Left Ventricular Wall Reconstruction with Autologous Vascularized Tunica Muscularis of Stomach in a Porcine Pilot Model.

INTRODUCTION: Surgical replacement of dysfunctional cardiac muscle with regenerative tissue is an important option to combat heart failure. But, current available myocardial prostheses like a Dacron or a pericardium patch neither have a regenerative capacity nor do they actively contribute to the heart's pump function. This study aimed to show the feasibility of utilizing a vascularized stomach patch for transmural left ventricular wall reconstruction. METHODS: A left ventricular transmural myocardial defect was reconstructed by performing transdiaphragmatic autologous transplantation of a vascularized stomach segment in six Lewe minipigs. Three further animals received a conventional Dacron patch as a control treatment. The first 3 animals were followed up for 3 months until planned euthanasia, whereas the observation period for the remaining 3 animals was scheduled 6 months following surgery. Functional assessment of the grafts was carried out via cardiac magnetic resonance tomography and angiography. Physiological remodeling was evaluated histologically and immunohistochemically after heart explantation. RESULTS: Five out of six test animals and all control animals survived the complex surgery and completed the follow-up without clinical complications. One animal died intraoperatively due to excessive bleeding. No animal experienced rupture of the stomach graft. Functional integration of the heterotopically transplanted stomach into the surrounding myocardium was observed. Angiography showed development of connections between the gastric graft vasculature and the coronary system of the host cardiac tissue. CONCLUSIONS: The clinical results and the observed physiological integration of gastric grafts into the cardiac structure demonstrate the feasibility of vascularized stomach tissue as myocardial prosthesis. The physiological remodeling indicates a regenerative potential of the graft. Above all, the connection of the gastric vessels with the coronary system constitutes a rationale for the use of vascularized and, therefore, viable stomach tissue for versatile tissue engineering applications.

Biocompatibility of an apical ring plug for left ventricular assist device explantation: Results of a feasibility pre-clinical study.

BACKGROUND: Patients receiving left ventricle assist devices (LVADs) as bridge to recovery remain a minority with 1%-5% of LVADs explanted after improvement of myocardial function. Nevertheless, considering the growing population of patients supported with LVADs, an increasing demand of new explantation strategies is expected in the near future. A novel plug for LVAD explantation has been developed and its biocompatibility profile needs to be proved. This study tested the biocompatibility of this novel plug in an in vivo ovine model. METHODS: Six adult Blackhead Persian female sheep received plug implantation on the cardiac apex via minimally invasive approach and were clinically observed up to 90 days. Echocardiography was performed to detect thrombus formation or further plug-related complications. After the observation period, euthanasia was performed and samples including the plug and the surrounding tissues were obtained to be analyzed with correlative light and electron microscopy. Organ necrosis, ischemia and peripheral embolism were investigated. RESULTS: Three animals survived surgery and completed the follow-up time without experiencing clinical complications. Echocardiographic controls excluded the presence of an intracavitary thrombus in the left ventricle (LV). Autopsy confirmed no signs of local infection, LV thrombus or peripheral embolism. Light and electron microscopy revealed an intact epithelium covering a layer of connective tissue on the plug surface facing the heart lumen. CONCLUSIONS: This novel apical plug for LVAD explantation allows for endothelial and connective tissue growth on its ventricular side within 90 days from surgery. Further studies are required to fully demonstrate the biocompatibility of this apical plug and investigate the optimal anticoagulation regimen to be applied after implantation.

A Comprehensive View on the Human Antibody Repertoire Against Staphylococcus aureus Antigens in the General Population.

Our goal was to provide a comprehensive overview of the antibody response to Staphylococcus aureus antigens in the general population as a basis for defining disease-specific profiles and diagnostic signatures. We tested the specific IgG and IgA responses to 79 staphylococcal antigens in 996 individuals from the population-based Study of Health in Pomerania. Using a dilution-based multiplex suspension array, we extended the dynamic range of specific antibody detection to seven orders of magnitude, allowing the precise quantification of high and low abundant antibody specificities in the same sample. The observed IgG and IgA antibody responses were highly heterogeneous with differences between individuals as well as between bacterial antigens that spanned several orders of magnitude. Some antigens elicited significantly more IgG than IgA and vice versa. We confirmed a strong influence of colonization on the antibody response and quantified the influence of sex, smoking, age, body mass index, and serum glucose on anti-staphylococcal IgG and IgA. However, all host parameters tested explain only a small part of the extensive variability in individual response to the different antigens of S. aureus.

A global Staphylococcus aureus proteome resource applied to the in vivo characterization of host-pathogen interactions.

Data-independent acquisition mass spectrometry promises higher performance in terms of quantification and reproducibility compared to data-dependent acquisition mass spectrometry methods. To enable high-accuracy quantification of Staphylococcus aureus proteins, we have developed a global ion library for data-independent acquisition approaches employing high-resolution time of flight or Orbitrap instruments for this human pathogen. We applied this ion library resource to investigate the time-resolved adaptation of S. aureus to the intracellular niche in human bronchial epithelial cells and in a murine pneumonia model. In epithelial cells, abundance changes for more than 400 S. aureus proteins were quantified, revealing, e.g., the precise temporal regulation of the SigB-dependent stress response and differential regulation of translation, fermentation, and amino acid biosynthesis. Using an in vivo murine pneumonia model, our data-independent acquisition quantification analysis revealed for the first time the in vivo proteome adaptation of S. aureus. From approximately 2.15 × 105 S. aureus cells, 578 proteins were identified. Increased abundance of proteins required for oxidative stress response, amino acid biosynthesis, and fermentation together with decreased abundance of ribosomal proteins and nucleotide reductase NrdEF was observed in post-infection samples compared to the pre-infection state.

Characterization of human and Staphylococcus aureus proteins in respiratory mucosa by in vivo- and immunoproteomics.

Staphylococcus aureus is a Gram-positive opportunistic bacterium which can be found as a commensal in the nares of about 50% of the human population. Besides asymptomatic carriage, S. aureus has also been found to colonize nasal polyps, a subform of chronic rhinosinusitis, in 60 to 100% of cases, and even reside intracellularly in nasal polyp tissue. The aim of this study was to shed light on the behavior of S. aureus in the human airways by analyzing S. aureus-specific proteins in nasal polyp tissue from patients with chronic rhinosinusitis and to characterize the immunogenic potential of the identified (mainly secreted) proteins. As a result, in total >600 S. aureus proteins were identified by high resolution mass spectrometry or multiple reaction monitoring. Of those roughly 180 are typically localized in the membrane, surface exposed or secreted. For 115 S. aureus proteins, partially also detected in vivo by mass spectrometry, IgA- and IgG-specific antibody signals were profiled. Strong antibody signals were predominantly found for surface expose or secreted proteins. SIGNIFICANCE: In this study, we used high resolution mass spectrometry to identify S. aureus proteins directly in infected nasal polyp tissue. We discovered bacterial proteins involved in invasion of tissue, virulence, bacterial signal transduction or acquisition of nutrients. Some of the detected superantigens and Spls are known to provoke secretion of a broad spectrum of cytokines. Therefore, our manuscript contains new information about the invasion of S. aureus in nasal polyp tissue and its protein-specific immunogenicity.

Defects in Peroxisomal 6-Phosphogluconate Dehydrogenase Isoform PGD2 Prevent Gametophytic Interaction in Arabidopsis thaliana.

We studied the localization of 6-phosphogluconate dehydrogenase (PGD) isoforms of Arabidopsis (Arabidopsis thaliana). Similar polypeptide lengths of PGD1, PGD2, and PGD3 obscured which isoform may represent the cytosolic and/or plastidic enzyme plus whether PGD2 with a peroxisomal targeting motif also might target plastids. Reporter-fusion analyses in protoplasts revealed that, with a free N terminus, PGD1 and PGD3 accumulate in the cytosol and chloroplasts, whereas PGD2 remains in the cytosol. Mutagenesis of a conserved second ATG enhanced the plastidic localization of PGD1 and PGD3 but not PGD2. Amino-terminal deletions of PGD2 fusions with a free C terminus resulted in peroxisomal import after dimerization, and PGD2 could be immunodetected in purified peroxisomes. Repeated selfing of pgd2 transfer (T-)DNA alleles yielded no homozygous mutants, although siliques and seeds of heterozygous plants developed normally. Detailed analyses of the C-terminally truncated PGD2-1 protein showed that peroxisomal import and catalytic activity are abolished. Reciprocal backcrosses of pgd2-1 suggested that missing PGD activity in peroxisomes primarily affects the male gametophyte. Tetrad analyses in the quartet1-2 background revealed that pgd2-1 pollen is vital and in vitro germination normal, but pollen tube growth inside stylar tissues appeared less directed. Mutual gametophytic sterility was overcome by complementation with a genomic construct but not with a version lacking the first ATG. These analyses showed that peroxisomal PGD2 activity is required for guided growth of the male gametophytes and pollen tube-ovule interaction. Our report finally demonstrates an essential role of oxidative pentose-phosphate pathway reactions in peroxisomes, likely needed to sustain critical levels of nitric oxide and/or jasmonic acid, whose biosynthesis both depend on NADPH provision.

Decellularized aortic allografts versus pulmonary autografts for aortic valve replacement in the growing sheep model: haemodynamic and morphological results at 20 months after implantation.

OBJECTIVES: Pulmonary autografts (PAs) represent the substitute of choice for aortic valve (AV) replacement, especially in children and young adults. Similarly, decellularized aortic valve allografts (DAVAs) have shown excellent mid-term function when implanted in the systemic circulation. The aim of this study was to compare the performance of DAVAs with that of pulmonary autografts after a Ross procedure in the growing sheep model. METHODS: AV root replacement was performed in female lambs (25 ± 3.4 kg) using either DAVAs (n = 5) or pulmonary autografts (n = 5) as in the Ross procedure. Sheep undergoing the Ross procedure received a decellularized pulmonary allograft in place of pulmonary valve. Haemodynamics was investigated by echocardiography and magnetic resonance imaging. The roots were explanted at 20 months and examined by histology to determine the degree of repopulation and quality of the extracellular matrix, and by immunohistochemistry to characterize the repopulating cells. RESULTS: The mean valve diameter increased from 16 to 21 and from 16 to 25 mm in DAVAs and PAs, respectively. At explantation, one PA and one DAVA exhibited moderate insufficiency. Significant differences in transvalvular gradient were only found in PAs between implantation and prior to explantation. The cusps of all implants were soft, pliable and showed no major signs of degeneration. In the decellularized allografts, cell repopulation occurred at the wall and cusp level with a well-maintained, three-layered cusp structure. Ventricular cusp surface of decellularized allografts was more strongly repopulated than the arterial surface. Cusps were covered with cells positive for endothelial markers and were also repopulated by interstitial cells. CONCLUSIONS: DAVAs and PAs provide adequate haemodynamics after AV replacement in the growing sheep. While decellularized grafts are repopulated by endothelial and interstitial cells, autografts maintain in general their native cell distribution. Maintenance of valvular competence during enlargement of the valve ring is, in our opinion, representative of the capacity for physiological growth in both graft types.

Orthotopic replacement of aortic heart valves with tissue-engineered grafts.

AIMS: Heart valve tissue engineering aims to create a graft with improved durability compared to routinely used valve substitutes. This study presents the function and morphological changes of a tissue-engineered aortic valve (TEV) compared to the cryopreserved valve (CPV), aortic valve (AV) allografts in an orthotopic position in sheep. METHODS AND RESULTS: Ovine AV conduits (n=5) were decellularized with detergents. Autologous endothelial cells (ECs) were seeded onto the valve surface and cultured under physiological conditions using a high pulsatile flow. Grafts were implanted as a root with reimplantation of coronary ostia in sheep. Crystalloid cardioplegia and isogenic blood transfusions from previous sacrificed sheep were used. Only antiplatelet aggregation therapy was used postoperatively. CPVs (n=4) served as controls. The grafts were investigated for function (echocardiography, magnetic resonance investigation), morpho/histological appearance, graft rejection, and calcification at 3 months. Decellularization led to cell-free scaffolds with preserved extracellular matrices, including the basement membrane. TEVs were covered with ECs expressing typical endothelial markers. Neither dilatation, stenosis, reductions of cusp mobility nor a significant transvalvular gradient, were observed in the TEV group. Explanted valves exhibited normal morphology without signs of inflammation. An endothelial monolayer covered cusps and the valve sinus. In the CPV group, sporadic, macroscopic, calcified degeneration with mild AV insufficiency was noted. Histology revealed signs of rejection and incipient calcification of the tissue. CONCLUSION: Tissue-engineered AV based on decellularized valve allografts satisfy short-term requirements of the systemic circulation in sheep. Although results of long-term experiments are pending, the lack of degenerative traits thus far, makes these grafts a promising alternative for future aortic heart valve surgery.

Image quality and radiation exposure with prospectively ECG-triggered axial scanning for coronary CT angiography: the multicenter, multivendor, randomized PROTECTION-III study.

OBJECTIVES: The purpose of this study was to evaluate image quality and radiation dose using a prospectively electrocardiogram (ECG)-triggered axial scan protocol compared with standard retrospective ECG-gated helical scanning for coronary computed tomography angiography. BACKGROUND: Concerns have been raised regarding radiation exposure during coronary computed tomography angiography. Although the use of prospectively ECG-triggered axial scan protocols may effectively lower radiation dose compared with helical scanning, it is unknown whether image quality is maintained in a clinical setting. METHODS: In a prospective, multicenter, multivendor trial, 400 patients with low and stable heart rates were randomized to either an axial or a helical coronary computed tomography angiography scan protocol. The primary endpoint was to demonstrate noninferiority in image quality with the axial scan protocol, which was assessed on a 4-point scale (1 = nondiagnostic, 4 = excellent image quality). Secondary endpoints included radiation dose and the rate of downstream testing during 30-day follow-up. RESULTS: Image quality in patients scanned with the axial scan protocol (score 3.36 ± 0.59) was not inferior compared with helical scan protocols (3.37 ± 0.59) (p for noninferiority <0.004). Axial scanning was associated with a 69% reduction in radiation exposure (dose-length product [estimated effective dose] 252 ± 147 mGy · cm [3.5 ± 2.1 mSv] vs. 802 ± 419 mGy · cm [11.2 ± 5.9 mSv] for axial vs. helical scan protocols, p < 0.001). The rate of downstream testing did not differ (13.8% vs. 15.9% for axial vs. helical scan protocols, p = 0.555). CONCLUSIONS: In patients with stable and low heart rates, the prospectively ECG-triggered axial scan protocol maintained image quality but reduced radiation exposure by 69% compared with helical scanning. Axial computed tomography data acquisition should be strongly recommended in suitable patients to avoid unnecessarily high radiation exposure.

Cardiovascular risk assessment based on the quantification of coronary calcium in contrast-enhanced coronary computed tomography angiography.

AIMS: The extent of coronary artery calcification (CAC) has been shown to be a strong and independent predictor for cardiovascular events. Usually, CAC scoring is performed in non-contrast-enhanced computed tomography (CT) examinations. The ability and accuracy of cardiovascular risk classification according to the degree of CAC determined in contrast-enhanced coronary CT angiography (CCTA) has not been investigated so far. The aim of this analysis was to develop and validate a method for CAC risk classification in CCTA. METHODS AND RESULTS: In a test series of 100 patients who underwent both non-enhanced CAC scoring and CCTA, we developed a method to assess the extent of coronary calcification and the associated cardiovascular risk category in CCTA. The accuracy of the developed approach of CAC assessment in CCTA was determined in 500 consecutive patients in comparison to CAC scoring in the non-enhanced scan. CAC scoring results in the non-enhanced scan and CCTA scan showed a high correlation (r = 0.954; P < 0.001). CAC quantification in CCTA correctly identified 98% of patients without CAC as shown in the non-enhanced scan (184 of 188 patients). When compared with non-enhanced CAC scoring, CAC scoring in CCTA grouped more than 95% of high-risk patients correctly into the same risk category according to the 75th age- and gender-specific percentiles or the absolute calcium scores. CONCLUSION: Assessing cardiovascular risk associated with CAC is feasible and accurate in contrast-enhanced CCTA. This new technique may allow for reducing the radiation exposure of coronary CT studies while maintaining an accurate cardiovascular risk assessment, because the addition of non-enhanced scans to CCTA becomes unnecessary for comprehensive coronary CT studies.

Alternative targeting of Arabidopsis plastidic glucose-6-phosphate dehydrogenase G6PD1 involves cysteine-dependent interaction with G6PD4 in the cytosol.

Arabidopsis peroxisomes contain an incomplete oxidative pentose-phosphate pathway (OPPP), consisting of 6-phosphogluconolactonase and 6-phosphogluconate dehydrogenase isoforms with peroxisomal targeting signals (PTS). To start the pathway, glucose-6-phosphate dehydrogenase (G6PD) is required; however, G6PD isoforms with obvious C-terminal PTS1 or N-terminal PTS2 motifs are lacking. We used fluorescent reporter fusions to explore possibly hidden peroxisomal targeting information. Among the six Arabidopsis G6PD isoforms only plastid-predicted G6PD1 with free C-terminal end localized to peroxisomes. Detailed analyses identified SKY as an internal PTS1-like signal; however, in a medial G6PD1 reporter fusion with free N- and C-terminal ends this cryptic information was overruled by the transit peptide. Yeast two-hybrid analyses revealed selective protein-protein interactions of G6PD1 with catalytically inactive G6PD4, and of both G6PD isoforms with plastid-destined thioredoxin m2 (Trx(m2) ). Serine replacement of redox-sensitive cysteines conserved in G6PD4 abolished the G6PD4-G6PD1 interaction, albeit analogous changes in G6PD1 did not. In planta bimolecular fluorescence complementation (BiFC) demonstrated that the G6PD4-G6PD1 interaction results in peroxisomal import. BiFC also confirmed the interaction of Trx(m2) with G6PD4 (or G6PD1) in plastids, but co-expression analyses revealed Trx(m2) -mediated retention of medial G6PD4 (but not G6PD1) reporter fusions in the cytosol that was stabilized by CxxC¹¹³S exchange in Trx(m2) . Based on preliminary findings with plastid-predicted rice G6PD isoforms, we dismiss Arabidopsis G6PD4 as non-functional. G6PD4 orthologs (new P0 class) apparently evolved to become cytosolic redox switches that confer thioredoxin-relayed alternative targeting to peroxisomes.

Prognostic value of coronary computed tomographic angiography in comparison with calcium scoring and clinical risk scores.

BACKGROUND: Several studies have demonstrated a high accuracy of coronary computed tomography angiography (CCTA) for detection of obstructive coronary artery disease (CAD), whereas some studies have also shown a good prediction of cardiac events. However, it remains to be proven whether CCTA is better predictive of events than conventional risk scores or calcium scoring. Therefore, we compared CCTA with calcium scoring and clinical risk scores for the ability to predict cardiac events. METHODS AND RESULTS: Patients (n=2223) with suspected CAD undergoing CCTA were followed up for a median of 28 months. The end point was the occurrence of cardiac events (cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, and coronary revascularization later than 90 days after CCTA). Patients with obstructive CAD had a significantly higher event rate (2.9% per year; 95% confidence interval, 2.1 to 4.0) than those without obstructive CAD, having an event rate 0.3% per year (95% confidence interval, 0.1 to 0.5; hazard ratio, 13.5; 95% confidence interval, 6.7 to 27.2; P<0.001). CCTA had significant incremental predictive value when compared with calcium scoring, both with scores assessing the degree of stenosis (P<0.001) and with scores assessing the number of diseased coronary segments (P=0.027). CONCLUSIONS: In patients with suspected CAD, CCTA not only detects coronary stenosis but also improves prediction of cardiac events over and above conventional risk scores and calcium scoring. This may result in a reclassification of cardiovascular risk in a substantial proportion of patients.

Image quality and radiation exposure with a low tube voltage protocol for coronary CT angiography results of the PROTECTION II Trial.

OBJECTIVES: The purpose of this study was to evaluate image quality and radiation dose using a 100 kVp tube voltage scan protocol compared with standard 120 kVp for coronary computed tomography angiography (CTA). BACKGROUND: Concerns have been raised about radiation exposure during coronary CTA. The use of a 100 kVp tube voltage scan protocol effectively lowers coronary CTA radiation dose compared with standard 120 kVp, but it is unknown whether image quality is maintained. METHODS: We enrolled 400 nonobese patients who underwent coronary CTA: 202 patients were randomly assigned to a 100 kVp protocol and 198 patients to a 120 kVp protocol. The primary end point was to demonstrate noninferiority in image quality with the 100 kVp protocol, which was assessed by a 4-point grading score (1 = nondiagnostic, 4 = excellent image quality). For the noninferiority analysis, a margin of -0.2 image quality score points for the difference between both scan protocols was pre-defined. Secondary end points included radiation dose and need for additional diagnostic tests during follow-up. RESULTS: The mean image quality scores in patients scanned with 100 kVp and 120 kVp were 3.30 ± 0.67 and 3.28 ± 0.68, respectively (p = 0.742); image quality of the 100 kVp protocol was not inferior, as demonstrated by the 97.5% confidence interval of the difference, which did not cross the pre-defined noninferiority margin of -0.2. The 100 kVp protocol was associated with a 31% relative reduction in radiation exposure (dose-length product: 868 ± 317 mGy × cm with 120 kVp vs. 599 ± 255 mGy × cm with 100 kVp; p < 0.0001). At 30-day follow-up, the need for additional diagnostic studies did not differ (13.4% vs. 19.2% for 100 kVp vs. 120 kVp, respectively; p = 0.114). CONCLUSIONS: A coronary CTA protocol using 100 kVp tube voltage maintained image quality, but reduced radiation exposure by 31% as compared with the standard 120 kVp protocol. Thus, 100 kVp scan protocols should be considered for nonobese patients to keep radiation exposure as low as reasonably achievable. (Prospective Randomized Trial on Radiation Dose Estimates of Cardiac CT Angiography in Patients Scanned With a 100 kVp Protocol [PROTECTION II]; NCT00611780).

Comparison of sequential and helical scanning for radiation dose and image quality: results of the Prospective Multicenter Study on Radiation Dose Estimates of Cardiac CT Angiography (PROTECTION) I Study.

OBJECTIVE: Concerns have been raised about the radiation exposure of coronary CT angiography (CTA). Recently, a prospective ECG-triggered sequential coronary CTA technique was developed to reduce exposure to ionizing radiation. The purpose of this analysis was to determine the impact of a sequential scanning technique on image quality and radiation dose in a prespecified subgroup analysis of the Prospective Multicenter Study on Radiation Dose Estimates of Cardiac CT Angiography I (PROTECTION I) Study when compared with a standard helical scanning technique. MATERIALS AND METHODS: This analysis comprises 685 64-MDCT coronary angiography studies of 47 international study sites in which the image quality was assessed by an experienced coronary CTA investigator using a 4-point score (1 = nondiagnostic, 4 = excellent image quality). Image quality was analyzed in all patients studied with the sequential scanning mode (n = 99) and in randomly selected patients of the population studied with the helical acquisition mode (n = 586). Radiation dose estimates were derived from the dose-length product (DLP) and a conversion coefficient for the chest (0.014 mSv x mGy(-1) x cm(-1)). RESULTS: Although the sequential scanning mode significantly reduced radiation dose estimates by 68% from 11.2 mSv for the helical mode to 3.6 mSv for the sequential mode (p < 0.001), the median diagnostic image quality scores were comparable in both groups. The median diagnostic score for both scanning modes was 3.5 (interquartile range: sequential vs helical mode, 3.25-3.75 vs 3.0-3.75, respectively; p = 0.62). CONCLUSION: The results of the PROTECTION I Study suggest that the prospective ECG-triggered sequential coronary CTA technique significantly reduces radiation dose without impairing image quality when compared with the standard retrospective helical data acquisition in patients with a low and stable heart rate.

Impact of a reduced tube voltage on CT angiography and radiation dose: results of the PROTECTION I study.

OBJECTIVES: The aim of this study was to determine the impact of a reduced 100-kV tube voltage on image quality and radiation exposure in a pre-defined subgroup analysis of the international, multicenter radiation dose survey PROTECTION I (Prospective Multicenter Study on RadiaTion Dose Estimates Of Cardiac CT AngIOgraphy I) study. BACKGROUND: Cardiac computed tomography angiography (CCTA) has become a frequently used diagnostic tool in clinical practice. Despite continually improving CT technology, there remain concerns regarding the associated radiation exposure. A reduced tube voltage of 100 kV has been proposed as an effective means for dose reduction in nonobese patients. METHODS: The study assessed the relevant radiation dose parameters as well as quantitative and qualitative diagnostic image quality data in a subgroup of 321 patients (100 kV: 82 patients; 120 kV: 239 patients), who were scanned at study sites that applied a 100-kV tube voltage in at least 1 patient. Diagnostic image quality was assessed by an experienced CCTA investigator with a 4-point score (1: nondiagnostic to 4: excellent image quality). Effective radiation dose was estimated from the dose-length-product of each CCTA study. RESULTS: The use of the 100-kV scan protocol was associated with 53% reduction in CCTA median radiation dose estimates, when compared with the conventional 120-kV scan protocol (p < 0.001). Although image noise significantly increased by 26.3% with 100 kV, signal- as well as contrast-to-noise ratios also increased by 7.9% (p = 0.254) and 10.8% (p = 0.027), respectively. Reduction of tube voltage did not impair diagnostic image quality (median diagnostic score: 3.5 [3.25 to 3.75] vs. 3.5 [3.0 to 3.75] for 100 kV vs. 120 kV; p = 0.22). CONCLUSIONS: In this nonrandomized PROTECTION I dose survey, reducing the CCTA tube voltage to 100 kV in nonobese patients is associated with a significant reduction in radiation exposure while maintaining diagnostic image quality. Thus, the 100-kV scan technique should be considered for CCTA dose reduction in adequately selected patients.

Viable vascularized autologous patch for transmural myocardial reconstruction.

OBJECTIVE: Various patch materials currently used for cardiac reconstruction represent non-viable tissue with high susceptibility to infection and degeneration. We therefore introduce an innovative, autologous vascularized matrix with high regenerative potential for myocardial reconstruction. METHODS: Autologous small bowel segments without mucosa, but with both the adjacent jejunal artery and vein, were harvested and used in a single-stage procedure for the replacement of right ventricular transmural defects (2 cm x 3 cm) in pigs (group A; n = 3). The autografts were revascularized by connecting jejunal vessels to the right internal thoracic artery and vein. Autologous pericardium was used as controls (group B; n = 3). All procedures were performed on beating hearts using a right heart bypass. After explantation (up to 6 months), the patches were investigated by standard histological analyses, immunohistochemistry and confocal microscopy. RESULTS: Postoperative complications, for example excessive bleeding, graft rupture or dislodgement due to the dynamic cardiac contractions, did not occur. In group A, newly formed cardiomyocytes positively stained for Nkx 2.5 and myosin heavy chain were identified 1 month after operation. The cardiomyocytes were localized in close proximity to mesenteric capillaries in a disseminated-like pattern and showed a strong tendency to form islets. In contrast, explanted pericardial patches appeared as fibrotic tissue without evidence of myocardial cells inside the patch. CONCLUSION: We developed a novel autologous graft with preserved vascularity that can be used for myocardial grafting. This vascularized matrix undergoes autologous repopulation with cardiomyocytes after transmural myocardial replacement. Vascularization represents an important prerequisite for myocardial guided tissue regeneration.

Estimated radiation dose associated with cardiac CT angiography.

CONTEXT: Cardiac computed tomography (CT) angiography (CCTA) has emerged as a useful diagnostic imaging modality in the assessment of coronary artery disease. However, the potential risks due to exposure to ionizing radiation associated with CCTA have raised concerns. OBJECTIVES: To estimate the radiation dose of CCTA in routine clinical practice as well as the association of currently available strategies with dose reduction and to identify the independent factors contributing to radiation dose. DESIGN, SETTING, AND PATIENTS: A cross-sectional, international, multicenter, observational study (50 study sites: 21 university hospitals and 29 community hospitals) of estimated radiation dose in 1965 patients undergoing CCTA between February and December 2007. Linear regression analysis was used to identify independent predictors associated with dose. MAIN OUTCOME MEASURE: Dose-length product (DLP) of CCTA. RESULTS: The median DLP of 1965 CCTA examinations performed at 50 study sites was 885 mGy x cm (interquartile range, 568-1259 mGy x cm), which corresponds to an estimated radiation dose of 12 mSv (or 1.2 x the dose of an abdominal CT study or 600 chest x-rays). A high variability in DLP was observed between study sites (range of median DLPs per site, 331-2146 mGy x cm). Independent factors associated with radiation dose were patient weight (relative effect on DLP, 5%; 95% confidence interval [CI], 4%-6%), absence of stable sinus rhythm (10%; 95% CI, 2%-19%), scan length (5%; 95% CI, 4%-6%), electrocardiographically controlled tube current modulation (-25%; 95% CI, -23% to -28%; applied in 73% of patients), 100-kV tube voltage (-46%; 95% CI, -42% to -51%; applied in 5% of patients), sequential scanning (-78%; 95% CI, -77% to -79%; applied in 6% of patients), experience in cardiac CT (-1%; 95% CI, -1% to 0%), number of CCTAs per month (0%; 95% CI, 0%-1%), and type of 64-slice CT system (for highest vs lowest dose system, 97%; 95% CI, 88%-106%). Algorithms for dose reduction were not associated with deteriorated diagnostic image quality in this observational study. CONCLUSIONS: Median doses of CCTA differ significantly between study sites and CT systems. Effective strategies to reduce radiation dose are available but some strategies are not frequently used. The comparable diagnostic image quality may support an increased use of dose-saving strategies in adequately selected patients.

Trends in radiation protection in CT: present and future status.

With the introduction of modern multislice scanner generations, computed tomography (CT) has emerged as a useful tool for evaluation of the coronary arteries. A common application of coronary CT angiography (CCTA) is the examination of patients with intermediate pretest probability for obstructive coronary artery disease. Despite the widespread use of cardiac CT examinations in clinical practice, concern remains about the exposure to ionizing radiation and its potential hazards. Therefore, radiation dose and strategies for dose reduction have become an important focus of interest. Several smaller analyses have shown an effective radiation dose between 6.4 and 27.8 mSv for spiral CCTA image acquisition. The international Prospective Multicenter Study On RadiaTion Dose Estimates Of Cardiac CT AngIOgraphy I (PROTECTION I) study, the largest observational study on radiation dose estimates of cardiac CT so far, determined radiation dose estimates of CCTA, as well as the effect of different strategies to reduce dose in clinical practice. The median dose-length-product of 1965 CCTA examinations was 885 mGy x cm, which corresponds to a median estimated effective radiation dose of 12 mSv. However, a large variation in dose between study sites was observed, indicating a large potential to reduce dose for individual sites. Several dose-saving scanning techniques and algorithms have been developed. This article discusses these strategies as well as their effect on radiation dose and image quality. Because the contrast-enhanced CT angiography is the largest part of the total study dose, the following described strategies focus on radiation dose reduction for CCTA image acquisition.

Tips to minimize radiation exposure.

The use of cardiac computed tomography (CT) to noninvasively visualize the coronary arteries has rapidly increased during the last few years but thereby also has raised concerns about the amount of radiation exposure and its potentially associated hazards. In this article, we summarize several strategies and new scanning techniques for dose reduction in cardiac CT, including the following: 1) Coronary CT angiography should not be performed in patients with extensive coronary calcifications because the probability to rule out obstructive coronary artery disease diminishes with increasing coronary artery calcium scores; 2) The scan length in CT angiography should be individually adjusted to the minimum needed length; 3) electrocardiogram-correlated modulation of the tube current should be applied in all patients with stable sinus rhythm; 4) The tube voltage should be reduced to 100 kV in non-obese patients (patient weight <85-90 kg); and 5) A sequential scan mode with prospective electrocardiogram triggering should be considered in patients with a stable heart rate

Reduction of radiation dose estimates in cardiac 64-slice CT angiography in patients after coronary artery bypass graft surgery.

OBJECTIVES: The objectives of this prospective investigation in patients after bypass graft surgery were (1) to estimate radiation dose for routine bypass graft computed tomography (CT) angiography, (2) to study the impact of anatomically adapted and ECG-controlled tube current modulation on radiation dose estimates, and (3) effects on qualitative and quantitative image quality parameters. METHODS: Radiation dose was estimated for 194 consecutive patients undergoing 64-slice CT angiography (Somatom Sensation 64 Cardiac, Siemens Medical Solutions). The impact of anatomically adapted tube current modulation was studied in 2 consecutive patients groups. Furthermore, the impact of ECG-controlled tube current modulation, applied as indicated, was evaluated in both groups. RESULTS: Mean radiation dose estimate for a 64-slice CT bypass graft study was 18.9 +/- 6.0 mSv (CTDIvol 42.3 +/- 12.9 mGy). The application of anatomically adapted tube current modulation had no effect on dose parameters (CTDIvol 43.3 +/- 13.2 vs. 40.1 +/- 12.1 mGy for those with versus those without anatomically adapted tube current modulation, P = 0.1). Additional implementation of ECG-controlled tube current modulation resulted in reduced dose parameters (CTDIvol of 32.9 +/- 2.6 vs. 58.9 +/- 3.9 mGy and radiation dose estimates: 14.7 +/- 1.9 mSv vs. 26.5 +/- 2.1 mSv for those with versus those without ECG pulsing, both P < 0.01). There was no deterioration in image quality with use of tube current modulation algorithms. CONCLUSIONS: The radiation burden associated with 64-slice bypass graft CT angiographies is substantial. Anatomically adapted tube current modulation does not reduce radiation dose parameters, whereas ECG-controlled tube current modulation was associated with a 45% reduction in dose estimates. Application of both tube current modulation algorithms did not result in reduced image quality.