Core Muscle Size Predicts Postoperative Outcome in Lung Transplant Candidates.

BACKGROUND: Careful patient selection is the prerequisite to raise transplant benefit. In lung transplant (LT) candidates, the effect of body mass index (BMI) on postoperative outcome remains controversial, possibly due to the inaccuracy of BMI in discriminating between fat and muscle mass. We therefore hypothesized that assessment of body composition by muscle mass measures is more accurate than by BMI regarding postoperative outcome. METHODS: All LT recipients from 2011 to 2014 were included and retrospectively analyzed. Lean psoas area (LPA) was assessed from pretransplant computed tomography scans, and associations with postoperative outcomes were investigated. RESULTS: Included were 103 consecutive LT recipients with a mean pre-LT BMI of 22.0 ± 4.0 kg/m(2) and a mean LPA of 22.3 ± 8.3 cm(2). LPA was inversely associated with length of mechanical ventilation (p = 0.03), requirement of tracheostomy (p = 0.035), and length of stay in the intensive care unit (p = 0.02), while controlling for underlying disease, BMI, sex, age, and procedure; in contrast, BMI was not (p = 0.25, p = 0.54, and p = 0.42, respectively.). Multiple regression analysis revealed that the 6-minute walk distance at the end of pulmonary rehabilitation was significantly associated with LPA (p = 0.02). CONCLUSIONS: LPA can easily be assessed in LT candidates as part of pretransplant evaluation and was significantly associated with short-term outcome, whereas BMI was not. Assessment of LPA may provide additional information on body composition beyond BMI. However, the clinical utility has to be further evaluated.

Independent prognostic value of MRI beyond existing methods of determining cardiovascular risk - is there a role?

Imaging is a highly attractive option for improved risk stratification, as it allows direct detection and quantification of subclinical and clinical disease burden. Among available imaging techniques, MRI may be particularly suited for comprehensive cardiovascular risk assessment given its non-ionizing nature and high soft-tissue contrast. In this editorial, the authors review the emerging evidence in different clinical scenarios, indicating the incremental role of MRI for determining risk for future cardiovascular events.

Reproducibility of area at risk assessment in acute myocardial infarction by T1- and T2-mapping sequences in cardiac magnetic resonance imaging in comparison to Tc99m-sestamibi SPECT.

Area at risk (AAR) is an important parameter for the assessment of the salvage area after revascularization in acute myocardial infarction (AMI). By combining AAR assessment by T2-weighted imaging and scar quantification by late gadolinium enhancement imaging cardiovascular magnetic resonance (CMR) offers a promising alternative to the "classical" modality of Tc99m-sestamibi single photon emission tomography (SPECT). Current T2 weighted sequences for edema imaging in CMR are limited by low contrast to noise ratios and motion artifacts. During the last years novel CMR imaging techniques for quantification of acute myocardial injury, particularly the T1-mapping and T2-mapping, have attracted rising attention. But no direct comparison between the different sequences in the setting of AMI or a validation against SPECT has been reported so far. We analyzed 14 patients undergoing primary coronary revascularization in AMI in whom both a pre-intervention Tc99m-sestamibi-SPECT and CMR imaging at a median of 3.4 (interquartile range 3.3-3.6) days after the acute event were performed. Size of AAR was measured by three different non-contrast CMR techniques on corresponding short axis slices: T2-weighted, fat-suppressed turbospin echo sequence (TSE), T2-mapping from T2-prepared balanced steady state free precession sequences (T2-MAP) and T1-mapping from modified look locker inversion recovery (MOLLI) sequences. For each CMR sequence, the AAR was quantified by appropriate methods (absolute values for mapping sequences, comparison with remote myocardium for other sequences) and correlated with Tc99m-sestamibi-SPECT. All measurements were performed on a 1.5 Tesla scanner. The size of the AAR assessed by CMR was 28.7 ± 20.9 % of left ventricular myocardial volume (%LV) for TSE, 45.8 ± 16.6 %LV for T2-MAP, and 40.1 ± 14.4 %LV for MOLLI. AAR assessed by SPECT measured 41.6 ± 20.7 %LV. Correlation analysis revealed best correlation with SPECT for T2-MAP at a T2-threshold of 60 ms (ms) (slope = 0.99, Pearson's r = 0.94), and for MOLLI at T1-threshold of 1,075 ms (slope 0.86, r = 0.91, Pearson's r = 0.45). For the assessment of AAR in AMI, the novel T2-mapping technique correlates best with SPECT size, T1-mapping with MOLLI and standard T2-weighted imaging showed similar good correlations.

Prognostic value of late gadolinium enhancement in cardiovascular magnetic resonance imaging after acute ST-elevation myocardial infarction in comparison with single-photon emission tomography using Tc99m-Sestamibi.

BACKGROUND: Infarct size is an important predictor of cardiac risk after acute myocardial infarction. The established modality for its assessment is Tc99m-Sestamibi Single-photon emission computed tomography (SPECT). In recent years, data are emerging demonstrating that scar size as assessed by late gadolinium enhancement in cardiovascular magnetic resonance imaging (CMR) as well as the presence of microvascular obstruction (MO) may also provide prognostic information, however, so far no direct comparisons of both modalities have been reported. METHODS: We retrospectively analysed patients (n = 281) with acute ST-elevation myocardial infarction and primary angioplasty who underwent Tc99m-Sestamibi-SPECT and CMR on a 1.5 T scanner at a median of 4.3 (IQR: 3.7-5.1) and 4.9 (IQR: 4.1-5.9) days after the acute event, respectively. The primary endpoint of the study was a composite of all-cause mortality, recurrent myocardial infarction and congestive heart failure requiring hospitalization. RESULTS: During a median follow-up of 3.0 (IQR: 2.0-4.5) years, 24 events occurred. The best predictor was MO (P < 0.0001), followed by infarct size by CMR (P = 0.0043) and infarct size by SPECT (P = 0.012) (all P-values corrected for clinical risk). In a multivariate model including clinical and periprocedural parameters, MO remained the only significant predictor in addition to clinical risk. CONCLUSIONS: The extent of MO as determined by CMR has an excellent prognostic value in predicting cardiac events following acute myocardial infarction and may be used as an alternative to infarct size assessment by Tc99m-Sestamibi-SPECT.

Gender differences in contrast-enhanced magnetic resonance imaging after acute myocardial infarction.

Besides different risk profiles for cardiovascular events in men and women, several studies reported gender differences in mortality after acute myocardial infarction (AMI). As infarct size has been shown to correlate with mortality, it is widely accepted as surrogate marker for clinical outcome. Currently, cardiovascular imaging studies covering the issue of gender differences are rare. As magnetic resonance scar characterization parameters are emerging as additional prognostic factors after acute myocardial infarction, we sought to evaluate gender differences in CMR infarct characteristics in patients after acute myocardial infarction. We prospectively analyzed patients (n = 448) with AMI and primary angioplasty, who underwent contrast-enhanced cardiac magnetic resonance (CMR) imaging on a 1.5 T scanner in median 5 [4, 6] days after the acute event. [corrected]. CMR scar size was measured 15 min after gadolinium injection. In addition presence and extent of microvascular obstruction (MVO) was assessed. A matched pair analysis was performed in order to exclude confounding by gender related co-morbidities and gender differences in established clinical risk factors. Matching process according to clinical risk defined by GRACE score resulted in 93 mixed gender couples. Women were significantly older than men (64.4 ± 11.9 vs. 60.5 ± 12.3, p = 0.03) and presented with a significantly better ejection fraction before angioplasty (48.9 ± 8.4 vs. 46.2 ± 8.9, p = 0.04). Infarct size did not differ significantly between women and men (13.5 ± 10.7 vs. 15.1 ± 11.8, p = 0.32). Size of MVO was significantly smaller in women than in men (0.48 ± 1.3 vs. 1.2 ± 3.0, p = 0.03). Comparing scar characterization between women and men with similar risk profiles revealed no gender differences in scar size. Size of MVO, however, was significantly smaller in women and might reflect better cardioprotective mechanisms in women. Whether these changes have prognostic implications has to be tested on a larger patient population.

The assessment of area at risk and myocardial salvage after coronary revascularization in acute myocardial infarction: comparison between CMR and SPECT.

OBJECTIVES: This study sought to compare cardiac magnetic resonance (CMR) and single-photon emission computed tomography (SPECT) for assessment of area at risk, scar size, and salvage area after coronary reperfusion in acute myocardial infarction. BACKGROUND: Myocardial salvage is an important surrogate endpoint assessing the success of coronary reperfusion in acute myocardial infarction. SPECT, the established modality for assessment of myocardial salvage, requires radiopharmaceutical injection before revascularization and 2 examinations. The combination of T2 and late enhancement imaging in CMR can assess myocardial salvage in 1 examination, but up to now, data comparing both modalities are very limited. METHODS: We analyzed 207 patients who were treated by primary revascularization in acute myocardial infarction and who underwent both SPECT and CMR for assessment of myocardial salvage. In CMR, T2-weighted turbo spin echo sequences for area at risk and contrast-enhanced inversion recovery gradient echo sequences were performed. RESULTS: Image quality was insufficient in 27 patients (13%). In the remaining 180 patients, mean area at risk was 29.4 ± 18.7% of the left ventricle (LV), and infarct size was 14.7 ± 16.9% LV, resulting in a mean salvage area of 14.9 ± 15.1% LV in SPECT, whereas in CMR, mean area at risk was 28.0 ± 14.5% LV, and infarct size was 16.0 ± 13.5% LV, resulting in a mean salvage area of 11.9 ± 12.3%. Results of both modalities correlated well for area at risk (r = 0.80), scar size (r = 0.87), and salvage area (r = 0.66, all p < 0.0001). CONCLUSIONS: Assessment of the salvage area by CMR using T2 and late enhancement imaging correlates well with the established modality of SPECT. CMR therefore may be an alternative to paired SPECT imaging for myocardial salvage assessment, but the contraindications of the modality and limitations in the established T2 imaging sequences currently cause a considerable rate of data loss.

The nuclear receptor PPAR gamma selectively inhibits Th17 differentiation in a T cell-intrinsic fashion and suppresses CNS autoimmunity.

T helper cells secreting interleukin (IL)-17 (Th17 cells) play a crucial role in autoimmune diseases like multiple sclerosis (MS). Th17 differentiation, which is induced by a combination of transforming growth factor (TGF)-beta/IL-6 or IL-21, requires expression of the transcription factor retinoic acid receptor-related orphan receptor gamma t (ROR gamma t). We identify the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) as a key negative regulator of human and mouse Th17 differentiation. PPAR gamma activation in CD4(+) T cells selectively suppressed Th17 differentiation, but not differentiation into Th1, Th2, or regulatory T cells. Control of Th17 differentiation by PPAR gamma involved inhibition of TGF-beta/IL-6-induced expression of ROR gamma t in T cells. Pharmacologic activation of PPAR gamma prevented removal of the silencing mediator for retinoid and thyroid hormone receptors corepressor from the ROR gamma t promoter in T cells, thus interfering with ROR gamma t transcription. Both T cell-specific PPAR gamma knockout and endogenous ligand activation revealed the physiological role of PPAR gamma for continuous T cell-intrinsic control of Th17 differentiation and development of autoimmunity. Importantly, human CD4(+) T cells from healthy controls and MS patients were strongly susceptible to PPAR gamma-mediated suppression of Th17 differentiation. In summary, we report a PPAR gamma-mediated T cell-intrinsic molecular mechanism that selectively controls Th17 differentiation in mice and in humans and that is amenable to pharmacologic modulation. We therefore propose that PPAR gamma represents a promising molecular target for specific immunointervention in Th17-mediated autoimmune diseases such as MS.