Clinical and prognostic role of ammonia in advanced decompensated heart failure. The cardio-abdominal syndrome?

Frea, Simone; Bovolo, Virginia; Pidello, Stefano; Canavosio, Federico Giovanni; Botta, Michela; Bergerone, Serena; Gaïta, Fiorenzo

doi:10.1016/j.ijcard.2015.05.061

Cited by 13 publications

(9 citation statements)

References 53 publications

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“…Sarcopenia or loss of skeletal muscle mass is a frequent complication of cirrhosis, advanced heart failure, and chronic lung disease that adversely impacts outcomes . Despite the high clinical significance, there are limited data on the mechanisms of sarcopenia and consequently a lack of effective therapies .…”

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confidence: 99%

“…S arcopenia or loss of skeletal muscle mass is a frequent complication of cirrhosis, advanced heart failure, and chronic lung disease that adversely impacts outcomes. (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) Despite the high clinical significance, there are limited data on the mechanisms of sarcopenia and consequently a lack of effective therapies. (3) Hyperammonemia is a consistent abnormality in cirrhosis due to impaired ureagenesis capacity and portosystemic shunting.…”

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confidence: 99%

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Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis

Kumar¹,

Davuluri²,

Silva³

et al. 2017

Hepatology

174

151

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Sarcopenia or skeletal muscle loss is a frequent, potentially reversible complication in cirrhosis that adversely affects clinical outcomes. Hyperammonemia is a consistent abnormality in cirrhosis that results in impaired skeletal muscle protein synthesis and breakdown (proteostasis). Despite availability of effective ammonia lowering therapies, whether lowering ammonia restores proteostasis and reverses muscle mass is unknown. Myotube diameter, protein synthesis and molecular responses in C2C12 murine myotubes to withdrawal of ammonium acetate following 24 h exposure to 10mM ammonium acetate were complemented by in vivo studies in the hyperammonemic portacaval anastomosis rat (PCA) and sham operated, pair-fed (SO) Sprague- Dawley rats treated with ammonia lowering therapy by L-ornithine L-aspartate and rifaximin orally for 4 weeks. We observed reduced myotube diameter, impaired protein synthesis and increased autophagy flux in response to hyperammonemia that were partially reversed following 24h and 48h withdrawal of ammonium acetate. Consistently, 4 weeks of ammonia lowering therapy resulted in significant lowering of blood and skeletal muscle ammonia, increase in lean body mass, improved grip strength and higher skeletal muscle mass, diameter and an increase in type II fibers in the treated compared to untreated PCA rats. Increased skeletal muscle myostatin expression, reduced mTORC1 function, and the hyperammonemic stress response including autophagy markers were also reversed in the PCA rats treated with ammonia lowering therapy. Despite significant improvement, molecular and functional readouts were not completely reversed by ammonia lowering measures. Conclusions Ammonia lowering therapy results in improvement in skeletal muscle phenotype, function and molecular perturbations of hyperammonemia. These preclinical studies complement previous studies on ammonia induced skeletal muscle loss and lay the foundation for prolonged ammonia lowering therapy to reverse sarcopenia of cirrhosis.

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confidence: 99%

mentioning

confidence: 99%

Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis

Kumar¹,

Davuluri²,

Silva³

et al. 2017

Hepatology

174

151

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“…They suggested that the occurrence of infection might aggravate the development of hyperammonemia through the effect of intestinal flora [12]. In contrast, Frea et al presented the idea of increased ammonia by "abdominal damage" [6]. Ammonia is mainly produced in the gut as a byproduct of protein digestion [4] and bacterial metabolism [5] and it is markedly increased due to abdominal hemodynamic damage derived from low perfusion or venous congestion derived from heart failure.…”

Section: Discussionmentioning

confidence: 99%

“…Ammonia is mainly produced in the gut as a byproduct of protein digestion [4], bacterial metabolism [5], and liver metabolism. Therefore, hypoperfusion or congestion due to heart failure may lead to increased abdominal and liver damage, which might lead to the failure of ammonia metabolic balance [6]. However, there are scanty reports on cases of hyperammonemic encephalopathy associated with heart failure.…”

Section: Introductionmentioning

confidence: 99%

The Efficacy of Lactulose for the Treatment of Hyperammonemic Encephalopathy Due to Severe Heart Failure

et al. 2020

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Hyperammonemic encephalopathy secondary to heart failure is rare and there had been little reports about effective treatment. Organ hypoperfusion or congestion by heart failure may lead to various organ dysfunctions, and liver and intestinal circulatory impairment might cause ammonia metabolic failure. Here, we report on the case of a patient with hyperammonemic encephalopathy that was secondary to heart failure, which was effectively treated by lactulose.

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“…Patients with severe heart disease and low serumammonia levels have a significantly lower mortality than patients with persistently high ammonia levels (12). In addition, the inflammatory response and multiple organ dysfunction in patients with sepsis are aggravated by higher blood ammonia levels (13,14).…”

Section: Introductionmentioning

confidence: 99%

Prognostic Role of Ammonia in Critical Care Patients Without Known Hepatic Disease

et al. 2020

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Background and Aims: Hyperammonemia usually develops because of hepatic disease, but it may occur in patients with non-hepatic hyperammonemia (NHH). But, studies on the prognosis and possible risk factors of this disorder are lacking. The aim of this study was to find possible prognostic and risk factors for NHH in critically ill patients. Methods: Data were extracted from MIMIC III Database. Survival was analyzed by the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify prognostic factors. Results: Valproic acid, carbamazepine, corticosteroids, recent orthopedic surgery, epilepsy, disorders of urea cycle metabolism, and obesity were found to be risk factors for NHH. Patients in the hyperammonemia group had a higher 30 day mortality than those in the non-hyperammonemia group. After final regression analysis, ammonia was found to be independent predictors of mortality. Conclusion: Ammonia was an independent prognostic predictor of 30 day mortality for critical care patients without liver disease.

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Clinical and prognostic role of ammonia in advanced decompensated heart failure. The cardio-abdominal syndrome?

Cited by 13 publications

References 53 publications

Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis

Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis

The Efficacy of Lactulose for the Treatment of Hyperammonemic Encephalopathy Due to Severe Heart Failure

Prognostic Role of Ammonia in Critical Care Patients Without Known Hepatic Disease

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