Biometal muscles to restore contractile function of weak heart

Objectives: Existing VADs are single-ventricle pumps needing anticoagulation. We developed a bi-ventricular external assist device that partially reproduces the physiological muscle function of the heart. This artificial muscle could wrap the heart and improve its contractile force.Methods: The device has a carbon fiber skeleton fitting a 30-40kg patient's heart, to which a Nitinol based artificial muscle is connected. The artificial muscle wraps both ventricles. The Nitinol fibers are woven on a Kevlar mesh surrounding each ventricle. The fibers are electrically driven with a dedicated control unit developed for this purpose. We assessed hemodynamic performances of this device using a previously described dedicated bench test. Volume ejected and pressure gradient have been measured with afterload ranging from 10 to 50mmHg.Results: With an afterload of 50mmHg the system has an ejection fraction of 4% on the right side and 5% on the left side. The system is able to generate a systolic ejection of 2.2mL on the right side and 3.25mL on the left side. With an afterload of 25mmHg the results are reduced of about 20%. The activation frequency can reach 80/minute resulting in a total volume displacement of 176mL/minute on the right side and 260mL/minute on the left side.Conclusions: These preliminary studies confirmed the possibility of improving the ejection fraction of a failing heart using artificial muscle for external cardiac compression avoiding anticoagulation therapy. This device could be helpful in weaning cardio-pulmonary bypass and/or for short-term cardio-circulatory support in pediatric population with cardiac failure.

Markers of atherosclerosis and inflammation for prediction of coronary heart disease in older adults.

Although both inflammatory and atherosclerosis markers have been associated with coronary heart disease (CHD) risk, data directly comparing their predictive value are limited. The authors compared the value of 2 atherosclerosis markers (ankle-arm index (AAI) and aortic pulse wave velocity (aPWV)) and 3 inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)) in predicting CHD events. Among 2,191 adults aged 70-79 years at baseline (1997-1998) from the Health, Aging, and Body Composition Study cohort, the authors examined adjudicated incident myocardial infarction or CHD death ("hard" events) and "hard" events plus hospitalization for angina or coronary revascularization (total CHD events). During 8 years of follow-up between 1997-1998 and June 2007, 351 participants developed total CHD events (197 "hard" events). IL-6 (highest quartile vs. lowest: hazard ratio = 1.82, 95% confidence interval: 1.33, 2.49; P-trend < 0.001) and AAI (AAI </= 0.9 vs. AAI 1.01-1.30: hazard ratio = 1.57, 95% confidence interval: 1.14, 2.18) predicted CHD events above traditional risk factors and modestly improved global measures of predictive accuracy. CRP, TNF-alpha, and aPWV had weaker associations. IL-6 and AAI accurately reclassified 6.6% and 3.3% of participants, respectively (P's </= 0.05). Results were similar for "hard" CHD, with higher reclassification rates for AAI. IL-6 and AAI are associated with future CHD events beyond traditional risk factors and modestly improve risk prediction in older adults.

Après votre arrêt cardiaque, vous prendrez bien un peu d'élixir de (sur)vie [After your heart arrest, would you like to test a medicinal elixir?].

So far, cardiac arrest is still associated with high mortality or severe neurological disability in survivors. At the tissue level, cardiac arrest results into an acute condition of generalized hypoxia. A better understanding of the pathophysiology of ischemia-reperfusion and of the inflammatory response that develops after cardiac arrest could help to design novel therapeutic strategies in the future. It seems unlikely that a single drug, acting as a <magic bullet>, might be able to improve survival or neurological prognosis. Lessons learned from pathophysiological mechanisms rather indicate that combined therapies, involving thrombolysis, neuroprotective agents, antioxidants and anti-inflammatory molecules, together with temperature cooling, might represent helpful strategies to improve patient's outcome after cardiac arrest.

GLUT8 is dispensable for embryonic development but influences hippocampal neurogenesis and heart function.

GLUT8 is a glucose transporter isoform expressed at high levels in testis; at intermediate levels in the brain, including the hippocampus; and at lower levels in the heart and several other tissues. GLUT8 is located in an intracellular compartment and does not appear to translocate to the cell surface, except in blastocysts, where insulin has been reported to induce its surface expression. Here, we generated mice with inactivation of the glut8 gene. We showed that expression of GLUT8 was not required for normal embryonic development and that glut8-/- mice had normal postnatal development, glucose homeostasis, and response to mild stress. Adult glut8-/- mice showed increased proliferation of hippocampal cells but no defect in memory acquisition and retention. Absence of GLUT8 from the heart did not alter heart size and morphology but led to an increase in P-wave duration, which was not associated with abnormal Nav1.5 Na+ channel or connexin expression. Thus, absence of GLUT8 expression in the mouse caused complex but mild physiological alterations.

Inflammatory markers and incident heart failure risk in older adults: the Health ABC (Health, Aging, and Body Composition) study.

OBJECTIVES: The purpose of this study was to evaluate the association between inflammation and heart failure (HF) risk in older adults. BACKGROUND: Inflammation is associated with HF risk factors and also directly affects myocardial function. METHODS: The association of baseline serum concentrations of interleukin (IL)-6, tumor necrosis factor-alpha, and C-reactive protein (CRP) with incident HF was assessed with Cox models among 2,610 older persons without prevalent HF enrolled in the Health ABC (Health, Aging, and Body Composition) study (age 73.6 +/- 2.9 years; 48.3% men; 59.6% white). RESULTS: During follow-up (median 9.4 years), HF developed in 311 (11.9%) participants. In models controlling for clinical characteristics, ankle-arm index, and incident coronary heart disease, doubling of IL-6, tumor necrosis factor-alpha, and CRP concentrations was associated with 29% (95% confidence interval: 13% to 47%; p < 0.001), 46% (95% confidence interval: 17% to 84%; p = 0.001), and 9% (95% confidence interval: -1% to 24%; p = 0.087) increase in HF risk, respectively. In models including all 3 markers, IL-6, and tumor necrosis factor-alpha, but not CRP, remained significant. These associations were similar across sex and race and persisted in models accounting for death as a competing event. Post-HF ejection fraction was available in 239 (76.8%) cases; inflammatory markers had stronger association with HF with preserved ejection fraction. Repeat IL-6 and CRP determinations at 1-year follow-up did not provide incremental information. Addition of IL-6 to the clinical Health ABC HF model improved model discrimination (C index from 0.717 to 0.734; p = 0.001) and fit (decreased Bayes information criterion by 17.8; p < 0.001). CONCLUSIONS: Inflammatory markers are associated with HF risk among older adults and may improve HF risk stratification.

Abnormal Lung Function and Risk for Heart Failure in the Elderly: The Health, Aging, and Body Composition Study

Background: Chronic obstructive pulmonary disease (COPD) has been associated with increased risk for heart failure (HF). The impact of subclinical abnormal spirometric findings on HF risk among older adults without history of COPD is not well elucidated. Methods: We evaluated 2125 participants (age 73.6±2.9 years; 50.5% men; 62.3% white; 45.6/9.4% past/current smokers; body mass index [BMI] 27.2±4.6 kg/m2) without prevalent COPD or HF who underwent baseline spirometry in the Health ABC Study. Abnormal lung function was defined either as forced vital capacity (FVC) below lower limit of normal (LLN) or forced expiratory volume in 1st sec (FEV1) to FVC ratio below LLN. Results: On follow-up (median, 9.4 years), 68 of 350 (19.4%) participants with abnormal lung function developed HF, as compared to 172 of 1775 (9.7%) participants with normal lung function (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.74 -3.06; P<.001). This increased risk persisted after adjusting for all other independent predictors of HF in the Health ABC Study, BMI, incident coronary events, and several inflammatory markers (HR, 1.82; 95% CI, 1.30 -2.54; P<.001), and remained constant over time. Baseline FVC and FEV1 had a linear association with HF risk (Figure). In adjusted models, HF risk increased by 21% (95% CI, 10 -36%) per 10% decrease in FVC and 18% (95% CI, 10 -28%) per 10% decrease in FEV1 (both P<.001); this association persisted among participants with normal lung function at baseline. Findings were consistent across sex, race, and smoking status. Conclusions: Subclinical abnormal spirometric findings are prevalent among older adults and are independently associated with risk for incident HF.

The predictive value of preoperative B-type natriuretic peptide in children undergooing heart surgery.

Introduction: Low cardiac output syndrome is frequent in childrenafter heart surgery for congenital heart disease and may result in pooroutcome and increased morbidity. In the adult population, preoperativebrain natriuretic peptide (BNP) was shown to be predictive of postoperative complications. In children, the value of preoperative BNP onpostoperative outcome is not so clear. The aim of this study was todetermine the predictive value of preoperative BNP on postoperativeoutcome and low cardiac output syndrome in children after heartsurgery for congenital heart disease.Methods: We examined, retrospectively, the postoperative course of97 pediatric patients (mean age 3.7 years, range 0-14 years old) whounderwent heart surgery in a tertiary care pediatric intensive caresetting. NTproBNP was measured preoperatively in all patients(median 412 pg/ml, range 12-35'000 pg/ml). Patients were divided intothree groups according to their NTproBNP levels (group 1: 0-300 pg/ml, group 2: 300-600 pg/ml, group 3: >600 pg/ml) and then,correlations with postoperative outcomes were examined.Results: We found that patients with a high preoperative BNP requiredmore frequently prolonged (>2 days) mechanical ventilation (33%vs 40% vs 61%, p = 0.045) and stayed more frequently longer than6 days in the intensive care unit (42% vs 50% vs 71%, p = 0.03).However, high preoperative BNP was not correlated with occurrenceof low cardiac output syndrome.Conclusion: Preoperative BNP cannot be used, in children, as areliable and sole predictor of postoperative low cardiac outputsyndrome. However it may help identify, before surgery, those patientsat risk of having a difficult postoperative course.

Use of 2D Sensitivity Encoding for Slow-Infusion Contrast-Enhanced Isotropic 3-T Whole-Heart Coronary MR Angiography.

OBJECTIVE. The purpose of this study was to improve the blood-pool signal-to-noise ratio (SNR) and blood-myocardium contrast-to-noise ratio (CNR) of slow-infusion 3-T whole-heart coronary MR angiography (MRA).SUBJECTS AND METHODS. In 2D sensitivity encoding (SENSE), the number of acquired k-space lines is reduced, allowing less radiofrequency excitation per cardiac cycle and a longer TR. The former can be exploited for signal enhancement with a higher radiofrequency excitation angle, and the latter leads to noise reduction due to lower data-sampling bandwidth. Both effects contribute to SNR gain in coronary MRA when spatial and temporal resolution and acquisition time remain identical. Numeric simulation was performed to select the optimal 2D SENSE pulse sequence parameters and predict the SNR gain. Eleven patients underwent conventional unenhanced and the proposed 2D SENSE contrast-enhanced coronary MRA acquisition. Blood-pool SNR, blood-myocardium CNR, visible vessel length, vessel sharpness, and number of side branches were evaluated.RESULTS. Consistent with the numeric simulation, using 2D SENSE in contrast-enhanced coronary MRA resulted in significant improvement in aortic blood-pool SNR (unenhanced vs contrast-enhanced, 37.5 +/- 14.7 vs 121.3 +/- 44.0; p < 0.05) and CNR (14.4 +/- 6.9 vs 101.5 +/- 40.8; p < 0.05) in the patient sample. A longer length of left anterior descending coronary artery was visualized, but vessel sharpness, coronary artery coverage, and image quality score were not improved with the proposed approach.CONCLUSION. In combination with contrast administration, 2D SENSE was found effective in improving SNR and CNR in 3-T whole-heart coronary MRA. Further investigation of cardiac motion compensation is necessary to exploit the SNR and CNR advantages and to achieve submillimeter spatial resolution.

Ruling out coronary heart disease in primary care patients with chest pain: a clinical prediction score.

ABSTRACT: BACKGROUND: Chest pain raises concern for the possibility of coronary heart disease. Scoring methods have been developed to identify coronary heart disease in emergency settings, but not in primary care. METHODS: Data were collected from a multicenter Swiss clinical cohort study including 672 consecutive patients with chest pain, who had visited one of 59 family practitioners' offices. Using delayed diagnosis we derived a prediction rule to rule out coronary heart disease by means of a logistic regression model. Known cardiovascular risk factors, pain characteristics, and physical signs associated with coronary heart disease were explored to develop a clinical score. Patients diagnosed with angina or acute myocardial infarction within the year following their initial visit comprised the coronary heart disease group. RESULTS: The coronary heart disease score was derived from eight variables: age, gender, duration of chest pain from 1 to 60 minutes, substernal chest pain location, pain increases with exertion, absence of tenderness point at palpation, cardiovascular risks factors, and personal history of cardiovascular disease. Area under the receiver operating characteristics curve was of 0.95 with a 95% confidence interval of 0.92; 0.97. From this score, 413 patients were considered as low risk for values of percentile 5 of the coronary heart disease patients. Internal validity was confirmed by bootstrapping. External validation using data from a German cohort (Marburg, n = 774) revealed a receiver operating characteristics curve of 0.75 (95% confidence interval, 0.72; 0.81) with a sensitivity of 85.6% and a specificity of 47.2%. CONCLUSIONS: This score, based only on history and physical examination, is a complementary tool for ruling out coronary heart disease in primary care patients complaining of chest pain.

Recent decrease in the prevalence of congenital heart defects in europe.

OBJECTIVES: To examine trends in the prevalence of congenital heart defects (CHDs) in Europe and to compare these trends with the recent decrease in the prevalence of CHDs in Canada (Quebec) that was attributed to the policy of mandatory folic acid fortification. STUDY DESIGN: We used data for the period 1990-2007 for 47 508 cases of CHD not associated with a chromosomal anomaly from 29 population-based European Surveillance of Congenital Anomalies registries in 16 countries covering 7.3 million births. We estimated trends for all CHDs combined and separately for 3 severity groups using random-effects Poisson regression models with splines. RESULTS: We found that the total prevalence of CHDs increased during the 1990s and the early 2000s until 2004 and decreased thereafter. We found essentially no trend in total prevalence of the most severe group (group I), whereas the prevalence of severity group II increased until about 2000 and decreased thereafter. Trends for severity group III (the most prevalent group) paralleled those for all CHDs combined. CONCLUSIONS: The prevalence of CHDs decreased in recent years in Europe in the absence of a policy for mandatory folic acid fortification. One possible explanation for this decrease may be an as-yet-undocumented increase in folic acid intake of women in Europe following recommendations for folic acid supplementation and/or voluntary fortification. However, alternative hypotheses, including reductions in risk factors of CHDs (eg, maternal smoking) and improved management of maternal chronic health conditions (eg, diabetes), must also be considered for explaining the observed decrease in the prevalence of CHDs in Europe or elsewhere.

The PPARbeta/delta agonist GW0742 relaxes pulmonary vessels and limits right heart hypertrophy in rats with hypoxia-induced pulmonary hypertension.

BACKGROUND: Pulmonary vascular diseases are increasingly recognised as important clinical conditions. Pulmonary hypertension associated with a range of aetiologies is difficult to treat and associated with progressive morbidity and mortality. Current therapies for pulmonary hypertension include phosphodiesterase type 5 inhibitors, endothelin receptor antagonists, or prostacyclin mimetics. However, none of these provide a cure and the clinical benefits of these drugs individually decline over time. There is, therefore, an urgent need to identify new treatment strategies for pulmonary hypertension. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that the PPARbeta/delta agonist GW0742 induces vasorelaxation in systemic and pulmonary vessels. Using tissue from genetically modified mice, we show that the dilator effects of GW0742 are independent of the target receptor PPARbeta/delta or cell surface prostacyclin (IP) receptors. In aortic tissue, vascular relaxant effects of GW0742 were not associated with increases in cGMP, cAMP or hyperpolarisation, but were attributed to inhibition of RhoA activity. In a rat model of hypoxia-induced pulmonary hypertension, daily oral dosing of animals with GW0742 (30 mg/kg) for 3 weeks significantly reduced the associated right heart hypertrophy and right ventricular systolic pressure. GW0742 had no effect on vascular remodelling induced by hypoxia in this model. CONCLUSIONS/SIGNIFICANCE: These observations are the first to show a therapeutic benefit of 'PPARbeta/delta' agonists in experimental pulmonary arterial hypertension and provide pre-clinical evidence to favour clinical trials in man.

New reference tables and user-friendly Internet application for predicted heart weights.

BACKGROUND: Knowledge of normal heart weight ranges is important information for pathologists. Comparing the measured heart weight to reference values is one of the key elements used to determine if the heart is pathological, as heart weight increases in many cardiac pathologies. The current reference tables are old and in need of an update. AIMS: The purposes of this study are to establish new reference tables for normal heart weights in the local population and to determine the best predictive factor for normal heart weight. We also aim to provide technical support to calculate the predictive normal heart weight. METHODS: The reference values are based on retrospective analysis of adult Caucasian autopsy cases without any obvious pathology that were collected at the University Centre of Legal Medicine in Lausanne from 2007 to 2011. We selected 288 cases. The mean age was 39.2 years. There were 118 men and 170 women. Regression analyses were performed to assess the relationship of heart weight to body weight, body height, body mass index (BMI) and body surface area (BSA). RESULTS: The heart weight increased along with an increase in all the parameters studied. The mean heart weight was greater in men than in women at a similar body weight. BSA was determined to be the best predictor for normal heart weight. New reference tables for predicted heart weights are presented as a web application that enable the comparison of heart weights observed at autopsy with the reference values. CONCLUSIONS: The reference tables for heart weight and other organs should be systematically updated and adapted for the local population. Web access and smartphone applications for the predicted heart weight represent important investigational tools.