The value of a new cardiac magnetic resonance imaging protocol in Myocardial Infarction with Non-obstructive Coronary Arteries (MINOCA) - a case-control study using historical controls from a previous study with similar inclusion criteria.

BACKGROUND: Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) is common with a prevalence of 6% of all patients fulfilling the diagnosis of myocardial infarction. MINOCA should be considered a working diagnosis. Cardiac Magnetic Resonance (CMR) imaging has recently been suggested to be of great value to determine the cause behind MINOCA. The objectives of this paper are to describe the rationale behind the second Stockholm Myocardial Infarction with Normal Coronaries (SMINC-2) study and to discuss the protocol for investigation of MINOCA patients in the light of the recently published position paper from the European Society of Cardiology. METHODS: The SMINC-2 study is an open non-randomised study using historical controls for comparison. The primary aim is to prove that MINOCA patients investigated with the latest CMR imaging technique can achieve a diagnosis in 70% of all cases entirely by imaging. By including 150 patients we will have >80% chance to prove that the diagnostic accuracy can be improved by 20 absolute % with a p-value of less than 0.05 when compared with CMR imaging in the SMINC-1 study. Furthermore, in addition to invasive coronary angiography, coronary arteries are evaluated by computed tomography angiography to investigate coronary causes and questionnaires are used to describe Quality-of-Life (QoL). By January 1st 2017, 75 patients have been included. DISCUSSION: Whether CMR imaging can provide a diagnosis to an adequate proportion of MINOCA patients is unknown. Well-defined inclusion and exclusion criteria will be used to compare a MINOCA cohort from the population with an appropriate control group. Positive results are likely to influence future guidelines of the management of MINOCA. Furthermore, the study will give mechanistic insights into MINOCA in particular in patients with "true" myocardial infarction and describe QoL in this vulnerable group of patients. TRIAL REGISTRATION: Clinical Trials NCT02318498 .

Therapeutic granulocyte and monocyte apheresis (GMA) for treatment refractory sarcoidosis: a pilot study of clinical effects and possible mechanisms of action.

Sarcoidosis is a systemic, inflammatory disorder, which in a proportion of patients runs a chronic progressive course despite immunosuppressive treatment. Therapeutic granulocyte and monocyte apheresis (GMA) has been shown to be an effective treatment option for other systemic inflammatory disorders, but has not yet been investigated in sarcoidosis. The aim of this study was to evaluate the response to GMA in sarcoidosis. Seven patients with sarcoidosis refractory to standard immunosuppressive therapy received 10 GMA sessions. All patients underwent chest X-ray, spirometry, a Chronic Respiratory Disease Questionnaire (CRQ-SAS), blood tests and bronchoscopy with bronchoalveolar lavage (BAL) before treatment and at 2-4 weeks and 3 months (except bronchoscopy) after the last treatment session. Bronchoalveolar lavage fluid (BALF) cell differential counts were recorded and T cells from blood and BALF were analysed for markers of activity, differentiation and T regulatory function. Compared to baseline, five of seven patients reported an improvement in dyspnoea score. In BALF there was an increase in the percentage of macrophages and a decrease in the percentage of lymphocytes and CD4(+) /FoxP3(+) T cells. Furthermore, the decrease in BALF CD4(+) /FoxP3(+) T cells correlated significantly with an improvement in dyspnoea score. In peripheral blood there was a statistically significant increase in the percentage of CD4(+) /CD27(-) T cells and a trend towards an initial increase in the percentage of CD4(+) /FoxP3(+) T cells, followed by a statistically significant decrease. The effects of GMA on regulatory T cells are consistent with those observed in other inflammatory disorders and could potentially translate into a clinical benefit.

HLA-DRB1* alleles and symptoms associated with Heerfordt's syndrome in sarcoidosis.

Heerfordt's syndrome (HS) consists in its complete form of uveitis, parotid or salivary gland enlargement and cranial nerve palsy. The objective of the present study was to analyse if there are also links between HLA-DRB1* alleles and HS, as it is a specific phenotype of sarcoidosis. 1,000 patients with sarcoidosis, out of whom 83 had symptoms associated with HS, were included in the study together with a group of 2,000 healthy individuals from the same population, matched for sex and age. HLA-DRB1* allelic groups were determined for all individuals, and comparisons were made between different disease subgroups and between patients and healthy controls. We found that the HLA-DRB1*04 allele was overrepresented in patients with symptoms associated with HS. 83 (8.3%) of all patients had one or more of the symptoms and 46 (55%) of them were HLA-DRB1*04 positive. 44 (55%) of the patients with ocular sarcoidosis, i.e. the most common symptom associated with HS, were HLA-DRB1*04 positive, compared with 35.9% of healthy controls (p=0.0008), and only 26.6% of the whole group of sarcoidosis patients (p<0.0001). HLA-DRB1*04 seems to protect against overall sarcoidosis but appears to be a significant risk factor for ocular sarcoidosis as well as for other manifestations associated with HS.

Limitations of 64-detector-row computed tomography coronary angiography: calcium and motion but not short experience.

BACKGROUND: Recently, 64-detector-row computed tomography coronary angiography (CTA) has been introduced for the noninvasive diagnosis of coronary artery disease. PURPOSE: To evaluate the diagnostic capacity and limitations of a newly established CTA service. MATERIAL AND METHODS: In 101 outpatients with suspected coronary artery disease, 64-detector-row CTA (VCT Lightspeed 64; GE Healthcare, Milwaukee, Wisc., USA) was performed before invasive coronary angiography (ICA). The presence of >50% diameter coronary stenosis on CTA was rated by two radiologists recently trained in CTA, and separately by an experienced colleague. Diagnostic performance of CTA was calculated on segment, vessel, and patient levels, using ICA as a reference. Segments with a proximal reference diameter <2 mm or with stents were not analyzed. RESULTS: In 51 of 101 patients and 121 of 1280 segments, ICA detected coronary stenosis. In 274 of 1280 (21%) segments, CTA had non-diagnostic image quality, the main reasons being severe calcifications (49%), motion artifacts associated with high or irregular heart rate (45%), and low contrast opacification (14%). Significantly more women (43%) had non-diagnostic scans compared to men (20%). A heart rate above 60 beats per minute was associated with significantly more non-diagnostic patients (38% vs. 18%). In the 1006 diagnostic segments, CTA had a sensitivity of 78%, specificity of 95%, positive predictive value (PPV) of 54%, and negative predictive value (NPV) of 98% for detecting significant coronary stenosis. In 29 patients, CTA was non-diagnostic. In the remaining 72 patients, sensitivity was 100%, specificity 65%, PPV 79%, and NPV 100%. The use of a more experienced CTA reader did not improve diagnostic performance. CONCLUSION: CTA had a very high negative predictive value, but the number of non-diagnostic scans was high, especially in women. The main limitations were motion artifacts and vessel calcifications, while short experience in CTA did not influence the interpretation.

Is training essential for interpreting cardiac computed tomography?

BACKGROUND: Cardiac computed tomography (CT) has gained increasing acceptance for diagnosing obstructive coronary artery disease (CAD). Several guidelines have been published on required education for proficiency in the interpretation of these examinations. PURPOSE: To describe the learning-curve effect of the interpretation of 100 consecutive cardiac CT examinations aimed at diagnosing CAD. The diagnostic accuracy of radiologists and radiographers was also compared. MATERIAL AND METHODS: Two radiologists and two radiographers, all with no prior experience in evaluation of cardiac CT, independently underwent a dedicated training program of 100 examinations randomized into 10 blocks (sessions), with 10 cases in each. They independently evaluated the coronary arteries regarding significant obstructive CAD. After every session, individual feedback on diagnostic accuracy and comparison with the corresponding invasive coronary angiography (currently regarded as the gold standard to detect coronary lesions) was given. The time required for interpretation was recorded. RESULTS: The mean review time decreased (P<0.0001) successively during the 10 sessions for all the observers together. The first session had a mean review time of 32 min, and the last session 16 min. No significant improvement in sensitivity, specificity, or negative predictive value (NPV) was observed. For positive predictive value (PPV), there was an improvement for the radiologists (P<0.05), but not for the radiographers. The radiographers had a higher total specificity compared to the radiologists (P<0.01). CONCLUSION: The review time for novices in cardiac CT was approximately halved during the first 100 cases, with maintained accuracy. There was a learning-curve effect in PPV for the radiologists. The diagnostic accuracy of dedicated radiographers indicates that they might be considered to be included as part of the evaluation team.

Computed tomography of the sternum and mediastinum after median sternotomy.

BACKGROUND: Computed tomography is used in our hospital to diagnose complications after median sternotomy, but its efficiency is unknown. Nor is the computed tomographic appearance of normal healing of a median sternotomy known. Computed tomography was evaluated for its ability to diagnose mediastinitis and sternal dehiscence, and a reference material of normally healing median sternotomies was created. METHODS: In a prospective study, 20 patients with a normally healing median sternotomy were examined 1 week, 1 month, 3 months, and 6 months after operation. In a retrospective study, 87 scans from 65 patients that were made because a postoperative complication was suspected were reviewed. RESULTS: In the prospective study, all patients had clinically uneventful healing. None of the computed tomographic scans showed radiologic signs of healing at 3 months. At 6 months, half of the patients had healed completely. In the retrospective study, 49 scans were performed on suspicion of infection; 7 of them indicated mediastinitis, 2 were false-positive, while mediastinitis was present in a total of 16 of the scans. Thirty-eight scans were made because of sternal pain or suspected dehiscence; after 21 of the scans, recovery was uneventful, and in 11, the definite diagnosis was dehiscence or pseudarthrosis. CONCLUSIONS: Clinical healing of the sternotomy does not correlate with the computed tomographic image. Computed tomography is not a sensitive tool for diagnosing mediastinitis, and in patients with sternal pain, it adds little information.

Haemostatic function in patients undergoing coronary artery bypass grafting: peroperative perturbations and relations to saphenous vein graft closure.

Vein graft failure remains a major problem after coronary artery bypass grafting. Occlusion in the first weeks usually is caused by thrombosis, whereas intimal hyperplasia and eventually atherosclerotic changes with superimposed thrombus formation underlie subsequent closure. The present investigation was conducted as a pilot study to examine whether perturbations of haemostatic function predispose to early saphenous vein graft occlusion after coronary artery bypass grafting. Pre- and postoperative determinations (performed on the first, third, and sixth postoperative days) of haemostatic factors and inhibitors were related to the presence of graft occlusion assessed by angiography at 3 months after surgery in 100 men undergoing elective coronary artery bypass grafting for stable angina pectoris. Occlusion of one or more vein grafts within three months of surgery occurred in 23 of the 100 patients examined. The percentage increase in plasma plasminogen activator inhibitor-1 activity on the first postoperative day was significantly higher in patients who subsequently were found to have vein graft occlusion (p<0.05). Otherwise no postoperative haemostatic measurements were found to predict early vein graft closure. A perturbed plasma plasminogen activator inhibitor-1 response to coronary artery bypass grafting tentatively could be added to the vessel-specific factors that remain the main determinants of early vein graft closure.

Improved lung function and quality of life following increased elastic recoil after lung volume reduction surgery in emphysema.

Lung volume reduction surgery for severe emphysema with removal of 20-30% of the most destroyed parts of the lung parenchyma has been reported to improve lung function substantially. Increased elastic recoil has been suggested as one underlying mechanism for the improvement. Fourteen patients, seven men and seven women with a mean age of 62 years, who underwent bilateral lung volume reduction surgery have been followed up for 3 months. We here report the data on quality of life, lung function and elastic recoil. FEV1.0 increased by a mean of 26% from 0.581 to 0.731 (P < 0.01). The mean TLC was reduced by 16% from 8.91 to 7.51 (P < 0.001). The level of hyperinflation decreased as implied by a reduction in the ratio of RV to TLC from 0.70 to 0.60 (P < 0.001). The pulmonary elastic recoil improved, with an increase in the transpulmonary pressure at maximal inspiration (PelTLC) from 0.95 kPa to 1.35 kPa (P < 0.05) and an average increase in the coefficient of retraction PelTLC/TLC) from 0.12 kPa l-1 to 0.19 kPa l-1 (P < 0.01). The resting PaO2 increased from a mean of 8.7 kPa to 9.8 kPa (P < 0.01). The patients reported a high degree of subjective improvement according to the St. George's Respiratory Questionnaire and the working capacity on a bicycle increased by 26% from a mean of 38 W to 48 W (P < 0.01). The promising short-term results of lung volume reduction surgery for severe emphysema appear to be related to improved pulmonary elastic recoil.

The impact of pleurodesis in malignant effusion on respiratory function.

Pleurodesis of malignant pleural effusion provides for a substantially better quality of life compared to onging exudation with the need for repeated evacuation of fluid. Successful pleurodesis leads to permanent cessation of fluid production as a result of the formation of fibrous adhesion between the lung and costal pleura which in theory, however, might restrict lung mobility. In patients with poor lung function, or with need for bilateral pleurodesis, the apprehension of further impairment of lung function often arises. The aim of this study was to evaluate the effects of pleurodesis on lung function. Therefore 10 patients with malignant pleurisy with very limited tumour were investigated. They were without radiological signs of tumour infiltration in the lung parenchyma, without visible tumour growth in the pleural space during thoracoscopy and had undergone a successful one-sided pleurodesis. Respiratory function tests were performed at different times, 1-102 months after pleurodesis. The assessment consisted of: static and dynamic spirometry, exercise testing with blood gas determination and radiospirometry. Spirometric values were slightly low, but in general within the reference limits. Blood gas determination showed no signs of alveolar hypoventilation. Radiospirometry showed a slight attenuation of activity in the treated lung but similar turnover of gas of the treated vs. the untreated side. The study showed that pleurodesis in malignant pleurisy has only minor impact on respiratory function.

Bronchoalveolar lavage in COPD: fluid recovery correlates with the degree of emphysema.

Bronchoscopy with bronchoalveolar lavage (BAL) is an important research tool for assessing airway inflammation in a variety of inflammatory lung diseases. In chronic obstructive pulmonary disease (COPD), BAL recovery is often low, making analysis of the recovered fluid difficult to interpret. The present authors hypothesised that the degree of emphysema may predict BAL recovery. A total of 20 COPD patients (mean age 57 yrs, range 49-69) with a median (interquartile range) forced expiratory volume in one second (FEV1) of 51 (33-69)% predicted underwent BAL. Matched "healthy" smokers and nonsmokers served as controls. Emphysema index in COPD patients was calculated on computed tomography scan as the percentage of the right lung with pixels <-950 Hounsfield units. The carbon monoxide diffusing capacity of the lung (DL,CO) was determined by the single-breath method. COPD patients had lower BAL recovery than controls. COPD patients with an emphysema index <1 had higher BAL recovery than patients with an emphysema index >1. BAL recovery correlated negatively to emphysema index and positively to DL,CO. However, no correlation was found between recovery and FEV1. In conclusion, the extent of emphysema evaluated by computed tomography-scan index and carbon monoxide diffusing capacity of the lung may predict a low bronchoalveolar lavage recovery in chronic obstructive pulmonary disease patients. These parameters may, therefore, be useful when chronic obstructive pulmonary disease patients are selected for bronchoscopy with bronchoalveloar lavage. The present study underlines the importance of careful phenotyping of chronic obstructive pulmonary disease patients.

Smoking preceded pulmonary involvement in adults with Langerhans cell histiocytosis diagnosed in childhood.

Two patients with childhood Langerhans cell histiocytosis (LCH) (aged 2 and 6 y at diagnosis) in whom pulmonary involvement was diagnosed in adulthood, 23 and 12 y later, respectively, are presented. In each patient, smoking preceded the diagnosis of pulmonary involvement by 3 y, providing further evidence that smoking is a risk factor in the development of pulmonary LCH.

Lung perfusion scintigraphy prior to lung volume reduction surgery.

PURPOSE: The aim of this study was to evaluate whether lung perfusion scintigraphy (LPS) contributes to the preoperative classification of emphysema heterogeneity in patients undergoing LVRS (lung volume reduction surgery) compared to classification based only on computed tomography (CT). MATERIAL AND METHODS: Forty-five potential candidates for LVRS were examined with CT and LPS. The distribution of emphysema within the lungs was visually classified into three categories: markedly heterogeneous, intermediately heterogeneous, or homogeneous. The results of the two imaging techniques were compared to an objective, CT-based computerized classification of heterogeneity. RESULTS: Visual evaluation of all 90 lungs resulted in 50 correct classifications based on CT, in 40 based on LPS and in 68 correct classifications based on the combination of CT and LPS. The combination was superior to CT alone (p<0.01) in classification of emphysema heterogeneity. There was no significant difference between the evaluations based on either CT or LPS. CONCLUSION: The combined information from CT and LPS are superior in assessing emphysema heterogeneity prior to LVRS.

Thin-section CT vs spiral CT in candidates for lung volume reduction surgery: a comparison based on radiologists' subjective preferences.

The aim of this study was to investigate whether high-resolution (HRCT) or spiral CT was preferred in evaluating severe emphysema in patients undergoing lung volume reduction surgery (LVRS), whether there is any difference in this regard between the cranial and caudal part of the lung, and whether the degree of emphysema has an impact on the radiologists' preference. The study was performed by letting four radiologists compare images obtained with the two techniques (film pairs) and decide which technique they preferred or if the techniques were considered as equal in evaluating emphysema. In evaluation of 188 film pairs, the HRCT images were preferred in 56 %, spiral CT in 19 % and the techniques considered as equal in 25 %. Spiral CT images were preferred more often in the caudal part of the lung and in more advanced emphysema compared with the HRCT images. The study confirms our clinical assumption that use of both CT techniques are valuable in evaluating advanced emphysema and there may be technical as well as histopathological reasons for this.

Visual classification of emphysema heterogeneity compared with objective measurements: HRCT vs spiral CT in candidates for lung volume reduction surgery.

The aim of this study was to investigate whether spiral CT is superior to high-resolution computed tomography (HRCT) in evaluating the radiological morphology of emphysema, and whether the combination of both CT techniques improves the evaluation in patients undergoing lung volume reduction surgery (LVRS). The material consisted of HRCT (with 2-mm slice thickness) and spiral CT (with 10-mm slice thickness) of 94 candidates for LVRS. Selected image pairs from these examinations were evaluated. Each image pair consisted of one image from the cranial part of the lung and one image from the caudal part. The degree of emphysema in the two images was calculated by computer. The difference between the images determined the degree of heterogeneity. Five classes of heterogeneity were defined. The study was performed by visual classification of 95 image pairs (spiral CT) and 95 image pairs (HRCT) into one of five different classes of emphysema heterogeneity. This visual classification was compared with the computer-based classification. Spiral CT was superior to HRCT with 47% correct classifications of emphysema heterogeneity compared with 40% for HRCT-based classification ( p<0.05). The combination of the techniques did not improve the evaluation (42%). Spiral CT is superior to HRCT in determining heterogeneity of emphysema visually, and should be included in the pre-operative CT evaluation of LVRS candidates.

Pulmonary abnormalities at long-term follow-up of patients with Langerhans cell histiocytosis.

BACKGROUND: In Langerhans cell histiocytosis (LCH) pulmonary involvement, which is often initially asymptomatic, may contribute to significant morbidity and mortality. To determine the long-term prognosis, a cross-sectional study was undertaken. PROCEDURE: Forty-one patients with > or = 5 years follow-up after the diagnosis of LCH were interviewed and underwent physical examination, blood tests, a chest X-ray and a high-resolution CT (HRCT) of the lungs. All patients included had been referred to the Department of Pediatrics at the Karolinska Hospital in Stockholm between July 1962 and February 1990 (median follow-up 16 years). Biopsies from all patients were reviewed and confirmed to be consistent with LCH. Information on previous clinical features including treatment and the results of chest X-rays were also collected for risk factor analysis. RESULTS: Radiographic abnormalities of the lungs (cysts and/or emphysema), found in 10/41 (24%) at follow-up, were classified into five groups according to the extent of the cysts. These patients had more often suffered from multisystem than from single-system disease (P = 0.01), were significantly older at diagnosis (P < 0.001), and had been more heavily treated with chemotherapy and/or radiotherapy. They were also more frequently smokers (P < 0.0001) and 7/10 (70%) had suffered lung involvement at diagnosis. At the time of diagnosis of the pulmonary involvement, 4/10 (40%) patients had respiratory symptoms, but only 2/10 (20%) had symptoms at follow-up. CONCLUSIONS: Ten (24%) of the 41 patients had abnormal findings on radiological examination of the lungs at long-term follow-up and seven are or had been smokers. It is of great importance that patients with LCH be informed about smoking-related pulmonary morbidity. Prolonged monitoring of the lungs for smokers and patients with known pulmonary involvement is recommended.