Fractional Flow Reserve or Intravascular Ultrasonography to Guide PCI.

BACKGROUND: In patients with coronary artery disease who are being evaluated for percutaneous coronary intervention (PCI), procedures can be guided by fractional flow reserve (FFR) or intravascular ultrasonography (IVUS) for decision making regarding revascularization and stent implantation. However, the differences in clinical outcomes when only one method is used for both purposes are unclear. METHODS: We randomly assigned 1682 patients who were being evaluated for PCI for the treatment of intermediate stenosis (40 to 70% occlusion by visual estimation on coronary angiography) in a 1:1 ratio to undergo either an FFR-guided or IVUS-guided procedure. FFR or IVUS was to be used to determine whether to perform PCI and to assess PCI success. In the FFR group, PCI was to be performed if the FFR was 0.80 or less. In the IVUS group, the criteria for PCI were a minimal lumen area measuring either 3 mm2 or less or measuring 3 to 4 mm2 with a plaque burden of more than 70%. The primary outcome was a composite of death, myocardial infarction, or revascularization at 24 months after randomization. We tested the noninferiority of the FFR group as compared with the IVUS group (noninferiority margin, 2.5 percentage points). RESULTS: The frequency of PCI was 44.4% among patients in the FFR group and 65.3% among those in the IVUS group. At 24 months, a primary-outcome event had occurred in 8.1% of the patients in the FFR group and in 8.5% of those in the IVUS group (absolute difference, -0.4 percentage points; upper boundary of the one-sided 97.5% confidence interval, 2.2 percentage points; P = 0.01 for noninferiority). Patient-reported outcomes as reported on the Seattle Angina Questionnaire were similar in the two groups. CONCLUSIONS: In patients with intermediate stenosis who were being evaluated for PCI, FFR guidance was noninferior to IVUS guidance with respect to the composite primary outcome of death, myocardial infarction, or revascularization at 24 months. (Funded by Boston Scientific; FLAVOUR ClinicalTrials.gov number, NCT02673424.).

Ten-Year Outcomes After Drug-Eluting Stents Versus Coronary Artery Bypass Grafting for Left Main Coronary Disease: Extended Follow-Up of the PRECOMBAT Trial.

BACKGROUND: Long-term comparative outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents and coronary-artery bypass grafting (CABG) for left main coronary artery disease are highly debated. METHODS: In the PRECOMBAT trial (Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease), patients with unprotected left main coronary artery disease were randomly assigned to undergo PCI with sirolimus-eluting stents (n=300) or CABG (n=300) in 13 hospitals in Korea from April 2004 to August 2009. The follow-up was extended to at least 10 years for all patients (median, 11.3 years). The primary outcome was the incidence of major adverse cardiac or cerebrovascular events (composite of death from any cause, myocardial infarction, stroke, or ischemia-driven target-vessel revascularization). RESULTS: At 10 years, a primary outcome event occurred in 29.8% of the PCI group and in 24.7% of the CABG group (hazard ratio [HR] with PCI vs CABG, 1.25 [95% CI, 0.93-1.69]). The 10-year incidence of the composite of death, myocardial infarction, or stroke (18.2% vs 17.5%; HR 1.00 [95% CI, 0.70-1.44]) and all-cause mortality (14.5% vs 13.8%; HR 1.13 [95% CI, 0.75-1.70]) were not significantly different between the PCI and CABG groups. Ischemia-driven target-vessel revascularization was more frequent after PCI than after CABG (16.1% vs 8.0%; HR 1.98 [95% CI, 1.21-3.21). CONCLUSIONS: Ten-year follow-up of the PRECOMBAT trial of patients with left main coronary artery disease randomized to PCI or CABG did not demonstrate significant difference in the incidence of major adverse cardiac or cerebrovascular events. Because the study was underpowered, the results should be considered hypothesis-generating, highlighting the need for further research. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03871127 and NCT00422968.

Usefulness of the trans-stent fractional flow reserve gradient for predicting clinical outcomes.

OBJECTIVES: We evaluated the usefulness of a fractional flow reserve (FFR) gradient across the stent (ΔFFRstent ) for long-term clinical outcomes after percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). BACKGROUND: The clinical meaning of a trans-stent pressure gradient after DES implantation has not been estimated adequately. METHODS: FFR pull-back and intravascular ultrasound (IVUS) were performed after successful PCI in 135 left anterior descending artery lesions. ΔFFRstent was defined as the FFR gradient across the stent. The ΔFFRstent/length was defined as the ΔFFRstent value divided by the total stent length multiplied by 10. Major adverse cardiac events (MACEs) were the composite of all-cause death, target vessel-related myocardial infarction, and target lesion revascularization. RESULTS: Despite successful PCI, ΔFFRstent > 0 was observed in 98.5% of cases. ΔFFRstent ≥ 0.04 and ΔFFRstent/length ≥ 0.009 predicted suboptimal stenting defined as final minimal stent area < 5.5 mm2 . During 2,183 ± 898 days, the MACE-free survival rate was significantly lower in patients with ΔFFRstent ≥ 0.04 and ΔFFRstent/length ≥ 0.009 compared to those with lower values (69.6 vs. 93.4%, log-rank p = .031; 72.1 vs. 97.7%, log-rank p = .003, respectively). ΔFFRstent/length ≥ 0.009 (hazard ratio 10.1, p = .032) was an independent predictor of MACE. CONCLUSION: A trans-stent FFR gradient was frequently observed. ΔFFRstent and ΔFFRstent/length are related to long-term outcomes in DES-treated patients.

Impact of new-onset diabetes on clinical outcomes after ST segment-elevated myocardial infarction.

Objective. Patients with diabetes have higher mortality rate than patients without diabetes after ST-segment elevated myocardial infarction (STEMI). Prognosis of patients with new onset diabetes (NOD) after STEMI remains unclear. The aim of this study was to evaluate the prognosis of patients with NOD compared to that of patients without NOD after STEMI. Design. This study was a retrospective observational study. We enrolled 901 STEMI patients. Patients were divided into diabetic and non-diabetic groups at index admission. Non-diabetic group was divided into NOD and non-NOD groups. Kaplan-Meier analysis and Cox's proportional hazard regression models were used to compare major adverse cardiac events (MACE) free survival rate and hazard ratio for MACE between NOD and non-NOD groups. Results. Mean follow-up period was 59 ± 28 months. Diabetes group had higher MACE than non-diabetes group (p = .038). However, MACE was not different between NOD and non-NOD groups (p = 1.000). After 1:2 propensity score matching, incidence of MACE was not different between the two groups. In Kaplan-Meier survival curves, MACE-free survival rates were not statistically different between NOD and non-NOD groups either (p = .244). Adjusted hazard ratios of NOD for MACE, all-cause of death, recurrent myocardial infarction, and target vessel revascularization were 0.697 (95% confidence interval [CI]: 0.362-1.345, p = .282), 0.625 (95% CI: 0.179-2.183, p = .461), 0.794 (95% CI: 0.223-2.835, p = .723), and 0.506 (95% CI: 0.196-1.303, p = .158), respectively. Conclusion. This retrospective observational study with a limited statistical power did not show a different prognosis in patients with and without NOD.

Comparison of the planned one- and elective two-stent techniques in patients with coronary bifurcation lesions with or without acute coronary syndrome from the COBIS II Registry.

OBJECTIVES: To evaluate the impacts of stent techniques on long-term clinical outcomes after percutaneous coronary intervention (PCI) using drug-eluting stents (DES) for coronary bifurcation lesions in patients with or without acute coronary syndrome (ACS). BACKGROUND: Few studies have investigated the impacts of stent techniques for treating coronary bifurcation lesions in patients with and without ACS. METHODS: This multicenter registry enrolled 2,897 patients undergoing PCI with DES for coronary bifurcation lesions. We investigated the impacts of planned one-stent and elective two-stent techniques in patients with (n = 1,798) and those without (n = 1,099) ACS. Primary endpoint was the incidence of 3-year target-lesion failure (TLF), defined as a composite of cardiac death, spontaneous myocardial infarction, and target-lesion revascularization. RESULTS: The planned one-stent technique reduced TLF rate compared to elective two-stent technique in the ACS cohort (hazard ratio [HR] 0.49; 95% confidence interval [CI] 0.34-0.74; P = 0.001), and not in the non-ACS cohort (HR 0.61; 95% CI 0.35-1.06; P = 0.079). After propensity score matching, the planned one-stent technique had a significantly lower TLF rate (HR 0.47; 95% CI 0.29-0.74; P = 0.001) in patients with ACS, and it also showed a trend toward lower TLF rate with the planned one-stent technique in patients without ACS (9.0 vs. 14.5%, HR 0.59; 95% CI 0.32-1.14; P = 0.116). CONCLUSIONS: Planned one-stenting reduced TLF in patients with ACS and it also might be beneficial in those without ACS for the treatment of coronary bifurcation lesions.

Myocardial Mass Contributes to the Discrepancy Between Anatomic Stenosis Severity Assessed by Intravascular Ultrasound and Fractional Flow Reserve in Intermediate Lesions of the Coronary Artery.

OBJECTIVES: The present study investigated the major contributors to the discrepancy between the minimal lumen area (MLA) and fractional flow reserve (FFR). BACKGROUND: There was considerable discrepancy between MLA or diameter stenosis (DS) and FFR. METHODS: We enrolled 744 patients with intermediate stenoses of the left anterior descending artery (LAD). Summed epicardial coronary artery length distal to the target stenosis was obtained from each longest view of the vessels on the coronary angiograms. Mismatching was defined as a lesion with FFR of >0.80 and MLA smaller than the best cut-off value (BCV) for predicting FFR of ≤0.80. Reverse mismatching was defined as a lesion with FFR of ≤0.80 and MLA larger than the BCV. RESULTS: Summed epicardial coronary artery length was longer at the lesions of proximal LAD than that of middle LAD (380 mm ± 82 mm vs. 341 mm ± 80 mm, P < 0.001). Reverse mismatching was found more frequently in the proximal than middle LAD (28.3% vs. 5.5%, P < 0.001). Independent predictors of FFR ≤ 0.80 were age, male, multi-vessel disease, proximal LAD lesion, MLA, DS, plaque burden at distal reference, lesion length and summed epicardial coronary artery length. Proximal LAD lesion was an independent predictor of reverse mismatching (hazard ratio 3.162, 1.858-5.382, P < 0.001). CONCLUSIONS: Myocardial mass subtended by a lesion is an important factor predicting FFR ≤0.80 and discrepancy between FFR and MLA. Myocardial mass subtended by a lesion should be considered when determining the revascularization therapy by intravascular ultrasound parameters. © 2017 Wiley Periodicals, Inc.

Impact of Age on the Functional Significance of Intermediate Epicardial Artery Disease.

BACKGROUND: The functional significance of an intermediate coronary lesion is crucial for determining the treatment strategy, but age-related changes in cardiovascular function could affect the functional significance of an epicardial stenosis. The aim of this study was therefore to investigate the impact of age on fractional flow reserve (FFR) measurements in patients with intermediate coronary artery disease (CAD). METHODS AND RESULTS: Intracoronary pressure measurements and intravascular ultrasound (IVUS) were performed in 178 left anterior descending coronary arteries with intermediate stenosis. The morphological characteristics and FFR of 91 lesions in patients <65 years old were compared with those of 87 patients ≥65 years old. There was no difference in lesion location, diameter stenosis, minimum lumen area, plaque burden, or lesion length between the 2 age groups. Elderly patients had higher FFR (0.81±0.06 vs. 0.79±0.06, P=0.004) and lower ∆FFR, defined as the difference between resting Pd/Pa and FFR (0.13±0.05 vs. 0.15±0.05, P=0.014). Age, along with the location and degree of stenosis, was independently associated with FFR and ∆FFR (ß=0.162, P=0.008; ß=-0.131, P=0.043, respectively). CONCLUSIONS: Elderly patients with intermediate CAD are more likely to have higher FFR and lower ∆FFR, despite a similar degree of epicardial stenosis, compared with younger patients. (Circ J 2016; 80: 1583-1589).

Echocardiographic epicardial fat thickness is a predictor for target vessel revascularization in patients with ST-elevation myocardial infarction.

BACKGROUND: The amount of epicardial adipose tissue (EAT) has been demonstrated to correlate with the severity of coronary artery disease (CAD) and the CAD activity. The aim of this study is to assess the impact of EAT on long term clinical outcomes in patients with ST elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI). METHODS: We analyzed the data and clinical outcomes of 761 patients (614 males, 57 ± 12 year-old) with STEMI who underwent successful primary PCI from 2003 to 2009. All patients were divided into two groups: thick EAT group, EAT ≥ 3.5 mm and thin EAT group, EAT < 3.5 mm. The primary end points were all-cause death, recurrent MI, target vessel revascularization (TVR) and major cardiac adverse events (MACEs), composite of all-cause death, recurrent MI and TVR, within 5 years. RESULTS: Median and mean EAT of 761 patients were 3.3 mm and 3.6 ± 1.7 mm, respectively. Mean follow up period was 46 ± 18 months. MACE-free survival rate in the thick EAT group was significantly lower than in the thin EAT group (log-rank P = 0.001). The event-free survival rate of all-cause death of the thick EAT group was significantly lower than that of the thin EAT group (log-rank P = 0.005). The TVR-free survival rate in the thick EAT group was significantly lower than in the thin EAT group (log-rank P = 0.007). The event-free survival rate of recurrent MI were not significantly different between the groups (log-rank P = 0.206). In the Cox's proportional hazard model, the adjusted hazard ratio of thick EAT thickness for TVR was 1.868 (95% confidence interval 1.181-2.953, P = 0.008). CONCLUSION: This study demonstrates that the EAT thickness is related with long term clinical outcome in patients with STEMI. The EAT thickness might provide additional information for future clinical outcome, especially TVR.

Clinical Outcomes in Patients with Deferred Coronary Lesions according to Disease Severity Assessed by Fractional Flow Reserve.

Data on the clinical outcomes in deferred coronary lesions according to functional severity have been limited. This study evaluated the clinical outcomes of deferred lesions according to fractional flow reserve (FFR) grade using Korean FFR registry data. Among 1,294 patients and 1,628 lesions in Korean FFR registry, 665 patients with 781 deferred lesions were included in this study. All participants were consecutively categorized into 4 groups according to FFR; group 1: ≥ 0.96 (n = 56), group 2: 0.86-0.95 (n = 330), group 3: 0.81-0.85 (n = 170), and group 4: ≤ 0.80 (n = 99). Primary endpoint was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction, and target vessel revascularization. The median follow-up period was 2.1 years. During follow-up, the incidence of MACE in groups 1-4 was 1.8%, 7.6%, 8.8%, and 13.1%, respectively. Compared to group 1, the cumulative rate by Kaplan-Meier analysis of MACE was not different for groups 2 and 3. However, group 4 had higher cumulative rate of MACE compared to group 1 (log-rank P = 0.013). In the multivariate Cox hazard models, only FFR (hazard ratio [HR], 0.95; P = 0.005) was independently associated with MACE among all participants. In contrast, previous history of percutaneous coronary intervention (HR, 2.37; P = 0.023) and diagnosis of acute coronary syndrome (ACS) (HR, 2.35; P = 0.015), but not FFR, were independent predictors for MACE in subjects with non-ischemic (FFR ≥ 0.81) deferred coronary lesions. Compared to subjects with ischemic deferred lesions, clinical outcomes in subjects with non-ischemic deferred lesions according to functional severity are favorable. However, longer-term follow-up may be necessary.

Long-Term Clinical Outcomes of True and Non-True Bifurcation Lesions According to Medina Classification- Results From the COBIS (COronary BIfurcation Stent) II Registry.

BACKGROUND: Little is known about the clinical outcomes of patients with different types of coronary bifurcation lesions. We sought to compare long-term clinical outcomes of patients with true or non-true bifurcation lesions who underwent percutaneous coronary intervention. METHODS AND RESULTS: We compared major adverse cardiac events (MACE: cardiac death, myocardial infarction [MI], or target lesion revascularization) between 1,502 patients with true bifurcation lesions (51.8%) and 1,395 with non-true bifurcation lesions (48.2%). True bifurcation lesions were defined as Medina classification (1.1.1), (1.0.1), or (0.1.1) lesions. During a median follow-up of 36 months, MACE occurred in 296 (10.2%) patients. Patients with true bifurcation lesions had a significantly higher risk of MACE than those with non-true bifurcation lesions (HR 1.39; 95% CI 1.08-1.80; P=0.01). Among true bifurcation lesions, Medina (1.1.1) and (0.1.1) were associated with a higher risk of cardiac death or MI than Medina (1.0.1) (HR 4.15; 95% CI 1.01-17.1; P=0.05). During the procedure, side branch occlusion occurred more frequently in Medina (1.1.1) and (1.0.1) than Medina (0.1.1) lesions (11.5% vs. 7.4%, P=0.03). CONCLUSIONS: Patients with true bifurcation lesions had worse clinical outcomes than those with non-true bifurcation lesions. Procedural and long-term clinical outcomes differed according to the type of bifurcation lesion. These findings should be considered in future bifurcation studies.

ß-Blocker Therapy in the Era of Primary Percutaneous Intervention for ST Elevation Myocardial Infarction.

OBJECTIVES: With the present therapeutic advances in the era of primary percutaneous coronary intervention (PCI), the role of ß-blockers in ST elevation acute myocardial infarction (STEMI) has remained contentious. METHODS: We analyzed the data and clinical outcomes of 901 STEMI patients who had undergone primary PCI. We classified the patients into ß-blocker (n = 598) and non-ß-blocker groups (n = 303). RESULTS: The cumulative incidence of all-cause death was 10.0% in the ß-blocker group and 25.4% in the non-ß-blocker group (p < 0.001). The incidence of major adverse cardiac events (MACE) was 22.1% in the ß-blocker group and 34.3% in the non-ß-blocker group (p < 0.001). The relative hazard ratio (HR) of ß-blockers for all-cause death and MACE with low left ventricle ejection fraction (LVEF; <50%) was 0.55 [95% confidence interval (CI) 0.35-0.86, p = 0.009] and 0.75 (95% CI 0.51-1.09, p = 0.125), respectively. In patients with normal LVEF (≥50%), the relative HR of ß-blockers for death and MACE were 0.50 (95% CI 0.29-0.88, p = 0.016) and 0.75 (95% CI 0.51-1.12, p = 0.162), respectively. After propensity score matching of the difference of the baseline characteristics, the Kaplan-Meier survival curve demonstrated lower mortality in the ß-blocker group than in the non-ß-blocker group with both low LVEF and normal LVEF (p = 0.02 and p = 0.001, respectively). CONCLUSIONS: ß-Blockers have beneficial clinical outcomes in the era of primary PCI for STEMI, regardless of the LVEF. © 2015 S. Karger AG, Basel.

Independent risk factors for mortality in patients with chronic obstructive pulmonary disease who undergo comprehensive cardiac evaluations.

BACKGROUND: Cardiovascular disease is the most common cause of death in chronic obstructive pulmonary disease (COPD). However, the impact of cardiovascular comorbidities on the prognosis of COPD is not well known. OBJECTIVES: This study was performed to investigate the effects of cardiovascular comorbidities on the prognosis of COPD. METHODS: We enlisted 229 patients with COPD who underwent comprehensive cardiac evaluations including coronary angiography and echocardiography at Ajou University Hospital between January 2000 and December 2012. Survival analyses were performed in this retrospective cohort. RESULTS: Kaplan-Meier analyses showed that COPD patients without left heart failure (mean survival = 12.5 ± 0.7 years) survived longer than COPD patients with left heart failure (mean survival = 6.7 ± 1.4 years; p = 0.003), and the survival period of nonanemic COPD patients (mean survival = 13.8 ± 0.8 years) was longer than that of anemic COPD patients (mean survival = 8.3 ± 0.8 years; p < 0.001). The survival period in COPD with coronary artery disease (CAD; mean survival = 11.37 ± 0.64 years) was not different from that in COPD without CAD (mean survival = 11.98 ± 0.98 years; p = 0.703). According to a multivariate Cox regression model, a lower hemoglobin level, a lower left ventricular ejection fraction, and the forced expiratory volume in 1 s (FEV1) were independently associated with higher mortality in the total COPD group (p < 0.05). CONCLUSIONS: Hemoglobin levels and left ventricular ejection fraction along with a lower FEV1 were identified as independent risk factors for mortality in COPD patients who underwent comprehensive cardiac evaluations, suggesting that multidisciplinary approaches are required in the care of COPD.

Left ventricular hypertrophy on long-term cardiovascular outcomes in patients with ST-elevation myocardial infarction.

BACKGROUND: Left ventricular hypertrophy (LVH) had been associated with increased adverse cardiovascular events in hypertensive patients. Prognostic significance of LVH in patients with ST-elevation myocardial infarction (STEMI) is not established. This study aimed to investigate prognostic impact of LVH on the patients with STEMI. METHODS: We analyzed the data and clinical outcomes of 30-day survivors with STEMI who underwent successful coronary intervention from 2003 to 2009. Definition of LVH was LV mass index (LVMI) >115 g/m(2) in male and >95 g/m(2) in female. Patients were classified into a LVH group and a non-LVH group. Occurrence of major adverse cardiovascular events (MACE; death, recurrent MI, target vessel revascularization (TVR)) within 5 years was evaluated. RESULTS: We enrolled 418 patients and mean follow-up duration was 43 ± 17 months. Two hundred and fourteen patients (51%) had LVH. The survival of the patients with LVH was significantly worse than the patients without LVH (log-rank p = 0.024). In a multivariate regression model, the presence of LVH was independently associated with increased risk for all-cause mortality (OR, 2.37; 95% CI, 1.096-5.123, p = 0.028). When the end points were analyzed based on LVH severity, all-cause mortality was significantly correlated with LVH severity (p = 0.011). The severe LVH was independently associated with increased risk for all-cause mortality (OR, 5.110; 95% CI, 1.454-17.9, p = 0.001). CONCLUSION: LVH was associated with increased rate of adverse clinical outcomes in 30-day survivors after STEMI, who underwent successful coronary intervention.

Depression and anxiety as predictors of recurrent cardiac events 12 months after percutaneous coronary interventions.

BACKGROUND: Anxiety and depression are associated with recurrent cardiac events after percutaneous coronary interventions (PCIs). However, few investigators have evaluated the impact of depression and anxiety on recurrent cardiac events in Korea. OBJECTIVE: The aim of this study was to examine the relationship among depression, anxiety, and recurrent cardiac events in Korean patients with coronary artery disease (CAD) after PCI. METHODS: A prospective longitudinal study was undertaken with a sample of 133 CAD patients with PCI. Data were collected between August 2009 and September 2010, and patients were followed after discharge through 2011 with self-report questionnaires on anxiety and depression using the Hospital Anxiety and Depression Scale and with patient medical records on sociodemographic and clinical characteristics. Recurrent cardiac events were collected for 12 months after discharge and were assessed by patient interviews and medical records. RESULTS: There were 18 recurrent cardiac events (13.5%) among the 133 participants. After adjustment for sociodemographic and clinical characteristics, a hierarchical Cox proportional hazards regression model found that a moderate or severe level of anxiety (hazard ratio, 6.21; 95% confidence interval, 1.64-23.54) and a moderate or severe level of depression (hazard ratio, 4.32; 95% confidence interval, 1.35-13.88) were independent predictors of recurrent cardiac events. CONCLUSIONS: Patients with CAD who have a high level of anxiety and depression are at increased risk for recurrent cardiac events after PCI. Screening should be focused on patients who experience anxious and depressive feelings in addition to traditional risk factors. Furthermore, psychoeducational support interventions to reduce anxiety and depression after PCI may improve health outcomes.

Randomized trial of stents versus bypass surgery for left main coronary artery disease.

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly used to treat unprotected left main coronary artery stenosis, although coronary-artery bypass grafting (CABG) has been considered to be the treatment of choice. METHODS: We randomly assigned patients with unprotected left main coronary artery stenosis to undergo CABG (300 patients) or PCI with sirolimus-eluting stents (300 patients). Using a wide margin for noninferiority, we compared the groups with respect to the primary composite end point of major adverse cardiac or cerebrovascular events (death from any cause, myocardial infarction, stroke, or ischemia-driven target-vessel revascularization) at 1 year. Event rates at 2 years were also compared between the two groups. RESULTS: The primary end point occurred in 26 patients assigned to PCI as compared with 20 patients assigned to CABG (cumulative event rate, 8.7% vs. 6.7%; absolute risk difference, 2.0 percentage points; 95% confidence interval [CI], -1.6 to 5.6; P=0.01 for noninferiority). By 2 years, the primary end point had occurred in 36 patients in the PCI group as compared with 24 in the CABG group (cumulative event rate, 12.2% vs. 8.1%; hazard ratio with PCI, 1.50; 95% CI, 0.90 to 2.52; P=0.12). The composite rate of death, myocardial infarction, or stroke at 2 years occurred in 13 and 14 patients in the two groups, respectively (cumulative event rate, 4.4% and 4.7%, respectively; hazard ratio, 0.92; 95% CI, 0.43 to 1.96; P=0.83). Ischemia-driven target-vessel revascularization occurred in 26 patients in the PCI group as compared with 12 patients in the CABG group (cumulative event rate, 9.0% vs. 4.2%; hazard ratio, 2.18; 95% CI, 1.10 to 4.32; P=0.02). CONCLUSIONS: In this randomized trial involving patients with unprotected left main coronary artery stenosis, PCI with sirolimus-eluting stents was shown to be noninferior to CABG with respect to major adverse cardiac or cerebrovascular events. However, the noninferiority margin was wide, and the results cannot be considered clinically directive. (Funded by the Cardiovascular Research Foundation, Seoul, Korea, and others; PRECOMBAT ClinicalTrials.gov number, NCT00422968.).

Relationship between intravascular ultrasound parameters and fractional flow reserve in intermediate coronary artery stenosis of left anterior descending artery: intravascular ultrasound volumetric analysis.

OBJECTIVES: The objective of this study was to assess the relationship between intravascular ultrasound (IVUS) parameters, including volumetric analysis, and fractional flow reserve (FFR). BACKGROUND: Although it is known that coronary atherosclerosis burden measured by IVUS volumetric analysis is related with clinical outcomes, its relationship with functional significance remains unknown. METHODS: Both IVUS and FFR were performed in 206 cases of intermediate stenosis of the left anterior descending artery (LAD). Myocardial ischemia was assessed by FFR and maximal hyperemia was induced by continuous intracoronary adenosine infusion. FFR < 0.80 was considered as significant inducible myocardial ischemia. We performed standard IVUS parameter measurements and volumetric analyses. IVUS parameter comparison was performed in the presence (n = 90) or absence (n =116) of significant myocardial ischemia. RESULTS: Lesions with minimal lumen area (MLA) ≥ 4.0 mm2 had FFR ≥ 0.80 in 91.4% of cases, while 50.9% of lesions with MLA < 4.0 mm2 had FFR < 0.80. The independent predictors of FFR < 0.80 were IVUS lesion length (odds ratio [OR]: 1.1, 95% confidence interval [CI] = 1.06­1.18, P < 0.001) and MLA significance according to the lesion location (OR: 7.01, 95% CI = 3.09­15.92, P = 0.001). FFR correlated with plaque volume (r = −0.345, P < 0.001) and percent atheroma volume (PAV) (r = −0.398, P < 0.001). Lesions with significant ischemia (FFR < 0.80) as compared to those with FFR > 0.80 were associated with larger plaque volume (181.8 ± 82.3 vs. 125.9 ± 77.9 mm3, P < 0.001) and PAV (58.9 ± 5.6 vs. 53.8 ± 7.9%, P < 0.001). CONCLUSIONS: IVUS parameters representing severity and extent of atheromatous plaque correlated with functional significance in LAD lesions with intermediate stenosis.

Optimal intravascular ultrasound criteria for defining the functional significance of intermediate coronary stenosis: an international multicenter study.

OBJECTIVE: We aimed to assess the ideal cut-off value of minimal lumen area (MLA) by intravascular ultrasound (IVUS) and its diagnostic performance to predict ischemia, using a large-scale, pooled analysis. METHODS: Eleven centers worldwide were invited to provide their clinical, IVUS and fractional flow reserve (FFR) data. A total of 881 lesions were enrolled. RESULTS: Angiographic % diameter stenosis (r = -0.373, p < 0.0001) and IVUS MLA (r = 0.289, p < 0.0001) correlated with FFR. Best cut-off value (BCV) of IVUS MLA to define the functional significance (FFR <0.8) was 2.75 mm(2) (AUC 0.646, 95% CI 0.609-0.684). When the diagnostic performance of IVUS MLA was tested according to the lesion location, BCV could be found only in lesions in the proximal artery and the mid-left anterior descending artery. Interestingly, Asians (n = 623) and Westerners (n = 258) showed different demographic and lesion characteristics as well as different BCVs to define ischemia. The BCV for the proximal/mid-left anterior descending artery lesions was 2.75 mm(2) (AUC 0.688, 95% CI 0.635-0.742) in Asians and 3.0 mm(2) (AUC 0.695, 95% CI 0.605-0.786) in Westerners. CONCLUSION: In this pooled analysis, an IVUS MLA of 2.75 mm(2) was the BCV to define the functional significance of intermediate coronary stenosis. However, when IVUS MLA is used to determine the functional significance, both the lesion and patient characteristics should be considered.

The pattern of Tpeak-Tend and QT interval, and J wave during therapeutic hypothermia.

BACKGROUND AND PURPOSE: The electrocardiogram manifestations of hypothermia include J waves and prolongation of QT intervals. This study described changes in repolarization patterns during therapeutic hypothermia (TH). METHODS: We measured the QTc and the interval from the peak to the end of the T wave (TpTe) from the V4 and V6 leads in 20 patients with TH. The TpTe was also expressed as a ratio to the duration of QT ([TpTe/QT]×100%), and to the corrected value for heart rate (TpTe/√RR). RESULTS: The QTc became prolonged in all patients during TH. While the TpTe/√RR did not change, the ([TpTe/QTe]×100%] decreased significantly during TH. The J wave developed during TH in seven patients. With one patient, ventricular fibrillation occurred preceded by an abnormal J wave and prolonged TpTe during TH. CONCLUSIONS: QTc prolongation without TpTe increase or abnormal J wave may not be arrhythmogenic during TH.

Phase III randomized clinical trial of efficacy and safety of amlodipine and candesartan cilexetil combination for hypertension treatment.

Effective antihypertensive therapy is essential for achieving optimal blood pressure (BP) control and reducing cardiovascular events. This double-blind, multicenter, randomized trial aimed to compare the antihypertensive efficacy and safety of a combination of amlodipine (AML) and candesartan cilexetil (CC) versus AML monotherapy in patients with essential hypertension (HTN). After a 4-week run-in period with AML 5 mg, patients whose HTN remained uncontrolled (diastolic BP [DBP]) ≥ 90 mmHg and < 120 mmHg) were randomized to receive either AML + CC or AML alone for 8 weeks. Efficacy was assessed by measuring changes in DBP and systolic BP (SBP). The primary safety measure was the incidence of adverse events (AEs). A total of 174 participants were included in the efficacy analysis. After 8 weeks, DBP decreased by -9.92 ± 0.86 mmHg in the AML + CC arm and - 2.08 ± 0.86 mmHg in the AML arm (p < 0.0001). SBP decreased by -14.27 ± 1.39 mmHg in the AML + CC arm versus - 2.77 ± 1.39 mmHg in the AML arm (p < 0.0001). AEs occurred in 11.24% of the AML + CC group and 5.62% of the AML group (p = 0.1773). AML + CC combination therapy demonstrated superior efficacy with good tolerance, making it a promising option for patients with inadequately controlled hypertension on amlodipine alone.

Prognostic Implications of Quantitative Flow Ratio and Plaque Characteristics in Intravascular Ultrasound-Guided Treatment Strategy.

BACKGROUND: Quantitative flow ratio (QFR) is a method for evaluating fractional flow reserve without the use of an invasive coronary pressure wire or pharmacological hyperemic agent. OBJECTIVES: The aim of this study was to investigate the prognostic implications of QFR and plaque characteristics in patients who underwent intravascular ultrasound (IVUS)-guided treatment for intermediate lesions. METHODS: Among the IVUS-guided strategy group in the FLAVOUR (Fractional Flow Reserve and Intravascular Ultrasound for Clinical Outcomes in Patients with Intermediate Stenosis) trial, vessels suitable for QFR analysis were included in this study. High-risk features were defined as low QFR (≤0.90), quantitative high-risk plaque characteristics (qn-HRPCs) (minimal lumen area ≤3.5 mm2, or plaque burden ≥70%), and qualitative high-risk plaque characteristics (ql-HRPCs) (attenuated plaque, positive remodeling, or plaque rupture) assessed using IVUS. The primary clinical endpoint was target vessel failure (TVF), defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization. RESULTS: A total of 415 (46.1%) vessels could be analyzable for QFR. The numbers of qn-HRPCs and ql-HRPCs increased with decreasing QFR. Among deferred vessels, those with 3 high-risk features exhibits a significantly higher risk of TVF compared with those with ≤2 high-risk features (12.0% vs 2.7%; HR: 4.54; 95% CI: 1.02-20.29). CONCLUSIONS: Among the IVUS-guided deferred group, vessels with qn-HRPC and ql-HRPC with low QFR (≤0.90) exhibited a significantly higher risk for TVF compared with those with ≤2 features. Integrative assessment of angiography-derived fractional flow reserve and anatomical and morphological plaque characteristics is recommended to improve clinical outcomes in patients undergoing IVUS-guided deferred treatment.