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2.
Am J Cardiol ; 188: 95-101, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36493607

ABSTRACT

In patients with non-ST-elevation myocardial infarction (NSTEMI), total occlusion of the culprit coronary artery (OCA) is not uncommon. We sought to determine the frequency and clinical impact of OCA at presentation in a large population of patients presenting with NSTEMI and who underwent systematic early invasive management. We performed a post hoc analysis of the TAO (Treatment of Acute Coronary Syndrome with Otamixaban) randomized trial, which included patients with NSTEMI with systematic coronary angiography within 72 hours. We compared the baseline characteristics and outcomes of patients according to whether the culprit vessel was occluded (thrombolysis in myocardial infarction flow grade [TFG] 0 to 1) or patent (TFG 2 to 3) at presentation. A total of 7,473 patients with NSTEMI with only 1 culprit lesion identified were enrolled, of whom 1,702 patients had OCA (22.8%). In the OCA group, coronary angiography was performed earlier (18 ± 15 vs 20 ± 16 hours, p <0.01), the culprit lesion was less likely to be the left anterior descending artery (26.5% vs 41.4%, p <0.001) but with more frequent angiographic thrombus (49.9% vs 22.7%, p <0.01). Culprit artery percutaneous coronary intervention during the index procedure was also more frequent (88.5% vs 78.1%, p <0.001) but with a lower rate of TFG grade 3 after the procedure and higher subsequent peak troponin I levels (8.3 ± 13.6 µg/L vs 5.6 ± 11.9 µg/L, p <0.001). At day 7, patients with OCA had higher mortality, and this persisted after adjustment on gender, Grace risk score, cardiovascular risk factors, and culprit vessel location (0.9% vs 0.4%, p = 0.02; adjusted odds ratio [OR] = 2.55, 95% confidence interval [CI] 1.23 to 5.29, p = 0.01). The absolute difference of mortality was maintained through 30 days: 1.2% versus 0.8%, p = 0.13; OR: 1.72, 95% CI 0.97 to 3.05, but mortality rates were similar by 180 days: 1.5% versus 1.6%, p = 0.8, adjusted OR = 1.11, 95% CI 0.69 to 1.80, p = 0.66. In conclusion, a significant proportion of patients with NSTEMI have a totally occluded culprit vessel at presentation. These patients are at higher risk of early mortality but not at 6 months.


Subject(s)
Myocardial Infarction , Non-ST Elevated Myocardial Infarction , Percutaneous Coronary Intervention , Humans , Non-ST Elevated Myocardial Infarction/diagnosis , Non-ST Elevated Myocardial Infarction/surgery , Non-ST Elevated Myocardial Infarction/etiology , Clinical Relevance , Percutaneous Coronary Intervention/adverse effects , Coronary Angiography/methods , Treatment Outcome
3.
JAMA Cardiol ; 7(11): 1091-1099, 2022 11 01.
Article in English | MEDLINE | ID: mdl-36129696

ABSTRACT

Importance: In patients with multivessel coronary artery disease (CAD) presenting with ST-segment elevation myocardial infarction (STEMI), complete revascularization reduces major cardiovascular events compared with culprit lesion-only percutaneous coronary intervention (PCI). Whether complete revascularization also improves angina-related health status is unknown. Objective: To determine whether complete revascularization improves angina status in patients with STEMI and multivessel CAD. Design, Setting, and Participants: This secondary analysis of a randomized, multinational, open label trial of patient-reported outcomes took place in 140 primary PCI centers in 31 countries. Patients presenting with STEMI and multivessel CAD were randomized between February 1, 2013, and March 6, 2017. Analysis took place between July 2021 and December 2021. Interventions: Following PCI of the culprit lesion, patients with STEMI and multivessel CAD were randomized to receive either complete revascularization with additional PCI of angiographically significant nonculprit lesions or to no further revascularization. Main Outcomes and Measures: Seattle Angina Questionnaire Angina Frequency (SAQ-AF) score (range, 0 [daily angina] to 100 [no angina]) and the proportion of angina-free individuals by study end. Results: Of 4041 patients, 2016 were randomized to complete revascularization and 2025 to culprit lesion-only PCI. The mean (SD) age of patients was 62 (10.7) years, and 3225 (80%) were male. The mean (SD) SAQ-AF score increased from 87.1 (17.8) points at baseline to 97.1 (9.7) points at a median follow-up of 3 years in the complete revascularization group (score change, 9.9 [95% CI, 9.0-10.8]; P < .001) compared with an increase of 87.2 (18.4) to 96.3 (10.9) points (score change, 8.9 [95% CI, 8.0-9.8]; P < .001) in the culprit lesion-only group (between-group difference, 0.97 points [95% CI, 0.27-1.67]; P = .006). Overall, 1457 patients (87.5%) were free of angina (SAQ-AF score, 100) in the complete revascularization group compared with 1376 patients (84.3%) in the culprit lesion-only group (absolute difference, 3.2% [95% CI, 0.7%-5.7%]; P = .01). This benefit was observed mainly in patients with nonculprit lesion stenosis severity of 80% or more (absolute difference, 4.7%; interaction P = .02). Conclusions and Relevance: In patients with STEMI and multivessel CAD, complete revascularization resulted in a slightly greater proportion of patients being angina-free compared with a culprit lesion-only strategy. This modest incremental improvement in health status is in addition to the established benefit of complete revascularization in reducing cardiovascular events.


Subject(s)
Coronary Artery Disease , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Male , Middle Aged , Female , ST Elevation Myocardial Infarction/surgery , ST Elevation Myocardial Infarction/complications , Percutaneous Coronary Intervention/methods , Quality of Life , Treatment Outcome , Coronary Artery Disease/complications , Coronary Artery Disease/surgery , Angina Pectoris/surgery
5.
Eur Heart J ; 42(18): 1760-1769, 2021 05 07.
Article in English | MEDLINE | ID: mdl-33580685

ABSTRACT

AIMS: The rapid endothelialization of bare metal stents (BMS) is counterbalanced by inflammation-induced neointimal growth. Drug-eluting stents (DES) prevent leukocyte activation but impair endothelialization, delaying effective device integration into arterial walls. Previously, we have shown that engaging the vascular CD31 co-receptor is crucial for endothelial and leukocyte homeostasis and arterial healing. Furthermore, we have shown that a soluble synthetic peptide (known as P8RI) acts like a CD31 agonist. The aim of this study was to evaluate the effect of CD31-mimetic metal stent coating on the in vitro adherence of endothelial cells (ECs) and blood elements and the in vivo strut coverage and neointimal growth. METHODS AND RESULTS: We produced Cobalt Chromium discs and stents coated with a CD31-mimetic peptide through two procedures, plasma amination or dip-coating, both yielding comparable results. We found that CD31-mimetic discs significantly reduced the extent of primary human coronary artery EC and blood platelet/leukocyte activation in vitro. In vivo, CD31-mimetic stent properties were compared with those of DES and BMS by coronarography and microscopy at 7 and 28 days post-implantation in pig coronary arteries (n = 9 stents/group/timepoint). Seven days post-implantation, only CD31-mimetic struts were fully endothelialized with no activated platelets/leukocytes. At day 28, neointima development over CD31-mimetic stents was significantly reduced compared to BMS, appearing as a normal arterial media with the absence of thrombosis contrary to DES. CONCLUSION: CD31-mimetic coating favours vascular homeostasis and arterial wall healing, preventing in-stent stenosis and thrombosis. Hence, such coatings seem to improve the metal stent biocompatibility.


Subject(s)
Drug-Eluting Stents , Neointima , Animals , Coronary Vessels , Endothelial Cells , Inflammation/prevention & control , Neointima/prevention & control , Prosthesis Design , Stents , Swine
6.
JACC Cardiovasc Interv ; 11(14): 1340-1350, 2018 07 23.
Article in English | MEDLINE | ID: mdl-30025727

ABSTRACT

OBJECTIVES: The purpose of this study was to assess neoatherosclerosis in a registry of prospectively enrolled patients presenting with stent thrombosis using optical coherence tomography. BACKGROUND: In-stent neoatherosclerosis was recently identified as a novel disease manifestation of atherosclerosis after coronary stent implantation. METHODS: Angiography and intravascular optical coherence tomography were used to investigate etiologic factors of neoatherosclerosis in patients presenting with stent thrombosis >1 year after implantation (very late stent thrombosis [VLST]). Clinical data were collected according to a standardized protocol. Optical coherence tomographic acquisitions were analyzed in a core laboratory. Cox regression analysis was performed to identify factors associated with the formation of neoatherosclerosis and plaque rupture as a function of time. RESULTS: Optical coherence tomography was performed in 134 patients presenting with VLST. A total of 58 lesions in 58 patients with neoatherosclerosis were compared with 76 lesions in 76 patients without neoatherosclerosis. Baseline characteristics were similar between groups. In-stent plaque rupture was the most frequent cause (31%) in all patients presenting with VLST. In patients with neoatherosclerosis, in-stent plaque rupture was identified as the cause of VLST in 40 cases (69%), whereas uncovered stent struts (n = 22 [29%]) was the most frequent cause in patients without neoatherosclerosis. Macrophage infiltration was significantly more frequent in optical coherence tomographic frames with plaque rupture compared with those without (50.2% vs. 22.2%; p < 0.0001), whereas calcification was more often observed in frames without plaque rupture (17.2% vs. 4%; p < 0.0001). Implantation of a drug-eluting stent was significantly associated with the formation of neoatherosclerosis (p = 0.02), whereas previous myocardial infarction on index percutaneous coronary intervention was identified as a significant risk factor for plaque rupture in patients with neoatherosclerosis (p = 0.003). No significant difference was observed in thrombus composition between patients with or without neoatherosclerosis. CONCLUSIONS: Neoatherosclerosis was frequently observed in patients with VLST. Implantation of a drug-eluting stent was significantly associated with neoatherosclerosis formation. In-stent plaque rupture was the prevailing pathological mechanism and often occurred in patients with neoatherosclerosis and previous myocardial infarction at index percutaneous coronary intervention. Increased macrophage infiltration heralded plaque vulnerability in our study and might serve as an important indicator.


Subject(s)
Coronary Artery Disease/therapy , Coronary Thrombosis/diagnostic imaging , Coronary Vessels/diagnostic imaging , Percutaneous Coronary Intervention , Plaque, Atherosclerotic , Stents , Tomography, Optical Coherence , Aged , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/pathology , Coronary Thrombosis/pathology , Coronary Vessels/pathology , Drug-Eluting Stents , Europe , Female , Humans , Male , Metals , Middle Aged , Neointima , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Predictive Value of Tests , Prospective Studies , Prosthesis Design , Registries , Risk Factors , Rupture, Spontaneous , Time Factors
7.
JACC Cardiovasc Interv ; 10(24): 2548-2556, 2017 12 26.
Article in English | MEDLINE | ID: mdl-29268884

ABSTRACT

OBJECTIVES: High platelet reactivity (HPR) was studied in patients presenting with ST-segment elevation myocardial infarction (STEMI) due to stent thrombosis (ST) undergoing immediate percutaneous coronary intervention (PCI). BACKGROUND: HPR on P2Y12 inhibitors (HPR-ADP) is frequently observed in stable patients who have experienced ST. The HPR rates in patients presenting with ST for immediate PCI are unknown. METHODS: Consecutive patients presenting with definite ST were included in a multicenter ST registry. Platelet reactivity was measured before immediate PCI with the VerifyNow P2Y12 or Aspirin assay. RESULTS: Platelet reactivity was measured in 129 ST patients presenting with STEMI undergoing immediate PCI. HPR-ADP was observed in 76% of the patients, and HPR on aspirin (HPR-AA) was observed in 13% of the patients. HPR rates were similar in patients who were on maintenance P2Y12 inhibitor or aspirin since stent placement versus those without these medications. In addition, HPR-ADP was similar in patients loaded with a P2Y12 inhibitor shortly before immediate PCI versus those who were not. In contrast, HPR-AA trended to be lower in patients loaded with aspirin as compared with those not loaded. CONCLUSIONS: Approximately 3 out of 4 ST patients with STEMI undergoing immediate PCI had HPR-ADP, and 13% had HPR-AA. Whether patients were on maintenance antiplatelet therapy while developing ST or loaded with P2Y12 inhibitors shortly before undergoing immediate PCI had no influence on the HPR rates. This raises concerns that the majority of patients with ST have suboptimal platelet inhibition undergoing immediate PCI.


Subject(s)
Blood Platelets/drug effects , Coronary Thrombosis/prevention & control , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Platelet Aggregation Inhibitors/therapeutic use , Purinergic P2Y Receptor Antagonists/therapeutic use , ST Elevation Myocardial Infarction/surgery , Stents/adverse effects , Adenosine Diphosphate/blood , Aged , Biomarkers/blood , Blood Platelets/metabolism , Coronary Thrombosis/blood , Coronary Thrombosis/diagnostic imaging , Coronary Thrombosis/etiology , Drug Resistance , Europe , Female , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Platelet Function Tests , Purinergic P2Y Receptor Antagonists/adverse effects , Receptors, Purinergic P2Y12/blood , Receptors, Purinergic P2Y12/drug effects , Recurrence , Registries , Risk Factors , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/etiology , Time Factors , Treatment Outcome
8.
Circulation ; 136(11): 1007-1021, 2017 Sep 12.
Article in English | MEDLINE | ID: mdl-28720725

ABSTRACT

BACKGROUND: Stent thrombosis (ST) is a serious complication following coronary stenting. Intravascular optical coherence tomography (OCT) may provide insights into mechanistic processes leading to ST. We performed a prospective, multicenter study to evaluate OCT findings in patients with ST. METHODS: Consecutive patients presenting with ST were prospectively enrolled in a registry by using a centralized telephone registration system. After angiographic confirmation of ST, OCT imaging of the culprit vessel was performed with frequency domain OCT. Clinical data were collected according to a standardized protocol. OCT acquisitions were analyzed at a core laboratory. Dominant and contributing findings were adjudicated by an imaging adjudication committee. RESULTS: Two hundred thirty-one patients presenting with ST underwent OCT imaging; 14 (6.1%) had image quality precluding further analysis. Of the remaining patients, 62 (28.6%) and 155 (71.4%) presented with early and late/very late ST, respectively. The underlying stent type was a new-generation drug-eluting stent in 50.3%. Mean reference vessel diameter was 2.9±0.6 mm and mean reference vessel area was 6.8±2.6 mm2. Stent underexpansion (stent expansion index <0.8) was observed in 44.4% of patients. The predicted average probability (95% confidence interval) that any frame had uncovered (or thrombus-covered) struts was 99.3% (96.1-99.9), 96.6% (92.4-98.5), 34.3% (15.0-60.7), and 9.6% (6.2-14.5) and malapposed struts was 21.8% (8.4-45.6), 8.5% (4.6-15.3), 6.7% (2.5-16.3), and 2.0% (1.2-3.3) for acute, subacute, late, and very late ST, respectively. The most common dominant finding adjudicated for acute ST was uncovered struts (66.7% of cases); for subacute ST, the most common dominant finding was uncovered struts (61.7%) and underexpansion (25.5%); for late ST, the most common dominant finding was uncovered struts (33.3%) and severe restenosis (19.1%); and for very late ST, the most common dominant finding was neoatherosclerosis (31.3%) and uncovered struts (20.2%). In patients presenting very late ST, uncovered stent struts were a common dominant finding in drug-eluting stents, and neoatherosclerosis was a common dominant finding in bare metal stents. CONCLUSIONS: In patients with ST, uncovered and malapposed struts were frequently observed with the incidence of both decreasing with longer time intervals between stent implantation and presentation. The most frequent dominant observation varied according to time intervals from index stenting: uncovered struts and underexpansion in acute/subacute ST and neoatherosclerosis and uncovered struts in late/very late ST.


Subject(s)
Coronary Thrombosis/diagnostic imaging , Coronary Thrombosis/prevention & control , Drug-Eluting Stents/trends , Percutaneous Coronary Intervention/trends , Research Report/trends , Tomography, Optical Coherence/trends , Aged , Coronary Thrombosis/epidemiology , Drug-Eluting Stents/adverse effects , Europe/epidemiology , Female , Humans , Male , Percutaneous Coronary Intervention/adverse effects , Prospective Studies , Registries , Tomography, Optical Coherence/methods
11.
Int J Cardiol ; 220: 137-42, 2016 Oct 01.
Article in English | MEDLINE | ID: mdl-27376570

ABSTRACT

AIM: To analyze the association between chronic metformin treatment and the development of contrast-induced acute kidney injury (CI-AKI) after primary percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI). METHODS: Patients with type 2 diabetes mellitus (T2DM) treated with PCI <24h in 2 coronary care units were included. Serum creatinine (Cr) was measured before and <48h after PCI. CI-AKI was defined as an increase in Cr>27µmol/l (0.3mg/dl) or >50% over baseline after PCI. Since PCI was urgent, metformin could not be withheld prior to PCI but was usually stopped after PCI. RESULTS: Among the 372 patients included, 147 (40%) were using metformin, which had older diabetes, but had risk factors similar to patients without metformin. Baseline eGFR was better in patients under metformin therapy. After PCI, we observed an increase of ≈10% in Cr, for both groups. There was a trend toward a lower rate of CI-AKI in patients under metformin (16% vs 25%, p=0.051). In patients with chronic kidney disease, 31 (26%) were under metformin therapy, and the rate of CI-AKI was similar in both groups (41% vs 40%, p=0.915). By multivariate analysis, metformin showed a trend toward a reduced rate of CI-AKI, even when adjusted for confounding (OR (95% CI): 0.548 (0.276-1.087)). No case of lactic acidosis was reported during the hospital stay. Moreover, there was no increased rate of cardiogenic shock or death with metformin treatment. CONCLUSION: In this multicenter observational study, chronic metformin treatment prior to primary PCI had no significant impact on CI-AKI.


Subject(s)
Acute Kidney Injury , Diabetes Mellitus, Type 2/drug therapy , Metformin/therapeutic use , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Aged , Contrast Media/adverse effects , Coronary Angiography/adverse effects , Coronary Angiography/methods , Creatinine/analysis , Diabetes Mellitus, Type 2/complications , Female , France/epidemiology , Humans , Hypoglycemic Agents/therapeutic use , Male , Medication Therapy Management , Middle Aged , Risk Assessment/methods , ST Elevation Myocardial Infarction/complications , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/surgery , Statistics as Topic
12.
Eur Heart J ; 37(19): 1538-49, 2016 05 14.
Article in English | MEDLINE | ID: mdl-26761950

ABSTRACT

BACKGROUND: Stent thrombosis (ST) is a rare but serious complication following percutaneous coronary intervention. Analysis of thrombus composition from patients undergoing catheter thrombectomy may provide important insights into the pathological processes leading to thrombus formation. We performed a large-scale multicentre study to evaluate thrombus specimens in patients with ST across Europe. METHODS: Patients presenting with ST and undergoing thrombus aspiration were eligible for inclusion. Thrombus collection was performed according to a standardized protocol and specimens were analysed histologically at a core laboratory. Serial tissue cross sections were stained with haematoxylin-eosin (H&E), Carstairs and Luna. Immunohistochemistry was performed to identify leukocyte subsets, prothrombotic neutrophil extracellular traps (NETs), erythrocytes, platelets, and fibrinogen. RESULTS: Overall 253 thrombus specimens were analysed; 79 (31.2%) from patients presenting with early ST, 174 (68.8%) from late ST; 79 (31.2%) were from bare metal stents, 166 (65.6%) from drug-eluting stents, 8 (3.2%) were from stents of unknown type. Thrombus specimens displayed heterogeneous morphology with platelet-rich thrombus and fibrin/fibrinogen fragments most abundant; mean platelet coverage was 57% of thrombus area. Leukocyte infiltrations were hallmarks of both early and late ST (early: 2260 ± 1550 per mm(2) vs. late: 2485 ± 1778 per mm(2); P = 0.44); neutrophils represented the most prominent subset (early: 1364 ± 923 per mm(2) vs. late: 1428 ± 1023 per mm(2); P = 0.81). Leukocyte counts were significantly higher compared with a control group of patients with thrombus aspiration in spontaneous myocardial infarction. Neutrophil extracellular traps were observed in 23% of samples. Eosinophils were present in all stent types, with higher numbers in patients with late ST in sirolimus-and everolimus-eluting stents. CONCLUSION: In a large-scale study of histological thrombus analysis from patients presenting with ST, thrombus specimens displayed heterogeneous morphology. Recruitment of leukocytes, particularly neutrophils, appears to be a hallmark of ST. The presence of NETs supports their pathophysiological relevance. Eosinophil recruitment suggests an allergic component to the process of ST.


Subject(s)
Coronary Thrombosis/prevention & control , Graft Occlusion, Vascular/prevention & control , Percutaneous Coronary Intervention/adverse effects , Stents , Aged , Blood Platelets , Coronary Thrombosis/metabolism , Drug-Eluting Stents , Eosinophils , Female , Fibrinogen/metabolism , Humans , Leukocyte Count , Lymphocyte Subsets , Male , Neutrophils , Prospective Studies , Prosthesis Failure , Thrombectomy/methods
13.
J Am Coll Cardiol ; 67(4): 392-403, 2016 Feb 02.
Article in English | MEDLINE | ID: mdl-26821627

ABSTRACT

BACKGROUND: Pulse pressure (PP) provides valuable prognostic information in specific populations, but few studies have assessed its value on cardiovascular outcomes in a broad, worldwide population. OBJECTIVES: The aim of this study was to determine whether PP is associated with major adverse cardiovascular outcomes, independently of mean arterial pressure. METHODS: Participants from the international REACH (Reduction of Atherothrombosis for Continued Health) registry, which evaluates subjects with clinical atherothrombotic disease or risk factors for its development, were examined. Those with incomplete 4-year follow-up or PP data (final n = 45,087) were excluded. Univariate and multivariate regression analyses were performed to determine the association between PP and cardiovascular outcomes, including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, all myocardial infarction, all stroke, cardiovascular hospitalization, and a combined outcome. PP was analyzed as a continuous and categorical (i.e., by quartile) variable. RESULTS: The mean age of the cohort was 68 ± 10 years, 35% were women, and 81% were treated for hypertension. The mean blood pressure was 138 ± 19/79 ± 11 mm Hg, rendering a mean PP of 49 ± 16 mm Hg. On univariate analysis, increasing PP quartile was associated with worse outcomes (p < 0.05 for all comparisons). After adjusting for sex, age, current smoking status, history of hypercholesterolemia, history of diabetes, aspirin use, statin use, blood pressure medication use, and mean arterial pressure, PP quartile was still associated with all outcomes except all stroke and cardiovascular death (p < 0.05 for all comparisons). Analysis of PP as a continuous variable yielded similar results. CONCLUSIONS: In an international cohort of high-risk subjects, PP, a readily available hemodynamic parameter, is associated with multiple adverse cardiovascular outcomes and provides prognostic utility beyond that of mean arterial pressure.


Subject(s)
Atherosclerosis/physiopathology , Blood Pressure/physiology , Registries , Risk Assessment/methods , Thrombosis/etiology , Aged , Atherosclerosis/complications , Atherosclerosis/diagnosis , Female , Follow-Up Studies , France/epidemiology , Humans , Incidence , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Survival Rate/trends , Thrombosis/diagnosis , Thrombosis/epidemiology , Time Factors , United States/epidemiology
14.
Eur Heart J Acute Cardiovasc Care ; 5(2): 193-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-25725017

ABSTRACT

AIM: There is uncertainty as to whether consenting and randomizing patients in randomized clinical trials (RCTs) in acute ST-segment elevation myocardial infarction (STEMI) delays reperfusion and increases mortality. The aim of this study was to determine whether participation of patients with STEMI in RCTs is associated with delay in implementation of reperfusion therapy and increased hospital mortality. METHODS AND RESULTS: A consecutive sample of 2523 patients, admitted within 6 hours of symptom onset without cardiogenic shock, was recruited from a single tertiary academic centre. They were categorized according to participation (n=392, 15.5%) or nonparticipation (n=2131, 84.5%) in RCTs of reperfusion therapy. Primary outcome was hospital mortality. Additional outcome was time from symptom onset to receipt of reperfusion therapy. Trial participants were more likely to receive fibrinolysis with a 37 min delay in comparison with patients not included in RCTs. Time from symptom onset to reperfusion (minutes) was longer for trial participants than nonparticipants (246 ± 85 vs 233 ± 93, p=0.01). Hospital mortality was 3.61% for nonparticipants. Expected mortality (based on risk modeling) for trial participants was 2.74% (p=0.014 vs nonparticipants). Observed mortality was 1.53% (p=0.034 vs nonparticipants; p=0.16 vs expected mortality). In a multivariable analysis using logistic regression, participation in a RCT was not an independent correlate of hospital mortality (odds ratio 0.54, 95% confidence interval 0.23-2.43, p=0.16). CONCLUSIONS: In this consecutive cohort, despite a longer delay to reperfusion, there was no indication that participation in a RCT, starting before initiation of reperfusion therapy, was associated with a detectable increase in risk of hospital mortality among patients with STEMI. These data suggest that it is possible to consent and randomize patients with STEMI into RCTs without jeopardizing their survival.


Subject(s)
Myocardial Infarction/mortality , Myocardial Infarction/therapy , Myocardial Reperfusion/methods , Myocardial Reperfusion/statistics & numerical data , Randomized Controlled Trials as Topic/statistics & numerical data , Aged , Female , Fibrinolysis , Humans , Logistic Models , Male , Middle Aged , Patient Admission , Survival Analysis , Time-to-Treatment
15.
Arch Cardiovasc Dis ; 108(12): 675-82, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26596251

ABSTRACT

Cardiovascular disease is still the main cause of death in the world, and coronary artery disease is the largest contributor. Screening asymptomatic individuals for coronary artery disease in view of preventive treatment is therefore of crucial interest. Apart from established risk scores based on traditional risk factors such as the Framingham or SCORE risk scores, new biomarkers and imaging methods have emerged (high-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2 and secretory phospholipase A2, coronary artery calcium score, carotid intima-media thickness and ankle-brachial index). Their added value on top of the classic risk scores varies considerably and the most convincing evidence exists for coronary artery calcium score in intermediate-risk asymptomatic individuals.


Subject(s)
Asymptomatic Diseases/epidemiology , Coronary Artery Disease , Mass Screening/methods , Coronary Artery Disease/diagnosis , Coronary Artery Disease/epidemiology , Coronary Artery Disease/prevention & control , Global Health , Humans , Morbidity/trends , Risk Factors
16.
Am J Cardiol ; 111(12): 1708-13, 2013 Jun 15.
Article in English | MEDLINE | ID: mdl-23523063

ABSTRACT

There is intense interest in examining hospital mortality in relation to gender in ST-segment elevation myocardial infarction. The aim of the present study was to determine whether gender influences outcomes in men and women treated with the same patency-oriented reperfusion strategy. The influence of gender on hospital mortality was tested using multivariate analysis and local regression. The influence of age was tested as a continuous and as a categorical variable. In the overall population of 2,600 consecutive patients, gender was not correlated with hospital mortality except in the subgroup of women aged ≥65 years. The risk for death increased linearly in logit scale for men. Up to the age of 65 years, the risk also increased linearly in women but thereafter increased faster than in men. Testing age as a categorical variable, hospital mortality was higher in women than in men aged ≥75 years but was similar between the genders in the younger age categories. In conclusion, despite following an equal patency-oriented management strategy in men and women with ST-segment elevation myocardial infarctions, the risk for hospital death increased linearly with age but with an interaction between age and gender such that older women had an independent increase in hospital mortality. Longer time to presentation and worse baseline characteristics probably contributed to determine a high-risk subset but reinforce the need to apply, as recommended in the international guidelines in the management of patients with ST-segment elevation myocardial infarctions, the same strategy of acute reperfusion in men and women.


Subject(s)
Angioplasty, Balloon, Coronary , Heart Conduction System/physiopathology , Hospital Mortality , Myocardial Infarction/mortality , Myocardial Infarction/physiopathology , Adult , Age Distribution , Aged , Aged, 80 and over , Angioplasty, Balloon, Coronary/methods , Electrocardiography , Female , France/epidemiology , Humans , Male , Middle Aged , Myocardial Infarction/diagnosis , Myocardial Infarction/therapy , Prognosis , Risk Factors , Sex Distribution
18.
Eur Heart J ; 32(12): 1561-71, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21118852

ABSTRACT

AIMS: P947 is a gadolinium-based magnetic resonance imaging (MRI) contrast agent with high affinity for several matrix metalloproteinases (MMPs) involved in arterial wall remodelling. We tested whether the intensity of enhancement detected in vivo in the arterial wall with P947 and MRI correlates with actual tissue MMP-related enzymatic activity measured in a rabbit atherosclerotic model subjected to dietary manipulations. METHODS AND RESULTS: Aortas of 15 rabbits in which atherosclerotic lesions were induced by balloon angioplasty and 4 months of hypercholesterolaemic diet were imaged at 'baseline' with P947-enhanced MRI. Atherosclerotic rabbits were divided into three groups: five rabbits were sacrificed ('baseline' group); five rabbits continued to be fed a lipid-supplemented diet ('high-fat' group); and five rabbits were switched from atherogenic to a purified chow diet ('low-fat' group). Four months later, a second P947-enhanced MRI was acquired in the 10 remaining rabbits. A significantly lower signal was detected in the aortic wall of rabbits from the 'low-fat' group as compared with rabbits from the 'high-fat' group (21 ± 6 vs. 46 ± 3%, respectively; P = 0.04). Such differences were not detected with the contrast agent P1135, which lacks the MMP-specific peptide sequence. In addition, the intensity of aortic wall enhancement detected with MRI after injection of P947 strongly correlated with actual MMP-2 gelatinolytic activity measured in corresponding aortic segments using zymography (r = 0.87). CONCLUSION: P947-enhanced MRI can distinguish dietary-induced variations in MMP-related enzymatic activity within plaques in an experimental atherosclerotic model, supporting its utility as a clinical imaging tool for in vivo detection of arterial wall remodelling.


Subject(s)
Aortic Diseases/pathology , Atherosclerosis/pathology , Matrix Metalloproteinases/metabolism , Animals , Aorta, Abdominal , Atherosclerosis/metabolism , Cholesterol/metabolism , Contrast Media , Diet, Fat-Restricted , Diet, High-Fat , Heterocyclic Compounds/metabolism , Magnetic Resonance Angiography , Organometallic Compounds/metabolism , Plaque, Atherosclerotic/metabolism , Plaque, Atherosclerotic/pathology , Rabbits
19.
Int J Cardiol ; 145(1): 15-20, 2010 Nov 05.
Article in English | MEDLINE | ID: mdl-19481280

ABSTRACT

BACKGROUND: There are limited recent data on the prevalence and potentially different adverse impact of the various types of recurrent ischemia (RI) in unselected patients with acute coronary syndromes(ACS). We examined the clinical features and treatment associated with, and the differential prognostic impact of, the various types of RI in unselected patients across the broad spectrum of ACS in the contemporary era. METHODS: The Global Registry of Acute Coronary Events (GRACE) was a prospective, multinational registry of patients hospitalized for ACS. Data were collected on standardized case report forms. RESULTS: Of the 29,400 ACS patients enrolled in May 2000-March 2007, 21% developed RI; 2.4%, 4.9%, and 16% had myocardial (re-)infarction [(re-)MI], RI with ST-segment changes, and RI without ST-segment changes (not mutually exclusive), respectively. Rates of in-hospital mortality and complications, and 6-month mortality were significantly higher among patients with RI compared to those without; the rates were highest for patients who developed (re-)MI, followed by those with RI and ST-segment changes. After adjusting for other validated prognosticators in the GRACE risk score, all three types of RI retained an independent association with both higher in-hospital and post-discharge 6-month mortality. Early revascularization was associated with lower in-hospital mortality only in the group with (re-)MI (P for interaction=0.003). CONCLUSIONS: Despite the current use of intensive medical therapies, RI remains a common and serious consequence across the spectrum of ACS. Different types of RI confer a variable adverse prognostic impact. Re-MI is associated with the worst outcome, which appears to be mitigated by early revascularization. Our findings underscore the persistent need to improve the treatment of ACS.


Subject(s)
Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/epidemiology , Myocardial Infarction/diagnosis , Myocardial Infarction/epidemiology , Registries , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myocardial Ischemia/diagnosis , Myocardial Ischemia/epidemiology , Prevalence , Prognosis , Recurrence
20.
Biomacromolecules ; 10(11): 3074-80, 2009 Nov 09.
Article in English | MEDLINE | ID: mdl-19761207

ABSTRACT

In patients receiving drug eluting stents, there is a growing concern about both the long-term toxicity/degradability of the polymers used for the coating, and the nature of the therapeutic agents. We hypothesized that the use of a functionalized biocompatible polymer for a stent coating could be appropriate for local arterial therapy. A cationized pullulan hydrogel was thus prepared to cover bare metal stents that could be further loaded with small interfering RNA (siRNA) targeted at MMP2 for gene silencing in vascular cells. The efficient coverage of the stent struts by a smooth polymeric layer, which can withstand the crimping of the stent on a balloon-catheter and its deployment, was demonstrated by fluorescence microscopy, scanning electron microscopy, and atomic force microscopy. The release of siRNA from the stents was modulated by the presence of the cationic groups, as compared to noncationized pullulan hydrogel. In vivo implantation of coated stents was successful and cationized pullulan-based hydrogels loaded with siRNA in rabbit balloon-injured carotid arteries induced an uptake of siRNA into the arterial wall and a decrease of pro-MMP2 activity. These results suggest that cationized pullulan-based hydrogel could be used as a new biocompatible and biodegradable stent coating for local gene therapy in the arterial wall.


Subject(s)
Carotid Arteries/surgery , Coated Materials, Biocompatible/administration & dosage , Coated Materials, Biocompatible/chemical synthesis , Drug-Eluting Stents , Gene Transfer Techniques , RNA, Small Interfering/administration & dosage , Animals , Carotid Arteries/physiology , Drug Discovery/methods , Genetic Therapy/methods , Polymers/administration & dosage , Polymers/chemistry , RNA, Small Interfering/genetics , Rabbits
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