Van De Werf Research Articles

Repolarization abnormalities at admission predict 30-day outcome in COVID-19

Funding AcknowledgementsType of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): BV is supported by a research grant of the Frans Van de Werf Fund for Clinical Cardiovascular Research.IntroductionCOVID-19 can be related with a poor clinical outcome. ECG abnormalities in COVID-19 have been widely described, but literature on the predictive value of a 12-lead ECG at hospital admission and normalization of these abnormalities after infection is limited.PurposeTo describe the predictive value of ECG abnormalities on admission and after recovery of COVID-19.MethodsAfter informed consent patients older than 18 years admitted with COVID-19 between March and July 2020 were included in a prospective registry. Diagnosis was confirmed by PCR-assay or based on suggestive clinical and radiological presentation. Demographic and clinical data were collected by review of the electronic medical record. All ECGs from admission until last follow-up were assessed lead by kead for repolarization abnormalities. The index ECG was defined as first ECG available after admission, a post-COVID ECG was obtained after hospital discharge in the absence of acute pathology. Minor abnormalities included iso-electric T-waves and ST-depression ≤2 mm. Major abnormalities were ST-depression >2 mm, ST-elevation, biphasic T-waves and T-wave inversion. Myocardial regions were defined as anterior (V1-V4), lateral (I, aVL, V5, V6) and inferior (II, III, aVF). Patients with a ventricular pacemaker were excluded.ResultsA total of 283 patients were included, median age 65 years and 64.7% were male. The 30-day mortality rate was 20.5%. In 96.8% of patients an ECG was available within 48 hours after admission.Repolarization abnormalities were observed in 48.8% of patients. In 27.2% this was limited to minor abnormalities. Abnormal repolarization was related to age, cardiovascular medical history, renal function, high-sensitive troponin-T and NT-proBNP levels. There were no significant differences in clinical presentation, ICU admission, need for ventilation or ECMO.On Kaplan-Meier analysis (figure) the presence (p < 0.001) and the extent of repolarization abnormalities (p < 0.001) were associated with 30-day mortality. Forward Cox regression modelling identiefied age (per year, HR 1.07, 95% CI 1.05-1.09), history of heart failure (HR 2.12, 95% CI 1.08-4.52), neurological disorders (HR 2.47, 95% CI 1.36-4.51), active oncological disease (HR 2.13, 95% CI 1.01-4.50) and the extent of repolarization abnormalities (per region, HR 1.37, 95% CI 1.05-1.79) as independent predictors.A post-COVID ECG was available in 172 patients (60.8%), the median time between index and post-COVID ECG was 63.3 days. There was 1 new first-degree AV-block and 1 new RBBB. Repolarization abnormalities were present in 32 patients (11.3%); however, only 3 patients (1.7%) had new abnormalities, 2 of whom died during further follow-up.ConclusionsThe extent of repolarization abnormalities on an ECG at admission for COVID-19 is an independent predictor of 30-day mortality. New ECG abnormalities after COVID-19 infection are uncommon but may be associated with adverse outcome. Figure.

Profile: Frans Van de Werf, MD, PhD, FESC, FACC, FAHA.

Profile: Frans Van de Werf, MD, PhD, FESC, FACC, FAHA.

Correction

HomeCirculationVol. 130, No. 7Correction Free AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCorrectionPDF/EPUBCorrection Originally published12 Aug 2014https://doi.org/10.1161/CIR.0000000000000091Circulation. 2014;130:e64This article corrects the followingPrimary Percutaneous Coronary Intervention Not Always the Best Reperfusion Strategy?In the article by Sinnaeve and Van de Werf, “Primary Percutaneous Coronary Intervention Not Always the Best Reperfusion Strategy?,” which published in the April 22, 2014 issue of the journal (Circulation. 2014;129:1623–1625), an error was made.In the fifth paragraph, the following sentence appears: “In this STREAM-like cohort, 5-year survival was significantly lower after fibrinolysis compared with primary PCI.”This sentence should read: “In this STREAM-like cohort, 5-year survival was significantly better after fibrinolysis compared with primary PCI.”The online version of the article has been corrected. The authors regret the error. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesPrimary Percutaneous Coronary Intervention Not Always the Best Reperfusion Strategy?Peter R. Sinnaeve, et al. Circulation. 2014;129:1623-1625 August 12, 2014Vol 130, Issue 7 Advertisement Article InformationMetrics © 2014 American Heart Association, Inc.https://doi.org/10.1161/CIR.0000000000000091 Originally publishedAugust 12, 2014 PDF download Advertisement

Gender inequality in the clinical outcomes of equally treated acute coronary syndrome patients in Saudi Arabia

BACKGROUND AND OBJECTIVESGender associations with acute coronary syndrome (ACS), remain inconsistent. Gender-specific data in the Saudi Project for Assessment of Coronary Events registry, launched in December 2005 and currently with 17 participating hospitals, were explored.DESIGN AND SETTINGSA prospective multicenter study of patient with ACS in secondary and tertiary care centers in Saudi Arabia were included in this analysis.PATIENTS AND METHODSPatients enrolled from December 2005 until December 2007 included those presented to participating hospitals or transferred from non-registry hospitals. Summarized data were analyzed.RESULTSOf 5061 patients, 1142 (23%) were women. Women were more frequently diagnosed with non ST-segment elevation myocardial infarction (NSTEMI [43%]) than unstable angina (UA [29%]) or ST-segment elevation myocardial infarction (STEMI [29%]). More men had STEMI (42%) than NSTEMI (37%) or UA (22%). Men were younger than women (57 vs 63 years) who had more diabetes, hypertension, and hyperlipidemia. More men had a history of coronary artery disease. More women received angiotensin receptor blockers (ARB) and fewer had percutaneous coronary intervention (PCI). Gender differences in the subset of STEMI patients were similar to those in the entire cohort. However, gender differences in the subset of STEMI showed fewer women given β-blockers, and an insignificant PCI difference between genders. Thrombolysis rates between genders were similar. Overall, in-hospital mortality was significantly worse for women and, by ACS type, was significantly greater in women for STEMI and NSTEMI. However, after age adjustment there was no difference in mortality between men and women in patients with NSTEMI. The multivariate-adjusted (age, risk factors, treatments, door-to-needle time) STEMI gender mortality difference was not significant (OR=2.0, CI: 0.7–5.5; P=.14).CONCLUSIONThese data are similar to other reported data. However, differences exist, and their explanation should be pursued to provide a valuable insight into understanding ACS and improving its management.

Recent Trends in the Incidence, Treatment, and Prognosis of Patients With Heart Failure and Atrial Fibrillation (the Worcester Heart Failure Study)

Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases and the co-occurrence of AF and HF has been associated with reduced survival. Data are needed on the potentially changing trends in the characteristics, treatment, and prognosis of patients with acute decompensated HF (ADHF) and AF. The study population consisted of 9,748 patients hospitalized with ADHF at 11 hospitals in the Worcester, Massachusetts, metropolitan area during 4 study years (1995, 2000, 2002, and 2004). Of the 9,748 patients admitted with ADHF, 3,868 (39.7%) had a history of AF and 449 (4.6%) developed new-onset AF during hospitalization. The rates of new-onset AF remained stable (4.9% in 1995; 5.0% in 2004), but the proportion of patients with pre-existing AF (34.5% in 1995; 41.6% in 2004) increased over time. New-onset and pre-existing AF were associated with older age, but pre-existing AF was more closely linked to a greater co-morbid disease burden. The use of HF therapies did not differ greatly by AF status. Despite this, new-onset AF was associated with a longer length of stay (7.5 vs 6.1 days) and greater in-hospital death rates (11.4% vs 6.6%). In contrast, pre-existing AF was associated with lower rates of postdischarge survival compared to patients with no AF (p <0.05 for all). The mortality rates improved significantly over time in patients with AF. In conclusion, AF was common among patients with ADHF, and the proportion of ADHF patients with co-occurring AF increased during the study period. Despite improving trends in survival, patients with ADHF and AF are at increased risk of in-hospital and postdischarge mortality.

Glioma Stem Cell Proliferation and Tumor Growth Are Promoted by Nitric Oxide Synthase-2

Malignant gliomas are aggressive brain tumors with limited therapeutic options, and improvements in treatment require a deeper molecular understanding of this disease. As in other cancers, recent studies have identified highly tumorigenic subpopulations within malignant gliomas, known generally as cancer stem cells. Here, we demonstrate that glioma stem cells (GSCs) produce nitric oxide via elevated nitric oxide synthase-2 (NOS2) expression. GSCs depend on NOS2 activity for growth and tumorigenicity, distinguishing them from non-GSCs and normal neural progenitors. Gene expression profiling identified many NOS2-regulated genes, including the cell-cycle inhibitor cell division autoantigen-1 (CDA1). Further, high NOS2 expression correlates with decreased survival in human glioma patients, and NOS2 inhibition slows glioma growth in a murine intracranial model. These data provide insight into how GSCs are mechanistically distinct from their less tumorigenic counterparts and suggest that NOS2 inhibition may be an efficacious approach to treating this devastating disease.

Inhibitors of the Platelet Thrombin Receptor

Not that long ago, aspirin, heparin, and warfarin were the only available antithrombotic agents for treating cardiovascular disease patients at risk of thrombotic events. These agents are still used in several places around the world, and it is remarkable how difficult it was to discover other agents that are more effective and/or safer. Since the mid-1980s we have been witnessing an explosion of research on new antithrombotic therapies, resulting in the availability of ticlopidine and clopidogrel (thienopyridine P2Y12-receptor inhibitors), low–molecular-weight heparins (eg, enoxaparin), and intravenous GPIIb/IIIa-receptor inhibitors (abciximab, eptifibatide, and tirofiban), later followed by fondaparinux (a synthetic indirect intravenous anti-Xa agent), bivalirudin (an intravenous direct anti-IIa agent), and more recently, prasugrel (a more potent thienopyridine) (Figure). Figure. The coagulation cascade, platelet activation pathways, and targets of antithrombotic agents. inhib indicates inhibition; LMWH, low–molecular-weight heparin; AT, antithrombin; vWF, von Willebrandt factor; TxA2, thromboxane A2; and ADP, adenosine diphosphate. Articles see pp 1843 and 1854 In the near future, several new oral antithrombotic agents may become available for treating patients with cardiovascular diseases: ticagrelor (the first direct reversible P2Y12 antagonist), dabigatran (an oral direct anti-IIa agent), rivaroxaban (an oral direct anti-Xa agent), and apixaban (also an oral direct anti-Xa agent). Other P2Y12 antagonists (eg, elinogrel) and oral anti-Xa agents (edoxaban, betrixaban, YM150, and TAK-442) are being studied or will be studied in phase-III programs (Figure). New antiplatelet therapies that target pathways not affected by aspirin or P2Y12-receptor antagonists could provide more comprehensive inhibition of platelet activation, and contribute to a greater inhibition of platelet-mediated thrombosis. Inhibition of protease-activated receptor-1 (PAR-1), a receptor for thrombin, is a new attractive approach in the development of better and safer antiplatelet therapy. As shown in the Figure, thrombin is the key effector of the coagulation cascade, but is also …

Upstream tirofiban reduces reperfusion cardiac arrhythmias in patients of acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention

“Open the artery in time” has become the dogma in treating ST-elevation myocardial infarction (STEMI) since the 1990s. It has been a consensus that the more patent the infarct-related artery (IRA), the better the clinical outcomes [ 1 Simes R.J. Topol E.J. Holmes Jr., D.R. et al. Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion. Importance of early and complete infarct artery reperfusion. GUSTO-I Investigators. Circulation. 1995; 91: 1923-1928 Crossref PubMed Scopus (463) Google Scholar , 2 Anderson J.L. Karagounis L.A. Califf R.M. Meta-analysis of five reported studies on the relation of early coronary patency grades with mortality and outcomes after acute myocardial infarction. Am J Cardiol. 1996; 78: 1-8 Abstract Full Text PDF PubMed Scopus (160) Google Scholar ]. In addition, the strategies of reperfusion, referring to intravenous thrombolytics and primary percutaneous coronary interventions (pPCI), have been proved to differ among themselves in acute success of reperfusion and long-term outcomes. The pPCI is better in restoring the coronary blood flow and renders less complications than thrombolytic therapy [ 3 Zijlstra F. de Boer M.J. Hoorntje J.C.A. Reiffers S. Reiber J.H. Suryapranata H. A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med. 1993; 328: 680-684 Crossref PubMed Scopus (1177) Google Scholar , 4 Zeymer U. Schroder R. Machnig T. Neuhaus K.L. Primary percutaneous transluminal coronary angioplasty accelerates early myocardial reperfusion compared to thrombolytic therapy in patients with acute myocardial infarction. Am Heart J. 2003; 146: 686-691 Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar ]. As the platelet plays the central role in triggering the acute thrombotic mechanism in STEMI, the complete inhibition of the platelet function, from adhesion, activation to aggregation, has been the focus of current optimal anti-platelet therapy. The standard dual anti-platelet therapy (DAT), consisting of aspirin and clopidogrel, exerts its function to counteract the platelet activation. The inadequacy and negligence to inhibiting platelet aggregation at the time of pPCI were proved to result in more major adverse cardiovascular events (MACE), especially in patients of clopidogrel resistance [ [5] Matetzky S. Shenkman B. Guetta V. et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation. 2004; 109: 3171-3175 Crossref PubMed Scopus (1282) Google Scholar ]. It is also said “the lower the platelet reactivity, the less the myocardial necrosis and the better the clinical outcomes [ [6] Campo G. Valgimigli M. Gemmati D. et al. Value of platelet reactivity in predicting response to treatment and clinical outcome in patients undergoing primary coronary intervention. Insights into the STRATEGY Study. J Am Coll Cardiol. 2006; 48: 2178-2185 Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar ].” In order to further block the platelet aggregation, adding a glycoprotein IIb/IIIa (GP IIb/IIIa) antagonist, thus formulating the triple anti-platelet therapy, has been recommended for high risk non-ST-elevation acute coronary syndromes (NSTEACS) [ [7] Bassand J.P. Hamm C.W. Ardissino D. et al. Task force for diagnosis and treatment of non ST elevation acute coronary syndromes. Eur Heart J. 2007; 28: 1598-1660 Crossref PubMed Scopus (49) Google Scholar ]. GP IIb/IIIa antagonist, especially tirofiban, could be adopted as one of the background therapy in dealing with NSTEACS [ [8] Hsin H.T. Li A.H. Yeih D.F. et al. Two-year follow-up of tirofiban-based management of non-ST-elevation acute coronary syndrome — a single center study. Acta Cardiol Sin. 2010; 26: 19-27 Google Scholar ]. On the other hand, peri-PCI abciximab has been demonstrated to significantly improve reperfusion in the infarct region and clinical outcomes of patients with STEMI undergoing pPCI, which has been regarded as class IIa recommendation since 2004 [ 9 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 , 10 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 ]. However, the role of tirofiban is rather obscure. The efficacy and timing to administer tirofiban in STEMI are still on debate.

Oxygen therapy in acute MI: role uncertainty

Administration of inhaled oxygen to patients with acute myocardial infarction (AMI) has been recommended in national and international guidelines (Kallstrom, 2002; Antman et al, 2004; American Heart Association, 2005; International Liaison Committee on Resuscitation, 2005; Anderson et al, 2007; Van de Werf, 2007) and has been a mainstay of prehospital management for decades.

Letter by Lin et al Regarding Article, “Triple Versus Dual Antiplatelet Therapy in Patients With Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention”

To the Editor: We read with interest the work by Chen et al,1 which reported that triple antiplatelet therapy seems to be superior to dual antiplatelet therapy in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention with drug-eluting stents. Chen et al1 reported the mortality benefits of triple antiplatelet therapy obtained mainly within 30 days after STEMI, reflecting the importance of the addition of cilostazol to aspirin and clopidogrel before stenting. Meanwhile, …

Automated Versus Visual Segmental Scoring

Echocardiography is the most widely used noninvasive test for assessing the structure and function of the heart, accounting for 14% of overall Medicare expenditures for imaging in 2007.1 Despite the availability of a variety of validated quantitative methods for assessing chamber size and cardiac function, many elements of echocardiographic interpretation remain qualitative rather than quantitative. This is particularly true of the assessment of regional wall motion. Notwithstanding progress in the field of myocardial perfusion echocardiography2 and earlier efforts to quantitate regional function with acoustic quantitation3 and Doppler tissue imaging-based methods,4 echocardiographic assessment of regional wall motion remains the principal method by which echocardiographers make the diagnosis of coronary disease. Moreover, the ability to visually identify stress-induced regional wall motion abnormalities is the foundation for stress echocardiography. Article see p 47 The ability to reproducibly and reliably detect regional wall motion abnormalities is an essential skill for any physician interpreting echocardiograms and conceded to be one of the most difficult skills to acquire.5 Consequently, an automated quantitative approach to assessing regional function would be invaluable as a tool for the interpretation of echocardiograms for teaching and research and could prove useful in training echocardiographers. The study of Liel Cohen6 in this issue of Circulation: Cardiovascular Imaging proposes just such a tool. In their article, the authors report their evaluation of a semiautomated method of measuring regional longitudinal strain to develop segmental scores, classifying segments as normal, hypokinetic, or akinetic/dyskinetic/aneurysmal. As the authors note, strain analysis based on speckle tracking as opposed to angle-dependent Doppler tissue imaging methods is appealing because it avoids translation artifact and angle dependence. Twelve expert echocardiographers of the Israeli Echocardiography Research Group at 9 major Israeli cardiology centers used this approach as well as qualitative visual segmental scoring in 15 patients …

Relationship of lipoprotein-associated phospholipase A2 and oxidized low density lipoprotein in carotid atherosclerosis

Plasma levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and oxidized low density lipoprotein (oxLDL) have been identified as risk factors for cardiovascular disease. Lp-PLA(2) is the sole enzyme responsible for the hydrolysis of oxidized phospholipids on LDL particles in atherosclerotic plaques. We have studied the relationship between Lp-PLA(2) and oxLDL in carotid endarterectomy (CEA) tissues and in matched plasmas. In extracts from CEA anatomical segments, the levels of oxLDL were significantly associated with the levels of Lp-PLA(2) protein (r = 0.497) and activity (r = 0.615). OxLDL and Lp-PLA(2) mass/activity were most abundant in the carotid bifurcation and internal segments where plaque was most abundant. In extracts from CEA atheroma, the levels of oxLDL and Lp-PLA(2) were significantly correlated (r = 0.634). In matched plasma and atheroma extracts, the levels of Lp-PLA(2) were negatively correlated (r = - 0.578). The ratio of Lp-PLA(2) to oxLDL was higher in atheromatous tissue (277:1) than in normal tissue (135:1) and plasma (13:1). Immunohistochemical experiments indicated that in plaques, oxLDL and Lp-PLA(2) existed in overlapping but distinctly different distribution. Fluorescence microscopy showed both oxLDL and Lp-PLA(2) epitopes on the same LDL particle in plasma but not in plaque. These results suggest that the relationship between Lp-PLA(2) and oxLDL in the atherosclerotic plaque is different from that in the plasma compartment.

The changing horizon of acute coronary syndrome

ST-elevation acute coronary syndromes are most commonly caused by thrombotic occlusion of an epicardial coronary artery. The immediate treatment goals are to re-establish coronary flow and to reduce clot burden as well as the risk of recurrent thrombus formation. Primary percutaneous coronary intervention (PCI), when delivered in a timely manner, is the preferred method to achieve reperfusion. 1 Keeley EC Boura JA Grines CL Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003; 361: 13-20 Summary Full Text Full Text PDF PubMed Scopus (3515) Google Scholar Drugs such as aspirin, thienopyridines, antithrombins, and glycoprotein IIb/IIIa antagonists are recommended by treatment guidelines 2 Antman EM Hand M Armstrong PW et al. 2007 focused update of the ACC/AHA 2004 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. Developed in collaboration With the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians: 2007 Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction, Writing on Behalf of the 2004 Writing Committee. Circulation. 2008; 117: 296-329 Crossref PubMed Scopus (1044) Google Scholar , 3 Van de Werf F Bax J Betriu A et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology. Eur Heart J. 2008; 29: 2909-2945 Crossref PubMed Scopus (1) Google Scholar in patients undergoing primary PCI to reduce periprocedural ischaemic events that are secondary to clot within the infarct-related artery. However, bleeding is a common complication resulting from administration of these adjunctive drugs, and occurs most frequently at the site of arterial access. Bivalirudin in patients undergoing primary angioplasty for acute myocardial infarction (HORIZONS-AMI): 1-year results of a randomised controlled trialIn patients with STEMI undergoing primary PCI, anticoagulation with bivalirudin reduced the rates of net adverse clinical events and major bleeding at 1 year compared with treatment with heparin plus a GPI. This finding has important clinical implications for the selection of optimum treatment strategies for patients with STEMI. Full-Text PDF

Should We Manage Patients With Non-ST Segment Elevation Myocardial Infarction With Renal Failure With an Invasive Strategy?

Szummer and colleagues raise an important question: Should we manage patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) with an early invasive strategy?1 It makes good sense to do this. We know that patients with renal dysfunction are at high risk,2 and the American College of Cardiology/American Heart Association and European Society of Cardiology guidelines both recommend an early invasive strategy for patients with unstable angina/NSTEMI who are high risk.3,4 Neither guideline, however, specifically notes that renal dysfunction should be a specific indication for an invasive strategy. Article see p 851 The investigators analyzed 23262 consecutive NSTEMI patients who had been included in a nationwide coronary care unit registry between 2003 and 2006 called the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART).1 Patients were divided into medically or invasively treated if revascularized within 14 days of admission. They found that for patients with worse renal function, the rate of performing revascularization was lower. This “risk paradox” has been seen in other registries, in which higher-risk patients are actually managed less intensively.5 They also found that 1-year mortality was substantially higher for those on dialysis or having an estimated glomerular filtration rate (GFR) <15 mL/min (≈55%) versus ≈40% for those with estimated GFR 15 to 29 mL/min and <5% for those with normal renal function. Thus, estimated GFR is clearly an important risk marker. They went on to compare mortality between medically managed patients and those who had revascularization and found overall a difference in mortality, with 36% lower adjusted mortality among those who had revascularization. They then split out the group by baseline renal function and found a lower mortality for those who had been revascularized versus not in most groups but not …

Letter by Ryding et al Regarding Article, “Impact of Pretreatment With Clopidogrel on Initial Patency and Outcome in Patients Treated With Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: A Systematic Review”

HomeCirculationVol. 120, No. 4Letter by Ryding et al Regarding Article, “Impact of Pretreatment With Clopidogrel on Initial Patency and Outcome in Patients Treated With Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: A Systematic Review” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Ryding et al Regarding Article, “Impact of Pretreatment With Clopidogrel on Initial Patency and Outcome in Patients Treated With Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: A Systematic Review” Alisdair Ryding, Saurabh Kumar and Ravinay Bhindi Alisdair RydingAlisdair Ryding Department of Cardiology, Westmead Hospital, Westmead, Sydney, Australia Search for more papers by this author , Saurabh KumarSaurabh Kumar Department of Cardiology, Westmead Hospital, Westmead, Sydney, Australia Search for more papers by this author and Ravinay BhindiRavinay Bhindi Department of Cardiology, Westmead Hospital, Westmead, Sydney, Australia Search for more papers by this author Originally published28 Jul 2009https://doi.org/10.1161/CIRCULATIONAHA.108.839746Circulation. 2009;120:e26To the Editor:The meta-analysis by Vlaar et al1 raises an important question about the timing of clopidogrel treatment at the time of primary percutaneous coronary intervention. The conclusion that pretreatment with clopidogrel results in higher arterial patency rates, lower early mortality, and reinfarction is plausible. In our opinion, however, the analysis failed to take account of important confounders. First, we estimate that glycoprotein inhibitor usage was documented in 2803 of 4114 patients in the clopidogrel pretreatment group compared with only 1341 of 4315 patients in the delayed treatment group (P<0.0001). Furthermore, although the data on symptom onset to percutaneous coronary intervention time interval are incomplete, a further bias exists in favor of the clopidogrel pretreatment group (weighted means: 3.2 hours versus 3.8 hours). These 2 variables are likely to have a significant impact on the study outcomes and may be sufficient to account for the effect attributed to clopidogrel.2,3 In our opinion, the benefit of clopidogrel pretreatment in primary percutaneous coronary intervention remains undetermined particularly in the context of adjunctive glycoprotein inhibitor.DisclosuresNone. References 1 Vlaar PJ, Svilaas T, Damman K, de Smet BJ, Tijssen JG, Hillege HL, Zijlstra F. Impact of pretreatment with clopidogrel on initial patency and outcome in patients treated with primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a systematic review. Circulation. 2008; 118: 1828–1836.LinkGoogle Scholar2 De Luca G, Suryapranata H, Stone GW, Antoniucci D, Tcheng JE, Neumann FJ, Van de Werf F, Antman EM, Topol EJ. Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials. JAMA. 2005; 293: 1759–1765.CrossrefMedlineGoogle Scholar3 Nallamothu B, Fox KA, Kennelly BM, Van de Werf F, Gore JM, Steg PG, Granger CB, Dabbous OH, Kline-Rogers E, Eagle KA, GRACE Investigators. Relationship of treatment delays and mortality in patients undergoing fibrinolysis and primary percutaneous coronary intervention: the global registry of acute coronary events. Heart. 2007; 93: 1552–1555.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails July 28, 2009Vol 120, Issue 4 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.108.839746PMID: 19635977 Originally publishedJuly 28, 2009 PDF download Advertisement SubjectsMyocardial InfarctionPharmacology

Stopping the Hemorrhage

Aggressive management of high-risk non–ST-elevation acute coronary syndrome patients has focused on reducing ischemic complications with potent medications and mechanical interventions1,2 but at the cost of increased rates of major bleeding and associated adverse outcomes.3,4 The American College of Cardiology/American Heart Association 2007 guidelines for management of patients with unstable angina/non–ST-elevation myocardial infarction (NSTEMI)1 stress the importance of balancing antithrombotic and interventional therapies with therapeutic risk, and they urge special attention in groups at high bleeding risk, including women, the elderly, and those with renal insufficiency. For risk-prone groups, careful selection and dose adjustment of antithrombotics is encouraged, but no specific instruction for calculating bleeding risk or modifying treatment is provided. Article p 1873 The European Society of Cardiology’s 2007 guidelines for the diagnosis and treatment of non–ST-segment elevation acute coronary syndromes2 also recognize and devote a special section to bleeding complications, covering predictors of bleeding risk, the impact of bleeding on prognosis, the management of bleeding complications, and the impact of blood transfusions on outcomes. Major bleeding has been reported in 2% to 8% of non–ST-elevation acute coronary syndrome patients, with higher rates noted in broad-based registries (as in CRUSADE: Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the ACC/AHA guidelines) than in controlled clinical trials. Complicating therapeutic decision making is the observation that baseline predictors of bleeding, ie, old age, female sex, renal dysfunction, and baseline anemia, also predict the risk of death due to ischemic complications. The impact of bleeding on prognosis is increasingly recognized. Major bleeding in the Global Registry of Acute Coronary Events (GRACE) was significantly associated with in-hospital death (adjusted OR 1.645). In registries and trials of more than 30 000 patients, major bleeding was associated with a 4-fold increase in the …

Duration of Symptoms Is Not Always the Key Modulator of the Choice of Reperfusion for ST-Elevation Myocardial Infarction

Fibrinolytic therapy (FT) and primary percutaneous coronary intervention (PCI) are both well-accepted reperfusion therapies in ST-segment elevation myocardial infarction (STEMI). The evidence of randomized clinical trials indicates a relatively modest difference in 30-day mortality (≈1%) in favor of primary PCI over fibrin-specific FT and was based on very timely primary PCI (ie, a primary PCI–related delay of 40 minutes [door-to-balloon less door-to-needle time]).1 Longer delays to primary PCI, which are far more frequent in clinical practice,2 are associated with attenuated benefit or no benefit at all, particularly when compared with fibrin-specific FT.3,4 The benefit of timely primary PCI over FT is likely to especially apply to higher-risk patients.5,6 Irrespective of the method of reperfusion, the potential for myocardial salvage and better clinical outcome is inversely proportional to ischemic time or its only available clinical surrogate, symptom duration.7–12 These considerations underpin the notion expressed in the American College of Cardiology/American Heart Association (ACC/AHA) guidelines on the treatment of STEMI that timely reperfusion therapy is likely more important in determining outcome than whether FT or primary PCI is the chosen reperfusion method.13 Response by Armstrong et al p 1310 The ACC/AHA STEMI guidelines highlight the time point of 3 hours of symptom duration in guiding the choice of reperfusion therapy. They state that if symptom duration is <3 hours, no preference exists between FT and primary PCI provided that treatment is timely (for FT, door-to-needle time <30 minutes; for primary PCI, door-to-balloon time <90 minutes and ≤60 minutes between estimated needle time and estimated balloon time). However, if symptom duration exceeds 3 hours, these guidelines favor primary PCI over FT, again provided that primary PCI can be performed in a timely fashion.13 This article reexamines the evidence that may or may not be the basis …

Retirement of Désiré Collen.

Retirement of Désiré Collen.

Primary Percutaneous Coronary Intervention With Drug-Eluting Stents

Primary percutaneous coronary intervention (P-PCI) is the preferred reperfusion strategy for patients with ST-segment elevation myocardial infarction if it can be performed rapidly by an experienced team.1 Compared with balloon angioplasty, routine bare-metal stent (BMS) implantation decreases risk for target vessel revascularization (TVR) and possibly reduces myocardial reinfarction rates but does not reduce mortality rates.2,3 Therefore, BMS has become the dominant P-PCI strategy, despite initial concern about increased stent thrombosis rates from delayed healing or inadequate late stent apposition due to initial thrombus trapping. Less established is the role of drug-eluting stents (DES) in P-PCI. DES have the potential to further decrease TVR rates but may increase risk for stent thrombosis. In fact, the risk of stent thrombosis might even be higher in P-PCI than in electively treated patients because of the combination of increased platelet activation, delayed healing, lack of endothelialization, and the proinflammatory and prothrombotic environment in the infarct artery.4 Article see p 103 Several relatively small randomized clinical trials have shown inconsistent efficacy for DES over BMS for P-PCI. Three meta-analyses of these trials have concluded that there is no difference in death or myocardial infarction rates, but TVR rates are decreased.5–7 Variably included were 12 studies that differed in trial design, inclusion criteria, end-point definitions, stent types, duration of clopidogrel treatment, and type of follow-up (angiographic versus clinical). They were limited by sample size and duration of follow-up and usually required angiographic documentation of stent thrombosis, which may have underestimated its true incidence. In this issue of Circulation: Cardiovascular Interventions , Kukreja et al8 report a single-center registry study that is an expanded version of a previous publication.9 Again including the 185 ST-segment elevation myocardial infarction patients treated with Sirolimus-eluting stents (SES) from April 2002 to February 2003, they compare …

Bleeding Is Bad…. Isn’t It?

Advances in antithrombin and antiplatelet therapy have traditionally been associated with reductions in myocardial infarction and other thrombotic events in patients who have experienced an acute coronary syndrome (ACS), are undergoing a percutaneous coronary intervention (PCI), or are receiving long-term therapy for secondary prevention of stable vascular disease. Although individual trials of antithrombotic therapy have rarely been able to demonstrate that the reduction in ischemic events leads to a reduction in mortality (the most important end point), meta-analyses have often suggested that this is the case.1 And because myocardial infarction is an independent correlate of mortality, a link between a reduction in ischemic events and reduced mortality makes intuitive sense. Article p 2793 Unfortunately, more potent anticoagulants and antiplatelet agents are also associated with an increased risk of bleeding, especially when used in combination with one another, as is usually the case. Furthermore, there is a well-established body of evidence that indicates an association between bleeding and ischemic events.2,3 It has been unclear, however, whether the link between bleeding and thrombosis is the result of bleeding after the initial development of a thrombotic complication (and its treatment) or if bleeding precedes the development of an ischemic complication and actually leads to (actually causes) thrombosis. In support of the former possibility is that patients who, because of the presence of thrombus, undergo a longer or more complicated procedure, receive a higher dose or longer duration of antithrombotic medication, or require an intra-aortic balloon pump are surely more prone to bleed. However, the possibility that hemorrhage actually leads to thrombosis rather than results from it is supported by the observation that hemorrhage is a potent stimulus for thrombosis; all patients would surely die if bleeding did not trigger at least a local thrombotic reaction. Furthermore, as the Global Registry of …