Sebastian Reinartz

Multicenter Evaluation of Dynamic Three-Dimensional Magnetic Resonance Myocardial Perfusion Imaging for the Detection of Coronary Artery Disease Defined by Fractional Flow Reserve

Background—First-pass myocardial perfusion cardiovascular magnetic resonance (CMR) imaging yields high diagnostic accuracy for the detection of coronary artery disease (CAD). However, standard 2D multislice CMR perfusion techniques provide only limited cardiac coverage, and hence considerable assumptions are required to assess myocardial ischemic burden. The aim of this prospective study was to assess the diagnostic performance of 3D myocardial perfusion CMR to detect functionally relevant CAD with fractional flow reserve (FFR) as a reference standard in a multicenter setting. Methods and Results—A total of 155 patients with suspected CAD listed for coronary angiography with FFR were prospectively enrolled from 5 European centers. 3D perfusion CMR was acquired on 3T MR systems from a single vendor under adenosine stress and at rest. All CMR perfusion analyses were performed in a central laboratory and blinded to all clinical data. One hundred fifty patients were successfully examined (mean age 62.9±10 years, 45 female). The prevalence of CAD defined by FFR (<0.8) was 56.7% (85 of 150 patients). The sensitivity and specificity of 3D perfusion CMR were 84.7% and 90.8% relative to the FFR reference. Comparison to quantitative coronary angiography (≥50%) yielded a prevalence of 65.3%, sensitivity and specificity of 76.5% and 94.2%, respectively. Conclusions—In this multicenter study, 3D myocardial perfusion CMR proved highly diagnostic for the detection of significant CAD as defined by FFR.

Vitamin K1 to slow vascular calcification in haemodialysis patients (VitaVasK trial): a rationale and study protocol.

BACKGROUND Patients on haemodialysis (HD) exhibit increased cardiovascular mortality associated with accelerated vascular calcification (VC). VC is influenced by inhibitors such as matrix Gla protein (MGP), a protein activated in the presence of vitamin K. HD patients exhibit marked vitamin K deficiency, and supplementation with vitamin K reduces inactive MGP levels in these patients. The VitaVasK trial analyses whether vitamin K1 supplementation affects the progression of coronary and aortic calcification in HD patients. METHODS VitaVasK is a prospective, randomized, parallel group, multicentre trial (EudraCT No.: 2010-021264-14) that will include 348 HD patients in an open-label, two-arm design. After baseline multi-slice computed tomography (MSCT) of the heart and thoracic aorta, patients with a coronary calcification volume score of at least 100 will be randomized to continue on standard care or to receive additional supplementation with 5 mg vitamin K1 orally thrice weekly. Treatment duration will be 18 months, and MSCT scans will be repeated after 12 and 18 months. Primary end points are the progression of thoracic aortic and coronary artery calcification (calculated as absolute changes in the volume scores at the 18-month MSCT versus the baseline MSCT). Secondary end points comprise changes in Agatston score, mitral and aortic valve calcification as well as major adverse cardiovascular events (MACE) and all-cause mortality. VitaVask also aims to record MACE and all-cause mortality in the follow-up period at 3 and 5 years after treatment initiation. This trial may lead to the identification of an inexpensive and safe treatment or prophylaxis of VC in HD patients.

Prevention of vasculopathy by vitamin K supplementation: Can we turn fiction into fact?

With the discovery that vitamin K-dependent matrix Gla-protein (MGP) is a strong and modifiable factor in the prevention of arterial calcification, vitamin K was put forward as novel treatment option in cardiovascular disease. The vasculoprotective properties of vitamin K are in part based on the ability to improve gamma-glutamylcarboxylation of MGP, which is a prerequisite for MGP as a calcification inhibitor. Data from experimental animal models reveal that high intake of vitamin K can prevent and even reverse vascular calcifications. In addition, clinical data demonstrate that prescription of vitamin K antagonists for long-term oral anticoagulant therapy accelerates vascular calcification. However, controlled data from randomized prospective vitamin K interventional trials are lacking, thereby weakening a general recommendation for supplementation. The present article summarizes our current knowledge on the association between vitamin K and cardiovascular health. Additionally, we focus on an outlook on important ongoing prospective vitamin K intervention studies. These studies address the issues whether vitamin K substitution helps modifying relevant cardiovascular surrogates such as vascular calcification and whether non-vitamin K oral anticoagulants provide an alternative to support cardiovascular health benefits. So research about cardiovascular protection by vitamin K is an evolving field in which we expect a boost of novel and relevant evidence shortly.

DICOM for Clinical Research: PACS-Integrated Electronic Data Capture in Multi-Center Trials.

Providing surrogate endpoints in clinical trials, medical imaging has become increasingly important in human-centered research. Nowadays, electronic data capture systems (EDCS) are used but binary image data is integrated insufficiently. There exists no structured way, neither to manage digital imaging and communications in medicine (DICOM) data in EDCS nor to interconnect EDCS with picture archiving and communication systems (PACS). Manual detours in the trial workflow yield errors, delays, and costs. In this paper, requirements for a DICOM-based system interconnection of EDCS and research PACS are analysed. Several workflow architectures are compared. Optimized for multi-center trials, we propose an entirely web-based solution integrating EDCS, PACS, and DICOM viewer, which has been implemented using the open source projects OpenClinica, DCM4CHEE, and Weasis, respectively. The EDCS forms the primary access point. EDCS to PACS interchange is integrated seamlessly on the data and the context levels. DICOM data is viewed directly from the electronic case report form (eCRF), while PACS-based management is hidden from the user. Data privacy is ensured by automatic de-identification and re-labelling with study identifiers. Our concept is evaluated on a variety of 13 DICOM modalities and transfer syntaxes. We have implemented the system in an ongoing investigator-initiated trial (IIT), where five centers have recruited 24 patients so far, performing decentralized computed tomography (CT) screening. Using our system, the chief radiologist is reading DICOM data directly from the eCRF. Errors and workflow processing time are reduced. Furthermore, an imaging database is built that may support future research.

Slower Progress of Aortic Valve Calcification With Vitamin K Supplementation Results From a Prospective Interventional Proof-of-Concept Study

Calcific aortic stenosis is a common degenerative disease characterized by progressive aortic valve calcification (AVC).1 Effective medical treatment options to retard the progression of AVC are sparse.1 Epidemiological data point to vitamin K as a potential protective factor for cardiovascular health, particularly for protection against vascular calcification.2,3 Matrix Gla-protein (MGP), a potent inhibitor of cardiovascular calcification, requires vitamin K for posttranslational carboxylation and hence full bioactivity.4 Thus, vitamin K supplementation might retard the progression of AVC.1,2 Dephosphorylated undercarboxylated MGP (dp-ucMGP) serves as a circulating marker for vitamin K deficiency.2,3 We performed a 12-month prospective, single-center, open-label, randomized interventional trial in patients with asymptomatic or mildly symptomatic AVC. Written informed consent was obtained before inclusion in the trial (URL: http://www.clinicaltrials.gov. Unique identifier: NCT00785109; RWTH Aachen Institutional Review Board No. 165/08). Inclusion criterion was a peak flow velocity exceeding 2 m/s. The main exclusion criteria were chronic kidney disease (estimated glomerular filtration rate <60 mL·min−1·1.73 m−2), expected valve replacement within the next year, and anticoagulation with vitamin K antagonists. Patients were randomized 1:1 to receive 2 mg phytomenadione (vitamin …

Reconstructions with identical filling (RIF) of the heart: a physiological approach to image reconstruction in coronary CT angiography

AbstractObjectivesTo compare image quality in coronary artery computed tomography angiography (cCTA) using reconstructions with automated phase detection and Reconstructions computed with Identical Filling of the heart (RIF).MethodsSeventy-four patients underwent ECG-gated dual source CT (DSCT) between November 2009 and July 2010 for suspected coronary heart disease (n = 35), planning of transcatheter aortic valve replacement (n = 34) or evaluation of ventricular function (n = 5). Image data sets by the RIF formula and automated phase detection were computed and evalutated with the AHA 15-segment model and a 5-grade Likert scale (1: poor, 5: excellent quality). Subgroups regarding rhythm (sinus rhythm = SR; arrhythmia = ARR) and potential premedication were evaluated by a per-segment, per-vessel and per-patient analysis.ResultsRIF significantly improved image quality in 10 of 15 coronary segments (P < 0.05). More diagnostic segments were provided by RIF regarding the entire cohort (n = 693 vs. 590, P < 0.001) and all of the subgroups (e.g. ARR: n = 143 vs. 72, P < 0.001). In arrhythmic patients (n = 19), more diagnostic vessels (e.g. LAD: n = 10 vs. 3; P < 0.014) and complete data sets (n = 7 vs. 1; P < 0.001) were produced.ConclusionsRIF reconstruction is superior to automatic diastolic non-edited reconstructions, especially in arrhythmic patients. RIF theory provides a physiological approach for determining the optimal image reconstruction point in ECG-gated CT angiography.Key Points• Conventional CT coronary angiography suffers from numerous artefacts in patients with irregular rhythms • Coronary computed tomography angiograms (cCTA) were reconstructed with identical cardiac filling (RIF) • RIF reconstructions provide improved image quality compared to non-edited standard reconstructions • RIF theory links physiology with cardiac CT.

An undiagnosed double aortic arch hampers a coronary angiography in a patient with LIMA graft.

A 48-year-old male patient with a history of coronary artery bypass surgery by MIDCAB [left internal mammary artery (LIMA) to left anterior descending artery (LAD) due to spontaneous dissection of the proximal vessel) and invasive coronary angiography 12 years ago presented with atypical chest pain. Transthoracic echocardiogram revealed akinesis of the apex, apical anterior wall, mid and apical septum. Subsequently, invasive coronary …

Full field image reconstruction is suitable for high-pitch dual-source computed tomography.

ObjectivesThe field of view (FOV) in high-pitch dual-source computed tomography (DSCT) is limited by the size of the second detector. The goal of this study was to develop and evaluate a full FOV image reconstruction technique for high-pitch DSCT. Materials and MethodsFor reconstruction beyond the FOV of the second detector, raw data of the second system were extended to the full dimensions of the first system, using the partly existing data of the first system in combination with a very smooth transition weight function. During the weighted filtered backprojection, the data of the second system were applied with an additional weighting factor. This method was tested for different pitch values from 1.5 to 3.5 on a simulated phantom and on 25 high-pitch DSCT data sets acquired at pitch values of 1.6, 2.0, 2.5, 2.8, and 3.0. Images were reconstructed with FOV sizes of 260 × 260 and 500 × 500 mm2. Image quality was assessed by 2 radiologists using a 5-point Likert scale and analyzed with repeated-measure analysis of variance. ResultsIn phantom and patient data, full FOV image quality depended on pitch. Where complete projection data from both tube-detector systems were available, image quality was unaffected by pitch changes. Full FOV image quality was not compromised at pitch values of 1.6 and remained fully diagnostic up to a pitch of 2.0. At higher pitch values, there was an increasing difference in image quality between limited and full FOV images (P = 0.0097). ConclusionWith this new image reconstruction technique, full FOV image reconstruction can be used up to a pitch of 2.0.

Multicenter evaluation of dynamic three-dimensional whole-heart myocardial perfusion imaging for the detection of coronary artery disease defined by fractional flow reserve

Background Cardiac magnetic resonance (CMR) perfusion imaging yields high diagnostic accuracy for the detection of coronary artery disease (CAD) [1]. However, standard 2D multislice CMR perfusion techniques only provide limited coverage and hence prohibit computation of myocardial ischemic burden. Recently, two single-center 3D CMR perfusion studies have proven highly diagnostic for the detection of CAD relative to quantitative coronary angiography (QCA) [2] and fractional flow reserve (FFR) [3]. The aim of our prospective multicenter study is to assess the diagnostic performance of 3D CMR perfusion imaging in comparison with FFR.

Left ventricular structure in patients with mild to moderate chronic kidney disease – an MRI study

Introduction The high burden of left ventricular (LV) abnormalities in patients with advanced chronic kidney disease (CKD) is well established. However, less is known about the prevalence, patterns, and determinants of LV abnormalities in patients with early CKD. Methods We examined LV structure in 290 patients with a median estimated glomerular filtration rate (eGFR) of 51 ml/min per 1.73 m2 by magnetic resonance imaging (MRI). We explored associations with clinical and hemodynamic parameters, hydration (bioimpedance), endothelial function, inflammation (including C-reactive protein and tumor necrosis factor−α and its soluble receptors) and mineral bone disease (MBD) markers (including vitamin D, parathyroid hormone, α-klotho and fibroblast growth factor−23). Results Normal geometry was found in 56% of patients, dilation in 4%, concentric remodeling in 10%, and LV hypertrophy in 29%. Linear regression analysis revealed that greater LV mass was independently associated with male sex, greater body mass index (BMI), and higher 24-hour systolic blood pressure (24-hour SBP). Concentric remodeling was independently associated with age, male sex, higher 24-hour SBP, and greater hemoglobin levels. Surprisingly, neither hydration status, nor endothelial function, nor any of the inflammatory or MBD parameters added significantly to these models. Conclusion Abnormal LV structure was found in almost one-half of the patients. Reducing BMI and 24-hour SBP and avoiding high hemoglobin concentrations appear to be the key factors to prevent abnormal LV remodeling in patients with mild-to-moderate CKD.