Longitudinal association between N-terminal B-type natriuretic peptide, anxiety and social support in patients with HFpEF: results from the multicentre randomized controlled Aldo-DHF trial.

BACKGROUND: Higher plasma levels of natriuretic peptides (NPs) have been associated with reduced anxiety in experimental research and a number of patient samples. As NP levels are elevated in heart failure patients, we investigate whether this elevation is related to anxiety in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: Post-hoc regression and mediation analyses were conducted, using data of 422 patients with HFpEF from the randomized, placebo-controlled, double-blinded, two-armed, multicentre aldosterone in diastolic heart failure trial, testing associations and their mediators between the N-terminal B-type natriuretic peptide (NT-proBNP) and anxiety at baseline and over 12-month follow-up. Anxiety was measured by the Hospital Anxiety and Depression Scale (HADS), social support by the ENRICHD Social Support Inventory and physical functioning by the Short Form 36 Health Survey. RESULTS: The mean age of the study population was 66.8 ± 7.6 years, 47.6% were male and 86.0% had NYHA class II. NT-proBNP showed a weak negative correlation with HADS anxiety scores at baseline (r = - 0.087; p = 0.092), which was significant (r = - 0.165; p = 0.028) in men but not in women. NT-proBNP also tended to predict lower anxiety at 12-months in men. On the other hand, higher anxiety at baseline was associated with lower NT-proBNP scores 12 months later (r = - 0.116; p = 0.026). All associations lost significance in multivariate regression for age, perceived social support (ESSI), physical function (SF-36) and study arm. Mediation analyses revealed that social support acts as a full mediator for the link between NT-proBNP levels and anxiety. CONCLUSION: The mechanisms linking NT-proBNP to anxiety may be more complex than originally assumed. While effects of NT-proBNP on anxiety may be mediated by perceived social support, there may be an additional negative effect of anxiety on NT-proBNP. Future research should consider this possible bi-directionality of the association and assess the potential influence of gender, social support, oxytocin and vagal tone on the interaction of anxiety and natriuretic peptide levels. Trial Registration http://www.controlled-trials.com  (ISRCTN94726526) on 07/11/2006. Eudra-CT-number: 2006-002,605-31.

Acute effects of oral triglyceride load on dynamic changes in peripheral endothelial function in heart failure patients with reduced ejection fraction and healthy controls.

BACHGROUND: Postprandial hyperlipaemia impairs endothelial function, possibly via oxidative-stress-mediated mechanisms. The aim of this study was to evaluate the acute effects of an oral triglyceride load (OTGL) on peripheral endothelial function in heart failure patients with reduced ejection fraction (HFrEF) compared to healthy controls. DESIGN: Prospective cross-sectional. METHODS: We enrolled 47 patients with HFrEF and 20 healthy controls. Peripheral endothelial function was assessed with EndoPAT2000 technology using a reactive hyperaemia index (RHI) and pulse wave amplitude (PWA) at baseline (after 8-h overnight fasting) as well as 1, 2, 3 and 4-h post-OTGL consumption (250-ml cream drink). Pulse wave amplitude index (PWAI) was calculated as a ratio of PWA at each time point to the baseline PWA. RESULTS: RHI at baseline was lower in HFrEF patients compared to controls (1.7 ± 0.3 and 2.3 ± 0.6, respectively; P = 0.001). The OTGL accounted for a physiologic increase in PWA in healthy controls (p = 0.01), but this change was not observed in HFrEF patients. After 4 h, vasodilator response was significantly increased in healthy controls but not patients with HFrEF (2.3 ± 1.3 vs. 1.3 ± 0.8 respectively, P < 0.05). CONCLUSIONS: The main finding of this study was the impaired postprandial dynamic changes in peripheral endothelial function in patients with HFrEF compared to healthy controls. A high-fat load that caused acute hypertriglyceridaemia significantly increased resting blood flow and peak flow at reactive hyperaemia in healthy subjects. By contrast, patients with HFrEF exhibited impaired dynamic changes in peripheral endothelial function after oral triglyceride load.

Segment-by-segment assessment of left ventricular myocardial affection in Anderson-Fabry disease by non-enhanced T1-mapping.

Background Anderson-Fabry disease (AFD) is an X-linked lysosomal enzyme disorder associated with an intracellular accumulation of sphingolipids, which shorten myocardial T1 relaxation times. Myocardial affection, however, varies between different segments. Purpose To evaluate the specific segmental distribution and degree of segmental affection in AFD patients. Material and Methods Twenty-five patients with AFD, 14 patients with hypertrophic cardiomyopathy (HCM), and 21 controls were included. A Modified Look-Locker Inversion Recovery sequence (MOLLI) was used for non-enhanced T1 mapping at 1.5 T in addition to standard cardiac imaging in 10-12 short axis views. T1 values were evaluated with a mixed model ANOVA and regression analysis to determine the best diagnostic cutoff values for T1 for each myocardial segment. Results Regression analysis showed the best diagnostic cutoff compared to controls in cardiac segments 1-4, 8-9, and 14. Mean differences between T1 for AFD versus HCM were greatest in segment 3, 4, and 9 (99 ms, 103 ms, 86 ms, respectively). Overall T1 times were 888 ± 70 ms and 903 ± 14 ms (AFD with and without LVH); 1014 ± 17 ms and 1001 ± 22 ms (HCM and controls, P < 0.05). Conclusion Myocardial segments are affected by a varying degree of T1 shortening in AFD patients. Segment-specific cutoff values allow the most specific detection and quantification of the extent of myocardial affection.

Intestinal congestion and right ventricular dysfunction: a link with appetite loss, inflammation, and cachexia in chronic heart failure.

AIMS: Mechanisms leading to cachexia in heart failure (HF) are not fully understood. We evaluated signs of intestinal congestion in patients with chronic HF and their relationship with cachexia. METHODS AND RESULTS: Of the 165 prospectively enrolled outpatients with left ventricular ejection fraction ≤40%, 29 (18%) were cachectic. Among echocardiographic parameters, the combination of right ventricular dysfunction and elevated right atrial pressure (RAP) provided the best discrimination between cachectic and non-cachectic patients [area under the curve 0.892, 95% confidence interval (CI): 0.832-0.936]. Cachectic patients, compared with non-cachectic, had higher prevalence of postprandial fullness, appetite loss, and abdominal discomfort. Abdominal ultrasound showed a larger bowel wall thickness (BWT) in the entire colon and terminal ileum in cachectic than in non-cachectic patients. Bowel wall thickness correlated positively with gastrointestinal symptoms, high-sensitivity C-reactive protein, RAP, and truncal fat-free mass, the latter serving as a marker of the fluid content. Logistic regression analysis showed that BWT was associated with cachexia, even after adjusting for cardiac function, inflammation, and stages of HF (odds ratio 1.4, 95% CI: 1.0-1.8; P-value = 0.03). Among the cardiac parameters, only RAP remained significantly associated with cachexia after multivariable adjustment. CONCLUSION: Cardiac cachexia was associated with intestinal congestion irrespective of HF stage and cardiac function. Gastrointestinal discomfort, appetite loss, and pro-inflammatory activation provide probable mechanisms, by which intestinal congestion may trigger cardiac cachexia. However, our results are preliminary and larger studies are needed to clarify the intrinsic nature of this relationship.

Influence of essential amino acids on muscle mass and muscle strength in patients with cerebral stroke during early rehabilitation: protocol and rationale of a randomized clinical trial (AMINO-Stroke Study).

BACKGROUND: Patients with stroke are at a high risk for long-term handicap and disability. In the first weeks after stroke muscle wasting is observed frequently. Early post-stroke rehabilitation programs are directed to improve functional independence and physical performance. Supplementation with essential amino acids (EAAs) might prevent muscle wasting and improve rehabilitation outcome by augmenting muscle mass and muscle strength. We aim to examine this in a double blinded, randomized placebo-controlled clinical trial. METHODS: Patients with ischemic or haemorrhagic stroke will be enrolled at begin of the early post-stroke rehabilitation in a parallel group interventional trial. Oral supplementation of EAAs or placebo will be given for 12 weeks in a double blinded manner. Physical and functional performance will be assessed by exercise testing before supplementation of EAAs as well as at discharge from the in-patient rehabilitation, at 12 weeks and 1 year afterwards. DISCUSSION: This is the first randomized double-blinded placebo-controlled clinical study aiming to assess the effect of the EAAs supplementation on muscle strength, muscle function and physical performance in stroke patients during early post-stroke rehabilitation. Supplementation of EAAs could prevent muscle mass wasting and improve functional independence after stroke. TRIAL REGISTRATION: The study is registered at the German registry for clinical trials as well as at World Health Organization (WHO; number DRKS00005577).

Muscle wasting in patients with chronic heart failure: results from the studies investigating co-morbidities aggravating heart failure (SICA-HF).

AIMS: To assess the prevalence and clinical impact of reductions in the skeletal muscle mass of patients with chronic heart failure (HF). Chronic HF is accompanied by co-morbidities that influence the quality of life and outcomes. METHODS AND RESULTS: We prospectively enrolled 200 patients with chronic HF. The appendicular skeletal muscle mass of the arms and the legs combined, was assessed by dual energy X-ray absorptiometry. We analysed the muscle strength in arms and legs, and all patients underwent a 6-min walk test, a 4-m walk test, and spiroergometry testing. Muscle wasting was defined as the appendicular muscle mass 2 SD below the mean of a healthy reference group of adults aged 18-40 years, as suggested for the diagnosis of muscle wasting in healthy ageing (sarcopenia). Muscle wasting was detected in 39 (19.5%) subjects. Patients with muscle wasting had significantly lower values for handgrip and quadriceps strength as well as lower total peak oxygen consumption (peakVO2, 1173 ± 433 vs. 1622 ± 456 mL/min), lower exercise time (7.7 ± 3.8 vs. 10.22 ± 3.0 min, both P < 0.001), and lower left ventricular ejection fraction (LVEF, P = 0.05) than patients without. The distance walked during 6 min and the gait speed during the 4-m walk were lower in patients with muscle wasting (both P < 0.05). Serum levels of interleukin-6 were significantly elevated in patients with muscle wasting (P = 0.001). Logistic regression showed muscle wasting to be independently associated with reduced peak VO2 adjusted for age, sex, New York Heart Association class, haemoglobin, LVEF, distance walked in 6 minutes, and the number of co-morbidities (odds ratio 6.53, p = 0.01). CONCLUSION: Muscle wasting is a frequent co-morbidity among patients with chronic HF. Patients with muscle wasting present with reduced exercise capacity and muscle strength, and advanced disease.

Transition from asymptomatic to symptomatic systolic chronic heart failure: rationale and design of TransitionCHF.

AIMS: Chronic systolic heart failure (CHF) is a major health burden. A relevant number of patients shows asymptomatic left ventricular dysfunction (ALVSD) before symptomatic CHF or becomes asymptomatic after initiating heart failure therapy. Clinical course, prognosis, and response to pharmacological and device-based treatment are largely unknown in these two distinct groups of patients. Current pharmacological and interventional therapies do neither properly address the underlying pathophysiology nor prevent malignant loss of function. New therapeutic paradigms are needed to stop the progression from asymptomatic to symptomatic heart failure. Key questions are what causes progression of clinically asymptomatic New York Heart Association (NYHA) I heart failure to overt heart failure (>NYHA I) in some but not all patients and the underlying reasons for this transition. This requires the identification of disease mechanisms and biomarkers that predict outcome in well-defined cohorts for innovative preclinical and clinical trials. METHODS AND RESULTS: TransitionCHF is a prospective, multicentre, longitudinal pathophysiological evaluation cohort study in patients with asymptomatic systolic dysfunction NYHA I and left ventricular ejection fraction ≤40%. The cohort comprises both incidental findings and patients who had become asymptomatic after a previous symptomatic event. TransitionCHF has recruited 1000 patients with ALVSD caused by various aetiologies in 20 university heart failure clinics across Germany. Both patients with and without comorbidities at study entry will be recruited. Patients will be systematically investigated and followed up annually over the course of the study. The primary composite endpoint is time to hospitalization for heart failure and cardiovascular death. The secondary endpoints assess time to all-cause mortality, to cardiovascular mortality, to heart failure mortality, to all-cause hospitalization, to heart failure hospitalization, and to recurrent heart failure hospitalizations, as well as time to assist device implantation/transplantation. Additional investigations focusing on biomarkers, comorbidities, gender aspects, nutrition, and functional parameters including quality of life will be performed. CONCLUSIONS: TransitionCHF will provide a more thorough pathophysiological understanding of the progression of asymptomatic systolic dysfunction into symptomatic heart failure that will help develop therapies tailored to prevent progressive heart failure.

Increased Expression of Proinflammatory Genes in Peripheral Blood Cells Is Associated with Cardiac Cachexia in Patients with Heart Failure with Reduced Ejection Fraction.

Background: Cardiac cachexia (CC) in chronic heart failure with reduced ejection fraction (HFrEF) is characterized by catabolism and inflammation predicting poor prognosis. Levels of responsible transcription factors like signal transducer and activator of transcription (STAT)1, STAT3, suppressor of cytokine signaling (SOCS)1 and SOCS3 in peripheral blood cells (PBC) are underinvestigated in CC. Expression of mediators was related to patients' functional status, body composition (BC) and metabolic gene expression in skeletal muscle (SM). Methods: Gene expression was quantified by qRT-PCR in three cohorts: non-cachectic patients (ncCHF, n = 19, LVEF 31 ± 7%, BMI 30.2 ± 5.0 kg/m2), cachectic patients (cCHF; n = 18, LVEF 27 ± 7%, BMI 24.3 ± 2.5 kg/m2) and controls (n = 17, LVEF 70 ± 7%, BMI 27.6 ± 4.6 kg/m2). BC was assessed by dual-energy X-ray absorptiometry. Blood inflammatory markers were measured. We quantified solute carrier family 2 member 4 (SLC2A4) and protein degradation by expressions of proteasome 20S subunit beta 2 and calpain-1 catalytic subunit in SM biopsies. Results: TNF and IL-10 expression was higher in cCHF than in ncCHF and controls (all p < 0.004). cCHF had a lower fat mass index (FMI) and lower fat-free mass index (FFMI) compared to ncCHF and controls (p < 0.05). STAT1 and STAT3 expression was higher in cCHF vs. ncCHF or controls (1.1 [1.6] vs. 0.8 [0.9] vs. 0.9 [1.1] RU and 4.6 [5.5] vs. 2.5 [4.8] vs. 3.0 [4.2] RU, all ANOVA-p < 0.05). The same applied for SOCS1 and SOCS3 expression (1.1 [1.5] vs. 0.4 [0.4] vs. 0.4 [0.5] and 0.9 [3.3] vs. 0.4 [1.1] vs. 0.8 [0.9] RU, all ANOVA-p < 0.04). In cCHF, higher TNF and STAT1 expression was associated with lower FMI (r = 0.5, p = 0.053 and p < 0.05) but not with lower FFMI (p > 0.4). In ncCHF, neither cytokine nor STAT/SOCS expression was associated with BC (all p > 0.3). SLC2A4 was upregulated in SM of cCHF vs. ncCHF (p < 0.03). Conclusions: Increased STAT1, STAT3, SOCS1 and SOCS3 expression suggests their involvement in CC. In cCHF, higher TNF and STAT-1 expression in PBC were associated with lower FMI. Increased SLC2A4 in cachectic SM biopsies indicates altered glucose metabolism.

Diabetes mellitus is associated with low exercise capacity and impaired peripheral vasodilation in patients with heart failure - a propensity score-matched study.

AIMS: Diabetes mellitus (DM) and heart failure (HF) share vascular, skeletal and metabolic abnormalities that can reduce exercise capacity. We investigated whether exercise capacity differ in patients with type 2 DM compared to those without DM with HF of similar severity. METHODS AND RESULTS: The Studies Investigating Co-morbidities Aggravating HF (SICA-HF) prospectively enrolled 615 patients with chronic HF, 259 (42.1 %) of whom had DM. We assembled a propensity score-matched cohort of 231 pairs of patients with HF with or without DM who were balanced on age, sex and variables reflecting HF severity. Patients with DM had lower median peak VO2 (15.7 [13.0-19.1] vs. 17.3 [14.1-21.0] ml/min/kg; p = 0.005). Forearm blood flow reserve (per 1 ml/min/100 ml increase) was associated with lower exercise capacity (peak VO2 ≤ 16.6 ml/min/kg) in patients with DM (OR, 0.92; 95 % CI, (0.85-0.98; p = 0.014), but not in those without DM (OR, 0.98; 95 % CI, 0.93-1.02). A similar heterogeneity was also observed for HDL cholesterol. CONCLUSIONS: Diabetes is associated with a reduced exercise capacity in patients with HF. Most predictors of lower exercise capacity in HF are similar regardless of DM except impaired vascular function and lower HDL cholesterol which predict lower exercise capacity only in those with DM.

[Gender-specific differences in cardiology]. / Geschlechtsspezifische Unterschiede in der Kardiologie.

BACKGROUND: Evidence in cardiovascular patient care is currently skewed to the disadvantage of women. This article provides a summary of the current state of knowledge on gender differences with a special focus on the epidemiology, pathophysiology, risk factors and treatment of the most frequent cardiovascular diseases. MATERIAL AND METHODS: Evaluation and discussion of background research and expert recommendations. RESULTS: The necessity for a gender-specific analysis of results is a relatively recent development in clinical trials. There is increasing evidence for pathogenic mechanisms specific for women as well as pharmacodynamic and pharmacokinetic differences between women and men. Women are currently less likely to receive treatment for cardiac diseases according to medical guidelines than men. CONCLUSION: For improvement of the treatment options and effective disease prevention, it is pivotal to investigate pathogenetic mechanisms specific to women.

Magnetic resonance imaging of organ iron before and after correction of iron deficiency in patients with heart failure.

AIMS: Intravenous iron therapy (IVIT) is known to improve functional status in chronic heart failure (CHF) patients. The exact mechanism is not completely understood. We correlated magnetic resonance imaging (MRI) patterns of T2* iron signal in various organs to systemic iron and exercise capacity (EC) in CHF before and after IVIT. METHODS AND RESULTS: We prospectively analysed 24 patients with systolic CHF for T2* MRI pattern of the left ventricle (LV), small and large intestines, spleen, liver, skeletal muscle, and brain for iron. In 12 patients with iron deficiency (ID), we restored iron deficit by IVIT using ferric carboxymaltose. The effects after 3 months were analysed by spiroergometry and MRI. Patients with vs. without ID showed lower blood ferritin, haemoglobin (76 ± 63 vs. 196 ± 82 µg/L and 12.3 ± 1.1 vs. 14.2 ± 1.1 g/dL, all P < 0.002), and in trend a lower transferrin saturation (TSAT) (19.1 [13.1; 28.2] vs. 25.1 [21.3; 29.1] %, P = 0.05). Spleen and liver iron was lower as expressed by higher T2* value (71.8 [66.4; 93.1] vs. 36.9 [32.9; 51.7] ms, P < 0.002 and 33.5 ± 5.9 vs. 28.8 ± 3.9 ms, and P < 0.03). There was a strong trend for a lower cardiac septal iron content in ID (40.6 [33.0; 57.3] vs. 33.7 [31.3; 40.2] ms, P = 0.07). After IVIT, ferritin, TSAT, and haemoglobin increased (54 [30; 104] vs. 235 [185; 339] µg/L, 19.1 [13.1; 28.2] vs. 25.0 [21.0; 33.7] %, 12.3 ± 1.1 vs. 13.3 ± 1.3 g/L, all P < 0.04). Peak VO2 improved (18.2 ± 4.2 vs. 20.9 ± 3.8 mL/min/kg-1 , P = 0.05). Higher peak VO2 at anaerobic threshold was associated with higher blood ferritin, reflecting higher metabolic exercise capacity after therapy (r = 0.9, P = 0.0009). Increase in EC was associated with haemoglobin increase (r = 0.7, P = 0.034). LV iron increased by 25.4% (48.5 [36.2; 64.8] vs. 36.2 [32.9; 41.9] ms, P < 0.04). Spleen and liver iron increased by 46.4 and 18.2%, respectively (71.8 [66.4; 93.1] vs. 38.5 [22.4; 76.9] ms, P < 0.04 and 33.5 ± 5.9 vs. 27.4 ± 8.6 ms, P < 0.007). Iron in skeletal muscle, brain, intestine, and bone marrow remained unchanged (29.6 [28.6; 31.2] vs. 30.4 [29.7; 30.7] ms, P = 0.7, 81.0 ± 6.3 vs. 82.9 ± 9.9 ms, P = 0.6, 34.3 ± 21.4 vs. 25.3 ± 14.1 ms, P = 0.2, 9.4 [7.5; 21.8] vs. 10.3 [6.7; 15.7] ms, P = 0.5 and 9.8 ± 1.5 vs. 13.7 ± 8.9 ms, P = 0.1). CONCLUSIONS: CHF patients with ID showed lower spleen, liver, and in trend lower cardiac septal iron. After IVIT, iron signal of the left ventricle as well as spleen and liver increased. Improvement in EC was associated with increase in haemoglobin after IVIT. In ID, liver, spleen, and brain but not heart iron were associated with markers of systemic ID.

Endothelial dysfunction of the peripheral vascular bed in the acute phase after ischemic stroke.

BACKGROUND: Endothelial dysfunction (ED) is relevant for the development of cerebrovascular and cardiovascular diseases. Asymmetric dimethylarginine (ADMA) competes with L-arginine and has been implicated in the development of ED. Increased levels of ADMA have been found in chronic heart failure (CHF). We hypothesized that peripheral ED in acute ischemic stroke is associated with increased ADMA levels. METHODS: We evaluated 60 patients with acute stroke in the territory of the middle cerebral artery. Stroke patients were classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. We compared these patients with patients of similar age without known cardiovascular disease (negative controls, n = 23) and patients with stable, ambulatorily treated CHF (n = 46, left ventricular ejection fraction = 33.8 ± 10.9) with known ED (positive controls). Peripheral endothelial function was assessed by EndoPAT2000 technology using the reactive hyperemia index (RHI). RESULTS: RHI was significantly decreased in stroke and in CHF compared to controls (1.8 ± 0.3 vs. 1.8 ± 0.4 vs. 2.2 ± 0.4, respectively, ANOVA p = 0.01). A decreased RHI was observed in cardioembolic and lacunar infarcts and stroke of undetermined etiology (1.7 ± 0.4, 1.8 ± 0.5 and 1.7 ± 0.3, p < 0.0001). The L-arginine/ADMA ratio was significantly decreased in stroke and in CHF (147.6 ± 31.7 and 126.1 ± 37.9 vs. controls: 161.5 ± 26.1, p < 0.0001) and was lowest in stroke patients in the cardioembolic group (133.0 ± 29.4, p < 0.0001). A lower L-arginine/ADMA ratio was associated with ED in cardioembolic stroke and CHF (r = 0.324, p < 0.05 and r = 0.429, p < 0.0001). CONCLUSION: Peripheral ED occurs to a similar degree in acute ischemic stroke and CHF. The impaired vasodilator capacity of peripheral arteries reflects the TOAST classification. ADMA may play a role in ED in both acute ischemic stroke and CHF.

Glucose-Induced Hemodynamic and Metabolic Response of Skeletal Muscle in Heart Failure Patients with Reduced vs. Preserved Ejection Fraction-A Pilot Study.

(1) Background: Insulin resistance (IR) is a characteristic pathophysiologic feature in heart failure (HF). We tested the hypothesis that skeletal muscle metabolism is differently impaired in patients with reduced (HFrEF) vs. preserved (HFpEF) ejection fraction. (2) Methods: carbohydrate and lipid metabolism was studied in situ by intramuscular microdialysis in patients with HFrEF (59 ± 14y, NYHA I-III) and HFpEF (65 ± 10y, NYHA I-II) vs. healthy subjects of similar age during the oral glucose load (oGL); (3) Results: There were no difference in fasting serum and interstitial parameters between the groups. Blood and dialysate glucose increased significantly in HFpEF vs. HFrEF and controls upon oGT (both p < 0.0001), while insulin increased significantly in HFrEF vs. HFpEF and controls (p < 0.0005). Muscle tissue perfusion tended to be lower in HFrEF vs. HFpEF and controls after the oGL (p = 0.057). There were no differences in postprandial increases in dialysate lactate and pyruvate. Postprandial dialysate glycerol was higher in HFpEF vs. HFrEF and controls upon oGL (p = 0.0016); (4) Conclusion: A pattern of muscle glucose metabolism is distinctly different in patients with HFrEF vs. HFpEF. While postprandial IR was characterized by impaired tissue perfusion and higher compensatory insulin secretion in HFrEF, reduced muscle glucose uptake and a blunted antilipolytic effect of insulin were found in HFpEF.

Iron Deficiency and Reduced Muscle Strength in Patients with Acute and Chronic Ischemic Stroke.

(1) Introduction: Iron deficiency (ID) contributes to impaired functional performance and reduced quality of life in patients with chronic illnesses. The role of ID in stroke is unclear. The aim of this prospective study was to evaluate the prevalence of ID and to evaluate its association with long-term functional outcome in patients with ischemic stroke. (2) Patients and Methods: 140 patients (age 69 ± 13 years, BMI 27.7 ± 4.6 kg/m², mean ± SD) admitted to a university hospital stroke Unit, with acute ischemic stroke of the middle cerebral artery were consecutively recruited to this observational study. Study examinations were completed after admission (3 ± 2 days after acute stroke) and at one-year follow up (N = 64, 382 ± 27 days after stroke). Neurological status was evaluated according to the National Institute of Health Stroke Scale (NIHSS) and the modified Rankin scale (mRS). Muscle isometric strength of the non-affected limb was assessed by the maximum handgrip test and knee extension leg test. ID was diagnosed with serum ferritin levels ≤ 100 µg/L (ID Type I) or 100-300 µg/L if transferrin saturation (TSAT) < 20% (ID Type II). (3) Results: The prevalence of ID in acute stroke patients was 48% (N = 67), with about two-thirds of patients (N = 45) displaying ID Type I and one-third (N = 22) Type II. Handgrip strength (HGS) and quadriceps muscle strength were reduced in patients with ID compared to patients without ID at baseline (HGS: 26.5 ± 10.4 vs. 33.8 ± 13.2 kg, p < 0.001 and quadriceps: 332 ± 130 vs. 391 ± 143 N, p = 0.06). One year after stroke, prevalence of ID increased to 77% (p = 0.001). While an improvement of HGS was observed in patients with normal iron status, patients with ID had no improvement in HGS difference (4.6 ± 8.3 vs. -0.7 ± 6.5 kg, p < 0.05). Patients with ID remained with lower HGS compared to patients with normal iron status (28.2 ± 12.5 vs. 44.0 ± 8.6 kg, p < 0.0001). (4) Conclusions: Prevalence of ID was high in patients after acute stroke and further increased one year after stroke. ID was associated with lower muscle strength in acute stroke patients. In patients with ID, skeletal muscle strength did not improve one year after stroke.

Influence of baseline parameters on one-year physical, mental, and health-related quality of life in patients with heart failure and preserved ejection fraction.

AIMS: To identify baseline parameters longitudinally influencing overall health-related quality of life (HRQoL), physical function and mental health 1 year later in patients with chronic heart failure and preserved ejection fraction (HFpEF). METHODS AND RESULTS: We performed post hoc analyses of the randomized aldosterone in diastolic heart failure (Aldo-DHF) trial, including 422 patients with HFpEF and NYHA class II or III. Overall HRQoL, measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ), physical functioning and mental health, both measured by the Short Form 36 Health Survey (SF-36), after 12 months were predicted in correlation analyses and multivariate regression analyses with continuous values and worst versus three better HRQoL quartiles as dependent variables. The mean age of the study population was 66.8 ± 7.6 years, 52.4% were female, and 86.0% had NYHA class II. All HRQoL variables at 1 year were predicted by their respective baseline values (all P < 0.001), which were also the best variables to predict lowest versus higher HRQoL quartiles (all P < 0.001). For overall HRQoL, six-minute-walking-distance (P = 0.009), Borg-score (P = 0.001), coronary heart disease (P = 0.036) and SF-36 role-emotional (P = 0.005) independently predicted one-year-outcome, while depression diagnosis (P = 0.044), self-reported health status (P = 0.023) and PHQ depression (P = 0.001) were only significant predictors when excluding MLHFQ total score at baseline. In logistic regression analyses, only SF-36 role-emotional (P = 0.016) independently predicted overall HRQoL group status at follow up. For physical functioning, Borg-score (P ≤ 0.001), 6 min walking distance (P = 0.005), coronary heart disease (P = 0.009), and SF-36 vitality (P = 0.001) were significant independent predictors, also when excluding baseline physical functioning. Low SF-36 vitality (P = 0.021) and presence of coronary heart disease (P = 0.027) independently predicted a patient's membership in the lowest quartile 1 year later. For mental health, SF-36 physical functioning (P = 0.025) and HADS anxiety (P = 0.046) were independent predictors, while self-rated fatigue and poor performance (P = 0.033) and SF-36 vitality (P = 0.008) only served as significant predictors when excluding mental health at baseline. HADS anxiety (P = 0.009) also served as independent predictor of a patient's group status after 1 year. CONCLUSION: Overall HRQoL, physical functioning, and mental health of HFpEF patients 1 year later are mainly influenced by their respective baseline values. Other self-rated baseline parameters also showed independent effects while objective severity measures had limited predictive value.

The gut and intestinal bacteria in chronic heart failure.

Chronic heart failure (CHF) is now recognized as a multisystem disorder with increased sympathetic tone, hormonal derangements, an anabolic/catabolic imbalance, endothelial dysfunction, and systemic low-grade inflammation affecting various organ systems. Pro-inflammatory cytokines appear to play important roles in that context. There is increasing evidence for the gut to have a pathophysiological role for both chronic inflammation and malnutrition in CHF. Indeed, disturbed intestinal microcirculation and barrier function in CHF seem to trigger cytokine generation, thereby contributing to further impairment in cardiac function. On the other hand, myocardial dysfunction can induce microcirculatory injuries leading to a disruption in the intestinal barrier. This amplifies the inflammatory response. Furthermore, alterations of specific absorption functions of the intestinal mucosa in CHF may aggravate symptoms of cachexia. The increased number of adherent bacteria seen in patients with CHF and elevated systemic levels of anti-lipopolysaccharide immunoglobulin A underscore this fact. Therefore, the gut poses an interesting target for therapeutic interventions in patients with CHF.

Nutrition in heart failure: an update.

PURPOSE OF REVIEW: Chronic heart failure (CHF) is increasingly recognized as a multisystem disease with important comorbidities such as anemia, insulin resistance, autonomic dysbalance, or cardiac cachexia. RECENT FINDINGS: Apart from these perturbations, increasing evidence points to alterations in intestinal morphology, permeability, and absorption function in patients with CHF. This review provides an overview of the sonographic, histological, and functional abnormalities of different gastrointestinal regions. This intestinal dysfunction and disturbed intestinal barrier may lead to both the chronic inflammatory state and catabolic/anabolic imbalance as seen in cardiac cachexia, as a terminal stage of CHF, which carries a particularly poor prognosis. This review highlights the current knowledge of nutritional abnormalities that may occur in CHF, including fat, carbohydrates, proteins, water, and micronutrients. The regulation of feeding is discussed, as are nutritional strategies with potentially anti-inflammatory effects in the treatment of CHF. SUMMARY: The gut and its role for inflammation and dietary interventions in heart failure patients are a crucial target of further heart failure research.

Iron deficiency in patients with heart failure with preserved ejection fraction and its association with reduced exercise capacity, muscle strength and quality of life.

BACKGROUND: The prevalence of iron deficiency (ID) in outpatients with heart failure with preserved ejection fraction (HFpEF) and its relation to exercise capacity and quality of life (QoL) is unknown. METHODS: 190 symptomatic outpatients with HFpEF (LVEF 58 ± 7%; age 71 ± 9 years; NYHA 2.4 ± 0.5; BMI 31 ± 6 kg/m2) were enrolled as part of SICA-HF in Germany, England and Slovenia. ID was defined as ferritin < 100 or 100-299 µg/L with transferrin saturation (TSAT) < 20%. Anemia was defined as Hb < 13 g/dL in men, < 12 g/dL in women. Low ferritin-ID was defined as ferritin < 100 µg/L. Patients were divided into 3 groups according to E/e' at echocardiography: E/e' ≤ 8; E/e' 9-14; E/e' ≥ 15. All patients underwent echocardiography, cardiopulmonary exercise test (CPX), 6-min walk test (6-MWT), and QoL assessment using the EQ5D questionnaire. RESULTS: Overall, 111 patients (58.4%) showed ID with 89 having low ferritin-ID (46.84%). 78 (41.1%) patients had isolated ID without anemia and 54 patients showed anemia (28.4%). ID was more prevalent in patients with more severe diastolic dysfunction: E/e' ≤ 8: 44.8% vs. E/e': 9-14: 53.2% vs. E/e' ≥ 15: 86.5% (p = 0.0004). Patients with ID performed worse during the 6MWT (420 ± 137 vs. 344 ± 124 m; p = 0.008) and had worse exercise time in CPX (645 ± 168 vs. 538 ± 178 s, p = 0.03). Patients with low ferritin-ID had lower QoL compared to those without ID (p = 0.03). CONCLUSION: ID is a frequent co-morbidity in HFpEF and is associated with reduced exercise capacity and QoL. Its prevalence increases with increasing severity of diastolic dysfunction.

Body weight changes and incidence of cachexia after stroke.

BACKGROUND: Body weight loss is a frequent complication after stroke, and its adverse effect on clinical outcome has been shown in several clinical trials. The purpose of this prospective longitudinal single-centre observational study was to investigate dynamical changes of body composition and body weight after ischemic stroke and an association with functional outcome. METHODS: Sixty-seven consecutive patients (age 69 ± 11 years, body mass index 27.0 ± 4.1 kg/m2 , 42% female patient, mean ± SD) with acute ischemic stroke with mild to moderate neurological deficit (National Institute of Health Stroke Scale median 4, ranged 0-12) were analysed in the acute phase (4 ± 2 days) and at 12 months (389 ± 26 days) follow-up. Body composition was examined by dual energy X-ray absorptiometry. Cachexia was defined according to the consensus definition by body weight loss ≥5% within 1 year and additional clinical signs. Lean tissue wasting was considered if a ratio of upper and lower limbs lean mass sum to squared height (kg/m2 ) was ≤5.45 kg/m2 for female patient and ≤7.25 kg/m2 for male patient. RESULTS: According to the body weight changes after 12 months, 42 (63%) patients had weight gain or stable weight, 11 (16%) patients had moderate weight loss, and 14 (21%) patients became cachectic. A relative decline of 19% of fat tissue and 6.5% of lean tissue was observed in cachectic patients, while no changes of lean tissue were observed in non-cachectic patients after 12 months. The modified Rankin Scale was 48% higher (2.1 ± 1.6, P < 0.05), Barthel Index was 22% lower (71 ± 39, P < 0.01), and handgrip strength was 34% lower (21.9 ± 13.0, P < 0.05) in cachectic compared to non-cachectic patients after 12 months. The low physical performance if defined by Barthel Index <60 points was linked to the lean tissue wasting (OR 44.8, P < 0.01), presence of cachexia (OR 20.8, P < 0.01), and low body mass index <25 kg/m2 (OR 11.5, P < 0.05). After adjustment for cofounders, lean tissue wasting remained independently associated with the low physical performance at 12 months follow-up (OR 137.9, P < 0.05). CONCLUSIONS: In this cohort study, every fifth patient with ischemic stroke fulfilled the criteria of cachexia within 12 months after index event. The incidence of cachexia was 21%. Cachectic patients showed the lowest functional and physical capacity.

Comparison of sarcopenia and cachexia in men with chronic heart failure: results from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF).

AIMS: Changes in heart failure (HF) patients' body composition may be associated with reduced exercise capacity. The aim of the present study was to determine the overlap in wasting syndromes in HF (cachexia and sarcopenia) and to compare their functional impact. METHODS AND RESULTS: We prospectively enrolled 207 ambulatory male patients with clinically stable chronic HF. All patients underwent a standardized protocol examining functional capacity, body composition, and quality of life (QoL). Cachexia was present in 39 (18.8%) of 207 patients, 14 of whom also fulfilled the characteristics of sarcopenia (sarcopenia + cachexia group, 6.7%), whereas 25 did not (cachectic HF group, 12.1%). Sarcopenia without cachexia was present in 30 patients (sarcopenic HF group, 14.4%). A total of 44 patients (21.3%) presented with sarcopenia; however, 138 patients showed no signs of wasting (no wasting group, 66%). Patients with sarcopenia had lower strength and exercise capacity than both the no wasting and the cachectic HF group. Handgrip strength, quadriceps strength, peak oxygen uptake (VO2 ), distance in the 6-minute walk test (6MWT), and QoL results were lowest in the sarcopenia + cachexia group vs. the no wasting group (P < 0.05 for all). Likewise, the sarcopenic HF group showed lower handgrip strength, quadriceps strength, 6MWT, peak VO2 , and QoL results vs. the no wasting group (P < 0.05 for all). CONCLUSION: Losing muscle with or without weight loss appears to have a more pronounced role than weight loss alone with regard to functional capacity and QoL among male patients with chronic HF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01872299.