Effect of disease-modifying agents and their association with mortality in multi-morbid patients with heart failure with reduced ejection fraction

Aims An increasing proportion of patients with heart failure with reduced ejection fraction (HFrEF) have co‐morbidities. The effect of these co‐morbidities on modes of death and the effect of disease‐modifying agents in multi‐morbid patients is unknown. Methods and results We performed a prospective cohort study of ambulatory patients with HFrEF to assess predictors of outcomes. We identified four key co‐morbidities—ischaemic aetiology of heart failure, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and chronic kidney disease (CKD)—that were highly prevalent and associated with an increased risk of all‐cause mortality. We used these data to explore modes of death and the utilization of disease‐modifying agents in patients with and without these co‐morbidities. The cohort included 1789 consecutively recruited patients who had an average age of 69.6 ± 12.5 years, and 1307 (73%) were male. Ischaemic aetiology of heart failure was the most common co‐morbidity, occurring in 1061 (59%) patients; 503 (28%) patients had diabetes mellitus, 283 (16%) had COPD, and 140 (8%) had CKD stage IV/V. During mean follow‐up of 3.8 ± 1.6 years, 737 (41.5%) patients died, classified as progressive heart failure (n = 227, 32%), sudden (n = 112, 16%), and non‐cardiovascular deaths (n = 314, 44%). Multi‐morbid patients were older (P 2.5‐fold and 1.5‐fold increased risk of sudden death, whilst higher doses of beta‐adrenoceptor antagonists were protective (hazard ratio per milligram 0.92, 95% confidence interval 0.86–0.98, P = 0.009). Each milligram of bisoprolol‐equivalent beta‐adrenoceptor antagonist was associated with 9% (P = 0.001) and 11% (P = 0.023) reduction of sudden deaths in patients with <2 and ≥2 co‐morbidities, respectively. Conclusions Higher doses of beta‐adrenoceptor antagonist are associated with greater protection from sudden death, most evident in multi‐morbid patients. Patients with COPD who appear to be at the highest risk of sudden death are prescribed the lowest doses and less likely to be implanted with implantable cardioverter defibrillators, which might represent a missed opportunity to optimize safe and proven therapies for these patients

Impact of QRS duration on left ventricular remodelling and survival in patients with heart failure

Aims In patients with chronic heart failure, QRS duration is a consistent predictor of poor outcomes. It has been suggested that for indicated patients, cardiac resynchronization therapy (CRT) could come sooner in the treatment algorithm, perhaps in parallel with the attainment of optimal guideline-directed medical therapy (GDMT). We aimed to investigate differences in left ventricular (LV) remodelling in those with narrow QRS (NQRS) compared with wide QRS (WQRS) in the absence of CRT, whether an early CRT strategy resulted in unnecessary implants and the effect of early CRT on outcomes. Methods Our cohort consisted of 214 consecutive patients with LV ejection fraction (LVEF) of 35% or less who underwent repeat echocardiography 1 year after enrolment. Of these, 116 patients had NQRS, and 98 had WQRS of whom 40 received CRT within 1 year and 58 did not. Results In the absence of CRT, patients with WQRS had less LV reverse remodelling compared with those with NQRS, with differences in ΔLVEF (+2 vs. +9%, P < 0.001) ΔLV end-diastolic diameter (−1 vs. −2 mm, P = 0.095), ΔLV end-systolic diameter (−2 vs. −4.5 mm, P = 0.038), LV end-systolic volume (−12.6 vs. −25.0 ml, P = 0.054) and LV end-diastolic volume (−7.3 vs. −12.2 ml, P = 0.071). LVEF was more likely to improve by at least 10% if patients had NQRS or received CRT (P = 0.08). Thirteen (24%) patients with WQRS achieved an LVEF greater than 35% in the absence of CRT; however, none achieved greater than 50%. Conclusion A strictly linear approach to heart failure therapy might lead to delays to optimal treatment in those patients with the most to gain from CRT and the least to gain from GDMT

Anaesthetic considerations of adults with Morquio's syndrome - a case report

<p>Abstract</p> <p>Background</p> <p>The anaesthetic management of patients with Morquio syndrome is complicated by a number of factors including odontoid hypoplasia, atlantoaxial instability, thoracic kyphosis, and deposition of mucopolysaccharides in the soft tissue of the oropharnyx.</p> <p>Case presentation</p> <p>Herein we describe the anaesthetic considerations and management of a 26 year old adult with Morquio syndrome, who presented for an elective hip replacement.</p> <p>Conclusion</p> <p>This report details an awake fiberoptic intubation in an adult with Morquio syndrome. We recommend that this approach be considered in patients with Morquio syndrome undergoing general anaesthesia.</p

Effect of salinity on the biosynthesis of n-3 long-chain polyunsaturated fatty acids in silverside Chirostoma estor

The genus Chirostoma (silversides) belongs to the family Atherinopsidae, which contains around 150 species, most of which are marine. However, Mexican silverside (Chirostoma estor) is one of the few representatives of freshwater atherinopsids and is only found in some lakes of the Mexican Central Plateau. However, studies have shown that C. estor has improved survival, growth and development when cultured in water conditions with increased salinity. In addition, C. estor displays an unusual fatty acid composition for a freshwater fish with high docosahexaenoic acid (DHA) : eicosapentaenoic acid (EPA) ratios. Freshwater and marine fish species display very different essential fatty acid metabolism and requirements and so the present study investigated long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis to determine the capacity of C. estor for endogenous production of EPA and DHA, and the effect that salinity has on these pathways. Briefly, C. estor were maintained at three salinities (0, 5 and 15 ppt) and the metabolism of 14C-labelled 18:3n-3 determined in isolated hepatocyte and enterocyte cells. The results showed that C. estor has the capacity for endogenous biosynthesis of LC-PUFA from 18-carbon fatty acid precursors, but that the pathway was essentially only active in saline conditions with virtually no activity in cells isolated from fish grown in freshwater. The activity of the LCPUFA biosynthesis pathway was also higher in cells isolated from fish at 15 ppt compared to fish at 5 ppt, The pathway was around 5-fold higher in hepatocytes compared to enterocytes, although the majority of 18:3n-3 was converted to 18:4n-3 and 20:4n-3 in hepatocytes whereas the proportions of 18:3n-3 converted to EPA and DHA were higher in enterocytes. The data were consistent with the hypothesis that conversion of EPA to DHA could contribute, at least in part, to the generally high DHA:EPA ratios observed in the tissue lipids of C. estor

Bioavailability of Iron, Zinc, Phytate and Phytase Activity during Soaking and Germination of White Sorghum Varieties

The changes in phytate, phytase activity and in vitro bioavailability of iron and zinc during soaking and germination of three white sorghum varieties (Sorghum bicolor L. Moench), named Dorado, Shandweel-6, and Giza-15 were investigated. Sorghum varieties were soaked for 20 h and germinated for 72 h after soaking for 20 h to reduce phytate content and increase iron and zinc in vitro bioavailability. The results revealed that iron and zinc content was significantly reduced from 28.16 to 32.16% and 13.78 to 26.69% for soaking treatment and 38.43 to 39.18% and 21.80 to 31.27% for germination treatments, respectively. Phytate content was significantly reduced from 23.59 to 32.40% for soaking treatment and 24.92 to 35.27% for germination treatments, respectively. Phytase enzymes will be activated during drying in equal form in all varieties. The results proved that the main distinct point is the change of phytase activity as well as specific activity during different treatment which showed no significant differences between the varieties used. The in vitro bioavailability of iron and zinc were significantly improved as a result of soaking and germination treatments

Unprecedented within-species chromosome number cline in the Wood White butterfly Leptidea sinapis and its significance for karyotype evolution and speciation

Background: Species generally have a fixed number of chromosomes in the cell nuclei while between-species differences are common and often pronounced. These differences could have evolved through multiple speciation events, each involving the fixation of a single chromosomal rearrangement. Alternatively, marked changes in the karyotype may be the consequence of within-species accumulation of multiple chromosomal fissions/fusions, resulting in highly polymorphic systems with the subsequent extinction of intermediate karyomorphs. Although this mechanism of chromosome number evolution is possible in theory, it has not been well documented. Results: We present the discovery of exceptional intraspecific variability in the karyotype of the widespread Eurasian butterfly Leptidea sinapis. We show that within this species the diploid chromosome number gradually decreases from 2n = 106 in Spain to 2n = 56 in eastern Kazakhstan, resulting in a 6000 km-wide cline that originated recently (8,500 to 31,000 years ago). Remarkably, intrapopulational chromosome number polymorphism exists, the chromosome number range overlaps between some populations separated by hundreds of kilometers, and chromosomal heterozygotes are abundant. We demonstrate that this karyotypic variability is intraspecific because in L. sinapis a broad geographical distribution is coupled with a homogenous morphological and genetic structure. Conclusions: The discovered system represents the first clearly documented case of explosive chromosome number evolution through intraspecific and intrapopulation accumulation of multiple chromosomal changes. Leptidea sinapis may be used as a model system for studying speciation by means of chromosomally-based suppressed recombination mechanisms, as well as clinal speciation, a process that is theoretically possible but difficult to document. The discovered cline seems to represent a narrow time-window of the very first steps of species formation linked to multiple chromosomal changes that have occurred explosively. This case offers a rare opportunity to study this process before drift, dispersal, selection, extinction and speciation erase the traces of microevolutionary events and just leave the final picture of a pronounced interspecific chromosomal difference