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Purpose: Despite the fact that techniques for recanalization of chronic total occlusions (CTO) are improved, the benefit of successful recanalization of the artery remains unclear. The aim of our study is to determine the success rate of percutaneous procedures and to evaluate the event free long-term survival in patients with CTO who underwent percutaneous coronary intervention (PCI).Methods: Our study included 283 consecutive patients with chronic total occlusions who underwent percutaneous coronary intervention on CTO at Clinic for Cardiology, between Jan 1st 2009 and Dec 31st 2010. Data were obtained retrospectively from Cath lab database at Clinic for Cardiology. Follow up data were obtained by direct phone contact.Results: Overall procedural success was achieved in 62.3% interventions. Independent predictors for procedural failure were presence of vessel tortuosity (P=0.007), vessel wall calcifications (P=0.000), blunt stump (P=0.000) and unstable angina pectoris as negative predictor (P=0.009). Overall MACE rates were similar in the procedural success and procedural failure groups (10% vs. 12.8%, p=0.455). There was no significant difference in the event free survival rate between success and failure group (89.8% vs. 87.2%, Log-Rank =0.468, p=0.494).Conclusions: Our study demonstrated that success rate of PCI in patients with CTO is acceptable and safe. Nevertheless, successful recanalization of CTO was not associated with an improved event free survival. [ABSTRACT FROM AUTHOR]

Background Microvascular dysfunction might be a major determinant of clinical deterioration and outcome in patients with hypertrophic cardiomyopathy (HCM). However, long-term prognostic value of transthoracic Doppler echocardiography (TDE) coronary flow velocity reserve (CFVR) on clinical outcome is uncertain in HCM patients. Therefore, the aim of our study was to assess long-term prognostic value of CFVR on clinical outcome in HCM population. Methods and Results We prospectively included 150 HCM patients (82 women; mean age 48±15 years). Patients' clinical characteristics, echocardiographic and CFVR findings (both for left anterior descending [LAD] and posterior descending artery [PD]), were assessed in all patients. The primary outcome was a composite of: HCM related death, heart failure requiring hospitalization, sustained ventricular tachycardia and ischemic stroke. Patients were stratified into 2 subgroups depending on CFVR LAD value: Group 1 (CFVR LAD>2, [n=87]) and Group 2 (CFVR LAD≤2, [n=63]). During a median follow-up of 88 months, 41/150 (27.3%) patients had adverse cardiac events. In Group 1, there were 8/87 (9.2%), whereas in Group 2 there were 33/63 (52.4%, P <0.001 vs. Group 1) adverse cardiac events. By Kaplan-Meier analysis, patients with preserved CFVR LAD had significantly higher cumulative event-free survival rate compared to patients with impaired CFVR LAD (96.4% and 90.9% versus 66.9% and 40.0%, at 5 and 8 years, respectively: log-rank 37.2, P <0.001). Multivariable analysis identified only CFVR LAD≤2 as an independent predictor for adverse cardiac outcome (HR 6.54; 95% CI 2.83-16.30, P <0.001), while CFVR PD was not significantly associated with outcome. Conclusions In patients with HCM, impaired CFVR LAD (≤2) is a strong, independent predictor of adverse cardiac outcome. When the aim of testing is HCM risk stratification and CFVR LAD data are available, the evaluation of CFVR PD is redundant.

Background: Coronary chronic total occlusion (CTO) is characterized by the presence of collateral blood vessels which can provide additional blood supply to CTO-artery dependent myocardium. Successful CTO recanalization is followed by significant decrease in collateral donor artery blood flow and collateral derecruitment, but data on coronary hemodynamic changes in relation to myocardial function are limited. We assessed changes in coronary flow velocity reserve (CFVR) by echocardiography in collateral donor and recanalized artery following successful opening of coronary CTO., Methods: Our study enrolled 31 patients (60 ± 9 years; 22 male) with CTO and viable myocardium by SPECT scheduled for percutaneous coronary intervention (PCI). Non-invasive CFVR was measured in collateral donor artery before PCI, 24 h and 6 months post-PCI, and 24 h and 6 months in recanalized artery following successful PCI of CTO., Results: Collateral donor artery showed significant increase in CFVR 24 h after CTO recanalization compared to pre-PCI values (2.30 ± 0.49 vs. 2.71 ± 0.45, p = 0.005), which remained unchanged after 6-months (2.68 ± 0.24). Baseline blood flow velocity of the collateral donor artery significantly decreased 24 h post-PCI compared to pre-PCI (0.28 ± 0.06 vs. 0.24 ± 0.04 m/s), and remained similar after 6 months, with no significant difference in maximum hyperemic blood flow velocity pre-PCI, 24 h and 6 months post-PCI. CFVR of the recanalized coronary artery 24 h post-PCI was 2.55 ± 0.35, and remained similar 6 months later (2.62 ± 0.26, p = NS)., Conclusions: In patients with viable myocardium, prompt and significant CFVR increase in both recanalized and collateral donor artery, was observed within 24 h after successful recanalization of CTO artery, which maintained constant during the 6 months., Trial Registration: ClinicalTrials.gov (Number NCT04060615 ).

Background: Microvascular dysfunction (MVD) is associated with adverse prognosis and may account for abnormal stress tests and angina symptoms in women with cardiac syndrome X (CSX). The aim of our study was to assess MVD by coronary flow velocity reserve (CFVR) and left ventricular (LV) contractile function by LV global longitudinal strain (LVGLS) in CSX patients with respect to presence of slow coronary flow (SCF). It was of additional importance to evaluate clinical status of CSX patients using Seattle Angina Questionnaire., Methods and Results: Study population included 70 women with CSX (mean age 61 ± 7 years) and 34 age-matched controls. CSX group was stratified into two subgroups depending on SCF presence: CSX-Thrombolysis In Myocardial Infarction (TIMI) 3- normal flow subgroup (n = 38) and CSX-TIMI 2- SCF subgroup (n = 32) as defined by coronary angiography. LVGLS measurements and CFVR of left anterior descending (LAD) and posterior descending (PD) artery were performed. CFVR-LAD and PD were markedly impaired in CSX group compared to controls (2.34 ± 0.25 vs 3.05 ± 0.21, p < 0.001; 2.32 ± 0.24 vs 3.01 ± 0.13, p < 0.001), and furthermore decreased in CSX-TIMI 2 patients. Resting, peak, and ΔLVGLS were all significantly impaired in CSX group compared to controls (for all p < 0.001), and furthermore reduced in CSX-TIMI 2 subgroup. Strongest correlation was found between peak LVGLS and CFVR LAD (r = -0.784, p < 0.001) and PD (r = -0.772, p < 0.001). CSX-TIMI 2 subgroup had more frequent angina symptoms and more impaired quality of life., Conclusions: MVD in CSX patients is demonstrated by reduction in CFVR and LVGLS values. SCF implies more profound impairment of microvascular and LV systolic function along with worse clinical presentation., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Treatment of nonculprit coronary stenosis during primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction may be beneficial, but the mode and timing of the intervention are still controversial. The aim of this study was to examine the significance and prognostic value of preserved coronary flow velocity reserve (CFVR) in patients with nonculprit intermediate stenosis early after primary percutaneous coronary intervention., Methods: Two hundred thirty patients with remaining intermediate (50%-70%) stenosis of non-infarct-related arteries, in whom CFVR was performed within 7 days after primary percutaneous coronary intervention, were prospectively enrolled. Twenty patients with reduced CFVR and positive results on stress echocardiography or impaired fractional flow reserve underwent revascularization and were not included in further analysis. The final study population of 210 patients (mean age, 58 ± 10 years; 162 men) was divided into two groups on the basis of CFVR: group 1, CFVR > 2 (n = 174), and group 2, CFVR ≤ 2 (n = 36). Cardiac death, nonfatal myocardial infarction, and revascularization of the evaluated vessel were considered adverse events., Results: Mean follow-up duration was 47 ± 16 months. Mean CFVR for the whole group was 2.36 ± 0.40. There were six adverse events (3.4%) related to the nonculprit coronary artery in group 1, including one cardiac death, one ST-segment elevation myocardial infarction, and four revascularizations. In group 2, there were 30 adverse events (83.3%, P < .001 vs group 1), including two cardiac deaths, two ST-segment elevation myocardial infarctions, and 26 revascularizations., Conclusions: In patients with CFVR > 2 of the intermediate nonculprit coronary lesion, deferral of revascularization is safe and associated with excellent long-term clinical outcomes., (Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

The objective of the study was to evaluate major adverse cardiovascular events (MACE) after successful versus failed percutaneous coronary intervention for chronic total occlusion (PCI-CTO).Limited data are available on long-term clinical follow-up in the treatment of chronic total occlusion (CTO).Between January 2009 and December 2010 PCI-CTO was attempted in 283 consecutive patients with 289 CTO lesions. Procedural success was 62.3% and clinical follow-up covered 83% (235/283) of the study population with a median follow-up of 66 months (range, 59-74).The total incidence of MACE was 57/235 (24.3%), and was significantly higher in the procedural failure group than in the procedural success group (33/87 (37.9%) versus 24/148 (16.2%), P < 0.001). All-cause mortality was significantly lower in patients with successful PCI-CTO compared to failed PCI-CTO (10.8% versus 20.7%, P < 0.05). Also, the rate of cardiovascular death in the procedural failure group (14.9%) was slightly higher than that in the procedural success group (7.4%, P = 0.066). The rate of TVR was statistically higher in the procedural failure group (P < 0.009). Propensity score-adjusted Cox regression showed that procedural success remained a significant predictor of MACE (adjusted HR 0.402; 95% CI 0.196-0.824; P = 0.013).Our study emphasizes the importance of CTO recanalization in improving long-term outcome including all-cause mortality with a borderline effect on cardiovascular mortality.

Endothelial cell markers are membrane-bound or cytoplasmic molecules expressed by endothelial cells, which help their easier identification and discrimination from other cell types. During vasculogenesis, endothelial cells differentiate from hemangioblasts to form new blood vessels. With the discovery of endothelial progenitor cells (EPC) and their ability to form new blood vessels, the term vasculogenesis is not only reserved for the embryonic development. Possibility of de novo blood vessel formation from EPC is now widely explored in different ischemic conditions, especially in cardiovascular medicine. Numerous clinical trials have tested enhancing tissue vascularization by delivering hematopoietic cells that expressed endothelial markers. This therapeutic approach proved to be challenging and promising, particularly for patients who have exhausted all conventional therapeutic modalities. Angiogenesis, which refers to the formation of new blood vessels from existing vasculature, is indispensable process during tumor progression and metastasis. Blockage of tumor angiogenesis by targeting and inhibiting endothelial cell has emerged as novel safe and efficacious method to control many advanced malignant diseases. Numerous clinical studies are currently testing new antiangiogenic drugs which target and inhibit endothelial cell markers, receptors or molecules which transmit receptor-mediated signals, therefore inhibiting endothelial cell proliferation, migration and vascular tube formation. Many of these drugs are now widely used in clinical settings as first- or second-line chemotherapy in advanced malignant conditions. So far, these therapeutic approaches gave modest, yet encouraging clinical improvements, prolonging survival and improving functional capacity and quality of life for many terminally ill patients. Here we present the most commonly used endothelial cell markers along with their applicability in contemporary clinical practice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Angiogenesis is the growth of both new vascular and lymphatic blood vessels from the existing vasculature. During this process, blood endothelial cells (BECs) and lymphatic endothelial cells (LECs) express specific markers, which help their discrimination and easier identification. Since the coronary thrombi material aspirated from patients with ST-elevation myocardial infarction (STEMI) proved as good angiogenesis model, we investigated the expression of CD34 and CD31 as BECs markers, and D2-40, LYVE-1 and VEGFR3 as LEC markers in this material., Materials and Methods: Aspirated thrombi were stained immunohistochemically for CD34, CD31, D2-40, LYVE-1 and VEGFR3. Organizational patterns of immunopositive cells were graded as single cells, clusters or microvessels. Double immunofluorescence for CD31, D2-40, LYVE-1 and VEGRF3 was done. Thrombi were also graded as fresh (<1day old), lytic (1-5days old) and organized (>5days old)., Results: Serial sections of aspirated thrombi showed concordant BEC and LEC markers immunopositivity. Double immunoflorescence proved co-expression of CD31 and LEC markers on the same cells. Cells expressing LEC markers organized in clusters and microvessels were mainly present in lytic and organized thrombi., Conclusion: Co-expression of BEC and LEC markers on the same non-tumorous cell during thrombus neovascularization indicates existing in vivo plasticity of endothelial cells under non-tumorous pathological conditions. It also points that CD34 and CD31 on one hand, and D2-40, LYVE-1 and VEGFR3 immunostaining on the other hand, cannot solely be a reliable indicators whether vessel is lymphatic or not., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: RISK-PCI score is a novel score for risk stratification of patients with ST elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI). The aim of this study was to evaluate the role of B-type natriuretic peptide (BNP) and the RISK-PCI score for early risk assessment in patients with STEMI treated by pPCI., Methods: In 120 patients with STEMI treated by pPCI, BNP was measured on admission before pPCI. The primary end point was 30-day mortality., Results: The ROC curve analysis revealed that the most powerful predictive factors of 30-day mortality were the plasma level of BNP ≥ 206.6 pg/mL with the sensitivity of 75% and specificity of 87.5% and the RISK-PCI score ≥ 5.25 with the sensitivity of 75% and specificity of 85.7%. Thirty-day mortality was 6.7%. After multivariate adjustment, admission BNP (≥ 206.6 pg/mL) (OR 2.952, 95% CI 1.072 - 8.133, p = 0.036) and the RISK-PCI score (≥ 5.25) (OR 2.284, 95% CI 1.140-4.578, p = 0.020) were independent predictors of 30-day mortality. The area under the ROC curve using the RISK-PCI score and BNP to detect mortality was 0.828 (p = 0.002) and 0.903 (p < 0.001), respectively. Addition of BNP to RISK-PCI score increased the area under the ROC to 0.949 (p < 0.001), but this increase measured by the c-statistic was not significant (p = 0.107). Furthermore, the significant improvement in risk reclassification (p < 0.001) and the integrated discrimination index (p = 0.042) were observed with the addition of BNP to RISK-PCI score for 30-day mortality., Conclusions: BNP on admission and the RISK-PCI score were the independent predictors of 30-day mortality in patients with the STEMI treated by pPCI. BNP in combination with the RISK-PCI score showed the way to more accurate risk assessment in patients with STEMI treated by pPCI.

Aim of the Study: Musculoskeletal tumors are relatively rare, and their geographic distribution varies greatly around the world. In this study, we present the incidence, age distribution and localization of musculoskeletal tumors diagnosed and/or treated at a tertiary referral orthopedic department, catering to an entire Southeastern European country., Methods: This was a retrospective study of prospectively collected data, in which all patients diagnosed and/or treated for musculoskeletal tumors at our Department in the period of 30 years (1981-2010) were included., Results: Data of a total of 3482 patients with musculoskeletal tumors were collected. Average age of patients was 33.5 years (range, 2 months-88 years), with even distribution according to sex. Malignant tumors were seen in 20.7% of patients, more often in men (56.9%). Most common malignant tumors were osteosarcoma (estimated incidence: 1.68/million/year), chondrosarcoma (0.79/million/year) and Ewing sarcoma (0.76/million/year). Benign tumors and tumor-like lesions were found in 79.3% of patients, with slight female predominance. Most common benign bone lesions were osteochondroma (5.81/million/year), simple bone cyst (2.13/million/year), and enchondroma (2.05/million/year)., Conclusion: This report represents a first of its kind in our region, and gives representative results to be compared to other middle and south European countries. Further nationwide studies are needed to improve strategies in bone tumor diagnosis and treatment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background and Purpose: To analyze plasma adiponectin kinetics in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI) and its association with coronary flow reserve (CFR), an index of coronary microcirculatory function., Methods: A total of 96 consecutive patients with the first anterior STEMI treated by pPCI without heart failure were included. CFR was assessed on the 7th day after pPCI. Plasma adiponectin was measured on admission before pPCI, and on the 2nd and 7th day after pPCI., Results: Adiponectin concentration was the highest on admission, declined to the lowest level on the 2nd day, and rose on the 7th day remaining below admission values. Impaired coronary microcirculatory function (CFR<2) was observed in 41% of the patients. Adiponectin concentrations significantly positively correlated with CFR, and the strongest correlation was with the 2nd day adiponectin (r=0.489, p<0.001). In multivariate models, adiponectin concentrations were independent predictors of impaired CFR [on admission: odds ratio (OR) 0.175, confidence interval (CI): 0.047-0.654, p=0.010; 2nd day: OR 0.146, 95% CI: 0.044-0.485, p=0.002; 7th day: OR 0.198, CI: 0.064-0.611, p=0.005]. The best power to predict impaired CFR was the 2nd day adiponectin. Delta values of adiponectin (differences between adiponectin concentrations) did not correlate with CFR., Conclusions: In patients with the first anterior STEMI treated by pPCI plasma adiponectin concentrations before and after pPCI are strongly associated with CFR. Our results support the hypothesis that low adiponectin, especially during the early post-pPCI period, carries the risk for impaired coronary microcirculatory function in STEMI patients., (Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

This prospective, first-in-man, open-label multicenter study sought to assess the pharmacokinetics of sirolimus after Ultimaster drug-eluting stent implantation (coated with sirolimus and bioabsorbable co-polymer) in patients with de novo coronary artery disease (the TCD-10023 PK study). The primary endpoint was sirolimus concentration in peripheral whole blood at 28 days after stent implantation. In addition, safety, tolerability, therapeutic outcome and vasomotor response after stent implantation were studied. Twenty patients were enrolled in the study. Blood samples for the measurements of sirolimus concentration were collected at eight time points during first 48 h, at 7 days and 28 days after stent implantation. Patients underwent 6-month angiographic and up to 12 months clinical follow-up. At 28 days, only two of 20 patients had sirolimus concentrations above lower limit of quantification (20.0 pg/mL). The highest sirolimus blood concentration was 105 pg/mL. The median maximum concentration was 36.8 pg/mL (range 22.9-41.5 pg/mL) for stent 3.0 × 15 mm and 87.2 pg/mL (range 60.0-105.0 pg/mL) for 3 × 28 mm stent. The median systemic exposure, as measured by the area under the time-concentration curve, was 8.3 ng h/mL (range 6.47-28.0 ng h/mL). At 6 months, endothelial function was well preserved, and up to 12 months, there were no signs of sirolimus toxicity nor any other safety concerns. Our results demonstrate that implantation of Ultimaster stent resulted in almost nondetectable sirolimus in blood after 28 days. These findings were translated into exceptional safety profile, without any sign of systemic toxicity., (© 2014 Société Française de Pharmacologie et de Thérapeutique.)

Coronary microcirculatory function after primary percutaneous coronary intervention (pPCI) in patients with acute myocardial infarction is important determinant of infarct size (IS). Our aim was to investigate the utility of coronary flow reserve (CFR) and diastolic deceleration time (DDT) of the infarct artery (IRA) assessed by transthoracic Doppler echocardiography after pPCI for final IS prediction. In 59 patients, on the 2nd day after pPCI for acute anterior myocardial infarction, transthoracic Doppler analysis of IRA blood flow was done including measurements of CFR, baseline DDT and DDT during adenosine infusion (DDT adeno). Killip class, myocardial blush grade, resolution of ST segment elevation, peak creatine kinase-myocardial band and conventional echocardiographic parameters were determined. Single-photon emission computed tomography myocardial perfusion imaging was done 6 weeks later to define final IS (percentage of myocardium with fixed perfusion abnormality). IS significantly correlated with CFR (r = -0.686, p < 0.01), DDT (r = -0.727, p < 0.01), and DDT adeno (r = -0.780, p < 0.01). CFR and DDT adeno in multivariate analysis remained independent IS predictors after adjustment for other covariates and offered incremental prognostic value in models based on conventional clinical, angiographic, electrocardiographic and enzymatic variables. In predicting large infarction (IS > 20 %), the best cut-off for CFR was <1.73 (sensitivity 65 %, specificity 96 %) and for DDT adeno ≤720 ms (sensitivity 81 %, specificity 96 %). CFR and DDT during adenosine are independent and powerful early predictors of final IS offering incremental prognostic information over conventional parameters of myocardial and microvascular damage and tissue reperfusion.

Introduction: Routine thrombus aspiration is proposed to be superior to conventional primary percutaneous coronary intervention (PCI) in terms of improved myocardial perfusion, in patients with ST-segment elevation acute myocardial infarction (STEMI). However, myocardial perfusion after thrombus aspiration has not been evaluated by a quantitative, invasive method. We intend to determine whether manual thrombus aspiration in the infarct-related coronary artery increases myocardial perfusion assessed by index of microcirculatory resistance (IMR) compared with conventional primary PCI., Study Design: PATA STEMI is a single-center, prospective, randomized trial with a planned inclusion of 128 patients with the first STEMI. Prior to coronary angiography, patients are randomly assigned to thrombus aspiration using the Eliminate aspiration catheter (Terumo Medical Supply, Japan) or to conventional primary PCI. After completion of primary PCI, IMR is determined both in infarct-related artery and in noninfarct-related arteries without critical stenoses. The primary end-point is a group mean value of IMR after thrombus aspiration compared with conventional primary PCI. Secondary end-points are myocardial perfusion grade, resolution of ST-segment elevation, enzymatic estimation of infarct size, left ventricular remodeling assessed by echocardiographic indices, and major adverse cardiac events rate at 1, 6, and 12 months., Conclusion: If manual thrombus aspiration significantly reduces microcirculatory resistance, thereby improving myocardial perfusion, it may become the routine strategy in primary PCI., (© 2014, Wiley Periodicals, Inc.)

First-generation drug-eluting stents (DES) have been associated with impaired localized coronary vasomotion and delayed endothelialization. We aimed to compare coronary vasomotion after implantation of a newer-generation everolimus-eluting stent (EES), with a first-generation paclitaxel-eluting stent (PES). Coronary vasomotion was studied in 19 patients with EES and 13 with PES. Vasomotor response was measured proximally and distally to the stent and in a remote vessel (reference segment). Quantitative coronary angiography was performed offline. Endothelium independent vasomotion did not differ significantly between the two groups. EES showed significant vasodilatation while PES showed vasoconstriction at both proximal (+4.5 ± 3.6 vs -4.2 ± 6.9, p < 0.001) and distal (+4.6 ± 7.9 vs -4.8 ± 9.3, p = 0.003) segments. The reference segment did not show any significant difference in vasodilatation between the two groups (+9.8 ± 6.4 vs +7.2 ± 5.2, p = 0.17). Endothelium-dependent vasomotion at adjacent stent segments is relatively preserved after EES implantation while vasoconstriction was observed after PES implantation.

Background: Insulin resistance (IR) assessed by the Homeostatic Model Assessment (HOMA) index in the acute phase of myocardial infarction in non-diabetic patients was recently established as an independent predictor of intrahospital mortality. In this study we postulated that acute IR is a dynamic phenomenon associated with the development of myocardial and microvascular injury and larger final infarct size in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI)., Methods: In 104 consecutive patients with the first anterior STEMI without diabetes, the HOMA index was determined on the 2nd and 7th day after pPCI. Worst-lead residual ST-segment elevation (ST-E) on postprocedural ECG, coronary flow reserve (CFR) determined by transthoracic Doppler echocardiography on the 2nd day after pPCI and fixed perfusion defect on single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) determined six weeks after pPCI were analyzed according to HOMA indices., Results: IR was present in 55 % and 58 % of patients on day 2 and day 7, respectively. Incomplete post-procedural ST-E resolution was more frequent in patients with IR compared to patients without IR, both on day 2 (p = 0.001) and day 7 (p < 0.001). The HOMA index on day 7 correlated with SPECT-MPI perfusion defect (r = 0.331), whereas both HOMA indices correlated well with CFR (r = -0.331 to -0.386) (p < 0.01 for all). In multivariable backward logistic regression analysis adjusted for significant univariate predictors and potential confounding variables, IR on day 2 was an independent predictor of residual ST-E ≥ 2 mm (OR 11.70, 95% CI 2.46-55.51, p = 0.002) and CFR < 2 (OR = 5.98, 95% CI 1.88-19.03, p = 0.002), whereas IR on day 7 was an independent predictor of SPECT-MPI perfusion defect > 20% (OR 11.37, 95% CI 1.34-96.21, p = 0.026)., Conclusion: IR assessed by the HOMA index during the acute phase of the first anterior STEMI in patients without diabetes treated by pPCI is independently associated with poorer myocardial reperfusion, impaired coronary microcirculatory function and potentially with larger final infarct size.

Introduction: A mouse model of progeria derived by insertion of the human mutant LMNA gene (mLMNA), producing mutant lamin A, shows loss of smooth muscle cells in the media of the ascending aorta. We hypothesized that high shear stress, in the presence of mutant lamin A, induces this vasculopathy and tried to define the molecular and cellular basis for aortic vasculopathy., Methods: Ascending and descending aortas from wild type (WT) and mLMNA+ mice were compared using proteomics, Western blots, PCR and immunostaining. To determine whether high fluidic shear stress, known to occur in the ascending aorta, contributed to the vasculopathy, we exposed descending aortas of mLMNA+ mice, with no apparent vasculopathy, to 75 dynes/cm2 shear stress for 30 minutes using a microfluidic system., Results: When the mice were one year of age, expression of several mechanotransduction proteins in the ascending aorta, including vimentin, decreased in mLMNA+ mice but no decrease occurred in the descending aorta. High fluidic shear stress produced a significant reduction in vimentin of mLMNA+ mice but not in similarly treated WT mice., Conclusions: The occurrence of mutant lamin A and high shear stress correlate with a reduction in the level of mechanotransduction proteins in smooth muscle cells of the media. Reduction of these proteins may contribute over time to development of vasculopathy in the ascending aorta in progeria syndrome.

This study evaluated additive prognostic value of the SYNTAX score over GRACE, TIMI, ZWOLLE, CADILLAC and PAMI risk scores in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). All six scores were calculated in 209 consecutive STEMI patients undergoing pPCI. Primary end-point was the major adverse cardiovascular event (MACE--composite of cardiovascular mortality, non-fatal myocardial infarction and stroke); secondary end point was cardiovascular mortality. Patients were stratified according to the SYNTAX score tertiles (≤12; between 12 and 19.5; >19.5). The median follow-up was 20 months. Rates of MACE and cardiovascular mortality were highest in the upper tertile of the SYNTAX score (p < 0.001 and p = 0.003, respectively). SYNTAX score was independent multivariable predictor of MACE and cardiovascular mortality when added to GRACE, TIMI, ZWOLLE, and PAMI risk scores. However, the SYNTAX score did not improve the Cox regression models of MACE and cardiovascular mortality when added to the CADILLAC score. The SYNTAX score has predictive value for MACE and cardiovascular mortality in patients with STEMI undergoing primary PCI. Furthermore, SYNTAX score improves prognostic performance of well-established GRACE, TIMI, ZWOLLE and PAMI clinical scores, but not the CADILLAC risk score. Therefore, long-term survival in patients after STEMI depends less on detailed angiographical characterization of coronary lesions, but more on clinical characteristics, myocardial function and basic angiographic findings as provided by the CADILLAC score.

Background:  Retrograde approach increases the success rate for percutaneous recanalization of complex chronic total occlusion (CTO) of coronary arteries., Objectives:  The purpose of this study was to describe our initial experience of retrograde percutaneous coronary intervention for CTO program, focusing on its safety and feasibility, and long-term clinical follow-up., Methods:  The study was a single center retrospective registry which included a total of 40 patients, of 590 CTO treated patients (6.7%), between January 2008 and October 2011, who underwent retrograde approach for CTO recanalization., Results:  Mean occlusion duration was 37.8 ± 40.3 months. Overall success recanalization rate was 87.5% (35/40). Septal collaterals were used to access the occlusion in all cases (100%). Retrograde guidewire crossing of collateral channels was successful in 36/40 (90.0%) patients with success rate of CTO recanalization in these patients of 97.2%. Retrograde approach as the primary strategy was applied in 23/40 (57.5%) patients, retrograde approach immediately after antegrade failure attempt was performed in 8/40 (20.0%) patients, and retrograde approach as elective procedure, after previously failed antegrade attempt, was performed in 9/40 (22.5%) patients. The success rate of these strategies was: 87.0% (20/23 patients) for primary, 87.5% (7/8 patients) for retrograde immediately after antegrade failure, and 88.9% (8/9 patients) for retrograde after previous failed antegrade attempt, respectively. Total in-hospital major adverse cardiac events (MACE) rate was 5.0% (2 non-Q-wave myocardial infarctions). The MACE free survival at median follow-up of 20 months was 89% (95% CI: 78-100%)., Conclusions:  This study has demonstrated that adequate training and international proctorship for this complex and demanding technique is a necessity and prerequisite to achieve high overall success rates, with acceptable complication rates and excellent long-term survival rate., (©2012, Wiley Periodicals, Inc.)

Background: In patients with previous myocardial infarction (MI), assessment of myocardial viability and physiological significance of coronary artery stenoses are essential for appropriate guidance of revascularization. The aim of the study was to evaluate the relation between fractional flow reserve (FFR) and myocardial viability as assessed by gated SPECT MIBI perfusion scintigraphy in patients with previous MI undergoing elective PCI., Methods: The study population consisted of 26 patients (mean age 55 ± 7 years; 21 male) with a previous MI and a significant coronary stenosis in a single infarct-related coronary vessel for which PCI was being performed. In all patients, FFR was evaluated before and immediately after PCI. SPECT imaging was done before and 3 ± 1 months after PCI. A region representing the MI was considered viable if MIBI uptake was ≥55% of the normal region. Improvement in perfusion after revascularization was considered achieved if perfusion abnormalities decreased by 5% or more and there was a decrease in segmental score of ≥1 in three segments in PCI-related vascular territory., Results: Extent of perfusion abnormalities decreased from 32 ± 16% to 27 ± 19% after PCI (P < .001). In patients with myocardial viability in comparison to patients with no viability, there was significant difference in FFR before PCI (.57 ± .14 vs .76 ± .12, P = .002), despite almost the same values of diameter stenosis of infarct-related artery (63 ± 8% vs 64 ± 3%, respectively, P = .572). In addition, FFR prior to PCI was related to improvement in perfusion abnormalities after revascularization (P = .047), as well as with peak activity of creatine-kinase measured during previous MI (r = .56, P = .005)., Conclusion: Lower values of FFR before angioplasty are associated with myocardial viability and functional improvement as assessed by SPECT perfusion scintigraphy.

Rationale: The ability of the human heart to regenerate large quantities of myocytes remains controversial, and the extent of myocyte renewal claimed by different laboratories varies from none to nearly 20% per year., Objective: To address this issue, we examined the percentage of myocytes, endothelial cells, and fibroblasts labeled by iododeoxyuridine in postmortem samples obtained from cancer patients who received the thymidine analog for therapeutic purposes. Additionally, the potential contribution of DNA repair, polyploidy, and cell fusion to the measurement of myocyte regeneration was determined., Methods and Results: The fraction of myocytes labeled by iododeoxyuridine ranged from 2.5% to 46%, and similar values were found in fibroblasts and endothelial cells. An average 22%, 20%, and 13% new myocytes, fibroblasts, and endothelial cells were generated per year, suggesting that the lifespan of these cells was approximately 4.5, 5, and 8 years, respectively. The newly formed cardiac cells showed a fully differentiated adult phenotype and did not express the senescence-associated protein p16(INK4a). Moreover, measurements by confocal microscopy and flow cytometry documented that the human heart is composed predominantly of myocytes with 2n diploid DNA content and that tetraploid and octaploid nuclei constitute only a small fraction of the parenchymal cell pool. Importantly, DNA repair, ploidy formation, and cell fusion were not implicated in the assessment of myocyte regeneration., Conclusions: Our findings indicate that the human heart has a significant growth reserve and replaces its myocyte and nonmyocyte compartment several times during the course of life.

Objectives: The aim of this study was to assess the role of short oral administration of rapamycin, without loading dose, in the reduction of restenosis rate after bare metal stent implantation., Background: Previous studies suggest that the administration of oral rapamycin reduces angiographic restenosis after bare metal stent implantation., Methods: This was prospective, open-label study of 80 patients randomized to either oral rapamycin (2 mg/day for 30 days, starting within 24 hr of stent implantation) or no therapy after implantation of a coronary bare metal stent. The primary study end point was incidence of angiographic binary restenosis and late loss at six months. The secondary end points were target lesion revascularization (TLR), target vessel revascularization (TVR), and incidence of major adverse cardiovascular events (MACE) at 6 months., Results: Angiographic follow up was completed in 72/80 (90%) of patients. In the rapamycin group, the drug was well tolerated (22.5% minor side effects) and was maintained in 100% of patients. At six months, the in-segment binary restenosis was 10.5% in rapamycin group vs. 51.4% in no-therapy group, P < 0.001) and the in-stent binary restenosis was 7.9% in rapamycin group vs. 48.7% in no-therapy group, P < 0.001. The in-segment late loss was also significantly reduced with oral therapy (0.29 + or - 0.39 vs. 0.86 + or - 0.64 mm, respectively, P < 0.001). Similarly, after six months, patients in the oral rapamycin group also showed a significantly lower incidence of TLR and TVR (7% vs. 22.7%, respectively, P = 0.039) and MACE (7% vs. 22.7%, respectively, P = 0.039)., Conclusions: This study showed that the administration of oral rapamycin (2 mg/day, without loading dose) during 30 days after stent implantation significantly reduces angiographic and clinical parameters of restenosis.

Aims: Bone marrow (BM)-derived endothelial progenitor cells (EPCs) in the circulation replace damaged vascular endothelium. We assessed the hypothesis that a BM transplant from healthy animals would restore normal arterial endothelium and prevent hypertension in young endothelial nitric oxide synthase-deficient (eNOS(-/-)) mice., Methods and Results: Radiation or busulfan-induced BM ablation in eNOS(-/-) mice on day 6, day 14, or day 28 was followed by a BM transplant consisting of enhanced green fluorescent protein positive (EGFP(+)) cells from C57BL/6J mice. Peripheral blood cell chimerism was always greater than 85% at 4 months after BM transplant. Molecular assays of heart, kidney, and liver revealed low-level chimerism in all treatment groups, consistent with residual circulating EGFP(+) blood cells. When aorta, coronary, renal, hepatic, and splenic arteries in BM-transplanted eNOS(-/-) mice were examined by confocal microscopy, there were no EGFP- or eNOS-positive endothelial cells detected in these vessels in any of the treatment groups. Likewise, telemetry did not detect any reduction in blood pressure. Thus, no differences were observed in our measurements using several different treatment protocols., Conclusion: We found no evidence for BM-derived EPC renewal of endothelium in this eNOS-deficient mouse model of a chronic vascular disease or in wild-type mice during postnatal growth. Hence, renewal of chronic dysfunctional endothelium and endothelial homeostasis may be dependent on resident vascular progenitor cells.

Objectives: The aim of this study was to assess the pharmacokinetics and tolerability of Biolimus A9 eluted from Nobori coronary stents., Background: : The release kinetics and pharmacokinetics of drugs delivered via coronary stents have been shown to play an essential role in the efficacy and safety of drug eluting stents., Methods: Twenty patients with coronary artery disease were treated with single 14-mm (10 patients) or 28-mm long stent (10 patients). Blood samples were drawn at 16 time points to determine the pharmacokinetics of Biolimus A9. At seven time points, complete laboratory and toxicology panels were assessed to screen for potential Biolimus A9 toxicity. The primary endpoint of the study was the systemic blood concentrations of Biolimus A9 after 28 days and 6 months as measured using highly specific and sensitive liquid chromatography- tandem mass spectrometry assay., Results: At 28 days, 6 patients (30%) had quantifiable Biolimus A9 concentrations in blood. The highest Biolimus A9 blood concentration measured in any sample was 32.2 pg/mL. The median time to maximum concentration was 2 hr, ranging from 0.05 hr to 3 months. Six months after stent implantation, only 1 of 20 patients had measurable Biolimus A9 concentrations at the lowest level of quantification, while at 9 months no sample had quantifiable Biolimus A9 concentrations. Laboratory and toxicology assessments did not indicate any impact of Biolimus A9 on the evaluated parameters., Conclusion: Results of this study suggest that systemic exposure to Biolimus A9 was very low and that Biolimus A9 was well tolerated., (Copyright 2008 Wiley-Liss, Inc.)