Pre-Angioplasty Instantaneous Wave-Free Ratio Pullback Provides Virtual Intervention and Predicts Hemodynamic Outcome for Serial Lesions and Diffuse Coronary Artery Disease

ObjectivesThe aim of this study was to perform hemodynamic mapping of the entire vessel using motorized pullback of a pressure guidewire with continuous instantaneous wave-free ratio (iFR) measurement.BackgroundSerial stenoses or diffuse vessel narrowing hamper pressure wire–guided management of coronary stenoses. Characterization of functional relevance of individual stenoses or narrowed segments constitutes an unmet need in ischemia-driven percutaneous revascularization.MethodsThe study was performed in 32 coronary arteries with tandem and/or diffusely diseased vessels. An automated iFR physiological map, integrating pullback speed and physiological information, was built using dedicated software to calculate physiological stenosis severity, length, and intensity (ΔiFR/mm). This map was used to predict the best-case post–percutaneous coronary intervention (PCI) iFR (iFR_exp) according to the stented location, and this was compared with the observed iFR post-PCI (iFR_obs).ResultsAfter successful PCI, the mean difference between iFR_exp and iFR_obs was small (mean difference: 0.016 ± 0.004) with a strong relationship between ΔiFR_exp and ΔiFR_obs (r = 0.97, p < 0.001). By identifying differing iFR intensities, it was possible to identify functional stenosis length and quantify the contribution of each individual stenosis or narrowed segment to overall vessel stenotic burden. Physiological lesion length was shorter than anatomic length (12.6 ± 1.5 vs. 23.3 ± 1.3, p < 0.001), and targeting regions with the highest iFR intensity predicted significant improvement post-PCI (r = 0.86, p < 0.001).ConclusionsiFR measurements during continuous resting pressure wire pullback provide a physiological map of the entire coronary vessel. Before a PCI, the iFR pullback can predict the hemodynamic consequences of stenting specific stenoses and thereby may facilitate the intervention and stenting strategy.     

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.     

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.     

Tricuspid Regurgitation Is Associated With Increased Risk of Mortality in Patients With Low-Flow Low-Gradient Aortic Stenosis and Reduced Ejection Fraction: Results of the Multicenter TOPAS Study (True or Pseudo-Severe Aortic Stenosis)

ObjectivesThis study sought to examine the impact of tricuspid regurgitation (TR) on mortality in patients with low-flow, low-gradient (LF-LG) aortic stenosis (AS) and reduced left ventricular ejection fraction (LVEF).BackgroundTR is often observed in patients with LF-LG AS and low LVEF, but its impact on prognosis remains unknown.MethodsA total of 211 patients (73 ± 10 years of age; 77% men) with LF-LG AS (mean gradient <40 mm Hg and indexed aortic valve area [AVA] ≤0.6 cm²/m²) and reduced LVEF (≤40%) were prospectively enrolled in the TOPAS (True or Pseudo-Severe Aortic Stenosis) study and 125 (59%) of them underwent aortic valve replacement (AVR) within 3 months following inclusion. The severity of AS was assessed by the projected AVA (AVA_proj) at normal flow rate (250 ml/s), as previously described and validated. The severity of TR was graded according to current guidelines.ResultsAmong the 211 patients included in the study, 22 (10%) had no TR, 113 (54%) had mild (grade 1), 50 (24%) mild-to-moderate (grade 2), and 26 (12%) moderate-to-severe (grade 3) or severe (grade 4) TR. During a mean follow-up of 2.4 ± 2.2 years, 104 patients (49%) died. Univariable analysis showed that TR ≥2 was associated with increased risk of all-cause mortality (hazard ratio [HR]: 1.82, 95% confidence interval [CI]: 1.22 to 2.71; p = 0.004) and cardiovascular mortality (HR: 1.85, 95% CI: 1.20 to 2.83; p = 0.005). After adjustment for age, sex, coronary artery disease, AVA_proj, LVEF, stroke volume index, right ventricular dysfunction, mitral regurgitation, and type of treatment (AVR vs. conservative), the presence of TR ≥2 was an independent predictor of all-cause mortality (HR: 1.88, 95% CI: 1.08 to 3.23; p = 0.02) and cardiovascular mortality (HR: 1.92, 95% CI: 1.05 to 3.51; p = 0.03). Furthermore, in patients undergoing AVR, TR ≥3 was an independent predictor of 30-day mortality compared with TR = 0/1 (odds ratio [OR]: 7.24, 95% CI: 1.56 to 38.2; p = 0.01) and TR = 2 (OR: 4.70, 95% CI: 1.00 to 25.90; p = 0.05).ConclusionsIn patients with LF-LG AS and reduced LVEF, TR is independently associated with increased risk of cumulative all-cause mortality and cardiovascular mortality regardless of the type of treatment. In patients undergoing AVR, moderate/severe TR is associated with increased 30-day mortality. Further studies are needed to determine whether TR is a risk marker or a risk factor of mortality and whether concomitant surgical correction of TR at the time of AVR might improve outcomes for this high-risk population.     

Diagnostic Accuracy of Myocardial Magnetic Resonance Perfusion to Diagnose Ischemic Stenosis With Fractional Flow Reserve as Reference: Systematic Review and Meta-Analysis

ObjectivesThis paper systematically analyzed the performance of magnetic resonance (MR) perfusion to diagnose coronary artery disease (CAD) with fractional flow reserve (FFR) as the reference standard.BackgroundMyocardial MR perfusion has passed the stage of a research technique and has demonstrated the ability to detect functional or ischemic stenosis of coronary arteries. However, the evidence is limited to single-center studies and small sample sizes.MethodsWe searched PubMed and Embase databases for all published studies that evaluated the accuracy of MR perfusion to diagnose CAD versus FFR. We used an exact binomial rendition of the bivariate mixed-effects regression model with test type as a random-effects covariate to synthesize the available data. Based on Bayes’ theorem, the post-test probability was calculated to guide MR perfusion’s clinical utility.ResultsWe identified 14 studies evaluating 1,073 arteries and 650 patients. The pooled sensitivity and specificity were 0.90 (95% confidence interval [CI]: 0.86 to 0.93) and 0.87 (95% CI: 0.82 to 0.90) at the patient level and 0.89 (95% CI: 0.83 to 0.92) and 0.86 (95% CI: 0.77 to 0.92) at the artery and territory levels, respectively. The area under the summary receiver-operating characteristic at the patient level was 0.95 (95% CI: 0.92 to 0.96) and 0.93 (95% CI: 0.91 to 0.95) at the artery and territory levels, respectively. MR perfusion could increase the post-test probability of CAD >80% in patients with a pre-test probability of >37% and can decrease post-test probability of CAD <20% with a pre-test probability of <72%.ConclusionsWith FFR as the reference standard, the diagnostic ability of MR perfusion to detect ischemic CAD is high.     

Safety and Effectiveness of Everolimus-Eluting Stents in Chronic Total Coronary Occlusion Revascularization: Results From the EXPERT CTO Multicenter Trial (Evaluation of the XIENCE Coronary Stent,Performance, and Technique in Chronic Total Occlusions)

ObjectivesThis study sought to evaluate procedural and clinical outcomes among patients undergoing chronic total occlusion (CTO) percutaneous coronary intervention (PCI) using contemporary methods and everolimus-eluting stents (EES).BackgroundLimited studies have detailed the procedural and late-term safety and efficacy of CTO revascularization among multiple centers applying modern techniques and with newer-generation drug-eluting stents.MethodsAmong 20 centers, 250 consecutive patients were enrolled for attempted CTO PCI. Procedural and in-hospital clinical outcomes were examined in addition to the 1-year primary endpoint of death, myocardial infarction, and target lesion revascularization (major adverse cardiac events [MACE]).ResultsDemographic, lesion, and procedural characteristics included prior bypass surgery: 9.9%; diabetes: 40.1%; lesion length: 36.1 ± 18.5 mm; and stent length: 51.7 ± 27.2 mm. Procedural success, defined as guidewire recanalization with no in-hospital MACE, was 96.4%. Success with antegrade-only methods was 97.9% and 86.2% by retrograde/combined methods, respectively. Compared with a pre-specified performance goal derived from 6 prior CTO drug-eluting stent trials (1-year MACE: 24.4%), treatment with EES was associated with significantly lower composite adverse events for both intent-to-treat (18.5%, 1-sided upper confidence interval: 23.4%, p = 0.025) and per-protocol populations (8.2%, 1-sided upper confidence interval: 12.3%, p < 0.0001). Target lesion revascularization at 1 year was 6.3%. Dual antiplatelet therapy adherence was 53.9% at 1 year, yet subacute definite stent thrombosis occurred in only 2 patients (0.9%), and late probable stent thrombosis occurred in 1 patient (0.5%).ConclusionsIn a multicenter registration trial representing contemporary technique and EES, favorable procedural success and late-term clinical outcomes support CTO PCI in a patient population with high lesion complexity. (EXPERT CTO: Evaluation of the XIENCE PRIME LL and XIENCE Nano Everolimus Eluting Coronary Stent Coronary Stents, Performance, and Technique in Chronic Total Occlusions; NCT01435031)     

Long-Term Clinical Outcomes of Final Kissing Ballooning in Coronary Bifurcation Lesions Treated With the 1-Stent Technique: Results From the COBIS II Registry (Korean Coronary Bifurcation Stenting Registry)

ObjectivesThis study investigated the impact of final kissing ballooning (FKB) after main vessel (MV) stenting on outcomes in patients with coronary bifurcation lesions after application of the 1-stent technique.BackgroundAlthough FKB has been established as the standard method for bifurcation lesions treated with a 2-stent strategy, its efficacy in a 1-stent approach is highly controversial.MethodsThis study enrolled 1,901 patients with a bifurcation lesion with a side branch diameter ≥2.3 mm, treated solely with the 1-stent technique using a drug-eluting stent from 18 centers in Korea between January 1, 2003 and December 31, 2009. The primary outcome was major adverse cardiac events (MACE)—cardiac death, myocardial infarction, or target lesion revascularization. Propensity score-matching analysis was also performed.ResultsFKB was performed in 620 patients and the post minimal lumen diameter of the MV and side branch was larger in the FKB group than in the non-FKB group. During follow-up (median 36 months), the incidence of MACE (adjusted hazard ratio [HR]: 0.68, 95% confidence interval [CI]: 0.46 to 0.99; p = 0.048) was lower in the FKB group than the non-FKB group. After propensity score matching (545 pairs), the FKB group had a lower incidence of MACE (adjusted HR: 0.50, 95% CI: 0.30 to 0.85; p = 0.01), and target lesion revascularization in the MV (adjusted HR: 0.51, 95% CI: 0.28 to 0.93; p = 0.03) and both vessels (adjusted HR: 0.47, 95% CI: 0.25 to 0.90; p = 0.02) than in the non-FKB group.ConclusionsIn coronary bifurcation lesions, we demonstrated that the 1-stent technique with FKB was associated with a favorable long-term clinical outcome, mainly driven by the reduction of target lesion revascularization in the MV or both vessels as a result of an increase in minimal lumen diameter. (Korean Coronary Bifurcation Stenting Registry II [COBIS II]: NCT01642992)     

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 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.     

Predictors and Outcomes of Recurrent Stent Thrombosis: Results From a Multicenter Registry

ObjectivesThe aim of this study was to determine the incidence, predictors, and outcomes of recurrent stent thrombosis (rST).BackgroundPatients who had an initial stent thrombosis (ST) develop may be at high risk of rST.MethodsWe analyzed a multicenter California registry of angiographic definite ST at 5 academic hospitals from 2005 to 2013. A detailed review of the angiogram and procedure was performed of patients with and without rST.ResultsAmong 221 patients with a median follow-up of 3.3 years, definite or probable rST developed in 29, including 19 with angiographic definite rST. The cumulative hazard ratio (HR) of definite or probable rST was 16% at 1 year and 24% at 5 years, whereas the cumulative HR of angiographic definite rST was 11% at 1 year and 20% at 5 years. Despite similar angiographic results, patients who had rST develop had significantly greater peak creatine kinase at the time of initial ST (mean, 2,655 mg/dl vs. 1,654 mg/dl; p = 0.05) than those without rST. The 3-year rate of major adverse cardiovascular events was 50% for patients with rST compared with 22% for patients with a single ST (p = 0.01). After multivariable adjustment, independent predictors of definite/probable rST were age (HR: 1.4; 95 confidence interval [CI]: 1.1 to 1.8 per 10 years), bifurcation ST (HR: 4.4; 95% CI: 1.8 to 10.9), and proximal vessel diameter (HR: 1.8; 95% CI: 1.1 to 3.2 per millimeter).ConclusionsrST represents an important cause of long-term morbidity and mortality after an initial ST. Bifurcation ST and a larger proximal reference vessel diameter are independently associated with an increased risk of rST.     

Correlates and Outcomes of Late and Very Late Drug-Eluting Stent Thrombosis: Results From DESERT (International Drug-Eluting Stent Event Registry of Thrombosis)

ObjectivesThe aim of this study was to identify clinical, procedural, and angiographic correlates of late/very late drug-eluting stent (DES) thrombosis as well as to determine the clinical outcomes of these events.BackgroundLate/very late DES thromboses are a poorly studied phenomenon, partly due to the relative infrequency of these events, even in large cohort studies.MethodsIn the DESERT (International Drug-Eluting Stent Event Registry of Thrombosis), a retrospective, case-control registry, 492 cases of late/very late definite DES thrombosis from 21 international sites were matched in a 1:1 fashion with controls without stent thrombosis (ST). Controls were matched according to 2 criteria: same enrolling institution and date of initial DES implantation. Baseline and procedural variables were collected, and clinical follow-up was obtained for patients with ST as long as 1 year after the event. Offline quantitative coronary angiography was performed for a subset of 378 case-control pairs.ResultsThe majority of ST events occurred after 1 year (75%) and continued to occur for as long as 7.3 years. The clinical presentation of late/very late ST events was mainly myocardial infarction (66.7% ST-segment elevation myocardial infarction and 22.0% non–ST-segment elevation myocardial infarction); in-hospital mortality was 3.8%. A minority of patients (30%) with ST were receiving dual-antiplatelet therapy at the time of the event. Independent clinical correlates of late/very late ST were younger age, African-American race, current smoking, multivessel disease, longer stented length, overlapping stents, and percutaneous coronary intervention of vein graft lesions. Independent angiographic correlates for late/very late ST were lesions within the left anterior descending artery or a bypass graft, thrombus, and a larger residual diameter stenosis after the initial DES implantation. Despite the large sample of ST cases, all identified correlates of late/very late ST had weak associations with subsequent ST (all odds ratios <2.5).ConclusionsDespite a large sample of ST cases and use of limited matching to maximize the identification of predictive factors associated with late/very late ST, the variables associated with the development of late/very late ST were only weakly predictive of subsequent events. Additionally, a relatively low observed mortality rate of ST in this series may reflect a different pathophysiology of these late/very late events compared with acute/subacute ST. (Drug Eluting Stent Registry of Thrombosis [DESERT]; NCT00812552).     

Coronary Computed Tomographic Prediction Rule for Time-Efficient Guidewire Crossing Through Chronic Total Occlusion: Insights From the CT-RECTOR Multicenter Registry (Computed Tomography Registry of Chronic Total Occlusion Revascularization)

ObjectivesThis study sought to establish a coronary computed tomography angiography prediction rule for grading chronic total occlusion (CTO) difficulty for percutaneous coronary intervention (PCI).BackgroundThe uncertainty of procedural outcome remains the strongest barrier to PCI in CTO.MethodsData from 4 centers involving 240 consecutive CTO lesions with pre-procedural coronary computed tomography angiography were analyzed. Successful guidewire (GW) crossing ≤30 min was set as an endpoint to eliminate operator bias. The CT-RECTOR (Computed Tomography Registry of Chronic Total Occlusion Revascularization) score was developed by assigning 1 point for each independent predictor, and then summing all points accrued. Continuous distribution of scores was used to stratify CTO into 4 difficulty groups: easy (score 0); intermediate (score 1); difficult (score 2); and very difficult (score ≥3). Discriminatory performance was tested by 10-fold cross-validation and compared with the angiographic J-CTO (Multicenter CTO Registry of Japan) score.ResultsStudy endpoint was achieved in 55% of cases. Multivariable analysis yielded multiple occlusions, blunt stump, severe calcification, bending, duration of CTO ≥12 months, and previously failed PCI as independent predictors for GW crossing. The probability of successful GW crossing ≤30 min for each group (from easy to very difficult) was 95%, 88%, 57%, and 22%, respectively. Areas under receiver-operator characteristic curves for the CT-RECTOR and J-CTO scores were 0.83 and 0.71, respectively (p < 0.001). Both the original model fit and 10-fold cross-validation correctly classified 77.3% of lesions.ConclusionsThe CT-RECTOR score represents a simple and accurate noninvasive tool for predicting time-efficient GW crossing that may aid in grading CTO difficulty before PCI. (Computed Tomography Angiography Prediction Score for Percutaneous Revascularization for Chronic Total Occlusions [CT-RECTOR]; NCT02022878)