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Background— Lack of high-fidelity simultaneous measurements of pressure and flow velocity distal to a coronary artery stenosis has hampered the study of stenosis pressure drop–velocity (ΔP-v) relationships in patients. Methods and Results— A novel 0.014-inch dual-sensor (pressure and Doppler velocity) guidewire was used in 15 coronary lesions to obtain per-beat averages of pressure drop and velocity after an intracoronary bolus of adenosine. ΔP-v relations from resting to maximal hyperemic velocity were constructed before and after stepwise executed percutaneous coronary intervention (PCI). Before PCI, half of the ΔP-v relations revealed the presence of a compliant stenosis, which was stabilized by angioplasty. Fractional flow reserve (FFR), coronary flow reserve (CFVR), and velocity-based indices of stenosis resistance (h-SRv) and microvascular resistance (h-MRv) at maximal hyperemia were compared. Stepwise PCI significantly lowered h-SRv, with an initial marked reduction in hyperemic pressure drop followed by further gains in velocity. A concomitant significant reduction of h-MRv accounted for half of the gain in velocity after PCI. The average magnitude of absolute incremental hemodynamic changes was highest for h-SRv (56.8±39.2%) compared with CFVR (35.3±34.5%, P P Conclusions— ΔP-v relations comprehensively visualize improvements in coronary hemodynamics after PCI. h-SRv is a powerful and sensitive descriptor of the functional gain achieved by PCI, combining information about both pressure gradient and velocity, which are oppositely affected by PCI. Simultaneous assessment of stenosis and microvascular resistance may provide a valuable tool for guidance of PCI.

Studies of myocardial ischemia-reperfusion (MI-R) in the mouse can be accomplished by use of reversible ligation of the left interventricular branch artery (LIB). To study interactions of coagulation, inflammation, and reperfusion injury, the model should not be influenced by effects of the surgery. In existing closed-thorax mouse models, the release of inflammatory factors attributable to surgical intervention could be separated from the release resulting from induction of MI-R. In these models, the final myocardial injury was induced by reversible closure of the LIB several days after preparative surgery that included median thoracotomy. In an attempt to develop a less invasive procedure to approach the LIB, we replaced median thoracotomy with lateral thoracotomy. After this procedure, body weight was regained within four days, and on days 9 to 11 after the preparative surgery, cytokine values were back to baseline. During one hour of ischemia, mean arterial pressure (MAP) remained at 78 +/- 2 mmHg. After induction of reperfusion, MAP was 67 +/- 4 mmHg, indicating better perfusion pressure of myocardial tissue at the microcirculatory level than that in simple open-thorax models. Electrocardiographic recording revealed transient ST elevation indicating reversible transmural ischemia and reperfusion. Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining visualized the extent of area of infarction (AOI) and area at risk (AAR). The procedure-related mortality was 13%, which compared well with published data from median thoracotomy studies. We conclude that our new model provides stable near-physiologic hemodynamics and allows study of the inflammatory response resulting from MI-R, with low procedure-related mortality.

PURPOSE: To assess the prognostic value of markers of inflammation for rule-out purposes in patients admitted to the emergency department with troponin T-negative chest pain. METHODS: Patients presenting to the emergency department within 6 hours of symptom onset and who had a normal or nondiagnostic electrocardiogram were eligible. The standard rule-out protocol, which included serial creatine kinase and creatine kinase-MB measurements, was applied, and markers of inflammation (C-reactive protein, erythrocyte sedimentation rate, and total white blood cell count and differential count) were measured. The study group comprised patients with negative serial troponin T results ( 0.3 mg/dL) was associated with future clinical events (hazard risk [HR] = 4.5; 95% confidence interval [CI]: 1.2 to 17.0; P = 0.03), as was a positive test (>13 mm/h) for erythrocyte sedimentation rate (HR = 5.6; 95% CI: 1.5 to 22.2; P = 0.01). Patients with positive results for both tests were at highest risk of clinical events (9.3%) compared with patients with other combinations of test results (1.1% to 2.1%; HR 7.5; 95% CI: 2.2 to 25.5; P = 0.001). CONCLUSION: The combination of C-reactive protein and erythrocyte sedimentation rate had prognostic value in patients with troponin T-negative chest pain and a normal or nondiagnostic electrocardiogram in whom unstable coronary artery disease was ruled out. (C) 2003 by Excerpta Medica Inc

PURPOSE: We investigated the associations between baseline C-reactive protein levels in patients undergoing percutaneous coronary angioplasty and death, nonfatal myocardial infarction, and repeat revascularization during 14 months of follow-up. METHODS: In a single-center, prospective, cohort study, plasma levels of C-reactive protein were measured in 1458 consecutive patients undergoing elective or urgent coronary angioplasty. Patients were followed at 12 to 14 months for the occurrence of death, nonfatal myocardial infarction, and repeat revascularization. RESULTS: The incidence of death or myocardial infarction was 6.1% (44/716) in patients with an increased C-reactive protein level (>3 mg/L) and 1.5% (11/742) in patients with a normal level (relative risk [RR] = 4.4; 95% confidence interval (Cl]: 2.2 to 8.5; P

PURPOSE: Patients with unstable coronary syndromes often have complex morphology of coronary stenoses at angiography. We evaluated the association between qualitative assessment of Coronary stenoses and plaque inflammation determined by immunohistochemistry. METHODS: A total of 79 patients with unstable (n = 46) or stable angina (n = 33) underwent directional coronary atherectomy for culprit lesions. Qualitative analysis of coronary angiograms was performed using a modified Ambrose classification. Coronary lesions were categorized as either simple (concentric and eccentric type 1, n = 29) or complex (eccentric type 11 and multiple irregularities, n = 50). Cryostat sections of retrieved atherosclerotic specimens were stained immunohistochemically with monoclonal antibodies, a-actin (smooth muscle cells), CD68 (macrophages), and CD3 (T lymphocytes). The extent of atherosclerotic inflammation within each coronary lesion was determined by the percentage of immunopositive macrophages per total tissue area (including smooth muscle cells) and the number of T lymphocytes per mm(2). RESULTS: The mean (+/- SD) percentage of macrophages in atherectomy specimens from patients with unstable angina was greater than in specimens from patients with stable angina (21% +/- 14% vs. 13% +/- 10%, P = 0.01); similar results were seen when complex coronary lesions were compared with simple lesions (23% +/- 13% vs. 9% +/- 8%, P

OBJECTIVES We prospectively studied the prognostic value of predischarge dobutamine stress echocardiography (I)SE) in low-risk chest pain patients with a normal or nondiagnostic electrocardiogram (ECG) and a negative serial troponin T. BACKGROUND Noninvasive stress testing is recommended before discharge or within 72 h in patients with low-risk chest pain. The prognostic value of immediate DSE has not been studied in a blinded, prospective fashion. METHODS Patients presenting at the emergency room within 6 h of symptom onset and a normal or nondiagnostic ECG were eligible. Dobutamine stress echocardiography was performed after unstable coronary artery disease was ruled out by a standard rule-out protocol and a negative serial troponin T; the occurrence of any new wall motion abnormality was considered positive. Results were kept blinded. End points were cardiac death, myocardial infarction, rehospitalization for unstable angina or revascularization. RESULTS In total, 377 patients were included. There were 2 deaths, 2 myocardial infarctions, 8 rehospitalization for unstable angina, and 10 revascularizations at six-month follow-up. The end points occurred in 8/26 (30.8%) patients with a positive versus 14/351 (4.0%) patients with a negative DSE (odds ratio, 10.7; 95% confidence interval, 4.0 to 28.8; p

We previously reported promising outcomes after treatment of coronary bifurcation lesions with the Tryton Side Branch Stent™ in more than 900 patients. Surprisingly, acute coronary syndrome (ACS) as percutaneous coronary intervention (PCI) indication did not predict for adverse outcomes compared

Near-physiologic hemodynamic conditions for several hours were needed to study cardiovascular physiology in a murine model. We compared two commonly used anesthetic treatments, urethane alpha-chloralose (U-alphaCh; 968 mg U and 65 mg alphaCh/kg) and 2,2,2-tribromoethanol (TBE; 435 mg/kg) and fentanyl fluanisone midazolam (FFM; 3.313 mg fentanyl, 104.8 mg fluanisone, and 52.42 mg midazolam/kg) with respect to mean arterial blood pressure (MAP) and heart rate (HR) for 100 min at similar levels of surgical anesthesia. Assessed every 10 to 15 min, the U-alphaCh+TBE group maintained a significantly (P0.001) lower mean MAP (49 4 mmHg) than did the FFM group (78 5 mmHg). Mean HR in the U-alphaCh+TBE group significantly (P0.001) increased from 308 34 bpm at the beginning to 477 43 bpm at the end of the experiment. In comparison, the FFM group showed a stable HR of 431 37 bpm. The MAP and HR of the U-alphaCh+TBE group were extremely unstable, with sudden and unpredictable changes in MAP when examined at 1-min intervals. The results of our study show that U-alphaCh+TBE anesthesia should not be used in murine models in which stable, near-physiologic hemodynamics are needed for cardiovascular studies.

Background — Both coronary blood flow velocity reserve (CFVR) and myocardial fractional flow reserve (FFR) are used to evaluate the hemodynamic severity of coronary lesions. However, discordant results between CFVR and FFR have been observed in 25% to 30% of intermediate coronary lesions. An index of stenosis resistance based on a combination of intracoronary pressure and flow velocity may improve the assessment of functional coronary lesion severity. Methods and Results — Single photon emission computed tomography (SPECT) was performed in 151 patients with angina to determine reversible perfusion defects within one-week before cardiac catheterization. Coronary pressure and flow velocity was measured distal to 181 single coronary lesions with a mean diameter stenosis of 56% (range: 32% to 85%). Maximum hyperemia was induced by 15 to 20 μg IC adenosine to determine CFVR, FFR, and the hyperemic stenosis resistance index (h-SRv), defined as the ratio of hyperemic stenosis pressure gradient (mean aorta pressure-mean distal pressure) and hyperemic average peak-flow velocity. Receiver-operating-characteristic curves of CFVR, FFR, and h-SRv were calculated to evaluate the predictive value for presence of reversible perfusion defects on SPECT with the use of the area under curve (AUC). The AUC was significantly higher for h-SRv (0.90±0.03) compared with those for CFVR (0.80±0.04; P =0.024) and FFR (0.82±0.03; P =0.018), respectively. Agreement with SPECT was particularly higher (73%) than for CFVR (49%, P =0.022) or FFR (51%, P =0.037) in the group of lesions showing discordant results between CFVR and FFR Conclusion — These results indicate that hyperemic stenosis resistance index is a more powerful predictor of reversible perfusion defects than CFVR or FFR.

Patients with non-ST-elevation myocardial infarction (NSTEMI) and three-vessel or left main coronary disease (3VD/LMD) have a high risk of long-term mortality when treated with a medical management strategy (MMS) compared with revascularization. We evaluated patterns of use and patient features across United States hospitals designated by MMS for NSTEMI patients with 3VD/LMD included in the ACTION Registry-GWTG from 2007-2012. A total of 42,535 patients without prior bypass surgery were found to have 3VD (≥50% stenosis in all major coronary vessels) or LMD (≥50% lesion) during in-hospital angiography at 423 hospitals with percutaneous and surgical revascularization capabilities. Hospitals (n = 316) with an adequate volume (≥25 NSTEMI patients treated) were stratified into tertiles defined by use of MMS; differences in patient characteristics and outcomes were analyzed. The proportion of NSTEMI patients treated with MMS at all hospitals varied from 16% to 19% each quarter and did not change significantly from 2007 to 2012 (P trend = .11). Among hospitals with adequate volume, the proportion of patients treated with MMS also varied widely (median 17.1%, range: 0.0-44.8%, P < .0001). Patient baseline characteristics, predicted mortality risk, actual in-hospital mortality rates, and discharge treatments were similar across hospital tertiles. Close to 20% of patients with NSTEMI and 3VD/LMD identified during in-hospital angiography are treated with MMS without revascularization in contemporary practice. Since the use of MMS varies widely across hospitals despite a relatively similar hospital-level case mix, these findings suggest that there is no standard threshold for the use of revascularization in NSTEMI patients with 3VD/LMD

An increasing body of evidence demonstrates that the acute coronary syndromes share a common pathophysiological background. New biochemical markers, and in particular cardiac troponins, are now available for risk stratification also in patients with minor myocardial damage. There is a linear relationship between the serum level of troponins and the risk of major cardiac events. However, in patients with normal cardiac troponins, the measurement of C-Reactive Protein (CRP) may add further information: in fact, an increased CRP is associated with an adverse outcome independent of an increased troponin. The time course of CRP and cardiac troponin elevation after the onset of myocardial damage may be one of the reasons of the independent prognostic value of the two markers.

Patients presenting with acute or rapid onset of ischemic chest pain may be diagnosed on admission as having acute coronary syndrome (ACS). Despite the heterogeneous nature of the disease and the wide spectrum of signs and symptoms, ACS is a working diagnosis that implies a common pathophysiology: damage of the atherosclerotic vessel wall, usually in the form of rupture of a thin-cap-fibro-atheroma or vulnerable plaque, intimal dissection or endothelial denudation, with superimposed intracoronary thrombus formation resulting in a reduction in bloodflow to the myocardium. On the basis of the standard 12-lead electrocardiogram on admission, we generally distinguish between patients with ST-segment elevation myocardial infarction (STEMI) who have complete occlusion of an epicardial coronary artery requiring immediate reperfusion therapy, and patients with non-STEMI ACS (NSTEACS) in whom the coronary artery is usually not completely occluded but there is reduction in blood flow, causing ischemia. In patients with STEMI, immediate reperfusion therapy, if possible with primary percutaneous coronary intervention in dedicated centers, is now the recommended approach. In patients with NSTEACS, initial anti-ischemic and anti-thrombotic medical therapy may reduce intra-coronary thrombus burden and improve coronary flow to such an extent that ischemia is completely alleviated. Medically stabilized patients may undergo ischemia detection with exercise testing at a later timepoint. However, for many years there has been fierce debate whether revascularization therapy or an early invasive—or aggressive—approach may be beneficial in patients with NSTEACS. Large registries have shown diverging results, although most studies have suggested that revascularization is associated with better clinical outcome.

In recent years rapid analytical techniques have been developed which allow accurate measurement of biochemical serum markers useful for the detection of early myocardial damage and acute myocardial infarction (AMI). Early diagnosis of AMI is likely to improve patient management and reduce complications. The availability of sensitive biochemical markers may result in the identification of low-risk patients and allow for early triage and rational use of Coronary Care Unit (CCU) beds. The potential clinical implications of rapid and accurate new assays are obvious and have triggered great interest. This is reflected by the large number of reports on the early diagnostic value of biochemical markers such as myoglobin [1–3], CK-MB mass [4,5],CK-isoforms [6], troponin T (TnT) [7–9], troponin I (TnI) [10,11] and fatty acid binding protein (FABP) [12]. At least partially, this interest may be “industry-driven” and for practically every biochemical marker, assays are currently available from different manufacturers. The interest is also driven by health economics and managed-care programs. For example in the United States health maintenance organizations (HMOs) may refuse the reimbursement of costs for patients “wrongly” admitted to CCU [13]. Growing interest in the novel biochemical markers is also driven by the obvious implications of the early and accurate diagnosis of myocardial damage. However, the advent of a large number of these markers has raised a series of practical issues. With the large choice of novel markers available, it is difficult for the treating physician to decide what marker(s) to use or even what strategy is appropriate for risk stratification and management of acute chest pain patients. The focus of this chapter will be on the role of biochemical markers in the detection or exclusion of myocardial damage in chest pain patients and the possible implications for triage and patient management in the first 24 hours from the onset of chest pain.

The ABSORBTM bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, CA, USA) is a resorbable polymeric scaffold that provides temporary scaffolding and everolimus drug delivery. The resorption of the BVS potentially overcomes the limitations of metallic stents. There is limited data on

Basal stenosis resistance index (BSR) is a novel adenosine–free index with a diagnostic accuracy for myocardial ischemia on perfusion scintigraphy mirroring fractional flow reserve (FFR). However, its diagnostic accuracy for myocardial ischemia identified by FFR is unknown, and the diagnostic

Background Ruling out acute myocardial infarction (AMI) on the basis of rapid assays for cardiac markers will allow early triage of patients and cost-effective use of available coronary care facilities. Methods and Results We studied the value of myoglobin, creatine kinase (CK)–MB mass , and troponin T in ruling out an AMI in the emergency room in 309 consecutive patients presenting with chest pain. The gold standard for AMI was the combination of history, ECG, and a typical curve of the CK-MB activity (CK-MB act ). Myoglobin was the earliest marker, and its negative predictive value (NPV) was significantly higher than for CK-MB mass and troponin T from 3 to 6 hours after the onset of symptoms (myoglobin versus CK-MB mass , P P mass reached 95% 7 hours after the onset of symptoms. Troponin T was not an early marker for ruling out AMI, and NPV changed over time, together with CK-MB act . The early NPV was higher in a subgroup of patients with a low probability of the presence of AMI for the three markers. Cardiac markers rise earlier in patients with large infarcts than in patients with small infarcts as indicated by the cumulative proportion of the marker above the upper reference limit at each time point (myoglobin, P =.04; CK-MB mass , P =.013; troponin T, P =.016). Conclusions For ruling out AMI in the emergency room, myoglobin is a better marker than CK-MB mass or troponin T from 3 until 6 hours after the onset of symptoms, but the maximal NPV reaches only 89%. At 7 hours, the NPV of CK-MB mass is 95%. The test characteristics are influenced by the probability of the presence of AMI in the patients studied and by the size of their AMI. Infarct size of AMI patients should be reported in studies evaluating cardiac markers.

Objective To evaluate gender differences in the prognostic value of renal function for mortality in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). Design Prospective single-center cohort. Setting Single tertiary referral center in Amsterdam, The Netherlands. Patients consecutive STEMI patients undergoing PPCI (1412 men and 558 women). Main outcome measure The authors calculated adjusted HRs for 3-year all-cause mortality according to the presence of a reduced renal function (estimated glomerular filtration rate, Article summary Article focus To evaluate gender differences in the prognostic value of renal function in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention. Key message Renal dysfunction has prognostic significance for mortality in both male and female patients. Strengths and limitations of this study Renal function was routinely measured at admission in a large tertiary referral center. Single-center cohort and information on the cause of death was not available.

A 68-year-old woman was treated for diffuse in-stent restenosis 5 months after implantation of a 13-mm Multilink stent (Guidant) in the proximal segment of the right coronary artery (Figure 1A). Debulking of the in-stent restenotic lesion was performed using directional coronary atherectomy (DCA) followed by adjunctive balloon angioplasty (Figure 1B). Six months after atherectomy, the patient was asymptomatic and …

The introduction of the ABSORB bioresorbable vascular scaffold (BVS) provides a new tool for stenting in interventional cardiology. Initially, relatively simple coronary artery lesions were treated with this novel device; nowadays, we are gaining clinical experience when treating a wide variety of lesions with the ABSORB BVS, including bifurcation lesions. Unfortunately, data are limited in terms of the use of the ABSORB BVS in coronary bifurcation lesions, so little is known about the safety and feasibility of these procedures. Bench testing and case reports showed that single provisional scaffold placement is feasible with fenestration of the scaffold towards the side branch and sequential non-compliant balloon inflation in the side and main branches. However, no prospective randomised clinical data with optical coherence tomography (OCT) imaging for different bifurcation stenting techniques are available. Based on the available data and our own experience we would recommend the use of the provisional single scaffold technique and only to fenestrate the scaffold if a severely pinched ostium combined with impaired flow seen on angiogram.

Background: Plaque disruption with superimposed thrombus is the predominant mechanism responsible for the onset of acute coronary syndromes. Studies have shown that plaque disruption and thrombotic occlusion are frequently separated in time. We established the histopathological characteristics of material aspirated during primary percutaneous coronary intervention (PCI) in a large consecutive ST-elevation myocardial infarction (STEMI) population. Methodology/Principal Findings: Thrombus aspiration during primary PCI was performed in 1,362 STEMI patients. Thrombus age was classified as fresh (5 day). Further, the presence of plaque was documented. The histopathological findings were related to the clinical, angiographic, and procedural characteristics. Material could be aspirated in 1,009 patients (74%). Components of plaque were found in 395 of these patients (39%). Fresh thrombus was found in 577 of 959 patients (60%) compared to 382 patients (40%) with lytic or organized thrombi. Distal embolization was present in 21% of patients with lytic thrombus compared to 12% and 15% of patients with fresh or organized thrombus. Conclusions/Significance: Material could be obtained in 74% of STEMI patients treated with thrombus aspiration during primary PCI. In 40% of patients thrombus age is older than 24 h, indicating that plaque disruption and thrombus formation occur significantly earlier than the onset of symptoms in many patients

We thank Dr Ikeda et al. for their comments on our paper. The focus of our paper was the relationship between activation of inflammation and coagulation, as these are interrelated by the possible role of IL-6 and IL-8. The findings of Ikeda et al. concerning simultaneous elevation of coronary sinus IL-6 and von Willebrand factor is very interesting in this respect. Although cellular components of the vascular tissue, such as the endothelium, can produce IL-6, it was also shown earlier that cardiac myocytes themselves are capable of producing IL-6, especially in the setting of ischaemia/reperfusion [1]. Whether in the setting …

The protective effect of rBPI23on the circulatory changes induced by experimental endotoxemia in humans was tested in a controlled blinded crossover study. Eight healthy male volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg) and concurrently received either rBPI23(1 mg/kg) or placebo. Hemodynamic parameters were obtained non-invasively over a period of twelve hours by means of M-mode-, Twodimensional- and Doppler Echocardiography. Blood Pressure was recorded using a Dynamap. rBPl23significantly reduced endotoxin-induced increase in Heartrate (85 ± 5 versus 67 ± 5 Beat/min, P = 00078). Cardiac Index (3.98 ± 0.25 versus 3.28 ± 0.27 L/min/m2, P = 00156), and Maximal Velocity in the Left Ventricular Outflow Tract (1.26 ± 0.07 versus 1.09 ± 0.05 m/sec,P l 0.05). rBPI23diminished the endotoxin-induced decrease in Systemic Vascular Resistance (1633 ± 79 versus 2051 ± 134 dyne*sec/cm-5, P = 0.0304). rBPI23did not prevent the endotoxin-induced rise in Body Temperature ( + 1.9°C) and Systolic, Diastolic and Mean Arterial Blood Pressure were comparable in the rBPI23- and placebo-treatment arm. Both treatment periods showed a small reduction in End-SystOlic and End-Diastolic Volumes as measured by M-mode. Circulatory changes induced by endotoxin lasted for 12 hours. The protective effect of rBPI23was maximal between 1:30 and 4:00 hours after the start of the endotoxin infusion. Conclusion These results indicate that rBPI23is capable of attenuating the circulatory effects of endotoxin in humans.

Objective Patients undergoing carotid endarterectomy (CEA) maintain a substantial residual risk of major cardiovascular events (MACE). Improved risk stratification is warranted to select high risk patients qualifying for secondary add on therapy. Plasma extracellular vesicles (EVs) are involved in atherothrombotic processes and their content has been related to the presence and recurrence of cardiovascular events. The association between pre-operative levels of five cardiovascular disease related proteins in plasma EVs and the post-operative risk of MACE was assessed. Methods In 864 patients undergoing CEA from 2002 to 2016 included in the Athero-Express biobank, three plasma EV subfractions (low density lipoprotein [LDL], high density lipoprotein [HDL], and tiny extracellular vesicles [TEX]) were isolated from pre-operative blood samples. Using an electrochemiluminescence immunoassay, five proteins were quantified in each EV subfraction: cystatin C, serpin C1, serpin G1, serpin F2, and CD14. The association between EV protein levels and the three year post-operative risk of MACE (any stroke, myocardial infarction, or cardiovascular death) was evaluated using multivariable Cox proportional hazard regression analyses. Results During a median follow up of three years (interquartile range 2.2 – 3.0), 137 (16%) patients developed MACE. In the HDL-EV subfraction, increased levels of CD14, cystatin C, serpin F2, and serpin C1 were associated with an increased risk of MACE (adjusted hazard ratios per one standard deviation increase of 1.30, 95% confidence interval [CI] 1.15–1.48; 1.22, 95% CI 1.06–1.42; 1.36, 95% CI 1.16–1.61; and 1.29, 95% CI 1.10–1.51; respectively), independently of cardiovascular risk factors. No significant associations were found for serpin G1. CD14 improved the predictive value of the clinical model encompassing cardiovascular risk factors (net re-classification index = 0.16, 95% CI 0.08–0.21). Conclusion EV derived pre-operative plasma levels of cystatin C, serpin C1, CD14, and serpin F2 were independently associated with an increased long term risk of MACE after CEA and are thus markers for residual cardiovascular risk. EV derived CD14 levels could improve the identification of high risk patients who may benefit from secondary preventive add on therapy in order to reduce future risk of MACE.

OBJECTIVES The aim of this study was to determine predictors of left ventricular (LV) function recovery at the time of primary percutaneous coronary intervention (PCI). BACKGROUND Angiographic, intracoronary Doppler flow, and electrocardiographic variables have been reported to be predictors of recovery of LV function after acute myocardial infarction (MI). We directly compared the predictive value of Thrombolysis In Myocardial Infarction (TIMI) flow grade, corrected TIMI frame count (cTfc), myocardial blush grade, coronary Doppler flow velocity analysis, and resolution of ST-segment elevation for recovery of LV function in patients undergoing primary PCI for acute MI. METHODS We prospectively studied 73 patients who underwent PCI for an acute anterior MI. Recovery of global and regional LV function was measured using an echocardiographic 16-segment wall motion index (WMI) before PCI, at 24 h, at one week, and at six months. Directly after successful PCI, coronary flow velocity reserve (CFR), cTfc, TIMI flow grade, and myocardial blush grade were assessed. RESULTS Mean global and regional WMI improved gradually over time from 1.86 +/- 0.23 before PCI to 1.54 +/- 0.34 at six-month follow-up (p

To the Editor: Unloading the left ventricle (LV) after ST-segment elevation myocardial infarction (STEMI) in addition to reperfusion therapy may reduce infarct size and may give the myocardium time to recuperate from ischemic stunning ([1][1]). This may be particularly true in STEMI patients with

Recent years have shown a rapidly growing interest among clinical chemists, clinical cardiologists and emergency physicians in the use of new biochemical markers for risk stratification of patients with acute coronary syndrome (ACS). It was demonstrated across a wide range of ACS patient populations

Background: Drug-eluting stents (DES) have dramatically reduced restenosis rates compared to bare metal stents and are widely used in coronary artery angioplasty. The anti-proliferative nature of the drugs reduces smooth muscle cell (SMC) proliferation effectively, but unfortunately also negatively affects endothelialization of stent struts, necessitating prolonged dual anti-platelet therapy. Cell-type specific therapy may prevent this complication, giving rise to safer stents that do not require additional medication. 6-Mercaptopurine (6-MP) is a drug with demonstrated cell-type specific effects on vascular cells both in vitro and in vivo, inhibiting proliferation of SMCs while promoting survival of endothelial cells. In rabbits, we demonstrated that DES locally releasing 6-MP during 4 weeks reduced in-stent stenosis by inhibiting SMC proliferation and reducing inflammation, without negatively affecting endothelialization of the stent surface. The aim of the present study was to investigate whether 6-MP-eluting stents are similarly effective in preventing stenosis in porcine coronary arteries after 3 months, in order to assess the eligibility for human application. Methods: 6-MP-eluting and polymer-only control stents (both n = 7) were implanted in porcine coronary arteries after local balloon injury to assess the effect of 6-MP on vascular lesion formation. Three months after implantation, stented coronary arteries were harvested and analyzed. Results: Morphometric analyses revealed that stents were implanted reproducibly and with limited injury to the vessel wall. Unexpectedly, both in-stent stenosis (6-MP: 41.1 +/- 10.3 %; control: 29.6 +/- 5.9 %) and inflammation (6-MP: 2.14 +/- 0.51; control: 1.43 +/- 0.45) were similar between the groups after 3 months. Conclusion: In conclusion, although 6-MP was previously found to potently inhibit SMC proliferation, reduce inflammation and promote endothelial cell survival, thereby effectively reducing in-stent restenosis in rabbits, stents containing 300 mu g 6-MP did not reduce stenosis and inflammation in porcine coronary arteries

Ceramides and phosphatidylcholines (PCs) are bioactive lipids and lipid bilayer membrane components. Distinct ceramides/PCs (ratios) predict cardiovascular outcome in patients with coronary artery disease. Extracellular vesicles (EVs) are proposed biomarkers for cardiovascular disease and contain ceramides/PCs. Ceramides/PCs have not been studied in patients undergoing carotid endarterectomy (CEA) nor in EVs. We therefore investigated whether levels of ceramides/PCs in plasma and EVs are associated with postoperative risk of major adverse cardiovascular events (MACE) following CEA. In 873 patients undergoing CEA of the Athero-Express biobank, we quantitatively measured seven ceramides/PCs in preoperative blood samples: Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), Cer(d18:1/24:1), PC(14:0/22:6), PC(16:0/16:0) and PC(16:0/22:5) in plasma and two plasma EV-subfractions (LDL and TEX). We analyzed the association of ceramides, PCs and their predefined ratios with the three-year postoperative risk of MACE (including stroke, myocardial infarction and cardiovascular death). A total of 138 patients (16%) developed MACE during the three-year follow-up. In the LDL-EV subfraction, higher levels of Cer(d18:1/24:1) and Cer(d18:1/16:0)/PC(16:0/22:5) ratio were significantly associated with an increased risk of MACE (adjusted HR per SD [95% CI] 1.24 [1.01–1.53] and 1.26 [1.04–1.52], respectively). In the TEX-EV subfraction, three ratios Cer(d18:1/16:0)/Cer(d18:1/24:0), Cer(d18:1/18:0)/Cer(d18:1/24:0) and Cer(d18:1/24:1)/Cer(d18:1/24:0) were positively associated with MACE (adjusted HR per SD 1.34 [1.06–1.70], 1.24 [1.01–1.51] and 1.31 [1.08–1.58], respectively). In conclusion, distinct ceramides and PCs in plasma EVs determined in preoperative blood were independently associated with an increased 3-year risk of MACE after CEA. These lipids are therefore potential markers to identify high-risk CEA patients qualifying for secondary preventive add-on therapy.