Cardiovascular-MR (CMR) is the gold standard for quantifying myocardial infarction using late gadolinium enhancement (LGE) technique. Both 2D- and 3D-LGE-sequences are used in clinical practise and in clinical and experimental studies for infarct quantification. Therefore the aim of this study was to investigate if image acquisitions with 2D- and 3D-LGE show the same infarct size in patients and ex vivo.Twenty-six patients with previous myocardial infarction who underwent a CMR scan were included. Images were acquired 10-20 minutes after an injection of 0.2 mmol/kg gadolinium-based contrast agent. Two LGE-sequences, 3D-inversion recovery (IR) and 2D-phase-sensitive (PS) IR, were used in all patients to quantify infarction size. Furthermore, six pigs with reperfused infarction in the left anterior descending artery (40 minutes occlusion and 4 hours of reperfusion) were scanned with 2D- and 3D-LGE ex vivo. A high resolution T1-sequence was used as reference for the infarct quantification ex vivo. Spearman’s rank-order correlation, Wilcoxon matched pairs test and bias according to Bland-Altman was used for comparison of infarct size with different LGE-sequences.There was no significant difference between the 2D- and 3D-LGE sequence in left ventricular mass (LVM) . Infarct size in vivo using 2D- and 3D-LGE showed high correlation and low bias for both LGE-sequences both in absolute volume of infarct  and infarct size as part of LVM . The 2D- and 3D-LGE-sequences ex vivo correlated well  for infarct size as part of the LVM. The IR LGE-sequences overestimated infarct size as part of the LVM ex vivo compared to the high resolution T1-sequence .Infarct quantification with 2D- and 3D-LGE gives similar results in vivo with a very low bias. IR LGE-sequences optimized for in vivo use yield an overestimation of infarct size when used ex vivo. Cardiac magnetic resonance (CMR) using late gadolinium enhancement (LGE) is the gold standard to assess myocardial viability in patients with ischemic heart disease. In LGE, infarcted myocardium yields a higher signal intensity compared to normal myocardium after the administration of an intravenous contrast agent -3. AccurThe study conforms to the Guide for the Care and Use of Laboratory animals US National Institute of Health  and was in compliance with the Helsinki Declaration. The study was approved by the Ethics Committee of Lund University, Lund, Sweden and patients have given informed consent.Twenty-six patients  with a documented ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) referred for viability assessment were prospectively included. A total of 19 patients had an acute myocardial infarction (CMR < 30 days after infarction) and 7 patients had a non-acute infarction (CMR > 30 days after infarction) . All patFor ex vivo imaging, a previously described pig model was used ,14. AfteImaging was performed at 1.5 T  using a 32 channel coil. Cine imaging was performed in all patients. ECG-triggered LGE imaging was performed with both a 2D-PSIR and a 3D-IR GRE sequence acquired during mid diastole during end-expiratory breath-hold. Both magnitude and phase-sensitive images were acquired with the 2D-LGE sequence. Short-axis slices covering the entire left ventricle from base to apex and three different long-axis projections were collected. The 2D-LGE sequence was acquired slice by slice during breathold whereas the 3D-LGE sequence was acquired 5 slices per breathold, 10-20 minutes after intravenous administration of 0.2 mmol/kg gadolinium based MR contrast agent . 2D-PSIR was acquired first in 10 patients, and 3D-IR acquisition was performed first in 16 patients. No additional contrast was administered between imaging with the different LGE-sequences. Typical image parameters for the 3D-IR sequence were: echo time 1.3 ms, effective repetition time every heartbeat, flip angle 15°, slice gap 0 mm, slice thickness 8 mm and inplane resolution 1.5 × 1.5. For the 2D-PSIR sequence the typical image parameters were: echo time 4 ms, effective repetition time every second heartbeat, flip angle 25°, slice gap 0 mm, slice thickness 8 mm and in-plane resolution 1.4 × 1.4. The inversion time was chosen to optimally null the myocardium and was typically 280 ms for 3D-IR and between 300-350 ms for 2D-PSIR.Ex vivo imaging with 2D-PSIR, 3D-IR and a high resolution T1w sequence was performed using a head coil covering the left ventricle from the base to the apex with the heart suspended in a plastic container. Acquisition with the T1w sequence typically resulted in 200-220 image slices per heart with a acquisition time of 30-40 minutes. Typical sequence parameters for the T1w sequence were: echo time 3.2 ms, repetition time 20 ms, flip angle 70°, slice gap 0 mm, slice thickness 0.5 mm, inplane resolution 0.5 × 0.5 mm. The sequence parameters for the 2D-PSIR and 3D IR sequences were the same as in patients using a simulated ECG with heart rate 60/min. The spatial resolution for 2D-PSIR was 0.6 × 0.6 × 4 mm and for 3D-IR 1 × 1 × 4 mm.http://segment.heiberg.se) [All MR images were evaluated by two blinded observers using the software Segment  . The lefberg.se) . Infarctberg.se) . The meaberg.se) . Manual Calculations and statistics were performed using Graph Pad Prism 5.0 software . Results are expressed as mean ± SD and Spearman’s rank-order correlation, Wilcoxon matched pairs test and bias according to Bland-Altman was used for comparison of infarct size with different LGE-sequences in patients and ex vivo. Statistical significance was defined as results with a p < 0.05.Three patients were excluded because of poor image quality due to breathing artefacts and inadequate nulling of the myocardium. A total of 23 patients were included in the study and all patients showed myocardial hyperenhancement on both 2D- and 3D-LGE sequences.Figure Figure This study has demonstrated that myocardial infarct quantification with a 2D-PSIR and a 3D-IR sequence show good agreement in patients with both acute and non-acute infarcts. This allows for the sequences to be used interchangeably in a clinical setting as well as for clinical studies using LGE-MR. The current study also demonstrates that in an experimental setting both the 2D- and the 3D-LGE-sequence overestimate infarct size compared to a high resolution T1 weighted sequence ex vivo.0 signal to recover before a new IR-pulse is given and is therefore less sensitive to arrhythmias [et al compared a 2D-IR and a single breathold 3D IR sequence in 13 patients and found good agreement between quantified infarct volumes (bias 0.3 cm3 ± 3.1) similar to what we found in the current study [et al[et al[The use of the clinical standard for viability imaging, 2D-IR-GRE, requires 10–16 slices each acquired over 14 heartbeats to assess the entire left ventricle. The 2D image is acquired on every second heartbeat which enables the Mhythmias . Imaginghythmias ,20. Sinchythmias  and visuhythmias -23. Dewedy [et al compared al[et al comparedet al showed [We used left ventricular mass on LGE-CMR to express infarct size as percentage of LVM and LVM on 2D-PSIR and 3D-IR agreed well. Stephensen l showed  that quaet al[Previous studies have shown good agreement between in vivo quantification of myocardial infarction on 2D and 3D-LGE in pigs ,11. Furtet al. The autIn clinical multicenter trials where infarct quantification is performed following revascularization or other therapies, the assessment of myocardial salvage is a predictor of therapy outcome ,26. MyocThe order of the acquisitions was not randomized but in a subset of patients 2D-LGE imaging was performed before 3D-LGE and vice versa. However, the images are comparable regarding hyperenhancement since it has been shown that normal myocardium is in equilibrium with the blood pool only minutes after contrast bolus administration and remains constant up to 25 minutes . In the In summary, infarct quantification with 2D PSIR- and 3D-IR provides similar results in vivo with a low bias and the two sequences can be used interchangeably. IR LGE-sequences optimized for in vivo use yield an overestimation of infarct size ex vivo.CMR: Cardiac magnetic resonance imaging; LGE: Late gadolinium enhancement; IR: Inversion recovery; PSIR: Phase sensitive inversion recovery; GRE: Gradient echo; TI: inversion time; T1w: T1 weighted; SNR: Signal-to-noise-ratio; CNR: Contrast-to-noise-ratio; LAD: Left anterior descending artery; TTC: Triphenyltetrazolium chloride; CE-SSFP: Contrast-enhanced steady state free precession; ROI: Region of interest; SD: Standard deviation.The authors declare that they have no competing interests.The authors have contributed as follows: RJ participated in the animal experiments, performed the analysis and drafted the manuscript. DN analyzed clinical data. SK, MK and JU participated in the animal experiments. HA, DE, EH, HE and MC conceived and designed the study. All authors read, critically revised and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/13/110/prepub


Coronary artery reimplantation is crucial step during the arterial switch (ASO) and Ross operation. Mortality and long-term outcome after the operation mainly depend on the patency and function of the reimplanted coronary arteries due to risk of stenosis, stretching, or occlusion.Cardiovascular magnetic resonance (CMR) imaging has emerged as a promising diagnostic tool for the evaluation of children heart. We utilized advanced CMR methods to perform a noninvasive assessment of myocardial blood flow, viability, function and diffuse fibrosis in patients after ASO and Ross operation to guide further therapy and for a better understanding of the microcirculation.MRI first-pass perfusion imaging  was performed in 36 patients  and in 10 age matched healthy controls. Myocardial blood flow (ml/g/min) was calculated in 6 LV segments per slice (2-3 slices/pt). Quantitative blood flow at rest and stress (Adenosin 140 µg/kg/min) was derived from signal intensity curves by model independent deconvolution. Late enhancement studies (Gd 0.1 mmol/kg) using T1 weighted inversion recovery sequences were performed to detect myocardial scar. A Look-Locker technique  for measurements of T1 was used for detecting of LV diffuse fibrosis. Furthermore, cine MRI and 3 D coronary artery imaging were performed to assess ventricular function and coronary anatomy.Of the entire cohort 15 pts (41.7 %) had known or suspected coronary problems such as occlusion, stenosis or hypoplasia. In 7/15 pts (46.7%) we found regional ischemia, scar tissue (28.6%) and regional or global impairment of LV function (30%). As a consequence of our findings one patient received MIDCAB surgery and 4 patients (26.7%) were treated medically.In pts with patent epicardial coronaries (58.3%) myocardial perfusion reserve (MPR) was significantly reduced as compared to the healthy controls  and only in one patient scar tissue was detected. No regional or global wall motion abnormalities were detected. Furthermore, T1 mapping showed increased extracellular matrix expansion suggestive of diffuse fibrosis .CMR imaging can provide a comprehensive assessment of myocardial perfusion, viability and function in patients after coronary reimplantation to guide further therapy such as surgical revascularisation. Of note, in patients with patent epicardial coronaries, we measured an impaired myocardial perfusion reserve and increased interstitial fibrosis.Kinderherzen-Wollen-Leben e. V, Neumünster, Germany.


Physiological cardiac hypertrophy and dilation are common findings in heavy physical load activity. We carried out this study to investigate the relationship between construction work and cardiac parameters adaptations, by comparing healthy masons to office workers on heart ultrasound.The study was carried out on, 50 construction workers and 50 office workers matched for their weight, height and age. Systolic and Diastolic blood pressures, Left Ventricular diameter and thickness, Septum wall thickness and Left ventricular mass index were measured and calculatedHeart rate, systolic and diastolic blood pressures were lower in construction workers, as compared to office workers: respectively 63±7 bpm vs. 75±6 bpm (p = 0.000); 120.1±7 mmHg vs. 130.5±9 mmHg (p = 0.000) and 68.5±7 mmHg vs. 77.0 ±9 mmHg (p = 0.000). Construction workers had a thicker septum and posterior wall: respectively 10.3 ± 1.1 mm vs. 8.9 ± 0.9 mm (p = 0.000); and 9.0 ± 1.2 mm vs. 8.1 ± 0.8 mm (p = 0.000).Conclusion We deducted that heavy load work has an impact on the heart mensuration. The past occupational history has to be taken into consideration during initial medical assessing of a worker in for a new job so as to avoid erroneous conclusions. Many studies showed the role of professional activities or environmental condition on cardiovascular system . WorkersThis research is a prospective cohort study designed to measure the dimensions of heart on ultrasound on 50 masons and compare to 50 office workers. The masons were recruited form different part of Douala town in Cameroon. Office workers were recruited form different companies. In all cases, they were randomly selected. We tried to match to two groups to reduce biases that could be due to weight, height and age. None of the subjects were exposed to sport activity. We obtained an informed consent from all the subjects participating to this study. The Cameroon Society of General Medicine approved our protocol. After approving the inform consent form, a health questionnaire was filled by each worker, with general information including age, weight and height. This was followed by a clinical examination with two consecutive measurement with a 5 min interval time between the two measurements of blood pressure at rest at the left upper arm, then cardiac and lung auscultation. Finally, heart ultrasound was performed by one ultrasound qualified operator, on a patient at a 30 degree left lateral position. For this study, we used an ultrasound from Siemens. Septum and posterior wall thickness were measured, followed by ventricular cavities measurements: left ventricle and atrium. The left ventricular relative mass was calculated using the formula All subjects with past medical history of cardiovascular diseases, regular sportive activity and ongoing cardiovascular treatment were excluded from our sample. The analyses were performed using IBM SPSS Statistics 20. From initial data recorded, some calculations were done. Devereux formula was used to calculate left ventricular mass. Dubois formula was used to calculate body surface. Reichek formula was used to calculate diastolic relative wall thickness. We used descriptive statistics median, minimum and maximum and non-parametric Mann-Whitney t tests for unmatched samples to compare cardiac ultrasound parameters between Construction and office workers. We calculated the Spearman correlation parameter to measure the correlation between continuous variables in the two categories of workers.Our two groups were comparable in terms of average age, weight, height, budy mass index and budy surface areas , Table 2The analysis indicated that there were larger left atrium diameter and left ventricular end diastolic diameter, thicker septum and posterior wall, as well as bigger sum of ventricular wall thickness and left ventricular mass index. All these differences were statistically significant (p < 0.001). Ejection time was longer in office workers, but the difference was not statistically significant, showing a physiological changes rather than a pathological one. Similarly, there were no statistical significance in the differences observed between the two groups in regards to DT_E, E wave, A wave and E/A ratio as well as shortening fraction, once more showing the physiological variation observed.Non parametric Spearman correlation shows a correlation between wall thickness and left ventricular mass index, and time spent at function in years, in construction workers . In offiThe major finding of this study in Cameroonian cohort is that constructors workers had had higher LV mass as compare to office workers. Echographically measured left ventricular mass is an important predictor of adverse events in the general population . LV massIn the present study, the fact that construction workers had lower heart rhythm and thicker ventricle wall is probably related to physical heaviness of activities needed in this profession. The same situation had been described in trained athletes and non-athletics population practicing regular exercise. Resistance training is associated with proportional increase in the left ventricular wall thickness , 15. TheThe increase in parameters found on echography in construction workers may be related to their heavy work activity. The suggestion is made by the fact that factors that could cause a bias in the conclusion such as smoking habit and sport are controlled. We suggest that special attention be taken in regards to assessment of construction workers as they may be at risk of cardiovascular complications as compare to other professionals.


Aortic stenosis has an increasing prevalence in the context of aging population. In these patients non-invasive imaging allows not only the grading of valve stenosis severity, but also the assessment of left ventricular function. These two goals play a key role in clinical decision-making. Although left ventricular ejection fraction is currently the only left ventricular function parameter that guides intervention, current imaging techniques are able to detect early changes in LV structure and function even in asymptomatic patients with significant aortic stenosis and preserved ejection fraction. Moreover, new imaging parameters emerged as predictors of disease progression in patients with aortic stenosis. Although proper standardization and confirmatory data from large prospective studies are needed, these novel parameters have the potential of becoming useful tools in guiding intervention in asymptomatic patients with aortic stenosis and stratify risk in symptomatic patients undergoing aortic valve replacement.This review focuses on the mechanisms of transition from compensatory left ventricular hypertrophy to left ventricular dysfunction and heart failure in aortic stenosis and the role of non-invasive imaging assessment of the left ventricular geometry and function in these patients. Aortic stenosis (AS) is the third most common cardiovascular disease in Western countries and the main indication for valve replacement in adult patients . The assLeft ventricular ejection fraction (LVEF) is currently the only LV function parameter that guides intervention in asymptomatic patients with severe AS . Even inConcentric hypertrophy is the main compensatory mechanism for pressure overload  in patieAlthough valvular obstruction is the most important stimulus for LVH in patients with AS, the LV response depends not only on the severity of AS, but also on a multitude of individual factors. Age, gender, genetic variation in the renin–angiotensin system, co-existing coronary artery disease, hypertension, or significant associated aortic regurgitation are additional factors influencing the response of the LV to increased valvular load -12.In patients with concomitant systemic hypertension, an increase in blood pressure superimposed on an increased valvular resistance leads to a significant increase in LV systolic wall stress. The contribution of vascular load is essential to be recognized in all patients with AS, as it further increases LV global afterload, which is associated with decreased stroke volume, impaired myocardial function and reduced survival .If the valvular obstacle is not removed, the adaptive mechanisms to pressure overload are exceeded, either because the limit of sarcomere extension is reached or because marked LVH with increased diastolic stiffness prevents adequate LV filling . The LV A large number of experimental and clinical studies addressed the transition from the "compensated state" of LVH to overt HF in AS and proposed a series of potential underlying mechanisms. Interstitial myocardial fibrosis, myocyte degeneration, and apoptosis are early structural changes in patients with severe AS, their extent being related to increasing LV filling pressures and decreased LVEF .Impaired coronary flow reserve and inadequate subendocardial blood flow are found in patients with AS even in the absence of significant coronary artery disease . These aDiastolic dysfunction has an important role in the pathogenesis of symptoms and the progression to HF in patients with AS . It appeAn accurate assessment of LV remodelling and function is warranted in all patients with significant AS. The identification of early signs of impaired myocardial contractility is particularly important in asymptomatic patients with severe AS. A series of new noninvasive imaging derived parameters of LV function emerged as predictors of disease progression in AS.Echocardiography remains the investigation of choice both for the assessment of AS severity and LV function. Linear LV dimensions should be measured in all patients based on existing recommendations  for furtThree-dimensional echocardiography overcomes the inherent geometrical assumptions from 2D echocardiography and its accuracy in measuring LV volumes and mass was already demonstrated against cardiac magnetic resonance imaging (CMR) , but lacConventional echocardiography allows the estimation of LV systolic function by measuring LV endocardial and midwall fractional shortening, LVEF, mitral annular plane systolic excursion (MAPSE), LV stroke volume and myocardial performance index. Both LV endocardial shortening fraction and LVEF are derived by measuring endocardial displacement, and both overestimate systolic function in the presence of concentric LVH. Mitral annular plane systolic excursion reflects global LV longitudinal systolic function and is a more sensitive marker of systolic dysfunction compared to LVEF. It declines with increasing AS severity independent of LVH, implying a direct relation with the increased haemodynamic load . Decreas2 is an essential criterion for the definition of paradoxical low-flow AS [Accurate calculation of LV stroke volume  must be included in the echocardiographic evaluation of patients with AS, especially in patients with severe AS , preserved LVEF (>50%) and a low transvalvular gradient (mean gradient < 40 mmHg). A cut-off value of < 35 ml/m-flow AS . These p-flow AS . Recentl-flow AS .Although LVEF below 50% is the only parameter of LV function that guides intervention in patients with severe AS , it is nA separate analysis of the various components of LV deformation by current echocardiographic techniques allows a better understanding of progression to HF in patients with AS and an early detection of asymptomatic patients who are most likely to benefit from more aggressive intervention.tissue Doppler imaging (TDI) assessed subtle changes in LV function in patients with significant AS and preserved LVEF. Peak systolic annular velocities (S') were significantly reduced in non-ischemic patients with moderate and severe AS, in the presence of normal LVEF and cardiac index [A series of clinical studies based on ac index ,25. Longac index . A rapidac index ,27.Two-dimensional speckle-tracking echocardiography (2D-STE) allows a multidirectional angle-independent evaluation of myocardial deformation providing a comprehensive assessment of LV function . The resA gradual impairment in longitudinal, circumferential, and radial deformation was found in a large number of patients with a wide range of AS severity, suggesting a progressive subendocardial to transmural impairment of myocardial function with increasing LV afterload . In asymHowever, data regarding circumferential and radial LV deformation are not consistent between studies ,31, in pOn the other hand, GLS seems to be a more robust parameter and emerged as a potentially useful tool in the assessment of subclinical LV dysfunction in AS Figure .Figure 2Echocardiographic parameters of longitudinal LV function (such as MAPSE and GLS) allow an indirect assessment of fibrotic changes in patients with AS. They are surrogate markers of the presence and severity of myocardial fibrosis and are superior to LVEF in the assessment of latent LV dysfunction. Although myocardial reflectivity is directly related to myocardium collagen content and can be quantitatively assessed using ultrasonic backscatter signal , this teLeft ventricular torsional deformation has an important role in both LV ejection and filling ,34. An iThe assessment of LV diastolic function in patients with AS should be performed using the existing recommendations  and takiDoppler transthoracic or transoesophageal echocardiography, usually with intravenous adenosine infusion, allow the noninvasive evaluation of coronary flow reserve, a surrogate for the coronary microcirculation in patients with normal angiographic coronary arteries. Most studies conducted in patients with significant AS showed that coronary flow under resting conditions is significantly higher and hyperemic flow velocity is lower compared with controls .The current recommendations for stress echocardiography in patients with AS are still limited ,3. The aThe evaluation of vascular afterload is a useful additional diagnostic tool in patients with AS. It was demonstrated that both carotid and aortic stiffness are associated with increased LV filling pressures, plasma BNP and symptoms in patients with moderate and severe AS . MoreoveValvulo-arterial impedance, which provides an estimate of the global LV haemodynamic load, is superior to the standard indexes of AS severity in predicting LV dysfunction. Its independent prognostic value was already demonstrated in both symptomatic and asymptomatic patients with significant AS ,46.In patients with AS, CMR allows the quantification of the severity of valve disease, provides additional information regarding the enlargement of the ascending aorta and the consequences of pressure overload on LV structure and function.There has been growing interest in the assessment of myocardial fibrosis by CMR. The development of diffuse fibrosis emerged as a key mechanism for the progression to HF of patients with AS  and a poLate gadolinium enhancement (LGE) CMR is the gold standard imaging method for assessing focal, replacement fibrosis  Figure . In sympPatients with paradoxical low-flow low gradient AS have a higher degree of myocardial fibrosis and a more impaired LV longitudinal function when compared to patients with normal flow high gradient AS . These cThe assessment of myocardial fibrosis by CMR may in the future refine the selection of asymptomatic patients with severe AS, who may benefit from early intervention, although this requires confirmation in larger prospective studies.Subclinical deterioration of LV function can also be assessed by CMR, which is considered the reference standard for the assessment of myocardial deformation . A few cGiven its complexity, high cost and limited availability, the utility of CMR for the assessment of LV strain in AS remains confined to research in certain academic centers.Myocardial perfusion reserve may also be assessed by CMR and is independently associated with objectively measured exercise capacity in patients with severe AS .Multi-slice cardiac computed tomography (CT) offers additional data regarding the ascending aorta and the LV outflow tract in patients with AS, and is useful in quantifying the valvular and coronary calcification, with specific application in patients who are eligible for a transcatheter AVR . This teAlthough the assessment of LV volumes and global function by cardiac CT has a wider availability when compared to CMR, its utility in patients with AS is not established in clinical practice.Positron emission tomography allows the noninvasive quantification of the transmural distribution of myocardial blood flow. Myocardial flow reserve can also be evaluated using dynamic perfusion imaging at rest and during dipyridamole stress. This parameter is more severely impaired in the subendocardial layers of the LV in patients with LV hypertrophy atributable to severe AS and angiographically normal coronary arteries. In patients with low-flow, low-gradient AS a higher resting myocardial blood flow and a reduced flow reserve (linked to the AS severity) were also found using this technique .The comparative role of currently used noninvasive imaging techniques in the assessment of LV structure and function in AS is illustrated in Table Varying degrees of mitral regurgitation  are often found in patients with severe AS. Concomitant severe mitral regurgitation may lead to an overestimation of LVEF and LV fractional shortening.Left ventricular remodelling is a determinant of functional mitral regurgitation not only in patients with AS and reduced LVEF but also in patients with preserved LVEF. A significant inverse correlation was found between effective regurgitant orifice area and LV systolic longitudinal shortening in these patients, suggesting that subclinical LV dysfunction might compromise proper mitral valve function .Significant CAD is present in more than 50% of patients with severe AS who are over 70 years . A lowerCurrent guidelines strongly recommend AVR in all patients with severe AS when associated with either symptom related to AS or an abnormal LVEF (<50%) . In clinIn symptomatic patients with severe AS, AVR is firmly indicated but further risk stratification may be needed in patients with severely impaired LV function or extensive comorbidities, especially with the recent extent of transcatheter AVR interventions.et al. [The prognostic value of LV dysfunction in patients with AS was demonstrated by Lund et al.  in symptet al. .Beyond LVEF, excessive LVH and abnormal TDI parameters of LV function are cited by the current guidelines  as prediMost of the available data suggest that TDI and STE derived indices of LV function might be useful for risk stratification in both symptomatic and asymptomatic patients with AS although they need validation in larger studies. A summary of the most important clinical studies addressing this issue is presented in Table Both E/e' ratio (as an expression of LV filling pressures) and GLS  can be easily measured in most patients with AS and have the potential of becoming useful tools for risk assessment in clinical practice. However, their incremental prognostic value over well-known haemodynamic parameters of AS severity was not clearly demonstrated. After accounting for the severity of AS, neither indexed LV mass nor any TDI derived parameter of LV function provided additional predictive information in asymptomatic patients . On the Echocardiographic parameters of LV longitudinal function are strongly linked to the extent of myocardial fibrosis, which has clear prognostic implications . MidwallTherefore, the echocardiographic assessment of LV longitudinal deformation allows estimation of LV subendocardial fibrotic changes and may become a tool for risk stratification in patients with significant AS. So far, the clinical utility of GLS is hindered by the lack of standardization on different echo machines and lack of specific cut-off values.B-type natriuretic peptide (BNP) is a useful tool in risk stratification of asymptomatic patients with AS, although absolute threshold values were not adequately validated for use in clinical practice. An increase in serial BNP levels may identify a subgroup of patients with a higher degree of diastolic LV dysfunction and latent LV systolic dysfunction that may precede symptom development . A serum2) was an independent predictor of cumulative all-cause and cardiovascular mortality [2 reduction in stroke volume index [In a retrospective study in a large cohort of high risk patients who underwent transcatheter AVR low flow  and myocardial fibrosis (estimated by CMR) will probably be increasingly used in the decision making process in patients with AS in the near future. Although proper standardization and confirmatory data from large prospective studies are needed before incorporating such new parameters into practical management algorithms, their close monitoring may prevent irreversible myocardial damage and the risk related to delayed symptom reporting. Exercise echocardiography may provide incremental prognostic value by assessing both exercise-induced symptoms and changes in valve haemodynamics, LV function, and pulmonary pressures. Such an inclusive approach can aid in timing the intervention in apparently asymptomatic patients with severe AS and stratify risk in patients undergoing AVR.In view of the fact that no single parameter of LV function predicts the optimal timing for AVR in asymptomatic patients, all available information must be considered for optimal decision-making in clinical practice.


Background. Polymicrogyric cortex demonstrates interindividual variation with regard to both extent of dyslamination and functional capacity. Given the relationship between laminar structure and white matter fibers, we sought to define the relationship between polymicrogyria (PMG), intrahemispheric association pathways, and network function. Methods. Each arcuate fasciculus (AF) was categorized as present or absent. Language was characterized by a pediatric neurologist. The presence of dysplastic cortex in the expected anatomic locations of Broca's (BA) and Wernicke's areas (WA) was evaluated by two pediatric neuroradiologists blinded to DTI and language data. Results. 16 PMG patients and 16 age/gender-matched controls were included. All normative controls had an identifiable left AF. 6/7 PMG patients with dysplastic cortex within BA and/or WA had no left AF; PMG patients without involvement of these regions had a lower frequency of absence of the left AF (p < 0.006). All patients without a left AF had some degree of language impairment. PMG patients without a left AF had a significantly greater frequency of language impairment compared to those PMG patients with a left AF (p < 0.003). Conclusion. In patients with PMG (1) the presence of dysplastic cortex within WA and/or BA is associated with absence of the left AF and (2) absence of the left AF is associated with language impairment. Polymicrogyria (PMG) is a malformation of cortical development that arises as a result of disturbed cortical organization and late neuronal migration . It is cThe normal human cerebral neocortex is composed of six discrete layers. In very general terms, layer 1 contains few neurons which primarily receive interhemispheric fibers. Pyramidal neurons in layers 2 and 3 originate and receive intra- and interhemispheric corticocortical fibers. Layer 4 is the principal target of thalamocortical fibers. Layer 5 is the major source of projection fibers to the basal ganglia, brainstem, and spinal cord. Finally, fibers originating in layer 6 primarily project to the thalamus. Although throughout the neocortex this fundamental organization is essentially invariant, the relative contribution of each layer to total cortical thickness reflects, to a significant degree, functional specialization . For exaPolymicrogyric cortex contains essentially the same principal classes of neurons as normal cortex; furthermore, neuronal subtypes are located at appropriate, or at least analogous, laminar levels –10. PathThere is an association between the presence of dysplastic cortex within the expected anatomic locations of WA and/or BA and absence of the left AF at diffusion tractography.There is an association between absence of the left AF and language impairment.The arcuate fasciculus (AF) is a major intrahemispheric association pathway which connects two cortical areas that play a major role in human language, Wernicke's (WA) and Broca's areas (BA) , 15. AltThis HIPAA-compliant study was approved by the local institutional review board. Patients were identified retrospectively with the following inclusion criteria: (1) pediatric age group ; (2) diagnosis of polymicrogyria (PMG) established by MRI; (3) MRI of the brain performed at 3 Tesla, including DTI; (4) language development characterized by a pediatric neurologist. Refinements to the above-defined population were based on the following exclusion criteria: (1) motion or other degradations to image quality; (2) exclusion of patients younger than 3 years of age, to increase confidence in the clinical determination of language delay.An age- and gender-matched normative control group was also retrospectively identified with the following inclusion criteria: (1) clinical indication of headache; (2) MRI of the brain performed at 3 Tesla, including DTI ; (3) language characterized as normal by a pediatric neurologist. Exclusion criteria were (1) any neurologic abnormality by history or physical exam; (2) any degree of language impairment; (3) any MRI abnormality; (4) significant motion or other degradations to image quality. It should be noted that the normative cohort was included to further inform interpretation of results in the polymicrogyric population not to definitively define the normal character of the arcuate fasciculus. While patients with headaches may in fact demonstrate white matter differences compared to the truly normal population, the typical headache patient in our practice very commonly demonstrates no anatomic or neurologic abnormalities.b value: 1000 sec/mm2). All images were visually inspected for artifacts, including subject motion.All imaging was performed on two 3-Tesla magnets . The following sequences were obtained: (1) sagittal magnetization prepared rapid gradient echo : 1 × 1 × 1); (2) axial FSE T2-weighted images : 0.6 × 0.4 × 2.5); (3) axial FLAIR : 0.7 × 0.7 × 4); (4) axial single-shot EPI DTI (TR/TE (ms): 7000/142; Flip: 90 degrees; 1 acquisition; voxel (mm): 2 × 2 × 2). For DTI, 35 image sets were acquired, five without diffusion weighting and thirty with noncollinear diffusion-weighting gradients  and/or Wernicke's  areas in the left hemisphere . For each voxel, a tensor matrix was derived. After diagonalization of the matrix, eigenvalues were obtained and MD and FA were quantified for each pixel according to standard equations [http://www.trackvis.org/) was used for deterministic tract reconstruction using a fiber association by continuous tracking algorithm (35-degree angular threshold). A DWI mask was used to remove cerebrospinal fluid, a process which has been shown to effectively prevent spurious tract reconstruction [http://www.trackvis.org/) was then used for isolation of the AF and fiber-track analysis. Regions of interest for tract segmentation were placed manually on the color FA maps cross referenced to the b0 images according to previously described methods [Maps of diffusivity (MD) and fractional anisotropy (FA) were created using Diffusion Toolkit (quations . Diffusitruction . Trackvi methods . The AF  methods . Mean MDPatients were divided into three groups based on characterization of their language development by a pediatric neurologist: (1) intact: age-appropriate; (2) mild-to-moderate impairment: delayed by comparison to peers (either expressive or receptive); (3) profound impairment: absence of verbal language.Proportions of subjects with versus without absence of the left AF and with versus without language impairment were compared using Fisher Exact test . The Wilcoxon rank sum test was used to compare continuous variables (mean FA and mean MD) between two groups . The relationships between tract diffusion parameters and age were assessed using linear regression. All statistical testing was performed using SAS software, Version 9.2 .Imaging was performed from January 2009 to December 2010. Of the 20 patients identified meeting the inclusion criteria, 1 was excluded on the basis of significant motion and 3 on the basis of age (less than 3 years). 16 PMG patients  and 16 age- and gender-matched normative controls  comprised the final study group.p < 0.0004). There was no significant difference between either the mean FA or mean MD of the identified left AF in PMG patients versus controls. Direct and inverse linear relationships to age were observed, respectively, for left arcuate FA and MD in both the PMG patient  and normative subject  groups. There was no significant gender difference in either the mean MD or mean FA of the identified left AF in either PMG patients or controls. Trends toward higher FA in the left versus right AF in PMG patients and controls did not meet statistical significance .All normative controls had an identifiable left AF. Nine (56%) PMG patients had an identifiable left AF. The frequency of absence of the left AF in PMG patients was significantly higher than that in normative controls (p < 0.006). There was a single patient who had dysplastic involvement of BA and WA and an identifiable left AF (Six (86%) PMG patients with dysplastic cortex within the left BA and/or WA had no left AF .All normative subjects had intact language. By comparison, seven (44%) PMG patients had intact language. Six (38%) were mildly-to-moderately impaired and three (19%) were profoundly impaired. The extent of PMG involvement in terms of the number of lobes involved did not differ between language impaired and intact patients. The likelihood of language impairment in PMG patients was not associated with gender (n = 4) and left- (n = 3) handed patients. PMG patients without a left AF had a significantly greater frequency of language impairment compared to the normative population (p < 0.00001). Language impairment was also significantly more prevalent in PMG patients without a left AF versus PMG patients with a left AF (p < 0.003). Test characteristics of absence of the left AF with respect to language impairment in an individual patient are presented in All normative subjects had an identifiable left AF. Similarly, all PMG patients with normal language had an identifiable left AF. By contrast, all PMG patients without a left AF had some degree of language impairment; this finding was observed consistently in both right-  dysplastic cortex within the expected anatomic locations of two key language areas was associated with absence of the left AF. (2) Absence of the left AF was strongly associated with impairment of language function.Formation of association pathways involves numerous developmental processes that act in a coordinated fashion to establish mature patterns of cerebral connectivity. These include, but are not limited to, differentiation and maturation of pyramidal cells in cortical layer 3, axonal genesis and guidance to the subplate, synapse formation and establishment of connectivity with the developing cortical plate, and selection (or pruning) of connections . The lasWe report a significant association between the presence of dysplastic cortex within the expected anatomic locations of WA and/or BA and absence of the left AF. This observation suggests a frequent impact on the establishment and/or preservation of corticocortical connections in patients with PMG. One possible explanation for this finding is that PMG patients frequently exhibit significant alterations within the cortical layers involved in corticocortical connectivity. It would follow that abnormal cortical lamination could result in a diminished and/or abnormal contribution to the AF and, therefore, failure to detect it at tractography. It is important to note that the histopathological significance of failure to identify a tract at diffusion tractography is yet to be established. In addition to absence of the tract in an absolute sense, this finding could reflect marked disorganization of white matter structure resulting in a profound loss of tissue coherence. In other words, superficial cortical layers that are absent, significantly attenuated, or that are otherwise associated with aberrant connections between the origin and target cortices could all theoretically result in an undetectable AF. Interestingly, Phillips et al. recently demonstrated a direct relationship between the FA of the AF and cortical thickness within the two language areas connected by this pathway ; these fAlthough it has not been well studied to date, the idea that corticocortical connections may be abnormal in PMG is consistent with a case report by Munakata et al., in which a case of unilateral left-sided PMG was associated with absence of the left AF . SimilarIt is important to consider that the output of quantitative functional imaging studies is always closely related to the specific technical parameters utilized during image acquisition, processing, and analysis. For this reason, it is crucial to tie any such imaging findings to an identifiable functional phenotype. We report an association between absence of the left AF and language impairment in a cohort of pediatric patients with PMG. In our study population, all PMG patients with absence of the left AF were language impaired while all subjects with normal language function (both in the PMG and normative groups) had an identifiable left AF. In addition to corroborating the significance of the observed relationship between the locale of dysplastic cortex and intrahemispheric association pathways, these findings suggest that absence of the left AF may be a specific marker of language impairment in this patient population. They further raise the possibility that successful formation of corticocortical connections may be more closely associated with network function than simply whether the relevant cortex is dysplastic. In other words, dysplastic cortex that can support the formation and preservation of intrahemispheric association pathways may also be capable of supporting normal language development. Interestingly, Loui et al. recently demonstrated a failure to identify a superior component of the right AF in 9 of 10 subjects with tone deafness  . This wo in toto. Although insufficient to define the functional relevance of all parts of the network, this study design was adopted in the service of simplicity and the well-defined relationship between two key language cortices and the AF. Future studies correlating individual subcomponents of the network with detailed neuropsychological analyses of a range of language subdomains would be of great value toward extending the relationships suggested by this study.Although our findings suggest that formation of the left AF may be an important step toward the development of normal language function, the observed language impairment in some patients with a left AF suggests that it is not sufficient. This finding is expected given our study design, which evaluated only the relevance of WA and BA. Although these two areas are clearly important, the fluent comprehension and production of language are predicated on the rapid transmission of information among numerous, distributed cortical areas . FurtherAlthough to our knowledge this is the first report on the functional significance of absence of the left AF in patients with MCDs, the importance of the left AF to language function has been suggested in other neurodevelopmental disorders. Abnormal, though identifiable, arcuate fasciculi have been reported in a range of disorders manifesting speech delay , 21, 39.This study has several limitations. First, this is a study of a highly selected cohort of patients with PMG. Extrapolation of these results to patients with other malformations or to other patient groups at risk for language impairment may not be valid. Second, as fMRI was not performed, the actual locations of receptive and expressive language were not definitively ascertained. In a related matter, the small patient number in this study precluded a statistical accounting for handedness. There is, however, some evidence to suggest that lateralization of the AF may not be consistently related to either functional lateralization or handedness . FurtherIn conclusion, we have used the language network to examine the relationship between the locale of dysplastic cortex and intrahemispheric association pathways in pediatric patients with PMG. In particular, we report the following: (1) an association between the presence of dysplastic cortex within the expected anatomic locations of WA and/or BA and absence of the left AF; (2) a strong association between absence of the left AF and language impairment. These findings suggest that the ability to form and/or maintain corticocortical connections is frequently impaired in polymicrogyria and, furthermore, may be closely related to network function. If these findings can be validated in larger studies, such approaches may form the basis for useful biomarkers of cortical function in patients with malformations of cortical development.


Left ventricular end-diastolic pressure (LVEDP) is the foundation of cardiac function assessment. Because of difficulties and risks associated with its direct measurement, correlates of LVEDP derived by pulmonary artery (PA) catheterization or transesophageal echocardiography (TEE) are commonly adopted. TEE has the advantage of being less invasive; however TEE-based estimation of LVEDP using correlates such as left ventricular end-diastolic volume (LVEDV) has technical difficulties that limit its clinical usefulness. Using intraoperative acute normovolemic hemodilution (ANH) as a controlled hemorrhagic model, we examined various mitral flow parameters and three-dimensional reconstructions of left atrial volume as surrogates of LVEDP. Our results demonstrate that peak E wave velocity and left atrial end-diastolic volume (LAEDV) correlated with known changes in intravascular volume associated with ANH. Although left atrial volumetric analysis was done offline in our study, recent advances in echocardiographic software may allow for continuous display and real-time calculation of LAEDV. Along with the ease and reproducibility of acquiring Doppler images of flow across the mitral valve, these two correlates of LVEDP may justify a more widespread use of TEE to optimize intraoperative fluid management. The clinical applicability of peak E wave velocity and LAEDV still needs to be validated during uncontrolled resuscitation. Blood flow across the mitral valve reflects the instantaneous pressure difference between the left atrium and left ventricle. The pattern of flow is modified by left ventricular diastolic function . ConsequTransthoracic and transesophageal echocardiography (TEE) are used with increasing frequency to evaluate and monitor cardiac function in the perioperative setting. The diagnosis and management of the patient with hemodynamic instability are a level 1 indication for intraoperative TEE . In addiFor acute patient management, the most common TEE characterization of ventricular function is the left ventricular end-diastolic volume (LVEDV) , 15. AltThese data were collected as part of a single center, prospective, nonrandomized, observational study recruiting from consecutive patients scheduled for elective open prostatectomy, cystectomy, cystoprostatectomy, or anterior/posterior spinal fusion procedures that included ANH as a routine part of the perioperative strategy to minimize the need for homologous blood transfusion. Other results from this protocol have been previously reported .2O. A radial arterial catheter was then placed, large bore peripheral venous access was established, and the stomach was suctioned with an 18Fr orogastric tube to enhance image acquisition prior to insertion of the TEE probe .After approval by the University of California Davis Human Subjects Research Committee, all patients provided written, informed consent prior to enrollment. Patients were excluded from consideration if there were contraindications to ANH or esophageal pathology that increased the risks associated with the placement of an ultrasound probe. All patients received preoperative intravenous sedative (midazolam 0.01–0.02 mg/kg). Upon arrival in the operating room, they were preoxygenated and standard physiological monitors were applied. All urological surgical patients received a single intrathecal injection of morphine (0.3 mg). Intravenous fentanyl (1–3 mcg/kg) and propofol (2-3 mg/kg) were then administered to induce general anesthesia. Neuromuscular blockade was established with rocuronium (1 mg/kg) to facilitate endotracheal intubation and provide muscle relaxation during surgery. General anesthesia was maintained with sevoflurane in an air/oxygen mixture to achieve a fractional inspired oxygen concentration of 0.6. Normocapnia was maintained with tidal volumes averaging 8 mL/kg and a positive end-expiratory pressure of 5 cm HAfter a stable anesthetic state had been established, baseline hemodynamic parameters were recorded along with the TEE images described below. The acute normovolemic hemodilution protocol was then initiated. Total blood volume was estimated using the standard formula of 70 mL/kg for male and 65 mL/kg for female patients. Blood removal was accomplished via the peripheral venous catheter with the use of a tourniquet or via the arterial line. 15% of the estimated blood volume (EBV) was removed in three separate aliquots, each one 5% of the EBV. Each aliquot was withdrawn over approximately 10 minutes, during which time the patient's vital signs were continuously monitored to ensure tolerance to this controlled hemorrhage. Blood was collected in standard citrate phosphate dextrose solution blood packs , agitated to prevent clotting, marked with the patient's information, and kept in the operating room at room temperature until it was reinfused after complete surgical hemostasis. After a total of 15% of the EBV had been removed, the intravascular volume was then replaced, also in three 5% of the EBV aliquots, using an equal volume of 6% hetastarch in lactated electrolyte solution . All hemodynamic measurements and TEE recordings were repeated after each 5% EBV aliquot removal and replacement. The time to complete the ANH and data collection averaged approximately 1 hour. Seven study points were thus defined by this protocol . If a patient became hemodynamically unstable at any time during the blood removal or replacement ) a phenylephrine bolus of 0.1 mg was given. If the hypotension did not resolve, a phenylephrine infusion was started and titrated to maintain the MAP ≥ 50 mmHg. The infusion was tapered and stopped when the MAP was ≥60 mmHg. Physiologic measurements were recorded at least five minutes after a phenylephrine bolus or change in the infusion rate. Two anesthesia care teams were involved in the study; one was solely focused on the patient's care and the other was responsible for data collection. fourSight . For these volumetric measurements, the endocardial border was traced in four equally spaced orthogonal pairs of images selected from the 3D reconstruction, that is, each one twenty-two and one-half degrees from the previous measurement. TEE image acquisition was supervised by an anesthesiologist board certified in advanced perioperative TEE and, for consistency, all of the left atrial volumetric analyses were performed by one researcher.For each study point defined above, the long axis view of the left ventricle was obtained with the TEE probe positioned in the mid-esophageal four-chamber (ME 4CH) view. Care was taken to optimize LV chamber size and avoid foreshortening. The probe was then rotated to position the left atria and ventricle in the center of the imaging plane. Three-dimensional software was then used to acquire a series of EKG-gated images spanning a 180° rotation of the transducer at 5° intervals . These images were then stored for offline 3D reconstruction and assessment of left atrium end-diastolic volume, end systolic volume, and ejection fraction using proprietary softwareWith the TEE probe in the same ME 4CH position, color flow Doppler imaging was used to detect any significant mitral valvular disease. Transmitral flow was then assessed using pulsed wave Doppler with the sample window placed at the tip of the mitral leaflets. After the transmitral flow image was optimized, a still image store was recorded for subsequent measurements of peak E wave amplitude, peak A wave amplitude, E/A ratio, E wave deceleration time, A wave deceleration time, and velocity-time integrals (VTI) for both waves.P value of <0.05 was considered statistically significant.Unless noted, all values are presented as mean ± SD. For measurements repeated over time, a one-way ANOVA was used with Dunnett's multiple comparison test to determine statistically significant differences compared to baseline across the seven conditions of graded blood removal and replacement . For all comparisons, a A total of 48 patients were consented for this protocol, all of whom were either ASA I or ASA II. No one was eliminated from the study due to intolerance of the hemodilution. However, a total of seven patients were dropped from analysis: two due to a change in the surgical procedure, one due to the loss of venous access, and four due to the TEE machine not being available. Of the remaining 41 patients, 36 had images of sufficient quality for volumetric analysis. This group included 31 males and 5 females. Their average age was 59 ± 6.4 years, weight 90 ± 14.4 kg, height 174 ± 9.5 cm, and BMI 29 ± 4.4. Surgical procedures included 26 prostatectomies, 4 cystectomies or cystoprostatectomies, and 6 anterior/posterior spinal fusions. Mitral flow data was attempted in 32 patients. All of these patients had images of adequate quality for analysis. This group included 26 males and 6 females. Their average age was 58 ± 6.6 years, weight 85 ± 13.4 kg, height 174 ± 8.8 cm, and BMI 28 ± 4.5. Surgical procedures included 26 prostatectomies, 5 cystectomies or cystoprostatectomies, and 5 anterior/posterior spinal fusions.No clinically significant changes in heart rate or blood pressure were observed during the ANH protocol . The meaAcute volume resuscitation and optimization of intracardiac pressures (preload) are a dynamic situation best guided by continuous monitors of cardiac function. The pulmonary arterial (PA) catheter has historically been considered the gold standard in this setting, but it is used with decreasing frequency due to the limits of the information it provides and the risks and complications associated with its placement and use . CentralIn the clinical setting of acute volume resuscitation, the goal is to optimize the preload of the left ventricle (LVEDP) to maximize cardiac function as guided by the Frank-Starling relationship between LVEDP and cardiac output. The PA catheter uses PCWP as a surrogate for LVEDP, but correlations may be limited by left atrial or mitral valvular pathology. In contrast, the TEE uses the left ventricular end-diastolic volume (LVEDV) as a more direct surrogate for LVEDP and is now a commonly used monitor for this application . It has TEE can also be used to indirectly calculate the LVEDP. Shortly following the initial description of Doppler measurement of mitral flows by Kitabatake et al. , the potThe results of this study demonstrate the potential utility of mitral flow patterns as guides in the acute care setting. In contrast to the transgastric short axis view of the left ventricle, Doppler flow images across the mitral valve are easily and reliably obtained even in critically ill patients . The meaThis study has some limitations that should be highlighted. First, these left atrial volume calculations were done offline using very early versions of the analytical software. Increasing computing capabilities have supported the evolution of TEE imaging options. The initial characterizations of left atrial volume applied Simpson's method of discs to biplanar images, despite the known inaccurate geometric assumptions. Three-dimensional imaging has become routine and provides particular advantages when applied to the irregular shape of the left atrium. Similarly, advances in echocardiographic edge detection software  combinedThe use of ANH as a controlled human hemorrhagic model allowed the demonstration of the potential utility of 3D left atrial volume measurements and peak E wave mitral flow velocity as echocardiographic monitors that may be used as guides for acute volume resuscitation. Further evaluation in other clinical scenarios is merited.


However, post-contrast cardiac T1 can also be influenced by a variety of confounders, including: cardiac function, renal function, hematocrit, magnetic field strength, contrast agent type and dosage, and specific delayed imaging time after contrast agent administration. To compensate for these confounders, investigators have proposed to measure extracellular volume (ECV). Despite the advantages of ECV over cardiac T1, systematic studies comparing the two measurements are lacking [1 and ECV for evaluating the temporal changes in left ventricular (LV) fibrosis in an established canine model with chronic atrial fibrillation (AF)[Post-contrast cardiac Ttion (AF).1 maps were acquired in 3 short-axis planes  using the arrhythmia-insensitive-rapid (AIR) cardiac T1 mapping pulse sequence [1-insensitive saturation-recovery of magnetization preparation, with the following relevant imaging parameters: spatial resolution = 1.4 × 1.4 × 7.0 mm, temporal resolution = 217 ms, saturation-recovery time = 600 ms. Cardiac T1 maps were acquired pre-contrast and 15 min after a bolus injection of Gd-BOPTA . Blood samples were drawn during MRI for hematocrit calculation. For image analysis, myocardial contours and blood pool were manually segmented, and T1 and ECV values were calculated. LV ejection fraction (LVEF) was calculated using cine MRI. Temporal changes in post-contrast LVEF, LV T1, blood T1, and ECV were modeled with linear mixed effect models to account for repeated measurements over disease duration. Four animals were sacrificed at different durations of AF (0-22.6 months) for histologic quantification of LV fibrosis.Seventeen mongrel dogs with different durations (0-22 months) of chronic AF were scanned multiple times for a total of 46 CMR scans at 3T . Cardiac T1 maps of a dog with disease duration = 15.2 months, as well as LV tissue samples with Masson's trichrome staining at baseline  and 22.6 months of AF duration . As shown in Figure 1 are similar. Compared with histologic quantification of fibrosis and extracellular space, ECV agreed better than LV T1.Figure 1, especially for evaluating temporal changes in LV fibrosis.This study suggests that ECV is a more robust measure of extracellular space than post-contrast LV TBen B. and Iris M. Margolis Foundation.


Myocardial T2 mapping has been recently developed that allows for direct measurement of local myocardial T2, overcoming some of the limitations of T2-weighted images. We aimed to obtain myocardial regional and global T2 values as a reference for normality, using a novel mapping technique both at 1.5T and at 3T.Between April and July 2014 we recruited 32 healthy subjects , aged between 20 and 80yrs. All of them underwent a cardiovascular magnetic resonance  protocol that included steady state free precession (SSFP) cines for measuring ventricular dimensions and function, TFisp 2D T2 mapping, dipyridamole stress myocardial perfusion study and late gadolinium enhancement study. T2 maps were obtained in three short axis orientations . Regional myocardial T2 values were measured in a 16 segment model and global T2 values were also obtained per slice. A multifactorial ANOVA design was used for the statistical analysis.Complete data were available for all 32 subjects . All of them had a normal CMR study, with preserved ventricular dimensions and systolic function, no regional wall motion abnormalities, no stress perfusion defects and no late gadolinium enhancement. No differences were found in regional or global T2 with respect to magnetic field (1.5T vs 3T), neither were there differences with regard to age, gender or ventricular parameters. In general, apical segments exhibited higher T2 values, but these did not reach statistical significance. Interestingly, 5 subjects had a total of 9 segments  with T2 ≥ 70 ms, one of them was a mid-anterolateral segment and all others were apical segments. On average, normal myocardial T2 value was 52±6ms with a reference range of 40-64ms.Myocardial T2 mapping is technically feasible and easy to obtain. Small regional differences can be seen that do not reach statistical significance. Higher values can be seen in a very limited number of segments, probably attributable to acquisition quality or partial volume effects.N/A.


Myocardial T2* mapping is a widely used method to detect and quantify cardiac iron overload in transfusion-dependent anemia patients . The ECG-triggered black-blood multi-echo gradient echo sequence typically used for myocardial T2* mapping acquires segmented k-space data across multiple heart beats (BH Seg-mGRE) (3). However, it is highly sensitive to respiratory motion and requires patient breath-hold. In this work, we present a new free-breathing technique to accurately quantify myocardial T2* by acquiring multiple, single heartbeat images insensitive to respiratory motion artifact, and applying automatic non-rigid motion correction (moco GRE-EPI) to register images prior to T2* map estimation.We developed a black-blood, multi-shot, GRE-EPI sequence with TR = 20 ms, echo-train-length = 5, GRAPPA acceleration rate = 2 and a water excitation pulse to minimize fat displacement artifacts. Eight images were acquired at echo times ranging from 1.2 ms to 15 ms; each T2*-weighted image was acquired in one heartbeat with an acquisition window of 240 ms and repeated with four measurements. The total acquisition duration was 64 heart beats. Automatic in-plane non-rigid motion correction  was used to compensate for mis-registration due to respiratory motion. Motion correction (moco) was applied first across the four measurements at each TE prior to averaging, and then across the averaged images at different TEs prior to generating the T2* map. T2* maps were calculated by fitting a mono-exponential model. Both acquisition techniques were attempted in 72 patients referred for clinical CMR cardiomyopathy evaluation on the 1.5 T scanner . Both moco GRE-EPI during free-breathing and BH Seg-mGRE during breath-hold were acquired in a single mid-short axis plane. T2* was measured in the interventricular septum and liver.r = 0.77 and 0.97) and no significant differences (p = 0.78 and 0.24).Conventional BH Seg-GRE failed in 24 out of 72 patients due to the inability to breath-hold while the new moco GRE-EPI technique failed in only 6 patients due to the severe respiratory motion or imperfect fat suppression (Figure We have described a technique for T2* mapping using moco GRE-EPI that enables accurate myocardial T2* measurements and is insensitive to respiratory motion. It could be especially beneficial for patients who are unable to breath-hold.


Rewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calcium sensitizer, on myocardial function after rewarming from DHCA.Forty male Wistar rats (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After DHCA (20 minutes) and CPB-assisted rewarming (60 minutes) rats were randomly assigned to 60 minute intravenous infusion with levosimendan , epinephrine  or saline . Systolic and diastolic functions were evaluated at different preloads with a conductance catheter.P<0.003 and PRSW: 78 ± 5% vs 48 ± 8%, P<0.005; baseline: 100%). Levosimendan but not epinephrine reduced left ventricular stiffness shown by the end-diastolic pressure-volume relationship and improved ventricular relaxation (Tau). Levosimendan preserved ATP myocardial content as well as energy charge and reduced plasma lactate concentrations. In normothermia experiments epinephrine in contrast to Levosimendan increased cTnI phosphorylation 3.5-fold. After rewarming from DHCA, cTnI phosphorylation increased 4.5-fold in the saline and epinephrine group compared to normothermia but remained unchanged with levosimendan.The slope of left ventricular end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) recovered significantly better with levosimendan compared to epinephrine (Ees: 85 ± 9% vs 51 ± 11%, Levosimendan due to prevention of calcium desensitization by cTnI phosphorylation is more effective than epinephrine for treatment of myocardial dysfunction after rewarming from DHCA. Deep hypothermic circulatory arrest (DHCA) is widely used during repair of the aortic arch and congenital heart defects as a method of cerebral protection. However, the effect of myocardial ischemia-reperfusion injury combined with hypothermia-rewarming has important clinical implications and remains a significant contributor to perioperative morbidity and mortality .Hypotension and low cardiac output are common after rewarming and up to 50 to 80% of patients have hemodynamic instability .2+ overload and the paradoxical myofilaments Ca2+ desensitization. Ca2+-dependent interactions among myofilament regulatory proteins primarily control cardiac muscle contraction. Among them, troponin and tropomyosin confer not only Ca2+ sensitivity to contraction, but also modulation by phosphorylation of troponin I (cTnI) [2+ sensitivity and could be mediated by phosphokinase A activated by β-adrenergic stimulation [Because of the limited knowledge of the pathophysiology of hypothermia- and rewarming-induced cardiac dysfunction either in the setting of cardiac surgical intervention or in accidental hypothermia, guidelines for pharmacological treatment are missing . Among tI (cTnI) . The latmulation .Thus, agents that target the regulatory apparatus by increasing the calcium sensitivity without deleterious effects on the intracellular calcium concentration or oxygen consumption are useful in the treatment of cardiac dysfunction. Epinephrine is currently used in the treatment of hypothermia-induced cardiac dysfunction . HoweverAgents that exert a positive-inotropic effect, by directly acting on thin filament regulatory proteins or on cross-bridge cycling, are commonly referred to as calcium sensitizers. Among them, levosimendan, in contrast to epinephrine, improves ventricular function without increasing oxygen demand . We prevThe present study was designed to investigate treatment with levosimendan or epinephrine after rewarming from DHCA when acute myocardial dysfunction represents a clinical problem. We aimed to investigate the effects of levosimendan and epinephrine on calcium desensitization mediated by cTnI phosphorylation. Moreover, we purposed to evaluate the acute overall hemodynamic, biochemical and metabolic effects of the two pharmacologic agents after rewarming from DHCA.The Institutional Animal Care and Use Committee of the University Animal Research Laboratory approved this study. All animals received standardized care in accordance with the National Institute of Health Guidelines. Adult male Wistar rats  were used for all experiments.2 in a plastic induction box. After orotracheal intubation with a 14G cannula, the animals were mechanically ventilated . The tidal volume was 7 ml/kg and the respiratory rate was 50 to 60 breaths/minute with an air-oxygen mixture (FiO2 = 0.5). Ventilation was adjusted to keep an arterial carbon dioxide tension (PaCO2) of 35 to 45 mm Hg. Anesthesia was maintained with isoflurane 2% and pancuronium-bromide (2 mg/kg iv) was administered for complete muscle relaxation. Adequate anesthesia was monitored by the withdrawal response to a paw pinch and respiration monitoring. Rats were secured supine on a heating board. ECG was monitored using limb leads. A thermocouple microprobe was inserted into the left femoral artery and advanced into the descending aorta for the measurement of blood temperature. The left femoral artery was cannulated with a heparinized 24-G Teflon catheter to monitor systemic arterial pressure and to collect arterial blood for lactate and gas analysis.Rats were anesthetized with 5% isoflurane in 50% OCentral cannulation was performed as previously described . In brie2O to facilitate venous drainage, all connected by 1.6 mm internal diameter plastic tubing. Total priming volume was 9.5 mL, the gas exchange surface was 450 cm2, and the heat exchange surface was 15.8 cm2.CPB was set up as previously described . The setCPB was instituted at a flow rate of 120 mL/kg/min. A core temperature of 15°C to 13°C was achieved over 30 minutes using CPB-assisted cooling. The roller pump was turned off and DHCA, as confirmed by asystole and lack of measurable mean arterial pressure, was maintained for 20 minutes at 13°C to 15°C.With the reinstitution of CPB, rewarming started at a flow rate of 100 mL/kg/min. CPB inflow rate was gradually increased, reaching the full rate of 120 mL/kg/min at the end of rewarming at 36°C in a period of 60 minutes. The temperature gradient between the CPB circuit and body core did not exceed 10°C. After full rewarming, the remaining priming volume was reinfused and animals were weaned from CPB (T1). Then animals were randomly assigned to treatment with levosimendan (0.2 μg/kg/min) or epinephrine (0.1 μg/kg/min) or saline as control. Infusion started immediately after hemodynamic recording and blood sampling post-weaning from CPB (T1) and lasted for 60 minutes in normothermia at 36°C to 37°C (Endpoint = T2).in vitro and in vivo volume calibrations using PVAN software [Hemodynamic parameters were collected continuously during the experiments with a 2 F micro-tip pressure-volume conductance catheter  inserted into the right carotid artery and advanced into the left ventricle. Signals were continuously recorded at a sampling rate of 1,000 samples/s using a P-V conductance system , stored, and displayed on a personal computer by the PowerLab Chart5 Software System . With the use of a special pressure-volume analysis program , heart rate (HR), mean arterial pressure (MAP), maximal slope of the systolic pressure increment (+dP/dt) and the diastolic pressure decrement (−dP/dt), and time constant of left ventricular pressure decay  were computed and calculated. Stroke volume (SV) and cardiac output (CO) were calculated and corrected according to software .In addition to the above parameters, left ventricle pressure-volume relations were measured by transiently occluding the inferior vena cava (reducing preload) under the diaphragm by tying a snare suture around the vein at baseline condition (T0), after CPB weaning (T1) and at the end of 60 minutes of infusion treatment (T2) .After euthanasia with a potassium bolus freeze-clamped left ventricle myocardial biopsies were snap-frozen. In particular, the tip of the freeze-clamp tong was pre-cooled in liquid nitrogen prior to taking the biopsies and thereafter the samples were stored at −80°C (protein isolation from tissue extracts) or in liquid nitrogen (high energy phosphates) until analysis.For Western blot analysis of cTnI phosphorylation, cardiac specimens were pulverized in liquid nitrogen and homogenized in ice-cold lyses buffer  containing a protease inhibitor cocktail  and a phosphatase inhibitor cocktail .The homogenates were centrifuged  for 30 minutes at 4°C, supernatants were recovered, snap-frozen in liquid nitrogen and stored at −80°C. Total protein content was determined with the Bradford method. Equal amounts of each sample were fractionated on 10% polyacrylamide gels by SDS-PAGE and transferred to polyvinylidene difluoride membranes . Membranes were blocked with 5% BSA  in TBS-0.1% Tween20, and incubated overnight with specific primary antibodies for either phospho-cTnI (Ser23/24)  or total cTnI  at 4°C. A horseradish peroxidase conjugated secondary antibody  was used to detect the blots by standard chemiluminescence substrate  on Kodak films . Bands were quantified by ImageJ software .For energy status determination, the sample preparation and high-performance liquid chromatography (HPLC) measurement of ATP, ADP, AMP and phosphocreatine, as well as hypoxanthine and xanthine, were performed as previously described . A pieceEnergy charge was calculated using the following formula: (ATP + 0.5ADP)/(AMP + ADP + ATP).Arterial blood samples were collected to measure lactate concentration.post hoc test was used. An unpaired two-tailed Student t-test or paired t test was employed to evaluate differences between groups and within groups versus the baseline, respectively. The statistical software GraphPad Prism 5.0  was used. A P-value of <0.05 was considered to be significant.The means ± SD are given. For between-group comparisons, analysis of variance with the Bonferroni Fifty rats were used for this study; 40 completed the experimental protocol and were included. Ten animals were excluded, including five rats due to their inability to wean from CPB and five due to instrumentation or technical failure during animal preparation.Among the three studied groups no differences in baseline hemodynamic parameters were observed Table . A markeFunctional indices derived from pressure-volume analysis at different preloads are less influenced by loading conditions. In particular, Ees and PRSW were calculated as load-independent indexes of left ventricular contractility. Ees was significantly higher after both levosimendan and epinephrine infusion than control, indicating a steeper end-systolic pressure-volume relationship and a better systolic performance Figure . Only leThe diastolic function after rewarming was described by the left ventricular relaxation index (Tau) and the stiffness index end-diastolic pressure-volume relationship (EDPVR). Only levosimendan significantly improved EDPVR and Tau Figure .P<0.001)   Figure  and enerDuring normothermia epinephrine was associated with a three-fold increase in cTnI phosphorylation, whereas levosimendan maintained cTnI phosphroylation at a physiological ratio Figure . After D2+ desensitization mediated by cTnI phosphorylation. Levosimendan, compared to epinephrine, led to a significantly better preservation of myocardial ATP content as well as energy charge and to a reduction in plasma lactate concentrations. In comparison, Levosimendan was superior in improving myocardial systolic and diastolic functions as demonstrated by PV-analysis.Data presented here clearly show that levosimendan administered after rewarming from DHCA prevents CaClinically deep hypothermia, either accidental or induced as a neuroprotective measure during aortic arch interventions, leads to an overall myocardial depression that aggravates ischemia-reperfusion injury . Althoug2+ overload, which is defined as mechanical or electrical contractile failure induced by elevated intracellular Ca2+ content in myocytes [Experimental models of deep hypothermia and rewarming confirm and explain these clinical findings ,16. In amyocytes ,16,18.2+ overload may induce cardiac contractile dysfunction through different pathways. In particular after hypothermia and rewarming, increase in reactive oxygen species, decreased ATP synthesis and damaged mitochondrial ultrastructure have been reported [Careported .2+ content, indicating that reduced contractile force after rewarming is related to a decrease in myofibrillar Ca2+ sensitivity rather than impairment in intracellular Ca2+ regulation [2+ concentration), which represent coarse dynamic indices of myofilaments Ca2+ sensitivity during the relaxation phase of the twitch force, a rightward shift was observed in the relaxation phase during stable hypothermia, as well as after rewarming, in intact papillary muscle [2+ sensitivity due to hypothermia and rewarming.YS Han and colleagues have observed that papillary muscle twitch force was reduced by 35% after rewarming despite a 15% increase in the intracellular Cagulation . Signifiy muscle . This in2+ sensitivity, which is not reversed by rewarming, thus contributing to post-hypothermic cardiac contractile dysfunction.These data propose that hypothermia decreases cardiac myofilaments Ca2+ sensitivity and shifts the force-Ca2+ relationship rightward under normothermic circumstances [Numerous studies have demonstrated that increased phospho-mediated phosphorylation of the sarcomeric protein cTnI reduces myofilament Camstances ,19,20.2+; another is to modulate the response of sarcomeres to Ca2+. The unique position of cTnI to regulate and modulate cardiac function under the influence of adrenergic signaling is well documented [2+and increases cross-bridge kinetics.One way to increase the contractile force of the sarcomere is to increase cytosolic Cacumented . In moreIn the present study, we found that after rewarming from DHCA, there was a significant increase in cTnI phosphorylation at phosphokinase A sites, as shown by Western blot analysis. Phosphorylation of cTnI is mediated by several kinases , but particularly phosphokinase A-mediated phosphorylation via-adrenergic stimulation plays a major physiological role in meeting the circulatory demand in the physiological state .2+ sensitivity and myocardial contractility.In general, changes in the cTnI phosphorylation status, as reported in the failing human heart are considered a change in the balance between kinase and phosphatase activities, and the optimal balance is realized during normal cardiac function. Thus, hypothermia and rewarming, depending on severity and depth, appear to tip the balance between kinase and phosphatase activities, leading to alterations in myofilament Caper se activate the receptor - cAMP - phosphokinase A pathway, one may conclude that an additional pharmacological stimulus of the receptor under these circumstances would achieve a markedly reduced cardiac inotropic effect.Furthermore, we have previously reported a lack of effect of pharmacological agents to support cardiac contractile function mediated via the receptor - cAMP - phosphokinase A pathway during, as well as after, rewarming . Likewis2+ overload, elevated myocardial oxygen consumption, arrhythmogenesis and regional hypoperfusion leading to organ damage [Moreover, cardiovascular effects mediated by β-adrenoceptors are significantly diminished after hypothermia, suggesting that the use of the β-adrenoceptor specific agonist should be reconsidered -9. Additn damage -10.2+ sensitizers. It exerts its positive inotropic effect by sensitizing cardiac troponin C to calcium during systole, thus increasing cardiac performance without increasing myocardial oxygen consumption. Levosimendan also has a weak arrhythmogenic effect [Levosimendan is a pyridazinone dinitrite derivative belonging to the new inotropic drugs class of Cac effect . Our groc effect .This study was conducted in a previously described and validated rat model of CPB . DHCA anEpinephrine produced an increased MAP without an improvement in SV. This increase in afterload during the rewarming phase may explain the significantly higher lactate plasma levels with epinephrine compared to levosimendan after rewarming from hypothermia. Moreover, levosimendan was superior in improving diastolic function, which is clearly evident from the left ventricular relaxation indexes. In line with these findings, levosimendan also significantly better preserved high-energy phosphates shown by energy charge and ATP myocardial content than epinephrine. The differences concerning phosphocreatine, hypoxanthine and xanthine between groups are due to the high standard deviation values  by HPLC and, therefore, do not directly reflect the bioenergetic situation of the free metabolites in the cytosol. The assessment of free fluctuating concentrations of these metabolites would require 31P NMR and a number of near equilibrium expressions using the creating kinase and adenylatekinase equilibrium . HoweverIn the present study and differently from the previously reported , there w2+ sensitizer drugs, such as levosimendan, seems rational in induced or accidental deep hypothermia.Further investigations are needed to validate these results in the clinical setting and to evaluate the cost/benefit ratio in this setting of high-risk patients. Nonetheless, on the basis of these findings, use of CaFinally, some important limitations remain. The animal model does not faithfully reproduce the clinical setting. Therefore, the outcome of this study in a rat model of CPB remains to be demonstrated in large-animal and clinical studies. However, because of the small animal size, this model allows rapid and precise control over body temperature, which is difficult to achieve in clinical practice at present, and it may be particularly appropriate for defining optimal hypothermia parameters. Another limitation of the present study is that we only investigated a single dose of epinephrine and levosimendan. One, therefore, cannot rule out the possibility that different dosages or treatment schemes might have generated different functional outcomes from the one herein. Nevertheless, the particular infusion rate for levosimendan and for epinephrine was deliberately chosen because it is the highest dose regimen suggested in the clinical setting.Levosimendan due to prevention of calcium desensitization by cTnI phosphorylation is more effective than epinephrine for treatment of myocardial dysfunction after rewarming from DHCA.•CPB-assisted rewarming after DHCA results in acute myocardial dysfunction.2+ desensitization mediated by cTnI phosphorylation after rewarming.•Levosimendan but not epinephrine prevents myofilaments Ca•In this setting, levosimendan is more effective than epinephrine in improving systolic and diastolic functions, high-energy phosphates myocardial content and in reducing lactate plasma concentrations.CO: Cardiac output; CPB: Cardiopulmonary by-pass; cTnI: Cardiac troponin I; DHCA: Deep hypothermic circulatory arrest; EDPVR: End-diastolic pressure-volume relationship; Ees: Slope of left ventricular end-systolic pressure volume relationship; HPLC: High-performance liquid chromatography; HR: Heart rate; MAP: Mean arterial pressure; PRSW: Preload recruitable stroke work; SV: Stroke volume; +dP/dt: Maximal slope of the systolic pressure increment; -dP/dt: Maximal slope of diastolic pressure decrement.The authors declare that they have no competing interests.AR, AM and GF designed the study. AR, DL, EM and MT performed the experiments. SH, AG and TS performed biochemical analysis. AR, SH, GBL and TS analyzed the results. AR, SH, GBL, TS, AM and GF wrote and corrected the manuscript. All authors read and approved the final manuscript.


Coronary artery disease (CAD) and left ventricular hypertrophy are prevalent in the chronic kidney disease (CKD) and renal transplant population. Advances in cardiovascular magnetic resonance (CMR) with the blood oxygen level-dependent (BOLD) technique provides unprecedented capability to assess myocardial oxygenation as a measure of ischaemia. We hypothesised that myocardial oxygenation would be reduced in advanced CKD and renal transplant patients and may provide a novel strategy for assessing myocardial ischaemia.We prospectively studied 20 advanced CKD subjects  ml/min and 12 CKD group with median eGFR 14 (range 8-18) ml/min), 8 renal transplant (RT) recipients with median eGFR 74.5 (range 57-114) ml/min and 7 hypertensive (HT) controls with median eGFR 107 (range 57-144) ml/min. All patients were asymptomatic for CAD and none had prior history of CAD. All groups had cine and BOLD CMR at 3T, and RT and HT groups also had late gadolinium CMR to assess infarction/replacement fibrosis. CKD group additionally underwent 2D echocardiography strain to assess fibrosis. Myocardial oxygenation was measured at rest and under stress with adenosine (140 µg/kg/min) using BOLD Signal Intensity (SI). Analyses were performed using linear mixed models.A total of 1074 myocardial segments of the advanced CKD group [522 myocardial segments of dialysis group and 552 myocardial segments of CKD group], 456 myocardial segments of RT and 324 myocardial segments of HT controls were analysed and compared using linear mixed modeling. Mean interventricular septal thickness and left ventricular mass indexed to body surface area was similar between the groups . None of the advanced CKD group had impaired global longitudinal strain (GLS) (mean GLS -18.39) and none of the RT/HT groups had late gadolinium hyperenhancement. The mean BOLD SI change was lower in advanced CKD and RT groups compared to HT controls . The global myocardial BOLD SI change was also lower in the advanced CKD subjects compared to RT recipients (p=0.045). In the advanced CKD and RT groups, the BOLD SI Change was associated with eGFR .Our study suggests myocardial oxygenation is impaired in advanced chronic kidney disease patients and renal transplant recipients, and unlikely to be related to LVH or myocardial scarring. The impaired myocardial oxygenation may be associated with declining renal function. Non-contrast BOLD CMR is a promising tool to detect myocardial ischaemia in advanced chronic kidney disease population.None.


Fibrosis determined by late enhancement (LE) is a predictor of progressive heart failure (HF) in dilated cardiomyopathy (DCM). The mechanism responsible for this association is not fully understood, though increased ventricular stiffness could be involved. We therefore hypothesised that pulmonary vascular resistance (PVR) should be increased in patients with DCM and LE.71 consecutive patients (p) with DCM, left ventricular systolic dysfunction (LVEF<35%) and normal coronary angiography followed in an outpatient HF clinic, were prospectively enrolled in two institutions. All p had to be in stable clinical condition in the last month. Exclusion criteria were: contraindications for contrast-enhanced cardiac MR (ce-CMR), significant impairment of lung function by clinical criteria or spirometry and history of thromboembolic disease. All patients underwent ECG, echo, blood test and a ce-CMR study in a Philips Intera ® 1.5 T scanner, which included cine imaging, phase contrast in the main pulmonary artery and aorta and late enhancement (LE). Postprocessing was performed with QMASS 7.2 ® . PVR was calculated following the equation: 19.38 -(4.62*Ln pulmonary artery average velocity) - (0.08 x RVEF %)Mean age was 61±12 years, 28 p (54%) were male. 41 p (58%) were in functional class II and 10 p (14%) in class III. 68 p(96%) were on beta-blockers, 61(86%) on ACE inhibitors and 15 (21%) on angiotensin II receptor antagonists. Mean LVEF was 29±10%. LE was normal in 37 p (52%), mesocardial in 23 p (39.6%), and subendocardial in 5 p (7%). In a multivariant regression model which included age, sex, LVEF, E/A ratio and the presence of any LE, the last three parameters were independent predictors of PVR.The presence of LE on CMR is a predictor of increased RVP, showing complimentary value to LVEF.Fondo de Investigación Sanitaria, Instituto Carlos III, Madrid, Spain.This study was supported by a grant from the


The systemic right ventricle (RV) is at increased risk of developing heart failure. Combined MRI-catheterization (XMR) techniques offer a unique opportunity to study this condition. We assess pressure-volume relations in children with hypoplastic left heart syndrome (HLHS) post Fontan with stepwise increments of dobutamine stress.Prospective data from anesthetized patients with HLHS undergoing clinical XMR were analyzed. A fluid filled MR compatible catheter placed in the systemic RV recorded pressures at rest, with dobutamine infusion at 10 mcg/kg/min and at 20 mcg/kg/min. Simultaneous cine short axis stacks of the ventricle were performed. Pressure-volume loops were constructed. End-systolic pressure-volume relationship was derived at each state from a validated maximal pressure (Pmax) estimation method. Ventriculo-arterial coupling (Ees:Ea) was compared to myocardial power and overall global function.Five patients with HLHS and exercise intolerance, mean age 7.8 years (range 3.5-11.6 yrs), weight 26 Kg (range 16-46 Kg), time since Fontan completion (mean 3.2 years). No significant tricuspid regurgitation in any patient. Statistical analysis was performed using one-way ANOVA with post-hoc comparisons to assess subgroup variation where p < 0.05. There were significant increases in EF, indexed cardiac output, power and ventricular contractility (Ees) with increases limited to between rest and dobutamine 10 (p < 0.01) with no further significant increase at 20. iEDV fell significantly between rest and dobutamine 20 (p < 0.01). EDP and arterial elastance (Ea) did not change throughout. Ees:Ea increased between rest and dobutamine 10 only. dP/dtmin a measure of rate of relaxation fell with dobutamine 10 only.In the systemic RV, load independent indices of contraction in response to dobutamine are similar to those recorded in the healthy left ventricle (LV). The systemic RV at rest works neither at maximal mechanical efficiency (Ees:Ea = 2) nor maximal stroke work efficiency at a given EDV (Ees:Ea = 1). Increased coupling with dobutamine, mediated through increased myocardial contractility, indicates at higher heart rates the RV moves towards improved mechanical efficiency though at higher levels of overall energy expenditure. The relative increase in stroke work (37%) is comparable to data published on the healthy LV. The systemic RV has a limited cardiac reserve. Despite appropriate responses in contractility to low dose dobutamine, the heart is unable to further augment power and cardiac output with administration of dobutamine 20. Indeed, the plateauing of dP/dtmin - a measure of relaxation - indicates that in the presence of tachycardia there is failure to adequately fill the heart. Hence cardiac output and contractility may be limited by a ceiling of maximal flow through the Fontan circuit. This gives us valuable insights into the physiology of children with HLHS post-Fontan.The Division of Imaging Sciences receives support as the Centre of Excellence in Medical Engineering  as well as the BHF Centre of Excellence (British Heart Foundation award RE/08/03). This work was also supported by the European Commission (FP7-ICT-224485:euHeart). The authors acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust.