ResearchPad - stenosis https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Pulmonary ductal coarctation and left pulmonary artery interruption; pathology and role of neural crest and second heart field during development]]> https://www.researchpad.co/article/elastic_article_14709 In congenital heart malformations with pulmonary stenosis to atresia an abnormal lateral ductus arteriosus to left pulmonary artery connection can lead to a localised narrowing (pulmonary ductal coarctation) or even interruption We investigated embryonic remodelling and pathogenesis of this area.Material and methodsNormal development was studied in WntCre reporter mice (E10.0–12.5) for neural crest cells and Nkx2.5 immunostaining for second heart field cells. Data were compared to stage matched human embryos and a VEGF120/120 mutant mouse strain developing pulmonary atresia.ResultsNormal mouse and human embryos showed that the mid-pharyngeal endothelial plexus, connected side-ways to the 6th pharyngeal arch artery. The ventral segment formed the proximal pulmonary artery. The dorsal segment (future DA) was solely surrounded by neural crest cells. The ventral segment had a dual outer lining with neural crest and second heart field cells, while the distal pulmonary artery was covered by none of these cells. The asymmetric contribution of second heart field to the future pulmonary trunk on the left side of the aortic sac (so-called pulmonary push) was evident. The ventral segment became incorporated into the pulmonary trunk leading to a separate connection of the left and right pulmonary arteries. The VEGF120/120 embryos showed a stunted pulmonary push and a variety of vascular anomalies.SummarySide-way connection of the DA to the left pulmonary artery is a congenital anomaly. The primary problem is a stunted development of the pulmonary push leading to pulmonary stenosis/atresia and a subsequent lack of proper incorporation of the ventral segment into the aortic sac. Clinically, the aberrant smooth muscle tissue of the ductus arteriosus should be addressed to prohibit development of severe pulmonary ductal coarctation or even interruption of the left pulmonary artery. ]]> <![CDATA[Retrospectively ECG-gated helical vs. non-ECG-synchronized high-pitch CTA of the aortic root for TAVI planning]]> https://www.researchpad.co/article/elastic_article_13825 Multidetector computed tomography (MDCT) plays a key role in patient assessment prior to transcatheter aortic valve implantation (TAVI). However, to date no consensus has been established on what is the optimal pre-procedural imaging protocol. Variability in pre-TAVI acquisition protocols may lead to discrepancies in aortic annulus measurements and may potentially influence prosthesis size selection.PurposeThe current study evaluates the magnitude of differences in aortic annulus measurements using max-systolic, end-diastolic, and non-ECG-synchronized imaging, as well as the impact of method on prosthesis size selection.Material and methodsFifty consecutive TAVI-candidates, who underwent retrospectively-ECG-gated CT angiography (CTA) of the aortic root, directly followed by non-ECG-synchronized high-pitch CT of the entire aorta, were retrospectively included. Aortic root dimensions were assessed at each 10% increment of the R-R interval (0–100%) and on the non-ECG-synchronized scan. Dimensional changes within the cardiac cycle were evaluated using a 1-way repeated ANOVA. Agreement in measurements between max-systole, end-diastole and non-ECG-synchronized scans was assessed with Bland-Altman analysis.ResultsMaximal dimensions of the aortic root structures and minimum annulus-coronary ostia distances were measured during systole. Max-systolic measurements were significantly and substantially larger than end-diastolic (p<0.001) and non-ECG-synchronized measurements (p<0.001). Due to these discrepancies, the three methods resulted in the same prosthesis size selection in only 48–62% of patients.ConclusionsThe systematic differences between max-systolic, end-diastolic and non-ECG-synchronized measurements for relevant aortic annular dimensions are both statistically significant and clinically relevant. Imaging strategy impacts prosthesis size selection in nearly half the TAVI-candidates. End-diastolic and non-ECG-synchronized imaging does not provide optimal information for prosthesis size selection. Systolic image acquisition is necessary for assessment of maximal annular dimensions and minimum annulus-coronary ostia distances. ]]> <![CDATA[High-resolution contrast-enhanced vessel wall imaging in patients with suspected cerebral vasculitis: Prospective comparison of whole-brain 3D T1 SPACE versus 2D T1 black blood MRI at 3 Tesla]]> https://www.researchpad.co/article/5c8c1948d5eed0c484b4d33a

Purpose

Vessel wall imaging (VWI) using T1 dark blood MRI can depict inflammation of intracranial arteries in patients with cerebral vasculitis. Recently, 3D VWI sequences were introduced at 3 Tesla. We aimed to compare 2D and 3D VWI for detection of intracranial vessel wall enhancement (VWE) in patients suspected of cerebral vasculitis.

Methods

44 MRI scans of 39 patients were assessed that included bi-planar 2D T1 and whole-brain 3D T1 SPACE dark blood VWI pre and post contrast. Visibility and VWE were analyzed in 31 pre-specified intracranial artery segments. Additionally, leptomeningeal and parenchymal contrast enhancement was assessed.

Results

Overall, more arterial segments were visualized with 3D VWI (p<0.0001). Detection of VWE showed fair agreement between 2D and 3D VWI (κ = 0.583). On segmental level, more VWE was detected in intradural ICA by 2D VWI (p<0.001) and in VA V4 segment by 3D VWI (p<0.05). 3D VWI showed more leptomeningeal (p<0.05) and parenchymal (p<0.01) contrast enhancement. In patients with positive diagnosis of cerebral vasculitis, sensitivity was of 67% (2D and 3D VWI) and specificity was 44% (2D VWI) and 48% (3D VWI); more VWE was seen in arteries distal to VA and ICA compared to non-vasculitic patients.

Conclusion

2D and 3D VWI differed in the ability to detect VWE. Whole brain coverage with better evaluability of VAs and distal intracranial artery segments, and depiction of more parenchymal and leptomeningeal enhancement make 3D VWI more favorable. As VWE in arteries distal to VA and ICA may be used for discrimination of vasculitic and non-vasculitic patients, future increase in spatial resolution of 3D VWI sequences may be beneficial.

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<![CDATA[Patency rates of arteriovenous fistulas created before versus after hemodialysis initiation]]> https://www.researchpad.co/article/5c58d614d5eed0c484031566

In an incident hemodialysis (HD) population, we aimed to investigate whether arteriovenous fistula (AVF) creation before HD initiation was associated with improved AVF patency compared with AVF creation from a central venous catheter (CVC), and also to compare patient survival between these patients. Between January 2011 and December 2013, 524 incident HD patients with identified first predialysis vascular access with an AVF (pre-HD group, n = 191) or an AVF from a CVC (on-HD group, n = 333) were included and analyzed retrospectively. The study outcome was defined as AVF patency and all-cause mortality (time to death). On Kaplan–Meier survival analysis, primary and secondary AVF patency rates did not differ significantly between the two groups (P = 0.812 and P = 0.586, respectively), although the overall survival rate was significantly higher in the pre-HD group compared with the on-HD group (P = 0.013). On multivariate analysis, well-known patient factors were associated with decreased primary (older age and diabetes mellitus [DM]) and secondary (DM and peripheral arterial occlusive disease) AVF patency, whereas use of a CVC as the initial predialysis access (hazard ratios, 1.84; 95% confidence intervals, 1.20–2.75; P = 0.005) was significantly associated with worse survival in addition to well-known patient factors (older age, diabetes mellitus, and peripheral arterial occlusive disease). Worse survival in the on-HD group was likely confounded by selection bias because of the retrospective nature of our study. Therefore, the observed lower mortality associated with AVF creation before HD initiation is not fully attributable to CVC use, but rather, affected by other patient-level prognostic factors. There were no CVC-related complications in the pre-HD group, whereas 10.2% of CVC-related complications were noted in the on-HD group. In conclusion, among incident HD patients, compared with patients who underwent creation of an AVF from a CVC, initial AVF creation showed similar primary and secondary AVF patency rates, but lower mortality risk. We also observed that an initial CVC use was an independent risk factor associated with worse survival. A fistula-first strategy might be the best option for incident HD patients who are good candidates for AVF creation.

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<![CDATA[Variations in pulsatile flow around stenosed microchannel depending on viscosity]]> https://www.researchpad.co/article/5c5369aed5eed0c484a463f8

In studying blood flow in the vessels, the characteristics of non-Newtonian fluid are important, considering the role of viscosity in rheology. Stenosis, which is an abnormal narrowing of the vessel, has an influence on flow behavior. Therefore, analysis of blood flow in stenosed vessels is essential. However, most of them exist as simulation outcomes. In this study, non-Newtonian fluid was observed in stenosed microchannels under the pulsatile flow condition. A polydimethylsiloxane channel with 60% stenosis was fabricated by combining an optic fiber and a petri dish, resembling a mold. Three types of samples were prepared by changing the concentrations of xanthan gum, which induces a shear thinning effect (phosphate buffered saline (PBS) solution as the Newtonian fluid and two non-Newtonian fluids mimicking normal blood and highly viscous blood analog). The viscosity of the samples was measured using a Y-shaped microfluidic viscometer. Thereafter, velocity profiles were analyzed under the pulsatile flow condition using the micro-particle image velocimetry (PIV) method. For the Newtonian fluid, the streamline was skewed more to the wall of the channel. The velocity profile of the non-Newtonian fluid was generally blunter than that of the Newtonian fluid. A highly oscillating wall shear stress (WSS) during the pulsatile phase may be attributed to such a bluntness of flow under the same wall shear rate condition with the Newtonian fluid. In addition, a highly viscous flow contributes to the variation in the WSS after passing through the stenosed structures. A similar tendency was observed in simulation results. Such a variation in the WSS was associated with plaque instability or rupture and damage of the tissue layer. These results, related to the influence on the damage to the endothelium or stenotic lesion, may help clinicians understand relevant mechanisms.

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<![CDATA[Evidence of association of circulating epigenetic-sensitive biomarkers with suspected coronary heart disease evaluated by Cardiac Computed Tomography]]> https://www.researchpad.co/article/5c521864d5eed0c484797f48

Circulating biomarkers available in clinical practice do not allow to stratify patients with coronary heart disease (CHD) prior the onset of a clinically relevant event. We evaluated the methylation status of specific genomic segments and gene expression in peripheral blood of patients undergoing Cardiac Computed Tomography (CCT) for CHD (n = 95).

We choose to investigate cholesterol metabolism. Methylation and gene expression of low density lipoprotein receptor (LDLR), sterol regulatory element-binding factor 2 (SREBF2) and ATP-binding cassette transporter 1 (ABCA1) were evaluated by qRT-PCR. Calcium score (CACS), stenosis degree, total plaque volume (TPV), calcified plaque volume (CPV), non-calcified plaque volume (NCPV) and plaque burden (PB) were assessed in all CHD patients (n = 65). The percentage of methylation at the specific analyzed segment of LDLR promoter was higher in CHD patients vs healthy subjects (HS) (n = 30) (p = 0.001). LDLR, SREBF2 and ABCA1 mRNAs were up-regulated in CHD patients vs HS (p = 0.02; p = 0.019; p = 0.008). SREBF2 was overexpressed in patients with coronary stenosis ≥50% vs subjects with stenosis <50% (p = 0.036). After adjustment for risk factors and clinical features, ABCA1 (p = 0.005) and SREBF2 (p = 0.010) gene expression were identified as independent predictors of CHD and severity. ROC curve analysis revealed a good performance of ABCA1 on predicting CHD (AUC = 0.768; p<0.001) and of SREBF2 for the prediction of disease severity (AUC = 0.815; p<0.001). Moreover, adjusted multivariate analysis demonstrated SREBF2 as independent predictor of CPV, NCPV and TPV (p = 0.022; p = 0.002 and p = 0.006) and ABCA1 as independent predictor of NCPV and TPV (p = 0.002 and p = 0.013).

CHD presence and characteristics are related to selected circulating transcriptional and epigenetic-sensitive biomarkers linked to cholesterol pathway. More extensive analysis of CHD phenotypes and circulating biomarkers might improve and personalize cardiovascular risk stratification in the clinical settings.

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<![CDATA[Does retinopathy predict stroke recurrence in type 2 diabetes patients: A retrospective study?]]> https://www.researchpad.co/article/5c605a3ad5eed0c4847ccc0b

Aims

To study if retinopathy increases the risk of stroke recurrence in stroke patients with type 2 diabetes. Also, to study if stroke patients with type 2 diabetes have an increased risk of stroke recurrence compared to non-diabetics and if stroke patients with type 2 diabetes, regardless of retinopathy, have a higher incidence of carotid stenosis. Also, to study if stroke patients with type 2 diabetes retinopathy have increased incidence of carotid stenosis.

Methods

We included 445 patients with type 2 diabetes mellitus and a matched control group of 445 patients without diabetes, who had all suffered their first stroke or TIA. Information on retinopathy, risk factors and stroke recurrence were obtained from registers and medical records.

Results

Retinopathy did not increase the risk of stroke recurrence in diabetes patients, HR 0.89 (0.51–1.53), p = 0.67. The risk of stroke recurrence was not increased in diabetics compared to non-diabetes. Diabetes patients had an increased prevalence of carotid stenosis compared to non-diabetics, 1.69 (1.15–2.48), p = 0.008. The prevalence of carotid stenosis in diabetics with retinopathy was not increased compared to diabetics without retinopathy.

Conclusion

Retinopathy is not a predictor of stroke recurrence or carotid stenosis in type 2 diabetes patients.

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<![CDATA[Relationship between FFR, CFR and coronary microvascular resistance – Practical implications for FFR-guided percutaneous coronary intervention]]> https://www.researchpad.co/article/5c3d017ad5eed0c48403bbb1

Objective

The aim was threefold: 1) expound the independent physiological parameters that drive FFR, 2) elucidate contradictory conclusions between fractional flow reserve (FFR) and coronary flow reserve (CFR), and 3) highlight the need of both FFR and CFR in clinical decision making. Simple explicit theoretical models were supported by coronary data analyzed retrospectively.

Methodology

FFR was expressed as a function of pressure loss coefficient, aortic pressure and hyperemic coronary microvascular resistance. The FFR-CFR relationship was also demonstrated mathematically and was shown to be exclusively dependent upon the coronary microvascular resistances. The equations were validated in a first series of 199 lesions whose pressures and distal velocities were monitored. A second dataset of 75 lesions with pre- and post-PCI measures of FFR and CFR was also analyzed to investigate the clinical impact of our hemodynamic reasoning.

Results

Hyperemic coronary microvascular resistance and pressure loss coefficient had comparable impacts (45% and 49%) on FFR. There was a good concordance (y = 0.96 x − 0.02, r2 = 0.97) between measured CFR and CFR predicted by FFR and coronary resistances. In patients with CFR < 2 and CFR/FFR ≥ 2, post-PCI CFR was significantly >2 (p < 0.001), whereas it was not (p = 0.94) in patients with CFR < 2 and CFR/FFR < 2.

Conclusion

The FFR behavior and FFR-CFR relationship are predictable from basic hemodynamics. Conflicting conclusions between FFR and CFR are explained from coronary vascular resistances. As confirmed by our results, FFR and CFR are complementary; they could jointly contribute to better PCI guidance through the CFR-to-FFR ratio in patients with coronary artery disease.

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<![CDATA[Prediction of functional outcome using the novel asymmetric middle cerebral artery index in cryptogenic stroke patients]]> https://www.researchpad.co/article/5c3667ded5eed0c4841a672d

Background

Etiology is unknown in approximately one-quarter of stroke patients after evaluation, which is termed cryptogenic stroke (CS). The prognosis of CS patients is largely undetermined. We created a novel index from transcranial Doppler parameters including mean flow velocity (MV) and pulsatility index (PI) and investigated whether the calculation of asymmetry in the novel parameter can predict functional outcomes in CS patients.

Methods

We made the middle cerebral artery (MCA) index (%) as a novel parameter, which was calculated as 100 X (MCA MV + MCA PI X 10) / (MCA MV–MCA PI X 10). The MCA asymmetry index (%) was also calculated as 100 X (|Rt MCA index–Lt MCA index|) / (Rt MCA index + Lt MCA index) / 2. Poor functional outcomes were defined as modified Rankin Scale score (mRS) ≥3 at 3 months after stroke onset.

Results

A total of 377 CS patients were included. Among them, 52 (13.8%) patients had a poor outcome. The overall MCA asymmetry index was two-fold higher in CS patients with a poor outcome (10.26%) compared to those with a good outcome (5.41%, p = 0.002). In multivariable analysis, the overall MCA asymmetry index (OR, 1.054, 95% CI, 1.013–1.096, p = 0.009) and the cutoff value of the overall MCA asymmetry index >9 were associated with poor outcomes at 3 months (OR, 3.737, 95% CI, 1.530–9.128, p = 0.004).

Conclusion

We demonstrated that the novel asymmetric MCA index can predict short-term functional outcomes in CS patients.

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<![CDATA[Reproducibility of quantitative coronary computed tomography angiography in asymptomatic individuals and patients with acute chest pain]]> https://www.researchpad.co/article/5c1d5b59d5eed0c4846eb6cb

Purpose

Quantitative computed tomography (QCT) provides important prognostic information of coronary atherosclerosis. We investigated intraobserver and interobserver QCT reproducibility in asymptomatic individuals, patients with acute chest pain without acute coronary syndrome (ACS), and patients with acute chest pain and ACS.

Methods

Fifty patients from each cohort, scanned between 01/02/2010-14/11/2013 and matched according to age and gender, were retrospectively assessed for inclusion. Patients with no coronary artery disease, previous coronary artery bypass graft surgery, and poor image quality were excluded. Coronary atherosclerosis was measured semi-automatically by 2 readers. Reproducibility of minimal lumen area (MLA), minimal lumen diameter (MLD), area stenosis, diameter stenosis, vessel remodeling, plaque eccentricity, plaque burden, and plaque volumes was assessed using concordance correlation coefficient (CCC), Bland-Altman, coefficient of variation, and Cohen’s kappa.

Results

A total of 84 patients (63 matched) were included. Intraobserver and interobserver reproducibility estimates were acceptable for MLA (CCC = 0.94 and CCC = 0.91, respectively), MLD (CCC = 0.92 and CCC = 0.86, respectively), plaque burden (CCC = 0.86 and CCC = 0.80, respectively), and plaque volume (CCC = 0.97 and CCC = 0.95, respectively). QCT detected area and diameter stenosis ≥50%, positive remodeling, and eccentric plaque with moderate-good intraobserver and interobserver reproducibility (kappa: 0.64–0.66, 0.69–0.76, 0.46–0.48, and 0.41–0.62, respectively). Reproducibility of plaque composition decreased with decreasing plaque density (intraobserver and interobserver CCC for dense calcium (>0.99; 0.98), fibrotic (0.96; 0.93), fibro-fatty (0.95; 0.91), and necrotic core tissue (0.89; 0.84). Reproducibility generally decreased with worsening clinical risk profile.

Conclusions

Semi-automated QCT of coronary plaque morphology is reproducible, albeit with some decline in reproducibility with worsening patient risk profile.

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<![CDATA[Anatomic measurements of cerebral venous sinuses in idiopathic intracranial hypertension patients]]> https://www.researchpad.co/article/5b28b404463d7e129299938f

Purpose

Magnetic resonance venography (MRV) has not been validated in pre-operative planning of the dural venous sinus stenting (VSS) among idiopathic intracranial hypertension (IIH) patients. We aim to prospectively evaluate dural venous sinus measurement in IIH patient population on two-dimensional time-of-flight (2D-TOF) MRV and Three-dimensional contrast-enhanced (3D-CE) MRV acquisitions and compare them against real-time endoluminal measurements with intravascular ultrasound (IVUS), served as the reference.

Materials and methods

The study has been approved by the Weill Cornell Medicine institutional review board. All patients signed written informed consent approved by IRB. Prospective evaluation of forty-five consecutive IIH patients treated with VSS at our institution were evaluated. Patients with pre-stent magnetic resonance venography (MRV) ≤ 6-months of VSS and intravascular ultrasound (IVUS) during VSS constituted the study population. Maximum diameter (in mm), Area (in cm2) and Perimeter (in cm) were measured at posterior 1/3rd of superior sagittal sinus (SSS), proximal transverse sinus (PTS), proximal sigmoid sinus (PSS) and mid sigmoid sinus (MSS) on 2D-TOF-MRV, 3D-CE-MRV and IVUS. Statistical analysis performed using box and whisker plots, Bland-Altman analysis and paired sample t-test.

Results

Twenty (n = 20) patients constituted our study population. The mean age was 30±11 years (7–59 years) and 18 out of 20 were female patients. Mean weight and BMI (range) were 86.3±18.3 kilograms (30.8–107.5 kgs) and 32.9±6.8 kg/M2 (16.4–48.3kg/M2) respectively. The CE-MRV significantly oversized the cerebral venous sinuses compared to TOF-MRV (Dmax: +2.0±1.35 mm, p<0.001; Area: +13.31±10.92 mm2, p<0.001 and Perimeter: +4.79±3.4 mm, p<0.001) and IVUS (Dmax: +1.52±2.16 mm, p<0.001; Area: +10.03±21.5 mm2, p<0.001 and Perimeter: +4.15±3.27 mm, p<0.001). The TOF-MRV sinus measurements were in good agreement with the IVUS measurements with no significant variation (Dmax: +.21±2.23 mm, p = 0.49; Area: +2.51±20.41mm2, p = 0.347 and Perimeter: +.001±1.11 mm, p = 0.991).

Conclusion

We report baseline cerebral venous sinus measurements (maximum diameter, area and perimeter) in patients with idiopathic intracranial hypertension. In our experience, TOF-MRV is a reliable representation of endoluminal cerebral venous sinus dimensions, and CE-MRV measurements reflected an overestimation of the endoluminal sinus dimensions when compared against the real time IVUS measurements.

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<![CDATA[Diagnosing Discogenic Low Back Pain Associated with Degenerative Disc Disease Using a Medical Interview]]> https://www.researchpad.co/article/5989db1dab0ee8fa60bce923

Purposes

To evaluate the usefulness of our original five questions in a medical interview for diagnosing discogenic low back pain (LBP), and to establish a support tool for diagnosing discogenic LBP.

Materials and Methods

The degenerative disc disease (DDD) group (n = 42) comprised patients diagnosed with discogenic LBP associated with DDD, on the basis of magnetic resonance imaging findings and response to analgesic discography (discoblock). The control group (n = 30) comprised patients with LBP due to a reason other than DDD. We selected patients from those who had been diagnosed with lumbar spinal stenosis and had undergone decompression surgery without fusion. Of them, those whose postoperative LBP was significantly decreased were included in the control group. We asked patients in both groups whether they experienced LBP after sitting too long, while standing after sitting too long, squirming in a chair after sitting too long, while washing one’s face, and in the standing position with flexion. We analyzed the usefulness of our five questions for diagnosing discogenic LBP, and performed receiver operating characteristic (ROC) curve analysis to develop a diagnostic support tool.

Results

There were no significant differences in baseline characteristics, except age, between the groups. There were significant differences between the groups for all five questions. In the age-adjusted analyses, the odds ratios of LBP after sitting too long, while standing after sitting too long, squirming in a chair after sitting too long, while washing one’s face, and in standing position with flexion were 10.5, 8.5, 4.0, 10.8, and 11.8, respectively. The integer scores were 11, 9, 4, 11, and 12, respectively, and the sum of the points of the five scores ranged from 0 to 47. Results of the ROC analysis were as follows: cut-off value, 31 points; area under the curve, 0.92302; sensitivity, 100%; and specificity, 71.4%.

Conclusions

All five questions were useful for diagnosing discogenic LBP. We established the scoring system as a support tool for diagnosing discogenic LBP.

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<![CDATA[Troponin I Assay for Identification of a Significant Coronary Stenosis in Patients with Suspected Acute Myocardial Infarction and Wide QRS Complex]]> https://www.researchpad.co/article/5989dae2ab0ee8fa60bbc1e9

Background

Common ECG criteria such as ST-segment changes are of limited value in patients with suspected acute myocardial infarction (AMI) and bundle branch block or wide QRS complex. A large proportion of these patients do not suffer from an AMI, whereas those with ST-elevation myocardial infarction (STEMI) equivalent AMI benefit from an aggressive treatment. Aim of the present study was to evaluate the diagnostic information of cardiac troponin I (cTnI) in hemodynamically stable patients with wide QRS complex and suspected AMI.

Methods

In 417 out of 1818 patients presenting consecutively between 01/2007 and 12/2008 in a prospective multicenter observational study with suspected AMI a prolonged QRS duration was observed. Of these, n = 117 showed significant obstructive coronary artery disease (CAD) used as diagnostic outcome variable. cTnI was determined at admission.

Results

Patients with significant CAD had higher cTnI levels compared to individuals without (median 250ng/L vs. 11ng/L; p<0.01). To identify patients needing a coronary intervention, cTnI yielded an area under the receiver operator characteristics curve of 0.849. Optimized cut-offs with respect to a sensitivity driven rule-out and specificity driven rule-in strategy were established (40ng/L/96ng/L). Application of the specificity optimized cut-off value led to a positive predictive value of 71% compared to 59% if using the 99th percentile cut-off. The sensitivity optimized cut-off value was associated with a negative predictive value of 93% compared to 89% provided by application of the 99th percentile threshold.

Conclusion

cTnI determined in hemodynamically stable patients with suspected AMI and wide QRS complex using optimized diagnostic thresholds improves rule-in and rule-out with respect to presence of a significant obstructive CAD.

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<![CDATA[Perivascular radiofrequency renal denervation lowers blood pressure and ameliorates cardiorenal fibrosis in spontaneously hypertensive rats]]> https://www.researchpad.co/article/5989db59ab0ee8fa60bdf159

Background

Catheter-based renal denervation (RDN) is a promising approach to treat hypertension, but innervation patterns limit the response to endovascular RDN and the post-procedural renal artery narrowing or stenosis questions the endovascular ablation strategy. This study was performed to investigate the anti-hypertensive and target organ protective effects of perivascular RDN in spontaneously hypertensive rats (SHR).

Methods

SHR and normotensive Wistar-Kyoto (WKY) rats were divided into sham group (n = 10), radiofrequency ablation group (n = 20) in which rats received bilateral perivascular ablation with radiofrequency energy (2 watts), and chemical (10% phenol in 95% ethanol) ablation group (n = 12). The tail-cuff blood pressure was measured before the ablation and on day 14 and day 28 after the procedure. The plasma levels of creatinine, urea nitrogen, and catecholamines, urinary excretion of electrolytes and protein, and myocardial and glomerular fibrosis were analyzed and compared among the groups on day 28 after the procedure.

Results

We identified that 2-watt is the optimal radiofrequency power for perivascular RDN in rats. Perivascular radiofrequency and chemical ablation achieved roughly comparable blood pressure reduction in SHR but not in WKY on day 14 and day 28 following the procedure. Radiofrequency-mediated ablation substantially destroyed the renal nerves surrounding the renal arteries of both SHR and WKY without damaging the renal arteries and diminished the expression of tyrosine hydroxylase, the enzyme marker for postganglionic sympathetic nerves. Additionally, perivascular radiofrequency ablation also decreased the plasma catecholamines of SHR. Interestingly, both radiofrequency and chemical ablation decreased the myocardial and glomerular fibrosis of SHR, while neither increased the plasma creatinine and blood urea nitrogen nor affected the urinary excretion of electrolytes and protein when compared to sham group.

Conclusions

Radiofrequency-mediated perivascular RDN may become a feasible procedure against hypertension, and provide similar anti-hypertensive and target organ protective effects as does the chemical ablation.

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<![CDATA[Cerebrospinal fluid biomarkers of infantile congenital hydrocephalus]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdcb6a

Introduction

Hydrocephalus is a complex neurological disorder with a pervasive impact on the central nervous system. Previous work has demonstrated derangements in the biochemical profile of cerebrospinal fluid (CSF) in hydrocephalus, particularly in infants and children, in whom neurodevelopment is progressing in parallel with concomitant neurological injury. The objective of this study was to examine the CSF of children with congenital hydrocephalus (CHC) to gain insight into the pathophysiology of hydrocephalus and identify candidate biomarkers of CHC with potential diagnostic and therapeutic value.

Methods

CSF levels of amyloid precursor protein (APP) and derivative isoforms (sAPPα, sAPPβ, Aβ42), tau, phosphorylated tau (pTau), L1CAM, NCAM-1, aquaporin 4 (AQP4), and total protein (TP) were measured by ELISA in 20 children with CHC. Two comparative groups were included: age-matched controls and children with other neurological diseases. Demographic parameters, ventricular frontal-occipital horn ratio, associated brain malformations, genetic alterations, and surgical treatments were recorded. Logistic regression analysis and receiver operating characteristic curves were used to examine the association of each CSF protein with CHC.

Results

CSF levels of APP, sAPPα, sAPPβ, Aβ42, tau, pTau, L1CAM, and NCAM-1 but not AQP4 or TP were increased in untreated CHC. CSF TP and normalized L1CAM levels were associated with FOR in CHC subjects, while normalized CSF tau levels were associated with FOR in control subjects. Predictive ability for CHC was strongest for sAPPα, especially in subjects ≤12 months of age (p<0.0001 and AUC = 0.99), followed by normalized sAPPβ (p = 0.0001, AUC = 0.95), tau, APP, and L1CAM. Among subjects ≤12 months, a normalized CSF sAPPα cut-point of 0.41 provided the best prediction of CHC (odds ratio = 528, sensitivity = 0.94, specificity = 0.97); these infants were 32 times more likely to have CHC.

Conclusions

CSF proteins such as sAPPα and related proteins hold promise as biomarkers of CHC in infants and young children, and provide insight into the pathophysiology of CHC during this critical period in neurodevelopment.

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<![CDATA[Magnetic Particle / Magnetic Resonance Imaging: In-Vitro MPI-Guided Real Time Catheter Tracking and 4D Angioplasty Using a Road Map and Blood Pool Tracer Approach]]> https://www.researchpad.co/article/5989da40ab0ee8fa60b8989b

Purpose

In-vitro evaluation of the feasibility of 4D real time tracking of endovascular devices and stenosis treatment with a magnetic particle imaging (MPI) / magnetic resonance imaging (MRI) road map approach and an MPI-guided approach using a blood pool tracer.

Materials and Methods

A guide wire and angioplasty-catheter were labeled with a thin layer of magnetic lacquer. For real time MPI a custom made software framework was developed. A stenotic vessel phantom filled with saline or superparamagnetic iron oxide nanoparticles (MM4) was equipped with bimodal fiducial markers for co-registration in preclinical 7T MRI and MPI. In-vitro angioplasty was performed inflating the balloon with saline or MM4. MPI data were acquired using a field of view of 37.3×37.3×18.6 mm3 and a frame rate of 46 volumes/sec. Analysis of the magnetic lacquer-marks on the devices were performed with electron microscopy, atomic absorption spectrometry and micro-computed tomography.

Results

Magnetic marks allowed for MPI/MRI guidance of interventional devices. Bimodal fiducial markers enable MPI/MRI image fusion for MRI based roadmapping. MRI roadmapping and the blood pool tracer approach facilitate MPI real time monitoring of in-vitro angioplasty. Successful angioplasty was verified with MPI and MRI. Magnetic marks consist of micrometer sized ferromagnetic plates mainly composed of iron and iron oxide.

Conclusions

4D real time MP imaging, tracking and guiding of endovascular instruments and in-vitro angioplasty is feasible. In addition to an approach that requires a blood pool tracer, MRI based roadmapping might emerge as a promising tool for radiation free 4D MPI-guided interventions.

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<![CDATA[Simplified Models of Non-Invasive Fractional Flow Reserve Based on CT Images]]> https://www.researchpad.co/article/5989da30ab0ee8fa60b840f4

Invasive fractional flow reserve (FFR) is the gold standard to assess the functional coronary stenosis. The non-invasive assessment of diameter stenosis (DS) using coronary computed tomography angiography (CTA) has high false positive rate in contrast to FFR. Combining CTA with computational fluid dynamics (CFD), recent studies have shown promising predictions of FFRCT for superior assessment of lesion severity over CTA alone. The CFD models tend to be computationally expensive, however, and require several hours for completing analysis. Here, we introduce simplified models to predict noninvasive FFR at substantially less computational time. In this retrospective pilot study, 21 patients received coronary CTA. Subsequently a total of 32 vessels underwent invasive FFR measurement. For each vessel, FFR based on steady-state and analytical models (FFRSS and FFRAM, respectively) were calculated non-invasively based on CTA and compared with FFR. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value were 90.6% (87.5%), 80.0% (80.0%), 95.5% (90.9%), 88.9% (80.0%) and 91.3% (90.9%) respectively for FFRSS (and FFRAM) on a per-vessel basis, and were 75.0%, 50.0%, 86.4%, 62.5% and 79.2% respectively for DS. The area under the receiver operating characteristic curve (AUC) was 0.963, 0.954 and 0.741 for FFRSS, FFRAM and DS respectively, on a per-patient level. The results suggest that the CTA-derived FFRSS performed well in contrast to invasive FFR and they had better diagnostic performance than DS from CTA in the identification of functionally significant lesions. In contrast to FFRCT, FFRSS requires much less computational time.

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<![CDATA[Thoracic Malignancies and Pulmonary Nodules in Patients under Evaluation for Transcatheter Aortic Valve Implantation (TAVI): Incidence, Follow Up and Possible Impact on Treatment Decision]]> https://www.researchpad.co/article/5989daf7ab0ee8fa60bc36f5

Background

Transcatheter aortic valve implantation (TAVI) has become the treatment of choice in patients with severe aortic valve stenosis who are not eligible for operative replacement and an alternative for those with high surgical risk. Due to high age and smoking history in a high proportion of TAVI patients, suspicious findings are frequently observed in pre-procedural chest computer tomography (CCT).

Methods

CCT scans of 484 consecutive patients undergoing TAVI were evaluated for incidentally discovered solitary pulmonary nodules (SPN).

Results

In the entire study population, SPN ≥ 5 mm were found in 87 patients (18%). These patients were compared to 150 patients who were incidentally collected from the 397 patients without SPN or with SPN < 5 mm (control group). After a median follow-up of 455 days, lung cancer was diagnosed in only two patients. Neither SPN ≥ 5 mm (p = 0.579) nor SPN > 8 mm (p = 0.328) were significant predictors of overall survival.

Conclusions

Despite the high prevalence of SPNs in this single center TAVI cohort lung cancer incidence at midterm follow-up seems to be low. Thus, aggressive diagnostic approaches for incidentally discovered SPN during TAVI evaluation should not delay the treatment of aortic stenosis. Unless advanced thoracic malignancy is obvious, the well documented reduction of morbidity and mortality by TAVI outweighs potentially harmful delays regarding further diagnostics. Standard guideline-approved procedure for SPN can be safely performed after TAVI.

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<![CDATA[Long Term Outcome after Application of the Angio-Seal Vascular Closure Device in Minipigs]]> https://www.researchpad.co/article/5989da50ab0ee8fa60b8da68

Minipigs are frequently used in (neuro-)interventional research. Longitudinal experiments may require repeated vessel access via the femoral artery. Anticoagulation and incompliance of the animals necessitates the use of a vascular closure device (VCD). The effects of the Angio-Seal VCD in minipigs were longitudinally assessed. Minipig (42±8.4 kg body weight) femoral arteries were sealed using the 8F (n = 6) or 6F (n = 7) Angio-Seal VCD. The pre-interventional femoral artery diameter was 5.1±0.4 mm (4.3–5.8 mm). Sealed puncture sites were analysed angiographically as well as by computed tomography angiography (CTA) for a mean period of 14.1±8.0 weeks (1–22 weeks). All animals were constantly treated with acetylsalicylic acid (ASS) (450 mg/d (n = 7) or 100 mg/d (n = 1)) and clopidogrel (75 mg/d (n = 8)). Non-instrumented (n = 2) and arteries sealed using the VCD (n = 2) were examined histologically. No postoperative hemorrhagic complications were observed. Three arteries were occluded after VCD placement (1 animal diagnosed after 4 weeks (8F), 2 animals after 1 week (6F)) and remained so until the end of the experiments after 22, 12 and 4 weeks, respectively. In one artery a 50% stenosis 8 weeks after application of a 6F Angio-Seal was detected. In 69.2% (n = 9) the VCD was applied without complications. Histopathological analysis of the sealed arterial segments showed subtotal obliteration of the vessel lumen, formation of collagenous tissue and partial damage of the internal elastic lamina. The Angio-Seal VCD prevents relevant hemorrhagic complications in minipigs treated with dual platelet inhibition, but is associated with increased vessel occlusion rates.

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<![CDATA[Increased M1 Macrophages Infiltration Is Associated with Thrombogenesis in Rheumatic Mitral Stenosis Patients with Atrial Fibrillation]]> https://www.researchpad.co/article/5989d9d3ab0ee8fa60b64e63

Atrial fibrillation (AF) is the most common arrhythmia. In patients with AF, the role of macrophage subsets in thrombogenesis is unclear. In the present study, we analyzed the role of M1 and M2 macrophages and related cytokines in thrombogenesis of AF. Immunohistochemistry, Western blot, and TUNEL assay were used to detect M1/M2 macrophage infiltration, the expression pattern of IL-1β and inflammasome components, and apoptosis of cardiomyocytes in 71 specimens obtained from the left atrial appendage of patients with rheumatic mitral stenosis (MS) with or without thrombosis. We demonstrated that proinflammatory M1 macrophages were predominant in the atrium of MS patients with AF and thrombus. NLRP3 inflammasomes and IL-1β, which are primarily functional in macrophages, were activated in those patients. We also showed that increased cell death was associated with thrombogenesis in MS patients. These data indicate that infiltration of M1 macrophages and over-activation of NLRP3 inflammasomes may play a role in progressive atrial inflammation and thrombogenesis in rheumatic mitral stenosis patients with AF.

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