Left Ventricular Systolic Dysfunction in Patients Diagnosed With Hypertrophic Cardiomyopathy During Childhood: Insights From the SHaRe Registry.

BACKGROUND: The development of left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM) is rare but serious and associated with poor outcomes in adults. Little is known about the prevalence, predictors, and prognosis of LVSD in patients diagnosed with HCM as children. METHODS: Data from patients with HCM in the international, multicenter SHaRe (Sarcomeric Human Cardiomyopathy Registry) were analyzed. LVSD was defined as left ventricular ejection fraction <50% on echocardiographic reports. Prognosis was assessed by a composite of death, cardiac transplantation, and left ventricular assist device implantation. Predictors of developing incident LVSD and subsequent prognosis with LVSD were assessed using Cox proportional hazards models. RESULTS: We studied 1010 patients diagnosed with HCM during childhood (<18 years of age) and compared them with 6741 patients with HCM diagnosed as adults. In the pediatric HCM cohort, median age at HCM diagnosis was 12.7 years (interquartile range, 8.0-15.3), and 393 (36%) patients were female. At initial SHaRe site evaluation, 56 (5.5%) patients with childhood-diagnosed HCM had prevalent LVSD, and 92 (9.1%) developed incident LVSD during a median follow-up of 5.5 years. Overall LVSD prevalence was 14.7% compared with 8.7% in patients with adult-diagnosed HCM. Median age at incident LVSD was 32.6 years (interquartile range, 21.3-41.6) for the pediatric cohort and 57.2 years (interquartile range, 47.3-66.5) for the adult cohort. Predictors of developing incident LVSD in childhood-diagnosed HCM included age <12 years at HCM diagnosis (hazard ratio [HR], 1.72 [CI, 1.13-2.62), male sex (HR, 3.1 [CI, 1.88-5.2), carrying a pathogenic sarcomere variant (HR, 2.19 [CI, 1.08-4.4]), previous septal reduction therapy (HR, 2.34 [CI, 1.42-3.9]), and lower initial left ventricular ejection fraction (HR, 1.53 [CI, 1.38-1.69] per 5% decrease). Forty percent of patients with LVSD and HCM diagnosed during childhood met the composite outcome, with higher rates in female participants (HR, 2.60 [CI, 1.41-4.78]) and patients with a left ventricular ejection fraction <35% (HR, 3.76 [2.16-6.52]). CONCLUSIONS: Patients with childhood-diagnosed HCM have a significantly higher lifetime risk of developing LVSD, and LVSD emerges earlier than for patients with adult-diagnosed HCM. Regardless of age at diagnosis with HCM or LVSD, the prognosis with LVSD is poor, warranting careful surveillance for LVSD, especially as children with HCM transition to adult care

Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment

Rotifer communities under variable predation-turbulence combinations

The effects of water turbulence on rotifer communities were experimentally studied under different predation pressures. When the larvae of the phantom midge (Chaoborus flavicans) were present in turbulent water, the abundance of most rotifer taxa was enhanced. Especially the genera Chromogaster, Keratella, Polyarthra, and Trichocerca, increased in abundance. In calm water, chaoborids did not affect the rotifer community. In turbulent water predation by chaoborids was targeted more towards cladocerans (Bosmina sp.) and predation pressure on rotifers was relaxed. Additionally, reduced competition with cladocerans probably contributed to the increase of rotifer abundance. Turbulence alone had no significant effect on rotifer abundance because their individual size was small compared with the diameter of the turbulent eddies. The study suggested that the effects of turbulence on rotifers is not direct but takes place through changed predator-prey relations, i.e., the effect depends on the abundance of invertebrate predators. In aquatic ecosystems with a high density of chaoborids, increasing turbulence can considerably increase the abundance of rotifers.Peer reviewe

Net pelagic heterotrophy in mesotrophic and oligotrophic basins of a large, temperate lake

Understanding the effects of trophic status and dissolved organic carbon concentration (DOC) on lake carbon cycling is essential for accurate ecosystem carbon models. Using isotopically labelled substrates we assessed spatial and temporal variability in bacterial respiration (BR) and algal primary production (PP) in two trophically, morphometrically and hydrologically different basins in Loch Lomond, a large temperate lake in Scotland. GIS modelling was used to construct a whole lake balance for bacterial production/respiration and PP, and from this the proportion of heterotrophy fuelled by allochthonous carbon was estimated. We tested the hypotheses that trophic status and DOC concentration affect the balance between PP and BR and examined which is the more significant driving factor. Additionally we estimated the percentage of BR that is fuelled by terrestrial carbon. PP varied seasonally and showed inter-basin homogeneity. BR was greatest in the mesotrophic south basin in autumn, which corresponded to measured peak DOC input, though over an annual cycle no relationship was observed between BR and DOC concentration. The PP:BR ratio was 0.37 ± 0.30 and 0.3 ± 0.45 in the north and south basins, respectively, assuming a bacterial growth efficiency of 0.1. We have found that allochthonous carbon potentially supports a substantial quantity of pelagic production, even during periods of high photosynthesis. Less productive systems are thought to be dominated by heterotrophic processes. However, we have found that the mesotrophic basin of a large lake to be as heterotrophic as its neighbouring oligotrophic basin, an observation that has implications for our understanding of modelling of the role of lakes in linking the terrestrial-atmospheric carbon cycle