Anatomic and Flow Characteristics of Left Anterior Descending Coronary Artery Angiographic Stenoses Predisposing to Myocardial Infarction.

The impact of the anatomic characteristics of coronary stenoses on the development of future coronary thrombosis has been controversial. This study aimed at identifying the anatomic and flow characteristics of left anterior descending (LAD) coronary artery stenoses that predispose to myocardial infarction, by examining angiograms obtained before the index event. We identified 90 patients with anterior ST-elevation myocardial infarction (STEMI) for whom coronary angiograms and their reconstruction in the three-dimensional space were available at 6 to 12 months before the STEMI, and at the revascularization procedure. The majority of culprit lesions responsible for STEMI occurred between 20 and 40 mm from the LAD ostium, whereas the majority of stable lesions not associated with STEMI were found in distances >60 mm (p < 0.001). Culprit lesions were significantly more stenosed (diameter stenosis 68.6 ± 14.2% vs 44.0 ± 10.4%, p < 0.001), and significantly longer than stable ones (15.3 ± 5.4 mm vs 9.2 ± 2.5 mm, p < 0.001). Bifurcations at culprit lesions were significantly more frequent (88.8%) compared with stable lesions (34.4%, p < 0.001). Computational fluid dynamics simulations demonstrated that hemodynamic conditions in the vicinity of culprit lesions promote coronary thrombosis due to flow recirculation. A multiple logistic regression model with diameter stenosis, lesion length, distance from the LAD ostium, distance from bifurcation, and lesion symmetry, showed excellent accuracy in predicting the development of a culprit lesion (AUC: 0.993 [95% CI: 0.969 to 1.000], p < 0.0001). In conclusion, specific anatomic and hemodynamic characteristics of LAD stenoses identified on coronary angiograms may assist risk stratification of patients by predicting sites of future myocardial infarction.

Prospective Assessment of Biomarkers of Hypercoagulability for the Identification of Patients With Severe Coronary Artery Disease. The ROADMAP-CAD Study.

In patients with stable coronary artery disease (CAD) blood hypercoagulability figures among factors leading to thrombosis. Tissue factor (TF) exposure at ruptured plaque initiates blood coagulation and hypercoagulability is responsible for thrombus formation. Early identification of patients eligible for angiography is a challenging issue for effective prevention of ACS. This pilot study aimed to identify biomarkers of hypercoagulability that can be prospectively used in risk assessment tools for the evaluation of CAD severity. Biomarkers of hypercoagulability could be a used for the evaluation of CAD severity. Platelet-poor plasma from 66 patients who were referred to coronary angiography was assessed for thrombin generation, phospholipid-dependent clotting time (Procoag-PPL ® ) and D-Dimers, and evaluated against atherosclerotic burden. Patients with CAD, as compared to controls, showed attenuated thrombin generation lag time: 4.7 (3.8-5.4) min versus 2.5 (2.1-2.9) min; p < 0.0001, shorter Procoag-PPL® clotting time 55.0(32-66) s versus 62.8 (42-85) s; p = 0.001), and higher D-Dimer levels 0.509 (0.27-2.58) µg/ml versus 0.309 (0.23-0.39) µg/ml; p = 0.038. Multivariate logistic regression model showed excellent discriminatory value in predicting CAD severity. The ROADMAP-CAD study showed that the Procoag-PPL® clotting time and thrombin Peak are informative for the the burden of the coronary atherosclerotic disease. The clinical relevance of this observation in the development of a new clinic-biological risk assessment model for early diagnosis of severe CAD has to be examined in a prospective study.

Radiological Risks From Potential Exposure of the Population to Radiation From Orphan Radioactive Sources.

People in their everyday lives are exposed to radiation. Natural radiation is emitted from space, subsoil, and various materials which contain radioactive materials. Humans are also exposed to radiation from medical and industrial applications that use radioactive sources with artificial radioactive materials. Such radioactive sources may nevertheless get out of the control system and become orphan sources. Because these radiation sources are usually contained within metal shields such as lead and iron, the shields can end up as scrap metal being used in the metallurgical industry as raw material. Incidents have been recorded around the world, and several are reported in the literature and described here, where orphan sources have caused direct radiation exposure and/or environmental and personal contamination when the sources leaked. Timely and prompt recognition of an orphan radioactive source or device is crucial in order to minimize the radiological risk and its implications for the general population.

Spatial relationship of organized rotational and focal sources in human atrial fibrillation to autonomic ganglionated plexi.

BACKGROUND: One approach to improve ablation for atrial fibrillation (AF) is to focus on physiological targets including focal or rotational sources or ganglionic plexi (GP). However, the spatial relationship between these potential mechanisms has never been studied. We tested the hypothesis that rotors and focal sources for AF may co-localize with ganglionated plexi (GP). METHODS: We prospectively identified locations of AF rotors and focal sources, and correlated these to GP sites in 97 consecutive patients (age 59.9±11.4, 73% persistent AF). AF was recorded with 64-pole catheters with activation/phase mapping, and related to anatomic GP sites on electroanatomic maps. RESULTS: AF sources arose in 96/97 (99%) patients for 2.6±1.4 sources per patient (left atrium: 1.7±0.9 right atrium: 1.1±0.8), each with an area of 2-3cm2. On area analyses, the probability of an AF source randomly overlapping a GP area was 26%. Left atrial sources were seen in 94 (97%) patients, in whom ≥1 source co-localized with GP in 75 patients (80%; p<0.05). AF sources were more likely to colocalize with left vs right GPs (p<0.05), and colocalization was more likely in patients with higher CHADS2VASc scores (age>65, diabetes; p<0.05). CONCLUSIONS: This is the first study to demonstrate that clinically detected AF focal and rotational sources in the left atrium often colocalize with regions of autonomic innervation. Studies should define if the role of AF sources differs by their anatomical location.

Derivation of flow related risk indices for stenosed left anterior descending coronary arteries with the use of computer simulations.

The geometry of the coronary vessel network is believed to play a decisive role in the initiation, progression and outcome of coronary artery disease (CAD) and the occurrence of acute coronary syndromes (ACS). It also determines the flow field in the coronary artery which can be linked to CAD evolution. In this work geometric 3D models of left anterior descending (LAD) coronary arteries associated with either myocardial infarction (MI) or stable (STA) CAD were constructed. Transient numerical simulations of the flow for each model showed that specific flow patterns develop in different extent in the different groups examined. Recirculation zones, present distal the stenosis in all models, had larger extent and duration in MI cases. For mild stenosis (up to 50%) areas with low time averaged wall shear stress TAWSS (<0.15Pa) as well as areas with high TAWSS (>3Pa) appeared only in MI models; in moderate and severe stenosis (>50%) these areas were present in all models but were significantly larger for MI than STA models. These differentiations were expressed via numerical indices based on TAWSS, oscillating shear index (OSI) and relative residence time (RRT). Additionally we introduced the coagulation activation index (CAI), based on the threshold behaviour of coagulation initiation, which exceeded the suggested threshold only for MI models with intermediate stenosis (up to 50%). These results show that numerical simulations of flow can produce arithmetic indices linked with the risk of CAD complications.

Aortic Flow Patterns After Simulated Implantation of Transcatheter Aortic Valves.

INTRODUCTION: The functional behavior and hemodynamic characteristics of percutaneously implanted bioprosthetic valves are not known. METHODS: We created aortic models after the simulated implantation of two of the most widely used bioprosthetic valves: the Edwards SAPIEN, and the Medtronic CoreValve. By using computational fluid dynamics analysis we sought to investigate variations in the aortic flow patterns induced by the two valve designs and their association with detrimental phenomena such as vascular remodeling, vascular wall damage and thrombosis. RESULTS: The simulated implantation of models that resemble the two valves resulted in different aortic flow conditions. Vortex formation in the upper ascending aorta was more persistent in the case of the simulated Medtronic valve. The ranges of average wall shear stress (WSS) values were 2.4-3.5 Pa for Edwards and 3.0-5.3 Pa for Medtronic; the calculated WSS values induced endothelial quiescence and an atheroprotective setting in both valves. The average shear stress on the simulated valve leaflets was low; however, hotspots were present in both valves (155.0 Pa for Edwards and 250.0 Pa for Medtronic) which would in theory be able to cause platelet activation and thus promote thrombosis. The pressure drops along the aorta were slightly lower for the Edwards compared to the Medtronic valve (198.0 Pa versus 218.0 Pa). CONCLUSIONS: The presented method allows the assessment of aortic flow conditions following the implantation of bioprosthetic valves. It may be useful in predicting detrimental flow phenomena, thus facilitating the selection of appropriate valve designs.

Introduction of an effective method for the optimization of CT protocols using iterative reconstruction algorithms: comparison with patient data.

OBJECTIVE: The purpose of this study is to introduce an efficient method for the optimization of iterative reconstruction CT protocols based on phantom image analysis and the comparison of obtained results with actual patient data. MATERIALS AND METHODS: We considered chest, abdomen, and pelvis CT examinations before the installation of an iterative reconstruction algorithm (iDose4) to define the exposure parameters used in clinical routine with filtered back projection (FBP). The body area of a CT phantom was subsequently scanned with various tube voltages and tube currents-exposure time products, and acquired data were reconstructed with FBP and different levels of iDose4. The contrast-to-noise ratio (CNR) for FBP with the original exposure parameters was calculated to define the minimum acceptable CNR value for each tube voltage. Then, an optimum tube current-exposure time products for each tube voltage and level of iterative reconstruction was estimated. We also compared findings derived by the phantom with real patient data by assessing dosimetric and image quality indexes from a patient cohort scanned with exposure parameters gradually adjusted during 1 year of adoption of iDose4. RESULTS: By use of the proposed phantom method, dose reduction up to 75% was achievable, whereas for an intermediate level of iteration (level 4), the dose reduction ranged between 50% and 60%, depending on the tube voltage. For comparison, with the gradual adjustment of exposure settings, the corresponding dose reduction for the same level of iteration was about 35%. CONCLUSION: The proposed method provides rapid and efficient optimization of CT protocols and could be used as the first step in the optimization process.

Effect of iDose4 iterative reconstruction algorithm on image quality and radiation exposure in prospective and retrospective electrocardiographically gated coronary computed tomographic angiography.

OBJECTIVES: The aims of this study were to compare a commercially available reconstruction algorithm (iDose4) with filtered back projection (FBP) in terms of image quality (IQ) for both retrospective electrocardiographically gated and prospective electrocardiographically triggered cardiac computed tomographic angiography (CCTA) protocols and to evaluate the achievable radiation dose reduction. METHODS: A total cohort of 58 patients underwent either prospective CTCA or retrospective CTCA with full or reduced tube current-time product (in milliampere-second) protocol on a 64-slice multidetector computed tomographic scanner. All images were reconstructed with FBP, whereas the reduced milliampere-second images were also reconstructed using 2 levels (levels 4 and 6) of iDose4. Subjective and objective IQ was evaluated. RESULTS: Dose reductions of 43% in the retrospective CCTA protocol and 27% in the prospective CCTA protocol were achieved without compromising IQ. In the prospective CCTA protocol, the reduced-dose images were highly scored; thus, additional reduction of exposure settings is feasible. In the retrospective acquisition, dose reduction has led to similar IQ scores between the reduced-dose iDose4 images and the full-dose FBP images. Considering different reconstructions (FBP, iDose-L4 and -L6) of the same acquisition data, increase in iDose4 level resulted in less noisy images. A slight improvement was also noticed in all IQ indices; however, this improvement was not statistically significant for both acquisition protocols. CONCLUSIONS: This study demonstrated that the application of iDose at CCTA facilitates significant radiation dose reduction by maintaining diagnostic quality. The combination of iDose4 with prospective acquisition is able to significantly reduce effective dose associated with CTCA at values of approximately 2 mSv and even lower.

Radiation dose and image noise evaluation in coronary computed tomography angiography (CCTA) using an iterative reconstruction algorithm.

INTRODUCTION: The purpose of this study was to evaluate radiation dose reduction in coronary computerised tomography angiography (CCTA), using a commercially available iterative reconstruction (IR) algorithm as well as the behaviour of the image noise. METHODS: A total cohort of 47 patients underwent CCTA examination on a 64-slice multi-detector CT. They were divided into four groups according to the time when the examination was performed (before or after the installation of iDose) and the acquisition protocol followed (prospective or retrospective electrocardiography-ECG gated). The images acquired with reduced dose settings were reconstructed using two levels (L4 and L6) of the iDose4 algorithm. Image noise was measured in all cases. RESULTS: In retrospective acquisition, images acquired with a 46% lower radiation dose and reconstructed with iDose4 L6 provided noise comparable to that in the full-dose filtered back-projection images. For the prospective acquisition mode, a slight decrease (26%) in radiation dose resulted in noise improvement in low-dose images reconstructed with iDose4 L4 (16% noise removal) and L6 (30% noise removal). CONCLUSIONS: The fact that image quality is improved while radiation exposure is reduced indicates that there is room for a further reduction in exposure settings. Additionally, the combination of iDose4 with prospective acquisition is able to significantly reduce the radiation dose associated with CCTA at values of about 2 mSv and even lower.

Renal denervation for resistant hypertension: acute results and long-term follow-up.

INTRODUCTION: Renal sympathetic hyperactivity is vital for the maintenance and progression of essential hypertension. Catheter-based renal denervation is an evolving concept with favourable results regarding the control of hypertension; however, clinical experience is still limited. METHODS: We enrolled 15 patients with resistant hypertension who underwent percutaneous, catheter-based radiofrequency treatment for renal artery denervation. Patients were followed up for 4 to 13 months. RESULTS: Baseline mean blood pressure was 169/96 mmHg (SD 9/11), and patients were receiving a mean 3.9 ± 0.8 antihypertensive medications. Blood pressure values were reduced to 136/79 mmHg (SD 10/7), and antihypertensive medications to 2.9 ± 0.8 at 6.9 ± 3.4 months after the procedure. All procedures were uneventful and technically easy. The only drawbacks of the procedure are pain that the patient may feel during energy delivery, and the inability to obtain a sustained impedance reduction that allows completion of radiofrequency current delivery at some sites in the renal artery. CONCLUSIONS: Renal denervation facilitates control of resistant hypertension with reduction of medication, and appears to be a safe and technically easy procedure to accomplish.

Fractional Flow Reserve Derived from Coronary Imaging and Computational Fluid Dynamics.

The assessment of functional severity of atherosclerotic stenoses in patients with coronary artery disease by invasive fractional flow reserve (FFR) measurement requires coronary artery cannulation, advancement of a wire and intravenous adenosine infusion with inherent procedure-related risk and costs. Coronary computed tomographic angiography (CCTA) and rotational coronary angiography (RA) have been recently used in conjunction with computational fluid dynamics (CFD) and image-based modelling for the determination of FFR without the need for additional imaging, modification of acquisition protocols or administration of medication. FFR derived from CCTA was demonstrated as superior to measures of CCTA stenosis severity for determination of lesion-specific ischaemia. Estimation of FFR from RA images and CFD provides a less invasive alternative to conventional FFR measurement while estimated values are in agreement with measured values. These new, combined anatomic-functional assessments have the potential to simplify the noninvasive diagnosis of coronary artery disease with a single study to identify patients with ischaemia-causing stenosis who may benefit from revascularisation.

A new era in computed tomographic dose optimization: the impact of iterative reconstruction on image quality and radiation dose.

The ongoing evolution of computer technology has made the use of iterative reconstruction (IR) algorithms clinically applicable. We reviewed current literature on the clinical use of IR against filtered back projection algorithms in terms of image quality and radiation dose. Iterative reconstruction algorithms provide equal or better image quality compared with filtered back projection, with dose reduction ranging from 25% to 98.6%. However, several studies have reported that the superior results of IR regarding objective evaluation are not always favorably interpreted by radiologists. Further clinical evaluation is needed to certify the optimal tradeoff between imaging quality and radiation dose, and radiologists need to become more familiar with the new appearance of computed tomographic images.

Temporal stability of atrial electrogram fractionation in patients with paroxysmal atrial fibrillation.

The atrial sites associated with fractionated activity and/or high-frequency signals are commonly considered as targets of ablation for atrial fibrillation (AF); however, their temporal stability has not been established. A total of 21 patients with paroxysmal AF were studied. Left atrial (LA) ganglionated plexi (GP) were identified by high-frequency stimulation, and prolonged (3-minute) electrogram sampling from the GP and the posterior wall of the left atrium during AF was acquired. Fast Fourier transformation was used to determine the dominant frequencies (DFs) of the recorded electrogram signals and to study their temporal variability. The DF at the identified GP was 5.34 ± 0.78 Hz and at the posterior LA wall was 5.58 ± 0.87 Hz. Fractionation, expressed as electrograms exhibiting consecutive DFs deferring >20%, was detected at 21 of the studied GP (84%) and 7 of the posterior LA wall sites (44%). Fractionation, expressed as electrograms exhibiting DFs >8 Hz, was detected at 6 GP (24%) and 1 posterior LA wall site (6%). During the 3-minute recordings, the derived DFs were temporally variable, exhibiting an average coefficient of variation of 15.2 ± 12.0%. Fractionation, expressed by significant consecutive DF variability (>20%), was detected only for 18.0 ± 19.0% of the recording period at GP and for 12.7 ± 13.4% at the posterior LA wall. In conclusion, atrial electrograms are temporarily variable, and fractionation is transient at atrial sites associated with fractionated electrical activity during AF. Our results question the clinical validity of fractionated atrial electrograms for ablation purposes.

Flow patterns at stented coronary bifurcations: computational fluid dynamics analysis.

BACKGROUND: The ideal bifurcation stenting technique is not established, and data on the hemodynamic characteristics at stented bifurcations are limited. METHODS AND RESULTS: We used computational fluid dynamics analysis to assess hemodynamic parameters known affect the risk of restenosis and thrombosis at coronary bifurcations after the use of various single- and double-stenting techniques. We assessed the distributions and surface integrals of the time averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (t(r)). Single main branch stenting without side branch balloon angioplasty or stenting provided the most favorable hemodynamic results (integrated values of TAWSS=4.13·10(-4) N, OSI=7.52·10(-6) m(2), t(r)=5.57·10(-4) m(2)/Pa) with bifurcational area subjected to OSI values >0.25, >0.35, and >0.45 calculated as 0.36 mm(2), 0.04 mm(2), and 0 mm(2), respectively. Extended bifurcation areas subjected to these OSI values were seen after T-stenting: 0.61 mm(2), 0.18 mm(2), and 0.02 mm(2), respectively. Among the considered double-stenting techniques, crush stenting (integrated values of TAWSS=1.18·10(-4) N, OSI=7.75·10(-6) m(2), t(r)=6.16·10(-4) m(2)/Pa) gave the most favorable results compared with T-stenting (TAWSS=0.78·10(-4) N, OSI=10.40·10(-6) m(2), t(r)=6.87·10(-4) m(2)/Pa) or the culotte technique (TAWSS=1.30· 10(-4) N, OSI=9.87·10(-6) m(2), t(r)=8.78·10(-4) m(2)/Pa). CONCLUSIONS: In the studied models of computer simulations, stenting of the main branch with our without balloon angioplasty of the side branch offers hemodynamic advantages over double stenting. When double stenting is considered, the crush technique with the use of a thin-strut stent may result in improved immediate hemodynamics compared with culotte or T-stenting.

Surgical ablation for atrial fibrillation.

This paper reviews the history of surgical procedures developed for eradication of atrial fibrillation (AF) during cardiac surgery for structural heart disease, and in patients with AF without other indication for cardiac surgery. Current evidence indicates that, despite their proven efficacy, the Cox-Maze procedure and its modifications require cardiopulmonary bypass and cannot be easily justified in the case of AF without other indication for cardiac surgery. In patients undergoing cardiac surgery for mitral valve disease, concomitant ablation techniques using modifications of the Maze and alternative energy sources appear to be safe and effective in treating AF, especially in non-rheumatic disease. Minimally invasive epicardial ablation has been recently developed and can be performed on a beating heart through small access incision ports. Various techniques combining pulmonary vein isolation, ganglionated plexi ablation, and left atrial lines have been tried. Initial results are promising but further clinical experience is required to establish ideal lesion sets, appropriate energy sources, and the benefit-risk ratio of such an approach in patients without other indication for cardiac surgery. The role of surgical ablation in the current management of AF is under investigation.

Catheter ablation of atrial fibrillation guided by electrogram fractionation and dominant frequency analysis.

Catheter ablation is an established therapeutic option for certain patients with atrial fibrillation (AF), but the reported success rates of anatomically oriented ablation techniques are low compared with those for other ablation indications, particularly for persistent AF. Electrophysiologically oriented ablation techniques have emerged over the last decade that aim at modifying the arrhythmogenic substrate to the extent that it cannot maintain fibrillatory activity. Electrogram-guided ablation procedures are the most common substrate-targeted ablation approaches and can be broadly divided into procedures that target atrial sites with particular electrogram characteristics in either the time domain (complex fractionated electrograms) or frequency components in the frequency domain (dominant frequencies). The concept of electrogram-based catheter ablation of AF by identifying complex fractionated electrograms and dominant frequency sites is valid only if these sites are temporally stable.

Ruptured versus stable plaques in human coronary arteries.

OBJECTIVE: To derive a model for the identification of left anterior descending (LAD) coronary artery stenoses predisposed to plaque rupture and thrombosis. METHODS: Coronary angiograms of 186 consecutive patients (original sample) with an anterior ST elevation myocardial infarction (STEMI) and a recanalized LAD were reconstructed in the three-dimensional space. Culprit lesions were compared with 293 stable LAD coronary stenoses on the same patients. A model for predicting stenoses with a high probability of thrombosis was derived and validated in 50 subsequent patients with STEMI, and 50 patients with stable lesions (validation sample). RESULTS: The majority of culprit lesions occurred between 20 and 40 mm from the LAD ostium, whereas the majority of stable lesions were found in a distance of more than 60 mm (P<0.001). Culprit lesions were statistically significantly longer than stable ones (23.2 ± 10.4 mm vs. 14.7 ± 7.2 mm; P<0.001). Bifurcations on culprit lesions were significantly more frequent (86.6%) compared with stable lesions (41.3%, P<0.001). Lesion angulation was significantly sharper in culprit lesions, which were symmetrical whereas stable lesions resided in the inner vessel wall in respect to the local vessel curvature. A simple additive tool was developed by using these parameters in a multiple regression model. The discriminating ability of the proposed index was high in both the original [area under the receiver operating characteristic curve: 0.88 (95% confidence interval: 0.85-0.91)] and validation sample [area under the receiver operating characteristic curve: 0.69 (95% confidence interval: 0.59-0.78)]. CONCLUSION: Specific anatomic characteristics of LAD segments associated with STEMI can be identified on coronary angiograms and assist the risk stratification of coronary stenoses.