The interplay between metabolic alterations,diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study

Background

Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity.

Methods

Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent ¹H-cardiovascular magnetic resonance spectroscopy (¹H-CMRS) to measure MTG (lipid/water, %), ³¹P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate.

Results

When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45?±?0.25% vs. 0.64?±?0.16%, p?=?0.009) and reduced PCr/ATP (1.60?±?0.09 vs. 2.00?±?0.10, p?=?0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO₂ max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO₂ max.

Conclusions

Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.

     

Fast-track laparoscopic bariatric surgery: a systematic review

This study aimed to systematically evaluate the evidence-based literature on fast-track laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic adjustable gastric banding (LAGB) to determine the feasibility and safety of fast-track laparoscopic bariatric surgery. A literature search of PubMed, EMBASE and Cochrane Library using the MeSH terms “bariatric surgery”, “ambulatory surgical procedures” and related terms as keywords was performed. The study included articles that reported on intended next-day discharge for LRYGB and same-day discharge for LAGB. Data were extracted on study design and size, patient demographics, patient-selection criteria, patient preparation, perioperative management, operative details, clinical outcomes, and follow-up. The review included 13 studies classified as level 3b or 4 evidence. There were seven studies that investigated LAGB, five studies investigated LRYGB and one study detailed outcomes from both LRYGB and LAGB. Next-day discharge rate ranged from 81 to 100 % for LRYGB. Same-day discharge rate ranged from 76 to 98 % for LAGB. In LRYGB and LAGB complication, re-admission and mortality rates (≤10.5, ≤7.5, ≤0.1 %, respectively) were comparable with the conventional perioperative care. From our results, the fast-track management of patients undergoing LRYGB and LAGB is feasible. With careful patient selection and preparation within high-volume centres, and application of care pathways including close outpatient follow-up, outcomes for fast-track bariatric procedures can compare favourably with those reported in the literature for standard management, but with decreased cost. However, further studies from independent researchers are required to determine the safety of a generalised adoption of this approach outside of dedicated bariatric units, and to formally demonstrate the cost-benefit of fast-track bariatric surgery.     

Biased Homozygous Haplotypes Across the Human Caveolin 1 Upstream Purine Complex in Parkinson’s Disease

The alpha-synuclein–caveolin 1 axis is suggested to be of role in the pathogenesis of Parkinson’s disease in cell line models. The objective of this study was to analyze the homozygous haplotype compartment of the human caveolin 1 gene upstream purine complex in patients afflicted with Parkinson’s disease. This complex was screened in patients with Parkinson’s disease (n?=?141) and compared with a group of controls (n?=?760) using polymerase chain reaction and sequencing. The expression activity of the homozygous haplotypes was then examined using luciferase Dual-Glo system in human neuronal cell line, LAN-5. Six haplotypes were found to be homozygous in the patients, and not in the control pool (Fisher exact p?<?1?×?10^?6). Three of those haplotypes were specific to Parkinson’s disease (Fisher exact p?<?0.002), and the remaining three overlapped with homozygous haplotypes in Alzheimer’s disease and multiple sclerosis (Fisher exact p?<?0.002). The disease haplotypes contained motif lengths that were nonexistent in the control homozygous haplotype pool and significantly increased gene expression (p?<?9?×?10^—6). We conclude that skew in the caveolin 1 purine complex homozygous haplotype compartment and an additive effect of those haplotypes may be linked with Parkinson’s disease.     

Remote ischemic preconditioning with – but not without – metabolic support protects the neonatal porcine heart against ischemia-reperfusion injury

Background

While remote ischemic preconditioning (rIPC) protects the mature heart against ischemia-reperfusion (IR) injury, the effect on the neonatal heart is not known. The neonatal heart relies almost solely on carbohydrate metabolism, which is modified by rIPC in the mature heart. We hypothesized that rIPC combined with metabolic support with glucose-insulin (GI) infusion improves cardiac function and reduces infarct size after IR injury in neonatal piglets in-vivo.

Methods and results

32 newborn piglets were randomized into 4 groups: control, GI, GI + rIPC and rIPC. GI and GI + rIPC groups received GI infusion continuously from 40 min prior to ischemia. rIPC and GI + rIPC groups underwent four cycles of 5 min limb ischemia. Myocardial IR injury was induced by 40 min occlusion of the left anterior descending artery followed by 2 h reperfusion. Myocardial lactate concentrations were assessed in microdialysis samples analyzed by mass spectrometry. Infarct size was measured using triphenyltetrazolium chloride staining. Systolic recovery (dP/dt_max as % of baseline) after 2 h reperfusion was 68.5 ± 13.8% in control, 53.7 ± 11.2% in rIPC (p < 0.05), and improved in GI (83.6 ± 18.8%, p < 0.05) and GI + rIPC (87.0 ± 15.7%, p < 0.01).

Conclusion

rIPC + GI protects the neonatal porcine heart against IR injury in-vivo. rIPC alone has detrimental metabolic and functional effects that are abrogated by simultaneous GI infusion.     

Is the structure of anatomy curriculum adequate for safe medical practice?

IntroductionAnatomy has been considered a core subject within the medical education curriculum. In the current setting of ever-changing diagnostic and treatment modalities, the opinion of both students and trainers is crucial for the design of an anatomy curriculum which fulfils the criteria required for safe medical practice.MethodsMedical students, trainees and specialist trainee doctors and specialists from the London (England) area were surveyed to investigate the how curriculum changes have affected the relevance of anatomical knowledge to clinical practice and to identify recommendations for optimum teaching methods. The survey employed 5-point Likert scales and multiple-choice questions. Where the effect of training level was statistically significant (p < 0.05), post-hoc analysis was carried out using Mann–Whitney U tests. Significance levels were modified according to the Bonferroni method.ResultsTwo hundred and twenty-eight individuals completed the survey giving a response rate of 53%. Medical students, trainees and specialists all agreed (mean Likert score 4.51, 4.79, 4.69 respectively) that knowledge of anatomy is important for medical practice. Most of the trainees (88.4%) and specialists (81.3%) used dissection to learn anatomy, but only 61.4% of medical students used this approach. Dissection was the most commonly recommended approach for learning anatomy across all the groups (41.7%–69.3%).ConclusionsKnowledge of anatomy is perceived to be important for safe clinical practice. Anatomy should be taught with other relevant system or clinical modules. Newer tools for anatomy teaching need further validation before incorporation into the curriculum.     

Insulin resistance,its consequences for the clinical course of the disease,and possibilities of correction in endometrial cancer

Objectives To study the frequency of insulin resistance (IR) in endometrial cancer patients, its relation to the clinical course of the disease and DNA damage, and to evaluate possible approaches to the pharmacological correction of IR in the patients studied.Methods The signs of insulin resistance syndrome and its association with the clinical and pathological features of the disease and DNA damage in somatic cells (micronucleus frequency in peripheral blood lymphocytes) and endometrial normal and tumor tissue (alkaline unwinding) were determined in 99 endometrial cancer patients.Results The frequency of insulin resistance syndrome counted on the basis of fasting plasma glucose and insulin concentrations according to Duncan et al. is equal to 0.35 (95% CI 0.24–0.46), or 35%, in endometrial cancer patients who do not have a history of diabetes mellitus. Patients with well- or moderately differentiated endometrial adenocarcinomas (mostly type I) had statistically significantly higher basal and stimulated plasma insulin and C-peptide concentrations than patients with poorly differentiated endometrial adenocarcinomas or rarely encountered tumors of the endometrium (primarily type II). Interestingly, the level of fasting insulinemia positively correlates with disease stage and with local and regional tumor dissemination only in the group of patients with well- or moderately differentiated endometrial adenocarcinomas. On the other hand, hyperinsulinemia and other hormonal-metabolic disturbances typical of insulin resistance syndrome do not increase the probability of DNA damage of somatic cells (according to the data of micronucleus test). In addition, no association between hormonal-metabolic disturbances and the degree of DNA unwinding in tumor and visually unchanged endometrium was found.Conclusion Thus, insulin resistance/hyperinsulinemia is associated with a more aggressive course of the disease in certain groups of the patients but—in contrast to excessive estrogenic stimulation—does not result in increased genotoxic damage in tumor and normal tissues. The data obtained once more confirm the need for treatment and prevention measures aimed at correcting hormonal-metabolic disturbances in endometrial cancer patients and groups at risk of this disease. Such an approach might include use of antidiabetic biguanides, thiazolidinediones (glitazones), and statins.