Quantitative Cardiovascular Magnetic Resonance (CMR) techniques have gained high interest in CMR research. Myocardial T2 mapping is thought to be helpful in diagnosis of acute myocardial conditions associated with myocardial edema. In this study we aimed to establish a technique for myocardial T2 mapping based on gradient-spin-echo (GraSE) imaging.The local ethics committee approved this prospective study. Written informed consent was obtained from all subjects prior to CMR. A modified GraSE sequence allowing for myocardial T2 mapping in a single breath-hold per slice using ECG-triggered acquisition of a black blood multi-echo series was developed at 1.5 Tesla. Myocardial T2 relaxation time (T2-RT) was determined by maximum likelihood estimation from magnitude phased-array multi-echo data. Four GraSE sequence variants with varying number of acquired echoes and resolution were evaluated in-vitro and in 20 healthy volunteers. Inter-study reproducibility was assessed in a subset of five volunteers. The sequence with the best overall performance was further evaluated by assessment of intra- and inter-observer agreement in all volunteers, and then implemented into the clinical CMR protocol of five patients with acute myocardial injury .In-vitro studies revealed the need for well defined sequence settings to obtain accurate T2-RT measurements with GraSE. An optimized 6-echo GraSE sequence yielded an excellent agreement with the gold standard Carr-Purcell-Meiboom-Gill sequence. Global myocardial T2 relaxation times in healthy volunteers was 52.2 ± 2.0 ms (mean ± standard deviation). Mean difference between repeated examinations (n = 5) was −0.02 ms with 95% limits of agreement (LoA) of  ms. Intra-reader and inter-reader agreement was excellent with mean differences of −0.1 ms, 95% LoA =  ms and 0.1 ms, 95% LoA =  ms, respectively (n = 20). In patients with acute myocardial injury global myocardial T2-RTs were prolonged (mean: 61.3 ± 6.7 ms).Using an optimized GraSE sequence CMR allows for robust, reliable, fast myocardial T2 mapping and quantitative tissue characterization. Clinically, the GraSE-based T2-mapping has the potential to complement qualitative CMR in patients with acute myocardial injuries.The online version of this article (doi:10.1186/s12968-015-0127-z) contains supplementary material, which is available to authorized users. Cardiovascular Magnetic Resonance (CMR) can provide safe and prompt diagnosis in patients with acute myocardial injury  ,2. Many Quantitative T2 mapping techniques may overcome some of these limitations in qualitative T2-w imaging. During the last decades, several techniques and sequences for myocardial T2 mapping have been described -9 with sIn summary, a readily available, phantom-validated T2 mapping sequence with high accuracy and reproducibility in healthy volunteers is desirable allowing for a good discrimination between diseased and healthy myocardium. Therefore, the purpose of this study was to develop and evaluate a sequence for accurate myocardial T2 mapping using the gradient-spin-echo (GraSE) technique ,15 whichThe local ethic committee approved this prospective study and written informed consent was obtained from all study subjects prior to CMR. All scans were performed using a 1.5 Tesla (T) MR system  with a maximum gradient strength of 45 mT/m and a maximum slew rate of 120 mT/m/ms. A 32 channel torso coil with digital interface was used for signal reception.For pixel-wise measurement of T2 relaxation times, a multi-echo dataset was acquired based on two well established MR techniques: 1) Turbo-spin-echo (TSE), originally dubbed rapid acquisition with relaxation enhancement (RARE)  and also Turbo-spA standard dual inversion recovery black blood module was applied to null the signal of flowing blood in the ventricles; the inversion delay was calculated automatically from the cardiac frequency assuming a T1 relaxation time of 1200 ms for blood at 1.5 T. The bandwidth of the second inversion pulse was increased to achieve complete re-inversion in the myocardium (with a slice thickness for re-inversion of 2.5 fold the imaging slice thickness). To avoid ghosting artifacts and possible signal contributions from pericardial or subcutaneous fat, which can severely confound T2 measurements, fat suppression was applied using a spectral selective inversion recovery pulse (SPIR).Signal acquisition was triggered by ECG and data were acquired during breath-hold. With parallel imaging the acquisition time was reduced to a maximum of 13 RR intervals per slice including one dummy TR. Hence, data could be acquired in a single breath-hold per slice even in cases with a low cardiac frequency. Finally, T2 maps were generated directly on the scanner applying a maximum likelihood estimation on the magnitude phased-array multi-echo data taking the non-Gaussian distribution of noise in magnitude images into account ,19.2 · 4 H20) in various concentrations covering the whole range of T2 relaxation times relevant for myocardial T2 mapping. With a T1 relaxation time of about 10 times T2 at 1.5 T, MnCl2 · 4 H20 solution is a well-suited phantom for sequence optimization.To test the accuracy of the method, six phantom tubes were filled with Manganese (II) chloride doped water , a six-echo variant (6 Ec), both with one start-up echo (i.e. the first echo is not used for data acquisition), a 6 echo variant with lower resolution (6 Ec LR) and therefore higher signal to noise ratio (SNR), and a 7 echo variant with the same setting as the 6 Ec variant but without a start-up echo (7 Ec no s.e.). Sequence details are listed in Table T2 mapping with all four sequence variants was performed in 20 healthy volunteers. All healthy volunteers had no medical history of cardiac or vascular disease and no cardiac risk factors. ECG-analyses showed no abnormalities in all volunteers. Breath-hold T2 mapping was performed in end-diastole in short axis orientation. Three short axis slices  were obtained for coverage of all 16 segments as described previously ). No segments were excluded from analysis. Figure Myocardial T2 mapping with four variants of the GraSE sequence was performed in 20 healthy volunteers (17/20 [85%] men and 3/20 [15%] women). Mean age was 32.4 ± 8.1 years (range: 18 to 50 years). Mean left ventricular ejection fraction was 62.1 ± 4.0%  over all volunteers was 53.3 ± 2.7 ms (for the 9 Ec variant), 52.2 ± 2.0 ms (6 Ec), 51.3 ± 3.3 ms (6 Ec LR), and 50.4 ± 2.7 ms (7 Ec no s.e.) with the lowest inter-subject variation in the 6 Ec variant. T2 relaxation times for the 9 Ec sequence were significantly longer compared to all other variants. No significant differences were found between the two variants with six echoes. Bland-Altman analysis of the inter-study repeatability revealed a mean difference and 95% limits of agreement (LoA) between the first and the second examination of −0.04 ms  ms for the 9 Ec variant, −0.02 ms  ms for the 6 Ec variant, 1.0 ms  ms for the 6 Ec LR variant, and 2.2 ms  ms for the 7 Ec no s.e. variant. Considering the results of the phantom study and the T2 analysis in healthy volunteers including the assessment of inter-study repeatability, the six-echo (6Ec) variant was selected for further analysis.The assessment of intra- and inter-observer agreement for the six-echo GraSE sequence revealed very small differences between repeated readings of the same reader  and between the measurements of different readers , with a linear correlation coefficient of R = 0.95 and R = 0.92, respectively. The Bland-Altman plots and the corresponding correlation plots are displayed in Figure ; 1.2 ms)T2 values for the individual segments are presented in Figure After implementing the six-echo variant into clinical routine protocol, myocardial T2 mapping was performed in five patients with acute myocardial injury. Mean time from onset of symptoms to CMR was 2.2 ± 0.7 days. Global myocardial T2 relaxation times were considerably prolonged in patients with acute myocardial conditions  . No significant differences were found between basal, midventricular, and apical sections (4.3 ± 0.8 vs. 4.6 ± 0.5 vs. 4.5 ± 0.5).In this prospective study, the applicability of myocardial T2 mapping using the GraSE technique was systematically evaluated. The specific sequence parameters derived from sequence optimization allowed for an accurate estimation of myocardial T2 relaxation times in clinically acceptable breath-hold times. After a phantom pre-study and the evaluation of four different sets of sequence parameters in an in-vivo volunteer study, the six-echo variant of the GraSE sequence was judged to offer the best performance for clinical use when taking into account the measurement accuracy and repeatability. The use of the six-echo variant was demonstrated in five clinical cases.The nine-echo variant suffered from a relatively high inter-study variance. This may be attributed to the relatively long shot duration of 118 ms making it more susceptible to motion artifacts. Subsequently, this increased susceptibility to motion artifacts may counterbalance if not even outweigh the benefit of acquiring more data points for estimation of T2. The evaluation of the six-echo variant with lower resolution revealed no benefit with respect to inter-study reproducibility and inter-subject variability. Here, the gain in SNR appears to be counteracted by partial-volume effects. The omission of a start-up echo yielded only a slight overestimation of T2-RT in the phantom measurements, therefore we also evaluated a variant without start-up echo in the in-vivo experiments, again with the aim to increase the SNR. Interestingly, the omission of a start-up echo did not lead to higher values for T2 in the in-vivo experiments, but also did not show a distinct benefit.In existing literature to date a large range of myocardial T2 values for healthy volunteers is reported. At a field-strength of 1.5 Tesla, T2 values from 50 ms  to 59 msThe segmental analyses reported in our study revealed only minor regional variations in healthy volunteers with slightly higher T2 relaxation times in apical segments compared to mid-ventricular and basal segments, similar to previous studies ,22, incl0 field in in-vivo applications may introduce a slight underestimation of T2. Another drawback of the GraSE sequence is that each echo is acquired at a slightly different heart phase. However, with the six-echo variant, the shot duration is less than 85 ms, which should not introduce a significant error in T2 estimation, as long as the trigger delay is set appropriately to achieve image acquisition in the end diastole.T2 mapping based on the GraSE sequence has several inherent pitfalls that must be addressed. First, the use of an EPI readout introduces some T2* weighting and can lead to an underestimation of T2 relaxation times. However, clinically acceptable breath-hold durations can already be achieved with a relatively modest EPI factor of 7, as applied in this study. In contrast, the use of a turbo-spin echo series for T2 mapping can result in a prolongation of observed T2 relaxation time, depending on echo spacing and the applied turbo factor . The GraOne problem using qualitative T2-w imaging is that subendocardial edema may be difficult to differentiate from low flow left ventricular blood , possiblOur study has several limitations. First, the reference values provided in this study are mainly for younger male adults. The reference values can probably not be generalized to older and female patients without further validation. Second, it should be noted that arrhythmia may degrade accuracy and robustness of T2 measurements.In conclusion, our study shows that myocardial T2 mapping using the GraSE technique can be performed within an acceptable acquisition time. However, appropriate sequence settings are necessary to obtain accurate and reliable results. The technique demonstrated here has the potential to overcome some limitations of qualitative T2-w imaging, and may further enhance the diagnostic quality of CMR in patients with suspected acute myocardial injuries.


S-nitrosothiol MitoSNO protects against acute ischaemia/reperfusion (IR) injury by inhibiting the reactivation of mitochondrial complex I in the first minutes of reperfusion of ischaemic tissue, thereby preventing free radical formation that underlies IR injury. However, it remains unclear how this transient inhibition of mitochondrial complex I-mediated free radicals at reperfusion affects the long-term recovery of the heart following IR injury. Here we determined whether the acute protection by MitoSNO at reperfusion prevented the subsequent development of post-myocardial infarction heart failure.Recently it has been shown that the mitochondria-targeted P = 0.01) and tissue fibrosis.Mice were subjected to 30 min left coronary artery occlusion followed by reperfusion and recovery over 28 days. MitoSNO (100 ng/kg) was applied 5 min before the onset of reperfusion followed by 20 min infusion (1 ng/kg/min). Infarct size and cardiac function were measured by magnetic resonance imaging (MRI) 24 h after infarction. MitoSNO-treated mice exhibited reduced infarct size and preserved function. In addition, MitoSNO at reperfusion improved outcome measures 28 days post-IR, including preserved systolic function (63.7 ±1.8% LVEF vs. 53.7 ± 2.1% in controls, MitoSNO action acutely at reperfusion reduces infarct size and protects from post-myocardial infarction heart failure. Therefore, targeted inhibition of mitochondrial complex I in the first minutes of reperfusion by MitoSNO is a rational therapeutic strategy for preventing subsequent heart failure in patients undergoing IR injury. We hypothesized that the burst of ROS emanating from the rapid reactivation of mitochondrial complex I during reperfusion drives the initial acute damage to the heart that leads over time to the development of subsequent heart failure. Therefore, prevention of acute ROS production by complex I during reperfusion by MitoSNO would not only decrease acute IR injury but would also protect the heart from post-MI heart damage and dysfunction measured weeks after the initial MI.in situ open chest mouse model was measured as previously described.12Infarct size following IR in an Cardiac late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) and cine MRI were performed as recently described.12S-nitrosating agent MitoSNO decreases acute cardiac IR injury by S-nitrosation of proteins within mitochondria, and that this protection is primarily due to the functional S-nitrosation of Cys39 on the ND3 subunit of complex I that decreases mitochondrial superoxide production upon reperfusion.We have recently demonstrated that administration of the mitochondria-selective S-nitrosation of ND3 Cys39 can only be achieved in this setting.FigureAn important observation from our previous work was that MitoSNO is only effective when it is perfused into ischaemic tissue, as protective inhibition of complex I by Figure2A). This showed that a systemic i.v. bolus and infusion of MitoSNO beginning 5 min before reperfusion resulted in a significant reduction in infarct size  as well as significantly lower values of the clinically used marker, serum troponin I, 24 h post-MI in the MitoSNO-treated group .We first assessed whether this MitoSNO administration protocol protected against heart tissue damage measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining 24 h post-reperfusion , as well as increased post-MI LV function . Numerical data of MRI analyses are provided in Supplementary material online, Table S1. These findings indicate that MitoSNO affords robust protection against IR injury as assessed by clinically relevant measures 24 h post-MI.In addition, cardiac LGE-MRI 24 h post-MI confirmed drastically reduced infarct size in the mice subjected to acute MitoSNO treatment . In addition, MitoSNO also had no effect on dP/dtmax  or heart rate . Together, these data confirmed that a dosing regimen of MitoSNO that was robustly cardioprotective and which included continual infusion for 20 min had no effect on haemodynamics or blood pressure. Therefore, MitoSNO can be administered as a bolus followed by continual infusion systemically at cardioprotective levels without affecting haemodynamics, which avoids a major limitation that restricts the use of other cardioprotective NO donors.A concern in the use of all NO-based drugs is that release of free NO may result in alterations to blood pressure or haemodynamics that can preclude their clinical use. This should not be a concern with MitoSNO as it is rapidly taken up into mitochondria within tissues where it transfers a nitrosonium moiety directly to mitochondrial thiols, with negligible release of free NO at therapeutic concentrations.The above data show that this dosing regimen of MitoSNO protects heart function against IR damage when measured 24 h after reperfusion. However, a common consequence of IR injury in MI is the subsequent long-term development of heart dysfunction and damage, and it was unknown whether MitoSNO—which acts only in the first minutes of reperfusion—could impact on these long-term sequelae. To see if MitoSNO treatment at reperfusion afforded long-term protection, we assessed how well heart damage resolved over 28 days.Figure4A; Supplementary material online, Videos S1b and S2b). In addition, measurement of tissue fibrotic remodelling 28 days post-MI showed a significant decrease in collagen content in the MitoSNO-treated hearts compared with the control hearts . Therefore, acute administration of MitoSNO upon reperfusion not only decreased acute heart damage but also led to an improved long-term functional outcome for the heart. These results are particularly striking in the context of our recent characterization of the kinetics of MitoSNO activity at reperfusion in vivo.S-nitrosation activity only in the first minutes of reperfusion, which is essential and necessary to mitigate mitochondrial ROS through mitochondrial complex I, and consequent initiation of acute cell death.Determination of LVEF indicated significant improvement in the heart function of MitoSNO-treated mice compared with controls 28 days post-MI (Although recent years have seen an increase in survival after an acute MI, the long-term implications of cardiac IR injury with the development of chronic heart failure remain. Here we find MitoSNO to be a highly promising and clinically applicable cardioprotective therapy, which could be applied acutely after an infarct and would protect the heart not only against acute damage but also against long-term injury. Furthermore, with previous elucidation of the mechanism of MitoSNO action, here we demonstrate that transient MitoSNO action in the first minutes of reperfusion is sufficient to protect from long-term post-MI sequelae. Additionally, since MitoSNO delivers NO highly selectively within mitochondria, the hindering side effects of generalized NO therapy are not present, facilitating the translation into vulnerable MI patients.


Intraaortic balloon pump counterpulsation (IABP) is often used in patients with acute coronary syndrome for its favourable effects on left ventricular (LV) systolic function and coronary perfusion. However, the effects of IABP on LV diastolic function have not been comprehensively investigated. Acute diastolic dysfunction has been linked to increased morbidity and mortality. The aim of this study was to examine the influence of IABP on LV diastolic dysfunction using standard TEE derived parameters.Intraoperative TEE was performed in 10 patients (mean age 65 ± 11 yrs) undergoing urgent coronary artery bypass graft surgery (CABG), who had received an IABP preoperatively. TEE derived measures of diastolic dysfunction included early to late transmitral Doppler inflow velocity ratio (E/A), deceleration time (Dt), pulmonary venous systolic to diastolic Doppler velocity ratio (S/D), transmitral propagation velocity (Vp), and the ratio of early to late mitral annular tissue Doppler velocities (e’/a’). Statistical analyses included the Wilcoxon Sign-Rank test, and a p<0.05 was considered significant.Transmitral inflow E/A ratios increased significantly from 0.86 to 1.07 (p < 0.05), while Dt decreased significantly from 218 to 180 ms (p < 0.05) with the use of IABP. Significant increases in Vp , and e’/a’  suggested a favourable influence of intraaortic counterpulsation on diastolic function.The use of perioperative IABP significantly improves TEE derived parameters of diastolic function consistent with a favourable impact on LV relaxation in cardiac surgery patients undergoing CABG. Congestive heart failure (CHF) remains a major public health concern that is associated with markedly increased mortality. A significant proportion of patients with CHF demonstrate diastolic dysfunction with a normal systolic ejection fraction . DiastolIntraaortic balloon pumping (IABP) was first described by Moulopoulos et al. in 1962 and has since become the most widely used temporary cardiac assist device, most frequently indicated for cardiogenic shock, hemodynamic support during catheterization and/or angioplasty, as well as for refractory post-myocardial infarction or unstable angina ,12. IABPTransesophageal echocardiography (TEE) has become a widely available, practical and safe tool to evaluate patients with diastolic dysfunction ,14. ManyThe data were collected as part of a prospective Institutional Review Board protocol at Brigham and Women’s Hospital, Harvard Medical School, Boston MA.approved protocol with a waiver of informed consent. The study population consisted of hemodynamically stable patients scheduled for CABG surgery who had full support from an IABP (1:1), placed preoperatively for signs and symptoms of myocardial ischemia refractory to medical therapy. Exclusion criteria for this study included intraoperative TEE evidence of significant valvular dysfunction, or either pseudonormal or restrictive patterns of diastolic dysfunction as previously defined . PatientGeneral anesthesia was conduced in all patients following the institutional standards using Fentanyl (3–5 mcg/kg), Etomidate  and Vecuronium  for induction and Fentanyl (up to 5 mcg/kg divided into multiple boli for the duration of the surgery) as well as Isoflurane . Patients did not receive more than 1,5l of i.v. crystalloid fluid total during surgery in addition to the CPB priming solution. On average patients received 500 ml of fluid before CPB and 500–1000 ml after CPB until the end of surgery. None of the enrolled patients needed inotropic support during the surgery (data not shown).Routine, comprehensive intraoperative TEE examinations were performed after induction of general anesthesia by National Board of Echocardiography diplomats. Immediately prior to aortic cannulation, the TEE acquired measures of diastolic function outlined below, were obtained as part of a standard comprehensive intraoperative TEE examination in patients with IABP support. During aortic cannulation, IABP support was paused per routine clinical protocol. Immediately before re-initiating IABP support, the acquisition of TEE measures of diastolic function were repeated again as part of a standard protocol in this patient population. All echocardiographic measurements were obtained over 3 heart beats, and the mean of these measurement used for analysis.Echocardiographic determinants of diastolic dysfunction were obtained according to ASE guidelines . SpecifiThe data were processed using JMP Software  for Statistical Analysis and figures were generated using Kaleidagraph . Wilcoxon Sign ranked test was used and a p-value < 0.05 was considered significant.The study population consisted of 5 female and 5 male patients, median age of 64.7 years ± 11 years. All patients were hemodynamically stable, in sinus rhythm with a heart rate between 80–100 beats/minute at the time of TEE examination, and were not requiring pharmacological hemodynamic support.Parameters of transmitral inflow (E/A-ratio) increased significantly from 0.86 without IABP to 1.07 with IABP support (p < 0.05) . The decIntraaortic balloon counterpulsation (IABP) is the most commonly used form of temporary cardiac assist device, and is often used in cardiac surgical patients with acute coronary syndrome or to facilitate difficulty weaning from CPB. A significant number of critically ill patients experience clinically significant diastolic dysfunction, which increases their overall morbidity and mortality during and after cardiac surgery . In thisIABP related improvements in diastolic function may be related to both physiologic and mechanical factors. Kass et al. previously demonstrated that increased coronary perfusion during IABP support improves tissue elasticity, a major determinant of diastolic dysfunction ,19. SimiThe practical utility and value of echocardiography for the evaluation of diastolic function has been well established over the last two decades and has become an important focus for the development of practice guidelines . The useWhile the impact of IABP on diastolic function has been reported, this concept has not been comprehensively investigated. Khir et al. studied 20 cardiac ICU patients within 36 hours post cardiac surgery, and evaluated left anterior descending (LAD) coronary artery and transmitral E-wave flow velocities, as well as LV long axis free-wall movement. Increased diastolic LAD coronary artery flow velocities and LV free-wall early diastolic lengthening velocity were consistent with improved diastolic function under IABP support when compared to control conditions without IABP . While tIn our present study, the robust association between the use of IABP with an increase in the E/A ratio and a decrease in Dt, as well as increases in the less load-dependent e’/a’ and Vp towards more normal values, is consistent with an improvement in LV relaxation and a favourable impact of IABP on LV diastolic function perhaps by facilitating ventricular unloading. While a decrease in the S/D ratio would also have been consistent with a favourable effect, the absence of a statistically significant result may reflect the low sensitivity of this load-dependent parameter in the volatile hemodynamic environment of the operating room setting. Nonetheless, identifying high-risk patients preoperatively and monitoring their diastolic function intraoperatively may warrant the use of intra-aortic counterpulsation to facilitate separation from CPB.Certain limitations of this presented work are worth noting including its small sample size and the absence of a control population to determine the potential clinical benefits of IABP associated improvements in perioperative diastolic function. Nonetheless, the demonstrated influence of IABP counterpulsation on the evaluated echocardiographic measurements of diastolic dysfunction appears favourable, and suggests that a larger study is warranted to elucidate a role of IABP in acute perioperative diastolic dysfunction.In conclusion, IABP counterpulsation has a positive impact on TEE derived parameters of diastolic dysfunction in patients undergoing urgent CABG, in addition to the previously known beneficial effects on systolic dysfunction. The mechanisms seem to include a favourable direct effect on improving LV relaxation. Further investigation is warranted to determine whether IABP could become a complimentary part of multi-targeted approach towards therapeutic intervention in patients experiencing acute perioperative diastolic dysfunction.


The global burden of disease has driven a broad shift from communicable, maternal, neonatal, and nutritional causes to noncommunicable diseases. Cardiovascular diseases (CVDs) remain the most prevalent cause of human morbidity and mortality all over the world . AccordiThe use of herbal medicines, one of the main therapeutic approaches of complementary and alternative medicine (CAM), can be tracked back thousands of years ago in the East . CurrentDespite enormous interests in the medicinal uses by consumers, there is still a great deal of confusion and misunderstanding about their identification, effectiveness, pharmacology, toxicology, and herb-drug interaction to science world . TherefoA multicentre randomized clinical trial on efficacy and safety of huxin formula in patients undergoing percutaneous coronary intervention” provided evidence on huxin formula, an experienced Chinese medicine formula, for the treatment of patients undergoing percutaneous coronary intervention. “Traditional formula, modern application: Chinese medicine formula sini tang improves early ventricular remodeling and cardiac function after myocardial infarction in rats” evaluated the improvement of early ventricular remodeling and cardiac function in myocardial infarction in rats by sini tang, which is a traditional Chinese classical herbal formula first described by Zhongjing Zhang (150–219 A.D.). “The comparative study on expression of SIRT1 signal transduction by xuefuzhuyu capsule” tested the protective effect of xuefuzhuyu formula, another classical herbal formula in traditional Chinese medicine (TCM), on ischemic myocardial cells induced by ischemia through SIRT1-mediated signal transduction pathway. “Protective effects of shen-yuan-dan, a traditional Chinese medicine, against myocardial ischemia/reperfusion injury in vivo and in vitro” investigated the effectiveness and mechanisms of shen-yuan-dan's pharmacological postconditioning on myocardial ischemia/reperfusion injury by targeting the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway. “β after AMI in ratsLigusticum wallichii extract inhibited the expression of IL-1” addressed the effects of Ligusticum wallichii (chuanxiong) extract on IL-1βexpression in myocardium and central nervous system after acute myocardial infarction.Altogether, we gathered 31 papers for publication, out of which 14 papers were accepted. The original research articles and reviews in this issue cover a wide range of topics, including coronary heart disease, hypertension, heart failure, dyslipidemia, and arrhythmia. Five papers addressed the clinical application and the mechanism of herbal medicines in the treatment of coronary heart disease. “Traditional Chinese medicine syndromes for essential hypertension: a literature analysis of 13,272 patients” analyzed the diagnosis rules and common TCM syndromes of hypertension and recommended the corresponding Chinese herbal medicines and formulas. “Chinese herbal medicine bushen qinggan formula for blood pressure variability and endothelial injury in hypertensive patients: a randomized controlled pilot clinical trial” examined the therapeutic effects of bushen qinggan formula as adjunctive therapy for antihypertensive drugs on mean blood pressure, blood pressure variability, and endothelial function for hypertension.Hypertension is an important public-health challenge worldwide and a major risk factor for stroke, myocardial infarction, vascular disease, and chronic kidney disease. Prevention, detection, treatment, and control of this condition should receive high priority. How about the role of TCM for managing hypertension? One review article “Yiqi huoxue recipe improves heart function through inhibiting apoptosis related to endoplasmic reticulum stress in myocardial infarction model of rats” explored the mechanism of cardioprotective effects of yiqi huoxue formula in rats with myocardial infarction-induced heart failure by inhibiting endoplasmic reticulum stress response pathway.One paper “Crataegus oxyacantha). “Effect of Crataegus usage in cardiovascular disease prevention: an evidence-based approach” reviewed the cardiovascular pharmacological properties of Crataegus in vivo and in vitro. “Evaluation of a Crataegus-based multiherb formula for dyslipidemia: a randomized, double-blind, placebo-controlled clinical trial” examined the effects of a multiherb formula containing Crataegus pinnatifida on plasma lipid and glucose levels in Chinese patients with dyslipidemia.Two papers discussed the cardiovascular protective effects of Hawthorn  polysaccharides on interleukin-1β expression by human aortic smooth muscle cells (HASMCs) and the underlying mechanism. A review article “Aspirin resistance and promoting blood circulation and removing blood stasis: current situation and prospectives” provided insight into the relationship between aspirin resistance and blood stasis syndrome and explored the therapeutic role of Chinese herbal medicines with promoting blood circulation and removing blood stasis for this condition.Finally, “Recently, a great progress has been made focusing on the effectiveness and safety of herbal medicines in patients with CVDs. Some RCTs and systematic reviews provided strong evidence for clinical usage. The special issue presented the updated knowledge of partial herbal medicines for CVDs, which unraveled a complex posttranscriptional gene-regulating machinery and paved the evidence-based way.Xingjiang XiongXingjiang XiongFrancesca BorrelliFrancesca BorrelliArthur de Sá FerreiraArthur de Sá FerreiraTabinda AshfaqTabinda AshfaqBo FengBo Feng


Cardiac complications are among the most serious problems of thalassemia intermedia patients. The current study was initiated to address the latter issue through the study of the echocardiographic findings and correlate it with clinical characteristics of thalassemia intermedia patients in Duhok, Kurdistan region, Iraq.An echocardiographic assessment of 61beta-thalassemia intermedia cases was performed. It included 30 males and 31 females, with a mean age 19.6 ± 7.5 years. The standard echostudy of two-dimension and M-mode measurements of cardiac chambers were done. The continuous doppler regurgitant jet of tricuspid and pulmonary valves were recorded. Left ventricle diastolic function was assessed by pulsed doppler of mitral valve inflow. To correlate the clinical with echocardiographic findings, patients were divided, according to tricuspid regurgitant velocity, into three groups .Tricuspid regurgitant velocity <2.5 m/sec, 2.5-2.9 m/sec and ≥3 m/sec occurred in 42(69%), 11(18%) and 8(13%) respectively. Comparing to other groups patients with tricuspid regurgitant velocity ≥3 m/sec were older and included more males. They had lower hemoglobin levels, but higher ferritin levels. Their age at diagnosis and the age of the initiation of blood transfusion were later. Most of them had significant exertional dyspnea. They also had relatively lower left ventricle ejection fraction values. Right ventricular diameter and right atrial size were larger in the same group. Tricuspid regurgitant velocity as a continuous predictor was associated positively with age, cardiac volumes and pulmonary regurgitation though negatively associated with ejection fraction.Echo-derived right and left side cardiac complications are not uncommon in thalassemia intermedia patients. Therapeutic trails targeting these complications are indicated, and echocardiographic assessment is necessary to be offered early for thalassemia intermedia. Thalassemia Intermedia (TI) is an inherited hemoglobin disorder that is characterized by a significant genetic and clinical heterogeneity.Cardiovascular involvement represents a well-known complication and the primary cause of mortality in TI. It is mainly determined by the fact that both ventricles have to maintain a high cardiac output level through a stiff vascular bed. Pulmonary hypertension and steady increase in tricuspid regurgitant jet followed by right heart failure dominates the clinical picture.The left ventricle has to maintain a high cardiac output in a continuous state of both volume and pressure overload which consequently contributes to left ventricular impairment with time –3.Several factors have been reported to interfere in the pathophysiology of cardiovascular abnormalities in TI. However, the key mechanism is the chronic tissue hypoxia and chronic hemolysis with its consequences . The scrThis is a prospective study of 61 beta-thalassemia intermedia patients . It included 30 males and 31 females, with a mean age of 19.6(SD7.5) years. All patients were evaluated by history taking and physical examination, laboratory studies, and underwent transthoracic echocardiography between June 2010 and June 2011. Either patients or their relatives provided written informed consent.Transthoracic echocardiography was performed for all patients by Vivid 3(GE) Echo systems. The standard two-dimension and M-mode measurements of the cardiac chambers including left ventricle ejection fraction (LVEF %) were taken. Cardiac volumes and dimensions were indexed by body surface area. Tricuspid regurgitation was assessed in the apical four chambers, parasternal short axis views, and a minimum of three sequential complexes were recorded. Continuous doppler sampling of the peak regurgitant jet to estimate the right ventricular to right atrial systolic pressure gradient by the modified Bernoulli equation was obtained. To assess the mean pulmonary artery pressure, the pulmonary artery to right ventricular pressure gradient was estimated from the peak pulmonary regurgitant flow velocity (V) in parasternal short axis view by the simplified Bernoulli equation PG = 4 V2) [ V2 [4]. To correlate between the clinical and Echo findings within the studied sample, the patients were divided according to tricuspid regurgitant velocity (TRV) into three groups  . AdditioSince patients have been classified into three groups according to the TRV, 42(69%) had TRV <2.5 m/sec, 813%) had ≥ 3 m/sec, the remaining 11(18%) had between these two values. Patients with highest TRV were older. Almost all of them were over 12 years old. Their age at diagnosis and first blood transfusion were later. Majority of them were male with significant exertional dyspnea. Their Hemoglobin level was lower, but ferritin was higher. Most of them were splenectomized. BSA was higher in the same group as shown in Table 3% had ≥ Higher TRV values were significantly associated with increased cardiac chamber indices. These indices included left ventricle end diastolic diameter (LVEDD), left ventricle end systolic diameter (LVESD), left atrial (LA) diameter, and right ventricle (RV) diameter and right atrial (RA) size. There was a relatively slight decrease in the ejection fraction at the highest levels of jet velocity. There was an increase in the mean of LV wall and septal thickness with higher TRV values, though it did not reach the significant difference. The peak gradients of tricuspid and pulmonary valves were significantly associated with an increasing degree of TRV as shown in Table Scatter plots of TRV with age and echocardiographic predictors showed a significant association with age, LVEDD, LVESD, LA diameter, RV diameter, RA area and PR peak gradient. But there was a negative association with LVEF % as shown in Figures The main findings of the study are the following: first, both the left and right cardiac chambers, especially the dimensions and volumes, were increased in TI patients with time. Second, patients with higher TRV were presented with advancing age, later age at diagnosis, later onset of initiation of blood transfusion, predominant male gender, lower hemoglobin level, higher ferritin rates, and higher percentage of splenectomised patients. Third, the LVEF % was normal. It was relatively lower for the patients with higher TRV. Three patients had features of congestive heart failure.Some of TI patients have an exceptional hemodynamic pattern consistent with right ventricular cardiomyopathy and PHT as well as the left ventricular abnormalities that can be a leading cause of cardiopulmonary problems in these patients. Frequent monitoring of cardiac function in patients may indicate that those at risk of developing symptomatic cardiac disease. These patients might then become candidates for more intensive therapy including blood transfusion and sustained iron chelation , 8.The present study showed that the left ventricular dimensions including (LVEDD and LVESD) in TI were increased with an increase in the TRV. This is in consistence with previous studies by Nouri et al., Aessopos et al. and Vaccari et al. , 2, 10. Evaluating LV systolic function, the mean LVEF % in the studied sample was normal. There was a negative association between TRV and LVEF % with correlation coefficient equal to -0.39). However, comparing LVEF % among subgroups, there was a significant difference because of a possible skew caused by a very small highest TRV sample that included three patients with features of congestive heart failure. According to Aessopos et al. 9. Howeve found siAssessing LV diastolic function in TI patients, the mean LA volume and diameter were significantly higher in TI with higher TRV. There was also a progressive increase of the late filling velocity and a relative decrease of the mitral inflow E/A ratio though statistically insignificant. This suggests an increase in LV end diastolic pressure, reflecting an alteration in diastolic property and impairment of LV relaxation, most probably caused by iron deposition which gradually, if not properly managed, leads to restrictive cardiomyopathy , 15, 16.Congestive heart failure (CHF) in this study was encountered in 3(4.9%) patients. Yet, the rates of CHF in Aessopos et al.  and AessIn the present study 8(13%) of cases had TRV ≥ 3.0 m/sec which corresponds to doppler peak systolic tricuspid gradient (PTG) greater than 30 mm Hg and 6(9%) had TRV > 3.2 m/sec. Despite the lack of cardiac catheterization data the last value was considered to represent the actual cases of PHT in this study relying on diagnostic conclusions of PHT from a recent Italian study . In AessThis study, similar to above analysis, proved that TRV was significantly higher in splenectomised cases, lower hemoglobin, higher ferritin levels, and later onset of blood transfusion. On the contrary, it concluded that higher TRV was associated with male gender. Unsurprisingly, despite of less regular blood transfusion among higher TRV subgroup in the year before this study, relative higher ferritin levels among them was found which was partly attributed to lesser utilization of iron chelation in the same subgroup, the increased risk of progressive ferritn accumulation with advancing age and increased rate of gasrointerstinal iron absorption in TI , 24.A recent study demonstrated a significant correlation between iron overload in the liver and pulmonary artery systolic pressure independent of LV filling pressures . Though Managing TI patients with cardiac involvement and PHT, regular transfusion and iron chelation therapy is indicated even without evidence of cardiac siderosis. This suggests that TI patients may still be at risk for iron related cardiac dysfunction through exposure to non-transferrin bound iron , 28. HowThe main limitations of this study, which is, to my best knowledge, the first attempt conducted in Iraq on echocardiographic evaluation of TI, include reliance on conventional echocardiography. Other diagnostic tools, such as tissue doppler, speckled tracking echocardiography, cardiac catheterization, and cardiac MRI, were not accessible. The studied sample is relatively small to generalize the outcomes, though it resulted in a correlation between accumulative changes in the clinical characteristics and echocardiographic parameters.Conventional echocardiography for TI cases is a useful tool for preliminary evaluation of cardiac status. It could uncover many cardiac abnormalities that possibly complicate TI. The abnormalities and the underlying pathophysiology could be targeted in the future.The author is a senior cardiologist at Duhok heart center and teaches cardiology at Department of Medicine, University of Duhok, Iraqi Kurdistan.


Veno-arterial extracorporeal membrane oxygenation (ECMO-CPR) is a life-saving rescue for selected patients when standard cardiopulmonary resuscitation fails. The use is increasing although the treatment modality is not fully established. Resuscitated patients typically develop a detrimental early post-arrest cardiac dysfunction that also deserves main emphasis. The present study investigates an ECMO-CPR strategy in pigs and assesses early post-arrest left ventricular function in detail. We hypothesised that a significant dysfunction could be demonstrated with this model using magnetic resonance imaging (MRI), not previously used early post-arrest.In eight anaesthetised pigs, a 15-min ventricular fibrillation was resuscitated by an ECMO-CPR strategy of 150-min veno-arterial ECMO aiming at high blood flow rate and pharmacologically sustained aortic blood pressure and pulse pressure of 50 and 15 mmHg, respectively. Pre-arrest cardiac MRI and haemodynamic measurements of left ventricular function were compared to measurements performed 300-min post-arrest.All animals were successfully resuscitated, weaned from the ECMO circuit, and haemodynamically stabilised post-arrest. Cardiac output was maintained by an increased heart rate post-arrest, but left ventricular ejection fraction and stroke volume were decreased by approximately 50 %. Systolic circumferential strain and mitral annular plane systolic excursion as well as the left ventricular wall thickening were reduced by approximately 50–70 % post-arrest. The diastolic function variables measured were unchanged.The present animal study demonstrates a successful ECMO-CPR strategy resuscitating long-lasting cardiac arrest with adequate post-arrest haemodynamic stability. The associated severe systolic left ventricular dysfunction could be charted in detail by MRI, a valuable tool for future cardiac outcome assessments in resuscitation research.FOTS 4611/13.Institutional protocol number: The online version of this article (doi:10.1186/s40635-015-0061-2) contains supplementary material, which is available to authorized users. Patients with cardiac arrest not responding to standard cardiopulmonary resuscitation (CPR) can be resuscitated by veno-arterial extracorporeal membrane oxygenation (ECMO-CPR). Advances in technology and equipment have made ECMO-CPR much more attractive during recent years, and its use is increasing. The enthusiastic quest for novel resuscitation techniques may be due to the fact that standard CPR frequently fails. Although ECMO-CPR is claimed to represent “a frontier of resuscitation” , it is nThe study was a controlled experimental animal study. A listing of experiment details is presented in Tables The experimental protocol was approved by the Norwegian National Animal Research Authority. The animal experiments were performed in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes . Personnel who handled the animals were certified with Federation of Laboratory Animal Science Associations category C. Detailed information according to the ARRIVE guidelines   is preseEight pigs were included in the study; each pig was kept fasting overnight-with free access to water, pre-medicated in the pig box housing and weighted before a short transport to the MRI research operating theatre. A mixture of intravenous anaesthesia standardised by weight and suspended in Ringer’s acetate solution was infused at 10 ml/kg/h (Table 2 within 20 ± 5 kPa and PaCO2 within 5.0 ± 0.5 kPa. Each pig had standard monitoring during the experiment-including electrocardiography (ECG), pulse oximetry, end-tidal expiratory CO2, hourly urine output and oesophageal temperature.Each pig received a tracheostomy and intravascular catheters by a midline neck incision. A micro-manometer pressure transducer was positioned in the LV via an 8 French vascular introducer in the right carotid artery Table . Both inAfter preparation and a following 30-min stabilisation period, baseline cardiac MRI and haemodynamic measurements of LV function were obtained. An arterial and a mixed venous blood sample were also analysed.2 surface area. An oxygen/air mixer enabled an adjusted sweep gas oxygen fraction and sweep gas flow rate. The circuit was without surface coating and primed with Ringer’s acetate solution. The machinery was initially set to standby with the vascular lines clamped.After baseline assessments, the pig was connected to a custom-made femoro-jugular veno-arterial ECMO circuit Table . The ECMVentricular fibrillation (VF) was induced by an electrical stimulator connected to the right ventricular pacing lead. VF was confirmed by ECG shape and aortic blood pressure drop, and the ventilator was set to standby. After 15 min of untreated VF, ECMO-CPR was initiated with initial blood pump speed at the maximum 4540 rounds per minute. The sweep gas was set at the same flow rate as the ECMO blood flow rate, the fraction of oxygen to 100 % and the circuit temperature to 38.0 °C (normothermia in the pig). After 5 min of ECMO-CPR, fibrillation was terminated by external damped sinusoidal waveform 360 Joule monofasic shocks through standard anterior/anterior pads until sinus rhythm was obtained. The extracorporeal support continued at the same blood flow rate for a total of 150 min. Repeated blood gas analyses were performed, and the sweep gas flow rate and the oxygen/air mixture were adjusted according to the protocol. The lowest acceptable mean aortic pressure (MAP) and pulse pressure after defibrillation and regain of spontaneous cardiac beating (ROSB) was set by protocol consensus to 50 and 15 mmHg, respectively. Intravenous adrenaline (epinephrine) 10–25 μg boluses were given to ensure these criteria were met initially. If in need of continued inotropic support, infusion of the beta-adrenergic agonist dobutamine 5 μg/kg/min was started , and theAt 285 min post-arrest, cardiac function was re-assessed by the PA catheter and the LV pressure transducer. Arterial and mixed venous blood samples were analysed, and a second cardiac MRI was made. Finally, the pig was euthanized.Image acquisition, interpretation and post-processing were done according to the recommendations from the Society for Cardiovascular Magnetic Resonance . CardiacThe LV was assessed by adjacent parallel short-axis slices covering the full volume of the LV and by long axis slices. Series of cinematographic images of the cardiac cycle were recorded by retrospective ECG-gating without breath-holds. The images were analysed to estimate end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV = EDV-ESV), ejection fraction (EF = SV/EDV) and cardiac output (CO = SV · heart rate (HR)). In addition, mid LV radial wall thickening and mitral annular plane systolic excursion (MAPSE) were measured. Wall thickening was averaged from measurements in the septum and the lateral wall, and MAPSE averaged from antero-septal-and postero-lateral measurements.Slices in short axis were also magnetically gridded throughout the cardiac cycle (tagging) to assess peak global systolic LV circumferential (Lagrangian) strain by harmonic phase analysis . Strain phase) and cardiac output (COphase). It has been stated that this technique “should provide the most accurate measurement available of cardiac output” . Th. Th21]. s method  in a 50-aO2 and CvO2) were calculated from the arterial and mixed venous blood samples, respectively. Oxygen delivery (DO2 = CO∙CaO2) and oxygen consumption (VO2 = CO∙arterio-venous oxygen difference (CaO2 -CvO2)) were calculated.The arterial and venous oxygen content  were recorded throughout the experiments Fig. .Fig. 1Coα was set to 0.05. A paired two-tailed t test was used to compare baseline- and post-arrest measurements. The degree to which volumetrically and phase-contrast estimates of SV change correlated was quantified by a Pearson’s correlation analysis.Statistical analyses of normality (D’Agostino-Pearson omnibus and Shapiro-Wilk) and of equality of variances (Levenes) supported the use of parametric tests. Data are reported as mean ± standard deviation if not otherwise stated. The statistical significance level The pigs weighed 49.7 ± 2.3 kg, preparation took 119 ± 29 min and cardiac MRI scan time was 63 ± 15 min. Prior to induction of cardiac arrest activated clotting time was 349 ± 83 s, and ECMO circuit priming volume was 538 ± 17 ml. The experiments lasted 747 ± 71 min.All animals were successfully defibrillated by a median of 1 shock (range 1–4). MAP at the time of defibrillation was 52 ± 8 mmHg with an ECMO blood flow rate of 4.60 ± 0.15 l/min. VF spontaneously reemerged after ROSB in two pigs demanding one additional defibrillation in both.Continuous HR, MAP and MPAP outside the MRI scanner are presented in Fig. max whereas LVPmax did not significantly change; neither did EDP, dP/dtmin nor tau.Haemodynamic measurements and blood gas values at baseline and post-arrest are presented in Table O2 was maintained due to the increased HR, but mixed venous oxygen saturation dropped from 69.4 ± 13.1 % to 44.0 ± 7.9 % (p < 0.001) post-arrest, corresponding to a 66 ± 38 % increase in VO2 at almost unchanged DO2 (mean difference –74 ml/min (p = 0.29)).Arterial blood gas values remained virtually unaltered post-arrest, and the haemoglobin concentration was stable Table . The DO2p < 0.001) and SV decreased from 62 ± 9 ml to 30 ± 7 ml (p < 0.001). The lowered EF was related to a 58 ± 39 % increase in ESV as EDV was maintained (mean difference −8.9 ml (p = 0.22)). The reduction in SV was consistent with the change in SVphase (Pearson r = 0.7). The minor reduction in CO (0.5–0.7 l/min) was not statistically significant. Consistent with the reduced SV the absolute value of global systolic circumferential strain decreased from −17.4 ± 4.2 % to −5.1 ± 3.3 % (p < 0.001) and MAPSE was reduced from 12 ± 1 mm to 6 ± 1 mm (p <0.001). Similarly, mid LV radial wall thickening was severely affected by a reduction from 58 ± 18 % to 20 ± 9 % (p < 0.001). The reductions in MAPSE and wall thickening were consistent between the different measuring locations in the LV.Cardiac MRI measurements at baseline and at 308 min ± 8 min post-arrest are presented in Table In this study, ECMO-CPR emerged as an effective tool resuscitating the heart from long-lasting cardiac arrest. Fifteen minutes of VF induced a severe early post-arrest LV dysfunction that was demonstrated in detail by cardiac MRI. This is the first study to describe early post-arrest LV dysfunction by cardiac MRI.There are no ECMO-CPR guidelines for patients with refractory cardiac arrest. As a consequence, several strategies are implemented targeting various circuit flows, arterial pressures, oxygen saturations and core temperatures. Indications may also differ between centres, although a refractory normothermic arrest with a no-flow period of less than 5 min will generally be accepted for ECMO-CPR. A 60-min time-frame is often stated as the clinical accepted limit of low-flow (the period of standard CPR) before ECMO is established. In animals, without extracorporeal support the probability of successful ROSC decreases drastically when VF is untreated for more than 10–12 min, and it is almost impossible to achieve sustainable ROSC in pigs after 15 min of untreated VF –26. In tAll pigs were successfully resuscitated by our protocol using a short (150 min) ECMO-CPR run with maximal flow, initially 100 % oxygen, normothermia, MAP above 50 mmHg and pulse pressure above 15 mmHg. The diameter, length and position of the venous cannula usually limit the ECMO blood flow rate. In our study, the venous cannula was placed as deep as the diaphragm, with its multiple side holes covering the full length of the caval veins and the right atrium. With this placement, the ECMO blood flow rate during ECMO-CPR could be kept as high as baseline CO pre-arrest without incidents of “suck down”, and increased CVP could be avoided. The low MPAP during ECMO-CPR indicated a relatively low blood flow through the pulmonary circulation, and thus a limited amount of blood entering the LV. This venous unloading, combined with adequate myocardial perfusion, is known to be particularly important to the post-arrest myocardium .In peripheral veno-arterial ECMO, blood from the arterial cannula flows upwards in the descending aorta, increasing LV afterload. LV distension may then develop with compromised myocardial perfusion and hydrostatic pulmonary oedema. Although coronary perfusion was not measured, serious hypo-perfusion was most likely prevented by our protocol with the attention to adequate MAP and pulse pressure, the latter to assure LV emptying. The pressures were maintained above the lower limits by the customised dosage of positive inotropic medication. Dobutamine enhance LV function post-arrest . All pigCardiac MRI is often considered as the reference standard for the assessments of LV volumes and function. In addition, we assessed post-arrest LV haemodynamics by a PA catheter and a LV pressure transducer. Cardiac MRI demonstrated a severe impairment of LV function after ECMO-CPR. The systolic dysfunction was evident both by the global volume and flow measurements and by the LV motion measurements, mid LV radial wall thickening, MAPSE, and global systolic circumferential strain. Interestingly, post-arrest dysfunction was characterised by almost similar reductions (approximately 50–70 %) of systolic LV motion in all three deformation directions, indicating a global LV impairment.max and HR [PA and SVPA measurements, however, corresponded well with the MRI measurements, but PA assessments gave less information.When compared to cardiac MRI the LVP and dP/dt measurements did not reflect the severity of systolic LV dysfunction. LVP was maintained because MAP was pharmacologically sustained as prescribed by the protocol. An increased inotropic state post-arrest-a result of the dobutamine infusion and an endogenous catecholamine response , 34 probx and HR , 36. In x and HR , 38. TheIn addition to the success of ECMO-CPR, our study demonstrates that a detailed assessment of early post-arrest LV dysfunction is feasible by cardiac MRI. The model may be relevant for future research on ECMO-CPR strategies and cardiac outcome.min post-arrest, indicating normal LV relaxation. Taken together, this can imply that LV dysfunction after ECMO-CPR is a failure of myocardial contractile function, not predominantly related to LV relaxation ability. Increased HR and dP/dtmax with reduced SV, and preserved diastolic function with maintained dP/dtmin, tau, and end-diastolic pressure-volume relationship have also been demonstrated after hypoxic cardiac arrest in pigs [Diastolic LV dysfunction was not demonstrated by the LV function variables included in this study. Post-arrest ESV increased without changes in EDV or EDP, indicating reduced systolic emptying of a ventricle adequately filled in diastole. A preserved diastolic function was supported by an unaltered tau and dP/dt in pigs . Early pO2. However, the substantial drop in mixed venous oxygen saturation indicates that DO2 was insufficient for the increased post-arrest metabolic needs. The increased VO2 may be due to recovery from oxygen debt and activation of other oxygen consuming processes such as systemic inflammation, induced by ischemia and reperfusion [The reduced SV post-arrest was compensated for by an increased HR, maintaining CO and Derfusion .Our experimental model was different from a clinical ECMO-CPR scenario. In our study, healthy pigs were included, and cardiac arrest was introduced electrically. The duration of no-flow-exceeding usual clinical limits was intended to achieve a combination of survival and a certainly measurable post-arrest cardiac dysfunction. Cardiovascular function was in focus, and no attention was paid to neurological or other organ outcome. Pre-arrest heparinisation is a common experimental approach that also differs from the later on (or omitted) clinical heparin administration. Sham-operated animals were decided not included as the experiments were completed without complications, haemodynamic stability was adequate Fig. , and venAn ECMO-CPR strategy of 150-min veno-arterial ECMO aiming at high blood flow rate and pharmacologically sustained aortic blood pressure and pulse pressure allowed successful resuscitation of long-lasting cardiac arrest with adequate post-arrest haemodynamic stability in pigs. MRI imaging of the in vivo beating heart demonstrated a severe early post-arrest LV dysfunction. Systolic LV function variables were substantially reduced whereas diastolic function was preserved. Cardiac MRI will be a valuable tool for future research on post-arrest cardiac dysfunction including assessment of cardiac outcome after ECMO-CPR.


Mitral valve repair (MVR) shows clinical and economic superiority over mitral valve replacement in patients with dystrophic and rheumatic regurgitation, but outcomes are less certain in chronic ischemic mitral regurgitation (IMR). We hypothesize that MVR may have adverse effects on LV hemodynamics resulting from suboptimal annuloplasty geometry and post-repair mitral valve stenosis whose consequences are most acutely felt in IMR patients because of their impaired LV function. To test this hypothesis, we qualitatively described post-repair hemodynamics and measured LV inflow quantities  after MVR in sheep.The University of Pennsylvania IACUC approved all experiments. Dorsett swine (n = 7) were anesthetized, underwent baseline MRI and echocardiography followed by MVR with varying annuloplasty size and shape . At 1 week post-repair, all animals underwent a follow-up MRI and echocardiography. The 4D PC MRI data was post-processed to remove static tissues, residual aliasing, and eddy currents. Blood flow velocity vectors were visualized using stream- and pathlines (CEI Ensight) and hemodynamics were qualitatively summarized. Peak transmitral flow velocity, pressure (modified Bernoulli equation) and the angle of the inflow jet were computed at the mitral valve vena contracta.Diastolic transmitral flow in naïve sheep was characterized by a single intraventricular vortex (toroid) visualized by two counter-rotating vortices in the 3 chamber long-axis view. The posterior mitral valve vortex was slightly smaller than the anterior vortex. The transmitral pressure significantly increased  in all animals post-repair causing mitral valve stenosis, including in the largest 32 mm Physio Ring. We found that there was a rotation 11.5 ± 1.3° to 19.8 ± 5.7° directed towards the anterior MV leaflet between the normal and post-repair diastolic inflow axis  as shown in Figure Mitral valve repair can result in significant mitral valve stenosis and abnormal LV hemodynamics.The authors gratefully acknowledge support from the National Institutes of Health through awards K99HL108157 and R01HL63904.


Ventricular volumetrics play a fundamental role in cardiac magnetic resonance imaging analysis. Accuracy is of course paramount, and thus crucial that the image data set is precise.This poster defines the correct positioning of the short axis (SA) cinematographic images, and the rationale behind it. Since most volume studies concentrate on the left ventricle (LV) slice positioning focuses on the mitral valve annulus.It is firstly important to define what you are measuring. The ventricles include the volume between the inlet/atrioventricular valve, the ventricular apex and outlet/ventriculo-arterial valve; imaging must cover this whole volume.At analysis a debate may then arise about how much an inlet valve indents the ventricle, or an outlet valve indents the artery.Typically the short axis slice has a thickness of 8-10 mm. It is recommended that the whole thickness of the slice be in the ventricle, otherwise partial voluming of the atrium will occur. Failure to do this may produce a 5-10% error in volumetrics.Using the 4 chamber and 2 chamber long axis images, position the first short axis slice using the end diastolic time point 0. The posterior aspect of the slice thickness should be on the mitral valve annulus to include all ventricle on the first slice, but not atrium Fig.  The slicYou will note in Fig. None as a reference poster.Accurate definition of the structure to be measured and subsequent optimal positioning of the basal SA slice will lead to greater confidence that both ventricles are imaged in their entirety. This leads to more precise diagnosis and better study reproducibility.National Institute of Health Research. Biomedical Research Unit.


This bird’s eye view from the 2015 European Society of Cardiology (ESC) congress hosted in London from August 29 to September 2 includes highlighted abstracts on multimodality imaging. At this ESC meeting, 407 imaging abstracts (40% of abstracts submitted under the topic of imaging) were presented. Four experts on echocardiography (VD), cardiac computed tomography (CT) (SA), cardiac magnetic resonance (CMR) (US), and nuclear imaging (JK) summarized 4 to 7 abstracts in these areas that were of most interest to them. These abstracts were integrated by one of the Editors of the Journal (JB).Speckle tracking echocardiography (STE) continues providing novel insights into cardiac mechanics and prognosis. The Berliner Frauen Risiko evaluation study assessed the association between left atrial (LA) reservoir, conduit and booster pump functions measured with STE and left ventricular (LV) diastolic dysfunction grade in 449 women.Early diagnosis of arrhythmogenic right ventricular dysplasia (ARVD) using STE was the objective of the study presented by Teske and coworkers.P = .02) compared with patients with reduced LV dyssynchrony, confirming observational results in heart failure patients with wide QRS complex.4The results of a sub-study from the EchoCRT trial (Cardiac resynchronization therapy in heart failure with narrow QRS complex) were presented, focusing on the prognostic implications of persistent or worsened LV dyssynchrony after CRT implantation.Three-dimensional transthoracic echocardiography (3D TTE) attracts significant attention. Tricuspid valve regurgitation in patients with RV pacing leads has poor prognosis.P = .95). However, this was not a primary outcome measure. Average radiation exposure was not increased by the use of CTA/FFR-CT in either cohort. Ninety-day major adverse cardiac event (MACE) rates were not increased in those patients who underwent CTA rather than invasive angiography. All in all, the study reassuringly showed that CTA/FFR-CT can reduce the number of unnecessary invasive angiograms, and specifically reduce the number of angiograms showing no stenosis, in patients with suspected coronary disease—hence well serving its “gatekeeper” role.In cardiac CT, most of the presented research at the ESC Congress 2015 was in relation to clinical applications, and relatively few abstracts concerned new technical developments. The use of “virtual” fractional flow reserve, derived from the anatomic information provided by coronary CT angiography (CTA), received most attention. The PLATFORM studyNumerous abstracts dealt with the prognostic value of coronary CTA. Bom et al evaluated 1551 patients with low-to-intermediate risk of coronary artery disease who underwent coronary CTA as well as calcium scoring.Marwan et al reported the results of the German cardiac CT registry regarding the presence of coronary artery lesions in coronary CTA of 2016 individuals without coronary calcium.3 of calcium measured with a lower threshold of 850 HU to accept a structure as “calcium.” The degree of aortic valve calcification (optimum cut-off: 267 mm3) was also a predictor for the need to perform balloon post-dilatation. Mitral valve interventions may also profit from CT imaging. In 25 patients planned for edge-to-edge mitral valve repair, CTA and transesophageal echocardiography showed excellent agreement regarding parameters such as leaflet length, annulus diameters, and left ventricular dimensions.12An increasingly important area is the use of cardiac CT for non-coronary interventions, for example, in heart valve disease. Fonseca et al presented a series of 131 patients who underwent transcatheter aortic valve implantation with a balloon-expandable (36%) or self-expanding (64%) prosthesis.Important topics in research with cardiac magnetic resonance (CMR) at the ESC Congress 2015 included assessment of diffuse myocardial fibrosis, advanced diagnosis of coronary artery disease, and risk stratification for ICD implantation.r = −0.23; P = .011). Moreover, an increase in extracellular volume of the remote area of ≥1% at 6 months follow-up was observed in 43% of patients.Validation of pre-contrast T1 mapping values and myocardial extracellular volume measurement with CMR techniques as surrogates of interstitial diffuse fibrosis was the objective of several studies including patients with different cardiomyopathies.Coronary microvascular disease is characterized by angina, positive tests for ischemia, and the absence of epicardial coronary stenoses. CMR can be useful in these patients to determine coronary flow reserve by measuring coronary sinus flow at rest and during pharmacologic stress, and then myocardial perfusion reserve is calculated as the ratio between stress coronary sinus flow/baseline coronary sinus flow in 245 consecutive patients. Patients with a myocardial perfusion reserve below or equal to the mean (2.75) had worse outcome compared to patients with preserved myocardial perfusion reserve (>2.75).P = .003) and higher frequency of myocardial scar  than patients who did not present with events.Patients with dilated cardiomyopathy and LVEF<35% are candidates for ICD implantation as primary prevention of sudden cardiac death. The incremental prognostic value of LVEF and the presence of myocardial scar assessed with CMR were evaluated in 270 patients with dilated cardiomyopathy.In addition, an interesting multicenter trial studied whether the extent and heterogeneity of late gadolinium enhancement (LGE) areas (identifying the infarct border zone) predicted appropriate ICD therapy in 55 patients with ischemic cardiomyopathy and 62 with dilated cardiomyopathy.In nuclear cardiology, not only a large fraction of abstracts focused on coronary artery disease and myocardial perfusion imaging (MPI) but also other methods such as innervation imaging gained increasing attention.Al-Mallah et alThe prognostic value of single-photon emission computed tomography (SPECT) MPI was addressed in 564 patients who were evaluated for renal transplantation.The detection of vulnerable plaques using non-invasive imaging has gained a lot of interest over the recent years. PET imaging using F-18-fluorodeoxyglucose (FDG) has been used in numerous studies to detect vascular inflammation in the aorta and carotid arteries. Recently, studies have used FDG and F-18-fluoride to detect active plaques in human coronary arteries. Locorotondo et alSeveral studies focused on cardiac innervation imaging using SPECT and I-123-iodine metaiodobenzylguanidine (MIBG) or PET with [11C]hydroxyephedrine (HED). Garcia Gonzalez et alExercise training has beneficial effects in heart failure patients. Valborgland et al evaluated whether cardiac MIBG uptake would improve after 3 months of exercise training.Finally, the effect of beta-blocker therapy on cardiac sympathetic nerve function in patients with idiopathic pulmonary arterial hypertension was studied by Rijnierse et al.


Heart failure is mostly caused by disease of the left ventricle, but the right ventricle may play a more important role in functional capacity and prognosis of heart failure patients than is often realised. Thus, right ventricular (RV) function has been well established to be a better marker for exercise capacity than left ventricular (LV) function in both ischaemic and dilated cardiomyopathy (DCM) , and is It is increasingly recognised that development, progression, prognosis and potentially also treatment of cardiovascular disease are not only dependent on the severity of disease, but are also influenced by age and gender. A potential explanation for the effect of gender on cardiovascular morbidity may be that RV function differs between men and women, with women generally having a smaller right ventricle with a higher ejection fraction (EF) . Indeed,In the present issue of the Netherlands Heart Journal, Martínez-Sellés and co-workers investigated whether differences in RV function between male and female patients could explain, at least in part, why women with DCM have a better prognosis than men. They found that RV dysfunction was only present in patients with more severe LV dysfunction (LVEF < 35) and that particularly in the group of patients with the worst LV function (LVEF < 25 %), RVEF was higher in women than men . AlthougCVON, the Netherlands Cardiovascular Research Initiative: Award Number: CVON2012-08 Phaedra.None declared.


Personalised treatment of heart disease requires an understanding of the patient-specific characteristics, which can vary over time. A newly developed implantable surface acoustic wave pressure sensor, capable of continuous monitoring of the left ventricle filling pressure, is a novel device for personalised management of patients with heart disease. However, a one-size-fits-all approach to device sizing will affect its positioning within the pulmonary artery and its relationship to the interrogating device on the chest wall on a patient-specific level. In this paper, we analyse the spatial orientation and morphology of the pulmonary artery and its main branches in patients who could benefit from the device and normal controls. The results could optimise the design of the sensor, its stent, and importantly its placement, ensuring long-term monitoring in patient groups. Heart failure is one of the leading causes of morbidity and mortality worldwide –4. The dSeveral implantable devices have been developed to monitor LV filling pressures noninvasively, either indirectly or directly –13. The The only device which can provide continuous monitoring of the filling pressure at rest and during exercise is the implantable surface acoustic wave pressure sensor (SAWPS)  currentlThe goal of this study is to analyse spatial orientation and morphology across different patient populations. While studies on the measurements of the PA diameter at the level of the bifurcation have been performed , the exaThe surface acoustic wave pressure sensor (SAWPS) is a novel wireless transponder used in conjunction with a miniature communication system for continuous evaluation of PA pressure in patients with severe heart failure and those with pulmonary hypertension. It allows for accurate measurements to be taken on a continuous basis, and then transmitted remotely, allowing for blood pressure to be continuously monitored throughout waking and sleeping activities . The impPrevious studies by Murphy et al. , 18 were2 for NYHA Class II patients, 51 ± 8/1.86 ± 0.20 m2 for NYHA Class III, 62 ± 10/2.07 ± 0.25 m2 for NYHA Class IV and 30 ± 5/1.84 ± 0.37 m2 for PH and 32 ± 3/1.92 ± 0.05 m2 for normal subjects.The study includes normal subjects and a representative sample of the patients who could potentially benefit from the SAWPS device Table . 15 hearFor each patient, images of the PA and chest wall structure were acquired. Selected heart failure and pulmonary hypertension patients had archived computed tomography (CT) images, scanned using a dual-source 128-slice FLASH Siemens CT scanner. The acquisition for heart failure patients followed a breath-hold, cardiac-gated scanning protocol with a slice thickness of 0.6 mm. Pulmonary hypertension patients had breath-hold, non-gated CT scans with a slice thickness of 1 mm. For the controls, gated scans were used.All subjects’ data utilised in this study were based on data previously acquired for clinical purposes after approval from the Ethics Committee.To determine the range of PA sizes and orientations the SAWPS device must accommodate, 3D analysis of the PA was performed to extract the necessary parameters to ensure that the final device(s) will fit in the majority of patients. The workflow is shown in Fig. The DICOM images were imported into Mimics  for segmentation of the PA (including left and right pulmonary arteries) and the chest wall. The models of the structures were then exported as triangular meshes in STL format. In addition, the centrelines of the PA models were automatically produced by Mimics and exported. The STL models were imported into MeshLab  to removThe proximal section of the PA was divided into two main segments. The first was the main pulmonary artery (MPA) leading to the left pulmonary artery (LPA), as shown in Table Pi is the ith point in the centreline, was used as the normal to the ith orthogonal cutting plane. There was one orthogonal cutting plane for each point in the centrelines.To attempt to normalise PA centreline lengths, the centreline for each MPA-LPA structure was linearly interpolated and the MPA and LPA were sampled to 50 points each, both separated by the bifurcation that leads to the RPA. Likewise, the centreline for each RPA structure was linearly interpolated and sampled to 40 points, with the number of points chosen empirically. These points were ordered and the lengths along the PA segments  for the ages of the different patient cohorts. Height and weight of patients from the groups were not statistically significant (p > 0.1).Statistical analysis of the basic data of the study population Table  showed sp = 0.02). However, when examining the entire length of the MPA through to the LPA .In Fig. LPA Fig. , this enp > 0.05).Figure 2/m) while the bottom row shows the average diameters of the same contours. The general trend over the average is greater cross sectional area and diameters for the PH group and lower parameters for the Controls. The average diameter from the MPA to the LPA, i.e. after the bifurcation, lowers by approximately 6 mm, indicating that the stent, if it is to straddle the bifurcation, needs to be flexible enough to adapt to the two diameters.Figure p < 0.05). No statistical significance was found at the start of the LPA across the patient groups. These measurements will affect the diameter required of the stent.From Table p > 0.05).Figure Regarding the orientation of the PA segments with respect to each other, the angles between the RPA and LPA did not change much across the patient groups Fig. . The aveIt is proposed that at least two separate stent sizes will be required to take into consideration the measurements found in this study. In particular, the length of the stent is recommended to be 45 mm for the NYHA Class 4 patients while 40 mm is sufficient for the HF patients. This is shown in Fig. The data presented in this paper was analysed to optimise the design of the SAWPS Device and could be used to select a range of different stent sizes to fit patient groups with similar PA morphology and spatial orientation. It will also guide clinicians to determine the most suitable position of the device within the PA and its branches.The SAWPS device is a permanent implant and therefore consideration of the progression of the morphology of the PA is essential. The first design decision was that the whole device should rest against the PA wall and become endothelialised to reduce the risk of thromboembolism. An alternative approach has been taken by CardioMems  where a The longitudinal aspect and low profile of the device are well suited to lying against the inner wall of a tube. The antenna is flexible and will naturally rest against the wall if the vessel has a concave longitudinal surface, which is the case on the anterior surface of the MPA. The distal part of the antenna will be further held against the wall by the flowing blood; the proximal part needs to be held against the wall during endothelialisation to avoid generating vortices in the blood flow and the risk of emboli.The stent can extend into the LPA or RPA—but given the significant discrepancy in size between the main PA and its branches it must be designed with different segmental radial sizes and strengths. The sharp angulation of the RPA means that the LPA is an easier choice for placement of the distal part of the device. The anterior wall from the MPA into the LPA is essentially a single concave surface. Extension across the bifurcation is permissible if the stent struts are spaced widely enough (open-cell design) to allow for unobstructed flow into the partially jailed right branch, as shown in Fig. Given the importance of placing the antenna as close as possible to the chest wall to enhance signal transmission, the antenna should be radiopaque to allow for optimal positioning and orientation within the pulmonary artery during implantation. For better wave propagation and RF signal noise reduction, positioning the device in the MPA segment is preferable. This is due to the fact that the MPA is the nearest segment to the sternum and chest wall and is not covered by other anatomical structures . With optimal placement of the implant, there will be much greater tolerance on the optimal location of the ID antenna on the chest wall and more freedom to make an ergonomically-driven decision on placing the external antenna—for instance, within clothing.At a recent initial preclinical test, an implantable SAWPS was delivered by an 18 F catheter into the main PA of a 75-kg swine via the femoral vein. The position and orientation of the device were adjusted using fluoroscopy and transoesophageal echocardiography before final deployment. The implanted sensor was interrogated and the signal quality was evaluated. The transmitting power and the received signal quality confirmed the previously measured performance of the implantable antenna with respect to the main PA orientation. The sensor orientation was observed to be parallel to the chest wall and the implantation depth was measured at 5 cm using the acquired images. The implanted sensor was interrogated for 30 min and the received signal was monitored in real time. The received signal quality was consistently good for about 25 min but started to deteriorate afterwards before the signal was completely lost at 30 min. The autopsy confirmed that migration of the implant into the LPA was the cause of signal loss. The migration occurred because the stent was undersized; the signal loss was due to the non-ideal orientation and depth of the LPA with respect to the chest wall in swine.Analysis has been performed on PA orientation and morphology from four patient groups and a control group and results show variance in PA segment lengths that will affect device placement. Initial preclinical tests confirmed the need for correct sizing and positioning of the device to ensure good received signal quality. These measurements will aid in stent design for future iterations of the SAWPS device and will ensure better management of patients with heart disease.


This study was designed to assess whether cardiovascular magnetic resonance imaging (CMR) in Duchenne muscular dystrophy carriers (DMDc) may index any cell milieu elements of LV dysfunction and whether this cardiac phenotype may be related to genotype. The null hypothesis was that myocardial fibrosis, assessed by late gadolinium enhancement (LGE), might be similarly accounted for in DMDc and gender and age-matched controls.Thirty DMDc patients had CMR and genotyping with 37 gender and age-matched controls. Systolic and diastolic LV function was assessed by 2D-echocardiography.Absolute and percent LGE were higher in muscular symptomatic (sym) than asymptomatic (asy) DMDc . There was no correlation between LGE and age. LGE was seen most frequently in segments 5 and 6; segment 5 was involved in all asy-DMDc. Subepicardial LGE predominated, compared to the mid-myocardial one (11 out of 14 DMDc). LGE was absent in the subendocardium. No correlations were seen between genotyping , confined to the exon’s study, and cardiac phenotype.A typical myocardial LGE-pattern location (LV segments 5 and 6) was a common finding in DMDc. LGE was more frequently subepicardial plus midmyocardial in sym-DMDc, with normal LV systolic and diastolic function. No genotype-phenothype correlation was found. Xp21-linked Duchenne muscular dystrophy carrier (DMDc) status is characterized by skeletal muscle weakness ranging from absence of muscular symptoms to mild or even rapidly progressive Duchenne-like muscular dystrophy. The muscle disease may be associated with cardiac involvement, from no symptoms to overt dilated cardiomyopathy (DCM). It is well established that a minority of carriers is more likely to develop early severe DCM -5 whose Myocardial fibrosis is best detected and quantified by cardiovascular magnetic resonance (CMR)  both in The present study was aimed at investigating a large consecutive series of DMDc, proven by DNA analysis and undergoing LGE. The null hypothesis was that myocardial fibrosis, assessed by LGE, might be similarly accounted for in DMDc and gender and age-matched controls. We investigated: a) the proportion of DMDc with myocardial LGE and cardiac involvement and b) the cardiac genotype-phenotype relationships if any.We enrolled 30 consecutive female DMDc aged 11 to 63 years (mean age 36 ± 5 years) followed at the Center for Neuromuscular Diseases (Uildm) of Rome, Italy and 37 age-matched healthy female controls . Controls had no cardiac symptoms, history of cardiomyopathy or skeletal muscle disorders and presented with normal electrocardiography (ECG), 2D-echocardiography and CMR. No drug was given to DMDc and controls. Creatine kinase levels were screened in the control group and in all DMDc. The study was approved by the Ethical Board of the Catholic University of Rome. Written informed consent was obtained from all patients and controls. Exclusion criteria were left ventricular (LV) systolic and diastolic dysfunction, diabetes, hypertension, ECG changes suggestive of ischemic heart disease, atrial flutter/fibrillation, any degree of atrioventricular block, valvular heart disease, and LV hypertrophy.DMDc and controls underwent physical examination and surface 12-lead ECG. DMDc, none with cardiac symptoms, were classified regarding muscle involvement as: (1) asymptomatic (asy), when characterized by the presence of high CK levels and/or minor myopathic signs like muscle cramps and myalgia, without muscle weakness and (2) symptomatic (sym), when presenting variable degrees of muscle weakness . The degConventional 2D-echocardiography was performed by the same operator (VG) in all patients, using a SONOS 5500 . LV systolic function was assessed by ejection fraction (EF) from LV volumes (derived using the modified Simpson’s rule). LV systolic dysfunction was defined as LVEF ≤55%. LV diastolic function was assessed by Doppler analysis as previously reported .Extensive molecular analysis was performed in all DMDc. Mutation detection was carried out using Multiplex-Ligation dependent Probe Amplification (MLPA) (deletions and duplications) or sequencing , accordingly to the DMD guidelines . AlthougCMR was performed using a 1.5-T MR system  with a cardiac 5-element phased-array receiver coil . All images were acquired with ECG-gating, breath-hold steady-state free precession (SSFP) cine sequence for functional analysis, in contiguous short-axis view  from the mitral annulus to the apex and 3 long-axis planes, with the patient in a supine position. To assess the contribution of cardiac edema, we performed a T2-weighted segmented triple inversion recovery (T2-wSTIR) imaging module, in 3 short axis slices  at the base, mid, and apex and a single long axis-slice in a 4 chamber view, using for imaging a functional surface coil intensity correction. All patients underwent an LGE imaging protocol  for myocardial scar using a segmented Inversion Recovery-Gradient Echo (IRGE) sequence, adjusting the inversion time and nulling the signal of normal myocardium. Contrast CMR images were acquired on average 10 to 15 min after injection of cumulative 0.1 mmol/kg gadolinium DTPA . Images were obtained in 8 to 14 short-axis and 3 radial long-axis planes. Myocardial enhancement on LGE images was assessed visually and considered positive to a signal-intensity threshold of >2 SD above the mean intensity of a remote reference region  and intehttp://www.ncss.com) was used. A value of p < 0.05 was considered statistically significant.After testing for normal distribution based on standard parameters, intergroup differences and relations were compared by analysis of variance (ANOVA), correlation matrices and/or unpaired Wilcoxon t-test. NCSS software version 2007 , clustered in the proximal rod domain, . The exon’s study, the mutation type analysis and the affected gene region and protein domain study, did not show correlation between the cardiac phenotype and genotype.Dystrophin, genomic analysis and dystrophin gene mutations study. We identified 16 different exons deletions of the dystrophin gene, two duplications and a nonsense mutation (Table in vivo histologic assessment [per se might be the result of combined factors including abnormal cardiac energetics and genetic factors [This is a cross-sectional study presenting a large group of DMDc in whom, although modest in absolute and relative quantities Table , we obsesessment  and althsessment ,29. LGE  factors . HistopaSome exons’ duplications were more frequently associated with DCM . In our A major limitation of our CMR technique was that T1 mapping for measuring diffuse myocardial fibrosis  was not The myocardium in DMDc is a cell milieu where LV dysfunction might be virtually present. We have shown that LGE is frequently found, it is not correlated with age and gene deletion type, and in absolute and relative terms it is modest. However, subepicardial LGE is present yet at an early age. We speculate that when LGE extends from basal infero-lateral subepicardial level to midmyocardium, cardiac involvement might be advanced. Presently, we ignore whether subepicardial or midwall LGE may progress towards other myocardial segments, and how long is needed and/or whether this potential progression may in some way influence DCM development. The association between LGE presence and quantities and the development of LV dysfunction while time passes, remain to be investigated. Based on the present study, the largest conducted thus far, CMR may be useful in DMDc to define the starting LV segment, an information which may not be obtained by ECG, conventional Doppler or 2D-echocardiography.Atl-201-MPS: Adenosine thallium-201 myocardial perfusion scintigraphy; CMR: Cardiovascular magnetic resonance; DCM: Dilated cardiomyopathy; DMDc: Duchenne muscular dystrophy carrier; ECG: Electrocardiography; EF: Ejection fraction; IRGE: Inversion recovery gradient echo; LGE: Late gadolinium enhancement; LV: Left ventricular; MLPA: Multiplex-Ligation Probe Amplification; Pcr/ATP: Phosphocreatine to adenosine triphosphate ratio; RV: Right ventricular; SSFP: Steady-state free precession; TDI: Tissue Doppler imaging.The authors declare that they have no competing interests.Conception and design: VG and PEP. Drafting of the manuscript: VG, PEP, ER. Analysis and interpretation of data: VG, GC, SW DellaS, SS. Molecular and genetic studies: AF, FG. Critically revision of the manuscript for important intellectual content: VG, PEP, M Di G, ER, GC, GA, FS. All Authors read and approved the final manuscript.