Cardiac lipomatous metaplasia (LM) occurs in patients with chronic ischemic heart disease and heart failure with unclear mechanisms. We studied coronary occlusion/reperfusion-induced myocardial infarction (MI) in rabbits during a 9-months follow-up using 3.0 T magnetic resonance scanner, and confirmed the presence of MI in acute phase and LM in chronic phase using histopathology.MI was surgically induced in 10 rabbits by 90-min coronary artery occlusion and reperfusion. Forty-eight hours later, multiparametric cardiac magnetic resonance imaging (cMRI) was performed at a 3.0 T clinical scanner for MI diagnosis and cardiac function analysis. Afterwards, seven rabbits were scarified for histochemical staining with triphenyltetrazolium chloride (TTC), and hematoxylin-eosin (HE), and 3 were scanned with cMRI at 2 days, 2 weeks, 2 months and 9 months for longitudinal observations of morphological and functional changes, and the fate of the animals. Post-mortem TTC, HE and Masson's trichrome (MTC) were studied for chronic stage of MI.2=0.83). Global cardiac morphology-function analysis showed significant correlation between increasing acute MI size and decreasing ejection fraction (p<0.001). During 9 months, cMRI documented evolving morphological and functional changes from acute MI to chronic scar transformation and fat deposition with a definite diagnosis of LM established by histopathology.The size of acute MI correlated well between cMRI and TTC staining (rAcute MI and chronic LM were induced in rabbits and monitored with 3.0 T MRI. Studies on this platform may help investigate the mechanisms and therapeutic interventions for LM. The moderate size rabbit model of occlusion/reperfusion-induced myocardial infarction (MI) has been used in cardiac imaging research -3. In pain vivo and ex vivo animal research.Myocardial fat develops with aging and is commonly seen at right ventricular (RV) free wall and RV outflow tract in humans. Substitution of myocardial tissue by fat is less common in the left ventricle, except for some pathologic conditions such as healed MI, dysplasia, cardiac lipoma, tuberous sclerosis complex, dilated and dystrophic cardiomyopathy, etc. . MyofibrThe purposes of this study were as follows: a) longitudinal evaluation of MI by a 3.0 T MRI scanner, and b) comparison of MI between MRI and histopathology findings on both acute and chronic phase. This way, we incidentally identified the presence of LM in rabbits. In this report, we describe such findings and further discuss their implications for translational cardiologic research by cross-referencing pertinent literature.This study was approved by the institutional ethical committee for animal care and use. Ten male New Zealand white rabbits  weighing 3.0 kg were sedated, endotracheally intubated and mechanically ventilated. The rabbit received intravenous (i.v.) injection of pentobarbital  at 40 mg/kg/h to maintain anesthesia during the open-chest operation. A left-side thoracotomy was performed at the fourth intercostal space and a suture was placed underneath the left coronary artery. Reperfused MI was induced by tying the suture with a single detachable knot. Ninety minutes after coronary occlusion and sixty minutes after closure of thoracic cavity, the knot was detached outside the thorax by pulling the exteriorized end of suture in the closed-chest condition . As showThe rabbit was gas-anesthetized with 2% isoflurane in the mixture of 20% oxygen and 80% room air, through a mask connected via a tube to a ventilation instrument  and placed supinely in a holder. Using a commercial 8-channal phased array knee coil, cMRI was performed at a 3.0 T clinical MRI scanner  with a maximum gradient capability of 45 mT/m. The acquisition of cMRI was triggered by ECG and gated by the respiration using a small animal monitoring and gating system . The two surface ECG electrodes were attached to the shaved thorax skin of apparent apical pulse and the left leg. The respiration control sensor was attached on the middle of the abdomen. As shown in Table in vivo cMRI. The slices were incubated at 37°C in 2% triphenyltetrazolium chloride (TTC) solution for 15 min and fixed with 10% formalin for 24 hours. The heart sections in the fresh condition, shortly after TTC staining, and 24 hours after formalin fixation were photographed with a digital camera. One day later, heart sections were imbedded into paraffin-blocks, which were then cut into 5 micron thick slices and stained with Masson's trichrome (MTC) and hematoxylin -eosin (HE) for microscopic assessment. MTC staining is used for the detection of collagen fibers in the heart, where the collagen fibers are stained blue and the nuclei are stained black and the background myocardium is stained red. HE and MTC macro- and microscopic photographs were further co-localized and interpreted cross-referencing cMRI findings.After the cMRI scans at day 2 and month 9, the rabbits were euthanized with overdosed pentobarbital. The excised heart was imbedded in and filled with 3% agar solution of 40°C in a Plexiglas heart matrix for ex vivo cMRI after cooling at −20°C for 15 min. After MRI, the imbedded heart was cut into 3 mm short axis slices similar to that with The global LV parameters including end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), cardiac output (CO), and LV-mass were determined by tracing the endocardial and epicardial contours on end-distolic and end-systolic cine images with a commercially available software Syngo Argus . The papillary muscles were included in LV mass measurement. Mass in grams was calculated assuming a specific gravity of 1.05 g/cm3.The planimetry of the percent of MI size on DE-cMRI and postmortem digital photographs were estimated on built in software of the system (SyngoMR A30) and the software Image J 1.38x . All the images were in different order, the estimation of MI size on cMRI and on pathology was performed by two authors separately.The MI size per slice by MRI was assessed semiautomatically by computer counting of all enhanced pixels within the short-axis image. Enhanced pixels were defined as pixels with signal intensities more than two standard deviations above the mean of image intensities in the remote normal myocardial region on the same images . The sumThe signal intensity (SI) ratio refers to myocardial lesion comparable to normal myocardium on T1WI and T2WI, which was performed on the Siemens workstation using the built-in software by two authors with consensus. For the quantification of SI ratios, a round of region of interesting about 1 cm2 was drawn on the lesion and normal myocardium.Data were reported as mean ± standard deviation (SD). Statistical analysis was performed with Graphpad Prism 5 software. The correlation relationship between EF and MIS was compared by the linear correlation analysis. The agreement between DE-cMRI and TTC measurements of infarct size was assessed by linear correlation analysis. A difference was considered statistically significant if the P value was less than 0.05.All rabbits tolerated well the procedures including systemic anesthesia, open-chest surgery, and cMRI. Seven rabbits were used for acute phase and 3 for chronic phase of MI studies. The presence of MI was evident by typical ECG alterations initially, on cMRI during follow-up and with histomorphology at the end. The 3 rabbits gained body weight from 3.0 to 4.2 kg during the 9 months after the MI insult. They manifested normal behaviors and diet without symptoms of heart failure such as dyspnea, tachycardia, tachypnea, cyanosis, stupor, arrhythmia, and hypothermia. There was no apparent difference that allowed distinguishing one from the other rabbits.2=0.95; p<0.001), confirming a successful model of AMI  on MRI and TTC  on DE-cMRI and TTC were 35.41% ± 12.2% and 31.62%± 13.74%, respectively with no significant difference between them (p=0.8). The representative MI on DE-MRI and histopathology of acute MI were shown in Figure The global functional parameters of EDV, ESV, SV, CO, EF and LV-mass were derived from cine cMRI for 48 hours and 9 months after MI and listed in Table The longitudinal changes of SI ratio on T1WI and T2WI averaged from three LM animals were showed in Figure The gradual identification of LM formation was shown in Figure Acute MI stage Figure  A1-A5: 4Early chronic MI Figure  B1-B5: 2Chronic MI Figure  C1-C5: 2ex vivo fat suppressed T1WI  the infarcted ventricular wall did not become thinning at 9 months after MI as expected; 2) the LM region was stained whitish by TTC in contrast to brick-red normal myocardium, which was confused with acute MI and left a question about its histological nature; 3) H&E photomicrographs indicate that damaged myocardium is replaced by large quantity of adipocytes infiltrated with macrophages, i.e. the MI was entirely substituted by LM; and 4) MTC stained photomicrographs reveal few collagen fibers left.By combining Post-infarct LM is increasingly reported in clinical patients with very limited histological evidence. It usually occurs several years or over one decade after MI ,22,25,26in vivo.The rabbit appears an ideal animal for cardiac research ,3,10,27.The major weakness of this work is the small sample size and only 3 rabbits with chronic MI were studied longitudinally with cMRI, partially due to the constrains of animal protection and limited housing space. Secondly, this study was not by intention to address the LM, and therefore only some cMRI sequences were applied for detection of fat. The LM was only recognized incidentally at 9 months after MI induction. Nevertheless, the collected evidences especially from the evolving features on cMRI and the characteristic changes on pathological specimens do justify this reliable finding of the LM in rabbits.in vivo cMRI corresponded well to ex vivo MRI and histomorphology, suggesting a promising animal model and research platform for further study on the mechanisms and possible therapeutic interventions of LM.We validated 3.0 T cMRI for evaluation of acute and chronic MI in rabbits and presented a new finding of the LM in rabbits with chronic MI after a longitudinal (from 48 hours to 9 months) follow-up using cMRI in correlation with histopathology. The All authors claim no conflict of interest what so ever in the context.All the authors 1) have made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; 2) have been involved in drafting the manuscript or revising it critically for important intellectual content; and 3) have given final approval of the version to be published.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2342/13/18/prepub


Myocardial fibrosis occurs in aortic stenosis and is associated with long-term clinical outcome. Myocardial fibrosis is detected by delayed contrast-enhanced cardiac magnetic resonance. The aim of this study was to investigate the influence of myocardial fibrosis on left ventricular (LV) global function and morphology in patients with symptomatic severe aortic stenosis (AS).Eighty-nine patients  with pure severe AS (n = 36) or severe AS with mild aortic regurgitation (n = 53) were included in the study. All patients underwent transthoracic echocardiography (TTE), cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) and subsequent valvuloplasty operation. Patients were analyzed according to the presence and absence of myocardial fibrosis  on CMR. The differences of cardiac function and morphology between two groups are statistically analyzed.3 vs 1631 ± 1106 mm3, p = 0.0001) and calcium grade by CCT (p =0.0002), more severe AS , higher indexed LV mass by CMR , lower LV ejection fraction by CMR , and larger indexed LV end-diastolic volume by CMR  compared with patients without myocardial fibrosis.Myocardial fibrosis was observed in 37 patients. There were no differences in valvular morphology and clinical characteristics between two groups. Patients with myocardial fibrosis had higher aortic valve calcium volume score (2960 ± 1934 mmMyocardial fibrosis is associated with more severe calcific AS, worse LV functional parameters and higher LV mass index in patients with severe AS. From these results, contrast-enhanced CMR may provide new strategies for the earlier diagnosis of severe AS with myocardial fibrosis.None.


To explore the clinical value of low-dose prospectively electrocardiogram-gated axial dual-source CT angiography  in patients with pulsatile bilateral bidirectional Glenn shunt (bBDG) as an alternative noninvasive method for postoperative morphological estimation.Twenty patients with pulsatile bBDG (mean age 4.2±1.6 years) underwent both low-dose PGA scanning and conventional cardiac angiography (CCA) for the morphological changes. The morphological evaluation included the anatomy of superior vena cava (SVC) and pulmonary artery (PA), the anastomotic location, thrombosis, aorto-pulmonary collateral circulation, pulmonary arteriovenous malformations, etc. Objective and subjective image quality was assessed. Bland–Altman analysis and linear regression analyses were used to evaluate the correlation on measurements between CTA and CCA. Effective radiation dose of both modalities was calculated.2>0.8, P<0.001) was observed between the measurements on CTA images and on CCA images. Bland–Altman analysis demonstrated a systematic overestimation of the measurements by CTA .The mean effective dose of CTA and CCA was 0.50±0.17 mSv and 4.85±1.34 mSv respectively.The CT attenuation value of bilateral SVC and PA was higher than 300 HU. The average subjective image quality score was 4.05±0.69. The morphology of bilateral SVC and PA was displayed completely and intuitively by CTA images. There were 24 SVC above PA and 15 SVC beside PA. Thrombosis was found in 1 patient. Collateral vessels were detected in 13 patients. No pulmonary arteriovenous malformation was found in our study. A strong correlation (RCT angiography with a low-dose PGA scanning is an accurate and reliable noninvasive examination in the assessment of morphological changes in patients with pulsatile bBDG. Historically the Bidirectional Glenn shunt (BDG) was a palliative surgical procedure typically done in children with a single effective ventricle as an intermediate step before completion of a Fontan operation. The bilateral BDG (bBDG) is an end-to-side anastomosis between the bilateral superior vena cava (SVC) and the pulmonary artery (PA) respectively . CompareThere is no doubt that medical imaging plays a critical role in the postoperative estimation. Conventional cardiac angiography (CCA), which is routinely performed after bBDG, gives an accurate estimation of the morphological and hemodynamic information. However, with the improvement in noninvasive imaging modalities, as well as the technical difficulty, expense, and ionizing radiation exposure  with high spatial resolution and reduced acquisition time has been validated as a precise examination in the evaluation of children with repaired congenital heart diseases (CHD), and only short time sedation  rather than general anesthesia was used in uncooperative patients This study received approval from the Shandong Medical Imaging Research Institute ethics board. The possible adverse effects of contrast medium injection and radiation exposure as well as the complications of CCA were explained to all patients (the guardians of patients). Written informed consent was obtained from all patients (the guardians of patients) to prospectively enter this research.Twenty children underwent pulsatile bBDG at a single institution. Both low-dose PGA scanning and CCA were performed in all patients  as a routine during a follow-up period of 6 to 12 months between April 2011 and July 2012.All examinations were performed on a first generation dual-source CT scanner . Younger children (≤15 kg) were sedated with oral chloral hydrate (50 mg/kg) CT parameters were as follows: 0.33 s gantry rotation time, 2×32×0.6 mm detector collimation, a slice collimation 2×64×0.6 mm by z-flying focal spot technique, 80 kV tube voltage and weight adapted setting for tube current (10 mAs/rot per kg up to 6 kg then 5 mAs/rot per kg up to 140 mAs/rot). We did not use β-blocker therapy to decrease the heart rate. The data acquisition window was set at 40% of the R-R interval.Iodinated contrast medium  was injected via unilateral peripheral veins in the elbow or back of the hand at a volume of 2.0 ml/kg body weight with a saline chaser of 1.0 ml/kg body weight Images were reconstructed with a slice thickness of 0.75 mm and increment of 0.5 mm using a medium smooth-tissue convolution kernel (B26f). All images were anonymous and transferred to an external workstation  for further analysis. In addition to the CT axial slices, Multiplanar reformation (MPR), maximum intensity projection (MIP) and volume rendering (VR) were used for image interpretation.2 circular ROIs at different regions. The noise was defined as the standard deviation of the attenuation value.As the postoperative changes of bilateral SVC and PA drawed pediatric cardiologists' attention, we paid great attention to the morphological evaluation of SVC and PA. Intraluminal attenuation and image noise of bilateral SVC and PA were assessed as objective image quality parameters. The magnitude and uniformity of arterial enhancement was measured using 1.0 cmBlinded to the results of CCA findings, two cardiac radiologists with more than 5 years' experience respectively interpreted the subjective image quality of great vessels  using a 5-grade scoring system  1) and distal (SVC0) part of SVC, as well as the maximum diameter (SVCmax) were measured /SVC0×100%. The dilation of SVC was observed visually according to VR image.The diameters of the proximal (SVCmeasured . As the 0) of PA and the descending aorta at the diaphragm (DA) were measured, and McGoon ratio =  (LPA0+ RPA0)/DA. The stenosis of PA was assessed visually according to VR image.The diameters of the prebranching point . Another potential complication is the development of pulmonary arteriovenous malformations (AVMs). Pulmonary AVMs are postulated to occur because the SVC blood lacks a humoral factor from the liver which is needed to prevent the development of AVMs in the lungs We paid great attention to thrombosis which is one of the severe postoperative complications of this procedure CCA was performed by means of a Phillips' machine  using a 4-6 Fr catheter 2 or 3 days after low-dose PGA scanning in all patients. They were kept fasting for 3–4 hr prior to the procedure. The procedure was done under general anesthesia with Midazolam (0.1 mg/kg) and Ketamine (1–2 mg/kg). Groin was cleaned and local anesthesia was given. All children were restrained by tying them over the board so as to avoid unnecessary movements. Arterial and venous access was obtained after puncturing right or left femoral artery and vein as well as unilateral or bilateral internal jugular veins by Seldinger's technique. Heparin was given 80 units/kg at the beginning of the procedure. Angiographic pictures were recorded on the Phillips' machine. The contrast medium used for angiography was non-ionic  with total dose limited to 5 ml/kg, and the average amount of contrast enhancement was 4.6±0.3 ml/kg.max. With regard to the hemodynamic evaluation, the oxygen saturation of cardiac atrium, ventricle, the aorta and PA as well as the pressures of cardiac ventricle, aorta, main pulmonary artery, bilateral SVC and PA were measured. Since we focused on the morphological evaluation, the corresponding measurements of CCA were recorded and compared with those of low-dose PGA scanning while the hemodynamic data of CCA was not listed below.As for the morphological assessment, biplane anteroposterior and lateral projection aortography by internal jugular vein was performed to evaluate the anatomy of SVC and PA, the anastomotic location between SVC and PA as well as thrombosis and pulmonary AVMs. Anteroposterior, lateral and left anterior oblique projection aortography or selective angiography was performed to observe the amount of APCs and APCThe volume CT dose index and dose length product (DLP) were obtained from the information generated by the CT system and the effective radiation dose was calculated from the DLP as follows. The recorded DLP was multiplied by 2.3 to adapt it to the 16-cm phantom, because on the machine used for the study, the DLP for body surface area was given on a 32-cm phantom and 2.3 is scanner specific for pediatric examinations at 80 kV as provided by the manufacturer. The corrected DLP value was then multiplied by the infant-specific conversion coefficient given for a 16-cm phantom: 0.018 mSv/(mGy•cm) between 1 year and 6 years of age 2) As for CCA, the dose-area product was displayed by the fluoroscopy system itself and the infant-specific coefficient 0.41 mSv/. With CCA results as the standard, linear regression analysis and Bland–Altman analysis were used to evaluate the correlation on measurements between CTA and CCA, and Pearson's correlation coefficient was calculated . P<0.05 was considered statistically significant.Statistical analysis was performed by SPSS 17.0 software  and Microsoft Windows Excel 2007 . Results were expressed as means ± standard deviations for quantitative variables and as frequencies or percentages for categorical variables. Interobserver agreement on grades of subjective image quality was assessed by kappa statistics . Mean scan length was 109.7±15.1 mm (85–136), resulting in a mean of 6±1 (5–8) slab acquisitions per examination. Mean scan time was 6.6±1.1 s (4.79–8.63).The CTA data of twenty children with pulsatile bBDG were successfully acquired. All patients were in sinus rhythm at the time of data acquisition. Mean heart rate was 98±11.7 bpm (range 77–119), mean heart-rate variability was 10.8±5.8 bpm (4–23). Data acquisition took place at every 2κ = 0.76, P<0.05). Artifacts due to respiratory motion were present in 6 examinations without impairing diagnostic quality.Objective image quality parameters are listed in 2>0.8, P<0.001) was observed between the measurements on CTA images and on CCA images. Bland–Altman analysis demonstrated a systematic overestimation of the measurements by CTA  2 = 0.96, P<0.001) (The measurements were listed in P<0.001) . Bland–AP<0.001) .max and SVC0 was as follows: ≤10%, n = 14; 10%–20%, n = 11; ≥20%, n = 14. The dilation was observed in 14 SVC by both CTA and CCA, and the corresponding SVCmax was 20% larger than SVC0 without exception. Therefore, we set ≥20% as the standard of dilation, and SVC1 was 20% larger than SVC0 in 10 of 14 dilated SVC. As for PA, 16 stenosis was found by CT and confirmed by CCA. There were 3 stenosis at the root  SVC above PA dilated while only 13.3% (2/15) SVC beside PA dilated.max measured by CTA and CCA was 2.7±0.5 mm (2.1–3.6) and 2.5±0.4 mm (1.9–3.3) respectively, and there was a strong correlation . Bland–Altman analysis demonstrated a systematic overestimation of the measurements by CTA (bias 0.11±0.20 mm).There were no pulmonary AVMs in 20 patients.Thrombosis was found in 1 patient, locating in the whole course of LSVC as well as the proximal part of left internal jugular vein and left sub-clavian vein . The thr2 (7.49–16.39), resulting in an average effective dose of 4.85 ±1.34 mSv (3.07–6.72).The mean volume CT dose index was 1.08±0.25 mGy (0.77–1.82), and the mean DLP was 12.1±4.1 mGy•cm (6.6–21.6), resulting in a mean estimated effective dose of 0.50±0.17 mSv (0.27–0.89). The mean dose-area product of CCA was 11.82±3.27 Gy•cmThe patients after bBDG had bilateral SVC. Then it comes to a question whether bilateral cavopulmonary anastomoses can be shown at the same time when the iodinated contrast medium was injected via unilateral peripheral veins. As we know, the blood containing the iodinated contrast medium mainly flushes into the unilateral PA from ipsilateral SVC after the injection. If the scanning had been performed at this time, higher attenuation would have been achieved at the ipsilateral SVC and PA of the injection while the contralateral SVC and PA would have lower attenuation. Therefore the scanning was delayed until the contrast medium came to the arteries of neck and upper limb and refluxed through the veins. Then the bilateral SVC was expected to achieve the preferable attenuation.As the dilation of SVC implied the obstructed blood reflow or the unfavorable hemodynamics and the dilation sometimes developed into aneurysm , much atTo the best of our knowledge, there was no study discussing the anastomotic relationship between SVC and PA. We found that 50% SVC above PA dilated while only 13.3% SVC beside PA dilated. This phenomenon implied that SVC beside PA was less likely to dilate and the surgery may be optimized by anastomosing SVC beside PA. Thrombosis was one of the most severe complications in the patients after pulsatile bBDG Our study demonstrated a close correlation between quantitative measurements by low-dose PGA scanning and CCA, although a small systematic overestimation by low-dose PGA scanning was observed. This overestimation may be attributed to partial volume effects and motion artifact by CT. The dilation of SVC, stenosis of PA, the anastomotic location between SVC and PA as well as thrombosis and APCs were also observed by both modalities. However, compared with the two-dimension CCA images, it was more accessible for doctors to understand the morphological changes by means of three-dimension reformation of CT images.On the other hand, the dose of contrast medium for low-dose PGA scanning (2 ml/kg) was less than half of that for CCA (4.6 ml/kg), and the radiation dosage of low-dose PGA scanning (0.50 mSv) was much lower than that of CCA (4.85 mSv). Besides the potential risk of a large amount of contrast and radiation exposure Computed tomography scanners are widely available and easy to use in practice, and require shorter image acquisition time. With improvements in multi-detector technology, the spatial and temporal resolution of CT angiography has been dramatically improved to allow for imaging of even the most complex forms of CHD Echocardiography remains a first-line noninvasive imaging tool for evaluation of postoperative anatomy and ventricular function. However, echocardiography is operator-dependent and limited by the acoustic window, especially the post-surgical case with sternal wires and mediastinal scar tissue Our study has several limitations. First of all, we included a relatively small group of patients as the number of the children repaired via pulsatile bBDG was relatively small. What's more, radiation is the inherent limitation of CT, and the HP mode of 128-slice dual-source CT may further lower the radiation dose.CT angiography with a low-dose PGA scanning is an accurate and reliable noninvasive examination in the assessment of morphological changes in patients with pulsatile bBDG.


Inherited dystrophinopathies  have a high rate of myocardial disease with a variable clinical phenotype. We have previously demonstrated that dystrophinopathic patients have significantly impaired myocardial energetics and fibrosis even in the presence of normal left ventricular ejection fraction. Furthermore, Coxsackie B3 induced viral cardiomyopathy has been shown to be a form of acquired dystrophinopathy.We therefore acquired 31-Phosphorus magnetic resonance spectroscopy (MRS), proton MRS and tagging to determine the relationship between energetics, lipidosis, fibrosis and regional systolic myocardial strain in patients with inherited dystrophinopathies with and without prior exposure to Coxsackie B3.Patients  with dystrophinopathy and preserved ejection fraction  were scanned using a Siemens Tim Trio 3 T. ELISA IgG assays were performed to determine prior exposure to Coxsackie B. 31P MRS was used to measure the cardiac phosphocreatine to adenosine triphosphate ratio (PCr/ATP) and proton MRS was used to interrogate the myocardial lipid/water ratio (%), both in the mid-ventricular septum . Peak systolic circumferential strain in the mid ventricular septum was impaired in patients with dystrophinopathy (14.1±5.0) compared with healthy controls  and declined with impaired PCr/ATP ratio (R2=0.51; P<0.001; Figure Abnormal myocardial energetics is strongly associated with impaired regional contractility in dystrophinopathies. Myocardial fibrosis, on the other hand, is increased with prior Coxsackie B3 exposure. This provides compelling evidence for a two-hit interaction between inherited and acquired mechanisms of myocardial damage in dystrophinopathies.


We recently found that overexpression of angiotensin (Ang)-converting enzyme 2, which metabolizes Ang-II to Ang-(1–7) and Ang-I to Ang-(1–9), may prevent diabetes-induced left ventricular remodeling and dysfunction in rats. Our objective was to evaluate the association of plasma Ang-(1–7) level and left ventricular function in patients with type 2 diabetes mellitus.We measured the left ventricular ejection fraction (EF), ratio of early to late left ventricular filling velocity (E/A) and ratio of early diastolic mitral inflow to annular velocity (E/Ea) by ultrasonography in 110 patients with type 2 diabetes mellitus for more than 5 years. Anthropometric and fasting blood values were obtained from medical records. The plasma Ang-(1-7) level in patients with a poor EF (<50%) was significantly lower than that in patients with EF ≥50%; the level in patients with E/A <1 was significantly lower than that in patients with E/A ≥1; and the level in patients with E/Ea >15 was significantly lower than that in patients with E/Ea ≤15. Ang-(1–7) level was negatively correlated with E/Ea and Log-N-terminal pro-B-type natriuretic peptide and positively with EF and E/A. Stepwise multiple regression analysis revealed that Ang-(1–7), hemoglobin A1c and Ang-II levels as well as duration of diabetes predicted EF; Ang-(1–7) level, fasting blood glucose, low-density lipoprotein cholesterol level and duration of diabetes predicted E/A; and Ang-(1–7) and hemoglobin A1c levels predicted E/Ea.Plasma Ang-(1–7) level is independently associated with left ventricular function in patients with type 2 diabetes mellitus and may be a biomarker for assessing cardiac function in such patients. The incidence of type 2 diabetes mellitus has been increasing worldwide and rapidly assuming epidemic proportions over the last several decades. A number of epidemiological, clinical and autopsy studies have proposed that the development of heart failure due to an ill-defined cardiomyopathy is a distinct clinical entity among diabetic patients, even in the absence of hypertension and coronary artery disease 1) blockers, which improve survival in patients with heart failure, slowing down and in some cases even reversing the deregulation of certain variables of cardiac remodeling An early phase in the development of heart failure is cardiac remodeling, which is thought to be an important aspect of disease progression in heart failure, regardless of cause. Cardiac remodeling is manifested clinically by changes in cardiac size, shape, and function in response to cardiac injury or inflammation Ang-(1–7) is formed in the heart from Ang-I or -II by several endopeptidases and carboxypeptidases, including ACE2. Recently, we and others reported that both ACE2 and Ang-(1–7) had cardioprotective effects in experimental animals as well as in cultured cardiac fibroblasts and myocytes In this study we aimed to quantify the association of various clinical and other characteristics with left ventricular (LV) dysfunction in patients with type 2 diabetes mellitus.The protocol was approved by the ethics committee of Qilu Hospital of Shandong University, and all patients gave their written informed consent to participate.This study was conducted at Qilu Hospital of Shandong University, Jinan, China. Between February and September 2012, we included 110 consecutive normotensive patients with type 2 diabetes mellitus for more than 5 years with no clinical evidence of cardiac disease. Diabetes was defined by fasting blood glucose (FBG) ≥7 mmol/l or use of glucose-lowering drugs. We excluded patients with evidence of coronary artery disease ; hypertension; valvular disease; end-stage hepatic or renal disease or malignancy; and poor transthoracic echo window.Values for anthropometric and fasting blood variables were obtained retrospectively from medical charts. Trained research staff measured height, weight and blood pressure. Blood pressure was based on the average of the last 3 of 7 measurements after patients rested for a few minutes in a sitting position. After a 12-hour fast, a venous blood sample was collected and sent to the biochemistry laboratory for estimating glycated hemoglobin A1c level, FBG, and serum lipid profile, including serum levels of triglyceride (TG), total serum cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and N-terminal pro-B-type natriuretic peptide (NT-proBNP).Blood was obtained in a cocktail of protease inhibitors and plasma Ang-(1–7) and Ang-II levels were determined by use of 2 commercial ELISA kits  of all samples in duplicate.Included patients underwent resting transthoracic 2D echocardiography to assess LV systolic and diastolic function by use of Philips iE33 ultrasound system  according to the standard protocol. M-mode images were obtained for measuring LV end-systolic volume (LVESV) and LV end-diastolic volume (LVEDV) according to American Society of Echocardiography guidelines t test, Welch’s test or Mann-Whitney U test. To test our hypothesis that Ang-(1–7) level was associated with LV function, we first investigated potential determinants of LV function by univariate analysis with Pearson’s or Spearman’s rank correlation coefficient following testing for normality, then identified variables that predicting cardiac variables by stepwise multiple regression analysis. Variables associated with cardiac variables at p<0.10 were entered in multivariate analyses, and when 2 independent variables showed strong collinearity (γ >0.70), one was selected. Interactions between any 2 sets of the variables remaining in the stepwise models were assessed by centered cross terms. A 2-sided p<0.05 was considered statistically significant for the final models.All continuous variables are expressed as mean ± SEM or median [interquartile range] unless otherwise stated. Data were analyzed by use of SPSS v19 . We compared characteristics of patients with EF <50% and ≥50%. Patients were also classified by thresholds of E/A and E/Ea. After testing for normality and equality of variance, continuous variables were compared by unpaired The characteristics of the 110 patients by EF<and ≥50% are in Diabetes duration, hemoglobin A1c level, FBG and Ang-II level showed a negative correlation  and Ang-β = –0.244, p = 0.004) and levels of hemoglobin A1c , Ang-(1–7)  and Ang-II  were independent predictors of EF , hemoglobin A1c level  and Ang-(1–7) level  predicted E/A. Levels of hemoglobin A1c  and Ang-(1–7)  predicted E/Ea. Finally, diabetes duration  and Ang-II level  predicted Log-NT-proBNP. Analysis with FBG instead of hemoglobin A1c level shown as model 2  level was negatively and significantly associated with E/Ea and Log-NT-proBNP and positively with EF and E/A in diabetic patients. Ang-(1–7) may be a protective mediator and may indicate cardiac remodeling and function in diabetic subjects.RAS has been suggested to participate in the pathogenesis of diabetic cardiomyopathy. Angiotensinogen, renin, Ang-I and Ang-II are important in diabetic cardiomyopathy. We found high Ang-II level negatively correlated with LV function, as was previously reported 1 blockers are effective in reducing Ang-II–mediated inflammation and end-organ damage in animals with diabetes. During ACE inhibition or AT1 blockade, ACE2 activity and mRNA level are elevated in plasma and the left ventricle 1 blockers and ACE2 appear to be mediated in part through Ang-(1–7). Despite lack of evidence supporting the ability of Ang-(1–7) to reduce Ang-II level, Ang-(1–7), which can be generated locally in the myocardium and bind to a distinct plasma membrane G protein-coupled receptor, the Mas receptor, can oppose the effects of Ang-II and has therapeutic effects similar to those of ACE2 on cardiac remodeling in diabetic and other models ACE inhibitors and ATAlthough we have not established a direct causal link among events, our results show that low endogenous Ang-(1–7) level predicts worse cardiac function in diabetic patients, as indicated by low EF and E/A and high E/Ea and Log-NT-proBNP. Consistent with this result, downregulation of ACE2 was previously found in the late phase of ventricular dysfunction in rats with myocardial infarction We recently found that plasma Ang-(1–7) levels could predict myocardial salvage after reperfusion treatment for acute myocardial infarction and might indicate long-term myocardial remodeling after acute myocardial infarction 2 receptors ACE2/Ang-(1–7) also have protective effects in the progression of atherosclerosis. We previously reported that ACE2 inhibited and stabilized atherosclerotic plaque via the conversion of Ang-II to vasoprotective Ang-(1–7) Clinical, epidemiological and experimental evidence suggests a ‘female advantage’ in the progression of cardiovascular diseases There were 2 major limitations in this study. First, it was only a small cross-sectional study and our primary conclusion needs confirmation by additional studies with a large sample size and a prospective design. Second, although the association of plasma Ang-(1–7) level and left ventricular function in patients with type 2 diabetes mellitus was evaluated and confirmed, the differences in Ang-(1–7) levels between subjects with and without diabetes were unclear because normal subjects without diabetes were not enrolled.In summary, we showed that Ang-(1–7) level could be a biomarker for assessing LV function in diabetic patients because plasma Ang-(1–7) level was independently and negatively correlated with LV remodeling and dysfunction in our diabetic patients. Whether the association of Ang-(1–7) and LV function is attributed to the inhibitory effect of Ang-(1–7) on diabetic myocardial remodeling merits future study. To increase the sample power and verify our results, additional studies with a prospective design and larger cohorts are warranted.


This study seeks to evaluate indices of pulmonary artery (PA) stiffness in patients with COPD and compare with normal controls. We hypothesize that patients with COPD would have increased pulmonary artery stiffness. To test this we determine the pulmonary artery area change (distensibility in %) by cardiac MRI and relate the distensibility to a wide range of severity of COPD.The MESA COPD Study recruited 290 patients (135 patients of various COPD severity and 155 controls) from four field centers in the US, age 50-79 years with ≥10 pack-years of smoking, all free of clinical cardiovascular disease. COPD was defined on post-bronchodilator spirometry by GOLD criteria . All participants underwent full-lung CTs. Percent emphysema was defined as the percentage of total voxels within the lung field that fell below -910 Hounsfield units. MRI studies were performed using 1.5T scanners. To measure ventricular function, the entire heart was imaged in short-axis orientation using a retrospectively gated steady-state free precession sequence. Phase-contrast images of the pulmonary arteries were obtained using a segmented fast gradient echo sequence with free breathing and analyzed quantitatively using dedicated software . Distensibility of the pulmonary vessels (in %) are measured by the following formula, 100×(maximum PA area-minimum PA area)/minimum PA area. The base model (model 1) was adjusted for age, gender, height, weight, race/ethnicity and cohort of selection, given relationships of COPD severity to the pulmonary distensibility. We then additionally adjusted for smoking status, pack-years, diabetes mellitus, hypertension, oxygen saturation, LDL, HDL and statin use (model 2).Table We conclude that in COPD patients without overt cardiovascular disease, pulmonary artery distensibility is reduced. Higher pulmonary arterial stiffness also correlated with the percent emphysema on CT scan and FEV1.National Institutes of Health R01-HL093081 R01-HL077612, R01-HL075476 and N01-HC95159-HC95169, UL1 RR024156.


Assessment of left ventricular function (LV) is one of the most important tasks of clinical cardiac magnetic resonance imaging (CMR). Regional and global LV function has been recognized to differentiate various myocardial disorders. The aim of the study was to provide normal values for myocardial deformation parameters derived from the feature tracking imaging (FTI) algorithm applied to standard CMR cine SSFP sequences in a large group of healthy subjects.The feature tracking algorithm , is a two dimensional deformation analysis of the myocardium that was originally designed for echocardiographic image analysis, which has now been transferred to CMR SSFP sequences without the need for additional scans. This novel approach may have potential advantages over existing methods, such as broad availability, vendor independency and lack of time-consuming post processing.Circumferential, radial and longitudinal peak systolic endocardial regional and global strain values of 110 healthy subjects  were measured using FTI within a standard protocol in a 1.5T CMR-scanner. FTI was applied to standard SSFP sequences. The strain values were derived from three cine long and three short axis views.Global peak systolic radial strain was 35 ± 8%, global peak systolic circumferential strain was -27 ± 4% and global peak systolic longitudinal strain was -24 ± 4%. In younger subjects (<43 years) versus older subjects (>58 years) radial (34 ± 7% vs. 34 ± 7%), circumferential (-27 ± 3% vs. -28 ± 4%) and longitudinal (-25 ± 4% vs. -23 ± 4%) strains were not significantly different. Women had higher levels for circumferential and longitudinal strain in comparison to men whereas radial strain was lower (p<0.05).Our study provides for the first time normal values derived from a large cohort of healthy subjects for cardiac deformation analysis with CMR using a feature tracking algorithm. Without performing any additional scans, FTI is feasible and provides the possibility for a reliable, objective and fast quantification of LV regional and global function. In summary, this novel method may have great importance in clinical routine and trials using CMR and provide further insight into LV function.None.


The mechanisms involved in cardiac remodeling in left (LV) and right ventricles (RV) after myocardial infarction (MI) are still unclear. We assayed factors involved in collagen turnover in both ventricles following MI in rats either presenting signs of heart failure (pulmonary congestion and increased LVEDP) or not .MI was induced in male rats by ligation of the left coronary artery. Four weeks after MI gene expression of collagen I, connective tissue growth factor (CTGF), transforming growth factor β (TGF-β) and lysyl oxidase (LOX), metalloproteinase-2 (MMP2) and tissue inhibitor metalloproteinase-2 (TIMP2) as well as cardiac hemodynamic in both ventricles were evaluated.Ventricular dilatation, hypertrophy and an increase in interstitial fibrosis and myocyte size were observed in the RV and LV from INF-HF animals, whereas only LV dilatation and fibrosis in RV was present in INF. The LV fibrosis in INF-HF was associated with higher mRNA of collagen I, CTGF, TGF-β and LOX expressions than in INF and SHAM animals, while MMP2/TIMP2 mRNA ratio did not change. RV fibrosis in INF and INF-HF groups was associated with an increase in LOX mRNA and a reduction in MMP2/TIMP2 ratio. CTGF mRNA was increased only in the INF-HF group.INF and INF-HF animals presented different patterns of remodeling in both ventricles. In the INF-HF group, fibrosis seems to be consequence of collagen production in LV, and by reductions in collagen degradation in RV of both INF and INF-HF animals. Heart failure (HF) due to myocardial infarction (MI) is one of the major health care issues in the world and leads to a high rate of hospitalization and mortality. MI is accompanied by a wound-repairing process of the damaged area. This process involves a cascade of coordinated events resulting in both replacement of injured contractile tissue by a fibrotic scar and a remodeling in the remaining ventricle Even though it is well established that the development of HF depends on the size of the scar area Ventricular remodeling following MI involves complex biochemical, molecular and morphological alterations in both ischemic and remote non-infarcted myocardial area. This remodeling involves phenotypic changes in the myocytes as well as in the extracellular matrix, which results in myocardial fibrosis consequence of an imbalance between its production and degradation Although several factors involved in ventricular remodeling following MI have been identified, the late mechanism responsible for fibrosis in the non-ischemic myocardium of left and right ventricles that can trigger the development of functional alterations is not yet well understood. Moreover, whether these changes are associated with functional alteration in both ventricles is not well-established. Therefore, the aim of this study was to evaluate the different factors involved in the interstitial collagen turnover late after MI in animals presenting signs of HF or not, and whether these changes could account for the functional and morphological alterations in the non-ischemic myocardium of left and right ventricles in a rat model.Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health  and follows the guidelines of the Committee on Care and Use of Laboratory Animal Resources of the University of Espirito Santo, Vitória, Espirito Santo. MI was induced by ligation of the left coronary artery as previously described i.m.) and Xylazine  and underwent left lateral thoracotomy between the fourth and the fifth intercostal space. After exteriorization of the heart, the left atrium was pushed aside and the left coronary artery was ligated with 6.0 mononylon thread  between the exit point of the pulmonary artery and left atrium. Next, the heart was returned to the thorax and it was closed with 1.0 cotton sutures. Weight-matched rats were used as controls and underwent all surgical steps except for coronary ligation (SHAM group). After recovery, the animals were kept in collective cages with free access to food and water.Male Wistar rats (220–240 g) were obtained from colonies maintained at Federal University of Espirito Santo. Rats were housed at constant room temperature (20 to 22°C), humidity (50 to 60%) and light cycle (12∶12 h light-dark), with free access to standard rat chow and tap water. The study conforms to the i.p.) four weeks later. The right jugular vein and right carotid artery were carefully isolated to avoid damage to any surrounding nerves. A taper-ending polyethylene cannula (PE 50) filled with heparinized saline (100 U/ml) was inserted into the right carotid artery for measurements of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), heart rate (HR) and then inserted into the left ventricle for measurements of left ventricular systolic pressure (LVSP), left ventricle end diastolic pressure (LVEDP) and positive (+dP/dt) and negative (−dP/dt) rates of pressure development. Another catheter was inserted into the right ventricle through the right jugular vein in order to measure the right ventricular systolic pressure (RVSP), right ventricle end diastolic pressure (RVEDP) and +dP/dt and −dP/dt rates of pressure development. Arterial and ventricular pressures were determined by connecting the catheter to a pressure transducer (TSD104A) coupled to a MP100 amplifier and to an acquisition system  for real-time pressure and HR recording and for subsequent analysis. The animals were killed and the lung and both right and left ventricles were separated and weighed. HF was considered to be present when at least two of the following criteria were met: Lung/BW ≥ Lung/BW sham +2 SD , RV/BW ≥ RV/BW sham +2 SD  and LVEDP greater than 15 mmHg MI rats were anesthetized with urethane . Interstitial collagen quantifications in right and left ventricles were performed using an image analysis system . The area of interstitial fibrosis was identified after excluding the vessel area and scar area from the region of interest and determined as the ratio of interstitial collagen deposit to the total remaining tissue area from each ventricle. For each sample, 10 to 15 fields were analyzed with a 40 X objective lens under transmitted light.Hearts were arrested in diastole using urethane before harvesting, and then dehydrated, embedded in paraffin for morphometric analyses. Myocyte cross-sectional area was used for the evaluation of the degree of ventricular hypertrophy A sample from the survival left ventricle and right ventricle tissue were used to RNA extraction. Total RNA extraction from left and right ventricles was performed using a nucleic acid purification lysis solution . One µg of total RNA was taken to perform Reverse Transcription. Genomic DNA was eliminated with a mixture of gDNA Wipeout Buffer and RNase free water incubated for 2 min at 42°C. Then, the mixture was completed with Quantiscript Reverse Transcriptase, Quantiscript RT Buffer and RT Primer Mix. This mixture was incubated for 15 min at 42°C and 3 min at 95°C  −ΔΔCT method analyzes relative changes in gene expression from real-time quantitative PCR experiments Gene expression was quantified by real-time PCR using TaqMan™ primers and probes for Collagen I, TGF-β, CTGF, MMP-2, TIMP-2, 18S ribosomal (Roche) and LOX (Applied Biosystems) . Real-tit test was performed to compare scar size using GraphPad Software Inc . The predetermined significance level was P<0.05.Results are expressed as mean ± SEM. Data was analyzed using a one-way analysis of variance, followed by Tukey or Dunnet test to assess specific differences among all groups or control animals, respectively; an unpaired Student As shown in 2; INF: 64.7±6.4 µm2; INF-HF: 54.1±7.2 µm2, p<0.05). As compared with control animals, all infarcted animals, independently of the presence or not of HF, show an increase in cross sectional area and diameter of left ventricle cavity, which was associated with a reduction in the thickness of its free wall  in the right ventricle, which could be partially due to increased RVEDP leading to a higher RVSP as described by Frank-Starling mechanism of the heart It has been demonstrated that the remodeling process in the ventricles begins soon after the ischemic injury and continue over months Our results demonstrated an increased expression of TGF-β and CTGF mRNA  in the left ventricle from INF-HF animals. TGF-β and CTGF have been considered to be mediators of collagen production in the heart. In fact, these growth factors promote extracellular matrix synthesis and mediate cardiac fibrosis associated with MI and other cardiac diseases in vivo and in vitro studies As already reported In summary, our results demonstrated that 30 days after MI animals presenting signs of HF or not showed a different pattern of remodeling in both chambers independent of scar size. MI produced LV dilatation and free wall thinning. The eccentric remodeling was also accompanied by fibrosis in the HF group, The mechanisms involved in the LV fibrosis that starts soon after ischemic injury are still present after 30 days since was found an increase in collagen production, as suggested by the increase in gene expression of collagen as well of the profibrotic factors CTGF and TGF-β. On the other hand, RV from HF animals presented dilatation, while fibrosis and reduction in collagen degradation occurred in the RV of both groups. One important limitation of this study is the fact that an analysis of MMPs, TIMPs, collagen isoforms, and cytokines gene expression and MMP activity or expression still necessary, in both chambers, in order to reinforce the present hypothesis.The data strengthens the complexity and clinical relevance of ventricular remodeling after MI because even if the fibroses ad scar area are already well defined in the ventricle, signaling pathways are still activated after 30 days and seems to be different in each chamber. Therefore, the understanding of molecular events occurring at the surviving area after MI is important to a better management of patients after coronary occlusion.


Considerable proportion of patients does not respond to the cardiac resynchronization therapy (CRT). This study investigated clinical relevance of left ventricular electrode local electrogram delay from the beginning of QRS (QLV). We hypothesized that longer QLV indicating more optimal lead placement in the late activated regions is associated with the higher probability of positive CRT response.We conducted a retrospective, single–centre analysis of 161 consecutive patients with heart failure and LBBB or nonspecific intraventricular conduction delay (IVCD) treated with CRT. We routinely intend to implant the LV lead in a region with long QLV. Clinical response to CRT, left ventricular (LV) reverse remodelling (i.e. decrease in LV end-systolic diameter - LVESD ≥10%) and reduction in plasma level of NT-proBNP >30% at 12-month post-implant were the study endpoints. We analyzed association between pre-implant variables and the study endpoints.Clinical CRT response rate reached 58%, 84% and 92% in the lowest (≤105 ms), middle (106-130 ms) and the highest (>130 ms) QLV tertile (p < 0.0001), respectively. Longer QRS duration (p = 0.002), smaller LVESD and a non-ischemic cardiomyopathy (both p = 0.02) were also univariately associated with positive clinical CRT response. In a multivariate analysis, QLV remained the strongest predictor of clinical CRT response (p < 0.00001), followed by LVESD (p = 0.01) and etiology of LV dysfunction (p = 0.04). Comparable predictive power of QLV for LV reverse remodelling and NT-proBNP response rates was observed.LV lead position assessed by duration of the QLV interval was found the strongest independent predictor of beneficial clinical response to CRT. Cardiac resynchronization therapy (CRT) has become an established treatment strategy in patients with advanced chronic systolic heart failure and a wide QRS complex. There is an overwhelming evidence suggesting that CRT improves exercise tolerance and the quality of life, prevents hospitalizations for heart failure and has a favorable impact on prognosis -5. UnforThe possible reasons for non-responsiveness to CRT include the amount of nonviable myocardium ,8, naturAs CRT aims principally to correct electrical ventricular dyssynchrony, optimal position of the LV lead could be expected in the LV region with the most delayed spontaneous depolarization. Based on our previous mapping studies in patients with LBBB , such reWe retrospectively analyzed data of all patients with implanted biventricular pacemaker or defibrillator at the Liberec Regional Hospital, Czech Republic between June 2005 and June 2010. CRT was indicated according to the guidelines of the European Society of Cardiology . In thisA total of 214 non-RBBB patients were implanted with the CRT system within the above-mentioned period. After analysis of all available data, 53 subjects were excluded from the study. The exclusion criteria were as follows: 1) death from other cause than heart failure during the first 12 months of the follow-up (n = 6), 2) insufficient electrophysiological data from the implant procedure (n = 35), 3) significant change in post-implantation clinical status  (n = 7), 4) unavailability of a patient for follow-up (n = 2), 5) ventricular non capture (n = 3).All patients signed an informed consent with the procedure. The study was performed in accordance with the guidelines proposed in the Declaration of Helsinki and the analysis was approved by Ethics Committee of the Regional Hospital in Liberec, reference number EK/158/2011.Commercially available CRT systems were implanted by two operators. The right ventricular lead was commonly placed in the midseptum region. The LV lead was inserted transvenously with a preference for lateral cardiac veins, followed by posterolateral or anterolateral position. Whenever possible, attempts were made to maximize QLV interval at implant, i.e. when the LV lead electrogram was not recorded in the terminal part of the QRS, other available veins were explored in order to achieve the longer QLV. In cases when the QLV interval was significantly longer in a proximal part of a vein, all efforts were made to provide stability of the lead in this position (sometimes changing the lead design).Empiric atrioventricular delay of 120 ms and V-V delay 0 ms were programmed at implant and were not routinely optimized. When no clinical improvement was observed during early follow- up visit, at least one echocardiographic-guided optimization of these intervals was performed.The QLV interval was measured from the beginning of the native QRS complex to the first sharp spike of LV electrogram Figure . After tLV end systolic diameter (LVESD), LV end diastolic diameter (LVEDD) measured in M-mode and LV ejection fraction (LVEF) assessed by planimetry were collected at baseline and 12-month later using scanners of one manufacturer . Measurements were performed according to the recommendations of American Society of Echocardiography  by one oPlasma levels of N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP) were assessed before implant and at 12-month follow-up using commercially available assay . A clinically meaningful decrease of >30% was considered significant. In 24 patients NT-proBNP datasets were not available.The primary endpoint of the study comprised positive clinical response to CRT at 12 months defined as an improvement of the functional status by at least 1 NYHA class and/or LV reverse remodelling (LVESD reduction of ≥10%). Patients who died of heart failure within one year after implantation were considered non-responders. Signs of LV reverse remodelling alone and NT-proBNP response were the other endpoints of the study.t-test for dependent or independent samples, as appropriate. Non-normally distributed variables were expressed as medians and interquartile range and compared by Mann–Whitney U test or Wilcoxon’s paired test, as appropriate. Categorical variables were expressed as percentages and compared by χ2-test. Relationship between variables (or their change) was assessed by Pearson’s correlation analysis. ANOVA with Scheffe’s post hoc test was used for the analysis of CRT response rate in subgroups defined by tertiles of individual baseline variables. Multivariate regression analysis that included all univariately significant factors was used to test the association of CRT response rate with baseline clinical, echocardiographic, and electrophysiological variables. A p-value <0.05 was considered significant. All analyses were performed using the STATISTICA vers. 6.1 software .Continuous variables were expressed after testing for normality of distribution (Shapiro Wilk’s test) as the means with standard deviations and compared with the 2-tailed The baseline characteristics of the study population are shown in Table Only exceptionally (n = 4), responders were identified by LV remodelling alone, i.e. without improvement in NYHA class. Baseline differences between responders and non-responders are shown in Table Among the baseline categorical variables, only ischemic etiology of cardiomyopathy was significantly associated with lower clinical CRT response rate  and with less reverse LV remodelling  as compared with non-ischemic cardiomyopathy. When continuous baseline variables were categorized by tertiles , significant association with clinical CRT response was found for the baseline QLV (p = 0.00005), QLV ratio (p = 0.0002), baseline QRSd (p = 0.002), and LVESD (p = 0.02). Similarly, significant association with reverse LV remodelling was found for the baseline QLV (p = 0.00001) and QLV ratio (p = 0.00007), baseline QRSd (p = 0.007), and LVESD (p = 0.004). Response rates in individual subgroups and their comparison are shown in Figure Table A mutual combination of the QLV, LVESD, and QRSd was used for further stratification of CRT effects. Patients who belonged either to the “high-risk” tertiles of QLV ≤ 105 ms and/or LVESD > 60 mm presented with lower CRT response rate of 64% (n = 80). Among them, 47 patients had ischemic cardiomyopathy and had even lower response rate of 57%. In a complementary subpopulation, i.e. in those with both QLV > 105 ms and LVESD ≤ 60 mm, the clinical CRT response reached 92% (n = 81). Among them, 41 patients had non-ischemic cardiomyopathy and had even greater CRT response of 98%. On the other hand, CRT response rate was only 52% in patients with both QLV ≤ 105 ms and LVESD > 60 mm (n = 23). Among them, 14 patients had ischemic cardiomyopathy and even lower response rate (36%).This study represents another piece of evidence on association between response to CRT and the LV lead position, expressed as the QLV interval. Patients in the lowest QLV tertile (QLV ≤ 105 ms) had significantly lower probability to become clinical responders or to show LV reverse remodelling at 12-month follow-up. On the contrary, the best clinical response to CRT (92% of subjects) was observed in patients with both QLV > 105 ms and LVESD ≤ 60 mm. Clinical relevance of the QLV interval was further confirmed by its correlation with the change in plasma levels of biochemical marker of heart failure. All these findings support the hypothesis that pacing within the late activated LV region has the highest potential to correct electrical dyssynchrony and associated LV mechanical dysfunction in patients with intraventricular conduction abnormality of the LBBB type.Similar to our study, Singh et al . analyzeOur results are also in concordance with two other recently published studies. The retrospective analysis by Fatemi et al . reporteIn contrast to the two above mentioned trials ,18 and cWe acknowledge that to dichotomize the effect of CRT responder vs. non-responder is an oversimplification. The response to CRT is a continuum with patients who worsen on one side and hyper-responders on the other. However, significant correlation between the QLV and LV reverse remodelling suggests that achieving higher QLV value at implant means not only higher likelihood of a positive clinical and echocardiographic response to CRT but also the greater magnitude of the effect. Thus, our results clearly imply that the QLV should be maximized during the LV lead implant as much as possible. On the contrary, patients with QLV ≤ 105 ms are less likely to show positive response to CRT.We also assessed predictive power of another parameter, QLV ratio that related the QLV to QRSd. The prediction characteristics of QLV ratio for response to CRT appeared somewhat inferior to the QLV interval. Obviously, this is because the QLV interval conveys not only information on the optimal lead position but also reflects the QRSd that is univarite predictor of CRT response per se. Such composite predictor has to be inherently better than QLV ratio that describes LV lead positioning only. Concordantly, QRSd became non-significant predictor of CRT effects when entered the multivariate model together with the QLV interval. For practical reasons, guiding the LV lead placement by readily available QLV interval can be recommended. On the other hand, QLV ratio  rather than QLV interval might be preferred for optimization of CRT effects in future interventional CRT trials investigating alternative methods of LV pacing.This study has several limitations. First, it was a retrospective, single-center study and this may limit generalization of its results. Second, LV lead positions were not recorded routinely on cineloops and therefore, we could not evaluate correlation between the QLV and actual pacing site location. Third, the amount and the location of LV scar tissue that may interfere with the CRT response was not assessed and included in multivariate analysis. Fourth, we assessed LV reverse remodelling using one-dimensional parameter, specifically LVESD, because LV end-systolic volume (LVESV) was not available in all patients. This might influence to some extent the results on reverse remodelling as LVESV is more frequently used for this purpose. On the other hand, our dichotomy of ≥10% for LVESD corresponds to ≥21-22% for LVESV when estimated by Teichholz formula, i.e. our definition of LV reverse remodelling was clearly more stringent than that used, for example, in SMART AV substudy (≥15% for LVESV). The measurement of LV end-systolic volume is also less reproducible as compared with LVESD. Some studies have shown that inter- (<20%) and intra-individual (5-10%) variability of LV end-systolic volume is higher as compared with variability of LVESD  . FinallyLV lead position assessed by the QLV interval was found the strongest independent predictor of beneficial response to CRT, followed by LVESD and etiology of LV dysfunction. In patients with long QLV (>130 ms), clinical CRT response and LV remodelling rates at one year after implant were higher by 58% and 124%, respectively, when compared with short QLV ≤ 105 ms. This association between the QLV and CRT effects was preserved both in ischemic and non-ischemic cardiomyopathy subgroups. Therefore, attempts to maximize the QLV during LV lead placement should be considered in all non-RBBB CRT patients. Clinical utility of this approach should be tested in prospective interventional trial.RP: none declared, PK: none declared, PN: none declared, TR: none declared, TB: none declared, JH: none declared, DH: none declared, DW: none declared, JK: received consulting fees or honoraria from Biotronik, Boston Scientific, Medtronic and St. Jude Medical. He is a recipient of research grants from Biotronik, Boston Scientific and Medtronic.RP: conception and design of the research, acquisition of data, analysis and interpretation of the data, drafting of the manuscript, PK: acquisition of data, PN: acquisition of data, TR: acquisition of data, drafting of the manuscript, TB: acquisition of data, JH: drafting of the manuscript, DH: acquisition of data, DW: statistical analysis, critical revision of the manuscript for important intellectual content, JK: conception and design of the research, critical revision of the manuscript for important intellectual content, supervision. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/12/34/prepub


Chronic obstructive pulmonary disease (COPD) has considerable effects on cardiac functions, including those of the right ventricle, left ventricle, and pulmonary blood vessels. Most of the increased mortality associated with COPD is due to cardiac involvement. Echocardiography provides a rapid, noninvasive, portable, and accurate method to evaluate the cardiac changes.To assess the cardiac changes secondary to COPD by echocardiography and to find out the correlation between echocardiographic findings and severity of COPD, if there is any.A total 40 of patients of COPD were selected and staged by pulmonary function test (PFT) and evaluated byechocardiography.On echocardiographic evaluation of COPD, 50% cases had normal echocardiographic parameters. Measurable tricuspid regurgitation (TR) was observed in 27/40 cases (67.5%). Pulmonary hypertension (PH), which is defined as systolic pulmonary arterial pressure (sPAP)> 30 mmHg was observed in 17/27 (63%) cases in which prevalence of mild, moderate, and severe PH were 10/17 (58.82%), 4/17 (23.53%), and 3/17 (17.65%), respectively. The frequencies of PH in mild, moderate, severe, and very severe COPD were 16.67%, 54.55%, 60.00%, and 83.33%, respectively. Right atrial pressure was 10 mmHg in 82.5% cases and 15 mmHg in 17.5% cases. Cor pulmonale was observed in 7/17 (41.17%) cases; 7.50% cases had left ventricle (LV) systolic dysfunction and 47.5% cases had evidence of LV diastolic dysfunction defined as A ≥ E , peak velocity of the late filling wave caused by atrial contraction (A) on mitral valve tracing) Left ventricle hypertrophy was found in 22.5% cases.Prevalence of PH has a linear relationship with severity of COPD and severe PH is almost associated with cor pulmonale. Echocardiography helps in early detection of cardiac complications in COPD cases giving time for early interventions. COPD is a leading cause of death and disability worldwide. According to World Bank data it is expected to move from its status in 2000 as the 4[r> 0.7).7Hence the present study was undertaken with the following aims and objectives:To assess the cardiac changes secondary to COPD by echocardiography, andTo find out the correlation between echocardiographic findings and the severity of COPD using GOLD guidelines.Forty patients of COPD confirmed by clinical history, radiology of chest, and pulmonary function test were selected from Chest and T.B. Hospital of R.N.T. Medical College, Udaipur, Rajasthan. During selection, patients with H/O of chronic lung disease other than COPD, hypertension, any primary cardiac disease, any systemic disease that can cause pulmonary hypertension, patients with poor echo window, and patients who were unable to perform spirometry were excluded from the study.All selected patients were subjected to routine investigations, including complete blood count, lipid profile, blood sugar, blood urea, serum creatinine, electrocardiography, and so on, as needed.1 /forced vital capacity (FVC) ratio < 70% predicted), mild (FEV 1 ≥ 80% of predicted), moderate (50% ≤ FEV 1 < 80% predicted), severe (30% ≤ FEV 1 < 50% predicted), and very severe (FEV 1 < 30% predicted), respectively.All the patients were investigated by spirometry and diagnosed and classified according to GOLD guidelines .[8Echocardiography was reviewed to assess the pericardium, valvular anatomy and function, left and right side chamber size and cardiac function. Tricuspid regurgitant flow was identified by color flow Doppler technique and the maximumjet velocity was measured by continuous wave Doppler withoutthe use of intravenous contrast. Right ventricular systolicpressure was estimated based on the modified Bernoulli equationand was considered to be equal to the sPAP in the absence ofright ventricular outflow obstruction: sPAP (mmHg) = rightventricular systolic pressure = trans-tricuspid pressure gradient (TTPG) + rightatrial pressure (RAP), where trans-tricuspid gradient is 4on, m/s).89 RAP wan, m/s).8Pulmonary hypertension (PH) was defined in this study as sPAP ≥ 30 mmHg. This valRight ventricle dimension was measured by M-Mode echo and right ventricular dilation or cor pulmonale was said to be present when it exceeded the normal range of 0.9–2.6 cm. Right ventricle contractility was also noted and right ventricular systolic dysfunction was said to be present when it was hypokinetic.Left ventricular function was also assessed by using the following parameters: EF (ejection fraction) = measure of how much end-diastolic value is ejected from LV with each contraction (56%–78%)FS  = it is a percentage change in LV dimension with each LV contraction (28%–44%).LV mass = left ventricular mass (88–224 g).E/A = diastolic filling of left ventricles usually classified initially on the basis of the peak mitral flow velocity of the early rapid filling wave (E), peak velocity of the late filling wave caused by atrial contraction (A). In normal subjects LV elastic recoil is vigorous because of normal myocardial relaxation, therefore more filling is completed during early diastolic, so left ventricular diastolic dysfunction (LVDD) is said to be present when E/A is <1.3 (age group 45–49 years), <1.2 (age group 50–59 years), <1.0 (age group 60-69 years), and <0.8 (age group ≥70 years).A total of 40 patients were recruited in our study and out of them, the number of patients with mild, moderate, severe, and very severe COPD were 18/40 = 45%, 11/40 = 27.5%, 5/40 = 12.5%, and 6/40 = 15%, respectively On echocardiography 20 patients (20/40 = 50%) had normal study.Measurable tricuspid regurgitation (TR) was observed in 27 patients (27/40 = 67.5%). Mean TTPG for the entire group in which TR could be measured was 37.04 mmHg.PH defined as sPAP> 30 mmHg was observed in 17 patients  (17/27 = 63% of measurable TR). Out of those 17 patients with pulmonary hypertension, 10 patients were in mild PH (sPAP 30-50 mmHg) (10/40 = 25%) (10/17 = 58.82%), 4 were in moderate PH (sPAP 50-70 mmHg) (4/40 = 10%) (4/17 = 23.53%), and 3 were in severe PH (sPAP> 70 mmHg) (3/40 = 7.5%) (3/17 = 17.65%) . The freThe frequencies of cor pulmonale in patients with mild, moderate, and severe PH were 10%, 75%, and 100%, respectively; so we can see a good co-relation between severity of PH and the development of cor pulmonale Tables  and 5.Comparative study of various stages of severity of COPD reveals that as severity of COPD increases the prevalence of cardiac dysfunction increases, so more severe COPD is associated with more prevalent and more severe cardiac manifestations .2 s (prostacyclin synthase), decrease in eNOS , and increase in ET1 (endothelin1) leads to remodeling, increase in blood viscosity, and alteration in respiratory mechanics. All these lead to a significant increase in pulmonary vascular resistance, the consequence of which is pulmonary hypertension. Severe PH increases right ventricular after load with a corresponding increase in right ventricular work, which results in uniform hypertrophy of the right ventricle. In patients with COPD, hypoxic vasoconstriction is associated with not only right ventricular hypertrophy but also right ventricular dilation which eventually leads to clinical syndrome of right heart failure with systemic congestion and inability to adapt right ventricular output to the peripheral demand on exercise.The cardiac manifestations of COPD are numerous. Impairment of right ventricular dysfunction and pulmonary blood vessels are well known to complicate the clinical course of COPD and co-relate inversely with survival. Significant structural changes occur in the pulmonary circulation in patients with COPD. The presence of hypoxemia and chronic ventilator insufficiency is associated with early evidence of intimal thickening and medial hypertrophy in the smaller branches of the pulmonary arteries. Coupled with these pathological changes are pulmonary vasoconstriction arising from the presence of alveolar hypoxemia, destruction of pulmonary vascular bed, changes in intrinsic pulmonary vasodilator substances , 30% in those with moderate-to-severe PH (30–50 mmHg), and 0% in the small group of patients with very severe PH (>50 mmHg). Thus a high degree of PH bears a poor prognosis, and this also has been observed in COPD patients receiving long-term oxygen therapy. The pres24Cor pulmonale is present in 17.5% of patients in our study. Approximately 25% patients with COPD eventually develop cor pulmonale. Cor pulm27Some studies indicate that LV function remains normal in persons with COPD, whereas others suggest that LV dysfunction may be present.31 AbnormIn our study, left ventricular systolic dysfunction (LVSD) is present in 7.5% patients, in previous studies it was present in 4%–32% patients of COPD.–36 LVDD Left ventricular hypertrophy (LVH) was present in 22.5% patients in our study, in one previous study LVH was found in 25%–60% patients dying of COPD mainly in patient who also had right ventricular hypertrophy.To conclude, the present study shows high prevalence of pulmonary hypertension, cor pulmonale, left ventricular dysfunction complicating COPD, more so with more severe COPD. We suggest screening of all COPD patients for cardiac complications. This would contribute to the assessment of prognosis in these patients and assist in identifying individuals likely to suffer increased mortality and morbidity warranting close monitoring and intense treatment.


Supraventricular tachycardia (SVT) is the most common arrhythmia in children and is especially common in infants. SVT is typically thought of as an acute condition; however, if unrecognized, a persistent tachyarrhythmia can progress to a state of cardiac contractile dysfunction known as tachycardia-induced cardiomyopathy. A high index of suspicion for an underlying arrhythmia is needed in the workup of any patient with new onset heart failure, and the 12-lead electrocardiogram can aid in the diagnosis. While this may be a rare cause of dilated cardiomyopathy and heart failure in children, the condition is usually reversible and should be considered in infants and young children. Tachycardia-induced cardiomyopathy is a deterioration in ventricular function secondary to sustained tachycardia, which is partially or completely reversible after normalization of the heart rate . Here, wA 4-week-old male infant was brought to the emergency room for a 3-day history of non bilious, non bloody emesis with feeds as well as fussiness and tachypnea. The frequency of emesis had increased to after almost every feeding, and he had decreased urine output. He otherwise had no fever, upper respiratory tract symptoms, diarrhea, or sick contacts. He was born at term via uncomplicated vaginal delivery and had previously been well.On initial physical examination, his weight was 3.9 kg, temperature was 36.5°C, heart rate was 147 bpm, blood pressure was 78/44 mmHg, respiratory rate was 70 breaths/min, and oxygen saturation was 100% on room air. He had mild tachypnea and mild abdominal distention with the liver edge palpated below the costal margin. The remainder of the exam including heart and lungs was within normal limits.2 64 mmHg, HCO3 11 mEq/L, and base deficit of 24. The infant was intubated, and two normal saline fluid boluses of 20 mL/kg were given. An abdominal ultrasound showed no evidence of pyloric stenosis. Therefore, an oral feeding trial was attempted. Upon reassessment, however, the infant was found to be in moderate respiratory distress. He was placed on oxygen, and a chest X-ray revealed mild cardiomegaly and mild pulmonary edema. A capillary blood gas revealed a pH 6.84, PCOZ score −0.6). Because of the finding of severe ventricular dysfunction, the patient was transferred to the neonatal intensive care unit and started on inotropic support with dopamine and milrinone infusions. An echocardiogram showed a structurally normal heart but with severely decreased right and left ventricular systolic function and a left ventricular shortening fraction of 13% . The cardiac size was normal with a left ventricular end-diastolic diameter of 2 cm  was obtained and showed sinus rhythm with a rate of 150 bpm. A short PR interval of 50 ms was seen as well as a delta wave resulting in a prolonged QRS duration of 110 ms . These fA follow-up echocardiogram was done on hospital day (HD) 2 that showed complete normalization of ventricular function with an LV shortening fraction of 44%. The patient was therefore weaned off inotropic support and successfully extubated the next day. Later on HD 3, however, the patient had multiple episodes of supraventricular tachycardia (SVT) to rates of 260 bpm . Vagal m2/day). Except for one very brief self-limited episode of SVT, there were no further sustained tachycardia episodes observed after starting flecainide, and the patient was discharged home on HD 10. He has not had any recurrences on flecainide therapy and has been feeding well without respiratory symptoms. Follow-up echocardiograms have continued to show normal biventricular function. This course confirmed the diagnosis of tachycardia-induced cardiomyopathy due to supraventricular tachycardia in a patient with underlying Wolff-Parkinson-White syndrome.Oral propranolol was initially started, but, due to persistent episodes of SVT, oral flecainide was initiated on HD 6 , ectopic atrial tachycardia (EAT), and permanent junctional reciprocating tachycardia (PJRT). Atrial fibrillation, atrial flutter, or incessant ventricular tachycardia may also lead to tachycardia-induced cardiomyopathy although these arrhythmias are typically seen in older patients .The typical clinical presentation of tachycardia-induced cardiomyopathy is similar to other forms of heart failure. Infants are recognized on the basis of respiratory distress, diaphoresis, and poor feeding, while older children may present with exercise intolerance, dyspnea on exertion, chest pain, or syncope , 4. OldeA high index of suspicion for an underlying tachyarrhythmia is needed in the evaluation of a patient with new onset heart failure. Systolic ventricular dysfunction is often the first manifestation of tachycardia-induced cardiomyopathy seen on echocardiogram, followed by left ventricular dilatation after prolonged dysfunction . Also imThe mechanisms responsible for the development of cardiomyopathy from incessant tachycardia are unclear, but several theories have been proposed. Abnormal cellular remodeling may occur with sustained tachycardia which diminishes the number of microtubules in the cardiac myocyte and contributes to myocardial contractile dysfunction . ChronicFocusing the differential diagnosis for infants or children presenting in acute heart failure with a structurally normal heart is often challenging because of the multiple possible etiologies. Infectious, familial, metabolic, mitochondrial, toxic, inflammatory, and neuromuscular processes may be responsible although most cases remain idiopathic . InfectiWhile any patient with new onset heart failure should have tachycardia-mediated cardiomyopathy considered as an underlying etiology, confirming this diagnosis is often challenging. First, as seen with our patient, the responsible tachycardia may not be evident at presentation . In addiThe main approach to treatment of tachycardia-induced cardiomyopathy is control of the tachyarrhythmia. This may be achieved by the initiation of antiarrhythmic medications in consultation with a pediatric cardiologist since the drug choice depends on the underlying arrhythmia. Often, beta-blocking agents (Class II antiarrhythmic medications by the Vaughan-Williams classification) or digoxin (Class V) are used as first line therapy for preventing recurrence of supraventricular tachycardias . Some peTachycardia-induced cardiomyopathy is an underappreciated, but treatable, cause of dilated cardiomyopathy leading to heart failure in pediatric patients with structurally normal hearts. This diagnosis should be considered even when the patient does not present with an arrhythmia since it may not be evident on initial presentation. It is important to consider that although supraventricular tachycardia is generally thought of as an acute medical condition, if unrecognized for an extended duration, it may present with heart failure rather than the symptoms of tachycardia alone. It is therefore essential to obtain an early 12-lead electrocardiogram in the workup of any patient with new onset heart failure. Unlike many other etiologies of heart failure, tachycardia-induced cardiomyopathy may show complete normalization of cardiac function and generally has an excellent prognosis once the arrhythmia is controlled.


Myocardial perfusion MRI with sliding-window conjugate-gradient HYPR (SW-CG-HYPR) allows increased spatial coverage (whole left ventricular coverage), resolution, signal-to-noise ratio and reduced motion artifacts. The accuracy of this technique for detecting coronary artery disease (CAD) has not been determined in a large number of patients.The purpose of this study was to prospectively evaluate the diagnostic performance of adenosine-induced stress myocardial perfusion MRI with SW-CG-HYPR in patients with suspected CAD.Forty consecutive patients  with suspected CAD who were scheduled for coronary angiography underwent myocardial adenosine stress perfusion MRI with SW-CG-HYPR at 3.0T. Perfusion defects were interpreted visually by 2 blinded observers and were correlated to x-ray angiographic stenoses ≥ 50%.The prevalence of CAD was 55%. In the per-patient analysis, the sensitivity, specificity and accuracy of SW-CG-HYPR myocardial perfusion imaging were 95%, 83% and 90%, respectively. In the per-vessel analysis, these values were 98%, 89% and 93%, respectively. Figure Adenosine-Induced stress myocardial perfusion MRI using SW-CG-HYPR allows whole left ventricular coverage and has high diagnostic accuracy in patients with suspected CAD.


Heart weight indices were determined and the myocardial pathological conditions were observed by hematoxylin and eosin (HE) staining. There was no death in the control group, while the survival rate of the model group was 73%. Compared with the control group, each index of serum and urine protein in the model group was significantly increased. Additionally, LVSP was decreased, LVDP and LVEDP were increased and heart weight index was increased, with a significant difference. The serum Cr was positively correlated to BNP levels in the model group. Three-quarters nephrectomy and subcutaneous injection of ISO induces left ventricular heart failure and renal failure at the same time, which is characterized in pathophysiology by left ventricular diastolic and systolic function failure, left ventricular myocardial hypertrophy and reconstruction complicated with renal insufficiency.This study aimed to investigate the pathophysiological changes in a rat chronic heart failure complicated with renal failure model, caused by three-quarters nephrectomy and subcutaneous injection of isoproterenol (ISO). Sprague-Dawley (SD) rats in the model group received three-quarters nephrectomy after twice undergoing surgical resections and subcutaneous injection of ISO  after one week, while rats in the control group received sham surgery and injection of normal saline. Survival rate, heart failure and renal failure were compared between the two groups after 4 weeks. Serum creatinine (Cr), blood urea nitrogen (BUN), B-type natriuretic protein (BNP), aldolase (ALD), angiotensin II (Ang II) and C-reactive protein (CRP) were determined by kit assay. Urine protein at 24 h was determined by the Bradford method and left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP) and left ventricular end-diastolic pressure (LVEDP), as well as the maximum rates of increased and decreased left ventricular pressure (±dP/dt Cardiorenal syndrome (CRS) is a complex problem. Patients complicated with heart failure and chronic renal insufficiencies are at a greater risk of poor prognosis. The incidences of heart failure and renal failure are gradually increasing, with poorer prognosis. CRS requires greater attention and research to develop therapeutic measures in reference to the fundamental mechanism of this disease. Currently, there are no animal models for studying heart and renal dysfunction. Therefore, it is necessary to establish an effective animal model of heart-kidney interaction in order to increase our understanding of this syndrome.At present, there are a number of methods for inducing heart ,2 and reThirty SD male rats, weighing 180±20 g, provided by the Laboratory Animal Center of Tongji Medical College of Huazhong University of Science and Technology (China) were used in this study. This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The animal use protocol has been reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of Wuhan Puai Hospital.Thirty SD male rats were randomly divided into a control group (n=15) and model group (n=15). After feeding for one week, the rats in the model group were narcotized with 10% chloral hydrate . The rats then received resection of the lower pole of the left kidney in the first week and radical resection of the right kidney after one week according to the previously described protocol of twice undergoing surgical resections . Rats inAfter 4 weeks, the rats in the two groups were placed into metabolism cages and urine was collected at 24 h. The Bradford method (Coomassie brilliant blue G-250 staining) was used to detect protein content in the urine and calculate the protein excretion of urine at 24 h. Intraocular venous blood was then collected to prepare serum and the levels of serum creatinine (Cr), blood urea nitrogen (BUN), B-type natriuretic protein (BNP), aldolase (ALD), angiotensin II (Ang II) and C-reactive protein (CRP) was detected.max). Changes in cardiac function were calculated.Approximately 24 h after blood collection, left ventricular intubation was administered via the left common carotid artery for left ventricular cardiac function testing. A neck incision was made to expose and bluntly separate the right common carotid artery. The left ventricular catheter was pre-charged with 10% heparin saline and was intubated against the right common carotid artery into the left ventricle. The other end of the catheter was connected to a pressure transducer   for hemodynamic detection of left ventricular end-diastolic pressure (LVEDP) and left ventricular systolic pressure (LVSP), as well as the maximum rates of increased and decreased left ventricular pressure .The left ventricular tissues were fixed in 10X PBS or 4% neutral formaldehyde. The tissues paraffin-embedded and sliced to produce 4 2 test and variance analysis. Data were analyzed with statistical software SPSS 11.5 . P<0.05 was considered to indicate a statistically significant difference.Data were expressed as the mean ± standard deviation. Comparison of the mean values between the groups was examined with the χCompared with the control group, rats in the model exhibited darker hair, reduced feeding, decreased early weight, gradually increased later weight, slow movement, cyanosis in the mouth and nose, asthma, edema in the feet and paws, reduced activity and a poor grab reaction. In the model group, 3 rats died within 1 week and 4 rats died 4 weeks following the subcutaneous injections of ISO, administered twice, with a survival rate of 73%. No death was noted in the control group.max , Ang II (43.36±4.63 μg/l) and CRP (282.9±47.58 μg/l) in the control group, the serum BNP (56.48±4.67 pg/ml), ALD (137.69±16.13 μg/l), Ang II (81.76±5.78 μg/l) and CRP (568.54±42.15 μg/l) were significantly increased in the model group , which indicates a successful modeling of renal failure . All the P<0.05; . Compare P<0.05; . Serum C P<0.05; .Compared with the control group, the weights of the rats in the model group were significantly reduced, whereas weights of the left ventricule and ventricular weight indices were significantly increased in the model group (P<0.01). A significant difference was detected between the weight of the left ventricle and the left ventricular weight index P<0.01; . CardiacFollowing HE staining, slices were examined and compared with the control group. There was clear cardiomyocyte hypertrophy in the model group, with coarsened myocardial cells in an uneven arrangement and myocardial fibrosis. In the control group, myocardial cells were in even distribution, with fewer and inconspicuous extracellular matrices .The incidences of heart failure and renal failure has gradually increased. Renal insufficiency is an independent predictor of heart failure, while myocardial hypertrophy and heart function failure are serious complications of chronic renal failure, closely associated with mortality –14. In tA successful model of CRS, not only simulates the clinical characteristics of CRS, including changes in the heart, kidney, hemodynamics and neuroendocrinology, but also evaluates the therapeutic effect. This model must include joint damages of kidney and heart, characterized by progressive deterioration of cardio-nephric function. The model must present systolic dysfunction confirmed by echocardiography and haemodynamics, resulting in decreased cardiac output. In addition, to further explore the latest clinical findings, increased enddiastolic pressure and venous congestion are also necessary conditions. At a histological level, the model must present characteristics of hypertrophy and fibrosis, particularly mismatched myocardial/capillary. To successfully represent kidney damage, the model must present characteristics of increased Cr and excretion of albumin, as well as decreased progressive renal function caused by a decrease in the glomerular filtration rate (GFR)/Cr clearance ratio. This study aimed to explore the physiopathological mechanism of a CRS model induced by three-quarters nephrectomy and subcutaneous injection of ISO.max and increased serum BNP. HE staining of the myocardium revealed clear hypertrophy of myocardial cells and myocardial fibrosis in the model group, indicating that reconstruction of myocardial hypertrophy had begun. Compared with heart failure caused only by ISO, the amount of subcutaneous injection of ISO was reduced in this model group. In the report of a CRS model by Van Dokkum et al and Windt et al and/or the sympathetic system, any of which may cause cascade reactions of other factors, leading to structural and functional damage to the heart and kidney ,18. The Due to the physiological changes of decreased renal function caused by three-quarters nephrectomy, this model had an increased sensitivity to adverse factors in chronic heart failure. Inflammation and activation of the RAAS promotes the occurrence and development of cardiorenal failure. Hemodynamic changes cause an increase in Ang II release, vasoconstriction, contraction of the efferent glomerular arteriole, cardiac remodeling and an increase in aldosterone release, as well as water and sodium retention, which promote myocardial fibrosis .This study demonstrated that three-quarters nephrectomy complicated with subcutaneous injection of ISO induces concurrent heart and renal failure, with a high success rate, providing a simple, reliable and easy animal model for clinical discussion of the interactive mechanism of heart and renal function. However, this study did not investigate the development time of CRS, which is required to examine the illness and possible preventive therapeutic measures. This model is likely to be useful for further studies on the pathogenesis and development of heart-renal interaction at different stages.