Gregory Ducrocq

Risk score to predict serious bleeding in stable outpatients with or at risk of atherothrombosis.

Aims To develop a risk score to quantify bleeding risk in outpatients with or at risk of atherothrombosis. Methods and results We studied patients in the REACH Registry, a cohort of 68 236 patients with/at risk of atherothrombosis. The outcome of interest was serious bleeding (non-fatal haemorrhagic stroke or bleeding leading to hospitalization and transfusion) over 2 years. Risk factors for bleeding were assessed using modified regression analysis. Multiple potential scoring systems based on the least complex models were constructed. Competing scores were compared on their discriminative ability via logistic regression. The score was validated externally using the CHARISMA population. From a final cohort of 56 616 patients, 804 (1.42%, 95% confidence interval 1.32–1.52) experienced serious bleeding between baseline and 2 years. A nine-item bleeding risk score (0–23 points) was constructed (age, peripheral arterial disease, congestive heart failure, diabetes, hypertension, smoking, antiplatelets, oral anticoagulants, hypercholesterolaemia). Observed incidence of bleeding at 2 years was: 0.46% (score ≤6); 0.95% (7–8); 1.25% (9–10); 2.76% (≥11). The scores discriminative performance was consistent in CHARISMA and REACH (c-statistics 0.64 and 0.68, respectively); calibration in the CHARISMA population was very good (modified Hosmer-Lemeshow c2 = 4.74; P = 0.69). Conclusion Bleeding risk increased substantially with a score >10. This score can assist clinicians in predicting the risk of serious bleeding and making decisions on antithrombotic therapy in outpatients.

Transfemoral Implantation of Transcatheter Heart Valves After Deterioration of Mitral Bioprosthesis or Previous Ring Annuloplasty

OBJECTIVES This study sought to evaluate the feasibility of transfemoral transcatheter heart valve (THV) implantation in failed mitral bioprostheses and ring annuloplasties. BACKGROUND Redo mitral surgery may be high risk or contraindicated due to comorbidity. THV implantation has been recently reported in this setting. METHODS Transfemoral implantation of Edwards Sapien prosthesis was performed in 17 patients for degenerated mitral bioprosthesis or previous ring annuloplasty (6 bioprostheses, 11 ring annuloplasties). The procedure was elective for 14 patients and attempted as a rescue in 3 patients. Mean age was 61 ± 24 years. All patients were in New York Heart Association class ≥III, and the surgical risk was high (EuroSCORE [European System for Cardiac Operative Risk Evaluation]: 37 ± 29%, Society of Thoracic Surgeons score: 18 ± 22%). RESULTS Procedure was successful in 14 patients (82%). Two complications occurred during rescue procedures: 1 procedural death and 1 THV migration. One patient had moderate paraprosthetic regurgitation following the procedure, whereas residual regurgitation was trace or less in 11 patients (69%) and mild in 4 patients (25%). Mean gradient decreased from 12 ± 6 mm Hg to 8 ± 3 mm Hg. During a mean follow-up of 22 months, 4 patients died, 3 from cardiac cause. The 18-month survival was 68 ± 14% in the overall population and 78 ± 14% for patients with elective procedure. One patient underwent mitral valve replacement due to periprosthetic mitral regurgitation. At last follow-up, 12 patients were in New York Heart Association class ≤II (75%) and 4 in class III (25%). CONCLUSIONS This single-center series suggests that transfemoral THV implantation for deterioration of mitral bioprosthesis or surgical repair is feasible in selected patients and improves early hemodynamic and midterm functional status.

Use of Invasive Strategy in Non–ST-Segment Elevation Myocardial Infarction Is a Major Determinant of Improved Long-Term Survival: FAST-MI (French Registry of Acute Coronary Syndrome)

OBJECTIVES This study sought to assess the impact of invasive strategy (IS) versus a conservative strategy (CS) on in-hospital complications and 3-year outcomes in patients with non-ST-segment elevation myocardial infarction (NSTEMI) from the FAST-MI (French Registry of Acute Coronary Syndrome). BACKGROUND Results from randomized trials comparing IS and CS in patients with NSTEMI are conflicting. METHODS Of the 3,670 patients in FAST-MI, which included patients with acute myocardial infarction (within 48 h) over a 1-month period in France at the end of 2005, 1,645 presented with NSTEMI. RESULTS Of the 1,645 patients analyzed, 80% had an IS. Patients in the IS group were younger (67 ± 12 years vs. 80 ± 11 years), less often women (29% vs. 51%), and had a lower GRACE (Global Registry of Acute Coronary Events) risk score (137 ± 36 vs. 178 ± 34) than patients treated with CS. In-hospital mortality and blood transfusions were significantly more frequent in patients with CS versus IS (13.1% vs. 2.0%, 9.1% vs. 4.6%). Use of IS was associated with a significant reduction in 3-year mortality and cardiovascular death (17% vs. 60%, adjusted hazard ratio [HR]: 0.44, 95% confidence interval [CI]: 0.35 to 0.55 and 8% vs. 36%, adjusted HR: 0.37, 95% CI: 0.27 to 0.50). After propensity score matching (181 patients per group), 3-year survival was significantly higher in patients treated with IS. CONCLUSIONS In a real-world setting of patients admitted with NSTEMI, the use of IS during the initial hospital stay is an independent predictor of improved 3-year survival, regardless of age. (French Registry of Acute Coronary Syndrome [FAST-MI]; NCT00673036).

A History of Stroke/Transient Ischemic Attack Indicates High Risks of Cardiovascular Event and Hemorrhagic Stroke in Patients with Coronary Artery Disease

Background— Randomized trials of antithrombotics in coronary artery disease have identified previous stroke/transient ischemic attack (TIA) as a marker of increased intracranial bleeding risk. We aimed to further characterize the risk of ischemic and bleeding events associated with a history of stroke/TIA in patients with coronary artery disease. Methods and Results— From the international REduction of Atherothrombosis for Continued Health (REACH) registry of atherothrombosis, baseline characteristics and 4-year follow-up of 26 389 patients with coronary artery disease, including 4460 patients (16.9%) with a history of stroke/TIA, were analyzed. Patients with previous stroke/TIA had a higher rate of recurrent cardiovascular events (cardiovascular death, myocardial infarction, or stroke) than patients without (adjusted hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.40–1.65; P<0.001) and specifically of nonfatal ischemic stroke (adjusted HR, 3.06; 95% CI, 2.62–3.57; P<0.001) and nonfatal hemorrhagic stroke rates (adjusted HR, 1.76; 95% CI, 1.00–3.08; P=0.05). Excess risk for nonfatal hemorrhagic stroke appeared confined to the 1st year after a stroke/TIA (adjusted HR, 3.03; 95% CI, 1.51–6.08 for the first year) and was particularly high in patients receiving dual antiplatelet therapy (adjusted HR, 5.21; 95% CI, 1.24–21.90). Conclusions— In patients with coronary artery disease, a history of stroke/TIA is associated with an independent increase in risk of death, myocardial infarction, or stroke, including both ischemic and hemorrhagic stroke (the latter being smaller in absolute terms). This excess risk of hemorrhagic stroke is particularly high in patients receiving dual antiplatelet therapy and in the 1st year after stroke/TIA. This observation is important for selection of antithrombotic therapy in these patients.

Association of Serum Concentration of TNFR1 With All-Cause Mortality in Patients With Type 2 Diabetes and Chronic Kidney Disease: Follow-up of the SURDIAGENE Cohort

OBJECTIVE Renal dysfunction is a key risk factor for all-cause mortality in patients with type 2 diabetes (T2D). Circulating tumor necrosis factor receptor 1 (TNFR1) was recently suggested as a strong biomarker for end-stage renal failure in T2D. However, its relevance regarding all-cause death has yet to be conclusively established. We aimed to assess the prognostic value of serum TNFR1 concentration for all-cause death in T2D and diabetic kidney disease (DKD) from the SURDIAGENE (Survie, Diabete de type 2 et Genetique) study. RESEARCH DESIGN AND METHODS A total of 522 T2D patients with DKD (estimated glomerular filtration rate [eGFR] <60 and/or urinary albumin-to-creatinine ratio [uACR] >30 mg/mmol) were followed for a median duration of 48 months, and 196 deaths occurred. RESULTS Incidence rate (95% CI) for death increased as quartiles of TNFR1 concentration increased (first quartile: 4.7% patient-years [3.0–6.3%]; second quartile: 7.7% [5.4–10.0%]; third quartile: 9.3% [6.7–11.9%]; fourth quartile: 15.9% [12.2–19.5%]). In multivariate analysis taking age, diabetes duration, HbA1c, uACR, and eGFR into account, compared with the first quartile, patients from the fourth quartile had an adjusted hazard ratio for death of 2.98 (95% CI 1.70–5.23). The integrated discrimination improvement index was statistically significant when adding TNFR1 concentration to the UK Prospective Diabetes Study outcome equation (P = 0.031). CONCLUSIONS TNFR1 is a strong prognostic factor for all-cause mortality in T2D with renal dysfunction, and its clinical utility is suggested in addition to established risk factors for all-cause mortality.

Association of spontaneous and procedure-related bleeds with short- and long-term mortality after acute coronary syndromes: an analysis from the PLATO trial

AIMS We sought to describe the differential effect of bleeding events in acute coronary syndromes (ACS) on short- and long-term mortality according to their type and severity. METHODS AND RESULTS The PLATO trial randomised 18,624 ACS patients to clopidogrel or ticagrelor. Post-randomisation bleeding events were captured according to bleeding type (spontaneous or procedure-related), with PLATO, TIMI, and GUSTO definitions. The association of bleeding events with subsequent short-term (<30 days) and long-term (>30 days) all-cause mortality was assessed using time-dependent Cox proportional hazard models. A model was fitted to compare major and minor bleeding for mortality prediction. Of 18,624 patients, 2,189 (11.8%) had at least one PLATO major bleed (mean follow-up 272.2±123.5 days). Major bleeding was associated with higher short-term mortality (adjusted hazard ratio [HR] 9.28; 95% confidence interval [CI]: 7.50-11.48) but not with long-term mortality (adjusted HR 1.28; 95% CI: 0.93-1.75). Spontaneous bleeding was associated with short-term (adjusted HR 14.59; 95% CI: 11.14-19.11) and long-term (adjusted HR 3.38; 95% CI: 2.26-5.05) mortality. Procedure-related bleeding was associated with short-term mortality (adjusted HR 5.29; 95% CI: 4.06-6.87): CABG-related and non-coronary-procedure-related bleeding were associated with a higher short-term mortality, whereas PCI or angiography-related bleeding was not associated with either short- or long-term mortality. Similar results were obtained using the GUSTO and TIMI bleeding definitions. CONCLUSIONS Major bleeding is associated with high subsequent mortality in ACS. However, this association is much stronger in the first 30 days and is strongest for spontaneous (vs. procedure-related) bleeding.

Correlates of pre-hospital morphine use in ST-elevation myocardial infarction patients and its association with in-hospital outcomes and long-term mortality: the FAST-MI (French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction) programme.

AIMS The use of opioids is recommended for pain relief in patients with myocardial infarction (MI) but may delay antiplatelet agent absorption, potentially leading to decreased treatment efficacy. METHODS AND RESULTS In-hospital complications (death, non-fatal re-MI, stroke, stent thrombosis, and bleeding) and 1-year survival according to pre-hospital morphine use were assessed in 2438 ST-elevation MI (STEMI) patients from the French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2010. The analyses were replicated in the 1726 STEMI patients of the FAST-MI 2005 cohort, in which polymorphisms of CYP2C19 and ABCB1 had been assessed. Specific subgroup analyses taking into account these genetic polymorphisms were performed in patients pre-treated with thienopyridines. The 453 patients (19%) receiving morphine pre-hospital were younger, more often male, with a lower GRACE score and higher chest pain levels. After adjustment for baseline differences, in-hospital complications and 1-year survival (hazard ratio = 0.69; 95% confidence interval: 0.35-1.37) were not increased according to pre-hospital morphine use. After propensity score matching, 1-year survival according to pre-hospital morphine was also similar. Consistent results were found in the replication cohort, including in those receiving pre-hospital thienopyridines and whatever the genetic polymorphisms of CYP2C19 and ABCB1. CONCLUSION In two independent everyday-life cohorts, pre-hospital morphine use in STEMI patients was not associated with worse in-hospital complications and 1-year mortality. CLINICAL TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT00673036 (FAST-MI 2005); NCT01237418 (FAST-MI 2010).

Geographic differences in outcomes in outpatients with established atherothrombotic disease: results from the REACH Registry.

Aims There are major differences in the prevalence and management of patients with atherothrombotic disease including coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral artery disease (PAD) across different geographical regions. There is, however, little data allowing comparisons of management and outcomes across broad geographic regions. We aimed to describe geographical differences in baseline characteristics, management and outcomes in stable outpatients with established atherothrombotic disease. Methods and results From the REACH Registry of atherothrombosis, patients with documented CAD, PAD or CVD and with 4-year follow-up were included. Baseline characteristics, treatments and 4-year outcomes were recorded. Event rates were compared between geographical regions and were adjusted for risk scores predicting ischemic and bleeding events. The analyses of baseline characteristics and medications according to geographical region showed marked differences. For the composite primary outcome (cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke), rates ranged from 12.1% in Japan to 18.2% in Eastern Europe. After adjustment, substantial variations remained: taking North America as a reference, patients from Western Europe and Japan had a lower risk of primary outcome event (hazard ratio (HR) 0.93; p = 0.045, and HR = 0.67; p < 0.001 respectively) whereas patients from Eastern Europe had a higher risk (HR = 1.24; p < 0.001). There were no obvious differences between patients from North America and those from Latin America, the Middle East and Asia. Conclusion There are important variations in the outcomes of patients with atherothrombotic across geographic regions. These observations have important implications for public health and clinical research.

Blood transfusion, bleeding, anemia, and survival in patients with acute myocardial infarction: FAST-MI registry

BACKGROUND An association between transfusion during index hospitalization and increased subsequent mortality has been reported in acute myocardial infarction (AMI). Whether this reflects the prognostic role of transfusion per se, or the impact of the index event leading to transfusion, remains unclear. We sought to evaluate the impact of transfusion on mortality in patients with AMI. METHODS Using the nationwide FAST-MI 2005 AMI registry, we recorded anemia on admission, Thrombolysis in Myocardial Infarction major or minor bleeding, and transfusions during hospital stay. Multivariable analyses were performed to identify independent predictors of in-hospital and 5-year mortality. Cohorts of patients matched for propensity to receive transfusion were compared. RESULTS Among 3541 patients with AMI, 827 (23.4%) had anemia on admission, 114 (3.2%) had minor or major bleeding, and 151 (4.3%) underwent transfusion. After multivariable analysis, both anemia and bleeding were independently associated with 5-year mortality (hazard ratio [HR] 1.4, 95% CI 1.2-1.6 and HR 1.4, 95% CI 1.1-1.8, respectively), whereas transfusion did not appear to be an independent predictor (HR 1.1, 95% CI 0.8-1.5). Mortality at 5 years did not differ between cohorts matched for propensity to receive transfusion. CONCLUSIONS In this cohort, anemia on admission and bleeding during hospitalization were both associated with increased 5-year mortality in patients with myocardial infarction. Conversely, transfusion per se was not associated with lower survival. Further work is needed to clarify the optimal transfusion strategy in patients with bleeding or anemia and myocardial infarction.

Successful Endovascular Stroke Rescue With Retrieval of an Embolized Calcium Fragment After Transcatheter Aortic Valve Replacement

A 90-year-old symptomatic woman with a critical aortic stenosis was referred for transcatheter aortic valve replacement (TAVR). The procedure was performed under locoregional anesthesia from a right femoral approach, with the successful implantation of a 23-mm CoreValve (Medtronic Inc, Minneapolis, MN). Echocardiographic assessment after TAVR showed a mean transprosthetic gradient of 16 mm Hg and trace paravalvular regurgitation. After percutaneous closure of the right femoral artery, the patient suddenly became unresponsive. After prompt intubation, emergency cerebral MRI was performed to assess the presence of reversible ischemia and exclude parenchymal hemorrhage, showing partial occlusion of the right middle cerebral artery with ischemia in the corresponding territory (Figure 1). Conventional cerebral angiography confirmed partial M1-M2 occlusion of the right middle cerebral artery (Figure 2A; Movie I in the Data Supplement). Complete revascularization …