Saeed Mirsadraee

Ultrasmall superparamagnetic particles of iron oxide in patients with acute myocardial infarction: early clinical experience.

Background—Inflammation following acute myocardial infarction (MI) has detrimental effects on reperfusion, myocardial remodelling, and ventricular function. Magnetic resonance imaging using ultrasmall superparamagnetic particles of iron oxide can detect cellular inflammation in tissues, and we therefore explored their role in acute MI in humans. Methods and Results—Sixteen patients with acute ST-segment elevation MI were recruited to undergo 3 sequential magnetic resonance scans within 5 days of admission at baseline, 24 and 48 hours following no infusion (controls; n=6) or intravenous infusion of ultrasmall superparamagnetic particles of iron oxide (n=10; 4 mg/kg). T2*-weighted multigradient-echo sequences were acquired and R2* values were calculated for specific regions of interest. In the control group, R2* values remained constant in all tissues across all scans with excellent repeatability (bias of −0.208 s−1, coefficient of repeatability of 26.96 s−1; intraclass coefficient 0.989). Consistent with uptake by the reticuloendothelial system, R2* value increased in the liver (84±49.5 to 319±70.0 s−1; P<0.001) but was unchanged in skeletal muscle (54±8.4 to 67.0±9.5 s−1; P>0.05) 24 hours after administration of ultrasmall superparamagnetic particles of iron oxide. In the myocardial infarct, R2* value increased from 41.0±12.0 s−1 (baseline) to 155±45.0 s−1 (P<0.001) and 124±35.0 s−1 (P<0.05) at 24 and 48 hours, respectively. A similar but lower magnitude response was seen in the remote myocardium, where it increased from 39±3.2 s−1 (baseline) to 80±14.9 s−1 (P<0.001) and 67.0±15.7 s−1 (P<0.05) at 24 and 48 hours, respectively. Conclusions—Following acute MI, uptake of ultrasmall superparamagnetic particles of iron oxide occurs with the infarcted and remote myocardium. This technique holds major promise as a potential method for assessing cellular myocardial inflammation and left ventricular remodelling, which may have a range of applications in patients with MI and other inflammatory cardiac conditions. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01323296.

MRI of the lung (3/3)—current applications and future perspectives

AbstractBackgroundMRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women.MethodsProvided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value.ResultsIn interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a “buffet” of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice.ConclusionNew developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed. Main Messages • MRI evolves as a third lung imaging modality, combining morphological and functional information.• It may be considered first choice in cystic fibrosis and pulmonary embolism of young and pregnant patients.• In other cases (tumours, pneumonia in children), it is an alternative or adjunct to X-ray and CT.• In interstitial lung disease, it serves for research, but the clinical value remains to be proven.• New users are advised to make themselves familiar with the particular advantages and limitations.

Aortic stenosis, atherosclerosis, and skeletal bone: is there a common link with calcification and inflammation?

AIMS The pathophysiology of aortic stenosis shares many similarities with atherosclerosis and skeletal bone formation. Using non-invasive imaging, we compared aortic valve calcification and inflammation activity with that measured in atherosclerosis and bone. METHODS AND RESULTS Positron emission and computed tomography was performed using 18F-sodium fluoride (18F-NaF, calcification) and 18F-fluorodeoxyglucose (18F-FDG, inflammation) in 101 patients with calcific aortic valve disease (81 aortic stenosis and 20 aortic sclerosis). Calcium scores and positron emission tomography tracer activity (tissue-to-background ratio; TBR) were measured in the aortic valve, coronary arteries, thoracic aorta, and bone. Over 90% of the cohort had coexistent calcific atheroma, yet correlations between calcium scores were weak or absent (valve vs. aorta r(2) = 0.015, P = 0.222; valve vs. coronaries r(2) = 0.039, P = 0.049) as were associations between calcium scores and bone mineral density (BMD vs. valve r(2) = 0.000, P = 0.766; vs. aorta r(2) = 0.052, P = 0.025; vs. coronaries r(2) = 0.016, P = 0.210). 18F-NaF activity in the valve was 28% higher than in the aorta (TBR: 2.66 ± 0.84 vs. 2.11 ± 0.31, respectively, P < 0.001) and correlated more strongly with the severity of aortic stenosis (r(2) = 0.419, P < 0.001) than 18F-NaF activity outwith the valve (valve vs. aorta r(2) = 0.167, P < 0.001; valve vs. coronary arteries r(2) = 0.174, P < 0.001; valve vs. bone r(2) = 0.001, P = 0.806). In contrast, 18F-FDG activity was lower in the aortic valve than the aortic atheroma (TBR: 1.56 ± 0.21 vs. 1.81 ± 0.24, respectively, P < 0.001) and more closely associated with uptake outwith the valve (valve vs. aorta r(2) = 0.327, P < 0.001). CONCLUSION In patients with aortic stenosis, disease activity appears to be determined by local calcific processes within the valve that are distinct from atherosclerosis and skeletal bone metabolism.

Optimization and comparison of myocardial T1 techniques at 3T in patients with aortic stenosis

Aims To determine the optimal T1 mapping approach to assess myocardial fibrosis at 3T. Methods and results T1 mapping was performed at 3T using the modified look-locker-inversion sequence in 20 healthy volunteers and 20 patients with aortic stenosis (AS). Pre- and post-contrast myocardial T1, the partition coefficient (λ; ΔRmyocardium/ΔRblood, where ΔR = 1/post-contrast T1 − 1/pre-contrast T1), and extracellular volume fraction [ECV; λ (1 − haematocrit)] were assessed. After establishing the optimal time point and myocardial region for analysis, we compared the reproducibility of these T1 measures and their ability to differentiate asymptomatic patients with AS from healthy volunteers. There was no segmental variation across the ventricle in any of the T1 measures evaluated. λ and ECV did not vary with time, while post-contrast T1 was relatively constant between 15 and 30 min. Thus, mid-cavity myocardium at 20 min was used for subsequent analyses. ECV displayed excellent intra-, inter-observer, and scan–rescan reproducibility [intra-class correlation coefficients (ICC) 1.00, 0.97, and 0.96, respectively], as did λ (ICC 0.99, 0.94, 0.93, respectively). Moreover, ECV and λ were both higher in patients with AS compared with controls (ECV 28.3 ± 1.7 vs. 26.0 ± 1.6%, P < 0.001; λ 0.46 ± 0.03 vs. 0.44 ± 0.03, P = 0.02), with the former offering improved differentiation. In comparison, scan–rescan reproducibilities for pre- and post-contrast myocardial T1 were only modest (ICC 0.72 and 0.56) with no differences in values observed between cases and controls (both P> 0.05). Conclusions ECV appears to be the most promising measure of diffuse myocardial fibrosis at 3T based upon its superior reproducibility and ability to differentiate disease from health.

Embolization for non-variceal upper gastrointestinal tract haemorrhage: A systematic review

AIM To assess the published evidence on the endovascular treatment of non-variceal upper gastrointestinal haemorrhage. MATERIALS AND METHODS An Ovid Medline search of published literature was performed (1966-2009). Non-English literature, experimental studies, variceal haemorrhage and case series with fewer than five patients were excluded. The search yielded 1888 abstracts. Thirty-five articles were selected for final analysis. RESULTS The total number of pooled patients was 927. The technical and clinical success of embolization ranged from 52-100% and 44-100%, respectively. The pooled mean technical/clinical success rate in primary upper gastrointestinal tract haemorrhage (PUGITH) only, trans-papillary haemorrhage (TPH) only, and mixed studies were 84%/67%, 93%/89%, and 93%/64%, respectively. Clinical outcome was adversely affected by multi-organ failure, shock, corticosteroids, transfusion, and coagulopathy. The anatomical source of haemorrhage and procedural variables did not affect the outcome. A successful embolization improved survival by 13.3 times. Retrospective comparison with surgery demonstrated equivalent mortality and clinical success, despite embolization being applied to a more elderly population with a higher prevalence of co-morbidities. CONCLUSIONS Embolization is effective in this very difficult cohort of patients with outcomes similar to surgery.

A clinical risk score of myocardial fibrosis predicts adverse outcomes in aortic stenosis

Abstract Aims Midwall myocardial fibrosis on cardiovascular magnetic resonance (CMR) is a marker of early ventricular decompensation and adverse outcomes in aortic stenosis (AS). We aimed to develop and validate a novel clinical score using variables associated with midwall fibrosis. Methods and results One hundred forty-seven patients (peak aortic velocity (Vmax) 3.9 [3.2,4.4] m/s) underwent CMR to determine midwall fibrosis (CMR cohort). Routine clinical variables that demonstrated significant association with midwall fibrosis were included in a multivariate logistic score. We validated the prognostic value of the score in two separate outcome cohorts of asymptomatic patients (internal: n = 127, follow-up 10.3 [5.7,11.2] years; external: n = 289, follow-up 2.6 [1.6,4.5] years). Primary outcome was a composite of AS-related events (cardiovascular death, heart failure, and new angina, dyspnoea, or syncope). The final score consisted of age, sex, Vmax, high-sensitivity troponin I concentration, and electrocardiographic strain pattern [c-statistic 0.85 (95% confidence interval 0.78–0.91), P < 0.001; Hosmer–Lemeshow χ2 = 7.33, P = 0.50]. Patients in the outcome cohorts were classified according to the sensitivity and specificity of this score (both at 98%): low risk (probability score <7%), intermediate risk (7–57%), and high risk (>57%). In the internal outcome cohort, AS-related event rates were >10-fold higher in high-risk patients compared with those at low risk (23.9 vs. 2.1 events/100 patient-years, respectively; log rank P < 0.001). Similar findings were observed in the external outcome cohort (31.6 vs. 4.6 events/100 patient-years, respectively; log rank P < 0.001). Conclusion We propose a clinical score that predicts adverse outcomes in asymptomatic AS patients and potentially identifies high-risk patients who may benefit from early valve replacement.

Impact of the introduction of integrated PET-CT into the preoperative staging pathway of patients with potentially operable oesophageal carcinoma

AIM To retrospectively evaluate the role of integrated positron emission tomography computed tomography (PET-CT) in oesophageal carcinoma staging, in predicting prognosis and its influence on surgical management. MATERIALS AND METHODS Twenty-five consecutive patients with potentially operable, biopsy-proven oesophageal malignancy who undergoing PET-CT from September 2004 to April 2007 were included in this study. Chi-square and Fishers exact tests were used to compare the accuracy of N staging with PET-CT and CT/endoscopic ultrasound (EUS) using postoperative loco-regional nodal histology as the reference standard. The prognostic value of primary tumour maximum standardized uptake value (SUVmax) was derived using logistic regression. RESULTS Seventeen men and eight women with a mean age of 62 years were studied. All tumours showed abnormal 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) uptake. Fifteen patients underwent surgical resection. There was high concordance between N staging at CT/EUS (14/15) and final histology. PET-CT N staging was discordant with final nodal histology in over half of the patients (8/15). PET-CT detected occult metastases in three patients (12%) that were not identified on CT and new synchronous tumours in two patients (8%). Patient management was altered in 10 patients (40%) as a direct result of PET-CT. No statistically significant association was observed between SUVmax and clinical outcome (p=0.65). CONCLUSION Integrated PET-CT has a significant incremental value over conventional staging investigations mainly in the detection of distant metastases and synchronous tumours and frequently impacts on patient management.

Assessing and addressing cardiovascular risk in adults with Turner syndrome

Turner syndrome (TS), the result of a structurally abnormal or absent X chromosome, occurs in one in 2 000 live born females. The phenotype is highly variable, but short stature and gonadal dysgenesis are usually present. The main objective in adults with TS is health surveillance, but TS still causes a reduction in life expectancy of up to 13 years, with cardiovascular disease, congenital or acquired, as the major cause of an early death. While it has been established that all women with TS should undergo in‐depth cardiovascular examination at diagnosis, advice on the cardiovascular management of women with TS is limited. Here, we provide a summary of our current practice within a multidisciplinary team, supported by our expertise in various aspects of cardiovascular risk management, and the evidence from research where it is available, with the aim of providing optimal support to our patients with TS.

Iterative reconstruction and individualized automatic tube current selection reduce radiation dose while maintaining image quality in 320-multidetector computed tomography coronary angiography

Aim To assess the effect of two iterative reconstruction algorithms (AIDR and AIDR3D) and individualized automatic tube current selection on radiation dose and image quality in computed tomography coronary angiography (CTCA). Materials and methods In a single-centre cohort study, 942 patients underwent electrocardiogram-gated CTCA using a 320-multidetector CT system. Images from group 1 (n = 228) were reconstructed with a filtered back projection algorithm (Quantum Denoising Software, QDS+). Iterative reconstruction was used for group 2 (AIDR, n = 379) and group 3 (AIDR3D, n = 335). Tube current was selected based on body mass index (BMI) for groups 1 and 2, and selected automatically based on scout image attenuation for group 3. Subjective image quality was graded on a four-point scale (1 = excellent, 4 = non-diagnostic). Results There were no differences in age (p = 0.975), body mass index (p = 0.435), or heart rate (p = 0.746) between the groups. Image quality improved with iterative reconstruction and automatic tube current selection [1.3 (95% confidence intervals (CI): 1.2–1.4), 1.2 (1.1–1.2) and 1.1 (1–1.2) respectively; p < 0.001] and radiation dose decreased [274 (260–290), 242 (230–253) and 168 (156–180) mGy cm, respectively; p < 0.001]. Conclusion The application of the latest iterative reconstruction algorithm and individualized automatic tube current selection can substantially reduce radiation dose whilst improving image quality in CTCA.

Effect of Two Different Bypass Techniques on the Serum Troponin-T Levels in Newborns and Children Does pH-Stat Provide Better Protection?

Background—Cardiac troponin-T is a sensitive marker of myocardial damage. In a prospective study, the effect of 2 different pH strategies during cardiopulmonary bypass on ischemic myocardial injury and clinical outcome was measured in a pediatric population. Methods and Results—One hundred one patients (31 neonates 13.2±8.3 days and 70 children 34.5±44.1 months of age) undergoing open-heart surgery were selected to either &agr;-stat (n=51) or pH-stat (n=50) acid-based management protocol. Serum troponin-T levels were measured before and 30 minutes after bypass and then 4 and 24 hours postoperatively. Surgical procedure, bypass details, inotropic support requirement, and postoperative recovery were recorded. Baseline troponin-T level was higher in neonates than in children (0.18±0.22 versus 0.04±0.05 &mgr;g/L, P =0.02). Also, a higher baseline level was found in patients with pulmonary hypertension (0.13±0.21 versus 0.04±0.05 &mgr;g/L, P =0.04). Cyanotic children showed a higher peak troponin-T level (3.76±3.11 versus 1.67±1.33 &mgr;g/L, P =0.04). Peak troponin levels showed a correlation with the length of circulatory arrest and aortic cross-clamp time. Postoperative levels remained high at 24 hours in patients requiring inotropic support. Peak troponin-T levels were significantly lower in the pH-stat group in patients with pulmonary hypertension (P =0.03) and in cases where circulatory arrest (P =0.01) or inotropic support (P =0.01) was necessary during operation than in those with &agr;-stat technique. Postoperative ventilation time and length of intensive care unit stay were also significantly longer with &agr;-stat than with pH-stat technique (P =0.005 and P =0.006, respectively). Conclusions—Cardiac troponin-T sensitively reflects myocardial damage in children. Our results suggest that pH-stat acid-based management protocol may provide better protection against ischemic myocardial damage than &agr;-stat technique.