in patients with functionally nonsignificant high-risk vulnerable plaques. METHODS: The PREVENT trial is a multinational, multicenter, prospective, open-label, active-treatment-controlled randomized trial. Eligible patients have at least 1 angiographically significant stenosis (diameter stenosis >50% by visual estimation) without functional significance (fractional flow reserve [FFR] >0.80). Target lesions are assessed by intracoronary imaging and must meet at least 2 imaging criteria for vulnerable plaque; (1) minimal lumen area <4.0 mm2; (2) plaque burden >70%; (3) maximal lipid core burden index in a 4 mm segment >315 by near infrared spectroscopy; and (4) thin cap fibroatheroma as determined by virtual histology or optical coherence tomography. Enrolled patients are randomly assigned in a 1:1 ratio to either preventive PCI with either bioabsorbable vascular scaffolds or metallic everolimus-eluting stents plus OMT or OMT alone. The primary endpoint is target-vessel failure, defined as the composite of death from cardiac causes, target-vessel myocardial infarction, ischemic-driven target-vessel revascularization, or hospitalization for unstable or progressive angina, at 2 years after randomization. RESULTS: Enrollment of a total of 1,608 patients has been completed. Follow-up of the last enrolled patient will be completed in September 2023 and primary results are expected to be available in early 2024. CONCLUSIONS: The PREVENT trial is the first large-scale, randomized trial to evaluate the effect of preventive PCI on non-flow-limiting vulnerable plaques containing multiple high-risk features that is appropriately powered for clinical outcomes. PREVENT will provide compelling evidence as to whether preventive PCI of vulnerable plaques plus OMT improves patient outcomes compared with OMT alone. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02316886. KEY POINTS: The PREVENT trial is the first, large-scale randomized clinical trial to evaluate the effect of preventive PCI on non-flow-limiting vulnerable plaque with high-risk features. It will provide compelling evidence to determine whether PCI of focal vulnerable plaques on top of OMT improves patient outcomes.

Prognostic Impact of Periprocedural Myocardial Infarction in Patients with Heavily Calcified Coronary Artery Disease Receiving Rotational Atherectomy.

Background: Periprocedural myocardial infarction (PMI) occurs more frequently in patients with heavily calcified lesion and undergoing rotational atherectomy (RA). However, there are limited studies addressing prognostic impact of PMI in patients requiring RA due to severe coronary artery calcification (CAC). Therefore, the objective of this study was to determine the prognostic impact of PMI in patients who underwent percutaneous coronary intervention (PCI) using RA. Methods: A total of 540 patients (583 lesions) who received PCI using RA were enrolled between January 2010 and October 2019. PMI was defined as elevations of creatine kinase-myocardial band (CK-MB) > 10 times the upper limited normal. Patients were divided into a PMI group and a non-PMI group. Primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), a composite of cardiac death, target-vessel myocardial infarction, target-vessel revascularization, and cerebrovascular accident. Results: Although in-hospital events occurred more frequently in the PMI group than in the non-PMI group (15 [3.0%] vs. 6 [13.3%], p = 0.005), the incidence of MACCEs at 1 month, 1-12 months, or 12 months failed to show a significant difference between the two groups (1 month, 10 [2.0%] vs. 1 [2.2%], p > 0.999; 1-12 months, 39 [7.9%] vs. 7 [15.6%], p = 0.091; 12 months, 49 [9.9%] vs. 8 [17.8%], p = 0.123). Conclusions: This study shows that PMI after RA in patients with severe CAC was associated with more frequent in-hospital events and a nonsignificant trend for more events during 1 year follow-up.

Effect of Angiotensin Receptor Blocker Dose in Myocardial Infarction With Preserved Left Ventricular Systolic Function.

ABSTRACT: There have been few studies of angiotensin receptor blocker (ARB) dose in myocardial infarction (MI) with preserved left ventricular (LV) systolic function. We evaluated the association of ARB dose with clinical outcomes after MI with preserved LV systolic function. We used MI multicenter registry. Six months after discharge, the ARB dose was indexed to the target ARB doses used in randomized clinical trials and grouped as >0%-25% (n = 2333), >25% of the target dose (n = 1204), and no ARB (n = 1263). The primary outcome was the composite of cardiac death or MI. Univariate analysis showed that mortality of those with any ARB dose was lower than those without ARB therapy. After multivariable adjustment, patients receiving >25% of target dose had a similar risk of cardiac death or MI compared with those receiving ≤25% or no ARB [hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.83-1.33; HR 0.94, 95% CI 0.82-1.08, respectively]. Propensity score analysis also demonstrated that patients with >25% dose had no difference in primary endpoint compared with those ≤25% dose or the no ARB group (HR 1.03, 95% CI 0.79-1.33; HR 0.86, 95% CI 0.64-1.14, respectively). The present study demonstrates that patients treated with >25% of target ARB dose do not have better clinical outcomes than those treated with ≤25% of target ARB dose or those with no ARB dose in MI patients with preserved LV systolic function.

Prognostic Impact of Atrial Fibrillation in Patients with Heavily Calcified Coronary Artery Disease Receiving Rotational Atherectomy.

Background and Objectives: Although both rotational atherectomy (RA) and atrial fibrillation (AF) have a high thrombotic risk, there have been no previous studies on the prognostic impact of AF in patients who undergo percutaneous coronary intervention (PCI) using RA. Thus, the aim of the present study was to determine the prognostic impact of AF in patients undergoing PCI using RA. Materials and Methods: A total of 540 patients who received PCI using RA were enrolled between January 2010 and October 2019. Patients were divided into AF and sinus rhythm groups according to the presence of AF. The primary endpoint was net adverse clinical events (NACEs) defined as a composite outcome of all-cause death, myocardial infarction, target vessel revascularization, cerebrovascular accident, or total bleeding. Results: Although in-hospital adverse events showed no difference between those with AF and those without AF (in-hospital events, 54 (11.0%) vs. 6 (12.2%), p = 0.791), AF was strongly associated with an increased risk of NACE at 3 years (NACE: hazard ratio, 1.880; 95% confidence interval, 1.096-3.227; p = 0.022). Conclusions: AF in patients who underwent PCI using RA was strongly associated with poor clinical outcomes. Thus, more attention should be paid to thrombotic and bleeding risks.

Impact of chronic total occlusion lesions on clinical outcomes in patients receiving rotational atherectomy: results from the ROCK registry.

The aim of this study was to investigate the impact of chronic total occlusion (CTO) on clinical outcomes in patients with calcified coronary lesions receiving rotational atherectomy (RA). This multi-center registry enrolled consecutive patients with calcified coronary artery disease who underwent RA during percutaneous coronary intervention (PCI) from 9 tertiary centers in Korea between January 2010 and October 2019. The primary outcome was target-vessel failure (TVF) which included the composite of cardiac death, target-vessel myocardial infarction (TVMI), and target-vessel revascularization (TVR). A total of 583 lesions were enrolled in this registry and classified as CTO (n = 42 lesions, 7.2%) and non-CTO (n = 541 lesions, 92.8%). The CTO group consisted of younger patients who were more likely to have a history of previous percutaneous coronary intervention or coronary artery bypass graft surgery. The incidence of the primary outcome was 14.1% and 16.7% for the non-CTO group and CTO group, respectively. The primary outcomes observed in the two groups were not significantly different (log-rank p = 0.736). The 18-month clinical outcomes of the CTO group were comparable to those of the non-CTO group in multivariate analysis. About 7% of patients requiring RA have CTO lesions and these patients experience similar clinical outcomes compared with those having non-CTO lesions. Use of RA for CTO lesions was safe despite higher procedural complexity.

Clinical Implication of 'Obesity Paradox' in Elderly Patients With Acute Myocardial Infarction.

BACKGROUND: The clinical impact of body mass index (BMI), especially in the elderly with acute myocardial infarction (AMI), has not been sufficiently evaluated. The purpose of this study was to elucidate the clinical impact of BMI in very old patients (≥80 years) with AMI. METHODS: The study analysed 2,489 AMI patients aged ≥80 years from the Korea Acute Myocardial Infarction Registry and the Korea Working Group on Myocardial Infarction (KAMIR/KorMI) registries between November 2005 and March 2012. The study population was categorised into four groups based on their BMI: underweight (n=301), normal weight (n=1,150), overweight (n=890), and obese (n=148). The primary endpoint was major adverse cardiovascular event (MACE), a composite of cardiac death, myocardial infarction, target lesion revascularisation, and target vessel revascularisation. RESULTS: Baseline characteristics among the four groups were similar, except for hypertension (45.1 vs 58.4 vs 66.2 vs 69.9%, respectively; p<0.001) and diabetes (16.6 vs 23.6 vs 30.7 vs 35.1%, respectively; p<0.001). Coronary care unit length of stay was significantly different among the four groups during hospitalisation (5.3±5.9 vs 4.8±6.8 vs 4.2±4.0 vs 3.5±2.1 days; p=0.007). MACE (16.9 vs 14.9 vs 13.7 vs 8.8%; p=0.115) and cardiac death (10.3 vs 8.4 vs 7.9 vs 4.1%; p=0.043) less frequently occurred in the obese group than in other groups during the 1-year follow-up. A multivariate regression model showed obese status (BMI ≥27.5 kg/m2) as an independent predictor of reduced MACE (hazard ratio [HR], 0.20; 95% confidence interval [CI], 0.06-0.69; p=0.010) along with reduced left ventricular ejection fraction (≤40%) as a predictor of increased MACE (HR,1.87; 95% CI, 1.31-2.68; p=0.001). CONCLUSION: Body mass index in elderly patients with acute myocardial infarction was significantly associated with coronary care unit stay and clinical cardiovascular outcomes.

Clinical Outcome of Rotational Atherectomy in Calcified Lesions in Korea-ROCK Registry.

Background and Objectives: Data is still limited regarding clinical outcomes of rotational atherectomy (RA) after percutaneous coronary intervention. We sought to evaluate clinical outcomes of RA. Materials and Methods: This multi-center registry enrolled patients who underwent RA during PCI from nine tertiary centers in Korea between January 2010 and October 2019. The primary endpoint was target-vessel failure (TVF; the composite outcome of cardiac death, target-vessel spontaneous myocardial infarction, or target-vessel revascularization). Results: Of 540 patients (583 lesions), the mean patient age was 71.4 ± 0.4 years, 323 patients (59.8%) were men, and 305 patients (56.5%) had diabetes mellitus. Technical success rate was 96.4%. In-hospital major adverse cerebral and cardiac events occurred in 63 cases (10.8%). At 1.5 years, 72 (16.0%) of TVFs were occurred. We evaluated independent predictors of TVF, which included current smoker (hazard ratio (HR), 1.92; 95% confidence interval (CI), 1.17-3.16; p = 0.01), chronic renal disease (HR, 1.87; 95% CI, 1.14-3.08; p = 0.013), history of cerebrovascular attack (HR, 2.14; 95% CI, 1.24-3.68; p = 0.006), left ventricle ejection fraction (HR, 0.98; 95% CI, 0.97-0.999; p = 0.037), and left main disease (HR, 1.94; 95% CI, 1.11-3.37; p = 0.019). Conclusions: From this registry, we demonstrated acceptable success rates, in-hospital and mid-term clinical outcomes of RA in the DES era.

Randomized Trial Evaluating Percutaneous Coronary Intervention for the Treatment of Chronic Total Occlusion.

BACKGROUND: Procedural results for percutaneous coronary intervention (PCI) in coronary vessels with chronic total occlusion (CTO) have improved in recent years, and PCI strategies have moved toward more complete revascularization with more liberal use of CTO-PCI. However, evidence evaluating CTO-PCI is limited to observational studies and small clinical trials. METHODS: In this open-label, multicenter, randomized, noninferiority trial, PCI-eligible patients were assigned to receive either 1 of 2 strategies: PCI or no PCI for the qualifying de novo CTO lesion with the option for PCI of obstructive non-CTO lesions at the discretion of the operator. The primary end point was a composite of death, myocardial infarction, stroke, or any revascularization. Health-related quality of life was assessed at baseline and at 1, 6, 12, 24, and 36 months. Because of slow recruitment, the trial was stopped before completion of the 1284 planned enrollments. RESULTS: Between March 2010 and September 2016, 834 patients were randomly assigned to the CTO-PCI (n=417) or no CTO-PCI (n=398) strategy. Among the patients assigned to the no CTO-PCI strategy, 78 (19.6%) crossed over to receive staged CTO-PCI within 3 days of randomization. The overall CTO-PCI success rate was 90.6%. Serious nonfatal complications associated with CTO-PCI occurred in 3 patients (1 stroke, 1 cardiac tamponade, and 1 patient with recurrent episodes of ventricular tachyarrhythmia induced by intracoronary thrombus). Approximately half of the patients in each group underwent PCI for an average of 1.3 non-CTO lesions, resulting in a comparable residual SYNTAX score (Synergy Between PCI With TAXUS and Cardiac Surgery; 3.7±5.4 versus 4.0±5.9, P=0.42) confined to non-CTO vessels. During a median follow-up of 4.0 years (interquartile range, 2.4 to 5.1 years), there was no significant difference between the CTO-PCI and the no CTO-PCI strategies in the incidence of the primary end point (22.3% versus 22.4%, hazard ratio, 1.03; 95% CI, 0.77 to 1.37; P=0.86). Both CTO-PCI and no CTO-PCI strategy were associated with significant improvements but without between-group differences in disease-specific health status that was sustained through 36 months. CONCLUSIONS: CTO-PCI was feasible with high success rates. There was no difference in the incidence of major adverse cardiovascular events with CTO-PCI versus no CTO-PCI, but the study was limited by low power for clinical end points and high crossover rates between groups. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01078051.

Clinical impact of statin therapy on vasospastic angina: data from a Korea nation-wide cohort study.

The effect of statin therapy on reducing adverse cardiovascular events in vasospastic angina (VSA) has been inconsistent. Therefore, we investigated the association between statin therapy and adverse cardiovascular events in a large, prospective VSA cohort. The Variant Angina Korea registry consecutively enrolled 2960 patients suspected VSA. Among them, we included 1713 patients who were diagnosed with VSA based on coronary provocation test. We divided the patients into the statin (n = 744) and no-statin group (n = 914) according to the medication prescribed at discharge. The primary outcome was a composite of cardiac death, acute coronary syndrome, and new-onset life-threatening arrhythmia during a 3-year follow-up period. The primary outcome occurred in 32 patients (4.3%) in the statin and 28 patients (3.1%) in the no-statin group. In Kaplan-Meier analysis before and after propensity score matching, there was no significant difference in the cumulative incidence of primary outcomes between both groups. Multivariate Cox regression analysis demonstrated that the focal type of VSA was independent predictor of primary outcomes, but statin therapy was not. Furthermore, the lack of benefit of statin therapy for primary outcomes was consistently observed across the statin intensity and spasm characteristics. In conclusion, the present study demonstrated that statin therapy did not reduce adverse cardiovascular events in patients with VSA.

Comparison of Spot versus Long Stenting for Femoropopliteal Artery Disease.

BACKGROUND: Optimal stenting strategy for long femoropopliteal artery lesions still remains undefined. Longer stent length has been shown to be associated with increased risk of restenosis. We sought to compare the efficacy of spot versus long stenting in the treatment of femoropopliteal artery disease. METHODS: This study was designed as a multicenter randomized controlled trial to compare immediate and mid-term outcomes of spot versus long primary stenting for femoropopliteal arterial lesions. A total of 125 patients were randomized 1:1 to spot stenting group (n = 59) or long stenting group (n = 66). RESULTS: All lesions were treated with self-expanding bare nitinol stents. Baseline clinical and lesion characteristics were similar between the 2 groups except for male gender and current smoker. The mean lesion length was 24.1 ± 8.8 cm. Technical success was achieved in all patients. The 1-year primary patency and TLR-free (target lesion revascularization) survival did not differ significantly between the 2 groups. However, the spot stenting group showed a trend toward higher primary patency (86.1% vs. 72.7%, P = 0.158) and TLR-free survival (94.2% vs. 82.5%, P = 0.120). The total stented length (hazard ratio [HR] 1.01, 95% confidence interval [CI] 1.00-1.01, P = 0.011) and age (HR 0.94, 95% CI 0.90-1.00, P = 0.035) were independent predictors of restenosis. CONCLUSIONS: The spot stenting appears to be more favorable than the long stenting in terms of primary patency and TLR-free survival, although the difference was not statistically significant. The stented length was an independent predictor of restenosis.

Fractional Flow Reserve and Cardiac Events in Coronary Artery Disease: 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.

Comparison of drug-eluting stents and drug-coated balloon for the treatment of drug-eluting coronary stent restenosis: A randomized RESTORE trial.

BACKGROUND: This study sought to evaluate the optimal treatment for in-stent restenosis (ISR) of drug-eluting stents (DESs). METHODS: This is a prospective, multicenter, open-label, randomized study comparing the use of drug-eluting balloon (DEB) versus second-generation everolimus-eluting stent for the treatment of DES ISR. The primary end point was in-segment late loss at 9-month routine angiographic follow-up. RESULTS: A total of 172 patients were enrolled, and 74 (43.0%) patients underwent the angiographic follow-up. The primary end point was not different between the 2 treatment groups (DEB group 0.15±0.49 mm vs DES group 0.19±0.41 mm, P=.54). The secondary end points of in-segment minimal luminal diameter (MLD) (1.80±0.69 mm vs 2.09±0.46 mm, P=.03), in-stent MLD (1.90±0.71 mm vs 2.29±0.48 mm, P=.005), in-segment percent diameter stenosis (34%±21% vs 26%±15%, P=.05), and in-stent percent diameter stenosis (33%±21% vs 21%±15%, P=.002) were more favorable in the DES group. The composite of death, myocardial infarction, or target lesion revascularization at 1 year was comparable between the 2 groups (DEB group 7.0% vs DES group 4.7%, P=.51). CONCLUSIONS: Treatment of DES ISR using DEB or second-generation DES did not differ in terms of late loss at 9-month angiographic follow-up, whereas DES showed better angiographic results regarding minimal MLD and percent diameter stenosis. Both treatment strategies were safe and effective up to 1year after the procedure.

Clinical implications of combined glucose intolerance in treatment-naïve hypertensive patients.

BACKGROUND: This study is the first study to evaluate clinical significance of combined glucose intolerance (CGI) in treatment-naïve hypertensive patients. METHODS: We compared the results of demographic, anthropometric, clinical, laboratory examinations, echocardiography, arterial stiffness, central blood pressure (BP) and ambulatory BP monitoring (ABPM) between the groups according to fasting blood sugar (FBS), postprandial 2 hour blood glucose (PP2) and gender in treatment-naïve hypertensive patients. A total of 376 concecutively-eligible patients were categorized as follows: (1) normal glucose tolerance (NGT); FBS<100 mg/dL and PP2 < 140 (2) isolated glucose intolerance (IGI); 100≤FBS<126 or 140≤PP2 < 200, but not both 100≤FBS<126 and 140≤PP2 < 200 (3) CGI; both 100≤FBS<126 and 140≤PP2 < 200. RESULTS: Males were divided into NGT (n = 58, 33.1%), IGI (n = 88, 50.3%), CGI (n = 29, 16.6%) and females were divided into NGT (n = 59, 43.1%), IGI (n = 48, 35%), CGI (n = 30, 21.9%). In males multivariate analyses revealed that mitral average E/Ea (IGI vs CGI, p = 0.022), brachial-ankle pulse wave velocity baPWV(Rt.) (IGI vs CGI, p = 0.026), baPWV(Lt.) (IGI vs CGI, p = 0.018), office systolic BP (SBP) (NGT vs. CGI, p = 0.005; IGI vs. CGI, p = 0.001), office diastolic BP (DBP) (NGT vs. CGI, p = 0.034; IGI vs. CGI, p = 0.019), night-time SBP (NGT vs. CGI, p = 0.049; IGI vs. CGI, p = 0.018) were significantly higher in the CGI group than in the NGT or IGI group. However, there were no significant differences between the female groups. CONCLUSIONS: Treatment-naïve hypertensive males with CGI revealed subclinical diastolic dysfunction, arterial stiffness, and BPs.

Impact of Postprocedural TIMI Flow on Long-Term Clinical Outcomes in Patients with Acute Myocardial Infarction.

This study aimed to evaluate the clinical prognostic implications of postprocedural Thrombolysis in Myocardial Infarction (TIMI) flow in acute myocardial infarction patients. A total of 2796 ST-elevation myocardial infarction (STEMI) and 1720 non ST-elevation myocardial infarction (NSTEMI) patients treated in 8 hospitals affiliated with the Catholic University of Korea and Chonnam National University Hospital were analyzed. The study populations were divided according to the final TIMI flow. The primary outcome were the major adverse cardiac events (MACE), defined as a composite of cardiac deaths (CD), nonfatal myocardial infarctions (MI), and target lesion revascularization (TLR). Over a median follow-up of 3.3 years (minimum 2 to maximum 5 years), MACE and CD occurred more frequently in STEMI patients with TIMI ≤ 2 group than those with TIMI 3 (MACE: adjusted hazard ratio [aHR], 1.962; 95% confidence interval [CI] 1.513 to 2.546, P < 0.001, CD: aHR, 3.154, CI 2.308 to 4.309, P < 0.001). However, there was no significant difference between the two subgroups in NSTEMI (aHR, 0.932; 95% CI 0.586 to 1.484, P = 0.087). In STEMI patients, good postprocedural TIMI flow after PCI was associated with favorable clinical outcomes. And the effect of poor TIMI flow in STEMI was on death, not the components of MACE. Meanwhile, postprocedural TIMI flow had no effect on long-term outcomes in NSTEMI patients.

Evaluation of the incremental prognostic value of the combination of CYP2C19 poor metabolizer status and ABCB1 3435 TT polymorphism over conventional risk factors for cardiovascular events after drug-eluting stent implantation in East Asians.

PURPOSE: We evaluated the incremental prognostic value of combining the CYP2C19 poor metabolizer (PM) and ABCB1 3435 TT for adverse clinical outcomes over conventional risk factors in a percutaneous coronary intervention (PCI) cohort. METHODS: We enrolled 2,188 patients. The primary end point was a composite of death from any cause, nonfatal myocardial infarction (MI), and stroke during 1-year follow-up. The population was stratified into the following four groups: CYP2C19 EM/IM+ABCB1 3435 CC/CT, CYP2C19 EM/IM+ABCB1 3435 TT, CYP2C19 PM+ABCB1 3435 CC/CT, and CYP2C19 PM+ABCB1 3435 TT. RESULTS: A total of 87 (3.97%) primary end-point events occurred (64 deaths, 8 non-fatal MIs and 15 strokes). Multivariate Cox analysis indicated that CYP2C19 PM+ABCB1 3435 TT status was a significant predictor of the primary end point (hazard ratio = 4.51, 95% confidence interval (CI) = 1.92-10.58). However, addition of combined genetic status to the clinical risk model did not improve the model discrimination (C-statistic = 0.786 (95% CI = 0.734-0.837) to 0.785 (95% CI = 0.733-0.838)) or risk reclassification (categorical net reclassification improvement (0.040, P = 0.32), integrated discrimination improvement (0.021, P = 0.026)). CONCLUSIONS: In a real-world East Asian PCI population taking clopidogrel, although the concurrent presence of CYP2C19 PM and ABCB1 TT is a strong independent predictor of adverse outcomes, the combined status of two at-risk variants does not have an incremental prognostic value beyond that of the conventional clinical risk factors.Genet Med 18 8, 833-841.

Impact of Metabolic Syndrome on Subclinical Atherosclerosis in Asymptomatic Individuals.

BACKGROUND: Little is known about subclinical atherosclerosis on coronary computed tomographic angiography (CCTA) in asymptomatic individuals with metabolic syndrome (MetS). METHODS AND RESULTS: We analyzed 5,213 asymptomatic individuals who underwent CCTA. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, or coronary revascularization. Of the study participants, 2,042 (39.2%) had MetS. MetS was an independent predictor of significant coronary artery disease (CAD) in at least 1 coronary artery (odds ratio [OR]=1.992, 95% confidence interval [CI]=1.623-2.445, P<0.001) and significant CAD in the left main (LM) or proximal left anterior descending (LAD) artery (OR=2.151, 95% CI=1.523-3.037, P<0.001). During the follow-up period (median 28.1 [interquartile range, 19.2-36.5] months), 111 individuals had 114 cardiac events. Individuals with MetS were significantly associated with more cardiac events than those without (RR [rate ratio]=1.67, 95% CI=1.15-2.43, P=0.007). In the MetS group, individuals with significant CAD had the majority of cardiac events (RR=64.33, 95% CI=29.17-141.88, P<0.001). Furthermore, in the MetS with significant CAD group, those with significant CAD in the LM or proximal LAD had more cardiac events (RR=2.63, 95% CI=1.51-4.59, P=0.001). CONCLUSIONS: MetS was associated with subclinical atherosclerosis on CCTA with subsequent high risk for cardiac events. These findings suggest the importance of reducing unfavorable metabolic conditions in asymptomatic individuals.

Usefulness of the parameters of quantitative myocardial perfusion contrast echocardiography in patients with chronic total occlusion and collateral flow.

BACKGROUND: Microvascular obstruction becomes more severe with longer duration of ischemia, such as chronic total occlusion (CTO) which used to have collateral flow. In this study, we explored the correlation between parameters measured using quantitative myocardial perfusion contrast echocardiography (MCE) and the angiographic collateral flow grades in patients with CTO. Furthermore, we investigated the usefulness of the parameters of quantitative MCE for the measurement of microvasculature changes after revascularization of CTO lesions. METHODS: Between January 2011 and January 2013, 44 patients who had undergone coronary angiography (CAG) due to chest pain and had confirmed CTO lesions were enrolled in this prospective observational study. All patients had baseline MCE within 24 hours after diagnostic CAG. Patients were then assigned to one of two groups: a medical therapy group (Group I, n = 20) or a reperfusion group with percutaneous coronary intervention (PCI) (Group II, n = 24). All patients had follow-up MCE 3 months later. RESULTS: Consistent with the CAG results in both groups, on baseline MCE, the myocardial blood flow (AI × ß) values were higher in Grade III collateral flow than in Grade I or II collateral flow (AI of collateral flow Grade I vs. Grade II vs. Grade III: 2.34 ± 2.65 vs. 2.52 ± 2.67 vs. 3.87 ± 4.57, P = 0.038). The plateau acoustic intensity (AI) and wall-motion score index (WMSI) were significantly improved at the 3-month follow-up after successful reperfusion with PCI (5.75 ± 3.52 before vs. 8.11 ± 6.02 after, P = 0.004) and (1.76 ± 0.83 before vs. 1.43 ± 0.64 after, P ≤ 0.001), respectively. However, the AI and WMSI values were not improved in the medical treatment group, (6.04 ± 4.64 before vs. 6.01 ± 5.52 after, P = 0.966) and (1.61 ± 0.82 before vs. 1.66 ± 0.67 after, P = 0.616), respectively. CONCLUSIONS: MCE is a useful tool for estimating microvascularity in patients with CTO lesions and correlates well with angiographic collateral flow.

The Prognostic Value of the Left Ventricular Ejection Fraction Is Dependent upon the Severity of Mitral Regurgitation in Patients with Acute Myocardial Infarction.

The prognostic value of the left ventricle ejection fraction (LVEF) after acute myocardial infarction (AMI) has been questioned even though it is an accurate marker of left ventricle (LV) systolic dysfunction. This study aimed to examine the prognostic impact of LVEF in patients with AMI with or without high-grade mitral regurgitation (MR). A total of 15,097 patients with AMI who received echocardiography were registered in the Korean Acute Myocardial Infarction Registry (KAMIR) between January 2005 and July 2011. Patients with low-grade MR (grades 0-2) and high-grade MR (grades 3-4) were divided into the following two sub-groups according to LVEF: LVEF ≤ 40% (n = 2,422 and 197, respectively) and LVEF > 40% (n = 12,252 and 226, respectively). The primary endpoints were major adverse cardiac events (MACE), cardiac death, and all-cause death during the first year after registration. Independent predictors of mortality in the multivariate analysis in AMI patients with low-grade MR were age ≥ 75 yr, Killip class ≥ III, N-terminal pro-B-type natriuretic peptide > 4,000 pg/mL, high-sensitivity C-reactive protein ≥ 2.59 mg/L, LVEF ≤ 40%, estimated glomerular filtration rate (eGFR), and percutaneous coronary intervention (PCI). However, PCI was an independent predictor in AMI patients with high-grade MR. No differences in primary endpoints between AMI patients with high-grade MR (grades 3-4) and EF ≤ 40% or EF > 40% were noted. MR is a predictor of a poor outcome regardless of ejection fraction. LVEF is an inadequate method to evaluate contractile function of the ischemic heart in the face of significant MR.