Physiopathology of the embryonic heart (with special emphasis on hypoxia and reoxygenation).

The adaptative response of the developing heart to adverse intrauterine environment such as reduced O2 delivery can result in alteration of gene expression with short- and long-term consequences including adult cardiovascular diseases. The tolerance of the developing heart of acute or chronic oxygen deprivation, its capacity to recover during reperfusion and the mechanisms involved in reoxygenation injury are still under debate. Indeed, the pattern of response of the immature myocardium to hypoxia-reoxygenation differs from that of the adult. This review deals with the structural and metabolic characteristics of the embryonic heart and the functional consequences of hypoxia and reoxygenation. The relative contribution of calcium and sodium overload, pH disturbances and oxidant stress to the hypoxia-induced cardiac dysfunction is examined, as well as various cellular signaling pathways (e.g. MAP kinases) involved in cell survival or death. In the context of the recent advances in developmental cardiology and fetal cardiac surgery, a better understanding of the physiopathology of the stressed developing heart is required.

Indications for cardiovascular magnetic resonance in children with congenital and acquired heart disease: an expert consensus paper of the Imaging Working Group of the AEPC and the Cardiovascular Magnetic Resonance Section of the EACVI.

This article provides expert opinion on the use of cardiovascular magnetic resonance (CMR) in young patients with congenital heart disease (CHD) and in specific clinical situations. As peculiar challenges apply to imaging children, paediatric aspects are repeatedly discussed. The first section of the paper addresses settings and techniques, including the basic sequences used in paediatric CMR, safety, and sedation. In the second section, the indication, application, and clinical relevance of CMR in the most frequent CHD are discussed in detail. In the current era of multimodality imaging, the strengths of CMR are compared with other imaging modalities. At the end of each chapter, a brief summary with expert consensus key points is provided. The recommendations provided are strongly clinically oriented. The paper addresses not only imagers performing CMR, but also clinical cardiologists who want to know which information can be obtained by CMR and how to integrate it in clinical decision-making.

Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs.

AIM: Heart disease is recognized as a consequence of dysregulation of cardiac gene regulatory networks. Previously, unappreciated components of such networks are the long non-coding RNAs (lncRNAs). Their roles in the heart remain to be elucidated. Thus, this study aimed to systematically characterize the cardiac long non-coding transcriptome post-myocardial infarction and to elucidate their potential roles in cardiac homoeostasis. METHODS AND RESULTS: We annotated the mouse transcriptome after myocardial infarction via RNA sequencing and ab initio transcript reconstruction, and integrated genome-wide approaches to associate specific lncRNAs with developmental processes and physiological parameters. Expression of specific lncRNAs strongly correlated with defined parameters of cardiac dimensions and function. Using chromatin maps to infer lncRNA function, we identified many with potential roles in cardiogenesis and pathological remodelling. The vast majority was associated with active cardiac-specific enhancers. Importantly, oligonucleotide-mediated knockdown implicated novel lncRNAs in controlling expression of key regulatory proteins involved in cardiogenesis. Finally, we identified hundreds of human orthologues and demonstrate that particular candidates were differentially modulated in human heart disease. CONCLUSION: These findings reveal hundreds of novel heart-specific lncRNAs with unique regulatory and functional characteristics relevant to maladaptive remodelling, cardiac function and possibly cardiac regeneration. This new class of molecules represents potential therapeutic targets for cardiac disease. Furthermore, their exquisite correlation with cardiac physiology renders them attractive candidate biomarkers to be used in the clinic.

Long-term continuous-flow left ventricular assist devices (LVAD) as bridge to heart transplantation.

Heart transplantation (HTx) is the treatment of choice for end-stage heart failure but the limited availability of heart's donors still represents a major issue. So long-term mechanical circulatory support (MCS) has been proposed as an alternative treatment option to assist patients scheduled on HTx waiting list bridging them for a variable time period to cardiac transplantation-the so-called bridge-to-transplantation (BTT) strategy. Nowadays approximately 90% of patients being considered for MCS receive a left ventricular assist device (LVAD). In fact, LVAD experienced several improvements in the last decade and the predominance of continuous-flow over pulsatile-flow technology has been evident since 2008. The aim of the present report is to give an overview of continuous-flow LVAD utilization in the specific setting of the BTT strategy taking into consideration the most representative articles of the scientific literature and focusing the attention on the evolution, clinical outcomes, relevant implications on the HTx strategy and future perspectives of the continuous-flow LVAD technology.

Reduction of respiratory motion artifacts for free-breathing whole-heart coronary MRA by weighted iterative reconstruction.

PURPOSE: To combine weighted iterative reconstruction with self-navigated free-breathing coronary magnetic resonance angiography for retrospective reduction of respiratory motion artifacts. METHODS: One-dimensional self-navigation was improved for robust respiratory motion detection and the consistency of the acquired data was estimated on the detected motion. Based on the data consistency, the data fidelity term of iterative reconstruction was weighted to reduce the effects of respiratory motion. In vivo experiments were performed in 14 healthy volunteers and the resulting image quality of the proposed method was compared to a navigator-gated reference in terms of acquisition time, vessel length, and sharpness. RESULT: Although the sampling pattern of the proposed method contained 60% more samples with respect to the reference, the scan efficiency was improved from 39.5 ± 10.1% to 55.1 ± 9.1%. The improved self-navigation showed a high correlation to the standard navigator signal and the described weighting efficiently reduced respiratory motion artifacts. Overall, the average image quality of the proposed method was comparable to the navigator-gated reference. CONCLUSION: Self-navigated coronary magnetic resonance angiography was successfully combined with weighted iterative reconstruction to reduce the total acquisition time and efficiently suppress respiratory motion artifacts. The simplicity of the experimental setup and the promising image quality are encouraging toward future clinical evaluation. Magn Reson Med 73:1885-1895, 2015. © 2014 Wiley Periodicals, Inc.

Associations of baroreflex sensitivity, heart rate variability, and initial orthostatic hypotension with prenatal and recent postnatal methylmercury exposure in the Seychelles Child Development Study at age 19 years.

BACKGROUND: A few studies have suggested an association between prenatal exposure to methylmercury and decreased heart rate variability (HRV) related to autonomic heart function, but no study has examined this association using baroreflex sensitivity (BRS). In this study we assessed the distribution of BRS and immediate orthostatic hypotension (IOH) in young Seychellois adults and their associations with exposure to prenatal and recent postnatal methylmercury. METHODS: Subjects in the Seychelles Child Development Study (SCDS) main cohort were evaluated at age 19 years. Non-invasive beat-to-beat blood pressure (BP) monitoring (Finapres, Ohmeda) was performed at rest and during active standing in 95 consecutive subjects. Recent postnatal mercury exposure was measured in subjects' hair at the age of 19 years and prenatal exposure in maternal hair grown during pregnancy. BRS was estimated by sequence analysis to identify spontaneous ascending and descending BP ramps. HRV was estimated by the following markers: PNN50 (relative numbers of normal-to-normal intervals which are shorter by more than 50 ms than the immediately following normal-to-normal intervals); rMSSD (root mean of the squared sum of successive interval differences); LF/HF (low frequency/high frequency component ratio); ratio of the mean expiratory/inspiratory RR intervals (EI ratio); and the ratio between the longest RR interval 30 s after active standing and the shortest RR interval at 15 s (Max30/Min15). IOH was estimated by the deepest BP fall within the first 15 s after active standing up. RESULTS: Prenatal MeHg exposures were similar in boys and girls (6.7±4.3, 6.7±3.8 ng/g) but recent postnatal mercury levels were higher in males than females (11.2±5.8 vs 7.9±4.3 ng/g, p=0.003). Markers of autonomic heart rate control were within the normal range (BRS: 24.8±7 ms/mm Hg, PNN50: 24.9±6.8%, rMSSD: 68±22, LF/HF: 0.61±0.28) in both sexes. After standing, 51.4% of subjects had a transient systolic BP drop>40 mm Hg, but only 5.3% reported dizziness or had syncope. Prenatal and recent postnatal MeHg levels, overall, were not associated with BRS, E/I ratio, PNN50, rMSSD, LF/HF ratio, Max30/Min15 ratio, and IOH. CONCLUSIONS: This study provides no support for the hypothesis that prenatal or recent postnatal MeHg exposure from fish consumption is associated with impaired autonomic heart rate control.

Postmortem magnetic resonance imaging of the heart ex situ: development of technical protocols.

Postmortem MRI (PMMR) examinations are seldom performed in legal medicine due to long examination times, unfamiliarity with the technique, and high costs. Furthermore, it is difficult to obtain access to an MRI device used for patients in clinical settings to image an entire human body. An alternative is available: ex situ organ examination. To our knowledge, there is no standardized protocol that includes ex situ organ preparation and scanning parameters for postmortem MRI. Thus, our objective was to develop a standard procedure for ex situ heart PMMR examinations. We also tested the oily contrast agent Angiofil® commonly used for PMCT angiography, for its applicability in MRI. We worked with a 3 Tesla MRI device and 32-channel head coils. Twelve porcine hearts were used to test different materials to find the best way to prepare and place organs in the device and to test scanning parameters. For coronary MR angiography, we tested different mixtures of Angiofil® and different injection materials. In a second step, 17 human hearts were examined to test the procedure and its applicability to human organs. We established two standardized protocols: one for preparation of the heart and another for scanning parameters based on experience in clinical practice. The established protocols enabled a standardized technical procedure with comparable radiological images, allowing for easy radiological reading. The performance of coronary MR angiography enabled detailed coronary assessment and revealed the utility of Angiofil® as a contrast agent for PMMR. Our simple, reproducible method for performing heart examinations ex situ yields high quality images and visualization of the coronary arteries.

Molecular insight into heart development and congenital heart disease: An update review from the Arab countries.

Congenital heart defect (CHD) has a major influence on affected individuals as well as on the supportive and associated environment such as the immediate family. Unfortunately, CHD is common worldwide with an incidence of approximately 1% and consequently is a major health concern. The Arab population has a high rate of consanguinity, fertility, birth, and annual population growth, in addition to a high incidence of diabetes mellitus and obesity. All these factors may lead to a higher incidence and prevalence of CHD within the Arab population than in the rest of the world, making CHD of even greater concern. Sadly, most Arab countries lack appropriate public health measures directed toward the control and prevention of congenital malformations and so the importance of CHD within the population remains unknown but is thought to be high. In approximately 85% of CHD patients, the multifactorial theory is considered as the pathologic basis. The genetic risk factors for CHD can be attributed to large chromosomal aberrations, copy number variations (CNV) of particular regions in the chromosome, and gene mutations in specific nuclear transcription pathways and in the genes that are involved in cardiac structure and development. The application of modern molecular biology techniques such as high-throughput nucleotide sequencing and chromosomal array and methylation array all have the potential to reveal more genetic defects linked to CHD. Exploring the genetic defects in CHD pathology will improve our knowledge and understanding about the diverse pathways involved and also about the progression of this disease. Ultimately, this will link to more efficient genetic diagnosis and development of novel preventive therapeutic strategies, as well as gene-targeted clinical management. This review summarizes our current understanding of the molecular basis of normal heart development and the pathophysiology of a wide range of CHD. The risk factors that might account for the high prevalence of CHD within the Arab population and the measures required to be undertaken for conducting research into CHD in Arab countries will also be discussed.

Influence of heart motion on cardiac output estimation by means of electrical impedance tomography: a case study.

Electrical impedance tomography (EIT) is a non-invasive imaging technique that can measure cardiac-related intra-thoracic impedance changes. EIT-based cardiac output estimation relies on the assumption that the amplitude of the impedance change in the ventricular region is representative of stroke volume (SV). However, other factors such as heart motion can significantly affect this ventricular impedance change. In the present case study, a magnetic resonance imaging-based dynamic bio-impedance model fitting the morphology of a single male subject was built. Simulations were performed to evaluate the contribution of heart motion and its influence on EIT-based SV estimation. Myocardial deformation was found to be the main contributor to the ventricular impedance change (56%). However, motion-induced impedance changes showed a strong correlation (r = 0.978) with left ventricular volume. We explained this by the quasi-incompressibility of blood and myocardium. As a result, EIT achieved excellent accuracy in estimating a wide range of simulated SV values (error distribution of 0.57 ± 2.19 ml (1.02 ± 2.62%) and correlation of r = 0.996 after a two-point calibration was applied to convert impedance values to millilitres). As the model was based on one single subject, the strong correlation found between motion-induced changes and ventricular volume remains to be verified in larger datasets.