Transesophageal echocardiographic evaluation of baboons during microgravity induced by parabolic flight

Transthoracic echocardiography (TTE) is a feasible method to noninvasively examine cardiac anatomy during parabolic flight. However, transducer placement on the chest wall is very difficult to maintain during transition to microgravity. In addition, TTE requires the use of low frequency transponders which limit resolution. Transesophical echocardiography (TEE) is an established imaging technique which obtains echocardiographic information from the esophagus. It is a safe procedure and provides higher quality images of cardiac structure than obtained with TTE. This study is designed to determine whether TEE was feasible to perform during parabolic flight and to determine whether acute central volume responses occur in acute transition to zero gravity by direct visualization of the cardiac chambers

Effects of cardiovascular lifestyle change on lipoprotein subclass profiles defined by nuclear magnetic resonance spectroscopy

<p>Abstract</p> <p>Background</p> <p>Low-density lipoprotein (LDL) cholesterol lowering is a primary goal in clinical management of patients with cardiovascular disease, but traditional cholesterol levels may not accurately reflect the true atherogenicity of plasma lipid profiles. The size and concentration of lipoprotein particles, which transport cholesterol and triglycerides, may provide additional information for accurately assessing cardiovascular risk. This study evaluated changes in plasma lipoprotein profiles determined by nuclear magnetic resonance (NMR) spectroscopy in patients participating in a prospective, nonrandomized lifestyle modification program designed to reverse or stabilize progression of coronary artery disease (CAD) to improve our understanding of lipoprotein management in cardiac patients.</p> <p>Results</p> <p>The lifestyle intervention was effective in producing significant changes in lipoprotein subclasses that contribute to CAD risk. There was a clear beneficial effect on the total number of LDL particles (-8.3%, p < 0.05 compared to matched controls), small dense LDL particles (-9.5%, p < 0.05), and LDL particle size (+0.8%; p < 0.05). Likewise, participants showed significant improvement in traditional CAD risk factors such as body mass index (-9.9%, p < 0.01 compared to controls), total cholesterol (-5.5%, p < 0.05), physical fitness (+37.2%, p < 0.01), and future risk for CAD (-7.9%, p < 0.01). Men and women responded differently to the program for all clinically-relevant variables, with men deriving greater benefit in terms of lipoprotein atherogenicity. Plasma lipid and lipoprotein responses to the lifestyle change program were not confounded by lipid-lowering medications.</p> <p>Conclusion</p> <p>In <it>at risk </it>patients motivated to participate, an intensive lifestyle change program can effectively alter traditional CAD risk factors and plasma lipoprotein subclasses and may reduce risk for cardiovascular events. Improvements in lipoprotein subclasses are more evident in men compared to women.</p

Gene expression profiling during intensive cardiovascular lifestyle modification: Relationships with vascular function and weight loss

Heart disease and related sequelae are a leading cause of death and healthcare expenditure throughout the world. Although many patients opt for surgical interventions, lifestyle modification programs focusing on nutrition and exercise have shown substantial health benefits and are becoming increasing popular. We conducted a year-long lifestyle modification program to mediate cardiovascular risk through traditional risk factors and to investigate how molecular changes, if present, may contribute to long-term risk reduction. Here we describe the lifestyle intervention, including clinical and molecular data collected, and provide details of the experimental methods and quality control parameters for the gene expression data generated from participants and non-intervention controls. Our findings suggest successful and sustained modulation of gene expression through healthy lifestyle changes may have beneficial effects on vascular health that cannot be discerned from traditional risk factor profiles. The data are deposited in the Gene Expression Omnibus, series GSE46097 and GSE66175

A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination.

Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined.The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization.New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV).New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group.Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized

Performance of Whole-Genome Amplified DNA Isolated from Serum and Plasma on High-Density Single Nucleotide Polymorphism Arrays

Defining genetic variation associated with complex human diseases requires standards based on high-quality DNA from well-characterized patients. With the development of robust technologies for whole-genome amplification, sample repositories such as serum banks now represent a potentially valuable source of DNA for both genomic studies and clinical diagnostics. We assessed the performance of whole-genome amplified DNA (wgaDNA) derived from stored serum/plasma on high-density single nucleotide polymorphism arrays. Neither storage time nor usage history affected either DNA extraction or whole-genome amplification yields; however, samples that were thawed and refrozen showed significantly lower call rates (73.9 ± 7.8%) than samples that were never thawed (92.0 ± 3.3%) (P < 0.001). Genotype call rates did not differ significantly (P = 0.13) between wgaDNA from never-thawed serum/plasma (92.9 ± 2.6%) and genomic DNA (97.5 ± 0.3%) isolated from whole blood. Approximately 400,000 genotypes were consistent between wgaDNA and genomic DNA, but the overall discordance rate of 4.4 ± 3.8% reflected an average of 11,110 ± 9502 genotyping errors per sample. No distinct patterns of chromosomal clustering were observed for single nucleotide polymorphisms showing discordant genotypes or homozygote conversion. Because the effects of genotyping errors on whole-genome studies are not well defined, we recommend caution when applying wgaDNA from serum/plasma to high-density single nucleotide polymorphism arrays in addition to the use of stringent quality control requirements for the resulting genotype data

Subject enrollment, exclusions and outcomes for two prospective cohorts, post-smallpox and annual trivalent influenza vaccine.

<p>Subject enrollment, exclusions and outcomes for two prospective cohorts, post-smallpox and annual trivalent influenza vaccine.</p

Prospective Cases of New Onset Myocarditis/Pericarditis or cTnT Elevation Following Immunization with Either Smallpox or Trivalent Influenza Vaccine.

<p>*<b>Healthy 2002</b>: DoD Defense Medical Surveillance System pre-SPX MP incidence data.³</p><p>^‡<b>Prospective clinical myocarditis/pericarditis</b> cases included 4 Caucasian male cases of probable myocarditis (new onset cardiac symptoms (chest pain, dyspnea on exertion and/or at rest, palpitations) and cTnT elevations ≥0.02 ng/ml with the pre-vaccine level <0.01 ng/ml). The 5^th case (female) was acute suspect pericarditis presenting with characteristic chest pain and no cTnT elevations or ECG changes. There were no cases in the TIV prospective study cohort.</p><p>^§<b>Comparison of Prospective Smallpox Vaccine Cohort with published historic retrospective epidemiologic estimate of myocarditis/pericarditis disease incidence in comparable population pre-SPX vaccine</b>: P<0.001.</p><p>^ǁSubclinical myocarditis is defined by increases in cTnT (above pre-immunization levels) without classic new onset cardiac symptoms. The comparison cohort does not reflect a dynamic change but a single level in time in healthy population subsequently followed for mortality relative risk. <b>Possible subclinical pericarditis</b>: There were no cases of possible subclinical pericarditis identified through the blinded ECG series review process.</p><p>Prospective Cases of New Onset Myocarditis/Pericarditis or cTnT Elevation Following Immunization with Either Smallpox or Trivalent Influenza Vaccine.</p

Pericarditis case definition for surveillance of adverse events after smallpox vaccination in the United States, 2003¹³.

<p>*<b>ECG findings</b>: Electrocardiogram findings not previously documented.</p><p>Pericarditis case definition for surveillance of adverse events after smallpox vaccination in the United States, 2003¹³.</p