Predicting Significant Iliac Vein Compression Using a Probability Scoring System Derived From Minimal Luminal Area on Computed Tomography Angiography in Patients 65 Years of Age or Younger.

BACKGROUND: The presence of 50% or more stenosis on intravascular ultrasound (IVUS) is considered diagnostic of iliac vein compression (ILVC) by most operators. We have previously developed a scoring system combining minimal luminal area (MLA) at the compression site and age to predict ILVC as seen on IVUS. We present a revised and improved scoring system following an additional number of patients and limited to patients 65 years of age and younger. METHODS: Patients were included from retrospective (n = 52) and prospective (n = 18) registries of consecutive patients who underwent computed tomography angiography (CTA) of the pelvis with venous filling and IVUS within a few weeks apart to evaluate for symptomatic ILVC at a single cardiovascular practice. Quantitative vascular analysis was performed on all images obtained. MLA and age were used to calculate a score derived from a previously published logistic regression formula. Patients >65 years in age were excluded. The predicted findings from the score were compared with the actual presence of compression on IVUS. The revised scoring system is based on a score of < or ≥ 0.533824 and MLA (mm²) of <140, ≥140 to <200, and ≥200. The negative predictive value (NPV) and positive predictive value (NPV and PPV) of each cut-off in predicting ILVC on IVUS were calculated. RESULTS: A total of 70 symptomatic patients were included (mean age, 52.6 ± 12.3 years). The model offered the following: accuracy = 54/70 (77.1%); sensitivity = 51/52 (98.1%); specificity = 3/18 (16.7%); PPV = 51/66 (77.3%); and NPV = 3/4 (75.0%). CONCLUSION: A scoring system using MLA on CTA and age provides a fairly accurate diagnostic test to predict the presence of significant ILVC as seen on IVUS.

Incremental Prognostic Value of Post-Intervention Pd/Pa in Patients Undergoing Ischemia-Driven Percutaneous Coronary Intervention.

OBJECTIVES: This study sought to evaluate the prognostic value of post-percutaneous coronary intervention (PCI) distal coronary pressure to aortic pressure ratio (Pd/Pa) in predicting long-term clinical outcomes and to determine whether Pd/Pa combined with fractional flow reserve (FFR) post-intervention provides additional prognostic information superior to either marker alone. BACKGROUND: Post-PCI FFR has been shown to be a predictor of long-term outcomes in numerous studies. The role of post-PCI resting Pd/Pa has not been previously studied in this setting. METHODS: Consecutive patients undergoing PCI who had pre- and post-PCI Pd/Pa and FFR were followed for major adverse cardiovascular events (MACE) including death, myocardial infarction, and target vessel revascularization. RESULTS: A total of 574 patients were followed for 30 months (25th to 75th percentile 18 to 46 months). Using receiver-operating characteristic curve analysis post-stenting FFR cutoff of ≤0.86 had the best predictive accuracy of MACE (17% vs. 23%; log-rank p = 0.02), whereas post-stenting Pd/Pa ≤0.96 was the best predictor of MACE (15% vs. 24%; log rank p = 0.0006). There was a significant interaction between post-PCI Pd/Pa and FFR on MACE risk such that patients with Pd/Pa ≤0.96 and FFR ≤0.86 had the highest event rate (25%), whereas those with Pd/Pa >0.96 and FFR >0.86 had the lowest event rate (15%), which was not different from patients with Pd/Pa >0.96 and FFR ≤0.86 (17%). In a fully adjusted Cox regression analysis, Pd/Pa was an independent predictor of MACE (hazard ratio: 2.07; 95% confidence interval: 1.3 to 3.3; p = 0.002). CONCLUSIONS: Post-PCI resting Pd/Pa is a powerful prognostic tool for MACE prediction. It adds complementary and incremental risk stratification over established factors including post-PCI FFR.

Predicting Iliac Vein Compression With Computed Tomography Angiography and Venography: Correlation With Intravascular Ultrasound.

BACKGROUND: Intravascular ultrasound (IVUS) is considered the gold standard in diagnosing common iliac vein (CIV) compression. The presence of >50% surface area reduction by IVUS is considered significant compression by most operators. Thus, we evaluated the role of computed tomography angiography (CTA) and venography in diagnosing CIV compression when compared to IVUS. METHODS: All patients who underwent CTA of the pelvis with venous filling phase, IVUS, and venography within a few weeks apart to evaluate for symptomatic CIV compression from one cardiovascular practice were retrospectively reviewed. Quantitative vascular analysis was performed on all images obtained to determine (1) percent stenosis (PS) by venogram; and (2) minimal lumen area (MLA) and PS by CTA and IVUS at the compression site (using ipsilateral distal CIV as reference area). Spearman's rank correlation, paired t-tests, or signed rank tests were performed as appropriate to compare between values of MLA and PS among the three different imaging modalities. RESULTS: A total of 96 patients were included (62.5% females; mean age, 62.3 ± 14.8 years). A significant correlation was found between MLA-CTA and MLA-IVUS (Spearman's rho, 0.27; P=.01) and PS-CTA and PS-IVUS (Spearman's rho, 0.327; P<.01). A significant correlation was also found between PS-venogram and PS-IVUS (Spearman's rho, 0.471; P<.001). MLA-CTA and MLA-IVUS had a median difference of +41 mm² (95% CI, 25.0-57.5; P<.001) whereas PS-CTA and PS-IVUS were not statistically different (median difference, -5.6 mm²; 95% CI, -12.2 to 0.7). Furthermore, PS-IVUS and PS-venogram had a median difference of +15.2% (95% CI, 10.4-20.1; P<.001). CONCLUSION: PS-venogram correlates with PS-IVUS, but venogram underestimates the PS by an average of 15.2%. In contrast, PS-CTA and PS-IVUS are not statistically different despite an over-estimation of MLA by CTA when compared to IVUS. Therefore, we conclude that PS-CTA and not PS-venogram can be used to predict PS on IVUS.

Clinical Decision-Making for the Hemodynamic "Gray Zone" (FFR 0.75-0.80) and Long-Term Outcomes.

BACKGROUND: Fractional flow reserve (FFR) value between 0.75 and 0.80 is considered the "gray zone" and outcomes data relative to treatment strategy (revascularization vs medical therapy alone [deferral]) are limited for this group. METHODS AND RESULTS: A total of 238 patients (64.3 ± 8.6 years; 97% male; 45% diabetic) with gray-zone FFR were followed for the primary endpoint of major adverse cardiovascular event (MACE), defined as a composite of death, myocardial infarction (MI), and target-vessel revascularization. Mean follow-up duration was 30 ± 17 months. Deferred patients (n = 48 [20%]) had a higher prevalence of smoking and chronic kidney disease compared with the percutaneous coronary intervention (PCI) group (n = 190 [80%]; P<.05). Patients who underwent PCI had significantly lower MACE compared with the deferred patients (16% vs 40%; log rank P<.01). While there was a trend toward a decrease in all-cause mortality (8% vs 19%; log rank P=.06), the composite of death or MI was significantly lower in the PCI group (9% vs 27%; P<.01). On multivariate Cox proportional hazards regression analysis, PCI was associated with lower MACE (hazard ratio, 0.5; 95% confidence interval, 0.27-0.95; P=.03). CONCLUSION: Revascularization for patients with gray-zone FFR was associated with a significantly reduced risk of MACE compared with medical therapy alone.

A novel stent inflation protocol improves long-term outcomes compared with rapid inflation/deflation deployment method.

BACKGROUND: High-pressure inflation for coronary stent deployment is universally performed. However, the duration of inflation is variable and does not take into account differences in lesion compliance. We developed a standardized "pressure optimization protocol" (POP) using inflation pressure stability rather than an arbitrary inflation time or angiographic balloon appearance for stent deployment. Whether this approach improves long-term outcomes is unknown. METHODS AND RESULTS: 792 patients who underwent PCI using either rapid inflation/deflation (n = 376) or POP (n = 416) between January 2009 and March 2014 were included. Exclusion criteria included PCI for acute myocardial infarction, in-stent restenosis, chronic total occlusion, left main, and saphenous vein graft lesions. Primary endpoint was target vessel failure [TVF = combined end point of target vessel revascularization (TVR), myocardial infarction, and cardiac death]. Outcomes were analyzed in the entire cohort and in a propensity analysis. Stent implantation using POP with a median follow-up of 1317 days was associated with lower TVF compared with rapid inflation/deflation (10.1 vs. 17.8%, P < 0.0001). This difference was driven by a decrease in TVR (7 vs. 10.6%, P = 0.0016) and cardiac death (2.9 vs. 5.8%, P = 0.017) while there was no difference in myocardial infarction (1 vs. 1.9%, P = 0.19). In the Cox regression model, deployment using POP was the only independent predictor of reduced TVF (HR 0.43; 0.29-0.64; P < 0.0001). In the propensity analysis (330 patients per group) TVF remained lower with POP vs. rapid inflation/deflation (10 vs. 18%, P < 0.0001). CONCLUSIONS: Stent deployment using POP led to reduced TVF compared to rapid I/D. These results recommend this method to improve long-term outcomes. © 2017 Wiley Periodicals, Inc.

Clinical and angiographic predictors of persistently ischemic fractional flow reserve after percutaneous revascularization.

AIMS: Despite optimal angiographic results after percutaneous coronary intervention (PCI), some lesions may continue to produce ischemia under maximal hyperemia. We evaluated the factors associated with persistently ischemic fractional flow reserve (FFR) after angiographically successful PCI. METHODS AND RESULTS: A total of 574 consecutive patients with 664 lesions undergoing PCI who had FFR pre- and post-PCI were analyzed. Percutaneous coronary intervention led to effective ischemia reduction from pre-FFR (0.65±0.14) to post-FFR (0.87±0.08; ∆FFR 0.22±0.16, P<.001). There were 63 (9.5%) lesions with a persistently ischemic FFR of ≤0.80 despite optimal angiographic PCI results. Multivariate analysis revealed the presence of diffuse disease (odds ratio [OR] 3.54, 95% CI 1.80-6.94, P<.01), left anterior descending artery PCI (OR 8.35, 95% CI 3.82-18.27, P<.01), use of intravenous adenosine for inducing hyperemia (OR 3.95, 95% CI 2.0-7.84, P<.01), and pre-PCI FFR (OR 0.03, 95% CI 0.004-0.23, P<.01) as independent predictors of persistently ischemic FFR (≤0.80) after PCI. The predictive accuracy of this model was robust, with an area under the curve of 0.85 (95% CI 0.82-0.88). CONCLUSION: Multiple factors are associated with persistently ischemic FFR after angiographically optimal PCI. It is recommended that in lesions with the above-identified factors, FFR should be remeasured after PCI, and if abnormal, further measures should be undertaken for functional optimization.

Clinical and prognostic value of poststenting fractional flow reserve in acute coronary syndromes.

OBJECTIVES: Fractional flow reserve (FFR) has been suggested to have value in acute coronary syndromes (ACSs). The clinical and prognostic value of ischaemia reduction assessed by post-percutaneous coronary intervention (PCI) FFR has not been studied in this population. METHODS: Consecutive stable ischaemic heart disease (SIHD) (N=390) and patients with ACS (N=189) who had pre-PCI FFR and post-PCI FFR were followed for 2.4±1.5 years. Primary endpoint was major adverse cardiac events (MACE) (composite of myocardial infarction, target vessel revascularisation and death). RESULTS: In patients with ACS, PCI led to significant improvement in FFR from 0.62±0.15 to post-PCI FFR 0.88±0.08 (p<0.0001). Post-PCI FFR identified 29 patients (15%) who had persistently low FFR<0.80 (0.75±0.06) despite angiographically optimal results prompting subsequent interventions improving repeat FFR (0.85±0.06; p<0.0001). The difference in MACE events between patients with ACS and patients with SIHD varied according to the post-PCI FFR value (interaction p=0.044). Receiver operator curve analysis identified a final FFR cut-off of ≤0.91 as having the best predictive accuracy for MACE in the ACS study population (30% vs 19%; p=0.03). Patients with ACS achieving final FFR of >0.91 had similar outcomes compared with patients who had SIHD (19% vs 16%; p=0.51). However, in patients with final FFR of ≤0.91 there was increased MACE versus patients with SIHD (30% vs 16%; p<0.01). CONCLUSIONS: Post-PCI FFR is valuable in assessing the functional outcome of PCI in patients with ACS. Use of post-PCI FFR in patients with ACS allows for functional optimisation of PCI results and is predictive of long-term outcomes in patients with ACS.

Utilizing Post-Intervention Fractional Flow Reserve to Optimize Acute Results and the Relationship to Long-Term Outcomes.

OBJECTIVES: This study sought to evaluate the impact of fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) on subsequent in-lab interventional management vessels that had undergone pre-PCI FFR and its prognostic value in predicting long-term (>1 year) outcomes. BACKGROUND: Post-PCI FFR has been shown to be a predictor of intermediate-term (6 months) adverse events. However, its impact on immediate post procedure clinical decision making and long-term outcomes is not known. METHODS: Consecutive patients undergoing PCI who had pre- and post-PCI FFR evaluations were followed for major adverse cardiovascular events (MACE). RESULTS: In the study 574 patients (664 lesions) were followed for 31 ± 16 months. PCI led to significant improvement in FFR from 0.65 ± 0.14 to 0.87 ± 0.08 (p < 0.0001). Despite satisfactory angiographic appearance, 143 lesions (21%) demonstrated post-PCI FFR in the ischemic range (FFR ≤0.81). After subsequent interventions, FFR in this subgroup increased from 0.78 ± 0.08 to 0.87 ± 0.06 (p < 0.0001). Final FFR cutoff of ≤0.86 had the best predictive accuracy for MACE and ≤0.85 for TVR. Patients who achieved final FFR >0.86 had significantly lower MACE compared to the final FFR ≤0.86 group (17% vs. 23%; log-rank p = 0.02). Final FFR ≤0.86 had incremental prognostic value over clinical and angiographic variables for MACE prediction. CONCLUSIONS: Post-PCI FFR reclassified 20% of angiographically satisfactory lesions, which required further intervention thereby providing an opportunity for complete functional optimization at the time of the index procedure. This is particularly important as FFR post-PCI FFR was a powerful independent predictor of long-term outcomes.

A change of heart: reopening of a foramen ovale.

Platypnea-orthodeoxia is a rare syndrome characterized by dyspnea and hypoxemia that is exacerbated by assuming an upright position. The most common cause is intracardiac shunting through an atrial septal defect or patent foramen ovale (PFO). We present a 63-year-old man with dyspnea after right pneumonectomy for lung cancer, who was found to have a large PFO with right-to-left shunt in the presence of normal right-sided pressures. Percutaneous closure of the PFO led to resolution of symptoms.

Prior exposure to oxidized low-density lipoprotein limits apoptosis in subsequent generations of endothelial cells by altering promoter methylation.

Oxidized LDL (ox-LDL) plays a critical role in atherogenesis, including apoptosis. As hypercholesterolemia causes epigenetic changes resulting in long-term phenotypic consequences, we hypothesized that repeated and continuous exposure to ox-LDL may alter the pattern of apoptosis in human umbilical vein endothelial cells (HUVECs). We also analyzed global and promoter-specific methylation of apoptosis-related genes. As expected, ox-LDL evoked a dose-dependent increase in apoptosis in the first passage HUVECs that was completely abrogated by lectin-like ox-LDL receptor (LOX-1)-neutralizing antibody. Ox-LDL-induced apoptosis was associated with upregulation of proapoptotic LOX-1, ANXA5, BAX, and CASP3 and inhibition of antiapoptotic BCL2 and cIAP-1 genes accompanied with reciprocal changes in the methylation of promoter regions of these genes. Subsequent passages of cells displayed attenuated apoptotic response to repeat ox-LDL challenge with blunted gene expression and exaggerated methylation of LOX-1, BAX, ANXA5, and CASP3 genes (all P < 0.05 vs. first exposure to ox-LDL). Treatment of cells with LOX-1 antibody before initial ox-LDL treatment prevented both gene-specific promoter methylation and expression changes and reduction of apoptotic response to repeat ox-LDL challenge. Based on these data, we conclude that exposure of HUVECs to ox-LDL induces epigenetic changes leading to resistance to apoptosis in subsequent generations and that this effect may be related to the LOX-1-mediated increase in DNA methylation.