Liver tests,cardiovascular outcomes and effects of empagliflozin in patients with heart failure and preserved ejection fraction: The EMPEROR-Preserved trial

Aim

The prognostic implication of elevated liver tests in heart failure with preserved ejection fraction (HFpEF) is uncertain. This analysis investigates the association of liver markers with hospitalization for heart failure (HHF) and cardiovascular death (CVD), and the treatment effect of empagliflozin across the range of liver marker levels.

Methods and results

The double-blind, placebo-controlled EMPEROR-Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure with Preserved Ejection Fraction) enrolled 5988 patients with HFpEF (ejection fraction >40%). Patients in New York Heart Association class II–IV and elevated N-terminal pro-B-type natriuretic peptide were randomized to receive empagliflozin 10 mg daily or placebo in addition to usual therapy. Patients with significant liver disease were excluded. The primary endpoint was time to first adjudicated HHF or CVD. We explored the association of liver function abnormalities with heart failure outcomes in patients on placebo, the effects of empagliflozin on liver tests and the treatment effects of empagliflozin on heart failure outcomes across categories of liver laboratory values. High alkaline phosphatase (p trend < 0.0001), low albumin (p trend < 0.0001) and high bilirubin (p = 0.02) were associated with poorer outcomes for HHF or CVD, while high aspartate aminotransferase was not, and high alanine aminotransferase was associated with better outcomes. Empagliflozin had no significant effects on liver tests compared to placebo except for albumin which was significantly increased. The treatment effect of empagliflozin on outcomes was not modified by liver tests.

Conclusion

Abnormalities of liver function tests are associated differently with heart failure outcomes. Salutary effects of empagliflozin on liver tests were not observed although albumin increased. The treatment benefits of empagliflozin were not affected by baseline values of liver parameters.     

Endothelial progenitor cells mobilization after maximal exercise according to heart failure severity

BACKGROUNDVascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure (CHF). Patients with CHF are characterized by impaired vasodilation and inflammation of the vascular endothelium. They also have low levels of endothelial progenitor cells (EPCs). EPCs are bone marrow derived cells involved in endothelium regeneration, homeostasis, and neovascularization. Exercise has been shown to improve vasodilation and stimulate the mobilization of EPCs in healthy people and patients with cardiovascular comorbidities. However, the effects of exercise on EPCs in different stages of CHF remain under investigation.AIMTo evaluate the effect of a symptom-limited maximal cardiopulmonary exercise testing (CPET) on EPCs in CHF patients of different severity.METHODSForty-nine consecutive patients (41 males) with stable CHF [mean age (years): 56 ± 10, ejection fraction (EF, %): 32 ± 8, peak oxygen uptake (VO₂, mL/kg/min): 18.1 ± 4.4] underwent a CPET on a cycle ergometer. Venous blood was sampled before and after CPET. Five circulating endothelial populations were quantified by flow cytometry: Three subgroups of EPCs [CD34⁺/CD45^-/CD133⁺, CD34⁺/CD45^-/CD133⁺/VEGFR₂ and CD34⁺/CD133⁺/vascular endothelial growth factor receptor 2 (VEGFR₂)] and two subgroups of circulating endothelial cells (CD34⁺/CD45^-/CD133^- and CD34⁺/CD45^-/CD133^-/VEGFR₂). Patients were divided in two groups of severity according to the median value of peak VO₂ (18.0 mL/kg/min), predicted peak VO₂ (65.5%), ventilation/carbon dioxide output slope (32.5) and EF (reduced and mid-ranged EF). EPCs values are expressed as median (25th-75th percentiles) in cells/10⁶ enucleated cells.RESULTSPatients with lower peak VO₂ increased the mobilization of CD34⁺/CD45^-/CD133⁺ [pre CPET: 60 (25-76) vs post CPET: 90 (70-103) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD45^-/CD133⁺/VEGFR₂ [pre CPET: 1 (1-4) vs post CPET: 5 (3-8) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD45^-/CD133^- [pre CPET: 186 (141-361) vs post CPET: 488 (247-658) cells/10⁶ enucleated cells, P < 0.001] and CD34⁺/CD45^-/CD133^-/VEGFR₂ [pre CPET: 2 (1-2) vs post CPET: 3 (2-5) cells/10⁶ enucleated cells, P < 0.001], while patients with higher VO₂ increased the mobilization of CD34⁺/CD45^-/CD133⁺ [pre CPET: 42 (19-73) vs post CPET: 90 (39-118) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD45^-/CD133⁺/VEGFR₂ [pre CPET: 2 (1-3) vs post CPET: 6 (3-9) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD133⁺/VEGFR₂ [pre CPET: 10 (7-18) vs post CPET: 14 (10-19) cells/10⁶ enucleated cells, P < 0.01], CD34⁺/CD45^-/CD133^- [pre CPET: 218 (158-247) vs post CPET: 311 (254-569) cells/10⁶ enucleated cells, P < 0.001] and CD34⁺/CD45^-/CD133^-/VEGFR₂ [pre CPET: 1 (1-2) vs post CPET: 4 (2-6) cells/10⁶ enucleated cells, P < 0.001]. A similar increase in the mobilization of at least four out of five cellular populations was observed after maximal exercise within each severity group regarding predicted peak, ventilation/carbon dioxide output slope and EF as well (P < 0.05). However, there were no statistically significant differences in the mobilization of endothelial cellular populations between severity groups in each comparison (P > 0.05).CONCLUSIONOur study has shown an increased EPCs and circulating endothelial cells mobilization after maximal exercise in CHF patients, but this increase was not associated with syndrome severity. Further investigation, however, is needed.     

Periprosthetic bone mineral density after total hip arthroplasty with an AMIStem or Quadra femoral component performed by a minimally invasive anterior approach (AMIS): a prospective randomized clinical dual-energy X-ray absorptiometry study

Introduction

This prospective 12 months of dual-energy X-ray absorptiometry (DEXA) study evaluated differences in periprosthetic bone mineral density in 40 patients undergoing cementless total hip arthroplasty (THA) by a minimally invasive anterior approach (AMIS), using Medacta AMIStem or Quadra stems. Both stems are straight rectangular. AMIStem shows reduced lateral flare and length in comparison to Quadra.

Objectives

The main goal of the study is to verify if bone mineral density is equivalent following THA with the AMIStem and Quadra femoral components.

Methods

Forty patients were randomly allocated to the Quadra and AMIStem groups. Three patients were lost to follow-up because they moved to another town, and revision surgery was performed on one patient due to periprosthetic fracture after a car accident. Patients were examined clinically and underwent DEXA preoperatively and at 1 week, 6 weeks, 6 months, and 1 year after THA. Patients enrolled had no preexisting lower limb arthroplasty and no osteoporosis.

Results

Harris hip score increased significantly for Quadra stem 5.3?±?14.1 and AMIStem 41.0?±?13.4. The high-activity hip score increased significantly for Quadra stem 3.8 ±2.2 and AMIStem 4.1?±?2.4. Considering 0.15 mg/cm² as an acceptable difference, bone mineral density for AMIStem and Quadra groups was statistically equivalent. A limited remodeling process with slight bone loss in the proximal calcar region R7, as expected after implantation of uncemented components, was observed for both stems.

Conclusions

The study demonstrates that the two stems are statistically equivalent in all zones at all time points investigated.     

ESPEN Guidelines on Parenteral Nutrition: On Cardiology and Pneumology

Nutritional support is becoming a mainstay of the comprehensive therapeutic approach to patients with chronic diseases. Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are frequently associated with the progressive development of malnutrition, due to reduced energy intake, increased energy expenditure and impaired anabolism. Malnutrition and eventually cachexia have been shown to have a negative influence on the clinical course of CHF and COPD, and to impinge on patients' quality of life. Nutritional support in these patients should be therefore considered, particularly to prevent progressive weight loss, since restoration of lean and fat body mass may not be achievable. In CHF and COPD patients, the gastrointestinal tract is normally accessible and functioning. Although recent reports suggest that heart failure is associated with modifications of intestinal morphology, permeability and absorption, the clinical relevance of these are still not clear. Oral supplementation and enteral nutrition should represent the first choices when cardiopulmonary patients need nutritional support, particularly given the potential complications and economic burden of parenteral nutrition. This appropriately preferential enteral approach partly explains the lack of robust clinical trials of the role of parenteral nutrition in CHF and COPD patients. Based on the available evidence collected via PubMed, Medline, and SCOPUS searches, it is recommended that parenteral nutrition is reserved for those patients in whom malabsorption has been documented and in those in whom enteral nutrition has failed.

Summary of statements: Parenteral Nutrition in Cardiology
Subject	Recommendations	Grade	Number
Background	The prevalence of cardiac cachexia, defined from weight loss of at least 6% in 6 months, has been estimated at about 12–15% in patients in New York Heart Association (NYHA) classes II–IV. The incidence of weight loss >6% in CHF patients with NYHA class III/IV is approximately 10% per year. CHF affects nutritional state, energy and substrate metabolism.	B	1.1
	The mortality in CHF patients with cardiac cachexia is 2–3 times higher than in non-cachectic CHF patients.	B	1.2
	Although there is limited evidence that gut function is impaired in CHF, decreased cardiac function can reduce bowel perfusion and lead to bowel wall oedema, resulting in malabsorption.	B	1.3
Indications	Although there is no evidence available from well-designed studies, PN is recommended to stop or reverse weight loss in patients with evidence of malabsorption, on the basis that it improves outcome in other similar conditions and there is a plausible physiological argument for it.	C	1.4
	Currently there is no indication for PN in the prophylaxis of cardiac cachexia. Further studies are needed to assess the impact of the parenteral administration of specific substrates on cardiac function.	C	1.5
Contra-indications	There are no specific contraindications to PN in CHF patients. However, considering that cardiac function is decreased and water retention is frequently found in CHF patients, it is recommended that PN should be avoided, other than in patients with evidence of malabsorption in whom enteral nutrition has been shown, or is strongly expected, to be ineffective.	B	1.6
Implementation	When feeding CHF patients, either enterally or parenterally, fluid overload must be avoided.	C	1.6
Summary of statements: Parenteral Nutrition in Respiratory Medicine
Subject	Recommendations	Grade	Number
Background	Between 25% and 40% of patients with advanced COPD are malnourished.	B	2.1
	Being underweight and having low fat-free mass are independently associated with a poor prognosis in patients with chronic respiratory insufficiency, especially in COPD.	B	2.2
Indications	There is no evidence showing that gut function is impaired in COPD patients. Therefore, considering that enteral nutrition is less expensive and associated with fewer and less severe complications than parenteral nutrition, enteral nutrition should represent the first approach to patients with COPD in need of nutritional support.	B	2.3
	There is limited evidence that COPD patients intolerant of EN profit from PN. Small studies do however suggest that, in combination with exercise and anabolic pharmacotherapy, PN has the potential to improve nutritional status and function.	C	2.4
Effect of PN	Loss of body weight is correlated with increased morbidity and mortality. However, due to the lack of studies of its effects, it is not possible to be sure if prognosis is influenced by the provision of PN.	B	2.5
Regimen selection	In patients with stable COPD, glucose-based PN causes an increase in the respiratory CO2 load. PN composition should accordingly be orientated towards lipids as the energy source. There is not sufficient evidence to recommend specific lipid substrates.	B	2.6

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