Effective cardiac resynchronization therapy for an adolescent patient with dilated cardiomyopathy seven years after mitral valve replacement and septal anterior ventricular exclusion

Cardiac resynchronization therapy (CRT) is a new treatment for refractory heart failure. However, most heart failure patients treated with CRT are middle-aged or old patients with idiopathic or ischemic dilated cardiomyopathy. We treated a 17 year 11 month old girl with dilated cardiomyopathy after mitral valve replacement (MVR) and septal anterior ventricular exclusion (SAVE). Seven years after the SAVE procedure, she presented complaining of palpitations and general fatigue with normal activity. Her echocardiogram showed reduced left ventricular function. Despite of optimal medical therapy, her left ventricular function continued to decline and she experienced regular arrhythmias such as premature ventricular contractions. We thus elected to perform cardiac resynchronization therapy with defibrillator (CRT-D). After CRT-D, her clinical symptoms improved dramatically and left ventricular ejection fraction (LVEF) improved from 31.2% to 51.3% as assessed by echocardiogram. Serum BNP levels decreased from 448.2 to 213.6 pg/ml. On ECG, arrhythmias were remarkably reduced and QRS duration was shortened from 174 to 152 msec. In conclusion, CRT-D is an effective therapeutic option for adolescent patients with refractory heart failure after left ventricular volume reduction surgery

Successful reduction of intraventricular asynchrony is associated with superior response to cardiac resynchronization therapy

<p>Abstract</p> <p>Background</p> <p>Cardiac resynchronization therapy (CRT) is generally associated with a low to moderate increase of the left ventricular ejection fraction (LVEF). In some patients, however, LVEF improves remarkably and reaches near-normal values. The aim of the present study was to further characterize these so called 'super-responders' with a special focus on the extent of intra- and interventricular asynchrony before and after device implantation compared to average responders.</p> <p>Methods</p> <p>37 consecutive patients who underwent CRT device implantation according to current guidelines were included in the study. Patients were examined by echocardiography before, one day after and six months after device implantation. Pre-defined criterion for superior response to CRT was an LVEF increase > 15% after six months.</p> <p>Results</p> <p>At follow-up, eight patients (21.6%) were identified as super-responders. There were no significant differences regarding age, gender, prevalence of ischemic heart disease and LVEF between average and super-responders at baseline. After six months, LVEF had significantly increased from 26.7% ± 5.7% to 33.1% ± 7.9% (<it>p </it>< 0.001) in average and from 24.0% ± 6.7% to 50.3% ± 7.4% (<it>p </it>< 0.001) in super-responders. Both groups showed a significant reduction of QRS duration as well as LV end-diastolic and -systolic volumes under CRT. At baseline, the interventricular mechanical delay (IVMD) was 53.7 ± 20.9 ms in average and 56.9 ± 22.4 ms in super-responders - representing a similar extent of interventricular asynchrony in both groups (<it>p </it>= 0.713). CRT significantly reduced the IVMD to 20.3 ± 15.7 (<it>p </it>< 0.001) in average and to 19.8 ± 15.9 ms (<it>p </it>= 0.013) in super-responders with no difference between both groups (<it>p </it>= 0.858). As a marker for intraventricular asynchrony, we assessed the longest intraventricular delay between six basal LV segments. At baseline, there was no difference between average (86.2 ± 30.5 ms) and super-responders (78.8 ± 23.6 ms, <it>p </it>= 0.528). CRT significantly reduced the longest intraventricular delay in both groups - with a significant difference between average (66.2 ± 36.2 ms) and super-responders (32.5 ± 18.3 ms, <it>p </it>= 0.022). Multivariate logistic regression analysis identified the longest intraventricular delay one day after device implantation as an independent predictor of superior response to CRT (<it>p </it>= 0.038).</p> <p>Conclusions</p> <p>A significant reduction of the longest intraventricular delay correlates with superior response to CRT.</p

Improvements in 25 Years of Implantable Cardioverter Defibrillator Therapy

In 1980, Dr. Michel Mirowski and his team inserted the first implantable cardioverter defibrillator (ICD) in a patient. Initially, ICD therapy was not widely accepted, and many physicians actually considered this therapy unethical. Large secondary and primary prevention trials, demonstrating a beneficial effect of ICD therapy in selected patients not only on arrhythmic death but also on all-cause mortality, stimulated a rapid growth in the number of implants and increased patient’s and physician’s acceptance. Improvements in size and weight, arrhythmia discrimination capabilities, battery technology, shock waveform and output, monitoring capabilities and defibrillator electrode technology eventually resulted in the current large number of yearly implants. Today, almost 40 years after the conception of the ICD and 25 years after the first human implant, ICD therapy is the treatment of choice for patients at risk for life-threatening arrhythmias either as secondary or primary prevention. Furthermore, with the more recent addition of resynchronisation therapy to standard ICD therapy, it became possible to treat selected patients with advanced symptoms of heart failure and to lower the risk of sudden death

The new cardioprotector Monohydroxyethylrutoside protects against doxorubicin-induced inflammatory effects in vitro

The new cardioprotector Monohydroxyethylrutoside protects against doxorubicin-induced inflammatory effects in vitro. Abou El Hassan MA, Verheul HM, Jorna AS, Schalkwijk C, van Bezu J, van der Vijgh WJ, Bast A. Department of Medical Oncology, Free University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected] Besides its cardiotoxic effect, doxorubicin also elicits inflammatory effects in vivo. 7-Monohydroxyethylrutoside (monoHER) has recently been used as a protector against doxorubicin-induced cardiotoxicity in vivo. It is not known yet whether monoHER can also protect against doxorubicin-induced inflammatory effects. The aim of the present study was (1) to illustrate the inflammatory effects of doxorubicin in vitro and (2) to evaluate a possibly protective effect of monoHER. In order to demonstrate the inflammatory effects of doxorubicin and the possible protection of monoHER, proliferating human umbilical cord vascular endothelial cells (HUVECs) were incubated with different concentrations of doxorubicin ranging from 12.5 to 600 nM with(out) 200 micro M monoHER. Resting (confluent) HUVECs were incubated with (0.5-25 micro M) doxorubicin with(out) monoHER (0.2-1.2 mM) and the viability of endothelial cells and their propensity to adhere to neutrophils were measured 24 h after treatment. The localisation of adhered neutrophils was determined with immunofluorescence microscopy. To further characterise the mechanism of doxorubicin-induced neutrophil adhesion, the expression of the HUVECs surface adhesion molecules was determined after doxorubicin treatment. Doxorubicin decreased the viability and proliferation capacity of HUVECs in a concentration-dependent manner. The proliferating HUVECs were much more sensitive to doxorubicin (IC(50)=60.0+/-20.8 nM) than resting cells (LC(50)=4.0+/-0.3 micro M). Doxorubicin also increased the adhesion of neutrophils reaching a plateau value at a doxorubicin concentration of > or =0.4 micro M (P=0.0113). The induced neutrophil adhesion was accompanied by overexpression of VCAM and E-selectin but not ICAM. Although monoHER did not reverse the effect of doxorubicin on the proliferation of endothelial cells, it significantly protected resting HUVECs against the cytotoxic effect of doxorubicin (< or =25 micro M, P<0.0015). In addition, monoHER completely protected against the stimulatory effect of doxorubicin on neutrophil adhesion, and inhibited the doxorubin-induced expression of VCAM and E-selectin on the surface of treated HUVECs. This study illustrates that monoHER, which protects against doxorubicin's cardiotoxic effect, can also protect against doxorubicin-induced inflammatory effects. These data prompt further investigation about the possible link between doxorubicin-induced inflammatory effects and its cardiotoxicity in viv

Marine oxygen production and open water supported an active nitrogen cycle during the Marinoan Snowball Earth

The Neoproterozoic Earth was punctuated by two low-latitude Snowball Earth glaciations. Models permit oceans with either total ice cover or substantial areas of open water. Total ice cover would make an anoxic ocean likely, and would be a formidable barrier to biologic survival. However, there are no direct data constraining either the redox state of the ocean or marine biological productivity during the glacials. Here we present iron-speciation, redox-sensitive trace element, and nitrogen isotope data from a Neoproterozoic (Marinoan) glacial episode. Iron-speciation indicates deeper waters were anoxic and Fe-rich, while trace element concentrations indicate surface waters were in contact with an oxygenated atmosphere. Furthermore, synglacial sedimentary nitrogen is isotopically heavier than the modern atmosphere, requiring a biologic cycle with nitrogen fixation, nitrification and denitrification. Our results indicate significant regions of open marine water and active biologic productivity throughout one of the harshest glaciations in Earth history

Congenital Cytomegalovirus Mortality in the United States, 1990–2006

Cytomegalovirus (CMV) is a member of the herpes family of viruses, which is transmitted by sexual and non-sexual contact. Human CMV causes a wide variety of infection and illness in healthy adults, in those with compromised immune systems (such as AIDS), in those with cardiovascular disease, and in pregnant women who can pass the infection to their unborn child (congenital CMV). Treatment options for congenital CMV are limited and no effective vaccine to protect against CMV currently exists. Previous studies have demonstrated that African Americans and Mexican Americans are at an increased risk for congenital CMV infections. In this study, the authors examined death certificate data of US Residents from 1990–2006 in which congenital CMV was listed as one of the diagnoses at death. The analysis demonstrated that there is a significant burden of congenital CMV deaths in infants (<1 year old) with African Americans and Native Americans overrepresented. This study helps quantify congenital CMV deaths among US residents and adds further support to the importance of funding CMV vaccine research

A review of economic evaluation models for cardiac resynchronization therapy with implantable cardioverter defibrillators in patients with heart failure

Objectives Cardiac resynchronization therapy with a biventricular pacemaker (CRT-P) is an effective treatment for dyssynchronous heart failure (DHF). Adding an implantable cardioverter defibrillator (CRT-D) may further reduce the risk of sudden cardiac death (SCD). However, if the majority of patients do not require shock therapy, the cost-effectiveness ratio of CRT-D compared to CRT-P may be high. The objective of this study was to systematically review decision models evaluating the cost-effectiveness of CRT-D for patients with DHF, compare the structure and inputs of these models and identify the main factors influencing the ICERs for CRT-D. Methods A comprehensive search strategy of Medline (Ovid), Embase (Ovid) and EconLit identified eight cost-effectiveness models evaluating CRT-D against optimal pharmacological therapy (OPT) and/or CRT-P. Results The selected economic studies differed in terms of model structure, treatment path, time horizons, and sources of efficacy data. CRT-D was found cost-effective when compared to OPT but its cost-effectiveness became questionable when compared to CRT-P. Conclusions Cost-effectiveness of CRT-D may increase depending on improvement of all-cause mortality rates and HF mortality rates in patients who receive CRT-D, costs of the device, and battery life. In particular, future studies need to investigate longer-term mortality rates and identify CRT-P patients that will gain the most, in terms of life expectancy, from being treated with a CRT-D.This work was supported by the Center for Translational Molecular Medicine and The Netherlands Heart Foundation under the ‘Biomarkers to predict cardiac failure, arrhythmias and success of treatment’ (COHFAR) projec

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV