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Objective: Quantitative extracellular volume fraction (ECV) mapping with MRI is commonly used to investigate in vivo diffuse myocardial fibrosis. This study aimed to validate ECV measurements against ex vivo histology of myocardial tissue samples from patients with aortic valve stenosis or hypertrophic cardiomyopathy., Materials and Methods: Sixteen patients underwent MRI examination at 3 T to acquire native T 1 maps and post-contrast T 1 maps after gadobutrol administration, from which hematocrit-corrected ECV maps were estimated. Intra-operatively obtained myocardial tissue samples from the same patients were stained with picrosirius red for quantitative histology of myocardial interstitial fibrosis. Correlations between in vivo ECV and ex vivo myocardial collagen content were evaluated with regression analyses., Results: Septal ECV was 30.3% ± 4.6% and correlated strongly (n = 16, r = 0.70; p = 0.003) with myocardial collagen content. Myocardial native T 1 values (1206 ± 36 ms) did not correlate with septal ECV (r = 0.41; p = 0.111) or with myocardial collagen content (r = 0.32; p = 0.227)., Discussion: We compared myocardial ECV mapping at 3 T against ex vivo histology of myocardial collagen content, adding evidence to the notion that ECV mapping is a surrogate marker for in vivo diffuse myocardial fibrosis., (© 2023. The Author(s).)

Background: Proton magnetic resonance spectroscopy ( 1 H-MRS) of the human heart is deemed to be a quantitative method to investigate myocardial metabolite content, but thorough validations of in vivo measurements against invasive techniques are lacking., Purpose: To determine measurement precision and accuracy for quantifications of myocardial total creatine and triglyceride content with localized 1 H-MRS., Study Type: Test-retest repeatability and measurement validation study., Subjects: Sixteen volunteers and 22 patients scheduled for open-heart aortic valve replacement or septal myectomy., Field Strength/sequence: Prospectively ECG-triggered respiratory-gated free-breathing single-voxel point-resolved spectroscopy (PRESS) sequence at 3 T., Assessment: Myocardial total creatine and triglyceride content were quantified relative to the total water content by fitting the 1 H-MR spectra. Precision was assessed with measurement repeatability. Accuracy was assessed by validating in vivo 1 H-MRS measurements against biochemical assays in myocardial tissue from the same subjects., Statistical Tests: Intrasession and intersession repeatability was assessed using Bland-Altman analyses. Agreement between 1 H-MRS measurements and biochemical assay was tested with regression analyses., Results: The intersession repeatability coefficient for myocardial total creatine content was 41.8% with a mean value of 0.083% ± 0.020% of the total water signal, and 36.7% for myocardial triglyceride content with a mean value of 0.35% ± 0.13% of the total water signal. Ex vivo myocardial total creatine concentrations in tissue samples correlated with the in vivo myocardial total creatine content measured with 1 H-MRS: n = 22, r = 0.44; P < 0.05. Likewise, ex vivo myocardial triglyceride concentrations correlated with the in vivo myocardial triglyceride content: n = 20, r = 0.50; P < 0.05., Data Conclusion: We validated the use of localized 1 H-MRS of the human heart at 3 T for quantitative assessments of in vivo myocardial tissue metabolite content by estimating the measurement precision and accuracy., Level of Evidence: 2 TECHNICAL EFFICACY STAGE: 2., (© 2021 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC. on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Helices and vortices in thoracic aortic blood flow measured with 4D flow cardiovascular magnetic resonance (CMR) have been associated with aortic dilation and aneurysms. Current approaches are semi-quantitative or when fully quantitative based on 2D plane placement. In this study, we present a fully quantitative and three-dimensional approach to map and quantify abnormal velocity and wall shear stress (WSS) at peak systole in patients with a bicuspid aortic valve (BAV) of which 52% had a repaired coarctation., Methods: 4D flow CMR was performed in 48 patients with BAV and in 25 healthy subjects at a spatiotemporal resolution of 2.5 × 2.5 × 2.5mm 3 / ~ 42 ms and TE/TR/FA of 2.1 ms/3.4 ms/8° with k-t Principal Component Analysis factor R = 8. A 3D average of velocity and WSS direction was created for the normal subjects. Comparing BAV patient data with the 3D average map and selecting voxels deviating between 60° and 120° and > 120° yielded 3D maps and volume (in cm 3 ) and surface (in cm 2 ) quantification of abnormally directed velocity and WSS, respectively. Linear regression with Bonferroni corrected significance of P < 0.0125 was used to compare abnormally directed velocity volume and WSS surface in the ascending aorta with qualitative helicity and vorticity scores, with local normalized helicity (LNH) and quantitative vorticity and with patient characteristics., Results: The velocity volumes > 120° correlated moderately with the vorticity scores (R ~ 0.50, P < 0.001 for both observers). For WSS surface these results were similar. The velocity volumes between 60° and 120° correlated moderately with LNH (R = 0.66) but the velocity volumes > 120° did not correlate with quantitative vorticity. For abnormal velocity and WSS deviating between 60° and 120°, moderate correlations were found with aortic diameters (R = 0.50-0.70). For abnormal velocity and WSS deviating > 120°, additional moderate correlations were found with age and with peak velocity (stenosis severity) and a weak correlation with gender. Ensemble maps showed that more than 60% of the patients had abnormally directed velocity and WSS. Additionally, abnormally directed velocity and WSS was higher in the proximal descending aorta in the patients with repaired coarctation than in the patients where coarctation was never present., Conclusion: The possibility to reveal directional abnormalities of velocity and WSS in 3D provides a new tool for hemodynamic characterization in BAV disease.

Background: Mediastinal radiation therapy (MRT) is a widely used therapy for thoracic malignancies. This therapy has the potential to cause cardiovascular injuries, which may require surgery. The primary aim of this study is to identify the perioperative outcomes of cardiac surgery in patients with a history of MRT. Second, potential predictors of mortality and adverse events were identified., Methods: A retrospective study was conducted among 59 patients with prior MRT who underwent cardiac surgery between December 2009 and March 2015. Included surgeries consisted of procedures through median- and ministernotomy. Baseline, perioperative, and follow-up data were obtained and analyzed., Results: The majority of patients had a history of breast cancer (n = 43), followed by Hodgkin lymphoma (n = 10) and non-Hodgkin lymphoma (n = 3). Preoperative estimated mortality with the Euroscore II was 3.4%. Overall 30-day mortality was 6.8% (n = 4), with a total in-hospital mortality of 10.2% (n = 6). Postoperatively, nine rethoracotomies (15.3%) had to be performed. During a mean follow-up of 53 months, an additional 10 patients (16.9%) died, of which 60% (n = 6) as a result of cancer-related events. Cox proportional modeling showed no differences in mortality between primary malignancies (P  > .05)., Conclusion: This study shows that cardiac surgery after mediastinal radiotherapy is associated with increased short- and long-term mortality when compared to preoperative mortality risks predicted by the Euroscore II. Surgery-related events caused all short-term mortality cases, while malignancy-related events were the main cause of death during the follow-up. Mortality was higher in patients with a previous stroke and a lower estimated glomerular filtration rate., (© 2020 The Authors. Journal of Cardiac Surgery published by Wiley Periodicals, Inc.)

Background: Radiation-associated aortic valve (AV) stenosis is frequently seen as a late sequela after thoracic radiotherapy (RT). Although the clinical relationship between thoracic radiotherapy and valvular dysfunction has been established, the process leading to accelerated aortic valve stenosis remains unclear. The aim of this study was to determine whether increased inflammatory cell infiltration, fibrosis, and calcification is present in aortic valves after radiotherapy at the time of aortic valve replacement., Methods: Stenotic aortic valve specimens from 43 patients were obtained after surgical aortic valve replacement. A total 28 patients had previously undergone radiotherapy for breast cancer or malignant lymphoma. A total 15 patients were included as control. The valve leaflets were assessed by (immuno)histochemistry for inflammatory cell composition (CD3, CD20, CD68, and CD163) and extracellular matrix changes (collagen and calcification)., Results: Aortic valve cell density after radiotherapy for lymphoma was markedly decreased when compared with other groups. Irradiated aortic valve show similar (low) degrees of late T and B lymphocyte infiltration as control valves, whereas macrophage marker CD68 was decreased after radiotherapy for breast cancer. Collagen content was increased following radiotherapy. Aortic valves of patients with lymphoma contained significantly less calcified tissue when compared with the other groups., Conclusion: High-dose radiation at a young age (patients with lymphoma) results in cell loss and premature fibrotic aortic valve stenosis as opposed to the degenerative calcific stenosis observed in patients with breast cancer. Our findings suggest a possible dose-dependent effect of radiotherapy on aortic valve fibrosis. The active presence of inflammatory cells may be limited to the acute phase after radiotherapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Progressive ascending aortic dilatation has been observed after mechanical aortic valve replacement (mAVR), possibly due to altered blood flow and wall shear stress (WSS) patterns induced by their bileaflet design. We examined the effect of mAVR on WSS in the ascending aorta using time-resolved 4D flow MRI. Fifteen patients with mechanical aortic valve prostheses, 10 patients with bicuspid aortic valve disease and 10 healthy individuals underwent thoracic 4D flow MRI. Peak systolic hemodynamic parameters (velocity and WSS) and vessel diameters were assessed in the ascending aorta. In addition, three-dimensional per-voxel analysis was used to compare velocity and WSS between patient groups and healthy controls. Peak aortic diameters were significantly higher in mAVR and BAV patients compared to healthy controls (p = 0.011). Mean aortic diameters were comparable between mAVR and BAV patients. No differences in 4D flow MRI-derived mean blood flow velocity and peak WSS were found between the three groups. Compared to healthy controls, mean WSS was significantly lower in mAVR patients (p = 0.031). Per-voxel analysis revealed no increased WSS in the ascending aortic wall and significantly lower velocity and WSS values in mAVR patients compared to healthy controls. In contrast, regions of significantly increased outer lumen velocities and WSS in BAV patients compared to healthy controls were found. This study shows that there is no increased ascending aortic WSS after mAVR. Our results suggest that, in contrast to BAV patients, there is no indication for intensified follow-up of the ascending aorta after mAVR.

Background: With the implementation of transcatheter aortic valve replacement (TAVR) in lower-risk patients, evaluation of blood flow characteristics and the effect of TAVR on aortic dilatation becomes of considerable interest. We employed 4D flow MRI in the ascending aorta of patients after TAVR to assess wall shear stress (WSS) and compare blood flow patterns with surgical aortic valve replacement (SAVR) and age- and gender-matched controls., Methods: Fourteen post-TAVR patients and ten age- and gender-matched controls underwent kt-PCA accelerated 4D flow MRI of the thoracic aorta at 3.0 Tesla. Velocity and wall shear stress was compared between the two groups. In addition, aortic flow eccentricity and displacement was assessed and compared between TAVR patients, controls and 14 SAVR patients recruited as part of an earlier study., Results: Compared to controls, abnormally elevated WSS was present in 30±10% of the ascending aortic wall in TAVR patients. Increased WSS was present along the posterior mid-ascending aorta and the anterior distal-ascending aorta in all TAVR patients. TAVR results in eccentric and displaced flow in the mid- and distal-ascending aorta, whereas blood flow displacement in SAVR patients occurs only in the distal-ascending aorta., Conclusion: This study shows that TAVR results in increased blood flow velocity and WSS in the ascending aorta compared to age- and gender-matched elderly controls. This finding warrants longitudinal assessment of aortic dilatation after TAVR in the era of potential TAVR in lower-risk patients. Additionally, TAVR results in altered blood flow eccentricity and displacement in the mid- and distal-ascending aorta, whereas SAVR only results in altered blood flow eccentricity and displacement in the distal-ascending aorta., Key Points: • TAVR results in increased blood flow velocity and WSS in the ascending aorta. • Longitudinal assessment of aortic dilatation after TAVR is warranted in the era of potential TAVR in lower-risk patients. • Both TAVR and SAVR result in altered blood flow patterns in the ascending aorta when compared to age-matched controls.

Objectives: Surgical repair of coarctation of the aorta (CoA) is often possible through left thoracotomy and without the use of cardiopulmonary bypass. Recent studies reporting the outcome after CoA repair through left thoracotomy are limited. Therefore, the aim of this study is to evaluate the results of CoA repair through left thoracotomy in children who were operated on in our centre over the past 21 years., Methods: From January 1995 to December 2016, 292 patients younger than 18 years underwent primary CoA repair through left thoracotomy at our 2 institutions. Peri- and postoperative data and follow-up data collected from our hospital and the referring hospitals were retrospectively reviewed., Results: Median age at operation was 64 days (range 2 days-17 years). Most patients underwent the resection of the CoA followed by an (extended) end-to-end anastomosis (93%). Six patients died perioperatively and 2 more patients died during the follow-up, of which 7 patients had other major comorbidities. Actuarial survival was 97% at 5 years, 96% at 10 years and 96% at 15 years. Second arch interventions due to recoarctation were performed in 9.9% (n = 29) of patients, consisting of balloon dilatation in all but 2 patients. Recoarctation occurred significantly more often after initial repair in the neonatal period (21%) and could occur as late as 14 years after initial surgery. There were 7 re-recoarctations, and 14% of patients were on hypertensive medication during the follow-up., Conclusions: Repair of CoA through left thoracotomy is a safe procedure with low rates of mortality. The long-term follow-up is necessary due to the significant risk of recoarctation requiring reintervention.

Background and Study Aims: Hepatitis C virus (HCV) infection is a severe problem among patients on maintenance haemodialysis who are at particular risk for blood-borne infections because of prolonged vascular access and potential for exposure to contaminated equipment. Occult hepatitis C virus infection (OCI) is defined as the presence of HCV RNA in liver or peripheral blood mononuclear cells (PBMCs) in the absence of detectable HCV antibody or HCV RNA in the serum. In this study, we aimed to investigate the existence of occult hepatitis C virus infection in PBMCs of haemodialysis (HD) patients in one center. Moreover, we tried to link the condition to risk factors associated with HCV infection in those patients., Patients and Methods: We included 40 patients with renal diseases undergoing regular haemodialysis who were repeatedly anti-HCV negative. HCV RNA detection was tested by Quantitative Real time PCR in serum and PBMCs., Results: The results of this study revealed that 23% of our haemodialysis patients have occult hepatitis C virus infection. There was a highly significant increase in ALT levels in patients with OCI versus the negative group. Also, there is a significant increase of history of blood transfusion in patients with occult HCV (p = 0.03) while the duration of haemodialysis showed no statistical significant difference between both groups. The viral load of the occult hepatitis C virus infection subjects ranged from 581to 74,307 copies/ml., Conclusion: These results highlight the potential risk of hepatitis C virus transmission from patients within haemodialysis units in Egypt. Isolation of patients on dialysis machines depending on the results of hepatitis serological markers is not enough. Testing for hepatitis C virus -RNA in peripheral blood mononuclear cells is more reliable in identifying patients with an OCI when a liver biopsy is not available., (Copyright © 2018 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

The most common types of left-sided valvular heart disease (VHD) in the Western world are aortic valve stenosis, aortic valve regurgitation, and mitral valve regurgitation. Comprehensive clinical evaluation entails both hemodynamic analysis and structural as well as functional characterization of the left ventricle. Cardiac magnetic resonance imaging (MRI) is an established diagnostic modality for assessment of left-sided VHD and is progressively gaining ground in modern-day clinical practice. Detailed flow visualization and quantification of flow-related biomarkers in VHD can be obtained using 4D flow MRI, an imaging technique capable of measuring blood flow in three orthogonal directions over time. In addition, recent MRI sequences enable myocardial tissue characterization and strain analysis. In this review we discuss the emerging potential of state-of-the-art MRI including 4D flow MRI, tissue mapping, and strain quantification for the diagnosis and prognosis of left-sided VHD., Level of Evidence: 1 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2018. J. MAGN. RESON. IMAGING 2018;48:318-329., (© 2018 International Society for Magnetic Resonance in Medicine.)

Background: Use of 4-dimensional flow magnetic resonance imaging (4D-flow MRI) derived wall shear stress (WSS) heat maps enables identification of regions in the ascending aorta with increased WSS. These regions are subject to dysregulation of the extracellular matrix and elastic fiber degeneration, which is associated with aortic dilatation and dissection., Purpose: To evaluate the effect of the presence of aortic valve stenosis and the aortic diameter on the peak WSS and surface area of increased WSS in the ascending aorta., Study Type: Prospective., Subjects: In all, 48 bicuspid aortic valve (BAV) patients (38.1 ± 12.4 years) and 25 age- and gender-matched healthy individuals., Field Strength/sequence: Time-resolved 3D phase contrast MRI with three-directional velocity encoding at 3.0T., Assessment: Peak systolic velocity, WSS, and aortic diameters were assessed in the ascending aorta and 3D heat maps were used to identify regions with elevated WSS., Statistical Tests: Comparisons between groups were performed by t-tests. Correlations were investigated by univariate and multivariate regression analysis., Results: Elevated WSS was present in 15 ± 11% (range; 1-35%) of the surface area of the ascending aorta of BAV patients with aortic valve stenosis (AS) (n = 10) and in 6 ± 8% (range; 0-31%) of the ascending aorta of BAV patients without AS (P = 0.005). The mid-ascending aortic diameter negatively correlated with the peak ascending aortic WSS (R = -0.413, P = 0.004) and the surface area of elevated WSS (R = -0.419, P = 0.003). Multivariate linear regression analysis yielded that the height of peak WSS and the amount of elevated WSS depended individually on the presence of aortic valve stenosis and the diameter of the ascending aorta., Data Conclusion: The extent of increased WSS in the ascending aorta of BAV patients depends on the presence of aortic valve stenosis and aortic dilatation and is most pronounced in the presence of AS and a nondilated ascending aorta., Level of Evidence: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2018;48:522-530., (© 2018 The Authors Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Hypertrophic cardiomyopathy is a heterogeneous myocardial disease and is characterized by increased left ventricular wall thickness. Left ventricular outflow tract obstruction occurs in up to 70% of patients and is often caused by systolic anterior motion of the mitral valve, a paradoxical phenomenon in which the anterior mitral valve leaflet is pulled into the left ventricular outflow tract during systole. We present the first case of hypertrophic cardiomyopathy with systolic anterior motion of both the mitral and the tricuspid valves and severe hypertrophy of both ventricles., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Intraoperative hypotension may contribute to perioperative strokes. We therefore tested the hypothesis that intraoperative hypotension is associated with perioperative stroke., Methods: After institutional review board approval for this case-control study, we identified patients who had nonneurological, noncardiac, and noncarotid surgery under general anesthesia at the Cleveland Clinic between 2005 and 2011 and experienced a postoperative stroke. Control patients not experiencing postoperative stroke were matched in a 4-to-1 ratio using propensity scores and restriction to the same procedure type as stroke patients. The association between intraoperative hypotension, measured as time-integrated area under a mean arterial pressure (MAP) of 70 mm Hg, and postoperative stroke was assessed using zero-inflated negative binomial regression., Results: Among 106 337 patients meeting inclusion criteria, we identified 120 who had confirmed postoperative stroke events based on manual chart review. Four-to-one propensity matching yielded a final matched sample of 104 stroke cases and 398 controls. There was no association between stroke and intraoperative hypotension. Stroke patients were not more likely than controls to have been hypotensive (odds ratio, 0.49 [0.18-1.38]), and among patients with intraoperative hypotension, stroke patients did not experience a greater degree of hypotension than controls (ratio of geometric means, 1.07 [0.76-1.53])., Conclusions: In our propensity score-matched case-control study, we did not find an association between intraoperative hypotension, defined as MAP < 70 mm Hg, and postoperative stroke.

Context: There is a paucity of accurate postmortem data pertinent to comorbid medical conditions in patients with dementia, including Alzheimer disease., Objectives: The purposes of this study were (a) to examine general autopsy findings in patients with a dementia syndrome and (b) to establish patterns of central nervous system comorbidity in these patients., Design: Review of autopsy reports and selected case material from 202 demented patients who had "brain-only" autopsies during a 17-year period (1984-2000) and from 52 demented patients who had general autopsies during a 6-year period (1995-2000)., Setting: Large academic medical center performing approximately 200 autopsies per year., Results: Among the 52 patients who underwent complete autopsy, the most common cause of death was bronchopneumonia, which was found in 24 cases (46.1%). Other respiratory problems included emphysema, found in 19 (36.5%) of 52 patients, and pulmonary thromboembolism, found in 9 (17.3%) of 52 patients. In 6 cases, pulmonary thromboembolism was the proximate cause of death. Twenty-one (40.3%) of the 52 patients had evidence of a myocardial infarct (varying ages) and 38 (73.1%) had atherosclerotic cardiovascular disease, 27 of a moderate to severe degree. Four clinically unsuspected malignancies were found: 1 each of glioblastoma multiforme, diffusely infiltrative central nervous system lymphoma, pancreatic adenocarcinoma, and adenocarcinoma of the lung. One patient with frontotemporal dementia and amyotrophic lateral sclerosis died of severe meningoencephalitis/ventriculitis, probably secondary to seeding of the central nervous system by an infected cardiac valve. Of the 202 demented patients who underwent brain-only autopsies, the following types of dementia were found: 129 (63.8%) cases showed changes of severe Alzheimer disease, 21 (10.4%) showed combined neuropathologic abnormalities (Alzheimer disease plus another type of lesion, such as significant ischemic infarcts or diffuse Lewy body disease), 12 (5.9%) cases of relatively pure ischemic vascular dementia, 13 (6.4%) cases of diffuse Lewy body disease, and 8 (4.0%) cases of frontotemporal dementia. The remaining 19 (9.4%) patients showed miscellaneous neuropathologic diagnoses, including normal pressure hydrocephalus and progressive supranuclear palsy. Among the demented patients, 92 (45.5%) had cerebral atherosclerosis, which was moderate to severe in 65 patients (32.2%)., Conclusions: Some of the conditions found at autopsy, had they been known antemortem, would likely have affected clinical management of the patients. Autopsy findings may be used as a quality-of-care measure in patients who have been hospitalized in chronic care facilities for a neurodegenerative disorder.