Antarctic icebergs reorganize ocean circulation during Pleistocene glacials.

The dominant feature of large-scale mass transfer in the modern ocean is the Atlantic meridional overturning circulation (AMOC). The geometry and vigour of this circulation influences global climate on various timescales. Palaeoceanographic evidence suggests that during glacial periods of the past 1.5 million years the AMOC had markedly different features from today1; in the Atlantic basin, deep waters of Southern Ocean origin increased in volume while above them the core of the North Atlantic Deep Water (NADW) shoaled2. An absence of evidence on the origin of this phenomenon means that the sequence of events leading to global glacial conditions remains unclear. Here we present multi-proxy evidence showing that northward shifts in Antarctic iceberg melt in the Indian-Atlantic Southern Ocean (0-50° E) systematically preceded deep-water mass reorganizations by one to two thousand years during Pleistocene-era glaciations. With the aid of iceberg-trajectory model experiments, we demonstrate that such a shift in iceberg trajectories during glacial periods can result in a considerable redistribution of freshwater in the Southern Ocean. We suggest that this, in concert with increased sea-ice cover, enabled positive buoyancy anomalies to 'escape' into the upper limb of the AMOC, providing a teleconnection between surface Southern Ocean conditions and the formation of NADW. The magnitude and pacing of this mechanism evolved substantially across the mid-Pleistocene transition, and the coeval increase in magnitude of the 'southern escape' and deep circulation perturbations implicate this mechanism as a key feedback in the transition to the '100-kyr world', in which glacial-interglacial cycles occur at roughly 100,000-year periods.

Ice loss from the East Antarctic Ice Sheet during late Pleistocene interglacials.

Understanding ice sheet behaviour in the geological past is essential for evaluating the role of the cryosphere in the climate system and for projecting rates and magnitudes of sea level rise in future warming scenarios1-4. Although both geological data5-7 and ice sheet models3,8 indicate that marine-based sectors of the East Antarctic Ice Sheet were unstable during Pliocene warm intervals, the ice sheet dynamics during late Pleistocene interglacial intervals are highly uncertain3,9,10. Here we provide evidence from marine sedimentological and geochemical records for ice margin retreat or thinning in the vicinity of the Wilkes Subglacial Basin of East Antarctica during warm late Pleistocene interglacial intervals. The most extreme changes in sediment provenance, recording changes in the locus of glacial erosion, occurred during marine isotope stages 5, 9, and 11, when Antarctic air temperatures11 were at least two degrees Celsius warmer than pre-industrial temperatures for 2,500 years or more. Hence, our study indicates a close link between extended Antarctic warmth and ice loss from the Wilkes Subglacial Basin, providing ice-proximal data to support a contribution to sea level from a reduced East Antarctic Ice Sheet during warm interglacial intervals. While the behaviour of other regions of the East Antarctic Ice Sheet remains to be assessed, it appears that modest future warming may be sufficient to cause ice loss from the Wilkes Subglacial Basin.

A two-million-year-long hydroclimatic context for hominin evolution in southeastern Africa.

The past two million years of eastern African climate variability is currently poorly constrained, despite interest in understanding its assumed role in early human evolution1-4. Rare palaeoclimate records from northeastern Africa suggest progressively drier conditions2,5 or a stable hydroclimate6. By contrast, records from Lake Malawi in tropical southeastern Africa reveal a trend of a progressively wetter climate over the past 1.3 million years7,8. The climatic forcings that controlled these past hydrological changes are also a matter of debate. Some studies suggest a dominant local insolation forcing on hydrological changes9-11, whereas others infer a potential influence of sea surface temperature changes in the Indian Ocean8,12,13. Here we show that the hydroclimate in southeastern Africa (20-25° S) is controlled by interplay between low-latitude insolation forcing (precession and eccentricity) and changes in ice volume at high latitudes. Our results are based on a multiple-proxy reconstruction of hydrological changes in the Limpopo River catchment, combined with a reconstruction of sea surface temperature in the southwestern Indian Ocean for the past 2.14 million years. We find a long-term aridification in the Limpopo catchment between around 1 and 0.6 million years ago, opposite to the hydroclimatic evolution suggested by records from Lake Malawi. Our results, together with evidence of wetting at Lake Malawi, imply that the rainbelt contracted toward the Equator in response to increased ice volume at high latitudes. By reducing the extent of woodland or wetlands in terrestrial ecosystems, the observed changes in the hydroclimate of southeastern Africa-both in terms of its long-term state and marked precessional variability-could have had a role in the evolution of early hominins, particularly in the extinction of Paranthropus robustus.

Role of commercial enzymes in wine production: a critical review of recent research.

Purified enzymes of microbial origin are applied in the beverage industry since decades because of their ability to enhance products and processes with minimal side effects and low costs. Commercial enzymes are widely used during different wine making steps providing a broad range of effects, such as to maximise juice yield, improve aroma compounds, flavour enhancement, colour extraction in red wines, and contribute in the removal of dissolved unwanted colloidal particles and pectin substances during wine stabilization and filtration. This review presents a study of recent advances in the application of commercial enzymes in the wine making of red, white and sweet wines that have been made in essentially the last 13 years (2005-2018). Literature has been critically analysed to discover general rules about previous research. Special attention is paid to the safety of enzyme application due to allergic issues. Future research efforts should be concentrated on application of immobilizated enzymes and the use of microorganisms with potential enzymatic side activities during wine production.

Desmoplakin truncations and arrhythmogenic left ventricular cardiomyopathy: characterizing a phenotype.

AIMS: Risk stratification for sudden death in arrhythmogenic right ventricular cardiomyopathy (ARVC) is challenging in clinical practice. We lack recommendations for the risk stratification of exclusive left-sided phenotypes. The aim of this study was to investigate genotype-phenotype correlations in patients carrying a novel DSP c.1339C>T, and to review the literature on the clinical expression and the outcomes in patients with DSP truncating mutations. METHODS AND RESULTS: Genetic screening of the DSP gene was performed in 47 consecutive patients with a phenotype of either an ARVC (n = 24) or an idiopathic dilated cardiomyopathy (DCM), who presented with ventricular arrhythmias or a family history of sudden death (n = 23) (aged 40 ± 19 years, 62% males). Three unrelated probands with DCM were found to be carriers of a novel mutation (c.1339C>T). Cascade family screening led to the identification of 15 relatives who are carriers. Penetrance in c.1339C>T carriers was 83%. Sustained ventricular tachycardia was the first clinical manifestation in six patients and nine patients were diagnosed with left ventricular impairment (two had overt severe disease and seven had a mild dysfunction). Cardiac magnetic resonance revealed left ventricular involvement in nine cases and biventricular disease in three patients. Extensive fibrotic patterns in six and non-compaction phenotype in five patients were the hallmark in imaging. CONCLUSION: DSP c.1339C>T is associated with an aggressive clinical phenotype of left-dominant arrhythmogenic cardiomyopathy and left ventricular non-compaction. Truncating mutations in desmoplakin are consistently associated with aggressive phenotypes and must be considered as a risk factor of sudden death. Since ventricular tachycardia occurs even in the absence of severe systolic dysfunction, an implantable cardioverter-defibrillator should be indicated promptly.

Early science and colossal stone engineering in Menga, a Neolithic dolmen (Antequera, Spain).

Megaliths represent the earliest form of monumental stone architecture. The earliest megalithic chambers in Europe appeared in France in the fifth millennium BCE. Menga is the oldest of the great dolmens in Iberia (approximately 3800 to 3600 BCE). Menga's capstone #5 weighing 150 tons is the largest stone ever moved in Iberia as part of the megalithic phenomenon and one of the largest in Europe. The research presented here proposes a completely innovative interpretation of how this colossal monument was built. It comprises a geoarchaeological analysis encompassing three major components: (i) the angles of the planes of each stone, (ii) the stratigraphic polarity of each structural element, and (iii) the depth of the foundations. Our results show that Menga is a unique example of creative genius and early science among Neolithic societies. It was designed as a completely original engineering project, for which we know of no precedents in Iberia.

School feeding, moving from practice to policy: reflections on building sustainable monitoring and evaluation systems.

OBJECTIVE: To provide an overview of the status of monitoring and evaluation (M&E) of school feeding across sub-Saharan Africa and to reflect on the experience on strengthening M&E systems to influence policy making in low-income countries. DESIGN: Literature review on the M&E of school feeding programmes as well as data from World Food Programme surveys. SETTING: Sub-Saharan Africa. SUBJECTS: Countries implementing school feeding. RESULTS: Only two randomized controlled impact evaluations have been implemented in sub-Saharan Africa. Where M&E data collection is underway, the focus is on process and service delivery and not on child outcomes. M&E systems generally operate under the Ministry of Education, with other Ministries represented within technical steering groups supporting implementation. There is no internationally accepted standardized framework for the M&E of school feeding. There have been examples where evidence of programme performance has influenced policy: considering the popularity of school feeding these cases though are anecdotal, highlighting the opportunity for systemic changes. CONCLUSIONS: There is strong buy-in on school feeding from governments in sub-Saharan Africa. In response to this demand, development partners have been harmonizing their support to strengthen national programmes, with a focus on M&E. However, policy processes are complex and can be influenced by a number of factors. A comprehensive but simple approach is needed where the first step is to ensure a valid mandate to intervene, legitimizing the interaction with key stakeholders, involving them in the problem definition and problem solving. This process has been facilitated through the provision of technical assistance and exposure to successful experiences through South­South cooperation and knowledge exchange.

Drought as a possible contributor to the Visigothic Kingdom crisis and Islamic expansion in the Iberian Peninsula.

The Muslim expansion in the Mediterranean basin was one the most relevant and rapid cultural changes in human history. This expansion reached the Iberian Peninsula with the replacement of the Visigothic Kingdom by the Muslim Umayyad Caliphate and the Muslim Emirate of Córdoba during the 8th century CE. In this study we made a compilation of western Mediterranean pollen records to gain insight about past climate conditions when this expansion took place. The pollen stack results, together with other paleohydrological records, archaeological data and historical sources, indicate that the statistically significant strongest droughts between the mid-5th and mid-10th centuries CE (450-950 CE) occurred at 545-570, 695-725, 755-770 and 900-935 CE, which could have contributed to the instability of the Visigothic and Muslim reigns in the Iberian Peninsula. Our study supports the great sensitivity of the agriculture-based economy and socio-political unrest of Early Medieval kingdoms to climatic variations.

The provenance of the stones in the Menga dolmen reveals one of the greatest engineering feats of the Neolithic.

The technical and intellectual capabilities of past societies are reflected in the monuments they were able to build. Tracking the provenance of the stones utilised to build prehistoric megalithic monuments, through geological studies, is of utmost interest for interpreting ancient architectures as well as to contribute to their protection. According to the scarce information available, most stones used in European prehistoric megaliths originate from locations near the construction sites, which would have made transport easier. The Menga dolmen (Antequera, Malaga, Spain), listed in UNESCO World Heritage since July 2016, was designed and built with stones weighting up to nearly 150 tons, thus becoming the most colossal stone monument built in its time in Europe (c. 3800-3600 BC). Our study (based on high-resolution geological mapping as well as petrographic and stratigraphic analyses) reveals key geological and archaeological evidence to establish the precise provenance of the massive stones used in the construction of this monument. These stones are mostly calcarenites, a poorly cemented detrital sedimentary rock comparable to those known as 'soft stones' in modern civil engineering. They were quarried from a rocky outcrop located at a distance of approximately 1 km. In this study, it can be inferred the use of soft stone in Menga reveals the human application of new wood and stone technologies enabling the construction of a monument of unprecedented magnitude and complexity.

Roman water management impacted the hydrological functioning of wetlands during drought periods.

During the Roman domain of the Iberian Peninsula (from 201 BCE to 460 CE) water management infrastructures were built to satisfy high water demand. However, whether the Roman activities affected the hydrological balance of Iberian wetlands remains unclear. Here, we investigate the paleo-hydrology of Lake Zóñar (southern Iberia) by using the stable isotopes (16O, 17O, 18O, 1H and 2H) of its gypsum (CaSO4·2H2O) sediments and reconstruct the isotopic composition of the lake water during Roman times. A period of recurrent lake low stand occurred between 2120 and 1890 cal. yr BP (ca. 170 BCE to 60 CE), coinciding with a relatively dry climate stage recorded by most regional paleoclimate archives. The stable isotopes and hydrochemistry of the lake water during gypsum precipitation are consistent with a shallow saline lake that evaporated under relative humidity ~ 10% lower than the present annual mean and at least 20% less rainfall amount. Our analytical and archeological findings support lake level lowering during the Roman period was probably caused by combined arid climate conditions and diversion of the inlets feeding the lake. Spring capturing was likely necessary to satisfy the high water demand of nearby Roman settlements, in the framework of a period of persistent droughts.

Recurrent genetic variants and prioritization of variants of uncertain clinical significance associated with hereditary breast and ovarian cancer in families from the Region of Murcia.

Objectives: Hereditary breast and ovarian cancer (HBOC) follows an autosomal dominant inheritance pattern of cancer susceptibility genes. The risk of developing this disease is primarily associated with germline mutations in the BRCA1 and BRCA2 genes. The advent of massive genetic sequencing technologies has expanded the mutational spectrum of this hereditary syndrome, thereby increasing the number of variants of uncertain clinical significance (VUS) detected by genetic testing. Methods: A prevalence study of HBOC was performed within 2,928 families from the Region of Murcia, in southeastern Spain. Genetic testing enabled the identification of recurrent pathogenic variants and founder mutations, which were mainly related to the BRCA1 and BRCA2 genes. VUS testing was performed using a prioritization algorithm designed by our working group. Results: Variants c.68_69del, c.212+1G>A, and c.5123C>A were detected in 30 % of BRCA1 carriers, whereas exon 2 deletion concurrent with c.3264dupT, c.3455T>G and c.9117G>A variants were found in 30 % of BRCA2 carriers. A total of 16 VUS (15 %) were prioritized. Conclusions: The genotype-phenotype correlation observed in our study is consistent with the scientific literature. Furthermore, the founder effect of c.1918C>T (BRCA1) and c.8251_8254del (ATM) was verified in the Murcian population, whereas exon 2 deletion (BRCA2) was proven to be a Spanish founder mutation. Our algorithm enabled us to prioritize potentially pathogenic VUS that required further testing to determine their clinical significance and potential role in HBOC.

Late survival of Neanderthals at the southernmost extreme of Europe.

The late survival of archaic hominin populations and their long contemporaneity with modern humans is now clear for southeast Asia. In Europe the extinction of the Neanderthals, firmly associated with Mousterian technology, has received much attention, and evidence of their survival after 35 kyr bp has recently been put in doubt. Here we present data, based on a high-resolution record of human occupation from Gorham's Cave, Gibraltar, that establish the survival of a population of Neanderthals to 28 kyr bp. These Neanderthals survived in the southernmost point of Europe, within a particular physiographic context, and are the last currently recorded anywhere. Our results show that the Neanderthals survived in isolated refuges well after the arrival of modern humans in Europe.

Clinical Outcomes after Surgical Resection Combined with Brachytherapy for Uveal Melanomas.

Currently, brachytherapy is the most commonly used therapeutic approach for uveal melanomas. Surgical resection by means of endoresection or exoresection is an alternative approach. The present report recounts our experience over 15 years in the treatment of uveal melanoma using a combined approach of resection surgery with brachytherapy. This is a single-center observational retrospective cohort study in which we describe clinical outcomes, complications and survival in 35 cases of melanoma of the iris or the ciliary body after a combination of surgery and brachytherapy or brachytherapy alone. Local treatment of the tumor was successful in all cases with surgery and brachytherapy. The most frequent complications were scleromalacia, bullous keratopathy, retinal toxicity, cataracts, hypotonia, and photophobia. There were three cases of recurrence, all of which were found in the group of patients who had received brachytherapy alone, and in one case we had to perform a secondary enucleation due to tumor growth after brachytherapy. At present, only one patient has died during follow-up due to liver metastases six years after the start of treatment. In carefully selected patients, this approach can be effective and safe, as long as a close follow-up is carried out after surgery.

Next step in molecular genetics of hereditary breast/ovarian cancer: Multigene panel testing in clinical actionably genes and prioritization algorithms in the study of variants of uncertain significance.

INTRODUCTION: BRCA1 and BRCA2 are the two main genes causing hereditary breast and ovarian cancer (HBOC). However, thanks to the development of Next Generation Sequencing (NGS), other genes linked to this syndrome (CHEK2, BRIP1, ATM and PALB2 among others) can be analysed. MATERIAL AND METHODS: an analysis by multigene panel testing was performed in 138 index cases (ICs) from HBOC Spanish families with a previous non-informative result for BRCA1/2. The BRCA Hereditary Cancer Master™ Plus kit, including 26 actionable and candidate genes related to HBOC was employed. Once classified, an algorithm was employed to prioritized those variants of unknown significance with a higher risk of having a deleterious effect. Moreover, a mRNA splicing assay was performed for the prioritized VUS c.3402+3A > C in ATM, located at intron 23. RESULTS: A total of 82 variants were found: 70 VUS and 12 pathogenic or probably pathogenic variants. The diagnostic yield in actionable genes non-BRCA was 7.97% of the total tested ICs. Overall, 19 VUS were prioritized, which meant 27% of the 70 total VUS. RNA analysis of the variant 3402+3A > C confirmed a deleterious impact on splicing. DISCUSSION: The implementation of a multigene panel in HBOC studied families improved the diagnostic yield, concordant with results obtained in previous publications. Due to the important number of VUS obtained in NGS, the application of a prioritization algorithm is needed in order to select those variants in which it is necessary to conduct further studies.

Deep Learning Techniques for Spanish Sign Language Interpretation.

Around 5% of the world population suffers from hearing impairment. One of its main barriers is communication with others since it could lead to their social exclusion and frustration. To overcome this issue, this paper presents a system to interpret the Spanish sign language alphabet which makes the communication possible in those cases, where it is necessary to sign proper nouns such as names, streets, or trademarks. For this, firstly, we have generated an image dataset of the signed 30 letters composing the Spanish alphabet. Then, given that there are static and in-motion letters, two different kinds of neural networks have been tested and compared: convolutional neural networks (CNNs) and recurrent neural networks (RNNs). A comparative analysis of the experimental results highlights the importance of the spatial dimension with respect to the temporal dimension in sign interpretation. So, CNNs obtain a much better accuracy, with 96.42% being the maximum value.

The costs and cost-efficiency of providing food through schools in areas of high food insecurity.

BACKGROUND: The provision of food in and through schools has been used to support the education, health, and nutrition of school-aged children. The monitoring of financial inputs into school health and nutrition programs is critical for a number of reasons, including accountability, transparency, and equity. Furthermore, there is a gap in the evidence on the costs, cost-efficiency, and cost-effectiveness of providing food through schools, particularly in areas of high food insecurity. OBJECTIVE: To estimate the programmatic costs and cost-efficiency associated with providing food through schools in food-insecure, developing-country contexts, by analyzing global project data from the World Food Programme (WFP). METHODS: Project data, including expenditures and number of schoolchildren covered, were collected through project reports and validated through WFP Country Office records. Yearly project costs per schoolchild were standardized over a set number of feeding days and the amount of energy provided by the average ration. Output metrics, such as tonnage, calories, and micronutrient content, were used to assess the cost-efficiency of the different delivery mechanisms. RESULTS: The average yearly expenditure per child, standardized over a 200-day on-site feeding period and an average ration, excluding school-level costs, was US$21.59. The costs varied substantially according to choice of food modality, with fortified biscuits providing the least costly option of about US$11 per year and take-home rations providing the most expensive option at approximately US$52 per year. Comparisons across the different food modalities suggested that fortified biscuits provide the most cost-efficient option in terms of micronutrient delivery (particularly vitamin A and iodine), whereas on-site meals appear to be more efficient in terms of calories delivered. Transportation and logistics costs were the main drivers for the high costs. CONCLUSIONS: The choice of program objectives will to a large degree dictate the food modality (biscuits, cooked meals, or take-home rations) and associated implementation costs. Fortified biscuits can provide substantial nutritional inputs at a fraction of the cost of school meals, making them an appealing option for service delivery in food-insecure contexts. Both costs and effects should be considered carefully when designing the appropriate school-based intervention. The costs estimates in this analysis do not include all school-level costs and are therefore lower-bound estimates of full implementation costs.

School feeding: outcomes and costs.

BACKGROUND: School-feeding programs are popular development assistance programs in developing countries but have previously had few sound, empirical analyses of their effectiveness and costs. OBJECTIVE: The goals of this study were to provide a realistic estimate of the costs of school feeding and combine these estimates with outcome information to obtain the cost per outcome. METHODS: Cost studies were conducted in three African countries by reviewing school-feeding costs provided by the World Food Programme and interviewing stakeholders in ministries of education and in the community. In another African country, existing costing information was used. To compare across the countries, costs were standardized for a 200-day school year, a 700-kcal per day ration, and when children were not fed. To obtain cost per outcome data, outcomes were obtained from a review of school-feeding studies. RESULTS: The cost of school feeding ranged from U.S. $28 to U.S. $63 per child per year (weighted mean cost of U.S. $40 per child per year). The cost for an extra day of attendance was less than U.S. $10 per student, while the cost per extra kilogram of weight ranged from U.S. $38 to U.S. $252. Costs for cognitive outcomes were similarly variable. CONCLUSIONS: This analysis estimates a higher average cost but a narrower range of costs when compared with previous estimates, reflecting the greater precision of the current analyses. The cost per outcome was high, but this analysis does not capture the full range of outcomes (e.g., social protection, educational achievement) potentially derived from school feeding.

An early Aurignacian arrival in southwestern Europe.

Westernmost Europe constitutes a key location in determining the timing of the replacement of Neanderthals by anatomically modern humans (AMHs). In this study, the replacement of late Mousterian industries by Aurignacian ones at the site of Bajondillo Cave (Málaga, southern Spain) is reported. On the basis of Bayesian analyses, a total of 26 radiocarbon dates, including 17 new ones, show that replacement at Bajondillo took place in the millennia centring on ~45-43 calibrated thousand years before the present (cal ka BP)-well before the onset of Heinrich event 4 (~40.2-38.3 cal ka BP). These dates indicate that the arrival of AMHs at the southernmost tip of Iberia was essentially synchronous with that recorded in other regions of Europe, and significantly increases the areal expansion reached by early AMHs at that time. In agreement with human dispersal scenarios on other continents, such rapid expansion points to coastal corridors as favoured routes for early AMH. The new radiocarbon dates align Iberian chronologies with AMH dispersal patterns in Eurasia.

Matrix metalloproteinases and tissue remodeling in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is defined by the presence of unexplained left ventricular hypertrophy, myocyte disarray, and interstitial fibrosis. An increase in extracellular matrix produces interstitial fibrosis, by raised amounts of collagen type I/III. Regions of myocardial late gadolinium enhancement by cardiac magnetic resonance (CMR) represented increased myocardial collagen. Regarding the role of matrix metalloproteinases (MMPs) in myocardial remodeling and subsequent fibrosis, the aim of our study was to explore the relation between MMP system and myocardial late gadolinium enhancement by CMR (as expression of image-documented fibrosis) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (as a marker of cardiac overload) in HCM. METHODS: We included 67 HCM patients (44 men aged 49 +/- 14 years) and were compared to 58 controls with similar age and sex. Risk factors for sudden death were recorded. A blinded CMR was performed with gadolinium. Matrix metalloproteinase 1, MMP-2, and MMP-9 plasma levels were assayed by enzyme-linked immunosorbent assay. Serum samples were used for measurement of NT-proBNP. RESULTS: In patients, >50% of MMP-1 values were below the lowest limit of detection of the technique. Raised levels of MMP-2, MMP-9, and NT-proBNP were observed in HCM patients (all P < .01). Matrix metalloproteinase 2 was associated with dyspnea (P = .049) and correlated with MMP-9 (r = 0.28, P = .025) and NT-proBNP (r = 0.39, P = .001). Matrix metalloproteinase 9 was associated with the presence of gadolinium enhancement in CMR (P = .001) and correlated with NT-proBNP (r = 0.52, P < .001). NT-proBNP was also associated with gadolinium enhancement (P = .006). Both MMP-2 and MMP-9 correlated negatively with exercise capacity (metabolic equivalent units), (r = -0.36 and r = -0.42 respectively, both P < .01). On multivariate analysis (adjusted by sudden death risk factors and echocardiographic markers), only MMP-9 was associated with fibrosis (P = .011). CONCLUSIONS: Matrix metalloproteinase 9 is independently associated with gadolinium enhancement on CMR in patients with hypertrophic cardiomyopathy, suggesting that the MMP system has an important role in cardiac remodeling and fibrosis in this condition.

Variables associated with contrast-enhanced cardiovascular magnetic resonance in hypertrophic cardiomyopathy: clinical implications.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) shows increased myocardial collagen and disarray. Late gadolinium enhancement in cardiovascular magnetic resonance (CMR) is observed in regions of increased myocardial collagen. The extent of late gadolinium enhancement has been associated with higher prevalence of risk factors of sudden death. The aim of the present study was to describe the clinical characteristics and the presence of risk factors for sudden death in a series of patients from 2 referral centers for HCM in relation to late gadolinium enhancement in CMR. METHODS AND RESULTS: A total of 120 patients (47 +/- 16 years) were included. All patients fulfilled conventional criteria for HCM. A complete history and clinical examination were performed. Risk factors for sudden death were evaluated. A blinded CMR was performed with late gadolinium enhancement in the left ventricular short-axis orientation. NT pro B-type natriuretic protein (BNP) and C-reactive protein were determined in serum samples. A total of 83 patients (69%) showed late gadolinium enhancement. These patients had higher maximal left ventricular wall thickness (22 +/- 5 versus 17 +/- 3 mm, P < .001), showed more frequently obstruction (42% versus 16%, P = .006), nonsustained ventricular tachycardia (38% versus 8%, P = .001), worse exercise capacity (8 +/- 4 versus 10 +/- 4 METs, P = .003) and increased levels of NT BNP (656 [300-1948] versus 290 [122-948] pg/mL, P = .020). On multivariate analysis, maximal left ventricular wall thickness (P < .001) and nonsustained ventricular tachycardia (P = .011) remained associated with gadolinium-enhanced imaging. Number of risk factors for sudden death was associated with late gadolinium enhancement (OR 2.18, 95%CI 1.45-3.20, P < .001). CONCLUSIONS: Late gadolinium enhancement in CMR is a common finding in HCM. Increased maximal left ventricular wall thickness and nonsustained ventricular tachycardia are associated with late gadolinium enhancement. Associations with risk factors for sudden death and functional status are observed.