An intensive, structured, mobile devices-based healthcare intervention to optimize the lipid-lowering therapy improves lipid control after an acute coronary syndrome.

Aims: Despite the evidence, lipid-lowering treatment (LLT) in secondary prevention remains insufficient, and a low percentage of patients achieve the recommended LDL cholesterol (LDLc) levels by the guidelines. We aimed to evaluate the efficacy of an intensive, mobile devices-based healthcare lipid-lowering intervention after hospital discharge in patients hospitalized for acute coronary syndrome (ACS). Methods and results: Ambiespective register in which a mobile devices-based healthcare intervention including periodic follow-up, serial lipid level controls, and optimization of lipid-lowering therapy, if appropriate, was assessed in terms of serum lipid-level control at 12 weeks after discharge. A total of 497 patients, of which 462 (93%) correctly adhered to the optimization protocol, were included in the analysis. At the end of the optimization period, 327 (70.7%) patients had LDLc levels ≤ 70 mg/dL. 40% of patients in the LDLc ≤ 70 mg/dL group were upgraded to very-high intensity lipid-lowering ability therapy vs. 60.7% in the LDLc > 70 mg/dL group, p < 0.001. Overall, 38.5% of patients had at least a change in their LLT. Side effects were relatively infrequent (10.7%). At 1-year follow-up, LDLc levels were measured by the primary care physician in 342 (68.8%) of the whole cohort of 497 patients. In this group, 71.1% of patients had LDLc levels ≤ 70 mg/dL. Conclusion: An intensive, structured, mobile devices-based healthcare intervention after an ACS is associated with more than 70% of patients reaching the LDLc levels recommended by the clinical guidelines. In patients with LDLc measured at 1-year follow-up, 71.1% had LDLc levels ≤ 70 mg/dL.

Socioeconomic Status and Prognosis of Patients With ST-Elevation Myocardial Infarction Managed by the Emergency-Intervention "Codi IAM" Network.

Background: Despite the spread of ST-elevation myocardial infarction (STEMI) emergency intervention networks, inequalities in healthcare access still have a negative impact on cardiovascular prognosis. The Family Income Ratio of Barcelona (FIRB) is a socioeconomic status (SES) indicator that is annually calculated. Our aim was to evaluate whether SES had an effect on mortality and complications in patients managed by the "Codi IAM" network in Barcelona. Methods: This is a cohort study with 3,322 consecutive patients with STEMI treated in Barcelona from 2010 to 2016. Collected data include treatment delays, clinical and risk factor characteristics, and SES. The patients were assigned to three SES groups according to FIRB score. A logistic regression analysis was conducted to estimate the adjusted effect of SES on 30-day mortality, 30-day composite cardiovascular end point, and 1-year mortality. Results: The mean age of the patients was 65 ± 13% years, 25% were women, and 21% had diabetes mellitus. Patients with low SES were younger, more often hypertensive, diabetic, dyslipidemic (p < 0.003), had longer reperfusion delays (p < 0.03) compared to participants with higher SES. Low SES was not independently associated with 30-day mortality (OR: 0.95;9 5% CI: 0.7-1.3), 30-day cardiovascular composite end point (OR: 1.03; 95% CI: 0.84-1.26), or 1-year all-cause mortality (HR: 1.09; 95% CI: 0.76-1.56). Conclusion: Although the low-SES patients with STEMI in Barcelona city were younger, had worse clinical profiles, and had longer revascularization delays, their 30-day and 1-year outcomes were comparable to those of the higher-SES patients.

Plasmatic PCSK9 Levels Are Associated with Very Fast Progression of Asymptomatic Degenerative Aortic Stenosis.

The aim of this work was to study the association of potential biomarkers with fast aortic stenosis (AS) progression. Patients with moderate-to-severe AS were classified as very fast progressors (VFP) if exhibited an annualized change in peak velocity (aΔVmax) ≥0.45m/s/year and/or in aortic valve area (aΔAVA) ≥-0.2cm2/year. Respective cut-off values of ≥0.3m/s/year and ≥-0.1cm2/year defined fast progressors (FP), whereas the remaining patients were non-fast progressors (non-FP). Baseline markers of lipid metabolism, inflammation, and cardiac overload were determined. Two hundred and nine patients (97 non-FP, 38 FP, and 74 VFP) were included. PCSK9 levels were significantly associated with VFP (OR 1.014 [95%CI 1.005-1.024], for every 10 ng/mL), as were active smoking (OR 3.48) and body mass index (BMI, OR 1.09), with an AUC of 0.704 for the model. PCSK9 levels, active smoking, and BMI were associated with very fast AS progression in our series, suggesting that inflammation and calcification participate in disease progression.

Importance of Tricuspid Regurgitation Velocity Threshold in Risk Assessment of Pulmonary Hypertension-Long-Term Outcome of Patients Submitted to Aortic Valve Replacement.

Background: The upper physiological threshold for tricuspid regurgitation velocity (TRV) of 2.8 m/s proposed by the Pulmonary Hypertension (PH) guidelines had been questioned. The aim of this study was to evaluate the prognostic significance of preoperative PH in patients with aortic stenosis, long-term after valve replacement, using two different TRV thresholds (2.55 and 2.8 m/s). Methods: Four hundred and forty four patients were included (mean age 73 ± 9 years; 55% male), with a median follow-up of 5.8 years (98% completed). Patients were divided into three PH probability groups according to guidelines (low, intermediate and high) for both thresholds (TRV ≤ 2.8 m/s and TRV ≤ 2.55 m/s), using right atrial area>18 cm2 and right ventricle/left ventricle ratio>1 as additional echocardiographic variables. Results: In patients with measurable TRV (n = 304), the low group mortality rate was 25% and 30%, respectively for 2.55 and 2.8 m/s TRV thresholds. The intermediate group with TRV > 2.55 m/s was an independent mortality risk factor (HR 2.04; 95% CI: 1.91 to 3.48, p = 0.01), in contrast to the intermediate group with TRV>2.8 m/s (HR 1.44; 95% CI: 0.89 to 2.32, p = 0.14). Both high probability groups were associated with an increased mortality risk, as compared to their respective low groups. When including all patients (with measurable and non-measurable TRV), both intermediate groups remained independently associated with an increased mortality risk: HR 1.62 (95% CI 1.11 to 2.35 p = 0.01) for the new cut-off point; and HR 1.43 (95% CI: 0.96 to 2.13, p = 0.07) for guidelines threshold. Conclusion: A TRV threshold of 2.55 m/s, together with right cavities measures, allowed a better risk assessment of patients with PH secondary to severe aortic stenosis, with or without tricuspid regurgitation.

Left Atrium Assessment by Speckle Tracking Echocardiography in Cryptogenic Stroke: Seeking Silent Atrial Fibrillation.

Silent atrial fibrillation (AF) may be the cause of some cryptogenic strokes (CrS). The aim of the study was to analyse atrial size and function by speckle tracking echocardiography in CrS patients to detect atrial disease. Patients admitted to the hospital due to CrS were included prospectively. Echocardiogram analysis included left atrial ejection fraction (LAEF) and atrial strain. Insertable cardiac monitor was implanted, and AF was defined as an episode of ≥1 min in the first year after stroke. Left atrial enlargement was defined as indexed volume > 34 mL/m2. Seventy-five consecutive patients were included, aged 76 ± 9 years (arterial hypertension 75%). AF was diagnosed in 49% of cases. The AF group had higher atrial volume and worse atrial function: peak atrial longitudinal strain (PALs) 19.6 ± 5.7% vs. 29.5 ± 7.2%, peak atrial contraction strain (PACs) 8.9 ± 3.9% vs. 16.5 ± 6%, LAEF 46.8 ± 11.5% vs. 60.6 ± 5.2%; p < 0.001. AF was diagnosed in 20 of 53 patients with non-enlarged atrium, and in 18 of them, atrial dysfunction was present. The multivariate logistic regression analysis demonstrated an independent association between detection of AF and atrial volume, LAEF, and strain. Cut-off values were obtained: LAEF < 55%, PALs < 21.4%, and PACs < 12.9%. In conclusion, speckle tracking echocardiography in CrS patients improves silent atrial disease diagnosis, with or without atrial enlargement.

Impact of Preoperative Measurement of Right Heart Chambers in the Evaluation of Pulmonary Hypertension Following Aortic Valve Replacement.

BACKGROUND: Severe pulmonary hypertension (PH) in patients with aortic stenosis is related to poor prognosis following aortic valve replacement (AVR). Current European PH guidelines recommend adding two different echocardiographic signs to tricuspid regurgitation velocity (TRV) in PH estimation, classifying its probability as low (TRV ≤ 2.8 m/s), intermediate (TRV 2.9-3.4 m/s), and high (TRV > 3.4 m/s). The right ventricle is an important determinant of prognosis in PH. The goal of this study was to analyze the value of right atrial area > 18 cm2 and right ventricular/left ventricular ratio > 1 in the long-term prognosis following AVR, mainly in the intermediate probability group. METHODS: This study included 429 consecutive patients (mean age, 73 ± 8 years; 55% male) with a median follow-up of 4.25 years (completed in 98%). Patients were divided into low (n = 247), intermediate (n = 117), and high probability groups (n = 65). The intermediate probability group was divided into two subgroups: subgroup 2a (n = 27; TRV nonmeasurable or ≤ 2.8 m/s and two signs present) and subgroup 2b (n = 90; TRV 2.9-3.4 m/s, and none or only one sign present). RESULTS: Overall mortality rates during follow-up of the low, intermediate, and high probability groups were 24%, 32%, and 42%, respectively. High PH probability was an independent predictor of all-cause mortality (hazard ratio [HR], 1.82; 95% CI, 1.11-3.00), but the intermediate probability group did not reach significance following multivariate analysis (HR, 1.40; 95% CI, 0.91-2.16). When the intermediate probability group was divided into subgroups, the subgroup 2a mortality rate (56%) was higher than that of both subgroup 2b (24%; P = .002) and the low probability group (24%; P < .001). Following multivariate analysis, subgroup 2a showed a significantly higher mortality (HR, 2.13; 95% CI, 1.11-4.10) in contrast to subgroup 2b (HR, 1.24; 95% CI, 0.75-2.05), both compared with the low probability group. CONCLUSIONS: Incorporating measurement of the right cavities into the PH probability model in the assessment of long-term prognosis following AVR allowed better risk discrimination, especially in the intermediate probability group.

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.

Association Between Norepinephrine Levels and Abnormal Iron Status in Patients With Chronic Heart Failure: Is Iron Deficiency More Than a Comorbidity?

Background Mechanisms underlying iron homeostasis dysregulation in patients with chronic heart failure remain unsettled. In cardiomyocyte models, norepinephrine may lead to intracellular iron depletion, but the potential association between catecholamines (sympathetic activation markers) and iron metabolism biomarkers in chronic heart failure is unknown. Methods and Results In this cross-sectional analysis, we studied the association between plasma norepinephrine levels and serum iron status biomarkers indicating iron storage (ferritin), iron transport (transferrin saturation), and iron demand (soluble transferrin receptor) in a prospective cohort of 742 chronic heart failure patients (mean age, 72±11 years; 56% male). Impaired iron status was defined as ferritin <100 µg/L or transferrin saturation <20%. Impaired iron status was observed in 69% of patients. In multivariate models, greater norepinephrine levels were associated with impaired iron transport (transferrin saturation <20%, odds ratio=2.28; 95% CI [1.19-4.35]; P=0.013), but not with impaired iron storage (ferritin <100 µg/L, odds ratio=1.25; 95% CI [0.73-2.16]; P=0.415). Norepinephrine was a significant predictor of increased iron demand (soluble transferrin receptor, standardized ß-coefficient=0.12; P=0.006) and low transferrin saturation (standardized ß-coefficient=-0.12; P=0.003). However, norepinephrine levels were not associated with iron or ferritin levels ( P>0.05). Adjusted norepinephrine marginal means were significantly higher in patients with impaired iron status compared with those with normal iron status (528 pg/mL [505-551] versus 482 pg/mL [448-518], respectively; P=0.038). Conclusions In chronic heart failure patients, increased sympathetic activation estimated with norepinephrine levels is associated with impaired iron status and, particularly, dysregulation of biomarkers suggesting impaired iron transport and increased iron demand. Whether the relationship between norepinephrine and iron metabolism is bidirectional and entails causality need to be elucidated in future research.

Current misconceptions in diagnosis and management of iron deficiency.

The prevention and treatment of iron deficiency is a major public health goal. Challenges in the treatment of iron deficiency include finding and addressing the underlying cause and the selection of an iron replacement product which meets the needs of the patient. However, there are a number of non-evidence-based misconceptions regarding the diagnosis and management of iron deficiency, with or without anaemia, as well as inconsistency of terminology and lack of clear guidance on clinical pathways. In particular, the pathogenesis of iron deficiency is still frequently not addressed and iron not replaced, with indiscriminate red cell transfusion used as a default therapy. In our experience, this imprudent practice continues to be endorsed by non-evidence-based misconceptions. The intent of the authors is to provide a consensus that effectively challenges these misconceptions, and to highlight evidence-based alternatives for appropriate management (referred to as key points). We believe that this approach to the management of iron deficiency may be beneficial for both patients and healthcare systems. We stress that this paper solely presents the Authors' independent opinions. No pharmaceutical company funded or influenced the conception, development or writing of the manuscript.

Iron Deficiency Is a Determinant of Functional Capacity and Health-related Quality of Life 30 Days After an Acute Coronary Syndrome.

BACKGROUND AND OBJECTIVES: Iron deficiency (ID) is a prevalent condition in patients with ischemic heart disease and heart failure. Little is known about the impact of ID on exercise capacity and quality of life (QoL) in the recovery phase after an acute coronary syndrome (ACS). METHODS: Iron status and its impact on exercise capacity and QoL were prospectively evaluated in 244 patients 30 days after the ACS. QoL was assessed by the standard EuroQoL-5 dimensions, EuroQoL visual analogue scale, and Heart-QoL questionnaires. Exercise capacity was analyzed by treadmill/6-minute walk tests. The effect of ID on cardiovascular mortality and readmission rate was also investigated. RESULTS: A total of 46% of the patients had ID. These patients had lower exercise times (366±162 vs 462±155seconds; P<.001), metabolic consumption rates (7.9±2.9 vs 9.3±2.6 METS; P=.003), and EuroQoL-5 dimensions (0.76±0.25 vs 0.84±0.16), visual analogue scale (66±16 vs 72±17), and Heart-QoL (1.9±0.6 vs 2.2±0.6) scores (P<.05). ID independently predicted lower exercise times (OR, 2.9; 95%CI, 1.1-7.6; P=.023) and worse QoL (OR, 1.9; 95%CI, 1.1-3.3; P<.001) but had no effect on cardiovascular morbidity or mortality. CONCLUSIONS: ID, a prevalent condition in ACS patients, results in a poorer mid-term functional recovery, as measured by exercise capacity and QoL.

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.

Iron Status in Chronic Heart Failure: Impact on Symptoms, Functional Class and Submaximal Exercise Capacity.

INTRODUCTION AND OBJECTIVES: To evaluate the effect of iron deficiency and anemia on submaximal exercise capacity in patients with chronic heart failure. METHODS: We undertook a single-center cross-sectional study in a group of stable patients with chronic heart failure. At recruitment, patients provided baseline information and completed a 6-minute walk test to evaluate submaximal exercise capacity and exercise-induced symptoms. At the same time, blood samples were taken for serological evaluation. Iron deficiency was defined as ferritin < 100 ng/mL or transferrin saturation < 20% when ferritin is < 800 ng/mL. Additional markers of iron status were also measured. RESULTS: A total of 538 heart failure patients were eligible for inclusion, with an average age of 71 years and 33% were in New York Heart Association class III/IV. The mean distance walked in the test was 285 ± 101 meters among those with impaired iron status, vs 322 ± 113 meters (P=.002). Symptoms during the test were more frequent in iron deficiency patients (35% vs 27%; P=.028) and the most common symptom reported was fatigue. Multivariate logistic regression analyses showed that increased levels of soluble transferrin receptor indicating abnormal iron status were independently associated with advanced New York Heart Association class (P < .05). Multivariable analysis using generalized additive models, soluble transferrin receptor and ferritin index, both biomarkers measuring iron status, showed a significant, independent and linear association with submaximal exercise capacity (P=.03 for both). In contrast, hemoglobin levels were not significantly associated with 6-minute walk test distance in the multivariable analysis. CONCLUSIONS: In patients with chronic heart failure, iron deficiency but not anemia was associated with impaired submaximal exercise capacity and symptomatic functional limitation.

Efficacy of an integrated hospital-primary care program for heart failure: a population-based analysis of 56,742 patients.

INTRODUCTION AND OBJECTIVES: The efficacy of heart failure programs has been demonstrated in clinical trials but their applicability in the real world practice setting is more controversial. This study evaluates the feasibility and efficacy of an integrated hospital-primary care program for the management of patients with heart failure in an integrated health area covering a population of 309,345. METHODS: For the analysis, we included all patients consecutively admitted with heart failure as the principal diagnosis who had been discharged alive from all of the hospitals in Catalonia, Spain, from 2005 to 2011, the period when the program was implemented, and compared mortality and readmissions among patients exposed to the program with the rates in the patients of all the remaining integrated health areas of the Servei Català de la Salut (Catalan Health Service). RESULTS: We included 56,742 patients in the study. There were 181,204 hospital admissions and 30,712 deaths during the study period. In the adjusted analyses, when compared to the 54,659 patients from the other health areas, the 2083 patients exposed to the program had a lower risk of death (hazard ratio=0.92 [95% confidence interval, 0.86-0.97]; P=.005), a lower risk of clinically-related readmission (hazard ratio=0.71 [95% confidence interval, 0.66-0.76]; P<.001), and a lower risk of readmission for heart failure (hazard ratio=0.86 [95% confidence interval, 0.80-0.94]; P<.001). The positive impact on the morbidity and mortality rates was more marked once the program had become well established. CONCLUSIONS: The implementation of multidisciplinary heart failure management programs that integrate the hospital and the community is feasible and is associated with a significant reduction in patient morbidity and mortality.

Iron deficiency and health-related quality of life in chronic heart failure: results from a multicenter European study.

Patients affected by chronic heart failure (CHF) present significant impairment of health-related quality of life (HRQoL). Iron deficiency (ID) is a common comorbidity in CHF with negative impact in prognosis and functional capacity. The role of iron in energy metabolism could be the link between ID and HRQoL. There is little information about the role of ID on HRQoL in patients with CHF. We evaluate the impact of ID on HRQoL and the interaction with the anaemia status, iron status, clinical baseline information and HRQoL, measured with the Minnesota Living with Heart Failure questionnaire (MLHFQ) was obtained at baseline in an international cohort of 1278 patients with CHF. Baseline characteristics were median age 68 ± 12, 882 (69%) were males, ejection fraction was 38% ± 15 and NYHA class was I/II/III/IV (156/247/487/66). ID (defined as ferritin level< 100 µg/L or serum ferritin 100-299 µg/L in combination with a TSAT<20%) was present in 741 patients (58%). 449 (35%) patients were anaemic. Unadjusted global scores of MLHFQ (where higher scores reflect worse HRQoL) were worse in ID and anaemic patients (ID+: 42 ± 25 vs. ID-: 37 ± 25; p-value=0.001 and A+: 46 ± 25 vs. A-: 37 ± 25; p-value<0.001). The combined influence of ID and anaemia was explored with different multivariable regression models, showing that ID but not anaemia was associated with impaired HRQoL. ID has a negative impact on HRQoL in CHF patients, and this is independent of the presence of anaemia.

Iron deficiency is a key determinant of health-related quality of life in patients with chronic heart failure regardless of anaemia status.

AIMS: To evaluate the effect of iron deficiency (ID) and/or anaemia on health-related quality of life (HRQoL) in patients with chronic heart failure (CHF). METHODS AND RESULTS: We undertook a post-hoc analysis of a cohort of CHF patients in a single-centre study evaluating cognitive function. At recruitment, patients provided baseline information and completed the Minnesota Living with Heart Failure questionnaire (MLHFQ) for HRQoL (higher scores reflect worse HRQoL). At the same time, blood samples were taken for serological evaluation. ID was defined as serum ferritin levels <100 ng/mL or serum ferritin <800 ng/mL with transferrin saturation <20%. Anaemia was defined as haemoglobin ≤12 g/dL. A total of 552 CHF patients were eligible for inclusion, with an average age of 72 years and 40% in NYHA class III or IV. The MLHFQ overall summary scores were 41.0 ± 24.7 among those with ID, vs. 34.4 ± 26.4 for non-ID patients (P = 0.003), indicating worse HRQoL. When adjusted for other factors associated with HRQoL, ID was significantly associated with worse MLHFQ overall summary (P = 0.008) and physical dimension scores (P = 0.002), whereas anaemia was not (both P > 0.05). Increased levels of soluble transferrin receptor were also associated with impaired HRQoL (P ≤ 0.001). Adjusting for haemoglobin and C-reactive protein, ID was more pronounced in patients with anaemia compared with those without (P < 0.001). CONCLUSION: In patients with CHF, ID but not anaemia was associated with reduced HRQoL, mostly due to physical factors.

Effects of preoperative intravenous erythropoietin plus iron on outcome in anemic patients after cardiac valve replacement.

Preoperative anemia is a risk factor for postoperative morbidity and in-hospital mortality in cardiac surgery. However, it is not known whether treatment of anemia before cardiac surgery by administering recombinant human erythropoietin (rhEPO) plus iron improves postoperative outcomes and decreases red blood cell transfusions in these patients. In 1998 a collection of consecutive data for patients who underwent valve replacement was initiated and the inclusion criterion was anemia. Treatment with rhEPO was given at a dose of 500 IU/kg/day every week for 4 weeks and the fifth dose 48 hours before valve replacement. During each rhEPO session, patients received intravenous iron sucrose supplementation. The intervention cohort (2006 to 2011) included 75 patients and the observation cohort was composed of 59 patients who did not receive any treatment (1998 to 2005). Multivariable logistic regression analysis showed that administration of combined therapy was independently associated with decreased postoperative morbidity (odds ratio [OR] 0.13, 95% confidence interval [CI] 0.03 to 0.59 p = 0.008) and in-hospital mortality (OR 0.16, 95% CI 0.28 to 0.95 p = 0.04) after adjusting for logistic European System for Cardiac Operative Risk Evaluation score, type of intervention, time of cardiopulmonary bypass, and year of surgery. Individually, this treatment also decreased postoperative renal failure (OR 0.23, 95% CI 0.06 to 0.88, p = 0.03). Rate of red blood cell transfusion decreased from 93% in the observation cohort to 67% in the intervention cohort as did days of hospitalization (median, 15 days, 10 to 27, versus 10 days, 8 to 14, respectively, p = 0.01 for all comparisons). In conclusion, administration of intravenous rhEPO plus iron in anemic patients before valve replacement improves postoperative survival, decreases blood transfusions, and shortens hospitalization.

In-hospital acquired anemia in acute coronary syndrome. Predictors, in-hospital prognosis and one-year mortality.

INTRODUCTION AND OBJECTIVES: Anemia at hospital admission predicts a poor outcome in patients presenting with acute coronary syndrome. It remains unclear whether in-hospital hemoglobin levels decrease (nosocomial anemia) not related to bleeding also implies a poor prognosis. We aimed to identify predictors of nosocomial anemia and its prognostic significance. METHODS: We prospectively included 221 acute coronary syndrome patients admitted in our institution during the years 2009-2010, with normal hemoglobin levels at admission. Nosocomial anemia was defined as a decrease in hemoglobin levels to <13 g/dL in men and <12 g/dL in women in the absence of apparent bleeding. Clinical variables and hematological inflammatory parameters were assessed in order to identify predictors for the development of nosocomial anemia. We compared the clinical outcome after a 1-year follow-up period of patients without anemia as opposed to those who developed nosocomial anemia. RESULTS: Nosocomial anemia was registered in 25% of study patients. A >3.1 mg/dL value of C-reactive protein was highly predictive of developing nosocomial anemia (odds ratio=5.9; 95% confidence interval, 2.6-13.4; P<.001). The incidence of mortality and cardio-vascular morbidity was higher in the patients who developed nosocomial anemia (34.5% vs 9%; P<.001). Nosocomial anemia was a strong predictor of cardio-vascular morbidity and mortality in the long-term follow-up (hazard ratio=2.47; 95% confidence interval, 1.23-4.96; P=.01). CONCLUSIONS: Nosocomial anemia predicts a poorer outcome in patients with acute coronary syndrome. Increased C-reactive protein levels, indicating inflammatory state, are predictive of developing in-hospital anemia unrelated to apparent bleeding.

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.

Long-term mortality predictors in patients with chronic bifascicular block.

AIMS: To evaluate the long-term mortality rate and to determine independent mortality risk factors in patients with bifascicular block (BFB). Patients with BFB are known to have a higher mortality risk than the general population, not only related to progression to atrio-ventricular block but also due to the presence of malignant ventricular arrhythmias. Previous observational and epidemiological studies including a high proportion of patients with structural heart disease have shown an important cardiac mortality rate and may not reflect the real outcome of patients with BFB. METHODS AND RESULTS: From March 1998 until December 2006, we prospectively studied 259 consecutive BFB patients, 213 (82%) of whom presenting with syncope/pre-syncope, undergoing electrophysiological study. After a median follow-up of 4.5 years (P25:2.16-P75:6.41), 53 patients (20.1%) died, 19 (7%) of whom due to cardiac aetiology. Independent total mortality predictors were age [hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.01-1.09], NYHA class>or=II (HR 2.17, 95% CI 1.05-4.5), atrial fibrillation (HR 2.96, 95% CI 1.1-7.92), and renal dysfunction (HR 4.26, 95% CI 2.04-9.01). An NYHA class of >or=II (HR 5.45, 95% CI 2.01-14.82) and renal failure (HR 3.82, 95% CI 1.21-12.06) were independent predictors of cardiac mortality. No independent predictors of arrhythmic death were found. CONCLUSION: Total mortality, especially of cardiac cause, is lower than previously described in BFB patients. Advanced NYHA class and renal failure are predictors of cardiac mortality.