Combining Baseline Distal-to-Aortic Pressure Ratio and Fractional Flow Reserve in the Assessment of Coronary Stenosis Severity

ObjectivesThis study sought to understand the physiological basis of baseline distal-to-aortic pressure ratio (Pd/Pa) and fractional flow reserve (FFR) agreement and discordance, using coronary flow reserve (CFR), stenosis resistance, and microcirculatory resistance measurements, and form there, to investigate the potential value of combining Pd/Pa with FFR in the diagnostic rationale.BackgroundPd/Pa is always available before FFR assessment, and emerging data supports the notion that baseline indices can determine the ischemic potential of coronary stenosis in selected subsets.MethodsA total of 467 stenosed vessels from 363 patients were investigated with pressure and flow sensors during baseline and hyperemia: 168 vessels (135 patients) with thermodilution-derived flow, and 299 vessels (228 patients) with Doppler-derived flow.ResultsPd/Pa correlated more strongly with CFR than FFR (ρ difference = 0.129; p for ρ comparison <0.001). Although Pd/Pa and FFR were closely correlated (ρ = 0.798; 95% confidence interval: 0.767 to 0.828), categorical discordance was observed in 19.3% of total vessels. Such discordance was associated with the patients’ clinical profile and was characterized by contrastive changes in stenosis resistance, microcirculatory resistance, and the underlying CFR. Notably, all stenosis with Pd/Pa ≤0.83 (n = 74, 15.8%) progressed to FFR ≤0.80, and although no Pd/Pa cutoff was able to exclude the development of FFR ≤0.80 in the high end of values, only 15 (10.1%) vessels with Pd/Pa ≥0.96 (n = 149, 31.9%) developed FFR ≤0.80, from which none had definite ischemia, as defined by CFR ≤1.74.ConclusionsCombining baseline Pd/Pa with FFR seems to provide a more comprehensive physiological examination of stenosed coronary arteries and a closer pressure-based appraisal of the flow reserve of the downstream myocardial bed.     

Intravascular Ultrasound-Derived Minimal Lumen Area Criteria for Functionally Significant Left Main Coronary Artery Stenosis

ObjectivesThis study sought to evaluate the intravascular ultrasound (IVUS) minimal lumen area (MLA) for functionally significant left main coronary artery (LMCA) stenosis using fractional flow reserve (FFR) as the standard.BackgroundThe evaluation of significant LMCA stenosis remains challenging.MethodsWe identified 112 patients with isolated ostial and shaft intermediate LMCA stenosis (angiographic diameter stenosis of 30% to 80%) who underwent IVUS and FFR measurement.ResultsThe FFR was ≤0.80 in 66 LMCA lesions (59%); these exhibited smaller reference vessels, smaller minimal lumen diameter, greater diameter of stenosis, longer lesion length, smaller MLA, larger plaque burden, and more frequent plaque rupture. The independent factors of an FFR of ≤0.80 were plaque rupture (odds ratio [OR]: 4.47; 95% Confidence Interval (CI): 1.35 to 14.8; p = 0.014); body mass index (OR: 1.19; 95% CI: 1.00 to 1.41; p = 0.05), age (OR: 0.95; 95% CI: 0.90 to 1.00; p = 0.031), and IVUS MLA (OR: 0.37; 95% CI: 0.25 to 0.56; p < 0.001). The optimal IVUS MLA cutoff value for an FFR of ≤0.80 was 4.5 mm² (77% sensitivity, 82% specificity, 84% positive predictive value, 75% negative predictive value, area under the curve: 0.83, 95% CI: 0.76 to 0.96; p < 0.001) overall and 4.1 to 4.5 mm² in various subgroups. Adjustment for the body surface area, body mass index, and left ventricular mass did not improve the diagnostic accuracy of the IVUS MLA.ConclusionsIn patients with isolated ostial and shaft intermediate LMCA stenosis, an IVUS-derived MLA of ≤4.5 mm² is a useful index of an FFR of ≤0.80.     

Randomized Comparison of FFR-Guided and Angiography-Guided Provisional Stenting of True Coronary Bifurcation Lesions: The DKCRUSH-VI Trial (Double Kissing Crush Versus Provisional Stenting Technique for Treatment of Coronary Bifurcation Lesions VI)

ObjectivesThis study sought to compare the outcomes of fractional flow reserve (FFR)–guided and angiography (Angio)–guided provisional side-branch (SB) stenting for true coronary bifurcation lesions.BackgroundAngio-guided provisional SB stenting after stenting of the main vessel provides favorable outcomes for the majority of coronary bifurcation lesions. Whether an FFR-guided provisional stenting approach is superior has not been studied.MethodsA total of 320 patients with single Medina 1,1,1 and 0,1,1 coronary bifurcation lesions undergoing stenting with a provisional SB approach were randomly assigned 1:1 to Angio-guided and FFR-guided groups. SB stenting was performed for Thrombolysis In Myocardial Infarction flow grade <3, ostial SB stenosis >70%, or greater than type A dissection after main vessel stenting in the Angio-guided group and for SB-FFR <0.80 in the FFR-guided group. The primary endpoint was the 1-year composite rate of major adverse cardiac events (cardiac death, myocardial infarction, and clinically driven target vessel revascularization).ResultsComparing the Angio-guided and FFR-guided groups, treatment of the SB (balloon or stenting) was performed in 63.1% and 56.3% of lesions respectively (p = 0.07); stenting of the SB was attempted in 38.1% and 25.9%, respectively (p = 0.01); and, when attempted, stenting was successful in 83.6% and 73.3% of SBs, respectively (p = 0.01). The 1-year composite major adverse cardiac event rate was 18.1% in both groups (hazard ratio: 0.91, 95% confidence interval: 0.48 to 1.88; p = 1.00). The 1-year target vessel revascularization and stent thrombosis rates were 6.9% and 5.6% (p = 0.82) and 1.3% and 0.6% (p = 0.56) in the Angio-guided and FFR-guided groups, respectively.ConclusionsIn this multicenter, randomized trial, angiographic and FFR guidance of provisional SB stenting of true coronary bifurcation lesions provided similar 1-year clinical outcomes. (Randomized Study on DK Crush Technique Versus Provisional Stenting Technique for Coronary Artery Bifurcation Lesions; ChiCTR-TRC-07000015)     

The Impact of Downstream Coronary Stenosis on Fractional Flow Reserve Assessment of Intermediate Left Main Coronary Artery Disease: Human Validation

ObjectivesThe aim of this study was to determine the impact of downstream coronary stenosis in the left anterior descending coronary artery (LAD) or left circumflex coronary artery (LCx) on the assessment of fractional flow reserve (FFR) across an intermediate left main coronary artery (LMCA) stenosis in humans with the pressure wire positioned in the nondiseased downstream vessel.BackgroundAccurate assessment of intermediate LMCA disease is critical for guiding decisions regarding revascularization. In theory, FFR across an intermediate LMCA stenosis will be affected by downstream disease, even if the pressure wire is positioned in the nondiseased downstream vessel.MethodsAfter percutaneous coronary intervention of the LAD, LCx, or both, an intermediate LMCA stenosis was created with a deflated balloon catheter. FFR was measured in the LAD and LCx coronary arteries before and after creation of downstream stenosis by inflating an angioplasty balloon within the newly placed stent. The true FFR (FFR_true) of the LMCA, measured in the nondiseased downstream vessel in the absence of stenosis in the other vessel, was compared with the apparent FFR (FFR_app) measured in the presence of stenosis.ResultsIn 25 patients, 91 pairs of measurements were made, 71 with LAD stenosis and 20 with LCx stenosis. FFR_true of the LMCA was significantly lower than FFR_app (0.81 ± 0.08 vs. 0.83 ± 0.08, p < 0.001), although the numerical difference was small. This difference correlated with the severity of the downstream disease (r = 0.35, p < 0.001). In all cases in which FFR_app was >0.85, FFR_true was >0.80.ConclusionsIn most cases, downstream disease does not have a clinically significant impact on the assessment of FFR across an intermediate LMCA stenosis with the pressure wire positioned in the nondiseased vessel.     

Diagnostic and Prognostic Implications of Coronary Flow Capacity: A Comprehensive Cross-Modality Physiological Concept in Ischemic Heart Disease

ObjectivesThe purpose of this study is to evaluate whether coronary flow capacity (CFC) improves discrimination of patients at risk for major adverse cardiac events (MACE) compared with coronary flow reserve (CFR) alone, and to study the diagnostic and prognostic implications of CFC in relation to contemporary diagnostic tests for ischemic heart disease (IHD), including fractional flow reserve (FFR).BackgroundAlthough IHD results from a combination of focal obstructive, diffuse, and microcirculatory involvement of the coronary circulation, its diagnosis remains focused on focal obstructive causes. CFC comprehensively documents flow impairment in IHD, regardless of its origin, by interpreting CFR in relation to maximal flow (hyperemic average peak flow velocity [hAPV]), and overcomes the limitations of using CFR alone. This is governed by the understanding that ischemia occurs in vascular beds with substantially reduced hAPV and CFR, whereas ischemia is unlikely when hAPV or CFR is high.MethodsIntracoronary pressure and flow were measured in 299 vessels (228 patients), where revascularization was deferred in 154. Vessels were stratified as having normal, mildly reduced, moderately reduced, or severely reduced CFC using CFR thresholds derived from published data and corresponding hAPV percentiles. The occurrence of MACE after deferral of revascularization was recorded during 11.9 years of follow-up (quartile 1: 10.0 years, quartile 3: 13.4 years).ResultsCombining CFR and hAPV improved the prediction of MACE over CFR alone (p = 0.01). After stratification in CFC, MACE rates throughout follow-up were strongly associated with advancing impairment of CFC (p = 0.002). After multivariate adjustment, mildly and moderately reduced CFC were associated with a 2.1-fold (95% confidence interval: 1.1 to 4.0; p = 0.017), and 7.1-fold (95% confidence interval: 2.9 to 17.1; p < 0.001) increase in MACE hazard, respectively, compared with normal CFC. Severely reduced CFC was identified by FFR ≤0.80 in 90% of cases, although ≥40% of vessels with normal or mildly reduced CFC still had an FFR ≤0.80.ConclusionsCFC provides a cross-modality platform for the diagnosis and risk-stratification of IHD and enriches the interpretation of contemporary diagnostic tests in IHD.     

Randomized Comparisons Between Different Stenting Approaches for Bifurcation Coronary Lesions With or Without Side Branch Stenosis

ObjectivesThis study sought to evaluate the optimal percutaneous coronary intervention techniques using drug-eluting stents for bifurcation coronary lesions.BackgroundThe optimal bifurcation stenting technique needs to be evaluated.MethodsThe trial included 2 randomization studies separated by the presence of side branch (SB) stenosis for patients having non–left main bifurcation lesions. For 306 patients without SB stenosis, the routine final kissing balloon or leave-alone approaches were compared. Another randomization study compared the crush or single-stent approaches for 419 patients with SB stenosis.ResultsBetween the routine final kissing balloon and leave-alone groups for nondiseased SB lesions, angiographic restenosis occurred in 17.9% versus 9.3% (p = 0.064), comprising 15.1% versus 3.7% for the main branch (p = 0.004) and 2.8% versus 5.6% for the SB (p = 0.50) from 214 patients (69.9%) receiving 8-month angiographic follow-up. Incidence of major adverse cardiac events including death, myocardial infarction, or target vessel revascularization over 1 year was 14.0% versus 11.6% between the routine final kissing balloon and leave-alone groups (p = 0.57). In another randomization study for diseased SB lesions, 28.2% in the single-stent group received SB stents. From 300 patients (71.6%) receiving angiographic follow-up, between the crush and single-stent groups, angiographic restenosis rate was 8.4% versus 11.0% (p = 0.44), comprising 5.2% versus 4.8% for the main branch (p = 0.90) and 3.9% versus 8.3% for the SB (p = 0.12). One-year major adverse cardiac events rate between the crush and single-stent groups was 17.9% versus 18.5% (p = 0.84).ConclusionsAngiographic and clinical outcomes were excellent after percutaneous coronary intervention using drug-eluting stents with any stent technique for non–left main bifurcation lesions once the procedure was performed successfully.     

Prospective Assessment of the Diagnostic Accuracy of Instantaneous Wave-Free Ratio to Assess Coronary Stenosis Relevance: Results of ADVISE II International,Multicenter Study (ADenosine Vasodilator Independent Stenosis Evaluation II)

ObjectivesThe purpose of this study was to assess the diagnostic accuracy of the instantaneous wave-free ratio (iFR) to characterize, outside of a pre-specified range of values, stenosis severity, as defined by fractional flow reserve (FFR) ≤0.80, in a prospective, independent, controlled, core laboratory–based environment.BackgroundStudies with methodological heterogeneity have reported some discrepancies in the classification agreement between iFR and FFR. The ADVISE II (ADenosine Vasodilator Independent Stenosis Evaluation II) study was designed to overcome limitations of previous iFR versus FFR comparisons.MethodsA total of 919 intermediate coronary stenoses were investigated during baseline and hyperemia. From these, 690 pressure recordings (n = 598 patients) met core laboratory physiology criteria and are included in this report.ResultsThe pre-specified iFR cut-off of 0.89 was optimal for the study and correctly classified 82.5% of the stenoses, with a sensitivity of 73.0% and specificity of 87.8% (C statistic: 0.90 [95% confidence interval (CI): 0.88 to 0.92, p < 0.001]). The proportion of stenoses properly classified by iFR outside of the pre-specified treatment (≤0.85) and deferral (≥0.94) values was 91.6% (95% CI: 88.8% to 93.9%). When combined with FFR use within these cut-offs, the percent of stenoses properly classified by such a pre-specified hybrid iFR-FFR approach was 94.2% (95% CI: 92.2% to 95.8%). The hybrid iFR-FFR approach obviated vasodilators from 65.1% (95% CI: 61.1% to 68.9%) of patients and 69.1% (95% CI: 65.5% to 72.6%) of stenoses.ConclusionsThe ADVISE II study supports, on the basis rigorous methodology, the diagnostic value of iFR in establishing the functional significance of coronary stenoses, and highlights its complementariness with FFR when used in a hybrid iFR-FFR approach. (ADenosine Vasodilator Independent Stenosis Evaluation II–ADVISE II; NCT01740895)     

Differential Prognostic Effect Between First- and Second-Generation Drug-Eluting Stents in Coronary Bifurcation Lesions: Patient-Level Analysis of the Korean Bifurcation Pooled Cohorts

ObjectivesThe purpose of this study was to investigate the differential clinical outcomes after percutaneous coronary intervention (PCI) for coronary bifurcation lesions with 1- or 2-stenting techniques using first- or second-generation drug-eluting stents (DES).BackgroundThe 2-stenting technique has been regarded to have worse clinical outcomes than the 1-stenting technique after bifurcation PCI with first-generation DES. However, there has been a paucity of data comparing the 1- and 2-stenting techniques with the use of second-generation DES.MethodsPatient-level pooled analysis was performed with 3,162 patients undergoing PCI using first- or second-generation DES for bifurcation lesions from the “Korean Bifurcation Pooled Cohorts” (COBIS [Coronary Bifurcation Stenting] II, EXCELLENT [Registry to Evaluate Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting], and RESOLUTE-Korea [Registry to Evaluate the Efficacy of Zotarolimus-Eluting Stent]). The 3-year clinical outcomes were compared between 1- and 2-stenting techniques, stratified by the type of DES.ResultsWith first-generation DES, rates of target lesion failure (TLF) or patient-oriented composite outcome (POCO) (a composite of all death, any myocardial infarction, any repeat revascularization, and cerebrovascular accidents) at 3 years were significantly higher after the 2-stenting than the 1-stenting technique (TLF 8.6% vs. 17.5%; p < 0.001; POCO 18.1% vs. 28.5%, p < 0.001). With second-generation DES, however, there was no difference between 1- and 2-stenting techniques (TLF 5.4% vs. 5.8%; p = 0.768; POCO 11.2% vs. 12.9%; p = 0.995). The differential effects of 2-stenting technique on the prognosis according to the type of DES were also corroborated with similar results by the inverse probability weighted model. The 2-stenting technique was a significant independent predictor of TLF in first-generation DES (hazard ratio: 2.046; 95% confidence interval: 1.114 to 3.759; p < 0.001), but not in second-generation DES (hazard ratio: 0.667; 95% confidence interval: 0.247 to 1.802; p = 0.425).ConclusionsPatient-level pooled analysis of 3,162 patients in Korean Bifurcation Pooled Cohorts demonstrated that the 2-stenting technique showed comparable outcomes to 1-stenting technique with second-generation DES, which is different from the results of first-generation DES favoring the 1-stenting technique.     

Repeatability of Fractional Flow Reserve Despite Variations in Systemic and Coronary Hemodynamics

ObjectivesThis study classified and quantified the variation in fractional flow reserve (FFR) due to fluctuations in systemic and coronary hemodynamics during intravenous adenosine infusion.BackgroundAlthough FFR has become a key invasive tool to guide treatment, questions remain regarding its repeatability and stability during intravenous adenosine infusion because of systemic effects that can alter driving pressure and heart rate.MethodsWe reanalyzed data from the VERIFY (VERification of Instantaneous Wave-Free Ratio and Fractional Flow Reserve for the Assessment of Coronary Artery Stenosis Severity in EverydaY Practice) study, which enrolled consecutive patients who were infused with intravenous adenosine at 140 μg/kg/min and measured FFR twice. Raw phasic pressure tracings from the aorta (Pa) and distal coronary artery (Pd) were transformed into moving averages of Pd/Pa. Visual analysis grouped Pd/Pa curves into patterns of similar response. Quantitative analysis of the Pd/Pa curves identified the “smart minimum” FFR using a novel algorithm, which was compared with human core laboratory analysis.ResultsA total of 190 complete pairs came from 206 patients after exclusions. Visual analysis revealed 3 Pd/Pa patterns: “classic” (sigmoid) in 57%, “humped” (sigmoid with superimposed bumps of varying height) in 39%, and “unusual” (no pattern) in 4%. The Pd/Pa pattern repeated itself in 67% of patient pairs. Despite variability of Pd/Pa during the hyperemic period, the “smart minimum” FFR demonstrated excellent repeatability (bias −0.001, SD 0.018, paired p = 0.93, r² = 98.2%, coefficient of variation = 2.5%). Our algorithm produced FFR values not significantly different from human core laboratory analysis (paired p = 0.43 vs. VERIFY; p = 0.34 vs. RESOLVE).ConclusionsIntravenous adenosine produced 3 general patterns of Pd/Pa response, with associated variability in aortic and coronary pressure and heart rate during the hyperemic period. Nevertheless, FFR – when chosen appropriately – proved to be a highly reproducible value. Therefore, operators can confidently select the “smart minimum” FFR for patient care. Our results suggest that this selection process can be automated, yet comparable to human core laboratory analysis.     

Prognostic Value of Fractional Flow Reserve: Linking Physiologic Severity to Clinical Outcomes

BackgroundFractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear.ObjectivesThe study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization.MethodsMeta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold.ResultsA total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief.ConclusionsFFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.     

Effect of Ischemia Duration and Door-to-Balloon Time on Myocardial Perfusion in ST-Segment Elevation Myocardial Infarction: An Analysis From HORIZONS-AMI Trial (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction)

ObjectivesThis study sought to investigate the effect of treatment delay on microvascular reperfusion in ST-segment elevation myocardial infarction (STEMI) patients from the large, multicenter, prospective HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial.BackgroundDespite restoration of epicardial blood flow during primary percutaneous coronary intervention (PCI), one-third of patients do not obtain myocardial perfusion due to impairment in the microvascular circulation.MethodsWe examined the effect of symptom onset-to-balloon time (SBT) and door-to-balloon time (DBT) on myocardial reperfusion during primary PCI in STEMI, utilizing resolution of ST-segment elevation (STR) and the myocardial blush grade (MBG). The primary analysis was the relationships between SBT ≤2, >2 to 4, and >4 h and DBT ≤1, >1 to 1.5, >1.5 to 2, and >2 h with MBG and STR. Clinical risk was assessed using a modified version of the Thrombolysis In Myocardial Infarction risk score for STEMI.ResultsIn 2,056 patients, absent microvascular perfusion (MBG 0/1) and STR (STR <30%) after primary PCI was significantly more common in patients with longer SBT, in patients with both low and high clinical risk profiles. By multivariable analysis, SBT (p < 0.0001), anterior infarction (p < 0.0001), reference vessel diameter (p = 0.005), lesion minimum lumen diameter (p < 0.0001), hyperlipidemia (p = 0.03), and current smoking (p = 0.001) were independent predictors of MBG 0/1, whereas SBT (p = 0.007), anterior infarction (p < 0.0001), and history of renal insufficiency (p = 0.0002) were independent predictors of absent STR. DBT (p < 0.0001) was an independent predictor of MBG 0/1. MBG 0/1 and STR<30% identified patients with increased 3-year mortality.ConclusionsThe present study suggests that delay in mechanical reperfusion therapy during STEMI is associated with greater injury to the microcirculation.     

Impact of the Complexity of Bifurcation Lesions Treated With Drug-Eluting Stents: The DEFINITION Study (Definitions and impact of complEx biFurcation lesIons on clinical outcomes after percutaNeous coronary IntervenTIOn using drug-eluting steNts)

ObjectivesThe present study established criteria to differentiate simple from complex bifurcation lesions and compared 1-year outcomes stratified by lesion complexity after provisional stenting (PS) and 2-stent techniques using drug-eluting stents.BackgroundCurrently, no criterion can distinguish between simple and complex coronary bifurcation lesions. Comparisons of PS and 2-stent strategies stratified by lesion complexity have also not been reported previously.MethodsCriteria of bifurcation complexity in 1,500 patients were externally tested in another 3,660 true bifurcation lesions after placement of drug-eluting stents. The primary endpoint was the occurrence of a major adverse cardiac event (MACE) at 12 months. The secondary endpoint was the rate of stent thrombosis (ST).ResultsComplex (n = 1,108) bifurcation lesions were associated with a higher 1-year rate of MACE (16.8%) compared with simple (n = 2,552) bifurcation lesions (8.9%) (p < 0.001). The in-hospital ST and 1-year target lesion revascularization rates after 2-stent techniques in the simple group (1.0% and 5.6%, respectively) were significantly different from those after PS (0.2% [p = 0.007] and 3.2% [p = 0.009], respectively); however, 1-year MACE rates were not significantly different between the 2 groups. For complex bifurcation lesions, 2-stent techniques had lower rates of 1-year cardiac death (2.8%) and in-hospital MACE (5.0%) compared with PS (5.3%, p = 0.047; 8.4%, p = 0.031).ConclusionsComplex bifurcation lesions had higher rates of 1-year MACE and ST. The 2-stent and PS techniques were overall equivalent in 1-year MACE. However, 2-stent techniques for complex lesions elicited a lower rate of cardiac death and in-hospital MACE but higher rates of in-hospital ST and revascularization at 1 year for simple lesions.     

A Combined Optical Coherence Tomography and Intravascular Ultrasound Study on Plaque Rupture,Plaque Erosion,and Calcified Nodule in Patients With ST-Segment Elevation Myocardial Infarction: Incidence,Morphologic Characteristics,and Outcomes After Percutaneous Coronary Intervention

ObjectivesThis study sought to evaluate the incidence of plaque rupture (PR), plaque erosion (PE), and calcified nodule (CN) using optical coherence tomography (OCT) in patients with ST-segment elevation myocardial infarction (STEMI); to compare detailed morphologic plaque characteristics of PR, PE, and CN with optical coherence tomography and intravascular ultrasound; and to compare the post-procedure outcomes among PR, PE, and CN.BackgroundThe incidence and detailed morphologic characteristics of PR, PE, and CN in STEMI patients and their outcome after percutaneous coronary intervention (PCI) are unknown.MethodsA total of 112 STEMI patients who underwent PCI within 12 h from symptom onset were included. Both optical coherence tomography and intravascular ultrasound were performed following aspiration thrombectomy.ResultsThe incidence of PR, PE, and CN was 64.3%, 26.8%, and 8.0%, respectively. PE and CN, compared with PR, had more fibrous plaque (p < 0.001 and p < 0.001) and less thin-cap fibroatheroma (p < 0.001 and p < 0.001) as well as smaller plaque burden (p = 0.003 and p = 0.001) and remodeling index (p = 0.003 and p < 0.001). PE had greater plaque eccentricity index than PR and CN (p < 0.001 and p < 0.001). CN had greater calcified arc and shallower calcium than PR (p < 0.001 and p < 0.001) or PE (p < 0.001 and p < 0.001). More than one-half of CN had negative remodeling. PE had a lower incidence of no-reflow phenomenon after PCI than PR (p = 0.011).ConclusionsPE was the underlying mechanism in one-fourth of STEMI. PE was characterized by eccentric fibrous plaque. CN was characterized by superficial large calcium and negative remodeling. PE was associated with less microvascular damage after PCI.     

Clinical Outcome After DK Crush Versus Culotte Stenting of Distal Left Main Bifurcation Lesions: The 3-Year Follow-Up Results of the DKCRUSH-III Study

ObjectivesThe present study aimed to investigate the difference in major adverse cardiac events (MACE) at 3 years after double-kissing (DK) crush versus culotte stenting for unprotected left main distal bifurcation lesions (LMDBLs).BackgroundThe multicenter and randomized DKCRUSH-III (Comparison of double kissing crush versus culotte stenting for unprotected distal left main bifurcation lesions: results from a multicenter, randomized, prospective study) showed that DK crush stenting was associated with fewer MACE at 1-year follow-up in patients with LMDBLs compared with culotte stenting. Here, we report the 3-year clinical outcome of the DKCRUSH-III study.MethodsA total of 419 patients with LMDBLs who were randomly assigned to either the DK crush or culotte group in the DKCRUSH-III study were followed for 3 year. The primary endpoint was the occurrence of a MACE at 3 years. Stent thrombosis (ST) was the safety endpoint. Patients were classified by simple and complex LMDBLs according to the DEFINITION (Definition and Impact of Complex Bifurcation Lesions on Clinical Outcomes After Percutaneous Coronary Intervention Using Drug-Eluting Stents) study criteria.ResultsAt 3 years, MACE occurred in 49 patients the culotte group and in 17 patients in the DK crush group (cumulative event rates of 23.7% and 8.2%, respectively; p < 0.001), mainly driven by increased myocardial infarction (8.2% vs. 3.4%, respectively; p = 0.037) and target-vessel revascularization (18.8% vs. 5.8%, respectively; p < 0.001) between groups. Definite ST rate was 3.4% in the culotte group and 0% in the DK crush group (p = 0.007). Complex LMDBLs were associated with a higher rate of MACE (35.3%) at 3 years compared with a rate of 8.1% in patients with simple LMDBLs (p < 0.001), with an extremely higher rate in the culotte group (51.5% vs. 15.1%, p < 0.001).ConclusionsCulotte stenting for LMDBLs was associated with significantly increased rates of MACE and ST. (Double Kissing [DK] Crush Versus Culotte Stenting for the Treatment of Unprotected Distal Left Main Bifurcation Lesions: DKCRUSH-III, a Multicenter Randomized Study Comparing Double-Stent Techniques; ChiCTR-TRC-11001877)     

Coronary Vessel Wall Contrast Enhancement Imaging as a Potential Direct Marker of Coronary Involvement: Integration of Findings From CAD and SLE Patients

ObjectivesThis study investigated the feasibility of visual and quantitative assessment of coronary vessel wall contrast enhancement (CE) for detection of symptomatic atherosclerotic coronary artery disease (CAD) and subclinical coronary vasculitis in autoimmune inflammatory disease (systemic lupus erythematosus [SLE]), as well as the association with aortic stiffness, an established marker of risk.BackgroundCoronary CE by cardiac magnetic resonance (CMR) is a novel noninvasive approach to visualize gadolinium contrast uptake within the coronary artery vessel wall.MethodsA total of 75 subjects (CAD: n = 25; SLE: n = 27; control: n = 23) underwent CMR imaging using a 3-T clinical scanner. Coronary arteries were visualized by a T2-prepared steady state free precession technique. Coronary wall CE was visualized using inversion-recovery T1 weighted gradient echo sequence 40 min after administration of 0.2 mmol/kg gadobutrol. Proximal coronary segments were visually examined for distribution of CE and quantified for contrast-to-noise ratio (CNR) and total CE area.ResultsCoronary CE was prevalent in patients (93%, n = 42) with a diffuse pattern for SLE and a patchy/regional distribution in CAD patients. Compared with control subjects, CNR values and total CE area in patients with CAD and SLE were significantly higher (mean CNR: 3.9 ± 2.5 vs. 6.9 ± 2.5 vs. 6.8 ± 2.0, respectively; p < 0.001; total CE area: median 0.8 [interquartile range (IQR): 0.6 to 1.2] vs. 3.2 [IQR: 2.6 to 4.0] vs. 3.3 [IQR: 1.9 to 4.5], respectively; p < 0.001). Both measures were positively associated with aortic stiffness (CNR: r = 0.61, p < 0.01; total CE area: 0.36, p = 0.03), hypercholesterolemia (r = 0.68, p < 0.001; r = 0.61, p < 0.001) and hypertension (r = 0.40, p < 0.01; r = 0.32, p < 0.05).ConclusionsWe demonstrate that quantification of coronary CE by CNR and total CE area is feasible for detection of subclinical and clinical uptake of gadolinium within the coronary vessel wall. Coronary vessel wall CE may become an instrumental novel direct marker of vessel wall injury and remodeling in subpopulations at risk.     

CMR-Verified Diffuse Myocardial Fibrosis Is Associated With Diastolic Dysfunction in HFpEF

ObjectivesThe purpose of this study was to investigate diffuse myocardial fibrosis in patients with systolic heart failure (SHF) and in patients with heart failure with preserved ejection fraction (HFpEF) and the association with diastolic dysfunction of the left ventricle (LV).BackgroundIncreased diffuse myocardial fibrosis may impair LV diastolic function. However, no study has verified the association between the degree of diffuse myocardial fibrosis and the severity of impaired diastolic function in SHF and HFpEF.MethodsForty patients with SHF, 62 patients with HFpEF, and 22 patients without HF underwent cardiac magnetic resonance (CMR), including T1 mapping and cine CMR on a 3-T system. Extracellular volume fraction (ECV), a measure of diffuse myocardial fibrosis, was quantified from T1 mapping. Systolic and diastolic functions of the LV were assessed by cine CMR. The ECV values and LV functional indexes were compared among the 3 groups. Associations between ECV and LV diastolic function were also investigated.ResultsCompared with patients without HF, significantly higher ECV was found in patients with SHF (31.2% [interquartile range (IQR): 29.0% to 34.1%] vs. 27.9% [IQR: 26.2% to 29.4%], p < 0.001) and HFpEF (28.9% [IQR: 27.8% to 31.3%] vs. 27.9% [IQR: 26.2% to 29.4%], p = 0.006). Peak filling rate, a diastolic functional index assessed by cine CMR, was significantly decreased in patients with SHF (1.00 s⁻¹ [IQR: 0.79 to 1.49 s⁻¹] vs. 3.86 s⁻¹ [IQR: 3.34 to 4.48 s⁻¹], p < 0.001) and HFpEF (2.89 s⁻¹ [IQR: 2.13 to 3.50 s⁻¹] vs. 3.86 s⁻¹ [IQR: 3.34 to 4.48 s⁻¹], p < 0.001). Myocardial ECV was significantly correlated with peak filling rate in the HFpEF group (r = −0.385, p = 0.002), but no correlation was found in the SHF and non-HF groups (r = 0.030, p = 0.856 and r = −0.238, p = 0.285, respectively).ConclusionsIn patients with HF, only those with HFpEF show a significant correlation between increased diffuse myocardial fibrosis and impaired diastolic function. Diffuse myocardial fibrosis plays a unique role in the pathogenesis of HFpEF.     

Outcomes After Emergency Percutaneous Coronary Intervention in Patients With Unprotected Left Main Stem Occlusion: The BCIS National Audit of Percutaneous Coronary Intervention 6-Year Experience

ObjectivesThis study sought to evaluate in-hospital outcomes and 3-year mortality of patients presenting with unprotected left main stem occlusion (ULMSO) treated with primary percutaneous coronary intervention (PPCI).BackgroundLimited data exists about management and outcome following presentation with ULMSO.MethodsFrom January 1, 2007 to December 21, 2012, 446,257 PCI cases were recorded in the British Cardiovascular Intervention Society database of all PCI cases in England and Wales. Of those, 568 were patients having emergency PCI for ST-segment elevation infarction (0.6% of all PPCI) who presented with ULMSO (TIMI [Thrombolysis In Myocardial Infarction] flow grade 0/1 and stenosis >75%), and they were compared with 1,045 emergency patients treated with nonocclusive LMS disease. Follow-up was obtained through linkage with the Office of National Statistics.ResultsPresentation with ULMSO, compared with nonocclusive LMS disease, was associated with a doubling in the likelihood of periprocedural shock (57.9% vs. 27.9%; p < 0.001) and/or intra-aortic balloon pump support (52.5% vs. 27.2%; p < 0.001). In-hospital (43.3% vs. 20.6%; p < 0.001), 1-year (52.8% vs. 32.4%; p < 0.001), and 3-year mortality (73.9% vs 52.3%, p < 0.001) rates were higher in patients with ULMSO, compared with patients presenting with a patent LMS, and were significantly influenced by the presence of cardiogenic shock. ULMSO and cardiogenic shock were independent predictors of 30-day (hazard ratio [HR]: 1.61 [95% confidence interval (CI): 1.07 to 2.41], p = 0.02, and HR: 5.43 [95% CI: 3.23 to 9.12], p<0.001, respectively) and 3-year all-cause mortality (HR: 1.52 [95% CI: 1.06 to 2.17], p = 0.02, and HR: 2.98 [95% CI: 1.99 to 4.49], p < 0.001, respectively).ConclusionsIn patients undergoing PPCI for ULMSO, acute outcomes are poor and additional therapies are required to improve outcome. However, long-term outcomes for survivors of ULMSO are encouraging.     

Fractional Flow Reserve in the Transradial Era: Will Hand Vein Adenosine Infusion Suffice?: A Comparative Study of the Extent,Rapidity, and Stability of Hyperemia From Hand and Femoral Venous Routes of Adenosine Administration

ObjectivesThe aim of this study was to assess adenosine infusion via a cannula in the back of the hand compared with central venous access to achieve peak hyperemia during fractional flow reserve (FFR).BackgroundAdenosine is often used to induce maximal hyperemia when measuring FFR. The gold standard is continuous infusion via a large central vein; however, the increasing use of the transradial route for angiography makes it desirable to have an alternative route for adenosine. Peripheral venous access is frequently obtained in the hand, but concern exists as to whether adenosine delivery from this site can achieve adequate vasodilation for accurate FFR measurement. Our aim was to address this.MethodsSubjects were selected from patients presenting for coronary angiography/intervention who required a pressure-wire study. Subjects received intravenous adenosine infusion sequentially via 2 routes: first, via a 20-gauge hand cannula, and then, after a washout period, via a 5- or 6-F femoral venous sheath. Adenosine was administered at 140 μg/kg/min from each site. Data interpretation was blinded. Minimal FFR achieved with intravenous adenosine from each infusion site was recorded as was the time to peak hyperemia.ResultsPaired (hand and femoral adenosine) recordings taken from 84 vessels in 61 patients were suitable for blinded analysis. The mean FFR measured using adenosine administered via hand and femoral routes was 0.85 with an SD of 0.08 (intraclass correlation = 0.986). Time to peak hyperemia was longer on average with hand-administered adenosine compared with femoral adenosine administration (63 s vs. 43 s; mean difference, 22 s with a 95% confidence interval: 18 s to 27 s; p < 0.0001). Formal comparison of FFR stability using Mann-Whitney analysis (2 tailed) gives p = 0.43, indicating no significant evidence of a difference in stability between the 2 routes.ConclusionsHand vein adenosine infusion produced FFR values very similar to those obtained using central femoral vein adenosine administration, with no systematic bias toward higher or lower reading from 1 site. This has important practical implications for radial access cases involving pressure-wire studies.     

Association of Epicardial Adipose Tissue With Progression of Coronary Artery Calcification Is More Pronounced in the Early Phase of Atherosclerosis: Results From the Heinz Nixdorf Recall Study

ObjectivesThis study sought to determine whether epicardial adipose tissue (EAT) volume predicts the progression of coronary artery calcification (CAC) score in the general population.BackgroundEAT predicts coronary events and is suggested to influence the development of atherosclerosis.MethodsWe included 3,367 subjects (mean age 59 ± 8 years; 47% male) from the population-based Heinz Nixdorf Recall study without known coronary artery disease at baseline. CAC was quantified from noncontrast cardiac electron beam computed tomography at baseline and after 5 years. EAT was defined as fat volume inside the pericardial sac and was quantified from axial computed tomography images. Association of EAT volume with CAC progression (log[CAC(follow-up) + 1] − log[CAC(baseline) + 1]) was depicted as percent progression of CAC + 1 per SD of EAT.ResultsSubjects with progression of CAC above the median had higher EAT volume than subjects with less CAC change (101.1 ± 47.1 ml vs. 84.4 ± 43.4 ml; p < 0.0001). In regression analysis, 6.3% (95% confidence interval [CI]: 2.3% to 10.4%; p = 0.0019) of progression of CAC + 1 was attributable to 1 SD of EAT, which persisted after adjustment for risk factors (6.1% [95% CI: 1.2% to 11.2%]; p = 0.014). For subjects with a CAC score of >0 to ≤100, progression of CAC + 1 by 20% (95% CI: 11% to 31%; p < 0.0001) was attributable to 1 SD of EAT. Effect sizes decreased with CAC at baseline, with no relevant link for subjects with a CAC score ≥400 (0.2% [95% CI: −3.5% to 4.2%]; p = 0.9). Likewise, subjects age <55 years at baseline showed the strongest association of EAT with CAC progression (20.6% [95% CI: 9.7% to 32.5%]; p < 0.0001). Interestingly, the effect of EAT on CAC progression was more pronounced in subjects with low body mass index (BMI), and decreased with degree of adiposity (BMI ≤25 kg/m²: 19.8% [95% CI: 9.2% to 31.4%]; p = 0.0001, BMI >40 kg/m²: 0.8% [95% CI: −26.7% to 38.9%]; p = 0.96).ConclusionsEAT is associated with the progression of CAC, especially in young subjects and subjects with low CAC score, suggesting that EAT may promote early atherosclerosis development.     

Echocardiographic assessment of right ventricular function in inferior wall myocardial infarction and angiographic correlation to proximal right coronary artery stenosis

BackgroundPresence of right ventricular (RV) infarction imposes a higher risk of adverse events in inferior wall myocardial infarction (IWMI). In this study, we attempted to correlate various indices of RV function assessed by echocardiography with presence of a proximal right coronary artery (RCA) stenosis in patients with first episode of acute IWMI.MethodsIn a prospective study, patients with first episode of acute IWMI underwent echocardiographic assessment within 24 h of symptom onset and indices of RV function viz. RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), myocardial performance index (MPI) and tissue Doppler velocities from RV free wall were measured. Patients who underwent coronary angiogram (CAG) within one month and they were classified into group 1 and group 2 based on the presence or absence, respectively, of a significant proximal RCA stenosis.ResultsThere were 90 patients with first episode of IWMI of which 67 patients underwent CAG. There was significant difference between group 1 (n = 26) and group 2 (n = 41) in TAPSE (13.5 ± 1.3 vs 21.3 ± 1.7, p < 0.001), MPI by tissue Doppler (0.87 ± 0.1 vs 0.55 ± 0.2, p < 0.001) and in tissue Doppler systolic velocity from RV free wall (S′ 9.8 ± 1.1 vs 15.0 ± 1.5, p < 0.001). There was a good interobserver correlation for TAPSE, MPI by TDI, and S′ velocity. TAPSE ≤ 16 (sensitivity 93%, specificity 100%), MPI-TDI ≥ 0.69 (sensitivity 94.7%, specificity 93.5%), S ≤ 12.3 (sensitivity 90.3%, specificity 94.3%) were useful in predicting presence of proximal RCA stenosis.ConclusionRV function indices like TAPSE, MPI-TDI and S′ velocity are useful in predicting proximal RCA stenosis in first episode of acute IWMI.