Rationale and design of the direct oral anticoagulants for prevention of left ventricular thrombus after anterior acute myocardial infarction (APERITIF) trial.

BACKGROUND: Anterior acute myocardial infarction (AMI) is associated with an increased risk of left ventricular (LV) thrombus formation. We hypothesized that adding low-dose oral rivaroxaban to the usual antiplatelet regimen would reduce the risk of LV thrombus in patients with large AMI. STUDY DESIGN: APERITIF is an investigator-initiated, multicenter randomized open-label, blinded end-point (PROBE) trial, nested in the ongoing "FRENCHIE" registry, a French multicenter prospective observational study, in which all consecutive patients admitted within 48 hours of symptom onset in a cardiac Intensive Care Unit (ICU) for AMI are included (NCT04050956). Among them, patients with anterior ST-elevation-myocardial infarction (STEMI) or very high-risk non- ST-elevation-myocardial infarction (NSTEMI) patients with involvement of the left anterior descending artery are randomized into 2 groups: Dual Antiplatelet Therapy (DAPT) alone or DAPT plus rivaroxaban 2.5mg twice daily for 4 weeks, started as soon as possible after completion of the initial percutaneous coronary intervention/angiography procedure. The primary endpoint is the presence of LV thrombus at 1 month, as detected by contrast enhanced CMR (CE-CMR). Secondary endpoints include LV thrombus dimension (greatest diameter), the rate of major bleedings and major cardiovascular events at 1 month. Based on estimated event rates, a sample size of 560 patients is needed to show superiority of DAPT plus rivaroxaban therapy versus DAPT alone, with 80% power. CONCLUSION: The APERITIF trial will determine whether, in patients with large AMIs, the use of rivaroxaban 2.5mg twice daily in addition to DAPT reduces LV thrombus formation, compared with DAPT alone. CLINICALTRIALS: gov Identifier: NCT05077683.

Impact of transfusion strategy on platelet aggregation and biomarkers in myocardial infarction patients with anemia.

BACKGROUND: Higher rates of thrombotic events have been reported in myocardial infarction (MI) patients requiring blood transfusion. The impact of blood transfusion strategy on thrombosis and inflammation is still unknown. OBJECTIVE: To compare the impact of a liberal vs. a restrictive transfusion strategy on P2Y12 platelet reactivity and biomarkers in the multicentric randomized REALITY trial. METHODS: Patients randomized to a liberal (hemoglobin ≤10 g/dL) or a restrictive (hemoglobin ≤8 g/dL) transfusion strategy had VASP-PRI platelet reactivity measured centrally in a blinded fashion and platelet reactivity unit (PRU) measured locally using encrypted VerifyNow; at baseline and after randomization. Biomarkers of thrombosis (P-selectin, PAI-1, vWF) and inflammation (TNF-α) were also measured. The primary endpoint was the change in the VASP-PRI (difference from baseline and post randomization) between the randomized groups. RESULTS: A total of 100 patients randomized were included in this study (n = 50 in each group). Transfused patients received on average 2.4 ± 1.6 units of blood. We found no differences in change of the VASP PRI (difference 1.2% 95% CI (-10.3-12.7%)) or by the PRU (difference 13.0 95% CI (-21.8-47.8)) before and after randomization in both randomized groups. Similar results were found in transfused patients (n = 71) regardless of the randomized group, VASP PRI (difference 1.7%; 95% CI (-9.5-1.7%)) or PRU (difference 27.0; 95% CI (-45.0-0.0)). We did not find an impact of transfusion strategy or transfusion itself in the levels of P-selectin, PAI-1, vWF, and TNF-α. CONCLUSION: In this study, we found no impact of a liberal vs. a restrictive transfusion strategy on platelet reactivity and biomarkers in MI patients with anemia. A conclusion that should be tempered due to missing patients with exploitable biological data that has affected our power to show a difference.

Very long-term outcomes after acute myocardial infarction in young men and women: Insights from the FAST-MI program.

AIMS: Conflicting data exists about long-term outcomes in young women and men experiencing acute myocardial infarction (AMI). METHODS: The FAST-MI program consists of three nationwide French surveys carried out 5years apart from 2005 to 2015, including consecutive patients with AMI over a 1-month period with up to 10-year follow-up. The present analysis focused on adults≤50 yo according to their gender. RESULTS: Women accounted for 17.5% (335) of the 1912 patients under 50 yo and had a similar age as men (43.9±5.1 vs. 43.9±5.5years, P=0.92). They received less percutaneous coronary interventions (PCI) than men (85.9% vs. 91.3%, P=0.005), even in ST-elevation myocardial infarction (83.6% vs. 93.5%, P<0.001). Recommended secondary prevention medications were less frequently prescribed at discharge in women (40.6% vs. 52.8%, P<0.001), a trend that persisted in 2015 (59.1% vs. 72.8% in 2015, P<0.001). Still, ten-year survival was similar in men (90.5%) and women (92.3%) (crude HR: 0.86 [95% CI: 0.55-1.35], P=0.52, adjusted HR: 0.63 [95% CI: 0.38-1.07], P=0.09); similar results were found for ten-year survival among hospital survivors (91.2% in men vs. 93.7% in women, adjusted HR: 0.87 [95% CI: 0.45-1.66], P=0.66). Of the 1684 patients alive at hospital discharge with morbidity follow-up≥6months available, death, AMI or stroke at 8years occurred in 12.9% men and 11.2% in women (adjusted HR: 0.90 [95% CI: 0.60-1.33], P=0.59). CONCLUSIONS: Young women with AMI undergo less cardiac interventions and are less often prescribed secondary prevention treatment than men, even when significant coronary artery disease is present, but keep a similar long-term prognosis after AMI. Optimal management of these young patients, regardless of gender, is necessary to ensure best outcomes after this major cardiovascular event.

Economic evaluation of restrictive vs. liberal transfusion strategy following acute myocardial infarction (REALITY): trial-based cost-effectiveness and cost-utility analyses.

AIMS: To estimate the cost-effectiveness and cost-utility ratios of a restrictive vs. liberal transfusion strategy in acute myocardial infarction (AMI) patients with anaemia. METHODS AND RESULTS: Patients (n = 666) with AMI and haemoglobin between 7-8 and 10 g/dL recruited in 35 hospitals in France and Spain were randomly assigned to a restrictive (n = 342) or a liberal (n = 324) transfusion strategy with 1-year prospective collection of resource utilization and quality of life using the EQ5D3L questionnaire. The economic evaluation was based on 648 patients from the per-protocol population. The outcomes were 30-day and 1-year cost-effectiveness, with major adverse cardiovascular events (MACEs) averted as the effectiveness outcome. and a 1-year cost-utility ratio.The 30-day incremental cost-effectiveness ratio was €33 065 saved per additional MACE averted with the restrictive vs. liberal strategy, with an 84% probability for the restrictive strategy to be cost-saving and MACE-reducing (i.e. dominant). At 1 year, the point estimate of the cost-utility ratio was €191 500 saved per quality-adjusted life year gained; however, the cumulated MACE was outside the pre-specified non-inferiority margin, resulting in a decremental cost-effectiveness ratio with a point estimate of €72 000 saved per additional MACE with the restrictive strategy. CONCLUSION: In patients with AMI and anaemia, the restrictive transfusion strategy was dominant (cost-saving and outcome-improving) at 30 days. At 1 year, the restrictive strategy remained cost-saving, but clinical non-inferiority on MACE was no longer maintained. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02648113. ONE SENTENCE SUMMARY: The use of a restrictive transfusion strategy in patients with acute myocardial infarction is associated with lower healthcare costs, but more evidence is needed to ascertain its long-term clinical impact.

Clinical events as a function of proton pump inhibitor use, clopidogrel use, and cytochrome P450 2C19 genotype in a large nationwide cohort of acute myocardial infarction: results from the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) registry.

BACKGROUND: Clopidogrel requires metabolic activation by cytochrome P450 2C19 (CYP2C19). Proton pump inhibitors (PPIs) that inhibit CYP2C19 are commonly coadministered with clopidogrel to reduce the risk of gastrointestinal bleeding. This analysis compares treatment outcomes for patients in the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) who did or did not receive clopidogrel and/or PPIs. METHODS AND RESULTS: The FAST-MI registry included 3670 patients (2744 clopidogrel- and PPI-naïve patients) presenting with definite MI. Patients were categorized according to use of clopidogrel and/or PPI within 48 hours after hospital admission. PPI use was not associated with an increased risk for any of the main in-hospital events (in-hospital survival, reinfarction, stroke, bleeding, and transfusion). Likewise, PPI treatment was not an independent predictor of 1-year survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; P=0.57) or 1-year MI, stroke, or death (hazard ratio, 0.98; 95% CI, 0.90 to 1.08; P=0.72). No differences were seen when the type of PPI or CYP2C19 genotype was taken into account. In the propensity-matched cohorts, the odds ratios for major in-hospital events in PPI versus no PPI were 0.29 (95% CI, 0.06 to 1.44) and 1.70 (95% CI, 0.10 to 30.3) for patients with 1 and 2 variant alleles, respectively. Similarly, the hazard ratio for 1-year events in hospital survivors was 0.68 (95% CI, 0.26 to 1.79) and 0.55 (95% CI, 0.06 to 5.30), respectively. CONCLUSION: PPI use was not associated with an increased risk of cardiovascular events or mortality in patients administered clopidogrel for recent MI, whatever the CYP2C19 genotype, although harm could not be formally excluded in patients with 2 loss-of-function alleles.

Genetic determinants of response to clopidogrel and cardiovascular events.

BACKGROUND: Pharmacogenetic determinants of the response of patients to clopidogrel contribute to variability in the biologic antiplatelet activity of the drug. The effect of these determinants on clinical outcomes after an acute myocardial infarction is unknown. METHODS: We consecutively enrolled 2208 patients presenting with an acute myocardial infarction in a nationwide French registry and receiving clopidogrel therapy. We then assessed the relation of allelic variants of genes modulating clopidogrel absorption (ABCB1), metabolic activation (CYP3A5 and CYP2C19), and biologic activity (P2RY12 and ITGB3) to the risk of death from any cause, nonfatal stroke, or myocardial infarction during 1 year of follow-up. RESULTS: Death occurred in 225 patients, and nonfatal myocardial infarction or stroke in 94 patients, during the follow-up period. None of the selected single-nucleotide polymorphisms (SNPs) in CYP3A5, P2RY12, or ITGB3 were associated with a risk of an adverse outcome. Patients with two variant alleles of ABCB1 (TT at nucleotide 3435) had a higher rate of cardiovascular events at 1 year than those with the ABCB1 wild-type genotype (CC at nucleotide 3435) (15.5% vs. 10.7%; adjusted hazard ratio, 1.72; 95% confidence interval [CI], 1.20 to 2.47). Patients carrying any two CYP2C19 loss-of-function alleles (*2, *3, *4, or *5), had a higher event rate than patients with none (21.5% vs. 13.3%; adjusted hazard ratio, 1.98; 95% CI, 1.10 to 3.58). Among the 1535 patients who underwent percutaneous coronary intervention during hospitalization, the rate of cardiovascular events among patients with two CYP2C19 loss-of-function alleles was 3.58 times the rate among those with none (95% CI, 1.71 to 7.51). CONCLUSIONS: Among patients with an acute myocardial infarction who were receiving clopidogrel, those carrying CYP2C19 loss-of-function alleles had a higher rate of subsequent cardiovascular events than those who were not. This effect was particularly marked among the patients undergoing percutaneous coronary intervention. (ClinicalTrials.gov number, NCT00673036.)

Trends in cardiogenic shock complicating acute myocardial infarction.

AIMS: Few studies describe recent changes in the prevalence, management, and outcomes of cardiogenic shock (CS) patients complicating acute myocardial infarction (AMI) in the era of widespread use of invasive strategies. The aim of the present study was to analyse trends observed in CS complicating AMI over the past 10 years, focusing on the timing of CS occurrence (i.e. primary CS, CS on admission vs. secondary CS, CS developed subsequently during hospitalization). METHODS AND RESULTS: Three nationwide French registries conducted and designed to evaluate AMI management and outcomes in 'real-life' practice included consecutive AMI patients (n = 9951) admitted to intensive cardiovascular care units (ICCUs) over a 1-month period, 5 years apart. The prevalence of CS complicating AMI decreased from 2005 to 2015: 5.9%, mean age 74.1 ± 12.7 in 2005; 4.0%, mean age 73.9 ± 12.7 in 2010, 2.8%, mean age 71.1 ± 15.0 in 2015 (P < 0.001). It decreased for both primary (1.8% to 1.0%) and secondary CS (4.1% to 1.8%). The profile of CS patients also changed over time with more patients presenting out-of-hospital cardiac arrest. In both primary and secondary CS, the use of percutaneous coronary intervention increased markedly over time, as did the use of mechanical ventilation and cardiac assist devices. Over the 10-year period, in-hospital mortality remained unchanged for both primary CS (41.8% to 37.8%) or secondary CS (57.3% to 58.8%). However, 1-year mortality decreased in patients with primary CS (from 60% to 37.8%, P = 0.038), and remained unchanged in patients developing secondary CS (from 64.5% to 69.1%, P = 0.731). CONCLUSION: Cardiogenic shock complicating AMI has become less frequent but, if present, CS, and particularly secondary CS, carries a very high mortality, which has not substantially improved over the past 10 years, in spite of the more frequent use of invasive strategies.

Fecal microbiota transplantation to maintain remission in Crohn's disease: a pilot randomized controlled study.

BACKGROUND: The role of the gut microbiota in Crohn's disease (CD) is established and fecal microbiota transplantation (FMT) is an attractive therapeutic strategy. No randomized controlled clinical trial results are available. We performed a randomized, single-blind, sham-controlled pilot trial of FMT in adults with colonic or ileo-colonic CD. METHOD: Patients enrolled while in flare received oral corticosteroid. Once in clinical remission, patients were randomized to receive either FMT or sham transplantation during a colonoscopy. Corticosteroids were tapered and a second colonoscopy was performed at week 6. The primary endpoint was the implantation of the donor microbiota at week 6 (Sorensen index > 0.6). RESULTS: Eight patients received FMT and nine sham transplantation. None of the patients reached the primary endpoint. The steroid-free clinical remission rate at 10 and 24 weeks was 44.4% (4/9) and 33.3% (3/9) in the sham transplantation group and 87.5% (7/8) and 50.0% (4/8; one patient loss of follow-up while in remission at week 12 and considered in flare at week 24) in the FMT group. Crohn's Disease Endoscopic Index of Severity decreased 6 weeks after FMT (p = 0.03) but not after sham transplantation (p = 0.8). Conversely, the CRP level increased 6 weeks after sham transplantation (p = 0.008) but not after FMT (p = 0.5). Absence of donor microbiota engraftment was associated with flare. No safety signal was identified. CONCLUSION: The primary endpoint was not reached for any patient. In this pilot study, higher colonization by donor microbiota was associated with maintenance of remission. These results must be confirmed in larger studies (NCT02097797). Video abstract.

Hospital admissions for acute myocardial infarction before and after lockdown according to regional prevalence of COVID-19 and patient profile in France: a registry study.

BACKGROUND: The COVID-19 pandemic has had a profound effect on general health care. We aimed to evaluate the effect of a nationwide lockdown in France on admissions to hospital for acute myocardial infarction, by patient characteristics and regional prevalence of the pandemic. METHODS: In this registry study, we collected data from 21 centres participating in the ongoing French Cohort of Myocardial Infarction Evaluation (FRENCHIE) registry, which collects data from all patients admitted for ST segment elevation myocardial infarction (STEMI) or non-ST segment elevation myocardial infarction (NSTEMI) within 48 h of symptom onset. We analysed weekly hospital admissions over 8 weeks: the 4 weeks preceding the institution of the lockdown and the 4 weeks following lockdown. The primary outcome was the change in the number of hospital admissions for all types of acute myocardial infarction, NSTEMI, and STEMI between the 4 weeks before lockdown and the 4 weeks after lockdown. Comparisons between categorical variables were made using χ2 tests or Fisher's exact tests. Comparisons of continuous variables were made using Student's t tests or Mann-Whitney tests. Poisson regression was used to determine the significance of change in hospital admissions over the two periods, after verifying the absence of overdispersion. Age category, region, and type of acute myocardial infarction (STEMI or NSTEMI) were used as covariables. The FRENCHIE cohort is registered with ClinicalTrials.gov, NCT04050956. FINDINGS: Between Feb 17 and April 12, 2020, 1167 patients were consecutively admitted within 48 h of acute myocardial infarction (583 with STEMI, 584 with NSTEMI) and were included in the study. Admissions for acute myocardial infarction decreased between the periods before and after lockdown was instituted, from 686 before to 481 after lockdown (30% decrease; incidence rate ratio 0·69 [95% CI 0·51-0·70]). Admissions for STEMI decreased from 331 to 252 (24%; 0·72 [0·62-0·85]), and admissions for NSTEMI decreased from 355 to 229 (35%; 0·64 [0·55-0·76]) following institution of the lockdown, with similar trends according to sex, risk factors, and regional prevalence of hospital admissions for COVID-19. INTERPRETATION: A marked decrease in hospital admissions was observed following the lockdown, irrespective of patient characteristics and regional prevalence of COVID-19. Health authorities should be aware of these findings, in order to adapt their message if the COVID-19 pandemic persists or recurs, or in case of future major epidemics. FUNDING: Recherche Hospitalo-Universitaire en Santé iVasc.

Importance of combined left atrial size and estimated pulmonary pressure for clinical outcome in patients presenting with heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome with various phenotypes and outcomes. The prognostic relevance of echocardiography and the E/e' ratio has previously been reported. We sought to study in addition, the value of estimated pulmonary pressure and left atrial size for diagnosing and determining a prognosis for HFpEF-patients in a prospective multi-centric cohort. METHODS AND RESULTS: Patients with an acute-HF event accompanied with NT-proBNP >300 pg/mL (BNP >100 pg/mL) and LVEF >45% were included (n = 237) and clinically reassessed using echo-Doppler after 4-8 weeks of HF treatment as part of the prospective KaRen HFpEF study. A core-centre performed the echocardiographic analyses. A combined primary endpoint of either HF hospitalizations and mortality over a span of 18-month, or simply mortality (secondary endpoint) were used. The mean LVEF was 62 ± 7%, E/e':12.9 ± 6.0, left atrial volume index (LAVI): 48.1 ± 15.9 ml/m2, TR: 2.9 ± 0.9 m/s. Patients with both LAVI > 40 ml/m2 and TR > 3.1 m/s had a significantly greater risk of death or heart failure related hospitalization than others (P = 0.014 after adjustment). CONCLUSION: The combination of enlarged LA and elevated estimated pulmonary pressure has a strong prognostic impact in patients suffering from HFpEF. Our results indicate that such patients constitute a risk group in HFpEF which requires dedicated medical attention. CLINICALTRIALS.GOV: NCT00774709.

Changes in One-Year Mortality in Elderly Patients Admitted with Acute Myocardial Infarction in Relation with Early Management.

BACKGROUND: Elderly patients are underrepresented in acute myocardial infarction trials. Our aim was to determine whether, in elderly patients, changes in management in the past 15 years are associated with improved 1-year mortality after hospital admission for myocardial infarction. METHODS: We used data from 4 1-month French registries, conducted 5 years apart from 1995 to 2010, including 3389 elderly patients (≥75 years of age). RESULTS: From 1995 to 2010, mean age remained stable (82.1 years), similar in ST- and non-ST-elevation myocardial infarction patients. Obesity, diabetes, hypertension, and hypercholesterolemia increased. History of prior myocardial infarction, stroke, and peripheral artery disease remained stable, while history of heart failure decreased. Major changes in management were noted: early percutaneous coronary intervention, early treatment with antiplatelet agents, low-molecular-weight heparin, beta-blockers, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and statins all increased. Early mortality after hospital admission decreased from 25.0% to 8.4%. One-year mortality decreased from 36.2% to 20.0% (adjusted hazard ratio 2010 vs 1995: 0.47, 0.39-0.57), both for ST-elevation myocardial infarction (36.8% to 21.1%) and non-ST-elevation myocardial infarction (34.8% to 19.1%). Mortality reduction was observed in all age groups, including those ≥85 years of age (from 46.2% to 31.4%). The study period, however, was no longer associated with decreased mortality when variables reflecting management changes were taken into account. CONCLUSIONS: Early and 1-year mortality after hospital admission of elderly patients with acute myocardial infarction has substantially decreased over the past 15 years. This improvement is likely mediated by increasing use of recommended management strategies. These data support the application of guidelines derived from trials mostly including younger patients to elderly populations as well.

French Registry on Acute ST-elevation and non-ST-elevation Myocardial Infarction 2015 (FAST-MI 2015). Design and baseline data.

BACKGROUND: The FAST-MI programme, consisting of 1-month surveys of patients admitted to hospital for acute myocardial infarction (AMI) in France, has run since 2005. AIM: To gather data on the characteristics, management and outcomes of patients hospitalized for AMI at the end of 2015 in France and to provide comparisons with the previous surveys. METHODS: Consecutive adults with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment-elevation myocardial infarction (NSTEMI) with symptom onset≤48hours were included over a 1-month period, with a possible extension of recruitment for 1 additional month. Patients with AMI following cardiovascular procedures were excluded. In all, 204 centres participated in the survey (114 community hospitals, 40 academic, 48 private clinics, 2 army hospitals), representing 78% of French centres managing AMI patients. Inclusion started from 5 October 2015. Data were collected on-site from source files by external research technicians, using an electronic case record form with automatic quality checks. Centralized biology was organized in voluntary centres to collect RNA and DNA samples, serum and stools. Long-term follow-up was organized centrally with interrogation of municipal registry offices, physicians and by direct contact with the patients or their families. RESULTS: A total of 5291 patients were included over the entire recruitment period, with 3813 included during the first month (STEMI: 49%, NSTEMI: 51%). Mean age was 66±14 years, 29% were≥75 years of age, 28% were women; 80% presented with typical chest pain. In STEMI patients, 6% received intravenous fibrinolysis and 71% underwent primary PCI. The hospital death rate was 2.7% (STEMI: 2.8%, NSTEMI: 2.5%). CONCLUSIONS: Recruitment was in line with expectations and the first data show that management has continued to evolve since the 2010 survey, with continued improvement in hospital outcomes.

Value of exercise echocardiography in heart failure with preserved ejection fraction: a substudy from the KaRen study.

BACKGROUND: KaRen is a multicentre study designed to characterize and follow patients with heart failure and preserved ejection fraction (HFpEF). In a subgroup of patients with clinical signs of congestion but left ventricular ejection fraction (LVEF) >45%, we sought to describe and analyse the potential prognostic value of echocardiographic parameters recorded not only at rest but also during a submaximal exercise stress echocardiography. Exercise-induced changes in echo parameters might improve our ability to characterize HFpEF patients. METHOD AND RESULTS: Patients were prospectively recruited in a single tertiary centre following an acute HF episode with NT-pro-BNP >300 pg/mL (BNP > 100 pg/mL) and LVEF > 45% and reassessed by exercise echo-Doppler after 4-8 weeks of dedicated treatment. Image acquisitions were standardized, and analysis made at end of follow-up blinded to patients' clinical status and outcome. In total, 60 patients having standardized echocardiographic acquisitions were included in the analysis. Twenty-six patients (43%) died or were hospitalized for HF (primary outcome). The mean ± SD workload was 45 ± 14 watts (W). Mean ± SD resting LVEF and LV global longitudinal strain was 57.6 ± 9.5% and -14.5 ± 4.2%, respectively. Mean ± SD resting E/e' was 11.3 ± 4.7 and 13.1 ± 5.3 in those patients who did not and those who did experience the primary outcome, respectively (P = 0.03). Tricuspid regurgitation (TR) peak velocity during exercise were 3.3 ± 0.5 and 3.7 ± 0.5 m/s (P = 0.01). Exercise TR was independently associated with HF-hospitalization or death after adjustment on baseline clinical and biological characteristics. CONCLUSION: Exercise echocardiography may contribute to identify HFpEF patients and especially high-risk ones. Our study suggested a prognostic value of TR recorded during an exercise. That was demonstrated independently of the value of resting E/e'.

New echocardiographic predictors of clinical outcome in patients presenting with heart failure and a preserved left ventricular ejection fraction: a subanalysis of the Ka (Karolinska) Ren (Rennes) Study.

OBJECTIVES: To identify electrocardiographic and echocardiographic predictors of mortality and hospitalizations for heart failure (HF) in the KaRen study. BACKGROUND: KaRen is a prospective, observational study of the long-term outcomes of patients presenting with heart failure and a preserved ejection fraction (HFpEF). METHOD: We identified 538 patients who presented with acute cardiac decompensation, a >100 pg/mL serum b-type natriuretic peptide (BNP) or >300 pg/mL N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and a left ventricular ejection fraction (LVEF) >45%. After 4-8 weeks of standard treatment, 413 patients (mean age = 76 ± 9 years, 55.9% women) returned for analyses of their clinical status, laboratory screen, and detailed electrocardiographic and Doppler echocardiographic recordings. They were followed for a mean of 28 months thereafter. The primary study endpoint was time to death from all causes or first hospitalization for heart failure. RESULTS: Mean LVEF was 62.4 ± 6.9% and median NT-proBNP 1410 pmol/L. PR interval >200 ms was present in 11.2% of patients and 14.9% had a >120 ms QRS duration, with left bundle branch block in only 6.3%. Over a mean follow-up of 28 months, 177 patients (42.9%) reached a primary study endpoint, including 61 deaths and 116 hospitalizations for heart failure. After adjustment for age, gender, New York Heart Association class, atrial fibrillation history, creatinine, sodium, BNP, ejection fraction, and right ventricular fractional shortening, only E/e' remained as a predictor, with a hazard ratio = 1.49 and P = 0.0012. CONCLUSION: The incidence of hospitalizations for HF and deaths in KaRen was high and E/e' predicted adverse clinical outcomes. These observations should help in the risk stratification and therapy of HFpEF.

Impact of age-adjusted insulin-like growth factor 1 on major cardiovascular events after acute myocardial infarction: results from the fast-MI registry.

BACKGROUND: The GH/IGF-1 axis is being targeted for therapeutic development in diseases such as short stature, cancer, and metabolic disorders. The impact of IGF-1 in cardiovascular disease remains controversial. We therefore studied whether IGF-1 at admission for acute myocardial infarction (AMI) predicted death, recurrent AMI, and stroke over a 2-year follow-up. METHODS: Using data from the French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction registry, we measured IGF-1 among all the 1005 patients with AMI who participated in the serum data bank. Because IGF-1 decreases with age, a standardized IGF-1 score was calculated as previously described [IGF-1 score = (log [IGF-1 (micrograms per liter)] + 0.00625 × age - 2.555)/0.104]. Impact of IGF-1 score (continuous and quartiles) on outcomes were compared using Cox proportional hazards regression models. RESULTS: During follow-up, 190 patients died or had a recurrent AMI or stroke. Patients in the lowest quartile of IGF-1 were older and more frequently female and diabetic compared with patients in the other quartiles. After adjustment for known cardiovascular factors, an increase of five units of IGF-1 score was associated with a 30% decrease of the risk of events during follow-up (adjusted hazard ratio 0.70; 95% confidence interval 0.54-0.92; P = .0093). Similarly, the lowest quartile of IGF-1 was associated with an increased risk of events (adjusted hazard ratio 1.52, 95% confidence interval 1.11-2.08; compared with others quartiles, P = .010). CONCLUSIONS: Low IGF-1 score is associated with an increased risk of all-cause death, recurrent myocardial infarction, and stroke in AMI patients. Whether patients treated by IGF-1 axis inhibitors have a specific clinical course after AMI would be worth studying.

Discharge heart rate and mortality after acute myocardial infarction.

BACKGROUND: We aimed to describe the determinants of discharge heart rate in acute coronary syndrome patients and assess the impact of discharge heart rate on 5-year mortality in hospital survivors. METHODS: French Registry of Acute ST-Elevation or non-ST-elevation Myocardial Infarction (FAST-MI) 2005 is a nationwide French registry that included all consecutive patients with acute myocardial infarction over 1 month in 223 institutions in 2005. Discharge heart rate was recorded in 3079 patients discharged alive; all had 5-year follow-up. Logistic regression was used to detect predictors of high heart rate at discharge. Cox's proportional hazards model was used to assess the hazard ratio for mortality at 5 years. Heart rate was categorized into 4 groups by quartiles (<60, 61-67, 68-75, >75 beats per minute). High heart rate was defined as ≥75 beats per minute. Landmark analysis was performed at 1 year. RESULTS: Independent predictors of heart rate ≥75 beats per minute at discharge were female sex, ST-segment elevation myocardial infarction, diabetes, chronic obstructive pulmonary disease, bleeding/transfusion during hospitalization, left ventricular dysfunction, renal dysfunction, and prescription (type, but not dose category) of beta-blockers at discharge. Discharge heart rate was significantly related to mortality at 1 year (hazard ratio 1.13; 95% confidence interval, 1.03-1.24 per 10 beats per minute, P = .02); this was confirmed by landmark analysis, with a 39% increase (hazard ratio 1.39; 95% confidence interval 1.05-1.84) in the risk of 1-year death for discharge heart rate ≥75 beats per minute vs <75 beats per minute. This relationship was no longer significant between 2 and 5 years. CONCLUSIONS: After acute myocardial infarction, patients discharged with high heart rate (≥75 beats per minute) are at higher risk of death during the first year, but not later, irrespective of beta-blocker use.

Baseline characteristics of patients with heart failure and preserved ejection fraction included in the Karolinska Rennes (KaRen) study.

BACKGROUND: Karolinska Rennes (KaRen) is a prospective observational study to characterize heart failure patients with preserved ejection fraction (HFpEF) and to identify prognostic factors for long-term mortality and morbidity. AIMS: To report characteristics and echocardiography at entry and after 4-8 weeks of follow-up. METHODS: Patients were included following an acute heart failure presentation with B-type natriuretic peptide (BNP)>100 ng/L or N-terminal pro-BNP (NT-proBNP)>300 ng/L and left ventricular ejection fraction (LVEF)>45%. RESULTS: The mean ± SD age of 539 included patients was 77 ± 9 years and 56% were women. Patient history included hypertension (78%), atrial tachyarrhythmia (44%), prior heart failure (40%) and anemia (37%), but left bundle branch block was rare (3.8%). Median NT-proBNP was 2448 ng/L (n=438), and median BNP 429 ng/L (n=101). Overall, 101 patients did not return for the follow-up visit, including 13 patients who died (2.4%). Apart from older age (80 ± 9 vs. 76 ± 9 years; P=0.006), there were no significant differences in baseline characteristics between patients who did and did not return for follow-up. Mean LVEF was lower at entry than follow-up (56% vs. 62%; P<0.001). At follow-up, mean E/e' was 12.9 ± 6.1, left atrial volume index 49.4±17.8mL/m(2). Mean global left ventricular longitudinal strain was -14.6 ± 3.9%; LV mass index was 126.6 ± 36.2g/m(2). CONCLUSIONS: Patients in KaRen were old with slight female dominance and hypertension as the most prevalent etiological factor. LVEF was preserved, but with increased LV mass and depressed LV diastolic and longitudinal systolic functions. Few patients had signs of electrical dyssynchrony (ClinicalTrials.gov.- NCT00774709).

Association between cardiovascular vs. non-cardiovascular co-morbidities and outcomes in heart failure with preserved ejection fraction.

AIMS: The prevalence of cardiovascular and non-cardiovascular co-morbidities and their relative importance for outcomes in heart failure with preserved ejection fraction (HFPEF) remain poorly characterized. This study aimed to investigate this. METHODS AND RESULTS: The Karolinska-Rennes (KaRen) Study was a multinational prospective observational study designed to characterize HFPEF. Inclusion required acute HF, defined by the Framingham criteria, LVEF ≥ 45%, and NT-pro-BNP ≥ 300 ng/L or BNP ≥ 100 ng/L. Detailed clinical data were collected at baseline and patients were followed prospectively for 18 months. Predictors of the primary (HF hospitalization or all-cause mortality) and secondary (all-cause mortality) outcomes were assessed with multivariable Cox regression. A total of 539 patients [56% women; median (interquartile range) age 79 (72-84) years; NT-pro-BNP/BNP 2448 (1290-4790)/429 (229-805) ng/L] were included. Known history of HF was present in 40%. Co-morbidities included hypertension (78%), atrial fibrillation/flutter (65%), anaemia (51%), renal dysfunction (46%), CAD (33%), diabetes (30%), lung disease (25%), and cancer (16%). The primary outcome occurred in 268 patients [50%; 106 deaths (20%) and 162 HF hospitalizations (30%)]. Important independent predictors of the primary and/or secondary outcomes were age, history of non-cardiovascular syncope, valve disease, anaemia, lower sodium, and higher potassium, but no cardiovascular co-morbidities. Renin-angiotensin system antagonist and mineralocorticoid receptor antagonist use predicted improved prognosis. CONCLUSION: HFPEF was associated with higher age, female gender, hypertension, atrial fibrillation/flutter, and numerous non-cardiovascular co-morbidities. Prognosis was determined by non-cardiovascular co-morbidities, but use of conventional heart failure medications may still be associated with improved outcomes.

[Acute myocardial infarction in the elderly. The FAST-MI registry]. / L'infarctus du sujet âgé : données du registre FAST-MI 2010.

The FAST-MI 2010 registry collected information on characteristics and management of patients hospitalized for acute myocardial infraction during a one-month period in 213 centers across France, at the end of 2010. Among the 3079 patients included, 31% were aged 75 years or over (25% of those with ST-elevation myocardial infarction, and 38% of those with non-ST-elevation myocardial infarction). The clinical profile and risk factors differ in elderly patients, but chest pain remains the most common presenting symptom, although a substantial percentage of patients also present with signs of heart failure. Elderly individuals receive less recommended medications, including reperfusion therapy for STEMI, with the largest difference observed beyond 85 years of age. In-hospital mortality increases with age, particularly after 85 years, but has decreased compared with previous French surveys.

Comparison of bleeding complications and one-year survival of low molecular weight heparin versus unfractioned heparin for acute myocardial infarction in elderly patients. The FAST-MI registry.

BACKGROUND: There are limited data on the safety and efficacy of low molecular weight heparin (LMWH) in elderly patients with acute myocardial infarction (AMI). METHODS: We aimed to compare LMWH with unfractioned heparin (UFH) in the management of AMI in elderly patients. FAST-MI is a nationwide registry carried out over a 1-month period in 2005, including consecutive patients with AMI admitted to intensive care unit <48 h from symptom onset in 223 participating centers. We assessed the impact of LMWH on bleeding, the need for blood transfusion and one-year survival in elderly patients (≥ 75 years). RESULTS: 963 patients treated with heparin were included (mean age 82 ± 5 years; 51% women; 42.5% ST-elevation myocardial infarction). Major bleeding (2.4% vs. 6.1%, P=0.004) and blood transfusions (4.6% vs. 9.7%, P=0.002) were significantly less frequent with LMWH compared with the UFH, a difference that persisted after multivariate adjustment (OR=0.41, 95% CI: 0.20-0.83 and OR=0.49, 95% CI: 0.28-0.85, respectively). One-year survival and stroke and reinfarction-free survival were also significantly higher with LMWH compared with UFH (OR=0.66, 95% CI: 0.50-0.85 and OR=0.71, 95% CI: 0.56-0.91, respectively). In two cohorts of patients matched on a propensity score for getting LMWH and with similar baseline characteristics (328 patients per group), major bleeding and transfusion were significantly lower while one-year survival was significantly higher in patients receiving LMWH. CONCLUSIONS: The present data show that in elderly patients admitted for AMI, use of LMWH is associated with less bleeding, less need for transfusion, and higher survival, compared with the use of UFH.