Florian Schwarz

Detection of hemodynamically significant coronary artery stenosis: incremental diagnostic value of dynamic CT-based myocardial perfusion imaging.

PURPOSE To determine the feasibility of computed tomography (CT)-based dynamic myocardial perfusion imaging for the detection of hemodynamically significant coronary artery stenosis, as defined with fractional flow reserve (FFR). MATERIALS AND METHODS Institutional review board approval and informed patient consent were obtained before patient enrollment in the study. The study was HIPAA compliant. Subjects who were suspected of having or were known to have coronary artery disease underwent electrocardiographically triggered dynamic stress myocardial perfusion imaging. FFR measurement was performed within all main coronary arteries with a luminal narrowing of 50%-85%. Estimated myocardial blood flow (MBF) was derived from CT images by using a model-based parametric deconvolution method for 16 myocardial segments and was related to hemodynamically significant coronary artery stenosis with an FFR of 0.75 or less in a blinded fashion. Conventional measures of diagnostic accuracy were derived, and discriminatory power analysis was performed by using logistic regression analysis. RESULTS Of 36 enrolled subjects, 33 (mean age, 68.1 years ± 10 [standard deviation]; 25 [76%] men, eight [24%] women) completed the study protocol. An MBF cut point of 75 mL/100 mL/min provided the highest discriminatory power (C statistic, 0.707; P <.001). While the diagnostic accuracy of CT for the detection of anatomically significant coronary artery stenosis (>50%) was high, it was low for the detection of hemodynamically significant stenosis (positive predictive value [PPV] per coronary segment, 49%; 95% confidence interval [CI]: 36%, 60%). With use of estimated MBF to reclassify lesions depicted with CT angiography, 30 of 70 (43%) coronary lesions were graded as not hemodynamically significant, which significantly increased PPV to 78% (95% CI: 61%, 89%; P = .02). The presence of a coronary artery stenosis with a corresponding MBF less than 75 mL/100 mL/min had a high risk for hemodynamic significance (odds ratio, 86.9; 95% CI:17.6, 430.4). CONCLUSION Dynamic CT-based stress myocardial perfusion imaging may allow detection of hemodynamically significant coronary artery stenosis.

Comparison of Dual-Energy Computed Tomography of the Heart With Single Photon Emission Computed Tomography for Assessment of Coronary Artery Stenosis and of the Myocardial Blood Supply

To evaluate the performance of dual-energy computed tomography (CT) for integrative imaging of the coronary artery morphology and the myocardial blood supply, 36 patients (15 women, mean age 57 +/- 11 years) with equivocal or incongruous single photon emission CT (SPECT) results were investigated by a single-contrast medium-enhanced, retrospectively electrocardiographic-gated dual-energy CT (DECT) scan with simultaneous acquisition of high and low x-ray spectra. Thirteen patients subsequently underwent invasive coronary angiography (ICA). The DECT data were used to reconstruct anatomic coronary CT angiographic images and to map the myocardial iodine distribution within the left ventricular myocardium. Two independent observers analyzed all DECT studies for stenosis and myocardial iodine defects. A segmental comparison was performed between the stress/rest SPECT perfusion defects and DECT iodine defects and between the ICA and coronary CT angiographic findings for stenosis. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were estimated, along with the kappa statistics. Overall, DECT had 92% sensitivity and 93% specificity, with 93% accuracy for detecting any type of myocardial perfusion defect seen on SPECT. Contrast defects at DECT correctly identified 85 (96%) of 89 fixed and 60 (88%) of 68 reversible myocardial perfusion defects. The interobserver agreement was very good (weighted kappa = 0.87). Compared with ICA, coronary CT angiography had 90% sensitivity, 94% specificity, and 93% accuracy for the detection of >50% stenosis. In conclusion, our initial experience suggests that DECT, as a single examination, might be promising for the integrative analysis of the coronary artery morphology and the myocardial blood supply and is in good agreement with ICA and SPECT.

Dual-energy CT of the heart—Principles and protocols

The introduction of coronary CT angiography (cCTA) has reinvigorated the debate whether management of patients with suspected coronary artery disease (CAD) should be primarily based on physiological versus anatomical testing. Anatomical testing (i.e., cCTA or invasive catheterization) enables direct visualization and grading of coronary artery stenoses but has shortcomings for gauging the hemodynamic significance of lesions for myocardial perfusion. Conversely, rest/stress myocardial perfusion imaging (MPI) has been extensively validated for assessing the clinical significance of CAD by demonstrating fixed or reversible perfusion defects but has only limited anatomical information. There is early evidence that contrast medium enhanced dual-energy cCTA (DECT) has potential for the comprehensive analysis of coronary artery morphology as well as changes in myocardial perfusion. DECT exploits the fact that tissues in the human body and iodine-based contrast media have unique absorption characteristics when penetrated with different X-ray energy levels, which enables mapping the iodine (and thus blood) distribution within the myocardium. The purpose of this communication is to describe the practical application of this emerging technology for the comprehensive diagnosis of coronary artery disease in the context of the currently used tomographic imaging modalities (cCTA, nuclear MPI, MR MPI).

Prevalence of nonstenosing, complicated atherosclerotic plaques in cryptogenic stroke

OBJECTIVES Our goal was to assess the prevalence of complicated American Heart Association (AHA) lesion type VI plaques in the carotid arteries of patients with cryptogenic stroke. BACKGROUND In up to 40% of ischemic stroke patients, no definite cause can be established despite extensive workup (i.e., cryptogenic stroke). To test the hypothesis if nonstenosing complicated carotid plaques may be the underlying etiology in some of these patients, we used high-resolution black-blood carotid magnetic resonance imaging (MRI), which can quantitatively assess plaque composition and morphology with good correlation to histopathology. Specifically, we focused on AHA type VI plaques, which are characterized by hemorrhage, thrombus, or fibrous cap rupture. METHODS Thirty-two consecutive patients (22 male; mean age 71.7 ± 11.9 years) with cryptogenic stroke and nonstenosing (<50%) eccentric carotid plaques were recruited from a single stroke unit. All patients underwent extensive clinical workup (brain MRI, duplex sonography, electrocardiography and Holter monitoring, transthoracic and transesophageal echocardiography, and laboratory investigations) to exclude other causes of stroke. All patients received a black-blood carotid MRI at 3-T with fat-saturated pre- and post-contrast T-1-, proton density-, and T-2-weighted and time-of-flight images using surface coils and parallel imaging techniques. Prevalence of AHA type VI plaque was determined in both carotid arteries on the basis of previously published MRI criteria. RESULTS AHA type VI plaques were found in 12 of 32 arteries (37.5%) ipsilateral to the stroke, whereas there were no AHA type VI plaques contralateral to the stroke (p = 0.001). The most common diagnostic feature of AHA type VI plaques was intraplaque hemorrhage (75%), followed by fibrous plaque rupture (50%) and luminal thrombus (33%). CONCLUSIONS This pilot study suggests that arterio-arterial embolism from complicated, nonstenosing carotid atherosclerotic plaques may play a role in a subgroup of patients previously diagnosed with cryptogenic stroke. To further evaluate the significance of AHA type VI plaques in cryptogenic stroke, future studies will have to analyze both clinical and imaging follow-up data, including event rates for secondary strokes.

Three-dimensional printing of models for preoperative planning and simulation of transcatheter valve replacement.

In this study, we show the use of three-dimensional printing models for preoperative planning of transcatheter valve replacement in a patient with an extreme porcelain aorta. A 70-year-old man with severe aortic stenosis and a porcelain aorta was referred to our center for transcatheter aortic valve replacement. Unfortunately, the patient died after the procedure because of a potential ischemic event. Therefore, we decided to fabricate three-dimensional models to evaluate the potential effects of these constructs for previous surgical planning and simulation of the transcatheter valve replacement.

CT stress perfusion imaging for detection of haemodynamically relevant coronary stenosis as defined by FFR

Objectives To evaluate the diagnostic accuracy (DA) of CT-myocardial perfusion imaging (CT-MPI) and a combined approach with CT angiography (CTA) for the detection of haemodynamically relevant coronary stenoses in patients with both suspected and known coronary artery disease. Design Prospective, non-randomised, diagnostic study. Setting Academic hospital-based study. Patients 65 patients (42 men age 70.4±9) with typical or atypical chest pain. Interventions CTA and CT-MPI with adenosine stress using a fast dual-source CT system. At subsequent invasive angiography, FFR measurement was performed in coronary arteries to define haemodynamic relevance of stenosis. Main outcome measures We tried to correlate haemodynamically relevant stenosis (FFR < 0.80) to a reduced myocardial blood flow (MBF) as assessed by CT-MPI and determined the DA of CT-MPI for the detection of haemodynamically relevant stenosis. Results Sensitivity and negative predictive value (NPV) of CTA alone were very high (100% respectively) for ruling out haemodynamically significant stenoses, specificity, Positive predictive value (PPV) and DA were low (43.8, 67.3 and 72%, respectively). CT-MPI showed a significant increase in specificity, PPV and DA for the detection of haemodynamically relevant stenoses (65.6, 74.4 and 81.5%, respectively) with persisting high sensitivity and NPV for ruling out haemodynamically relevant stenoses (97% and 95.5% respectively). The combination of CTA and CT-MPI showed no further increase in detection of haemodynamically significant stenosis compared with CT-MPI alone. Conclusions Our data suggest that CT-MPI permits the detection of haemodynamically relevant coronary artery stenoses with a moderate DA. CT may, therefore, allow the simultaneous assessment of both coronary morphology and function.

Accuracy of dynamic computed tomography adenosine stress myocardial perfusion imaging in estimating myocardial blood flow at various degrees of coronary artery stenosis using a porcine animal model.

Objective:To determine the accuracy of computed tomography (CT) dynamic stress myocardial perfusion imaging to estimate myocardial blood flow (MBF) in a porcine animal model with variable degrees of induced coronary artery stenosis in comparison with microsphere-derived MBF. Methods and Materials:Seven domestic pigs (36 ± 4 kg) received stents (confirmed 3.0 mm diameter) in the left anterior descending coronary artery distal to first diagonal branch. A balloon catheter was placed within the stent and inflated to various degrees to obtain a defined luminal narrowing (50% and 75% diameter stenosis) as confirmed by intra-arterial flow wire measurement. All models underwent adenosine-mediated (140 &mgr;g/kg/min) dynamic stress and rest myocardial perfusion CT imaging using a dual-source CT scanner (shuttle-mode with 100 kV/300 mAs, 20 mL iopromide) with prospective acquisitions every second heartbeat for 30 seconds. CT-estimated MBF (MBFCT) was calculated using a model-based parametric deconvolution method and correlated to that of fluorescent microspheres (MBFmic) injected at each perfusion state. Results:All study procedures were performed without complications, and all animals completed the study protocol. Among 448 myocardial segments, 31 (7%) were considered nonevaluable because of motion artifacts. With stress, MBFCT increased significantly (1.10 ± 0.25 vs. 0.80 ± 0.28 mL/g/min, P < 0.001; at stress and rest, respectively) in all myocardial segments and correlated with MBFmic (r = 0.67, P < 0.001). MBFCT overestimated MBFmic, independently of adenosine-stress and degree of coronary stenosis (&bgr; = 2.3, 95% confidence interval: 1.81–2.79 mL/g/min, P < 0.001). Although there were no differences in MBFCT between 50% and 75% coronary stenosis at rest (0.01 ± 0.08 mL/g/min, P = 0.86), MBFCT was significantly lower at 75% than at 50% under stress conditions (0.53 ± 0.19 vs. 0.71 ± 0.24 mL/g/min, P = 0.002). Conclusions:CT-derived MBF measurements at rest and stress with varying degrees of coronary stenosis show a valid difference but an underestimated correlation with microsphere-derived MBF in a porcine animal model.

Induction of MesP1 by Brachyury(T) generates the common multipotent cardiovascular stem cell.

AIMS Our recent work demonstrated that common cardiovascular progenitor cells are characterized and induced by the expression of the transcription factor mesoderm posterior1 (MesP1) in vertebrate embryos and murine embryonic stem cells. As the proliferative potential of stem cell-derived cardiomyocytes is limited, it is crucial to understand how MesP1 expression is mediated in order to achieve reasonable and reliable yields for novel stem cell-based therapeutic options. As potential upstream regulators of MesP1, we therefore analysed Eomes and Brachyury(T), which had been controversially discussed as being crucial for cardiovasculogenic lineage formation. METHODS AND RESULTS Wild-type and transgenic murine embryonic stem cell lines, mRNA analyses, embryoid body formation, and cell sorting revealed that the MesP1 positive population emerges from the Brachyury(T) positive fraction. In situ hybridizations using wild-type mouse embryos confirmed that Brachyury(T) colocalises with MesP1 in vivo. Likewise, shRNA-based loss of Brachyury(T) causes a dramatic decrease in MesP1 expression accompanied by reduced cardiac markers in differentiating embryonic stem cells, which is reflected in vivo via in situ hybridizations using Brachyury(T) knock-out embryos where MesP1 mRNA is greatly abolished. We finally defined a 3.4 kb proximal MesP1-promoter fragment which is directly bound and activated by Brachyury(T) via a T responsive element as shown via bandshift, chromatin immuneprecipitation, and reporter assays. CONCLUSION Our work contributes to the understanding of the earliest cardiovasculogenic events and may become an important prerequisite for cell therapy, tissue engineering, and pharmacological testing in the culture dish using pluripotent stem cell-derived as well as directly reprogrammed cardiovascular cell types.

Transcutaneous aortic valve replacement with the Edwards SAPIEN XT and Medtronic CoreValve prosthesis under fluoroscopic guidance and local anaesthesia only

Objective To assess the feasibility of transcatheter aortic valve implantation (TAVI; Medtronic CoreValve and Edwards SAPIEN XT) under local anaesthesia with only mild analgesic medication and fluoroscopic guidance. Methods 461 patients underwent TAVI under local anaesthesia with lidocaine. The procedure was performed successfully in 459 of the cases. All patients were also treated with piritramide, metoclopramide hydrochloride and 62 mg dimenhydrinate. Monitoring consisted of a six-electrode, virtual 12-lead ECG, pulse oximetry, and invasive arterial pressure measurement. There was no continuous surveillance by an anaesthesiologist. Results There was no need for conversion to general anaesthesia except in four patients who required cardiopulmonary resuscitation. Conscious sedation with intravenous administration of midazolam for agitation or inotropic medication for prolonged hypotension was necessary in only seven of the 461 patients. The combined safety end point according to the Valve Academic Research Consortium consensus document was reached in 12.6%. Conclusions Our results show that TAVI performed under local anaesthesia with only mild analgesic medication and under fluoroscopic guidance is feasible, with good outcome comparable to published data.

Time-resolved CT Angiography for the Detection and Classification of Endoleaks

PURPOSE To assess the feasibility and diagnostic performance of time-resolved computed tomographic (CT) angiography in the detection and classification of endoleaks after endovascular aortic aneurysm repair (EVAR) in high-risk patients. MATERIALS AND METHODS The study was approved by our ethics committee. Written informed consent was obtained from all participating patients. Fifty-four patients (42 male and 12 female patients; mean age, 70.9 years ± 9.3 [standard deviation]) with either thoracic (n = 8) or abdominal (n = 46) aortic aneurysms treated with a stent-graft were prospectively included. The patients were examined with a time-resolved CT angiographic protocol consisting of 12 low-dose phases (80 kVp; 120 mAs [effective]; scan range, 27 cm), with 60 mL of iomeprol. Patients with abdominal aneurysm repair also underwent contrast material-enhanced (CE) ultrasonography (US). The time delay between contrast enhancement within the stent lumen and the endoleak was measured. Effective radiation dose was calculated from the scanner protocols. Measures of diagnostic performance for the detection of endoleaks were calculated for time-resolved CT angiography, with CE US serving as the reference standard. RESULTS All time-resolved CT angiographic data sets were diagnostic. Mean effective radiation dose was 14.6 mSv. Four thoracic and 19 abdominal endoleaks were identified by using time-resolved CT angiography. Seventeen of 19 abdominal endoleaks were confirmed with CE US. This rate resulted in a sensitivity of 94%, a specificity of 93%, a positive predictive value of 89%, and a negative predictive value of 96% for time-resolved CT angiography after abdominal EVAR. Type I endoleaks showed significantly earlier mean peak contrast enhancement (0.28 second ± 0.83) compared with that for type II endoleaks (9.17 seconds ± 3.59, P < .0001). CONCLUSION Time-resolved CT angiography with 12 low-dose phases is feasible for patients after thoracic and abdominal EVAR. The protocol approximates the radiation dose of standard triphasic protocols. Its dynamic information differentiates types of endoleaks and shows high diagnostic performance.