Objective: To explore the effects of preoperative administration of conventional doses of atorvastatin plus trimetazidine on the myocardial injury of patients during the perioperative period of percutaneous coronary intervention (PCI).Methodology: 475 cases of acute coronary syndrome patients before PCI were randomly divided into the control group (238 cases) and experimental group (237 cases).The control group was treated with conventional doses of atorvastatin calcium , and the experimental group was treated with conventional doses of atorvastatin calcium plus trimetazidine hydrochloride  for 3 d. After PCI, preoperative and postoperative 24 h concentrations of serum creatine kinase MB isoenzyme (CK-MB), cardiac troponin I (cTnI) and high sensitivity C-reactive protein (hs-CRP) as well as activity of myeloperoxidase (MPO) were investigated. Left ventricular ejection fractions of the patients were then examined 4 weeks later.Results: Postoperative 24 h cTnI concentration and elevated MPO activity of the experimental group were significantly lower than those of the control group (P <0 05). CK-MB activities and hs-CRP concentrations of the two groups did not differ significantly (P> 0 05).Conclusion: The administration of conventional doses of atorvastatin plus trimetazidine three days before PCI is able to protect the perioperative patients from myocardial injury. However, balloon dilatation and stent implantation operations during PCI will both induce myocardial ischemia and myocardial microembolization, which will lead to perioperative myocardial injury and affect therapy efficacy.2,3Cardiovascular diseases, such as coronary heart disease, have become a prominent public health problem seriously threatening life expectancy and quality of life of people all over the world.4 which may not be safely applied in the clinic treatment in China. It has been previously reported that atorvastatin plus trimetazidine could improve the symptoms of coronary heart disease and heart failure patients.ARMYDA-ACS study revealed that preoperative statins could reduce perioperative myocardial infarction (MI), but a large dosage of atorvastatin was used (80 mg/d),5Thereby motivated, this study aims to investigate the effects of preoperative administration of conventional doses of atorvastatin plus trimetazidine on the myocardial injury of patients during the perioperative period of PCI.Object: Seven hundred ninety six (796) patients were diagnosed as acute coronary syndrome and scheduled for coronary angiography from January 2010 to December 2011 in Department of Cardiovascular Internal Medicine of The First Affiliated Hospital of Medical College of Xi'an Jiaotong University. Four hundred seventy five patients that were going to have PCI surgeries were included in this study. Inclusion criteria: non- MI patients with normal baseline myocardial enzyme graphs, typical angina symptoms, positive treadmill test results as well as middle or severe lesion performance in at least one of coronary CT three-dimensional reconstruction. Besides, the following two requirements should be met simultaneously.6 1) Single or multi-vessel lesions that have been confirmed by coronary angiography (vascular stenosis 70%) and were suitable for PCI; 2) patients who did not take trimetazidine in the last three months before hospitalization. Exclusion criteria: 1) obviously combined with liver and kidney dysfunctions, tumors, or other diseases such as myocarditis, heart failure and left ventricular ejection fraction <30% that may elevate creatine kinase-MB isoenzyme (CK-MB) activities and cardiac troponin I (cTnI) levels; 2) without combined diseases but with elevated preoperative baseline cTnI levels and CKMB activities; 3) Application of rotational ablation or directional coronary atherectomy; 4) intraoperative serious blood vessel complications and main branch obliteration, below grade 2 Thrombolysis in Myocardial Infarction (TIMI) confirmed by postoperative angiography; 5) patients who were allergic to trimetazidine.7 All the included patients have signed the informed consent forms. 475 patients were divided into trial group  and control group  using a random number table.Apparatus: TDL-5-A centrifuge (Shanghai Anting Scientific Instrument Factory), AXIOM Artis dBc cardiac imaging equipment , ACS180 automatic chemiluminescence immunoassay analyzer , PRONTO Evolution automatic biochemical analyzer  and CK-MB kit  were utilized. ELISA kits  were utilized for the detection of human myeloperoxidase (MPO).Methods: Medical record data of all the selected patients were sampled, including smoking history, hypertension history, hyperlipidemia history, diabetes history and preoperative medication history, etc. Their body mass index (BMI) and left ventricular ejection fraction were also recorded.8 On the preoperative 3rd day, patients in the control group were orally administered atorvastatin calcium  . Patients in the trial group were treated with trimetazidine hydrochloride   besides equivalent doses of atorvastatin calcium. PCI procedures were performed according to routine operations. Angina symptoms induced by balloon dilatation and stent implantation during PCI as well as ST segment and T wave changes of their preoperative and postoperative electrocardiograms were recorded. Patients in the two groups were followed up within the postoperative 30 days, mainly including telephone follow-up of angina, MI, death, heart failure, re-hospitalization and re-intervention treatment and etc. Four weeks after PCI, ultrasound cardiograms of the patients were reexamined and left ventricular ejection fractions were recorded in the Outpatient Department.9MPO, high sensitivity C-reactive protein (hs-CRP), and cTnI levels before and after PCI were determined, perioperative MI incidences were counted , 32 cases were administered angiotensin receptor antagonists (ARB), and 28 cases were administered calcium channel blockers (CCB). Differences in the risk factors such as case number, gender, age and coronary heart disease, preoperative CK-MB activity, left ventricular ejection fraction, total cholesterol (TC), past medical history, and applications of ACEI, ARB, CCB of the two groups were not statistically significant. All the selected patients showed normal baseline cTnI levels, the mean values were less than 10 mg/L and did not affect the experimental results , whereas CK-MB activities of the two groups did not differ significantly (P>0.05). As shown in 10 However, PCI still frequently encounters perioperative myocardial injury, which together with inflammation have also been verified to be associated with long-term prognosis of patients. Currently, PCI-related regional myocardial injuries are mainly resulted from side branch occlusion, microsphere loss and transient myocardial ischemia that lead to the impaired blood perfusion of myocardial microcirculation.11 Bahrmann et al. have demonstrated that intracoronary microembolization during PCI was closely related to perioperative non-ST-segment elevation MI. Therefore, successful PCI is able to improve both the blood flow in epicardial great vessels and myocardial microcirculation.12PCI techniques and equipment have been developing rapidly in interventional cardiology, and the success rates have already reached above 90% in most cardiac centers.13 Subsequently published ARMYDA-ACS study revealed that postoperative 30 d cardiac event incidence of the acute coronary syndrome patients who received high-dose atorvastatin (80 mg/d) in preoperative 12 h instead of other statins significantly reduced to 5%, whereas that of the control group was 17%. Naples II assay also obtained similar clinical outcomes utilizing the same dose of atorvastatin.14 Besides, post-hoc analysis showed that cardioprotective effects of statins were more obvious in the patients with higher baseline CRP levels. All the above phenomena are all ascribed to the pleiotropic effects of statins. In addition to lipid regulation, statins are also able to alleviate inflammation, improve endothelial function, reduce the expression of adhesion molecules, stabilize plaques, inhibit thrombus and etc. that all can protect myocardial cells.15 Many studies have initiated the prevention or treatment of PCI perioperative myocardial injuries utilizing preoperative atorvastatin, trimetazidine, XZK, heart-protecting musk pills and etc. commonly. In particular, ARMYDA study published in 2004 showed that preoperative statins could reduce perioperative MI.16 In the present study, conventional doses of atorvastatin plus trimetazidine were employed, and the preliminary experimental results show that PCI postoperative myocardial injury marker cTnI and inflammatory marker of the trial group were all significantly lower than those of the control group, confirming that the combination therapy could effectively reduce myocardial injury.17,18 Owing to the relatively short follow-up time, left ventricular ejection fractions of the two groups did not differ significantly, which may be associated with the intrinsic mechanism of trimetazidine. As a common drug for the treatment of angina, trimetazidine transforms myocardial metabolism from the metabolism of fatty acids to the oxidation of glucose by primarily inhibiting the long-chain 3-Ketoacyl-CoA-thiolase in mitochondrion.19 As a result, trimetazidine can effectively control the energy supply equilibrium of free fatty acids or glucose oxidation, which thus can improve myocardial energy metabolism, reduce intracellular acidosis and calcium deposition and prevent cell membranes from oxygen free radical damages utilizing more generated ATP in the presence of limited oxygen during myocardial ischemia.20 Considering that follow-up time in this study was relatively short, perioperative MI still cannot be clearly demonstrated to be transformed into a certain medium-term or long-term benefit. In summary, this study provides a novel concept for reducing PCI perioperative MI, but further large-scale clinical study is still in need to determine a safe and effective perioperative myocardial protection program that is suitable for Chinese people.21 Nevertheless, 80 mg statins were all adopted in the above clinical trials, which are too high for Chinese people and will thus hinder their clinical application due to security concerns. Main adverse reactions of statins include elevated liver enzymes and myopathy or even rhabdomyolysis. Although the reactions scarcely occur, they tend to depend on the dosage. Therefore, simultaneously reducing PCI-related myocardial injury and drug side effects have been widely spotlighted.


Simultaneously, the PV, VTI and IV of the right heart decreased significantly (p<0.05) at the first cycle, decreased rapidly to the lowest at the 6±0.8th beat  and then increased gradually to the 9±1.3th beat . These results suggest that the left heart and right heart have different physiological responses to the Valsalva maneuver. These could be explained by our hypothesis, the interaction between the partially-intrathoracic system and the fully-intrathoracic system, which might help to disclose the mechanism of how intrathoracic pressure influences the heart and circulatory system.Although the influence of the Valsalva maneuver on the heart and circulatory system has been investigated, the mechanism of intrathoracic pressure influencing cardiovascular function is unclear. To test our hypothesis that the interaction between the anatomy-determined partially-intrathoracic system and the fully-intrathoracic system might explain those issues and help to disclose the mechanism, we used the Hitachi dual pulse wave Doppler echocardiographic apparatus to investigate simultaneously the beat-by-beat influence of 40-mmHg Valsalva maneuver on left and right cardiac ventricular filling in 30 male adult volunteers. The mitral and tricuspid blood inflow velocity spectra during the Valsalva maneuver were recorded simultaneously. The peak velocity (PV), velocity–time integral (VTI) and inflow volume (IV) of each cycle were measured or calculated. The PV, VTI and IV of the left heart remained unchanged at the first beat after the Valsalva maneuver onset (compared with those at rest,  The Valsalva maneuver (VM) has been used to raise intrathoracic pressure to investigate cardiovascular hemodynamic responses to changes in intrathoracic pressure in healthy volunteers and patients for many years However, measuring simultaneously the beat-by-beat left and right cardiac functional parameters has not been available because of technical problems. Presently, the dual pulse wave (PW/PW) Doppler echocardiographic technique developed by Hitachi  enables simultaneous recording and measurement of the relative parameters in two parts of cardiac blood flow in each cycle. This echocardiographic technique may be expected to be used to test and verify our proposed hypothesis on the mechanism of action. That is, the cardiovascular system can be divided into fully-intrathoracic and partially-intrathoracic enclosed fluid systems based on hydromechanics, and that their interactions may reflect and explain the underlying mechanism. Our proposed hypothesis is also expected to provide a further understanding on the nature of interactions between the respiratory and circulatory systems (e.g. Pulsus Paradoxus) which have puzzled us for so long time The purpose of the present study was to simultaneously explore and analyze the beat-by-beat changes in inflow volume and peak blood flow in left and right ventricular filling during the VM in normal subjects using dual PW/PW Doppler echocardiography and discuss the potential mechanism.The study protocol was approved by the Ethics Committee of the Fourth Military Medical University . Written informed consent was obtained from each subject after the study was explained to him. All procedures were undertaken according to the Declaration of Helsinki.Thirty male adult volunteers aged from 20 years to 45 years  participated in this study. Subjects were normotensive, non-smoking, non-obese (body mass index (BMI) <30), and without cardiac or pulmonary abnormalities or other chronic diseases . All subjects were asked to refrain from consumption of tea, alcohol, or coffee for ≤24 h before the study commenced.Echocardiography was undertaken in all subjects using an Hi Vision Preirus Ultrasonography system (Hitachi) with a 1–5-MHz transducer (EUP-S70). The dual PW/PW function of this system with two independent PW sample volumes (length was set at 3.5 mm) enabled us to record simultaneously mitral and tricuspid blood flow spectra at apical four-chamber views during the VM.th cycle, the release (phase III) began by giving the subject a sign, and the recording lasted to the 25th cardiac cycle. All of the cardiac cycles were marked by an independent observer by counting the beat numbers from real-time echocardiography. All subjects were instructed to practice each maneuver several times to become accustomed to the procedure.A 40-mmHg VM was carried out by each subject with nose clips using a mask connected to a watch-shaped manometer. This manometer could read the positive or negative pressure, and had been calibrated using a standard mercurial sphygmomanometer according to a previous study Each subject adopted the left oblique position at rest. The transducer was located at the point of the apical impulse or made a slight adjustment at this area to get a clear display of an apical four-chamber view of the heart, with good visualization of the left and right ventricular cavity with maximal excursion of the valve leaflets. Then, the two sample volumes were placed at the level of the mitral and tricuspid valve annulus, respectively, as guided by real-time two-dimensional (2D) imaging. We slightly adjusted the inception angle  if we needed to maximize inflow velocity and the graphic quality of the spectrum. After five stable cardiac cycles, the subject was asked to carry out the VM. Electrocardiography (ECG) was recorded simultaneously.2, where D is the mid-diastolic transverse diameter of the mitral annulus obtained by measuring the inner edge of the lateral bright corner of the annulus to the inner edge of the medial corner just below the insertion of the mitral leaflets in clear 2D imaging at the apical four-chamber view. The cross-sectional area of the tricuspid annulus (T-CSA) was determined by dividing the tricuspid VTI (T-VTI) by IV derived from the mitral inflow method. The baseline values of M-CSA and T-CSA were determined as an average of five cardiac cycles at rest as well as with respiration hold. The beat-by-beat IV of the left or right heart during the VM was calculated by using the corresponding value of mitral VTI (M-VTI) or T-VTI and multiplying it by the baseline value of M-CSA or T-CSA.The peak velocity (PV) of each beat inflow  through the mitral and tricuspid valves was measured on the PW/PW recording spectrum, and the velocity–time integral (VTI) of each beat was derived by tracing the velocity curve outline. The inflow volume (IV) of the left heart was calculated using the mitral inflow method by the equation:Fifteen subjects were selected randomly to assess the intra-observer variability by the same observer as well as by another independent experienced observer to test the inter-observer variability. The repeated measurements of the cross-sectional area of the annuli, PV and VTI were undertaken in the same condition with an interval of one day. Observers were blinded to each other’s measurements. Inter- and intra-observer variability was calculated as the absolute difference between the corresponding repeated measurements divided by their mean, and expressed as a percentage.t tests  were used to assess differences between two data groups. p<0.05 was considered significant.Data are the mean ± SD. Results were analyzed using SPSS ver15.0 . Paired 2 (D was 2.3±0.11 cm) and 4.93±0.39 cm2, respectively.All subjects completed the experimental protocol. The baseline characteristics of the subjects are presented in p = 0.13), began to decrease gradually, fell to the lowest value at the 11±1.2th beat  and then kept at this stable level until the release phase   at the first cycle, then decreased rapidly to the lowest at 6±0.8th beat , and then increased gradually to the 9±1.3th beat  and kept at this level until the release phase (th to 11th) beat, and then was higher than the left IV until almost the 22nd beat (between the 21st and 23rd beat). The changes of IV in the right heart were before those of the left heart during and after 40-mmHg VM.The beat-by-beat responses of the left and right heart to the 40-mmHg VM were recorded simultaneously by the dual PW/PW echocardiographic technique . The resth beat) . Simultase phase . After tThe inter- and intra-observer variations in the measurements are shown in This present study investigated simultaneously the beat-by-beat influences of 40-mm Hg VM on left and right cardiac ventricular filling in 30 male adult subjects using a dual PW/PW echocardiographic technique. The results showed that the right heart and left heart had different physiological responses with regard to the PV, VTI and IV during the VM. This was the first study to investigate these issues non-invasively, simultaneously as well as on a beat-by-beat basis. This could be a new method to further explore the mechanism of heart-lung interactions.The VM was firstly described by Valsalva in 1704. Since then, it has been employed frequently to mark changes such as pressure, cardiac-chamber size and single ventricular stroke volume during the VM The heart is confined to the chest cavity but is connected functionally to the outside through an artery and vein system by absorbing venous return through the tricuspid valve in diastole and ejecting blood through the aortic valve in systole. When the VM was carried out, the intrathoracic pressure increased rapidly and was transmitted into the heart and other tissues within the chest cavity. At the diastole of the first cycle, for the left heart, the LA and LV belong to the fully-intrathoracic system . The incStudies According to our hypothesis, at the beginning of the VM , the pressure difference between the interventricular septum increases because the RV  has a limited increase in pressure due to decreased venous return whereas the pressure in the LV (fully-intrathoracic system) increases equally by the VM according to Pascal’s law. As a result, this increased pressure difference may push the interventricular septum shift rightward, which may theoretically increase filling of the LV. However, the interventricular septum has already shifted rightward at rest and will have a certain tension because the diastolic pressure in the LV is higher at physiological conditions. This increase in LV filling is limited and might be dependent upon the individual, so it does not cause hemodynamic changes in the left heart, which was also confirmed by another study The limitation of the present study was that, although the accuracy and practicality of the mitral inflow method has been confirmed by Lewis et al. The results of this simultaneous beat-by-beat study suggested that the left heart and right heart have different physiological responses to cardiac filling during the VM in humans. Our proposed hypothesis  might help to explain the mechanism of intrathoracic pressure influencing the heart and circulatory system.


Assessment of regional and global left ventricular (LV) function and strain are important in the setting of prior myocardial infarction (MI). Feature tracking (FT-MRI) is a novel cardiac MRI method for assessment of myocardial strain, similar to speckle tracking in 2-D echocardiography, which provides multi-planar strain data without the need for tagged images.The goal of our study was to characterize LV global and regional strains in patients with prior MI using FT-MRI and determine the relationship of strains to infarct size, location and LV ejection fraction (EF).Eighty patients with history of past MI were grouped by MI coronary territory {left anterior descending (LAD), left circumflex (LCX), right coronary (RCA)}. Scar quantification was done by computer-assisted planimetry (Medis Qmass v7.2) of gadolinium enhanced delayed images and MI percentage was determined. Global and regional circumferential subendocardial (Ecc Endo) and subepicardial (Ecc Epi) and longitudinal (Ell) strains were derived from three long axis  and three short axis  steady state free procession cine planes. Semi-automated tracing of endocardial and epicardial borders using FT-MRI  was performed and strains were mapped to a 17 segment AHA model. Repeated measures ANOVA was used to compare normal strain values from 60 healthy subjects to MI patients controlling for scar percentage.The mean age was 64.412) years and mean EF was 42.1%(11). Peak global Ecc Epi and Ecc Endo were decreased in all MI patients, except in Ecc endo LCx infarcts, compared to normals  (Table 2 years aFT-MRI permits detailed assessment of global and regional strains in patients with MI. Global Ecc was decreased in all MI patients, while Ell was preserved in the majority on infarcts except LAD infarcts. The best predictor of reduced LV EF was reduced global Ecc Endo strain, which was superior to infarct size.


Tissue water transverse relaxation times (T2) are highly sensitive to fluid and lipid accumulations in skeletal muscles whereas the related T2* is sensitive to changes in tissue oxygenation in addition to factors affecting T2. Diabetes mellitus (DM) affects muscles of lower extremities progressively by impairing blood flow at the macrovascular and microvascular levels. This study is to investigate whether T2 and T2* are sensitive enough to detect abnormalities in skeletal muscles of diabetic patients in the resting state. T2 and T2* values in calf muscle of 18 patients with type 2 DM (T2DM), 22 young healthy controls (YHC), and 7 age-matched older healthy controls (OHC) were measured at 3T using multi-TE spin echo and gradient echo sequences. Regional lipid levels of the soleus muscle were also measured using the Dixon method in a subset of the subjects. Correlations between T2, T2*, lipid levels, glycated hemoglobin (HbA1c) and presence of diabetes were evaluated. We found that T2 values were significantly higher in calf muscles of T2DM subjects, as were T2* values in anterior tibialis, and gastrocnemius muscles of T2DM participants. However, soleus T2* values of the T2DM subjects were significantly lower than those of the older, age-matched HC cohort . The soleus T2* values in the T2DM cohort were inversely correlated with the presence of diabetes  and with an increase in HbA1c, but not with body mass index or regional lipid levels. Although multiple factors may contribute to changes in T2* values, the lowered T2* value observed in the T2DM soleus muscle is most consistent with a combination of high oxygen consumption and poor regional perfusion. This finding is consistent with results of previous perfusion studies and suggests that the soleus in individuals with T2DM is likely under tissue oxygenation stress. Tissue oxygenation is vitally important for the metabolism and function of skeletal muscles Magnetic resonance imaging (MRI) methods have been developed to assess cerebral blood oxygenation non-invasively. Numerous studies have shown that T2* MRI is highly sensitive to the level of deoxyhemoglobin in blood BOLD MRI of the skeletal muscle has recently been undertaken in healthy volunteers and patients The study was conducted under protocols approved by The McLean Hospital Institutional Review Board (IRB). All subjects gave written informed consent before participating and had no contraindications to MRI. Three groups of subjects, i) eighteen subjects with T2DM , ii) twenty two young healthy male subjects ), and iii) seven age-matched healthy subjects ), were recruited for comparison . None ofThe MR images were acquired on a 3T MR scanner  using a volume coil (inner diameter 27.3 cm) for transmission and reception. The subjects were placed in a supine position with their lower legs centered within the coil at the location of greatest circumference and imaged. In one T2DM subject, images were acquired from only one leg using a knee coil his legs were too large to be accommodated simultaneously in the volume coil. As mentioned in the introduction that T2* signals may also be influenced by factors other than level of blood oxygenation, T2 measurement was added as a control to help with the interpretation of possible T2* changes. T2, the transverse relaxation time, and T2* are related via the relationship 1/T2* = 1/T2+1/T2′, where T2′ is the component due to microscopic field gradients. T2 is sensitive to levels of fluid and lipid in the calf muscles. Proton T2 and T2* values were measured at identical locations with a multi-TE spin echo scheme  and a multi-TE gradient echo sequence , respectively.http://rib.info.nih.gov). Regions of interest (ROIs) were placed within the bilateral anterior tibial muscles, soleus muscles, medial and lateral gastrocnemius muscles and regional fat tissues by hand tracing the shapes of the muscles in anatomic images, then copied and pasted onto the corresponding T2 and T2* maps. The T2 and T2* values for the healthy controls and DM subjects are presented as means ± standard errors of the mean (SEM).After reviewing the linearity of log(s) vs TE plot, T2 and T2* maps were constructed using least square fits from multi-TE spin echo images and multi-TE gradient echo images, respectively, based on the relationship ln(s/so) = −TE/T2. The T2* fits were also made between the echoes at in-phase TEs (even multiples of 1.23 ms) and opposed-phase TEs (odd multiples of 1.23 ms) to evaluate the possible impact of lipid signals. The MR T2 and T2* maps were analyzed with ImageJ /2 and water = (in-phase+opposed-phase)/2. The fat spatial ratio (FSR) = fat/(water+fat) was calculated and the value of FSR in the soleus was extracted in a similar manner to that used in the T2* extraction from the T2DM and healthy comparison subjects.Group differences in demographic variables involving continuous and categorical data were calculated using independent t-tests and Fisher's exact test for a 2xk table, respectively. For comparison of T2* values in soleus, anterior tibialis, and gastrocnemius muscles, analysis of covariance (ANCOVA) or a multiple linear-regression method was used, controlling for age, BMI, and FSR. As there was a high co-linear correlation between HbA1c and group variables (namely HC vs DM), we did not include HbA1c in the regression modeling. The normality assumption was verified for each variable of interest using the Shapiro-Wilk test. Statistical significance was defined at an alpha level of p<0.05, two tailed.The images and corresponding T2 and T2* maps of the calf cross sections include anterior tibialis, soleus, gastrocnemius, and other muscles . T2DM soIn healthy subjects, gastrocnemius muscles had a relatively high T2* value (25.3±0.6 ms) compared to soleus (23.9±0.5 ms) and anterior tibialis muscles (23.9±0.3 ms) . The T2*As a control measure in the skeletal muscles, T2 values of the calf cross-sections were also calculated. T2 maps of the calf cross-sections for the healthy controls and T2DM subjects showed a T2 value distribution pattern, T2 (G)≈T2 (soleus)>T2 (AT) . In the Lipid maps demonstrated that T2DM subjects had a dramatic increase in lipid deposition in the soleus and gastrocnemius muscles compared to the young and age-matched healthy control groups . Values 2 = 0.23 Slope −0.21). There was almost no FSR-age relationship among the T2DM subjects evaluated in this study (Pearson coefficient −0.11). Analysis of multiple linear regression indicates that a significant correlation existed between the soleus T2* values and the subject groups  (p<0.001) and between the T2* value and age (p = 0.03), but no significant correlation between the T2* values and BMI or FSR (p = 0.62 for BMI and 0.77 for FSR) (see A weak relationship was found between FSR and age  in youngFSR) see . This fiFSR) see .Although their calf circumference was insignificantly larger than those of the controls , the T2DThe major finding of this study is that at resting state, the soleus T2* value was significantly correlated with age and associated with the presence of diabetes (or elevated HbA1c) see . The diaThe shorter T2* values in the soleus muscles of T2DM subjects  and 2, hAbnormally low soleus T2* values in diabetic calf muscle have been observed in a previous study. Ledermann et al applied a cuff compression paradigm for reactive hyperemia and BOLD MRI with four-echo EPI to patients with peripheral arterial occlusive disease (PAOD) and found soleus had the larger T2* changes (ΔT2*) and longer time-to-peak compared to anterior tibialis and gastrocnemius after cuff deflation In addition to the lower soleus T2*, lipid significantly accumulated, and was noticeably visible in the MR images as a thickening subcutaneous fat layer, with infiltration into the gastrocnemius and soleus of the T2DM subjects  and 3. TCompared to muscle exercise and kinetic paradigms, resting state studies use a lower temporal resolution and a higher spatial resolution to measure the T2* values in calf muscles. This imaging scheme is simple, short in duration (less than 7 minutes for acquisitions of both T2 and T2* images), and more acceptable to patients with clinical disabilities and may thus have broader utility in applications that require high spatial resolution. The resting state approach may provide complementary information regarding regional tissue oxygen consumption, to perfusion studies in nuclear medicine In summary, we have measured T2 and T2* values of calf muscles at rest and found that soleus T2* is significantly correlated with age, the presence of T2DM or elevated HbA1c. The T2* of T2DM soleus muscle was significantly lower than that of age matched healthy controls and that of young and healthy controls as well as the T2* values of T2DM anterior tibialis and gastrocnemius. Our data indicate that the soleus T2* measures provide valuable information reflecting underlying physiology and are consistent with previous findings of other studies. Among factors that may contribute to T2* values, the lowered T2* in the T2DM soleus muscle is most consistent with a combination of high oxygen consumption and poor regional microvascular circulation which suggests that the T2DM soleus is likely under tissue oxygenation stress.


Heart failure poses an increasing problem for global healthcare systems. The epidemiological data which has been accrued over the last thirty years has predominantly been accumulated from experience within North America and Europe. Initial large cohort, prospective longitudinal studies produced the first publications; however latterly the focus has shifted onto epidemiological data governing hospitalisation and mortality. The emphasis behind this shift has been the resource implications with regards to repetitive, costly and prolonged hospitalisation. The European experience in heart failure, though similar to North America has recently demonstrated differences in hospitalisation which may underlie the differences between healthcare system configuration. Heart failure however remains an increasing global problem and the endpoint of a variety of cardiovascular diseases. Allied with the fact of increasingly elderly populations and prior data demonstrating a steep rise in prevalent cases within more elderly populations, it is likely that the increasing burden of disease will continue to pose challenges for modern healthcare. Despite the predicted increase in the number of patients affected by heart failure, over the last thirty years, a clear management algorithm has evolved for the use of pharmacotherapies , device based therapies (Implantable Cardioverting Defibrillator (ICD) and Cardiac Resynchronisation Therapy (CRT)) and mechanical therapies including left ventricular assist devices and cardiac transplantation. Though the management of such patients has been clearly delineated in national and international guidelines, the underuse of all available and appropriate therapies remains a significant problem. When comparing various epidemiological studies from different settings and timepoints, it should be remembered that rates of prevalence and incidence may vary depending upon the definition used, methods of accumulating information (with the possibility of bias) and the chosen cut point of defining left ventricular systolic dysfunction (LVSD). Heart failure is a collection of signs, symptoms and pathophysiology. The definition of heart failure has evolved, with the current European Society of Cardiology saying that it is ‘Heart failure is a clinical syndrome in which patients have typical symptoms and signs resulting from an abnormality of cardiac structure and function .1). However, this is not the entire problem. There is a growing cohort of patients who exhibit signs, symptoms and some aspects of the pathophysiology of heart failure (evidence of raised left ventricular filling pressures on echocardiography) who have preserved left ventricular systolic function (Heart Failure with Preserved Ejection Fraction – HF-PEF). This group of patients has a similar mortality to populations with LVSD, yet remains relatively poorly within compared to systolic dysfunction. Further data is needed within such groups to clarify appropriate management and identification of such individuals. Many historical methods of sub classification have been proposed for dividing patients into cohorts including forward and backward, high and low output states. In the 1990s, the emphasis was on systolic dysfunction as the main cardiac abnormality underlying heart failure. If proven via cardiac imaging, then the patient is a candidate for the management algorithm demonstrated in ).Whereas in the US, longitudinal cohorts were created to study the effects of cardiovascular disease from the 1950s onwards, which led to the publications from Framingham and Olmsted county cohorts. In Europe the ‘Men born in 1913 study’ was the first to report -4. WithiThe Hillingdon heart failure study group created a study in the 1990s, to ascertain incidence . Using tThe prevalence of heart failure can be divided between those studies which are focused on community and those which are specific to certain populations. One of the initial population based studies was based in North-West London, where 30, 204 primary care case records were reviewed . This pret al. demonstrated that the prevalence of HF within the general Scottish population rose from 7.1 per 1000 in the below 65 years of age, rising to 90.1 per 1000 in the above 85 year old population [Another study based in Utrecht, Netherlands found that patients who were under a cardiologist were likely to be younger, with an aetiology of ischaemic heart disease . This ilThe initial study which described the population prevalence was the MONICA study set in North Glasgow . The stuSimilar findings have been documented within other studies. The ECHOES Study based within the Midlands, United Kingdom documented a prevalence of 1.8-3.5% with again 50% of patients having asymptomatic LVSD . The croDue to the relationship with age, some studies have exclusively studied more elderly cohorts. The Helsinki Ageing Study based in Finland, evaluated 501 subjects aged between 75-86 years of age . The oveWith the increase in incidence and prevalence with age, some groups have even examined prevalence rates within the very elderly. In the BELFRAIL study performed in Belgium, 567 individuals over the age of 80 were identified. Using domiciliary based echocardiography 5.8% of the cohort had LVSD, with preserved LV systolic function HF being 3.1% . The studies described above were predominately tailored towards the detection of LVSD. This is due to the large evidence base for recommended pharmacotherapies and device based therapies for this population. However most of the prevalence studies also reveal a similar rate of HF-PEF i.e. heart failure symptoms and signs with preserved LV systolic function. A review of prevalence of the condition suggests prevalence ranging between 1.5 -4.8% depending on the study . Within the ECHOES study 1.1% had HF and a LVEF >50%, whereas in the Helsinki study 72% of all the cases of HF had preserved LV systolic function , 14. TheHeart failure is responsible in most Westernised economies for 1-2% of all healthcare expenditure . The bulThe prognosis for HF patients has remained alarmingly poor over the last twenty years. Differing mortality rates have been described depending on whether the study was community or hospital based. Mortality rates within the ECHOES study were 47% over five years for those with LVSD and 38% for those with HF-NEF . The MONThe mortality amongst patients in the community remains high, but the most lethal place for heart failure patients remains those hospitalised. Several studies and registries have documented high rates of mortality. The Euroheart II registry published in 2006 showed a 6.6% mortality rate in –hospital . The NatThe issues of case detection, management and accessibility to in and out patient cardiac investigations are cyclical and problematic. Despite the wealth of evidence which spawned several national and international guidelines, it is clear that several hospitalised patients with HF remain on sub optimal medical therapy and prone to repeat admission . Also wiInitial epidemiological studies revealed the leading cause of LVSD to be hypertension . HoweverPopulations with high rates of IHD normally also have high rates of co-morbidities such as hypertension, with an example being a rate of 68% of hypertension in the MONICA study. The majority of heart failure epidemiology has been collected from Western Europe, with notable pan European data predominately coming from European Society of Cardiology initiatives such as the EuroHeart II study .The Bromley Heart Failure study located within Bromley, South-East London was devised to investigate the aetiology of incident heart failure . Using aHowever European populations are seeing a large scale influx of immigration with descendants of first generation immigrants settling within European countries. This raises the possibility of similar disease states such as IHD but a different disease trajectory. South Asians have a seemingly higher rate of diabetes, hypertension and tobacco usage. This superimposed upon a genetic predisposition means that they may endure accelerated coronary artery disease with resulting LVSD. Data from Leicester, United Kingdom is supportive of such findings . RheumatHeart failure remains a pertinent problem across Europe. It is responsible for large economic costs, frequent hospitalisation and high levels of mortality. Much epidemiological work has been done across Europe to illustrate prevalence with the acknowledgement that increasing numbers of elderly patients are likely to cause significant problems over the next few decades. Large numbers of particularly elderly patients remain undiagnosed and also on sub-optimal therapies. The problem is likely to become hyper acute over the next two decades with increased accessibility to revascularization and survival following myocardial infarction. The combination of increasingly elderly populations and IHD management will ensure higher prevalence of LVSD amongst most European countries. Another important point which is relevant to European populations is the increase in immigration, from different areas of the world with different disease entities. These groups will also undergo an epidemiological transition within the host country and may be subject to conventional risk factors for HF progression e.g. IHD. The disease processes also may behave differently within such individuals. However little is know about these cohorts and further work needs to be carried out in such areas. Ultimately similar to other global regions, the real challenge facing European healthcare systems is how to cope with the rise in prevalence and the consequent care at primary, secondary and tertiary care levels. All of this becomes even more relevant with the current global economic backdrop and financial limitations. A large proportion of European citizens are transitioning to becoming elderly or very elderly and will ask further questions of existing systems and models of heart failure care.


Systemic right ventricle (RV) hypertrophy and impaired function occur after atrial switch for dextro-transposition of the great arteries (d-TGA). Echocardiography is limited in its ability to assess the RV. We sought to evaluate systemic RV myocardial-mass index (MMI) and function after atrial switch and to analyse the role of hypertrophy for ventricular function with special consideration of the interventricular septal (IVS) movement.Thirty-seven consecutive patients (median age 22.9 years) after atrial switch were studied using cardiac magnetic resonance imaging  with a dedicated 5-channel phased-array surface cardiac coil. Cine steady-state free-precession sequences were acquired to obtain myocardial masses and function. The systolic movement of the IVS was defined as positive when moving towards the centroid of the RV and was defined as non-positive otherwise. Patient parameters were compared to controls.p < 0.001) than the left ventricles of the control group, systolic function was significantly impaired (p < 0.001) and MMI including the IVS was comparable (p = n.s.). RV-MMI excluding the IVS and RV ejection fraction (EF) demonstrated a quadratic correlation , meaning that patients with RV-MMI ≤29 g/m2 and >68 g/m2 had a reduced level of systolic function. Positive septal movement improved RV function compared with non-positive septal movement (p = 0.024).The systemic RVs were significantly larger (There seems to be a range of beneficial RV hypertrophy after atrial switch in which a sufficient RV-EF can be expected. A positive septal movement, probably the result of hypertrophic septal RV fibres, improves RV function and might be regarded as a beneficial contraction pattern. Dextro-transposition of the great arteries (d-TGA) is one of the most common severe cardiac lesions . Before Today, there are many patients who are in need of regular follow-up assessment of cardiac function. However, assessment of RV dimensions and function by echocardiography is difficult, due to the retrosternal position and complex chamber shape of the RV. It has been shown, that compared with cardiac magnetic resonance (CMR), echocardiography underestimates systemic RV function, and has a constantly lower image quality and an impaired capability to visualise the baffles , 7. TherSome studies have analysed the specific changes associated with the function of the RV as the systemic ventricle , 11, butThe aim of this study was to analyse the role of RV hypertrophy in patients following atrial switch for d-TGA and to acquire volumetric and functional values as a backup for therapeutic monitoring.VO2max) from spiroergometry [This is a retrospective study. Thirty-seven consecutive patients who were regular outpatients at our tertiary care institution were referred for CMR. The eligibility criteria were an atrial switch operation in childhood for correction of d-TGA and the absence of associated haemodynamically significant heart defects. The exclusion criteria consisted of the usual CMR contraindications, such as ferromagnetic metallic implants like defibrillators. Patients underwent echocardiography by experienced cardiologists within 2 days of the CMR. Tricuspid insufficiency (TI) was categorised as absent, mild, moderate or severe according to the current guidelines of the European Society of Cardiology . Baffle rgometry  was obtaAll CMR examinations were performed on a 1.5 T scanner  using a dedicated 5-channel phased-array surface cardiac coil. For volumetric and functional imaging, breath-hold standard cine steady-state free-precession sequences in short-axis, 4-chamber view and RV vertical long-axis orientation were acquired. Short-axis images covered the whole heart gapless from the apex to the base (30 phases per heart cycle). The following sequence parameters were used: echo time, 1.8 ms; repetition time, 3.6 ms; flip angle, 50°; matrix size, 256 × 128; and slice thickness, 8 mm.CMR image analysis was performed by two fully blinded observers (M.G. and J.H.) with 13 and 5 years of experience in CMR, respectively, using a Philips ViewForum workstation  in our CMR laboratory, which has demonstrated expertise in the imaging of congenital heart disease and has proven low intra- and inter-observer variability in the assessment of biventricular volumes and function –19. EndoEnd-diastolic volume index (EDVI)End-systolic volume index (ESVI)Stroke volume indexMyocardial mass index (MMI)Ejection fraction (EF).The following parameters were calculated for the RV and left ventricle (LV) and were related to body surface area :End-diasFor calculation of the myocardial mass, a specific density of 1.05 g/ml was used. The mass of the interventricular septum (IVS) was assessed separately. The movement of the IVS was classified as positive or non-positive. A positive septal movement was defined as a systolic movement of the septum toward the centroid of the RV cavity and systolic wall thickening  was used.The analyses were performed using 2-sided tests with a significance level of The length of the CMR imaging was ≤1 h in all 37 patients and 19 controls, and diagnostic image quality was obtained. The patient and control group characteristics are presented in Table p = 0.58).All patients presented with typical postoperative morphology, which included a large dilated hypertrophic RV, a small hypotrophic LV and a systemic venous and pulmonary venous baffle. There were two systemic venous baffle narrowings of the superior limb with a diameter of <10 mm. None of these patients showed a pulse-wave Doppler peak velocity of ≥1.5 m/s. These baffle narrowings were therefore regarded as not hemodynamically significant. Seven patients demonstrated a peak velocity of >3.2 m/s in the pulmonary trunk. In two of these patients a cardiac catheterization was also performed and the diagnosis of a pulmonary stenosis with pressure gradients of above 40 mmHg was confirmed. Of the seven patients with a pulmonary stenosis, two had a positive and five a non-positive septal movement. This difference was not statistically significant (p = 0.58), RV-ESVI (p = 0.81) and RV-EF (p = 0.92).Echocardiography showed that 10 patients had nonexistent, 18 had mild and 9 had moderate TI. There were no differences between the patients without TI and patients with TI regarding RV-EDVI (n = 23) presented with relatively sufficient RV-EFs of >40 % according to the guidelines of the European Society of Cardiology [VO2 values from spiroergometry were only available in 27 patients .The systemic RV-EF showed different grades of systolic function Table ; howeverrdiology . The RV-2 − 2.404 × RV-MMI − 8.25) is acceptably well . It explains 36 % of the variance. In this context r2 can be regarded as goodness of fit. The lower threshold for a RV-EF >40 % was a RV-MMI excluding the IVS of 29 g/m2, the upper threshold a RV-MMI excluding the septum of 68 g/m2  and with the RV-ESVI . There was no significant difference in RV-EDVI (p = 0.65) and RV-ESVI (p = 0.33) in patients with a RV-EF of <40 % and RV-MMI of <29 g/m2 as compared to the remaining patients. There was also no difference in RV-EDVI (p = 0.21) and RV-ESVI (p = 0.20) in patients with a RV-EF <40 % and RV-MMI <29 g/m2 as compared to patients with a RV-EF <40 % and a RV-MMI >68 g/m2. However, when the latter two groups were combined to one group, there was a significantly higher RV-ESVI as compared to the remaining patients . There was a negative correlation of RV-EF and RV-EDVI  and a negative correlation of RV-EF and RV-ESVI .The fit of a quadratic model for the nonlinear relationship between the RV-EF and RV-MMI excluding the IVS . No differences were found in the RV-MMI excluding the IVS, LV-EF and LV-MMI between the positive septal movement patients and the non-positive septal movement patients.Fourteen patients had a positive septal movement. The systemic RV-EF was substantially higher in the positive septal movement patients (49 %) than in the non-positive septal movement patients . There was a weak correlation of the duration of the postoperative interval and the RV-EF . RV-EDVI and RV-ESVI did not correlate with the postoperative interval. Age at atrial repair did not correlate with either RV-MMI or RV-EF. There was no gender predominance for RV hypertrophy.There was a weak correlation between the RV-MMI excluding the IVS and the duration of the postoperative interval  and the global systolic function was significantly impaired . MMI showed no significant differences between patients and controls, irrespective of whether the IVS was excluded  or included  to the systemic ventricles.Systemic RVs of the patient group were significantly larger compared with systemic LVs of the control group .Although our patient cohort was relatively homogeneous with regard to the age and method of surgical repair, it is not possible to define general concrete upper and lower cut-off values for the RV-MMI, given that patients after atrial switch as a whole are a heterogeneous group. Nevertheless, our cut-off values of 29–68 g/m2, above which RV function was impaired compared to patients with a RV-MMI below 95 g/m2. Figure The study of Hornung et al. , with a In our study, the patients’ RV-MMI showed a wide distribution of measured values. There was no single parameter that clearly correlated with inadequate or excessive hypertrophy, but a weak correlation with the duration of the postoperative interval was found. Furthermore, there was a weak dependency of systemic RV function on the duration of the postoperative interval. A previously published non-CMR study has also demonstrated impaired systemic RV function in the late follow-up after atrial switch . The timPatients with an inadequate hypertrophic or excessive response to pressure load and an impaired RV function showed increased RV-ESVIs, which were also found in the subgroup of patients with a non-positive septal movement. These changes might reflect abnormal RV dilatation in the absence of TI. An increase of the end-systolic volume is a marker of remodelling and the most frequent cause of impaired EF in systemic LVs. Also in the present study RV-ESVI was the parameter with the strongest correlation to systolic function. We conclude that remodelling is also present in systemic RVs after atrial switch and results in impaired function.VO2max values with higher RV-EFs. In our opinion, these results do not contradict our findings. The lack of correlation between exercise capacity and ejection fraction in rest is a well-known finding in systemic LVs [There was no correlation between the degree of systemic RV hypertrophy and exercise tolerance tests and only a tendency of higher emic LVs  and mighWe also did not find a male predominance in RV hypertrophy as has been described previously . It remaWe defined positive septal movement as an active movement of the IVS toward the RV free wall, which is indicated by a systolic wall thickening. More than a third of our patients presented with positive septal movement, which was found beneficial for the calculated RV-EF without impairing global LV-EF. Positive septal movement might, therefore, be regarded as a beneficial contraction pattern after atrial switch because it supports systemic RV function without impairing LV function, which is probably caused by disproportionate hypertrophy of the septal RV fibres. Patients with a positive septal movement showed a slightly higher IVS-MMI compared with patients without a positive septal movement. The missing statistical difference between these two subgroups might again be caused by the small sample size. It is also possible, that the underlying mechanism of a positive septal movement is multifactorial an even a marginal increase of RV-MMI could be the determining factor. The distribution of RV-MMI excluding the septum shows, that the presence of a positive septal movement is associated with adequate hypertrophic response in most cases Fig. . TherefoFurthermore, the septum consists of RV and LV fibres. If the hypertrophy of RV fibres is not much more than the LV fibres’ hypotrophy due to the adaptational process, the measurement of the absolute volumes of the septal muscle mass by MRI cannot reveal this effect and may mask the septal RV fibres’ hypertrophy.Nevertheless, further larger studies will have to prove or disprove our assumption of a disproportionate hypertrophy of the septal RV fibres.The pattern of IVS movement was not dependent on the presence or absence of pulmonary stenosis. This is contradictory to the results of a previous study that reported a commitment of the IVS to the LV in the presence of a pulmonary stenosis . One reaLV-MMI was not different between the patients with positive and non-positive septal movement, thereby emphasising that positive septal movement is not simply the absence of LV hypertrophy . Since the myocardial septum is a structural part of both the RV and the LV, remodelling in the LV portion may compensate or even exceed the hypertrophy of the RV portion, resulting in equal or impaired IVS-MMI compared with that of the controls. However, the RV portion of the IVS is difficult to obtain separately in standard CMR because it contains a thin compacted layer and many trabeculations . Modern Systemic RV size was markedly increased compared with both RV and LV size of the controls. Dilatation of the systemic RV is a common finding after atrial switch , 11 and This is a retrospective study. Exercise testing was only available in 27/37 patients, which limits the statistical power of this analysis. The NYHA classification has limitations because self-reported ability sometimes does not match the result of standardised exercise capacity. We did not perform a systematic evaluation of NT-pro-BNP levels, although the emerging importance of biomarkers in the diagnosis of heart failure has been described in recent studies .Patients with a manifest ventricular tachycardia and an implanted cardioverter/defibrillator had to be excluded from the study. Thus, it was not possible to correlate the obtained parameters with an interesting subgroup of patients. Since most patients after atrial switch are in good clinical condition over a long period of time, “hard” clinical endpoints, such as death or congestive heart failure, are rare and can only be used in large multicentre studies. Furthermore, we did not perform CMR delayed enhancement imaging to measure systemic RV myocardial fibrosis.Systemic RV hypertrophy after atrial switch procedure in d-TGA is a physiologic adaptational process that allows for building up systemic pressure. Excessive RV hypertrophy, however, can result in impaired systolic function as described before. Our results support the concept of an upper threshold but, additionally, introduce a lower threshold of RV hypertrophy, because patients with a low hypertrophic response to pressure load also presented with systemic dysfunction. It remains unclear though, which patients are at risk of this inadequate response.An active movement of the IVS towards the RV cavity, which is probably caused by disproportionate hypertrophy of the septal RV fibres, supports systemic RV function without impairing LV function and might therefore be regarded as a beneficial contraction pattern after atrial switch procedure.


It is recognized that one of the causes of atrial fibrillation (AF) is pathological degeneration of the left atrium (LA). However, prospective study that elucidated the relationship between the incidence of persistent AF and pathological degeneration has not been performed. The purpose of this study was to elucidate the usefulness of integrated backscatter (IBS) values for the prediction of progression from paroxysmal AF (PAF) to persistent AF.We measured IBS values of the entire LA wall at 5 mm intervals  in 27 patients with paroxysmal AF and evaluated progression to persistent AF for three years. IBS values were acquired with transesophageal echocardiography (TEE) using a 4–7 MHz transducer. IBS values were calculated as the average power of the backscattered signal from regions of interest (ROI). Each IBS value was color-coded to construct three dimensional maps.Average IBS values of total voxels in color-coded maps in the persistent AF group were significantly greater than those in the non-persistent AF group , whereas there was no significant difference in LA diameter between the persistent AF and the non-persistent AF group. There was significant difference in persistent AF-free survival after the baseline measurements in the subjects stratified by IBS value (<20 dB versus ≥20 dB) .Using IBS values measured by TEE, we can identify an increase in atrial degeneration that may predict the occurrence of persistent AF before LA dilation. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with increased mortality and morbidity ,2. Left To predict the occurrence of AF, it is important to evaluate the degeneration of LA tissue. Investigation of LA tissue characteristics based on atrial biopsies demonstrated abnormal histological features in multiple biopsy specimens in all patients with lone AF . Howeverin vivo is integrated backscatter (IBS) ultrasound. We have shown that IBS values of left atrium obtained from transesophageal echocardiography (TEE) reflected an increase in atrial degeneration that may predict the occurrence of AF [A promising technique to evaluate tissue characteristics ce of AF . We democe of AF .The purpose of this study was to elucidate the usefulness of IBS values measured by TEE for the prediction of progression from paroxysmal AF (PAF) to persistent AF.2), severe mitral regurgitation or prevalent esophageal varices. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured and conventional transthoracic echocardiography (TTE) was performed at the same time as TEE. Risk factors for coronary artery disease were evaluated in each patient including diabetes mellitus , hypertension (medication-dependent only), smoking status (current smoker or quit <6 months before the study) and dyslipidemia (medication-dependent only). We performed monthly electrocardiogram (ECG) examinations in all enrolled patients, regardless of symptoms of arrhythmia during the follow-up period. All patients who had palpitations and/or symptoms of arrhythmia underwent both ECG and Holter ECG examinations to confirm progression from PAF to persistent AF. Persistent AF was defined as AF that was sustained >7 days or lasts <7 days but necessitates pharmacologic or electrical cardioversion [This was a prospective study that elucidated diagnostic accuracies of IBS values for the prediction of the progression from PAF to persistent AF. From January 2006 until February 2007, 27 patients with PAF who underwent TEE in order to evaluate valvular disease or the presence of thrombus in the cardiac chambers were enrolled in the present study. Exclusion criteria include unstable angina or myocardial infarction within the previous three months, an ejection fraction < 30 %, chronic heart failure (≥ NYHA III), mitral valve stenosis , left ventricular ejection fraction (LVEF) and LAD were measured by transthoracic echocardiography . LA volume was calculated using an ellipsoid model that was reported in recommendation for chamber quantification . After tEach IBS value was color coded to construct three-dimensional (3D) IBS maps of the entire lateral, septal and anterior walls of the left atrium. Three-dimensional image construction of LA tissue degeneration was performed by computer software . We employed mean cIBS values of the entire LA wall  to evaluate LA degeneration.We previously determined inter-observer variability of cIBS values in 30 TEE recordings that were measured by two observers at randomly selected cross-sections. The inter-observer variability of cIBS values was 1.1 ± 3.0 % . The intNumerical data are expressed as the mean ± one standard deviation. The Kolmogorov-Smirnov test was used to determine if data were normally distributed. If data were not normally distributed testing for significant differences of each parameter was performed with a Mann–Whitney U test between two groups. Categorical data were summarized as percentages and compared using a Chi-square test. Survival curves were plotted by the Kaplan-Meier method and hazard ratios were calculated by univariate Cox regression analysis. A p value <0.05 was considered to be significant. Statistical analyses were performed using Stat View version 5.0 .The patients’ clinical characteristics at baseline are listed in Table Ultrasound parameters are shown in Table Three dimensional 3D) IBS-TEE color-coded images were consisted of a total of 228 ± 122 pixels in each atrium. The area with a high degree of degeneration was indicated by red and yellow colors and no or a low degree of degeneration was indicated by green and blue colors. The 3D IB-TEE images allowed visualization of LA degeneration as signified by a red color in the color-coded maps (Figure D IBS-TEEThe findings in the present study demonstrated that cIBS values in patients that developed persistent AF were greater than those in patients that did not develop persistent AF. However, the LAD was similar in patients with and without persistent AF. These findings indicated that the LA myocardium in patients with persistent AF had already degenerated before enlargement of the left atrium. Therefore, we may predict the patients who were likely to progress from PAF to persistent AF by evaluating cIBS values of the left atrium. To the best of our knowledge, this is the first prospective study to elucidate clinically the relationship between tissue characteristics of the left atrium and the progression to persistent AF.Ultrasound backscatter power is proportional to the difference of acoustic characteristic impedance that was determined by the density of tissue multiplied by the speed of sound. Because of the complex geometry of the left atrium, the acoustic characteristic impedance is highly variable. Based on these principles, we previously reported that it was possible to evaluate the degeneration of LA tissue by applying IBS analysis to TEE . In a paWe previously demonstrated that there was histological remodeling of the left atrium in PAF patients before LA enlargement . The strPrevious studies have reported that treatment with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers can delay the progression of PAF to chronic AF -25. The There are several limitations of the present study. First, because the number of patients in our analysis was small and the statistical power was low, the significance of differences in echocardiographic parameters between the groups except for cIBS values could not be evaluated. A large-scale prospective follow-up study will be required in the future. Second, evaluation of echocardiographic parameters was performed only at baseline, although patients were followed-up for three years to determine the incidence of persistent AF. It is possible that the patient characteristics changed during the follow-up period of three years. Third, only patients with valvular or other cardiac disease were enrolled. Therefore, the findings of the present study may not be applicable to the general population. Finally, the number of incident AF cases may have been underestimated because some patients with persistent AF had no symptoms and only AF episodes that were confirmed by Holter ECG were considered an endpoint.Using cIBS values measured by IBS-TEE, we identified increased degeneration in the LA wall in patients with persistent AF, and this may be useful to predict the progression from PAF to persistent AF.AF, Atrial Fibrillation; LA, Left Atrial; LAD, Left Atrial Dimension; LAV, Left Atrial Volume; IBS, Integrated Backscatter; TEE, Transesophageal Echocardiography; PAF, Paroxysmal Atrial Fibrillation; ANP, Atrial Natriuretic Peptide; BNP, Brain natriuretic Peptide; TTE, Transthoracic Echocardiography; ECG, Electrocardiogram; LVEDD, Left Ventricular End-Diastolic Dimension; LVEF, Left Ventricular Ejection Fraction; 3D, Three-Dimensional; cIBS, Corrected IBS.TK and NT carried out subject recruitment and analyzed data. MK analyzed data and wrote the manuscript. HI, YI, MO, ST and HS performed integrated backscatter ultrasound analysis. KN, GT and SM analyzed data. All authors read and approved the final manuscript.The authors declare that they have no competing interests.


Management of patients with peripartum cardiomyopathy (PPCM) is still a major clinical problem, as only half of them or slightly more show complete recovery of left ventricular (LV) function despite conventional evidence-based treatment for heart failure. Recent observations suggested that bromocriptine might favor recovery of LV systolic function in patients with PPCM. However, no evidence exists regarding its effect on LV diastolic dysfunction, which is commonly observed in these patients. Tissue Doppler (TD) is an echocardiographic technique that provides unique information on LV diastolic performance. We report the case of a 37-year-old white woman with heart failure (NYHA class II), moderate LV systolic dysfunction (ejection fraction 35%), and severe LV diastolic dysfunction secondary to PPCM, who showed no improvement after 2 weeks of treatment with ramipril, bisoprolol, and furosemide. At 6-week followup after addition of bromocriptine, despite persistence of LV systolic dysfunction, normalization of LV diastolic function was shown by TD, together with improvement in functional status (NYHA I). At 18-month followup, the improvement in LV diastolic function was maintained, and normalization of systolic function was observed. This paper might support the clinical utility of bromocriptine in patients with PPCM by suggesting a potential benefit on LV diastolic dysfunction. Peripartum cardiomyopathy (PPCM) is a condition of unknown etiology characterized by acute development of heart failure and left ventricular (LV) dysfunction in the last month of pregnancy or within 5 months of delivery , 2. RiskEchocardiography allows accurate assessment of LV diastolic function. The standard approach was historically based on the assessment of transmitral flow by pulsed Doppler. The typical Doppler pattern of transmitral flow  is charaIn this report, we describe the changes in LV diastolic function, as assessed by TD, after 6-week treatment with bromocriptine in a patient with PPCM and severe LV diastolic dysfunction at baseline.A 37-year-old woman with PPCM underwent echocardiographic reevaluation 2 weeks after initial diagnosis. Acute LV enlargement and dysfunction  with clinical evidence of heart failure (NYHA class II) had been diagnosed on day 2 after a normal vaginal delivery. Delivery had occurred at the 36th week of a twin, bicorial, biamniotic pregnancy complicated by a HELLP syndrome. Treatment with ramipril, bisoprolol, and furosemide had been promptly started. Coronary angiography had showed normal coronary arteries, and gadolinum-enhanced cardiac magnetic resonance imaging had confirmed significant LV enlargement  and systolic dysfunction (ejection fraction 36%), with no signs of inflammation or fibrosis, no abnormalities in myocardial perfusion, no signs of right ventricular enlargement or dysfunction, and a mild pericardial effusion . · 103/μL, n.v. <10.1 · 103/μL). Bromocriptine 2.5 mg bid was added to therapy. The patient was discharged, and careful followup was planned.At the current examination, the patient was still in NYHA class II. Echocardiography showed persistence of LV enlargement and dysfunction . Doppler imaging of transmitral flow  showed aAt 6-week followup, the patient reported improvement in symptoms (NYHA class I). Echocardiography showed an improvement in ejection fraction (45%) with small changes in LV dimensions (end-diastolic volume 175 mL). The mitral E/A ratio was substantially unchanged (1.2), but a considerable increase in E′  and a decrease in the E/E′ ratio (8.1) were detected, suggesting improved LV relaxation and decreased LV filling pressure Figures . AccordiAt 18-month followup, the patient was still asymptomatic and in good general conditions, and a slight further increase in E′  and E/E′ (7.7) was observed, together with normalization of LV ejection fraction (60%). n = 20) and to an unexpected excess mortality rate in the control group [Several therapies have been proposed in PPCM in addition to conventional treatment for heart failure, including apheresis, intravenous gamma-globulin, immunomodulators, anti-viral agents, and particularly prolactin release inhibitors such as bromocriptine . The ratol group . Also, tol group . Cases wol group . Cautionol group , 24. This report illustrates a case of PPCM with evidence of advanced LV systolic and diastolic impairment, in which an early improvement in TD indexes of LV diastolic function was observed after bromocriptine treatment. Of note, the improvement in measures of LV relaxation and filling pressure was larger than that in systolic ones, so that normalization of LV diastolic function and improvement in NYHA class occurred despite persistence of depressed LV ejection fraction and abnormal N-terminal probrain natriuretic peptide plasma concentration. Interestingly, color TD velocity curves also showed a reduction in early diastolic dyssynchrony at 6-week followup. Considering the initial 2-week persistence of LV dysfunction despite standard therapy, these findings support the hypothesis that bromocriptine might have played a role in determining the observed changes in LV diastolic performance. The association between reduction in mechanical dyssynchrony and improvement in LV diastolic function observed in our patient may also be in accordance with a recent study by Tanaka et al., where resolution of mechanical dyssynchrony was found to be related to a reduction in the E/E′ ratio in a population with acute-onset cardiomyopathy with narrow QRS that included subjects with PPCM . On the Considering the clinical relevance of LV diastolic dysfunction, this report also points out the importance of obtaining adequate information on LV diastole using TD in the serial assessment of patients with PPCM. In accordance with the position statement on PPCM from the Heart Failure Association of the European Society of Cardiology , echocarIn conclusion, this report suggests that (1) bromocriptine might be effective in improving LV diastolic function in PPCM; (2) the improvement can be detected by TD in the early phases of treatment; (3) even if the prognostic impact of LV diastolic dysfunction in the specific population with PPCM is still to be quantified, TD may be considered as a useful tool to assess the impact of therapy on LV diastolic performance in these patients. However, larger randomized, controlled, and possibly blinded comparison studies are needed to provide conclusive evidences about the potential clinical utility of bromocriptine for the treatment of PPCM.


Pulmonary involvement, manifested as pulmonary arterial hypertension or pulmonary fibrosis, is the most common cause of death in systemic sclerosis (SSc). We aimed to explore the feasibility of detecting early pulmonary involvement in SSc using recently developed non-invasive quantitative measures of pulmonary physiology using cardiovascular magnetic resonance (CMR).Twenty-seven SSc patients  and 10 healthy controls  underwent CMR to determine the pulmonary blood volume (PBV) and the PBV variation (PBVV) throughout the cardiac cycle. Patients underwent Doppler echocardiography, high-resolution computed tomography (HRCT), and pulmonary function testing by spirometry. Comparisons were performed using the unpaired t-test and linear regression analysis was performed with Pearson’s correlation coefficient (r).CO) (p = 0.09), vital capacity (p = 0.45), or pulmonary fibrosis by HRCT (p = 0.74).Compared to healthy controls, the PBV indexed to lung volume (PBVI) was lower in patients . There was no difference in PBV  or PBVV/stroke volume . There were no significant correlations between PBVI and pulmonary artery pressure estimated by Doppler (p = 0.08) the lung’s diffusion capacity for carbon monoxide  but unchanged pulmonary vascular distensibility (PBVV/stroke volume). PBVI is unrelated to DL CO) [The diagnosis of systemic sclerosis (SSc) entails a 10–15% lifetime risk of developing pulmonary arterial hypertension (PAH) . PAH devCO) .Cardiovascular magnetic resonance (CMR) has proven to be a highly accurate and precise tool for flow quantification and detection of small changes in blood flow . Recent We hypothesized that, compared to healthy individuals, patients with SSc would have a decreased PBVI due to arteriolar involvement, and a lower PBVV/SV as a result of decreased pulmonary vascular distensibility. Therefore, the aim of this study was to prospectively explore the PBV, PBVI, and PBVV in healthy controls and patients with newly diagnosed SSc using CMR.http://segment.heiberg.se) [Twenty-seven consecutive newly diagnosed SSc patients, presenting to the Department of Rheumatology, Lund University Hospital, Lund and 10 healthy volunteers underwent CMR using a 1.5-T scanner  and a five-element cardiac coil. Out of 27 patients, 18 (67%) were diagnosed with limited cutaneous SSc, and three (11%) with diffuse cutaneous SSc. Six patients (22%) fulfilled the criteria for early SSc suggested by LeRoy . Diseaseberg.se) .The pulmonary transit time (PTT) was defined as the time for a 2 ml intravenously administered contrast bolus  to pass from the pulmonary trunk to the left atrium Figures  and 2. TThe pulmonary blood volume (PBV) was measured as the product of the PTT and cardiac output, as previously described and validated . CardiacFlow measurement of the pulmonary trunk and all the pulmonary veins, respectively, were acquired as previously described Figure , panel CThe pulmonary blood volume indexed to lung volume (PBVI) was defined as PBV/pulmonary volume. The pulmonary volume was measured by manual planimetry in a transverse SSFP CMR image stack covering the lungs during end-expiratory breathhold Figure . TypicalLeft and right ventricular end diastolic volume, end systolic volume, stroke volume, and ejection fraction were measured by CMR and manual planimetry using established techniques . In patiHRCT was performed using a Philips Brilliance 16-slice or 40-slice CT system . Data was visually assessed with regards to the presence of fibrosis-related pathology. Fibrosis was defined by the presence of traction bronchiectasis within areas of ground-glass opacity, and reticulations . PatientEchocardiography included Doppler measurement of the maximum velocity gradient across the tricuspid valve, and assessment of inferior vena cava size and variation in diameter during respiration. Central venous pressure was estimated in increments of 5, 10, or 15 mmHg by an experienced observer based on caval physiology. Systolic pulmonary artery pressure was calculated using the tricuspid velocity gradient and caval physiology  using a CO) by the single-breath test.Pulmonary function testing included assessment of the vital capacity (VC) and the diffusion capacity for carbon monoxide . Following visual inspection of the data, comparisons between groups was tested using the parametric unpaired t-test. Differences between groups were also tested using non-parametric tests and this yielded results with identical levels of significance in all comparisons. Linear regression analysis was performed with Pearson’s correlation coefficient (r). p < 0.05 was deemed statistically significant. Data are presented as mean ± SD.Subject characteristics are described in Table 2, p < 0.05, respectively)  in 27 patients compared to 10 healthy controls was 16 ± 4 vs 20 ± 5%, p < 0.05  had a suitable trace. There was no correlation between the estimated systolic pulmonary artery pressure assessed by Doppler echocardiography, and the PBVI . The estimated systolic pulmonary arterial pressure ranged between 26–94 mmHg.Fifteen out of 24 patients (63%) were classified as having pulmonary fibrosis-related pathology by HRCT. Patients with pulmonary fibrosis by HRCT did not differ from those without pulmonary pathology with regards to PBVI  or PBVV/stroke volume .CO was assessed in 23 out of 27 patients (85%) and the VC was assessed in 25 out of 27 patients (93%). There were no correlation between the PBVI and DLCO or VC .The DLTwo observers independently evaluated 10 randomly selected patient data sets. The interobserver variability for pulmonary volume, PBV, PBVI, and PBVV was 1 ± 1%, 4 ± 12%, 2 ± 12% and 1 ± 6%, respectively.CO, and presence of pulmonary fibrosis-related pathology measured either on HRCT or as reduced VC did not influence PBVI. Early pathophysiological changes in the pulmonary circulation may be the reason why patients with newly diagnosed SSc differ in PBVI compared to healthy individuals. Such changes may be important to recognize as a tool to select patients eligible for right heart catheterization since an early diagnosis of PAH is paramount to improve survival in SSc.The major finding in this study is that patients with newly diagnosed SSc, as a group, have a reduced amount of blood in the pulmonary vasculature normalized to lung size (PBVI) but an unaffected pulmonary vascular distensibility (PBVV/stroke volume), compared to healthy controls. There was no difference in absolute PBV between the groups. Furthermore, there was no relationship between PBVI and systolic pulmonary arterial pressure estimated by Doppler echocardiography. It remains unclear what the mechanisms are, however, our findings are compatible with previously suggested pathophysiological changes in the pulmonary vasculature . DopplerThe current study is, to our knowledge, the first to measure the PBV by CMR in healthy controls and patients. The PBV has previously been assessed only in valvular heart disease using dye-dilution based techniques during invasive cardiac catheterization, radioactive isotope injection or echocardiography -24. HoweThere was a lower absolute stroke volume in SSc patients compared to healthy controls. This difference may be related to myocardial disease in the SSc patients. However, there was no difference in pulmonary vascular distensibility (PBVV/stroke volume) when comparing the groups. Previously, the PBVV/stroke volume has been shown to decrease in pigs that developed increased pulmonary arterial pressure following experimental acute myocardial infarction . It appeCO but normal VC was a key feature. However, there was no correlation between the PBVI and DLCO, which suggests that the PBVI may reflect pulmonary involvement prior to changes severe enough to alter DLCO.Pulmonary fibrosis-related pathology seen on HRCT may lead to non-perfused pulmonary volumes . This, pThe SSc patients in the present study displayed a wide range of PBVI values. This may be because the patients are in different stages of disease. However, some patients even had a higher value than the controls. This may be related to left ventricular dysfunction, leading to backward failure and an increased amount of blood in the pulmonary circulation. There was no correlation between estimated pulmonary artery pressure and PBVI. Previously, catheter-based techniques have been used to show an increased PBV in patients with stenosis or regurgitation in the mitral valve, ,28 presuOne limitation of the study may be the accuracy of measuring PBVV, since the PBVV is derived from up to 6 different flow measurements comprised of one measurement each from the pulmonary artery and at most 5 pulmonary veins, respectively. However, the interobserver variability between two experienced observers was low, and a previous study with identical methodology has shown good correspondence between the volumes of measured in- and outflow from the pulmonary circulation  and exceCO or reduced VC. This implies that the PBVI may reflect the morphology of the SSc lung since the majority of the patients did not show any clinical sign of pulmonary involvement. These findings are consistent with an involvement of pulmonary arterioles in SSc. Therefore, in the case of reduced PBVI, an earlier medical treatment may be indicated in order to stall the progress of further pulmonary involvement. Also, this study shows the feasibility of assessing the PBV in healthy individuals and clinical SSc patients by using CMR. Further studies are justified to assess the clinical utility of PBVI as a non-invasive diagnostic and prognostic measure of pathophysiological changes in the pulmonary circulation.Compared to healthy controls, patients with newly diagnosed SSc have, as a group, a reduced amount of blood in the pulmonary vasculature (PBVI) but an unaffected pulmonary vascular distensibility (PBVV/stroke volume), not related to the presence of pulmonary fibrosis-related pathology on HRCT, estimated pulmonary artery pressure, DLThe authors declare that they have no competing interests.MK participated in data acquisition, performed the image analysis and data analysis, and drafted the manuscript. DMW participated patient recruitment. GB performed computed tomography image analysis. RH performed data acquisition, and coordinated patient recruitment. MU conceived the study, participated in data analysis, drafting the manuscript, and had full access to and was responsible for the integrity of the data. All authors participated in the design of the study, critically revised the manuscript for important intellectual content, and approved the final manuscript.


Patients with Turner's syndrome have increased cardiovascular (CV) morbidity and mortality, potentially over and above that explained by the higher rate of both congenital heart disease and associated endocrine disorders and hypertension. GH administration to maximise adult height is a well-established treatment form but may affect cardiovascular status, ventricular mechanics and myocardial function. Furthermore, given the adverse CV effects of supra-physiological GH levels associated with acromegaly and in the field of sports doping, concern has been voiced about potential risks associated with this form of treatment.CMR based strain derivatives offer advanced analysis of myocardial deformation and function. Such technologies are thought to increase sensitivity and may allow detection of "pre-clinical" disease not apparent by assessment of conventional parameters such as ventricular volumes and ejection fraction (EF).52 patients with Turner syndrome underwent a comprehensive CV CMR study. Patients with structural heart disease such as aortic coarctation, haemodynamically important valve disease, previous myocardial infarction or cardiac surgery were excluded. Of the remaining 35 adult patients 14 had a history of previous exposure to GH (GH +ve), 21 had no history of GH treatment (GH -ve).Assessment of ventricular mass, volumes and derived EF was performed by means of signal intensity thresholding based detailed endocardial contouring using commercial software . LV/RV longitudinal and LV circumferential strain was analysed using an endocardial feature tracking software package .The demographic and haemodynamic data of both groups is summarised in Table Childhood GH exposure appears to have no detectable detrimental late effects on LV/RV ventricular performance. This study therefore provides further reassurance regarding the long term safety of childhood GH administration in patients with Turner's syndrome.None.


Left ventricular rotation and twist can be assessed noninvasively by speckle tracking echocardiography. We sought to characterize the effects of acute load change and change in inotropic state on rotation parameters as a measure of left ventricular (LV) contractility.Seven anesthetised juvenile pigs were studied, using direct measurement of left ventricular pressure and volume and simultaneous transthoracic echocardiography. Transient inflation of an inferior vena cava balloon (IVCB) catheter produced controlled load reduction. First and last beats in the sequence of eight were analysed with speckle tracking (STE) during the load alteration and analysed for change in rotation/twist during controlled load alteration at same contractile status. Two pharmacological inotropic interventions were also included to examine the same hypothesis in additionally conditions of increased and decreased myocardial contractility in each animal. Paired comparisons were made for different load states using the Wilcoxon’s Signed Rank test.The inferior vena cava balloon occlusion (IVCBO) load change compared for first to last beat resulted in LV twist increase  during the load alteration and under adrenaline stimulation LV twist increase 12.56° ±5.1° vs. 16.57° ±4.6° (p < 0.013), and though increased, didn’t reach significance in negative inotropic condition. Untwisting rate increased significantly at baseline from −41.7°/s ±41.6°/s vs.−122.6°/s ±55.8°/s (P < 0.039) and under adrenaline stimulation untwisting rate increased (−55.3°/s ±3.8°/s vs.−111.4°/s ±24.0°/s (p < 0.05), but did not systematically changed in negative inotropic condition.Peak systolic LV twist and peak early diastolic untwisting rate are load dependent. Differences in LV load should be included in the interpretation when serial measures of twist are compared. Normal heart function incorporates an aspect of twisting during systole and ejection,2, and uThe relation between ventricular twist and heart function is still not entirely understood. There are suggestions that the amount of ventricular twist during systole is related to not just systolic function and well-being, but also to loading conditions and LV vWhile there have been suggestions of a strong relation between twist/untwist and load,21, no r−1, xylazine 2.2 mg.kg−1, and atropine 50 μg.kg−1 i.m. Anaesthesia was induced with pentobarbital 12 mg.kg−1 i.v. and maintained by a continuous infusion of pentobarbital 5 mg.kg−1.h−1, midazolam 0.3 mg.kg−1.h−1 and fentanyl 20 μg.kg−1.h−1. After tracheotomy, animals were ventilated  to achieve normoxia and normocapnea . Intravenous fluids were administered: Ringer’s Acetate 15 ml·kg−1 h−1 throughout the study period. Arterial and venous catheters were placed through cutdowns to the jugular and carotid vessel systems. Arterial line and central venous catheters, including a 7 F Swan-Ganz catheter  was placed first. A combined pressure-conductance catheter, with 12 electrodes and 8 mm spacing in between electrodes , was placed in the long axis of the LV with the help of fluoroscopy. A 7.5 F balloon occlusion catheter  was placed in the inferior vena cava in order to facilitate a controlled transient restriction of venous return during measurement periods. Although it has to be mentioned that very large and abrupt loading changes associated with transient inferior vena cava balloon occlusion (IVCBO) can result in short-term alterations in sympathetic tone and ventricular interaction, which can influence the pressure-volume (PV) relationship, a careful load alteration within physiological or normal load ranges, this method belongs to an established method comparing LV function under changing load[With approval of the Ethics Committee of Umeå University, and in conformation with the Guide for the Care and Use of Laboratory Animals  seven juvenile Yorkshire/Hampshire pigs  were anaesthetised and instrumented using methods that have been well described previously. In brieing load.max), and load-independent LV function by the linear slope of the end-systolic PV relationship, defined as end-systolic elastance (EES) and PRSW. Diastolic load-dependent LV function was assessed by the LV end-diastolic pressure (LVEDP), isovolumic relaxation time constant (tau), maximal rate of LV pressure decrease (dP/dtmin) and ratio of end-systolic elastance/arterial elastance (EES/EA)[The conductance catheter allows continuous online measurements of LV pressure and volume and the method of left ventricular volume measurement with dual field conductance volume measurements is well described elsewhere. The con(EES/EA). EchocarEach measurement sequence was recorded during a period of apnea with 0 cm H2O airway pressure. The inferior vena cava balloon was inflated, and progressive beat-to-beat decreases in left ventricular volume and pressure were recorded. Beats selected for analysis from the balloon inflation period were those where there was a progressive beat by beat decrease in both LV end-diastolic and end-systolic volume and pressure at the beginning and end of the sequence. Each measurement was collected at rest, and then during adrenaline infusion with target pulse rate raise of at least 20% from the baseline. After a second rest period, 30 min after discontinuation of adrenaline infusion, a slow injection of metoprolol 40 mg and verapamil 15 mg was administrated, together with infusion of phenylephrine to counterbalance the vascular effects of verapamil and keep the blood pressure stable. Measurements were then collected during cardiovascular steady-state conditions.Speckle tracking analysis was used to measure LV rotation and LV twist as previously described. The anaAll data are presented as mean ± 95% confidence intervals. Paired measurements were tested for differences using Wilcoxon’s Signed Rank test in the case of first and last beats in a preload alteration sequence, and for increase or decrease from preceding measure for systolic function parameters derived from preload alteration sequences (comparison of 2 beats). A p value < 0.05 was considered statistically significant.max/end-diastolic volume) showed differences from control for the inotropic experimental interventions, with increased and decreased contractile status demonstrated for the inotropic interventions. Concerning single beat parameters and load, the systolic parameters, including stroke work and ejection fraction, showed decreases related to decreased load , as shown for the control group with no inotropic intervention  increased significantly during load reduction  expressed as more rapid untwisting in these lower load conditions where systolic twist amount was greater. There were small but significant decreases in dP/dtmin with load reduction where end-systolic pressure was also lower in these last (load-reduced) beats compared to the resting load first beat.While there were clear changes in measured parameters reflecting contractile status related to the positive and negative inotropic interventions Table, the inoThe main findings were that twist and untwist were found to be load-dependent in this experimental model where both load and contractile conditions were well controlled. Also, this load-dependence for twist and untwist seemed to be present in the setting of altered inotropy, though the findings were less clear during the negative inotropic intervention. These results confirm those published by Gibbon et al., though Recent studies of left ventricular torsion have employed echocardiographic speckle tracking based on validation versus magnetic resonance imaging of torsion,32, thouThe model included an undisturbed thorax together with separate controlled experimental interventions for load and contractility, allowing examination of each load and contractile interventions individually as well as allowing assessment of the interaction of load and contractility. Even though there were both positive and negative inotropic interventions in this large animal model, these results reflect normal (non-diseased) heart function.The strength of this model and these findings is that the model separates load conditions from ventricular performance. In this way, 2 beats, in the same sequence with different loads but with the same contractile status, can be compared for a variety of ventricular performance indicators, including twist and untwist. Furthermore, this model allowed assessment of load effects from beat to beat also in the setting of experimentally altered contractile status. The distinctive value of this study lies in simultaneously using controlled load-specific interventions and detailed measurement of absolute load and ventricular performance in shoving load dependency of LV twist and untwist rate.While it has been shown clearly that contractility affects twist, it has nIn this model, ventricular volumes, pressures, and relative inotropic status were very carefully controlled, though these parameters are not generally available during routine bedside cardiovascular examination. Still, in order for twist or torsion to be used in the serial assessment of ventricular function, there needs to be a systematic coupling of twist findings to some indices of load and contractile status. While twist and untwist are not part of the standard basic echocardiographic assessment by today’s community standard, twist or torsion and untwist are increasingly being used as a complementary assessment of ventricular function,35. SomeIn summary, these results showed that LV-twist and untwisting rate are strongly dependent on load. We conclude that before left ventricular twist and untwist can be used as routine clinical tool for serial quantitative assessment of systolic and diastolic LV dysfunction, they need to be interpreted in the context of load.All authors declare that they have no competing interests concerning this study.All authors participated in the initiation and design of the study. All authors except JP participated in the experiments and data collection.All authors participated in the analysis of the results. All authors read and approved the final manuscript.


After repair of tetralogy of Fallot (rTOF), left (LVEF) and right (RVEF) ventricular ejection fraction are important markers of clinical status and outcome, but may not improve after pulmonary valve replacement. Strain is a sensitive marker of ventricular dysfunction, but the potential relation to quality of life in this population has not been evaluated.Fifty-nine patients with rTOF  underwent cardiovascular magnetic resonance (CMR) from 2008-2009 and completed the Short Form 36 . A midventricular short-axis slice was analyzed for left ventricular global circumferential strain (LVGCS) with feature tracking software . A four-chamber slice was analyzed for left ventricular longitudinal strain (LVGLS), and right ventricular longitudinal strain (RVLS), using the three segments of the right ventricular free wall. A subset of 30 patients was re-analyzed for intraobserver and interobserver variability. The physical component summary (PCS) and subscales of physical functioning (PF), role-physical (RP) and general health (GH) were chosen for analysis, and age-adjusted z-score ≤-1 was considered a clinically significant decreased quality of life.Strain analysis was feasible in 58/59 patients (98%). LVGCS correlated with LVGLS  and LVEF . RVLS correlated with LVEF  but not with RVEF. Patients with RVLS below the median had increased odds of decreased PF and GH subscale scores, with strong trends for PCS and RP (Table). Among patients with normal RVEF (≥45%) these associations remained significant . Intraobserver and interobserver variability was acceptable for LVGCS , but lower for LVGLS , and poor for RVLS .Although RVLS reflects right ventricular sinus function and not necessarily overall RVEF, it appears to have discriminative ability in this population for decreased quality of life, and may yield incremental prognostic value beyond global RVEF assessment. However, clinical use may be limited by reproducibility. Further study is needed to evaluate techniques to limit variability, and to evaluate longitudinal changes in this population.The authors have nothing to disclose.