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Objective To evaluate the spontaneous progression of cervical intraepithelial neoplasia grade 2 (CIN2) in accordance with Chlamydia trachomatis (chlamydia) serology. Methods A prospective observational study included women diagnosed with CIN2 by cervical biopsy and managed conservatively for 24 months at Hospital del Mar, Barcelona, between December 2011 and October 2013. Serum anti-chlamydia immunoglobulin G (IgG), previous cytology, and high-risk human papillomavirus (HPV) genotyping were recorded at baseline. The outcome was regression, persistence, or progression of CIN2. Results Overall, 93 women aged 18-56 years were enrolled. Spontaneous regression was observed for 61 (66%) women, and 21 (23%) progressed to CIN3. Eight (9%) women had chlamydia seropositivity at baseline. Multivariate analysis showed that anti-chlamydia IgG seropositivity (odds ratio [OR], 19.1; 95% confidence interval [CI], 1.9-189.7), previous high-grade squamous intraepithelial lesion cytology (OR, 5.0; 95% CI, 1.7-14.6), and HPV16 (OR, 4.8; 95% CI, 1.7-13.7) increased the risk of CIN2 persistence or progression. Conclusion Women with CIN2 and chlamydia IgG seropositivity had increased risk of progression to CIN2+ and immediate treatment may be recommended for these women. Larger clinical studies are needed to confirm the results, but chlamydia serology might be introduced into CIN2 management to better individualize treatment.

mRNA-based vaccines effectively induce protective neutralizing antibody responses against SARS-CoV-2, the etiological agent of COVID-19. The specific compositional patterns of these responses remain largely unknown. We found that SARS-CoV-2-naïve individuals receiving the first dose of an mRNA vaccine developed a SARS-CoV-2-specific antibody response with a subclass profile comparable to that induced by the natural infection, except IgA2, which did not increase. SARS-CoV-2-naïve subjects also mounted a robust virus-specific recall response after receiving the second dose. This response increased all IgG subclasses, but boosted neither IgM nor IgA1 and IgA2 subclasses. In contrast, individuals recovered from COVID-19 mounted peak virus-specific antibody responses upon primary immunization and did not further augment such responses following secondary immunization. Remarkably, compared to SARS-CoV-2-naïve subjects, individuals with pre-existing immunity showed increased levels of all virus-specific antibodies but IgG3 following primary vaccination. By dissecting the heterogeneity of mRNA vaccine-induced humoral responses to SARS-CoV-2, our findings indicate that the induction of optimal immune protection may require the development of personalized vaccination programs.

Background Cardiac magnetic resonance (CMR) constitutes a gold standard in the diagnosis of cardiomyopathies. Regardless of CMR advantages, the method is time-consuming, high-cost, with limited availability in some European regions. Purpose To assess the availability and applicability of CMR for establishing the diagnosis in different populations of patients with cardiomyopathies. Methods Overall, 3208 adult patients with cardiomyopathy (1119 / 34.9% females; median age at diagnosis: 49.0 years): 1260 with dilated (DCM), 1739 with hypertrophic (HCM), 66 with restrictive (RCM) and 143 with arrhythmogenic right ventricular cardiomyopathy (ARVC) enrolled in EURObservational Research Programme (EORP) – Cardiomyopathy/Myocarditis Long-Term Registry were analysed. Results CMR scan was performed as a baseline diagnostic method in 29.4% of patients; CMR was a single diagnostic method in 0.9% of patients and in 28.6% of patients CMR was used along with transthoracic echocardiography (TTE). In 67.6% of patients TTE was at the baseline the single diagnostic imaging method. Prevalence of CMR use in different cardiomyopathies was as follows: 20.6% in DCM, 33.8% in HCM, 36.4% in RCM and 51.1% in ARVC (p The population with CMR use was younger, less symptomatic, with decreased prevalence of other cardiovascular risk factors and of associated cardiovascular diseases as compared to the population diagnosed without CMR scanning (p Abnormal CMR results were present in 93.4% of patients with the highest percentage in RCM (95.8%) and HCM (94.9%) followed by DCM (91.5%) and the lowest abnormal CMR scan ratio in ARVC (87.7%) (p=0.030). The majority of CMR examinations comprised the assessment of late gadolinium enhancement (LGE, 93.3% at baseline). Presence of CMR LGE was observed in 69.3% of all patients: 59.1% in DCM, 73.8% in HCM, in 63.9% in ARVC and with the highest prevalence in RCM (83.3%) (p Conclusion The study reveals real-life data on the low availability and applicability of CMR in adult patients with cardiomyopathies. The analysis shows the advantages of CMR imaging but also identifies the gaps between recommendations and clinical practice. Improvement regarding access, training and reimbursement is necessary to offer CMR to cardiomyopathy patients in accordance with the ESC guidelines. Funding Acknowledgement Type of funding source: None

Use of adoptive immunotherapy with virus-specific T cells (VST) in patients with inborn errors of immunity prior to hematopoietic stem cell transplantation (HSCT) has been reported in few patients. We report our experience, reviewing all the cases previously reported. We report four children with inborn errors of immunity who received VST infusion in a pre-HSCT setting in two reference centers in Spain and review all inborn errors of immunity cases previously reported. Taking into account our four cases, nine children have been reported to receive VST prior to HSCT to date: 3 severe combined immunodeficiency, 2 CTPS1 deficiency, 1 dyskeratosis congenital, 1 ORAI1 deficiency, 1 Rothmund-Thomson syndrome, and 1 combined immunodeficiency without confirmed genetic defect. In four patients, immunotherapy resulted in clinical improvement, allowing to proceed to HSCT. In these cases, the infusion was started closely to viral diagnosis [mean time 28 days (IQR; 17–52 days)], and the VST was followed shortly thereafter by HSCT [mean time 28 days (IQR; 10–99 days)]. Viremia was controlled after HSCT in two cases (performed 7 and 36 days after the infusion). Multiple infusions were required in many cases. Five out of nine patients died before receiving HSCT. These patients presented with a prolonged and uncontrolled infection before VST administration [mean time from viral diagnosis to VST infusion was 176 days (IQR; 54–1687)]. In patients with inborn errors of immunity, the efficacy of VST for treating disseminated viral infections in pre-transplant settings seems to have a limited efficacy. However, this therapy could be used in a pre-emptive setting before severe viral disease occurs or closely to HSCT.

Autoinflammatory diseases (AIDs) were first described as clinical disorders characterized by recurrent episodes of seemingly unprovoked sterile inflammation. In the past few years, the identification of novel AIDs expanded their phenotypes toward more complex clinical pictures associating vasculopathy, autoimmunity, or immunodeficiency. Herein, we describe two unrelated patients suffering since the neonatal period from a complex disease mainly characterized by severe sterile inflammation, recurrent bacterial infections, and marked humoral immunodeficiency. Whole-exome sequencing detected a novel, de novo heterozygous PLCG2 variant in each patient (p.Ala708Pro and p.Leu845_Leu848del). A clear enhanced PLCγ2 activity for both variants was demonstrated by both ex vivo calcium responses of the patient's B cells to IgM stimulation and in vitro assessment of PLC activity. These data supported the autoinflammation and PLCγ2-associated antibody deficiency and immune dysregulation (APLAID) diagnosis in both patients. Immunological evaluation revealed a severe decrease of immunoglobulins and B cells, especially class-switched memory B cells, with normal T and NK cell counts. Analysis of bone marrow of one patient revealed a reduced immature B cell fraction compared with controls. Additional investigations showed that both PLCG2 variants activate the NLRP3-inflammasome through the alternative pathway instead of the canonical pathway. Collectively, the evidences here shown expand APLAID diversity toward more severe phenotypes than previously reported including dominantly inherited agammaglobulinemia, add novel data about its genetic basis, and implicate the alternative NLRP3-inflammasome activation pathway in the basis of sterile inflammation. This work has been partially funded by the following: CERCA Programme/Generalitat de Catalunya (JIA), SAF2015-68472-C2-1-R grant from the Spanish Ministry of Economy and Competitiveness co-financed by European Regional Development Fund (ERDF) (JIA), RTI2018-096824-B-C21 grant from the Spanish Ministry of Science, Innovation and Universities co-financed by ERDF (JIA), AC15/00027 grant from the Instituto de Salud Carlos III/Transnational Research Projects on Rare Diseases (JIA), PI14/00405 grant from the Instituto de Salud Carlos III co-financed by ERDF (RC), PI13/00174 grant from the Spanish Ministry of Economy and Competitiveness co-financed by ERDF (PP), SAF2017-88276-R grant from the Spanish Ministry of Economy, Industry and Competitiveness co-financed by ERDF (PP), ERC-2013-CoG project 614578 from the European Research Council (PP), 20859/PI/18 grant from Fundación Séneca (PP), SAF2015-68472-C2-2-R grant from the Spanish Ministry of Economy and Competitiveness co-financed by ERDF (FC) and RTI2018-096824-B-C22 grant from the Spanish Ministry of Science, Innovation and Universities co-financed by ERDF (FC). MK acknowledges support from CRUK (A16567) and MRC (P028160). H M-B is a Rio Hortega fellowship from Instituto de Salud Carlos III (CM14/00008) and DB acknowledges support from the UCL Impact Studentship.

Although the efficacy of omalizumab has been clearly demonstrated in the treatment of chronic spontaneous urticaria (CSU), its mechanism of action, which results in improvement in CSU symptoms, is not entirely understood. This study investigated the effect of omalizumab on expression of the high-affinity IgE receptor (FcεRI) on blood basophils from patients with active CSU, and its association with the clinical response. Patients exhibiting significant clinical improvement showed a sharp reduction in the levels of basophil FcεRI after 4 weeks, which was maintained throughout the total duration of the treatment. Such evolution was not observed in non-responder patients. Furthermore, non-responders showed significantly lower baseline levels of FcεRI than responders. Baseline basophil FcεRI expression was found to be a potential immunological predictor of response to omalizumab (100% sensitivity and 73.2% specificity). The results of this study contribute to our knowledge of the therapeutic benefit and mechanism of action of anti-IgE therapy in CSU.

Recent research has proven the existence of statistical relation among fragmented QRS and several highly prevalence diseases, such as cardiac sarcoidosis, acute coronary syndrome, arrythmogenic cardiomyopathies, Brugada syndrome, and hypertrophic cardiomyopathy. One out of five hundred people suffer from hypertrophic cardiomyopathies. The relation among the fragmentation and arrhythmias drives the objective of this work, which is to propose a valid method for QRS fragmentation detection. With that aim, we followed a two-stage approach. First, we identified the features that better characterize the fragmentation by analyzing the physiological interpretation of multivariate approaches, such as principal component analysis (PCA) and independent component analysis (ICA). Second, we created an invariant transformation method for the multilead electrocardiogram (ECG), by scrutinizing the statistical distributions of the PCA eigenvectors and of the ICA transformation arrays, in order to anchor the desired elements in the suitable leads in the feature space. A complete database was compounded incorporating real fragmented ECGs, surrogate registers by synthetically adding fragmented activity to real non-fragmented ECG registers, and standard clean ECGs. Results showed that the creation of beat templates together with the application of PCA over eight independent leads achieves 0.995 fragmentation enhancement ratio and 0.07 dispersion coefficient. In the case of ICA over twelve leads, the results were 0.995 fragmentation enhancement ratio and 0.70 dispersion coefficient. We conclude that the algorithm presented in this work constructs a new paradigm, by creating a systematic and powerful tool for clinical anamnesis and evaluation based on multilead ECG. This approach consistently consolidates the inconspicuous elements present in multiple leads onto designated variables in the output space, hence offering additional and valid visual and non-visual information to standard clinical review, and opening the door to a more accurate automatic detection and statistically valid systematic approach for a wide number of applications. In this direction and within the companion paper, further developments are presented applying this technique to fragmentation detection.

BACKGROUND: The high-affinity IgE receptor (FcεRI) expression on effector cells has been poorly characterized in patients with chronic urticaria (CU) to date. OBJECTIVES: To investigate the FcεRI expression on blood basophils in a large cohort of patients with CU and its potential relationship with relevant features of the disease. METHODS: Basophil FcεRI expression was measured by flow cytometry in 287 patients with CU (192 with chronic spontaneous urticaria and 95 with chronic inducible urticaria) at their initial evaluation in our department. A control group of healthy nonatopic individuals was included to provide reference data, and the effect of antihistamine and anti-IgE therapy on the basophil FcεRI expression was also evaluated in a cohort of patients with CU. RESULTS: The median FcεRI expression was found significantly higher in patients with CU compared with healthy controls (P < .0001). A positive correlation was found between serum IgE levels and basophil FcεRI expression (R = 0.422; P < .001). Significantly higher FcεRI levels on basophils were detected in patients with CU who presented with concomitant atopic features (P = .003), negative autologous serum skin test (P = .002), negative autologous plasma skin test (P = .009), or undetected levels of antithyroid antibodies (P = 0.01). Baseline FcεRI expression was not related to the activity and duration of the disease, and was not significantly modified during antihistamine therapy; however, it correlated with the clinical response to omalizumab (P = .003). CONCLUSIONS: Although further multicenter studies are needed to corroborate these findings, the assessment of basophil FcεRI levels might be relevant in daily clinical practice supporting an autoimmune pathogenesis and predicting response to anti-IgE treatment.

The aim of the study was to assess drug levels, immunogenicity and sacroiliitis on MRI in patients with axial spondyloarthritis under biologic tapering strategy. Consecutive patients with axial spondyloarthritis who remained in low disease activity more than 1 year after dose tapering of infliximab and adalimumab were included. Plasma drug concentrations of TNF inhibitors and anti-drug antibodies were determined, and MRI of sacroiliac joints was evaluated. Of twenty patients included, eighteen had therapeutic drug levels, no patient had anti-drug antibodies, and no patient had active sacroiliitis on MRI. These data could support the biologic tapering strategy and their maintenance over time.

Hypertrophic cardiomyopathy (HCM) is a myocardial disorder that affects 0.2% of the population and it is genetically transmitted. Several ECG findings have been related to the presence of fibrosis in other cardiac diseases, but data for HCM in this setting are lacking. Our hypothesis is that fibrosis affects the electrical cardiac propagation in patients with HCM in a relatively specific way and that this effect may be detected with suitable postprocessing applied to the ECG signals. We used 43 standard 12-lead ECGs from patients with previous clinical diagnosis of HCM. Principal Component Analysis (PCA) was applied by combining the ECG-leads oriented to different anatomic regions, hence assessing the potential fibrosis effects in the resulting leads for postprocessing convenience. Linear classifier of Support Vector Machine type were used with several statistics extracted from the resulting PCA-components, including normalized power, standard deviation, kurtosis, skewness, and local maxima. Results reached 75.0% sensitivity, 80.0% specificity, 85.7% positive predictive value, 66.7% negative predictive value, and 76.9% accuracy in our database. There is evidence that myocardial fibrosis can be detected in patients with HCM by postprocessing their ECG signals.

Cytomegalovirus encephalitis is a challenging life-threatening complication following hematopoietic stem cell transplantation for which medical treatment is usually ineffective or toxic. However, in recent years, adoptive T-cell therapy has been reported to provide a significant chance of cure for patients with viral infections. Herein, two cases of pediatric patients successfully treated with third-party donor-derived virus-specific T cells for CMV meningoencephalitis are reported.

The CD45RA T cell depletion (TCD) method has been used to deplete naive T cells, preventing graft-versus-host disease (GVHD) but preserving memory cells, providing immediate functional T cells with anti-infection, antileukemia, and antirejection effects. We describe a series of 25 consecutive high-risk patients with leukemia who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with CD45RA TCD. Each patient received 2 cell products: 1 created by CD34 positive selection and the other through CD45RA depletion from the CD34 negative fraction by a CliniMACS device. CD45RA-depleted haplo-HSCT was well tolerated, with rapid engraftment and low risk of severe acute GVHD and chronic GVHD. Although this treatment achieved a good control of viral reactivations, such as cytomegalovirus and adenovirus, we observed an unexpectedly high rate of limbic encephalitis due to human herpesvirus-6 (HHV-6; 8 cases). Characteristically, the infection appeared early in almost all patients, just after the engraftment. Although no patient died from encephalitis, 1 patient showed neuropsychological sequelae, and another experienced secondary graft failure just after the HHV-6 reactivation. (C) 2018 American Society for Blood and Marrow Transplantation.

Objectives Atrial fibrillation (AF) is associated with increased morbidity and mortality in patients with hypertrophic cardiomyopathy (HCM). The primary aim of this study (HCM Risk-AF) was to determine the predictors of AF in a large multicentre cohort of patients with HCM. Exploratory analyses were performed to investigate the association between AF and survival and the efficacy of antiarrhythmic therapy in maintaining sinus rhythm (SR). Methods A retrospective, longitudinal cohort of patients recruited between 1986 and 2008 in seven centres was used to develop multivariable Cox regression models fitted with preselected predictors. HCM was defined as unexplained hypertrophy (maximum left ventricular wall thickness of ≥15 mm or in accordance with published criteria for the diagnosis of familial disease). 28% of patients (n=1171) had coexistent hypertension. The primary end point was paroxysmal, permanent or persistent AF detected on ECG, Holter monitoring or implantable device interrogation. Results Of the 4248 patients with HCM without pre-existing AF, 740 (17.4%) reached the primary end point. Multivariable Cox regression revealed an association between AF and female sex, age, left atrial diameter, New York Heart Association (NYHA) class, hypertension and vascular disease. The proportion of patients with cardiovascular death at 10 years was 4.9% in the SR group and 10.9% in the AF group (difference in proportions=5.9%; 95% CI (4.1% to 7.8%)). The proportion of patients with non-cardiovascular death at 10 years was 3.2% in the SR group and 5.9% in the AF group (difference in proportions=2.8%; 95% CI (0.1% to 4.2%)). An intention-to-treat propensity score analysis demonstrated that β-blockers, calcium channel antagonists and disopyramide initially maintained SR during follow-up, but their protective effect diminished with time. Amiodarone therapy did not prevent AF during follow-up. Conclusion This study shows that patients with HCM who are at risk of AF development can be identified using readily available clinical parameters. The development of AF is associated with a poor prognosis but there was no evidence that antiarrhythmic therapy prevents AF in the long term.

Hypertrophic cardiomyopathy, according to its prevalence, is a comparatively common disease related to the risk of suffering sudden cardiac death, heart failure and stroke. This illness is characterized by the excessive deposition of collagen among healthy myocardium cells. This situation, which is medically known as fibrosis, constitutes effective conduction obstacles in the myocardium electrical path, and when severe enough, it can be outlined as additional peaks or notches in the QRS, clinically entitled as fragmentation. Nowadays, the fragmentation detection is performed by visual inspection, but the fragmented QRS can be confused with the noise present in the electrocardiogram (ECG). On the other hand, fibrosis detection is performed by magnetic resonance imaging with late gadolinium enhancement, the main drawback of this technique being its cost in terms of time and money. In this work, we propose two automatic algorithms, one for fragmented QRS detection and another for fibrosis detection. For this purpose, we used four different databases, including the subrogated database described in the companion paper and incorporating three additional ones, one compounded by more accurate subrogated ECG signals and two compounded by real and affected subjects as labeled by expert clinicians. The first real-world database contains QRS fragmented records and the second one contains records with fibrosis and both were recorded in Hospital Cl&iacute, nico Universitario Virgen de la Arrixaca (Spain). To deeply analyze the scope of these datasets, we benchmarked several classifiers such as Neural Networks, Support Vector Machines (SVM), Decision Trees and Gaussian Na&iuml, ve Bayes (NB). For the fragmentation dataset, the best results were 0.94 sensitivity, 0.88 specificity, 0.89 positive predictive value, 0.93 negative predictive value and 0.91 accuracy when using SVM with Gaussian kernel. For the fibrosis databases, more limited accuracy was reached, with 0.47 sensitivity, 0.91 specificity, 0.82 predictive positive value, 0.66 negative predictive value and 0.70 accuracy when using Gaussian NB. Nevertheless, this is the first time that fibrosis detection is attempted automatically from ECG postprocessing, paving the way towards improved algorithms and methods for it. Therefore, we can conclude that the proposed techniques could offer a valuable tool to clinicians for both fragmentation and fibrosis diagnoses support.

Summary We conducted a multicentre study of 1844 patients from 42 Spanish intensive care units, and analysed the clinical characteristics of brain death, the use of ancillary testing, and the clinical decisions taken after the diagnosis of brain death. The main cause of brain death was intracerebral haemorrhage (769/1844, 42%), followed by traumatic brain injury (343/1844, 19%) and subarachnoid haemorrhage (257/1844, 14%). The diagnosis of brain death was made rapidly (50% in the first 24 h). Of those patients who went on to die, the Glasgow Coma Scale on admission was ≤ 8/15 in 1146/1261 (91%) of patients with intracerebral haemorrhage, traumatic brain injury or anoxic encephalopathy; the Hunt and Hess Scale was 4–5 in 207/251 (83%) of patients following subarachnoid haemorrhage; and the National Institutes of Health Stroke Scale was ≥ 15 in 114/129 (89%) of patients with strokes. Brain death was diagnosed exclusively by clinical examination in 92/1844 (5%) of cases. Electroencephalography was the most frequently used ancillary test (1303/1752, 70.7%), followed by transcranial Doppler (652/1752, 37%). Organ donation took place in 70% of patients (1291/1844), with medical unsuitability (267/553, 48%) and family refusal (244/553, 13%) the main reasons for loss of potential donors. All life-sustaining measures were withdrawn in 413/553 of non-donors (75%).

Though alternans phenomena in the cardiac repolarization phase has been shown to be related to arrhythmgenesis, a definitive estimation method from the T wave of ECG recordings is not yet available. We propose a statistical signal processing scheme which compares the T-wave morphology of even and odd beats by using a running matched filter, in order to increase the signal to noise ratio of the estimation. Given that previously proposed hypothesis tests for alternans detection rely on the knowledge of noise statistical distribution, we also analyzed the usefulness of a nonparametric bootstrap test. Data set composed of 100 ECG recordings included in the Challenge Database were used. Principal Component Analysis was previously made for multilead recordings. Subsequent preprocessing for each available lead consisted of conventional baseline removing, filtering, R-wave detection, exclusion of too noisy segments, T-wave segmentation, and template generation for even and odd beats. The difference between the template and a given beat was obtained by minimizing the absolute error of their comparison with a windowed circular shift. A paired bootstrap resampling test was made for deciding whether the averaged differences between the template and the T-waves were significant compared to the noise level. Teoría de la Señal y Comunicaciones

Experimental autoimmune encephalomyelitis (EAE) constitutes a paradigm of antigen (Ag)-specific T cell driven autoimmune diseases. In this study, we transferred bone marrow cells (BMCs) expressing an autoantigen (autoAg), the peptide 40-55 of the myelin oligodendrocytic glycoprotein (MOG(40-55)), to induce preventive and therapeutic immune tolerance in a murine EAE model. Transfer of BMC expressing MOG(40-55) (IiMOG-BMC) into partially myeloablated mice resulted in molecular chimerism and in robust protection from the experimental disease. In addition, in mice with established EAE, transfer of transduced BMC with or without partial myeloablation reduced the clinical and histopathological severity of the disease. In these experiments, improvement was observed even in the absence of engraftment of the transduced hematopoietic cells, probably rejected due to the previous immunization with the autoAg. Splenocytes from mice transplanted with IiMOG-BMC produced significantly higher amounts of interleukin (IL)-5 and IL-10 upon autoAg challenge than those of control animals, suggesting the participation of regulatory cells. Altogether, these results suggest that different tolerogenic mechanisms may be mediating the preventive and the therapeutic effects. In conclusion, this study demonstrates that a cell therapy using BMC expressing an autoAg can induce Ag-specific tolerance and ameliorate established EAE even in a nonmyeloablative setting.

Summary Background A previous study suggested that severe left-ventricular hypertrophy (maximum wall thickness ⩾30 mm) in patients with hypertrophic cardiomyopathy is associated with a risk of sudden cardiac death sufficient to warrant consideration for implantation of a cardioverter defibrillator (ICD). However, the prognostic significance of left-ventricular hypertrophy in relation to other clinical risk factors is poorly characterised. Methods We studied 630 patients consecutively referred to one hospital in London, UK (mean age 37 years [SD 16]; 382 male; mean follow-up 59 months). Patients underwent two dimensional and doppler echocardiography, upright exercise testing, and Holter monitoring. Findings 39 patients died suddenly or had an appropriate ICD discharge; nine died from progressive heart failure; 11 from other cardiovascular causes and 23 from non-cardiac causes. There was a trend towards higher probability of sudden death or ICD discharge with increasing wall thickness (p=0·029, relative risk per 5 mm increment 1·31 [95% CI 1·03–1·66]). Of the 39 patients who died suddenly or had an ICD discharge, ten had a wall thickness of 30 mm or more. Patients with wall thickness of 30 mm or more had higher probability of sudden death or ICD discharge than patients with wall thickness less than 30 mm (p=0·049, 2·07 [1·00–4·25]. When considered together, the number of additional risk factors (one to three) was a better predictor of risk of sudden death or ICD discharge than wall thickness (p=0·0001, relative risk per additional factor 2·00 [1·43–2·79] vs p=0·058, 1·26 per 5 mm increment [0·99–1·60]). There was no relation between the pattern of hypertrophy and survival. Interpretation The risk of sudden death associated with a wall thickness of 30 mm or more in patients without other risk factors is insufficient to justify aggressive prophylactic therapy. Most sudden deaths occurred in patients with wall thickness less than 30 mm, so the presence of mild hypertrophy cannot be used to reassure patients that they are at low risk.

Aims Cardiac magnetic resonance (CMR) is recommended in the diagnosis of cardiomyopathies, but it is time-consuming, expensive, and limited in availability in some European regions. The aim of this study was to determine the use of CMR in cardiomyopathy patients enrolled into the European Society of Cardiology (ESC) cardiomyopathy registry [part of the EURObservational Research Programme (EORP)]. Methods and results Three thousand, two hundred, and eight consecutive adult patients (34.6% female; median age: 53.0 ± 15 years) with cardiomyopathy were studied: 1260 with dilated (DCM), 1739 with hypertrophic (HCM), 66 with restrictive (RCM), and 143 with arrhythmogenic right ventricular cardiomyopathy (ARVC). CMR scans were performed at baseline in only 29.4% of patients. CMR utilization was variable according to cardiomyopathy subtypes: from 51.1% in ARVC to 36.4% in RCM, 33.8% in HCM, and 20.6% in DCM (P, Graphical Abstract

AIMS: Cardiomyopathies are a heterogeneous group of disorders associated with premature death due to ventricular arrhythmia or heart failure. The purpose of this study was to examine the characteristics of patients enrolled in the pilot phase of the EURObservational Research Programme (EORP) cardiomyopathy registry. METHODS AND RESULTS: Between 1 December 2012 and 30 November 2013, four cardiomyopathy phenotypes were studied: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM). Twenty-seven centres in 12 countries participated; 1115 patients were enrolled. The commonest cardiomyopathy was HCM (n = 681), followed by DCM (n = 346), ARVC (n = 59), and RCM (n = 29); 423 patients (46.4% of those reported) had familial disease; and 56 (5.0%) had rare disease phenocopies. Median age at enrolment and diagnosis was 54 [interquartile range (IQR), 42-64] and 46 years (IQR, 32-58), respectively; fewer patients with ARVC and more with RCM were diagnosed in the upper age quartile (P < 0.0001). There was a male predominance for all cardiomyopathies except RCM (P = 0.0023). Most patients were in New York Heart Association functional class I (n = 813) at enrolment; 139 (12.5%) reported syncope, most frequently in ARVC (P = 0.0009). Five hundred and seven (45.5%) patients underwent cardiac magnetic resonance imaging, 117 (10.6%) endomyocardial biopsy, and 462 (41.4%) genetic testing with a causative mutation reported in 236 individuals (51.1%). 1026 patients (92.0%) were receiving drug therapy; 316 (28.3%) had received an implantable cardioverter defibrillator (highest proportion in ARVC, P < 0.0001). CONCLUSION: This pilot study shows that services for patients with cardiomyopathy are complex, requiring access to a large range of invasive and non-invasive investigations and involvement of multidisciplinary teams. Treatment regimens are equally multifaceted and show that patients are likely to need long-term follow-up in close liaison with expert centres.