Why is Iron Deficiency Recognised as an Important Comorbidity in Heart Failure?

There is an increasing awareness of the prevalence of iron deficiency in patients with heart failure (HF), and its contributory role in the morbidity and mortality of HF. Iron is a trace element necessary for cells due to its capacity to transport oxygen and electrons. The prevalence of iron deficiency increases with the severity of HF. For a long time the influence of iron deficiency was underestimated, especially in terms of worsening of cardiovascular diseases and developing anaemia. In recent years, studies with intravenous iron agents in patients with iron deficiency and HF showed new insights into the improvement of iron therapy. Additionally, experimental studies supporting the understanding of iron metabolism and the resulting pathophysiological pathways of iron have been carried out. The aim of this mini review is to highlight why iron deficiency is recognised as an important comorbidity in HF

Changes in serum creatinine in the first 24 hours after cardiac arrest indicate prognosis: an observational cohort study

INTRODUCTION: As patients after cardiac arrest suffer from the consequences of global ischemia reperfusion, we aimed to establish the incidence of acute kidney injury (AKI) in these patients, and to investigate its possible association to severe hypoxic brain damage. METHODS: One hundred and seventy-one patients (135 male, mean age 61.6 +/- 15.0 years) after cardiac arrest were included in an observational cohort study. Serum creatinine was determined at admission and 24, 48 and 72 hours thereafter. Serum levels of neuron-specific enolase (NSE) were measured 72 hours after admission as a marker of hypoxic brain damage. Clinical outcome was assessed at intensive care unit (ICU) discharge using the Pittsburgh cerebral performance category (CPC). RESULTS: AKI as defined by AKI Network criteria occurred in 49% of the study patients. Patients with an unfavourable prognosis (CPC 3-5) were affected significantly more frequently (P = 0.013). Whilst serum creatinine levels decreased in patients with good neurological outcome (CPC 1 or 2) over the ensuing 48 hours, it increased in patients with unfavourable outcome (CPC 3-5). ROC analysis identified DeltaCrea24 <-0.19 mg/dl as the value for prediction with the highest accuracy. The odds ratio for an unfavourable outcome was 3.81 (95% CI 1.98-7.33, P = 0.0001) in cases of unchanged or increased creatinine levels after 24 hours compared to those whose creatinine levels decreased during the first 24 hours. NSE levels were found to correlate with the change in serum creatinine in the first 24 hours both in simple and multivariate regression (both r = 0.24, P = 0.002). CONCLUSIONS: In this large cohort of patient after cardiac arrest, we found that AKI occurs in nearly 50% of patients when the new criteria are applied. Patients with unfavourable neurological outcome are affected more frequently. A significant association between the development of AKI and NSE levels indicating hypoxic brain damage was observed. Our data show that changes in serum creatinine may contribute to the prediction of outcome in patients with cardiac arrest. Whereas a decline in serum creatinine (> 0.2 mg/dL) in the first 24 hours after cardiac arrest indicates good prognosis, the risk of unfavourable outcome is markedly elevated in patients with constant or increasing serum creatinine

IGF-1 treatment reduces weight loss and improves outcome in a rat model of cancer cachexia

Background: A hallmark symptom of cancer cachexia is the loss of skeletal muscle. This is at least partially due to a deregulation of the growth hormone/IGF-1 axis and a subsequently impaired protein synthesis in skeletal muscle. Here, we investigated the effect of IGF-1 supplementation in a rat model of cancer cachexia. Methods: Juvenile rats were inoculated with the Yoshida AH-130 hepatoma and treated once daily with 0.3 mg kg−1 day−1 (low dose) or 3 mg kg−1 day−1 (high dose) IGF-1 or placebo for a period of maximal 16 days. Body weight and body composition (by NMR) were assessed at baseline and at the end of the study or day of death. Locomotor activity and food intake were assessed at baseline and day 10/11 after tumour inoculation for 24 h. Results: Untreated tumour-bearing rats lost 55.3 ± 2.14 g body weight, which was reduced by low-dose to −39.6 ± 11.1 g (p = 0.0434) and high-dose IGF-1 to −42.7 ± 8.8 g (p = 0.057). Placebo-treated rats lost 41.4 ± 2.0-g lean mass, which was attenuated by low-dose IGF-1 (−28.8 ± 8.3 g, p = 0.041) and high-dose IGF-1 (−30.9 ± 7.4, p = 0.067). Spontaneous activity and food intake were improved by low-dose IGF-1 only. No effect on fat mass was observed. Low-dose IGF-1 significantly reduced mortality (HR = 0.45, 95%CI = 0.21–0.93, p = 0.0315), whilst the high dose did not reach significance (HR = 0.68, 95%CI = 0.26–1.74, p = 0.42). Conclusion: Low-dose IGF-1 reduced mortality and attenuated loss of body weight as well as muscle mass in the Yoshida hepatoma rat model. Moreover, an improved quality of life was observed in these animals. Further experiments using different doses are necessary

Efficacy and safety of intravenous iron repletion in patients with heart failure : a systematic review and meta-analysis

Introduction AFFIRM-AHF and IRONMAN demonstrated lower rates of the combined endpoint recurrent heart failure (HF) hospitalizations and cardiovascular death (CVD) using intravenous (IV) ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), respectively in patients with HF and iron defciency (ID) utilizing prespecifed COVID-19 analyses. Material and methods We meta-analyzed efcacy, between trial heterogeneity and data robustness for the primary endpoint and CVD in AFFIRM-AHF and IRONMAN. As sensitivity analysis, we analyzed data from all eligible exploratory trials investigating FCM/FDI in HF. Results FCM/FDI reduced the primary endpoint (RR=0.81, 95% CI 0.69–0.95, p=0.01, I 2=0%), with the number needed to treat (NNT) being 7. Power was 73% and fndings were robust with fragility index (FI) of 94 and fragility quotient (FQ) of 0.041. Efects of FCM/FDI were neutral concerning CVD (OR=0.88, 95% CI 0.71–1.09, p=0.24, I 2=0%). Power was 21% while fndings were fragile with reverse FI of 14 and reversed FQ of 0.006. The sensitivity analysis from all eligible trials (n=3258) confrmed positive efects of FCM/FDI on the primary endpoint (RR=0.77, 95% CI 0.66–0.90, p=0.0008, I 2=0%), with NNT being 6. Power was 91% while fndings were robust (FI of 147 and FQ of 0.045). Efect on CVD was neutral (RR=0.87, 95% CI 0.71–1.07, p=0.18, I 2=0%). Power was 10% while fndings were fragile (reverse FI of 7 and reverse FQ of 0.002). Rate of infections (OR=0.85, 95% CI 0.71–1.02, p=0.09, I 2=0%), vascular disorder (OR=0.84, 95% CI 0.57–1.25, p=0.34, I 2=0%) and general or injection-site related disorders (OR=1.39, 95% CI 0.88–1.29, p=0.16, I 2=30%) were comparable between groups. There was no relevant heterogeneity (I 2>50%) between the trials for any of the analyzed outcomes. Conclusions Use of FCM/FDI is safe and reduces the composite of recurrent HF hospitalizations and CVD, while efects on CVD alone are based on available level of data indeterminate. Findings concerning composite outcomes exhibit a high level of robustness without heterogeneity between trials with FCM and FDI

Ursodeoxycholic acid treatment in a rat model of cancer cachexia

UDCA treatment in the Yoshida hepatoma model showed a trend towards attenuation of tissue loss in animals with progressive weight loss in cancer cachexia. Tumor growth and activity indicators were not altered. Both doses of UDCA tended to reduce the mortality rates in tumor-bearing animals. Larger studies with longer follow-up are required to verify these findings

Impact of the COVID-19 pandemic on implementation of novel guideline-directed medical therapies for heart failure in Germany: a nationwide retrospective analysis

Background Guideline-directed medical therapy (GDMT) is the cornerstone in the treatment of patients with heart failure and reduced ejection fraction (HFrEF) and novel substances such as sacubitril/valsartan (S/V) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) have demonstrated marked clinical benefits. We investigated their implementation into real-world HF care in Germany before, during, and after the COVID-19 pandemic period. Methods The IQVIA LRx data set is based on ∼80% of 73 million people covered by the German statutory health insurance. Prescriptions of S/V were used as a proxy for HFrEF. Time trends were analysed between Q1/2016 and Q2/2023 for prescriptions for S/V alone and in combination therapy with SGLT2i. Findings The number of patients treated with S/V increased from 5260 in Q1/2016 to 351,262 in Q2/2023. The share of patients with combination therapy grew from 0.6% (29 of 5260) to 14.2% (31,128 of 219,762) in Q2/2021, and then showed a steep surge up to 54.8% (192,429 of 351,262) in Q2/2023, coinciding with the release of the European Society of Cardiology (ESC) guidelines for HF in Q3/2021. Women and patients aged >80 years were treated less often with combined therapy than men and younger patients. With the start of the COVID-19 pandemic, the number of patients with new S/V prescriptions dropped by 17.5% within one quarter, i.e., from 26,855 in Q1/2020 to 22,145 in Q2/2020, and returned to pre-pandemic levels only in Q1/2021. Interpretation The COVID-19 pandemic was associated with a 12-month deceleration of S/V uptake in Germany. Following the release of the ESC HF guidelines, the combined prescription of S/V and SGLT2i was readily adopted. Further efforts are needed to fully implement GDMT and strengthen the resilience of healthcare systems during public health crises

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

Intestinal blood flow in patients with chronic heart failure: A link with bacterial growth, gastrointestinal symptoms, and cachexia

Background: Blood flow in the intestinal arteries is reduced in patients with stable heart failure (HF) and relates to gastrointestinal (GI) symptoms and cardiac cachexia. Objectives: The aims of this study were to measure arterial intestinal blood flow and assess its role in juxtamucosal bacterial growth, GI symptoms, and cachexia in patients with HF. Methods: A total of 65 patients and 25 controls were investigated. Twelve patients were cachectic. Intestinal blood flow and bowel wall thickness were measured using ultrasound. GI symptoms were documented. Bacteria in stool and juxtamucosal bacteria on biopsies taken during sigmoidoscopy were studied in a subgroup by fluorescence in situ hybridization. Serum lipopolysaccharide antibodies were measured. Results: Patients showed 30% to 43% reduced mean systolic blood flow in the superior and inferior mesenteric arteries and celiac trunk (CT) compared with controls (p < 0.007 for all). Cachectic patients had the lowest blood flow (p < 0.002). Lower blood flow in the superior mesenteric artery and CT was correlated with HF severity (p < 0.04 for all). Patients had more feelings of repletion, flatulence, intestinal murmurs, and burping (p < 0.04). Burping and nausea or vomiting were most severe in patients with cachexia (p < 0.05). Patients with lower CT blood flow had more abdominal discomfort and immunoglobulin A–antilipopolysaccharide (r = 0.76, p < 0.02). Antilipopolysaccharide response was correlated with increased growth of juxtamucosal but not stool bacteria. Patients with intestinal murmurs had greater bowel wall thickness of the sigmoid and descending colon, suggestive of edema contributing to GI symptoms (p < 0.05). In multivariate regression analysis, lower blood flow in the superior mesenteric artery, CT (p < 0.04), and inferior mesenteric artery (p = 0.056) was correlated with the presence of cardiac cachexia. Conclusions: Intestinal blood flow is reduced in patients with HF. This may contribute to juxtamucosal bacterial growth and GI symptoms in patients with advanced HF complicated by cachexia