ABSTRACT
BACKGROUND: Cardiogenic shock (CS) is the most severe form of acute heart failure. Discrepancies have been reported between sexes regarding delays, pathways and invasive strategies in CS complicating acute myocardial infarction. However, effect of sex on the prognosis of unselected CS remains controversial. OBJECTIVES: The aim was to analyze the impact of sex on aetiology, management and prognosis of CS. METHODS: The FRENSHOCK registry included all CS admitted in 49 French Intensive Care Units (ICU) and Intensive Cardiac Care Units (ICCU) between April and October 2016. RESULTS: Among the 772 CS patients included, 220 were women (28.5%). Women were older, less smokers, with less history of ischemic cardiac disease (20.5% vs 33.6%) than men. At admission, women presented less cardiac arrest (5.5 vs 12.2%), less mottling (32.5 vs 41.4%) and higher LVEF (30 ± 14 vs 25 ± 13%). Women were more often managed via emergency department while men were directly admitted at ICU/ICCU. Ischemia was the most frequent trigger irrespective of sex (36.4% in women vs 38.2%) but women had less coronary angiogram and PCI (45.9% vs 54% and 24.1 vs 31.3%, respectively). We found no major difference in medication and organ support. Thirty-day mortality (26.4 vs 26.5%), transplant or permanent assist device were similar in both sexes. CONCLUSION: Despite some more favorable parameters in initial presentation and no significant difference in medication and support, women shared similar poor prognosis than men. Further analysis is required to cover the lasting gap in knowledge regarding sex specificities to distinguish between differences and inequalities. NCT02703038.
Subject(s)
Registries , Shock, Cardiogenic , Humans , Shock, Cardiogenic/therapy , Shock, Cardiogenic/mortality , Shock, Cardiogenic/epidemiology , Female , Male , Aged , Sex Factors , France/epidemiology , Middle Aged , Intensive Care Units/statistics & numerical data , PrognosisABSTRACT
Objectives: The aim of this postmarket clinical study was to assess the safety and efficacy of the latest generation polymer-free sirolimus-eluting stents (PF-SES) in an all-comers population comparing outcomes in stable coronary artery disease (CAD) versus acute coronary syndrome (ACS) in France. Background: The efficacy and safety of the first-generation PF-SES have already been demonstrated by randomized controlled trials and "all-comers" observational studies. Methods: For this all-comers observational, prospective, multicenter study, 1456 patients were recruited in 22 French centers. The primary endpoint was target lesion revascularization (TLR) rate at 12 months and secondary endpoints included major adverse cardiac events (MACE) and bleeding. Results: 895 patients had stable CAD and 561 had ACS. At 12 months, 2% of patients had a TLR, with similar rates between stable CAD and ACS (1.9% vs 2.2%, p = 0.7). The overall MACE rate was 5.2% with an expected higher rate in patients with ACS as compared to those with stable CAD (7.3% vs 3.9%, p = 0.007). The overall bleeding event rate was 4.5%, with similar rates in stable CAD as compared to ACS patients (3.8% vs 5.6%, p = 0.3). Dual antiplatelet therapy (DAPT) interruptions prior to the recommended duration occurred in 41.7% of patients with no increase in MACE rates as compared to patients who did not prematurely interrupt DAPT (3.9% vs 6.1%, p = 0.073). Conclusions: The latest generation PF-SES is associated with low clinical event rates in these all-comers patients. There was a high rate of prematurely terminated DAPT, without any effect on MACE at 12 months. This trial is registered with NCT03809715.
Subject(s)
Acute Coronary Syndrome , Coronary Artery Disease , Drug-Eluting Stents , Sirolimus , Humans , Acute Coronary Syndrome/surgery , Acute Coronary Syndrome/drug therapy , Coronary Artery Disease/surgery , Coronary Artery Disease/drug therapy , Drug-Eluting Stents/adverse effects , Hemorrhage/chemically induced , Hospitals , Polymers , Prospective Studies , Sirolimus/adverse effects , Treatment Outcome , Dual Anti-Platelet TherapyABSTRACT
A 20-year-old patient is admitted to the emergency room for chest pain occurring in the context of recurrent left complete pneumothorax. Ultrasensitive troponinemia is elevated to 20 times normal. Myocardial distress is attributed to pneumothorax following the negativity of cardiological examinations (EKG, TTE, cardiac MRI). The pneumothorax is drained with a favorable evolution. This is the first reported case of pneumothorax associated with a significant elevation of troponin without ECG change, TakoTsubo syndrome, or myocardial inflammation. Several mechanisms are considered: rotation of the myocardium around its axis, increase in pulmonary vascular resistance with overload of right ventricular pressure, disturbance of coronary blood flow on significant mediastinal compression with decrease in systolo-diastolic myocardial perfusion.
Subject(s)
Pneumothorax , Takotsubo Cardiomyopathy , Adult , Chest Pain/etiology , Emergency Service, Hospital , Humans , Pneumothorax/diagnosis , Troponin , Young AdultABSTRACT
BACKGROUND: A strong association between on-thienopyridine platelet reactivity (PR) and the risk of both thrombotic and bleeding events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) has been demonstrated. However, no study has analyzed the relationship between on-ticagrelor PR and clinical outcome in this clinical setting. OBJECTIVES: We aimed to investigate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein (VASP) index, and clinical outcome in patients with ACS undergoing PCI. METHODS: We performed a prospective, multicenter, observational study of patients undergoing PCI for ACS. PR was measured using the VASP index following ticagrelor loading dose. The primary study endpoint was the rate of Bleeding Academic Research Consortium (BARC) type ≥2 at 1 year. The key secondary endpoint was the rate of major adverse cardiovascular events (MACE) defined as the composite of cardiovascular death, myocardial infarction, stroke, and urgent revascularization. RESULTS: We included 570 ACS patients, among whom 33.9% had ST-elevation myocardial infarction. BARC type ≥2 bleeding occurred in 10.9% and MACE in 13.8%. PR was not associated with BARC ≥2 or with MACE (p = 0.12 and p = 0.56, respectively). No relationship between PR and outcomes was observed, neither when PR was analyzed quantitatively nor when it was analyzed qualitatively (low on-treatment PR [LTPR] vs. no LTPR). CONCLUSION: On-ticagrelor PR measured by the VASP was not associated with bleeding or thrombotic events in ACS patients undergoing PCI. PR measured by the VASP should not be used as a surrogate endpoint in studies on ticagrelor.
Subject(s)
Acute Coronary Syndrome/drug therapy , Percutaneous Coronary Intervention/methods , ST Elevation Myocardial Infarction/therapy , Ticagrelor/pharmacology , Aged , Blood Platelets/cytology , Cell Adhesion Molecules/metabolism , Female , Hemorrhage , Humans , Male , Microfilament Proteins/metabolism , Middle Aged , Phosphoproteins/metabolism , Platelet Activation/drug effects , Platelet Aggregation Inhibitors/therapeutic use , Platelet Function Tests , Prospective Studies , Purinergic P2Y Receptor Antagonists/chemistry , Treatment OutcomeABSTRACT
BACKGROUND: Ticagrelor induces more potent platelet reactivity (PR) inhibition with reduced interindividual variability compared to clopidogrel. Although on-clopidogrel PR was shown to correlate with ischemia and bleeding events, no study has investigated the relationship between on-ticagrelor PR and outcome. OBJECTIVES: We aimed to evaluate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein index (VASP), and thrombotic and bleeding events in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI). METHODS: We performed a prospective, multicenter observational study on patients treated with PCI for ACS. The VASP index was used to assess PR after ticagrelor loading dose (LD). The primary endpoint was the link between major adverse cardiovascular events (MACE) and PR. RESULTS: Among the 530 patients with ACS included, 183 (34.5%) were admitted for ST elevation myocardial infarction. We observed high potency and limited interindividual variability after the ticagrelor LD (VASP 19.1% ± 16.6%). At 1 month, 21 (3.8%) MACE and 29 (5.5%) bleedings ≥ 2 according to the Bleedings Academic Research Consortium (BARC) scale were recorded. Neither MACE nor bleeding was associated with PR (P = .34 and P = .78, respectively). However, there was a strong association between PR and the occurrence of definite acute stent thrombosis (P = .03). Platelet reactivity was the only factor associated with acute definite stent thrombosis. CONCLUSION: In patients receiving a ticagrelor LD while undergoing PCI for ACS, PR using the VASP did not predict MACE or bleeding, but it was significantly associated with the occurrence of definite acute stent thrombosis.
Subject(s)
Acute Coronary Syndrome/therapy , Blood Platelets/drug effects , Coronary Thrombosis/prevention & control , Non-ST Elevated Myocardial Infarction/therapy , Percutaneous Coronary Intervention , Platelet Activation/drug effects , Platelet Aggregation Inhibitors/administration & dosage , ST Elevation Myocardial Infarction/therapy , Ticagrelor/administration & dosage , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/mortality , Aged , Biomarkers/blood , Blood Platelets/metabolism , Cell Adhesion Molecules/blood , Coronary Thrombosis/blood , Coronary Thrombosis/diagnosis , Coronary Thrombosis/mortality , Female , France , Hemorrhage/chemically induced , Humans , Male , Microfilament Proteins/blood , Middle Aged , Non-ST Elevated Myocardial Infarction/blood , Non-ST Elevated Myocardial Infarction/diagnosis , Non-ST Elevated Myocardial Infarction/mortality , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Percutaneous Coronary Intervention/mortality , Phosphoproteins/blood , Platelet Aggregation Inhibitors/adverse effects , Prospective Studies , Risk Factors , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/mortality , Stents , Ticagrelor/adverse effects , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3 before percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) is associated with improved outcomes. However, no recent data are available on its impact beyond 1 year and/or by type of AMI. AIMS: To assess the prognostic impact of prePCI TIMI flow at 30 days and 3 years in patients with ST-segment elevation (STEMI) or non-ST-segment elevation (NSTEMI) AMI. METHODS: We compared long-term outcomes associated with TIMI flow grade 2/3 versus 0/1 in patients referred for PCI in the nationwide French registry of acute ST-segment elevation or non-ST-segment elevation myocardial infarction (FAST-MI) 2010. RESULTS: TIMI flow grade 2/3 was found in 41% of patients with STEMI and 69% of patients with NSTEMI; it was associated with a lower risk of 30-day death in patients with STEMI (odds ratio 0.30, 95% confidence interval [CI] 0.12-0.77; P=0.01), but not in patients with NSTEMI (odds ratio 0.57, 95% CI 0.22-1.42; P=0.23). TIMI grade flow 2/3 was also associated with a lower risk of 3-year death in patients with STEMI (hazard ratio 0.69, 95% CI 0.49-0.98; P=0.04), but not in patients with NSTEMI (hazard ratio 0.79, 95% CI 0.56-1.11; P=0.17). CONCLUSION: TIMI flow grade 2/3 is observed more often in patients with NSTEMI; it is an independent predictor of early and late survival in patients with STEMI, but is not significantly related to early or long-term survival in patients with NSTEMI.
Subject(s)
Coronary Circulation , Non-ST Elevated Myocardial Infarction/therapy , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction/therapy , Aged , Blood Flow Velocity , Chi-Square Distribution , Female , France , Humans , Kaplan-Meier Estimate , Logistic Models , Male , Middle Aged , Multivariate Analysis , Non-ST Elevated Myocardial Infarction/diagnosis , Non-ST Elevated Myocardial Infarction/mortality , Non-ST Elevated Myocardial Infarction/physiopathology , Odds Ratio , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Registries , Risk Assessment , Risk Factors , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/physiopathology , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction (NSTEMI) management has evolved considerably over the past 2 decades. Little information on mortality trends in the most recent years is available. We assessed trends in characteristics, treatments, and outcomes for acute myocardial infarction in France between 1995 and 2015. METHODS: We used data from 5 one-month registries, conducted 5 years apart, from 1995 to 2015, including 14 423 patients with acute myocardial infarction (59% STEMI) admitted to cardiac intensive care units in metropolitan France. RESULTS: From 1995 to 2015, mean age decreased from 66±14 to 63±14 years in patients with STEMI; it remained stable (68±14 years) in patients with NSTEMI, whereas diabetes mellitus, obesity, and hypertension increased. At the acute stage, intended primary percutaneous coronary intervention increased from 12% (1995) to 76% (2015) in patients with STEMI. In patients with NSTEMI, percutaneous coronary intervention ≤72 hours from admission increased from 9% (1995) to 60% (2015). Six-month mortality consistently decreased in patients with STEMI from 17.2% in 1995 to 6.9% in 2010 and 5.3% in 2015; it decreased from 17.2% to 6.9% in 2010 and 6.3% in 2015 in patients with NSTEMI. Mortality still decreased after 2010 in patients with STEMI without reperfusion therapy, whereas no further mortality gain was found in patients with STEMI with reperfusion therapy or in patients with NSTEMI, whether or not they were treated with percutaneous coronary intervention. CONCLUSIONS: Over the past 20 years, 6-month mortality after acute myocardial infarction has decreased considerably for patients with STEMI and NSTEMI. Mortality figures continued to decline in patients with STEMI until 2015, whereas mortality in patients with NSTEMI appears stable since 2010.
Subject(s)
Disease Management , Non-ST Elevated Myocardial Infarction/mortality , Non-ST Elevated Myocardial Infarction/surgery , Registries , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/surgery , Aged , Aged, 80 and over , Cohort Studies , Female , Follow-Up Studies , France/epidemiology , Humans , Male , Middle Aged , Non-ST Elevated Myocardial Infarction/diagnosis , Percutaneous Coronary Intervention/trends , ST Elevation Myocardial Infarction/diagnosis , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVES: The aim of this study was to test the hypothesis that 6-month dual antiplatelet therapy (DAPT) is noninferior to 24-month DAPT in aspirin-sensitive patients. BACKGROUND: The ITALIC (Is There a Life for DES After Discontinuation of Clopidogrel) trial showed that rates of bleeding and thrombotic events at 1 year were much the same with 6 versus 12 months of DAPT after percutaneous coronary intervention with second-generation drug-eluting stents. In this report, 2-year follow-up is presented. METHODS: In a multicenter randomized study, patients with confirmed nonresistance to aspirin undergoing drug-eluting stent implantation were allocated to 6 or 24 months of DAPT. The primary endpoint was a composite of death, myocardial infarction, urgent target vessel revascularization, stroke, and major bleeding at 12 months post-percutaneous coronary intervention. The secondary endpoints comprised the same composite endpoint at 24 months and each individual component. RESULTS: Overall, 2,031 patients from 70 centers were screened; 926 were randomized to 6-month and 924 to 24-month DAPT. Noninferiority was demonstrated for 6- versus 12-month DAPT, with an absolute risk difference of 0.11% (95% confidence interval: -1.04% to 1.26%; p = 0.0002). At 2 years, the composite endpoint was unchanged, at 3.5% for 6 months and 3.7% for 24 months (p = 0.79), and rates of myocardial infarction (1.3% vs. 1.0%; p = 0.51), stroke (0.6% vs. 0.8%; p = 0.77), and target vessel revascularization (1.0% vs. 0.3%; p = 0.09) were likewise similar. There was a trend toward higher mortality with longer DAPT (2.2% vs. 1.2%; p = 0.11). Four patients (0.4%) in the 24-month group and none in the 6-month group had major bleeding. CONCLUSIONS: Two-year outcomes in the ITALIC trial confirmed the 1-year results and showed that patients receiving 6-month DAPT after percutaneous coronary intervention with second-generation drug-eluting stent have similar outcomes to those receiving 24-month DAPT.
Subject(s)
Aspirin/administration & dosage , Coronary Artery Disease/therapy , Drug-Eluting Stents , Percutaneous Coronary Intervention/instrumentation , Platelet Aggregation Inhibitors/administration & dosage , Ticlopidine/analogs & derivatives , Aged , Aspirin/adverse effects , Clopidogrel , Coronary Artery Disease/diagnosis , Coronary Artery Disease/mortality , Coronary Thrombosis/etiology , Drug Administration Schedule , Drug Therapy, Combination , Female , France , Hemorrhage/chemically induced , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Myocardial Infarction/etiology , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Platelet Aggregation Inhibitors/adverse effects , Proportional Hazards Models , Prospective Studies , Prosthesis Design , Risk Factors , Ticlopidine/administration & dosage , Ticlopidine/adverse effects , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Takotsubo cardiomyopathy (TTC) is a rare condition characterized by a sudden temporary weakening of the heart. TTC can mimic acute myocardial infarction and is associated with a minimal release of myocardial biomarkers in the absence of obstructive coronary artery disease. AIMS: To provide an extensive description of patients admitted to hospital for TTC throughout France and to study the management and outcomes of these patients. METHODS: In 14 non-academic hospitals, we collected clinical, electrocardiographic, biological, psychological and therapeutic data in patients with a diagnosis of TTC according to the Mayo Clinic criteria. RESULTS: Of 117 patients, 91.5% were women, mean ± SD age was 71.4 ± 12.1 years and the prevalence of risk factors was high (hypertension: 57.9%, dyslipidaemia: 33.0%, diabetes: 11.5%, obesity: 11.5%). The most common initial symptoms were chest pain (80.5%) and dyspnoea (24.1%). A triggering psychological event was detected in 64.3% of patients. ST-segment elevation was found in 41.7% of patients and T-wave inversion in 71.6%. Anterior leads were most frequently associated with ST-segment elevation, whereas T-wave inversion was more commonly associated with lateral leads, and Q-waves with septal leads. The ratio of peak B-type natriuretic peptide (BNP) or N-terminal prohormone BNP (NT-proBNP) level to peak troponin level was 1.01. No deaths occurred during the hospital phase. After 1 year of follow-up, 3 of 109 (2.8%) patients with available data died, including one cardiovascular death. Rehospitalizations occurred in 17.4% of patients: 2.8% due to acute heart failure and 14.7% due to non-cardiovascular causes. There was no recurrence of TTC. CONCLUSIONS: This observational study of TTC included primarily women with atherosclerotic risk factors and mental stress. T-wave inversion was more common than ST-segment elevation. There were few adverse cardiovascular outcomes in these patients after 1-year follow-up.
Subject(s)
Hospitalization , Takotsubo Cardiomyopathy/therapy , Ventricular Function, Left , Aged , Aged, 80 and over , Atherosclerosis/epidemiology , Biomarkers/blood , Diagnostic Imaging/methods , Electrocardiography , Female , France/epidemiology , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Patient Readmission , Peptide Fragments/blood , Predictive Value of Tests , Prevalence , Prospective Studies , Recovery of Function , Registries , Retrospective Studies , Risk Factors , Stress, Psychological/epidemiology , Takotsubo Cardiomyopathy/blood , Takotsubo Cardiomyopathy/diagnosis , Takotsubo Cardiomyopathy/mortality , Takotsubo Cardiomyopathy/physiopathology , Time Factors , Treatment Outcome , Troponin/bloodABSTRACT
OBJECTIVE: The influence of initial-thrombolysis in myocardial infarction (i-TIMI) coronary flow in the culprit coronary artery on myocardial infarct and microvascular obstruction (MVO) size is unclear. We assessed the impact on infarct size of i-TIMI flow in the culprit coronary artery, as well as on MVO incidence and size, by contrast-enhanced cardiac magnetic resonance (ce-CMR). METHODS: In a prospective, multicenter study, pre-percutaneous coronary intervention (PCI) coronary occlusion was defined by an i-TIMI flow ≤1, and patency was defined by an i-TIMI flow ≥2. Infarct size, as well as MVO presence and size, were measured on ce-CMR 72h after admission. RESULTS: A total of 140 patients presenting with ST-elevated myocardial infarction referred for primary PCI were included. There was no significant difference in final post-PCI TIMI flow between the groups (2.95±0.02 vs. 2.97±0.02, respectively; p=0.44). In the i-TIMI flow ≤1 group, infarct size was significantly larger (32±17g vs. 21±17g, respectively; p=0.002), MVO was significantly more frequent (74% vs. 53%, respectively; p=0.012), and MVO size was significantly larger [1.3 IQR (0; 7.1) vs. 0 IQR (0; 1.6)], compared to in the i-TIMI ≥2 patient group. CONCLUSION: Initial angiographic TIMI flow in the culprit coronary artery prior to any PCI predicted final infarct size and MVO size: the better was the i-TIMI flow, the smaller were the infarct and MVO size.
Subject(s)
Coronary Angiography/methods , Coronary Circulation , Coronary Vessels/diagnostic imaging , Embolism/pathology , Myocardial Infarction/pathology , Aged , Coronary Vessels/physiopathology , Embolism/etiology , Female , Humans , Male , Microvessels/pathology , Middle Aged , Myocardial Infarction/complications , Myocardial Infarction/surgery , Percutaneous Coronary Intervention , Preoperative Period , Prospective StudiesABSTRACT
BACKGROUND: Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS: In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS: A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS: In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).
Subject(s)
Cyclophilins/antagonists & inhibitors , Cyclosporine/administration & dosage , Enzyme Inhibitors/administration & dosage , Myocardial Infarction/drug therapy , Percutaneous Coronary Intervention , Ventricular Remodeling/drug effects , Aged , Combined Modality Therapy , Cyclosporine/adverse effects , Double-Blind Method , Electrocardiography , Enzyme Inhibitors/adverse effects , Female , Heart Failure/epidemiology , Humans , Injections, Intravenous , Kaplan-Meier Estimate , Male , Middle Aged , Mortality , Myocardial Infarction/therapyABSTRACT
BACKGROUND: Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. METHODS: CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow ≤1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1:1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in the minutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction. RESULTS: Recruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015. CONCLUSIONS: The CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up.
Subject(s)
Cyclosporine/adverse effects , Cyclosporine/therapeutic use , Myocardial Infarction/surgery , Percutaneous Coronary Intervention , Biomarkers/blood , Coronary Angiography , Double-Blind Method , Echocardiography , Electrocardiography , Female , Humans , Male , Myocardial Infarction/physiopathology , Prospective Studies , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: The currently recommended duration of dual antiplatelet therapy (DAPT) in drug-eluting stent (DES) recipients is 12 months to reduce the risk of late stent thrombosis, particularly in those with acute coronary syndrome (ACS). OBJECTIVES: This study hypothesized that antiplatelet treatment with DAPT for 6 months may be noninferior to 24-month DAPT in aspirin-sensitive patients. METHODS: A multicenter, randomized study assigned patients undergoing implantation of everolimus-eluting stents with confirmed nonresistance to aspirin to receive 6- or 24-month DAPT. The primary endpoint was a composite of death, myocardial infarction, urgent target vessel revascularization, stroke, and major bleeding at 12 months post-stenting. RESULTS: A total of 2,031 patients were enrolled in 70 European and Middle Eastern centers. The trial was prematurely terminated due to recruitment problems, leaving 941 patients randomized to 24-month DAPT and 953 to 6-month DAPT. The 2 treatment groups had similar baseline and procedural characteristics. There was no significant difference in the primary endpoint (24-month: 1.5% vs. 6-month: 1.6%; p = 0.85). Noninferiority was demonstrated for 6- versus 24-month DAPT, with an absolute risk difference of 0.11% (95% confidence interval: -1.04% to 1.26%; p for noninferiority = 0.0002). There were no significant differences in stent thrombosis or bleeding complications. In the 792 (44%) high-risk patients with ACS, primary and secondary endpoints did not significantly differ (hazard ratio: 1.7 [95% confidence interval: 0.519 to 6.057; p = 0.361]). CONCLUSIONS: Rates of bleeding and thrombotic events were not significantly different according to 6- versus 24-month DAPT after PCI with new-generation DES in good aspirin responders. (Is There A LIfe for DES After Discontinuation of Clopidogrel [ITALICplus]; NCT01476020).
Subject(s)
Aspirin , Coronary Artery Disease/therapy , Coronary Restenosis , Drug-Eluting Stents/adverse effects , Hemorrhage , Percutaneous Coronary Intervention , Ticlopidine/analogs & derivatives , Aged , Aspirin/administration & dosage , Aspirin/adverse effects , Clopidogrel , Coronary Artery Disease/diagnosis , Coronary Artery Disease/mortality , Coronary Artery Disease/physiopathology , Coronary Restenosis/diagnosis , Coronary Restenosis/etiology , Coronary Restenosis/prevention & control , Coronary Vessels/pathology , Coronary Vessels/surgery , Early Termination of Clinical Trials , Europe , Everolimus , Female , Hemorrhage/etiology , Hemorrhage/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Middle East , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Postoperative Complications/diagnosis , Postoperative Complications/prevention & control , Sirolimus/analogs & derivatives , Sirolimus/therapeutic use , Ticlopidine/administration & dosage , Ticlopidine/adverse effects , Time Factors , Treatment OutcomeABSTRACT
Despite the fact that numerous clinical trials investigating infarct size have been completed over the last two to three decades, the methods for treating lethal reperfusion injury efficiently have only become established very recently. After several years of accumulating evidence in experimental preparations that lethal reperfusion injury might exist, the description of the phenomenon of ischaemic post-conditioning in animal models has fully convinced us of the existence and importance of irreversible myocardial damage occurring after reflow. Transfer to the clinics was possible in small phase II trials, provided care was taken to assess the determinants of infarct size and, most importantly, to consider the timing of drug administration with respect to the time of reflow. Technical questions remain to be resolved regarding the assessment of the area at risk in the difficult setting of emergency care for reperfusion therapy. Nevertheless, convincing pharmacological trials are being performed that mark the start of a new era that will, in the future, improve the prognosis of patients with ST-segment elevation myocardial infarction through the prevention of lethal myocardial reperfusion injury. At present, while erythropoietin and adenosine have not proved efficient for alleviation of lethal reperfusion injury, a significant benefit has been reported for cyclosporin and exenatide. New pharmacological agents need to be identified and tested in phase II trials. In the meantime, clinical outcome studies are currently being conducted for cyclosporin.
Subject(s)
Myocardial Infarction/drug therapy , Myocardial Reperfusion Injury/drug therapy , Emergency Medical Services , Humans , Myocardial Reperfusion Injury/prevention & controlABSTRACT
OBJECTIVES: The aim of this study was to investigate the relationship between platelet reactivity (PR) after a loading dose (LD) of prasugrel and thrombotic events. BACKGROUND: Post-treatment PR has been shown to be strongly associated with the occurrence of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) in the clopidogrel era. Prasugrel is a new P2Y(12)-adenosine diphosphate receptor with a higher potency on PR. METHODS: A prospective multicenter study included patients who underwent successful PCI for acute coronary syndromes and received prasugrel therapy. Vasodilator-stimulated phosphoprotein (VASP) index was measured after the prasugrel LD. High on-treatment PR was defined as a VASP index ≥50%. MACE included cardiovascular death, myocardial infarction, and definite stent thrombosis at 1 month. RESULTS: Three hundred one patients were enrolled. The mean VASP index after 60 mg of prasugrel was 34.3 ± 23.1%. High on-treatment PR was observed in 76 patients (25.2%). Patients experiencing thrombotic events after PCI had significantly higher VASP indexes compared with those free of events (64.4 ± 14.4% vs. 33.4 ± 22.7%; range: 51% to 64% and 5% to 47.6%, respectively; p = 0.001). Kaplan-Meier analysis comparing good responders and patients with high on-treatment PR demonstrated a significantly higher rate of MACE in patients with suboptimal PR inhibition (log-rank p < 0.001). Receiver-operating characteristic curve analysis found a cutoff value of 53.5% of the VASP index to predict thrombotic events at 1 month (r = 0.86, p < 0.001). Patients with minor or major Thrombolysis In Myocardial Infarction unrelated to coronary artery bypass grafting bleeding and those without had similar VASP indexes (30 ± 17.8% vs. 34.3 ± 23%, p = 0.70). CONCLUSIONS: Despite the use of prasugrel, a significant number of patients undergoing PCI in the setting of acute coronary syndromes do not achieve optimal PR inhibition. Such patients have a higher risk for MACE after PCI.
Subject(s)
Acute Coronary Syndrome/therapy , Angioplasty, Balloon, Coronary , Blood Platelets/metabolism , Phosphoproteins/metabolism , Piperazines/therapeutic use , Purinergic P2Y Receptor Antagonists/therapeutic use , Thiophenes/therapeutic use , Coronary Thrombosis/epidemiology , Female , Humans , Hypercholesterolemia/epidemiology , Male , Middle Aged , Myocardial Infarction/epidemiology , Prasugrel Hydrochloride , Predictive Value of Tests , Prospective Studies , ROC Curve , Sensitivity and Specificity , StentsABSTRACT
Within the framework of an air quality study of the French alpine valleys (POVA program), an atmospheric emission inventory concerning major pollutants: CO, NOx, SO(2), CH(4), particles (PT) and non-methane volatile organic compounds (NMVOC) was carried out. This inventory has a spatial resolution of 1 km(2) and was established for the reference year 2003. The coexistence of economic activities and the Vanoise national park makes the Maurienne valley a sensitive site, particularly representative of the problems of sustainable development in alpine areas, where air pollution is one of the most important aspects. The area, which covers 4588 km(2), is an alpine valley that is sensitive to air pollution due to the emission sources (traffic, industries, private heating, etc.), its morphology (a narrow valley surrounded by high ranges), and local meteorology (temperature inversions and slope winds). As expected, the result which includes both biogenic and anthropogenic sources shows serious emissions of pollutants that are mainly due to the presence of highways and industries around. Two emission inventories were drawn up: one with emission factors determined by CORINAIR (from the European Environment Agency) and the other with emission factors determined by BUWAL-OFEFP (from Swiss Agency for the Environment, Forests and Landscape). The inventories were then compared thanks to concentrations calculated from a numerical model. Computations were run for an intensive field observation period from 25 June to 2 July 2003.
Subject(s)
Air Pollutants/analysis , Models, Theoretical , Carbon Monoxide/analysis , Computer Simulation , Environmental Monitoring , France , Heating , Industry , Nitrogen Oxides/analysis , Organic Chemicals/analysis , Poaceae , Solvents , Sulfur Dioxide/analysis , Trees , Vehicle EmissionsABSTRACT
The primary objective of the present study was to assess the feasibility and the safety of the Seaquence stent (CathNet-Science) deployment for the treatment of coronary artery disease and the event-free survival of patients treated with this coronary stent. The study was conducted as a multicenter, prospective, observational registry. Patients with stable or unstable angina pectoris who were candidates for percutaneous coronary intervention with elective stenting of one single de novo lesion in a native coronary artery > or =3 mm in diameter were included in the study. Clinical follow-up was performed at 1 month and 9 months. Major adverse coronary events (MACE), that is, cardiac death, myocardial infarction, and target vessel revascularization (re-PTCA or CABG), were recorded over a period of 9 months. Using this stent, a 99% in-hospital success rate was achieved. A total of 17 patients presented MACE (8.7%) during the whole follow-up period and target lesion revascularization was needed for 14 (7.1%) patients. Using multivariate analysis only some clinical parameters (patients treated for unstable angina, with a history of CABG or of female gender) were found as independent predictors of MACE after coronary stenting. Procedural related factors, angiographic characteristics, or reference diameter were not found to influence clinical outcome. Because the study was performed in patients with a high proportion of complex lesions (relative high-risk nonselected population with nearly one third calcified lesions, many long and type B2 and C lesions) we can conclude that the coronary Seaquence stent can be considered as a stent of reference in routine practice.
Subject(s)
Coronary Stenosis/therapy , Registries , Stents , Adult , Aged , Aged, 80 and over , Angina, Unstable/classification , Angina, Unstable/mortality , Angina, Unstable/therapy , Angioplasty, Balloon, Coronary , Blood Vessel Prosthesis Implantation , Coronary Angiography , Coronary Artery Bypass , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/mortality , Device Removal , Disease-Free Survival , Equipment Safety , Europe , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Complications/mortality , Postoperative Complications/surgery , Prospective Studies , Recurrence , Reoperation , Time Factors , Treatment OutcomeABSTRACT
The aim of the study was to evaluate, in recipients of biventricular pacing systems, the risk of asystole due to ventricular pacing inhibition by sensing the left atrial signals by the LV lead at conventional sensitivity. Long-term ventricular sensitivity was programmed at > or = 4 m V in 17 consecutive recipients of ventricular resynchronization systems implanted for chronic management of congestive heart failure. Ventricular pacing inhibition due to AV cross-talk on spontaneous left atrial electrogram (AVCSA) was tested at a 2 mV ventricular sensitivity immediately after implantation of the stimulation system and 1 month later. Pacemaker dependence was also tested during temporary VVI pacing at a rate of 30 beats/min. AVCSA was observed in three patients. It was present on the day of implantation in one patient, and developed within the first month in two others. Asystole was observed in two of the three cases of AVCSA. Three pacemaker nondependent patients at the time of system implantation had become pacemaker dependent at 1 month. AVCSA was observed only with LV leads positioned in the great cardiac vein. In conclusion, asystole due to AVCSA was observed in 11% of recipients of ventricular resynchronization stimulation systems. Care should be taken in these patients to minimize the risk of atrial sensing by the LV lead, preferably avoiding its placement in the great cardiac vein. This phenomenon could be eliminated by the programmability of a right ventricular only sensing configuration.