Prediction of AF in Heart Failure With Preserved Ejection Fraction: Incremental Value of Left Atrial Strain

ObjectivesThis study sought to identify the factors associated with incident atrial fibrillation (AF) in a well-characterized heart failure with preserved ejection fraction (HFpEF) population, with special focus on left atrial (LA) strain.BackgroundAF is associated with HFpEF, with adverse consequences. Effective risk evaluation might allow the initiation of protective strategies.MethodsClinical evaluation and echocardiography, including measurements of peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and LA volume index (LAVI), were obtained in 170 patients with symptomatic HFpEF (mean age, 65 ± 8 years), free of baseline AF. AF was identified by standard 12-lead electrocardiogram, review of relevant medical records (including Holter documentation), and surveillance with a portable single-lead electrocardiogram device over 2 weeks. Results were validated in the 103 patients with HFpEF from the Karolinska-Rennes (KaRen) study.ResultsOver a median follow-up of 49 months, incident AF was identified in 39 patients (23%). Patients who developed AF were older; had higher clinical risk scores, brain natriuretic peptide, creatinine, LAVI, and LV mass; lower LA strain and exercise capacity; and more impaired LV diastolic function. PACS, PALS, and LAVI were the most predictive parameters for AF (area under receiver-operating characteristic curve: 0.76 for PACS, 0.71 for PALS, and 0.72 for LAVI). Nested Cox regression models showed that the predictive value of PACS and PALS was independent from and incremental to clinical data, LAVI, and E/e’ ratio. Classification and regression trees analysis identified PACS ≤12.7%, PALS ≤29.4%, and LAVI >34.3 ml/m² as discriminatory nodes for AF, with a 33-fold greater hazard of AF (p < 0.001) in patients categorized as high risk. The classification and regression trees algorithm discriminated high and low AF risk in the validation cohort.ConclusionsPACS and PALS provide incremental predictive information about incident AF in HFpEF. The inclusion of these LA strain components to the diagnostic algorithm may help guide screening and further monitoring for AF risk in this population.     

Experimental ocean acidification alters the allocation of metabolic energy

Energy is required to maintain physiological homeostasis in response to environmental change. Although responses to environmental stressors frequently are assumed to involve high metabolic costs, the biochemical bases of actual energy demands are rarely quantified. We studied the impact of a near-future scenario of ocean acidification [800 µatm partial pressure of CO₂ (pCO₂)] during the development and growth of an important model organism in developmental and environmental biology, the sea urchin Strongylocentrotus purpuratus. Size, metabolic rate, biochemical content, and gene expression were not different in larvae growing under control and seawater acidification treatments. Measurements limited to those levels of biological analysis did not reveal the biochemical mechanisms of response to ocean acidification that occurred at the cellular level. In vivo rates of protein synthesis and ion transport increased ∼50% under acidification. Importantly, the in vivo physiological increases in ion transport were not predicted from total enzyme activity or gene expression. Under acidification, the increased rates of protein synthesis and ion transport that were sustained in growing larvae collectively accounted for the majority of available ATP (84%). In contrast, embryos and prefeeding and unfed larvae in control treatments allocated on average only 40% of ATP to these same two processes. Understanding the biochemical strategies for accommodating increases in metabolic energy demand and their biological limitations can serve as a quantitative basis for assessing sublethal effects of global change. Variation in the ability to allocate ATP differentially among essential functions may be a key basis of resilience to ocean acidification and other compounding environmental stressors.Studies of biological responses to future scenarios of global change are of significant interest, given the most recent projections of future environmental conditions (1). In addition to important impacts in the atmosphere and on terrestrial systems, anthropogenic CO₂ emission is causing acidification of the world’s oceans (2, 3). Determining the biological responses to ocean acidification is a critical component of the study of how marine ecosystems may be altered under future scenarios of anthropogenic global environmental change. Predicting the potential for evolutionary adaptation to global change requires an understanding of the biochemical mechanisms that maintain homeostasis of physiological systems (4, 5).The developmental stages of many marine organisms have evolved cellular defenses to mitigate the impact of current environmental stressors (6). Whether these protective mechanisms can respond to future, rapid anthropogenic changes is still an open question. Marine invertebrate larvae, and particularly those with calcareous structures, have been used in numerous investigations of the biological impact of ocean acidification (2, 7–10). Although the magnitude of a response appears to be species specific, acidification can, to varying degrees, impact a wide range of biological processes in developmental forms (7–14). For instance, under near-future global mean CO₂ conditions [720–1,000 µatm partial pressure of CO₂ (pCO₂)] (1), species of larval sea urchins generally are reduced in size by 10% or less (7, 9, 15–17), but studies of metabolic rate and ion regulation suggest that acidification may result in increased metabolic costs to maintain homeostasis (11, 12). By studying responses to seawater acidification at several levels of biological organization during the development of the sea urchin, Strongylocentrotus purpuratus—from whole-organism growth, to macromolecular synthesis rates, enzyme activities, and gene expressions—we show that, although the impact of acidification at the organismal level is minimal, dramatic compensation occurs at the cellular level. Specifically, growth is maintained by changes in energy allocation to accommodate the costs required to sustain increases in protein synthesis and ion transport. We conclude that measurements limited to morphological characteristics, metabolic rate, biochemical content, and gene expression do not reveal the major biochemical response mechanisms underlying the apparent resilience to acidification in developing sea urchins.     

Characterization of Responder Profiles for Cardiac Resynchronization Therapy through Unsupervised Clustering of Clinical and Strain Data

1. Download : Download high-res image (249KB)
2. Download : Download full-size image

     

Exercise and the treatment of diabetes and obesity

An active lifestyle increases general health and is protects from a number of different conditions, including exercise and obesity. There is emerging evidence that exercise by itself exerts clinically beneficial effects in both lean and obese subjects, even in the absence of effects on weight.1 Recent results have brought an increasing understanding of the molecular mechanisms underlying the beneficial effects of exercise at the level of metabolism and changes in gene expression. There is a significant dose-response to the effect of exercise, and the current guidelines regarding exercise amount may need to be revised upwards. Furthermore, this treatment option should not be overlooked.