Reel syndrome, a diagnostic conundrum: a case report.

BACKGROUND: Pacemaker lead dislodgement and failure, related to device manipulation, is a rare complication of permanent pacemaker (PPM) insertion. Reel's, Twiddler's, and Ratchet syndrome are rare causes of pacemaker failure with varying mechanisms, defined by their classical lead and generator findings on chest X-ray imaging. Misleading patient presentations may be attributed to lead stimulation of surrounding structures. CASE SUMMARY: A 77-year-old female was admitted with abdominal wall pulsations, abdominal pain, and lower limb jerking 3 months following PPM insertion. Following exclusion of a ruptured abdominal aortic aneurysm, the presence of Reel syndrome was noted on the patient's chest X-ray and the electrocardiogram showed inappropriate pacing. Deactivation of the pacemaker resulted in immediate symptom cessation and urgent repositioning of pacemaker leads was undertaken. DISCUSSION: This case highlights the importance of considering pacemaker complications causing non-cardiac symptomatology. Pacemaker lead stimulation of surrounding structures can present in an unconventional fashion, veiling the diagnosis. However, a structured approach to undifferentiated neuromuscular presentations in patients with PPMs should consider lead dislodgement as a differential diagnosis. Rapid recognition of lead dislodgement, device deactivation, and re-implantation or repositioning of the leads are critical in preventing potentially life-threatening complications.

The Impact of Intraoperative Patient Blood Management on Quality Development in Cardiac Surgery.

OBJECTIVES: Patient blood management (PBM) is increasingly introduced into clinical practice. Minimizing effects on transfusion have been proven, but relevance for clinical outcome has been sparsely examined. In regard to this, the authors analyzed the impact of introducing intraoperative PBM to cardiac surgery. DESIGN: Retrospective case-control study. SETTING: Single center. PARTICIPANTS: A total of 3,170 patients who underwent either coronary artery bypass grafting, isolated aortic valve replacement, or a combined procedure at the authors' institution between January 1, 2007, and December 31, 2015. INTERVENTION: In 2013, an intraoperative PBM service was established offering therapy recommendations on the basis of real-time laboratory monitoring. Comparisons to conventional coagulation management were adjusted for optimization of general, surgical, and perioperative care standards by interrupted time-series analysis and risk-dependent confounding by propensity- score matching. MEASUREMENTS AND MAIN RESULTS: Primary study endpoints were in-hospital mortality and morbidity. Morbidity was defined as clinically relevant prolongation of hospital stay, which was related to accumulation of postoperative complications. Transfusion requirements, bleeding, and thromboembolic complications were not treated as primary endpoints, but were also explored. The recommendations on the basis of real-time laboratory monitoring were adopted by the operative team in 72% of patients. Intraoperative PBM was associated independently with a reduction of morbidity (8.3% v 6.3%, p = 0.034), whereas in-hospitalmortality (3.0% v 2.6%, p = 0.521) remained unaffected. The need for red blood cell transfusion decreased (71.1% v 65.0%, p < 0.001), as did bleeding complications requiring surgical re-exploration (3.5% v 1.8%, p = 0.004). At the same time, stroke increased by statistical trend (1.0% v 1.9%, p = 0.038; after correction for imbalanced type of surgical procedure p = 0.085). CONCLUSIONS: Real-time laboratory recommendations achieved a high acceptance rate early after initiation. Improvement of clinical outcome by intraoperative PBM adds to the optimized surgical care. However, the corridor between hemostatic optimization and thromboembolic risk may be narrow.

Cornea donation in Germany: Obtaining consent.

Tissue donation is important to reverse cornea-related blindness. Unfortunately, the willingness to make a decision concerning organ and tissue donation while still alive remains low despite all efforts. By analyzing anonymized archived data from 25 654 next-of-kin interviews from our database over a period of 5 years (2013-2018), it was found that only 20.8% of all potential cornea donors have declared their own wishes. While still alive, refusal was communicated more often than consent by potential donors. Overall consent rates were 39.2%, with parents and siblings consenting more often than other relatives and females refusing more often than male family members. Personal interviews and interviews via telephone handled by staff known to the family resulted in better consent rates (up to 75.6%) with male interviewers receiving higher consent rates in general. The gender of the approached relatives in relation to a male/female interviewer was of low importance. The results also show that it is important to allow discussion about that topic between family members-the more relatives that were involved the higher the probability of consent.

Valve-Sparing Aortic Root Replacement as First-Choice Strategy in Acute Type a Aortic Dissection.

Background: Although, in theory, valve-sparing aortic root replacement (David procedure) is an ideal surgical option for acute aortic dissection type A (AADA) it is usually not regarded as the first-choice treatment due to the emergency setting and the relative complexity of the procedure. Here, we report the results of a consecutive, single-surgeon series of 45 AADA patients with the David procedure as first-choice treatment strategy. Methods and Results: Between September 2009 and July 2013 a total of 49 patients with AADA were consecutively operated by the same surgeon at our institution. The David procedure was the treatment of choice for the proximal aorta unless aortic valve pathology or critical preoperative patient status advocated against it. Median follow-up was 5.0 years (CI95%, 4.0-6.0). Out of the 45 patients included in this study the David procedure was performed in 28 patients (62.2%), while in 17 patients (37.8%) an alternative surgical strategy had to be pursued. Although X-clamping (168.5 ± 41.7 vs. 110.3 ± 51.1 min; p = 0.001), cardiopulmonary bypass (CPB) (245.0 ± 62.4 vs. 211.8 ± 123 min; p = 0.029) and total operation time (383.8 ± 88.5 vs. 312.8 ± 144.8; p = 0.047) were significantly longer in the David-group as compared to the non-David group, there was no difference in major complication rate as well as 30-day (17.9 vs. 23.5%; p = 0.645) and 5-year mortality (28.6 vs. 35.3%) between groups. Conclusions: This small series indicates that the David procedure may be safe and feasible as a primary surgical treatment strategy for AADA.

Ionization injection of highly-charged copper ions for laser driven acceleration from ultra-thin foils.

Laser-driven ion acceleration is often analyzed assuming that ionization reaches a steady state early in the interaction of the laser pulse with the target. This assumption breaks down for materials of high atomic number for which the ionization occurs concurrently with the acceleration process. Using particle-in-cell simulations, we have examined acceleration and simultaneous field ionization of copper ions in ultra-thin targets (20-150 nm thick) irradiated by a laser pulse with intensity 1 × 1021 W/cm2. At this intensity, the laser pulse drives strong electric fields at the rear side of the target that can ionize Cu to charge states with valence L-shell or full K-shell. The highly-charged ions are produced only in a very localized region due to a significant gap between the M- and L-shells' ionization potentials and can be accelerated by strong, forward-directed sections of the field. Such an "ionization injection" leads to well-pronounced bunches of energetic, highly-charged ions. We also find that for the thinnest target (20 nm) a push by the laser further increases the ion energy gain. Thus, the field ionization, concurrent with the acceleration, offers a promising mechanism for the production of energetic, high-charge ion bunches.

Causes of plasma column contraction in surface-wave-driven discharges in argon at atmospheric pressure.

In this work we compute the main features of a surface-wave-driven plasma in argon at atmospheric pressure in view of a better understanding of the contraction phenomenon. We include the detailed chemical kinetics dynamics of Ar and solve the mass conservation equations of the relevant neutral excited and charged species. The gas temperature radial profile is calculated by means of the thermal diffusion equation. The electric field radial profile is calculated directly from the numerical solution of the Maxwell equations assuming the surface wave to be propagating in the TM_{00} mode. The problem is considered to be radially symmetrical, the axial variations are neglected, and the equations are solved in a self-consistent fashion. We probe the model results considering three scenarios: (i) the electron energy distribution function (EEDF) is calculated by means of the Boltzmann equation; (ii) the EEDF is considered to be Maxwellian; (iii) the dissociative recombination is excluded from the chemical kinetics dynamics, but the nonequilibrium EEDF is preserved. From this analysis, the dissociative recombination is shown to be the leading mechanism in the constriction of surface-wave plasmas. The results are compared with mass spectrometry measurements of the radial density profile of the ions Ar^{+} and Ar_{2}^{+}. An explanation is proposed for the trends seen by Thomson scattering diagnostics that shows a substantial increase of electron temperature towards the plasma borders where the electron density is small.

Four-year experience of providing mobile extracorporeal life support to out-of-center patients within a suprainstitutional network-Outcome of 160 consecutively treated patients.

AIM: Mobile extracorporeal life support (ECLS) may soon be on the verge to become a fundamental part of emergency medicine. Here, we report on our four-year experience of providing advanced mechanical circulatory support for out-of-center patients within the Düsseldorf ECLS Network (DELSN). METHODS: This retrospective cohort study analyses the outcome of 160 patients with refractory circulatory failure consecutively treated with mobile veno-arterial extracorporeal membrane oxygenation (vaECMO) between July 2011 and October 2015 within the DELSN. RESULTS: Out of the 160 patients (56±16years, vaECMO initiation under CPR 68%), 59 patients (36%) survived to primary discharge, with 50 patients (31%) still alive after a median follow-up of 1.74 years. Time-discrete mortality was highest during the first 24h. There was no difference between survivors and non-survivors regarding age, etiology of circulatory failure, presence of CPR during implantation or distance to implantation site. Incidence of kidney injury requiring dialysis (61% vs. 24%, p<0.0001), shock liver (27% vs. 12%, p=0.031) and visceral ischemia (19% vs. 3%, p=0.013) were the only complications increased in non-survivors. Subgroup analysis showed no significant outcome difference for ECPR vs. non-ECPR patients. Outcome was significantly impaired with initial neuron-specific enolase ≥45.4µg/L (AUC 0.75, p<0.0001) and lactate ≥5.5mmol/L (AUC 0.70, p<0.0001). Program-year-dependent in-center mortality showed an increasing trend, while program-year-dependent follow-up mortality decreased over time. CONCLUSIONS: This study illustrates that regional mobile ECLS rescue therapy can be provided with encouraging outcomes, although patient selection criteria and early outcome parameters reflecting on therapy success or futility still need to be refined.

Moving evidence based guidelines for seizures into practice in the emergency department: What's stopping us?

PURPOSE: To identify barriers to implementation of an evidence based integrated care pathway (ICP) for seizure management in the Emergency Department (ED). METHODS: A site specific bespoke questionnaire was designed to solicit anonymous responses from all grades of ED medical and nursing staff to a series of questions regarding utility, feasibility, significance and implementation of a locally designed and championed ICP for seizure management and onward referral. RESULTS: While 95% of respondents agreed that the pathway ensured patients were treated according to best practice, a number of human factors were identified as barriers to use. These fell into three categories 1) environmental 2) pathway design/process and 3) user related issues. CONCLUSIONS: Most respondents understood and endorsed the evidence based utility of the pathway. Barriers to use, however, are broad with interactions involving many complex human factors. Nevertheless, solutions can be relatively easily formulated but departmental-wide effort is required to comprehensively address all issues.

Reduction of apoptosis and preservation of mitochondrial integrity under ischemia/reperfusion injury is mediated by estrogen receptor ß.

BACKGROUND: Estrogen improves cardiac recovery after ischemia/reperfusion (I/R) by yet incompletely understood mechanisms. Mitochondria play a crucial role in I/R injury through cytochrome c-dependent apoptosis activation. We tested the hypothesis that 17ß-estradiol (E2) as well as a specific ERß agonist improve cardiac recovery through estrogen receptor (ER)ß-mediated mechanisms by reducing mitochondria-induced apoptosis and preserving mitochondrial integrity. METHODS: We randomized ovariectomized C57BL/6N mice 24h before I/R to pre-treatment with E2 or a specific ERß agonist (ERßA). Isolated hearts were perfused for 20min prior to 30min global ischemia followed by 40min reperfusion. RESULTS: Compared with controls, ERßA and E2 treated groups showed a significant improvement in cardiac recovery, i.e. an increase in left ventricular developed pressure, dP/dtmax and dP/dtmin. ERßA and E2 pre-treatment led to a significant reduction in apoptosis with decreased cytochrome c release from the mitochondria and increased mitochondrial levels of anti-apoptotic Bcl2 and ACAA2. Protein levels of mitochondrial translocase inner membrane (TIM23) and mitochondrial complex I of respiratory chain were increased by ERßA and E2 pre-treatment. Furthermore, we found a significant increase of myosin light chain 2 (MLC2) phosphorylation together with ERK1/2 activation in E2, but not in ERßA treated groups. CONCLUSIONS: Activation of ERß is essential for the improvement of cardiac recovery after I/R through the inhibition of apoptosis and preservation of mitochondrial integrity and can be a achieved by a specific ERß agonist. Furthermore, E2 modulates MLC2 activation after I/R independent of ERß.

Heart transplantation bridged by mechanical circulatory support in a HIV-positive patient.

We report on the unique clinical course of a 44-year-old male HIV-positive heart transplant recipient, who was bridged by mechanical circulatory support (MCS). The patient was admitted with acute ischemic heart failure due to severe myocardial infarction. After emergency coronary artery bypass grafting and nine days of extracorporeal life support, we implanted a left ventricular assist device. As HIV infection was effectively treated and other contraindications were not present, we decided to perform a heart transplantation (HTX). At the current time, 34 months after unremarkable HTX, rejection or opportunistic infections have not occurred.

A Suprainstitutional Network for Remote Extracorporeal Life Support: A Retrospective Cohort Study.

OBJECTIVES: This study sought to evaluate patient outcome within the Düsseldorf Extracorporeal Life Support (ECLS) Network, a suprainstitutional network for rapid-response remote ECLS and to define survival-based predictors. BACKGROUND: Mobile venoarterial extracorporeal membrane oxygenation (vaECMO) used for ECLS has become a treatment option for a patient population with an otherwise fatal prognosis. However, outcome data remain scarce and institutional standards required to manage these patients are still poorly defined. METHODS: This retrospective cohort study analyzes the outcome of 115 patients consecutively treated between July 2011 and October 2014 within the Düsseldorf ECLS Network due to refractory circulatory failure. RESULTS: Of the 115 patients (56 ± 15 years of age, vaECMO initiation under cardiopulmonary resuscitation [CPR] 77%, CPR duration 45 [range 5 to 90] min), 50 patients (44%) survived to primary discharge and 38 patients (33%) were alive after a median follow-up of 1.5 years (95% confidence interval [CI]: 1.2 to 1.7). Thirty-seven (97%) of the long-term survivors showed a favorable neurological outcome. Risk factors associated with mortality during vaECMO were CPR duration (hazard ratio [HR]: 1.006; 95% CI: 1.00 to 1.01) and ischemic stroke (HR: 2.63; 95% CI: 1.52 to 4.56). Risk factors associated with mortality after vaECMO weaning were renal failure (HR: 6.60; 95% CI: 2.72 to 16.01) and sepsis (HR: 3.6; 95% CI: 1.50 to 8.69). Visceral ischemia had a negative impact (HR: 0.30; 95% CI: 0.11 to 0.84) whereas assist device implantation promoted successful vaECMO weaning (HR: 2.95; 95% CI: 1.65 to 5.25). Further, 3 distinct risk groups with significant differences in survival could be identified, demonstrating that in patients with no or short CPR mortality was not conditioned by age, whereas in patients with prolonged CPR young age was associated with increased survival. CONCLUSIONS: This study illustrates the implementation of a suprainstitutional ECLS Network. Further, our data suggest that mobile vaECMO is beneficial for a larger patient population than actually expected, especially regarding young patients presenting with prolonged CPR or patients regardless of age with no or short CPR.

Incremental cost-effectiveness of dobutamine stress cardiac magnetic resonance imaging in patients at intermediate risk for coronary artery disease.

AIMS: The effectiveness of stress cardiac magnetic resonance (CMR) as a gatekeeper for coronary angiography (CA) has been established. Level five HTA studies according to the hierarchical model of diagnostic test evaluation are not available. METHODS: This cohort study included 1,158 consecutive patients (mean age 63 ± 11 years, 42 % women) presenting at our institution between January 1, 2003 and December 31, 2004 with suspected coronary artery disease (CAD) for an elective CA. The patients were assessed for eligibility and propensity score matching was applied to address selection bias regarding the patients' allocation to CMR or direct CA. Median patient follow-up was 7.9 years (95 % CI 7.8-8.0 years). The primary effect was calculated as relative survival difference. The cost unit calculation (per patient) at our institute was the source of costs. RESULTS: Survival was similar in CMR and CA (p = 0.139). Catheterizations ruling out CAD were significantly reduced by the CMR gate-keeper strategy. Patients with prior CMR had significantly lower costs at the initial hospital stay and at follow-up (CMR vs. CA, initial: 2,904 vs. 3,421, p = 0.018; follow-up: 2,045 vs. 3,318, p = 0.037). CMR was cost-effective in terms of a contribution of 12,466 per life year to cover a part of the CMR costs. CONCLUSION: Stress CMR prior to CA was saving 12,466 of hospital costs per life year. Lower costs at follow-up suggest sustained cost-effectiveness of the CMR-guided strategy.

Sex-dependent regulation of fibrosis and inflammation in human left ventricular remodelling under pressure overload.

AIMS: Women with aortic stenosis develop a more concentric form of LV hypertrophy than men. However, the molecular factors underlying sex differences in LV remodelling are incompletely understood. We took an unbiased approach to identify sex-specific patterns in gene expression and pathway regulation, and confirmed the most prominent findings in human hearts. METHODS AND RESULTS: Echocardiography was performed in 104 patients (53.8% women) with aortic stenosis before aortic valve replacement. LV mass, LV end-diastolic diameter, and relative wall thickness were included in a factor analysis to generate an index classifying LV remodelling as adaptive or maladaptive. Maladaptive remodelling was present in 64.6% of male and in 32.7% of female patients (P < 0.01). Genome-wide expression profiling of LV samples was performed in a representative subgroup of 19 patients (52.6% women) compared with samples from healthy controls (n = 18). Transcriptome characterization revealed that fibrosis-related genes/pathways were induced in male overloaded ventricles, while extracellular matrix-related and inflammatory genes/pathways were repressed in female overloaded ventricles (adjusted P < 0.05). We confirmed gene regulation by quantitative real-time reverse transcription-polymerase chain reaction and immunoblotting analysis, and we further demonstrate the relevance of our findings by histological documentation of higher fibrosis in men than in women. CONCLUSION: We conclude that in pressure overload distinct molecular processes are regulated between men and women. Maladaptive LV remodelling occurs more frequently in men and is associated with greater activation of profibrotic and inflammatory markers. Collectively, sex-specific regulation of these processes may contribute to sex differences in the progression to heart failure.

Maladaptive remodeling is associated with impaired survival in women but not in men after aortic valve replacement.

OBJECTIVES: The purpose of this study was to test whether adaptive or maladaptive remodeling is associated with survival in women and men after aortic valve replacement (AVR). BACKGROUND: Women with isolated aortic valve stenosis (AS) develop more concentric left ventricular hypertrophy (LVH) than men in similar disease states. We recently reported less up-regulation of profibrotic genes at AVR and faster LVH regression post-operatively in women than in men, suggesting that there are sex differences in the adaptation to pressure overload and its regression. METHODS: The study cohort included 128 patients (age 70.0 ± 9.6 years, 49% women) undergoing AVR for AS. Echocardiography was obtained before and 4.0 ± 1.6 years after surgery. Factor analysis was used to classify LVH as adaptive (combining smaller left ventricular [LV] mass/diameters and greater relative wall thicknesses) or maladaptive. Myocardial tissue samples from the LV septum were obtained during AVR to analyze cardiac fibrosis and associated key molecular regulators. RESULTS: Before AVR, LVH was classified as adaptive in 62% of women and 45% of men (p < 0.050). Four years after AVR, adaptive LVH was observed in 75% of women and 49% of men (p < 0.031). At surgery, more cardiac fibrosis was present in men compared with women (p < 0.05). Higher levels of transforming growth factor beta 1 (p < 0.01), SMAD2 phosphorylation (p < 0.001), and periostin expression (p < 0.05) were found in men than in women. Women with maladaptive LVH had worse survival than women with adaptive LVH (p < 0.050), whereas the pattern of LVH did not affect survival in men (p < 0.307). CONCLUSIONS: Women more frequently exhibit adaptive LV remodeling with less fibrosis than men. Maladaptive LVH is associated with worse survival in women. Thus, sex should be considered as a strong modulating factor when management of patients with AS is discussed.

Mapping nanoscale absorption of femtosecond laser pulses using plasma explosion imaging.

We make direct observations of localized light absorption in a single nanostructure irradiated by a strong femtosecond laser field, by developing and applying a technique that we refer to as plasma explosion imaging. By imaging the photoion momentum distribution resulting from plasma formation in a laser-irradiated nanostructure, we map the spatial location of the highly localized plasma and thereby image the nanoscale light absorption. Our method probes individual, isolated nanoparticles in vacuum, which allows us to observe how small variations in the composition, shape, and orientation of the nanostructures lead to vastly different light absorption. Here, we study four different nanoparticle samples with overall dimensions of ∼100 nm and find that each sample exhibits distinct light absorption mechanisms despite their similar size. Specifically, we observe subwavelength focusing in single NaCl crystals, symmetric absorption in TiO2 aggregates, surface enhancement in dielectric particles containing a single gold nanoparticle, and interparticle hot spots in dielectric particles containing multiple smaller gold nanoparticles. These observations demonstrate how plasma explosion imaging directly reveals the diverse ways in which nanoparticles respond to strong laser fields, a process that is notoriously challenging to model because of the rapid evolution of materials properties that takes place on the femtosecond time scale as a solid nanostructure is transformed into a dense plasma.

Observation and control of shock waves in individual nanoplasmas.

Using an apparatus that images the momentum distribution of individual, isolated 100-nm-scale plasmas, we make the first experimental observation of shock waves in nanoplasmas. We demonstrate that the introduction of a heating pulse prior to the main laser pulse increases the intensity of the shock wave, producing a strong burst of quasimonoenergetic ions with an energy spread of less than 15%. Numerical hydrodynamic calculations confirm the appearance of accelerating shock waves and provide a mechanism for the generation and control of these shock waves. This observation of distinct shock waves in dense plasmas enables the control, study, and exploitation of nanoscale shock phenomena with tabletop-scale lasers.

Effects of estrogen, an ERα agonist and raloxifene on pressure overload induced cardiac hypertrophy.

The aim of this study was to investigate the effects of 17ß-estradiol (E2), the selective ERα agonist 16α-LE2, and the selective estrogen receptor modulator (SERM) raloxifene on remodeling processes during the development of myocardial hypertrophy (MH) in a mouse model of pressure overload. Myocardial hypertrophy in ovariectomized female C57Bl/6J mice was induced by transverse aortic constriction (TAC). Two weeks after TAC, placebo treated mice developed left ventricular hypertrophy and mild systolic dysfunction. Estrogen treatment, but not 16α-LE2 or raloxifene reduced TAC induced MH compared to placebo. E2, 16α-LE2 and raloxifene supported maintenance of cardiac function in comparison with placebo. Nine weeks after induction of pressure overload, MH was present in all TAC groups, most pronounced in the raloxifene treated group. Ejection fraction (EF) was decreased in all animals. However, 16α-LE2 treated animals showed a smaller reduction of EF than animals treated with placebo. E2 and 16α-LE2, but not raloxifene diminished the development of fibrosis and reduced the TGFß and CTGF gene expression. Treatment with E2 or 16α-LE2 but not with raloxifene reduced survival rate after TAC significantly in comparison with placebo treatment. In conclusion, E2 and 16α-LE2 slowed down the progression of MH and reduced systolic dysfunction after nine weeks of pressure overload. Raloxifene did not reduce MH but improved cardiac function two weeks after TAC. However, raloxifene was not able to maintain EF in the long term period.

17ß-Estradiol-induced interaction of ERα with NPPA regulates gene expression in cardiomyocytes.

AIMS: 17ß-Oestradiol (E2) and its receptors (ERα and ERß) are important regulators of physiological and pathological processes in the cardiovascular system. ER act in concert with other regulatory factors mediating oestrogenic effects. However, the underlying mechanisms modulating ER transcriptional activity are not fully elucidated. To gain better understanding of E2-induced ERα action in the human heart, we aimed to identify and functionally analyse interaction partners of ERα. METHODS AND RESULTS: Using yeast two-hybrid assays with a human heart cDNA library, we identified atrial natriuretic peptide precursor A (NPPA), a well-known cardiac hypertrophy marker, as a novel ERα interaction partner interacting in an E2-dependent manner. Mutation analyses and immunofluorescence data indicated that the LXXLL motif within NPPA is necessary for its E2-induced interaction with ERα, its action as a co-repressor of ERα, and its translocation into the nucleus of human and rat cardiomyocytes. Expression analysis and chromatin immunoprecipitation assays in a human left ventricular cardiomyocyte cell line, AC16, showed that NPPA interacts with E2/ERα, suppressing the transcriptional activity of ERα on E2-target genes, such as NPPA, connexin43, αactinin-2, nuclear factor of activated T-cells, and collagens I and III. CONCLUSION: We characterize for the first time an E2-regulated interaction of NPPA with ERα in cardiomyocytes, that may be crucial in physiological and/or pathological cardiac processes, thereby representing a potential therapeutic target.

Genetic association study identifies HSPB7 as a risk gene for idiopathic dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a structural heart disease with strong genetic background. Monogenic forms of DCM are observed in families with mutations located mostly in genes encoding structural and sarcomeric proteins. However, strong evidence suggests that genetic factors also affect the susceptibility to idiopathic DCM. To identify risk alleles for non-familial forms of DCM, we carried out a case-control association study, genotyping 664 DCM cases and 1,874 population-based healthy controls from Germany using a 50K human cardiovascular disease bead chip covering more than 2,000 genes pre-selected for cardiovascular relevance. After quality control, 30,920 single nucleotide polymorphisms (SNP) were tested for association with the disease by logistic regression adjusted for gender, and results were genomic-control corrected. The analysis revealed a significant association between a SNP in HSPB7 gene (rs1739843, minor allele frequency 39%) and idiopathic DCM (p = 1.06 × 10⁻6, OR  = 0.67 [95% CI 0.57-0.79] for the minor allele T). Three more SNPs showed p < 2.21 × 10⁻5. De novo genotyping of these four SNPs was done in three independent case-control studies of idiopathic DCM. Association between SNP rs1739843 and DCM was significant in all replication samples: Germany (n =564, n = 981 controls, p = 2.07 × 10⁻³, OR = 0.79 [95% CI 0.67-0.92]), France 1 (n = 433 cases, n = 395 controls, p =3.73 × 10⁻³, OR  = 0.74 [95% CI 0.60-0.91]), and France 2 (n = 249 cases, n = 380 controls, p = 2.26 × 10⁻4, OR  = 0.63 [95% CI 0.50-0.81]). The combined analysis of all four studies including a total of n = 1,910 cases and n = 3,630 controls showed highly significant evidence for association between rs1739843 and idiopathic DCM (p = 5.28 × 10⁻¹³, OR= 0.72 [95% CI 0.65-0.78]). None of the other three SNPs showed significant results in the replication stage.This finding of the HSPB7 gene from a genetic search for idiopathic DCM using a large SNP panel underscores the influence of common polymorphisms on DCM susceptibility.