Lessons Learned from the European Cardiovascular Magnetic Resonance (EuroCMR) Registry Pilot Phase

The data from 11,040 patients of the European Cardiovascular Magnetic Resonance (EuroCMR) registry pilot phase offer the first documentation of the clinical use of CMR in a routine setting. The pilot data show that CMR is frequently performed in clinical practice, is a safe procedure with excellent image quality, and has a strong impact on patient management. In the future, the EuroCMR registry will help to set international benchmarks on appropriate indications, quality, and safety of CMR. In addition, outcome and cost effectiveness will be addressed on an international level in order to develop optimized imaging-guided clinical pathways and to avoid unnecessary or even harmful testing

Left ventricular apical diseases

There are many disorders that may involve the left ventricular (LV) apex; however, they are sometimes difficult to differentiate. In this setting cardiac imaging methods can provide the clue to obtaining the diagnosis. The purpose of this review is to illustrate the spectrum of diseases that most frequently affect the apex of the LV including Tako-Tsubo cardiomyopathy, LV aneurysms and pseudoaneurysms, apical diverticula, apical ventricular remodelling, apical hypertrophic cardiomyopathy, LV non-compaction, arrhythmogenic right ventricular dysplasia with LV involvement and LV false tendons, with an emphasis on the diagnostic criteria and imaging features

Cardiac resynchronization therapy guided by cardiovascular magnetic resonance

Cardiac resynchronization therapy (CRT) is an established treatment for patients with symptomatic heart failure, severely impaired left ventricular (LV) systolic dysfunction and a wide (> 120 ms) complex. As with any other treatment, the response to CRT is variable. The degree of pre-implant mechanical dyssynchrony, scar burden and scar localization to the vicinity of the LV pacing stimulus are known to influence response and outcome. In addition to its recognized role in the assessment of LV structure and function as well as myocardial scar, cardiovascular magnetic resonance (CMR) can be used to quantify global and regional LV dyssynchrony. This review focuses on the role of CMR in the assessment of patients undergoing CRT, with emphasis on risk stratification and LV lead deployment

T2-weighted cardiovascular magnetic resonance in acute cardiac disease

Cardiovascular magnetic resonance (CMR) using T2-weighted sequences can visualize myocardial edema. When compared to previous protocols, newer pulse sequences with substantially improved image quality have increased its clinical utility. The assessment of myocardial edema provides useful incremental diagnostic and prognostic information in a variety of clinical settings associated with acute myocardial injury. In patients with acute chest pain, T2-weighted CMR is able to identify acute or recent myocardial ischemic injury and has been employed to distinguish acute coronary syndrome (ACS) from non-ACS as well as acute from chronic myocardial infarction

Quantitative cardiovascular magnetic resonance for molecular imaging

Cardiovascular magnetic resonance (CMR) molecular imaging aims to identify and map the expression of important biomarkers on a cellular scale utilizing contrast agents that are specifically targeted to the biochemical signatures of disease and are capable of generating sufficient image contrast. In some cases, the contrast agents may be designed to carry a drug payload or to be sensitive to important physiological factors, such as pH, temperature or oxygenation. In this review, examples will be presented that utilize a number of different molecular imaging quantification techniques, including measuring signal changes, calculating the area of contrast enhancement, mapping relaxation time changes or direct detection of contrast agents through multi-nuclear imaging or spectroscopy. The clinical application of CMR molecular imaging could offer far reaching benefits to patient populations, including early detection of therapeutic response, localizing ruptured atherosclerotic plaques, stratifying patients based on biochemical disease markers, tissue-specific drug delivery, confirmation and quantification of end-organ drug uptake, and noninvasive monitoring of disease recurrence. Eventually, such agents may play a leading role in reducing the human burden of cardiovascular disease, by providing early diagnosis, noninvasive monitoring and effective therapy with reduced side effects

Climatic and topographic changes since the Miocene influenced the diversification and biogeography of the tent tortoise (Psammobates tentorius) species complex in Southern Africa

Background: Climatic and topographic changes function as key drivers in shaping genetic structure and cladogenic radiation in many organisms. Southern Africa has an exceptionally diverse tortoise fauna, harbouring one-third of the world’s tortoise genera. The distribution of Psammobates tentorius (Kuhl, 1820) covers two of the 25 biodiversity hotspots in the world, the Succulent Karoo and Cape Floristic Region. The highly diverged P. tentorius represents an excellent model species for exploring biogeographic and radiation patterns of reptiles in Southern Africa. Results: We investigated genetic structure and radiation patterns against temporal and spatial dimensions since the Miocene in the Psammobates tentorius species complex, using multiple types of DNA markers and niche modelling analyses. Cladogenesis in P. tentorius started in the late Miocene (11.63–5.33 Ma) when populations dispersed from north to south to form two geographically isolated groups. The northern group diverged into a clade north of the Orange River (OR), followed by the splitting of the group south of the OR into a western and an interior clade. The latter divergence corresponded to the intensifcation of the cold Benguela current, which caused western aridifcation and rainfall seasonality. In the south, tectonic uplift and subsequent exhumation, together with climatic fuctuations seemed responsible for radiations among the four southern clades since the late Miocene. We found that each clade occurred in a habitat shaped by diferent climatic parameters, and that the niches difered substantially among the clades of the northern group but were similar among clades of the southern group. Conclusion: Climatic shifts, and biome and geographic changes were possibly the three major driving forces shaping cladogenesis and genetic structure in Southern African tortoise species. Our results revealed that the cladogenesis of the P. tentorius species complex was probably shaped by environmental cooling, biome shifts and topographic uplift in Southern Africa since the late Miocene. The Last Glacial Maximum (LGM) may have impacted the distribution of P. tentorius substantially. We found the taxonomic diversify of the P. tentorius species complex to be highest in the Greater Cape Floristic Region. All seven clades discovered warrant conservation attention, particularly Ptt-B–Ptr, Ptt-A and Pv-

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe