High prevalence of interstitial lung abnormalities in middle-aged never-smokers.

Background: Interstitial lung abnormalities (ILA) are incidental findings on chest computed tomography (CT). These patterns can present at an early stage of fibrotic lung disease. Our aim was to estimate the prevalence of ILA in the Swedish population, in particular in never-smokers, and find out its association with demographics, comorbidities and symptoms. Methods: Participants were recruited to the Swedish CArdioPulmonary BioImage Study (SCAPIS), a population-based survey including men and women aged 50-64 years performed at six university hospitals in Sweden. CT scan, spirometry and questionnaires were performed. ILA were defined as cysts, ground-glass opacities, reticular abnormality, bronchiectasis and honeycombing. Findings: Out of 29 521 participants, 14 487 were never-smokers and 14 380 were men. In the whole population, 2870 (9.7%) had ILA of which 134 (0.5%) were fibrotic. In never-smokers, the prevalence was 7.9% of which 0.3% were fibrotic. In the whole population, age, smoking history, chronic bronchitis, cancer, coronary artery calcium score and high-sensitive C-reactive protein were associated with ILA. Both ILA and fibrotic ILA were associated with restrictive spirometric pattern and impaired diffusing capacity of the lung for carbon monoxide. However, individuals with ILA did not report more symptoms compared with individuals without ILA. Interpretation: ILA are common in a middle-aged Swedish population including never-smokers. ILA may be at risk of being underdiagnosed among never-smokers since they are not a target for screening.

Diffusely Increased Myocardial Extracellular Volume With or Without Focal Late Gadolinium Enhancement: Prevalence and Associations With Left Ventricular Size and Function.

PURPOSE: Myocardial extracellular volume fraction (ECV) using cardiovascular magnetic resonance (CMR) can identify diffuse lesions not detected by late gadolinium enhancement (LGE). We aimed to determine the prevalence of increased ECV and its relation to other CMR findings. MATERIALS AND METHODS: Consecutive patients (n=609, age median [interquartile range] 53 [39 to 66] y, 62% male) underwent CMR at 1.5 T. Focal lesions on LGE images were noted. ECV in regions without focal LGE findings defined diffuse changes. Pronounced increases in left ventricular (LV) end-diastolic volume index and LV mass index, and pronounced decreases in LV ejection fraction were defined as >3 SD from the sex-specific mean in healthy volunteers. RESULTS: Of 609 patients without amyloidosis or hypertrophic cardiomyopathy, 8% had diffusely increased ECV and 5% of all patients had diffusely increased ECV without any focal LGE findings. Multivariate analysis showed that a pronounced increase in the LV end-diastolic volume index was associated with increased ECV (P=0.001), but not LGE (P=0.52). A pronounced decrease in LV ejection fraction was associated with the presence of LGE (P<0.001), but not with increased ECV (P=0.41). CONCLUSIONS: Eight percent of patients in this clinical cohort with known or suspected heart disease had diffusely increased ECV and 60% of these lacked focal LGE findings. LV size is independently associated with increased ECV, whereas systolic dysfunction is independently associated with LGE. This image-based clinical study demonstrates that ECV-CMR provides additional information negligibly related to the results of LGE imaging, and thereby increases the diagnostic yield of CMR.

Females have higher myocardial perfusion, blood volume and extracellular volume compared to males - an adenosine stress cardiovascular magnetic resonance study.

Knowledge on sex differences in myocardial perfusion, blood volume (MBV), and extracellular volume (ECV) in healthy individuals is scarce and conflicting. Therefore, this was investigated quantitatively by cardiovascular magnetic resonance (CMR). Healthy volunteers (n = 41, 51% female) underwent CMR at 1.5 T. Quantitative MBV [%] and perfusion [ml/min/g] maps were acquired during adenosine stress and at rest following an intravenous contrast bolus (0.05 mmol/kg, gadobutrol). Native T1 maps were acquired before and during adenosine stress, and after contrast (0.2 mmol/kg) at rest and during adenosine stress, rendering rest and stress ECV maps. Compared to males, females had higher perfusion, ECV, and MBV at stress, and perfusion and ECV at rest (p < 0.01 for all). Multivariate linear regression revealed that sex and MBV were associated with perfusion (sex beta -0.31, p = 0.03; MBV beta -0.37, p = 0.01, model R2 = 0.29, p < 0.01) while sex and hematocrit were associated with ECV (sex beta -0.33, p = 0.03; hematocrit beta -0.48, p < 0.01, model R2 = 0.54, p < 0.001). Myocardial perfusion, MBV, and ECV are higher in female healthy volunteers compared to males. Sex is an independent contributor to perfusion and ECV, beyond other physiological factors that differ between the sexes. These findings provide mechanistic insight into sex differences in myocardial physiology.

Leaflet thickening and stent geometry in sutureless bioprosthetic aortic valves.

Underexpansion of transcatheter heart valves and the surgically implanted Perceval sutureless aortic valve bioprosthesis has been suggested as an underlying mechanism for hypo-attenuated leaflet thickening (HALT). This was a single-center prospective observational study that included 47 patients who underwent surgical aortic valve replacement with the Perceval sutureless bioprosthesis (LivaNova, London, United Kingdom) from 2012 to 2016 and were studied by four-dimensional cardiac computed tomography (CT). The association between overall and regional expansion and the prevalence of HALT was analyzed. In total 46 patients were included in the analysis. HALT was found in 39.1% of patients and the mean overall prosthesis expansion was 75.5 ± 5.2% (range 64.6-84.8%). Overall expansion did not differ between patients with HALT compared with patients without HALT (mean overall expansion 74.0 ± 5.2% vs. 76.5 ± 5.0%, P = 0.11). The prevalence of HALT was lower in patients with overall expansion > 80% compared to patients with expansion < 80% expansion though not significantly (20% vs. 44.4%, P = 0.16). None or trivial regional underexpansion was found in 94.7% of coronary cusps. There was no significant association between regional underexpansion and the prevalence of HALT (mean coronary cusp angle 120 ± 8° vs. 119 ± 10°, P = 0.53). The prevalence of HALT and overall underexpansion was high in the Perceval sutureless bioprosthetic valve. Overall underexpansion was not associated with HALT. Whether severe overall underexpansion increases the risk for HALT requires further study. Regional underexpansion was uncommon in the Perceval sutureless bioprosthetic valve and not associated with HALT.Clinical trial registration Unique identifier: NCT03753126 (http://www.clinicaltrials.gov).

Synthetic tracheal grafts seeded with bone marrow cells fail to generate functional tracheae: First long-term follow-up study.

OBJECTIVE: Synthetic tracheal grafts seeded with autologous bone marrow-mononuclear cells (BM-MNCs) have been described as becoming living and functional grafts representing a promising option for tracheal replacement for pathologies unamenable by segmental resection or autologous repair. This study aimed to present the first long-term follow-up of these procedures in humans. METHODS: We retrospectively analyzed 3 patients who received synthetic tracheal grafts seeded with BM-MNCs implanted. RESULTS: Patient 1 was a 37-year-old man with mucoepidermoid carcinoma, the first-ever human to receive a synthetic tracheal graft seeded with BM-MNCs. Patient 2 was a 30-year-old man with adenoid cystic carcinoma, and patient 3 was a 22-year-old woman with an iatrogenic tracheal injury. All patients developed graft-related complications necessitating multiple surgical reinterventions. Patient 1 was hospitalized for 8 months before dying from respiratory failure secondary to graft dehiscence 32 months after implantation. Patient 2 died 3.5 months after implantation from undisclosed causes. Patient 3 received a second synthetic tracheal graft after 11 months and an allogeneic trachea and lung transplantation 45 months after the primary implantation. Patient 3 underwent 191 surgical interventions after the primary implantation and spent 55 months in the intensive care unit before dying from airway bleeding. All patients' bronchoscopic, histologic, and radiologic investigations demonstrated graft-associated complications, including anastomotic fistulae and obstructive granulation tissue, without graft vascularization, mucosal lining, or integration into adjacent tissues. CONCLUSIONS: Synthetic tracheal grafts seeded with BM-MNCs do not become living functional tracheal grafts and lead to debilitating complications and death.

The relative contributions of myocardial perfusion, blood volume and extracellular volume to native T1 and native T2 at rest and during adenosine stress in normal physiology.

BACKGROUND: Both ischemic and non-ischemic heart disease can cause disturbances in the myocardial blood volume (MBV), myocardial perfusion and the myocardial extracellular volume fraction (ECV). Recent studies suggest that native myocardial T1 mapping can detect changes in MBV during adenosine stress without the use of contrast agents. Furthermore, native T2 mapping could also potentially be used to quantify changes in myocardial perfusion and/or MBV. Therefore, the aim of this study was to explore the relative contributions of myocardial perfusion, MBV and ECV to native T1 and native T2 at rest and during adenosine stress in normal physiology. METHODS: Healthy subjects (n = 41, 26 ± 5 years, 51% females) underwent 1.5 T cardiovascular magnetic resonance (CMR) scanning. Quantitative myocardial perfusion [ml/min/g] and MBV [%] maps were computed from first pass perfusion imaging at adenosine stress (140 microg/kg/min infusion) and rest following an intravenous contrast bolus (0.05 mmol/kg, gadobutrol). Native T1 and T2 maps were acquired before and during adenosine stress. T1 maps at rest and stress were also acquired following a 0.2 mmol/kg cumulative intravenous contrast dose, rendering rest and stress ECV maps [%]. Myocardial T1, T2, perfusion, MBV and ECV values were measured by delineating a region of interest in the midmural third of the myocardium. RESULTS: During adenosine stress, there was an increase in myocardial native T1, native T2, perfusion, MBV, and ECV (p ≤ 0.001 for all). Myocardial perfusion, MBV and ECV all correlated with both native T1 and native T2, respectively (R2 = 0.35 to 0.61, p < 0.001 for all). Multivariate linear regression revealed that ECV and perfusion together best explained the change in native T2 (ECV beta 0.21, p = 0.02, perfusion beta 0.66, p < 0.001, model R2 = 0.64, p < 0.001), and native T1 (ECV beta 0.50, p < 0.001, perfusion beta 0.43, p < 0.001, model R2 = 0.69, p < 0.001). CONCLUSIONS: Myocardial native T1, native T2, perfusion, MBV, and ECV all increase during adenosine stress. Changes in myocardial native T1 and T2 during adenosine stress in normal physiology can largely be explained by the combined changes in myocardial perfusion and ECV. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02723747. Registered March 16, 2016.

Variable size of aortic subvalvular pseudoaneurysm.

Aortic subvalvular pseudoaneurysms (PSA) are particularly subjected to strain and shear stress forces from blood flow and therefore their size can vary along the heart cycle. Here we describe a case of an aortic subvalvular PSA that shows significant variation in size between systolic and diastolic phase during retrospective ECG-triggered cardiac computed tomography angiography.

Hypo-Attenuated Leaflet Thickening and Reduced Leaflet Motion in Sutureless Bioprosthetic Aortic Valves.

BACKGROUND: The prevalence of hypo-attenuated leaflet thickening (HALT) and reduced leaflet motion (RLM) is unknown in surgically implanted bioprostheses because systematic investigation of HALT and/or RLM is limited to a few catheter-based valves. The aim of this study was to investigate the prevalence of HALT and RLM by cardiac computed tomography in patients who underwent surgical aortic valve replacement and received a Perceval sutureless aortic valve bioprosthesis. METHODS AND RESULTS: This was a single-center prospective observational study that included 47 patients (83.5% of the total number of implantations) who underwent surgical aortic valve replacement with implantation of the Perceval sutureless bioprosthesis (LivaNova PLC, London, UK) at Karolinska University Hospital in Stockholm, Sweden from 2012 to 2016 and were studied by cardiac computed tomography. Cardiac computed tomography was performed at a median of 491 days (range 36-1247 days) postoperatively. HALT was found in 18 (38%) patients and RLM in 13 (28%) patients. All patients with RLM had HALT. Among patients with HALT, 5 out of 18 patients (28%) were treated with anticoagulation (warfarin or any novel oral anticoagulant) at the time of cardiac computed tomography. Among patients with RLM, 3 out of 13 patients (23%) were treated with anticoagulation. CONCLUSIONS: HALT and RLM were prevalent in the surgically implanted Perceval sutureless aortic valve bioprosthesis. Both HALT and RLM were found in patients with ongoing anticoagulation treatment. Whether these findings are associated with adverse events needs further study. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02671474.

Myocardial perfusion cardiovascular magnetic resonance: optimized dual sequence and reconstruction for quantification.

BACKGROUND: Quantification of myocardial blood flow requires knowledge of the amount of contrast agent in the myocardial tissue and the arterial input function (AIF) driving the delivery of this contrast agent. Accurate quantification is challenged by the lack of linearity between the measured signal and contrast agent concentration. This work characterizes sources of non-linearity and presents a systematic approach to accurate measurements of contrast agent concentration in both blood and myocardium. METHODS: A dual sequence approach with separate pulse sequences for AIF and myocardial tissue allowed separate optimization of parameters for blood and myocardium. A systems approach to the overall design was taken to achieve linearity between signal and contrast agent concentration. Conversion of signal intensity values to contrast agent concentration was achieved through a combination of surface coil sensitivity correction, Bloch simulation based look-up table correction, and in the case of the AIF measurement, correction of T2* losses. Validation of signal correction was performed in phantoms, and values for peak AIF concentration and myocardial flow are provided for 29 normal subjects for rest and adenosine stress. RESULTS: For phantoms, the measured fits were within 5% for both AIF and myocardium. In healthy volunteers the peak [Gd] was 3.5 ± 1.2 for stress and 4.4 ± 1.2 mmol/L for rest. The T2* in the left ventricle blood pool at peak AIF was approximately 10 ms. The peak-to-valley ratio was 5.6 for the raw signal intensities without correction, and was 8.3 for the look-up-table (LUT) corrected AIF which represents approximately 48% correction. Without T2* correction the myocardial blood flow estimates are overestimated by approximately 10%. The signal-to-noise ratio of the myocardial signal at peak enhancement (1.5 T) was 17.7 ± 6.6 at stress and the peak [Gd] was 0.49 ± 0.15 mmol/L. The estimated perfusion flow was 3.9 ± 0.38 and 1.03 ± 0.19 ml/min/g using the BTEX model and 3.4 ± 0.39 and 0.95 ± 0.16 using a Fermi model, for stress and rest, respectively. CONCLUSIONS: A dual sequence for myocardial perfusion cardiovascular magnetic resonance and AIF measurement has been optimized for quantification of myocardial blood flow. A validation in phantoms was performed to confirm that the signal conversion to gadolinium concentration was linear. The proposed sequence was integrated with a fully automatic in-line solution for pixel-wise mapping of myocardial blood flow and evaluated in adenosine stress and rest studies on N = 29 normal healthy subjects. Reliable perfusion mapping was demonstrated and produced estimates with low variability.

Thoracic and abdominal aortic dimension in 70-year-old men and women--a population-based whole-body magnetic resonance imaging (MRI) study.

OBJECTIVE: The aim of this population-based study was to determine the optimal dividing-line between normal aorta and aneurysm for different aortic segments in 70-year-old men and women by means of whole-body magnetic resonance imaging. METHODS: Two hundred thirty-one subjects (116 men), randomly recruited from a population-based cohort study, were included. The smallest outer diameter (dia) was measured on the axial survey scan on six predefined aortic segments: (1) ascending aorta, (2) descending aorta, (3) supraceliac aorta, (4) suprarenal aorta, (5) largest infrarenal abdominal aorta, and (6) aortic bifurcation. Relative aortic dia were calculated by dividing a given aortic dia by the suprarenal aortic dia. The dividing-line between normal aorta and aneurysm at different aortic segments was estimated by taking the mean dia +2 SD and/or mean ratio of the aortic segment to the suprarenal aorta +2 SD. RESULTS: The mean dia of the six segments were 4.0 cm (SD 0.4), 3.2 cm (0.3), 3.0 cm (0.3), 2.8 cm (0.3), 2.4 cm (0.5), and 2.3 cm (0.3) in men. The corresponding dia in women were 3.4 cm (0.4), 2.8 cm (0.3), 2.7 cm (0.3), 2.7 cm (0.3), 2.2 cm (0.3), and 2.0 cm (0.2). The mean ratio to the suprarenal aorta was 1.4 (SD 0.2) for the ascending aorta, 1.2 (0.1) for the descending aorta, and 0.9 (0.2) for the infrarenal aorta in men. The corresponding ratios in women were 1.3 (0.2), 1.0 (0.1), and 0.8 (0.1). CONCLUSION: For men the suggested dividing-line (dia and ratio) between normal aorta and aneurysm for the ascending aorta is 4.7 cm dia and 1.8 ratio, for the descending aorta 3.7 cm dia and 1.5 ratio, and for the infrarenal aorta is 3.0 cm dia and 1.1 ratio. The corresponding dividing-lines for women are 4.2 cm dia and 1.7 ratio, 3.3 cm dia and 1.3 ratio, and 2.7 cm dia and 1.0 ratio.