Practical guide on left atrial appendage closure for the non-implanting physician: an international consensus paper.

A significant proportion of patients who suffer from atrial fibrillation (AF) and are in need of thromboembolic protection are not treated with oral anticoagulation or discontinue this treatment shortly after its initiation. This undertreatment has not improved sufficiently despite the availability of direct oral anticoagulants which are associated with less major bleeding than vitamin K antagonists. Multiple reasons account for this, including bleeding events or ischaemic strokes whilst on anticoagulation, a serious risk of bleeding events, poor treatment compliance despite best educational attempts, or aversion to drug therapy. An alternative interventional therapy, which is not associated with long-term bleeding and is as effective as vitamin K anticoagulation, was introduced over 20 years ago. Because of significant improvements in procedural safety over the years, left atrial appendage closure, predominantly achieved using a catheter-based, device implantation approach, is increasingly favoured for the prevention of thromboembolic events in patients who cannot achieve effective anticoagulation. This management strategy is well known to the interventional cardiologist/electrophysiologist but is not more widely appreciated within cardiology or internal medicine. This article introduces the devices and briefly explains the implantation technique. The indications and device follow-up are more comprehensively described. Almost all physicians who care for adult patients will have many with AF. This practical guide, written within guideline/guidance boundaries, is aimed at those non-implanting physicians who may need to refer patients for consideration of this new therapy, which is becoming increasingly popular.

The erythropoietin-derived peptide ARA 284 reduces tissue wasting and improves survival in a rat model of cancer cachexia.

BACKGROUND: Cancer cachexia (CC) is a severe complication during the last stages of the disease, which is characterized by the substantial loss of muscle and fat mass. Currently, there is no effective treatment of CC. Erythropoietin plays tissue-protective role in different tissues. Based on the structure of erythropoietin, small non-erythropoietic peptides were synthesized, which activate tissue-protective signalling pathways. METHODS: Here, we investigated the influence of the tissue-protective peptide ARA 284 on CC in rats using the Yoshida hepatoma model. RESULTS: Treatment with ARA 284 (1.7 µg/kg/day) counteracted the loss of body weight (12.46 ± 4.82% ARA 284 vs. 26.85 ± 0.88% placebo, P < 0.01), fat mass (P < 0.01), and lean mass (P < 0.01). It improved spontaneous activity of ARA 284-treated animals. Further, gastrocnemius mass was increased (13.2% ARA 284 vs. placebo, P < 0.01) in association with induced p-Akt (P < 0.01) and decreased in p-p38 MAPK, GSK-3ß, and myostatin (all P < 0.01), suggesting an induction of anabolic pathways. At the same time, we observed the significant increase in the survival of animals by high-dose ARA 284 treatment (hazard ratio: 0.46, 95% confidence interval: 0.23-0.94, P = 0.0325). CONCLUSIONS: Taken together these results suggest that ARA 284 can be considered beneficial in experimental CC and it remains to be seen, if it can have similar beneficial effects in CC patient.

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.

Erythropoietin improves cardiac wasting and outcomes in a rat model of liver cancer cachexia.

BACKGROUND: Erythropoietin administration, which is clinically used in cancer patients with cancer-induced anemia, has also potentially beneficial effects on nonhematopoietic organs. We assessed the effects of erythropoietin on cancer cachexia progression and cardiac wasting compared with placebo using the Yoshida hepatoma model. METHODS: Wistar rats were divided in a sham group (n=10) and a tumor-bearing group (n=60). The tumor-bearing group was further randomized to placebo (n=28), 500Unit/kg/day (n=16) or 5000Unit/kg/day of erythropoietin (n=16). Body composition was measured using nuclear magnetic resonance spectroscopy, cardiac function using echocardiography, physical activity using infrared monitoring system. RESULTS: Tumor-bearing rats with high dose erythropoietin led to a significant improvement on survival compared with placebo (hazard ratio: 0.43, 95%CI: 0.20-0.92, p=0.030), though low dose erythropoietin did not reach significance (hazard ratio: 0.46, 95%CI: 0.22-1.02, p=0.056). Loss of body weight, wasting of lean mass, fat mass, and reduced physical activity were ameliorated in rats treated with both low and high doses of erythropoietin (p<0.05, all). Moreover, reduced left ventricular mass and left ventricular systolic function were also ameliorated in rats treated with low and high doses of erythropoietin (p<0.05, respectively). CONCLUSIONS: Overall, the present data support that cardiac wasting induced by cancer cachexia plays an important role which leads to impaired survival, provided that the erythropoietin could be an effective therapeutic approach for cancer cachexia progression and cardiac wasting.

Extraordinarily favorable left ventricular reverse remodeling through long-term cardiac resynchronization: super-response to cardiac resynchronization.

BACKGROUND: Some chronic heart failure (CHF) patients show remarkable improvement in left ventricular (LV) remodeling after cardiac resynchronization therapy (CRT), for unclear reasons. This study aimed at identifying predictors of an extraordinarily favorable response to CRT. METHODS: We studied 136 CRT patients (104 men, median 66 years, QRS 162 ms, left ventricular ejection fraction 24 ± 7%, 70% coronary disease, all left bundle branch block [LBBB]). We measured LV end diastolic diameter (LVEDD) before and after long-term (9.4 ± 6.3 months) CRT. At baseline, LV pre-ejection interval (LVPEI), interventricular mechanical delay (IVMD), LV dyssynchrony (standard deviation of electromechanical delays [SDEMD] in eight LV segments), exercise capacity (pVO(2)), and ventilatory efficiency (VE/VCO(2)) were assessed. Patients with a LVEDD reduction beyond the 80th percentile (high responders [HR]) were compared to low responders (LR). RESULTS: In the HR group (n = 22), LVEDD was reduced from 71 to 52 mm (LR 64-61 mm, P < 0.001). HR had predominantly nonischemic heart disease (HR: 72%, LR: 44%, P = 0.019), tended to have a wider QRS (HR: 178 ms, LR: 162 ms, P = 0.066), had a longer LVPEI (HR: 179 ms, LR: 155 ms, P = 0.004), wider IVMD (HR: 60 ms, LR 48 ms, P = 0.05), larger LVEDD (P = 0.002), higher SDEMD (HR: 69 ms, LR: 46 ms, P = 0.044), but higher pVO(2) (HR: 17.5 mL/min/kg, LR: 13.5 mL/kg/min, P = 0.025) and lower VE/VCO(2) (HR: 31, LR: 35, P = 0.043), all compared to LR patients. CONCLUSION: Extraordinarily favorable reverse LV remodeling through CRT in CHF and LBBB appears to require a particularly dilated LV due to nonischemic heart disease with pronounced electromechanical alteration, but with a fairly preserved functional capacity before CRT.