Background: Animal models are essential for translating diagnostic and therapeutic strategies into clinical practice and offer valuable insights into the pathophysiology of diseases such as aortic dissection. This study presents a novel acute in vivo large animal model of Stanford type A aortic dissection, combining open surgical access with endovascular techniques to leverage the advantages of both. The model aims to reproducibly simulate acute dissections in swine, providing a standardized platform for evaluating diagnostics, disease mechanisms, and treatment strategies. Methods: Six pigs underwent a standardized protocol to induce aortic dissection. Arterial pressure was monitored via femoral and carotid catheterization. A conventional sternotomy was performed, followed by tangential cross-clamping of the ascending aorta and a controlled incision proximal to the brachiocephalic trunk. The intima and the media were separated using a guidewire and catheter-based technique to create a false lumen. A re-entry tear was also established to allow for controlled intraluminal access. Animals were monitored for 12 h post-intervention, with serial blood sampling. At the end of the experiment, the animals were euthanized and the aortas harvested for macroscopic and histological analysis. Results: In all 6 animals, the placement of arterial catheters in femoral and carotid arteries, as well as the sternotomy, was established without any complications. The dissection model was successfully created in 5 out of 6 animals by clinical signs such as adventitial hematoma, macroscopic wall separation and/or decreased femoral blood pressure. One animal experienced complete aortic perforation. Five animals completed the full observation period of 12 h. Conclusion: A standardized, reproducible, and robust large animal model of acute Stanford type A aortic dissection using a hybrid approach was developed. This model closely simulates the clinical and pathological features of human aortic dissection, making it a valuable tool for preclinical research in diagnostics, pathophysiology, and treatment development.
Regenerative grafts for myocardial reconstruction are often mechanically not stable enough to withstand the left ventricle’s high blood pressure. Hence, decellularized pericardium may serve as a stabilizing structure for biological myocardium prostheses. The efficacy of detergent- and enzyme-based protocols to decellularize porcine pericardium was compared. Then, the decellularized pericardium was employed for a primary cover of a transmural left ventricular defect in minipigs (n = 9). This pericardium patch was applied to mitigate the high-pressure load on an autologous stomach tissue, which was utilized as a regenerative tissue prosthesis. Decellularization of the porcine pericardium with deoxycholic acid (DOA)- and enzyme-based protocols (trypsin/EDTA) removed 90% of the original cells (p < 0.001). The trypsin/EDTA protocol significantly altered the matrix architecture compared to the DOA protocol. There were no infections or clinical signs of graft rejection following the transplantation of the decellularized pericardium and the autologous segment of the stomach in the surviving animals (n = 7). A good left ventricular function could be detected via MRI six months following surgery. The biological integration of the graft into the host’s tissue was found histologically. The stabilization of initially fragile grafts with decellularized pericardium facilitates the application of regenerative myocardial prostheses even on the left ventricle.
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 three animals were followed up for 3 months until planned euthanasia, whereas the observation period for the remaining three animals was scheduled 6 months following surgery. Functional assessment of the grafts was carried out via cardiac magnetic resonance tomography (MRI) and angiography. Physiological remodeling was evaluated histologically and immunohistochemically after heart explanation. 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 a rupture of the stomach graft. Functional integration of the heterotopically transplanted stomach into the surrounding myocardium was observed. Angiography showed the 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 a 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.
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.
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.
In patients with severe heart failure, the surgical reconstruction of the damaged myocardium with regenerative biological grafts is an innovative therapeutic option. However, natural patch materials are often too delicate for a full wall repair of the left ventricle. A degradable magnesium scaffold could provide temporary mechanical stability until the sufficient physiological remodeling of such grafts. An autologous vascularised gastric patch was employed for the reconstruction of the left ventricular myocardium in a porcine model. Magnesium alloy (LA63) scaffolds were fixed over the biological patch. The function of the implant was assessed via magnetic resonance imaging. Angiography was carried out to detect a connection between the gastric and coronary vasculature. The explants were examined via µ-computer tomography and light microscopy. All the test animals survived. The prostheses integrated biologically and functionally into the myocardium. No rupture of the prostheses occurred. An anastomosis of the gastric and coronary vasculature had developed. The magnesium scaffolds degraded, on average, to 30.9% of their original volume. This novel technique responds to the increasing demand for regenerative myocardial grafts. The magnesium scaffolds’ biocompatibility and degradation kinetics, as well as their stabilizing effects, indicate their applicability in the surgical treatment of terminal heart failure.
Tissue-engineered (TE) grafts based on decellularized grafts have shown very promising results in preclinical and clinical studies. However, in animal models valves have either been tested in juvenile models or in the clinically less relevant pulmonary valve position. In this study, we tested the grafts in the aortic valve (AV) position of 6-year-old sheep, as geriatric patients in need of an AV substitute due to calcification are the largest patient group benefiting from TE grafts. Decellularized AV (DAV; n = 4) and DAV additionally re-endothelialized with autologous cells (n = 3) were implanted in the AV position of 6-year-old female sheep. Function was investigated at implantation and explantation 12 months later. Regeneration capacity was analyzed by the repopulation degree of the graft with recipient's cells, by the generation of a new endothelial layer and by intracellular staining against pro-collagen type I. DAV and re-endothelialized AV demonstrated excellent function with only two valves developing mild insufficiencies (1°). Of the repopulating cells only few cells were identified as inflammation cells, while the majority was found to be interstitial cells producing procollagen type I. Endothelial coverage was found, but seemed to be reduced. The regenerative capacity of decellularized matrix is not only a feature exhibited when implanted in juvenile individuals but also is evident when implanted in the high-pressure AV position of older sheep, revealing the potential of TE grafts in age-advanced patients.
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.
In vivo repopulation of decellularized allografts with recipient cells leads to a positive remodeling of the graft matrix in juvenile sheep. In light of the increasing number of heart valve replacements among older patients (>65 years), this study focused on the potential for matrix-guided tissue regeneration in elderly sheep. Pulmonary valve replacement was performed in seven-year old sheep using decellularized (DV), decellularized and CCN1-coated (RV), or decellularized and in vitro reendothelialized pulmonary allografts (REV) (n=6, each group). CCN1 coating was applied to support re-endothelialization. In vitro re-endothelialization was conducted with endothelial-like cells derived from peripheral blood. Echocardiograms of all grafts showed adequate graft function after implantation and at explantation 3 or 6 months later. All explants were macroscopically free of thrombi at explantation, and revealed repopulation of the allografts on the adventitial side of valvular walls and proximal in the cusps. Engrafted cells expressed vimentin, sm α-actin, and myosin heavy chain 2, while luminal cell lining was positive for vWF and eNOS. Cellular repopulation of valvular matrix demonstrates the capacity for matrix-guided regeneration even in elderly sheep but is not improved by in vitro endothelialization, confirming the suitability of decellularized matrix for heart valve replacement in older individuals.
Background: Several patch materials are used to replace diseased cardiac tissue segments. Most of these conduits represent either non-viable materials or bio-artificial grafts with high susceptibility to infection, tissue degeneration and calcification. Hereby, we present our experience of using autologous vascularized matrix (AutoVaM) as a viable graft for myocardial tissue repair. Methods and Results: AutoVaM patches based on small bowel segments without mucosa with adjacent jejunal artery and vein were used for the replacement of right atrial (RA) defects (2x3 cm) in pigs (n=6). The AutoVaMs were revascularized by connecting jejunal vessels to the right internal thoracic artery and vein. Intraoperative angiography revealed regular blood perfusion of the patches. Autologous pericardium grafts were used as controls (N=6). Complications such as bleeding, graft rupture or dislodgement did not occur. Histological investigations (up to 6 months) by using Nkx 2.5 and myosin heavy chain revealed newly formed cardiomyocytes inside of AutoVaM explants mostly localized in a disseminated pattern in close proximity to mesenteric capillaries. With increasing time these cells showed strong tendency to form islets and to communicate with each other via Connexin 43 containing gap-junctions. In contrast, pericardial patches appeared as a fibrotic tissue with no evidence of myocytes inside the patch. Based on these experimental results, 2 patients, one with myocardial sarcoma and one with thymus-carcinoma with atrial involvement underwent subtotal resection of the RA. Resulting defects were grafted using AutoVaM. No signs of thromboembolic complications or endocarditis were observed. Follow-up angiography revealed patent jejunal vessels and permeable capillary bed of the cardiac neo-chamber. Transesophageal Echocardiography (TEE) revealed systolic and diastolic motion of the graft along with the left atrium during the cardiac cycle. In one patient 2 years follow-up TEE showed an RA ejection fraction of 25%. Conclusion: RA replacement with vascularized intestinal graft is more superior then pericardium in terms of higher regenerative potential by repopulation with cardiomyocytes. The procedure is clinically safe and promising.
Rotavirus infection is the leading cause of acute diarrhea in children and is preventable with a vaccine. Malnutrition increases the risk for the development of enteric and respiratory diseases, but also diarrhea increases the risk for stunting, having a negative effect in height-for-age Z score (HAZ). Therefore, Rotavirus can be considered as one of the contributing factors to stunting. The objective was to determine if vaccination against rotavirus was associated with changes in HAZ of children aged 6–60 months. We analyzed the data of Demographic and Health Survey (DHS) 2015–2017 for Peru, which is a nationwide representative. We fitted linear regression models controlling for complex sampling. The vaccine coverage was close to 75.5%, and the mean HAZ was −0.76 standard deviations. After adjusting by demographic, health, and household characteristics, children who received rotavirus vaccine, had a mean HAZ 0.06 standard deviations higher than children who did not receive it. Additionally, BCG vaccination, a higher education level of the mother, a higher wealth index, and treating water for drinking were positively associated with HAZ. On the other hand, we found low birth weight, lack of flush toilet, and altitude higher than 2500 m above sea level negatively associated with HAZ. Rotavirus vaccine is associated with better anthropometric measurements.
Synthetic or biological patch materials used for surgical myocardial reconstruction are often fragile. Therefore, a transient support by degradable magnesium scaffolds can reduce the risk of dilation or rupture of the patch until physiological remodeling has led to a sufficient mechanical durability. However, there is evidence that magnesium implants can influence the growth and physiological behavior of the host's cells and tissue. Hence, we epicardially implanted scaffolds of the magnesium fluoride-coated magnesium alloy LA63 in a swine model to assess biocompatibility and degradation kinetics. Chemical analysis of the pigs' organs revealed no toxic accumulation of magnesium ions in the skeletal muscle, myocardium, liver, kidney, and bone of the pigs 1, 3, and 6 months postimplantation. The implants were surrounded by a fibrous granulation tissue, but no signs of necrosis were histologically evaluable. A sufficiently slow degradation rate of the magnesium alloy scaffold can be demonstrated via micro-computed tomography investigation. We conclude that stabilizing scaffolds of the magnesium fluoride-coated magnesium alloy LA63 can be used for epicardial application because no significant adverse effects to myocardial tissue were noted. Thus, degradable stabilizing scaffolds of this magnesium alloy with a slow degradation rate can extend the indication of innovative biological and synthetic patch materials.
Evaluation of the feasibility to use novel tissue engineered grafts for right ventricular outflow tract reconstruction by magnetic resonance imaging Dagmar Hartung, Serghei Cebotari, Igor Tudorache, Karolina Theodoridis, Tanja Meyer, Alexandru Mogaldea, Robert Ramm, Katja Hueper, Frank Wacker, Andres Hilfiker, and Axel Haverich Radiology, Hannover Medical School, Hannover, Germany, Division of Cardiothoracic, Transplantation, and Vascular Surgery, Hannover Medical School, Hannover, Germany, Leibniz Research Laboratory for Biotechnology and Artificial Organs, Hannover Medical School, Hannover, Germany
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.
Concerns have been raised about the radiation exposure during coronary CT angiographies (CCTAs). For a prospectively ECG-triggered high-pitch scan protocol very low and even sub-millisievert radiation doses have been reported for CCTA, but it is unclear, whether image quality is maintained when
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. (Prospective Randomized Trial on Radiation Dose Estimates of CT Angiography in Patients Scanned With a Sequential Scan Protocol [PROTECTION-III]; NCT00612092) (J Am Coll Cardiol Img 2012;5:484-93) (C) 2012 by the American College of Cardiology Foundation
Patients with arterial hypertension have a high risk of developing coronary artery disease (CAD), but noninvasive diagnosis of CAD remains difficult. We assessed the ability of coronary CT angiography (CCTA) to detect CAD and to predict subsequent cardiac events in hypertensive patients. We compared 906 hypertensive patients without known CAD undergoing CCTA with 906 matched normotensive patients. Besides calcium score and the degree of the most severe stenosis, the number of coronary segments with atherosclerotic changes was recorded. The primary endpoint was the occurrence of hard cardiac events defined as all cause death, nonfatal myocardial infarction or unstable angina requiring hospitalization. During a median follow-up of 29 months, there were 17 hard cardiac events in the hypertensive group and 13 events in the control group. The best predictor of events in hypertensive patients was the degree of the most severe stenosis (C-index 0.705, P < 0.001, both corrected for clinical risk). The annual event rate was 0.3% for patients without obstructive CAD and 1.5% for patients with obstructive CAD. In hypertensive patients without known CAD, coronary CT angiography allows for the identification of patients at high risk for incident cardiac events.
AbstractBioprosthetic heart valve replacement, recommended for patients older than 65 years of age, increases the quality of life, however grafts exhibit limited functionality due to degradation and calcification. Decellularized and tissue-engineered pulmonary valves (PV) get repopulated by autologous interstitial cells when implanted into juvenile sheep. Thus, in vivo matrix guided regeneration results in restored valve function. In this study, we investigated the regeneration capacity in elderly sheep. Sheep (Ø 7 yrs old, Ø weight of 88.5 kg) received pulmonary valve replacement. Decellularized PV (n=6), decellularized PV coated with proangiogenic CCN1 (n=6), and decellularized, CCN1 coated and reendothelized PV (n=6) were implanted in orthotopic position. For endothelialization PV were seeded with autologous endothelial cells (EC) differentiated from EPC from peripheral blood. Cells were flow adapted in a pulsatile bioreactor system prior implantation. PV functional analysis in vivo was realized by echocardiography, directly after implantation and prior explantation. Allografts were explanted after six and twelve months in vivo and investigated in respect to endothelium coverage, to the integrity of the extracellular matrix, and to the degree and cellular identity of invaded cells by histological and immunochemical stains. All allografts showed good to adequate function, no stenosis, low gradients and only occasional insufficiency without clinical symptoms. No signs of degradation of the extracellular matrix and minimal calcification restricted at the anastomosis of the grafts were found. All grafts were repopulated with cells but to various degree. Only one, explanted after one year, showed complete repopulation including the leaflets. In general, cell-density in the pulmonary artery was higher on the adventitial than on the luminal side and leaflets were better repopulated at the ventricular than at the arterial side. The majority of cells expressed sm-alpha-actin. Endothelial cells located on the luminal side appeared in some grafts as intact complete monolayer. Beside a slight tendency of better repopulation observed in the reendothelialized PV group, no significant difference of cell densities was found among the groups. Autologous repopulation of decellularized heart valve matrices implanted in the orthotopic position in the elderly sheep demonstrates retained regenerative capacity even in the older organism. This observation combined with the fact that no functional loss must have taken into account, implantation of decellularized heart valves matrices in patients over age 65 remains a therapy option to overcome the drawbacks of current used bioprosthesis.
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.