Van De Werf Research Articles

Letter by Weidemann et al Regarding Article, “Global Diastolic Strain Rate for the Assessment of Left Ventricular Relaxation and Filling Pressure”

HomeCirculationVol. 116, No. 14Letter by Weidemann et al Regarding Article, “Global Diastolic Strain Rate for the Assessment of Left Ventricular Relaxation and Filling Pressure” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Weidemann et al Regarding Article, “Global Diastolic Strain Rate for the Assessment of Left Ventricular Relaxation and Filling Pressure” Frank Weidemann and Joerg M. Strotmann Bart Bijnens Frank WeidemannFrank Weidemann Department of Internal Medicine I, University Hospital Wuerzburg, Germany Search for more papers by this author and Joerg M. StrotmannJoerg M. Strotmann Department of Internal Medicine I, University Hospital Wuerzburg, Germany Search for more papers by this author Bart BijnensBart Bijnens Medical School and Faculty of Electronic Engineering, University of Zagreb, Croatia Search for more papers by this author Originally published2 Oct 2007https://doi.org/10.1161/CIRCULATIONAHA.107.708784Circulation. 2007;116:e368To the Editor:We have read with interest the paper by Wang et al1 on diastolic function assessed by strain rate in the isovolumetric relaxation period (SRIVR) derived from 2-dimensional speckle tracking. In principle, 2-dimensional speckle tracking is a useful progression toward an automated assessment of left ventricular deformation.We would like to comment on the fact that the authors had some difficulties with patients with wall motion abnormalities. It is known from many studies that different conditions such as acute ischemia, regional fibrosis, and increased afterload result in ongoing (postsystolic) deformation during isovolumic relaxation (IVR).2,3 This deformation will change local SRIVR independently from tau, which thus limits the assessment of diastolic function by analysis of SRIVR in a wide range of important clinical conditions.In addition, we agree that E/Ea has some limitations when diastolic function is assessed, especially in the gray zone between 8 and 15. However, although it has merits in the assessment of strain, we think that 2-dimensional speckle tracking is not satisfactory when strain rate is assessed, especially during IVR. It is well known that speckle tracking can only be performed at relatively low frame rates. However, this low frame rate prevents resolution of the fast change in deformation (ie, strain rate) that occurs during IVR. This lack of resolution leads, as correctly mentioned in the paper,1 to an underestimation of peak strain-rate value. Thus, we would suggest use of Doppler-derived strain rate (with its high temporal resolution), and not speckle tracking strain rate, to accurately assess SRIVR.The authors could nicely show the limitations of diastolic function assessment by pulsed-wave tissue Doppler imaging and suggest a greater focus on diastolic deformation. However, we believe that assessment of strain rate during IVR with 2-dimensional speckle tracking and its inherent technical limitations will prove a real challenge in clinical conditions.DisclosuresNone.1 Wang J, Khoury DS, Thohan V, Torre-Amione G, Nagueh SF. Global diastolic strain rate for the assessment of left ventricular relaxation and filling pressures. Circulation. 2007; 115: 1376–1383.LinkGoogle Scholar2 Weidemann F, Dommke C, Bijnens B, Claus P, D’hooge J, Mertens P, Verbeken E, Maes A, Van de Werf F, De Scheerder I, Sutherland GR. Defining the transmurality of a chronic myocardial infarction by ultrasonic strain-rate imaging: implications for identifying intramural viability: an experimental study. Circulation. 2003; 107: 883–888.LinkGoogle Scholar3 Voigt JU, Lindenmeier G, Exner B, Regenfus M, Werner D, Reulbach U, Nixdorff U, Flachskampf FA, Daniel WG. Incidence and characteristics of segmental postsystolic longitudinal shortening in normal, acutely ischemic, and scarred myocardium. J Am Soc Echocardiogr. 2003; 16: 415–423.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Chiang S, Daimon M, Ishii K, Kawata T, Miyazaki S, Hirose K, Ichikawa R, Miyauchi K, Yeh M, Chang N and Daida H (2014) Assessment of Elevation of and Rapid Change in Left Ventricular Filling Pressure Using a Novel Global Strain Imaging Diastolic Index, Circulation Journal, 10.1253/circj.CJ-13-0513, 78:2, (419-427), . October 2, 2007Vol 116, Issue 14 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.107.708784PMID: 17909112 Originally publishedOctober 2, 2007 PDF download Advertisement SubjectsEchocardiography

How many cath labs do we need to perform primary percutaneous coronary interventions in a particular population?

According to the current guidelines on the management of acute ST-elevation myocardial infarction (STEMI) of the American College of Cardiology/American Heart Association and those of the European Society of Cardiology, primary percutaneous coronary intervention (PCI) is the preferred choice of treatment (Class I indication), provided that it is performed within 12 h after the onset of symptoms, in a timely manner (within 90 min after the first medical contact), and by experienced physicians (who perform >75 PCIs per year) in high-volume centres that perform >200 PCIs (at least 36 primary) per year [ 1 Antman E.M. Anbe D.T. Armstrong P.W. et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction; A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial infarction). J Am Coll Cardiol. 2004; 44: E1-E211 Abstract Full Text PDF PubMed Google Scholar , 2 Van de Werf F. Ardissino D. Betriu A. et al. Management of acute myocardial infarction in patients presenting with ST-segment elevation. The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J. 2003; 24: 28-66 Crossref PubMed Scopus (1491) Google Scholar , 3 Silber S. Albertsson P. Aviles F.F. et al. Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Eur Heart J. 2005; 26: 804-847 Crossref PubMed Scopus (0) Google Scholar ].

Oxidant Stress during Simulated Ischemia Primes Cardiomyocytes for Cell Death during Reperfusion

Ischemia-reperfusion injury induces oxidant stress, and the burst of reactive oxygen species (ROS) production after reperfusion of ischemic myocardium is sufficient to induce cell death. Mitochondrial oxidant production may begin during ischemia prior to reperfusion because reducing equivalents accumulate and promote superoxide production. We utilized a ratiometric redox-sensitive protein sensor (heat shock protein 33 fluorescence resonance energy transfer (HSP-FRET)) to assess oxidant stress in cardiomyocytes during simulated ischemia. HSP-FRET consists of the cyan and yellow fluorescent protein fluorophores linked by the cysteine-containing regulatory domain from bacterial HSP-33. During ischemia, ROS-mediated oxidation of HSP-FRET was observed, along with a decrease in cellular reduced glutathione levels. These findings were corroborated by measurements using redox-sensitive green fluorescent protein, another protein thiol ratiometric sensor, which became 93% oxidized by the end of simulated ischemia. However, cell death did not occur during ischemia, indicating that this oxidant stress is not sufficient to induce death before reperfusion. However, interventions that attenuate ischemic oxidant stress, including antioxidants or scavengers of residual O(2) that attenuate/prevent ROS generation during ischemia, abrogated cell death during simulated reperfusion. These findings reveal that, in isolated cardiomyocytes, sublethal H(2)O(2) generation during simulated ischemia regulates cell death during simulated reperfusion, which is mediated by the reperfusion oxidant burst.

Electrical Coupling of Cardiac Myocyte Cell Sheets to the Heart

See related article, pages 705–712 The past 20 years have seen tremendous progress in the medical treatment of cardiac diseases, a progress that actually translated into decreased cardiovascular morbidity and mortality in clinical practice.1 Yet evidence accumulates that interventions intended to slow down the progression of chronic heart diseases have approached their limit. This may be one of the reasons why the recent progress in stem cell biology has stirred so much attention. In addition, recent studies suggesting the existence of cell populations in the adult organism that, albeit at a low rate and insufficiently, endogenously replace cardiac myocytes and endothelial and smooth muscle cells have challenged the dogma of the heart as a nonregenerating organ.2–5 Such cell populations could be accessed in biopsies and principally serve as a source to replace cardiac myocytes and other cardiac cell types lost after myocardial infarction or other pathologies. Human embryonic stem cell lines, on the other hand, can nowadays be generated from human blastocysts (accessible from IVF leftovers6) at a high success rate and have been unambiguously shown to generate human cardiac myocytes.7–9 Thus, despite many open questions and some controversy in the field (reviews in references 10,11), cardiac regenerative therapy has become a realistic perspective. But what to do with stem cells or their derivatives, given that means will be provided to generate them at sufficient numbers? The most straightforward strategy is to infuse or inject these cells into the injured heart and to develop methods to increase the fraction of cells that home and survive in the heart and differentiate to the desired functional elements. This strategy has already been clinically evaluated, but gave mixed results,12–16 potentially also because the homing rate after infusion and the survival rate after intramyocardial injections are very low. …

High postclopidogrel platelet reactivity in non-ST-elevation acute coronary syndrome treated with stenting: a clue for adverse prognosis?

Patients presenting to the hospital with an acute coronary syndrome without ST-segment elevation (NSTE-ACS) are characterized by a common underlying pathophysiological mechanism represented by the rupture or erosion of an atherosclerotic coronary plaque with differing degrees of superimposed thrombosis and distal embolization [1]. They are, however, a heterogeneous group, ranging from low to high risk, partly because the tendency to the progression of coronary thrombosis to total coronary occlusion is highly variable. The Clinical Guidelines of both the European Society of Cardiology (ESC) [2] and the American College of Cardiology/ American Heart Association (ACC/AHA) [3] have identified the importance of early risk stratification for patients with NSTE-ACS for selecting the intensity of antiplatelet therapy and the need of early revascularization, frequently represented by percutaneous coronary intervention (PCI). For patients in whom the diagnosis is in doubt, only aspirin is suggested; for those in whom the diagnosis is confirmed based on the electrocardiographic or biochemical criteria, the addition of clopidogrel is encouraged. Finally, in the presence of high-risk features, the use of a platelet GP IIB/IIIA inhibitor is recommended followed by an early revascularization. These recommendations are based on the assumption that the extent and magnitude of platelet activation are causally linked to an adverse prognosis [4], particularly at the short term, and that the suppression of platelet reactivity should be pursued in order to minimize the occurrence of thrombotic events before, during, and after PCI [5]. In this issue of the Journal of Thrombosis and Haemostasis, Cuisset et al. [6] report on the prognostic importance of low platelet response to dual antiplatelet therapy in patients with NSTE-ACS. They studied 106 patients admitted within 12 h after the last chest pain episode, undergoing PCI with stenting within 48 h after admission. All patients received standard dose clopidogrel on top of aspirin and, at the time of PCI, tirofiban were administered at discretion of the interventional cardiologist (25% of patients). A single blood sample was obtained just before PCI and analyzed by platelet aggregometry using both ADP (10 lmol L) and arachidonic acid (0.5 mg mL) as agonists to explore the responses to clopidogrel and aspirin, respectively. Twelve recurrent cardiovascular events (11.3%) occurred during 30 day follow-up. They consisted of 10 hospitalizations for recurrent ACS (one sub-acute stent thrombosis), one stroke and one death. Patients were divided into quartiles according to the ADP or arachidonic acidinduced maximal intensity of platelet aggregation. Patients of the highest quartile (Quartile 4) were defined as low responders . The authors found that the clinical outcome was significantly associated with platelet response to clopidogrel [Quartile 4 vs. 1,2,3: OR (95%CI) 22.4 (4.6–109)] and, to a lower extent, to aspirin [Quartile 4 vs. 1,2,3: OR (95%CI): 5.76 (1.54–35.61)]. The authors conclude that a platelet aggregation test performed just before PCI identifies low responders to dual antiplatelet therapy with an increased risk of recurrent cardiovascular events. A possible explanation for these findings is the presence, in patients with NSTE-ACS, of a high-baseline platelet reactivity and thrombotic burden, which may contribute to a lower clopidogrel antiplatelet effect particularly during the first days of treatment [7]. Accordingly, a 450 mg clopidogrel loading dose given ‡3 h before PCI resulted in a lower inhibition of platelet aggregation in patients with a higher unstable angina class on presentation when compared with patients having stable angina or lower unstable angina class [8]. The results of the study of Cuisset et al. [6] are noteworthy as, for the first time, they show that, among patients with NSTEACS treated with both aspirin and clopidogrel and undergoing Correspondence: Marcello Galvani, Fondazione Cardiologica Sacco, P.zza F.lli Ruffini, 6, 47100 Forli, Italy. Tel.: +39 0543 33263; fax. +39 0543 735115; e-mail: galvanim@tin.it Journal of Thrombosis and Haemostasis, 4: 536–538

Echocardiographic Strain Imaging for Myocardial Viability

Echocardiographic strain imaging was introduced by Heimdal et al in 19981 as a means to calculate myocardial regional function from tissue Doppler velocity data.2,3 Strain imaging is a variation of the previous concept of tissue Doppler myocardial velocity gradient, which calculates regional thickening independent of passive whole heart motion.4,5 Because routine clinical evaluation of regional function is usually by visual wall-motion assessment, strain imaging has great promise to improve objective quantification of regional function. Strain imaging calculates deformation, which translates clinically to percent shortening in the longitudinal dimension (assessed from apical views) or percent thickening in the radial dimension (assessed from parasternal views).1,6,7 Theoretically, it has the important advantage of differentiating active myocardial motion from passive translational or tethering movements that other echocardiographic-Doppler approaches cannot differentiate. Indeed, there have been literally hundreds of publications over the last 10 years detailing a wide range of experimental and potential clinical applications of strain imaging; however, currently, few centers have adopted strain imaging in their routine clinical practice, preferring visual “eyeball” assessment, even though this is inherently subjective and requires a high level of experience and training.8 An important question remains: Is it now time for strain imaging to be adopted in a widespread clinical sense? Articles pp 3892 and 3901 Two important articles are contained in this issue of Circulation that address the application of strain imaging as a tool to assess myocardial viability: an animal study of experimental ischemia and infarction by Lyseggen et al9 and a clinical study using dobutamine echocardiography with outcome data after revascularization by Hanekom et al.10 The article by Lyseggen et al illustrates the additive value of strain imaging in an elegant open-chest animal model of coronary occlusion and reperfusion. Echocardiographic strain imaging was performed along with simultaneous dimensional …

Wound model of myocardial infarction

ischemic heart disease is the major etiology for heart failure today ([3][1]). The initial event is frequently a large or recurrent myocardial infarction. Acute myocardial infarction starts with thrombotic occlusion of a coronary artery, develops during several hours, and terminates when necrosis

Half‐dose Recombinant Tissue Plasminogen Activator plus Abciximab for Stroke

Academic Emergency MedicineVolume 11, Issue 12 p. 1368-1368 Free Access Half-dose Recombinant Tissue Plasminogen Activator plus Abciximab for Stroke Ron M. Walls MD, Ron M. Walls MD ([email protected]), Department of Emergency Medicine, Brigham & Women's Hospital, Boston, MASearch for more papers by this authorDiane Birnbaumer MD, Diane Birnbaumer MD ([email protected]), Department of Emergency Medicine, Harbor–UCLA Medical Center, Torrance, CASearch for more papers by this author Ron M. Walls MD, Ron M. Walls MD ([email protected]), Department of Emergency Medicine, Brigham & Women's Hospital, Boston, MASearch for more papers by this authorDiane Birnbaumer MD, Diane Birnbaumer MD ([email protected]), Department of Emergency Medicine, Harbor–UCLA Medical Center, Torrance, CASearch for more papers by this author First published: 28 June 2008 https://doi.org/10.1197/j.aem.2004.07.002AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. References Morris DC, Sliver B, Mitsias P et al. Treatment of acute stroke with recombinant tissue plasminogen activator and abciximab. Acad Emerg Med. 2003; 10: 1396– 9. Lincoff, AM, Califf, RM, Van de Werf, F, For the Global Use of Strategies to Open Coronary Arteries Investigators (GUSTO). Mortality at 1 year with combination platelet glycoprotein IIb/IIIa Iinhibition and reduced-dose fibrinolytic therapy vs conventional fibrinolytic therapy for acute myocardial infarction: GUSTO V randomized trial. JAMA. 2002; 288: 2130– 2135. Heo, JH, Lee, KY, Kim, SH, Kim, DI. Immediate reocclusion following a successful thrombolysis in acute stroke: a pilot study. Neurology. 2003; 60: 1684– 7. Volume11, Issue12December 2004Pages 1368-1368 ReferencesRelatedInformation

Formin homology domain protein (FHOD1) is a cyclic GMP-dependent protein kinase I-binding protein and substrate in vascular smooth muscle cells.

Cyclic GMP-dependent protein kinase I (PKGI) mediates vascular relaxation by nitric oxide and related nitrovasodilators and inhibits vascular smooth muscle cell (VSMC) migration. To identify VSMC proteins that interact with PKGI, the N-terminal protein interaction domain of PKGIalpha was used to screen a yeast two-hybrid human aortic cDNA library. The formin homology (FH) domain-containing protein, FHOD1, was found to interact with PKGIalpha in this screen. FH domain-containing proteins bind Rho-family GTPases and regulate actin cytoskeletal dynamics, cell migration, and gene expression. Antisera to FHOD1 were raised and used to characterize FHOD1 expression and distribution in vascular cells. FHOD1 is highly expressed in human coronary artery, aortic smooth muscle cells, and in human arterial and venous endothelial cells. In glutathione S-transferase pull-down experiments, the FHOD1 C terminus (amino acids 964-1165) binds full-length PKGI. Both in vitro and intact cell studies demonstrate that the interaction between FHOD1 and PKGI is decreased 3- to 5-fold in the presence of the PKG activator, 8Br-cGMP. Immunofluorescence studies of human VSMC show that FHOD1 is cytoplasmic and is concentrated in the perinuclear region. PKGI also directly phosphorylates FHOD1, and studies with wild-type and mutant FHOD1-derived peptides identify Ser-1131 in the FHOD1 C terminus as the unique PKGI phosphorylation site in FHOD1. These studies demonstrate that FHOD1 is a PKGI-interacting protein and substrate in VSMCs and show that cyclic GMP negatively regulates the FHOD1-PKGI interaction. Based on the known functions of FHOD1, the data are consistent with a role for FHOD1 in cyclic GMP-dependent inhibition of VSMC stress fiber formation and/or migration.

Durability of platelet inhibition by clopidogrel

1. Oparil S, Oberman A. Nontraditional cardiovascular risk factors. Am J Med Sci 1999;317:193–207. 2. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med 1999;340: 115–126. 3. Moss AJ, Goldstein RE, Marder VJ, Sparks CE, Oakes D, Greenberg H, Weiss HJ, Zareba W, Brown MW, Liang CS, et al. Thrombogenic factors and recurrent coronary events. Circulation 1999;99:2517–2522. 4. Rifai N, Tracy RP, Ridker PM. Clinical efficacy of an automated highsensitivity C-reactive protein assay. Clin Chem 1999;45:2136–2141. 5. Rohde LE, Hennekens CH, Ridker PM. Survey of C-reactive protein and cardiovascular risk factors in apparently healthy men. Am J Cardiol 1999;84: 1018–1022. 6. Mendall MA, Patel P, Ballam L, Strachan D, Northfield TC. C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study. BMJ 1996;312:1061–1065. 7. St-Pierre AC, Ruel IL, Cantin B, Dagenais GR, Bernard PM, Despres JP, Lamarche B. Comparison of various electrophoretic characteristics of LDL particles and their relationship to the risk of ischemic heart disease. Circulation 2001;104:2295–2299. 8. Holvoet P, Mertens A, Verhamme P, Bogaerts K, Beyens G, Verhaeghe R, Collen D, Muls E, Van de Werf F. Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2001;21:844–848. 9. Koenig W, Rothenbacher D, Hoffmeister A, Griesshammer M, Brenner H. Plasma fibrin D-dimer levels and risk of stable coronary artery disease: results of a large case-control study. Arterioscler Thromb Vasc Biol 2001;21:1701–1705. 10. Ridker PM, Rifai N, Pfeffer MA, Sacks FM, Moye LA, Goldman S, Flaker GC, Braunwald E. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1998;98:839–844.

Late-Breaking Clinical Trial Abstracts

Late-Breaking Clinical Trial Abstracts

Comparison of positron emission tomography with the resting electrocardiogram for assessing viable myocardium in chronic ischemic cardiomyopathy involving the anterior left ventricular wall

patients with acute coronary syndromes. Am Heart J 2000;140:917–927. 3. Braunwald E. Unstable angina. A classification. Circulation 1989;80:410–414. 4. Morrow DA, Rifai N, Tanasijevic MJ, Wybenga DR, de Lemos JA, Antman EM. Clinical efficacy of three assays for cardiac troponin I for risk stratification in acute coronary syndromes: a Thrombolysis In Myocardial Infarction (TIMI) 11B Substudy. Clin Chem 2000;46:453–460. 5. Cole CR, Blackstone EH, Pashkow FJ, Snader CE, Lauer MS. Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med 1999;341:1351–1357. 6. Cannon CP, Weintraub WS, Demopoulos LA, Vicari R, Frey MJ, Lakkis N, Neumann FJ, Robertson DH, DeLucca PT, DiBattiste PM, Gibson CM, Braunwald E. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med 2001;344:1879–1887. 7. Anonymous. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study. Lancet 1997;349:1429–1435. 8. Kaul P, Fu Y, Chang WC, Harrington RA, Wagner GS, Goodman SG, Granger CB, Moliterno DJ, Van de Werf F, Califf RM, Topol EJ, Armstrong PW. Prognostic value of ST segment depression in acute coronary syndromes: insights from PARAGON-A applied to GUSTO-IIb. PARAGON-A and GUSTO IIb Investigators. Platelet IIb/IIIa Antagonism for the Reduction of Acute Global Organization Network. J Am Coll Cardiol 2001;38:64–71. 9. Abrahamsson P, Andersen K, Grip L, Wallentin L, Dellborg M. Early assessment of long-term risk with continuous ST-segment monitoring among patients with unstable coronary syndromes. Results from 1-year follow-up in the TRIM study. J Electrocardiol 2001;34:103–108. 10. Holmvang L, Andersen K, Dellborg M, Clemmensen P, Wagner G, Grande P, Abrahamsson P. Relative contributions of a single-admission 12-lead electrocardiogram and early 24-hour continuous electrocardiographic monitoring for early risk stratification in patients with unstable coronary artery disease. Am J Cardiol 1999;83:667–674. 11. Morrow DA, Cannon CP, Rifai N, Frey MJ, Vicari R, Lakkis N, Robertson DH, Hille DA, DeLucca PT, DiBattiste PM, et al, and the TACTICS-TIMI 18 Investigators. Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction: results from a randomized trial. JAMA 2001; 286:2405–2412.

Principles from clinical trials relevant to clinical practice: Part II.

Principles from clinical trials relevant to clinical practice: Part II.

Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study.

The role of C-reactive protein (CRP) as a novel plasma marker of atherothrombotic disease is currently under investigation. Previous studies have mostly related CRP to coronary heart disease, were often restricted to a case-control design, and failed to include pertinent risk factors to evaluate the joint and net effect of CRP on the outcome. We related plasma CRP levels to incidence of first ischemic stroke or transient ischemic attack (TIA) in the Framingham Study original cohort. There were 591 men and 871 women free of stroke/TIA during their 1980 to 1982 clinic examinations, when their mean age was 69.7 years. CRP levels were measured by using an enzyme immunoassay on previously frozen serum samples. Analyses were based on sex-specific CRP quartiles. Risk ratios (RRs) were derived, and series of trend analyses were performed. During 12 to 14 years of follow-up, 196 ischemic strokes and TIAs occurred. Independent of age, men in the highest CRP quartile had 2 times the risk of ischemic stroke/TIA (RR=2.0, P=0.027), and women had almost 3 times the risk (RR=2.7, P=0.0003) compared with those in the lowest quartile. Assessment of the trend in risk across quartiles showed unadjusted risk increase for men (RR=1.347, P=0.0025) and women (RR=1.441, P=0.0001). After adjustment for smoking, total/HDL cholesterol, systolic blood pressure, and diabetes, the increase in risk across CRP quartiles remained statistically significant for both men (P=0.0365) and women (P=0.0084). Independent of other cardiovascular risk factors, elevated plasma CRP levels significantly predict the risk of future ischemic stroke and TIA in the elderly.

News From the European Society of Cardiology Congress XXIII

The XXIII Congress of the European Society of Cardiology opened to cool blue skies in Stockholm, Sweden, on September 1, 2001, as >20 000 cardiologists, scientists, and other healthcare providers gathered for the largest heart-related meeting on the continent. With “Hotline” sessions spotlighting the latest research spanning 3 days, the Congress drew large morning crowds to hear their colleagues explain the newest studies. Those spotlighted included: ### ESCAMI On September 1, 2001, the day before scientific presentations began, Martin Simoons, MD, president of the European Society of Cardiology, predicted the results reported at the first Hotline for the newest information would change the way he and his staff treat acute myocardial infarction. After the session on September 2, 2001, he said he would add the use of low-molecular-weight heparin to his armamentarium. Uwe Zeymer, MD, of the Staedtische Kliniken in Kassel, Germany, reported that the sodium hydrogen exchange inhibitor eniporide did not add to the positive effects of thrombolysis in patients with acute myocardial infarctions. His trial, the Evaluation of the Safety and Cardioprotective Effects of Eniporide in Acute Myocardial Infarction (ESCAMI), involved 2 stages. The first was designed to prove efficacy and safety and to select 2 doses for the second stage of the trial. The stage 2 part of the trial was designed to select the dose for a large-scale mortality trial. In that trial, ≈320 patients in each group received placebo, 100 mg of eniporide, or 150 mg of eniporide (the 2 doses chosen from phase 1). In the study, patients with acute myocardial infarction were scheduled for the reperfusion therapy of their physicians’ choice: thrombolysis or primary percutaneous transluminal angioplasty (PTCA). Eniporide was given later with the goal of reducing the size of the infarct and saving heart muscle. Dr Zeymer noted that, “The overall result of the …

Comparison of impact of primary percutaneous transluminal coronary angioplasty and primary stenting on short-term mortality in patients with cardiogenic shock and evaluation of prognostic determinants

sestamibi in patients undergoing cardiac transplantation. A scintigraphic/pathological study. Circulation 1996;94:1010–1017. 9. Maes AF, Borgers M, Flameng W, Nuyts JL, van de Werf F, Ausma JJ, Sergeant P, Mortelmans LA. Assessment of myocardial viability in chronic coronary artery disease using technetium-99m sestamibi SPECT. Correlation with histologic and positron emission tomographic studies and functional followup. J Am Coll Cardiol 1997;29:62–68. 10. Dakik HA, Howell JF, Lawrie GM, Espada R, Weilbaecher DG, He ZX, Mahmarian JJ, Verani MS. Assessment of myocardial viability with 99m Tcsestamibi tomography before coronary bypass graft surgery: correlation with histopathology and postoperative improvement in cardiac function. Circulation 1997;96:2892–2898. 11. Miller TD, Christian TF, Hopfenspirger MR, Hodge DO, Gersh BJ, Gibbons RJ. Infarct size after acute myocardial infarction measured by quantitative tomographic 99m Tc sestamibi imaging predicts subsequent mortality. Circulation 1995;92:334–341. 12. Miller TD, Hodge DO, Sutton JM, Grines CL, O’Keefe JH, DeWood MA, Okada RD, Fletcher WO Jr, Gibbons RJ. Usefulness of technetium-99m sestamibi infarct size in predicting posthospital mortality following acute myocardial infarction. Am J Cardiol 1998;81:1491–1493. 13. Gibbons RJ, Holmes DR, Reeder GS, Bailey KR, Hopfenspirger MR, Gersh BJ. Inmediate angioplasty compared with the administration of a thrombolytic agent followed by a conservative treatment for myocardial infarction. N Engl J Med 1993;328:685–691. 14. O’Keefe JH, Grines CL, DeWood MA, Schaer GL, Browne K, Magorien RD, Kalbfleisch JM, Fletcher WO Jr, Bateman TM, Gibbons RJ. Poloxamer-188 as an adjunct to primary percutaneous transluminal coronary angioplasty for acute myocardial infarction. Am J Cardiol 1996;78:747–750. 15. Collaborative Organization for RheothRx Evaluation (CORE). Effects of RheothRX on mortality, morbidity, left ventricular function and infarct size in patients with acute myocardial infarction. Circulation 1997;96:192–201. 16. Anglo Scandinavian Study of Early Thrombolysis Study Group. Trial of tissue plasminogen activator for mortality reduction in acute myocardial infarction. Anglo-Scandinavian Study of Early Thrombolysis (ASSET). Lancet 1988; 2:525–530. 17. Christian TF, Gibbons RJ, Gersh BJ. Effect of infarction location on myocardial salvage assessed by technetium-99m isonitrile. J Am Coll Cardiol. 1991; 17:1303–1308. 18. The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl Med 1993;329:1615–1622. 19. Galli M, Marcassa C, Bolli R, Giannuzzi P, Temporelli PL, Imparato A, Silva Orrego PL, Giubbini R, Giordano A, Tavazzi L. Spontaneous delayed recovery of perfusion and contraction after the first 5 weeks after anterior infarction. Evidence for the presence of hibernating myocardium in the infarcted area. Circulation 1994;90:1386–1397.

Diabetes doubles the risk of death among patients presenting with acute coronary syndromes: Insights from SYMPHONY, a large international trial Darren K. McGuire, L. Kristin Newby, Manju V. Bhapkar, David J. Moliterno, E. Magnus Ohman, F. Chris Dougherty, Robert A. Harrington, Harvey D. White, Frans Van de Werf, Robert M. Califf, Eric J. Topol, the SYMPHONY Investigators. Duke Clinical Research

Diabetes doubles the risk of death among patients presenting with acute coronary syndromes: Insights from SYMPHONY, a large international trial Darren K. McGuire, L. Kristin Newby, Manju V. Bhapkar, David J. Moliterno, E. Magnus Ohman, F. Chris Dougherty, Robert A. Harrington, Harvey D. White, Frans Van de Werf, Robert M. Califf, Eric J. Topol, the SYMPHONY Investigators. Duke Clinical Research

Weight-based dosing of thrombolysis: How well do we estimate weight? How often would this translate into errors with administration of thrombolytic drugs? A comparison of single-bolus TNK with t-PA in TIMI B Christopher P. Cannon, Michael Gibson, Sabina A. Murphy, Frans Van de Werf, Carolyn H. McCabe. Brigham and Women's Hospital, Boston, MA

Weight-based dosing of thrombolysis: How well do we estimate weight? How often would this translate into errors with administration of thrombolytic drugs? A comparison of single-bolus TNK with t-PA in TIMI B Christopher P. Cannon, Michael Gibson, Sabina A. Murphy, Frans Van de Werf, Carolyn H. McCabe. Brigham and Women's Hospital, Boston, MA

Applying the evidence in acute coronary syndromes: A report card from the global registry of acute coronary events Christopher Granger, Jos� L�pez-Send�n, Frans Van de Werf, Eva Kline-Rogers, Frederick A. Anderson, Jeanna Johnson, Immad Sadiq, Werner Klein, Kim A. Eagle, for the GRACE Investigators. Duke University Medical Center, Durham, NC, University of Michigan Health System, Ann Arbor, MI

Applying the evidence in acute coronary syndromes: A report card from the global registry of acute coronary events Christopher Granger, Jos� L�pez-Send�n, Frans Van de Werf, Eva Kline-Rogers, Frederick A. Anderson, Jeanna Johnson, Immad Sadiq, Werner Klein, Kim A. Eagle, for the GRACE Investigators. Duke University Medical Center, Durham, NC, University of Michigan Health System, Ann Arbor, MI

Risk of major bleeding in patients treated with PTCA early following thrombolysis with TNK vs. t-PA John H. Alexander, Xin Li, Richard Chin, Hal Barron, Christopher B. Granger, Paul W. Armstrong, Frans Van de Werf. Duke University Medical Center, Durham, NC

Risk of major bleeding in patients treated with PTCA early following thrombolysis with TNK vs. t-PA John H. Alexander, Xin Li, Richard Chin, Hal Barron, Christopher B. Granger, Paul W. Armstrong, Frans Van de Werf. Duke University Medical Center, Durham, NC