Wall Shear Stress Predicts Media Degeneration and Biomechanical Changes in Thoracic Aorta.

Objectives: In thoracic aortic aneurysm (TAA) of the ascending aorta (AA), AA is progressively dilating due to the weakening of the aortic wall. Predicting and preventing aortic dissections and ruptures in TAA continues to be challenging, and more accurate assessment of the AA dilatation, identification of high-risk patients, and timing of repair surgery are required. We investigated whether wall shear stress (WSS) predicts pathological and biomechanical changes in the aortic wall in TAA. Methods: The study included 12 patients with bicuspid (BAV) and 20 patients with the tricuspid aortic valve (TAV). 4D flow magnetic resonance imaging (MRI) was performed a day before aortic replacement surgery. Biomechanical and histological parameters, including assessing of wall strength, media degeneration, elastin, and cell content were analyzed from the resected AA samples. Results: WSSs were greater in the outer curves of the AA compared to the inner curves in all TAA patients. WSSs correlated with media degeneration of the aortic wall (ρ = -0.48, p < 0.01), elastin content (ρ = 0.47, p < 0.01), and aortic wall strength (ρ = -0.49, p = 0.029). Subsequently, the media of the outer curves was thinner, more rigid, and tolerated lower failure strains. Failure values were shown to correlate with smooth muscle cell (SMC) density (ρ = -0.45, p < 0.02), and indicated the more MYH10+ SMCs the lower the strength of the aortic wall structure. More macrophages were detected in patients with severe media degeneration and the areas with lower WSSs. Conclusion: The findings indicate that MRI-derived WSS predicts pathological and biomechanical changes in the aortic wall in patients with TAA and could be used for identification of high-risk patients.

Flow displacement and decreased wall shear stress might be associated with the growth rate of an ascending aortic dilatation.

OBJECTIVES: Our goal was to evaluate whether four-dimensional (4D) flow magnetic resonance imaging (MRI) can predict the growth rate of dilatation of the ascending aorta (AA) in patients with a tricuspid, normally functioning aortic valve. METHODS: In this prospective clinical study, aortic 4D flow MRI was performed at the Kuopio University Hospital on 30 patients diagnosed with AA dilatation (maximum diameter >40 mm) between August 2017 and July 2020. The MRI was repeated after a 1-year follow-up, with AA dimensions and 4D flow parameters analysed retrospectively at both time points. The standard error of measurement was used to assess the statistical significance of the growth rate of AA dilatation. Flow displacement (FD) was transformed to a class-scaled parameter using FD ≥5% as a threshold. RESULTS: Statistically significant growth [median 2.1 mm (1.5-2.2 mm); P = 0.03] was detected in 6 male patients (20%); the AA diameter remained unchanged [0.2 mm (-0.3 to 0.9 mm)] in 24 patients (80%). An increased FD at the baseline was associated with significant growth during the 1-year follow-up in the proximal AA. An association was detected between decreased total wall shear stress and significant aortic growth in the inner curve of the sinotubular junction [529 mPa (449-664 mPa) vs 775 mPa (609-944 mPa); P = 0.03] and the anterior side of the proximal aortic arch [356 mPa (305-367 mPa) vs 493 mPa (390-586 mPa); P < 0.001]. CONCLUSIONS: FD and decreased wall shear stress seem to be associated with significant growth of AA dilatation at the 1-year follow-up. Thus, 4D flow MRI might be useful in assessing risk for AA diameter growth in patients with a tricuspid aortic valve.

Excess of visceral adipose tissue with or without aortic elongation leads to a steeper heart position.

BACKGROUND: The heart's position determined as the heart-aorta angle (HAA) has been demonstrated to associate with ascending aortic (AA) dilatation. Visceral adipose tissue (VAT) and aortic elongation may shift the heart to the steeper position. PURPOSE: To investigate whether VAT and aortic length influence the HAA. MATERIAL AND METHODS: We examined 346 consecutive patients (58.4% men; mean age = 67.0 ± 14.1 years) who underwent aortic computed tomography angiography (CTA). HAA was measured as the angle between the long axis of the heart and AA midline. The amount of VAT was measured at the level of middle L4 vertebra from a single axial CT slice. Aortic length was measured by combining four anatomical segments in different CTA images. The amount of VAT and aortic length were determined as mild with values in the lowest quartile and as excessive with values in the other three quartiles. RESULTS: A total of 191 patients (55.2%) had no history of aortic diseases, 134 (38.7%) displayed AA dilatation, 8 (2.3%) had abdominal aortic aneurysm (AAA), and 13 (3.8%) had both AA dilatation and AAA. There was a strong nonlinear regression between smaller HAA and VAT/height, and HAA and aortic length/height. Median HAA was 124.2° (interquartile range 119.0°-130.8°) in patients with a mild amount of VAT versus 120.5° (interquartile range 115.4°-124.7°) in patients with excessive VAT (P < 0.001). CONCLUSION: An excessive amount of VAT and aortic elongation led to a steeper heart position. These aspects may possess clinical value when evaluating aortic diseases in obese patients.

Pulmonary Artery Dilatation Is a Common Finding in a Coronary Artery CT Angiography Population.

BACKGROUND/AIM: Dilatation of the main pulmonary artery (mPA) is a common incidental finding in chest imaging and often leads to consultation. The aim of this study was to determine the prevalence of mPA dilatation in a coronary artery CT angiography (CCTA) population. PATIENTS AND METHODS: The study investigated 985 consecutive patients scheduled for diagnostic CCTA. The transverse axial diameter of the mPA was measured. The prevalence of mPA dilatation was estimated using different reference values (Framingham Heart Study: 28.9 mm for males and 26.9 mm for females, Bozlar: 29.5 mm for both genders and Karazincir: 32.6 mm for males and 31.9 mm for females). RESULTS: The patient mean age was 53.0±9.7 years (66.5% were women). Body surface area (BSA) correlated moderately with the mPA diameter (r=0.423, p<0.001). The prevalence of mPA dilatation varied from 5.9% (Karazincir) to 33.7% (Framingham Heart Study) in the overall study population. CONCLUSION: The prevalence of mPA dilatation is high in a CCTA patient population when using a cut-off value from the Framingham Heart Study.

A smaller heart-aorta-angle associates with ascending aortic dilatation and increases wall shear stress.

OBJECTIVES: The aim of this study was to evaluate whether the orientation of the heart, measured as an angle between the long axis of the heart and ascending aorta midline (heart-aorta-angle, HAA), associates with ascending aortic (AA) dilatation. Furthermore, the association between HAA and wall shear stress (WSS) was studied. METHODS: HAA was retrospectively measured in 1000 consecutive coronary artery computed tomographic angiography (CCTA) images in patients with low-to-moderate pretest probability for coronary artery disease (CAD). To evaluate the effects of HAA on AA flow, 4D flow MRI was performed for 28 patients with AA dilatation (> 40 mm) and WSS was analyzed. RESULTS: The mean age of patients undergoing CCTA was 52.9 ± 9.8 years; 66.5% were women. Their median HAA was 128.7° and interquartile range 123.3-134.1°. HAA was significantly smaller in patients with dilated AA (median 126.7° [121.3-130.8°]) compared with the patients with normal AA (median 129.5° [124.3-135.3°], p < 0.001). HAA was smaller in males (p < 0.001) and in patients with diabetes (p = 0.016), hypertension (p = 0.001), CAD (p = 0.003), hypercholesterolemia (p < 0.001), and bicuspid aortic valve (p = 0.025) than without these factors. In a subpopulation without any of these underlying diseases (n = 233), HAA was still significantly smaller in the patients with dilated AA (median 127.9° [124.3-134.3°]) compared with patients with normal AA (median 131.9° [127.6-136.9°], p = 0.013). In 4D flow MRI, a smaller HAA correlated with increased total WSS in the outer curvature of the proximal AA (r = - 0.510, p = 0.006). CONCLUSION: A smaller HAA associates with AA dilatation and affects the blood flow in the proximal AA. KEY POINTS: • A smaller angle between the long axis of the heart and ascending aorta midline associated with ascending aortic dilatation. • A smaller heart-aorta-angle correlated with increased total wall shear stress in the outer curvature of the proximal ascending aorta.

High prevalence of ascending aortic dilatation in a consecutive coronary CT angiography patient population.

OBJECTIVES: To clarify the prevalence and risk factors of ascending aortic (AA) dilatation according to ESC 2014 guidelines. METHODS: This study included 1000 consecutive patients scheduled for diagnostic coronary artery computed tomographic angiography. AA diameter was retrospectively measured in 3 planes: sinus valsalva, sinotubular junction, and tubular part. The threshold for AA dilatation was set to > 40 mm which has been suggested as an upper normal limit for AA diameter in ESC 2014 guidelines on aortic diseases. Aortic size index (ASI) using the ratio between aortic diameter and body surface area (BSA) was applied as a comparative measurement. The threshold for AA dilatation was set to the upper limit of normal distribution exceeding two standard deviations (95%). Risk factors for AA dilatation were collected from medical records. RESULTS: The patients' mean age was 52.9 ± 9.8 years (66.5% women). The prevalence of AA dilatation was 23.0% in the overall study population (52.5% males) and 15.1% in the subgroup of patients with no coronary artery disease or bicuspid (BAV)/mechanical aortic valve (n = 365). According to the normal-distributed ASI values, the threshold for sinus valsalva was defined as 23.2 mm/m2 and for tubular part 22.2 mm/m2 in the subgroup. Higher BSA was associated with larger AA dimensions (r = 0.407, p < 0.001). Male gender (p < 0.001), BAV (p < 0.001), hypertension (p = 0.009) in males, and smoking (p < 0.001) appeared as risk factors for AA dilatation. CONCLUSIONS: The prevalence of AA dilatation is high with current ESC guidelines for normal AA dimension, especially in males. Body size is strongly associated with AA dimensions; it would be more reliable to use BSA-adjusted AA diameters for the definition of AA dilatation. KEY POINTS: • The prevalence of AA dilatation is high in patients who are candidates for coronary CT angiography. • Body size is strongly associated with AA dimensions.

Aortic dilatation associates with flow displacement and increased circumferential wall shear stress in patients without aortic stenosis: A prospective clinical study.

BACKGROUND: The relationship between blood flow characteristics and ascending aortic (AA) dilatation has not been studied in patients with a tricuspid aortic valve (TAV) without aortic stenosis. PURPOSE: To evaluate whether 4D flow characteristics determined in MRI are related to AA dilatation by comparing dilated AA and nondilated AA subjects with TAV. STUDY TYPE: Prospective. POPULATION: Twenty patients with dilated AA and 20 age-matched patients with nondilated AA. FIELD STRENGTH/SEQUENCE: 1.5T/4D flow, 2D flow, and anatomic images. ASSESSMENT: Altogether, 16 different 4D flow parameters were assessed in 10 planes in the thoracic aorta. Intra- and interobserver reproducibility were analyzed. STATISTICAL TESTS: Independent t-test for normally distributed and the Mann-Whitney test for skewed distributed parameters were used. A paired-samples t-test was used to compare 2D and 4D flow parameters. Intraclass correlation coefficient (ICC) was used in intra- and interobserver reproducibility analysis. RESULTS: Aortic flow was displaced from the centerline of the aorta in the proximal and tubular planes. Flow displacement (FD) was greatest in the proximal plane of AA and was higher in dilated AA (4.5%, range 3.0-5.8%) than in nondilated AA (2.0%, 1.0-3.0%, P < 0.001). Total wall shear stress (WSS) values were 1.3 ± 0.4 times higher on the displaced side than on the opposite side of the aorta (P < 0.01). The circumferential WSS (WSSC ) ratio to total WSS was greater in dilated AA, being 0.48 ± 0.11 vs. 0.32 ± 0.09 in the inner curvature of the proximal AA (P < 0.001) and 0.37 ± 0.11 vs. 0.26 ± 0.07 in the whole aortic ring in the distal AA (P < 0.001). Depending on 4D flow parameters, reproducibility varied from excellent (ICC = 0.923) to very low (ICC = 0.204). DATA CONCLUSION: The present study demonstrates that 4D flow measurements help to visualize the pathological flow patterns related to aortic dilatation. Flow displacement and an increased WSSc/WSS ratio are significantly associated with AA dilatation. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:136-145.

Cost savings in outpatient versus inpatient reduction mammaplasty.

BACKGROUND AND AIMS: Reduction mammaplasties are increasingly performed as outpatient procedures. Cost savings are assumed, but published data on the subject are scarce. The aim of this study was to retrospectively determine the possible cost savings achieved by performing reduction mammaplasties as outpatient procedures. MATERIAL AND METHODS: Reduction mammaplasty was performed for 90 outpatients and 44 inpatients, with comparable health status. Demographic, surgical, and complication data were collected retrospectively. Data on the costs of the entire treatment process were acquired and statistical analyses performed. RESULTS: The average total cost of the process was 5039 € for inpatients and 4114 € for outpatients. Thus, the total costs were 925 € (18%) lower for the outpatient procedures. On average, cost saving per patient was 294 € (43%) on ward expenditures. Higher ward expenditure was a statistically significant cause of the increased cost of the inpatient group on uni- and multivariable analyses; however, for total costs, the effects of complications and reoperations were significant. CONCLUSIONS: Reduction mammaplasty performed as an outpatient procedure results in up to 18% cost savings compared with inpatient treatment.

Reduction mammaplasty as an outpatient procedure: a retrospective analysis of outcome and success rate.

BACKGROUND AND AIMS: Reduction mammaplasty is an increasingly common plastic surgical procedure. In the United States, majority of breast reductions are performed as outpatient surgery. In European public health care, outpatient breast reductions have still been rare. Our aim was to retrospectively determine clinical outcome and the success rate of outpatient reduction mammaplasty. MATERIAL AND METHODS: A total of 110 consecutive patients underwent bilateral reduction mammaplasty with a minimum resection of 200 g per breast in an outpatient unit between 2006 and 2009. A comparison group consisted of 28 inpatients. Demographic data and pre-, intra-, and postoperative events as well as complications were recorded. RESULTS: A total of 83 outpatients (75%) were successfully discharged on the day of operation. Reasons for unexpected overnight admission were lack of adult company for the first postoperative night (13 patients, 12%), surgeon's wish (4 patients, 4%), hematoma requiring evacuation (5 patients, 5%), nausea (3 patients, 3%), and pain (2 patients, 2%). Minor complications, especially delayed healing, were common (45 patients, 41%), but major complications were rare (18 patients, 16%). Complication rate was not increased in the outpatient group. Increased duration of operation correlated with increasing complications. CONCLUSION: Reduction mammaplasty can be successfully and safely performed as an outpatient procedure in European public health care.

Adverse Histopathology and Imaging Findings in Reduction Mammaplasty Day-surgery Patients.

BACKGROUND AND AIMS: Reduction mammaplasty is a popular procedure in plastic surgery. Occasionally, occult invasive breast carcinoma or findings demonstrating increased risk of breast cancer occur in reduction mammaplasty specimens. The incidences have been studied elsewhere, but in Finland, the data on this subject are lacking. Our aim was to analyze the incidence of occult invasive and in situ carcinoma and benign breast disease causing increased risk of breast cancer in reduction mammaplasty specimens. We also analyzed preoperative mammograms and ultrasound images and compared findings with reduction mammaplasty specimens. MATERIAL AND METHODS: We performed a retrospective study of 100 women who underwent reduction mammaplasty during 1 January 2007 to 30 April 2009 in Jorvi Hospital day-surgery unit. Demographic data, findings in preoperative imaging, pathology reports, postoperative follow-up, and retrospective reanalysis of preoperative imaging were recorded. RESULTS: Histological abnormality occurred in 14.6% of the patients. In situ carcinoma was diagnosed in 4.5% of the patients, and findings demonstrating increased risk of breast cancer were diagnosed in 13.5% of the patients. More than one lesion demonstrating increased risk of breast cancer was diagnosed in 4.5% of the patients. No invasive carcinoma occurred. Preoperative mammogram was performed for the majority (94.0%) of the patients. CONCLUSIONS: We detected a considerable amount of findings in reduction mammaplasty specimens with prognostic value with regard to future breast cancer risk. We recommend histological analysis for reduction mammaplasty specimens and focus attention on systematically performed preoperative imaging.

Clinical PET imaging of insulinoma and beta-cell hyperplasia.

Persistent hyperinsulinemic hypoglycemia (PHH) is caused by solitary benign insulinoma or hyperplasia of pancreatic beta cells. In infants, PHH is caused by functionally defective hyperplastic beta cells, which are either diffusely or focally distributed in the pancreas. In adults, insulinoma is the most common cause of PHH, but recently, an increasing number of beta-cell hyperplasias has been reported among adults. The cause of adult beta-cell hyperplasia is not known. Whether the increased use of bariatric surgery in the treatment of severe obesity plays a role here is under investigation. Accurate localization of disease focus in both insulinoma and focal beta-cell hyperplasia provides an important support for surgery, especially as the use of laparoscopic surgery has increased. Conventional imaging of these challenging pancreatic lesions has evolved during recent years, but current imaging methods still lack sufficient sensitivity or are invasive. In most pancreatic NETs, the usefulness of positron emission tomography (PET) with fluorine-labeled fluorodeoxyglucose ([(18)F]FDG) for lesion detection is limited because of the low glucose turnover of these tumors. Based on the capacity of pancreatic beta cells to take up and decarboxylate amine precursors, several investigators have studied patients with pancreatic NETs using aminoacid precursors, such as [(18)F]dihydroxyphenylalanine (DOPA) and [(11)C]hydroxytryptophan (5-HTP), in an attempt to increase the sensitivity of PET scanning. Another characteristic of NETs is the expression of somatostatin receptors, and thus encouraging studies with somatostatin receptor imaging with [(18)Ga]-labeled somatostatin analogs have emerged as a new interesting imaging tool for the diagnosis of pancreatic NETs. This article provides an overview of our experiences and the current literature on PET imaging in patients with PHH caused by insulinoma or beta-cell hyperplasia.

Satellite cell proliferation in rabbit hindlimb muscle following immobilization and remobilization: an immunohistochemical study using MIB 1 antibody.

The time course and pattern of mitotic activity in the deep part of the vastus intermedius muscle (VIP) immobilized in a shortened position in 16 adult NZW rabbit hindlimbs for time periods ranging from 12 h to 56 days and in VIP muscles from 10 rabbit hindlimbs immobilized from 3 to 28 days and subsequently remobilized for 4 weeks were compared. Paraffin sections were stained immunohistochemically with monoclonal MIB 1 antibody raised against recombinant fragments of Ki-67 antigen, and a double staining with modified reticulin stain was carried out to facilitate differentiation between satellite cells and other proliferating cells outside the muscle. In samples taken 24 h after the onset of immobilization, the tissue was mitotically quiescent and at 3, 14, 28, and 56 days of immobilization 5.7%, 1.3%, 1.1% and 0.7%, respectively, of all counted nuclei were mitotically active. However, all of them were localized outside the basement membrane (BM) of the myofiber and were presumably proliferating fibroblasts, capillary endothelial cells or inflammatory cells. Satellite cell mitotic activity was first seen after 2 weeks of immobilization followed by 4 weeks of remobilization. In VIP muscle immobilized for 3 weeks and remobilized for 4 weeks the numbers of all proliferating cells as well as proliferating satellite cells reached a concomitant peak, and they were 7.5% and 3% respectively. The results indicate a late activation of satellite cell proliferation, which may relate to the initial lack of stretch and mechanical load during the cast immobilization followed by a late release of mitogenic factors during eccentric muscle work performed by the VIP muscle after removal of the cast.

Abnormal mitochondria and sarcoplasmic changes in rabbit skeletal muscle induced by immobilization.

Immobilization of the rabbit knee in extended position results in damage to the vastus intermedius profundus (VIP) muscle. To examine the mechanisms involved in initiation of the injury, we studied the light and electron microscopic morphology of the VIP muscle, as well as the activity and distribution of NADH tetrazolium reductase (NADH-TR) in the affected muscle, and determined serum total creatine kinase (CK) activity in immobilized rabbits. The VIP muscle of the immobilized right hindlimb was removed at various time points (10 h, 24 h, 36 h and 48-72 h, n=5 for each time point). The nonimmobilized left hindlimb and five nonimmobilized animals served as controls. No morphological changes were observed by light microscopy within 48-72 h in routine stainings. Transient ultrastructural abnormalities, including abnormal cristae, matrix lucencies and mild swelling of mitochondria, were observed between 10 h and 36 h of immobilization, subsiding by 48-72 h. On the other hand, progressive disorganization of myofibrils with breaking-up of Z-bands and an increase in the number and size of sarcoplasmic lipid vacuoles was seen with increasing duration of immobilization. NADH-TR activity at subsarcolemmal locations had decreased by 10 h and disappeared by 24 h of immobilization, while the intermyofibrillar mitochondria remained unaltered. Serum total CK activity began to increase by 2 h of immobilization and reached a peak by 24 h. The results indicate that already a few hours of immobilization of the rabbit knee in extension leads to signs of metabolic disturbance of the VIP muscle and sarcolemmal leakage. The simultaneous occurrence of transient mitochondrial abnormalities, transient CK efflux and progressive myofibrillar damage suggests the operation of multiple adverse mechanisms already at the onset of disuse muscle atrophy.

Recovery of skeletal muscle after immobilization of rabbit hindlimb. A light microscopic study.

The histopathology of the deep portion of the vastus intermedius (VIP) muscle from 13 rabbit hindlimbs immobilized in shortened position for 2-2.5 (n = 4), 3 (n = 3), 14 (n = 3) and 28 (n = 3) days and VIP muscles from 13 rabbit hindlimbs immobilized for the same time periods and subsequently remobilized for 4 weeks were compared. After 3 days of immobilization the VIP muscles displayed a 15% (p < 0.004) decline in muscle fibre diameter. By 2 weeks of immobilization fatty change was prominent and muscle fibre diameters had decreased to 56% (p < 0.0001) of control values. By 4 weeks of immobilization severe fibrotic damage of myofibres was observed and fibre diameters had decreased to 47% (p < 0.0001) of control values. Three days of immobilization followed by 4 weeks of remobilization led to marked fatty change as well as an increase in connective tissue in the affected VIP muscles. The muscle fibre diameter in these muscles was 71% (p < 0.0001) compared to the VIP immobilized for 3 days and 61% (p < 0.0001) compared to the control muscles. By 2-4 weeks of immobilization the subsequent remobilization did not aggravate the initial damage. We conclude that the morphology of VIP muscle immobilized for 3 days suffers more during a subsequent remobilization period than those immobilized for 14-28 days. These findings focus attention on the mechanisms operating at the onset of disuse muscle atrophy.

Early muscle changes after immobilization. An experimental study on muscle damage.

Immobilization of the rabbit knee in extension has previously been shown to damage the vastus intermedius profundus (VIP) muscle. To examine the mechanism of the early stages of the muscle damage, the authors studied creatine kinase activity in serum, and both light and electron microscopic changes in the affected muscle. The right knee was immobilized in an extended position using a splint, and thigh muscles were removed at various intervals, up to 48 hours after immobilization. The left hindlimb served as a control. Creatine kinase levels in serum rose ten hours after the onset of the immobilization. The enzyme levels reached a substantial peak by 24 hours, and plateaued thereafter. Light microscopic changes were not observed within 48 hours, but in electron microscopy distinct mitochondrial swelling and crystal abnormalities were seen as early as ten hours. The ultrastructural changes of mitochondria remained constant for up to 36 hours and decreased thereafter. At 48 hours of immobilization, also myofibrillar disorganization was seen. It appears that immobilization of the rabbit knee in extension rapidly leads to signs of remarkable damage to the VIP muscle. These suggest leakage of the cell membrane and metabolic disturbances. The ultrastructural changes observed share common features with muscle damage caused by ischemia, uncoupling agents, and inherited mitochondrial myopathies.