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.

Predictors of lower exercise capacity in patients with cancer.

Maintaining cancer patients' exercise capacity and therefore patients' ability to live a self-determined life is of huge importance, but little is known about major determinants. We sought to identify determinants of exercise capacity in patients with a broad spectrum of cancer types, who were already receiving cancer treatment or about to commence such therapy. Exercise capacity was assessed in 253 consecutive patients mostly suffering from advanced cancer using the 6-min walk test (6-MWT). All patients underwent echocardiography, physical examination, resting electrocardiogram, hand grip strength (HGS) measurement, and laboratory assessments. Patients were divided into two groups according to the median distance in the 6-MWT (459 m). Patients with lower exercise capacity were older, had significantly lower HGS and haemoglobin and higher values of high sensitive (hs) Troponin T and NT-proBNP (all p < 0.05). Whilst the co-morbidity burden was significantly higher in this group, no differences were detected for sex, body mass index, tumor type, or cachexia (all p > 0.2). Using multivariable logistic regression, we found that the presence of anaemia (odds ratio (OR) 6.172, 95% confidence interval (CI) 1.401-27.201, p = 0.016) as well as an increase in hs Troponin T (OR 3.077, 95% CI 1.202-5.301, p = 0.019) remained independent predictors of impaired exercise capacity. Increasing HGS was associated with a reduced risk of a lower exercise capacity (OR 0.896, 95% CI 0.813-0.987, p = 0.026). Screening patients for elevated hs troponin levels as well as reduced HGS may help to identify patients at risk of lower exercise capacity during cancer treatment.

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.

Bone status in men with heart failure: results from the Studies Investigating Co-morbidities Aggravating Heart Failure.

AIM: To assess bone status expressed as hip bone mineral density (BMD) in men with heart failure (HF). METHODS AND RESULTS: A total of 141 male patients with HF underwent dual energy X-ray absorptiometry to assess their BMD. We analysed markers of bone metabolism. Patients were classified as lower versus higher BMD according to the median hip BMD (median = 1.162 g/cm2 ). Survival was assessed over 8 years of follow-up. Patients with lower BMD were older (71 ± 10 vs. 66 ± 9 years, p = 0.004), more likely to be sarcopenic (37% vs. 7%, p < 0.001) and to have lower peak oxygen consumption (absolute peak VO2 1373 ± 480 vs. 1676 ± 447 ml/min, p < 0.001), had higher osteoprotegerin and osteocalcin levels (both p < 0.05) compared to patients with higher BMD. Among 47 patients with repeated BMD assessments, a significant reduction in BMD was noted over 30 months of follow-up. In multivariate logistic regression analysis, serum osteocalcin remained independently related with lower BMD (odds ratio [OR] 1.738, 95% confidence interval [CI] 1.136-2.660, p = 0.011). Hip BMD and serum osteoprotegerin were independent predictors of impaired survival on Cox proportional hazard analysis (hazard ratio [HR] 0.069, 95% CI 0.011-0.444, p = 0.005, and HR 0.638, 95% CI 0.472-0.864, p = 0.004, respectively). CONCLUSIONS: Patients with HF lose BMD over time. Markers of bone turnover can help in identifying patients at risk with osteocalcin being an independent marker of lower hip BMD and osteoprotegerin an independent predictor of death. HF patients with increased osteocalcin and osteoprotegerin may benefit from BMD assessment as manifest osteoporosis seems to be too late for clinically meaningful intervention in HF.

Cardiovascular and metabolic determinants of quality of life in patients with cancer.

AIMS: Maintaining quality of life (QoL) in patients with cancer has gathered significant interest, but little is known about its major determinants. We sought to identify determinants of QoL in patients undergoing cancer treatment as well as in treatment-naïve patients about to commence such therapy. METHODS AND RESULTS: QoL was assessed in 283 patients with cancer using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 questionnaire. All patients underwent a battery of tests including physical examination, resting electrocardiogram, hand grip strength, and biochemistry assessment. Using multivariable logistic regression, we found that age [odds ratio (OR) 0.954, 95% confidence interval (CI) 0.916-0.994], resting heart rate (OR 1.036, 95% CI 1.004-1.068), hand grip strength (OR 0.932, 95% CI 0.878-0.990), and the presence of cachexia (OR 4.334, 95% CI 1.767-10.631) and dyspnoea (OR 3.725, 95% CI 1.540-9.010; all P < 0.05) remained independently predictive of reduced QoL. CONCLUSIONS: Therefore, it may be reasonable to address circumstances that are affecting muscle mass, body weight, and heart rate to maintaining QoL; however, prospective studies to test these endpoints are required.

[Management of chronic heart failure: state of the art according to the 2021 guideline]. / Therapie der chronischen Herzinsuffizienz ­ State of the Art nach den europäischen Leitlinien von 2021.

Treatment of heart failure with reduced ejection fraction (HFrEF) requires four drug classes that should be initiated simultaneously and up-titrated rapidly. All four have received class I recommendations. Sacubitril/valsartan can be considered in initial treatment, even for patients in whom no previous treatment with an angiotensin converting enzyme inhibitor has been given. Treatment with dapagliflozin and empagliflozin is started irrespective of diabetes mellitus to reduce mortality and hospitalization rates for heart failure. Most drug treatment recommendations for HFrEF can be extrapolated to heart failure with mildly-reduced ejection fraction, even though the evidence base is not as robust as in HFrEF. Treatment individualization considers co-morbidities such as atrial fibrillation, valvular disease and iron deficiency as well as advanced heart failure. Following cardiac decompensation, verciguat is now available as an additional treatment option.

Cardiac Cachexia Revisited: The Role of Wasting in Heart Failure.

Cardiac cachexia is a co-morbidity of heart failure (HF) defined by a non-edematous weight loss of ≥6% within the previous 6-12 months. Cachexia affects about 10-39% patients with HF and occurs typically in advanced stages of HF, especially in the presence of congestive right ventricular dysfunction. This review elucidates the approaches and pitfalls in the diagnosis of cachexia. It summarizes the prevalence and impact of cardiac cachexia. It also discusses changes in body composition over the course of HF and provides an overview of the mechanisms involved in wasting in HF.

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.

Muscle wasting as an independent predictor of survival in patients with chronic heart failure.

BACKGROUND: Skeletal muscle wasting is an extremely common feature in patients with heart failure, affecting approximately 20% of ambulatory patients with even higher values during acute decompensation. Its occurrence is associated with reduced exercise capacity, muscle strength, and quality of life. We sought to investigate if the presence of muscle wasting carries prognostic information. METHODS: Two hundred sixty-eight ambulatory patients with heart failure (age 67.1 ± 10.9 years, New York Heart Association class 2.3 ± 0.6, left ventricular ejection fraction 39 ± 13.3%, and 21% female) were prospectively enrolled as part of the Studies Investigating Co-morbidities Aggravating Heart Failure. Muscle wasting as assessed using dual-energy X-ray absorptiometry was present in 47 patients (17.5%). RESULTS: During a mean follow-up of 67.2 ± 28.02 months, 95 patients (35.4%) died from any cause. After adjusting for age, New York Heart Association class, left ventricular ejection fraction, creatinine, N-terminal pro-B-type natriuretic peptide, and iron deficiency, muscle wasting remained an independent predictor of death (hazard ratio 1.80, 95% confidence interval 1.01-3.19, P = 0.04). This effect was more pronounced in patients with heart failure with reduced than in heart failure with preserved ejection fraction. CONCLUSIONS: Muscle wasting is an independent predictor of death in ambulatory patients with heart failure. Clinical trials are needed to identify treatment approaches to this co-morbidity.

Heart failure and sleep-disordered breathing: susceptibility to reduced muscle strength and preclinical congestion (SICA-HF cohort).

AIMS: Increased sympathetic activation in patients with heart failure (HF) and sleep-disordered breathing (SDB) provokes cardiac decompensation and protein degradation and could lead to muscle wasting and muscle weakness. The aim of this study was to investigate the differences in body composition, muscle function, and the susceptibility of preclinical congestion among patients with HF and SDB compared with those without SDB. METHODS AND RESULTS: We studied 111 outpatients with stable HF who were enrolled into the Studies Investigating Co-morbidities Aggravating Heart Failure. Echocardiography, short physical performance battery (SPPB), cardiopulmonary exercise testing, dual-energy X-ray absorptiometry, bioelectrical impedance analysis (BIA), tests of muscle strength, and polygraphy were performed. SDB was defined as apnoea/hypopnoea index (AHI) >5 per hour of sleep. Central sleep apnoea (CSA) and obstructive sleep apnoea (OSA) were defined as AHI >50% of central or obstructive origin, respectively. A total of 74 patients (66.7%) had any form of SDB [CSA (24 patients, 32.4%), OSA (47 patients, 63.5%)]. Patients with SDB showed increased muscle weakness (chair stand), reduced muscle strength, and lower values of SPPB score (P < 0.05). Patients with SDB did not show overt clinical signs of cardiac decompensation compared with those without SDB (P > 0.05) but had increased amounts of water (total body water, intracellular, and extracellular) measured using BIA (P < 0.05). Increased amounts of total body water were associated with the severity of SDB and inversely with muscle strength and exercise capacity measured by anaerobic threshold (P < 0.05). Altogether, 17 patients had muscle wasting. Of these, 11 (65%) patients had SDB (statistically not significant). CONCLUSIONS: SDB is highly prevalent in patients with HF. Patients with SDB have lower muscle strength and tend to be more susceptible to preclinical congestion.

Hypokalaemia and outcomes in older patients hospitalized for heart failure.

AIMS: Hypokalaemia is a risk factor for ventricular arrhythmias and sudden death in ambulatory patients with chronic heart failure (HF). The objective of this study was to examine the association between hypokalaemia and outcomes in hospitalized patients with decompensated HF in whom sudden death is less common. METHODS AND RESULTS: Of the 5881 hospitalized patients with HF, 1052 had consistent hypokalaemia (both admission and discharge serum potassium <4.0 mmol/L), and 2538 had consistent normokalaemia (both admission and discharge serum potassium 4.0-5.0 mmol/L). Propensity scores for consistent hypokalaemia, estimated for each of 3590 (1052 + 2538) patients, were used to assemble a matched cohort of 971 pairs of patients with consistent hypokalaemia vs. consistent normokalaemia, balanced on 54 baseline characteristics (mean age, 75 years; 60% women; 28% African American). We repeated the above process to assemble 2327 pairs of patients with discharge potassium <4.0 vs. 4.0-5.0 mmol/L and 449 pairs of patients with discharge serum potassium <3.5 vs. 4.0-5.0 mmol/L. Hazard ratios (HR) and 95% confidence intervals (CIs) associated with hypokalaemia were estimated in matched cohorts. 30 day all-cause mortality occurred in 5% and 4% of patients with consistent normokalaemia vs. consistent hypokalaemia, respectively (HR, 0.78; 95% CI, 0.52-1.18; P = 0.241). HRs (95% CI) for 30 day mortality associated with discharge serum potassium <4.0 and <3.5 mmol/L were 0.90 (0.70-1.16; P = 0.419) and 1.69 (0.94-3.04; P = 0.078), respectively. Hypokalaemia (<4.0 or <3.5 mmol/L) had no association with long-term mortality or other outcomes. CONCLUSIONS: In hospitalized older patients with HF, compared with normokalaemia (serum potassium 4.0-5.0 mmol/L), hypokalaemia (<4.0 or <3.5 mmol/L) had no significant associations with outcomes.

Inferior vena cava ultrasound in acute decompensated heart failure: design rationale of the CAVA-ADHF-DZHK10 trial.

AIMS: Treating patients with acute decompensated heart failure (ADHF) presenting with volume overload is a common task. However, optimal guidance of decongesting therapy and treatment targets are not well defined. The inferior vena cava (IVC) diameter and its collapsibility can be used to estimate right atrial pressure, which is a measure of right-sided haemodynamic congestion. The CAVA-ADHF-DZHK10 trial is designed to test the hypothesis that ultrasound assessment of the IVC in addition to clinical assessment improves decongestion as compared with clinical assessment alone. METHODS AND RESULTS: CAVA-ADHF-DZHK10 is a randomized, controlled, patient-blinded, multicentre, parallel-group trial randomly assigning 388 patients with ADHF to either decongesting therapy guided by ultrasound assessment of the IVC in addition to clinical assessment or clinical assessment alone. IVC ultrasound will be performed daily between baseline and hospital discharge in all patients. However, ultrasound results will only be reported to treating physicians in the intervention group. Treatment target is relief of congestion-related signs and symptoms in both groups with the additional goal to reduce the IVC diameter ≤21 mm and increase IVC collapsibility >50% in the intervention group. The primary endpoint is change in N-terminal pro-brain natriuretic peptide from baseline to hospital discharge. Secondary endpoints evaluate feasibility, efficacy of decongestion on other scales, and the impact of the intervention on clinical endpoints. CONCLUSIONS: CAVA-ADHF-DZHK10 will investigate whether IVC ultrasound supplementing clinical assessment improves decongestion in patients admitted for ADHF.

Cardiac Cachexia Revisited: The Role of Wasting in Heart Failure.

Cardiac cachexia is a co-morbidity of heart failure (HF) defined by a non-edematous weight loss of ≥6% within the previous 6-12 months. Cachexia affects about 10-39% patients with HF and occurs typically in advanced stages of HF, especially in the presence of congestive right ventricular dysfunction. This review elucidates the approaches and pitfalls in the diagnosis of cachexia. It summarizes the prevalence and impact of cardiac cachexia. It also discusses changes in body composition over the course of HF and provides an overview of the mechanisms involved in wasting in HF.

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.

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.

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.

Anorexia, functional capacity, and clinical outcome in patients with chronic heart failure: results from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF).

AIMS: We aimed to assess determinants of anorexia, that is loss of appetite in patients with heart failure (HF) and aimed to further elucidate the association between anorexia, functional capacity, and outcomes in affected patients. METHODS AND RESULTS: We assessed anorexia status among 166 patients with HF (25 female, 66 ± 12 years) who participated in the Studies Investigating Co-morbidities Aggravating HF. Anorexia was assessed by a 6-point Likert scale (ranging from 0 to 5), wherein values ≥1 indicate anorexia. Functional capacity was assessed as peak oxygen uptake (peak VO2 ), 6 min walk test, and short physical performance battery test. A total of 57 patients (34%) reported any anorexia, and these patients showed lower values of peak VO2 , 6 min walk distance, and short physical performance battery score (all P < 0.05). Using multivariate analysis adjusting for clinically important factors, only high-sensitivity C-reactive protein [odds ratio (OR) 1.24, P = 0.04], use of loop diuretics (OR 5.76, P = 0.03), and the presence of cachexia (OR 2.53, P = 0.04) remained independent predictors of anorexia. A total of 22 patients (13%) died during a mean follow-up of 22.5 ± 5.1 months. Kaplan-Meier curves for cumulative survival showed that those patients with anorexia presented higher mortality (Log-rank test P = 0.03). CONCLUSIONS: Inflammation, use of loop diuretics, and cachexia are associated with an increased likelihood of anorexia in patients with HF, and patients with anorexia showed impaired functional capacity and poor outcomes.

Sleep-Disordered Breathing in Acute Ischemic Stroke: A Mechanistic Link to Peripheral Endothelial Dysfunction.

BACKGROUND: Sleep-disordered breathing (SDB) after acute ischemic stroke is frequent and may be linked to stroke-induced autonomic imbalance. In the present study, the interaction between SDB and peripheral endothelial dysfunction (ED) was investigated in patients with acute ischemic stroke and at 1-year follow-up. METHODS AND RESULTS: SDB was assessed by transthoracic impedance records in 101 patients with acute ischemic stroke (mean age, 69 years; 61% men; median National Institutes of Health Stroke Scale, 4) while being on the stroke unit. SDB was defined by apnea-hypopnea index ≥5 episodes per hour. Peripheral endothelial function was assessed using peripheral arterial tonometry (EndoPAT-2000). ED was defined by reactive hyperemia index ≤1.8. Forty-one stroke patients underwent 1-year follow-up (390±24 days) after stroke. SDB was observed in 57% patients with acute ischemic stroke. Compared with patients without SDB, ED was more prevalent in patients with SDB (32% versus 64%; P<0.01). After adjustment for multiple confounders, presence of SDB remained independently associated with ED (odds ratio, 3.1; [95% confidence interval, 1.2-7.9]; P<0.05). After 1 year, the prevalence of SDB decreased from 59% to 15% (P<0.001). Interestingly, peripheral endothelial function improved in stroke patients with normalized SDB, compared with patients with persisting SDB (P<0.05). CONCLUSIONS: SDB was present in more than half of all patients with acute ischemic stroke and was independently associated with peripheral ED. Normalized ED in patients with normalized breathing pattern 1 year after stroke suggests a mechanistic link between SDB and ED. CLINICAL TRIAL REGISTRATION: URL: https://drks-neu.uniklinik-freiburg.de. Unique identifier: DRKS00000514.