Cardiac dysfunction in boys with Duchenne muscular dystrophy (DMD) is a leading cause of death. Cardiac resynchronization therapy (CRT) has been shown to dramatically decrease mortality in eligible adult population with congestive heart failure. We hypothesized that mechanical dyssynchrony is present in DMD patients and that cardiovascular magnetic resonance (CMR) may predict CRT efficacy.cc). The calculated indices included cross-correlation delay (XCD), uniformity of strain (US), regional vector of variance (RVV), time to maximum strain (TTMS) and standard deviation (SD) of TTMS. Abnormal XCD value was defined as > normal + 2SD. US, RVV, TTMS and SD were calculated for patients with abnormal XCD.DMD patients (n = 236) were stratified into 4 groups based on age, diagnosis of DMD, left ventricular (LV) ejection fraction (EF), and presence of myocardial fibrosis defined as positive late gadolinum enhancement (LGE) compared to normal controls (n = 77). Dyssynchrony indices were calculated based on timing of CMR derived circumferential strain . All but one DMD patient with mechanical dyssynchrony exhibited normal QRS duration suggesting absence of electrical dyssynchrony. The calculated US and RVV values  indicate disperse rather than clustered dyssynchrony.Mechanical dyssynchrony is frequent in boys with end stage DMD-associated cardiac dysfunction. It is associated with normal QRS complex as well as extensive lateral fibrosis. Based on these findings, it is unlikely that this patient population will benefit from CRT. In patients with New York Heart Association (NYHA) class III, ambulatory class IV systolic heart failure (HF) and recently class I and II, with electrocardiographic evidence of ventricular dyssynchrony, cardiac resynchronization therapy (CRT) improves quality of life and functional status, reduces heart failure-related hospitalizations, and prolongs survival -4. WhileA major cause of pediatric HF, Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by disruption of the dystrophin protein. The resulting cell membrane degradation in skeletal and cardiac muscle tissue -13 leadsThis is a retrospective cohort analysis and was conducted with the approval of the Institutional Review Board at the Cincinnati Children's Hospital Medical Center. Patients were identified using the clinical CMR database at the Heart Institute at Cincinnati Children's Hospital Medical Center from September 2005 to March 2009. This study included all DMD patients > 7 years of age who had previously undergone clinical CMR studies. Subjects < 7 years of age were excluded in order to eliminate the need for sedation to undergo the CMR study. A diagnosis of DMD was confirmed by a skeletal muscle biopsy and/or a DNA analysis demonstrating a characteristic dystrophin mutation.Genetic testing was performed at Athena Diagnostics, Inc. or Medical Genetics Laboratories, Baylor College of Medicine (prior to 2006) and at Emory University Genetics Laboratory, Atlanta, Georgia (since 2006).DMD patients (n = 236) were stratified into 4 groups based on age, left ventricular (LV) ejection fraction (EF), presence of myocardial fibrosis defined as positive late gadolinum enhancement (LGE) and compared to normal controls Figure .Trio  or on a 1.5 Tesla GE Signa Excite . The type and field strength of MRI system was based solely on clinical availability and scheduled independent of the patient's clinical status or prior type or field strength of the first study.Clinical CMR studies were conducted on either a Siemens 3 Tesla Routine cardiac functional imaging was performed with a retrospectively vectorcardiographic (VCG) gated, segmented Steady State Free Precession (SSFP) technique after localized shimming and/or frequency adjusting. Subjects were breath-held as tolerated; for those subjects who could not adequately breath-hold, a free breathing technique with multiple signal averaging was used. Standard functional imaging included a short axis stack of cine SSFP images from cardiac base to apex; the short axis was prescribed as the perpendicular plane to the left ventricular long axis in 2 and 4 chamber views as per previously published protocols. Typical scan parameters were as follows: FOV = 32-38 cm, slice thickness = 5-6 mm, gap = 1-2 mm, NEX = 2 , TE/TR = 1.4/2.8 (Siemens), TE/TR = 2.0/4.0 (GE), in-plane resolution = 1.2- 2.2 mm. Minimums of 12 slices were performed with 20 phases/slice.Tagged cine CMR images were acquired in the short axis of the mid ventricle at the level of the papillary muscles based on the four chamber view using an ECG-triggered segmented k-space fast gradient echo sequence with spatial modulation of magnetization in orthogonal planes. Grid tag spacing was 8 mm. The scan parameters used were: TE/TR = 3/15 ms. field of view = (30-32) × (25-26) cm, slice thickness = 6 mm, acquisition matrix = 256 × 144, flip = 20°, views per segments = 8-9. Only good quality tagged cine MRIs were included for analysis (confirmed by 2 independent expert readers: NA and KNH).LGE imaging was performed on DMD patients when intravenous access was obtained (n = 121); no LGE imaging was performed in the control group. LGE imaging was performed via a FLASH inversion sequence recovery protocol 10 min after 0.2 mmol/kg gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) injection. LGE imaging was considered positive if any area of the mid-myocardium showed hyperenhancement as assessed by consensus of 3 readers Standard 12 lead ECG was obtained in all patients; QRS duration was measured manually.® platforms for internal validation of the stroke volume determined by ventricular planimetry. Ventricular volumes, mass, and ejection fraction were tabulated for each subject.Left ventricular volumes, mass and global function were assessed via standard planimetry techniques using semi automated computer software  by expert readers (KNH and WMG). Left ventricular stroke volume was also determined by analysis of cine velocity encoded phase contrast gradient echo (GRE) sequence of the ascending aorta via Medis QFLOWcc) analysis have been previously described ..26].cc reached maximum) to Fourier analysis. If all sub-regions shorten simultaneously (synchronously), the plot appears as a straight line, with power only in the zero-order Fourier term (A0), whereas regionally clustered dyssynchrony generates an undulating plot with higher power in the first-order term (A1). The US index is defined as (1) Uniformity of Strain (US)  was dericc value of the nth sub-region at a given time point by a vector with magnitude εcc (n) and phase 2πn/24, (n = 1..24). RVV was calculated as the vector sum of all εcc (n) giving a zero value for perfect synchrony. The maximum value of RVV depends on the number of segments analyzed. For 24 segments the maximum RVV value is 7.66.(2) Regional vector of variance (RVV)  was deriPatients with abnormal XCD were presumed to have mechanical dyssynchrony and TTMS, SD, RVV, US were also calculated and compared for groups A-E.Results are expressed as mean ± SD for continuous data and as percentages and numbers for categorical data. Pearson's correlation coefficients were calculated to assess for linear relationships between relevant variables. Dunnett test was used to compare groups (B-E) to the control group (A) on variables of interest.cc greater than 17 and all DMD patients had absolute εcc less than 17. In DMD patients but not normal controls, strain declined with age as previously described [236 consecutive patients with DMD where evaluated. Patient demographic, EF, mass volume ratio and mean values for all dyssynchrony indices are presented in Table escribed .LGE was observed in group E only, involving anterolateral and inferolateral segments, with extent of enhancement over 50% of wall thickness Figure .Summary statistics for QRS duration by groups are given in Table Comparison of boys with identified dyssynchrony to control group is presented in Table This study demonstrated that there is a significant prevalence of mechanical ventricular dyssynchrony (17%) in DMD patients with EF < 55%. Additionally, the prevalence of dyssynchrony was greater in patient subsets with more advanced cardiac disease (low EF and fibrosis).This is the first study to our knowledge to use an automated MRI derived cross correlation technique for assessment of mechanical dyssynchrony. It is also the first study to assess prevalence and characteristics of dyssynchrony in a large DMD patient population. Previous application of the XCD method utilized echocardiography  data. Succ or EF likely due to low number of boys with low EF. Of interest, in those with dyssynchrony, US and RVV values indicate the presence of disperse rather than clustered dyssynchrony. Disperse dyssynchrony patients would not be expected to respond favourably to CRT  and to 31.2% in the most advanced stage (group E). All but one of the boys with DMD and mechanical dyssynchrony exhibited normal QRS duration suggesting absence of electrical dyssynchrony. Only weak relationships were found between dyssynchrony indices and εLocation of scar tissue is concerning as well, as most common LGE location was in the inferolateral segments. In patients with ischemic CMP, inferolateral scar involving over 50% of wall thickness virtually excluded improvement with CRT , as did Do these barriers preclude the possibility that LV pacing might benefit these patients? The favourable effect of LV pacing on the failing heart's contractility and external constraint may help to slow the progression of disease. LV pacing also reduces the work performed by the LV as well as beat to beat transmural stress. It is possible that with chronic treatment, a small change in detrimental physiology might realize clinical benefit. Further studies are warranted to evaluate these hypotheses.We had a relatively small number of patients with low EF and mechanical dyssynchrony; all had advanced DMD associated cardiac disease (2 from group D and 7 from group E). All of the patients in group E had extensive fibrosis, obviously due to selection bias less advanced cases were missed. To prove that our analysis is valid, response to biventricular pacing would be most optimal. Tag analysis was performed up to 3rd frame after peak systole, (due to tag fading), it is possible that very dyssynchronous segments were missed, however the prevalence of mechanical dyssynchrony in boys with most advanced disease was similar to that seen in adult heart failure patients.Mechanical dyssynchrony was seen in 17.1% of DMD boys with EF < 55% and in 31.2% of boys with most advanced stages of disease (low EF and fibrosis); however, the observed dyssynchrony was dispersed in nature. It remains to be seen if those patients would respond to CRT.The authors declare that they have no competing interests.KNH, WM and WMG contributed to all aspects of the manuscript's conception, design, data analysis, collection, critical revision and final approval. JPW, MDT, HAR, SFN, NA, ESC and DWB contributed in data analysis, critical revision and final approval of the manuscript.


The determination of coronary flow reserve (CFR) is an essential concept at the moment of decision-making in ischemic heart disease. There are several direct and indirect tests to evaluate this parameter. In this sense, dobutamine stress echocardiography is one of the pharmacological method most commonly used worldwide. It has been previously demonstrated that CFR can be determined by this technique. Despite our wide experience with dobutamine stress echocardiography, we ignored the necessary heart rate to consider sufficient the test for the analysis of CFR. For this reason, our main goal was to determine the velocity of coronary flow in each stage of dobutamine stress echocardiography and the heart rate value necessary to double the baseline values of coronary flow velocity in the territory of the left anterior descending (LAD) coronary artery.A total of 33 consecutive patients were analyzed. The patients included had low risk for coronary artery disease. All the participants underwent dobutamine stress echocardiography and coronary artery flow velocity was evaluated in the distal segment of LAD coronary artery using transthoracic color-Doppler echocardiography.The feasibility of determining CFR in the territory of the LAD during dobutamine stress echocardiography was high: 31/33 patients (94%). Mean CFR was 2.67 at de end of dobutamine test.There was an excellent concordance between delta HR (difference between baseline HR and maximum HR) and the increase in the CFR (correlation coefficient 0.84). In this sense, we found that when HR increased by 50 beats, CFR was ≥ 2 (CI 93-99.2%). In addition, 96.4% of patients reached a CFR ≥ 2 (IC 91.1 - 99%) at 75% of their predicted maximum heart rate.We found that the feasibility of dobutamine stress echocardiography to determine CFR in the territory of the LAD coronary artery was high. In this study, it was necessary to achieve a difference of 50 bpm from baseline HR or at least 75% of the maximum predicted heart rate to consider sufficient the test for the analysis of CFR. Coronary atherosclerosis is a highly prevalent disease in our population, and not just the expression of an anatomic condition . The funThe use of dobutamine stress test as an alternative to exercise testing started in 1984  and its 1- The target HR for each patient to reach a CFR ≥ 2  -13 and, 2- The feasibility of the test.The goal of the present study was to determine at which value of heart rate, CFR should be measured during stress echocardiography. Thus, we evaluated the velocity in the LAD coronary artery in each stage of dobutamine stress echocardiography using transthoracic Doppler echocardiography, in order to find:1- The delta heart rate and the percentage of maximum predicted heart rate that should be reached to determine CFR during dobutamine stress echocardiography.2- The feasibility of estimating CFR during dobutamine stress echocardiography.We prospectively included 33 patients without history of heart disease and low pre-test probability of coronary artery disease, who were referred to the echo-laboratory with indication of dobutamine stress echocardiography. Patients at high risk of coronary artery disease, history of ischemic heart disease, moderate to severe valvular heart disease, cardiomyopathy, left ventricular dysfunction and regional wall motion abnormalities were excluded. Also, cases with positive test results or CFR that did not reach the normal predetermined value (≥ 2) were not included in the analysis. Beta blockers were withdrawn 24 hours before the study. All participants gave informed consent before examinations. Table The echocardiographic procedure was performed using two ultrasound systems, an ATL HDI-5000 Ultrasound System with a frequency of 4-7 MHz (Doppler frequency: 4 MHz) and a 2- 4 MHz matrix array transducer .In color Doppler flow mapping, velocity range was set at an average Nyquist limit of 19.2 cm/s and, when heart rate increased, the Nyquist scale was adjusted at higher limit for a better visualization of the LAD flow.The color gain was adjusted to provide optimal images, setting the color-write priority threshold above the tissue grey-scale gain in order to identify color blood flow in the LAD coronary artery. The anatomical position of the LAD running along the interventricular groove, a few centimeters beneath the surface of the skin, provides an excellent opportunity for its visualization and study.With the patient in the left lateral decubitus position, the left ventricle was imaged in the low parasternal long-axis section, and the ultrasound beam was then tilted clockwise until the right ventricle disappeared and the interventricular groove was visualized with the mid-portion of the LAD. The distal LAD can be explored from the modified apical 3-chamber view.The LAD coronary artery was visualized as a tubular red structure 2-4 mm long along the anterior interventricular groove, with a flow directed towards the apex (and transducer), generating a Doppler waveform above the baseline. Flow velocity was measured using pulsed Doppler echocardiography with a 2-3 mm sample volume wide, generating a typical biphasic pattern, with a smaller systolic component and a larger diastolic one.The long axis sections were carefully adjusted to minimize the angle between the Doppler beam and the LAD flow; we did not perform angle correction to calculate CRF, as the potential error remains constant in the numerator and denominator of the equation, without changing the final results. We measured the flow velocity from the same position at each stage of dobutamine stress echocardiography.Coronary flow reserve was calculated as the ratio between peak diastolic flow velocity and baseline diastolic flow velocity; final values of flow velocity represented an average of 3 cardiac cycles.Continuous variables were expressed as mean and standard deviation and categorical variables as percentage. The association between variables was evaluated using Pearson's correlation coefficient. All calculations were performed using MedCalc statistical software.All patients underwent complete color Doppler echocardiography. Digital images were obtained for wall motion analysis following conventional dobutamine stress echocardiography protocol. Diastolic velocities in the LAD coronary artery were measured during each stage. The hemodynamic variables - heart rate and blood pressure - were monitored. Dobutamine was administered by infusion pump in all patients. We did not use any contrast enhancement agent. Dobutamine infusion started at 5mcg/kg/min and increased in 3-minute stages to 10, 20, 30, 40 and 50 mcg/kg/min or until target heart rate was attained. Intravenous atropine was given (0.5 mg) until a maximum of 1.5 mg if the patient did not reach 85% of maximum HR with 30 mcg of dobutamine .Among the 31 patients in whom CRF could be measured, only one did not reach the normal reference value (≥ 2)No major complications were reported. One patient presented supraventricular tachycardia that reverted spontaneously when the infusion was stopped.Mean arterial pressure (MAP) showed a small decrease due to the effect of the drug; the other variables did not present significant changes Table . IntraveRegional wall motion analysis was performed after digital image acquisition using a 16-segment model.The test was negative for myocardial ischemia in all patients as wall motion improved in all the territories and systolic wall thickness increased.Coronary flow velocity increased from a mean value of 24.9 ± 7.11 cm/s at baseline to a peak value of 69.24 ± 20.132 cm/s. The mean CFR at the end of the dobutamine test was 2.67 ± 0.62  and the increase in the CFR (correlation coefficient 0.84). In this sense, we found that when HR increased ≥ 50 bpm, CFR was ≥ 2 in 97.2% of patients    and HR decreased in other patient with dobutamine infusion of 30 mcg/kg/min; this patient required intravenous atropine and 50 mcg/kg/min of dobutamine to attain an adequate CFR.The estimation of CFR using the method we have utilized is interesting due to its clinical and physiopathological value .Despite dipyridamole is more suitable for the assessment of CFR ,6, dobutDobutamine exerts a complex effect on the coronary arteries: heart rate and myocardial contractility increase due to adrenergic stimulation, producing greater oxygen (O2) uptake and reactive hyperemia . The dirDobutamine hyperemia is equivalent to adenosine-induced vasodilatation in patients with ischemic response to dobutamine, but lower than that observed in non-ischemic patients. In normal patients, the effect of dobutamine on CFR is lower than that of adenosine according to studies using paired Doppler Flowires in the catheterization laboratory ,21.In addition, dobutamine increases contractility and myocardial O2 consumption, and produces release of vasodilatory substances such as adenosine, which act on epicardial arteries and microvasculature. Finally, dobutamine, by increasing the heart rate, induces flow mediated epicardial vasodilation ,23.The analysis of CFR has been studied in different clinical scenarios; however there is little information about coronary flow in each stage.In a study performed at the Mayo Clinic by P. Pellikka et al., the feasibility of assessing the CFR was 97% from peak diastolic velocity. The authors concluded that CFR assessment during dobutamine stress echocardiography correlated well with wall thickening and detected ischemia early before development of wall motion abnormality, emphasizing the importance of determining CFR in this type of study .We have not found any study analyzing and measuring the relation between heart rate and coronary flow reserve during this test.In an excellent study, P. Meimoun et al. assessed CFR during dobutamine stress echocardiography and compared it to the CFR obtained with adenosine in the same group of patients and found a good correlation and concordance between the tests, in a wide range of LAD disease. Although a clear cut-off of heart rate was not established in that study, it was emphasized along the manuscript that a maximal achievable target heart rate was necessary during dobutamine infusion to obtain the good correlation and concordance between CFR-dobutamine and CFR-adenosine. Furthermore, a significant correlation was found in that study between CFR during dobutamine and change of rate-pressure product in patients with abnormal results .In addition, the normal and abnormal values of CFR during dobutamine stress were clearly described in that study. A CFR < 2 with dobutamine stress echocardiography was found in all patients who had a positive test in the LAD territory (n = 8) and interestingly the same low CFR < 2 was obtained with adenosine in these patients .Takeuchi et al.  studied It should be noted that the feasibility of analyzing CFR during dobutamine stress (around 90%) according to our previous experience and the results of previously mentioned studies ,11 is a Finally, 97% patients achieved an adequate CFR with a delta HR of 50 bpm from the baseline stage. In the same sense, 95.6% of patients reached a normal CFR with 75% of their predicted maximum heart rate.This study puts in evidence that it is technically recommended to obtain coronary artery flow in baseline conditions and after reaching the predicted heart rate (50 bpm greater than baseline HR or 75% of maximum predicted HR) without forgetting about wall motion response.The importance of this study is that there is no need to measure CFR at each stage of the test; it can be determined at baseline and during high-dose of dobutamine infusion if HR is 50 bpm greater compared to baseline or has reached 75% of the maximum value predicted.Further investigations are necessary to confirm the added value of estimating CFR using dobutamine stress echocardiography. Possibly, it may provide additional information regarding mid- and long-term prognosis besides increasing the sensitivity of the test as it has been already demonstrated with dipyridamole ,26.The feasibility of the procedure might have been overestimated due to the relatively low number of patients included and to the selection of patients with low pre-test probability of coronary artery disease. However, as this is a physiopathological study, the hemodynamic data of the relation between drug dose, heart rate attained and CFR are enough to draw conclusions.CFR was only evaluated in the territory of the LAD coronary artery as the feasibility of obtaining flow velocities from the other coronary arteries is low due to increased contractility secondary to dobutamine infusion.As we did not perform coronary angiography in any patient, some doubts may arise regarding the absence of coronary artery lesions; yet the post-test probability was enough to rule them out.It should be taken into account that CFR may be abnormal not only in lesions of the epicardial coronary arteries but also in several conditions that modify baseline coronary flow and its response to a stimulus. In this sense, the analysis of the result is complex ,28. HoweThe fact that only beta-blockers, and no other medical therapy, were withdrawn before dobutamine infusion could have had some hemodynamic influence .We did not use contrast agents which could have improved the visualization of the LAD coronary artery .It is extremely important to reach a delta HR of at least 50 bpm or a HR of at least 75% of the maximum predicted heart rate to consider abnormal a CFR value.The feasibility of determining CFR in the territory of the LAD during dobutamine stress echocardiography was high.CFR: Coronary Flow Reserve; HR: Heart Rate; LAD: Left Anterior Descending; MHz: Megahertz; MAP: Mean Arterial Pressure; O2: Oxygen.The authors declare that they have no competing interests.JAL has had the main idea and has participated in the making of the study. EHF has participated in the making of the study and drafted the manuscript. GR has performed the statistical analysis. All authors have participated in the discussion and correction.All authors read and approved the final manuscript.


There is a graded inverse relationship from early stages of chronic kidney disease (CKD) (GFR<75ml/min/1.73m2) with increased cardiovascular risk that is driven by high rates of heart failure and sudden cardiac death. Abnormal left ventricular (LV) deformation is an independent predictor of poor prognosis in end-stage CKD and is thought to reflect the extensive interstitial fibrosis and myocyte disarray documented on LV biopsy in uremic cardiomyopathy (UC). There remains a paucity of data relating to the onset of UC in early stage CKD.Eighteen patients (mean age 51 +/- 15 years) with non-diabetic stage 3 CKD (mean eGFR 50 +/- 16 ml/min/1.73m2 MDRD) were compared with 18 healthy age and sex matched controls. Patients all had well controlled blood pressure (mean 24 hour BP 123 ± 14 / 73 ± 6 mmHg) on an average of 1.1 antihypertensive agents and had no history of cardiovascular disease. Cardiac MRI (1.5T Siemens Avanto) with (SPAMM) tagging was performed. Data was analysed using commercially available software  to assess global and transmural LV deformation at SAX basal, mid, apical and long-axis HLA levels.Longitudinal and circumferential strain (S) increased in a graded fashion from epicardium (epi) to mid-wall (mw) to endocardium (endo) at basal, mid and apical ventricular levels in both CKD and controls. Global basal circumferential S  and strain rate (SR)  were reduced in CKD. Basal circumferential S and SR at epi, mw and endo levels were reduced but there was no transmural difference at mid and apical ventricular levels (Table The earliest systolic abnormalities of UC are altered circumferential basal S and SR and reduced longitudinal function. These parameters might serve as early imaging biomarkers that could be used to activate pharmacological intervention. The circumferential abnormalities differ to those observed with aging, hypertension and HFPEF, suggesting a different pathophysiology and necessitate future studies to address whether focal changes in myocardial interstitial fibrosis are responsible for these changes in deformation.British Heart Foundation FS/11/17/28700, PG /04/109


Evaluate Internal Flow Fraction (IFF) in Tetralogy of Fallot (TOF) patients before Pulmonary Valve Replacement (PVR) to examine the progression of left ventricular dyssynchrony.Standard of care for TOF patients is a complete surgical repair in infancy but this results in free pulmonary regurgitation as no suitable long-term substitute for the obstructive valve is available. Although chronic pulmonary regurgitation can be well tolerated for decades, many patients (>20%) eventually develop right ventricular dysfunction and often require PVR. Determining the optimal timing of PVR is difficult, and there is no clear consensus within the medical community.In TOF patients before PVR, clinical studies have demonstrated a correlation between QRS duration and RV size with negative electromechanical interaction and dyssynchrony that progresses with RV enlargement. IFF is a quantitative measure of the energy loss throughout the cardiac cycle due to dyssynchronous contraction. We have developed a means of quantifying IFF non-invasively from cardiac magnetic resonance (CMR) images. In this study, we hypothesized that IFF within the left ventricle would increase in serial CMR exams prior to PVR.We retrospectively analyzed two serial CMR studies in 24 pediatric patients with TOF and complete surgical repair before PVR. The average age at the first CMR was 10.8 +/- 5 years and the average age at the second CMR was 14.1 +/- 5.4 years. Images were obtained with 1.5T MRI systems; cine SSFP sequences were acquired in short axis with no gap and covered the entire left ventricle. Global left ventricular IFF was evaluated using an in-house developed MATLAB program.Global left ventricular IFF was significantly increased between the two CMR exams , Figure Left ventricular IFF increased over time in pediatric TOF patients with complete surgical repair. The increased IFF indicated more dyssynchronous contraction developed over time before PVR. The IFF could be a new marker for PVR timing in TOF patients and warrants further investigation.


Womersleyella setacea  is causing increasing concern in the Mediterranean Sea because of its invasive behavior. After its introduction it has colonized most Mediterranean areas, but the mechanism underlying its acclimatization and invasion process remains unknown. To understand this process, we decided i) to assess in situ the seasonal biomass and phenological patterns of populations inhabiting the Mediterranean Sea in relation to the main environmental factors, and ii) to experimentally determine if the tolerance of W. setacea to different light and temperature conditions can explain its colonization success, as well as its bathymetric distribution range. The bathymetric distribution, biomass, and phenology of W. setacea were studied at two localities, and related to irradiance and temperature values recorded in situ. Laboratory experiments were set up to study survival, growth and reproduction under contrasting light and temperature conditions in the short, mid, and long term.Results showed that, in the studied area, the bathymetric distribution of W. setacea is restricted to a depth belt between 25 and 40 m deep, reaching maximum biomass values (126 g dw m−2) at 30 m depth. In concordance, although in the short term W. setacea survived and grew in a large range of environmental conditions, its life requirements for the mid and long term were dim light levels and low temperatures. Biomass of Womersleyella setacea did not show any clear seasonal pattern, though minimum values were reported in spring. Reproductive structures were always absent. Bearing in mind that no herbivores feed on Womersleyella setacea and that its thermal preferences are more characteristic of temperate than of tropical seaweeds, low light (50 µmol photon m−2 s−1) and low temperature (12°C) levels are critical for W. setacea survival and growth, thus probably determining its spread and bathymetric distribution across the Mediterranean Sea.The tropical red alga  Womersleyella setacea (Hollenberg) R.E. Norris is one of at least eight species that can be assigned to the category of invasive macroalgae in the Mediterranean Womersleyella setacea was described originally from the Hawaiian Islands The spread of non-indigenous species is claimed to cause dramatic ecological impacts and is considered a major threat for biodiversity conservation W. setacea are unknown. In fact, there is little published information about the phenology of the introduced Mediterranean populations  study seasonal patterns of W. setacea in relation to daylength, light and temperature, and 2) assess short- (1 month), mid- (3 months), and long-term (1 year) light and temperature requirements and tolerance for survival, growth and reproduction of specimens of a Mediterranean population of W. setacea. Further, we try to relate these results to its natural bathymetric distribution and its colonization success. And the adaptive capacity of W. setacea to winter environmental conditions, the most critical season in the Mediterranean Sea for tropical algae, was also investigated.Only a small fraction of the many marine species introduced outside of their native range are able to invade and thrive in new habitats  but see , and theW. setacea was first recorded in the Scandola MPA in 1989 although it was probably introduced somewhat earlier The present study was carried out in the Scandola Natural Reserve , Corsica, France . This maW. setacea was estimated by means of quadrats of 25×25 cm divided into 25 subquadrats of 5×5 cm W. setacea appeared was recorded and used as a unit of measure. Twenty quadrats  were randomly positioned within each 5 m depth range.Within the Scandola MPA two rocky bottom sites  by drying the sample in an oven at 60°C to constant weight.At each study site three randomly positioned plots of 20×20 cm were periodically sampled throughout one year by SCUBA divers. The plots were scraped and specimens were stored in individual plastic bags. Sorting of W. setacea distribution habitats, photon flux density was recorded at both localities by HOBO® LI data loggers , at 25, 30, 35 and 40 m depth, hourly during one week both in summer (June) and in autumn (October).To characterize light intensity in in situ in the Scandola MPA at 5, 10, 20, 25, 30, 35 and 40 m depth by Stowaway Tidbits  autonomous sensors  (see www.t-mednet.org). Temperature measures were recorded hourly during 15 months.Water temperature was recorded seasonal experiments), in order to confirm the seasonal pattern of W. setacea populations in relation to these factors. Furthermore, some specimens were submitted to constant conditions of light and temperature to study the tolerance of W. setacea to those factors .Assays were performed in laboratory culture with specimens submitted to conditions simulating the seasonal changes of daylength, light and temperature in the field  were exited and cultured in 250 ml vessels in incubators  equipped with 30 W cool white fluorescent bulbs. Photosynthetic photon flux densities (PPFD) were measured by means of a Li-1400-501 quantometer  and adjusted to the desired levels by neutral density filters. The culture medium was a quarter-strength modified Von Stosch enriched seawater medium −1 GeO2−1 Penicillin-G Specimens were collected by SCUBA divers at Imbutu, on 16 October 2009, from coralligenous assemblages situated at 30 m depth. Material was placed The survival of cultured thalli was determined as the time between the collecting date and the death of the specimen. At the beginning of the cultures , all the thalli looked rosy and healthy, but over the course of the culture the specimens went through two different survival phases. The first phase, Phase SI, began at the initial time and finished when the thalli were more than 95% damaged; and a second phase, Phase SII, began at the end of Phase SI and continued until the death of the specimens.−2 s−1  were maintained successively at daylength and temperature conditions of winter, spring, summer and autumn, combined with PPFD of 5, 10, 20, 50 and 75 µmol photon m−2 s−1 . Changes−2 s−1 .In both seasonal and ecophysiological experiments the length of the SI phase, the survival, and reproduction of the thalli were followed for up to one year. Cultures were monitored every week during the first three months of culture and monthly thereafter, by means of a photograph taken with a Canon EOS 350D . If quick changes were observed in the specimens, photographs were once again taken weekly.2) was determined at the initial time of the culture and every two months using ImageJ . Representative specimens of material used in cultures have been deposited in the Herbarium of the University of Girona (HGI).The thallus surface  and within each site for time (five levels) by means of a Kruskal-Wallis non-parametric analysis. A non-parametric approach was used because of heteroscedasticity and departures from normality. In seasonal experiments and ecophysiological experiments a one-way ANOVA on thallus surface values obtained during the first day of the experiment was carried out to verify that all thalli undergoing different treatments started at similar conditions. In seasonal experiments, after one year of culture, final thallus surface, survival and length of Phase SI were analyzed with a one-way ANOVA with PPFD (four levels) as a fixed factor, whereas in ecophysiological experiments, thallus surface, survival and length of Phase SI were analyzed by a two-way ANOVA, where temperature (six levels) and PPFD (four levels) were fixed orthogonal factors. Tukey tests were used for a posteriori multiple comparisons of means data. Assumptions of normality and homogeneity of variances were examined using the Kolmogorov-Smirnov and Barlett tests, respectively. Variables were rank-transformed prior to the analysis when assumptions were not fulfilled. The analyses were performed using the STATISTICA 6.0 package.Womersleyella setacea displayed the highest quantitative dominance between 30 and 35 m depth, with a maximum coverage at 30 m depth, both at Imbutu and Cala Solana, while it was absent at depths shallower than 20 m , ranging between 0.62±0.34 (mean ±SE) g·dw·sample−1 on April 08 and 5.03±0.47 (mean ±SE) g·dw·sample−1 on November 07 at Imbutu , and only in spring W. setacea biomass showed a decrease in Imbutu (Tukey test p>0.05) (t Imbutu . During  p>0.05) . The min−2 s−1 remained in Phase SI, looked healthy and survived all year round , higher than at 5 µmol photon m−2 s−1, and lower than at 50 µmol photon m−2 s−1  most specimens cultured at high temperatures died, and in the long term (1 year) only those cultured below 18°C survived , the specimens that still were in Phase SI, looked healthier and continued to maintain an increase in thallus surface were those cultured at 10°C and 20–75 µmol photon m−2 s−1 and at 12°C and 50 µmol photon m−2 s−1 , either in the field or in the cultured specimens.W. setacea in the field. We observed high values of W. setacea biomass (up to 126 g dw m−2 in November at Imbutu), which are of the same order of magnitude as those recorded in other Mediterranean areas Caulerpa racemosa, although they can be much higher, rarely exceed 100 g dw m−2Lophocladia lallemandii range between 50 and 200 g dw m−2Caulerpa taxifolia in Mediterranean rocky bottoms range between 200 and 500 g dw m−2C. taxifolia populations exhibit lower biomass values (from 50 to 200 g dw m−2) The present study provides data on the abundance and temporal variability of W. setacea. A dense thick red filamentous turf was widespread and persistent throughout the year at both localities studied, except in April, when biomass showed a slight decrease, in agreement with previous studies on W. setacea populations in other Mediterranean areas W. setacea from the Scandola MPA seem to propagate only by vegetative ways, what also agrees with other observations available for other Mediterranean regions in the field In general, no seasonal variation pattern has been found in the Scandola MPA populations of W. setacea is considered to be a sciaphilic species constituting thick carpets in deep waters W. setacea shows that in the Scandola MPA it is restricted to depths between 25 and 35 m.Mediterranean W. setacea, which presents a maximal survival and growth at PPFD ranging between 10 and 75 µmol photon m−2 s−1. Depth limits of algal distributions at increasing depths are related to the decrease of survival at lower PPFD W. setacea were observed at lower PPFD (5 µmol photon m−2 s−1), explaining that in the Scandola MPA W. setacea almost disappeared or, at least, did not form dense carpets below 40 m depth, where PPFD were usually below 10 µmol photon m−2 s−1.The present light requirements confirm the sciaphilic behavior of W. setacea are adapted to relatively cold waters, specifically below 16°C. In the western Mediterranean these temperature conditions are common in the entire water column in winter and spring but are restricted to below the thermocline in summer and autumn  in the upper infralittoral only at 20 µmol photon m−2 s−1 combined with temperatures ≤24°C. This explains in part the absence of W. setacea at the shallow infralittoral algal assemblages in the Scandola MPA, where temperatures commonly exceed 24°C (W. setacea has been reported it never develops thick carpets above 10 m depth, where temperatures can rise up to 25–30°C (Results show that Mediterranean populations of d autumn , at depteed 24°C . SimilarW. setacea biomass in the field is in agreement with the seasonal experiments at the laboratory, where no differences were found in the surface increase among the different periods of the year, probably because seasonality of underwater PPFD, temperature, hydrodynamics, and nutrient availability are minimized with depth W. setacea is capable of continuous asexual vegetative spread throughout the year The lack of seasonality of Womersleyella setacea can thrive as an epiphyte and is able to overgrow other sessile benthic organisms. Therefore it is not limited by the availability of free substrate, and avoids competition with natives for substrate. On the other hand, invulnerability to native herbivores may be an important determinant of invasion success of marine macroalgae. While some studies reject the biological resistance hypothesis for marine macroalgae (e.g. W. setacea is not consumed either by sea urchins nor Sarpa salpaW. setacea development are light, temperature, and probably physical disturbance. The importance of light and temperature as major factors determining seaweed distribution has been stressed by many authors (see review in W. setacea survival and growth, and they are probably determining the spread and bathymetric distribution of this species across the Mediterranean Sea.gae e.g. , others W. setacea in Mediterranean deep water assemblages probably relies on two different abilities. The first one is the ability to maintain permanent carpets all year long, outcompeting both perennial and ephemeral native species. The second ability would be the enhanced and sustained growth of W. setacea, higher than those recorded for other Mediterranean perennial or pseudoperennial native macroalgae growing in deep waters and cultured under the same conditions Womersleyella setacea's capacity to outcompete native and engineering macroalgae and invertebrates from deep-water Mediterranean bottoms Womersleyella setacea traps sediment and, in this way, it may pre-empt space and prevent the attachment of possible spatial competitors The invasion success of W. setacea thriving in Mediterranean coastal waters exhibit thermal features of a temperate seaweed rather than a tropical one. Thus, winter temperatures are not a limiting factor in the survival and spread of W. setacea all over the Mediterranean Sea, and hot summer temperatures prevent its distribution in shallow waters. Womersleyella setacea also performs much better at low light intensities around 50 µmol photon m−2 s−1, which is in accordance with the depth distribution found in the field. We suggest that the invasion success of W. setacea in Mediterranean environments relies on its high growth, persistence and resistance to herbivores, which outcompetes both perennial and ephemeral native species growing at the same depth intervals where W. setacea develops.In brief, populations of


Patients with symptoms of heart failure and preserved left ventricular (LV) systolic function are commonly encountered in clinical practice especially in peritoneal dialysis (PD) patients. We hypothesized that adiposity might influence LV diastolic function through systemic inflammation in this specific group.We designed a cross-sectional study in 173 prevalent PD patients. LV diastolic dysfunction was diagnosed by echocardiography. PD patient without LV diastolic dysfunction served as the control group. Serum inflammatory biomarkers were examined including tissue necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The location and amount of adipose tissue were assessed by computerized tomography (CT) at the level of the fourth lumbar vertebra.Subjects with LV diastolic dysfunction had higher levels of the pro-inflammation cytokines and more visceral and peritoneal fat  than control subjects. A significant correlation was found between visceral adipose tissue and pro-inflammatory cytokines . Multivariable regression analysis found that the relationship between visceral adipose tissue and LV diastolic dysfunction became insignificant when either TNF-α or IL-6 were introduced into the model, although TNF-α and IL-6 were both significantly associated with LV diastolic dysfunction even after adjusting for visceral fat .Larger amounts of adipose tissue were associated with higher serum pro–inflammatory levels in PD patients, which might be related to the development of LV diastolic dysfunction. Modulating inflammatory reactions in PD patients can be a useful therapeutic approach for managing LV diastolic dysfunction. Left ventricular (LV) diastolic dysfunction has become an increasing concern in recent years. Studies suggest that at least one–third of patients with congestive heart failure have diastolic heart failure (DHF) despite having normal or near normal LV ejection fractions 2+-ATPase gene expression Inflammation and oxidative stress are reportedly associated with the high rate of cardiovascular events in hemodialysis and continuous ambulatory peritoneal-dialysis (PD) patients alike 2+-ATPase protein, which is a major determinants for LV diastolic dysfunction are more apparently than the conventional inflammatory cytokines, such as C-reactive protein. Therefore, we chose TNF-α and IL-6 as our targeting inflammatory markers in current study.The distribution of body fat, which is modified in PD patients play a pivotal role in the development and progression of both diastolic and systolic heart failure We certify that all the applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during this research. Written informed consent was obtained from every participating subject, and the study was approved by the institutional review board of the National Taiwan University Hospital.Between July 2007 and March 2009, 242 homogenous Taiwanese patients aged over 20 who had received PD catheter surgery and PD with a conventional glucose-based lactate-buffered PD solutions  for >6 months at the special clinics of peritoneal dialysis of the National Taiwan University Hospital were consecutively enrolled. Patients with hypertension, diabetic and chronic glomerular nephritis would also be included . PatientBlood samples were collected from the antecubital vein between 8:00 AM and 10:00 AM from all patients in a supine or sitting position following 12 hr of fasting. Plasma glucose and serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG) were determined using an automatic analyzer . Plasma insulin levels were measured using an AxSYMautoanalyzer , and insulin resistance was assessed by calculating the homeostasis model of insulin resistance (HOMA-IR) using the following formula: [fasting glucose (mmol/L) ×fasting insulin (μ U/mL)]/22.5 Left atrial (LA) diameter, LV end diastolic diameter, systolic diameter, interventricular septum thickness, LV posterior wall thickness, E/A ratio and DT were measured according to the American Society of Echocardiography guidelines using a Vivid 7 Dimension echocardiography . LV ejection fraction was calculated as previously described 2. The visceral/subcutaneous adipose tissue area ratio (V/S ratio) was subsequently calculated. The intra- and inter-reader reproducibility for current study is 91.2 to 97.4% and 89.7 to 95.5% respectively for measurement of visceral fat, subcutaneous fat, peritoneal fat and retroperitoneal fat measurements after repeat measurements for 50 patients.Imaging of each subject was performed using a 16-MDCT scanner . Image analysis software  was employed with an attenuation range of −50 to −250 Hounsfield units to quantify subcutaneous, visceral, and total abdominal adipose tissue areas on a single cross-sectional image obtained at the level of the umbilicus with the summation of adipose tissue in 5mm thickness http://www.dssresearch.com/KnowledgeCenter/toolkitcalculators/samplesizecalculators.aspx). Based on our previous study, if PD patients with LV diastolic function had an TNF-α level of 15.7±4.8 and patients otherwise had an TNF-α level of 10.4±4.2, Analyses were performed using SPSS 16.0 for Windows XP . To test whether the data were normally distributed, the Kolmogorov-Smirnov test was applied. All the continuous variables were normally distributed. Therefore, between group baseline characteristics and echocardiographic findings were compared using the Student's unpaired t test for continuous data and a chi-square test for categorical data. Comparisons of mean values across groups and correlations between continuous variables were assessed via linear regression. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Associations between cytokines and Doppler parameters were calculated with Pearson's correlation coefficient. To assess the association between adipose tissue, serum biomarkers, and LV diastolic dysfunction, multivariable models were applied. Covariates that were associated with LV diastolic dysfunction such as age, gender, hypertension, smoking, and body mass index (BMI) were incorporated. All p values were two-sided and p values <0.05 were considered statistically significant. We used two sample average method of the DSS research power calculator to estimate the required sample size , including visceral fat, peritoneal fat, and retroperitoneal fat  than subjects included in the control group.Compared to the control group, subjects with LV diastolic dysfunction had a larger end-diastolic LV volume and end-LV systolic volume (p = 0.009 and p = 0.004), greater thickness of both end-diastolic septum and posterior wall (both p< 0.05), and a larger left atrial diameter at end-systole (p<0.0001). Patients with LV diastolic dysfunction also had a prolonged DT (p<0.0001), a decreased mitral inflow E/A ratio (p<0.0001), and a decreased Em (p<0.0001) compared to the PD patients. In addition, subjects allocated to the LV diastolic dysfunction group had significantly higher total amount of fat , HOMA, and TG all had significant low to moderate correlations with visceral fat : group 1, <6.48; group 2, 6.48∼16.72; group 3, >16.72 and IL-6 (pg.ml): group 1, <17.37; group 2, 17.37∼48.80; group 3, >48.80]. A significant difference in the distribution of patients with LV diastolic dysfunction was noted for both serum pro-inflammatory cytokine levels . BivariaPro-inflammation cytokine levels of TNF-α and IL-6 were higher in subjects with LV diastolic dysfunction. To adjust for the confounding effect of other clinical factors, multivariable analysis was performed. TNF-α and IL-6 were still associated with LV diastolic dysfunction after adjusting for age, gender, BMI, diabetes mellitus, hypertension, HOMA, TNF-α or IL6, LDL, and LV mass index  as described in Multivariable regression analysis was subsequently performed for fat distribution and its association with LV diastolic dysfunction in PD patients. Only visceral fat  and peritoneal fat  were associated with the development of LV diastolic dysfunction as described in In this study, we found that PD patients with LV diastolic dysfunction had significantly higher levels of pro-inflammatory cytokines. In addition, a significant association between LV diastolic dysfunction and inflammatory cytokine levels was noted in this specific group of patients. In PD patients with higher levels of pro-inflammatory cytokines, the relationship between fat distribution, inflammation, and LV diastolic dysfunction was examined. We also adjusted factors associated with LV diastolic dysfunction using several logistic regression models. These analyses showed that certain fat deposits might act partly through inflammation to affect LV diastolic dysfunction in PD patients.Immuno-inflammatory activation plays a pivotal role in the development and in the progression of heart failure by some studies To the best of our knowledge, this is the first study to address the relationship between adipose tissue contents and diastolic dysfunction in PD patients. Elevated or excessive amounts of adipose tissue are regarded as risk factors for a number of diseases such as insulin resistance, type 2 diabetes mellitus, and atherosclerosis, which can lead to major cardiovascular sequelae. Further, adipose tissue is associated with changes in both inflammatory cells and biochemical markers of inflammation. For example, the levels of circulating fibrinogen and other acute phase reactants are elevated in obese patients In our recent study examining inflammation and LV diastolic dysfunction in PD patients The present study showed that adipose tissue may be associated with LV diastolic dysfunction partly through the effect of inflammation in PD patients. There exerts some explanations. First, a recent report demonstrated that inflammation can reduce myocardial function by inhibiting myocyte contractility and by remodeling the extracellular matrix In our current studies, we showed that both total fat and visceral fat had a strong correlation with inflammation which is consisted with previous study Our study had limitations; first, we only use cross-sectional data to infer longitudinal relationship. Although a model is identifiable, more other associations and possible pathways may be demonstrated and a precise causal relationship should be relied on further prospective studies. Second, the patients included in our current study are all Taiwanese. The generalizability to other population should be proved by further study. Third, besides TNF-α and IL-6 we did not measure additional pro-inflammatory cytokines that were not easily discerned in usual clinical practice. In addition, since the actual duration of ESRD or PD was missed in some patients, we could not correlate the relationship between the duration of PD with circulating biomarkers or diastolic dysfunction.In conclusion, for the first time, we delineated the complex relationship between adipose tissue accumulation, inflammation, and LV diastolic dysfunction in PD patients. The strength of this study is in its precise definitions. We measured central obesity by CT and defined LV diastolic dysfunction by a combination of variable echocardiographic parameters. This study demonstrated that a greater amount of visceral adipose tissue was associated with inflammation, which was related to subclinical LV diastolic dysfunction in PD subjects.


The heart failure “growing epidemic” is an important public health issue that the health care systems of all developed countries are facing. Over the last decade, the annual number of heart failure hospitalizations has almost doubled with approximately 50% of patients being rehospitalized within 6 months of discharge . The comIn this special issue we have invited a few papers that address such issues and explain why, despite the emergence of novel therapeutic approaches that promise life prolongation and hospital length reduction, this patient population will still be needing rehospitalization and will often have a poor prognosis. This special issue is the extension of an effort that was initiated in 2011 with the first heart failure-focused issue, .We have divided this issue into 4 categories: the pathophysiology section, the pharmacological treatment section, the nonpharmacological treatment section, and the comorbidity section.pathophysiology section, K. Komamura and colleagues provide a comprehensive review of the similarities and differences between the pathogenesis and pathophysiology of diastolic and systolic heart failure.According to the ejection fraction, patients with heart failure have traditionally been divided into two different groups: heart failure with preserved and heart failure with reduced ejection fraction. In recent years, accumulating studies showed that increased mortality and morbidity rates of these two groups are nearly equal. Although heart failure with preserved ejection fraction  is an increasingly frequent condition of heart failure worldwide, its pathophysiology has not been sufficiently elucidated. This is thought to be the most significant reason for a lack of established treatment methods in this patient population. In the pharmacological section, J. Li and colleagues focus on the tested as well as the promising therapeutic options that are currently studied in patients with heart failure with preserved ejection fraction and provide a brief discussion on the pathophysiological mechanisms and diagnostic options that are helpful to increase our understanding of these novel therapeutic strategies. In an original study, A. Orea-Tejeda et al. evaluate the effect of ivabradine on endothelial function in diastolic and right heart failure patients. Ivabradine is an I(f) ion current inhibitor that has proved to reduce mortality in patients with systolic heart failure by slowing heart rate without decreasing myocardial contractility but has not been tested in patients with preserved ejection fraction. Diastolic and right heart failure patients underwent photoplethysmography, a simple, low-cost optical technique that can evaluate vascular function, before and after induced ischemia and before and 6 months after treatment with ivabradine (mean 12.5 mg a day). Ivabradine administration significantly improved endothelial function (shear stress) in this patient population.Shedding light in a very similar topic, in the non-pharmacological treatment section, M. Khosravi and colleagues study the effects of cardiac rehabilitation on echocardiography parameters in coronary artery disease patients with left ventricular dysfunction. Following an eight-week exercise-based rehabilitation program, all subjects significantly increased their left ventricular ejection fraction and peak exercise capacity without experiencing any serious cardiac complication.The accurate impact of exercise on coronary artery disease patients with left ventricular dysfunction is still debatable. In the comorbidity section, we demonstrate how certain comorbid conditions may affect patients' decision-making capacity and interfere with their ability to comply with treatment requirements, recognize and self-manage disease worsening symptoms [A shared understanding of medical conditions between patients and their health care providers has been shown to improve self-care and outcomes . In the symptoms . Sleep dsymptoms . E. StopWe hope that the readers of the journal will find the topics as interesting and important as we did.Gregory  GiamouzisFilippos  Triposkiadis  GeorgiopoulouVasiliki  V.Dimitrios  FarmakisDirk  WestermannJohn  Skoularigis


Long-term intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs), especially eicosapentaenoic acid (EPA) is associated with a low risk for cardiovascular disease. Phase-contrast cine cardiovascular magnetic resonance (PC cine CMR) can assess coronary flow reserve (CFR). The present study investigates the relationship between CFR evaluated by PC cine CMR and the serum EPA.We studied 127 patients ; mean age, 72.2 ± 7.4 years) with known or suspected coronary artery disease (CAD). X-ray coronary angiography revealed no significant coronary arterial stenoses  analysis) in all study participants. Breath-hold PC cine CMR images of the coronary sinus (CS) were acquired to assess blood flow of the CS both at rest and during adenosine triphosphate (ATP) infusion. We calculated CFR as CS blood flow during ATP infusion divided by that at rest. Patients were allocated to groups according to whether they had high  or low  median serum EPA.CFR was significantly lower in the low, than in the high EPA group . Serum EPA positively correlated with CFR . We defined preserved CFR as > 2.5, which is the previously reported lower limit of normal flow reserve without obstructive CAD. Multivariate analysis revealed that EPA is an independent predictor of CFR > 2.5 .The serum EPA is significantly correlated with CFR in CAD patients without significant coronary artery stenosis. Long-term intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs), especially eicosapentaenoic acid (EPA), is associated with a low risk for cardiovascular disease -7. SeverPhase-contrast cine cardiovascular magnetic resonance (PC cine CMR) is a promising approach to quantifying global myocardial blood flow in the left ventricular (LV) myocardium without exposure to radiation -19. The Whether or not serum EPA levels correlated with the CFR of patients with known or suspected coronary artery disease (CAD) remains unclear. Therefore, the present study aimed to determine the relationship between serum EPA and CFR in patients with CAD using PC cine CMR. As the presence of significant coronary artery stenosis affects the CFR, we enrolled the CAD patients without ≥50% diameter stenosis on X-ray coronary angiography (CAG).This study included 237 patients with known or suspected CAD who were assessed by X-ray coronary angiogram and cardiovascular magnetic resonance (CMR) including cine CMR, PC cine CMR, late gadolinium enhancement (LGE) CMR. Figure CMR was performed on a 1.5-T MR system equipped with 32 channel cardiac coils . All patients were assessed by cine CMR, PC cine CMR and LGE CMR. Imaging was performed after overnight fasting. Serum fatty acid measurement was performed on the same day as CMR.Vector-electrocardiographic (VCG) monitoring leads were positioned on supine patients and then imaging started. Scout images were acquired in three orthogonal planes for cardiac orientation. Vertical and horizontal long-axis cine CMR of the LV was acquired using a steady-state free precession (SSFP) sequence. The LV volume and mass were calculated from short-axis cine images of the LV acquired from the apex to the base .–1 · min–1) into the left antecubital vein for 4 min. PC cine CMR images of the coronary sinus were acquired during ATP stress and at rest. The duration between stress and resting image acquisition was at least 10 min. All patients were asked to refrain from caffeinated beverages for at least 24 hours prior to CMR.Cine CMR in the axial plane was obtained through the atrioventricular groove to locate the coronary sinus Figure . The imaAfter acquiring phase-contrast cine CMR, the patients were injected with 0.15 mmol/kg of gadopentetate dimeglumine . Late gadolinium-enhanced CMR was obtained in the same planes as cine images 15 min later using an inversion recovery–prepared gradient-echo sequence. The imaging parameters for late gadolinium-enhanced imaging comprised: repetition time, 4.3 ms; echo time, 1.3 ms; flip angle, 15°; field of view, 380 × 380 mm; acquisition matrix, 256 × 180; and slice thickness, 10 mm. The null point of the normal myocardium was determined using a Look-Locker sequence.An observer who was blinded to the results of CMR interpreted the conventional X-ray CAG using quantitative software . Intracoronary administration of isosorbide dinitrate (2 to 3 mg) was performed in all patients before contrast injection. We performed quantitative coronary angiography (QCA) analysis for evaluating the degree of coronary arterial stenosis on X-ray CAG. In our trial, significant coronary arterial stenosis was defined as reduction in luminal diameter ≥50% by QCA analysis.Blood was sampled from all patients after an overnight fast for at least 12 h. Serum levels of EPA, AA, and docosahexaenoic acid (DHA) were measured using a gas chromatograph  and a capillary column  at a central laboratory .Two observers used a workstation  to analyze the cine MR, PC cine MR, and LGE images. All CMR images were rendered anonymous and reviewed in random order. To measure the LV cardiac mass, epi- and endocardial borders of the LV on the short axis cines were manually traced with exclusion of the papillary muscles at each anatomic level that encompassed the LV. The LV mass was calculated by the consensus of two observers as the sum of the myocardial volume areas multiplied by the specific gravity (1.05 g/mL) of the myocardial tissue .The contours of the coronary sinus were manually traced on each frame of all PC cine images to quantify blood flow in the coronary sinus and velocity in the adjacent tissue was measured for phase-offset correction. Blood flow in the coronary sinus was calculated by integrating the product of the cross-sectional area and the mean velocity in the coronary sinus and corrected using mean velocity in the adjacent tissue for all cardiac phases in the cardiac cycle. In line with other studies, we also corrected coronary sinus blood flow using rate pressure products (RPP) ,19,23-26The ΔCS flow and CFR were calculated as:The coronary vascular resistance (CVR) was calculated as follows.Late gadolinium-enhancement was visually assessed and interpreted by the consensus of two observers who were blinded to the patients’ information. The mass with LGE was measured on short-axis slices using manual planimetry. The total mass of LGE was calculated by summing the late gadolinium-enhanced mass of all sections, and the ratio (%) of LGE is expressed as:None of the patients had atypical enhancement defined as mid-myocardial or sub-epicardial enhancement with multifocal distribution.t-test for normally distributed variables, and the Mann–Whitney U test for skewed variables. The relationship between serum fatty acids and CFR determined by CMR was determined using Pearson’s correlation coefficient. Preserved CFR was defined as CFR > 2.5 by PC cine CMR, which is the lower limit of normal flow reserve without obstructive CAD [Data were statistically analyzed using SPSS software, version 17.0 . Continuous values are presented as means ± standard deviation (SD). Skewed values are presented as medians with the interquartile range (IQR). Normality was determined by the Shapiro-Wilk test. Coronary flow reserve determined by CMR was compared between the high and low EPA groups. Differences between the groups were evaluated using an unpaired tive CAD . IndepenWe acquired PC cine CMR from all patients in the resting state and during ATP stress Figure . Figure Table Figure Table This is the first investigation of the relation between CFR evaluated as changes in coronary sinus flow induced by ATP infusion, and serum EPA. In patients without significant coronary arterial stenosis on X-ray coronary angiography, serum EPA and DHA levels significantly and positively correlated with CFR. Multivariate linear regression analysis showed that the EPA was an independent predictor of impairment of CFR evaluated by CMR. These results indicated that the serum EPA plays an important role in the regulation of CFR in patients with CAD.The results of multivariate regression analysis in this study revealed that presence of DM, LVMI and serum EPA were the independent predictors of preserved CFR (CFR > 2.5). The CFR is an index of coronary microvascular function in patients without epicardial coronary arterial stenosis, therefore, we assessed the relationship between microvascular function and serum EPA concentration. It’s well known that the women more frequently develop microvascular disease (MVD) in comparison to men, however, men and women who have coronary MVD often have conventional risk factors, such as hypertension and DM . The preLV hypertrophy is another important mechanism of CFR impairment. presence of significant coronary arterial stenosis that results in dilatation already at rest. The patients with LV hypertrophy have a higher level of auto-regulated blood flow at rest to meet the demand of an increased myocardial mass . TherefoEpidemiological studies have shown that the incidence of acute myocardial infarction is substantially lower among non-emigrated inhabitants of Greenland (5.3%), than in individuals from the United States (40.4%) and Denmark (34.7%), with age- and sex adjusted death rates for ischemic heart disease . This isIn this study, we enrolled the CAD patients without ≥50% diameter stenosis on X-ray CAG, and assessed the microvascular function by calculating the CFR by PC-cine CMR. It is important to evaluate the disease severity in patients with non-obstructive CAD, because the prognosis of MVD is not as benign as commonly thought . RandomiFirst, this was a single center study with a relatively small patient cohort. Although CFR assessment by PC cine CMR is non-invasive and useful, CMR is contraindicated for patients implanted with pacemakers or cardiovascular defibrillators and those with claustrophobia. Such patients were excluded from the present study. Second, we excluded the CAD patients with significant coronary arterial stenosis . Therefore, the findings of this study can only be applied to the CAD patients without ≥50% diameter stenosis. The reason to exclude the patients with significant CAD was that the fall of blood pressure induced by ATP should have too much compromised coronary flow with the risk to produce an unwanted myocardial ischemia. Third, CVR assessed in the current study mean the resistance throughout the entire cardiac cycle, included the systolic period during which a compressive resistance is added to the resistance due to the coronary vasomotor tone, usually indicated as coronary “vascular” resistance (auto-regulative resistance).Serum EPA is significantly correlated with CFR in CAD patients without significant coronary artery stenosis.The authors declare that they have no competing interests.SK designed the study protocol, carried out the MR studies, analyzed the data and drafted the manuscript. KF and JK analyzed the data and drafted the manuscript. NI, MK, YK, IK, TN, TN, YT, KU, KK and SU helped to draft the manuscript. All authors read and approved the final manuscript.


Adipokines are linked to the development of cardiovascular dysfunction in type 2 diabetes (DM2). In DM2-patients, circulating levels of omentin-1, an adipokine preferentially expressed in epicardial adipose tissue, are decreased. This study investigated whether omentin-1 has a cardioprotective function.Omentin-1 levels in plasma and cardiac fat depots were determined in DM2-patients versus controls. Moreover, the relation between omentin-1 levels and cardiac function was examined in men with uncomplicated DM2. Finally, we determined whether omentin-1 could reverse the induction of cardiomyocyte dysfunction by conditioned media derived from epicardial adipose tissue from patients with DM2.P<0.05). The improved diastolic function following pioglitazone treatment associated with increases in omentin-1 levels (P<0.05). In vitro, exposure of cardiomyocytes to conditioned media derived from epicardial adipose tissue from patients with DM2 induced contractile dysfunction and insulin resistance, which was prevented by the addition of recombinant omentin.Omentin-1 was highly expressed and secreted by epicardial adipose tissue, and reduced in DM2. Circulating omentin-1 levels were lower in DM2 versus controls, and positively correlated with the diastolic parameters early peak filling rate, early deceleration peak and early deceleration mean (all These data identify omentin-1 as a cardioprotective adipokine, and indicate that decreases in omentin-1 levels could contribute to the induction of cardiovascular dysfunction in DM2. In vitro, omentin-1 enhances insulin-mediated stimulation of Akt-phosphorylation, glucose uptake and inhibits tumor necrosis factor α-induced inflammation Cardiac dysfunction and myocardial insulin resistance are common in patients with type 2 diabetes (DM2) Omentin-1 is abundantly expressed in epicardial adipose tissue (EAT), a visceral fat depot located around the heart and coronary arteries The patient samples used in this study were collected from two distinct cohorts.At the University Hospital in Duesseldorf (Germany), Caucasian men undergoing coronary artery bypass grafting with or without additional valve replacement surgery consented to the collection of biopsies from EAT, pericardial, and intrathoracic subcutaneous adipose tissue after written informed consent. The procedure to obtain adipose tissue samples was approved by the medical ethical committee of the Heinrich-Heine-University , and the study was conducted in accordance with the principles of the Declaration of Helsinki. Patients of other ethnic origins, diagnosed as having human immunodeficiency virus infection, lipodystrophy or chronic coexistent inflammatory disease were excluded from participation. Participants were distributed into two groups, i.e. those with and those without DM2, on the basis of the diagnosis ‘DM2’ in the medical record of the patient. Adipose tissue biopsies were either used to generate conditioned media (CM), or snap-frozen in liquid nitrogen and stored at −80°C for protein extraction.http://www.controlled-trials.com/ISRCTN53177482). Participating healthy controls and men with uncomplicated DM2 had a body mass index (BMI) between 25–32 kg/m2, and a blood pressure lower than 150/85 mm Hg (with or without the use of antihypertensive drugs). Furthermore, only DM2 patients with glycosylated hemoglobin (HbA1c) between 6.5–8.5% were eligible for inclusion. Patients with DM2 diagnosed as having any symptoms or history of diabetes-related complications, or cardiovascular or liver disease, as well as prior use of thiazolidinediones or insulin, were excluded from participation. Exclusion criteria for healthy controls were a history or current cardiovascular disease, dyslipidemia, and the use of any prescribed medication. The clinical studies were conducted at two university medical hospitals in the Netherlands , were approved by the medical ethics committee of both centers, and performed in full compliance with the Declaration of Helsinki. Eligible participants with DM2 ceased their regular blood glucose lowering agents before entering a 10-week run-in period in which they were transferred to glimepiride monotherapy and titrated until a stable dose was reached 2 weeks before randomization. Then, participants with DM2 were randomized to pioglitazone  or metformin  in addition to glimepiride throughout the study. Details on assessment of cardiac function, aortic pulse wave velocity and distensibility, and volume of pericardial and visceral abdominal adipose tissue in the study groups have been described elsewhere −2.min−1 as previously described Circulating omentin-1 levels were determined in 78 men with uncomplicated DM2 from the previously described PIRAMID (Pioglitazone Influence on tRiglyceride Accumulation in the Myocardium in Diabetes) study 2) at 37°C. Then, CM was generated by culturing the explants in serum-free adipocyte medium (100 mg explants/mL) for 24 h. The CM was collected and stored as aliquots at −80°C until further use.CM was generated as described previously 3VO4, 2 mM MgCl2, 1 mM DTT, and protease inhibitors . Then, homogenates were cleared by centrifugation , and protein content was determined using Bradford reagent . Protein expression was determined by Western blot analysis of ten microgram of protein using omentin-1 antibody . Immunoblots were quantified using a LUMI Imager system , and normalized by reprobing the stripped filters with glyceraldehyde 3-phosphate dehydrogenase (GAPDH) antibody .Omentin-1 levels in human plasma and CM were determined using an omentin-1 Enzyme Linked Immuno Sorbent Assay . The intra- and interassay coefficients of variation for the omentin-1 ELISA were less than 6.7% and 9.1%, respectively. For protein expression, biopsies were homogenized in 50 mM Tris.HCl [pH 7.5], 150 mM NaCl, 0.5% Triton X-100, 1 mM NaF, 1 mM NaAnimal experiments were performed in accordance with the ‘Principle of laboratory animal care’  and the current version of the German Law on the protection of animals, and were approved by the animal ethics committee of the Heinrich Heine University . Cardiomyocytes were isolated from male Lewis rats (Lew/Crl) weighing 150–300 gram using a Langendorff perfusion system as described 2+-transients were analyzed using an IonOptix system  as described To determine contractile function, isolated cardiomyocytes were cultured overnight and then preloaded with Fura-2-AM  for 25 min at room temperature. Then, cultures were washed twice with adipocyte medium and incubated for 30 min with CM (diluted 1∶6 with adipocyte medium) or adipocyte medium in the presence or absence of 300 ng/mL recombinant human omentin . Subsequently, sarcomere shortening and CaP<0.05 was considered as statistically significant.Data are presented as mean ± standard error of the mean or median (interquartile range) in case of a non-Gaussian distribution. Significant differences between the variables were evaluated as indicated in the legends to the Figures and Tables. Correlation coefficients were calculated using the Pearson’s correlation. Linearity of the regression models was judged based on histograms and scatter plots. Because no interactions were found between group and dependent variables, both groups were analyzed as one for regression analysis. Additional potential confounders were investigated by adding group state, BMI, and M-value for insulin sensitivity for associations of omentin-1. Variables that changed the regression coefficients by more than 10% were included in the adjusted model. IBM SPSS Statistics version 20 was used for these analyses. A value of P<0.01) (Omentin-1 expression was determined in adipose tissue biopsies collected from patients with and without DM2 undergoing open heart surgery. As shown in P<0.01) . AnalysiP<0.01) . FurtherP<0.01) .P<0.05) (P<0.05) (P = 0.008)  . Further(P<0.05) . As comp= 0.008) .P = 0.04; β = 0.255, P = 0.004). The association between omentin-1 plasma levels and early deceleration peak was borderline significant in this analysis .Univariate regression analysis identified inverse correlations between plasma omentin-1 levels and BMI, fasting plasma glucose, insulin and HbA1c, visceral fat volume, heart rate, and rate pressure product, and positive associations with the diastolic parameters early peak filling rate, early deceleration peak and early deceleration mean, M-value for insulin sensitivity, adiponectin and HDL-cholesterol . Only inP = 0.002), but not metformin, treatment . Exposure of primary rat cardiomyocytes to CM-EAT reduced peak sarcomere shortening and the departure and return velocity of contraction as compared to cardiomyocytes exposed to control medium . Omentin omentin . Finally omentin .Here we show that decreases in circulating omentin-1 levels associate with left ventricular diastolic dysfunction. In patients with DM2, circulating omentin-1 levels were lower as compared to controls. Pioglitazone treatment, which improved left ventricular diastolic function in this study cohort This study confirmed that circulating omentin-1 levels are lower in patients with DM2 versus controls A major finding in our study is the association of plasma omentin-1 levels with left ventricular diastolic function. Because of the strong positive association with adiponectin levels, omentin-1 levels may be regulated by adiponectin In vitro studies have indeed ascribed a signaling function to omentin-1 because it promotes Akt-phosphorylation in isolated blood vessels, vascular smooth muscle cells, and microvascular endothelial cells 2+-fluxes and Akt-phosphorylation in cardiomyocytes. Rather, omentin-1 was found to protect against the induction of cardiomyocyte contractile dysfunction and insulin resistance by EAT-released factors from patients with DM2. This suggests that omentin-1 could exert its cardioprotective effects by acting as a scavenger for detrimental factors secreted by adipose tissue.Yet, several issues remain to be addressed. First of all, this study was conducted in men, and it is unclear to what extent our findings can be applied to women. In this respect, the clinical studies that addressed this issue reported no impact of gender on circulating omentin-1 levels This study shows that omentin-1 levels in plasma and EAT are decreased in patients with DM2. Furthermore, the positive association of omentin-1 levels with left ventricular diastolic function and the experiments in isolated rat cardiomyocytes suggest that omentin-1 could have a cardioprotective function. Accordingly, a reduction in omentin-1 expression in EAT might contribute to the induction of cardiac dysfunction in patients with DM2.


Despite a high worldwide prevalence of left ventricular hypertrophy among black patients, the association of a specific left ventricular geometric pattern with left ventricular dysfunction is rare. The aim of this study was to explore the possibility of such an association in Nigerian hypertensives.This was a retrospective study consisting of 188 treated hypertensives. Echocardiography was used to allocate the patients to the following four groups: normal geometric pattern, concentric remodelling, eccentric hypertrophy and concentric hypertrophy.The mean age of the study population was 55.95 ± 10.71 years. There were 75 females (39.9%). Concentric hypertrophy occurred in 72 (38.3%) patients and concentric remodelling in 53 (28.2%). Only 30 (16%) had a normal left ventricular geometric pattern. Hypertensive subjects with eccentric hypertrophy had the lowest ejection fraction, fractional fibre shortening and left ventricular ejection time but these did not reach statistical significance. The mean left atrial dimension was highest in the subjects with eccentric hypertrophy.In this study population of treated Nigerian hypertensives, concentric remodelling and hypertrophy were the predominant left ventricular geometrical patterns. Left ventricular hypertrophy is an important determinant of adverse cardiovascular events in subjects with hypertension.Several authors have demonstrated an increased cardiovascular risk associated with increased left ventricular mass (LVM).Blacks have been noted to have an increased prevalence of left ventricular hypertrophy and increased associated cardiovascular risk. The association of geometric patterns with left ventricular systolic and diastolic function has not been well studied. The development of heart failure in hypertensives with LVH results from depressed left ventricular systolic function and/or diastolic dysfunction. The deleterious effect of left ventricular remodelling may be an important determinant of progression to overt heart failure.9The aim of this study was to determine any possible association between left ventricular dysfunction and left ventricular geometrical patterns in this population of treated Nigerian hypertensives, using echocardiography.2 (kg/m2).This was a retrospective study among adult hypertensive subjects (≥ 18 years) who had had complete echocardiographic examination as part of their work-up in a teaching hospital. Hypertension was diagnosed with standard protocols when blood pressure was ≥ 140/90 mmHg on at least two occassions.In all patients, an abdominal ultrasound and urinalysis were performed. Echocardiography was done in all patients to document the presence or absence of LVH and also to document the left ventricular geometrical pattern. These studies were performed as part of the initial evaluation of hypertension or as part of the ongoing care of known hypertensive patients.Echocardiography was performed on all the subjects using a Suis Apogee machine and a 3.5-MHz probe. Two-dimensional colour Doppler and pulse-wave Doppler were carried out. Echocardiography was done according to the American Society of Echocardiography guidelines.11LVM was calculated from measurements of the left ventricle (LV) using the equation:3 – 3] + 0.6.12LVM (g) = 0.81 [1.04 2.7 Correcting LVM for height2.7 minimises the effect of gender, race, age and obesity on the validity of various parameters for the diagnosis of left ventricular hypertrophy.2.7. As reported by de Simone et al.,2.7 have been found to be at a fourfold greater risk of cardiovascular morbidity outcomes. LV geometry was determined after calculation of the relative wall thickness (RWT) using the formula /LV end-diastolic internal dimension.16 RWT was considered abnormal if it was ≥ 0.45.16LVM index (LVMI) was calculated as LVM/height (m).Four left ventricular geometric patterns were described: normal geometry, concentric remodelling, eccentric hypertrophy and concentric hypertrophy. LV geometry was defined as concentric hypertrophy (elevated LVMI and RWT), concentric remodelling , eccentric hypertrophy  and normal geometry . LV ejection fraction was calculated using Teichholz’s formula.17t-test and chi-squared test were used as appropriate for intergroup comparisons. Values of p < 0.05 were taken as statistically significant.Statistical analysis was done using the Statistical Package for Social Sciences, SPSS 15.0 (Chicago Ill.) Quantitative data were summarised using means ± standard deviation (SD) while qualitative data were summarised using percentages and proportions. The Student’s The mean left ventricular ejection time was reduced among those with abnormal geometry compared with those with normal geometry. Left ventricular dimensions (in both diastole and systole), left ventricular mass (LVM), relative wall thickness (RWT) and left ventricular mass index (LVMI) were statistically different between subjects with normal and abnormal geometry, as shown in LVH has been recognised as an important predictor of adverse cardiovascular events, such as malignant arrhythmias, sudden cardiac death, heart failure and coronary heart disease.24et al.,This study demonstrated increased prevalence of left ventricular hypertrophy and abnormal left ventricular geometric patterns among treated Nigerian hypertensive subjects. This relatively increased prevalence has been documented among blacks worlwide. Subjects with eccentric hypertrophy had the lowest ejection fraction in this study. Others have reported similar associations among hypertensive subjects.The aortic valve velocity–time interval is an echocardiographic index of left ventricular output. It was lowest among those in this study with eccentric hypertrophy. Diastolic dysfunction including LV relaxation abnormality, pseudonormalisation  occurred in various LV geometric patterns. They have been associated with an additive effect on cardiovascular and all-cause mortality.In this study, left atrial dimension was highest among subjects with eccentric hypertrophy. This pattern is also associated with other indices of diastolic dysfunction such as abnormal IVRT and deceleration time. Left atrial dimension has been shown to be a good index of left ventricular diastolic dysfunction.32Although, the mean e/a ratio and deceleration time across the groups were not statistically different, the differing left atrial dimension is a good index of the presence of diastolic dysfunction among the subjects. These findings suggest that abnormal LV geometry  was associated with systolic and diastolic dysfunction among treated hypertensive Nigerians. In regional left ventricular function studies such as tissue Doppler studies, cardiac MRI may demonstrate more significant evidence of left ventricular dysfunction.It is important to note that LVH prevalence is still high, as revealed among treated hypertensive subjects. Similar studies from Ibadan, Nigeria also revealed a high prevalence of LVH and abnormal geometry among treated hypertensives. However, the study reported a higher prevalence among women.This study further highlights the relatively increased prevalence of left ventricular hypertrophy and abnormal left ventricular geometric pattern among treated hypertensive Nigerian subjects. Hypertensive subjects with eccentric hypertrophy had reduced ejection fraction, fractional shortening and left ventricular ejection time than those with other geometric patterns. They also had increased left atrial dimension. Eccentric and concentric hypertrophy were the commonest forms of left ventricular geometry among the subjects.


Percutaneous transthoracic left ventricular (LV) access and closure would be an enabling technology for a wide range of structural heart, electrophysiologic and proximal aorta procedures. We propose a real-time MRI guided approach to access and close the LV using novel active devices.Sixteen Yorkshire swine underwent percutaneous transthoracic LV access and followed up to three months (n=8).All procedures were guided by real-time bSSFP MRI  using two slices along the needle trajectory and a short-axis slice for cardiac monitoring.Transthoracic ventricular puncture was performed using a customized 18G active needle with integrated loop coil. Puncture trajectory was planned using real-time MRI to identify optimal LV puncture target and trajectory with respect to intraventricular and valvular structures Figure . After nVentricular puncture hole was closed using a modified Amplatzer muscular VSD occluder with a titanium screw to improve MR appearance. A custom active delivery cable incorporating a loopless antenna was used to enhance the visibility of the device deployment.Occluder device was deployed by opening the distal disk at the endocardial surface Figure , separatReal time MRI guidance enabled access to the LV without injuring intraventricular structures in 15/16 animals. In one animal the sheath injured the inter-ventricular septum.Real-time MRI guided LV closure was achieved using the occluder device. Three types of failure modes of VSD occluder device mediated closure were observed during follow up. (1) Device was pulled out of the LV wall and resulted in fatality . (2) Pericardial entrapment by the proximal disc of the device resulted in continuous bleed and mortality . (3) In one animal the puncture was apical and despite appropriate delivery, the device could not effectively occlude the puncture hole.During follow-up (n=9), small pericardial effusion was aspirated on days 3-6 (196±127 ml). LV function was preserved and histology analysis indicated complete healing process around the device with no distant myocardial effects.Percutaneous transthoracic LV access and closure is a feasible approach using real time MRI and active devices. Transient “permissive pericardial tamponade” is important for effective deployment of the closure device.


Left ventricular non-compaction is a rare congenital heart disease, and is most commonly diagnosed via two-dimensional echocardiography according to echocardiographic criteria. Recently, transthoracic three-dimensional echocardiography has become available in the clinical setting.We present two isolated cases of left ventricular non-compaction from Japan (in an 84-year-old woman and 47-year-old man) that were confirmed by two-dimensional echocardiography, contrast-enhanced two-dimensional echocardiography, three-dimensional echocardiography and cardiac magnetic resonance imaging. In both cases, three-dimensional echocardiography successfully demonstrated the trabecular meshwork of the left ventricle, referred to as a ‘honeycomb appearance’.Three-dimensional echocardiography has the advantage of visualizing an en-face view of the trabecular meshwork, which is not possible with two-dimensional echocardiography. We further emphasize the clinical utility of three-dimensional echocardiography, which is not limited to just the observation of the trabeculations and inter-trabecular recesses, but can also visualize the trabecular meshwork with a ‘honeycomb appearance’. Chin et pattern . The cli pattern .LVNC can be recognized by multiple imaging modalities, such as cardiac magnetic resonance imaging (CMR), two-dimensional echocardiography (2DE), contrast-enhanced 2DE, and angiography ,5. CMR, In this report, we present two cases of isolated LVNC that were confirmed using 3DE by the typical trabecular meshwork of the left ventricle, referred to as a ‘honeycomb appearance’.An 84-year-old Japanese woman was admitted to our hospital with dyspnea. Her physical examination results indicated a pulse rate of 84 beats per minute, blood pressure of 124/72mmHg, fine crackles in both lungs, and pre-tibial edema in her legs. Her neurological examination results did not show neuromuscular abnormalities. Her electrocardiogram results showed normal sinus rhythm and a complete left bundle block. Laboratory study results showed mild anemia . Other basic laboratory data were normal. The results of a chest X-ray revealed pleural effusion in both lungs and cardiomegaly with a cardiothoracic ratio of 65 percent. 2DE performed in the emergency room showed mild to moderate mitral regurgitation, a normal size of left ventricle by 55mm, an enlargement of the left atrium by 47mm, and globally reduced left ventricular function with an ejection fraction of 26 percent. She received standard medical therapy for heart failure, which comprised intravenous and oral diuretics, a beta-adrenergic blocker, and an angiotensin-converting enzyme inhibitor. Once her condition stabilized, further medical investigation of the etiology was performed, including cardiac catheterization, contrast-enhanced 2DE, real-time 3DE, and CMR. Her coronary angiogram indicated severe stenosis in the proximal left anterior descending coronary artery and right coronary artery, which was successfully treated by percutaneous coronary angioplasty. Repeated 2DE showed marked trabeculations protruding from the left ventricular wall in the apex (Figure A 47-year-old Japanese man with no history of heart disease was admitted to our hospital for medical investigation of an abnormal electrocardiogram of atrial premature contractions during an annual health check-up. His physical examination results revealed a pulse rate of 64 beats per minute, blood pressure of 134/80mmHg, normal respiratory sounds, and third heart sounds. His neurological examination results did not show any neuromuscular abnormalities. His electrocardiogram results showed normal sinus rhythm without conduction abnormalities, abnormal Q waves and ST-T changes. Laboratory test results were normal. The results of a chest X-ray revealed cardiomegaly with a cardiothoracic ratio of 58 percent. Holter monitoring revealed atrial and ventricular premature contractions. 2DE imaging showed mild mitral regurgitation, an enlargement of the left ventricle by 60mm, and globally reduced left ventricular function with an ejection fraction of 26 percent. Additionally, contrast-enhanced 2DE, real-time 3DE, myocardial perfusion imaging, CMR, and cardiac catheterization were performed. He was diagnosed as having LVNC on the basis of the findings derived from the above-mentioned imaging modalities. A ‘honeycomb appearance’ in the apex was observed on 3DE (Figure In the early embryo stage of human development, the heart is a loose, interwoven mesh of muscle fibers that form trabeculae with deep inter-trabecular recesses . During Recent studies have reported that the diagnosis of LVNC is often delayed because of difficulty revealing the diagnostic findings . Multiplet al. reported the usefulness of 3DE to visualize the trabecular meshwork, referred to as a ‘honeycomb appearance’, for the purpose of differentiating LVNC from other diseases such as right ventricular dysplasia [3DE facilitates accurate diagnosis, detailed characterization, and description of the extent of the affected myocardium in LVNC. Entire trabeculations and inter-trabecular recesses are visualized and the boundary between the compact and non-compact myocardium is easily separated . Moreoveysplasia . Howeverysplasia . In both3DE has the advantage of visualizing an en-face view of the trabecular meshwork, which is not possible by 2DE. We further emphasize the clinical utility of 3DE, which is not limited to the observation of the trabeculations and inter-trabecular recesses, but also the trabecular meshwork with a ‘honeycomb appearance’.Written informed consents were obtained from the patients for publication of this manuscript and any accompanying images. A copy of the written consents are available for review by the Editor-in-Chief of this journal.2DE: two-dimensional echocardiography; 3DE: three-dimensional echocardiography, LVNC, left ventricular non-compaction; MRI: magnetic resonance imaging.The authors declare that they have no competing interests.TK and TN wrote and revised the manuscript. AH and JA gave support in performing the cardiac magnetic resonance imaging. HH and MY gave support in performing the three-dimensional echocardiography and the contrast echocardiography. HT gave final approval of the version to be published. All authors read and approved the final manuscript.


Cardiac perfusion imaging is a recognized method for non-invasive evaluation for myocardial ischemia. However, it is unclear how global heart failure affects myocardial perfusion. In this study, we explore semi-quantitative perfusion in a Yorkshire swine heart failure study.In this study, five Yorkshire swine were implanted with pacemakers with the intent of producing tachycardia-induced heart failure. Each pig was scanned on a 1.5T MR scanner  at baseline and at time of heart failure. For MR acquisition, we used a standard fast gradient echo perfusion acquisition with an 8-channel cardiac coil, 40 phases, 128x128, 7mm slice, 2RR, and with free breathing. 0.2mmol/kg dose of Gadoteridol was injected intravenously at 1ml/sec. Signal intensity (SI) time courses were evaluated for the myocardium and the blood pool. Arrival time, peak time, slope, maximum upslope, and contrast enhancement ratio (CER) were calculated using Cine Tool . Index is defined as the value of myocardium weighted by the value of the blood pool. In addition, semi-quantitative analysis of slope index, maximum upslope index, and CER index were calculated. A paired t-test was evaluated in each measured parameter group to identify the statistical difference between two scans.Average left ventricular ejection fraction at baseline was 45% ± 4%, and at heart failure was 16% ± 7%. Example signal intensity curves are shown in Figure There is currently limited report of myocardial perfusion applied in heart failure. In this study of tachycardia-induced heart failure in swine, perfusion shows delayed arrival time, delayed peak time, and reduced slope of enhancement in myocardium. Future work is needed to explore the potential role of myocardial perfusion imaging applied to heart failure patients, as the ability to identify coexistent myocardial ischemia may be problematic in this population.