Probing the intravascular and interstitial compartments of remodeled myocardium in heart failure patients with preserved and reduced ejection fraction: a CMR study.

Recent autopsy studies found microvascular rarefaction in remodeled myocardium of patients who died of heart failure with preserved ejection-fraction (HFpEF). This condition has not been investigated so far by non-invasive methods in patients with HFpEF. The aim was to quantify the intravascular volume (IVV) compartment by CMR in HFpEF patients. In two separate CMR examinations, HFpEF patients (n = 6; 12 examinations) and post-myocardial infarction patients (post-MI; n = 6; 12 examinations) were studied with T <sub>1</sub> -mapping (MOLLI-sequence) before and after IV bolus of 0.03 mmol/Kg of the intravascular contrast-medium (CM) Gadofosveset and 0.2 mmol/Kg of the extravascular CM Gadobutrol yielding IVV and extracellular volume (ECV), respectively. Healthy controls (n = 10 with Gadofosveset only, n = 10 with Gadobutrol only) were also studied with the same protocol. IVV and ECV were measured in the basal septum (without ischemic scar in post-MI patients). In post-MI patients, ECV and IVV were also measured in the ischemic scar. Left ventricular (LV) volumes, mass, and ejection-fraction were measured by standard protocol. LV global longitudinal strain (GLS) was calculated by feature tracking on long-axis cine acquisitions. LV mass to end-diastolic volume ratio and GLS in HFpEF were higher and lower, respectively, than in healthy controls and post-MI patients, whereas the post-MI patients showed lower LV ejection-fraction. Compared to healthy myocardium of controls, IVV in scar was reduced (0.135 ± 0.018 vs 0.109 ± 0.008, respectively, p = 0.005), while ECV was increased (0.244 ± 0.037 vs 0.698 ± 0.106, respectively, p < 0.001). However, IVV did not differ among HFpEF, post-MI, and healthy controls (0.155 ± 0.033, 0.146 ± 0.038, and 0.135 ± 0.018, respectively, p = 0.413), whereas ECV was higher in HFpEF than in post-MI and healthy controls (0.304 ± 0.159, 0.270 ± 0.017, and 0.244 ± 0.037, respectively, p = 0.003). The T <sub>1</sub> -mapping technique combined with an intravascular CM shows potential to measure IVV. In infarct scar with substantially increased ECV, IVV was significantly reduced. Unlike in infarct scar, in remodeled myocardium of HFpEF patients, increased ECV was not accompanied by a reduction of IVV

Fetal cardiac cine magnetic resonance imaging in utero.

Fast magnetic resonance imaging (MRI) led to the emergence of 'cine MRI' techniques, which enable the visualization of the beating heart and the assessment of cardiac morphology and dynamics. However, established cine MRI methods are not suitable for fetal heart imaging in utero, where anatomical structures are considerably smaller and recording an electrocardiogram signal for synchronizing MRI data acquisition is difficult. Here we present a framework to overcome these challenges. We use methods for image acquisition and reconstruction that robustly produce images with sufficient spatial and temporal resolution to detect the heart contractions of the fetus, enabling a retrospective gating of the images and thus the generation of images of the beating heart. To underline the potential of our approach, we acquired in utero images in six pregnant patients and compared these with their echocardiograms. We found good agreement in terms of diameter and area measurements, and low inter- and intra- observer variability. These results establish MRI as a reliable modality for fetal cardiac imaging, with a substantial potential for prenatal evaluation of congenital heart defects

A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics

The European Lung Cancer Working Party (ELCWP) designed a 3-arm phase III randomised trial to determine the role of accelerated chemotherapy in extensive-disease (ED) small-cell lung cancer (SCLC). Eligible patients were randomised between the 3 following arms: (A) Standard chemotherapy with 6 courses of EVI (epirubicin 60 mg m−2, vindesine 3 mg m−2, ifosfamide 5 g m−2; all drugs given on day 1 repeated every three weeks. (B) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support. (C) Accelerated chemotherapy with EVI and oral antibiotics (cotrimoxazole). Primary endpoint was survival. 233 eligible patients were randomised. Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity. Best response rates, in the population of evaluable patients, were, respectively for arm A, B and C, 59%, 76% and 70%. The response rate was significantly higher in arm B in comparison to arm A (P = 0.04). There was, however, no survival difference with respective median duration and 2-year rate of 286 days and 5% for arm A, 264 days and 6% for arm B and 264 days and 6% for arm C. Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding. Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C. Our trial failed to demonstrate, in ED-SCLC, a survival benefit of chemotherapy acceleration by using GM-CSF support.   http://www.bjcancer.co

Second-line paclitaxel in non-small cell lung cancer initially treated with cisplatin: a study by the European Lung Cancer Working Party

In the context of a phase III trial comparing in advanced non-small cell lung cancer (NSCLC) sequential to conventional administration of cisplatin-based chemotherapy and paclitaxel, we evaluated the activity of paclitaxel as second-line chemotherapy and investigated any relation of its efficacy with the type of failure after cisplatin. Patients received three courses of induction GIP (gemcitabine, ifosfamide, cisplatin). Non-progressing patients were randomised between three further courses of GIP or three courses of paclitaxel. Second-line paclitaxel was given to patients with primary failure (PF) to GIP and to those progressing after randomisation to further GIP (secondary failure or SF). One hundred sixty patients received second-line paclitaxel. Response rates were 7.7% for PF and 11.6% for SF (P=0.42). Median survival times (calculated from paclitaxel start) were 4.1 and 7.1 months for PF and SF (P=0.002). In multivariate analysis, three variables were independently associated with better survival: SF (hazard ratio (HR)=1.55, 95% confidence interval (CI) 1.08–2.22; P=0.02), normal haemoglobin level (HR=1.56, 95% CI 1.08–2.26; P=0.02) and minimal weight loss (HR=1.79, 95% CI 1.26–2.55; P=0.001). Paclitaxel in NSCLC patients, whether given for primary or for SF after cisplatin-based chemotherapy, demonstrates activity similar to other drugs considered active as second-line therapy

European Lung Cancer Working Party Clinical Practice Guidelines. Small Cell Lung Cnacer: IV. Limited disease

The present guidelines on the management of limited disease small cell lung cancer (SCLC) were formulated by the ELCWP in April 2007. They are designed to answer the following seven questions: 1) What is the definition of limited disease? 2) Should chest radiotherapy be provided and what are the benefits? 3) What is the optimal timing and mode of administration of chest irradiation? 4) Which are the optimal radiotherapy parameters: dose, fractionation, target volume? 5) What is the optimal chemotherapy regimen for limited disease SCLC? 6) Should prophylactic cranial irradiation be provided, when and for which patients? 7) What is the additional role of thoracic surgery in early SCLC

European Lung Cancer Working Party. Clinical Practice Guidelines. Small Cell Lung Cancer: V. Extensive disease

The present guidelines on the management of extensive disease small cell lung cancer (SCLC) were formulated by the ELCWP in October 2007. They are designed to answer the following nine questions: 1) What is the definition of extensive disease? 2)What are the active drugs? 3) What is the best induction regimen? 4) Is there a role for maintenance chemotherapy? 5) Is there a role for dose-intensive chemotherapy? 6) Is there a role for the use of haemopoietic growth factors and stem cells support? 7) Is there a role for alternating or sequential chemotherapy? 8) Is there a role for biological treatments? 9) Is there a place for second-line chemotherapy

European Lung Cancer Working Party Clinical Practice Guidelines. Non-Small Cell Lung Cancer: III. Metastatic disease

The present guidelines on the management of advanced non-small cell lung cancer (NS CLC) were formulated by the ELCWP in October 2006. They are designed to answer the following twelve questions: 1) What benefits can be expected from chemotherapy and what are the treatment objectives? 2) What are the active chemotherapeutic drugs for which efficacy has been shown? 3) Which are the most effective platinum-based regimens? 4) Which is the indicated dosage of cisplatin? 5) Can carboplatin be substituted for cisplatin? 6) Which is the optimal number of cycles to be administered? 7) Can non-platinum based regimens be substituted for platinum based chemotherapy as first-line treatment? 8) Is there an indication for sequential chemotherapy? 9) What is the efficacy of salvage chemotherapy and which drugs should be used in that indication? 10) What is the place of targeted therapies? 11) What is the place of chemotherapy in the management of a patient with brain metastases? 12) Which specific drugs can be used for the patient with bone metastases

Head-to-head comparison of multiple cardiovascular magnetic resonance techniques for the detection and quantification of intramyocardial haemorrhage in patients with ST-elevation myocardial infarction.

T2*-weighted (T2*w) is deemed as a reference standard for post-infarction intramyocardial haemorrhage (IMH). However, high proportion of T2* images is affected by off-resonance artefacts hampering image interpretation. Diagnostic accuracy and precision of alternative techniques for IMH diagnosis and quantification have been seldomly investigated. Between April 2016 and May 2017, 50 ST-segment elevation myocardial infarction patients (66% male, 57 ± 17 years) and 15 healthy controls (60% male, 58 ± 13) were consecutively enrolled. Subjects underwent head-to-head comparison of single mid-infarct slice acquired on black-blood T2-weighted short-TI-inversion recovery (T2w-STIR), bright-blood T2prep-steady-state-free precession (T2prep-SSFP), and T2/T1 maps for IMH diagnosis and quantification against T2*w. All images were graded for quality (grade 1: very poor; grade 4: excellent) and diagnostic confidence (Likert scale, 1: very unsure and 5: highly confident). Reduced relaxation time/hypointense region (hypocore) embedded in infarct-related oedema on T2 map, T1 map, and T2w-STIR had the best overall diagnostic accuracy (per-subject: 91%, 86%, and 86%, respectively; per segment: 95%, 93%, and 93%, respectively). By mixed-effects analysis, image quality, and diagnostic confidence were higher for T2 map and T1 maps than T2*w (p < 0.05 for both scores). For IMH quantification, hypocore on T2 map and T1 map strongly correlated (Spearman's r > 0.7, p < 0.001 for both) with IMH extent on T2*w and presented an overall excellent agreement on Bland-Altman analysis. By linear mixed model analysis, absolute hypocore size did not differ among T1-, T2 map, and T2*w. T2/T1 maps had the best intra- and inter-observer reproducibility among CMR techniques. Hypocore on T2/T1 map is the best alternative technique to T2*w for diagnosing and quantifying IMH in post-STEMI patients. • Mapping techniques are the best alternatives for diagnosing post-infarction intramyocardial haemorrhage. • Mapping techniques are valuable tools for imaging intramyocardial haemorrhage