Gly389Arg and Ser49Gly polymorphisms of β1-adrenoreceptors (β1-AR) can influence the cardiovascular prognosis. However, the possible effect of Gly389Arg and Ser49Gly polymorphisms on heart function in thyrotoxicosis has not been studied. We investigated the possible link between Gly389Arg and Ser49Gly polymorphisms and echocardiography parameters in 165 normotensive patients with a thyrotoxicosis without any cardiovascular disorders. Echo-CG was performed according to standard protocol before and during the thyreostatic treatment. Our data demonstrate that both Gly389Arg and Ser49Gly polymorphisms have very moderate influence on the risk of left ventricular hypertrophy and atrial fibrillation with no statistically significant effects on cardiac function and the development of cardiovascular complications.Human cardiac  In thyrotoxicosis (TT), identification of genetic predictors, defining remission, and the risk of cardiovascular complications are of a great importance. Candidates for genetic prediction are the genes regulated by triiodothyronine and playing a key role in changing of the myocardial contractility and arrhythmogenesis. Among them are type 2 deiodinase gene polymorphisms, affecting the severity of clinical manifestations and cardiac complications in thyrotoxicosis , 2. Anotogenesis –5. Sinceications , 7.β1-AR [ ADRB1 polymorphisms in cardiovascular diseases such as ischemic heart disease and arterial hypertension gave only modest results. In several studies, a link between the Arg389Gly polymorphism and resting heart rate (HR) and diastolic arterial pressure was reported, while in other studies only a slight correlation with the left ventricular hypertrophy was noted [ in vitro showed that Ser49Ser homozygous subjects have lower functional activity of adenylate cyclase compared to Gly49Gly homozygous subjects, but higher sensitivity to stimulation by isoproterenol [Arg389Gly genotype has 73% frequency in Caucasians and is associated with threefold increase in basal and stimulated adenylate cyclase activity and sensitivity to stimulation of as noted , 11. Stuoterenol . In the oterenol –17. Seveoterenol , 19. Howoterenol . ADRB1 on clinical and EchoCG parameters and arrhythmias in patients with Graves' disease (GD) and TT. The dynamics of these parameters after euthyroidism achievement was also evaluated depending on genotype.The impact of these polymorphisms on HR, blood pressure, and echocardiographic (EchoCG) parameters was not studied in patients with Graves' disease and thyrotoxicosis (TT). The aim of our study was to investigate the influence of Arg389Gly and Ser49Gly polymorphisms ofage 18–55,thyrotoxicosis associated with Graves' disease at the primary examination.The study was performed according to Helsinki declaration, the study protocol was approved by local Ethical Committee of Almazov Federal Medical Research Centre, and written informed consent was obtained from all subjects prior to investigation. We included 165 patients with GD according to the following criteria:concomitant cardiovascular diseases that can cause persistent abnormal changes of Echo CG parameters ,condition which has contraindications with long thyrostatic therapy ,chronic intoxication ,pregnancy or plan of pregnancy,amiodarone therapy.Control group (CG) included 101 age- and gender-matched euthyroid blood donors  receptor, and/or increased radioactive iodine uptake at the moment of examination or in anamnesis. Investigation included clinical examination , level of TH and TSH, EchoCG, and ECG, genotyping. The thyrostatic therapy included thioamides (mercasolil) in dose 30 mg followed by dose decreased to 10 mg (supporting dose) after restoration of euthyroidism. Patients had initial metoprolol therapy within 3–5 weeks discontinued after normal heart rate and euthyroidism achievement. The patients were reexamined 1 year following the beginning of the therapy.Free thyroid hormones and antibody serum levels were measured by immune-enzyme assay using ACCESS 2 analyzer  and immunochemical test systems : free triiodothyronine , free thyroxin , and TSH . The levels of common T3  and common T4  were detected by immunoenzyme assay .The echocardiography examination was performed on Sonoline GGOS (Siemens) and included the following parameters: left atrial diameter (LAD), left ventricular mass index (LVMI), interventricular septum (IVS), left ventricle posterior wall (PWT), left ventricular end-diastolic volume (LVEDV), relative wall thickness (RWT), and isovolumic relaxation time (IVRT).Left ventricular mass was calculated according to the formula recommended by ASE-2005 . For desμL volume of the peripheral blood by phenol-chloroform extraction. Genotyping was performed by real time polymerase chain reaction on Applied Biosystems 7500 Real Time PCR System using reaction premix purchased from “Applied Biosystems.”DNA was isolated from 200 χ2 test. Clinical and laboratory data were addressed using χ2 test, unpaired Student's t-test, Mann-Whitney U-test, ANOVA, Kruskal-Wallis H-test, and Fisher exact test. A two-tailed P < 0.05 was considered statistically significant, and all analyses were performed by STATISTICA 6.0 software package .The results were expressed as frequencies, mean ±S.D., or median and percentiles 25–75 (P25–75). Allelic frequencies were determined by gene counting, and deviations from the Hardy-Weinberg equilibrium were verified using an P = 0.01) (Genotype distribution for Gly389Arg polymorphism is presented in  = 0.01) .We performed comparative analysis of clinical and laboratory parameters in patients with thyrotoxicosis depending on genotype . During The EchoCG parameters did not differ significantly in groups with different genotype. Left ventricular hypertrophy (LVH) was detected in 11% of patients in group 1 (GG), 26.5% of patients in group 2 (CG), and 22.6% of patients in group 3 (CC). Interestingly, concentric LVH was not observed in patients with GG genotype. The prevalence of pulmonary hypertension was measured in 107 patients and was confirmed in 60 (56%). The mean values of pulmonary hypertension did not differ between the genotype groups. Clinical investigation was repeated in all patients after a year of thyrostatic therapy and euthyroidism. No significant difference in blood pressure, heart rate, and TH was revealed see .In EchoCG parameters, there was multidirectional dynamics of LVMI in allele GG carriers compared with allele CC carriers .Follow-up examination after one year showed the change in patients groups with different type of LV geometry: in GG group LVM was normalized, in CC group LV hypertrophy reduced to 21%, and in heterozygous group the number of patients with LV hypertrophy increased to 27.5%. Multidirectional dynamics for these groups was presented in The evaluation of rhythm disturbances associated with thyrotoxicosis showed that AF was not present in GG genotype carriers; heterozygous patients had AF in 19% (18/94) and homozygous CC carriers in 9.7% (6/62). Supraventricular extrasystoles were also less frequent among GG genotype patients .In summary, analysis performed for Gly389Arg polymorphism did not reveal any significant difference in the parameters studied but showed a tendency for lower frequency of LV hypertrophy and absence of concentric hypertrophy in GG genotype carriers. The tendency for higher frequency of AF was observed in heterozygous genotype carriers.Genotype distribution for Ser49Gly polymorphism is presented in The clinical characteristic of patients with Graves' disease and thyrotoxicosis according to genotype is presented in P = 0.06) was noted when we compare all three genotypes and when we compare A allele with GG genotype (P = 0.02)  . ADRB1 Ser49Gly variant with LVM, we performed more detailed analysis of LV geometry in this group. In patients with GG genotype, LV hypertrophy was observed in 55.6% , AA genotype carriers had LV hypertrophy only in 15.5% , and heterozygous patients had LV hypertrophy in 26% . There was no significant difference in CH and EH, but tendency for less frequency of LVH was in AA genotype carriers (P = 0.09).Due to the correlation of GG genotype ofPulmonary hypertension was detected in 75% of GG carriers, 55.9% of AG carriers, and 56.7% of AA carriers. There was no difference in the presence and degree of pulmonary hypertension between various genotypes.Follow-up examination after one year showed no significant difference in blood pressure, heart rate, and TH dynamics between genotype groups . At follThere was no difference in atrial arrhythmias between patients with various Ser49Gly genotypes. In summary, the carriers of AA genotype of polymorphism of Ser49Gly had lower frequency of LV hypertrophy.We also analyzed the possible effect of haplotype combination in Ser49Gly and Arg389Gly polymorphisms on clinical parameters and frequency of LVH and AF in patients with TT. There was no statistically significant effect of haplotypes on any of the clinical parameters analyzed, in spite of several tendencies which did not reach the significance level . ADRB1. These results concur with the majority of studies that investigated these parameters in other cardiovascular disorders. Earlier, analysis of heart rate during stress echocardiography and heart rate in patients with hypertension gave no evidence linking heart rate with different ADRB1 genotypes [Our study revealed no significant difference in heart rate and blood pressure level in patients with thyrotoxicosis carrying different genotypes in polymorphisms Gly389Arg and Ser49Gly ofenotypes –25. In cenotypes . The samenotypes . Thus, wOur data demonstrate that both polymorphism Gly389Arg and polymorphism Ser49Gly have a very moderate tendency to influence the LV hypertrophy risk. While in several studies the association of LV hypertrophy with CC genotype in polymorphism Gly389Arg was confirmed, there are no data on Ser49Gly and the risk of LVH. According to well-known influence of heart rate on LV hypertrophy, such correlation would be logical.The separate analysis of polymorphisms Gly389Arg and Ser49Gly did not show a significant difference in blood pressure level and the risk of AF between various genotype carriers. Some studies reported that AA genotype (Ser49) carriers of polymorphism Ser49Gly have a lower heart rate and lower frequency of rhythm disturbances and therefore lower mortality . HoweverA significant limitation of this study is the small size of the groups. There is a possibility that the accumulation of additional data will reveal more significant differences. Further analysis on larger population of patients is needed.


Left ventricular (LV) remodelling in the setting of the chronic pressure overload of aortic stenosis (AS) appears to differ according to gender. Women appear to have an improved survival compared to men following transcatheter aortic valve implantation (TAVI) but the reasons for this are yet to be established. Potential mechanisms include differing patterns of LV reverse remodelling, LV fibrosis regression and reduced aortic regurgitation in females. We sought to establish using cardiac magnetic resonance (CMR) imaging, the reference standard non-invasive technique for LV mass and scar quantification, whether there were any gender differences in these parameters before and after TAVI.42, Circle Cardiovascular Imaging, Alberta, Canada).53 patients with symptomatic severe aortic stenosis undergoing TAVI were prospectively enrolled between April 2009 and March 2014. Patients with contraindications to CMR were excluded and all patients provided informed written consent. All patients underwent an identical 1.5T CMR protocol  prior to and at a median of 6 months following TAVI (IQR 5-6 months). Multi slice, multiphase imaging was carried out using a standard steady-state free procession pulse sequence in the short axis to cover the entire left ventricle. Late gadolinium enhancement imaging was performed 10min after the administration of 0.2mmol/kg of gadoteric acid . Quantitative analysis was performed using dedicated computer software  less baseline myocardial scar  and a smaller indexed LV end diastolic volume (LVEDVi) than men . A trend towards a smaller indexed left atrial volume (LAVi)  and better ejection fraction  was also seen in women when compared with men. Six months following TAVI, there was no significant difference seen between genders with regards to LV mass regression, change in ejection fraction, change in myocardial scar burden, change in left atrial volume or change in aortic regurgitant fraction  (PG/11/126/29321).


AAR measurement is useful when assessing the efficacy of reperfusion therapy and novel cardioprotective agents after myocardial infarction. Multi-slice  T2-STIR has been used widely for its measurement, typically with a short axis stack (SAX) covering the entire left ventricle, which can result in long acquisition times and multiple breath holds. This study sought to compare 3-slice T2-short-tau inversion recovery (T2- STIR) technique against conventional multi-slice T2-STIR technique for the assessment of area at risk (AAR).CMR imaging was performed on 167 patients after successful primary percutaneous coronary intervention. 82 patients underwent a novel 3-slice SAX protocol and 85 patients underwent standard 10-slice SAX protocol. AAR was obtained by manual endocardial and epicardial contour mapping followed by a semi- automated selection of normal myocardium; the volume was expressed as mass (%) by two independent observers.p < 0.0001) and a low Bland-Altman limit  between the 2 analysis techniques. A further 82 patients underwent 3-slice imaging alone, both the 3-slice and the 10-slice techniques showed statistically significant correlations with angiographic risk scores . There was low inter-observer variability demonstrated in the 3-slice technique, which was comparable to the 10-slice method . Acquisition and analysis times were quicker in the 3-slice compared to the 10-slice method (3-slice median time: 100 seconds (IQR: 65-171 s) vs (10-slice time: 355 seconds (IQR: 275-603 s); p < 0.0001.85 patients underwent both 10-slice and 3-slice imaging assessment showing a significant and strong correlation  contains supplementary material, which is available to authorized users. Cardiac magnetic resonance (CMR) imaging has become the reference standard in the quantification of ventricular volumes, function and tissue characterisation . T2 weigCurrently methods for assessing AAR require coverage of the whole left ventricle with the acquisition of 10–12 continuous myocardial short axis slices, with each slice acquired with a single breath hold of 10–15 seconds. This lengthens the overall duration of a CMR scan in patients early after a myocardial infarction and therefore techniques that shorten examination times may be advantageous to improve patient compliance. Furthermore, despite advances in semi-automated software, post processing and analysis of these images requires time-consuming manual analysis.Our goal was to assess the AAR using 3 non-contiguous slices in comparison to conventional multi-slice contiguous slices in patients following successful primary percutaneous coronary intervention (PPCI) for acute myocardial infarction.Between April 2008 and November 2012, 167 patients with ST-segment elevation MI successfully reperfused through primary percutaneous coronary intervention (PPCI) and undergoing CMR within the first week after reperfusion were studied. All of these patients had been consented into interventional clinical trials including stem cell trial and pharmacological intervention trials (REGENERATE-AMI NCT00765453), NITRITE-AMI (NCT01584453) and myocardial oedema in acute myocardial infarction (NCT00987259)) [453, NITRCardiac magnetic resonance (CMR) imaging was performed on a 1 · 5 T Philips Achieva scanner with a cardiac 32-channel phased array coil. Balanced steady-state free precession cine imaging was used to acquire 10–12 short axis slices  with one slice per breath-hold. Sequence parameters were 1.5 ms echo time (TE), 3.1 ms repetition time (TR), and acquired voxel size was 1.8 × 1.86 mm with a typical FOV of 360 mm in the phase encoding direction. We acquired 45 phases with 25 % phase sharing. Parallel imaging (SENSE) was used with an acceleration factor of 2.0.Myocardial oedema was assessed using fat suppressed T2-weighted triple inversion turbo spin echo STIR (Short tau inversion recovery) imaging . Either 10-slices  or 3-slices  with one slice per breath-hold  images were acquired ten minutes after injection of a dose of 0 · 2 mmol/kg of gadoterate meglumine (Dotarem). A T1-weighted segmented inversion-recovery gradient echo pulse sequence  was used to obtain 10–12 short axis slices (matched with the short-axis cine images) with one slice per breath-hold. The inversion time was adjusted individually according to a T1 scout sequence (Look-Locker). Images were acquired every other heart beat with 2 signal averages.All patients underwent coronary angiography according to local cardiac catheterisation laboratory protocols and standard primary percutaneous coronary intervention (PCI) with insertion of at least one stent after admission with a an acute STEMI with an ECG showing ST-segment elevation of 0.1 mV in two or more limb leads or 0.2 mV in two or more contiguous precordial leads, or presumed new left bundle branch block. Flow of the infarct related artery prior to PCI was characterized using the TIMI system  . The AAR42, Circle Cardiovascular Imaging Inc, Calgary, Alberta, Canada). All images were anonymised, batched and analysed in a blinded fashion by two experienced CMR operators. Manual endocardial and epicardial contours were drawn to calculate myocardial mass (MM), followed by semi-automated selection of normal myocardium with the oedema volumes being expressed as a mass (%). Area at risk  was described as >2SD in signal intensity from remote normal myocardium [All analysis was performed using a dedicated software reporting system  are given. Intra-observer variability and correlation between methods was calculated using the coefficient of intraclass correlation coefficient (ICC). All p-values are 2-sided and a value of <0.05 was considered to indicate statistical significance. The comparison of the different correlation coefficients was performed using a 2-tailed Fisher’s z-transformation statistical analysis. Data plotting used in analyzing the agreement between the different methods was made with Bland-Altman analysis . All stan = 85) or 3-slice (n = 82) T2-STIR imaging for AAR assessment as previously described , were included in the analysis. The mean ages of patient was 56.2 ± 10 · 2 years and 88 % were male. Clinical, CMR and angiographic characteristics of the population are shown in Table p = 0.9800). There were strong correlations between 3-slice AAR and 10-slice AAR in this patient group   . Within the 10-slice AAR group the AAR ranged from 11.5 % of the myocardium to 46.8 % (mean 27.8 ± 7.3) and the 3-slice AAR assessment of the same patients showed similar values ranging from 10.0 to 52.0 % (mean 27.9 ± 8.3) . There was a statistically significant correlation with discrepant strength between the 10-slice AAR and the APPROACH angiographic risk score  with a weaker correlation seen between the 10-slice AAR and BARI angiographic risk score  , there was a low correlation between 10-slice AAR and infarct EAS .Angiographic risk assessment was performed for all patients in this study. In the 10-slice AAR group the BARI angiographic risk score ranged from 10.5 % to 47.4 % (mean 26.6 ± 10.1), and the APPROACH angiographic risk score ranged from 6.5 % to 47.8 % (mean 29.2 ± 9.0 %) of the left ventricle (LV) myocardium. There was good correlation between the 2 angiographic risk scores (24) Fig. . For ther = 0.88 p < 0.0001). Within the 3-slice AAR group the AAR ranged from 3 to 56 % (mean 30.1 ± 9.8). The 3-slice AAR assessment was correlated with both angiographic risk scores  , there was a low correlation between 3-slice AAR and infarct EAS .In all 3-slice AAR studies the BARI angiographic risk score ranged from 10.5 to 47.4 % (mean 30.9 ± 10.5) and the APPROACH angiographic risk score ranging from 6.5 to 47.8 % (mean 33.4 ± 9.3 %) of the LV myocardium. As was seen within the 10-slice group there was a good correlation between the 2 angiographic risk scores , with a lower correlation seen between infarct size and 3-slice AAR studies (r = 0.48 p < 0.0001)  . There was a significant correlation between infarct size and 10-slice AAR (01) Fig. . Myocard12) Fig. .Fig. 5Cop < 0.0001)  and the 10-slice group had a median acquisition time of 355 seconds (range: 275–603 seconds), with a significant difference seen between the two groups (01) Fig. .Fig. 7Cop < 0.0001). The inter-observer timing variability correlated well between analysers; 3-slice r = 0.96 p < 0.0001, 10-slice r = 0.93 p < 0.0001)  and 10-slice group had a median time of 137 seconds (IQR: 133–144 seconds), with a significant difference seen between the two groups (01) Fig. .p < 0.0001). The median time of 143 seconds (IQR: 131–171 seconds) in the 3-slice group was on average 5 minutes quicker than the 10-slice group (median time of 492 seconds (IQR: 472–565 seconds).Combined acquisition and analysis time showed a significant difference between the two groups (p = 0.0057).Overall scan time was taken from initiation of first scouting image to the end of the final image. Within the 3-slice group there was a median time of 2163 seconds (IQR: 1740–2520 seconds) and 10-slice group had a median time of 2448 seconds (IQR: 1986–2835 seconds), with a significant difference seen between the two groups (p = 0.15). For the Bland-Altman plot, the 95 % limits of agreement  contained 94.1 % (80/85) of the difference scores. The mean bias of the measurements between observers was −0.32 %, and the maximum and minimum difference was 5.0 % and −5.6 % respectively.3-slice STIR imaging showed low inter-observer variability. For the Bland-Altman plot, the 95 % limits of agreement  contained 95.1 % 78/82) of the difference scores. The mean bias of the measurements between observers was 0.08 %, and the maximum and minimum difference was 8.0 % and −7.0 % respectively  equal clinical information; 2) reduced imaging protocol time; 3) reduced breath holding time; and 4) reduced combined acquisition and analysis time.The present study was performed on a small limited patient population in patients who after suffered a STEMI and underwent successful PPCI with the majority of patients receiving a novel cardioprotective intervention at the time prior to undergoing CMR imaging within 3 days. One of the studies included in the analysis recruited only patients with anterior infarcts due to occlusions of the LAD which may have lead to bias in the results.This study was able to validate 3-slice oedema CMR quantification of AAR showing good correlations with current full coverage imaging techniques. The quicker and easier analysis method is advantageous for both patients and clinicians and could shorten acquisition time in patients who are either claustrophobic or have difficulty with breath holding technique.Additional file 1: Figure S1.Consort diagram. Flow chart of study design summarizing flow of patients through study. (JPG 25 kb)Additional file 2: Figure S2.Correlation coefficient between 3-slice MM and 10-slice MM. Association between 3-slice MM quantification and 10-slice MM quantification assessed by CMR. (TIFF 114 kb)Additional file 3: Figure S3.Difference between T2-STIR distributions after myocardial infarction. Screenshot demonstrating the increased signal seen in the basal, mid and apical slices in a T2-STIR imaging technique after a ST elevation myocardial infarction involving each of the major epicardial coronary arteries. (JPG 88 kb)


Background. Hypertrophic cardiomyopathy (HCM) is mostly autosomal dominant disease of the myocardium, which is characterized by myocardial hypertrophy. Vascular endothelial growth factor (VEGF) is involved in myocyte function, growth, and survival. The aim of study was to analyze the clinical significance of VEGF in structural and functional changes in patient with HCM. Methods. In a group of 21 patients with nonobstructive HCM, we assessed serum VEGF and analyzed its association with morphological and functional parameters. Compared to healthy controls, serum VEGF was increased: 199 (IQR: 120.4–260.8) ng/L versus 20 (IQR: 14.8–37.7) ng/L, P < 0.001. VEGF levels were associated with left atrium diameter , left ventricle ejection fraction , fractional shortening , left ventricular mass , LV mass index , vena cava inferior diameter , and peak gradient of tricuspid regurgitation . Conclusions. Increased VEGF level is associated with structural and functional parameters in patients with HCM and serves as a potential tool for diagnostic process of these patients. The incidence of HCM is approximately 1 in 500 0.2%) of the general population % of the . Systemi in vitro and angiogenic inducer in in vivo models. VEGF is secreted as a glycosylated homodimeric protein of 46 kDa that is made up of two 24 kDa subunits linked by disulphide bonds.Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogenThe tissue distribution of these VEGF receptors includes vascular smooth muscle cells, osteoblasts, cardiomyocytes, myofibroblasts, neurons, and various tumor cells . It has Study population consisted of patients with nonobstructive hypertrophic cardiomyopathy. The diagnosis of hypertrophic cardiomyopathy was based on a history of illness, physical examination, echocardiography, and cardiac catheterization in accordance with European Society of Cardiology recommendations . Based oEchocardiography was performed in agreement with the American Society of Echocardiography and European Association of Cardiovascular Imaging standards evaluating the following parameters: left ventricular end-diastolic (LVEDD) and end-systolic (LVESD) diameters, left atrium diameter (LA), right ventricle diameter (RV), end-diastolic interventricular septum (IVST) and posterior wall thickness (PWT), inferior vena cava diameter (IVC), LV ejection fraction (LV EF), left ventricle fractional shortening (FS), peak gradient of tricuspid regurgitation (Pgrad TR), left ventricle mass (LVM), and left ventricle mass index (LVMI) . Left veBlood samples were obtained from venous catheters, introduced into tube collectors containing no preservatives. Within 1 h, the blood samples were centrifuged for 10 min at 2500 g and the supernatant was removed and kept at −70°C until the assay was performed.n = 20) was, for 146.4 ng/L, 10.8% and, for 456.3 ng/L, 7.4%. Internal quality control measurements were carried out using samples provided by the kit manufacturer.VEGF concentrations were measured using cytokine array for the evidence investigator protein biochip system . Simultaneous quantitative detection of multiple analytes based on sandwich chemiluminescent immunoassay was carried out from a single patient sample. The core technology consists of a solid plate containing discrete test regions with immobilized antibodies specific to different markers. Increased levels of marker in a specimen lead to increased binding of antibody labeled with horseradish peroxidase and thus to an increase in the luminescent signal emitted. The light signals generated from each of the test regions on the biochip are simultaneously detected using a charge coupled device camera. The analytical range of the VEGF assay was 3.24–1000 ng/L. The interassay coefficient of variability . Normally distributed variables are expressed as means ± standard deviation, while nonnormally distributed variables are expressed as median (interquartile range). Categorical variables are presented as percentages. Continuous variables were compared using Student's P < 0.001  ng/L versus 158.5 (IQR: 121.8–250.1) ng/L, P 0.43.Serum VEGF was increased in all 21 patients. Compared with controls, HCM patients had significantly increased serum VEGF level 199 (IQR: 120.4–260.8) ng/L versus 20 (IQR: 14.8–37.7) ng/L,  < 0.001 . In pati−2, and it exceeded reference values for two-dimensional method  in all patients. The mean of the left ventricle ejection fraction was 65.4 ± 12.2%, and, only in 1 (5%) patient, the LV ejection fraction was below the reference values . The mean of the left ventricle fractional shortening was 0.32 ± 0.09, and it exceeded the reference values  in 3 (15%) patients. The mean peak tricuspid regurgitation gradient was 22.6 ± 11.8 mmHg. The inferior vena cava diameter was 18 ± 3.7 mm.All patients underwent two-dimensional and Doppler echocardiography. None of the patients had left ventricle outflow tract obstruction. The peak left ventricle outflow tract gradients were 6 (IQR: 1–7.5) mmHg during at rest measurement and 15 (IQR: 2.2–29) mmHg during Valsalva maneuver. The median values for the peak LVOT pressure gradient were 3 (IQR: 2.2–5) mmHg for at rest measurements and 14 (IQR: 2–22) mmHg during Valsalva maneuver.r = 0.51, 95% CI: 0.09–0.77, and P = 0.01), left ventricle ejection fraction , LV fractional shortening , LV mass , LV mass index , vena cava inferior diameter , and peak gradient of tricuspid regurgitation . Figures The analysis of echocardiographic parameters showed association of the morphological and functional parameters with serum VEGF level. Serum levels of increased vascular endothelial growth factor left were significantly associated with left atrium diameter ; functional parameters of the left ventricle showed negative association. Serum VEGF correlated also with peak tricuspid regurgitation gradient (marker of pulmonary circulation pressure), inferior vena cava diameter, and left atrium diameter (markers of volume and pressure overload).Despite the study limitations , serum VEGF has emerged as an interesting and promising parameter useful for risk stratification of patients with hypertrophic cardiomyopathy.


Introduction: Pulmonary insufficiency (PI) frequently develops in patients who underwent repair of tetralogy of fallot (TOF). The aim of present study was to assess the effect of pulmonary valve replacement (PVR) on hemodynamics of patients who underwent repair of TOF.Methods: This retrospective cohort carried out between July 2010 and October 2012 among consecutive PVRs of 19 patients who underwent TOF surgery. The PVRs was performed using bioprosthetic (n=17) and mechanical (n=2) valves. Our data was collected during follow up visits within 6 to 12 month after PVR.Results: Our results show that PVR significantly decreased right ventricular end-diastolic volume , right ventricular end-systolic volume , RV mass , and PI . Moreover, left ventricular end-diastolic volume significantly increased  after PVR. The other hemodynamics indexes did not change, significantly.Conclusion: Despite the controversies about efficacy of PVR after repair of TOF, the remarkable improvement of hemodynamic is a supportive rationale for performing PVR surgery in TOF patients. Chronic cardiac overload which caused by PI, can result in cardiac (RV) wall enlargement, RV failure, heart failure, arrhythmias and unfortunately sudden cardiac death. Pulmonary valve replacement (PVR) may be indicated for the purpose of preventing permanent alterations of cardiac walls and hemodynamics.3 Although PVR performed by numerous surgeons for many years, the effect of PVR still remains controversial. Despite the evidences of recovered cardiac function and hemodynamics post-PVR, the beneficial effect of PVR on prevention of alterations of ventricular mass, volumes, and hemodynamics remains unclear and indications for PVR are restricted to limited conditions such as RVOT dysfunction.1 In our center, symptomatic patients with the symptoms like as exercise intolerance, clinical arrhythmia, and right ventricular failure that unequivocally caused by severe PI and the asymptomatic patients with RVEDV greater than 170 ml/m2 in cardiac MRI (CMRI) were routinely undergoing PVR. This study was carried out with aim of assessment of the effect of PVR surgery on hemodynamic indexes of patients who undergone total repair of TOF.Tetralogy of fallot (TOF) is one of the most common congenital heart disease.TM) and 2 PVRs with mechanical valves .After approval of institutional committee of ethic, 19 consecutive TOF patients who underwent PVR between July 2010 and October 2012 were included in our cohort. All patients was underwent TOF correction prior to PVR. Our study population included a number of 17 PVRs with bioprosthetic valves  or on beating heart (in the absent of right to left shunt). The size of valve was selected based on surgeon’s preference . Both of mechanical or bioprosthetic valves were inserted into orthotopic position.All data of these PVRs was collected from review of medical records of surgeon and hospital database. Moreover, results of CMRI studies were collected during follow up clinical visits at the time between 6th and 12th month after PVR.t test was used to find any significant difference between hemodynamic parameters before and after surgery. The P value less than 0.05 was considered as significant level for all tests.Data were analyzed using SPSS software . Categorical data described as frequency (percent) and continuous data presented as mean ± standard deviation. The student The perioperative and late outcomes of patients after PVR surgery was summarized in P <.01). Also, the Right ventricular end-systolic volume (RVESV) significantly decreased after surgery . Correspondingly, the CMRI results show the substantially shrinkage of right ventricular (RV) mass after PVR . Moreover, right ventricular ejection fraction (RVEF) improved after valve replacement, but this improvement was not statistically significant .As the As depicted in 4 Therefore, correction of PI can result in shrinkage of RV mass by decrease of RV load. In accordance with previous studies, our results indicate a significant decrease in RVEDV and RVESV after PVR.6 These results confirm the hypothesis that RV mass can significantly decreased by PVR. In other words, PVR can gradually result in RV remodeling by removal of overloaded pressure on RV myocytes. Surprisingly, despite the shrinkage of expanded RV wall and improvement of RV hemodynamic, RVEF failed to show a significant improvement. Bove and colleagues5 founded a significant shrinkage of dilated RV (RVD) and improvement in exercise tolerance after PVR surgery but they reported only a trivial increase in RVEF. In contrary, the report of Vliegen et al7 indicated that RVD and RVEF can improve after the surgery.Chronic forces against the cardiomyocytes is a trigger for muscular hypertrophy and cardiac wall thickening.2 or RVESV>80-90 ml/m2.6 Therefore, we concluded that the efficacy of PVR is limited to the RV volumes lower than this limit. Despite the fact that PVR can effectively reduce RV size, its effects on RV function may be limited because of the increased scar and fibrotic tissue in the RV wall.Evidences suggest that the probability of RV regression considerably decreases in presence of preoperative RVEDV>160-170 ml/m4 studied the behavior of ventricles after implantation of stentless valves, by assessment of gradients and effective orifice area (EOA) index in patients who underwent aortic valve surgery. They concluded that rapid improvement of ventricular function is highly depended on valve performance rather than ventricular regression. High gradient across the functioning prosthetic valve can suspend recovery of RV function. Therefore, another probability is that improvement of RV function is a long-term process that may need more time to develop. The current evidences suggest that early restoration of pulmonary valve function can fully normalize the RV hemodynamic, but the exact time of PVR remains unknown.9Silberman et al10 Likewise, our results show that the PVR surgery could effect on LV volumes as well as RV volumes. It was postulated that interaction between LV and RV chambers is mainly related to mutual myocardial fibers between LV and RV. Additionally, incline of the nestled interventricular septum into the LV cavity can decrease left ventricular refilling during diastole phase. Hence, LV hypertrophy (LVH) could result as an important compensatory mechanism for unfilled LV to increase cardiac output.11 Our study supports this experience and show that parameters of LVEDV (significantly), LVESV, and LVEF (non-significantly) increased after PVR.LV dysfunction frequently is a common finding in symptomatic patients with TOF and implies that the presence of the severe RV disease may be a cause for LV dysfunction. Therefore, management of congenital RV anomalies may improve the LV function and clinical symptoms.This study has several limitations. There is a noticeable difficulty in homogeneous surgical recruitment of patients because patients may be referred for surgery at different stages of PI or RVOT dysfunction. Moreover, small size of our study population counts as another major limitation of this study.2 or RVESV>80-90 ml/m2.In conclusion, our study indicates that PVR surgery can successfully normalize the impaired hemodynamic of patients who previously underwent repair of TOF. Although there is a controversy about effect of PVR in TOF patients among experts, the remarkable improvement of hemodynamic after PVR is a supportive rationale of performance of this surgery before RV hemodynamic reaches to RVEDV>160-170 ml/mUnexpectedly, despite the fact that PVR significantly improves RV size and volume, RV function remained impaired after PVR. We concluded that early PVR surgery can initiate RV remodeling and improvement of RV function. Hence, in order to prevention of development irreversible alterations in cardiac walls, the PVR surgery should be consider in TOF patients with the upper threshold levels as soon as possible.


Current semi-quantitative cardiovascular magnetic resonance (CMR) techniques are of limited diagnostic value in patients with suspected myocarditis. T1- and T2-mapping CMR are promising novel quantitative approaches to assess myocardial injury. This study evaluated the performance of T1 and T2 mapping CMR to identify patients with myocarditis in comparison with conventional CMR techniques.This study included 104 patients with myocarditis and 26 controls, who underwent CMR at 1.5 Tesla. The CMR protocol included conventional sequences to assess myocardial edema (T2w-STIR), Early- (T1w-TSE) and Late-Gadolinium-Enhancement (PSIR). T1 quantification was performed using the modified Look-Locker inversion-recovery (MOLLI) sequence before and 15 minutes after administration of 0.075 mmol/kg Gadolinium-BOPTA. T2 quantification was performed using a free-breathing, navigator-gated multi-echo sequence. T1, T2 and extracellular volume (ECV) maps were calculated with a dedicated plug-in written for the OsiriX software. The diagnostic performance was compared between conventional parameters and global myocardial T1 (native and post-contrast), ECV and T2.The ROC areas-under-the-curve (AUC) to discriminate between patients with myocarditis and controls were 0.58 (p = 0.19) for the signal-intensity ratio myocardium/skeletal muscle on T2w-STIR, 0.67 (p = 0.01) for early myocardial enhancement on T1w-TSE and 0.80 (p < 0.0001) for presence of Late-Gadolinium-Enhancement, respectively. Furthermore, the AUC to discriminate between patients with myocarditis and controls were 0.77 (p < 0.0001) for native global myocardial T1, 0.59 (p = 0.14) for post-contrast global myocardial T1, 0.85 (p < 0.0001) for global myocardial ECV and 0.79 (p = 0.0001) for global myocardial T2, respectively.T1 and T2 mapping provide a superior performance to identify patients with myocarditis compared to conventional CMR techniques. In particular, the estimation of global myocardial ECV by T1 mapping improves the diagnostic value of CMR in patients with clinically suspected myocarditis.Marija-Orlovic-Foundation.


Despite this observation, several indices of systolic and diastolic mechanics were maintained in TETRA but attenuted in PARA including circumferential strain at the level of the papillary muscle  and apex  and their corresponding diastolic strain rates . All blood pressures were lower in TETRA. The absence of an association between reduced global systolic function and mechanical dysfunction in either TETRA or PARA suggests any reductions in SV are likely attributed to impaired loading rather than inherent left ventricular dysfunction.Following a spinal cord injury, there are changes in resting stroke volume (SV) and its response to exercise. The purpose of the following study was to characterize resting left ventricular structure, function, and mechanics in Paralympic athletes with tetraplegia (TETRA) and paraplegia (PARA) in an attempt to understand whether the alterations in SV are attributable to inherent dysfunction in the left ventricle. This retrospective study compared Paralympic athletes with a traumatic, chronic (>1 year post-injury), motor-complete spinal cord injury . Eight male TETRA wheelchair rugby players  and eight male PARA alpine skiers  were included in the study. Echocardiography was performed in the left lateral decubitus position and indices of left ventricular structure, global diastolic and systolic function, and mechanics were derived from the average across three cardiac cycles. Blood pressure was measured in the supine and seated positions. All results are presented as TETRA vs. PARA. There was no difference in left ventricular dimensions between TETRA and PARA. Additionally, indices of global diastolic function were similar between groups including isovolumetric relaxation time, early (E) and late (A) transmitral filling velocities and their ratio (E/A). While ejection fraction was similar between TETRA and PARA (59 ± 4 % vs. 61 ± 7 %,  The classification of Paralympic athletes is sports specific and considers physical, visual and/or intellectual impairments. Typically athletes with a spinal cord injury (SCI) are competing against individuals with a similar lesion level . However, there are sporting competitions where individuals with cervical and thoracic SCI are competing against each other, in addition to other non-SCI athletes. The consideration of how the lesion level may influence exercise performance is therefore necessary to ensuring fair competition between the diverse population of Paralympic athletes.One contributing factor to exercise performance is the capacity of the cardiovascular system to adequately respond to the body's demands. This includes the responses of the heart, vasculature, and adrenal medulla. Following SCI, there are lesion level dependent alterations in how the cardiovascular system responds to an exercise stimulus. While sympathetic preganglionic neurons originate in the thoracic and upper lumbar segments of the spinal cord (T1-L2), sympathetic innervation of target organs is segmental. Innervation of the heart and vascular smooth muscle of the upper body arise from the high thoracic segments (T1-T5), while innervation of the vascular smooth muscle of the lower body and adrenal medulla arise from the lower thoracic and lumbar segments (T6-L2). Cervical SCI results in the most dramatic alterations in cardiovascular outcomes at rest and in response to exercise, due to the disruption of descending sympathetic input to target organs below the level of injury  and strain rates (SR) which assess the degree and rate of myocardial deformation in longitudinal, radial and circumferential axes; rotation (Rot) and rotation rates (RotR) of the base and apex of the LV; and overall LV twist and twisting/untwisting rates  Theisen, . HoweverThis was a retrospective comparison of echocardiography data collected at both summer and winter Paralympic events. Inclusion criteria included males between 18-60 years of age who had sustained a chronic (>1 year post-injury), motor-complete [American Spinal Injury Association Impairment Scale (AIS) A-B], traumatic SCI, and who have been competing at the international level for at least 3 years. Eight Paralympic wheelchair rugby players with a cervical SCI (TETRA) and eight Paralympic alpine skiers with a thoracic SCI (PARA) met the criteria and were included in the study. The neurological level of injury and AIS was confirmed using the International Standards for Neurological Classification of SCI . Seated and supine measurements were collected in duplicate following 5 and 10 min of quiet rest, respectively.Cardiac images were collected with the participants in the left lateral decubitus position using two-dimensional echocardiography  according to the recommendations of the American Society for Echocardiography  and end-systole (s) from the parasternal long axis view, including LV internal diameter (LVID), and interventricular septal wall (SWT), and posterior wall (PWT) thickness. Relative wall thickness (RWT) was calculated as [(2 × PWTd)/LVIDd]. LV mass (LVMI) was calculated according to an established formula , papillary muscle (mid), and apex  using established guidelines . Data were assessed for normality using Shapiro-Wilk tests and Q-Q plot analyses. Between group differences were determined using independent 2) and PARA . Self-reported training history was available in 5 of 8 TETRA and all 8 PARA athletes. There was no significant difference in the number of years competing at an international level  or weekly training volume . For seated and supine hemodynamics, heart rates were similar between groups while all blood pressure values were lower in TETRA compared to PARA  and the acute exercise protocol . Nevertheless, the absence of apparent LV mechanical dysfunction at rest in high-performance athletes with SCI in the present study suggests any abnormal SV responses during exercise are likely attributable to reduced loading.The observation of lower systolic and diastolic mechanics in our PARA group may be indicative of two scenarios: LV dysfunction/disease or a “resetting” of resting mechanics. Lower resting LV mechanics have been documented in clinical populations .In conclusion, high-performance athletes with TETRA and PARA experience differential changes in LV indices. While we would speculate these changes are attributed to lesion level, they may also be influenced by their training modality. TETRA athletes can be characterized as having normal diastolic function but reduced systolic function, an observation likely attributed to impaired venous return. On the other hand, PARA athletes demonstrated lower values for LV mechanics yet had no evidence of global systolic or diastolic dysfunction. We speculate this observation may be attributed to training induced improvements in LV efficiency rather than indicative of inherent LV dysfunction.KC—Conception of the work; data acquisition, analysis and interpretation; drafting and revising manuscript; approved final copy; and agrees to be accountable. CW—Conception of the work; data acquisition and interpretation; critically revised manuscript; approved final copy; and agrees to be accountable. AK—Conception of the work; data acquisition and interpretation; revising manuscript; approved final copy; and agrees to be accountable.Research at the Paralympic events was supported by donations from the International Collaboration on Repair Discoveries, Coloplast, Wellspect HealthCare, and the Shkreli Foundation. Dr. KC was supported by a Craig H. Neilsen Foundation Postdoctoral Fellowship (281863).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Telomere length has been associated with coronary artery disease and heart failure. We studied whether leukocyte telomere length is associated with left ventricular ejection fraction (LVEF) after ST-elevation myocardial infarction (STEMI).P < 0.01), gender , TIMI flow pre-PCI , TIMI flow post-PCI , myocardial blush grade , serum glucose levels , and total leukocyte count . At 4 months after STEMI, LVEF was well preserved (54.1 ± 8.4 %) and was not associated with baseline LTL (P = 0.95). Baseline LTL was associated with n-terminal pro-brain natriuretic peptide (NT-proBNP) at 4 months , albeit not independent for age and gender.Leukocyte telomere length (LTL) was determined using the monochrome multiplex quantitative PCR method in 353 patients participating in the glycometabolic intervention as adjunct to primary percutaneous coronary intervention in STEMI III trial. LVEF was assessed by magnetic resonance imaging. The mean age of patients was 58.9 ± 11.6 years, 75 % were male. In age- and gender-adjusted models, LTL at baseline was significantly associated with age (beta ± standard error; −0.33 ± 0.01; Our study does not support a role for LTL as a causal factor related to left ventricular ejection fraction after STEMI. ST-segment elevation myocardial infarction (STEMI) is a life-threatening medical condition with a high incidence in Western societies . Timely n located at the terminal end of chromosomes, which protect genes from degradation during cell division due to the ‘end replication problem’ , and n-terminal pro-brain natriuretic peptide (NT-proBNP).®Taq DNA Polymerase ; 1X Titanium®Taq PCR Buffer ; 0.2 mM of each dNTP (Promega); 0.75X SYBR® Green I nucleic acid gel stain (Sigma-Aldrich); 1 M Betaine (Sigma-Aldrich); 1 mM DL-Dithiothreitol (Sigma-Aldrich). DNA of a human leukemia cell line (1301) with extreme long telomeres was used as a positive control [Blood for DNA isolation was collected from the patients at arrival at the catheterization laboratory (baseline) which was used for telomere length determination. White blood cell DNA extraction was performed by LGC genomics. Telomere length was measured in quadruplicate on 4 different plates with each replicate in the same well position on the polymerase chain reaction (PCR) plate by the monochrome multiplex quantitative PCR method, originally developed by Cawthon . The tel control . The the control . The medP value of <0.05 was used as nominal level of statistical significance. The analyses were performed using StataMP version 13.1 (StataCorp).Continuous variables are reported as mean  for normally distributed data. Since LTL and NT-proBNP were non-normally distributed, log transformation was performed to obtain a near normal distribution. Outliers were defined as >2 SD from the median of LTL. For continuous and dichotomous data, we performed linear regression analyses using LTL as dependent variable and baseline characteristics and outcome parameters as independent variables; categorical data were tested using expanded interaction linear regression analyses. All analyses were first performed univariately and then adjusted for age and gender. Graphical representation of interaction analyses were performed using the “margins” command in STATA. Statistical tests were performed two-tailed and a P = 0.15). Another 3 samples were regarded as outliers based on >2 SD deviation of the mean LTL, leaving 353 samples for the current analyses. MRI data at 4 months after STEMI were available for 253 (71.6 %) patients of patients whose LTL was determined. Baseline characteristics of the study cohort are represented in Table Genomic DNA was successfully extracted from 362 (95.5 %) patients of the GIPS-III cohort. LTL was successfully determined in 356 (98.3 %) of the DNA samples . ANOVA test revealed no significant difference between LTL of both treatment groups  −5.5 × 10−3 to 6.1 × 10−3; P = 0.91; interaction coefficient TIMI flow pre-PCI ≤0.01; 95 % CI −0.01 to 0.01; P = 0.97; interaction coefficient TIMI flow post-PCI ≤0.01; 95 % CI −0.02 to 0.00; P = 0.15; interaction coefficient total leukocyte count = −0.14; 95 % CI −0.29 to 0.01; P = 0.08).Leukocyte telomere length was negatively associated with age Fig. . UnivariMean LVEF, as determined by MRI, was well preserved at 4 months after STEMI (54.1 ± 8.4 %). LVEF, left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), left ventricular end diastolic mass (LVEDM), and infarct size are represented in Table P = 0.41, Table P = 0.04). NT-proBNP levels were similar for patients with different levels of LTL after placebo treatment but in patients treated with metformin, longer LTL was associated with lower NT-proBNP levels  without evidence of previous myocardial infarction, LTL was strongly and independently associated with LVEF as determined by echocardiography [N = 1106; average age 57.9-year old). A 1.5 fold larger LTL was associated with 0.6 % increase in absolute LVEF [N = 610; average age 66.2-year old), we did not observe an association with LVEF [N = 223; average age 51.1-year old), LTL was also not associated with LVEF as determined [N = 139; average age 60.3-year old), there was also no association with LTL and LVEF [In our study, we did observe the well-established association of LTL with baseline characteristics such as the inverse association with age , 24 and iography . In thisute LVEF . On the ith LVEF . In anottermined . Also intermined . In an aand LVEF .Our data contribute to the previous studies by investigating a specific population (STEMI) in which the role of LTL might be more prominent. However, our data demonstrate that even in the setting of STEMI and the subsequent remodeling process of the heart, LTL does not seem to be associated and, therefore, is unlikely to be involved. Biomarkers for predicting outcomes in coronary heart disease outcomes have been reported , but theThe major limitation of our study that needs to be considered is that the cells we investigated are leukocytes. Therefore, we cannot exclude an important role of telomere length in other cell types, e.g., cardiomyocytes or endothelial cells . For praIn conclusion, LTL measured in the setting of STEMI is not associated with cardiac remodeling or LVEF as determined by MRI after 4 months. Our study does not lend support for a role of LTL as a causal factor in LV remodeling or for the use as a biomarker to predict clinical outcome in patients with acute myocardial infarction.


To document clinical experience of treating congenital heart disease combined with large patent ductus arteriosus with pulmonary artery closure in combination with patch technique.Thirty-six patients  who suffered from congenital heart disease and underwent hybrid surgery in the First Affiliated Hospital of Zhengzhou University from October 2010 to February 2014 were selected for this study. They aged 14 to 39 years and weighed 32.20 to 61.50 kg. Diameter of arterial duct was between 10 mm and 13 mm; 28 cases were tube type, 4 cases were funnel type and four cases were window type. All patients had moderate or severe pulmonary arterial hypertension; besides, there were 28 cases of ventricular septal defect, 16 cases of atrial septal defect, eight cases of aortic insufficiency, four cases of mitral stenosis and insufficiency and four cases of infectious endocarditis. Cardz Pulmonary Bypass (CPB) was established after chest was opened along the middle line. With the help of Transesophageal echocardiography, large patent ductus arteriosus was blocked off through pulmonary artery. Pulmonary artery was cut apart after blocking of heart. Large patent ductus arteriosus on the side of pulmonary artery was strengthened with autologous pericardial patch.Of 36 patients, 32 patients had patent ductus arteriosus closure device and four patients had atrial septal defect closure device. Pulmonary arteries of 36 cases were all successfully closed. Systolic pressure declined after closure ((54.86±19.23) mmHg vs (96.05±23.07) mmHg, p<0.05); average pulmonary arterial pressure also declined after closure ((39.15±14.83) mmHg vs (72.88±15.76) mmHg, p<0.05). The patients were followed up for one to fifty one months (average 11.5 months). Compared to before surgery, left atrial diameter, left ventricular diameter and pulmonary artery diameter all narrowed after surgery. Besides, clinical symptoms were relieved and cardiac function of the patients also improved.Hybrid surgery is feasible and safe in treating patients with large patent ductus arteriosus and congenital heart disease, which decreases surgical problems, shortens surgical time and lowers the incidence of complications. Patent ductus arteriosus, a commonly seen congenital heart disease, accounts for 12%~15% of congenital heart disease; 10% of cases of patent ductus arteriosus also combine other heart malformations; large patent ductus arteriosus (diameter larger than 10 mm) is more likely to induce severe pulmonary arterial hypertension.7Conventionally after establishment of Cardio Pulmonary Bypass (CPB), patent ductus arteriosus is closed by patching and then the other malformations are processed.Thirty-six cases including 8 males and 28 females were confirmed by transthoracic echocardiography before surgery. They aged from 14 to 39 years and weighed from 32.30 kg to 61.50 kg. Diameter of arterial duct was between 10 mm and 13 mm; 28 cases were tube type, four cases were funnel type and four cases were window type. The pattern of arterial duct shunt of all cases was left-to-right and they all developed moderate or severe pulmonary arterial hypertension . Besides, there were 28 cases of ventricular septal defect, 16 cases of atrial septal defect, 8 cases of aortic insufficiency, four cases of mitral stenosis and insufficiency and four cases of infectious endocarditis. All patients gave informed consent. Patients who suffered from infectious endocarditis, neoplasm contained patent ductus arteriosus, other intracardiac malformations or other organ diseases were excluded. All patients had different degrees of palpitation and short of breath when overworked, which has lasted for one month to 20 years; there were 12 cases of hoarseness, 8 cases of chest pain, 6 cases of abdominal distension and edema of both lower limbs and one case of hemoptysis.First general anesthesia and tracheal intubation were performed. After patients in supine position were processed with whole body heparinization, chest was open along the middle line and sternum was vertically split. Main pulmonary artery was exposed by suspending pericardium. Then the surface of pulmonary artery was sutured with purse string suture using 4-Oprolene suture. The selection of closure device was determined based on the diameter of patent arterial duct and the pattern of large patent ductus arteriosus measured using preoperative transthoracic echocardiography and intraoperative transesophageal echocardiogaphy. Close device selected was 4 mm~6 mm larger than the diameter of patent arterial duct and window-type patent dutus arteriosus with large diameter could be closed with atrial septal defect closure device. The products used were all produced by Shanghai Shanghai Shape Memory Alloy Material Co., Ltd. 14G trocar was used to puncture purse. After pin core was withdrawn, guiding wire was inserted through tubes. Under the guidance of transesophageal echocardiogaphy, the guiding wire entered descending aorta through arterial duct. Then the tube was withdrawn. The head end of sheathing canal was inserted into descending aorta along the guidance wire . After tUnder the guidance of transesophageal echocardiogaphy, the closure device was pushed to the head end of sheath canal to release arterial plane and then retracted to close to aorta wall. The closure effect of four cases of window-type patent ductus arteriosus was poor; afterwards, 20 mm atrial septal defect was used. Transesophageal echocardiogaphy suggested the position of closure devices was appropriate and there was no residue shunt or residual shunt bundle was no more than 2 mm. After the delivery wire and sheath canal were removed, the preset safety wire was slightly pulled and fixed. CPB was established. After main artery was blocked, main pulmonary artery was cut apart to expose pulmonary artery plane. Bovine pericardium in proper size was selected and threaded with 3-Oprolene wire which was taken as safety wire. Then a knot was tied to firmly fix the pericardium . Patent Indexes of pulmonary arterial systolic pressure, mean pulmonary arterial pressure, aortic systolic pressure, mean aortic pressure, left atrium diameter (LAD), left ventricular end-diastolic diameter (LVEDD), pulmonary artery diameter (PAD) and left ventricular ejection fraction (LVEF) were observed before and after surgery.Patients were followed up one day, one month, three months, six months and one year after surgery. One year later, electrocardiography and transesophageal echocardiogaphy were performed every other year.Data collected were statistically analyzed using SPSS19.0. Measurement data were expressed as mean±SD. Comparison of mean was performed using pair t test or repeated measures analysis of variance. p<0.05 suggested difference was statistically significant.Of 36 patients, 32 patients were equipped with patent ductus arteriosus closure device (14 mm~28 mm single rivet in column shape) and four patient was equipped with atrial septal defect closure device (20 mm). All cases were observed with well located closure device and without residual shunt by intraoperative transesophageal echocardiography and postoperative transthoracic echocardiography . BesidesAll patients had successful surgery and released closure device. Pulmonary arterial systolic pressure and mean pressure both declined after closure, while aortic systolic pressure and mean pressure both rose; differences were statistical significant (p<0.05) .Compared to before surgery, LAD, LVEDD and PA all declined after surgery and the difference had statistical significance; but LVEF had no obvious changes. LAD recovered faster than left ventricular diameter and main pulmonary artery diameter. One year later, LAD recovered to the normal level, but left ventricular diameter and main pulmonary artery diameter remained abnormal .One patients developed descending aortic stenosis and five patients showed chest pain. But the complications were mild and could be tolerated; afterwards, the symptoms gradually relieved. One patient was observed with trivial residual shunt but without hemolysis during follow up.Patent ductus arteriosus is a commonly seen congenital heart disease. Limited by economical and medical conditions in China, many patients suffering from patent ductus arteriosus go to hospital only when the symptoms are quite serious, but at that time, severe pulmonary hypertension has been induced. The measures for treating patent ductus arteriosus of patients with composite congenital heart disease are as follow. For young patients with patent ductus arteriosus but without pulmonary arterial hypertension, ligation or transfixion can be directly performed through median approach before CPB.16Our department innovatively applied the therapy combining pulmonary artery closure and patch technique for treating congenital heart disease combined with large patent ductus arteriosus, which combines the advantages of minimal traumatic occlusion and conventional extracorporeal circulation direct-view inner heart operation.The size of closure device is usually 4 mm~6 mm larger than the diameter of arterial duct detected by transesophageal echocardiogaphy. In this study, 32 patients applied columnar and single-rivet closure device; 4 patients were treated with atrial septal defect closure device (20 mm). For window-type patent ductus arteriosus with diameter larger than 10 mm, many researchers advocate the application of atrial septal defect closure device.This is a single-center retrospective study and included small size of samples; therefore, the follow up results might be biased and prospective clinical studies with large sample size and multiple centers remain to be carried out. Besides, limited by invasiveness of the treatment and economical condition, follow up of most patients could only be possible through conventional physical examination, electrocardiograph and transthoracic and transesophageal echocardiography; and invasive cardiac catheterization were rarely used to confirm hemodynamic changes.Pulmonary artery closure in combination with patch technique is a simple operation which can shorten surgical time, lower the incidence of surgical complications, improve success rate and avoid X-ray radiation and contrast agent. Hence it is a new technology worth promotion.


The prevalence of heart failure is expected to increase almost 50% in the next 15 years because of aging of the general population, an increased frequency of comorbidities, and an improved survival following cardiac events. Conventional treatments for heart failure have remained largely static over the past 20 years, illustrating the pressing need for the discovery of novel therapeutic agents for this patient population. Given the heterogeneous nature of heart failure, it is important to specifically define the cellular mechanisms in the heart that drive the patient’s symptoms, particularly when considering new treatment strategies. This report highlights the latest research efforts, as well as the possible pitfalls, in cardiac disease translational research and discusses future questions and considerations needed to advance the development of new heart failure therapies. In particular, we discuss cardiac remodeling and the translation of animal work to humans and how advancements in our understanding of these concepts relative to disease are central to new discoveries that can improve cardiovascular health. Heart failure is a syndrome of major public health significance, impacting 5.7 million worldwide with an incidence of 870,000 adults in the United States alone. The prevalence of heart failure is expected to increase by 46% by 2030, and this is due in large part to aging of the general population but also to the improved survival following events such as myocardial infarction and the increased prevalence of comorbidities such as obesity and diabetes2. The cost to society is consequential. The 5-year mortality for heart failure remains approximately 50%, despite current therapies. Moreover, the financial costs associated with heart failure are expected to balloon to over $70 billion per year by 20301. As a result, the discovery of new drug targets for heart failure prevention or treatment (or both) remains an area of pressing concern.Heart failure, the common end stage of heart disease, is defined clinically by fatigue, shortness of breath, and fluid retention, including pulmonary edema3. The mainstays of heart failure pharmacotherapy include β-blockers , angiotensin-converting enzyme inhibitors , angiotensin II receptor blockers , aldosterone antagonists, hydralazine and isosorbide dinitrate, and diuretics4. Ventricular assist devices, such as the implantable cardioverter-defibrillator, left ventricular (LV) assist device, and cardiac resynchronization therapy, are widely used, and cardiac transplant remains a therapy of last resort for some patients. There has been tremendous excitement this year as the first new drugs since 1999 have been approved by the US Food and Drug Administration for chronic heart failure. Ivabradine (Corlanor) is a sinoatrial node If current inhibitor that has been shown to have efficacy in a variety of clinical trials, including SHIFT 7. LCZ696 (Entresto™) is a combination drug including a neprilysin endopeptidase inhibitor (sacubitril) and angiotensin receptor blocker . In the PARADIGM-HF  trial, LCZ696 was shown to reduce mortality in comparison with enalapril8. Finally, ranolazine improved hemodynamic status in the proof-of-concept RALI-DHF (RAnoLazIne for the Treatment of Diastolic Heart Failure) trial9. However, even with these new drugs, heart failure morbidity and mortality are expected to increase substantially in the near future.Current therapies for heart failure are both medicinal and device-driven12. As the names suggest, HFrEF includes prominent systolic cardiac dysfunction, whereas HFpEF is more closely associated with diastolic dysfunction. Although the current therapies for heart failure have been established in clinical trials involving HFrEF patients, none has been therapeutically useful for HFpEF patients14. Instead, exercise may be the only clinically effective, currently available HFpEF treatment15, and several small-scale clinical trials show that exercise improves cardiorespiratory variables such as oxygen consumption (VO2), diastolic dysfunction, and quality of life in HFpEF patients16. The Exercise Training in Diastolic Heart Failure (EX-DHF) (ISRCTN 86879094) study will examine these findings on a larger scale and hopefully provide insight regarding the use of exercise to improve mortality. The lack of drug therapies for HFpEF may be due to the limited efficacy of current drugs to treat diastolic dysfunction. Alternatively, it was recently suggested that many patients with diagnosed HFpEF, typically older women with diabetes and obesity, do not have structural heart disease but instead exhibit fairly general signs that define heart failure due to non-cardiac problems17. For example, although pulmonary edema is usually a reliable indicator of LV dysfunction (and high diastolic pressures), it can also be caused by primary pulmonary disease  or low plasma colloid oncotic pressure due to other etiologies18. HFpEF should also be distinguished from high-output heart failure, a form of heart failure that typically is secondary to a non-cardiac disease19. In high-output heart failure, the heart responds normally and reversibly to extra-cardiac stress, often undergoing physiologic hypertrophy that is induced by low afterload and volume overload on the heart. Thus, when novel approaches to the treatment of heart failure are considered, it is important to precisely define the cohort of patients being considered and whether the heart is in fact the relevant target for therapeutic intervention.In considering the future of heart failure therapies, it is important to remember that heart failure is not a homogenous entity but instead a clinical syndrome related to end-stage heart disease. Heart failure can be divided into two groups: (a) reduced ejection fraction (HFrEF) and (b) preserved ejection fraction (HFpEF) (ejection fraction >45%); the two forms confer a similar prognosis and have similar prevalence20. Cardiac hypertrophy at the whole-organ level reflects non-mitotic growth of the cardiac myocytes. The generally cylindrical adult myocyte can grow in either width (diameter) or length, resulting in thickened ventricular walls or chamber dilation, respectively. In theory, concentric myocyte growth increases the width of cardiomyocytes, inducing parallel assembly of sarcomeres and thereby reducing ventricular wall stress (Laplace’s law). In contrast, eccentric myocyte growth increases cardiomyocyte length, inducing serial addition of sarcomeres to accommodate greater ventricular volumes without stretching individual sarcomeres beyond the optimum length for contraction (Frank-Starling law)21. In pressure overload diseases, such as aortic stenosis or hypertension, there is increased systolic wall stress, and concentric hypertrophy initially predominates. In volume overload diseases, such as following a myocardial infarction or dilated cardiomyopathy, eccentric hypertrophy predominates, presumably in response to increased diastolic wall stress. Although sarcomeric assembly is considered initially compensatory, myocyte hypertrophy is eventually concomitant with altered myocyte gene expression, metabolism, excitation-contraction coupling, increased cell death, and myocardial fibrosis. Together, these factors contribute to systolic and diastolic cardiac dysfunction and promote pathological cardiac remodeling and subsequent heart failure.A long-term goal of heart failure therapies is to reverse or prevent cardiac remodeling, the general term referring to the structural changes in the heart induced by chronic stress. While the heart can respond to acute demands for increased output by changes in chronotropy (heart rate), inotropy (contractility), and lusitropy (relaxation), the adult heart is generally limited to hypertrophy as a compensatory mechanism23. We propose the following issues as central to advancing the treatment of heart failure, including questions to stimulate discussion about the underlying assumptions concerning disease development:The above description of heart failure is the basis for the underlying paradigm driving most research in the field, primarily the identification of potential drug targets that protect cardiac contractility and inhibit myocyte death and interstitial fibrosisCirculation25, concentric LV hypertrophy is often considered compensatory in diseases of increased afterload. The current first-line therapies for heart failure target the adrenergic and renin-angiotensin systems, having effects both on cardiac myocytes and on the vasculature25. It has been argued that lowering afterload and LV wall stress is essential to the efficacy of these drugs in patients  and that attenuating hypertrophy without lowering afterload would not be tolerated in humans26. However, diverse studies in rodents using pharmacological agents such as cyclosporine, and more elegantly with genetically modified mice, have shown that inhibition of hypertrophy not only is tolerated in the face of persistent pressure overload but also can prevent or treat heart failure22.1. A fundamental question concerns whether any of the features in cardiac remodeling are necessarily compensatory . For example, as recently discussed in a point-counterpoint editorial series in2+/calmodulin-dependent protein kinase II had improved cardiac function and decreased fibrosis but persistent hypertrophy following transverse aortic constriction27. Whereas some aspects of the changes in myocyte gene expression, metabolism, and excitation-contraction coupling may be detrimental , others may be beneficial . These exciting findings suggest that the beneficial aspects of remodeling may be retained while therapeutically combatting the deleterious aspects that lead to heart failure.2. It remains unclear which features in cardiac remodeling are co-regulated by signal pathways that may be targeted and which features may be specifically targeted independently of other aspects of remodeling. Although most studies show that hypertrophy and fibrosis are tightly associated in disease, recent findings by the Backs laboratory showed that mice lacking the γ and δ isoforms of Ca2+ reuptake during diastole primarily through SERCA2a, and reduced SERCA2a activity is associated with heart failure. Accordingly, in animal models, SERCA2a replacement has been effective in improving overall cardiac function28. Decreased compliance and associated atrial hypertrophy have long been associated with interstitial fibrosis30. However, the relative extent of fibrosis and altered Ca2+ reuptake can vary in different models for diastolic dysfunction31, raising the question of what should be targeted in diastolic dysfunction under different clinical scenarios. In numerous animal models, reversal or reduction of LV hypertrophy has been shown to improve diastolic function independently of hemodynamic alteration, implying that hypertrophy itself plays a role in diastolic dysfunction. However, clinical studies have shown that this relationship is less apparent in humans32. Finally, coronary vascular dysfunction may have a profound impact on myocardial oxidative capacity and diastolic dysfunction in heart failure33. Recent work has shown that swine with diastolic dysfunction have myocardial oxygen supply/demand imbalance34. This suggests that impaired coronary vasculature function may contribute to the inability of HFpEF patients to respond to situations of increasing stress by limiting ATP production and subsequent active relaxation.3. It remains unclear what causes diastolic dysfunction, especially in HFpEF. Diastolic dysfunction is the result of reduced active relaxation or ventricular compliance. Active relaxation occurs in large part due to ATP-dependent Ca25. Differences between large and small mammals include life span, heart rate, excitation-contraction coupling and Ca2+ handling, α:β-myosin heavy chain ratio, tolerance for myocardial injury, and rate of progression of cardiac remodeling25. The successful development of therapeutics for human patients is dependent upon the identification of mechanisms that are in fact relevant to the large mammalian heart. For example, many question whether large animals subject to pressure overload can tolerate diminished hypertrophy similar to mice24. A review by Dixon and Spinale discusses the importance of large animal models in translating basic science findings to the clinic and addresses the lack of studies using large animals to address pressure overload LV hypertrophy and its role in the development of heart failure35. An advantage of large animal models is that key determinants of myocardial work and energy consumption, including LV wall tension, heart rate, and vascular wall-to-lumen ratios36, are similar to those in humans. Thus, large animal models could provide an essential link to implement discoveries made in murines into models exhibiting functional and anatomical similarities more analogous to humans as a means to assess therapeutic potential for treating heart failure clinically. Significant financial challenges exist in generating, sustaining, and implementing large animal models of heart failure into research programs. Specific programs aimed at soliciting and supporting large animal cardiovascular research from both federal and private sources would help stimulate more large animal studies in the future and aid in bridging the gap between small animals, large animals, and humans.4. Humans are not large mice. Little is known or being investigated about cardiac signal transduction in large mammals, despite the significant differences between large and small mammalian hearts. Instead, most of what is known about the regulation of myocyte hypertrophy and cardiac remodeling has been defined in mice and ratsin vitro. Our knowledge of cardiac cell regulation continues to rapidly increase, and new tools, including novel methods for visualizing signaling in real time, are being developed37. In addition, adeno-associated viruses are emerging as a viable therapeutic approach to deliver both small interfering RNA (siRNA) and proteinsin vivo for both scientific and clinical purposes38. These advances portend the discovery of additional cardiac therapeutics in the coming years.It is an exciting time to be involved in heart failure research. There are ample animal models, both small and large, addressing diverse types of heart diseases, as well as protocols to study cardiac cell types


Trypanosoma cruzi. The estimated global prevalence ofT. cruzi infections declined from 18 million in 1991,when the first regional control initiative began, to 5.7 million in 2010.Myocarditis is an inflammatory disease due to infectious or non-infectiousconditions. Clinical manifestation is variable, ranging from subclinicalpresentation to refractory heart failure and cardiogenic shock. Severalreports suggest that the use of extracorporeal membrane oxygenation inpatients presenting with severe refractory myocarditis is a potentialbridging therapy to heart transplant when there is no spontaneous recoveryof ventricular function. In a 6-month follow-up outpatient consult, thepatient presented well and was asymptomatic.A 17-year-old Brazilian male presented with progressive dyspnea for 15 days,worsening in the last 24 hours, and was admitted in respiratory failure andcardiogenic shock, with multiple organ dysfunctions. Echocardiographyshowed a left ventricle ejection fraction of 11%, severe diffusehypokinesia, and a systolic pulmonary artery pressure of 50mmHg, resultingin the need for hemodynamic support with dobutamine (20mcg/kg/min) andnoradrenaline (1.7mcg/kg/min). After 48 hours with no clinical orhemodynamic improvement, an extracorporeal membrane oxygenation wasimplanted. The patient presented with hemodynamic, systemic perfusion andrenal and liver function improvements; however, his cardiac function didnot recover after 72 hours, and he was transfer to another hospital. Airtransport was conducted from Salvador to Recife in Brazil. A hearttransplant was performed with rapid recovery of both liver and kidneyfunctions, as well as good graft function. Histopathology of the explantedheart showed chronic active myocarditis and amastigotes of Extracorporeal membrane oxygenation (ECMO) for acute heart failure in adults canbe used as a bridge to myocardial recovery, cardiac transplantation orimplantation of a left ventricular assist device. The ECMO system, a modified heart-lungmachine, generally consists of a centrifugal pump, a heat exchanger and amembrane oxygenator. Desaturated venous blood is aspirated from the right atriuminto a centrifugal pump through a long steel wire-reinforced cannula insertedinto the right atrium via the femoral vein. The pump outflow is directed into amembrane oxygenator, and it is guided via an outflow cannula into the descendingaorta via the femoral artery. Typical ECMO complications include systemic inflammatoryresponse syndrome, renal failure, limb ischemia and bleeding.There are two main types of ECMO: venovenous and venoarterial; venoarterial is themethod of choice for acute heart failure in adults.Hospital Ana Nery, Salvador-Brazil.Echocardiography showed a left ventricle ejection fraction of 11%, severediffuse hypokinesia and a systolic pulmonary artery pressure of 50mmHg, whichresulted in the need for hemodynamic support with dobutamine (20mcg/kg/min) andnoradrenaline (1.7mcg/kg/min).A 17-year-old Brazilian male presented with progressive dyspnea for 15 days,worsening in the last 24 hours, and was admitted in respiratory failure andcardiogenic shock, with multiple organ dysfunctions, to the cardiac intensivecare unit at the ®/Quadrox-i Adult/Biolinecoated/MAQUET Cardiopulmonary AG, Hirrlingen, Germany). Heparin treatment(100UI/kg bolus and 20UI/Kg/h) was initiated. Blood flow was initially at4.571mL/min, with 6.000mL/min gas flow (pure oxygen Sweeper). Hemodynamic, systemic perfusion (lactate of17mmol/L dropped to 2.5mmol/L and increase diuresis volume), and renal (serumcreatinine from 3.5 to 1.2mg/dL) and liver  function improvement were evident in 24 hours  Transplant Center in Recife, Brazil wasthen executed.After 36 hours with no clinical or hemodynamic improvement, peripheralveno-arterial extracorporeal membrane oxygenation (VA-ECMO) was implanted usinga centrifuge magnetic pump with a polymethylpentene oxygenation membrane. The logistics of inter-hospitaltransport involved approximately 50 professionals from different specialties,including physicians, nurses, physiotherapists, paramedics, perfusionists andpolice officers due to the lack of a specialized team trained in ECMO transport (ma cruzi , presentT. cruzi infections declinedfrom 18 million in 1991, when the first regional control initiative began, to5.7 million in 2010.Myocarditis is an inflammatory disease due to infectious or non-infectiousconditions. Clinical manifestation is variable, ranging from subclinicalpresentations to refractory heart failure and cardiogenic shock. Mechanical circulatorysupport with an intra-aortic balloon or ventricular assist devices should beconsidered in cases refractory to medical therapy. Several reports suggest that the use of ECMOin patients presenting with severe refractory myocarditis is a potentialbridging therapy to heart transplantation when there is no spontaneous recoveryof ventricular function.,6 The VA-ECMO can bepercutaneously implanted at the bedside and can be kept for several weeks withproper care. It is the preferred device when patients present with biventriculardysfunction and often promotes rapid improvement of the hemodynamic status,oxygenation parameters and organ function.,8 In the faceof heart function improvement, the mechanical support device can beprogressively withdrawn, but when cardiac function impairment is maintained, thetreatment of choice would be a long-term device or heart transplant.,10 In a 6-month follow-up outpatient consult, thepatient presented himself in good health, ratifying the cost-utility of thisprocedure in Brazil.The estimated global prevalence of In the presented case, veno-arterial extracorporeal membrane oxygenation was usedon a patient with multiple organ failure secondary to a defined and refractorycardiogenic shock. The benefit of the method was unquestionable, even in theadvanced stages of renal and liver failure. The patient presented with a partialrecovery of the affected systems, making possible the implementation of thedefinitive therapy to severe myocarditis or heart transplant. Long- andshort-distance inter-hospital transport on extracorporeal membrane oxygenationcan be safely performed, but it demands a subspecialized team, highly competentin intensive care and be aware of the risks involved in transporting thesepatients.