Review : Physiologic approach for coronary intervention

( William F. Fearon ) 대한내과학회 2013 The Korean Journal of Internal Medicine Vol.28 No.1

When invasively assessing coronary artery disease, the primary goal should be to determine whether the disease is causing a patient`s symptoms and whether it is likely to cause future cardiac events. The presence of myocardial ischemia is our best gauge of whether a lesion is responsible for symptoms and likely to result in a future cardiac event. In the catheterization laboratory, fractional flow reserve (FFR) measured with a coronary pressure wire is the reference standard for identifying ischemia-producing lesions. Its spatial resolution is unsurpassed with it not only being vessel-specific, but also lesion-specific. There is now a wealth of data supporting the accuracy of measuring FFR to identify ischemia-producing lesions. FFR-guided percutaneous coronary intervention of these lesions results in improved outcomes and saves resources. Non-hemodynamically significant lesions can be safely managed medically with a low rate of subsequent cardiac events.

The Promoted Inhibition of Complement Activation by Modified Complement Receptor Type 1

Seok-Yong Kim(김석용),Douglas T.Fearon 大韓微生物學會 1994 大韓微生物學會誌 Vol.29 No.4

Fractional Flow Reserve Versus Angiography in Left Circumflex Ostial Intervention After Left Main Crossover Stenting

남창욱,허승호,구본권,도준형,조윤경,박형섭,윤혁준,김형섭,정인성,김윤년,William F. Fearon,탁승제,김권배 대한심장학회 2011 Korean Circulation Journal Vol.41 No.6

Background and Objectives: Discrepancy between angiographic percent (%) diameter stenosis and fractional flow reserve (FFR) exists in non-left main bifurcation lesions. The aim of this study was to compare angiographic stenosis severity and FFR in jailed ostial left circumflex artery (LCX) lesions after left main (LM)-to-left anterior descending artery (LAD) crossover stenting. Subjects and Methods: Twenty-nine (n=29) patients with distal LM or ostial LAD lesions treated by LM-to-LAD crossover stenting were consecutively enrolled. After successful stenting, FFR was measured at the jailed LCX. Additional intervention was performed in lesions with FFR <0.8. Results: The mean reference diameter of LCX was 3.1±0.4 mm, and percent diameter stenosis after crossover stenting was 56±21%. Angiographically significant stenosis (>50%) at the ostial LCX occurred in 59% (17/29) of cases. Among them, only five (29%) lesions had functional significance, and underwent additional procedure. During follow-up, three patients in the deferral group and two patients in the additional intervention group had target lesion revascularization. Conclusion: There was a discrepancy between angiographic percent diameter stenosis and FFR in jailed LCX lesions after LM crossover stenting.

Does Pre-Treatment with High Dose Atorvastatin Prevent Microvascular Dysfunction after Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome?

Bong-Ki Lee,Chang-Wook Nam,Joon-Hyung Doh,Woo-Young Chung,William F. Fearon,Byung-Ryul Cho,Bon-Kwon Koo 대한심장학회 2016 Korean Circulation Journal Vol.46 No.4

Background and Objectives: There is controversy surrounding whether or not high dose statin administration before percutaneous coronary intervention (PCI) decreases peri-procedural microvascular injury. We performed a prospective randomized study to investigate the mechanisms and effects of pre-treatment high dose atorvastatin on myocardial damage in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing PCI. Subjects and Methods: Seventy seven patients with NSTE-ACS were randomly assigned to either the high dose group (atorvastatin 80 mg loading 12 to 24 h before PCI with a further 40 mg loading 2 h before PCI, n=39) or low dose group (atorvastatin 10 mg administration 12 to 24 h before PCI, n=38). Index of microcirculatory resistance (IMR) was measured after stent implantation. Creatine kinasemyocardial band (CK-MB) and high sensitivity C-reactive protein (CRP) levels were measured before and after PCI. Results: The baseline characteristics were not different between the two patient groups. Compared to the low dose group, the high dose group had lower post PCI IMR (14.1±5.0 vs. 19.2±9.3 U, p=0.003). Post PCI CK-MB was also lower in the high dose group (median: 1.40 ng/mL (interquartile range [IQR: 0.75 to 3.45] vs. 4.00 [IQR: 1.70 to 7.37], p=0.002) as was the post-PCI CRP level (0.09 mg/dL [IQR: 0.04 to 0.16] vs. 0.22 [IQR: 0.08 to 0.60], p=0.001). Conclusion: Pre-treatment with high dose atorvastatin reduces peri-PCI microvascular dysfunction verified by post-PCI IMR and exerts an immediate anti-inflammatory effect in patients with NSTE-ACS.

A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial–mesenchymal transition

Kim, Nam Hee,Kim, Hyun Sil,Li, Xiao-Yan,Lee, Inhan,Choi, Hyung-Seok,Kang, Shi Eun,Cha, So Young,Ryu, Joo Kyung,Yoon, Dojun,Fearon, Eric R.,Rowe, R. Grant,Lee, Sanghyuk,Maher, Christopher A.,Weiss, Ste The Rockefeller University Press 2011 The Journal of cell biology Vol.195 No.3

<▼1><P>Expression of the essential EMT inducer Snail1 is inhibited by miR-34 through a p53-dependent regulatory pathway.</P></▼1><▼2><P>Snail1 is a zinc finger transcriptional repressor whose pathological expression has been linked to cancer cell epithelial–mesenchymal transition (EMT) programs and the induction of tissue-invasive activity, but pro-oncogenic events capable of regulating Snail1 activity remain largely uncharacterized. Herein, we demonstrate that p53 loss-of-function or mutation promotes cancer cell EMT by de-repressing Snail1 protein expression and activity. In the absence of wild-type p53 function, Snail1-dependent EMT is activated in colon, breast, and lung carcinoma cells as a consequence of a decrease in miRNA-34 levels, which suppress Snail1 activity by binding to highly conserved 3′ untranslated regions in Snail1 itself as well as those of key Snail1 regulatory molecules, including β-catenin, LEF1, and Axin2. Although p53 activity can impact cell cycle regulation, apoptosis, and DNA repair pathways, the EMT and invasion programs initiated by p53 loss of function or mutation are completely dependent on Snail1 expression. These results identify a new link between p53, miR-34, and Snail1 in the regulation of cancer cell EMT programs.</P></▼2>

Outcomes of Percutaneous Coronary Intervention in Intermediate Coronary Artery Disease

Nam, C.W.,Yoon, H.J.,Cho, Y.K.,Park, H.S.,Kim, H.,Hur, S.H.,Kim, Y.N.,Chung, I.S.,Koo, B.K.,Tahk, S.J.,Fearon, W.F.,Kim, K.B. Elsevier 2010 JACC. Cardiovascular interventions Vol.3 No.8

Objectives: This study sought to evaluate the long-term clinical outcomes of a fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) strategy compared with intravascular ultrasound (IVUS)-guided PCI for intermediate coronary lesions. Background: Both FFR- and IVUS-guided PCI strategies have been reported to be safe and effective in intermediate coronary lesions. Methods: The study included 167 consecutive patients, with intermediate coronary lesions evaluated by FFR or IVUS (FFR-guided, 83 lesions vs. IVUS-guided, 94 lesions). Cutoff value of FFR in FFR-guided PCI was 0.80, whereas that for minimal lumen cross sectional area in IVUS-guided PCI was 4.0 mm<SUP>2</SUP>. The primary outcome was defined as a composite of major adverse cardiac events including death, myocardial infarction, and ischemia-driven target vessel revascularization at 1 year after the index procedure. Results: Baseline percent diameter stenosis and lesion length were similar in both groups (51 +/- 8% and 24 +/- 12 mm in the FFR group vs. 52 +/- 8% and 24 +/- 13 mm in the IVUS group, respectively). However, the IVUS-guided group underwent revascularization therapy significantly more often (91.5% vs. 33.7%, p < 0.001). No significant difference was found in major adverse cardiac event rates between the 2 groups (3.6% in FFR-guided PCI vs. 3.2% in IVUS-guided PCI). Independent predictors for performing intervention were guiding device: FFR versus IVUS (relative risk [RR]: 0.02); left anterior descending coronary artery versus non-left anterior descending coronary artery disease (RR: 5.60); and multi- versus single-vessel disease (RR: 3.28). Conclusions: Both FFR- and IVUS-guided PCI strategy for intermediate coronary artery disease were associated with favorable outcomes. The FFR-guided PCI reduces the need for revascularization of many of these lesions.