Prognostic implications of several non-invasive imaging techniques have been thefocus of some landmark studies published in 2015. Non-invasive characterization ofatherosclerosis processes and vulnerable plaques have been possible with advances incardiac magnetic resonance imaging and nuclear imaging techniques. In addition,3-dimensional echocardiography and multidetector-row computed tomography haveimproved our understanding of valvular heart disease. Finally, data on the clinicalrole of integration of non-invasive imaging techniques (fusion imaging) areaccumulating and its use is expected to increase in the coming years. The currentreview provides a summary of selected articles on prognostic impact of currentnon-invasive imaging techniques and technological innovations.1 In addition, this position document includes referencevalues for chamber quantification with three-dimensional (3D) echocardiographyand myocardial deformation with strain imaging. These normative data permitdifferentiation between normal and abnormal findings. From a clinicalperspective however, definition of the degree of abnormality  may be more meaningful. The document acknowledges the difficulties todetermine cut-off values that define the degree of abnormality and providesexperience-based partition values only for left ventricular (LV) size, functionand mass, and for left atrial (LA) volume.In 2015, the new recommendations for cardiac chamber quantification usingechocardiography in adults were published providing updated normative values forall four cardiac chambers based on multiple databases compiling data from alarge number of normal subjects.2 On multivariable analysis, each1 standard deviation (SD) change in LV GS was independently associated withall-cause mortality  compared with LVEF, indicating that the HR per each 1 SD change in LVGLS was 1.62 times greater than that of LVEF . Inpatients with MI, regional LV longitudinal strain may clinically be moremeaningful than GLS. A subanalysis of the VALIANT  trial including 248 patients with LV systolic dysfunction,heart failure, or both demonstrated that regional LV longitudinal strain wassignificantly impaired even in segments with normal wall motion score indexcompared with healthy controls .3 Abnormallongitudinal strain segments were defined as having a strain value higher (lessnegative) than the 95% percentile of corresponding normal control segments. Anincreasing number of LV segments with abnormal regional strain was associatedwith an increased risk of all-cause mortality .Data showing the prognostic value of LV global longitudinal strain (GLS) areaccumulating. A recent meta-analysis pooling data from 16 studies (n = 5721),encompassing different cardiac diseases , showed that theprognostic value of LV GLS exceeds that of LV ejection fraction (EF).4 The presence of persistent or worsened LV dyssynchrony wasassociated with increased risk of all-cause mortality and heart failurehospitalization . These results were alsoobserved in the large multicentre registry PREDICT-CRT.5 Left ventricular apical rockingand septal flash visualized on echocardiography are markers of left bundlebranch block-induced LV dyssynchrony. In 1060 patients treated with CRT,correction of apical rocking and septal flash at 6-12 months echocardiographywas associated with LV reverse remodelling and better survival at long-termfollow-up. In contrast, patients who still exhibited LV apical rocking or septalflash at follow-up showed less LV reverse remodelling and worse outcome.Echocardiographic assessment of heart failure patients who are candidates forcardiac resynchronization therapy (CRT) remains of interest. Results of theEchoCRT (CRT in heart failure with narrow QRS complex) substudy showed that 77%of the 614 patients with echocardiographic follow-up at 6 months had persistentor worsened LV dyssynchrony (≥130 ms as measured with STE or ≥80ms using tissue Doppler imaging).7 In 96 patients with heartfailure with preserved LVEF and 46 controls who underwent clinically indicatedright-sided heart catheterization and transthoracic echocardiography, Melenovskyand coworkers showed that male gender, LVEF, atrial fibrillation, coronaryartery disease (CAD), and systemic systolic blood pressure were independentlyassociated with RV dysfunction after adjusting for RV pulmonary arterial pressures.6 Patients with RV dysfunction showed lower 2-yearsurvival compared with patients without (56 vs. 93%). Right ventriculardysfunction was the strongest associate of all-cause mortality in a modelcorrected for systolic pulmonary artery pressure . Advances in 3D strain imaging have allowed characterization of RVremodelling in patients with pulmonary hypertension.7 Right ventricular morphological and functionaldata of 92 patients with pulmonary hypertension were analysed with novel 3Dmotion tracking echocardiography. Based on pressure-volume loops obtained duringright-sided heart catheterization, patients were divided into three groups: RVadapted, RV adapated-remodelled, and RV adverse-remodelled. A progressiveimpairment in RVEF and global area strain was observed across the three groupswith the RV adverse-remodelled group having the worst values. Patients withinthe RV adapted group showed better 6-month free-survival from hospitalization,death, or lung transplantation compared with the other groups , whereas patients within the RV adverse-remodelled groupshowed the worst outcome .The prognostic value of right ventricular (RV) function was also evaluated inseveral studies.8 Insufficient leaflet remodelling relative toannular and LV dilatation resulted in reduced coaptation, which wasindependently associated with MR severity in patients with functional MR. 9 The authors demonstrated important differencesin LV remodelling, annular, and valvular dimensions, associated with differencesin MR severity between patients with fibro-elastic deficiency and diffusemyxomatous degeneration.Three-dimensional echocardiography is increasingly used in heart valve disease.Debonnaire and coworkers demonstrated that 3D transoesophageal echocardiographycould adequately depict mitral valve leaflet remodelling in patients with LVdysfunction and functional mitral regurgitation (MR).10 In 353 patients with variousdegrees of isolated functional TR, the effective regurgitant orifice area (EROA)was calculated with the proximal flow convergence method. An EROA ≥40mm2 defined severe TR and was observed in 40% of patients. Duringa mean follow-up of 5.8 years, 82 patients died. An EROA ≥40mm2 was independently associated with all-cause mortality  after adjusting for clinicalcharacteristics, LVEF, RV size, RV function, and RV systolic pressure.Finally, the incremental value of quantification of tricuspid regurgitation (TR)to predict survival was demonstrated by Topilsky et al.11 A CACS = 0 was associated with an invariablylow death rate of 4.7% (i.e. 0.3%/year on average), and thereby extends thewarranty period of zero CACS over a period of almost 15 years, particularly inlow and intermediate risk patients, and regardless of gender. In a recentpublication from the COronary CT Angiography EvaluatioN For Clinical Outcomes:An InteRnational Multicenter registry, investigators observed in 3217asymptomatic subjects that CT coronary angiography (CTCA) possessed incrementalprognostic value over FRS only in patients with a CACS >100 , but not among those with CACS≤100.12However, in high and very high CACS subgroups (i.e. >400 and >1000), theincremental value of CTCA was lost again, probably through less reliable CTCAinterpretation. However, conclusions in these subgroups were limited due to lowsample sizes and event rates.Very long-term prognostic data for coronary artery calcium score (CACS) werepublished by Valenti and coworkers in 9715 asymptomatic subjects followed for14.6 years: CACS emerged as the strongest predictor of death, and wasindependent from Framingham risk score (FRS) or National Cholesterol EducationProgram Adult Treatment Panel III risk category.13 A total of955 patients with vascular risk factors were included, of which 74 (8%) suffereda perioperative event (cardiovascular death/MI). Computed tomography coronaryangiography findings provided independent prognostic information over revisedcardiac risk indices with increasing HRs for non-obstructive , obstructive , and extensive obstructive  disease. However, the c-index increased only from 0.62 to 0.66 whenadding CTCA to the clinical risk prediction models, mostly because ofreclassification of a sizable number of patients (~10%) into a higher-riskcategory who would not suffer any subsequent event. Thus, the results of thecoronary CTA VISION raise concerns about overestimation of risk by CTCA comparedwith clinical risk indices.The Coronary computed tomography angiography (CTA) vascular events in non-cardiacsurgery patients cohort evaluation (VISION) study assessed the value of CTCA forpredicting the risk of cardiovascular complications of non-cardiacsurgery.14The overall diagnostic yield was similar for TRO CT compared with CTCA only and was driven mainly by CAD detection ; TRO CT, however, yielded slightly more PE  and AD  diagnoses, although at a higher medianradiation  and mean contrast dose , and higher non-diagnostic image qualityrate . Thus, although TRO CT may be useful inselected patients ,the study does not support its indiscriminate use in emergency departments.The diagnostic yield of CT for triple rule-out (TRO) of MI, pulmonary embolism(PE), and aortic dissection (AD) in patients with acute chest pain is a debatedissue, and was investigated in the Advanced Cardiovascular Imaging Consortiumdatabase in 12 834 patients.15 At 25 monthsfollow-up, there were no differences in the primary endpoint of death, MI,hospitalization for unstable angina, or major procedural complications. However,CTCA resulted in fewer catheterizations showing no obstructive CAD , although more patients in the CTCA group underwentcatheterization (12.2 vs. 8.1%) and were revascularized  within 90 days of randomization. The Scottish COmputed Tomography of theHEART trial randomized 4146 patients to standard care (SC)  plus CACS and CTCA vs. SC alone.16 The use of CTCA increaseddiagnostic certainty [relative risk (RR) 1.79; p < 0.001) for the primaryendpoint of angina due to CAD, resulted in cancellation of 121 functional testsand 29 invasive angiograms, and more changes in preventive and antianginal drugtherapies. At follow-up of 1.7 years, there was a numerical  38% reduction of the composite endpoint of CAD death/MI in the CTCAgroup (p = 0.053).The results of two large randomized CT studies were eagerly awaited in 2015: inthe prospective multicenter imaging study for evaluation of chest pain trial, 10003 symptomatic patients with intermediate CAD pretest probability wererandomized to a strategy of initial anatomical testing with CTCA vs. traditionalfunctional testing .CT) continuesto raise interest in 2015 through its latest publication, the ProspectiveLongitudinAl Trial of FFRct: Outcome and Resource IMpacts study.17 In this trial, 584 symptomaticpatients with intermediate CAD pretest probability were prospectively (but notrandomly) assigned to receive either usual testing  or CTCA (n = 297) with additionalFFRCT where requested. Among those with intended ICA (n = 380),FFRCT resulted in a significant reduction in the number ofinvasive catheterizations showing no obstructive CAD (from 73 to 12%) andavoided ICA in 117 (61%) patients, while no differences were noted in the groupof patients with intended non-invasive testing  were not significant .18However, in the non-invasive arm, patients undergoing FFRCT showedbetter scores on quality-of-life questionnaires compared with patientsundergoing usual care, whereas in the invasive arm, there were no differencesbetween FFRCT and ICA.Computed tomography-derived fractional flow reserve (FFR testing . Althoug19Seventy-seven patients with stable angina and significant coronary arterylesions (>70% stenosis on invasive angiography) underwent 1.5T MRI 48 h priorto PCI and coronary plaque composition was assessed with non-contrastT1-weighted MRI. High-intensity plaques (considered vulnerable plaques) weredefined by a 'coronary plaque to myocardium signal intensity' ratio of≥1.4. Percutaneous coronary intervention-related myocardial injury wasdefined as an increased high-sensitivity cardiac troponin T >5 times the 99thpercentile upper reference limit. Patients with high-intensity plaques (n = 31)showed greater plaque burden, larger lipid pool, more frequently positiveremodelling, ultrasound attenuation, and intracoronary thrombus on intravascularultrasound analysis, compared with patients without high-intensity plaques(20Characterization of coronary artery plaques with non-contrast T1-weightedmagnetic resonance imaging (MRI) has provided novel insights into thepathophysiology of percutaneous coronary intervention (PCI)-related myocardialinjury, a procedural complication which has important prognosticimplications. plaques. Importa21Patients underwent cine CMR, native T1 mapping, T2 mapping, T2* mapping and lategadolinium contrast-enhanced (LGE) sequences 2 days after index MI and at 6months follow-up. Native T1 times were measured in the infarct zone, injuredmyocardium, and remote myocardium. The infarct zone region was defined asmyocardium with pixel values (T1 or T2) >2 SD from the remote zone onT2-weighted CMR sequences. The hypo-intense infarct core was defined as areaswithin the infarct zone with pixel T1 values <2 SD of the values observed inperiphery of the infarct zone. Infarct core native T1 was significantlyassociated with native T2 . Native T1 values within theinfarct core were associated with LV adverse remodelling at 6 months follow-up and were independentpredictors of all-cause mortality or heart failure hospitalization .In survivors of ST-segment elevation acute MI (STEMI), assessment of infarct sizeand microvascular obstruction with contrast-enhanced CMR has importantprognostic value. Interestingly, non-contrast CMR-derived parameters such asnative T1 mapping permit characterization of the infarct core tissue. After MI,there is an increase in water content in the ischaemic area that will result inlonger native T1 times. Carrick and coworkers investigated in 300 survivors ofSTEMI, the correlation between native T1 time of the infarct core, infarct sizeand microvascular obstruction and the prognostic implications of native T1 timein terms of LV adverse remodelling (≥ 20% increase in end-diastolicvolume at 6 months follow-up), all-cause mortality and heart failurehospitalization.26 In 65 patients who underwentpotentially cardiotoxic chemotherapy, LVEF decreased significantly after 3months of therapy  whilemyocardial T1-weighted LGE-signal intensity increased  without an increase in myocardial oedema onT2-weighted CMR sequences.22Whether these changes may predict irreversible myocardial damage afterwithdrawal of chemotherapy, remains unknown. The presence of subclinical diffusemyocardial fibrosis was evaluated measuring the ECV in 35 patients withasymptomatic moderate and severe primary MR and preserved LVEF.23 Compared with controls,patients with MR exhibited larger ECV . Increasing myocardial ECV was significantly associated withlarger LV end-systolic volume index  and left atrialvolume index , lower LVEF  andworse functional capacity as measured with peak oxygen consumption . In 139 patients with hypertrophic cardiomyopathy (HCM), Ellims etal. investigated the correlations of macroscopic myocardial fibrosis (assessedwith LGE CMR) and diffuse myocardial fibrosis (assessed with post-contrast T1mapping) with LV function and genotype.24 The presence of LGE was associated with LVEF andpresence of LV outflow tract obstruction whereas shorter post-contrastT1-mapping values (more diffuse fibrosis) were significantly associated with LVdiastolic dysfunction and dyspnoea symptoms. Interestingly, patients withidentifiable HCM genetic mutations showed larger extent of LGE  but longer post-contrast T1-mapping values  compared with patients withoutmutations. Using LGE CMR, Nadel et al. investigated in 106 patients withbiopsy-proven extracardiac or cardiac sarcoidosis the association between thepresence of focal macroscopic fibrosis and occurrence of the composite endpointall-cause mortality, sudden cardiac death, ventricular tachycarrhyhtmia orventricular fibrillation.25Thirty-two (30%) patients showed focal myocardial fibrosis on LGE CMR which wasof patchy distribution in the majority of patients (72%) followed bysubepicardial (59%) and midwall (25%) distribution. During a mean follow-up of37 months, 16 patients reached this composite endpoint. The presence of focalmyocardial fibrosis on LGE CMR was independently associated with the compositeendpoint . In 100 patients with systemiclight-chain amyloidosis, Banypersad and coworkers evaluated the prognostic valueof ECV, pre-contrast (native), and post-contrast T1 values.26 During a median follow-up of23 months, 25% of patients died. A cut-off value of ECV ≥0.45  and a cut-off value of native T1 time ≥1044ms  were independently associated withall-cause mortality, whereas post-contrast T1 mapping values were not predictiveof mortality.Several CMR-derived variables have been used to define and quantify the presenceof myocardial fibrosis . While focal macroscopic fibrosis iscommonly assessed with LGE CMR, diffuse fibrosis can be characterized bycalculating the extracellular volume (ECV), after primed contrast infusion oradministration of bolus of gadolinium, post-contrast T1-mapping values andpre-contrast (native) T1-mapping values. In addition, changes in T1-weightedLGE-signal intensity have been associated with myocardial injury. These measureshave been correlated with LV function and prognosis in several cardiacdiseases.28 Van der Falk et al. aimed atassessing the role of leukocytes in atherogenesis by performing single photonemission computed tomography (SPECT)-CT with 99mTechnetium-labeledperipheral blood mononuclear cells (PBMC).27 In 10 patients with known cardiovascular disease and 5healthy controls, a markedly enhanced accumulation of PBMC was found in patientswith advanced atherosclerotic lesions. This represents a novel-imaging approachto visualize leukocyte migration and PBMC accumulation to atherosclerosis inhumans, potentially lending support to strategies aimed at attenuating leukocyterecruitment as a therapeutic target in patients with cardiovascular disease. VanWik et al. demonstrated that lipoprotein apheresis leads to a marked reductionof arterial wall inflammation in patients with familial hypercholesterolaemia(FH) characterized by severely elevated plasma low-density lipoproteincholesterol levels.2818-F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) was used toassess the target-to-background ratio (TBR) of FDG uptake within the arterialwall in 24 patients with known FH and in 14 normolipidemic controls. A secondPET scan was acquired after 3 days in 12 patients in whom lipoprotein apheresiswas performed and demonstrated a significant reduction of TBR compared with thebaseline scan . Thesesuggest that apoprotein B-containing lipoproteins play a role in arterial wallinflammation and support the concept of a beneficial effect of lipoproteinapheresis.In patients with cardiovascular risk factors, characterization of inflammationand lipid accumulation in the arterial wall using nuclear imaging has been thetarget of several studies.29 Carotid FDG uptake and CIMT were measured in1089 asymptomatic adults who underwent PET imaging. Cardio-cerebrovascularevents occurred in 19 participants (1.74%) during an average follow-up of 4.2years. Multivariate Cox regression analysis revealed that high carotid FDGuptake  and high CIMT  were independent predictors of these events. Furthermore,carotid FDG uptake improved discrimination of risk prediction when added to theFRS independently CIMT.In addition, Moon et al. sought to investigate the added prognostic value ofFDG-PET over the FRS and carotid intima-media thickness (CIMT) for theprediction of future cardio-cerebrovascular events.30 Littleis known on the potential role of nuclear myocardial perfusion imaging (MPI) inthis context. Cremer et al. reported on the yield of SPECT-MPI for detectingischaemia, its prognostic value for short-term events, and its impact ondownstream resource utilization.31 Among 5354 patients referred from the emergency departmentafter negative troponin T tests and non-diagnostic ECGs, only 6.1% of patientswith a thrombolysis in myocardial infarction (TIMI) score ≤ 2 presentedwith > 5% ischaemic myocardium, while 19.6% of patients with TIMI scores≥ 3 had >5%. Furthermore, short-term adverse events were rare at 30days with only 0.1% mortality and 0.1% of patients undergoing revascularizationfor acute MI. These findings suggest that SPECT-MPI before discharge after twonegative troponins should be helpful in patients with TIMI scores ≥3.In patients with suspected acute coronary syndrome and negative cardiacbiomarkers routine exercise testing is recommended by currentguidelines.32 All patients underwent heparinpre-treatment to suppress FDG uptake in remote myocardium. The metabolic rate ofglucose was significantly increased in infarcted vs. remote myocardium . Regionally, FDG score was highest insegments with LGE vs. oedema only and to remote myocardium . Thus, increased FDG uptake after heparin-induced suppression ofmyocyte uptake appears to reflect inflammatory activity in acutely infarctedmyocardial tissue.In the field of acute MI, it has been shown that FDG-PET may be able to detectinflammation in the acutely infarcted myocardium, if information on latecontrast enhancement (scar tissue) from concomitant CMR or CT is integrated.Wollenweber et al. have translated these concepts into 15 patients early afterMI by performing PET and CMR within 7 days of first MI.33 Patient effective radiationdose ranged between 0.8 and 35.6 mSv (median 10.0 mSv). Average laboratoryeffective dose ranged from 2.2 to 24.4 mSv (median 10.4 mSv) and only 30% of alllaboratories achieved a median effective dose of ≤ 9 mSv as recommendedby guidelines. The lowest effective dose (median 8.0 mSv) was administered inEurope, coinciding with the highest best-practice adherence rate.Finally, the radiation burden associated with nuclear imaging remains of concernand was the objective of the INCAPS Investigators Group which conducted anobservational cross-sectional study of nuclear MPI protocols in 308 nuclearcardiology laboratories in 65 countries around the world, characterizing patientradiation doses and the use of radiation optimizing 'best practices'.34The number of studies published on the use of integrated or fusion imaging isincreasing, indicating increasing use of integrated PET-CT and PET-MRIequipment, but also the fusion of independently obtained data from (for example)SPECT and fluoroscopy. Zhou and colleagues developed a 3D fusion tool kit tofuse LV venous anatomy (derived from fluoroscopy) with SPECT-MPI  to guide LV lead placement in CRT.36 Valenta and colleagues evaluated 24 patientswith PET-CT using N13-ammonia to assess different myocardial blood flowvariables (flow reserve and flow gradients), which were related with CTCA,resulting in better understanding of the haemodynamic significance of coronarystenoses.35 Dey et al.reported on PET-CT data from 51 patients: CTCA  wasfused with myocardial flow reserve (derived from rest-stress N13-ammoniaPET).36 Prediction ofreduced myocardial flow reserve (indicating ischaemia) was optimal when CTCAstenosis severity was integrated with various other CTCA variables, includingtotal  plaque burden. These findings indicate that an integratedCTCA score  may better predict reduced myocardial flow reserve.Fusion imaging with PET-CT has been applied in patients with suspectedCAD.18F-FDG-PET-CT in the diagnosis of cardiac implantableelectronic device generator pocket infection.37 To this end, 46 patients with suspectedgenerator pocket infection and 40 without any infection underwent PET imaging,and FDG activity in the region of the generator pocket  but the small valve area (indicating severestenosis) may be related to the assumption of a circular shape of the LV outflowtract with 2D echocardiography . Since this parameter contributes significantly to the calculation of theaortic valve area (2/m2) and preserved LVEF (≥ 50%), this fusionapproach was applied and reclassified 52% of patients with low gradient butsevere aortic stenosis and preserved LVEF into moderate aortic stenosis (Fusion imaging of CT and echocardiography in heart valve disease was reported byKamperidis et al.lve area , this mastenosis 5.


Ebstein's anomaly (EA) is a rare but clinically important congenital heart disease with potential affection of right ventricular(RV), right atrial (RA), left ventricular (LV) and left atrial (LA) function that may play a role in heart failure development. Thus, we sought to assess quantitative atrial and ventricular function in EA with CMR feature tracking, and to correlate changes in biatrial and biventricular performance with the severity of disease and clinical parameters of heart failure.Atrial and ventricular deformation parameters were calculated from myocardial feature tracking  from 30 EA and 20 healthy control subjects at 1.5 Tesla. RA and LA performance was characterized using longitudinal strain and strain rate parameters quantifying reservoir function , conduit function  and booster pump function . Ventricular performance was characterized using RV and LV global longitudinal strain (Ell) and LV circumferential and radial short axis strain (Ecc and Err). Additionally, volumetric measurements  for all cardiac chambers including the Total right/left volume-index and heart failure markers  were quantified.RA reservoir and booster pump function were significantly impaired in the EA group as compared to controls using strain and volume metrics (see table Right atrial function is impaired in EA and can be quantified using CMR-FT. In combination with reduced quantitative RV longitudinal strain in the presence of preserved RV-EF, these quantitative changes may potentially represent early stages in heart failure development in EA. This is underpinned by a close correlation of decreased RA and RV deformational function with heart failure parameters such as NYHA, BNP and Total R/L-Volume Index. LA function is also impaired in EA, while LV function is still normal.We suggest that in EA patients, CMR derived RA function and RV longitudinal strain may be used as more sensitive markers to detect early deterioration of right heart function. Moreover, LA deformation should be monitored for early detection of left heart dysfunction. Incorporating these measures into CMR assessment may help to improve clinical management of EA patients.


The purpose of this study was to identify the optimal pacing site for the left ventricular (LV) lead in ischemic patients with poor response to cardiac resynchronization therapy (CRT).LV endocardial pacing may offer benefit over conventional CRT in ischemic patients.We performed cardiac magnetic resonance, invasive electroanatomic mapping (EAM), and measured the acute hemodynamic response (AHR) in patients with existing CRT systems.max vs. baseline) . This was associated with a similar first ventricular depolarization (Q-LV) , shorter stimulation–QRS duration  and shorter paced QRS duration . The mean best achievable AHR was higher with endocardial pacing . Furthermore, AHR was significantly greater pacing the same site endocardially versus epicardially  with a shorter paced QRS duration  despite a similar Q-LV . Lack of capture due to areas of scar (corroborated by EAM and cardiac magnetic resonance) was associated with a poor AHR.In all, 135 epicardial and endocardial pacing sites were tested in 8 patients. Endocardial pacing was superior to epicardial pacing with respect to mean AHR (% change in dP/dtIn ischemic patients with poor CRT response, biventricular endocardial pacing is superior to epicardial pacing. This may reflect accessibility to sites that cannot be reached via coronary sinus anatomy and/or by access to more rapidly conducting tissue. Furthermore, guidance to the optimal LV pacing site may be aided by modalities such as cardiac magnetic resonance to target delayed activating sites while avoiding scar.  Cardiac resynchronization therapy (CRT) is a highly effective treatment for patients with heart failure, severe left ventricular (LV) impairment and a prolonged QRS duration We hypothesized that in a group of ischemic patients  and a high prevalence of CRT nonresponse, LVendo pacing would produce a superior hemodynamic response compared with the optimal epicardial response (LVepi). Furthermore, by pacing multiple sites, we sought to investigate whether the optimal site of LV stimulation  could be predicted on the basis of scar and/or the latest point of electrical activation. By comparing endocardial contact mapping data with CMR, we further sought to elucidate the mechanisms of improved response with LVendo pacing and whether these imaging modalities could be used to guide the optimal LVendo pacing sites.The study complied with the Declaration of Helsinki and the protocol was approved by the local ethics committee. Informed consent was obtained from each patient. Patients with ischemic cardiomyopathy , QRS duration of <150 ms, and previously implanted CRT (mean duration of implant 26 ± 21 months) have a phenotype of suboptimal response to CRT and were intentionally selected for study Cases were performed under conscious sedation (mean 2.5 mg midazolam and 3 mg morphine) between March and December 2014. Patients with a mechanical aortic valve or significant peripheral vascular disease were excluded. CMR before CRT was performed with a standardized protocol including cine imaging and delayed enhancement sequences in both long and short axis views. Delayed enhancement was performed 10 to 15 min after administration of 0.2 mmol/kg Gadovist  to identify myocardial fibrosis. Contact LV endocardial scar mapping was performed in sinus rhythm with a roving decapolar catheter  via femoral arterial access with a retrograde aortic approach and displayed using EnSite Velocity NavX system . Multiple contact points were taken to create the endocardial geometry (mean 328 ± 133) with particular focus of delineating areas of scar. Points with a sensed bipolar electrogram amplitude of <0.5 mV were defined as scar and colored grey, points >1.5 mV were defined as representing healthy tissue and colored purple and those points in between defined as border zone with a color range Temporary placement of a high right atrial quadripolar catheter was used for atrial sensing. Initially, the optimal epicardial site with atrial synchronous biventricular pacing was assessed using the patient’s chronically implanted LV lead (LVepi1) and a second, temporary epicardial LV lead placed via the femoral vein (LVepi2) to allow multiple epicardial pacing sites from different veins and along the same vein . The optmax , sensed LV electrogram amplitude (mV), sensed electrical delay (first ventricular depolarization [Q-LV]) in sinus rhythm (ms), stimulation-QRS onset (ms), and paced QRS duration (ms). Default band pass filter settings of 30 to 300 Hz were used to measure a sensed, bipolar peak-to-peak voltage signal for the temporary epicardial LV lead (LVepi2) and endocardial catheter (LVendo) on the EnSite Velocity NavX system. The sensed LV signal from the implanted (LVepi1) lead was obtained through a printed recording from the pacing systems analyzer with manual calculation of the peak-to-peak signal. We identified whether pacing locations were in or adjacent to myocardial scar identified on the EAM and CMR and measured the distance between the LV tip and the central scar zone for each data point. Field scaling was applied to account for impedance anomalies and to ensure a 1:1 representation of the patient’s cardiac geometry (EnSite Velocity NavX system). An AHR was deemed positive at a pacing location if the dP/dtmax increased by >10% compared with baseline measurements The acute hemodynamic response (AHR) was measured using an 0.014-inch high-fidelity Certus RADI PressureWire in the LV as previously described t test. Analysis of variance was performed to compare the means of several groups. Results were considered significant at p < 0.05. Analysis was performed on PASW Statistics 22  and Stata .Continuous variables with a Gaussian distribution were described using mean ± SD. Categorical data were described by an absolute number of occurrences and associated frequency (%). Acute hemodynamic and electrical data passed the Shapiro-Wilk test for normality. To account for the clustering of data and multiple measurements within each patient, a mixed effect model was applied for all data points that achieved capture. For the best and worst achievable AHR per patient, in addition to endocardial opposite epicardial AHR data, mean differences between epicardial and endocardial datasets were compared with a 2-tailed, paired Mean native QRS duration was 140 ± 7 ms on surface ECG. Seven patients (88%) were labelled as having left bundle branch block; however, only 3 (38%) fulfilled the stricter Strauss criteria Using a mixed effect model analysis for all data points, the mean AHR of LVendo positions (11.81% [range -7.2% to 44.6%]) was significantly superior to the mean AHR of LVepi positions  . This waEpicardial stimulation sites were limited according to the coronary venous anatomy and the best achievable epicardial pacing locations were therefore confined to the AHA segments subtended by these veins. In 7 of 8 patients, the optimal LVepi pacing site was inferolateral/inferior; in the other patient the basal anterior site was best in keeping with the belief that pacing from the inferolateral/inferior wall is the optimal site of epicardial stimulation in the majority of subjects. LVendo pacing was not limited to the distribution of the coronary veins and there was substantial individual variation in the optimal site producing the best AHR .When the endocardial catheter was placed opposite the pacing tip of the epicardial lead on the basis of screening and EAM  . Of the LVendo stimulation sites, 16 did not capture and were in scar at a maximal output of 10 V (confirmed by voltage contact mapping and CMR). The mean electrogram amplitude within scar sites with noncapture was 0.18 ± 0.12 mV (n = 16). The optimal hemodynamic LVendo site was not at the site of latest electrical activation on the EAM in 6 of 8 patients .1.Indiscriminate endocardial pacing was superior to epicardial stimulation, associated with a similar first ventricular depolarization, shortened stimulation-QRS duration and shortened paced QRS duration.2.Optimal achievable endocardial AHR was superior to the optimal achievable epicardial AHR.3.There was significant interindividual variability of the position of the optimal LVendo site which was not predicted by the site of latest electrical activation on EAM.4.Pacing within scar on EAM and CMR  resulted in failure to capture and a poor AHR.5.LVendo stimulation at a site approximating LVepi stimulation resulted in a better AHR and shorter paced QRS duration despite a similar Q-LV.We studied the optimal site for both LVepi and LVendo stimulation in a cohort of patients with ischemic heart disease with poor response to conventional CRT. The principal findings were as follows.In keeping with the current study, LVendo pacing has been found to be superior to conventional CRT in both ischemic and nonischemic patients The current study has some important differences and new findings in comparison with previous studies that may be of clinical importance. First, our subjects were selected on the basis of having factors associated with a suboptimal response to conventional CRT, namely, male sex, ischemic cardiomyopathy, myocardial fibrosis (on CMR), and a QRS duration of 120 to 150 ms. Although all patients were ischemic in the study by Spragg et al. max by 36% from baseline compared with 29% via LVepi although this increase was not statistically significant. These differences may be related to the different population studied, but also that we assessed and optimized LVepi pacing in both the anterior and posterolateral regions. Our data are in keeping with both animal studies A notable finding of the current study was the superiority of LVendo over LVepi at the same site. Previous studies have suggested no difference in ischemic and nonischemic patients, however we found a significant benefit with endocardial pacing . Spragg et al. In the study from Spragg et al. Indiscriminate stimulation of the LVendo produced a superior hemodynamic effect compared with conventional epicardial stimulation. The benefit of LVendo pacing may be related to the lack of coronary venous constraints and the ability to access all regions of the myocardium resulting in the ability to obtain the best achievable AHR. The broad variation in hemodynamic response and notable lack of capture in areas of scar, clearly visible on CMR/EAM suggest a targeted approach avoiding scar may be helpful. The superiority of the optimal LVendo over the optimal LVepi AHR at the same site with an associated shorter paced QRS duration may support more rapid activation of the ventricles by fast conducting tissue including the His-Purkinje network CRT nonresponse occurs in one-third of patients receiving this treatment and is higher in ischemic patients with myocardial fibrosis and modest QRS prolongation (120 to 150 ms). Strategies to improve response in this group are required. The recently published ALSYNC (ALternate Site Cardiac ResYNChronization) study demonstrated the feasibility and safety of LV endocardial CRT delivered, through the atrial trans-septal approach The ALSYNC study used an empirical approach to LV lead placement and despite this reported a significant improvement compared with conventional epicardial pacing. Our results support image guidance on the basis that a broad range of AHR values were obtained and therefore not all endocardial positions are equal in this cohort. Although an indiscriminate approach showed endocardial pacing was superior to epicardial pacing , an evenNCT01464502) may help to clarify this.The main limitation of the current study is the low number of patients studied. Due to the highly invasive nature of the study and the difficulty in identifying a group of nonresponders, this is understandable. The protocol was, however, extremely rigorous with a large number of data points . The EAM study is invasive and not likely to be of use in routine clinical practice. Due to the length of the procedures no changes in atrioventricular or ventriculoventricular delay were studied and it is possible that such manipulations may have produced a different response. Finally, hemodynamic response may not necessarily translate to chronic response to CRT and therefore longer term studies are required; results from a multicenter, randomized, controlled trial, RADI-CRT (Pressure Wire Guided Cardiac Resynchronisation Therapy; PerspectivesCOMPETENCY IN MEDICAL KNOWLEDGE: Biventricular pacing delivered through LV endocardial stimulation seems to provide superior acute hemodynamics and a shortening of the paced QRS duration compared with LV epicardial stimulation in the equivalent territory. A lack of coronary venous constraint and preferential access to fast conducting tissue are likely to under pin the superiority of this method for delivery of CRT. Cardiac magnetic resonance–derived myocardial fibrosis corroborates with scar derived from electroanatomic maps and may be helpful in guiding LV lead placement. Furthermore, targeting nonscarred segments identified through cardiac magnetic resonance cine sequences can aid optimal lead placement in an attempt to improve response to CRT.TRANSLATIONAL OUTLOOK: Biventricular pacing has been offered to selected patients with heart failure for more than 20 years; however, a significant proportion of individuals receiving this therapy do not derive significant clinical benefit. Certain groups such as male patients with ischemic etiology, myocardial scar and QRS duration of 120 to 150 ms have a high prevalence for poor response and alternative options for improving the effectiveness of CRT are urgently required. Recently, animal and human data have suggested superior hemodynamics and shorter electrical activation for endocardial versus epicardial LV stimulation in delivery of biventricular pacing. Clinical studies have demonstrated the feasibility of endocardial LV stimulation through transatrial septal and transventricular septal approaches, as well as leadless LV pacing in combination with an implanted right-sided system. Coupled with advanced cardiac imaging to guide LV placement away from areas of scar and toward those activating lately, CRT delivery through permanent LV endocardial stimulation may represent a new method to improve outcomes for heart failure patients over the coming decades.Our findings suggest that, in ischemic patients with poor CRT response, endocardial pacing is superior to epicardial pacing with an even greater response achievable with optimization for each set of protocols. The mechanism of benefit may be due to the ability to access more optimal sites that cannot be reached by the constraints of the CS anatomy. Furthermore, guidance to the optimal LV pacing site may be aided by modalities such as CMR to target nonscarred and delayed activating sites.


Myocardial fibrosis is a potential pathophysiological mechanism leading to systemic right ventricular (SRV) deterioration. We hypothesize that circulating levels of collagen deposition markers are elevated in patients with SRV remodeling and this elevation may have a predictive value.We prospectively evaluated 56 patients with D-TGA after the atrial switch procedure . Serum levels of procollagen type III amino-terminal propeptide (PIIINP), collagen type I carboxy-terminal telopeptide (CITP), procollagen type I N-terminal propeptide (PINP), matrix metalloproteinase  and a tissue inhibitor of matrix metalloproteinase (TIMP 1) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) were measured and compared with healthy controls. The relationship between these serum markers, echocardiographic and cardiac magnetic resonance parameters and the outcome at a follow-up of 61 months  was determined.Compared with the healthy control group, the study group had significantly higher levels of TIMP1, PIIINP, CITP, PINP and NT-pro-BNP . The levels of PIIINP and CITP were significantly higher among patients with an SRV mass index above the mean value. The level of PIIINP was significantly higher among patients with an SRV EDV index above the mean value. CITP was significantly elevated in SRV late gadolinium enhanced (LGE) positive patients, compared to patients without SRV LGE. MMP9 and TIMP1 predicted an adverse clinical outcome on univariate Cox proportional hazard survival analysis in addition to well proven predictors of outcome (SRV EF and NYHA).We demonstrated a pattern of altered collagen turnover adversely related with the indices of SRV remodeling and an adverse clinical outcome in patients with SRV. D-transposition of the great arteries (D-TGA) is one of the most common, severe cyanotic congenital heart diseases.  The arteMyocardial fibrosis is a potential pathophysiological mechanism leading to a systemic ventricular deterioration. The late gadolinium enhancement cardiovascular magnetic resonance (LGE CMR) imaging of the SRV is able to visualize focal fibrosis. However, data on the incidence of LGE positive results among patients with SRV are ambiguous. –14 Some This was a prospective cross-sectional study. Fifty-six adult patients  with D-TGA after the atrial switch procedure, attending the adult congenital heart disease outpatient clinic at our institution, were screened between 1 June 2010 and 31 December 2011 for possible participation in the study. Patients with active inflammation, chronic inflammatory disease, conditions known to alter collagen turnover including chronic liver disease, connective tissue disease, metabolic bone disease, malignancy, severe chronic kidney disease (estimated glomerular filtration rate < 30 ml/Kg/min) or patients after recent trauma or surgery (< 6 months) were excluded from the study. The control group consisted of 29 healthy staff members at our institution. Comparisons between healthy volunteers and patients were limited to biomarkers assessment. All subjects gave written informed consent to participate in the study. The study protocol was approved by the local Institutional Review Board. Ethics Committee of the Institute of Cardiology approved this study.Peripheral venous blood samples were obtained during clinical assessment and centrifuged at 4°C at 2500 g. Samples were aliquoted and stored at– 70°C until analysis (less than 6 months). Serum concentration of C-terminal telopeptide of type I collagen (CITP) was assayed using the the UniQ CITP RIA kit. The sensitivity of the assay was about 0.4 g/L. Intra- and inter-assay CV was 6.3 and 9.0%, respectively. Serum concentration of PINP was determined with the UniQ PINP RIA kit. Sensitivity of the assay was 2.0 μg/L. Intra- and inter-assay CV were 10.2 and 9.8%, respectively. For the determination of PIIINP the UniQ PIIINP RIA kit was applied. Sensitivity of the assay was 0.3 μg/L. Intra- and inter-assay CV were 7.0 and 7.2%, respectively. The UniQ RIA kits were obtained from Orion Diagnostica Oy, Espoo, Finland. Concentration of the MMPs and TIMP-1 were assayed using the quantitative sandwich enzyme immunoassay technique. All kits were purchased from R&D Systems, Inc., Minneapolis, MN, USA. Sensitivity for MMP-2 was 0.047 ng/mL, intra- and inter-assay CV were 5.4 and 6.9% respectively. Sensitivity for MMP-9 was 0.156 ng/mL, intra- and inter-assay CV were 2.9 and 7.8% respectively. Sensitivity for TIMP-1 was 0.08 ng/mL, intra- and inter-assay CV were 5.0 and 4.9% respectively. N-terminal brain natriuretic peptide (NT-pro-BNP) was determined using an immunoradiometric assay . Aldosterone concentration in the serum samples was quantified using the ALDOCTK-2 RIA (Radio ImmunoAssay) kit from DiaSorin Inc. Stillwater, MN, USA.>60 frames per second (fps). The following standard echocardiographic parameters were measured offline: (1) the SRV diastolic diameter just below the tricuspid valve, (2) the SRV fractional area change (FAC), (3) the tricuspid annular plane systolic excursion (TAPSE), (4) s’ velocities at the lateral tricuspid annulus using pulsed-wave tissue Doppler with >140 fps. [All patients underwent a complete transthoracic echocardiographic study  by a cardiologist with experience in congenital heart disease (ML) blinded to the clinical data. A cine loop of at least three consecutive heartbeats was stored digitally for off-line analysis. Echopac software  was used to analyze the stored data. Right ventricular function was assessed in a modified apical four-chamber view, with a minimization of sector width and a slight tilt of the transducer if needed to optimize SRV visualization. Gray scale images were performed with frame rates 140 fps.  Conventi140 fps.  Right ve140 fps. , 24CMR studies were performed with a 1.5T scanner . The CMR protocol included cine steady-state free precession (SSFP) breath hold sequences in 2-, 3-, and 4-chamber views and a stack of short axis images (slice of thickness 8–10 mm) acquired parallel to the atrioventricular groove from base to apex. The SRV endocardial and epicardial borders were outlined manually at end-diastole and end-systole. On the basis of these data, analysis of SRV volumes and the ejection fraction were obtained by using dedicated software . Approximately 10–15 min after the administration of 0.2 mmol/kg body weight gadolinium-diethylenetriaminepentaacetate , a late enhancement study using a 3D spoiled turbo Gradient Echo sequence with a selective 180° inversion recovery pre-pulse was acquired in the short and long axis of the left ventricle. Inversion times were individually selected using a Look-Locker sequence to optimally null the signal of normal myocardium. Post-acquisition analysis of ventricular size and function as well as LGE were done using commercially available software packages. Right ventricular fibrosis was assessed in a binary way—as either present or absent.We routinely used CMR for the assessment of the systemic right ventricle, therefore only patients not eligible for CMR due to: (1) implanted pacemakers, (2) a mental handicap precluding cooperation during CMR, (3) pregnancy and those who (4) did not consent to undergo CMR, were excluded from the study. Based on these criteria 15 out of 56 patients did not take part in the CMR study, including 3 patients who declined to participate on personal grounds , and 8 who were excluded because of an implanted pacemaker and 4 because of a mental disorder.The cardiologist working in the adult congenital heart disease outpatient clinic at our institution prospectively followed up all patients. A combined adverse clinical end point was defined as: (1) an increase in the NYHA class to ≥ 3, (2) the occurrence of symptomatic arrhythmia requiring medical or interventional therapy, (3) death. Data on clinical events was collected during (1) regular or unplanned (attributable to new signs or symptoms) visits at our institution, and (2) hospitalizations.< 0.05.Continuous data are presented as the mean ± SD. Categorical data are presented as counts and percentages. The normal distribution of data was assessed using the Kolmogorov-Smirnov test. Depending on the distribution, comparisons between groups were made by the Student t test for unpaired data for continuous variables and by the chi-square test for categorical variables or by the Mann-Whitney test, for not normally distributed variables. Pearson or Spearman correlation coefficients were used according to the distribution type identified for each variable. The univariate logistic regression analysis was performed to test the predictive value of selected parameters. The ability of clinical, CMR and echocardiographic parameters to predict adverse clinical outcomes, was assessed by univariate Cox proportional—hazard survival analysis. The concentrations of NT-pro-BNP and aldosterone were transformed with natural logarithm, as they were not normally distributed. The statistical significance was set at p Analyses were performed using the SPSS version 16 .Fifty-six patients with D-TGA following the atrial switch procedure and 29 healthy age and sex matched controls were prospectively evaluated. The basic clinical characteristics as well as the results of the CMR and the echocardiographic evaluation of the SRV in D-TGA patients are presented in There was no difference between D-TGA patients and controls in terms of age and sex  Compared with the healthy control group, the study group had significantly higher levels of TIMP1, PIIINP, CITP, PINP and NT-pro-BNP . There wWe found no relation between sex and the concentrations of serum fibrosis markers either in patients or in controls. There was a correlation between CTB levels and age in D-TGA group for: PIIINP , CITP , and PINP , but not in healthy controls.The levels of PIIINP and NT-pro-BNP were significantly higher among patients with low GLS (> − 13%)  There was a weak correlation between SRV GLS and TIMP1 , PIIINP  and CITP  and no correlation between standard echocardiographic parameters of systolic SRV function  and any of the CTB levels . On univThe levels of PIIINP and CITP were significantly higher among patients with an RV mass index above the mean value . There was a positive weak-to-moderate correlation between the RV mass index and PIIINP , CITP  and PINP  . NeitherThe level of PIIINP was significantly higher among patients with an RV EDV index above the mean value . Right ventricular end-diastolic volume index correlated positively only with PIIINP  .2).On univariate logistic regression analysis PIIINP  was the only predictor of an enlarged SRV cavity . There was no correlation between NT-pro-BNP and SRVEF.On univariate logistic regression analysis TIMP 1  was the only predictor of reduced SRV systolic function (CMR SRVEF < 45%).2 vs 123.4 ml/m2, p = 0.01) and a higher SRV mass index , compared to patients without LGE. CITP was significantly elevated in SRV LGE positive patients, compared to patients without RV LGE . Other biochemical markers of collagen turnover did not achieve significant difference. NT-pro-BNP was increased in LGE positive patients but didn’t reach statistical significance . Aldosterone levels were not elevated in SRV LGE positive compared to LGE negative patients. Neither CTB parameters nor NT-pro-BNP and aldosterone predicted positive LGE results on univariate regression analysis.In 4 (10%) out of 41 (73%) patients in whom CMR studies were obtained, the small foci of LGE were detected. In all cases they were located at the insertion between the SRV and the interventricular septum. These patients had significantly lower SRV EF , a larger SRV cavity (end diastolic volume index 144.1 ml/mDuring a median follow-up time of 61 months (range 24–85 months), 12 patients (21%) reached the specified composite end point. There were 2 sudden cardiac deaths, 4 patients progressively deteriorated to NYHA class 3 or 4, and 6 had clinically relevant arrhythmias . The median time between the study entry and the occurrence of the composite endpoint was 32 ± 21 months. On univariate Cox proportional hazard survival analysis MMP9, TIMP1, SRV EF and NYHA class ≥ 2 predicted an adverse clinical outcome .This is the second paper concerning CTB among patients with D-TGA after the atrial switch operation.  In a proThere is growing evidence that myocardial fibrosis may be a pathophysiological substrate behind SRV dysfunction.  AlthoughThe only study concerning SRV done by Dos et al., even in a population showing a good baseline profile in terms of SRV mass (57.4 ± 17 g/m2), ejection fraction (54.9 ± 7.5%) and clinical condition (100% NYHA class I or II) exhibits a pattern of altered collagen turnover  and neurohormonal (NT-pro-BNP) activation.  ComparedEnhanced signals from tissue growth factors and angiotensin-II induce the production of PIIINP, which is the most frequently and extensively studied marker of tissue fibrogenesis. PIIINP is cleaved off during conversion from type III procollagen to type III collagen in the fibroblasts, and is subsequently released into the bloodstream.  There isWe assessed associations of biomarker levels with CMR parameters of myocardial fibrosis. The results of our study indicating augmented fibrosis in SRV patients are consistent with several previously reported data demonstrating ventricular myocardial fibrosis indicated by LGE of MRI. , 30 UsinIt is also noteworthy that NT-pro-BNP was significantly increased in patients with systemic right ventricle. In most previously published studies the levels of natriuretic peptides were higher in SRV patients compared with controls even when no signs or symptoms of heart failure were present. , 34 In aThe added value of our work is that besides well proven predictors of outcome (SRV EF and NYHA class) we also found TIMP-1 and MMP9 as outcome predictors. Little is known about CTB’s prognostic value in cardiovascular diseases and no data is available from congenital heart disease patients. Most of the data point to the value of PIIINP and CITP in patients with heart failure, after myocardial infarction, dilated cardiomyopathy or hypertension.  Frantz eAlthough the study group was relatively small it is the largest one concerning CTB among D-TGA patients. We analyzed biomarkers obtained from peripheral blood. For ethical reasons, it was not possible to sample myocardial biopsies or to investigate blood samples from the coronary sinus, which could be beneficial. Myocardial extracellular volume measurements with CMR T1 mapping techniques correlate with myocardial collagen volume fraction determined in myocardial samples of the left ventricle. Although the technique is evolving rapidly, assessment of right ventricular free wall with T1 mapping remains a challenge.In summary, while our cohort of patients with D-TGA was in good clinical condition, we demonstrated a pattern of altered collagen turnover and neurohormonal activation adversely correlated with indices of systemic right ventricular function and remodeling and assessed both by echocardiography and CMR. Even more importantly some of CTB were associated with an adverse clinical outcome in these patients.These data provide the basis for the development of new diagnostic and therapeutic strategies in patients with SRV. However, because this is one of the first studies to investigate these relationships, further research is necessary.S1 Data(XLS)Click here for additional data file.


Segmented phase-sensitive inversion recovery (PSIR) cardiovascular magnetic resonance (CMR) sequences are reference standard for non-invasive evaluation of myocardial fibrosis using late gadolinium enhancement (LGE). Several multi-slice LGE sequences have been introduced for faster acquisition in patients with arrhythmia and insufficient breathhold capability.The aim of this study was to assess the accuracy of several multi-slice LGE sequences to detect and quantify myocardial fibrosis in patients with ischemic and non-ischemic myocardial disease.Patients with known or suspected LGE due to chronic infarction, inflammatory myocardial disease and hypertrophic cardiomyopathy (HCM) were prospectively recruited. LGE images were acquired 10–20 min after administration of 0.2 mmol/kg gadolinium-based contrast agent. Three different LGE sequences were acquired: a segmented, single-slice/single-breath-hold fast low angle shot PSIR sequence (FLASH-PSIR), a multi-slice balanced steady-state free precession inversion recovery sequence (bSSFP-IR) and a multi-slice bSSFP-PSIR sequence during breathhold and free breathing. Image quality was evaluated with a 4-point scoring system. Contrast-to-noise ratios (CNR) and acquisition time were evaluated. LGE was quantitatively assessed using a semi-automated threshold method. Differences in size of fibrosis were analyzed using Bland-Altman analysis.n = 212 chronic infarction, n = 47 inflammatory myocardial disease, n = 53 HCM) Of which 201 patients  had detectable LGE . Image quality and CNR were best on multi-slice bSSFP-PSIR. Acquisition times were significantly shorter for all multi-slice sequences  as compared to FLASH-PSIR (361.5 ± 95.33 s). There was no significant difference of mean LGE size for all sequences in all study groups .Three hundred twelve patients were enrolled . Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is a well-established method for assessment of focal myocardial fibrosis and scarring in ischemic and non-ischemic cardiomyopathies –4. The pThe reference standard technique for LGE assessment is typically based on phase-sensitive inversion recovery (PSIR) sequences that are acquired in a single-slice, single-breathhold fashion , 12. TheHowever, with the more widespread use of CMR in clinical routine increasing numbers of patients referred for CMR present with arrhythmias or an inability for sufficient breathhold for CMR scan. In these patients, conservative segmented PSIR LGE sequences sometimes fail to provide satisfactory image quality for accurate assessment.Furthermore, standard segmented LGE sequences typically require 5 to 10 min of scan time for complete myocardial coverage. There is a need for faster and more efficient imaging in CMR in order to enable a more wide-spread use of CMR in clinical routine as well as in smaller institutions where access to CMR scanners maybe more restricted . CMR alsIn order to address these issues, multi-slice LGE sequences have been developed with acquisition of the entire k-space of an individual image slice within one heart cycle . DiffereSeveral small clinical studies have shown that multi-slice LGE sequences provide similar image quality to standard segmented LGE sequences , 19. HowIn this prospective study we intended to determine the comparability of standard segmented PSIR LGE imaging with two different multi-slice LGE sequences with and without breathhold in a large number of patients with ischemic and non-ischemic cardiomyopathy, namely chronic myocardial infarction, HCM and inflammatory heart disease. Furthermore, we explicitly did not exclude patients with arrhythmia. We aimed to assess if multi-slice LGE sequences represent a robust alternative for LGE assessment independent of pathophysiologic origin of LGE, heart rhythm and patient breathhold capabilities.312 consecutive patients with known or suspected LGE were prospectively recruited. All patients were referred for clinical LGE assessment using CMR for both, ischemic and non-ischemic cardiomyopathies, based on the clinical information provided by the referring cardiologist. A total of 212 patients had chronic myocardial infarction, 53 patients had HCM and 47 patients had inflammatory heart disease.2. All studies were performed in accordance with the local institutional review board and local ethics committee approval.All patients underwent a single CMR scan with three different LGE sequences. Exclusion criteria were contraindications to CMR and severe chronic renal disease with an estimated glomerular filtration rate < 30 ml/min/1.73mAll CMR studies were performed on a 1.5 Tesla scanner . Patients were scanned with electrocardiogram (ECG)-triggering in the supine position using 16-channel surface phased array coils.All imaging protocols included assessment of myocardial function in balanced steady-state free precession (bSSFP) cine sequences and of myocardial morphology by LGE imaging.bSSFP cine imaging  was performed in long axis two- and four-chamber view for biplanar assessment of left ventricular (LV) end-diastolic volume (LVEDV), LV mass (LVM) and LV ejection fraction (LVEF). Contours were drawn manually and biplanar anatomical and functional parameters calculated automatically by the post-processing software according to an established in-line biplane ellipsoid model.  The stanFor LGE imaging, a 0.2 mmol/kg intravenous injection of contrast agent was administered into an antecubital vein. In patients with myocardial infarction or HCM assessment gadoteridol  was used. For patient with known or suspected inflammatory heart disease gadopentetate  was administered due to established normal values for this contrast agent for the early enhancement technique which was clinically assessed in these patients independently from this study .Ten minutes after contrast administration, a segmented IR cine bSSFP inversion time (TI) scouting sequence was performed at a mid-ventricular short axis location to determine optimal TI . TI was Sequence details are displayed in Table All LGE sequences were acquired in end-expiratory breathhold while the bSSFP-PSIR sequence was additionally acquired in free breathing. In case of suspected artifacts in the LGE images a second perpendicular slice through the affected region was acquired or read-out of the phase encoding direction was swapped. Segmented and multi-slice LGE images were acquired in random order. Acquisition times and occurrence of arrhythmia during image acquisition were noted for all sequences.For all post-processing analyses commercially available software was used . A blinded reader performed LV function assessment in bSSFP cine long axis slices. For assessment of LVEF endocardial contours were drawn in the end-diastolic and end-systolic phase of two- and four-chamber view. All parameters were automatically calculated after contouring by the post-processing software. Separately, image quality and quantitative LGE assessment were performed in a random and blinded order.For 30 randomly selected individuals, the same reader and a second experienced reader repeated analyses for assessment of intra- and interobserver variability.Visual assessment of image quality was performed on all LGE sequences for each patient using a previously established 4-point-scale using the following grading: excellent quality, no artifacts (score of 1); good quality, minimal artifacts (score of 2); moderate quality, some artifacts which may impair diagnostic quality (score of 3); poor quality, unacceptable artifacts (score of 4) .Signal intensities were measured in regions of interest (ROIs) that covered areas of contrast-enhanced myocardium, as well as areas of remote non-enhanced myocardium with an additional ROI located outside the patient for calculation of background noise. Signal enhancement was measured as recommended by Simonetti et al. .In detail, we calculated signal intensities and their standard deviations in ROIs of LGE-positive myocardium, as well as areas of remote myocardium. Contrast was defined as difference between mean signal intensity of both ROIs. Image noise was defined as the standard deviation of the signal intensity in the normal-appearing myocardium ROI. Contrast-to-noise ratios (CNR) were calculated by using these values. Measurement of signal-to-noise ratios (SNR) is limited on PSIR images conventionally because the measurement of background noise is invalid in the reconstructed images . TherefoThe distribution area and transmurality of fibrosis was evaluated according to the American Heart Association (AHA) 16-segment model. The distribution area of scar in each segment was scored by the proportion of scar to each segment .For each subject, the number of segments with presence or absence of fibrosis and location within the myocardial wall  was noted for each LGE sequence as previously described .Quantification of LGE was performed with the established semi-automated signal threshold versus reference mean (STRM) method as published previously by our and other groups , 25, 26.True LGE was defined by myocardial signal intensity plus 6 standard deviations (SD) above that of remote, normal-appearing myocardium within the same slice in patients with myocardial infarction. For subjects with HCM and inflammatory heart disease, plus 3 SDs were defined as true LGE .The automated LGE detection could be manually corrected by the reader for a specific location to exclude obvious artifacts. After segmentation, myocardial and scar tissue mass (in grams) were calculated and compared for each AHA segment in each sequence.All statistical analyses were conducted by using statistical software package SPSS 17.0 . Quantitative data are expressed as means ± SD. Sample size was calculated by using power analysis for two proportions to reach a statistical power of more than 80% to detect differences of 5%, using the assumption of 16 ± 12 g scar tissue for patients with chronic myocardial infarction, and 9 ± 5 g for HCM and inflammatory heart disease which were reported previously by our group .Image quality scores were compared by using the Mann-Whitney U test. Interobserver and intraobserver agreement was assessed by using Cohen k statistics.Statistical comparison of means of LGE size in each individual multi-slice technique against the segmented reference standard technique was performed by using two-tailed paired t tests and Bland-Altman analysis. Scar tissue percentages per segment, CNR and signal enhancement ratios were assessed using the Wilcoxon signed rank test, as these values did not show normal distribution.In total, 312 patients were recruited. Fourteen of these patients were excluded due to incomplete image acquisition. All remaining 298 patients were successfully scanned using all techniques and were included in subsequent analyses . Patient characteristics are shown in Table p < 0.01 of all sequences against reference standard).The average scan time was significantly longer for the reference standard sequence (361.5 ± 95.3 s including breaks between slice acquisitions) than for any multi-slice sequence , and on bSSFP-IR lower than reference standard (p < 0.01). Free breathing acquisition of bSSFP-PSIR slightly decreased mean infarcted-to-remote area CNR as compared to acquisition under breathhold, however, was still superior to reference standard (p < 0.01). LGE due to chronic infarction showed significantly higher CNR values in all sequences than LGE due to HCM or inflammatory heart disease (p < 0.01).Assessment of infarcted-to-remote area CNR is shown in Table n = 143 with chronic infarction, n = 31 with HCM and n = 27 with inflammatory heart disease). All 201 LGE-positive patients also had detectable LGE on bSSFP-IR. With both bSSFP-PSIR sequences, two small LGE lesions (< 1 g scar size) were visually not detected in one patient with chronic infarction and one patient with HCM by two blinded readers.Using reference standard sequence, 201 patients (67.4%) had detectable LGE  for bSSFP-PSIR with  and without breathhold  while on bSSFP-IR circumferential scar extent was slightly underestimated . Details are shown in Fig. On all multi-slice sequences, the visual allocation of LGE within the myocardial wall  showed good matching with FLASH-PSIR for the chronic infarction and inflammatory heart disease group while for inflammatory heart disease there was a higher number of visually transmural LGE areas on bSSFP-PSIR versus FLASH-PSIR  on LGE size was > 0.95 for all sequences. Interobserver agreement was 0.92 for bSSFP-PSIR under free breathing and 0.88 for all other sequences.In patients with arrhythmia during image acquisition mean LGE size did not differ in any multi-slice sequence, with bSSFP-IR 7.6 ± 6.1 g and bSSFP-PSIR 7.7 ± 5.6 g under breathhold and 7.4 ± 5.6 g under free breathing. Reference standard FLASH-PSIR sequence was not evaluated in arrhythmic patients due to mostly non-diagnostic image quality.The present study compared for the first time a reference standard segmented (FLASH-PSIR) with two multi-slice LGE sequences (bSSFP-IR and bSSFP-PSIR) in 298 patients with ischemic and non-ischemic cardiomyopathies.Our key findings were: Firstly, image quality and CNR were highest on multi-slice bSSFP-PSIR with and without breathhold. Secondly, acquisition time is relevantly shorter on any multi-slice sequence compared to reference standard. Thirdly, visual detection of LGE and visual assessment of LGE extent was consistently very good and equivalent in all sequences. Fourthly, quantification showed no significant difference in LGE size for any multi-slice sequence. Fifthly, in patients with arrhythmia all multi-slice sequences generated good image quality and consistent LGE quantification results, whereas the reference standard provided non-diagnostic image quality in half of all exams. Finally, acquisition of bSSFP-PSIR under free breathing or under breathhold had no impact on LGE detection and quantification. Results were independent of the cause of LGE from ischemic or non-ischemic etiology.The assessment of myocardial fibrosis has enormous diagnostic and prognostic impact in ischemic and non-ischemic cardiomyopathy –7. Over Our study demonstrates that bSSFP-PSIR and bSSFP-IR multi-slice LGE sequences provide excellent alternatives to segmented FLASH-PSIR in routine CMR protocols. We showed that not only for ischemic LGE lesions but also for more diffuse lesions in inflammatory heart disease or HCM multi-slice sequences are sufficient to visualize fibrosis and – when quantified in size – show equivalent results compared to the reference standard. The equivalence of multi-slice LGE sequences to segmented sequences has previously been shown in studies for either HCM, ischemic or inflammatory heart disease , 19, 30.The superiority of multi-slice over segmented PSIR sequences in regard to image quality and CNR is in line with other publications , 19. ThiWe have also seen variations in CNR between the different disease entities. Since CNR is dependent on the voxel composition of fibrotic tissue, LGE in chronic infarction with more compact fibrosis is expected to result in higher CNR values than LGE in more diffusely fibrotic tissue such as in HCM and inflammatory heart disease.On bSSFP-PSIR sequence visual assessment revealed slightly larger scar transmurality as compared to the reference standard. We believe that visual assessment of bSSFP-PSIR images is impacted by its comparably higher CNR values which may lead to subjectively higher transmurality of scars.In two patients, small LGE lesions detectable with the reference standard sequence, were not detected with multi-slice bSSFP-PSIR but, nevertheless, could be visualized with bSSFP-IR. Note that for these two patients LGE amount was less than one gram, which suggests that partial volume effects or shifted slice position due to heavy respiratory motion may have caused the missed lesion. However, it cannot be safely excluded that very small LGE lesions may be missed with multi-slice bSSFP-PSIR due to its different matrix size as compared to the reference standard.It has been shown that even a small amount of LGE has prognostic implications in cardiomyopathies –34. In cOur results suggest that in patients with known or suspected myocardial infarction bSSFP-PSIR or bSSFP-IR multi-slice sequences can be primarily utilized for LGE detection. In case of an unknown cardiomyopathy or for assessment of HCM and inflammatory heart disease segmented FLASH-PSIR images should be used in scenarios of stable sinus rhythm and sufficient breathhold capabilities. For patients with arrhythmia and/or insufficient breathhold capabilities at the time of CMR scan we showed that segmented sequences fail to provide sufficient image quality. This is in line with previous studies , 38. In In this study two different contrast media were used; gadoteridol in CAD and HCM patients and gadopentate for inflammatory heart disease. The reason for use of gadopentate was established normal values for relative enhancement sequences, which were acquired in these patients independently from this study. However, there is good evidence that relaxivity and contrast enhancement are nearly identical for both agents so that impact on results should be neglectable. In our study we explicitly did not exclude patients with arrhythmia. We demonstrated good to excellent image quality and equivalent amount of LGE quantification with all multi-slice sequences. There is no gold standard for LGE detection and quantification in arrhythmic patients. Hence, we cannot definitely state that results are perfectly correct using multi-slice sequences. Still, due to the consistently high image quality scores and – as compared to patients with sinus rhythm – similar CNR values we feel confident that usage of any multi-slice sequence is superior to attempts of segmented image acquisition and shortens scan protocols significantly in these patients.Interestingly, presence or absence of breathhold during image acquisition on bSSFP-PSIR did not affect detection or quantification of LGE across all study groups. While there must be minimal slice shifting due to respiratory motion on acquisition of an entire LV short axis package within approximately 20 s of acquisition time we could show in a large number of patients that this has no statistically significant effect on diagnostic value. Lower numbers of breathhold cycles may also positively affect patient comfort and may be considered in all patients when SSFP-PSIR sequence is used.Alternative methods for LGE assessment include 3D sequences, which have been shown to also accurately visualize fibrosis and scarring , 41. TheIn another recent study dark blood PSIR imaging was published using T2 preparation pulses for improved visualization of fibrosis close to the adjacent LV blood pool in 30 patients with subendocardial infarction . This prLGE sequences are a mandatory part of most CMR protocols in ischemic and non-ischemic cardiomyopathy . The broFor that reason we suggest further strengthening the role of multi-slice sequences in routine CMR protocols whenever it is reliable to use.In spite of the large patient number in this study, all patients were scanned and analyzed in a single CMR center. Male gender was overrepresented in all study groups. Comparability of LGE sequences maybe impacted by different matrix size and, hence, different in-plane resolution used for each sequence. This may also affect SNR and CNR as well as assessment of LGE-positive areas.


To report a critical analysis of major and ancillary MR imaging features in assessment of HCC.Retrospectively we evaluated 70 cirrhotic patients with 173 nodules, which were subjected to MR study at 0 time (MR0), after 3 (MR3) and 6 months (MR6) using two different contrast media. EOB-GD-DTPA was injected at MR0 and MR6, while Gd-BT-DO3A at MR3. Three expert hepatic radiologists reviewed all images, recording, according to LI-RADS, the size, the presence and quality of arterial-phase hyperenhancement, washout and capsule appearance, threshold growth. Additionally, we recorded signal intensity (SI) on T2-W images, on DWI, on apparent diffusion coefficient (ADC) maps and SI on T1-W images of EOB-GD-BPTA hepatospecific phase. Median value of ADC and of Intravoxel incoherent motion related parameters were assessed.127 HCCs and 24 dysplastic nodules were assessed. Hypervascular on arterial phase was found in 84 HCCs, washout appearance in 124, capsule appearance in 111, hypointensity on hepatospecific phase in 127, hyperintensity on T2-W sequences and restricted diffusion in 107. Hyper vascular on arterial phase was found in 17 dysplastic nodules, wash-out appearance in 2, hypointensity on hepatospecific phase in 7 while no dysplastic nodules showed capsule appearance, hyperintensity on T2-W and restricted diffusion. Highest accuracy was obtained by washout appearance and hypointense signal on hepatospecific phase (97% and 95%).Hypointensity on hepatospecific phase and washout appearance are the most relevant diagnostic sign for differentiating low-risk from high-risk HCC nodules. The capsule appearance, T2-W hyperintensity and restricted diffusion have high positive predictive value. Liver Imaging Reporting and Data System (LI-RADS) is a score to report and interpret hepatic imaging characteristics on computed tomography (CT) and magnetic resonance (MR) studies in patients with risk for hepatocellular carcinoma (HCC) –2. EuropAmong 173 nodules, eight were combined hepatocellular-cholangiocarcinoma, seven metastases, 7 cirrhotic regenerative nodules, 24 dysplastic nodules and 127 HCCs (median 1.8 lesions for patients). All HCCs were histologically classified according to the major Edmondson-Steiner grade on final pathologic reports as follows: grade 1 (n = 30), grade 2 (n = 61), grade 3 (n = 36), and grade 4 (n = 0).We does not evaluated the imaging features of combined nodules, metastases and cirrhotic regenerative nodules while we analyzed HCCs and dysplastic nodules.We analyzed only lesions with a diameter between 12 and 20 mm.When we evaluated T2-W images, arterial phase, portal phase and hepatospecific phase of contrast study we found difference of measured lesion size on different sequences, but this is not statistically significant . So we reported a median value of lesion size measured by 4 sequences that was 18 mm (range 12- 20 mm)  had typical hallmark   were HCCs (2 grade 1 and 1 grade 2), 5  dysplastic nodules and 7  cirrhotic regenerative nodules.All 127 HCCs were hypointense on hepatospecific phase Figure .Among the 3 HCC detected by hepatospecific phase, one (grade 2) at MR6 became hypervascular on arterial phase Figure  with wasNo nodule grew during follow up.-3 mm2/s , for fp was 33,3% , for Dp 45,3 x10-3 mm2/s  and for Dt 0.9×10-3 mm2/s . Among typical and atypical nodules we found an overlapping of ADC and IVIM derived parameters values. We not found difference significant statistically between typical and atypical nodules using ADC or IVIM parameters values .All typical nodules were hyperintense on T2-W and DWI, with diffusion restriction and hypointense signal on ADC maps, 23  out of atypical nodules were hyperintense on T2-W and DWI, with diffusion restriction and hypointense signal on ADC maps, while 17  were iso-hypointense on T2-W and DWI and isointense on ADC maps. The median value for ADC was 1,47 x10Among 24 dysplastic nodules, 5  were detected only during hepatospecific phase. Seventeen lesions  were isointense on T2-W, DW and ADC map with hyperenhancement during arterial phase and isointense signal during portal, equilibrium and hepatospecific phase of contrast studies. Two lesions  were isointense on T2-W, DW, ADC map and hypointense on arterial, portal and hepatospecific phase of contrast studies Figure .We evaluated 210 arterial phases  to assess the image quality degradation. The median score for all arterial phase with Gd-BT-DO3A (70 studies) was 1, while the median score for all arterial phase with GD-EOB-DTPA (140 studies) was 3 (range 1-4); there was significant statistically difference between the quality on arterial phase with Gd-BT-DO3A and the quality on arterial phase with GD-EOB-DTPA . In 25  cases the images, during arterial phase with GD-EOB-DTPA, were uninterpretable  using GD-EOB-DTPA; there was significant statistically difference between the degree of hyperenhancement of arterial phase with Gd-BT-DO3A and the degree of hyperenhancement of arterial phase with GD-EOB-DTPA .Our results are summarized in Table Table In the management of patients with HCC is crucial its early diagnosis –13. The Arterial phase hyperenhancement is a crucial precondition to define HCC (LR-5) –2. HowevCapsule presence is identified as a peripheral rim of smooth hyperenhancement in the portal or delayed phase. The enhancement rim is not always a true tumor capsule, but may represent a pseudocapsule conforming to fibrous tissue and dilated sinusoids around a nodule –23. In oThreshold growth is defined as a diameter increase (a minimum of 5 mm and a sufficient rate). The necessary growth rate is either at least a 50% increase in diameter compared with baseline within 6 months or at least a 100% increase in diameter over more than 6 months . In our All HCCs in this study were hypointense on hepatospecific phase of contrast study, with sensitivity of 100,00%, specificity of 70,83%, PPV of 94,78, NPV of 100,00 and a diagnostic accuracy of 95,36. Our results are in agreement with those reported by others –36. Acco2), although the DWI and Signal Intensity of the HCCs increased in higher grade. We found that the median value for ADC was 1,47 x10-3 mm2/s , for fp was 33,3% , for Dp was 45,3 x10-3 mm2/s  and for Dt was 0.9×10-3 mm2/s  with an overlapping of ADC and IVIM parameters values among typical and atypical nodules. There was not difference significant statistically between typical and atypical nodules using ADC or IVIM parameters values . These results suggested that there was not a correlation between ADC or IVIM parameters values and hypervascularization during arterial phase.According to LI-RADS, T2-W hyperintensity is an ancillary imaging features. Previous study demonstrated that T2-W hyperintensity was a highly precise indicator of nodule malignancy, although poorly sensitive –40, whilIn this study we employed a 1.5T MR scanner, however we think that our results could not change with use of a 3T scanner. In fact, although 3T systems are advantageous for musculoskeletal, neuroimaging, and angiographic applications few articles have been published regarding their use for abdominal and, particularly, liver examinations –50. The A retrospective study, approved by National Cancer Institute Pascale Foundation of Naples, was performed through a computerized search of medical records on 160 patients underwent liver MR imaging and followed by biopsy for HCC from August 2010 to February 2017. After reviewing the medical records, 52 patients were excluded because the tumors were bigger than 2 cm; 34 patients because the tumors were smaller than 1 cm and 4 were excluded because the final pathology report was confirmed not to be HCC. The final study population included 70 patients  with 173 nodules . All patients had chronic liver disease which was related to hepatitis C virus infection in 29 patients, hepatitis B virus in 39 cases, and alcohol abuse in 2; all were stage A according to the Barcelona-Clinic Liver Cancer (BCLC) classification; alpha-fetoprotein levels were >4 ng/ml  in all patients. All patients underwent MR study at 0 time (MR0), after 3 (MR3) and 6 months (MR6) using two different contrast media (CM). Liver-specific agent, taken up by hepatocytes (Gd-EOB-BTPA), was injected at MR0 and MR6, non-specific cm that distributes into the vascular and extravascular extracellular spaces (Gd-BT-DO3A) was injected at MR3. The mean interval standard deviation between pathologic examination and last MR study (MR6) was 15 days (range 4–28 days).b value 0, 50, 100, 200, 400, 600, and 800 s/mm2. As liver-specific CM, the EOB-Gd-BPTA  was employed. All patients received 0.1 ml/kg of EOB-Gd-BPTA by means of a power injector , at an infusion rate of 1 ml/s. As non-specific agent the Gd-BT-DO3A  was employed. All patients received 0.1 ml/kg of Gd-BT-DO3A by means of a power injector , at an infusion rate of 2 ml/s. After contrast medium administration, VIBE T1-weighted FS (SPAIR) sequences were acquired in different phases: hepatic arterial (35 s delay), portal venous (90 s), equilibrium (120 s), and hepatobiliary excretion (20 minutes). Details of sequence parameters were reported in Table MR imaging was performed by using a 1.5T MR  with 8-element body and phased array coils. The MRI examination consisted of basal images taken before IV administration of contrast medium and then functional dynamic sequences obtained after IV injection of cm, acquiring the last series of images, when we used hepatospecific cm, with a delay of 20 minutes during the hepatobiliary excretion of the cm. The baseline sequences obtained before IV contrast medium were coronal True fast imaging with steady state precession (TrueFISP) T2-weighted free breathing; axial Half-Fourier Acquisition Single-Shot Turbo Spin-Echo (HASTE) T2-weighted, with controlled respiration, without and with fat-suppressed (FS) gradient-echo pulse; coronal HASTE T2-weighted, without FS; axial flash in-out phase T1-weighted, with controlled respiration; Volumetric Interpolated Breath-hold Examination (VIBE) T1-weighted SPAIR with controlled respiration; diffusion weighted imaging (DWI) with planar echo-pulse sequence (EPI) at several b value Three expert hepatic radiologists retrospectively and independently reviewed all images and served as the consensus. The observers were blinded to clinical history and previous imaging studies. We analyzed only lesion smaller than 2 cm and greater than 1 cm. We used LI-RADS v2014 classification and histological analysis served as the standard of reference.For each nodule we recorded, according to LI-RADS classification, the size, the presence and quality of arterial-phase hyperenhancement, washout appearance, capsule appearance, threshold growth. Additionally, we recorded signal intensity (SI) on T2-W images, on DWI, on maps of apparent diffusion coefficient (ADC) and, when we used EOB-GD-BPTA, SI on T1-W images during hepatospecific phase on contrast study. For each nodule, we reported the median ADC value and median values of Intravoxel incoherent motion (IVIM) related parameters of pseudo-diffusivity (Dp), perfusion fraction (fp), and tissue diffusivity (Dt).When we found arterial-phase hyperenhancement, washout and capsule appearance, we defined the HCC as typical. When we found, washout and capsule appearance, but not the arterial-phase hyperenhancement, we defined the HCC as atypical.The lesion was categorized hyperintense, isointense or hypointense relative to the surrounding liver parenchyma. The lesions that were seen only as hypointense on the hepatobiliary phase were graded as LI-RADS 3.For lesion detection with DWI, the observers analyzed all b values.Each observer independently evaluated the presence of arterial phase hyperenhancement using a four-point scale , to compare the efficacy of the two different contrast media to evaluate hyperenhancement.Also, each observer independently evaluated the degree of image quality degradation caused by respiratory ghost, pulsatile blood flow ghost, and susceptibility artifacts using a four-point scale . A “severe” score indicated that an image was uninterpretable and a “mild” score indicated that the artifact did not affect interpretation.A consensus read was performed when there was disagreement between the readers.In this study the diffusion parameters estimation was performed using the intravoxel incoherent motion method –7.p), perfusion fraction (fp), and tissue diffusivity (Dt) was described by the following equationBi-exponential model to estimate the IVIM-related parameters of pseudo-diffusivity  the Letting Therefore, a separable nonlinear least square model known as VARiable PROjection (VARPRO) can be used to calculate the diffusion parameters. If we knew, the estimate of the nonlinear parameters Dp and Dt the estimate of the linear parameter f could be obtained by:where 2. No motion correction algorithm was used but ROIs were drawn taking care to exclude areas in which movement artifacts or blurring caused voxel misalignments.This analysis was ROI-based using median value of single voxel signals for each b value. ROIs for the tumor were manually drawn to include such hyperintense voxels on image at b value 800 s/mmThe data analysis was performed using an in-house software written in Matlab .Data were expressed in terms of median value ± range. Kruskal Wallis non-parametric test was performed to emphasize significant statistically difference between median value in different population subgroups. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were assessed. Fisher's exact test was used to evaluate statistical significance of dichotomous 2×2 tables. A p value < 0.05 was considered statistically significant. All analyses were performed using Statistics Toolbox of Matlab R2007a .LI-RADS is a system score to interpret and report imaging features in patients at risk for HCC. Although the arterial phase hyperenhancement is an essential prerequisite for definitely HCC, it not sufficient for LR-5 categorization. Moreover the degree of hyperenhancement is higher with Gd-BT-DO3A than GD-EOB-DTPA, so as the image quality degradation was lower with Gd-BT-DO3A compared to GD-EOB-DTPA. However considering that the hyperenhancement during arterial phase has a lower sensitivity, specificity, PPV, NPV and diagnostic accuracy than hypointensity on hepatospecific phase and that hypointensity in the hepatospecific phase and wash-out appearance are the most significant diagnostic signs to discriminate low-risk from high-risk nodules, patients at risk for HCC may be evaluated alternating these contrast media. The capsule appearance, T2-W hyperintensity and restricted diffusion have a high positive predictive value for HCC while threshold growth may be associated to other features as the appearance of arterial phase hyperenhancement.


Catheter ablation of atrial fibrillation is difficult when the left atrium is compressed by the vertebra. The heart may shift forward, and compression of the left atrium may be relieved in the left lateral decubitus position. Therefore, catheter ablation could be performed in the left lateral decubitus position even in such cases. Catheter ablation (ABL) has become a commonly practiced therapy for atrial fibrillation (AF), especially against drug resistant AF. However, compression of the left atrium by the aorta and the vertebra is not uncommon A 67‐year‐old man was referred for ABL of AF. However, enhanced computed tomography (CT) performed before ABL revealed that the left atrium was compressed by mildly enlarged aortic root and the vertebra Fig. A and thaABL was performed in the left lateral decubitus position. Taking into account the range of the fluoroscopic projection angle, the patient was fixed in the left lateral decubitus position of approximately 45° using a patient immobilization system  Fig. . ElectroTransseptal puncture is necessary for the approach to the left atrium, but there is a risk of cardiac perforation by puncturing the left atrial wall if the left atrium does not have enough space In the present case, we suspected that the heart was shifted backward during supine position because there was a space in front of the heart Fig. A. AlthouThe most known cause for a large shift of the heart is congenital defects of the pericardium In the present case, cardiac magnetic resonance imaging was evaluated after ABL; however, defects of the pericardium were not observed. It seems that the fixation of the heart by the supporting tissue was loose in the present case. There were no clinical characteristics suggesting Marfan syndrome or Ehlers–Danlos syndrome except for mild enlargement of the aortic root in the present case. It is important to recognize that the position of the heart can largely shift even in patients without comorbidities such as defects of the pericardium.Straight back syndrome is a thoracic deformity with absence of upper thoracic spine kyphosis The present case suggests that ABL could be performed in the left lateral decubitus position even in some patients where the left atrium is compressed by aortic root and the vertebra.None declared.YN: contributed to concept/design and drafted the article. YY, TS, and KK: made critical revision of article.


Iron deficiency can be related to patients with chronic heart failure. Although T2* mapping by MRI could be used as a non-invasive interrogator for the assessment of the iron loading, unfortunately the result is only with limited success. Quantitative susceptibility mapping is a further development using susceptibility weighted image. Previous studies suggested a strong linear co-relation between the iron concentration and the magnetic susceptibility. Therefore we used this technique to determine the iron loading and the measured susceptibility from the heart of patients with chronic heart failure.50 patients with chronic heart failure were recruited from the local community. The study was approved by the institutional review board and is complied with the declaration of Helsinki. Informed consent was acquired from all participants. MR images were acquired using a 3 T scanner . 3D fully flow compensated T2* weighted images were acquired with multiple TE of 2.21;4.18;6.15;8.12;10.09;12.06;14.3 and 16 msec. Additional imaging parameters included TR(844.8 msec), Field of View (332 mm by 379 mm) and matrix size (118 by 224). The quantitative susceptibility map was calculated by using software downloaded from Cornell MRI research Lab. Both the susceptibility weighted images and the T2 * map were calculated for comparison.Patients were divided into 2 groups by the left ventricle ejection fraction. The result showed that patients with the left ventricle ejection fraction smaller than 50%, both the T2* and the quantitative susceptibility map were significantly smaller, when compared to patients with a larger left ventricle ejection fraction. The increased iron loading can be related to the cardiac function of the patients. Because T2* could vary from scanner to scanner, it is expected that quantitative susceptibility map can be a potentially useful image based biomarker for the early prognosis of chronic heart failure.The quantitative susceptibility mapping in the diseased heart is feasible. It provides quantitative estimation of the iron loading and therefore can be of great interest in the studies related to iron deficiency in chronic heart failure.