Secondary prevention strategies after an acute ST-segment elevation myocardial infarction in the AMI code era: beyond myocardial mechanical reperfusion.

BACKGROUND: The AMI code is a regional network enhancing a rapid and widespread access to reperfusion therapy (giving priority to primary angioplasty) in patients with acute ST-segment elevation myocardial infarction (STEMI). We aimed to assess the long-term control of conventional cardiovascular risk factors after a STEMI among patients included in the AMI code registry. DESIGN AND METHODS: Four hundred and fifty-four patients were prospectively included between June-2009 and April-2013. Clinical characteristics were collected at baseline. The long-term control of cardiovascular risk factors and cardiovascular morbidity/mortality was assessed among the 6-months survivors. RESULTS: A total of 423 patients overcame the first 6 months after the STEMI episode, of whom 370 (87%) underwent reperfusion therapy (363, 98% of them, with primary angioplasty). At 1-year follow-up, only 263 (62%) had adequate blood pressure control, 123 (29%) had LDL-cholesterol within targeted levels, 126/210 (60%) smokers had withdrawn from their habit and 40/112 (36%) diabetic patients had adequate glycosylated hemoglobin levels. During a median follow-up of 20 (11-30) months, cumulative mortality of 6 month-survivors was 6.1%, with 9.9% of hospital cardiovascular readmissions. The lack of assessment of LDL and HDL-cholesterol were significantly associated with higher mortality and cardiovascular readmission rates. CONCLUSIONS: Whereas implementation of the AMI code resulted in a widespread access to rapid reperfusion therapy, its long-term therapeutic benefit may be partially counterbalanced by a manifestly suboptimal control of cardiovascular risk factors. Further efforts should be devoted to secondary prevention strategies after STEMI.

Right Ventricular Response During Exercise in Patients with Chronic Obstructive Pulmonary Disease.

AIM: Right ventricular (RV) pump function is of essential clinical and prognostic importance in a variety of heart and lung diseases. While the evaluation of RV performance at rest has been implemented in the clinical setting, it is unknown whether this assessment during exercise may provide additional benefit. With this aim, we evaluated the exercise-induced pulmonary arterial systolic pressure (PASP) increase during exercise in patients with severe chronic obstructive pulmonary disease (COPD) as an expression of RV contractile reserve. METHOD: Cardiopulmonary exercise testing (CPET) with synchronic echocardiography was performed in 81 patients. Patients were classified into two groups according to an exercise-induced PASP increase above 30mmHg (High PSAP) or below 30mmHg (Low PSAP) during maximal exercise. Patients were then followed for three years. RESULTS: Sixteen patients (20%) had low PSAP and 65 (80%) showed high PSAP. These were not significant clinical and functional differences. Low PSAP was associated with a significantly lower peak VO2 (mean (SD), 35 (2) % predicted) compared to high PSAP response (peak VO2 45 (3) % predicted), p=0.045. Factors associated with mortality were age and exercise-induced PASP. Seventeen patients died during the three years of follow-up (7 (39%) in the low PSAP group and only 10 (1%) in the high PSAP group, p=0.041). CONCLUSION: Cardiopulmonary exercise testing with a synchronic echocardiography may be a useful tool for the assessment of RV contractile reserve in severe COPD patients. Exercise-induced PSAP emerges as a possible prognostic factor in these patients.

Ischemic aetiology, self-reported frailty, and gender with respect to cognitive impairment in chronic heart failure patients.

BACKGROUND: Decisive information on the parameters involved in cognitive impairment in patients with chronic heart failure is as yet lacking. Our aim was to determine the functional and psychosocial variables related with cognitive impairment using the mini-mental-state examination (MMSE) with age-and education-corrected scores. METHODS: A cohort study of chronic heart failure patients included in an integrated multidisciplinary hospital/primary care program. The MMSE (corrected for age and education in the Spanish population) was administered at enrolment in the program. Analyses were performed in 525 patients. Demographic and clinical variables were collected. Comprehensive assessment included depression (Yesavage), family function (family APGAR), social network (Duke), dependence (Barthel Index), frailty (Barber), and comorbidities. Univariate and multivariate logistic regression were performed to determine the predictors of cognitive impairment. RESULTS: Cognitive impairment affected 145 patients (27.6 %). Explanatory factors were gender (OR: 2.77 (1.75-4.39) p < 0.001), ischemic etiology (OR: 1.99 (1.25-3.17) p = 0.004), frailty (OR: 1.58 (0.99 to 2.50, p =0.050), albumin > 3.5 (OR: 0.59 (0.35-0.99) p = 0.048), and beta-blocker treatment (OR: 0.36 (0.17 to 0.76, p = 0.007)). No association was found between cognitive impairment and social support or family function. CONCLUSION: The observed prevalence of cognitive impairment using MMSE corrected scores was 27.6 %. A global approach in the management of these patients is needed, especially focusing on women and patients with frailty, low albumin levels, and ischemic aetiology heart failure.

Clinical value of ankle-brachial index in asymptomatic aortic stenosis patients.

BACKGROUND AND AIM OF THE STUDY: The study aim was to assess the prevalence and clinical value of the pathological ankle-brachial index (ABI) in asymptomatic aortic stenosis (AS) patients. METHODS: This prospective study included 203 asymptomatic AS patients, with a mean follow up of 18 ± 10.6 months. Six-minute walk tests (6MWT) and ABI measurements were performed when patients were included in the study. Study events were defined as death, hospital admission due to related symptoms, or a need for surgery. RESULTS: A total of 198 patients (95 females, 103 males; mean age 74.6 ± 9.5 years) completed the study. An abnormal ABI was found in 35.8%. Mean (± SD) values were: peak velocity Vmax 4.1 ± 0.8 m/s; maximum/mean gradient 70.5 ± 25.1/43.3 ± 16.3 mmHg; aortic valve area 0.8 ± 0.7 cm2; indexed aortic valve area 0.4 ± 0.1 cm2/m2. A pathological ABI was associated with diabetes (p = 0.01), previous peripheral vascular disease (p = 0.04) and previous stroke (p = 0.04). In multivariate analyses, diabetes was an independent factor related to pathological ABI (relative risk 1.71, 95% CI 1.22-2.19). Patients with a pathological ABI walked less in the 6MWT (263.9 m versus 328.3; p = 0.002), but did not present a worse prognosis at follow up (p = NS). CONCLUSION: Among asymptomatic AS patients, 35.8% had an abnormal ABI and this was related to previous diabetes. These patients walked less in the 6MWT but did not have a worse prognosis at follow up.

Association of atherosclerosis with expression of the LILRB1 receptor by human NK and T-cells supports the infectious burden hypothesis.

OBJECTIVE: The contribution of human cytomegalovirus (HCMV) to vascular disease may depend on features of the immune response not reflected by the detection of specific antibodies. Persistent HCMV infection in healthy blood donors has been associated with changes in the distribution of NK cell receptors (NKR). The putative relationship among HCMV infection, NKR distribution, subclinical atherosclerosis, and coronary heart disease was assessed. METHODS AND RESULTS: NKR expression was compared in acute myocardial infarction (AMI) patients (n=70) and a population-based control sample (n=209). The relationship between NKR expression and carotid intima-media thickness (CIMT) in controls (n=149) was also studied. HCMV infection was associated with higher proportions of NKG2C+ and LILRB1+ NK and T-cells. In contrast, only LILRB1+ NK and CD56+ T-cells were found to be increased in AMI patients, independent of age, sex, conventional vascular risk factors, and HCMV seropositivity. Remarkably, LILRB1 expression in NK and T-cells significantly correlated with CIMT in controls. CONCLUSIONS: The association of overt and subclinical atherosclerotic disease with LILRB1+ NK and T-cells likely reflects a relationship between the immune challenge by infections and cardiovascular disease risk, without attributing a dominant role for HCMV. Our findings may lead to the identification of novel biomarkers of vascular disease.

Phenotype and genotype characterization and twin association in patients with Anderson-Fabry cardiomyopathy.

Anderson-Fabry disease (FD), an X-linked recessive lysosomal storage disorder caused by a deficiency of α-galactosidase A (α-Gal A) activity, is associated with cardiac manifestations including arrhythmias, valvular abnormalities, and cardiomyopathy. Early initiation of enzyme replacement therapy (ERT) may have the potential to delay the underlying clinical outcomes in patients with FD. Clinical electrocardiogram (ECG) and echocardiography were used to characterize the cardiomyopathy. Diagnosis of FD was performed by measuring the α-Gal A activity in plasma and mutation analysis by direct sequencing using capillary electrophoresis. We identified four adult hemizygous male patients with cardiomyopathy and other symptoms related to FD; two of them were monozygotic twins. In all cases, ECG and echocardiography showed severe left ventricular (LV) hypertrophy. Some years later, all patients showed typical symptoms of FD, including angiokeratomas and neurological, renal, gastrointestinal, and ocular involvement. A deficiency of α-Gal A activity and point mutations in exon 5 of the GLA gene were detected in all patients. ERT (agalsidase-alfa) was administered every other week as a 0.2 mg/kg intravenous infusion over 40 min. In conclusion, these findings highlight the importance of screening middle-aged patients with LV hypertrophy for the early detection of FD, particularly in direct-line relatives such as twins.

Seven-year mortality in heart failure patients with undiagnosed diabetes: an observational study.

BACKGROUND: Patients with type 2 diabetes mellitus and heart failure have adverse clinical outcomes, but the characteristics and prognosis of those with undiagnosed diabetes in this setting has not been established. METHODS: In total, 400 patients admitted consecutively with acute heart failure were grouped in three glycaemic categories: no diabetes, clinical diabetes (previously reported or with hypoglycaemic treatment) and undiagnosed diabetes. The latter was defined by the presence of at least two measurements of fasting plasma glycaemia ≥ 7 mmol/L before or after the acute episode.Group differences were tested by proportional hazards models in all-cause and cardiovascular mortality during a 7-year follow-up. RESULTS: There were 188 (47%) patients without diabetes, 149 (37%) with clinical diabetes and 63 (16%) with undiagnosed diabetes. Patients with undiagnosed diabetes had a lower prevalence of hypertension, dyslipidaemia, peripheral vascular disease and previous myocardial infarction than those with clinical diabetes and similar to that of those without diabetes. The adjusted hazards ratios for 7-year total and cardiovascular mortality compared with the group of subjects without diabetes were 1.69 (95% CI: 1.17-2.46) and 2.45 (95% CI: 1.58-3.81) for those with undiagnosed diabetes, and 1.48 (95% CI: 1.10-1.99) and 2.01 (95% CI: 1.40-2.89) for those with clinical diabetes. CONCLUSIONS: Undiagnosed diabetes is common in patients requiring hospitalization for acute heart failure. Patients with undiagnosed diabetes, despite having a lower cardiovascular risk profile than those with clinical diabetes, show a similar increased mortality.

The Guideliner™ catheter for stent delivery in difficult cases: tips and tricks.

INTRODUCTION: Stent delivery in complex coronary anatomy with severe calcification and tortuosity is still a common cause of percutaneous coronary interventions (PCI) failure. Recently, a new support rapid exchange catheter, the Guideliner, has been designed specifically for device delivery. METHODS: From June 2010 to December 2010, we performed 10 cases using the Guideliner catheter to improve backup support and facilitate stent delivery: 2 emergent PCI for ST elevation myocardial infarction, and 8 stable elective PCI. In 3 cases the operator chose the femoral access, in 2 cases crossover from radial to femoral access was needed, and the other cases were performed radially. In 2 cases PTCA with drug-eluting balloon was performed; in the other cases second-generation drug-eluting stent was implanted. RESULTS: One case, the first one, failed, as stent could not be delivered to the target lesion. The other 9 cases were performed successfully. Three proximal dissections were detected and sealed with stent implantation. In 2 cases, we had stent damage due to the passage of the stent through the Guideliner metal collar. Another stent had to be used. CONCLUSIONS: In our experience, the Guideliner catheter is safe to use and helps device delivery in difficult settings. We describe here our experience with the Guideliner catheter for stent delivery and backup support; we discuss its utility and drawbacks in acute and stable clinical settings. Moreover, the aim of this article is to help interventional cardiologists using the device in difficult lesions to avoid potential complications.

Incremental pacing for the diagnosis of complete cavotricuspid isthmus block during radiofrequency ablation of atrial flutter.

BACKGROUND: Complete conduction block of the cavotricuspid isthmus (CTI) reduces atrial flutter recurrences after ablation. Incremental rapid pacing may distinguish slow conduction from complete CTI conduction block. METHODS AND RESULTS: Fifty-two patients (67 +/- 9 years) undergoing 55 CTI ablation procedures were included. With ablation, double potentials (DPs) separated by an isoelectric line of > or =30 ms were obtained. Incremental atrial pacing (600-250 ms) was performed from coronary sinus (CS) and low lateral right atrium (LLRA). A <20 ms increase in the DPs distance during incremental pacing was indexed as complete CTI block. In 8 patients, an initial <20 ms DPs distance increase was noted; direct complete isthmus block was suggested and no additional ablation performed. In the remaining, the CTI line was remapped for conduction gaps and additional radiofrequency energy pulses applied. Complete block, as indexed by incremental pacing, occurred in 46 of 55 procedures, with one flutter recurrence (follow-up 8 +/- 2 months): DPs interval variation of 116 +/- 20 to 123 +/- 20 ms (CS), P = 0.21; and 122 +/- 25 to 135 +/- 35 ms (LLRA), P = 0.17. The remaining 9 patients (persistent rate-dependent DPs increase) presented 3 flutter recurrences, P = 0.01: DP distance from 127 +/- 15 to 161 +/- 18 ms (CS), P < 0.001; and 114 +/- 24 to 142 +/- 10 ms (LLRA), P = 0.007. CONCLUSION: Incremental pacing distinguishes complete CTI block from persistent conduction. Such identification, accompanied by additional ablation to achieve block, should minimize flutter recurrences after ablative therapy.

Subtelomeric MLPA: is it really useful in prenatal diagnosis?

OBJECTIVE: To evaluate the usefulness of subtelomeric multiplex ligation-dependent probe amplification (MLPA) in both the detection of subtelomeric rearrangements in fetuses with ultrasound abnormalities and normal karyotype, and the characterization of cytogenetically detectable rearrangements. METHOD: We studied by subtelomeric MLPA 229 pregnancies with ultrasound findings and normal karyotype (Group 1) and five pregnancies with a cytogenetically visible but not microscopically characterizable rearrangement (Group 2). The detected imbalances were confirmed by fluorescence in situ hybridization (FISH) and parents were also studied. RESULTS: In Group 1, two clinically relevant subtelomeric imbalances (14qter deletion and 20pter deletion) and one subtelomeric imbalance of uncertain significance (X/Ypter duplication) were diagnosed, showing a detection rate of cryptic subtelomeric imbalances in these pregnancies of 1.3%. However, only 14qter deletion seems to be clearly associated with the observed prenatal findings. In Group 2, MLPA contributed to the precise description of the chromosome abnormalities. CONCLUSION: The low detection rate of subtelomeric imbalances and the poor genotype-phenotype correlations in pregnancies with ultrasound abnormalities and normal karyotype suggest that subtelomeric MLPA is not a crucial tool in the prenatal diagnosis of these cases. However, our work provides evidence that MLPA is very useful for the characterization of unbalanced karyotypes. Copyright © 2010 John Wiley & Sons, Ltd.

[Body mass index in the prognosis of first myocardial infarction]. / Índice de masa corporal como factor pronóstico en pacientes tras un primer infarto de miocardio.

BACKGROUND AND OBJECTIVES: The value of body mass index in the prognosis of patients with ischemic heart disease is not well defined. The objective of our study was to determine the association of body mass index with classic and emergent cardiovascular risk factors and with intra-hospital and 6-months mortality. PATIENTS AND METHODS: We conducted a prospective, multicenter study with a 6-months follow-up. We included 1063 patients between the ages of 25-75 years old who were consecutively admitted to the hospital within the first 24 hours of the onset of symptoms between years 2001 and 2003. We determined demographic and anthropometric variables, as well as classic and emergent factors of risk, clinical variables and the treatment administered. We carried out a univariate and multivariate analysis. RESULTS: The percentage of patients with overweight or obesity in this population was 73.56%. Overweight and obesity were associated with classical risk factors, except for smoking, and emergent risk factors. Body mass index was not associated with short-or mid-term prognosis. CONCLUSIONS: Body mass index is not a useful anthropometric measure to determine the prognosis of patients after a first myocardial infarction.

A pilot evaluation of the long-term effect of combined therapy with intravenous iron sucrose and erythropoietin in elderly patients with advanced chronic heart failure and cardio-renal anemia syndrome: influence on neurohormonal activation and clinical outcomes.

BACKGROUND: The prognosis in elderly patients with advanced chronic heart failure (CHF) and cardio-renal anemia syndrome (CRAS) is ominous, and treatment alternatives in this subset of patients are scarce. METHODS AND RESULTS: To assess the long-term influence of combined therapy with intravenous (IV) iron and erythropoietin (rHuEPO) on hemoglobin (Hb), natriuretic peptides (NT-proBNP), and clinical outcomes in elderly patients with advanced CHF and mild-to-moderate renal dysfunction and anemia (CRAS) who are not candidates for other treatment alternatives, 487 consecutive patients were evaluated. Of them, 65 fulfilling criteria for entering the study were divided into 2 groups and treated in an open-label, nonrandomized fashion: intervention group (27, combined anemia therapy) and control group (38, no treatment for anemia). At baseline, mean age was 74 +/- 8 years, left ventricular ejection fraction was 34.5 +/- 14.1, Hb was 10.9 +/- 0.9 g/dL, creatinine was 1.5 +/- 0.5 mg/dL, NT-proBNP was 4256 +/- 4952 pg/mL, and 100% were in persistent New York Heart Association (NYHA) Class III or IV. At follow-up (15.3 +/- 8.6 months), patients in the intervention group had higher levels of hemoglobin (13.5 +/- 1.5 vs. 11.3 +/- 1.1; P < .0001), lower levels of natural log of NT-proBNP (7.3 +/- 0.8 vs. 8.0 +/- 1.3, P = .016), better NYHA functional class (2.0 +/- 0.6 vs. 3.3 +/- 0.5; P < .001), and lower readmission rate (25.9% vs. 76.3%; P < .001). In the multivariate Cox proportional hazards model, combined therapy was associated with a reduction of the combined end point all-cause mortality or cardiovascular hospitalization (HR 95%CI 0.2 [0.1-0.6]; P < .001). CONCLUSION: Long-term combined therapy with IV iron and rHuEPO may increase Hb, reduce NT-proBNP, and improve functional capacity and cardiovascular hospitalization in elderly patients with advanced CHF and CRAS with mild to moderate renal dysfunction.

Prenatal diagnosis of two different unbalanced forms of an inherited (Y;12) translocation.

The identification of an unexpected structural chromosome rearrangement at prenatal diagnosis can be problematic and raises unique genetic counseling issues. We describe two consecutive prenatal cases within a family with an inherited unbalanced (Y;12) translocation and discuss the genotype-phenotype correlation. The first fetus presented with 12qter monosomy and pseudoautosomal region 2 trisomy, while the second fetus had the alternative unbalanced state. Although the first fetus had a structural heart defect, such small imbalances might not give sonographic findings, making their prenatal diagnosis difficult. However, congenital abnormalities are expected in both unbalanced forms of the translocation, including mental retardation, which could be explained by the gene dosage variation of P2RX2. To our knowledge, these are the first published cases reporting this subtype of (Y;12) translocation, in both balanced and unbalanced states.

Angiographic quantification of thrombus in ST-elevation acute myocardial infarction presenting with an occluded infarct-related artery and its relationship with results of percutaneous intervention.

INTRODUCTION: Routine thrombectomy has been advocated for ST-segment-elevation myocardial infarction (STEMI), but it is unknown how many patients present with a large thrombus. We aimed to quantify the intracoronary thrombus in STEMI and to correlate it with procedure results. METHODS: In 98 patients with STEMI and TIMI flow grades 0-2 in the infarct-related artery, thrombus was qualified as small (ST) when its maximal dimension was <2 vessel diameters and large (LT) when >or=2. Main outcome measures were TIMI flow, myocardial blush grade (MBG), corrected TIMI frame count (cTFC), and ST-segment elevation resolution (STSER). RESULTS: Only a third of the patients presented with an LT. Thrombus grade was independent of the initial vessel patency. Diabetes (OR 3.1, 95% CI 1.20-8.02, P = 0.027) and pretreatment with clopidogrel (OR 0.27, 95% CI 0.08-0.86, P = 0.034) were independent predictors of LT. LT was an independent predictor of unfavorable results: <3 TIMI flow (OR 2.87, 95% CI 1.04-8.00, P = 0.043), MBG 0-1 (OR 3.36, 95% CI 1.10-10.26, P = 0.033), cTFC > 21 (OR 2.86, 95% CI 1.09-7.49, P = 0.033) and <50% STSER (OR 3.19, 95% CI 1.06-9.63, P = 0.039). CONCLUSION: Only a third of STEMI patients present with an LT, being diabetes and lack of clopidogrel pretreatment independent predictors. An LT is strongly associated with worse PCI results.

Efficacy of a nurse-led lipid-lowering secondary prevention intervention in patients hospitalized for ischemic heart disease: A pilot randomized controlled trial.

BACKGROUND AND AIMS: Lack of achievement of secondary prevention objectives in patients with ischaemic heart disease remains an unmet need in this patient population. We aimed at evaluating the six-month efficacy of an intensive lipid-lowering intervention, coordinated by nurses and implemented after hospital discharge, in patients hospitalized for an ischaemic heart disease event. METHODS: Randomized controlled trial, in which a nurse-led intervention including periodic follow-up, serial lipid level controls, and subsequent optimization of lipid-lowering therapy, if appropriate, was compared with standard of care alone in terms of serum lipid-level control at six months after discharge. RESULTS: The nurse-led intervention was associated with an improved management of low-density lipoprotein (LDL) cholesterol levels compared with standard of care alone: LDL cholesterol levels ⩽100 mg/dL were achieved in 97% participants in the intervention arm as compared with 67% in the usual care arm ( p value <0.001), the LDL cholesterol ⩽70 mg/dL target recommended by the 2016 European Society of Cardiology guidelines was achieved in 62% vs. 37% participants ( p value 0.047) and the LDL cholesterol reduction of ⩾50% recommended by the American College of Cardiology/American Heart Association in 2013 was achieved in 25.6% of participants in the intervention arm as compared with 2.6% in the usual care arm ( p value 0.007). The intervention was also associated with improved blood pressure control among individuals with hypertension. CONCLUSIONS: Our findings highlight the opportunity that nurse-led, intensive, post-discharge follow-up plans may represent for achieving LDL cholesterol guideline-recommended management objectives in patients with ischaemic heart disease. These findings should be replicated in larger cohorts.

Cytogenetic study of spontaneous abortions using semi-direct analysis of chorionic villi samples detects the broadest spectrum of chromosome abnormalities.

Conventional tissue culturing and karyotyping of spontaneous abortions has limitations such as culture failure, external contamination and selective growth of maternal cells. Molecular cytogenetic techniques such as FISH, QF-PCR, and CGH allow diagnosis on uncultured cells but are also limited as to the spectrum of cytogenetic abnormalities detected. We describe the cytogenetic findings in a series of 116 first trimester arrested pregnancies, obtained through chorionic villi sampling (CVS) and semi-direct analysis that avoids some of the long-culture pitfalls such as maternal contamination, and compare our results with those that would have been obtained theoretically using molecular cytogenetic techniques. Samples were obtained by transcervical CVS from women with a diagnosis of missed abortion, most of them referred for cytogenetic prenatal diagnosis. Cytogenetic analysis was performed using semi-direct technique. A karyotype was obtained in 103 cases. Eighty-two abnormal karyotypes were found (80%), including 12 triploidies, 10 monosomies, 61 trisomies, and 9 structural abnormalities; a double abnormality being present in 10 cases. Between 10% and 50% of our abnormal results would have been missed using the most common molecular cytogenetic techniques. Semi-direct analysis of CVS may still be considered as a comprehensive, reasonably rapid, cost-effective and reliable method for detecting the broadest spectrum of chromosome abnormalities in missed abortions.

Heart failure in acute ischemic stroke.

BACKGROUND: To determine the impact of heart failure (HF), with preserved or decreased left ventricular function (LVF), on outcome in patients with acute ischemic stroke (AIS). METHODS: We studied 503 unselected ischemic stroke patients. Poor outcome was defined as moderate-severe disability or death at 90 days. We analyzed the association between poor outcome and HF with preserved LVF or decreased LVF (systolic HF: ejection fraction lower than 50%). We tested this association adjusted by possible confounders in a logistic regression model. RESULTS: 89 patients (17.7 %) had HF; 49 patients (9.7%) with systolic HF, and 40 (8%) patients with HF and preserved LVF. HF with preserved LVF patients were older [79.4 (7.9) vs. 74.3 (10.4), p = 0.013],more likely to be women [p < 0.001,OR = 8.61, 95% CI (3.3-22.6)], and with lower current smoking habits [p = 0.018, OR = 8.77 (1.1-72.6)] than patients with systolic HF. 151 patients (30 %) had poor outcome. We found an independent association with initial stroke severity, systolic HF (adjusted OR = 3.01), HF with preserved LVF (adjusted OR = 2.52), thrombolytic treatment, statin pre-treatment (as protectors) and poor outcome. CONCLUSION: Both forms of HF (with or without decreased systolic function) are associated with poor outcome in AIS.

Long-term endurance sport practice increases the incidence of lone atrial fibrillation in men: a follow-up study.

AIMS: The aim of this study is to determine the incidence of lone atrial fibrillation (LAF) in males according to sport practice and to identify possible clinical markers related to LAF among marathon runners. METHODS AND RESULTS: A retrospective cohort study was designed. A group of marathon runners (n = 252) and a population-based sample of sedentary men (n = 305) recruited in 1990-92 and 1994-96, respectively, were contacted in 2002-03 and invited to attend an outpatient clinic to identify suggestive symptoms of having experienced an arrhythmia requiring medical attention. In those with suggestive symptoms of atrial fibrillation, medical records were reviewed. Finally, LAF was diagnosed on the basis of the presence of atrial fibrillation in an electrocardiographic recording. In the group of marathon runners, an echocardiogram was performed at inclusion and at the end of the study. The annual incidence rate of LAF among marathon runners and sedentary men was 0.43/100 and 0.11/100, respectively. Endurance sport practice was associated with a higher risk of incident LAF in the multivariate age- and blood pressure-adjusted Cox regression models (hazard ratio = 8.80; 95% confidence interval: 1.26-61.29). In the group of marathon runners, left atrial inferosuperior diameter and left atrial volume were both associated with a higher risk of incident LAF. CONCLUSION: Long-term endurance sport practice is associated with a higher risk of symptomatic LAF in men. This risk is associated with a larger left atrial inferosuperior diameter and volume in physically active subjects.

Efficacy and safety of intermittent intravenous outpatient administration of levosimendan in patients with advanced heart failure: the LION-HEART multicentre randomised trial.

AIMS: The LION-HEART study was a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial evaluating the efficacy and safety of intravenous administration of intermittent doses of levosimendan in outpatients with advanced chronic heart failure. METHODS AND RESULTS: Sixty-nine patients from 12 centres were randomly assigned at a 2:1 ratio to levosimendan or placebo groups, receiving treatment by a 6-hour intravenous infusion (0.2 µg/kg/min without bolus) every 2 weeks for 12 weeks. The primary endpoint was the effect on serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) throughout the treatment period in comparison with placebo. Secondary endpoints included evaluation of safety, clinical events and health-related quality of life (HRQoL). The area under the curve (AUC, pg.day/mL) of the levels of NT-proBNP over time for patients who received levosimendan was significantly lower than for the placebo group (344 × 103 [95% Confidence Interval (CI) 283 × 103 -404 × 103 ] vs. 535 × 103 [443 × 103 -626 × 103 ], p = 0.003). In comparison with the placebo group, the patients on levosimendan experienced a reduction in the rate of heart failure hospitalisation (hazard ratio 0.25; 95% CI 0.11-0.56; P = 0.001). Patients on levosimendan were less likely to experience a clinically significant decline in HRQoL over time (P = 0.022). Adverse event rates were similar in the two treatment groups. CONCLUSIONS: In this small pilot study, intermittent administration of levosimendan to ambulatory patients with advanced systolic heart failure reduced plasma concentrations of NT-proBNP, worsening of HRQoL and hospitalisation for heart failure. The efficacy and safety of this intervention should be confirmed in larger trials.

Defining quantification methods and optimizing protocols for microarray hybridization of circulating microRNAs.

MicroRNAs (miRNAs) have emerged as promising biomarkers of disease. Their potential use in clinical practice requires standardized protocols with very low miRNA concentrations, particularly in plasma samples. Here we tested the most appropriate method for miRNA quantification and validated the performance of a hybridization platform using lower amounts of starting RNA. miRNAs isolated from human plasma and from a reference sample were quantified using four platforms and profiled with hybridization arrays and RNA sequencing (RNA-seq). Our results indicate that the Infinite® 200 PRO Nanoquant and Nanodrop 2000 spectrophotometers magnified the miRNA concentration by detecting contaminants, proteins, and other forms of RNA. The Agilent 2100 Bioanalyzer PicoChip and SmallChip gave valuable information on RNA profile but were not a reliable quantification method for plasma samples. The Qubit® 2.0 Fluorometer provided the most accurate quantification of miRNA content, although RNA-seq confirmed that only ~58% of small RNAs in plasma are true miRNAs. On the other hand, reducing the starting RNA to 70% of the recommended amount for miRNA profiling with arrays yielded results comparable to those obtained with the full amount, whereas a 50% reduction did not. These findings provide important clues for miRNA determination in human plasma samples.