A 56-year-old male with a history of hypertension and coronary disease was admitted after complaining of mild shortness of breath and palpitations. He had undergone coronary bypass surgery 4 years prior to admission and had been followed regularly by his physicians. His resting heart rate at his last office visit <6 months before was 58/min and his hypertensive regimen, consisting of lisinopril only, was recently intensified. He had been under severe stress recently and had not been eating well. His caffeine intake was limited to one large coffee daily.2 saturation was 99%. The physical exam was unremarkable except for tachycardia. No murmurs, gallops, or rubs were present. His labs were: Hct 52.6 WBC 11,000 Na 139 K 3.8 BUN 16 Creatinine 0.65. The chest X-ray showed no cardiomegaly or vascular congestion and possible left basilar atelectasis.A left pleural effusion marked his postoperative course after bypass 4 years before, and he underwent thoracentesis without reaccumulation of the fluid. He also had what was felt to have been either atrial flutter or AV nodal re-entrant tachycardia (AVNRT), which reverted to sinus rhythm with a dose of adenosine, followed by 3 months of amiodarone. He reported no recurrent palpitations until this admission. His only other medication was aspirin. His initial blood pressure was 150/85, pulse was 125 and regular, and respirations were 18. He was afebrile. His OEchocardiography revealed mild concentric left ventricular hypertrophy and some evidence of reduced diastolic compliance, but no pericardial effusion or other abnormalities. The initial electrocardiogram  was inteInitial diagnostic measures were directed toward the usual causes of sinus tachycardia, such as anemia, dehydration, fever, pulmonary issues , and thyroid disease. The relatively high hematocrit suggested dehydration and he was given intravenous fluids, but no significant heart rate drop was noted. Metoprolol 50 mg orally was administered in the emergency department and he received one 5 mg intravenous dose 8 hours later. Soon thereafter the heart rate dropped to 55 and he became asymptomatic.A follow-up electrocardiogram  revealedThe graphic trend from telemetry is seen in While the monitor did not capture the rhythm at the exact time of the abrupt drop in heart rate, the graphic trend monitor proved crucial in confirming the fact that the rate drop did indeed occur abruptly, and not gradually, as would be expected in sinus rhythm. Based on this observation, a diagnosis of SANRT was felt to be very likely.The concept of SANRT was postulated in 1943, when Barker suggested the presence of circus rhythms within the sinus node (SANRT is usually not associated with severe symptoms. One study demonstrated SANRT in <2% of 379 patients undergoing diagnostic electrophysiologic study (Clinically, the only way to distinguish SANRT from sinus tachycardia is by recognizing its abrupt onset and termination. Sinus tachycardia would manifest a gradual change in rate. Other supraventricular tachyarrhythmias, such as atrial flutter and AVNRT, would demonstrate P-wave morphologies that differ from normal. The rate in SANRT is typically 100–150.Vagal maneuvers may be effective in terminating SANRT. Carotid massage or Valsalva maneuver may convert SANRT to sinus. Because of the relatively low frequency of the arrhythmia, no large pharmacologic studies are available and therapy is usually empiric and includes beta blockers, amiodarone, verapamil, and/or digitalis. Radiofrequency ablation can also be effective and may allow freedom from antiarrhythmic agents .


Objective: The purpose of this study was to find whether Cardiac Magnetic Resonance (CMR) could assess the myocardial interstitium in patients suffering from systemic amyloidosis with normal left ventricular ejection fraction.Methods: Twenty Six patients in whom systemic amyloidosis was confirmed by kidney biopsy were investigated. Five patients with normal left ventricular ejection fraction were selected. The heart function of the patients was diagnosed by two-dimensional transthoracic echocardiography. The main MR sequences include an inversion recovery prepared echo planar imaging perfusion sequence, inversion recovery TrueFISP sequence (delayed enhancement) and TrueFISP cine sequence for heart function measurement (including ejection fraction (EF), end diastolic volume (EDV), end systolic volume (ESV), stroke volume (SV) and cardiac output (CO)).Results: Perfusion defects were seen in three patients. In these patients, myocardial enhancement was visible on late gadolinium enhancement images. The enhancement pattern was diffuse in three patients and focal in two patients. Heart dysfunction was mild, as follows: EF normal , ESV normal , EDV decreased , SV decreased  and CO normal . Hematoxylin and eosin stain and Congo red stain demonstrated typical amyloid deposits. Amyloidosis was classified as amyloid light chain by kappa and lambda stain.Conclusions: Cardiac Magnetic Resonance could detect abnormal myocardial interstitium in systemic amyloidosis patients with normal left ventricular ejection fraction. Amyloid light chain (AL) is the most common pathologic subtype of amyloidosis. AL amyloidosis is usually caused by a smouldering clonal plasma cell disorder producing monoclonal light chains that undergo conformational modifications and aggregate into amyloid fibrils.2,3 Amyloid fibril deposits commonly affect the kidneys, heart, liver and peripheral and autonomic nervous systems.4 Cardiac involvement is common in AL amyloidosis and is associated with various treatment options and prognoses.5-7 In AL amyloidosis, the heart is affected in nearly 50% of cases.6 Previous reports indicated cardiac involvement as the cause of death in approximately 50% of patients with AL amyloidosis.8-10Amyloidosis are uncommon systemic diseases characterized by the extracellular deposition of pathologic insoluble amyloid protein in organs and tissues. Amyloidosis are usually classified into four major types: primary (systemic), familial, secondary and senile.2 In clinical practice, however, the diagnosis of cardiac amyloidosis is usually made by echocardiography7, electrocardiography (ECG)8 and scintigraphy8 with the aid of a radiolabelled serum amyloid P component so as to avoid invasive and problematic biopsy. According to previous reports, cardiac involvement in diagnosis of AL amyloidosis by these modalities has some limitations  scintigraphy is unable to image amyloid in the moving heart.).11-13Assessment of cardiac function is important in the diagnostic work-up, therapeutic follow-up and prognosis of AL amyloidosis, as well as in the clinical management of these patients. Currently, myocardial biopsy is regarded as the gold standard test for diagnosis of cardiac involvement in AL amyloidosis.5,14 Now the ability of CMR detecting early cardiac involvement caused by AL amyloidosis is unknown. Although the condition is extremely rare, herein we investigate the diagnostic value of CMR in AL amyloidosis patients with normal left ventricular (LV) eject fraction (EF) on echocardiography.Cardiac magnetic resonance (CMR) has been reported as a promising modality in the evaluation of suspected amyloid heart disease, especially using the late gadolinium enhancement (LGE) technique to detect significant findings indicating cardiac involvement in AL amyloidosis.We retrospectively reviewed 26 patients  with documented amyloidosis by kidney biopsy at the inpatient clinic of West China Hospital. Then the heart function of the patients was assessed by two-dimensional transthoracic echocardiography. Exclusion criteria included myocardial ischemia, myocarditis. Five patients with normal LVEF were recruited while 21 patients were excluded by the criteria.Five patients  with normal left ventricular ejection fraction were chosen by two-dimensional transthoracic echocardiography. All of these 5 patients suffered from proteinuria, puffiness around the eyes or pitting oedema of the legs. And nephrotic syndrome was diagnosed according to the measurement of 24-h urinary protein level.Our study was approved by the Ethics Committee of West China Hospital of Sichuan University. Informed consent was obtained from each of the patients for echocardiography and MRI.Histopathology: All patients underwent renal biopsy. Histopathological methods include hematoxylin and eosin (HE), Congo red, kappa and lambda staining. Electron microscopy was also performed for all the patients.Echocardiography: About 10 days after renal biopsy, Two-dimensional transthoracic echocardiography and colour Doppler flow imaging were performed in all patients using a phased array 2-5-MHz transducer  according to the guidelines of the American Society of Echocardiography.10The following parameters were evaluated: bi-ventricular and bi-atrial internal diameter, LV wall thickness and inter-ventricular and atrial septal thickness. All morphological parameters were measured at end diastole. LV function parameters were calculated by Simpson’s modified bi-plane method.Cardiac Magnetic Resonance Imaging: On the day of echocardiography examination, CMR imaging was performed with a 3.0-T whole-body MR system  for all the patients. Data was acquired during end-inspiratory breath holding. After scout images, TrueFISP cine sequence , 340 × 276 mm; matrix size, 192 × 125; flip angle, 50°; slice thickness, 9 mm) with retrospective ECG-gating was used to acquire dynamic cine loops of the LV for function analysis. The LV was imaged in its entirety from the base to the apex in 9-12 short-axis cine images without inter-slice gaps or overlaps.First-pass myocardial perfusion imaging was performed using an inversion recovery prepared echo planar imaging sequence . All patients received 0.1 mmol/kg bodyweight gadolinium-diethylene-triamine penta-acetic acid  through an intravenous ante-cubital catheter infused by an automated injector  at a flow rate of 2.0 ml/sec. Contrast injection was followed by a saline bolus chaser of 20 ml at the same flow rate. LGE images were obtained using an inversion recovery TrueFISP sequence with retrospective ECG-gating 10-15 minutes after administration of a second gadolinium-DTPA bolus . TIs for LGE were selected according to TI Scout which was performed before LGE.Cine function analysis was performed off-line with commercial software  by two experienced radiologists blinded to the echocardiograph results. In every short-axis slice, endocardial and epicardial boundaries were traced semi-automatically during the end-diastolic and end-systolic phases in order to obtain the volumetric parameters of LV  via the section summation method. Two experienced radiologists analyzed and interpreted first-pass myocardial perfusion and LGE images. Discrepancies in their interpretations were resolved by consensus.Statistical Analysis: Paired-Samples T Test was used to compare heart functional parameters  measured by ultrasound and MRI. Statistical analysis was performed using SPSS 13.0 .Histopathological Results: HE and Congo red stain demonstrated a typical amyloid deposit. Amyloidosis was classified as AL by kappa and lambda stain (kappa stain was negative while lambda stain was positive). Deposits composed of non-branching fibrils were viewed by electron microscopy  and increased LV wall thickness . 4 patients had depressed LV diastolic function . EF was normal . Systolic function  was normal. Perfusion defects were seen in 3 patients. Focal defects were located mainly in the anterior, lateral and septal myocardium. In all patients, the myocardium was enhanced on LGE images. The enhancement pattern was diffuse in three patients and focal in two patients. Focal areas of LV contrast enhancement were located mainly in the mid and basal segments of the anterior, lateral and septal myocardium. In all cases, CMR found pleural and pericardial effusions .The results of this study demonstrated that cardiac MR imaging was comparable to echocardiography in accurately assessing the cardiac function of AL amyloidosis patients. Furthermore, perfusion defects were observed on first-pass myocardial perfusion images and various enhancements of the myocardium on LGE images in most patients. In patients with normal EF values, however, echocardiography detected abnormalities of the septum in only one patient.13,15 Of the patients with normal EF values in the present study, however, echocardiography subjectively evaluated myocardial abnormalities in only one case. While all patients suffered from nephrotic syndrome, none had clinical signs or symptoms of cardiac involvement. These findings indicated that echocardiography may be less sensitive for assessing mild cardiac involvement at the early clinical stage. Further studies with a larger sample of patients within normal EF ranges are needed to confirm these results.In clinical settings, the diagnosis of cardiac involvement in AL amyloidosis is frequently made by echocardiography. As shown in our study, echocardiographic examination could quantitatively assess cardiac involvement via measurement of LV wall thickness, evaluation of restricted diastolic function and assessment of disproportionate atrial enlargement. These physiological changes indicate that deposition of amyloid fibrils in myocardial tissue results in reduced ventricular compliance, impairment of relaxation and eventually contraction.16 Similar to previous reports, in this study, CMR without LGE technique detected the typical cardiac features of AL amyloidosis, including LV wall thickening, restriction of diastolic filling and disproportionate atrial enlargement. At present, no direct non-invasive method is available to assess and monitor the myocardial amyloid burden. Gadolinium CMR techniques may be an appealing method in the evaluation and diagnosis of suspected amyloid heart disease, especially using first-pass myocardial perfusion and LGE techniques. In our study, perfusion defects were observed in 3 of the 5 patients on first-pass myocardial perfusion scanning. As significant epicardial coronary artery disease was not present in these patients, these perfusion defects may result from either significant subendocardial deposition of amyloid protein or possible infiltration of small-calibre coronary vessel walls by amyloid.17,18Currently, CMR is considered the reference standard for non-invasive measurement of cardiac ventricular function and an important tool for accurate evaluation of morphologic features.5 The characteristics of cardiac amyloidosis on LGE images include focal (heterogeneous) and diffuse (homogeneous) enhancement, depending on the deposition and expansion of amyloid into the myocardium.19 In the cases described here, diffuse enhancement was observed in three patients and focal enhancement in two patients. A previous study reported MR findings in patients with mild global depression of systolic function .20 However, special ability of MR to elucidate features of AL amyloidosis in patients with normal EF values has not been reported. In our study, myocardial abnormalities were detected in all patients using the LGE technique, but echocardiography detected only one case. Because cardiac involvement changes treatment options and adversely impacts prognosis, early detection is important for AL patients.5LGE has been used to evaluate cardiac amyloidosis and interstitial expansion due to amyloid deposition to some extent. Features of cardiac amyloidosis detectable by LGE-CMR have been well documented.Our study has several limitations. First, AL amyloidosis is extremely rare, only a limited number of patients were enrolled. Another limitation is that no patient underwent endomyocardial biopsy due to invasive injury.In summary, CMR techniques could detect earlier myocardium abnormalities in AL amyloidosis patients with normal EF.


The presens of myocardial scar tissue as a potential arrhythmogen substrate may influence the treatment of patients with coronary artery disease (CAD). Delayed enhancement MRI (DE-MRI) allows accurate detection and visualization of myocardial scar tissue. We thought to detect myocardial scar tissue in patients with CAD and preserved left ventricular (LV) function without regional wall motion abnormalities (RWMA) in transthoracic echocardiography (TTE) using DE-MRI.83 patients  with a history of CAD and with normal LV function without RWMA in TTE were examined for viability determination using DE-MRI .45 54.2%) of these patients suffered from an acute coronary syndrome  shortly before the MRI examination while 8 patients were found with a history of ACS further in the past. Myocardial scar tissue was found in 57 patients (68.7%), whereas 26 patients (31.3%, Figure % of thesFrom our preliminary results, a significant numbers of patients with CAD, preserved LV function and without regional wall motion abnormalities suffer from myocardial scar tissue. DE-MRI examinations of the heart for determination of myocardial viability should be considered in these patients to assess the extent of myocardial injury as TTE might underestimate the extent of myocardial scar tissue in patients with preserved left ventricular function.none


Myocardial disarray is an important histological feature of hypertrophic cardiomyopathy (HCM) which has been studied post-mortem, but its in-vivo prevalence and extent is unknown. Cardiac Diffusion Tensor Imaging (cDTI) provides information on mean intravoxel myocyte orientation and potentially myocardial disarray. Recent technical advances have improved in-vivo cDTI, and the aim of this study was to assess the interstudy reproducibility of quantitative in-vivo cDTI in patients with HCM.-3 mm2/s and HA was epicardium −34.3 ± 7.6°, mesocardium 3.5 ± 6.9° and endocardium 38.9 ± 8.1°. Comparison of initial and repeat studies showed global interstudy reproducibility for FA  = 7.2%), MD  and HA . Reproducibility of FA was superior to MD (p = 0.003). Global MD was significantly higher in the septum than the reference lateral wall . Septal HA was significantly lower than the reference lateral wall in all 3 transmural layers .A stimulated-echo single-shot-EPI sequence with zonal excitation and parallel imaging was implemented. Ten patients with HCM were each scanned on 2 different days. For each scan 3 short axis mid-ventricular slices were acquired with cDTI at end systole. Fractional anisotropy (FA), mean diffusivity (MD), and helix angle (HA) maps were created using a cDTI post-processing platform developed in-house. The mean ± SD global FA was 0.613 ± 0.044, MD was 0.750 ± 0.154 × 10To the best of our knowledge, this is the first study to assess the interstudy reproducibility of DTI in the human HCM heart in-vivo and the largest cDTI study in HCM to date. Our results show good reproducibility of FA, MD and HA which indicates that current technology yields robust in-vivo measurements that have potential clinical value. The interpretation of regional differences in the septum requires further investigation. Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and affects 1 in 500 of the general population. The majCardiovascular magnetic resonance (CMR) is assuming an increasingly important role in the diagnosis and evaluation of HCM,14. It aWe prospectively enrolled 10 patients with HCM referred for CMR at Royal Brompton Hospital. HCM was diagnosed in accordance with standard clinical guidelines. PatientImages were acquired using a clinical 3.0 T scanner  with an anterior 18 element matrix coil and 8–12 elements of a matrix spine coil. The 10 patients were each scanned on two separate days  in order to assess interstudy reproducibility.2 plus 6 diffusion encoding directions, fat saturation, TR = 2 RR intervals = 2000 ms (assuming a heart rate of 60 beats per minute), TE = 23 ms, BW = 2442 Hz/pixel, GRAPPA parallel imaging acceleration factor of 2,[2, slice thickness 8 mm, EPI echo train length = 22–28 readouts depending on field of view, EPI readout duration = 11–14 ms, in-plane spatial resolution = 2.7 × 2.7 mm2 interpolated to 1.35 × 1.35 mm2, 3 slices, 4 mm slice gap. Typically 10 image repetitions were obtained for each slice and each diffusion direction before averaging to improve signal to noise ratio (SNR). When motion artefacts were present due to inadequate breath holding and ectopy, up to 13 repetitions were acquired and the order that the diffusion directions were acquired in was rotated to avoid losing data from the same direction at the end of each breath hold. For diffusion encoding, the maximum available on axis gradient strength of 45 mT/m was used with a trapezoidal gradient pulse duration of 10 ms, leading to a diffusion sensitivity of b = 350 s/mm2. Breathold duration was for 18 cardiac cycles, which was typically 18 s. The typical duration of the patient scan was 45 minutes.After the localization steps to determine the short axis of the left ventricle (LV), a retro-gated cine sequence with a temporal resolution of 40 ms, acquired in a mid-ventricular short axis plane, was used to find the timing and duration of the subject-specific end-systolic pause. Localized first and second-order shimming and frequency adjustment were performed with an adjustment box positioned to cover the extent of the left ventricle in the imaged slices. cDTI was performed in the end-systolic pause in the mid left ventricle using a diffusion-weighted stimulated echo acquisition mode (DW-STEAM) single-shot echo-planar imaging (EPI) sequence gated to every other cardiac cycle. Zonal-eor of 2, field ofIn order to provide functional and morphological data, breath-hold CMR was performed. Retrospectively gated balanced steady-state free-precession cine sequences were acquired in three long-axis planes, followed by a contiguous stack of short axis slices from the atrioventricular ring to the apex.A cDTI post-processing software tool was custom-built in house using MATLAB . It included an interface to reject images corrupted by artefacts based on a visual analysis and an automatic cross-correlation algorithm to perform a rigid co-registration of the remaining images before averaging . A rank The principal eigenvector of the diffusion tensor was taken to represent mean intravoxel myocyte orientation. The Helix Angle (HA) was then calculated as the angle between the short axis plane and the projection of the myocyte vector onto a plane tangential to the local endocardium. Left-haFor quantitative analysis, the myocardium was divided into 4 segments for each slice and the same segments in each slice were grouped into the conventional LV walls . Care waVentricular volumes, function, mass, and ejection fraction for all patients were measured for the LV using a semi-automated threshold-based technique . All volume and mass measurements were indexed to body surface area calculated using the Du Bois method,38. LateMD and FA values were analysed globally , by slice (3 slices), and by LV wall . HA was also analysed globally, by slice and by wall but also in 3 layers  because of the known transmural variation in HA. Values from the initial study were compared between LV walls, slices and layers (for HA) using a hierarchical  mixed effects model. The lateral wall and mid slice were chosen as reference regions for comparison, because the lateral wall is less commonly affected by hypertrophy in HCM, and the mid-wall is furthest from any anomalous measurement relating to the apex or mitral valve. All values were found to be normally distributed using the Kolmogorov-Smirnov test, and are therefore shown as mean ± standard deviation (SD). Statistical significance was set to p <0.01 to account for the number of statistical tests performed. Interstudy reproducibility was assessed using the SD of the difference between the scans, and the coefficient of variation (CoV) where reasonable (SD of the difference between the scans divided by the measurement mean). Bland-Altman analysis was also performed. Differences in the CoV were assessed using a variance ratio test.The baseline demographic, clinical and CMR characteristics of the study population are summarised in TableDTI was successfully acquired in all cases. FigureThe mean global FA in the 10 patients in the initial study was 0.613 ± 0.044 Table. When an-3 mm2/s (Table-3 mm2/s) and least in the basal slice (0.726 ± 0.145 × 10-3 mm2/s), but there were no statistically significant differences between slices. When analysed by LV wall, MD was significantly greater in the septal wall than the reference lateral wall .The mean global MD was 0.750 ± 0.154 × 10Global LV helical angles Table showed tInitial and repeat studies were performed 167 ± 21 days apart. There were no clinical events or changes in treatment in the intervening period. FA, MD and HA maps appeared similar between initial and repeat studies in the majority of cases .MD reproducibility data, comparing the initial and repeat studies, are provided in TableHA reproducibility data, comparing the initial and repeat studies are provided in detail in TableIn-vivo cDTI is challenging due to cardiac motion and the intrinsically low SNR of the technique. However, our previous study showed that cDTI using the DW-STEAM sequence at 3T can be performed in-vivo in healthy volunteers with good reproducibility. We now -3 mm2/s and was significantly higher in the septum . The interstudy reproducibility of global MD was reasonable at 18.6%, with values ranging from 15.4% to 30.9% for slices and walls. The interstudy reproducibility of MD was significantly less good than for FA (p = 0.003).FA had a global value of 0.613 ± 0.044 and analysis by slice and wall yielded similar results with no statistical differences. The interstudy reproducibility of global FA was very good at 7.2%, with values ranging from 6.8% to 9.7% for slices and walls. This very robust reproducibility suggests that the values have clinical validity. MD had a global value of 0.750 ± 0.154 × 10One possible interpretation of the finding of higher MD in the septum might be that it resulted from the commonly found septal hypertrophy in HCM in association with an enlarged interstitial space from disarray or fibrosis. However, considerable caution must be observed in the interpretation of this result because of known and unknown technical issues. One issue might be that the SNR across the LV is not homogeneous due to the decreasing sensitivity of the receiver surface coils with depth . It is well documented in diffusion tensor imaging that FA and MD values are biased by SNR due to the Rician noise distribution and due to the fact that only magnitude images are used to derive the diffusion tensor parameters. TherefoAnalysis of HA was divided into 3 transmural layers because of prior findings. The global value for endocardial HA was 38.9° ± 8.1°, and SD of the difference between the measurement for the 2 scans was 4.8°. For the mesocardium, the global value was 3.5° ± 6.9° with an interstudy SD of 3.4°. For the epicardium, the global value was −34.3° ± 7.6° with an interstudy SD of 2.9°. These findings indicate very good reproducibility between scans of HA in all 3 layers and suggest clinical validity. CoVs were not calculated because their magnitude is a function of the coordinate angles chosen, and in the current system were incalculable in the mesocardial layer as the mean helical angle approximates to zero as myocyte orientation rotates from a left-handed to right-handed helix creating unstable values by division. Significant differences in HA were found between the reference lateral wall and the septum in all 3 transmural layers . Significant differences also affected the inferior wall in the endo and mesocardium (p < 0.001), and the anterior wall in the epicardium (p = 0.004). One possible interpretation of the finding of different HA values in the septum is disturbance from myocardial disarray. However, once again this interpretation needs to be regarded with considerable caution. In this study the myocardium was segmented transmurally into 3 equal thickness layers. This does not necessarily represent the real left-handed, circular and right-handed HA structure of the myocardium and therefore averaging within these 3 layers is bound to happen. Although this should not largely affect the reproducibility, it could influence the LV wall comparison due to the varying myocardial thickness per wall segment. The segmentation might be subject-dependent due to the fact that the papillary muscles and RV wall are visually excluded and might differ between initial and repeat scans, affecting the values due to mis-registration of the region of interest, and also across patients. The design, implementation, optimisation and comparison of segmentation algorithms to extract robust and meaningful quantitative HA data will be a very important task for the translation of cardiac DTI into routine, and is the subject of ongoing research. On the other hand, HA distribution maps appeared healthy in the majority of cases. We hypothesise that this might be due to the fact that the patient cohort scanned for this study was composed of stable HCM patients. There is a possibility that this is the reason why the HA maps appear normal, and that more severe forms of HCM might correlate with disturbed HA distribution maps.-3 mm2/s using a similar breath hold DW-STEAM protocol,[-3 mm2/s, which are both within one standard deviation of the global value of 0.750 ± 0.154 × 10-3 mm2/s found in the current study of HCM patients. Tseng et al. performed in-vivo DTI in 5 patients with HCM and 5 volunteers[-3 mm2/s in the lateral wall and 0.610 ± 0.059 × 10-3 mm2/s in the septum, with no significant difference between our values (p = 0.77). Further studies will be needed to compare measures, standardise and optimise the methods and further validate results. It should be noted that the quantitative results in this study are obtained from acquisitions at end-systole. We might expect differences between in-vivo and ex-vivo data, and also between fresh and fixed ex-vivo data, and finally also between data acquired at different cardiac phases.There is relatively little previous in-vivo work on the absolute values of FA and MD. In healthy human subjects we reported an MD value of 0.8 ± 0.2 × 10rotocol, and Reesrotocol, reportedlunteers. They meThe general limitations of this study are the following: The modest in-plane resolution of 2.7 mm might lead to volume averaging of the blood pool in endocardial layers or the RV papillary muscles in epicardial layers, which could bias the FA, MD and HA values in these areas; Data acquisition was performed at end-systole, which is considered a phase when the diffusion acquisition is not affected by strain, and althIn conclusion, we have implemented a robust quantitative in-vivo cDTI technique that has the potential to enhance our understanding of in-vivo structure-function relationships in the HCM heart. We have shown that cDTI of the human HCM heart in-vivo can be performed using a recently reported technique, and we have assessed the reproducibility of the results of this technique in HCM patients.AHA: American Heart Association; cDTI: Cardiac Diffusion Tensor Imaging; CMR: Cardiovascular Magnetic Resonance; CoV: Coefficient of Variation; DTI: Diffusion Tensor Imaging; DW-STEAM: Diffusion Weighted Stimulated Echo Acquisition Mode; EPI: Echo Planar Imaging; FA: Fractional Anisotropy; HA: Helix Angle; LGE: Late Gadolinium Enhancement; LV: Left Ventricle; HCM: Hypertrophic Cardiomyopathy; MD: Mean Diffusivity; SD: Standard Deviation; SNR: Signal to Noise Ratio.Prof Dudley Pennell is a consultant to Siemens and a director of Cardiovascular Imaging Solutions. Royal Brompton Hospital has research collaboration agreements with Siemens and Medical Solutions. The other authors declare that they have no competing interests.LAM, TFI, SNV, PF, ADS, SKP, DNF recruited patients, acquired patient data and performed image analysis and data handling. MR performed all study statistics. SNV, PF, PS, TF, CM, DES, PDG, ADS, DNF contributed to image acquisition and processing. DJP, DNF, PJK, SYH, KPM, RDS conceived the study. DJP, DNF were responsible for the final manuscript. All authors read and approved the final manuscript.David N Firmin and Dudley J Pennell are joint senior authors.Laura-Ann McGill, Tevfik F Ismail, Sonia Nielles-Vallespin and Pedro Ferreira are joint first authors.


This study aimed at evaluating the early effects of successful elective percutaneous coronary intervention (PCI) on systolic and diastolic function.We consecutively studied the systolic and diastolic function in 21 patients with stable coronary artery disease (CAD) and left ventricular ejection fraction (LVEF) > 40% before and 48 hours after successful elective PCI.p-value = 0.008) following PCI. Diastolic velocities, E/A ratio, deceleration time (DT), early and late diastolic velocities of mitral annulus in TDI, pulmonary vein systolic (PVs) and diastolic flow velocity (PVd) did not show significant improvement.Tei index and systolic indices  did not change significantly. Among the diastolic indices, only velocity propagation (Vp) improved significantly (from 42.9 ± 10.8 to 51.8 ± 10.7, Propagation velocity of mitral inflow was the earliest index to recover following successful PCI in patients with stable CAD. Percutaneous coronary intervention (PCI) is a very common revascularisation procedure performed in patients with stable coronary artery disease (CAD).Echocardiography provides a feasible and non-invasive technique for assessment of global and regional myocardial function.The present study was designed to evaluate the early effects of successful elective PCI on systolic and diastolic function globally and regionally through thorough echocardiographic examinations, including two-dimensional (2-D), M-mode, colour Doppler and TDI.Our study participants were recruited from 31 consecutive patients with stable CAD who were scheduled for elective PCI in Rajaie Heart Centre. Patients were considered for inclusion if they had angiographically documented coronary artery stenosis > 70% in diameter in the culprit lesion by visual assessment, and documented ischaemia. Ischaemia was documented using stress testing in patients with typical stable angina, according to the Canadian Cardiovascular Society (class I or II).Exclusion criteria were bundle branch block, pacemaker implantation, left ventricular ejection fraction (LVEF) < 40%, valvular heart disease, cardiomyopathy, history of coronary artery bypass grafting (CABG), refractory angina or acute myocardial infarction (MI) requiring emergency revascularisation, and left main stem disease.All patients were evaluated by an experienced echocardiologist, using conventional  and tissue Doppler echocardiography examinations one day before and 48 hours after successful PCI, in order to assess cardiac systolic and diastolic function. Successful revascularisation was defined as a residual stenosis of < 30% in luminal diameter with TIMI flow grade 3. Patients with unsuccessful PCI (10 people) were excluded.All patients were on an optimal medical regimen consisting of nitrates, aspirin, β-blockers, angiotensin converting enzyme inhibitors and lipid-lowering agents (statins) along with a low-fat diet on an individual basis.The institutional review board of the hospital approved the study protocol. All participants gave written informed consent. This investigation was in accordance with the Declaration of Helsinki.Direct stenting or stenting after successful angioplasty was performed in all the participants according to published guidelines.Echocardiographic data were obtained using a commercially available ultrasound system Vivid-3 (GE) equipped with a 3-MHz transducer. Measurements were obtained by averaging values recorded in three consecutive cycles, according to the current American Society of Echocardiography guidelines.14For two-dimensional and M-mode echocardiography, 2-D images were obtained in standard parasternal and apical views. All patients were examined at rest in the left lateral decubitus position.The LV end-diastolic and end-systolic dimensions (LVEDD and LVESD) were measured at the level of the mitral leaflet tips from the parasternal long-axis with two-dimensional targeted M-mode echocardiography. LVEF was calculated from the apical two- and four-chamber views using the modified Simpson’s rule.The regional wall motion abnormality (RWMA) score of the LV was assessed for each LV segment individually, and the wall motion abnormality score index (WMSI) was obtained using the 16-segment model, according to the American Society of Echocardiography recommendations.For RV systolic functional assessment, the tricuspid annular plane systolic excursion (TAPSE) was measured using two-dimensionally guided M-mode imaging from the apical four-chamber view.Mitral inflow velocities were measured with pulsed-wave colour Doppler echocardiography, with the sample volume positioned between the tips of the mitral leaflets in the apical four-chamber view. Peak early diastolic velocity (E), peak late diastolic velocity (A), E/A ratio and deceleration time (DT) were obtained.Mitral inflow propagation velocity (Vp) was measured as the maximum slope of the first aliasing velocity during early filling from the mitral valve plane to 4 cm distal to the LV cavity in the apical four-chamber view using colour M-mode Doppler.Pulmonary vein systolic flow velocity (PVs) and diastolic flow velocity (PVd) were measured from the apical four-chamber by placing a sample volume in the right upper pulmonary vein with Doppler echocardiography. Isovolumetric contraction time (IVCT), isovolumetric relaxation time (IVRT) and ejection time (ET) were assessed by simultaneously measuring the flow into the LV outflow tract and the mitral inflow, using Doppler echocardiography. The index of myocardial performance (IMP or Tei index) was calculated by dividing the sum of IVRT and IVCT by ET.Pulsed-wave TDI was performed by activating the tissue Doppler function in the same echocardiographic machine. Mitral annulus velocities  were measured using the pulsed-wave TDI technique, by placing a 1–2-mm sample volume at the levels of septal, lateral, inferior, anterior and posterior annulus.Peak systolic velocity of the mitral annulus (Sa), and early (Ea) and late diastolic (Aa) velocities of the mitral annulus were determined from septal, lateral, inferior, anterior and posterior aspects. Peak systolic velocity of the tricuspid annulus (TA-Sa) was also derived from pulsed Doppler tissue imaging of the lateral tricuspid annulus.t-test. The Wilcoxon signed rank test was used to test for the difference between the mean RWMA scores before and after PCI. The statistical software SPSS-13  for Windows was used for all analyses; p-values < 0.05 were considered statistically significant.Continuous variables are presented as means ± standard deviations (SD) and categorical data are expressed as frequencies and percentages. Comparisons of continuous variables pre and post PCI were carried out using the paired-samples p = 0.008). Other diastolic indices did not show improvement A total of 21 patients who had had successful PCI were considered for the study analysis. Baseline characteristics of participants are summarised in This study presents a comprehensive echocardiographic assessment of regional and global myocardial function, both systolic and diastolic, following blood flow restoration with PCI electively performed in patients with stable CAD. Our findings indicate that the propagation velocity of early flow into the LV cavity (Vp), measured by colour M-mode Doppler, was the most sensitive index to recover after successful PCI.LV ejection fraction calculated by the biplanar Simpson’s method, along with other parameters of myocardial systolic function including the regional wall motion index evaluated by 2-D and TDI-derived systolic myocardial velocities at the mitral (Sa) and tricuspid annulus (TA-Sa), did not change significantly early after PCI. Previous studies have shown different results regarding systolic functional improvement following PCI. In a study performed in 41 patients with stable CAD, successful elective PCI did not improve ejection fraction at the one-day and six-month follow up.5However, in another study, peak systolic velocities of three annular sites, but not the ejection fraction, showed substantial improvement.It is postulated that patients with severely depressed ventricular dysfunction (LVEF < 40%) benefit most from revascularisation.et al.16Among various echo-technique parameters assessing diastolic function, only colour M-mode Vp was found to have improved significantly 48 hours after PCI. There have been various reports on improvements observed in diastolic parameters following PCI. Diller A study performed on 31 patients with chronic CAD showed that most echocardiographic diastolic indices, including IVRT, EDT, E/A ratio, IVCT and diastolic indices of both the mitral and tricuspid annulus sites on TDI improved significantly 24 hours following elective PCI.9There is evidence that abnormalities in diastolic function may precede systolic dysfunction during myocardial ischaemia.et al.21Vp, which was initially proposed by Brun The reason for persistence of abnormal indices of LV performance (other than Vp) may be the duration of disease before PCI.A limitation to the current study could have been the relatively small number of patients evaluated. Moreover, since functional improvement following PCI may increase over time,Unlike studies that showed an improvement in TDI parameters of systolic and diastolic function in patients with stable CAD after successful PCI, in our population only the colour M-mode Doppler parameter improved 48 hours after successful elective PCI in patients with stable CAD. More studies should be done to corroborate the results presented here.


To evaluate the ability of velocity encoded (VENC) magnetic resonance imaging (MRI) to identify patients with diastolic dysfunction in comparison with Doppler-echocardiography.Diastolic dysfunction was recently recognized as an important cause for heart failure in patients with preserved ejection fraction. Diastolic dysfunction is typically assessed in clinical routine using transmitral and pulmonary-venous flow characteristics by Doppler-echocardiography. We hypothesized that VENC-MRI has a similar ability to identify patients with diastolic dysfunction compared to Doppler-echocardiography.The study included 76 patients with normal systolic left-ventricular function and a high probability of diastolic dysfunction. Transmitral flow and pulmonary venous flow profiles were obtained by VENC-MRI and Doppler-echocardiography. Measurements included maximal early- and late-diastolic transmitral velocities (E- and A-waves) as well as maximal systolic and diastolic pulmonary venous velocities (S- and D-wave). Furthermore, VENC-MRI was used to assess total diastolic left ventricular (LV) filling as well as the early and late portions of diastolic LV filling.Doppler-echocardiography identified 38 patients with diastolic dysfunction. 24 patients had grade I diastolic dysfunction, 8 patients hat grade II diastolic dysfunction and 3 patients had grade 3 diastolic dysfunction. There was a very good correlation between VENC-MRI and Doppler-echocardiography for the E/A-ratio using peak velocities . A moderate correlation was found for the S/D-ratio between VENC-MRI and Doppler-echocardiography using peak velocities . In grade I diastolic dysfunction, the contribution of early LV filling to total LV filling was significantly lower compared to patients with normal diastolic function or higher grades of diastolic dysfunction (Figure VENC-MRI has the ability to identify diastolic dysfunction by measurements of transmitral flow velocities. Furthermore, the assessment of early and late LV diastolic filling volumes may provide additional information for the grading of diastolic dysfunction.


Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.The aim of this article is to describe a novel hardware perfusion phantom that simulates myocardial first-pass perfusion allowing comparisons between different MR techniques and validation of the results against a true gold standard. MR perfusion images were acquired at different myocardial perfusion rates and variable doses of gadolinium and cardiac output. The system proved to be sensitive to controlled variations of myocardial perfusion rate, contrast agent dose, and cardiac output. It produced distinct signal intensity curves for perfusion rates ranging from 1 to 10 mL/mL/min. Quantification of myocardial blood flow by signal deconvolution techniques provided accurate measurements of perfusion. The phantom also proved to be very reproducible between different sessions and different operators. This novel hardware perfusion phantom system allows reliable, reproducible, and efficient simulation of myocardial first-pass MR perfusion. Direct comparison between the results of image-based quantification and reference values of flow and myocardial perfusion will allow development and validation of accurate quantification methods.  First-pass myocardial MR perfusion has become a reliable tool for the diagnosis of myocardial ischemia . AlthougThe phantom was designed to simulate dynamic of first-pass myocardial MR perfusion after the injection of a bolus of a gadolinium-based contrast agent. The system is made up of three main parts: the main pump generating water flow in the circuits located outside the MR room, the MR-compatible unit (the phantom) located in the scanner, and the control unit located outside the MR scanner room  and 2.2) would be equivalent to a cardiac index ranging from 1.2 to 6.6 L/min/m2.The main pump maintains the water flow across the phantom and is located outside the MR room . VariousTo reproduce the dilution of the contrast bolus and its mixing with blood that occurs in the large thoracic vessels and in the heart, the phantom was designed to resemble the anatomy of the thoracic circulation and of the heart of a 60 kg human subject  and 2a. The core of the system is a four-chamber heart and two cylinders representing the myocardial compartments  and 2a. The heart receives a positive pressure water flow from a pipe connecting the vena cava (VC) to the main pump and to the control unit. Just before the VC (15 cm before the RA), a three-way stopcock allows direct injection of contrast agent into the water flowing in the circuit. This operation was performed by a clinical power injector , which allows contrast to be administered in the same way as it is for usual clinical protocols.After the injection, the bolus of contrast agent travels in the water through the chambers and vessels and it is progressively mixed and diluted in water. Similar to the fragmentation of the bolus of gadolinium observed in vivo, the system generates the arterial input function (AIF) measured in the proximal aorta that can be used for quantification of myocardial perfusion by means of signal deconvolution techniques.The bolus flows through the RA and the right ventricle, which is connected to the left atrium by a silicone tube a. After Both myocardial compartments are plastic cylinders of 4-cm diameter containing 124 pipes with a thin (0.1 mm) polypropylene wall and with a diameter of 3 mm. Coronary blood flow enters the myocardial compartments from a lateral inlet, ensuring an even distribution of the perfusion flow during first pass across the section of the cylinder. The mechanism by which physiological first-pass SI curves for the myocardial compartments are generated and a detailed description of the myocardial compartments are explained in detail in the legend of To relate the gold standard flow rate across the myocardial compartments with the measured perfusion rate, the myocardial compartments were titrated to define the distribution volume of the contrast agent during first pass. The distribution volume is the water effectively modifying the distribution of the contrast agent and the characteristics of the SI curves during first pass and was defined as the volume of water comprised between the point where the aortic AIF is sampled (just before the take off of the coronary circulation) and the myocardial volume preceding and including the imaging plane. Because of the complex geometry of this section, the position of the imaging plane was defined by weighing each myocardial compartment  and its coronary vessel on a precision scale and adding 45 g of distilled water, corresponding to 45 mL of volume. To facilitate the identification of the correct geometry during scanning, the level corresponding to the imaging plane was marked on the outer surface by a multimodality marker  regulate precisely and independently the perfusion rate in each myocardial compartment. The roller pumps were positioned distal to the myocardial compartments to minimize the dead space between the ascending aorta and the myocardial compartments. Positioning the pumps between the ascending aorta and the myocardium might interfere with the dilution of the contrast agent and therefore affect quantitative perfusion measurements. At the exit of the roller pumps, the flow rate in the right and left myocardial compartment lines is measured by two vertical flow meters .3, and saturation recovery delay 120 ms). Vector-electro-cardiographic triggering was simulated at a cardiac frequency of 60 beats per minute. Data were acquired during first pass of a bolus of gadobutrol  injected at 4 mL/s followed by a 20 mL saline flush. Each bolus of gadobutrol was preceded by a diluted prebolus with 10% of the dose to allow quantification of myocardial blood flow, according to published methods (n = 6) were carried out to test the reproducibility of the SI measurements.All data were acquired on a 3T Philips Achieva TX system, equipped with a 32-channel cardiac phased array receiver coil . Perfusion data were acquired in a transverse geometry, visualizing the progression of the bolus of contrast agent in the large thoracic vessels and the myocardial compartments in the same image . We used methods . To avoiTo assess the effects of different dosages of contrast agent on the SI of the AIF and to calculate the saturation ratio (expected peak SI/observed peak SI), gadobutrol was injected at 0.0005, 0.001, 0.0025, 0.005, 0.01, and 0.1 mmol/kg in the following experimental conditions: cardiac output 3 L/min, right and left myocardial perfusion rate 10 mL/mL/min. To assess the effects of different dosages of contrast agent on the SI of the myocardial compartments and to calculate the saturation ratio, gadobutrol was injected at 0.001, 0.0025, 0.005, and 0.01 mmol/kg in the following experimental conditions: cardiac output 3 L/min, right and left myocardial perfusion rate 10 mL/mL/min.To assess the sensitivity of the system to different myocardial perfusion rates, first-pass perfusion measurements were performed varying the perfusion rate in the L-myoc , in the following experimental conditions: cardiac output 3 L/min, contrast agent dosage 0.01 mmol/kg body weight.To assess the effect of variations of the dilution of a bolus of contrast agent on the measured SI curves, the acquisition was performed for different values of cardiac output of 3 and 4 L/min, injecting 0.01 mmol/kg of gadolinium, with right and left myocardial perfusion rate constant at 5 mL/mL/min.To assess the reproducibility of the measurements, two operators repeated this last group of experiments twice on different days. Moreover, reproducibility was also assessed by repeating the experiments six times under the same experimental conditions of 4 L/min of cardiac output, using 0.01 mmol/kg of gadolinium, and a perfusion rate of 1 and 5 mL/mL/min in the right and 10 mL/mL/min in the left myocardial compartment.Data were analysed using ViewForum v6.3.1.2 (Philips) modified with software made in-house, which allows efficient segmentation of the images and export of the SI curves for analysis. Data were analysed by one of the authors who was unaware of the protocol and perfusion rate used in each experiment. Quantification of myocardial perfusion was performed using a Fermi deconvolution method .cin(t) and myocardial compartment SI curve q(t) values were entered into the deconvolution model that is based on the central volume principle  denote the contrast concentrations in the venous outflow. The tissue impulse response h(t) is estimated by using a Marquardt–Levenberg nonlinear least square optimization method to fit a Fermi function with the following analytical expression:in which F and k represent indices of the contrast agent influx and efflux parameters, θ(τd) is the unit step function, τd accounts for the delay time between the appearance of signal in LV blood pool cin(t) and myocardial region of interest q(t), and finally τ0 characterizes the width of the shoulder of the Fermi function during which little or no contrast agent has left region of interest. This fitting procedure yielded the time curves for tissue impulse response function, h(t), from which perfusion values were calculated as (h(t = 0)) ) .SI curves were compared to assess reproducibility by means of a linear regression analysis using the Pearson's correlation coefficient. Multiple measurements were compared using the analysis of variance (ANOVA) test. All data analysis was performed with Predictive Analytics SoftWare (PASW) statistics for Mac 18.0.0 .A progressive increase in the peak AIF SI was noted with increasing doses of gadolinium a. A veryA progressive increase of SI in the myocardial compartments was also obtained in the myocardial compartments following an increase in the dosage of contrast agent administered b. At a dThe system showed good sensitivity for different perfusion rates, generating independent curves for the different perfusion values tested (between 1 and 10 mL/mL/min). P < 0.0001 among different flow rates; n = 6).Quantification of myocardial perfusion provided results consistent with the gold standard perfusion measurements obtained by the phantom's flow meters. The results were as follows : 10.4 ± 0.4/10, 7.4 ± 0.3/7.5, 4.7 ± 0.1/5, 2.9 ± 0.2/2.5, and 1.3 ± 0.4/1 mL/mL/min , showing excellent reproducibility between different operators and on different days both for cardiac output of 3 L/min  and 4 L/min . Reproducibility was also demonstrated for different myocardial perfusion rates, as described in Methods section. The aortic, right, and left myocardial SI curves showed a very good correlation between experiments, with an adjusted R2 of 0.99 and a P < 0.0001 consistently.The latter experiment was repeated several times  before a new perfusion experiment can be performed. Our data demonstrate that the perfusion phantom provides data suitable for quantification by means of signal deconvolution. Future work will be needed to validate existing analysis methods and to develop and validate novel approaches toward full quantification. However, the phantom is likely to allow a reduction of the number of animal studies required to develop and validate novel MR techniques.The main limitation of the current setup of the perfusion phantom is that the distribution dynamics of the contrast agent in the myocardial compartments only simulates the physiological appearance of the SI curves and does not involve diffusion of the contrast from the vascular to the interstitial space see  as occurThere are some other differences between the myocardial compartments of the phantom and the real myocardial tissue. The average resistance to blood flow in the synthetic myocardium is lower than the physiological one and does not vary over time as result of the complex interaction between cardiac contraction and small intramyocardial vessels. Moreover, the myocardial compartments show a relatively narrow distribution and a lower incoherence of flow compared with the myocardial capillary bed. For this reasons, we feel that the perfusion phantom cannot completely replace animal experiments or human validation studies. However, the capability of the perfusion phantom to offer a controlled and highly reproducible simulation of first-pass perfusion, with selective alterations of myocardial blood flow in one or both myocardial compartments, is likely to expedite the development and comparison of different acquisition sequences or hardware or direct comparison of different quantification techniques, which is very difficult to achieve in vivo.A possible confounding effect in first-pass perfusion quantification is due to bolus dispersion that occurs during the transit through the epicardial vessels to the myocardium . Even thT1 relaxation leading to an apparent TOther limitations of the setup presented are intrinsic to the methods currently used to acquire first-pass perfusion images. Turbo gradient-echo sequences cause an acceleration of ected SI , 32. TheThe use of Fermi deconvolution is meant, in this study, as a means to demonstrate that the perfusion phantom is capable, in the described setup, to provide realistic simulations of myocardial perfusion that are suitable for quantification by means of deconvolution algorithms. We have decided to apply Fermi deconvolution, instead of any of the other mathematical methods previously described in the literature, as it has been extensively used in the past to quantify myocardial perfusion. However, the validation of Fermi deconvolution or any other deconvolution method is outside the aim of this article and specific comparative studies will be required to compare different deconvolution algorithms and to define the most accurate quantification method.This novel hardware perfusion phantom allows reliable, reproducible, and efficient simulation of myocardial perfusion. The availability of a direct comparison between the image data and reference values of flow and perfusion will allow rapid development and validation of accurate quantification methods.


Due to the shortage of donor hearts, the criteria for acceptance have been considerably expanded. Hearts with regional or global left ventricular dysfunction are excluded from donation, but stress echo might be useful to identify patients with reversible wall motion abnormalities, potentially eligible for donation.Six marginal candidate donors  were enrolled. Resting echocardiography showed in all subjects a LV ejection fraction ≥ 45% (mean 51 ± 5%), but multiple risk factors were present. All donors had either global or discrete wall motion abnormalities: Wall Motion Score Index (WMSI) rest = 1.33 ± 0.25. Stress echocardiography was performed with the dipyridamole high dose of 0.84 mg/kg given over 6 min.The stress echo results were abnormal in three donors (WMSI rest = 1.51 ± 0.19 vs peak = 1.41 ± 0.30). These hearts were excluded from donation and cardiac pathology verification was available in two cases of confirmed LV myocardial fibrosis and/or severe coronary stenosis. The remaining three hearts improved during stress (WMSI rest = 1.15 ± 0.13 vs peak = 1.04 ± 0.06) and were transplanted uneventfully. Recipients  underwent post-TX coronary angiography, IVUS and endomyocardial biopsies. No recipient had primary graft failure, and all showed normal coronary angiography and normal LV function  at 1-month post-TX. The recipients were alive at 12-month median follow-up.Dipyridamole stress echo performed in brain-dead potential donors with LV resting global or discrete wall motion abnormalities identifies hearts with severe morphologic abnormalities excluded from donation (with fixed response during stress echo) from hearts eligible for donation, showing improvement in regional wall motion during stress (viability response) and normal function and coronary anatomy following transplantation. Brain death is a hostile environment for the donor heart and undoubtedly contributes to the occurrence of primary graft failure after HT. Donor heart dysfunction results from the “catecholamine storm”  that produces an increase in myocardial oxygen demand and potentially myocardial ischemia. These phenomena may mediate myofibrillar degeneration, a process characterized by injury and death of myofibers in a hypercontracted state . MyocardAs far as function is concerned, a donor heart should not be used in the presence of intractable ventricular arrhythmias, the need for excessive inotropic support, discreet wall motion abnormalities on echocardiography or LVEF < 45% despite optimization of hemodynamics with inotropic support . Given tAim of this study was to evaluate the usefulness of dipyridamole stress echocardiography in selecting for heart TX hearts with “standard” donor age but with multiple risk factors for early graft failure and discreet LV wall motion abnormalities in resting echocardiogram. The study hypothesis was that hearts with fixed abnormalities were not eligible as proven at cardio-autoptic verification, whereas those with reversible abnormalities were potentially eligible for transplantation as shown by subsequent angiographic evaluation in transplanted hearts.After legal declaration of brain death, marginal donors underwent baseline echocardiography for evaluation of regional wall motion, global ventricular function, and ventricular mass, according to American Society of Echocardiography recommendations .Stress echocardiography was performed following the European Association of Echocardiography and American Society of Echocardiography [iography ,11 protoiography ,12. At biography  to calcuiography . Potentiiography ,11; a fiiography , and a siography ,11. Eligiography . Hearts iography .Eligible hearts  were retrieved using a standard technique and preserved with cold cardioplegic arrest and topical hypothermia. Primary graft failure after HT was defined as need for immediate post-HT mechanical circulatory support . The recHearts deemed unsuitable as a result of stress echocardiographic results were removed from donors and sent to the Pathology Department Center for a very detailed macroscopic and microscopic study . AutopsiP values < .05 were considered statistically significant.SPSS version 11 for Windows  was used for statistical analyses. The statistical analyses included descriptive statistics . Six marginal candidate donors  were enrolled  of the test relies on the demonstration of residual contractile reserve in a basally dysfunctional region; improved myocardial thickening of segments that are dyssynergic in resting conditions is a sign of viability, whereas necrotic segments show no functional improvement. Such reserve can be elicited through a flow-mediated increase in contractile function linked to endogenous adenosine accumulation achieved by intravenous infusion of dipyridamole.Left ventricular dysfunction is a common finding in patients with intracranial pathologies and brain stem death. In 147 patients with subarachnoid hemorrhage, global or regional LV dysfunction was found in 30 20%) patients on echocardiography. Regional wall motion abnormalities tended to cover multiple arterial territories and occurred in the absence of coronary artery disease % patient. SecondlLeft ventricular dysfunction is common in donor hearts and in several cases does not correspond to a detectable pathological abnormality. Abnormal regional or global resting LV dysfunction is a functionally heterogeneous entity, encompassing patients both unsuitable and suitable for donation. The former group shows fixed or worsening  wall motion response during stress echo, and significant myocardial and/or coronary alterations at pathology verification. The second group shows normal  wall motion response during stress echo, and absence of myocardial and/or coronary alterations at angiography verification, and can be transplanted uneventfully. The promising data obtained in this proof-of-concept study should now be substantiated in a larger series in order to change current guidelines ruling out donation on the basis of probably too-restrictive criteria of global or discreet regional wall motion abnormalities.BSD: Brain stem death; DIP: Dipyridamole; EF: Ejection fraction; EMBs: Endomyocardial biopsies; HT: Heart transplant; IVUS: Intra Vascular ultra sound; LV: Left Ventricular; TX: Transplant; WMSI: Wall motion score index.The authors declare that they have no competing interests.TB conceived this report, performed the data analysis, and drafted the manuscript; OL performed the anatomic and histology examinations of non transplanted and transplanted hearts and revised the manuscript; SG was responsible for data collection and revised the manuscript; EP and RS gave a contribution to the preparation of study design, data discussion, and critical revision of the manuscript. All authors read and approved the final manuscript.TB, Scientific Coordinator of the CCM project n. 48 “Aged Donor Heart Rescue by Stress Echo – ADONHERS” Institute of Clinical Physiology, National Research Council, Pisa, Italy. SG, Cardiology Division and Intensive Care Unit, M. Bufalini Hospital, Cesena, Italy. OL, Pathology Department, University of Bologna, Italy. RS, is the Head of the Echocardiography Lab, IFC, CNR, Pisa. EP, Director IFC, CNR, Pisa, Italy.Quad screen DIP stress echo of a potential heart donor with discrete wall motion abnormalities at rest showing incomplete improvement in regional wall motion during stress. Upper panels rest; lower panels peak stress.Click here for fileLV apical wall akinesia is shown at baseline (left upper panel) and 1-min stress (right upper panel). At 3- and 4-min stress (lower panels) a worsening of LV function is shown accompanied by hemodynamic instability.Click here for fileIn both the two-chamber (upper panel) and short-axis (lower panel) views note the inferior and lateral left ventricular dysfunction.Click here for fileLeft ventricular lateral wall hypokinesia and inferior wall akinesia are shown in 4- and 3-chamber views at baseline (left and right upper panels). At peak stress a viability response is shown with recovery of normal lateral and inferior wall motion (lower panels).Click here for fileQuad screen DIP stress echo: global and regional wall motion is shown in 4- and 2-chamber views at baseline (upper panels) and at peak stress (lower panels).Click here for file


Cardiac function is important for patients treated by venovenous extracorporeal membrane oxygenation (VV ECMO), but data about the effect of VV ECMO on the heart in nonneonates is absent. We studied the effect of VV ECMO on cardiac performance, cardiomyocyte and mitochondria in an animal model.Twelve farm piglets were randomly assigned into two groups: control group and ECMO group. In the ECMO group, ECMO cannulaes were placed and ECMO was instituted. Hemodynamics was recorded at baseline, 1 hour after induction, and every 4 hours thereafter, to assess the cardiac performance. All animals were monitored for 24 hours and were euthanized and myocardium was harvested. Myocardial histology, ultrastructure of cardiomyocyte and mitochondria were observed, and activities of mitochondrial complexes I-V were measured, to assess the effect to cardiomyocyte and mitochondria.Hemodynamics were stable in each group of animals throughout the experiment. Interstitial edema, disorderd and dissolved of focal myofilament, morphological deformations of mitochondria were observed in the ECMO group. The activities of mitochondrial complexes were decreased in the ECMO group, and complex I and IV reached significance.VV ECMO therapy is associated with changes of ultrastructure and function of cardiomyocyte and mitochondria, inducing myocardium injury. However, the injury was mild and had no effect on the cardiac performance for healthy piglets. Venovenous extracorporeal membrane oxygenation (VV ECMO) is a life-saving treatment for severe respiratory failure patient refractory to conventional therapy. VV ECMO maintains sufficient tissue oxygenation and carbon dioxide elimination, so that ventilator settings can be reduced which minimizes ventilator-induced lung injury, and provides time for lung to rest and recovery ,2. The iVV ECMO does not provide direct cardiac support, which depends on intrinsic cardiac function to maintain cardiac output. In the clinical practice, we found that there are some patients developing cardiac dysfunction during VV ECMO therapy, and finally lead to adverse outcome. Therefore, we postulate that myocardial dysfunction plays an important role in determining the outcome of patients treated by VV ECMO, and the possibility of VV ECMO inducing cardiac injury is important.Very little is known about the effect of VV ECMO on the heart, limited to some clinical observations in neonates ,10, and The aim of the study was to investigate the effect of VV ECMO on the heart in nonneonatal population. Patients with severe respiratory failure have a high prevalence of cardiac dysfunction ,12. To aThis study was approved by the Animal Care Committee of Jinling Hospital. All animals received humane care in accordance with the “Principles of Laboratory Animal Care” formulated by the Ministry of Health of the People’s Republic of China.Twelve farm piglets of either sex (25–35 kg) were fasted for 24 hrs. Anesthesia was induced with ketamine (20 mg/kg), diazepam (8 mg/kg), and atropine (0.1 mg/kg) intramuscularly, maintained with ketamine (10-20 mg/kg/hr) and diazepam (8 mg/kg/hr) intravenously. The animals were intubated through a cervical tracheotomy, and ventilated on volume-control mode with room air at a tidal volume setting of 5–8 mL/kg, positive end expiratory pressure of 5 mmHg, and respiratory rate of 15 breaths per minute. Internal jugular vein and femoral arterial catheters were aseptically placed for intravenous access, blood pressure monitoring, and sample collection, pulmonary artery catheter was inserted in the proximal pulmonary artery via the jugular vein catheter for monitoring of pulmonary artery pressure (PAP) and pulmonary artery occlusion pressure (PAOP).After instrumentation and baseline data collection, animals were randomly assigned into two groups: control group and ECMO group (n =6/each). In the ECMO group, after a 150 U/kg intravenous bolus of heparin, ECMO cannulaes  were placed in the superior vena cava through internal jugular vein and inferior vena cava through femoral vein, and ECMO circulation was instituted. Placement of the cannulaes was confirmed via ultrasonograph. Heparin was infused to keep activated clotting time of 180–220 seconds after insertion.The ECMO system consisted of a membrane oxygenator and tubing , a centrifugal pump , a heat exchange . The circuit was primed with 500 ml hydroxyethyl starch 130/0.4 and 200-300 ml Ringer’s lactate. Blood in circuit was drained from femoral vein cannulae and infused into internal jugular vein cannulae at a flow rate of 50 ml/(kg.min). 100% oxygen was given at a flow rate equal to the blood flow rate.Hemodynamic parameters, including heart rate (HR), mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP) and pulmonary artery occlusion pressure (PAOP) were monitored  and recorded at baseline, 1 hour after induction, and every 4 hours thereafter until 24 hours. All pressures were determined at end-expiration. Each animal received lactated Ringer’s solution at a rate of 3 ml/kg/h, and bolus fluid was provided as required to maintain MAP above 60 mmHg. The whole volume of fluid intake of each animal was recorded. Temperature, Serum pH, glucose and ionized calcium concentration were monitored and maintained normally.All animals were monitored for 24 hours and were euthanized with a bolus injection of potassium chloride . Myocardium was harvested immediately for further measuring.Samples from the apex of left ventricular muscle were fixed and dehydrated with 10% formalin, embedded in paraffin, cutted into sections, stained with hematoxylin and eosin (H and E staining), and observed by an optical microscopy .Fresh myocardial tissues from the apex of left ventricular muscle were cut into pieces (1*1*1 mm), fixed with 3% glutaraldehyde, flushed with phosphate-buffered saline, fixed with 1% perosmic acid, and dehydrated with acetone. Ultrathin sections were placed on 200-mesh copper grids and double stained with 4% uranyl acetate and 0.2% lead citrate. Sections were examined under transmission electron microscopy . Ultrastructure of cardiomyocyte and mitochondria was observed.The histology and ultrastructure were examined by an independent pathologist blinded to the grouping.Heart tissues from the apex of left ventricular muscle were put in the ice-cold homogenization buffer. The mitochondrial pellet was isolated by differential centrifugation , and finActivities of mitochondrial respiratory chain complexes I-V were measured using spectrophotometry . The actpost hoc analyzed, using the least significance difference (LSD) tests. Statistical significance was established as p <0 .05.All the statistical analyses of the data were performed by the SPSS 17.0 software . Data are expressed as mean ± SD or median (interquartile range). Data were statistically analyzed using one-way analysis of variance (ANOVA). Significant results were There was no difference in body weight and other characteristic between groups.Hemodynamic parameters, including heart rate (HR), mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP) and pulmonary artery occlusion pressure (PAOP) were stable in each group of animals throughout the experiment, and no significance was presented between groups Table . HoweverH and E staining in the control group showed that cardiomyocytes were arranged in rows, the fiber structure of cardiomyocyte was clear. There was no obvious damage to myocardial fibers in the ECMO group, but interstitial edema was observed, myocardial fiber spacing was increased Figure .Under TEM, samples from the control group showed myofilament was ordered, the structure was clear, the sarcolemma was intact. Samples from the ECMO group showed myofilament was mildly disorderd, dissolved of focal myofilament can be observed Figure .The mitochondria from the control group exhibited well-defined double membranes with normal cristae arrangement Abnormal mitochondria can be observed in the ECMO, characterized by mitochondrial swollen, decreased density of inner membrane cristae, along with vacuolation, but the outer membrane was integrated Figure .The activities of mitochondrial complexes were decreased in the ECMO group versus the control group Figure , and actAs a lifesaving treatment, VV ECMO is becoming more and more essential for children and adults with refractory respiratory failure, and such patients have a high prevalence of cardiac dysfunction ,12. VV EIn this study, the volume of fluid intake was significantly more in the ECMO group. Golej et al.  found MAIn addition, the ECMO group disorderd and dissolved of focal myofilament, morphological deformations of mitochondria and decreased activities of mitochondrial complexes compared with the control group, suggesting that VV ECMO therapy is associated with myocardium injury.The mechanisms of these findings require further research. Several factors may contribute to it, such as activation of systemic inflammatory response, increase of reactice oxygen species (ROS), and release of toxic substances by ECMO.The instigation of a systemic inflammatory state with exposure to ECMO is well accepted -21. FortIt is well established that cardiopulmonary bypass is associated with increased production of reactice oxygen species (ROS) ,29, and In addition, it is not clear whether the ECMO circuit adds some toxic substances such as endotoxin  and plasDespite changes of ultrastructure and function of cardiomyocyte and mitochondria induced by VV ECMO, we found hemodynamics during VV ECMO therapy was stable, suggesting that the injury was mild, and had no effect on the cardiac performance for healthy piglets, consistently with the results of Strieper  and RobeHowever, energy is the base to maintain normal cardiac pump function, continuously produced by mitochondrial respiration . TherefoFurthermore, under disease conditions with severe hypoxia, hypoxia itself plays an important role in myocardial injury , and theTherefore, the effect of VV ECMO on the myocardium and cardiac performance would be more complicated for patients under hypoxemic condition, and should be further investigated. However, we present the potentially adverse effect of VV ECMO alone on the heart for the first time, calling for attention to the impact on heart during VV ECMO, and provide a potentially aspect to improve the survival of VV ECMO.In conclusion, the results of our study showed that VV ECMO is associated with changes of ultrastructure and function of cardiomyocyte and mitochondria, inducing myocardium injury. The underlying mechanisms should be further investigated. However, the injury was mild and had no effect on the cardiac performance for healthy piglets.VV: Venovenous; ECMO: Extracorporeal membrane oxygenation; HR: Heart rate; MAP: Mean arterial pressure; MPAP: Mean pulmonary artery pressure; PAOP: Pulmonary artery occlusion pressure; H and E staining: Stained with hematoxylin and eosin; TEM: Transmission electron microscopy; NADH: Nicotinamide adenine dinucleotide reduced; DCIP: 2,6-Diclorophenol indophenol; ROS: Reactice oxygen species; IL: Interleukin; TNF-α: Tumor necrosis factor α.The authors declare that they have no competing interests.JL, WY, NL, JS contributed to the experiment conception and design; JS, QC, JS, YH, CH participated in the animal experiment and were responsible for histology and ultrastructure section; JZ, TG, FX, JG participated in the animal experiment and were responsible for the biochemistry section; JS did the statistics and drafted the manuscript; WY, NL and JL provided critical revision of the manuscript; all the authors read and approved the final manuscript.


Patients with sickle cell disease (SCD) and pulmonary hypertension (PH) have increased mortality. SCD-PH is often complicated by high cardiac output (CO) related to anemia. The transpulmonary gradient (TPG) reflects a pressure differential across the pulmonary vascular bed without the confounding effect of CO (PVR=TPG/CO). Based on the cardiac transplant literature, a TPG ≥ 12 mmHg indicates significant pulmonary arterial hypertension (PAH). With PH, there is often morphologic adaptation by the right ventricle (RV). In idiopathic PAH, RV dilation and decreased function have been correlated with poor prognosis. We hypothesize that patients with SCD and a TPG ≥ 12 mmHg would have lower functional capacity, increased mortality, and evidence of RV dysfunction on cardiac MRI (CMR).Five hundred and twenty nine consecutive patients  female, 73% (n=387) HbSS) with SCD were prospectively screened for PH using echocardiography (tricuspid regurgitant jet ≥ 2.5 m/s) without any exclusion criteria. Eighty four  female, 82% (n=69) HbSS) underwent right heart catheterization (RHC), and 41  female, 80% (n=33) HbSS) underwent CMR within one week of RHC. CMR sequences consisted of cine and late gadolinium enhancement imaging.Those with a TPG ≥ 12 mmHg had higher mortality (p=0.008), poorer functional class (p=0.007), shorter 6-minute walk distance (p=0.003), and lower cardiac index (p=0.001). High TPG patients demonstrated more abnormal CMR markers of RV dysfunction (lower tricuspid annular plane excursion (p=0.001) and RV ejection fraction (p=0.002)). Recently validated CMR markers of PAH including septal-to-LV-free-wall curvature ratio (p=0.013), septomarginal trabeculae mass index (p=0.002), and ventricular mass index ratio (p=0.016) were significantly different in the high TPG group. Left ventricular (LV) eccentricity index (EI) at end-systole (ES) was greater in the high TPG group (p=0.026) without a significant change between ES and end-diastole (ED)—consistent with RV pressure overload. In the low TPG group, the EI-ED was greater than EI-ES (p=0.001)—consistent with RV volume overload. LV ejection fraction was similar in both groups. Late gadolinium enhancement at the RV insertion points indicative of myocardial fibrosis occurred more frequently with higher TPG (p=0.030).CMR evidence of RV dysfunction was associated with a TPG ≥ 12 mmHg. A TPG ≥ 12 mmHg effectively identified patients with a lower functional capacity and overall worse prognosis. The TPG, being less subject to the confounding effects of CO, further demonstrates the functional severity of pulmonary arterial disease in SCD using objective thresholds established in the cardiac transplant literature.None.


There are over 270,000 childhood cancer survivors in the US. Of these survivors, more than 50% have been treated with anthracyclines and are at risk of developing progressive cardiotoxicity. Novel cardiac magnetic resonance imaging (CMRI) techniques are now able to reliably detect diffuse myocardial fibrosis and changes in regional myocardial function. We hypothesized that these novel CMRI techniques will identify occult asymptomatic cardiotoxicity in a cohort of childhood cancer survivors with normal global systolic function.Twenty seven long-term childhood cancer survivors between 11.8-28.8 years with a cumulative dose >240mg/m2 (mean 363±89) and normal systolic function (SF>29%) were studied 2.4-24 years after exposure to anthracycline therapy. Patients underwent CMRI techniques to characterize changes in T1 relaxation time, left ventricular myocardial peak circumferential and longitudinal strain parameters and were analyzed using the 17-segment model. Extracellular volume (ECV) was measured in 13 subjects all of whom were late gadolinium enhancement (LGE) negative. We performed standard CMRI assessment and quantification of myocardial mass, end-systolic and end-diastolic volumes, ejection fraction, and end systolic fiber stress.Twenty seven of 60 planned subjects have been imaged. End systolic fiber stress was significantly increased with higher cumulative anthracycline dose R2=0.18, p<0.03) and younger age at diagnosis . Lower average circumferential strain magnitude (εcc) and regional changes in peak circumferential strain were seen in multiple segments despite normal values of global systolic function by echocardiography and CMRI (Figure8, p<0.03In this study we demonstrate that changes in T1 mapping-derived relaxation time and left ventricular myocardial peak circumference strain are present in asymptomatic post-chemotherapy childhood patients who have normal standard CMRI parameters. Circumferential strain analysis and measurement of the T1 myocardial relaxation time by CMRI may accurately identify occult cardiovascular dysfunction in patients exposed to high dose anthracyclines. Thus, this may aid in the evaluation of therapies aimed at reducing adverse cardiac remodeling and preventing heart failure in childhood cancer survivors exposed to anthracyclines.St. Baldrick's Foundation Supportive Care Research Grant


Relative edema volume, computed from T2-based CMR images, has been used to define the Area-At-Risk in myocardial infarction and in the determination of salvagable myocardium in patients. Following infarction, edema presents as hyperintense regions in T2-weighted CMR, however, the literature reports disparate data resulting from delayed imaging and type of MR acquisition.To investigate the time course and extent of myocardial edema in reperfused myocardial infarction on the basis of T2 maps and T2-weighted STIR imaging.2-weighted STIR imaging and T2 maps. LAD instrumented canines (n=9) underwent three hours of no-flow ischemia followed by reperfusion and were studied [using Siemens 1.5 T Espree scanner] at five time points . Scan parameters for T2-STIR acquisitions were: TE=64ms, TR=2-3 R-R intervals, resolution=0.9x0.9x8.0mm3. T2 maps were computed from multiple T2-prepared acquisitions with different preparation times  with spatial-resolution of 1.0x1.0x8.0mm3. Late-enhancement imaging confirmed LAD infarction. Areas of interest were determined as follows: For T2 maps - region with T2 values greater than 2SD from remote territories; and for T2-STIR images- regions exceeding 2SD of the signal intensity of the remote regions. Edema volume was computed as highlighted areas multiplied by imaging slice thickness. Percent volume of edema was computed relative to total myocardial volume. Results are reported as mean ± SEM for each time point.Cardiac MR was used to investigate the development and persistence of edema volume increases in the acute post-infarct period using both T2 Maps:T Pre-ischemia: 0.8±0.4%; Ischemia: 2.5±1.4%; Day 2: 18.3±3.9%; Day 5: 29.7±5.4%; Day7: 23.0±5.1%; and Day 56: 1.4±0.6%. 2-STIR:T Pre-ischemia: 2.1±1.0%; Ischemia: 8.4±2.6%; Day 2: 33.6±2.9%; Day 5: 26.1±5.2%; Day7: 28.5±3.0%; and Day 56: 4.9±1.9%. p<0.01 by ANOVA. T2 maps showed a continuous rise in relative edema volume post reperfusion that peaked at day 5. Although edema volume decreased by day 7, it remained significantly elevated from pre-ischemic levels. In T2-STIR analysis, edema volume rose rapidly, peaking at day 2 and remaining elevated throughout the acute study period. T2-STIR images showed an earlier peak in edema volume compared to that determined from T2 maps. Both measures demonstrated regression of edema after 56 days. Figure Percent volume of edema (Area-At-Risk) - This data indicates that the time following ischemia-reperfusion injury, as well as the mode of MR interrogation, are critical variables in the determination of Area-at-Risk.


Right ventricular heart rupture is a devastating complication associated with negative pressure wound therapy (NPWT) in cardiac surgery. The use of a rigid barrier has been suggested to offer protection against this lethal complication, by preventing the heart from being drawn up and damaged by the sharp edges of the sternum. The aim of the present study was to investigate whether a rigid barrier protects the heart and lungs against injury during NPWT.Sixteen pigs underwent median sternotomy followed by NPWT at -120 mmHg for 24 hours, in the absence (eight pigs) or presence (eight pigs) of a rigid plastic disc between the heart and the sternal edges. The macroscopic appearance of the heart and lungs was inspected after 12 and 24 hours of NPWT.2 when no protective disc was used, and 1.15 ± 0.19 cm2 when using the disc (p < 0.001). Heart rupture was observed in three of the eight animals treated with NPWT without the disc. Lung rupture was observed in two of the animals, and lung contusion and emphysema were seen in all animals treated with NPWT without the rigid disc. No injury to the heart or lungs was observed in the group of animals treated with NPWT using the rigid disc.After 24 hours of NPWT at -120 mmHg the area of epicardial petechial bleeding was 11.90 ± 1.10 cmInserting a rigid barrier between the heart and the sternum edges offers protection against heart rupture and lung injury during NPWT. Cardiac surgery is complicated by poststernotomy mediastinitis in 1 to 5% of all procedures . The repThere are, however, increasing numbers of reports of deaths and serious complications associated with the use of NPWT, where right ventricle rupture and bypass graft rupture resulting in death are the most devastating complications; the incidence being 4 to 7% of the patients treated for deep sternal wound infection with NPWT after cardiac surgery . We haveThe present study was conducted to investigate whether a rigid disc offers protection against heart and lung injury during NPWT. Sixteen pigs underwent median sternotomy followed by NPWT at -120 mmHg for 24 hours, in the absence (eight pigs) or presence (eight pigs) of a rigid plastic disc between the heart and the sternal edges. In the present article we measure epicardial bleeding after NPWT of a sternotomy wound. Petechial refers to one of the three major classes of purpuric conditions. The most common cause of petechial is through physical trauma. In the present article we believe that the epicardial bleeding is caused by trauma from the NPWT. The macroscopic appearance of the heart and lungs was inspected and the area of epicardial petechial bleeding was measured after 12 and 24 hours of NPWT.A porcine sternotomy wound model was used. Sixteen domestic landrace pigs with a mean body weight of 70 kg were fasted overnight with free access to water. The study was approved by the Ethics Committee for Animal Research, Lund University, Sweden. All animals received humane care in compliance with the European Convention on Animal Care.® vet. 20 mg/ml; Bayer AG, Leverkusen, Germany; 2 mg/kg) mixed with ketamine . Before surgery, a tracheotomy was performed and an endo-tracheal tube was inserted. Anesthesia was maintained with a continuous infusion of ketamine . Complete neuromuscular blockade was achieved by continuous infusion of pancuronium bromide . Fluid loss was compensated for by continuous infusion of Ringer's acetate at a rate of 300 ml/kg/h. Mechanical ventilation was established with a Siemens-Elema ventilator  in the volume-controlled mode . Ventilatory settings were identical for all animals . A positive end-expiratory pressure of 5 cmH2O was applied. A Foley catheter was inserted into the urinary bladder through a suprapubic cystostomy. Upon completion of the experiments, the animals were given a lethal dose (60 mmol) of intravenous potassium chloride.Premedication was performed with an intramuscular injection of xylazine . Statistical analysis was performed using the Mann-Whitney test when comparing two groups, and the Kruskal-Wallis test with Dunn's test for multiple comparisons when comparing three groups or more. Significance was defined as p < 0.05 (*), p < 0.01 (**), p < 0.001 (***), and p > 0.05 . All differences referred to in the text have been statistically verified. Values are presented as means ± the standard error on the mean (S.E.M.).2) than with the disc (1.03 ± 0.20 cm2, p < 0.001, Figure 2 without the disc and 1.15 ± 0.19 cm2 with the disc, Figure The surface of the right ventricle of the heart was red and mottled as a result of epicardial petechial bleeding in all cases following NPWT Figure . After 1Right ventricular heart rupture was observed in three of the eight animals treated with NPWT without the rigid disc, while no ruptures were observed in the animals treated with NPWT when using the disc Figure .Lung ruptures were observed in two of the eight animals treated with NPWT without the disc, while none was seen when using the disc Figure . Lung coThe intention of this study was to investigate whether a rigid disc offers protection against heart and lung injury during NPWT. The results show both heart and lung injury after NPWT without the rigid disc. When NPWT is applied, the tissues are drawn together, towards the source of the vacuum. It is well known that NPWT results in wound contraction -16, howeet al. described 5 cases of injury following NPWT of deep sternal wound infection in Sweden, 3 of which were fatal [et al. reported that one of a total of 5 mortalities was due to right ventricular rupture [et al. also reported one fatality due to right ventricular rupture among 54 deep sternal wound infection patients treated with NPWT [et al. reviewed 3 of their own cases of heart rupture following NPWT, together with literature reports of 39 earlier cases, and found the incidence of heart rupture to be 7.5% [The importance of protecting exposed organs during NPWT has received increasing attention recently, following reports of heart rupture and death. Sartipy re fatal . In a se rupture . Ennker ith NPWT . KhoynezIn November 2009, the FDA filed an alert  to draw In summary, right ventricle rupture is a feared complication of NPWT in sternotomy wounds. The cause may be that the heart and lungs are drawn up towards the anterior thoracic wall and forced against the sharp sternal edges during NPWT. Inserting a rigid barrier between the heart and the sternum offers protection against heart rupture and lung injury during NPWT.The authors declare that they have no competing interests.SL, MM, and RI carried out the animal studies. SL, MM, and RI carried out the design of the study and MM and SL performed the statistical analysis. All authors read and approved the final manuscript.


Increased inflammation has been linked to myocardial dysfunction and heart failure. We investigated whether T1 mapping by cardiovascular magnetic resonance (CMR) in patients with systemic lupus erythematosus (SLE) can detect subclinical cardiac involvement.A total of 37 SLE female patients subjects (mean age 41±11years) underwent CMR for routine assessment of cardiac perfusion, function and scar. T1 mapping was performed in single short axis slice before and 15 minutes after gadolinium administration.Sixteen age-matched subjects from the clinical pool with a low pre-test probability and normal CMR acted as a control group. Both groups had normal volumes and global systolic function (ejection fraction (%): control vs. SLE group: 60±13 vs. 56±12, p=0.57) and similar LV mass index (LVmass index (g/ m2): 43±12 vs. 51±12 g/ m2, p=0.18). SLE patients had significantly reduced longitudinal strain  and showed intramyocardial (70%) or pericardial (63%) late gadolinium enhancement. SLE patients had significantly increased preconstrast myocardial T1 (T1native ) values and lambda (p<0.01). In comparison of significant measures, we identified T1native as the strongest discriminator between the patients and controls.We demonstrate that in SLE patients without significant coronary artery disease there is evidence of subclinical perimyocardial involvement. Among variables to discern the subclinical cardiomyopathic process, T1 mapping performs best to discriminate between health and disease.National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award.