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BACKGROUND: Chronic right ventricular pacing has been reported to promote cardiac dyssynchrony. The PAVE trial prospectively compared chronic biventricular pacing to right ventricular pacing in patients undergoing ablation of the AV node for management of atrial fibrillation with rapid ventricular rates. METHODS AND RESULTS: One hundred and eighty-four patients requiring AV node ablation were randomized to receive a biventricular pacing system (n = 103) or a right ventricular pacing system (n = 81). The study endpoints were change in the 6-minute hallway walk test, quality of life, and left ventricular ejection fraction. Patient characteristics were similar (64% male; age: 69 +/- 10 years, ejection fraction: 0.46 +/- 0.16; 83%, NYHA Class II or III). At 6 months postablation, patients treated with cardiac resynchronization had a significant improvement in 6-minute walk distance, (31%) above baseline (82.9 +/- 94.7 m), compared to patients receiving right ventricular pacing, (24%) above baseline (61.2 +/- 90.0 m) (P = 0.04). There were no significant differences in the quality-of-life parameters. At 6 months postablation, the ejection fraction in the biventricular group (0.46 +/- 0.13) was significantly greater in comparison to patients receiving right ventricular pacing (0.41 +/- 0.13, P = 0.03). Patients with an ejection fraction <or=45% or with NYHA Class II/III symptoms receiving a biventricular pacemaker appear to have a greater improvement in 6-minute walk distance compared to patients with normal systolic function or Class I symptoms. CONCLUSION: For patients undergoing AV node ablation for atrial fibrillation, biventricular pacing provides a significant improvement in the 6-minute hallway walk test and ejection fraction compared to right ventricular pacing. These beneficial effects of cardiac resynchronization appear to be greater in patients with impaired systolic function or with symptomatic heart failure.

BACKGROUND: The National Cardiogenic Shock Initiative is a single-arm, prospective, multicenter study to assess outcomes associated with early mechanical circulatory support (MCS) in patients presenting with acute myocardial infarction and cardiogenic shock (AMICS) treated with percutaneous coronary intervention (PCI). METHODS: Between July 2016 and February 2019, 35 sites participated and enrolled into the study. All centers agreed to treat patients with AMICS using a standard protocol emphasizing invasive hemodynamic monitoring and rapid initiation of MCS. Inclusion and exclusion criteria mimicked those of the "SHOCK" trial with an additional exclusion criteria of intra-aortic balloon pump counter-pulsation prior to MCS. RESULTS: A total of 171 consecutive patients were enrolled. Patients had an average age of 63 years, 77% were male, and 68% were admitted with AMICS. About 83% of patients were on vasopressors or inotropes, 20% had a witnessed out of hospital cardiac arrest, 29% had in-hospital cardiac arrest, and 10% were under active cardiopulmonary resuscitation during MCS implantation. In accordance with the protocol, 74% of patients had MCS implanted prior to PCI. Right heart catheterization was performed in 92%. About 78% of patients presented with ST-elevation myocardial infarction with average door to support times of 85 ± 63 min and door to balloon times of 87 ± 58 min. Survival to discharge was 72%. Creatinine ≥2, lactate >4, cardiac power output (CPO) <0.6 W, and age ≥ 70 years were predictors of mortality. Lactate and CPO measurements at 12-24 hr reliably predicted overall mortality postindex procedure. CONCLUSION: In contemporary practice, use of a shock protocol emphasizing best practices is associated with improved outcomes.

A balance between programmed cell death and survival of vascular smooth muscle cells (VSMC) in the fibrous cap, which is primarily composed of VSMC and extracellular matrix, appears to best correlate with plaque instability or stability and is controlled by growth factors and cytokines. Autophagy is also involved in programmed cell death. We assessed the effect of TNF-alpha and insulin-like growth factor-1 (IGF-1) on the expression of autophagic genes, microtubule-associated protein 1 light chain 3 (MAPLC-3) and Beclin-1 in VSMC isolated from atherosclerotic plaques. Transmission electron microscopy showed a significantly higher number of vacuolated cells in the TNF-alpha-treated VSMC and a markedly lower number in the IGF-1-treated VSMC when compared with the untreated control group. TNF-alpha-induced MAPLC-3 mRNA expression through c-jun N-terminal kinase and protein kinase B pathways and induced Beclin-1 protein expression through the c-jun N-terminal kinase pathway. Expression of MAPLC-3 and Beclin-1 correlated with autophagic cell death of plaque VSMC. IGF-1 inhibited MAPLC-3 mRNA transcripts through the Akt pathway. These findings suggest that the expression of autophagy genes can be influenced by IGF-1 and TNF-alpha through c-jun N-terminal kinase or Akt pathways and autophagy might be involved in the regulation of plaque stability.

Of the 400,000-500,000 permanent pacemaker leads implanted worldwide each year, around 10% may eventually fail or become infected, becoming potential candidates for removal. Intravascular techniques for removing problematic or infected leads evolved over a 5-year period (1989-1993). This article analyzes results from January 1994 through April 1996, a period during which techniques were fairly stable. Extraction of 3,540 leads from 2,338 patients was attempted at 226 centers. Indications were: infection (27%), nonfunctional or incompatible leads (25%), Accufix or Encore leads (46%), or other causes (2%). Patients were 64+/-17 years of age (range 5-96); 59% were men, 41% women. Leads were implanted 47+/-41 months (maximum 26 years), in the atrium (53%), ventricle (46%), or SVC (1%). Extraction was attempted via the implant vein using locking stylets and dilator sheaths, and/or transfemorally using snares, retrieval baskets, and sheaths. Complete removal was achieved for 93% of leads, partial for 5%, and 2% were not removed. Risk of incomplete or failed extraction increased with implant duration (P<0.0001), less experienced physicians (P<0.0001), ventricular leads (P<0.005), noninfected patients (P<0.0005), and younger patients (P<0.0001). Major complications were reported for 1.4% of patients (<1% at centers with >300 cases), minor for 1.7%. Risk of complications increased with number of leads removed (P<0.005) and with less experienced physicians (P<0.005); risk of major complications was higher for women (P<0.01). Given physician experience, appropriate precautions, and appropriate patient selection, contemporary lead removal techniques allow success with low complication rates.

Coronary artery disease, leading to myocardial infarction and ischaemia, affects millions of persons and is one of the leading causes of morbidity and mortality worldwide. Invasive techniques such as coronary artery bypass grafting are used to alleviate the sequelae of arterial occlusion. Unfortunately, restenosis or occlusion of the grafted conduit occurs over a time frame of months to years with a gradual reduction in patency, especially in vein grafts. The events leading to intimal hyperplasia (IH) formation involve numerous cellular and molecular components. Various cellular elements of the vessel wall are involved as are leucocyte-endothelial interactions that trigger the coagulation cascade leading to localized thrombus formation. Subsequent phenotypic modification of the medial smooth muscle cells and their intimal migration is the basis of the lesion formation that is thought to be propagated by an immune-mediated reaction. Despite intense scrutiny, the pathophysiology of IH remains an enigma. Although several growth factors, cytokines and numerous other biomolecules have been implicated and their relationship to prohyperplasia pathways such as the phosphatidyl-inositol 3-kinase (PI3K)-Akt pathway has been established, many pieces of the puzzle are still missing. An in-depth understanding of early vein graft adaptation and progression is necessary to improve the long-term prognosis and develop more effective therapeutic measures. In this review, we have critically evaluated and summarized the literature to elucidate and interlink the numerous established and emerging factors that play a key role in the development of IH leading to vein graft restenosis.

INTRODUCTION: Intracardiac delay optimization of biventricular and dual-chamber pacing devices currently relies on time-consuming echocardiographic measurements. A novel intracardiac electrogram (IEGM) method for atrioventricular (AV/PV) and interventricular (VV) delay optimization was developed, which can be performed during routine device follow-up. METHODS AND RESULTS: In this prospective, nonrandomized, multi-center trial, patients previously implanted with St. Jude Medical cardiac resynchronization therapy defibrillator (CRT-D) devices or dual-chamber implantable cardioverter defibrillators (ICDs) underwent standard AV/PV and/or VV delay optimization guided by Doppler echocardiogram measurements of the maximum aortic velocity time integral (aortic VTI). Aortic VTI measurements applying the IEGM method recommended delays were then obtained in all patients. Fifty-eight patients (age: 68 +/- 11 years; 81% male; 74% ischemic) and 57 patients (age: 71 +/- 10 years; 74% male; 71% ischemic) were enrolled for AV/PV and VV delay evaluation, respectively. An independent core lab determined the maximum aortic VTIs. Data analysis of the AV, PV, and VV delays demonstrated the concordance correlation coefficient (CCC) between the standard method aortic VTI values and the IEGM method aortic VTI values was 97.5%, 96.1%, and 96.6%, respectively. All analyses demonstrated that the CCC > 90% (P < 0.05). CONCLUSION: The automated programmer-based IEGM method provides a reliable and simpler alternative to standard techniques for the optimization of AV/PV and VV delay settings in patients with CRT-D devices and dual-chamber ICDs.

The effectiveness of an Internet-based intervention, the New Fathers Network, was tested in improving first-time fathers' parenting self-efficacy and parenting satisfaction during the first 8 weeks following their infants' birth as compared with no intervention (Comparison Group). Parenting self-efficacy and satisfaction scores for the Intervention Group significantly improved from 4 to 8 weeks; parenting self-efficacy and satisfaction scores for the Comparison Group to which no intervention was given did not change significantly. Participants were primarily satisfied with the New Fathers Network.

BACKGROUND: A dry epicardial access (EA) is increasingly used for advanced cardiovascular procedures. Conventionally used large bore needles (Tuohy or Pajunk needle; LBN) have been associated with low but definite incidence of major complications with EA. Use of micropuncture needle (MPN) may decrease the risk of complications. We intended to compare the outcomes of LBN with MPN for EA. METHODS AND RESULTS: We report a multicenter observational study of consecutive patients who underwent EA for ventricular tachycardia ablation or Lariat procedure using the LBN or MPN. Oral anticoagulation was stopped before the procedure. Baseline characteristics and procedure-related complications were collected and compared. Of the 404 patients, LBN and MPN were used in 46% and 54% of patients, respectively. There was no significant difference in the incidence of inadvertent puncture of myocardium between LBN and MPN (7.6% versus 6.8%, P=0.76). However, there was a significantly higher rate of large pericardial effusions with LBN compared with MPN (8.1% versus 0.9%; P<0.001). The incidence of pleural effusions were not significantly different between both (1.6% versus 2.3%; P=0.64). LBN group had an increase in other complications compared with MPN (open heart surgery to repair cardiac laceration [6 versus 0], injury to liver [1 versus 0], coronaries [1 versus 0], and superior epigastric artery requiring surgical exploration [0 versus 1]). CONCLUSIONS: The use of MPN is associated with decreased incidence of major complications, and the need for surgical repair and routine use should be considered for EA.

Objective/Background Historically, the sole option for patients with a dysfunctional native right ventricular outflow tract (RVOT) requiring re-establishment of pulmonary competence has been surgical PVR. We sought to compare early outcomes of hybrid pulmonary valve replacement (PVR) combining surgical plication of the main pulmonary artery followed by transcatheter PVR, with a contemporary cohort of surgical PVR patients. Methods Retrospective chart analysis of all patients with a dilated native RVOT eligible for surgical PVR over 36 months was performed. The cohorts included patients with previous tetralogy of Fallot repair (n = 14), and previous intervention for congenital abnormality of the pulmonary valve (n = 7). Results Twenty-one patients with a dysfunctional native RVOT met criteria for PVR; 8 using the hybrid procedure (group 1: age, 31.5 +/- 17.4 years) and 13 with cardiopulmonary bypass (CPB) (group 2: age, 31 +/- 18.4 years). Valve delivery was successful in all patients with no procedural mortality. Group 1 had a lesser requirement for blood products (P =< 0.001) and a trend toward shorter hospital stay and higher post-operative hemoglobin. No patients in group 1 received inotropic support post-operatively compared to 54% of patients in group 2. Mean follow-up was 3.4 months for group 1 and 13.6 months for group 2 with the average peak gradient across the RVOT of 20.1 and 15.1 mm Hg respectively (P = 0.12), all with no more than mild PI. Conclusions Transcatheter hybrid PVR following RVOT plication provides a reasonable alternative to surgical PVR particularly in higher risk cohorts, reducing possible longer-term consequences of repeated runs of CPB. © 2016 Wiley Periodicals, Inc.

AIMS: This study sought to investigate the 2-year outcomes of patients treated with the paclitaxel-eluting TAXUS((R)) stent (PES) or vascular brachytherapy (VBT), the previous 'gold standard therapy', for bare metal stent in-stent restenosis (ISR). METHODS AND RESULTS: In the TAXUS V-ISR trial, 396 patients with bare metal stent ISR referred for percutaneous coronary intervention were prospectively randomized to either PES or beta source VBT. The present analysis reports 24-month clinical outcomes from that study. Between 9 and 24 months, ischaemia-driven target lesion revascularization tended to be required less frequently with assignment to PES compared to VBT (5.3 vs. 10.3%, P = .07). As a result, ischaemia-driven target lesion revascularization at 24 months was significantly reduced with PES compared with VBT (10.1 vs. 21.6%, P = 0.003), as was ischaemia-driven target vessel revascularization (18.1 vs. 27.5%, P = .03). There were no significant differences between the two groups with regard to death, myocardial infarction, or target vessel thrombosis either between 12 and 24 months, or cumulative to 24 months. CONCLUSION: Freedom from clinical restenosis at 2 years is significantly enhanced after PES placement compared with VBT for bare metal stent ISR, with similar rates of death, myocardial infarction, and target vessel thrombosis.

Vascular calcification predicts an increased risk for cardiovascular events in atherosclerosis, diabetes, and end-stage kidney diseases. Matrix Gla protein (MGP), an inhibitor of calcification, limits calcium phosphate deposition in the vessel wall. There are many factors contributing to the progression of atherosclerosis, including hypertension, hyperlipidemia, the renin-angiotensin system, and inflammation. Angiotensin II (ANG II) plays a crucial role in the atherogenic process through not only its pressor responses but also its growth-promoting and inflammatory effects. In this study, we investigated the role of MGP in ANG II-induced exacerbation of vascular calcification in human vascular smooth muscle cells (VSMCs). The expression of MGP, calcification, and apoptosis in human VSMCs were examined by Western blot analysis, real-time PCR, in situ terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, and enzyme-linked immunosorbent assay, respectively. Increase in VSMC calcification in human atherosclerotic plaques upregulates MGP expression and apoptosis in a negative feedback manner. ANG II inhibited MGP expression in VSMCs via and in vitro in a dose- and time-dependent manner through ANG II type 1 receptor and NF-κB signaling pathway. Meanwhile, MGP inhibited the calcification, caspase-3 activity, activation of runt-related transcription factor 2, and release of inflammatory cytokines by VSMCs induced by calcification medium (2.5 mM P(i)) and ANG II in vitro. These observations provide evidence that ANG II exacerbates vascular calcification through activation of the transcription factors, runt-related transcription factor 2 and NF-κB, and regulation of MGP, inflammatory cytokines expression in human VSMCs.

In Brief Background This prospective study evaluated the early increase in markers of inflammation after coronary stenting, and the predictors of early rise. Elevation of markers of inflammation after percutaneous coronary intervention correlates with an increased risk of adverse events. The role of soluble CD40 ligand (sCD40L) as a potential initiator of inflammation after stenting has not been described. Methods Seventy-five patients were treated with heparin alone (n=25), or randomized to adjuvant treatment with eptifibatide (n=26) or abciximab (n=24) during stenting. Systemic blood was obtained before coronary stenting and at 10 min after stenting. C-reactive protein (CRP), interleukin (IL)-6, IL-1 receptor antagonist and sCD40L were determined by enzyme liberated immunosorbent assay. Results sCD40L exhibited the greatest relative rise (35%, P=0.01 compared to concentrations before intervention) in the first 10 min after stenting. In a logistic regression model, an early increase in the concentration of sCD40L was predicted by baseline laboratory values (white blood count and sCD40L level before stenting) and procedural characteristics (number of stents and glycoprotein IIb-IIIa inhibitor assignment). Conclusions In conclusion, a systemic inflammatory response is detectable 10 min after coronary stent placement. The early increase in sCD40L suggests a possible role for this marker in the initiation of inflammation after coronary stenting. In this prospective study of 75 patients undergoing coronary stenting, a systemic inflammatory response was evident within 10 min of coronary stenting. Soluble CD40 ligand had the greatest relative rise in the first 10 min after stenting suggesting a possible role for this cytokine in the initiation of the inflammatory response; predictors of this early rise included preprocedural white blood count, preprocedural soluble CD40 ligand level, use of multiple stents and randomization to eptifibatide.

BACKGROUND: Real-time myocardial contrast echocardiography (RTMCE) directly measures capillary flow (CBF), which in turn is a major regulator of coronary flow and resistance during demand or hyperemic stress. Although fractional flow reserve (FFR) was developed to assess the physiological relevance of an epicardial stenosis, it assumes maximal microvascular vasodilation and minimal resistance during vasodilator stress. Therefore, we sought to determine the relationship between CBF assessed with RTMCE during stress echocardiography and FFR in intermediate coronary lesions. METHODS AND RESULTS: Sixty-seven vessels with 50% to 80% diameter stenoses by quantitative coronary angiography in 58 consecutive patients were examined with FFR and RTMCE (mean age, 60±13 years). RTMCE was performed using an incremental dobutamine (n=32) or exercise (n=26) stress protocol, and myocardial perfusion was assessed using a continuous infusion of ultrasound contrast. The presence or absence of inducible perfusion defects and wall motion abnormalities were correlated with FFR. Mean percent diameter stenosis was 60±9%. Eighteen stenoses (27%) had an FFR ≤ 0.8. Although 17 of the 18 stenoses that were FFR+ had abnormal CBF during RTMCE, 28 of the 49 stenoses (57%) that were FFR had abnormal CBF, and 24 (49%) had abnormal wall motion in the corresponding coronary artery territory during stress echocardiography. CONCLUSIONS: In a significant percentage of intermediate stenoses with normal FFR values, CBF during demand stress is reduced, resulting in myocardial ischemia.

Determination of the optimal interventricular (VV) delay in cardiac resynchronization therapy currently relies on costly, time-consuming echocardiographic (ECHO) methods. This study evaluated the performance of a new intracardiac electrogram (IEGM)-based VV method compared to the aortic velocity time integral (AVTI) method of VV delay optimization. The study included two patient groups. Eleven patients enrolled by a single center in the Rhythm II ICD trial underwent prospective comparisons of the AVTI at the VV interval determined by the IEGM VV method versus the maximum AVTI at the echocardiographically determined optimal VV delay. In 61 patients enrolled in the RHYTHM VV trial, the same testing methods were compared retrospectively. In the prospective study, the maximum AVTI by the ECHO-based method (24.3 +/- 7.9 cm), was closely correlated with maximum AVTI by the IEGM-based method (23.9 +/- 7.9 cm; concordance correlation coefficient = 0.99; 95% confidence, lower limit of 98%. Likewise, in the retrospective analysis, the ECHO-determined maximum AVTI (22.1 +/- 8.2 cm) was similar to that determined by the IEGM-based method (20.9 +/- 8.3 cm; concordance correlation coefficient = 0.98; 95% confidence, lower limit of 97%).

INTRODUCTION: Left atrial appendage (LAA) can be effectively and safely excluded using a novel percutaneous LARIAT ligation system. However, due to pericardial catheter manipulation and LAA ligation and subsequent necrosis, postprocedural course is complicated by pericarditis. We intended to evaluate the preprocedural use of colchicine on the incidence of postprocedural pericardial complications. METHODS AND RESULTS: In this multicenter observational study, we included all consecutive patients who underwent LARIAT procedure at the participating centers. Many patients received periprocedural colchicine at the discretion of the physician. We compared the postprocedural outcomes of patients who received prophylactic periprocedural colchicine (colchicine group) with those who did not receive colchicine (standard group). A total of 344 consecutive patients, 243 in the "colchicine group" and 101 in the "standard group," were included. The mean age, median CHADS2VASc score, and HASBLED scores were 70 ± 11 years, 3 ± 1.7, and 3 ± 1.1, respectively. There were no significant differences in major baseline characteristics between the two groups. Severe pericarditis was significantly lower in the "colchicine group" compared to the "standard group" (10 [4%] vs. 16 [16%] P<0.0001). The colchicine group, compared to the standard group, had lesser pericardial drain output (186 ± 84 mL vs. 351 ± 83, P<0.001), shorter pericardial drain duration (16 ± 4 vs. 23 ± 19 hours, P<0.04), and similar incidence of delayed pericardial effusion (4 [1.6%] to 3 [3%], P = 0.42) when compared to the standard group. CONCLUSION: Use of colchicine periprocedurally was associated with significant reduction in postprocedural pericarditis and associated complications.

Vascular restenosis following coronary artery bypass graft can cause major clinical complications due to intimal hyperplasia in venous conduits. However, the precise underlying mechanisms of intimal hyperplasia are still unclear. We have recently reported that increased expression of connexin43 (Cx43) is involved in the proliferation of vascular smooth muscle cells (SMCs) in human saphenous vein (SV). In this study, we investigated the signalling transduction pathway involved in Cx43 expression and SV SMC proliferation. Angiotensin-II (AT-II, 100 ng/ml) increased AT-II receptor 1 (AT-1R) protein expression and insulin-like growth factor-1 (IGF-1) (100 ng/ml) up-regulated IGF-1 receptor (IGF-1R) protein expression in SV SMCs. Interestingly, AT-1R expression was also increased by IGF-1 treatment, and IGF-1R expression was increased by AT-II treatment, which was blocked by siRNA-IGF-1R and siRNA-AT-1R, respectively. Furthermore, the effect of AT-II and IGF-1 signal cross-talk i nducing up-regulation of their reciprocal receptors was blocked by siRNA against extracellular signal-regulated kinases 1/2 (Erk 1/2) in SMCs of SV. Moreover, AT-II and IGF-1-induced Cx43 expression via phosphorylation of Erk 1/2 and activation of transcription factor activator protein 1 (AP-1) through their reciprocal receptors in SV SMCs. These data demonstrate a cross-talk between IGF-1R and AT-1R in AT-II and IGF-1-induced Cx43 expression in SV SMCs involving Erk 1/2 and downstream activation of the AP-1 transcription factor.

BACKGROUND AND PURPOSE: Ischemic stroke is an uncommon but devastating complication of myocardial infarction (MI). It is possible that delay in the acute revascularization of these patients influences the risk of peri-MI ischemic stroke independent of size of infarction or residual ventricular function. The influence of the timing and type of revascularization on risk of ischemic stroke in the patient with MI has not previously been assessed. METHODS: We used the National Registry of Myocardial Infarction 3 and 4 databases to identify 45,997 subjects who received thrombolytic therapy and 47,876 patients who were treated with primary percutaneous transluminal coronary angioplasty for MI. In-hospital ischemic stroke occurred in 248 (0.54%) and 150 (0.31%) patients in the two groups, respectively. Patients were stratified based on time from presentation to initial therapy. RESULTS: A statistically significant linear relationship between time to revascularization therapy and risk of in-hospital ischemic stroke was seen on univariate analysis. A multivariate model incorporating 26 other variables showed thrombolytic therapy within 15 minutes was associated with a lower risk of ischemic stroke (odds ratio, 0.58; 95% CI, 0.36-0.94). Primary angioplasty within 90 minutes of arrival was associated with a nonsignificant trend toward lower stroke risk (odds ratio, 0.68; 95% CI, 0.41-1.12). Interestingly, his benefit of early reperfusion therapy did not appear to be related to improvements in left ventricular function. CONCLUSIONS: Risk of in-hospital ischemic stroke with MI is closely tied to the time to revascularization with both thrombolytic and percutaneous transluminal coronary angioplasty therapies. Early revascularization is independently predictive of a lower risk of ischemic stroke, but the mechanism of this does not appear to be related to improved cardiac function. The records of 45,997 subjects who received thrombolytic therapy and 47,876 patients who were treated with primary percutaneous transluminal coronary angioplasty for myocardial infarction were analyzed to determine the relationship between time to revascularization and the occurrence of ischemic stroke. A statistically significant linear relationship between time to revascularization therapy and risk of in-hospital ischemic stroke was seen on univariate analysis. A multivariate model incorporating 26 other variables showed thrombolytic therapy within 15 minutes of presentation was associated with a lower risk of ischemic stroke, and angioplasty within 90 minutes was similarly associated with a nonsignificant trend toward lower stroke risk.

This article will review the development of glycoprotein IIb-IIIa antagonists, with particular emphasis on the characteristics and pharmacodynamic studies of each agent that is available for clinical use. Abciximab is a Fab fragment of the 7E3 antibody that has high affinity and a slow rate of dissociation from glycoprotein IIb-IIIa. In contrast, the small molecules eptifibatide and tirofiban, have a much more rapid rate of dissociation, with an off time of 10 to 15 s. Accordingly, the circulating pool of abciximab is predominantly associated with platelets, whereas maintenance of a consistent concentration of tirofiban and eptifibatide in the blood is critical in order to achieve and sustain their inhibitory effects. The affinity of abciximab and tirofiban for glycoprotein IIb-IIIa are substantially greater than that of eptifibatide, necessitating maintenance of greater molar concentrations of eptifibatide in blood in order to achieve effective inhibition of the binding of fibrinogen to the activated conformer of glycoprotein IIb-IIIa.

Proliferation of smooth muscle cells (SMCs) is the key event in the pathogenesis of intimal hyperplasia (IH) leading to coronary artery bypass graft (CABG) occlusion. The saphenous vein (SV) conduits are often affected by IH, while the internal mammary artery (IMA) conduits remain remarkably patent. SMC proliferation is mediated by the cell cycle, under the control of cyclin-dependent kinases (cdks), cdk-inhibitors and the retinoblastoma protein (Rb). Early passage of the SMCs through the cell cycle involves crossing the non-reversible G(1) checkpoint, the restriction (R) point. In this study, we investigated the effect of mitogenic insulin-like growth factor (IGF)-1 stimulation on the R-point and its relationship with the phosphorylation of Rb protein and the cdk inhibitors p21 and p27 in SV and IMA SMCs. We observed no change in the R-point following IGF-1 activation in either SV or IMA SMCs. However, Rb-phosphorylation occurred much earlier and was quantitatively greater in SV SMCs than IMA. Overexpression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in SV SMCs followed by IGF-1 activation significantly decreased the expression of cyclin E and pRb and induced p27 expression in SV SMCs, while, pRb levels were markedly decreased and p27 levels were significantly increased in IMA SMCs. Silencing the PTEN gene by siRNA transfection of IMA SMCs significantly induced the expression of pRb and inhibited p27 expression, while, the expression levels of cyclin E, pRb, p21 and p27 were unaffected by the silencing of PTEN in SV SMCs. These results demonstrate that the PTEN plays a critical role in regulating cell cycle entry. Therefore, overexpression of PTEN possibly by means of gene therapy could be a viable option in regulating the cell cycle in SV SMCs in the treatment of vein graft disease.

Coronary artery perforation is a rare complication of percutaneous transluminal coronary angioplasty (PTCA) and coronary stenting, most commonly creating a communication between the coronary artery lumen and the pericardial space. We report a case where vessel rupture following stent deployment led to the development of a fistula between the left anterior descending coronary artery and the right ventricle.