Anja Sandek

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.

The emerging role of the gut in chronic heart failure

Purpose of reviewChronic heart failure is a multisystem disease with increased sympathetic tone, an anabolic/catabolic dysbalance, and chronic inflammation. Recent studies suggest an altered morphology, permeability, and absorption of the digestive tract in chronic heart failure. Due to nonocclusive mesenterial ischaemia and disturbed intestinal microcirculation, bacterial endotoxin is thought to enter the bloodstream through the hypoperfused, oedematous gut wall, thereby triggering an inflammatory response. Circulating cytokines act as cardiosuppressors. Their plasma levels predict increased mortality in chronic heart failure. Recent findingsThe present article focuses on specific alterations of the gastric, small intestinal, and large intestinal region in chronic heart failure. It describes the leaky intestinal barrier with an augmented bacterial biofilm that may contribute to chronic inflammation and malnutrition. Furthermore, we review methods for bowel perfusion measurement and potential therapeutic approaches. SummaryIt remains unclear whether increased adherent bacteria in patients with chronic heart failure are a primary or secondary event and whether they contribute to systemic inflammation. Both lack of mucosal integrity with consecutive local and systemic inflammation and dysfunction of transport proteins may worsen the clinical symptoms of chronic heart failure. Therefore, future studies need to address the pathophysiology of the intestinal barrier whose reactivity seems to be crucial for heart function.

Studies on bacterial endotoxin and intestinal absorption function in patients with chronic heart failure

BACKGROUND Small intestinal function may be altered in decompensated chronic heart failure (CHF) and translocating LPS may contribute to systemic inflammation observed in CHF. METHODS We measured intestinal permeability (melibiose and rhamnose), active (3-O-methyl-d-glucose (3-OMG)) and passive (d-xylose) carrier-mediated absorption in 20 CHF patients (12 edematous and 8 non-edematous) and 8 controls by saccharide absorption technique assessing urinary recovery of orally administered sugars. We additionally measured LPS concentrations in 42 patients with decompensated heart failure and after recompensation. RESULTS CHF patients had a 54% reduction of active carrier-mediated intestinal transport compared to controls (p<0.0001). This reduction was strongest in edematous compared to non-edematous patients and controls (recovery in urine: 13.2±2.0% vs. 20.8±2.4% vs. 36.0 ± 3.7%, all p ≤ 0.05). Patients showed a 34% reduction of passive carrier-mediated transport, strongest in edematous patients (p=0.006). A greater impairment of active carrier-mediated transport remained significant after adjustment for non-mucosal factors in CHF (p=0.0004). Non carrier-mediated intestinal permeability was not altered. Data from 42 decompensated patients showed a decrease in LPS after recompensation (p=0.004). Edematous patients had highest blood concentrations of LPS, TNF and sTNF-R1 (p<0.04). CHF patients with abnormal LPS concentrations >0.50EU/mL (n=7) had the highest concentrations of TNF (7.0 ± 1.6 vs. 3.1 ± 0.3pg/mL, p<0.02), and sTNF-R1 (3499 ± 52 vs. 1599±219 pg/mL, p=0.02). CONCLUSION Active carrier-mediated intestinal transport is reduced in decompensated CHF indicating epithelial dysfunction possibly as a consequence of intestinal ischemia. Higher LPS concentrations in edematous CHF relate to inflammation. LPS decreased after recompensation. This suggests a cause/effect relationship between edematous gut wall, epithelial dysfunction and translocating LPS.

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 reviewChronic heart failure (CHF) is increasingly recognized as a multisystem disease with important comorbidities such as anemia, insulin resistance, autonomic dysbalance, or cardiac cachexia. Recent findingsApart 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. SummaryThe gut and its role for inflammation and dietary interventions in heart failure patients are a crucial target of further heart failure research.

Stroke-related sarcopenia: specific characteristics.

Sarcopenia is characterized by muscle wasting and is primarily a disease of the elderly. A stroke-specific sarcopenia has been described recently. Stroke-related sarcopenia has a number of features that distinguish it from the age-related sarcopenia. The disability from stroke depends on the brain lesion leading to impairment of the efferent neuronal pathways. However, the alterations of structural and functional muscle capacity are secondary and depend rather on complex pathophysiological reactions including imbalanced efferent neurovegetative control, systemic and local metabolic imbalance, feeding difficulties, and inflammation. Muscle structural changes start to develop within hours after stroke, followed by rapid reduction of muscle mass. The pathophysiological mechanisms leading to the muscle mass decline are still not understood in details. This review provides insights into the specific features of the stroke-related sarcopenia. Recent research achievements in this area and clinical implications will be discussed.

Cardiovascular Function and Predictors of Exercise Capacity in Patients With Colorectal Cancer

BACKGROUND Patients with colorectal cancer (CRC) often present with dyspnea and fatigue. These are also frequent symptoms in patients with chronic heart failure (CHF). OBJECTIVES We hypothesized that similar patterns of cardiovascular perturbations are present in CRC and CHF. METHODS We prospectively studied 50 patients with CRC, 51 patients with CHF, and 51 control subjects. The CRC group was divided into 2 subgroups: patients who underwent chemotherapy (n = 26) and chemotherapy-naive patients (n = 24). We assessed exercise capacity (spiroergometry), cardiac function (echocardiography), heart rate variability (Holter electrocardiography), body composition (dual-energy x-ray absorptiometry), and blood parameters. RESULTS Compared with the control arm, the left ventricular ejection fraction (CRC group 59.4%; control group 62.5%) and exercise performance as assessed by peak oxygen consumption (peak VO2) (CRC group 21.8 ml/kg/min; control group 28.0 ml/kg/min) were significantly reduced in CRC patients (both p < 0.02). Markers of heart rate variability were markedly impaired in CRC patients compared with control subjects (all p < 0.008). Compared with the control group, the CRC group also showed reduced lean mass in the legs and higher levels of the endothelium-derived C-terminal-pro-endothelin-1 (both p < 0.02). Major determinants of cardiovascular function were impaired in chemotherapy-treated patients and in the chemotherapy-naive patients, particularly with regard to exercise capacity, left ventricular ejection fraction, lean mass, and heart rate variability (all p < 0.05 vs. control subjects). CONCLUSIONS Some aspects of cardiovascular function are impaired in patients with CRC. More importantly, our findings were evident independently of whether patients were undergoing chemotherapy.

The impact of iron deficiency and anaemia on exercise capacity and outcomes in patients with chronic heart failure. Results from the Studies Investigating Co-morbidities Aggravating Heart Failure.

UNLABELLED Anaemia and iron deficiency (ID) are important co-morbidities in patients with chronic heart failure (HF) and both may lead to reduced exercise capacity. METHODS We enrolled 331 out-patients with stable chronic HF (mean age: 64 ± 11 years, 17% female, left ventricular ejection fraction [LVEF] 35 ± 13%, body mass index [BMI] 28.5 ± 5.2 kg/m(2), New York Heart Association [NYHA] class 2.2 ± 0.7, chronic kidney disease 35%, glomerular filtration rate 61.7 ± 20.1 mL/min). Anaemia was defined according to World Health Organization criteria (haemoglobin [Hb] < 13 g/dL in men, < 12 g/dL in women). ID was defined as serum ferritin < 100 μg/L or ferritin < 300 μg/L with transferrin saturation (TSAT) < 20%. Exercise capacity was assessed as peak oxygen consumption (peak VO2) by spiroergometry and 6-minute walk test (6MWT). RESULTS A total of 91 (27%) patients died from any cause during a mean follow-up of 18 months. At baseline, 98 (30%) patients presented with anaemia and 149 (45%) patients presented with ID. We observed a significant reduction in exercise capacity in parallel to decreasing Hb levels (r = 0.24, p < 0.001). In patients with anaemia and ID (n = 63, 19%), exercise capacity was significantly lower than in patients with ID or anaemia only. Cox regression analysis showed that after adjusting for NYHA, age, hsCRP and creatinine anaemia is an independent predictor of mortality in patients with HF (hazard ratio [HR]: 0.56, 95% confidence interval [CI]: 0.33-0.97, p = 0.04). CONCLUSION The impact of anaemia on reduced exercise capacity and on mortality is stronger than that of ID. Anaemia remained an independent predictor of death after adjusting for clinically relevant variables.

Detection of muscle wasting in patients with chronic heart failure using C-terminal agrin fragment: results from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF).

Skeletal muscle wasting affects 20% of patients with chronic heart failure and has serious implications for their activities of daily living. Assessment of muscle wasting is technically challenging. C‐terminal agrin‐fragment (CAF), a breakdown product of the synaptically located protein agrin, has shown early promise as biomarker of muscle wasting. We sought to investigate the diagnostic properties of CAF in muscle wasting among patients with heart failure.

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.