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Background: Trans-cathetervalve implantation (TAVI) is a non- surgical alternative for patients with severe aortic stenosis (AS). Pre-procedural computed tomography angiography (CTA) allows accurate "road mapping," aortic annulus sizing and the detection of incidental findings.To document the prevalence of non-valvular extracardiac findings on CTA prior to TAVI and the impact of these findings on the procedure.Ninety AS patients underwent CTA as part of pre-TAVI planning. Scans extended from the clavicles to the groin. Non-vascular non-valvular findings were documented and graded as follows: (A) significant findings causing TAVI cancellation or postponement, (B) significant findings leading to a change in the TAVI procedure approach, (C) non-significant findings not affecting the TAVI procedure.TAVI was planned for 90 patients; their average age was 80.2 ± 7.5 years, 53% were females. Overall, non-valvular cardiac, extracardiac and extravascular significant and non-significant incidental findings were documented in 97% of scans (87/90). Significant pathologies causing TAVI cancellation or postponement (category A) were documented in 8%. Significant findings affecting the TAVI procedure (category B) were found in 16% of patients.Pre-TAVI CTA detected non-valvular extravascular pathologies leading to procedure cancellation/postponement or procedure modification in 8% and 16%, respectively. Comprehensive CTA evaluation that acknowledges the importance of such findings is of major importance since it might alter the TAVI procedure or even render it inappropriate.

Background Accurate risk stratification is pivotal for appropriate selection of patients with severe symptomatic aortic stenosis for either surgical or transcatheter aortic valve replacement (TAVR). We sought to determine whether recent risk prediction models developed specifically in TAVR patients enhance prognostication in comparison with previous surgical scores used in clinical practice (EuroScore I, EuroScore II, STS). Methods The Israeli TAVR Registry Risk Model Accuracy Assessment (IRRMA) study utilized a multicenter prospective TAVR database (n=1327) to perform a quantitative comparison between previous risk scores developed in either surgical or TAVR populations, with the present registry serving as an independent external validation set. Results In the IRRMA population, 4 variables (NYHA functional class IV, chronic obstructive pulmonary disease, systolic pulmonary artery pressure ≥60mmHg, vascular access other than by the femoral route) identified by cross-validation and leave-one-out analyses provided the most discriminative model (C-statistic=0.63) for predicting 30-day mortality. Previous scores developed in surgical (EuroScores I and II, STS), TAVR (FRANCE-2, OBSERVANT), or mixed (German AV score) populations were applied to the IRRMA cohort. Resultant C-statistics ranged between 0.52–0.71 (for the German AV and FRANCE-2 scores, respectively) and did not differ significantly (p=0.07 for the comparison between the lowest and highest C-statistics). The observed C-statistic for 5 of these 6 scores was lower than originally reported when applied to the IRRMA population. Conclusion Available TAVR risk scores showed limited accuracy when applied to an independent validation set and did not enhance prognostication in comparison to previous surgical scores.

Introduction Information regarding immediate response to novel P2Y12 inhibitors in ST-elevation myocardial infarction (STEMI) is scarce and has been associated with adequate reperfusion. Recent studies have shown that the onset of anti-platelet effects of novel P2Y12 inhibitors in patients with STEMI might be slower and more variable than in stable coronary syndrome. We aimed to assess the predictors and significance of immediate platelet response to prasugrel loading in STEMI. Methods Platelet aggregation (PA) was prospectively evaluated in STEMI patients upon prasugrel loading and at primary percutaneous coronary intervention (PPCI). Early platelet responsiveness was defined as percent reduction of PA from baseline to PPCI, divided by the time lapse from loading to PPCI. High- and low-platelet responsiveness was defined as above and below the median value respectively. Results Fifty consecutive STEMI patients (age 58 ± 8, 90% male) underwent PPCI with a mean door-to-balloon time of 42 ± 15 min. Mean PA upon prasugrel loading and at PPCI was 76 ± 9% and 63 ± 19%, respectively. Older age and prior aspirin use were predictors of low platelet responsiveness to prasugrel [β = (− 0.33), p = 0.02 and β = (− 0.28), p = 0.04, respectively]. Fast compared with slow responders demonstrated more frequent early ST resolution (93% vs. 72%, p = 0.02) and lower peak troponin levels (76 ± 62 μg/L vs. 48 ± 28 μg/L, p = 0.05). Conclusions Immediate platelet responsiveness to prasugrel among STEMI patients is highly variable and inversely associated with older age and prior aspirin use. Fast compared with slow responders have improved reperfusion and infarct size markers.

International audience; Objective: To assess outcomes following primary percutaneous coronary intervention (PCI) for ST-segment elevation acute myocardial infarction (STEMI) in nonagenarian patients.Methods: We conducted a multicentre retrospective study between 2006 and 2013 in five international high-volume centres and included consecutive all-comer nonagenarians treated with primary PCI for STEMI. There were no exclusion criteria. We enrolled 145 patients and collected demographic, clinical and procedural data. Severe clinical events and mortality at 6 months and 1 year were assessed.Results: Cardiogenic shock was present at admission in 21%. Median (IQR) delay between symptom onset and balloon was 3.7 (2.4–5.6) hours and 60% of procedures were performed through the transradial approach. Successful revascularisation of the culprit vessel was obtained in 86% of the cases (thrombolysis in myocardial infarction flow of 2 or 3). Major or clinically relevant bleeding was observed in 4% of patients. Median left ventricular ejection fraction post PCI was 41.5% (32.0–50.0). The in-hospital mortality was 24%, with 6 months and 1-year survival rates of 61% and 53%, respectively.Conclusions: In our study, primary PCI in nonagenarians with STEMI was achieved and feasible through a transradial approach. It is associated with a high rate of reperfusion of the infarct-related artery and 53% survival at 1 year. These results suggest that primary PCI may be offered in selected nonagenarians with acute myocardial infarction

A regional truncation surface developed during the Oligocene in the northern Red Sea and southern Levant as a result of the combined effects: (1) the formation of an ∼3000 km × 1500 km crustal dome affecting the northeastern sector of the Afro-Arabian continent above the Afar plume, and (2) widespread fluvial erosion that truncated the northern edge of this dome. The regional truncation surface separates two main stratigraphic divisions: (1) middle Eocene–early Oligocene prerift clastics preserved below the regional truncation surface and (2) late Oligocene–Holocene Red Sea Supergroup deposited after the regional truncation surface developed. The prerifting sequence is composed of two major units: (1) Eocene marine intraformational debris flows (Themed clastics), and (2) fluviolacustrine continental conglomerates, most of them monomictic (Mahatardi Conglomerate). The Red Sea Supergroup is composed of polymictic conglomerates, which include fragments of older rock units, down to the Precambrian. The reconstructed regional truncation surface and its subcrop map shed new light on the initial stages of the Afro-Arabian breakup, indicating two principal phases: (1) an Oligocene slow crustal doming, with reactivation of preexisting faults and the development of the regional truncation surface, all triggered by the upwelling of the Afar plume; and (2) late Oligocene–early Miocene rifting of the Red Sea and Suez rift, which refaulted the region, including the initiation of the Dead Sea Transform along a preexisting suture line. This two-stage model indicates the mutual genetic relationship between the early Oligocene phase of tectonic development following the penetration of the Afar plume and the post-Oligocene rifting and continental breakup of the Afro-Arabian continent.

Objectives The purpose of this study was to assess deformation dynamics and in vivo mechanical properties of the aortic annulus throughout the cardiac cycle. Background Understanding dynamic aspects of functional aortic valve anatomy is important for beating-heart transcatheter aortic valve implantation. Methods Thirty-five patients with aortic stenosis and 11 normal subjects underwent 256-slice computed tomography. The aortic annulus plane was reconstructed in 10% increments over the cardiac cycle. For each phase, minimum diameter, ellipticity index, cross-sectional area (CSA), and perimeter (Perim) were measured. In a subset of 10 patients, Young's elastic module was calculated from the stress-strain relationship of the annulus. Results In both subjects with normal and with calcified aortic valves, minimum diameter increased in systole (12.3 ± 7.3% and 9.8 ± 3.4%, respectively; p Conclusions The aortic annulus, generally elliptic, assumes a more round shape in systole, thus increasing CSA without substantial change in perimeter. Perimeter changes are negligible in patients with calcified valves, because tissue properties allow very little expansion. Aortic annulus perimeter appears therefore ideally suited for accurate sizing in transcatheter aortic valve implantation.

Data concerning Trans-catheter aortic valve replacement (TAVR) in patients with prior mitral surgery is limited, although preliminary reports appear to be encouraging. The aim of the study was to identify predictors of adverse outcomes in these patients. Clinical, imaging and angiographic records

Transcatheter aortic valve implantation (TAVI) is a novel treatment for high risk or inoperable patients with symptomatic severe aortic stenosis. However, significant atrioventricular (AV) conduction system abnormalities requiring permanent pacemaker (PPM) implantation might complicate this procedure. We used best subsets logistic regression analysis to identify the independent predictors for the development of high-degree AV block (HDAVB) among 70 patients who underwent TAVI at 3 referral centers in Israel from 2008 to 2010. The mean age of the study patients was 83 ± 4.6 years. Of the 70 patients, 28 (40%) developed AV conduction abnormalities requiring PPM implantation within 14 days (median 2) of the procedure. The indications for PPM implantation were HDAVB (n = 25), new-onset left bundle branch block with PR prolongation (n = 2), and slow atrial fibrillation (n = 1). Best subsets logistic regression analysis showed that, among the 15 prespecified clinical, electrocardiographic, and echocardiographic candidate risk factors, only right bundle branch block at baseline (odds ratio 43; p = 0.002) and deep valve implantation (6 mm from the lower edge of the noncoronary cusp to the ventricular end of the prosthesis, odds ratio 22; p0.001) were independently associated with the development of periprocedural HDAVB. At 3 months of follow-up, HDAVB was still present in 40% of the patients who received PPM implantation for this indication. In conclusion, 40% of the patients who undergo CoreValve TAVI require PPM implantation after the procedure, with most cases (36%) associated with the development of postprocedural HDAVB. Baseline conduction abnormalities (right bundle branch block) and deep valve implantation (6 mm) independently predicted the development of HDAVB and the need for PPM implantation after CoreValve TAVI.

Aims Multi-detector computed tomography (MDCT) has emerged as an efficient tool for detection of obstructive coronary artery disease (CAD) and assessment of patients with acute chest pain. MDCT may detect premature, non-obstructive atherosclerotic lesions which otherwise would have not been detected upon functional cardiac imaging tests. Currently, there is scarce data regarding the clinical significance of these lesions. The purpose of this study was to prospectively analyse the intermediate term outcome of patients admitted to chest pain unit (CPU) with findings of non-obstructive CAD upon MDCT. Method and results The study comprised 444 patients admitted to the CPU at Sheba Medical Center and underwent evaluation by MDCT for complaints of acute chest pain. Studies were classified as: normal; non-obstructive CAD (defined as any narrowing

The Galilee study area, northern Israel, is at present an uplifted, steep continental margin that formed mainly during the Jurassic and has a large positive isostatic anomaly. Since the Jurassic, it was modified by several tectonomagmatic events, which this study attempts to define and classify by updating, reprocessing and reinterpreting gravity, aeromagnetic and geological data. The prominent Rehovot-Carmel N–S positive reduced-to-pole (RTP) magnetic anomaly caused by the Gevim Volcanics, as well as the coexisting Helez-Gaash high Bouguer gravity and the Pleshet low Bouguer gravity, represent the deep (>5 km) Permo-Triassic dominant horst and graben structure of Israel. The Jonah Ridge and Beirut high SW–NE RTP magnetic anomalies in the Levant basin delineate the Levant continental edge that is marked by a deeply buried horst covered by a Late Cretaceous volcanic complex. The Asher and Devora Jurassic volcanics appear to be responcible for the Atlit and Galilee negative magnetic anomalies and for significant negative gravity anomalies which became clear after removing gravity effect of the upper (post-Turonian) light density sediments from the observed gravity. The volcanics extend along a SW–NE belt parallel to the strike of the Moho. It is suggested here that the Carmel-Gilboa fault propagated during the Late Cretaceous from the Levant basin across the Galilee area southeastward to form the Azraq-Sirhan graben in Jordan. As such, it forms a right-step, en echelon, dextral strike-slip fault with associated tectonic basins of various shapes. During the Oligocene and before formation of the Dead Sea transform (DST), the reactivation of the Azraq-Sirhan graben was accompanied by tectonic driven rift propagation in the opposite direction, from Azraq-Sirhan to northwest. It dispersed into many faults and terminated ∼10 km west of the present DST. During the Miocene it propagated in the same direction and includes internal volcanic activity. The numerous Miocene-Pliocene volcanic centers on the margins of the DST indicate that the preferred pathway for magmas at that time was not within the deep basins of the DST.

We evaluated the role of p15(Ink4), a member of the INK4 family of CDK inhibitors on vascular smooth muscle cells (VSMCs) proliferation, cell cycle progression and intimal hyperplasia after stenting. Aortic VSMCs transduced with either adenovirus encoding for p15(Ink4) or β-galactosidase were assessed for DNA synthesis, cell cycle progression, and pRb phosphorylation. Rabbit carotid arteries were stented and treated with peri-adventitial delivery of saline or adenovirus encoding for p15(Ink4) or β-galactosidase. p15(Ink4) transgene and protein expression were evaluated at 24 h and 72 h, respectively. In-stent cell proliferation was evaluated by BrdU at day 7. Histomorphometric analysis of in-stent intimal hyperplasia was performed at 10 weeks. Human p15(Ink4) DNA was detected in transduced VSMCs at 24h. p15(Ink4) over-expression reduced VSMCs DNA synthesis by 60%. Cell cycle progression was inhibited, with a 30% increase in G1 population accompanied by inhibition of pRb phosphorylation. Human p15(Ink4) transgene was identified in transduced stented arteries but not in control arteries. p15(Ink4) immunostaining was increased and cell proliferation significantly reduced by 50% in p15(Ink4) transduced arteries. Intimal cross-sectional area (CSA) of p15(Ink4)-treated group was significantly lower than the β-gal treated and non-transduced groups (p=0.008). There were no differences in the intimal or medial inflammatory response between groups. p15(Ink4) over-expression blocks cell cycle progression leading to inhibition of VSMCs proliferation. Peri-adventitial delivery of p15(Ink4) significantly inhibits in-stent intimal hyperplasia.

Objectives: To assess whether visible angiographic complication is related to outcome in patients with elevated creatine phosphokinase (CK-MB) following percutaneous coronary intervention (PCI). Background: Elevated biomarkers following PCI are associated with increased incidence of adverse events but the absolute risk of such events is low. A more specific marker of risk is needed. Methods: Consecutive patients with elevated post-PCI CK-MB were divided into two groups according to presence (n = 115, 43%) or absence (n = 150, 57%) of an angiographic complication. A control group (n = 250) was randomly chosen from 2,403 patients undergoing PCI during the same period without CK-MB elevation. Major adverse cardiac events (MACE) were assessed at 30 days and 1 year. Results: Patients with an identifiable angiographic complication and elevated postprocedural CK-MB had significantly worse outcomes at 30 days and 1 year compared with biomarker positive patients without an identifiable complication and control patients (30 day MACE rate: 8% vs 0% vs 0.4%, respectively, p < 0.001; 1 year MACE rate: 26% vs 11% vs 11%, respectively, p = 0.002, all p-values for angiographic complication vs no angiographic complication and for angiographic complication vs control). Biomarker positive patients without identifiable angiographic complication had an excellent short and long term outcome, which was no different from biomarker negative patients (1 year MACE rate: 11% vs 11%, p = 0.53). Conclusion: Post-PCI patients without visible angiographic complications have an excellent short and long term outcome. These findings call into question the need for routine CK-MB monitoring after PCI in the absence of clinical symptoms or angiographic complication. © 2010 Wiley-Liss, Inc.

Introduction Myocardial hypoperfusion following percutaneous coronary intervention, termed “no-reflow”, may be initiated by distal coronary embolization. This study examined the effects of distal embolization on the extent and timing of inflammation and platelet activation in an experimental model of coronary no-reflow. Material and Methods A no-reflow model was established in 9 Yorkshire pigs by injecting incremental doses of biologically inert polystyrene microspheres into the left anterior descending artery every 20 minutes via a transit catheter. A control group included 3 pigs that received corresponding intra-coronary boluses of normal saline. At predefined time points, coronary sinus blood samples were drawn and immediately analyzed by flow cytometry analysis for a panel of white blood cell and platelet activation markers, and the inflammatory cytokine TNFα. Results No-reflow was achieved after delivery of 1,169,000 ± 303,000 (range: 680,000 to 2,600,000) microspheres. In the distal embolization group, there were significant increases above baseline values in polymorphonuclear-platelet aggregates (146%-218%), in monocyte-platelet aggregates (51%-94%) and in TNFα levels (54%-84%) at multiple time points prior to no- reflow (15% cumulative dose and higher). For Annexin A5, there was a significant increase at 52% of cumulative dose (177% above baseline). Controls only showed one significant increase above baseline value for polymorphonuclear-platelet aggregates at the time of the last injection. Conclusions Widespread activation of interacting inflammatory and coagulation pathways following microsphere embolization occurred prior to the onset of angiographic no-reflow. This activation pattern cannot be attributed to prolonged coronary sinus instrumentation. Interactions between white blood cells (polymorphonuclears and monocytes) and platelets likely play an important role in the pathogenesis of no-reflow following distal embolization and may represent important therapeutic targets.

This study synthesizes geological and geophysical evidence concerning the structure and character of the central and southern Jurassic Levant continental margin during Cretaceous–Tertiary time. From the beginning of the Cretaceous and until Cenomanian time, the Levant margin was strongly affected by extensional tectonics, cyclical igneous activity and rifting coupled with thermal and vertical fluctuations. It is suggested here that during the Senonian–Maastrichtian convergence of Afro-Arabia and the Mesotethys, and the Tauride part of Eurasia, the Herodotus basin oceanic crust subducted along the Eratosthenes Arc, below the short-lived abandoned Levant back-arc basin. Such a plate configuration assumes regional shear zones, as follows: (1) between the Eratosthenes Arc from the south and the Kyrenia Arc from the north: the NW–SE Carmel–Azraq–Sirhan fault system; (2) between the Sinai and the African plates: the Suez fault system; (3) between the Mesotethys and the African plates: the northern Egypt–Sinai–Negev west–east transversal fault system. Distinct tectonomagmatic quiescence between Late Maastrichtian and Late Eocene time allowed thermal relaxation and subsidence of the Levant margin until the apparent achievement of local isostatic compensation and the consequent development of the longest transgression over the Afro-Arabian ramp. Supplementary material: Details on the construction of the Bouguer gravity map are available at http://www.geolsoc.org.uk/SUP18404.

AIMS Perlecan is the major heparan sulfate proteoglycan in the arterial wall. Previous studies have suggested that perlecan is a potent inhibitor of smooth muscle cell (SMC) activity. Therefore, perlecan overexpression may serve as a therapeutic modality to prevent in-stent restenosis (ISR). We have investigated a novel compound (RUS3108), identified in a SMC based screen to induce perlecan synthesis in SMC. The aims of this study were to assess the in vitro effects of RUS3108 and the effects of RUS3108-eluting stents in preventing ISR. METHODS AND RESULTS Rabbit aortic SMC and bovine aortic endothelial cells (EC) were used in this study. Immunohistochemistry showed that RUS3108-treated SMC over-expressed perlecan indicating the drug effects. Furthermore, RUS3108 induced a SMC differentiated phenotype by SMembryonic staining. RUS3108 (1 microM) inhibited 3H-thymidine incorporation by >50%, which was completely reversed by a perlecan antibody. RUS3108 also inhibited SMC migration (Boyden chamber) and MMP-9 activity. In contrast, RUS3108 (100nM) modestly stimulated EC 3H-thymidine incorporation by 22% (p

Acute coronary syndrome (ACS) is associated with activation of platelets and the coagulation system which could influence the incidence of early stent thrombosis (EST). We aimed to determine the incidence and predictors of EST in patients undergoing coronary stenting during ACS.The study comprised 1202 consecutive patients, drawn from a nationwide ACS survey, who underwent coronary stenting during ACS and were followed up for 30 days. Early stent thrombosis was based on the Academic Research Consortium definition.Thirty patients (2.5%) sustained EST. The occurrence of EST in patients with unstable angina/non-ST-elevation myocardial infarction and ST-elevation myocardial infarction (STEMI) was 0.9% and 3.9%, respectively (P.05), and was even higher (5.2%) in STEMI patients who underwent primary percutaneous coronary intervention. On multivariate analysis, STEMI (OR 6.3, 95% CI 2.1-18, P = .0008), multivessel disease (OR 5.9, 95% CI 1.9-21, P = .003) and Killip class/=2 (OR 2.9, 95% CI 1.3-6.6, P = .008) were independent correlates of EST. The use of bare versus drug-eluting stents was not associated with any significant difference in EST.Patients presenting with STEMI who are hemodynamically unstable and have multivessel coronary disease undergoing coronary stenting during ACS, are at increased risk of EST.

Importance Dual anti-platelet therapy represents standard care for treating patients with ST-segment elevation myocardial infarction (STEMI). Ticagrelor is a direct-acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation. Objective To evaluate whether chewing a loading dose (LD) of ticagrelor, 180 mg, vs traditional oral administration of an equal dose enhances platelet inhibition at 30 minutes and 1 hour after LD administration in patients with STEMI. Design, Setting, and Participants A randomized clinical trial was conducted in adults aged 30 to 87 years from May to October 2016 in a large tertiary care center. Analyses were intention-to-treat. Interventions Fifty patients with STEMI were randomized to either chewing an LD of ticagrelor, 180 mg, or standard oral administration of an equal dose. Main Outcomes and Measures P2Y12 reaction units were evaluated using VerifyNow (Accumentrics) at baseline, 30 minutes, 1 hour, and 4 hours after LD. Results Baseline characteristics were similar in both groups. The mean (SD) of P2Y12 reaction units in the chewing group compared with the standard group at baseline, 30 minutes, 1 hour, and 4 hours after ticagrelor LD were 224 (33) vs 219 (44) (95% CI, −16.77 to 27.73; P = .26), 168 (78) vs 230 (69) (95% CI, −103.77 to −19.75; P = .003), 106 (90) vs 181 (89) (95% CI, −125.15 to −26.29; P = .005), and 43 (41) vs 51 (61) (95% CI, −36.34 to 21.14; P = .30), respectively. Platelet reactivity in the chewing group was significantly reduced by 24% at 30 minutes after LD (95% CI, 19.75 to 103.77; P = .001). The relative inhibition of platelet aggregation in the chewing vs the standard group were 51% vs 10% (95% CI, 13.69 to 67.67; P = .005) at 1 hour and 81% vs 76% (95% CI, −12.32 to 16.79; P = .24) at 4 hours, respectively. Major adverse cardiac and cardiovascular event rate at 30 days was low (4%) and occurred in 1 patient in each group (95% CI, 0.06 to 16.93; P > .99). Conclusions and Relevance Chewing an LD of ticagrelor, 180 mg, in patients with STEMI is feasible and facilitates better early platelet inhibition compared with a standard oral LD. Larger studies are warranted to see if our preliminary findings translate into clinical outcomes. Trial Registration clinicaltrials.gov Identifier:NCT02725099

We evaluated the effect and optimal dose of clopidogrel pretreatment in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PPCI). The study included 383 consecutive patients with ST-elevation myocardial infarction who had undergone PPCI and were prospectively followed up for a prespecified primary end point of recurrent acute coronary syndrome, stent thrombosis, congestive heart failure, and/or death at 30 days. Of these patients, 217 (57%) received clopidogrel loading before and 166 (43%) after PPCI. A similar number received low (300 mg) and high (600 mg) clopidogrel doses before and after PPCI. Clopidogrel loading before, compared with after, PPCI was associated with a lower incidence of the primary end point (21.7% vs 33.7%, p = 0.008). Clopidogrel pretreatment remained a significant predictor of the primary outcome after adjusting for potential confounders (odds ratio 0.54, 95% confidence interval 0.42 to 0.91). When patients were further stratified into 4 groups according to the timing and dosage of clopidogrel loading, the incidence of the primary outcome was 16% and 27% in those receiving 600 and 300 mg before and 28% and 39% in those receiving 600 and 300 mg after PPCI, respectively (p for trend

Ar/ 39 Ar and K-Ar ages of whole rock and mineral separates from the Mount Hermon region accurately constrain the time span of the first Early Cretaceous tectonomagmatic event (''Tayasir Volcanics''; C.V.-1) in northern Israel. The igneous activity started with shallow microgabbro intrusions within the Jurassic formations, dated to 140.9 � 1.6 Ma (Berriasian), and ended with explosive volcanism and lava flow sequences at 133.5 � 1.5 Ma (Hauterivian). The Cenomanian ''Carmel Volcanics'', which consist mainly of basic pyroclastic rocks with some lava flows, are exposed in the Mount Carmel - Umm el Fahm area and characterize the fourth Cretaceous tectonomagmatic event (C.V.-4) in the Levant region. This event is typified by four volcanic phases that dated to 99.0 � 1.0 Ma, 98.2 � 1.1 Ma, 96.7 � 0.5 Ma and 95.4 � 0.5 Ma. The five Cretaceous tectonomagmatic events are attributed to mantle plume activity and mark the initiation of a geodynamic process that controlled the evolution of the Levant region. Using the radio- metric-dated volcanic rock units as chronostratigraphic horizons for the Levant (northwestern Arabian plate) area enable improving the Berriasian - Turonian lithostratigraphic correlation along Israel and Lebanon, as well as defining two tectonostratigraphic megasequences. The first Berriasian-Barremian megasequence (140-125 m.y.) includes the Tayasir and Helez formations and the second, the Aptian- Turonian megasequence (125-89 m.y.), includes several formations consisting mainly of alternating quartz-arenitic continental sandstones in the south and mainly shallow marine carbonates in central and northern Israel.

Background and objectives The main limitation of primary PCI in acute MI is lack of tissue reperfusion due to distal embolization. We sought to examine the safety and feasibility of a manual thrombus aspiration device in patients undergoing primary PCI. Methods Seventy-eight consecutive patients with ST-elevation MI eligible for primary PCI were included. The device was used immediately after guidewire crossing only if a total occlusion (thrombolysis in myocardial infarction [TIMI] flow 0) existed or if a large filling defect was observed. End points were TIMI flow immediately after thrombus aspiration and at the end of procedure and ST resolution of more than 70%. Results Mean age was 59±12 years, and 79% of patients were males. Risk factor profile included smoking in 62%, diabetes in 21%, hypertension in 46%, and hyperlipidemia in 45%. The infarct-related artery was LAD in 42%, RCA in 36%, and LCX in 22%. Initial TIMI flow was 0 in 71%, I in 10%, and II/III in 19%. Immediately after aspiration, TIMI flow was II/III in 89% of patients and I in 9%. Direct stenting was performed in 73%. Final TIMI flow was III in 90%, II in 9%, and 0 in 1%. ST-segment resolution of more than 70% was observed in 76% of patients. No major device-related complications occurred. Conclusions Based on this preliminary data, manual thrombus aspiration using the Export device during primary PCI appears to be feasible and safe. The advantages over routine primary PCI should be further evaluated in randomized trials.

Background Diabetes mellitus (DM) and aortic stenosis (AS) are frequent findings in the elderly population. Data regarding the influence of DM on the outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) due to AS are limited. The aim of this study was to examine the impact of DM on TAVR outcomes. Methods We investigated 443 patients with severe AS undergoing TAVR. Subjects were divided into insulin-dependent diabetic mellitus (IDDM) patients (N = 44), non-dependent insulin diabetic mellitus (NIDDM) patients (N = 114) and non-diabetics (N = 285) of whom 31 (74 %), 86 (79 %) and 209 (76 %) respectively had trans-femoral TAVR. Peri-procedural complications and outcomes were recorded according to the Valve Academic Research Consortium-2 criteria. Results Patients with IDDM as well as NIDDM demonstrated similar complication rates compared with non-diabetic patients, except for acute kidney injury (AKI) grade 3 [4 (2 %) and 3 (3 %) vs. 1 (0.4 %) respectively, p = 0.032]. Kaplan–Meier survival analysis showed that DM, regardless of the type of treatment, was not associated with increased 2 years mortality (Log-rank p value 0.44). Multivariate cox regression analysis adjusted for age, gender, coronary artery disease, DM, AKI3, hypertension, chronic renal failure and peripheral vascular disease found that AKI3 was associated with increased risk of 2 years mortality [HR = 7.35, 95 % CI 2.16–25.07, p = 0.001] whereas female gender was found as a protective factor [HR = 0.47, 95 % CI 0.28–0.8, p = 0.005], and DM was not associated with increased risk. Conclusions Following TAVR, DM patients seem to have similar peri-procedural and mid-term outcomes compared with patients without DM, while IDDM patients seem to suffer greater incidence of AKI. Further research in larger cohorts of patients is needed to validate our results. Electronic supplementary material The online version of this article (doi:10.1186/s12933-015-0291-3) contains supplementary material, which is available to authorized users.

Intermediate- or low-risk patients with severe aortic stenosis were excluded from earlier transcatheter aortic valve implantation (TAVI) clinical trials; however, they are already being treated by TAVI despite a lack of data regarding the safety and efficacy in these patients. We aimed to assess the safety and efficacy of TAVI in patients at intermediate or low risk. Patients undergoing TAVI during 2008 to 2014 were included into a shared database (n = 1,327). Procedural outcomes were adjudicated according to Valve Academic Research Consortium 2 definitions. Patients were stratified according to their Society of Thoracic Surgeons (STS) score into 3 groups: high (STS ≥8, n = 223, 17%), intermediate (STS 4 to 8; n = 496, 38%), or low risk (STS

We present a case of an 83-year-old female who suffered from annular rupture with contained hematoma immediately after trans-apical implantation of balloon-expandable Sapien valve. The patient developed acute cardiogenic shock which resulted from an extrinsic compression of the left main coronary artery. We report the successful management of this complication.

The Syntax score (SS) is a helpful tool for determining the optimal revascularization strategy regarding coronary artery bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) in patients with complex coronary disease. While an association between higher SS and mortality was found for PCI patients, no such association was found for CABG patients.To assess whether the SS predicts late mortality in patients undergoing CABG in a real-world setting.The study included 406 consecutive patients referred for CABG over a 2 year period. Baseline and clinical characteristics were collected. Angiographic data SS were interpreted by an experienced angiographer. Patients were divided into three groups based on SS tertiles: low ≤ 21 (n = 205), intermediate 22-31 (n = 138), and high ≥ 32 (n = 63). Five year mortality was derived from the National Mortality Database.Compared with low SS, patients with intermediate and high scores were significantly older (P = 0.02), had lower left ventricular ejection fraction (64% vs. 52% and 48%, P0.001) and greater incidence of acute coronary syndrome, left main disease, presence of chronic total occlusion of the left anterior descending and/or right coronary artery, and a higher EuroSCORE (5% vs. 5% and 8%, P0.01). Patients with intermediate and high SS had higher 5 year mortality rates (18.1% and 19%, respectively) compared to patients with low score (9.8%, P = 0.04). On multivariate analysis, SS was not an independent predictor of late mortality.Patients with lower SS had lower mortality after CABG, which is attributable to lower baseline risk. SS is not independently predictive of late mortality in patients with multi-vessel coronary artery disease undergoing CABG.

Background The majority of transcatheter aortic valve implantation (TAVI) procedures are currently performed by percutaneous transfemoral approach. The potential contribution of the type of vascular closure device to the incidence of vascular complications is not clear. Aim To compare the efficacy of a Prostar XL- vs. Perclose ProGlide-based vascular closure strategy. Methods The ClOsure device iN TRansfemoral aOrtic vaLve implantation (CONTROL) multi-center study included 3138 consecutive percutaneous transfemoral TAVI patients, categorized according to vascular closure strategy: Prostar XL- (Prostar group) vs. Perclose ProGlide-based vascular closure strategy (ProGlide group). Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics. Results Propensity matching identified 944 well-matched patients (472 patient pairs). Composite primary end point of major vascular complications or in-hospital mortality occurred more frequently in Prostar group when compared with ProGlide group (9.5 vs. 5.1%, P = 0.016), and was driven by higher rates of major vascular complication (7.4 vs. 1.9%, P < 0.001) in the Prostar group. However, in-hospital mortality was similar between groups (4.9 vs. 3.5%, P = 0.2). Femoral artery stenosis occurred less frequently in the Prostar group (3.4 vs. 0.5%, P = 0.004), but overall, Prostar use was associated with higher rates of major bleeding (16.7 vs. 3.2%, P < 0.001), acute kidney injury (17.6 vs. 4.4%, P < 0.001) and with longer hospital stay (median 6 vs. 5 days, P = 0.007). Conclusions Prostar XL-based vascular closure in transfemoral TAVI procedures is associated with higher major vascular complication rates when compared with ProGlide; however, in-hospital mortality is similar with both devices.

A 3-D layered structure of the Levant and the southeastern Mediterranean lithospheric plates was constructed using interpretations of seismic measurements and borehole data. Structural maps of three principal interfaces, elevation, top basement and the Moho, were constructed for the area studied. This area includes the African, Sinai and Arabian plates, the Herodotus and the Levant marine basins and the Nile sedimentary cone. In addition, an isopach map of the Pliocene sediments, as well as the contemporaneous amount of denuded rock units, was prepared to enable setting up the structural map of the base Pliocene sediment. Variable density distributions are suggested for the sedimentary succession in accord with its composition and compaction. The spatial density distribution in the crystalline crust was calculated by weighting the thicknesses of the lower mafic and the upper felsic crustal layers, with densities of 2.9 g/cm 3 and 2.77 g/cm 3 , respectively. Results of the local (Airy) isostatic modeling with compensation on the Moho interface show significant deviations from the local isostasy and require variable density distribution in the upper mantle. Moving the compensation level to the base of the lithosphere (∼100 km depth) and adopting density variations in the mantle lithosphere yielded isostatic compensation (±200 m) over most of the area studied. The spatial pattern obtained of a density distribution with a range of ±0.05 g/cm 3 is supported by a regional heat flux. Simulations of the flexure (Vening Meinesz) isostasy related to the Pliocene to Recent sedimentary loading and unloading revealed concentric oscillatory negative and positive anomalies mostly related to the Nile sedimentary cone. Such anomalies may explain the rapid subsidence in the Levant Basin and the arching in central Israel, northern Sinai and Egypt during Pliocene–Recent times. Comparison between the observed (Bouguer) gravity and the calculated gravity for the constructed 3-D lithospheric structure, which has variable density distributions, provided a good match and an independent constraint for the large-scale structure suggested and confirmed an oceanic nature for the Levant Basin lithosphere. © 2006 Elsevier B.V. All rights reserved.

We evaluated the in-hospital and 1-year outcomes and predictors of admission heart failure in patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs) without previous heart failure. We analyzed 4,825 patients with NSTE-ACS without a history of congestive heart failure who were included in the multicenter Canadian ACS Registries. Patients in Killip's class II/III on admission (n = 559, 11.6%) were compared with patients in Killip's class I. Patients with heart failure on admission were older (72 [64, 79] vs 64 [54, 73] years, p0.0001), with higher baseline creatinine levels (96 vs 88 mmol/dl, p0.0001), more diabetes (32.2% vs 22.8%, p0.0001), hypertension (58% vs 52.4%, p = 0.014), previous myocardial infarction (MI; 38.9% vs 30.3%, p0.0001), previous stroke (13.5% vs 7.4%, p0.0001), and had more ST depression on admission (27.7% vs 17.3%, p0.0001). In-hospital treatment was similar except for a lower rate of aspirin therapy and fewer coronary interventions. Crude event rates were significantly higher in patients with heart failure (in-hospital death 3.6% vs 1.1%, p0.0001; death or MI 7.9% vs 4.7%, p = 0.0011; stroke 1.1% vs 0.4%, p = 0.03). One-year event rates were also higher in patients with heart failure (death 14.6% vs 4.4%, p0.0001; MI 9.3% vs 6.6%, p = 0.03; death or MI 21.5% vs 10.3%, p0.0001). Variables independently associated with heart failure were age (odds ratio 1.57, 95% confidence interval 1.43 to 1.73), diabetes mellitus (odds ratio 1.53, 95% confidence interval 1.24 to 1.89), admission ST depression (odds ratio 1.52, 95% confidence interval 1.22 to 1.90), previous MI, and baseline creatinine. Heart failure on admission was an independent predictor of in-hospital death, death or MI, and stroke and of 1-year death and death or MI. In conclusion, in patients with NSTE-ACS, heart failure on admission is associated with increased short- and long-term rates of death and MI.

This study sought to examine whether imaging of the atrioventricular (AV) membranous septum (MS) by computed tomography (CT) can be used to identify patient-specific anatomic risk of high-degree AV block and permanent pacemaker (PPM) implantation before transcatheter aortic valve implantation (TAVI) with self-expandable valves.MS length represents an anatomic surrogate of the distance between the aortic annulus and the bundle of His and may therefore be inversely related to the risk of conduction system abnormalities after TAVI.Seventy-three consecutive patients with severe aortic stenosis underwent contrast-enhanced CT before TAVI. The aortic annulus, aortic valve, and AV junction were assessed, and MS length was measured in the coronal view.In 13 patients (18%), high-degree AV block developed, and 21 patients (29%) received a PPM. Multivariable logistic regression analysis revealed MS length as the most powerful pre-procedural independent predictor of high-degree AV block (odds ratio [OR]: 1.35, 95% confidence interval [CI]: 1.1 to 1.7, p = 0.01) and PPM implantation (OR: 1.43, 95% CI: 1.1 to 1.8, p = 0.002). When taking into account pre- and post-procedural parameters, the difference between MS length and implantation depth emerged as the most powerful independent predictor of high-degree AV block (OR: 1.4, 95% CI: 1.2 to 1.7, p0.001), whereas the difference between MS length and implantation depth and calcification in the basal septum were the most powerful independent predictors of PPM implantation (OR: 1.39, 95% CI: 1.2 to 1.7, p0.001 and OR: 4.9, 95% CI: 1.2 to 20.5, p = 0.03; respectively).Short MS, insufficient difference between MS length and implantation depth, and the presence of calcification in the basal septum, factors that may all facilitate mechanical compression of the conduction tissue by the implanted valve, predict conduction abnormalities after TAVI with self-expandable valves. CT assessment of membranous septal anatomy provides unique pre-procedural information about the patient-specific propensity for the risk of AV block.

Ar/ 39 Ar and K-Ar ages of whole rock samples and kaersutite (amphibole) crystals obtained from basanite and tephrite flows, lava lake series and pyroclastic rocks in Makhtesh Ramon (central Negev, southern Israel) define a Late AptianeEarly Albian time span of the Cretaceous magmatic event (Ramon Volcanics) and the order of the local volcanic activity, which had only been partly resolved by stratigraphic relations. The igneous activity started with volcanic flows that originated from several centres between 116.4 G 3.4 Ma and 112.5 G 1 Ma, continued with a lava lake series at 110.3G 6.1 Ma and terminated by explosive activity at 108.8 G 1.2 Ma. The Late AptianeEarly Albian magmatic event is one of five events that are attributed to Cretaceous mantle plume activity and mark the termination of a geodynamic process involved in the evolution of the passive continental margin and the Levantine Basin of the Eastern Mediterranean. The Cretaceous plume head is postulated to be beneath northern Israel and the central Palmyrides (Syria), where fault-controlled depressions with volcanic fill of the first Cretaceous magmatic event were developed. Subsequent expansion of magmatic melts to more marginal areas (the Negev and the Coastal Range in Syria) resulted in the emplacement and eruption of igneous rocks during the second (Barremian) and third (AptianeAlbian, this paper) magmatic events, whereas sporadic and small volcanic eruptions of the fourth (Cenomanian) and fifth (Campanian) Cretaceous magmatic events were still active in the head area of the plume. The Late AptianeEarly Albian magmatic activity followed the differential uplifting and denudation of the central and southern Negev terrain, and the igneous rocks occupy a common stratigraphic interval bounded by continental formations. The lower boundary of this interval is set at the unconformable surface, which represents different levels of truncation, whereas the overlying formation covers all volcanic rocks and structures. The radiometric ages define the sedimentary gap and put constraints on the upper and lower age limits of the bounding sandstone formations that yielded only non-diagnostic fossils. The age of the volcanic interval matches the biostratigraphic data of a contemporaneous fossiliferous shallow marine intercalation (Deragot marine tongue) which occupies a similar stratigraphic position in the northern Negev. The extension of the Late AptianeEarly Albian marine invasion to the central and southern Negev was barred by the relative elevation of that terrain, which had been uplifted prior to the local volcanism and by the depositional slope. Whole rock basanite samples from the lower part of the lava lake series in Mount Arod yielded a 40 Ar/ 39 Ar age of 110.3 G 6.1 Ma. Since some samples studied from this series display a reverse magnetic polarity, and the whole series was cooled simultaneously, the age obtained represents the entire series as well as the reversal event. This exclusively apparent Early Albian reversal event within the long Cretaceous Normal Polarity Superchron (C34n) adds new data to the global magnetostratigraphy. 2005 Elsevier Ltd. All rights reserved.

Purpose Chronic total occlusions (CTO) remain a major limitation of percutaneous interventions. Procedural failure is usually due to the inability to cross the lesion with a guide wire. We have previously shown that local administration of a laboratory-grade collagenase followed by a 72-h waiting period may facilitate guide-wire crossing. The aim of the present study was to evaluate the efficacy and toxicity of a human-grade purified collagenase, suitable for clinical use, in facilitating guide-wire crossing in a rabbit model of femoral artery CTO. Methods and results A chronic total arterial occlusion was constructed in femoral arteries of New Zealand white rabbits. The local administration of purified collagenase solution (150 μg) via an over-the-wire balloon system was performed in 10 CTO. Guide-wire crossing was attempted after 24 h and was successful in all cases. Different doses (50–500 μg) were administered to an additional 17 rabbits to assess collagenase effects. Local subcutaneous bruising was observed at higher doses. Histological evaluation showed no damage to the arterial wall structure. Arterial extracts from collagenase-treated arteries showed increased MMP-2 and MMP-9 activities and higher levels of local MMP-1 and degraded collagen. Conclusions Local administration of a human-grade purified collagenase degrades collagen in CTO and is highly effective for the facilitation of guide-wire crossing in CTO.

Thrombophilia refers to series of acquired and inherited conditions that confer a tendency to thrombus formation. The exact relationship between thrombophilia and MI is not well established.To determine the prevalence of thrombophilia in young patients with their first MI and few conventional risk factors.We evaluated the baseline characteristics and the thrombophilia profile, including anti-cardiolipin antibodies, activated protein C resistance (APCR) with the factor V Leiden mutation, prothrombin G20210A mutation, protein C, protein S, and antithrombin-III levels, among 85 consecutive patients (50 year old) who were admitted to CCU with their first MI. Patients were divided into two groups: group A-patients withor =1 risk factor and group B-patients withor =2 risk factors.92% were male and 55% with anterior wall MI. Overall, the risk factor profile was: smoking in 60%, hyperlipidemia in 42%, positive family history in 29%, hypertension in 18%, diabetes mellitus in 13%, and obesity in 8%. Forty-seven percent of patients hador =1 risk factor (n=40, group A) and 53% hador =2 risk factors (n=45, group B). The prevalence of the prothrombin mutation was 15% in group A compared to 7% in group B (p=0.12). APCR secondary to a heterozygous genotype of factor V Leiden mutation was found in 20% in group A compared to 2% in group B (p0.01). Anti-cardiolipin antibodies were found in 16% in group A compared to 22% in group B (p=ns). Finally, we have found that the likelihood of identifying at least one thrombophilia marker was 50% in group A compared to 29% in group B (p=0.046).The likelihood to detect at least one thrombophilia marker in young patients with MI and few conventional risk factors is significantly high. Thrombophilia may contribute to the development of MI in this specific group of young patients.

Despite major advancements in the technology used for the percutaneous treatment of coronary artery disease, chronic total occlusions (CTOs) persist as a major challenge to the interventional cardiologist with relatively low success rates. CTOs are evident in 20% of patients undergoing cardiac catheterization and are responsible for the majority of cases that are referred to bypass surgery. There is growing evidence that patients may benefit from recanalization of a CTO by alleviation of angina, improving left ventricular function, and potentially long-term survival. The major obstacle to percutaneous recanalization of CTOs is the inability to cross the occlusion with coronary guidewires. Even when crossed, the operator has to deal with the exact location of the distal wire (e.g., dissection or true lumen) and the existence of relatively long lesion requiring multiple stents with high restenosis rates. New technologies for CTO revascularization have been focused mainly on a mechanical approach including specialized guidewires and more recently, specific devices using highly sophisticated technology such as laser guidewire, optical coherence reflectometry, and a blunt microdissection catheter. An alternate biological approach involves the local administration of enzymes such as plasminogen activators (urokinase) or collagenase, which can act locally to specifically degrade the collagen content of the CTO, thereby "softening" the occlusion and allowing easier guidewire crossing. In conclusion, CTOs emerge as a great technical challenge and are the focus of novel series of mechanical and biological approaches.

Background— This study was performed to assess whether oxidized low-density lipoprotein (OxLDL) levels are elevated after percutaneous coronary intervention (PCI). Methods and Results— Patients (n=141) with stable angina pectoris undergoing PCI had serial venous blood samples drawn before PCI, after PCI, and at 6 and 24 hours, 3 days, 1 week, and 1, 3, and 6 months. Plasma levels of OxLDL-E06, a measure of oxidized phospholipid (OxPL) content on apolipoprotein B-100 detected by antibody E06, lipoprotein(a) [Lp(a)], autoantibodies to malondialdehyde (MDA)-LDL and copper-oxidized LDL (Cu-OxLDL), and apolipoprotein B-100-immune complexes (apoB-IC) were measured. OxLDL-E06 and Lp(a) levels significantly increased immediately after PCI by 36% ( P P r =0.68, P Conclusions— PCI results in acute plasma increases of Lp(a) and OxPL and results in short-term and long-term immunologic responses to OxLDL. OxPL that are released or generated during PCI are transferred to Lp(a), suggesting that Lp(a) may contribute acutely to a protective innate immune response. In settings of enhanced oxidative stress and chronically elevated Lp(a) levels, the atherogenicity of Lp(a) may stem from its capacity as a carrier of proinflammatory oxidation byproducts.

To study the molecular characteristics of lens epithelial cells from patients with senile cataract by cDNA microarray technique. Lens epithelial cells adhering to anterior capsules taken during cataract surgery collected from 108 patients, aged 56−92 years (senile cataract group), were pooled. Pooled epithelial cells of normal, noncataractous lenses from one patient with ocular trauma, one patient with lens subluxation, and 25 cadaveric eyes, all under the age of 55 years, served as a control. Total RNA was extracted by conventional methods from the two groups of cells, and a fluorescent probe was prepared for each group. The probes were hybridized on 9700 known human cDNA clones. Hybridized clones were analysed using a scanning laser and the results were processed by GEMTools (Incyte Genomics) software. A total of 1827 clones hybridized with the two probes. Of these, 400 showed differences of more than two-fold in gene expression between the two probes. Relative to controls, gene expression in the senile cataract lenses was upregulated in 318 clones and downregulated in 82. Three genes-filensin, inwardly rectifying potassium channel (IRPC), and pigment epithelium-derived factor (PEDF) were strongly downregulated (by 41.3-, 6.8-, and 5.9-fold, respectively) in senile cataract. Cataractogenesis is associated with numerous changes in the genetic profile of the lens epithelial cells. Since filensin, IRPC, and PEDF genes are known to have important roles in the physiology and morphology of the transparent lens, substantial downregulation of their expression might contribute to the formation of senile cataract.

Percutaneous coronary interventions (PCIs) are often complicated by postprocedural myocardial necrosis as manifested by elevated cardiac markers.To assess the incidence and risk factors of elevated troponin-I (TnI) after PCI.We performed a retrospective analysis on 522 PCI cases over a 1-year period at a single center. An elevated postprocedural TnI (1.0 ng/ml) occurred in 213 patients (40.8%). Overall, glycoprotein (GP) IIb/IIIa inhibitors were used in 52% of cases. Baseline clinical characteristics were similar between the positive and the negative TnI groups. A univariate analysis revealed that patients with elevated TnI post-PCI had significantly more multivessel (28% vs. 15%, P = .001) and multilesion interventions (44% vs. 27%, P.0001). The lesions were longer, more often angulated and involving bifurcations, and more complex in the TnI-positive group. Stent use and number of stents was higher in the TnI-positive group, and longer inflation times (30 s) or higher inflation pressures (14 atm) were used more often in the TnI-positive group. GP IIb/IIIa inhibitor use was higher in the TnI-positive group (61% vs. 45%, P = .0007). After multivariable analysis, independent predictors of elevated TnI after PCI included multilesion intervention, lesion length, lesion angulation, and GP IIb/IIIa inhibitor use.TnI is elevated in approximately 40% of cases after PCI. TnI is more likely to be elevated after intervention on multiple lesions, angulated or long lesions.

Background Subacute stent thrombosis (SAT) is a dramatic complication of percutaneous coronary stenting occurring in 0.4–20% of cases depending on several angiographic and clinical variables. The role of postprocedural low molecular weight heparin (LMWH) in preventing early events after high-risk PCI is not well established. In this study we describe our experience with postprocedural LMWH in patients deemed to be at high risk of SAT. Methods Thirty-six patients who were treated with subcutaneous LMWH for at least 7 days after the intervention were identified from our database. All cineangiograms and charts were retrospectively reviewed to confirm the high-risk intervention properties. Thirty-day and long-term major adverse coronary events (MACEs) were documented in all patients. Results The most common indications for LMWH were the deployment of ≥3 consecutive stents, the presence of intracoronary thrombus or ulceration, poststenting residual stenosis, contraindication to aspirin or thienopyrideines, and persistent dissection. The majority of patients (61%) had ≥2 risk factors. Mean postprocedural treatment period was 12±3 days. At 30 days, none of the patients experienced a MACE including death, myocardial infarction, and repeat revascularization. No major bleeding occurred and one patient (2.7%) had a minor bleeding. At a mean follow-up of 31 months, MACE occurred in 17% of patients. Conclusions Postprocedural LMWH is safe and effective in preventing SAT in patients undergoing high-risk coronary intervention.

Patients with intractable angina pectoris due to end-stage coronary artery disease who are not amenable to conventional revascularization provide a therapeutic challenge. We describe the first published case of a young patient with intractable coronary artery disease that was successfully treated by endocardial cryotherapy.

Background— Chronic total occlusions (CTOs) are associated with significant angina, impaired left ventricular function, and worse long-term outcomes. Percutaneous coronary interventions in CTO are unsuccessful in up to 50% of cases, primarily because of inability to cross the lesion with a guide wire. Collagen is the predominant component of the atherosclerotic plaque. The objective of this study was to determine the efficacy and toxicity of local delivery of a collagen-degrading enzyme to facilitate guide wire crossing in CTO. Methods and Results— Type IA collagenase (100 or 450 μg) or placebo was locally administered to 45 CTOs in a rabbit femoral artery model. Mean occlusion duration was 16±5 weeks. Attempts to cross the CTO (mean length, 28±9 mm) with conventional guide wires were assessed at 72 hours after treatment. An additional 3 arteries per group were assessed for collagenase effects at 24 hours after treatment. Successful guide wire crossings were significantly higher in collagenase-treated arteries (13 of 21, 62%) than in placebo-treated arteries (7 of 24, 29%) ( P =0.028). No adverse effects on arterial structure were observed in collagenase-treated arteries. At 24 hours, collagenase-treated arteries demonstrated increased collagenase protein, gelatinase activity, and collagen fragments. Conclusions— Local delivery of collagenase can safely facilitate guide wire crossing of CTO. This novel approach could lead to higher percutaneous coronary intervention success rates in CTO.

40 Ar/ 39 Ar dating. Isr. J. Earth Sci. 52: 77‐95. Vents (diatremes) filled with volcaniclastic breccia cut across Lower Cretaceous formations and the underlying Cambrian strata in the northern Timna Valley. The vents are the result of an ascending gabbroic intrusion interacting with groundwater, breaching the surface atop the Avrona Formation. A small plug of microgabbro, which intrudes the Cambrian dolomites near one of the volcaniclastic remnants, belongs to the same event. The volcaniclastic fill consists of hetrogeneous fall-back tephra and epiclastic debris of partly altered volcanic and sedimentary clasts of various sizes, and dispersed xenoliths and xenocrysts. 40 Ar/ 39 Ar and K/Ar analyses of three biotite crystals and one hornblende crystal from a single vent (Tamar) yield a weighted average age of 108.4 ± 1.7 Ma (late Early Albian). This age also marks the boundary between the Avrona and Samar formations, constraining their ages. Contemporaneous exposures of volcanic rocks, crossing or overlying strata equivalent to the Avrona Formation and terminating below the Samar equivalent, occur also in Makhtesh Ramon 90 km to the north. These volcanic and volcaniclastic occurrences constitute an important marker for correlation of the Lower Cretaceous clastic sequence in the Negev.

SummaryThe fibrinolytic system is closely related to several processes that are involved in restenosis. We previously showed that low PAI-1 plasma levels predicted restenosis. Recently, a different fibrinolytic inhibitor, TAFI, has been described. The aims of this study were to evaluate the relationship between pre-procedural plasma levels of TAFI and late angiographic restenosis and the interaction between TAFI and PAI-1. We prospectively studied 159 patients with stable angina who underwent successful elective angioplasty or stenting of de novo native coronary artery lesions. TAFI and PAI-1 antigen levels were measured in plasma samples drawn before the procedure. Follow-up coronary angiography was performed in 92% of patients. There was a significant correlation between pre-procedural TAFI levels and 6-month % diameter stenosis (DS) (r = 0.21; p = 0.013). The overall angiographic restenosis rate (DS>50%) was 31%. Pre-procedural TAFI levels were significantly higher in patients with restenosis (108 ± 33% versus 94±30%, p = 0.011). Restenosis rates for patients in the upper tertile of TAFI levels were 2-fold higher than for those in the lowest tertile (45% versus 22%; p = 0.016). A combination of high TAFI and low PAI-1 levels identified patients at the highest risk of restenosis (53%) compared to 14% in patients with low TAFI and high PAI-1 levels; p = 0.027. In conclusion, pre-procedural plasma TAFI antigen levels identify patients at increased risk for restenosis after PCI.

Young women are usually protected against coronary artery disease due to hormonal and risk-factor profile. Previous studies have suggested poorer outcome in women hospitalized with acute coronary syndrome as compared with men. However, when adjusted for age and other risk factors, this difference does not remain significant. We compared the risk profile and outcome between young (≤55 years) women and men admitted with acute coronary syndrome.We analyzed clinical characteristics, management strategies, and outcomes of men and women ≤55 years of age enrolled in the biennial Acute Coronary Syndrome Israeli Surveys between 2000 and 2013.Among 11,536 patients enrolled, 3949 (34%) were ≤55 years old (407 women, 3542 men). Women were slightly older (48.9 ± 5.7 vs 48.3 ± 5.5, P = .007) and suffered more from diabetes (34% vs 24%) and hypertension (47% vs 37%, P.001 for both). Rates of prior myocardial infarction were high in both sexes (18% vs 21%). Women presented less often with ST-elevation myocardial infarction (50% vs 57%, P = .007) and with typical chest pain (73% vs 80%, P = .004), and had higher rates of Global Registry of Acute Coronary Events (GRACE) score ≥140 (19% vs 12%, P = .007). After adjustment for GRACE score, diabetes, and enrollment year, women had a lower likelihood to undergo coronary angiography during hospitalization (odds ratio 0.6, P = .007). Female sex was independently associated with higher risk of in-hospital mortality (hazard ratio [HR] 4.1; 95% confidence interval [CI], 1.15-14.0), 30-day major adverse cardiac and cerebral events (HR 2.1; 95% CI, 1.31-3.36), and 5-year mortality (HR 1.96; 95% CI, 1.3-2.8).Young women admitted with acute coronary syndrome are a unique high-risk group that presents a diagnostic challenge for clinicians. Women receive less invasive therapy during hospitalization and have worse in-hospital and long-term outcomes.

Late Cretaceous volcanism in northern Israel is represented by basaltic pyroclastics and lavas at two adjacent localities at Mount Carmel and the Umm el Fahm area. Four Cenomanian and one Senonian volcanic intercalation occur in the marine succession. These volcanic rocks were dated by the 40 Ar/ 39 Ar and K‐Ar techniques using whole rock, amphibole megacrysts, and plagioclase fractions. Paleomagnetic measurements were performed on the Senonian pyroclastics. Amphibole from the oldest Cenomanian volcanic unit in Mount Carmel (the Kerem Maharal pyroclastics, at the base of the Chalk Complex) yielded an age of 97.1 ± 1.7 Ma. The penultimate Cenomanian volcanic unit in Mount Carmel (basalt at Nahal Raqefet and Muhraqa) yielded a whole-rock age of 96.7 ± 0.5 Ma. The youngest Cenomanian volcanic intercalation in the Umm el Fahm area (basalt at Me-Ammi) yielded a whole-rock age of 95.4 ± 0.5 Ma. Amphiboles from the Senonian Bat Shelomo pyroclastics, the youngest volcanic unit in the area, yielded an age of 82.0 ± 1.3 Ma. Three conclusions may be drawn from our new radiometric ages: (1) The major volcanic events operated synchronously at Mount Carmel and the Umm el Fahm area. (2) The chalk complex of Mount Carmel and the Deir Hanna Formation in the Umm el Fahm area are stratigraphically correlated. (3) The new radiometric results agree with biostratigraphically-derived ages, but provide better time constraints for the lithostratigraphic units. The data help to settle previous correlation controversies: the Albian‐Cenomanian boundary is set below the top of the Yagur Formation, and the Cenomanian‐Turonian boundary, above the base of the Muhraqa Formation.

Background: Rapid ventricular pacing (RVP) is frequently performed during transcatheter aortic valve replacement (TAVR) in order to temporarily reduce cardiac output. The clinical impact of these hypotensive episodes is unknown. Our aim was to assess correlation between RVP, its duration, and