Direct Link Between Cardiac Failure and Global Cerebral Atrophy in a Young Adult: A Case Report on Reduced Cerebral Artery Blood Flow.

BACKGROUND Heart failure is associated with structural brain abnormalities, including atrophy of multiple brain regions. Previous studies have reported brain atrophy in middle-aged patients with systolic heart failure. In this report, we present the case of a 21-year-old woman with idiopathic dilated cardiomyopathy, cardiac failure, and global cerebral atrophy due to reduced cerebral artery blood flow. We also discuss the impact of brain atrophy in this young adult patient with severe heart failure and no risk factors for atherosclerosis. CASE REPORT A 21-year-old woman with dyspnea and leg edema was admitted to our hospital. After several examinations, an endomyocardial biopsy led to a diagnosis of idiopathic dilated cardiomyopathy, and transthoracic ultrasound cardiography revealed that her left ventricular ejection fraction was 36%. One year after the first hospitalization, her heart failure was classified as New York Heart Association Class III. Magnetic resonance imaging showed severe global brain atrophy, and single-photon emission computed tomography combined with brain computed tomography showed reduced blood flow to the entire brain. She had no risk factors for atherosclerosis and no atherosclerotic changes to her brain or carotid arteries, but her neuropsychological and neurological findings indicated more pronounced brain and cognitive dysfunction. CONCLUSIONS This young adult patient with idiopathic dilated cardiomyopathy, cardiac failure, and global cerebral atrophy showed reduced cerebral artery blood flow and cognitive impairment. The findings of this report indicate that low cardiac output may directly cause brain atrophy in patients with systolic heart failure.

VEGF-B hypertrophy predisposes to transition from diastolic to systolic heart failure in hypertensive rats.

AIMS: Cardiac energy metabolism is centrally involved in heart failure (HF), although the direction of the metabolic alterations is complex and likely dependent on the particular stage of HF progression. Vascular endothelial growth factor B (VEGF-B) has been shown to modulate metabolic processes and to induce physiological cardiac hypertrophy; thus, it could be cardioprotective in the failing myocardium. This study investigates the role of VEGF-B in cardiac proteomic and metabolic adaptation in HF during aldosterone and high-salt hypertensive challenges. METHODS AND RESULTS: Male rats overexpressing the cardiac-specific VEGF-B transgene (VEGF-B TG) were treated for 3 or 6 weeks with deoxycorticosterone-acetate combined with a high-salt (HS) diet (DOCA + HS) to induce hypertension and cardiac damage. Extensive longitudinal echocardiographic studies of HF progression were conducted, starting at baseline. Sham-treated rats served as controls. To evaluate the metabolic alterations associated with HF, cardiac proteomics by mass spectrometry was performed. Hypertrophic non-treated VEGF-B TG hearts demonstrated high oxygen and adenosine triphosphate (ATP) demand with early onset of diastolic dysfunction. Administration of DOCA + HS to VEGF-B TG rats for 6 weeks amplified the progression from cardiac hypertrophy to HF, with a drastic drop in heart ATP concentration. Dobutamine stress echocardiographic analyses uncovered a significantly impaired systolic reserve. Mechanistically, the hallmark of the failing TG heart was an abnormal energy metabolism with decreased mitochondrial ATP, preceding the attenuated cardiac performance and leading to systolic HF. CONCLUSIONS: This study shows that the VEGF-B TG accelerates metabolic maladaptation which precedes structural cardiomyopathy in experimental hypertension and ultimately leads to systolic HF.

Poor efficacy of oral iron replacement therapy in pediatric patients with heart failure.

INTRODUCTION: Iron deficiency is associated with worse outcomes in children and adults with systolic heart failure. While oral iron replacement has been shown to be ineffective in adults with heart failure, its efficacy in children with heart failure is unknown. We hypothesised that oral iron would be ineffective in replenishing iron stores in ≥50% of children with heart failure. METHODS: We performed a single-centre retrospective cohort study of patients aged ≤21 years with systolic heart failure and iron deficiency who received oral iron between 01/2013 and 04/2019. Iron deficiency was defined as ≥2 of the following: serum iron <50 mcg/dL, serum ferritin <20 ng/mL, transferrin >300 ng/mL, transferrin saturation <15%. Iron studies and haematologic indices pre- and post-iron therapy were compared using paired-samples Wilcoxon test. RESULTS: Fifty-one children with systolic heart failure and iron deficiency (median age 11 years, 49% female) met inclusion criteria. Heart failure aetiologies included cardiomyopathy (51%), congenital heart disease (37%), and history of heart transplantation with graft dysfunction (12%). Median dose of oral iron therapy was 2.9 mg/kg/day of elemental iron, prescribed for a median duration of 96 days. Follow-up iron testing was available for 20 patients, of whom 55% (11/20) remained iron deficient despite oral iron therapy. CONCLUSIONS: This is the first report on the efficacy of oral iron therapy in children with heart failure. Over half of the children with heart failure did not respond to oral iron and remained iron deficient.

Left ventricular dimensions and cardiovascular outcomes in systolic heart failure: the WARCEF trial.

AIMS: There is limited information on the association between left ventricular (LV) dimensions and cardiovascular (CV) outcomes in patients with heart failure (HF) with reduced LV ejection fraction (HFrEF) receiving recommended HF treatment. We investigated the association between LV dimensions and CV outcomes in HFrEF patients receiving recommended HF treatment. METHODS AND RESULTS: We investigated the association between LV echocardiographic dimensions and CV outcomes using conventional Cox models in 1138 HFrEF patients in sinus rhythm randomized to warfarin or aspirin treatment in the Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. LV enlargement, whether by diameter [LV end-diastolic diameter index (LVEDDI) and LV end-systolic diameter index (LVESDI)] or volume [LV end-diastolic volume index (LVEDVI) and LV end-systolic volume index (LVESVI)], was independently associated with all-cause death [LVEDDI: hazard ratio (HR) per cm/m2 1.53, LVESDI: HR per cm/m2 1.65, LVEDVI: HR per 10 mL/m2 1.07, and LVESVI: HR per 10 mL/m2 1.10; all P values < 0.001], CV death (HR 1.68, 1.79, 1.09, and 1.12, respectively; all P values < 0.001), and HF hospitalization (HR 1.59, 1.79, 1.06, and 1.08, respectively; all P values < 0.001). No association was observed with myocardial infarction or stroke. The associations were independent of LV ejection fraction values, and incremental to them. LV volumes conferred additional predictive value over LV diameters. CONCLUSIONS: Left ventricular enlargement is an independent predictor of CV events in patients with HFrEF and recommended HF treatment. LV dimensions should be considered in the risk assessment.

Reciprocal organ interactions during heart failure: a position paper from the ESC Working Group on Myocardial Function.

Heart failure-either with reduced or preserved ejection fraction (HFrEF/HFpEF)-is a clinical syndrome of multifactorial and gender-dependent aetiology, indicating the insufficiency of the heart to pump blood adequately to maintain blood flow to meet the body's needs. Typical symptoms commonly include shortness of breath, excessive fatigue with impaired exercise capacity, and peripheral oedema, thereby alluding to the fact that heart failure is a syndrome that affects multiple organ systems. Patients suffering from progressed heart failure have a very limited life expectancy, lower than that of numerous cancer types. In this position paper, we provide an overview regarding interactions between the heart and other organ systems, the clinical evidence, underlying mechanisms, potential available or yet-to-establish animal models to study such interactions and finally discuss potential new drug interventions to be developed in the future. Our working group suggests that more experimental research is required to understand the individual molecular mechanisms underlying heart failure and reinforces the urgency for tailored therapeutic interventions that target not only the heart but also other related affected organ systems to effectively treat heart failure as a clinical syndrome that affects and involves multiple organs.

Evaluation of the C2HEST Risk Score as a Possible Opportunistic Screening Tool for Incident Atrial Fibrillation in a Healthy Population (From a Nationwide Danish Cohort Study).

A simple clinical score, C2HEST (C2: CAD/COPD [1 point each]; H: Hypertension; E: Elderly [Age ≥75, doubled]; S: Systolic HF [doubled]; T: Thyroid disease [hyperthyroidism]) has been proposed to predict incident atrial fibrillation (AF), with good discrimination and internal calibration. To define high-risk patients at particular age strata for incident AF in a nationwide population cohort, who could potentially be targeted for AF screening, we used a nationwide cohort study of all Danish citizen aged ≥65 years to evaluate the performance of the C2HEST score. "High risk" subjects at age 65, 70, and 75 had 5-year risks of new onset AF of 11.8%, 14.2% and 13.6%, respectively, and the corresponding event rates were 2.99, 3.67, and 3.38 per 100 person years, respectively. Associated hazard ratios (HR) were 4.08 (95% confidence interval [CI] 3.84 to 4.34), 3.80 (95% CI: 3.68 to 3.92) and 2.17 (95% CI: 2.13 to 2.22), respectively compared with the lowest risk strata within age category. At all age cohorts, the greatest risk component of the C2HEST score on multivariable analysis was by having 2 points for C (C2), that is both CAD and COPD followed by systolic heart failure (S) both with HRs up to 2.0. CAD or COPD alone (C1) or hypertension (H) were associated with increased risk of new onset AF corresponding to HR between 1.44 and 1.64. In conclusion, this nationwide population cohort addresses the question on clinical risk prediction for new onset AF in a population at different age strata, whereby the C2HEST score may help in identifying those at 'high risk' of new onset AF at 3 distinct age cohorts (65, 70, and 75 years). A high risk C2HEST score stratum was associated with a greater risk of new onset AF. These patients could be considered for more intensive efforts for screening and detection of incident AF.

Prevalence of cardiac amyloidosis among elderly patients with systolic heart failure or conduction disorders.

Objective: Cardiac amyloid infiltration can lead to systolic heart failure (HF) or to conduction disorders (CD). Patients with transthyretin (ATTR) amyloidosis are particularly exposed. We sought to determine the prevalence of ATTR and AL among patients >60 years admitted with CD or unexplained systolic HF and increased wall thickness. Materials and Methods: We studied 143 patients (57% males, 79 ± 9 years) with HF (N = 28) or CD requiring pacemaker implantation (N = 115). In total, 139 (97%) patients (28 with HF and 111 with CD) underwent 99mTc-DPD scintigraphy to detect ATTR, and 105 (73%; 19 HF and 86 CD) underwent AL screening. Results: Five patients (4%; 95%CI:0-7%) exhibited wild-type ATTR (ATTRwt) amyloidosis, 2 (2%; 95%CI:0-4%) had CD and 3 (11%; 95%CI:0-23%) HF. No patient showed AL. The 2 ATTRwt patients with CD were previously asymptomatic, did not show classical ECG signs and exhibited mild LV hypertrophy with preserved LVEF. By contrast, all ATTRwt patients with HF had ECG and echocardiographic signs of amyloid. During a mean follow-up of 18 ± 11 months, 3(60%) patients with ATTRwt amyloidosis (1 CD and 2 HF) and 14(10.4%) without died. Conclusion: Prevalence of ATTRwt amyloidosis in patients with CD requiring pacemaker is low. Although, additional studies are needed, prevalence seems to be higher in elderly patients with systolic HF.

T cell and monocyte/macrophage activation markers associate with adverse outcome, but give limited prognostic value in anemic patients with heart failure: results from RED-HF.

BACKGROUND: Activated leukocytes may contribute to the development and progression of heart failure (HF). We investigated the predictive value of circulating levels of stable and readily detectable markers reflecting both monocyte/macrophage and T-cell activity, on clinical outcomes in HF patients with reduced ejection fraction (HFrEF). METHODS: The association between baseline plasma levels of soluble CD163 (sCD163), macrophage migration inhibitory factor (MIF), granulysin, soluble interleukin-2 receptor (sIL-2R), and activated leukocyte cell adhesion molecule (ALCAM) and the primary endpoint of death from any cause or first hospitalization for worsening of HF was evaluated using multivariable Cox proportional hazard models in 1541 patients with systolic HF and mild to moderate anemia, enrolled in the Reduction of Events by darbepoetin alfa in Heart Failure (RED-HF) trial. Modifying effects and interaction with darbepoetin alfa treatment were also assessed. RESULTS: All leukocyte markers, except granulysin, were associated with the primary outcome and all-cause death in univariate analysis (all p < 0.01) and remained significantly associated in multivariable analysis adjusting for conventional clinical variables (e.g. age, gender, BMI, NYHA class, creatinine, LVEF, etiology) and CRP. However, after final adjustment for TnT and NT-proBNP no associations were found with outcomes. No interaction with darbepoetin alpha treatment was observed for any marker. CONCLUSIONS: Leukocyte activation markers sCD163, MIF, sIL-2R, and ALCAM were associated with adverse outcome in patients with HFrEF, but add little as prognostic markers on top of established biochemical risk markers. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00358215 .

Myocardial perfusion during atrial fibrillation in patients with non-ischaemic systolic heart failure: a cross-sectional study using Rubidium-82 positron emission tomography/computed tomography.

Aims: Patients with non-ischaemic systolic heart failure often have reduced myocardial blood flow without significant coronary atherosclerosis. Likewise, patients with atrial fibrillation (AF) have reduced myocardial perfusion during AF compared with sinus rhythm. The aim of this study was to explore whether there is an additive negative effect of AF during scan on the myocardial perfusion in patients with non-ischaemic systolic heart failure. Methods and results: We included 27 young healthy controls and 114 patients with non-ischaemic systolic heart failure to a Rubidium-82 positron emission tomography/computed tomography perfusion scan (23 with AF during scan). To obtain the myocardial flow reserve (MFR = stress flow/rest flow), patients were scanned at rest and during adenosine-induced stress. Among patients, those with AF were older [years: 73; interquartile range (IQR) 65-78 vs. 67; IQR 60-74; P = 0.03] and more were men (87% vs. 62%; P = 0.02). Distribution of sex in controls did not differ from either patient group. Patients with AF had significantly lower MFR than patients without [MFR: 1.87; 95% confidence interval (CI) 1.58-2.22 vs. 2.50; 95% CI 2.06-2.86; percent difference: -21.5%; P = 0.01]. MFR remained significantly lower in the group with AF (estimate -24.2%; 95% CI -39.6% to -4.8%; P = 0.02) in an adjusted multivariable regression analysis. Further, patients had lower MFR compared with controls: 3.46; 95% CI 3.03-3.94; P < 0.0001. Additionally, coronary vascular resistance was highest in patients with AF and lowest in controls. Conclusion: Patients with systolic heart failure had lower flow reserve than healthy controls and even lower MFR if they had AF during scan.

Daily non-invasive haemodynamic telemonitoring for efficacy evaluation of MitraClip® implantation in patients with advanced systolic heart failure.

AIM: Patients with advanced systolic chronic heart failure frequently suffer from progressive functional mitral regurgitation. We report our initial experience in patients with an implanted pulmonary artery pressure (PAP) sensor, who developed severe mitral regurgitation, which was treated with the MitraClip system. We non-invasively compared changes in PAP values in patients after MitraClip with PAP changes in patients without MitraClip. METHODS AND RESULTS: Among 28 patients with New York Heart Association III heart failure with implanted PAP sensor for haemodynamic telemonitoring from a single centre, four patients (age 66 ± 6 years, left ventricular ejection fraction 21 ± 3%, and cardiac index 1.8 ± 0.3) received a MitraClip procedure and were compared with 24 patients (age 72 ± 8 years, left ventricular ejection fraction 26 ± 9.9%, and cardiac index 2.0 ± 1.0) without MitraClip procedure in a descriptive manner. Ambulatory PAP values were followed for 90 days in both groups. In comparison with the PAP values 4 weeks before MitraClip procedure, PAP was profoundly reduced in all four patients after 30 days (ΔPAPmean -11 ± 5, ΔPAPdiast -7 ± 3 mmHg, P < 0.02) as well as after 90 days (ΔPAPmean -6.3 ± 6, ΔPAPdiast -1 ± 3 mmHg). Reductions in PAP were accompanied by a profound reduction in N terminal pro brain natriuretic peptide as well as clinical and echocardiographic improvement. When analysing the dynamics with a regression model, reductions in all PAP values were significantly greater after MitraClip compared with conservative haemodynamic monitoring (P < 0.001). CONCLUSIONS: The efficacy of the interventional MitraClip procedure on clinical symptoms can be confirmed by haemodynamic telemonitoring. Thus, daily non-invasive haemodynamic telemonitoring allows, for the first time, for a continuous assessment of the haemodynamic efficacy of novel therapies in patients with chronic heart failure.

Hyporesponsiveness to Darbepoetin Alfa in Patients With Heart Failure and Anemia in the RED-HF Study (Reduction of Events by Darbepoetin Alfa in Heart Failure): Clinical and Prognostic Associations.

BACKGROUND: A poor response to erythropoiesis-stimulating agents such as darbepoetin alfa has been associated with adverse outcomes in patients with diabetes mellitus, chronic kidney disease, and anemia; whether this is also true in heart failure is unclear. METHODS AND RESULTS: We performed a post hoc analysis of the RED-HF trial (Reduction of Events by Darbepoetin Alfa in Heart Failure), in which 1008 patients with systolic heart failure and anemia (hemoglobin level, 9.0-12.0 g/dL) were randomized to darbepoetin alfa. We examined the relationship between the hematopoietic response to darbepoetin alfa and the incidence of all-cause death or first heart failure hospitalization during a follow-up of 28 months. For the purposes of the present study, patients in the lowest quartile of hemoglobin change after 4 weeks were considered nonresponders. The median initial hemoglobin change in nonresponders (n=252) was -0.25 g/dL and +1.00 g/dL in the remainder of patients (n=756). Worse renal function, lower sodium levels, and less use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were independently associated with nonresponse. Although a low endogenous erythropoietin level helped to differentiate responders from nonresponders, its predictive value in a multivariable model was poor (C statistic=0.69). Nonresponders had a higher rate of all-cause death or first heart failure hospitalization (hazard ratio, 1.25; 95% confidence interval, 1.02-1.54) and a higher risk of all-cause mortality (hazard ratio, 1.30; 95% confidence interval, 1.04-1.63) than responders. CONCLUSIONS: A poor response to darbepoetin alfa was associated with worse outcomes in heart failure patients with anemia. Patients with a poor response were difficult to identify using clinical and biochemical biomarkers. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00358215.

Myocardial perfusion in patients with non-ischaemic systolic heart failure and type 2 diabetes: a cross-sectional study using Rubidium-82 PET/CT.

Both patients with non-ischaemic systolic heart failure and patients with type 2 diabetes (T2DM) often have reduced myocardial blood flow without significant coronary atherosclerosis. However, the mechanisms are not fully understood. The aim of this study was to investigate whether perfusion is reduced additionally when the 2 are combined. In a cross-sectional study, we scanned patients with non-ischaemic systolic heart failure with and without T2DM using Rubidium-82 positron emission tomography/computed tomography at rest and adenosine-induced stress, thereby obtaining the myocardial flow reserve (myocardial flow reserve (MFR) = stress flow/rest flow) as a measure of the myocardial vasomotor function; 28 patients with T2DM and 123 without T2DM were included. All patients received heart failure treatment according to guidelines. Multiple regression analysis was performed to assess the association between T2DM and MFR. Age [68 (60-75) years vs. 68 (62-72) years; P = 0.84] and female sex (21% vs. 33%; P = 0.26) were similar between patients with and without T2DM. Patients with T2DM had higher body mass index, (29.9 vs. 26.5 kg/m2; P = 0.02), higher blood glucose (6.2 vs. 5.7 mmol/L; P = 0.03), more often hypertension (50 vs. 27%; P = 0.02) and received more cholesterol lowering medication (61 vs. 35%; P = 0.02). Apart from this, the groups were similar. In a multivariable analysis, MFR was 16% lower in patients with T2DM compared with patients without [estimate - 16%; 95% confidence interval (CI) - 29 to - 0.7%; P = 0.04]. Patients with T2DM and systolic heart failure have lower myocardial flow reserve compared with heart failure patients without T2DM.

Influence of renal impairment on aldosterone status, calcium metabolism, and vasopressin activity in outpatients with systolic heart failure.

AIMS: Renal dysfunction (RD) is associated with increased morbidity and mortality in heart failure (HF). At present, no specific treatment for patients with RD, to prevent progression of HF, has been developed. How different hormone axes-and thereby potential treatment options-are affected by RD in HF warrants further investigations. METHODS AND RESULTS: Patients with left ventricular ejection fraction (LVEF) <0.45% were enrolled prospectively from an outpatient HF clinic. Glomerular filtration rate was estimated by the Chronic Kidney Disease Epidemiology Collaboration equation (eGFR), and patients were grouped by eGFR: eGFR group I, ≥90 mL/min/1.73 m2 ; eGFR group II, 60-89 mL/min/1.73 m2 ; and eGFR group III, ≤59 mL/min/1.73 m2 . Multivariate linear regression models were developed to evaluate the associations between eGFR groups and hormones. A total of 149 patients participated in the study. Median age was 69 [interquartile range (IQR): 64-73] and 26% were female; LVEF was 33% (IQR: 27-39), 78% were in functional class II-III, median eGFR was 74 (54-89) mL/min/1.73 m2 , and median N-terminal pro-brain natriuretic peptide was 1303 pg/mL (IQR: 441-2740). RD was associated with increased aldosterone, parathyroid hormone (PTH), and copeptin concentrations (P < 0.05 for all) after adjustment for traditional confounders and medical treatment. CONCLUSIONS: RD is associated with increased concentrations of aldosterone, PTH, and copeptin in systolic HF outpatients. Our results underscore the importance of treatment with mineralocorticoid receptor antagonist in systolic HF in particular in patients with RD and suggest that vasopressin and parathyroid receptor antagonism are potential treatment options in HF patients with known RD.

Mortality prediction using CHADS2/CHA2DS2-VASc/R2CHADS2 scores in systolic heart failure patients with or without atrial fibrillation.

The CHADS2, CHA2DS2-VASc, and R2CHADS2 scores are well-known predictors of stroke caused by atrial fibrillation (AF), but no studies have evaluated their use for stratifying all-cause mortality risk in patients discharged for systolic heart failure (SHF) with or without AF.This study analyzed data in the Taiwan Society of Cardiology-heart failure with reduced ejection fraction (TSOC-HFrEF) registry. These data were obtained by a prospective, multicenter, observational survey of patients treated at 21 medical centers in Taiwan after hospitalization for acute, pre-existing or new onset SHF from May, 2013 to October, 2014. During 1 year follow-up, 198 patients were lost follow-up, and final 1311 (86.8%) patients were included for further analysis. During the follow-up period, 250 (19%) patients died. Multivariate analysis revealed that body mass index, thyroid disorder, valvular surgery history, chronic kidney disease (CKD), and scores for CHADS2, CHA2DS2-VASc, and R2CHADS2 were significant independent predictors of mortality in the overall population of SHF patients (all P < .05) The c-indexes showed that CHADS2, CHA2DS2-VASc, and R2CHADS2 scores were significantly associated with mortality in SHF patients with or without AF (all P < 005). However, R2CHADS2 had significantly higher accuracy in predicting mortality in all SHF patients compared with CHADS2 and CHA2DS2-VASc (DeLong test, P < .0001), especially in SHF without AF (DeLong test, P = .0003).Scores for CHADS2, CHA2DS2-VASc, and R2CHADS2 can be used to predict 1-year all-cause mortality in SHF patients with or without AF. For predicting all-cause mortality in SHF patients, R2CHADS2 is more accurate than CHADS2 and CHA2DS2-VASc.

Prevalence of airflow obstruction in patients with stable systolic heart failure.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an important differential diagnosis in heart failure (HF). However, routine use of spirometry in outpatient HF clinics is not implemented. The aim of the present study was to determine the prevalence of both airflow obstruction and non obstructive lung function impairment in patients with HF and to examine the effect of optimal medical treatment for HF on lung function parameters. METHODS: Consecutive patients with HF (ejection fraction (EF) < 45%) and New York Heart Association (NYHA) functional class II-IV at 10 different outpatient heart failure clinics were examined with spirometry at their first visit and after optimal medical treatment for HF was achieved. airflow obstruction was classified and graded according to the GOLD 2011 revision. RESULTS: Baseline spirometry was performed in 593 included patients and 71 (12%) had a clinical diagnosis of COPD. Mean age was 69 ± 11 years and mean EF was 30 ± 9%. Thirty-two % of the patients were active smokers and 53% were previous smokers. Mean FEV1 and FVC was 77.9 ± 1.7% and 85.4 ± 1.5% of predicted respectively. Obstructive pattern was observed in 233 (39%) of the patients. Of these, 53 patients (9%) had mild disease (GOLD I) and 180 (30%) patients had moderate to very severe disease (GOLD II-IV). No difference in spirometric variables was observed following up titration of medication. CONCLUSION: In stable patients with HF airflow obstruction is frequent and severely underdiagnosed. Spirometry should be considered in all patients with HF in order to improve diagnosis and treatment for concomitant pulmonary disease.

Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials.

AIMS: The aim of this study was to assess the net clinical and prognostic effects of intravenous (i.v.) iron therapy in patients with systolic heart failure (HF) and iron deficiency (ID). METHODS AND RESULTS: We performed an aggregate data meta-analysis (random effects model) of randomized controlled trials that evaluated the effects of i.v. iron therapy in iron-deficient patients with systolic HF. We searched electronic databases up to September 2014. We identified five trials which fulfilled the inclusion criteria (509 patients received i.v. iron therapy in comparison with 342 controls). Intravenous iron therapy has been shown to reduce the risk of the combined endpoint of all-cause death or cardiovascular hospitalization [odds ratio (OR) 0.44, 95% confidence interval (CI) 0.30-0.64, P < 0.0001], and the combined endpoint of cardiovascular death or hospitalization for worsening HF (OR 0.39, 95% CI 0.24-0.63, P = 0.0001). Intravenous iron therapy resulted in a reduction in NYHA class (data are reported as a mean net effect with 95% CIs for all continuous variables) (-0.54 class, 95% CI -0.87 to -0.21, P = 0.001); an increase in 6-min walking test distance (+31 m, 95% CI 18-43, P < 0.0001); and an improvement in quality of life [Kansas City Cardiomyopathy Questionnaire (KCCQ) score +5.5 points, 95% CI 2.8-8.3, P < 0.0001; European Quality of Life-5 Dimensions (EQ-5D) score +4.1 points, 95% CI 0.8-7.3, P = 0.01; Minnesota Living With Heart Failure Questionnaire (MLHFQ) score -19 points, 95% CI:-23 to -16, P < 0.0001; and Patient Global Assessment (PGA) +0.70 points, 95% CI 0.31-1.09, P = 0004]. CONCLUSION: The evidence indicates that i.v. iron therapy in iron-deficient patients with systolic HF improves outcomes, exercise capacity, and quality of life, and alleviates HF symptoms.

Modified T-Graft for Extracorporeal Membrane Oxygenation in a Patient with Small-Caliber Femoral Arteries.

Extracorporeal membrane oxygenation (ECMO) is generally used as a last resort to provide cardiopulmonary support in patients whose advanced cardiac or respiratory failure does not respond to less invasive treatments. Lower-limb ischemia secondary to the large diameter of the arterial cannula is one of ECMO's major limitations: in patients who have small-caliber arteries, the cannulas can reduce native blood flow. The creation of a T-graft-a well-described technique to avoid limb ischemia-enables flow into the ECMO cannula without jeopardizing blood flow to the limb. However, leaving the graft exposed through an open groin wound can result in dislodgment, and it increases the risk of infection. We describe our modification of a conventional T-graft in an 18-year-old woman who had systolic heart failure, acute respiratory distress syndrome, and small-caliber femoral vessels. We tunneled a polytetrafluoroethylene graft inside a Dacron graft, then ran the combined graft through a subcutaneous tunnel similar to that created for a peripheral bypass. Thus, the graft was protected from environmental exposure and the risk of infection. Our technique seems safer and more secure than the original T-graft technique, and we recommend its consideration during ECMO cannulation.

Osteoprotegerin is associated with depletion of circulating endothelial progenitor cells and elevation in pulmonary arterial pressure in patients with systolic heart failure.

OBJECTIVE: Osteoprotegerin (OPG) may predict progression of chronic congestive heart failure (CHF) with increased mortality and play an important role in the development of pulmonary arterial hypertension (PAH). Mounting evidence suggests that PAH developed during CHF is not solely caused by a "passive" increase from the left ventricular enddiastolic pressure, but rather a "reactive" response from contributing lung endothelial dysfunction and vascular remodelling, a pathological process that can be significantly influenced by endothelial progenitor cells (EPCs).This study aims to examine whether circulating EPCs from patients with CHF are affected and if OPG could be implicated during disease progression. METHODS: In this study EPCs were isolated, cultured, and quantified from patients of CHF with (n = 20) or without PAH (n=40) as measured by right heart catheterization. Serum levels of OPG and N-terminal pro-brain natriuretic peptide (NT-pro BNP) were analysed and correlated with EPCs. RESULTS: A significant decrease in circulating EPCs (39.3 ?9.1 vs 67.1 ?10.5 EPCs/x200 field; P <0.05) was found in CHF patients who developed PAH compared to those without PAH. Both OPG (551.90 +/- 49.83 vs. 312.29 +/- 31.12 pg/ml; P<0.05) and NT-pro BNP (2,946.50 +/- 1,434.50 vs. 1,328.20 +/- 811.90; P < 0.05) were also significantly elevated in CHF patients with PA H. Circulating level of OPG correlated inversely with EPCs (r = -0.45, P = 0.037) but positively with mPAP (r =0.53, P=0.011). CONCLUSIONS: Our study demonstrates that OPG elevation and EPC depletion are associated with CHF patients who have developed PAH. The inverse relationship of circulating OPG with EPCs suggests a possible mechanism for OPG in the development of pulmonary vascular dysfunction, thus worsening prognosis for CHF patients.