Physical activity (PA) is beneficial in reducing pain and improving function in lower limb osteoarthritis (OA), and is recommended as a first line treatment. Self-administered questionnaires are used to assess PA, but knowledge about reliability and validity of these PA questionnaires are limited, in particular for patients with OA. The purpose of this study was to evaluate the reliability and validity of the Physical Activity Scale for the Elderly (PASE) in patients with hip OA.Forty patients with hip OA  were included. For test-retest reliability PASE was administered twice with a mean time between tests of 9 ± 4 days. Intraclass correlation coefficient (ICC), standard error of measurement (SEM) and minimal detectable change (MDC) were calculated for the total score and for the particular items assessing different PA intensity levels. In addition a Bland-Altman analysis for the total PASE score was performed. Construct validity was evaluated by comparing the PASE results with the Actigraph GT1M accelerometer and the International Physical Activity Questionnaire (IPAQ), using the Spearman rank correlation coefficient.p = 0.089), and ranging from 0.20-0.38 for the different PA intensity categories. The Spearman rank correlation between IPAQ and PASE was 0.61 (p = 0.001) for the total scores.ICC for the total PASE score was 0.78, with relatively large error of measurement; SEM = 31 and MDC = 87. ICC for the intensity items was 0.20 for moderate PA intensity, 0.46 for light PA intensity and to 0.68 for vigorous PA intensity. The Spearman rank correlation coefficient between the Actigraph GT1M total counts per minute and the total PASE score was 0.30 (In patients with hip OA the test-retest reliability of the total PASE score was moderate, with acceptable ICC, but with large measurement errors. The construct validity of the PASE was poor when compared to the Actigraph GT1M accelerometer. Test-retest reliability and construct validity revealed that the PASE was unable to assess PA intensity levels. PASE is not recommended as a valid tool to examine PA level for patients with hip OA. Physical inactivity is considered to be a risk factor for many life-threatening diseases and regarded as a major burden on general public health, therefore international and national guidelines recommend that all adults engage in moderate to vigorous physical activity (MVPA) for at least 30 minutes per day-3. PatieValid and reliable methods for PA assessment are essential for studying its health effects. Frequency, duration and intensity are important factors when evaluating PA as a protective factor against OA progression and functional decline. NumerouDespite the fact that many self-administered questionnaires are available, evidence for validity and reliability is limited . PASE haForty patients with hip OA from a larger ongoing randomized controlled trial (RCT), evaluating the effect of patient education and supervised exercise in patients with hip OA, were inAnthropometrical  and sociodemographic data , as well as data on Harris Hip Score, minimal joint space width, bilateral hip pain and pain duration was recorded at time of inclusion in the original RCT. Data on age has been altered to reflect the actual age at the time of data collection in this validation study.The study was approved by The Regional Committee for Medical Research Ethics for South-Eastern Norway. All participants received both oral and written information and signed a written informed consent, before inclusion. The data collection was carried out in accordance with the directives given in the Declaration of Helsinki.http://www.neri.org). The questions included in PASE address leisure-time, household and work-related PA, with the different items weighted differently. Participation in leisure-time PA, including light, moderate and vigorous PA intensity, and strengthening activities, is recorded as never, seldom (1-2 days per week), sometimes (3-4 days per week), and often (5-7 days per week). Duration is categorized as less than 1 hour, 1-2 hours, 2-4 hours and more than 4 hours. Housework activities are recorded as yes or no, and paid or unpaid work, requiring some PA, is recorded in hours/week. The total PASE score is computed by multiplying time spent in each activity (hours per day) (for leisure and work-related activities) or participation (yes/no) in an activity (for household-related activities), by empirically derived weighting, and then summarizing all items[PASE is a brief, self-administered, 7-day recall questionnaire designed to assess PA in older adults. It has all items. From thConstruct validity of the PASE was evaluated by comparing it to the Actigraph GT1M accelerometer  and to the short form of the International Physical Activity Questionnaire (IPAQ). The Actigraph GT1M is an electronic motion sensor comprising a single plane  accelerometer. Movement in the vertical plane is detected as a combined function of the frequency and intensity of the movement. Counts are summed over 10 second epochs and downloaded to memory. All sequences of 60 minutes or more of consecutive zero counts were excluded from each individuals recording. For the analyses, a valid day was defined as having 10 or more hours of monitor wear. Six or more valid days of registration were considered sufficient. Accelerometers were initialized and downloaded using the software program ActiLife . Data were reduced using the SAS-based software program  called CSA Analyzer (csa.svenssonsport.dk). From the Actigraph GT1M registrations we calculated average counts per minute representing the overall activity level. In addition we calculated total minutes spent in 0-99 counts per minute, 100-2019 counts per minute, 2020-5999 counts per minute and above 6000 counts per minute, representing minutes spent inactive, and in light, moderate and vigorous PA intensity, respectively,28. The http://www.ipaq.ki.se. For the IPAQ we calculated the total MET-minutes per week, representing the overall activity level. In addition we calculated MET-minutes per week for walking activities, moderate activities and vigorous activities.The development of the IPAQ was initiated in 1996, and conducted by an International Consensus Group, with the intention to develop a measure suitable for assessing population levels of PA across countries. IPAQ isth -7th day), se Figure th day, and filled in on the 8th day, the day after finishing the accelerometry registration period, and returned by mail. For evaluation of test-retest reliability PASE was also filled out seven days later (on the 15th day).Data collection for the evaluation of test-retest reliability and construct validity was carried out during October 2010. The Actigraph GT1M was administered by postal mail to all included patients, and it was worn in an elastic belt placed on the right hip. All participants were instructed to wear the accelerometer during all waking hours, except during bathing and swimming, over a period of seven consecutive days  was calculated. In addition, ICC2.1 was calculated for the sub-score for household/work-related PA, the sub-score for leisure-time PA, and for the PASE score of the items for light, moderate and vigorous PA intensity. Measurement error was assessed by estimating the standard error of measurement (SEM), minimal detectable change (MDC) and limits of agreement (LoA). SEM was calculated as the square root of the within-subject total variance of an ANOVA analysis, SEM = √totvar, and the MDC was calculated as MDC = 1.96 × √2 × SEM [Baseline characteristics and descriptive data for the Actigraph GT1M, the PASE and the IPAQ calculations are presented as mean and standard deviation (SD) or number and percentage (%). To evaluate the test-retest reliability for the total PASE score the intraclass correlation coefficient (ICC√2 × SEM . LoA wer√2 × SEM .ρ) for the total PASE score and the Actigraph GT1M , and for the total PASE score and the total IPAQ score . A priori hypotheses were made based on previous studies comparing PA questionnaires and PA measured by accelerometry. As recommended by Terwee et al.[ρ between 0.15 and 0.5) between the total PASE score and the Actigraph GT1M counts per min. We hypothesized a moderate to strong positive correlation (ρ between 0.6 and 0.9) between the total PASE score and the IPAQ total MET-minutes per week. Terwee et al.[The construct validity of the PASE was evaluated by calculating the Spearmans rank correlation coefficients  the PASE light PA intensity with the Actigraph GT1M minutes of light PA intensity and the IPAQ walking MET-minutes per week, 2) the PASE moderate PA intensity with the Actigraph GT1M minutes of moderate PA intensity and the IPAQ walking MET-minutes per week and IPAQ moderate MET-minutes per week, and 3) the PASE vigorous PA intensity with the Actigraph GT1M minutes of vigorous PA intensity and the IPAQ vigorous MET-minutes per week.In addition, Spearmans All statistical analyses were performed using the PASW Statistics 18 for Windows .All 40 patients completed PASE at day 8, but at day 15 PASE were missing or inadequately filled out for seven patients. Calculation of the test-retest reliability was therefore based on the 33 patients with complete PASE questionnaires both at test and retest. Thirty-six patients had completed the Actigraph GT1M recording period and had readable files. Two patients returned the Actigraph GT1M unused, and data from two patients were not successfully downloaded. Six or more days of registration were considered to be sufficient. Three patients had less than six days of registration and were thus excluded from the analysis. In total, recordings from 33 patients were included to calculate correlation coefficients between the PASE and the Actigraph GT1M. The average days of registration were 7.0 (0.6). For the IPAQ, 15 patients had missing or incomplete questionnaires, leaving 25 patients to be included to calculate correlation coefficients between the PASE and the IPAQ. This was mainly due to inability to calculate the IPAQ score because the response alternative "don't know" was chosen.Demographic and clinical characteristics of the patients are shown in Table p = 0.02), but no significant differences was revealed for any of the sub scores/items. ICC2.1 for the total PASE score was 0.77, SEM was 31 and MDC was 87 (Table Mean days between test and retest was nine days (SD 4.0), ranging from six to 25 days. Mean PASE score at test (n = 33) was 143 (SD 71) and at retest 125 (SD 56). The decline in the total PASE score from test to retest was significant (ρ) between the PASE score and the Actigraph GT1M, and the PASE score and the IPAQ score is shown in Table p = 0.089). When comparing the total PASE score with the IPAQ total MET-minutes per week the correlation coefficient was 0.61 (p = 0.001).The Spearman's rank correlation coefficient . The levels of PA found in this study may therefore not be representative for the hip OA population in general.In our study we found that 67% of patients with hip OA fulfilled the recommendations of achieving at least 30 minutes of accumulated MVPA per day, but only 30% fulfilled the recommendations of achieving at least 30 minutes of MVPA per day in blocks of minimum 10 minutes. However, a larger percentage of the hip OA patients did fulfill the recommendations compared to the general Norwegian population. Only 20% of the general adult Norwegian population fulfill these recommendations, and a decline in the amount of PA was present after the age of 64 years. Mean counts per minute was 338, compared to 370 in our study. The patPA has also been estimated in a representative sample of elderly Norwegians using PASE to assess physical activity. The mea2.1, and in addition estimating the standard error of measurement (SEM) and the minimal detectable change (MDC). There are no absolute consensus regarding limits for what should be considered an acceptable ICC value. When instruments for assessing PA is evaluated, Terwee et al.[2.1 of 0.77. However, Terwee et al.[Measurement properties of an instrument are related to the population and context in which it is being used. In this study we evaluated the test-retest reliability of the PASE in patients with hip OA by calculating the ICCee et al.,15 and Fee et al. have sugee et al. also sugee et al..The SEM and MDC of the total PASE score were 31 and 87, respectively, indicating that 87 represents the smallest within-person change in score that can be interpreted as a real change, exceeding measurement error. However, a change exceeding the measurement error is not necessarily clinically relevant, which can be evaluated by estimating the Minimal Clinically Important Difference (MCID). It is advised that the MCID is estimated by using an anchor-based approach -37. HoweIn our study, a significant decline in total PASE score of 18 points was present from test to retest, indicating a systematic error. We may therefore question whether the situation or the subjects actually were stable. When systematic error is present, this is often believed to occur due to a learning effect. However, this is not likely to be the case when the instrument of interest is a self-administered questionnaire. A more plausible explanation may be that wearing the Actigraph GT1M encouraged the patients to increase their activity levels, during the week the PASE referred to. According to Reiser and Schlenk direct oFurthermore, this study evaluated the construct validity of the PASE by comparing it to an accelerometer, the Actigraph GT1M, and with another PA questionnaire, the IPAQ. As proposed by Terwee et al. we testeThe correlation between total PASE score and IPAQ MET-minutes per week was moderate, with a correlation of 0.61, and barely within our a priori hypothesize of correlation between 0.6 and 0.9. Both PASE and IPAQ are self-administered with a seven day recall period, but household- and work activities is included in the PASE and weighed quite highly, whereas the IPAQ mainly captures leisure-time PA. This may, at least partly, explain the discrepancy between the two questionnaires. Both questionnaires were originally developed for use in a general population (generic), with PASE being specifically designed for an elderly population.2.1 for the sub-scores for household/work-related PA and for leisure-time PA was 0.69 and 0.53, respectively, and the ICC2.1 for the items for light, moderate and vigorous PA intensity was 0.46, 0.20 and 0.68, respectively. None of the ICC's for the sub-scores or the single item scores exceeded 0.7, which we interpreted as a cut-off for acceptable reliability, and the 95% CI were wide for all the sub-scores and items. The SEM and the MDC were also large compared to the mean values of the sub-scores and items, indicating moderate to low reliability.The PASE is not designed to be used to measure and report different PA intensity levels separately. One might therefore argue that acceptable test-retest reliability for the overall score is what is important. However, assessment of intensity seems valuable when investigating the effect of exercise and PA, especially for evaluating the dose-response relationship and to establish recommendations for patients with OA regarding amount and intensity. We therefore wanted to evaluate these specific items, to evaluate whether a PA questionnaire is able to provide reliable and valid data for PA intensity. The ICCOur a priori hypothesis; that the respective intensity categories of the PASE would correlate strongest with the respective intensity categories of the Actigraph GT1M, was confirmed for moderate PA intensity and vigorous PA intensity, but not for light PA intensity. However, all correlation coefficients were below 0.46. This indicated that the intensity items of the PASE were not able to distinguish between light, moderate and vigorous PA intensity, and we therefore consider the PASE not to be valid or reliable for assessing PA intensity. The item for moderate PA intensity of PASE correlated stronger with the IPAQ category for walking than the IPAQ category for moderate PA intensity. This may be due to the fact that the IPAQ includes a specific item for assessing walking activities, whereas walking activities are included in the items for light, moderate and vigorous PA intensity in the Norwegian version of PASE. Walking is a widespread leisure time activity in Norway, and is likely to be scored in the item for moderate PA intensity of the PASE, giving a higher correlation with the IPAQ walking compared to the IPAQ moderate PA intensity.This study has some limitations. Both analysis of test-retest reliability and construct validity by comparing PASE to the Actigraph GT1M were based on data obtained from 33 patients. After referring a statistician, and based on that other studies have used similar sample sizes,33, we dThe use of Actigraph GT1M and the IPAQ to evaluate construct validity have some weaknesses. The doubly labeled water method is often considered to be the gold standard for measuring PA, but is 2.1, but the large SEM, SDC and LoA indicate large measurement errors. The construct validity of the total PASE score was found to be poor when compared to the Actigraph GT1M accelerometer.The test-retest reliability of the total PASE score in patients with hip OA was found to be moderate, based on an acceptable ICCThese findings suggest that PASE is not sufficient for assessing PA levels and intensity in patients with hip OA. Accelerometers provide a more precise tool of assessing amount and intensity of PA, and should preferably be included if feasible in studies where these dimensions are considered important.The authors declare that they have no competing interests.All authors participated in the design of the study, contributed in drafting the article, and read and approved the final manuscript. IS carried out the patient inclusion, handled the administration of questionnaires and accelerometers, and carried out the statistical analysis. EK carried out the processing of the Actigraph GT1M data.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/13/26/prepub


The role of cardiac nerves on development of myocardial tissue injury after acute coronary occlusion remains controversial. We investigated whether acute cardiac decentralization  modulates coronary flow reserve and myocardial protection in preconditioned dogs subject to ischemia-reperfusion. Experiments were conducted on four groups of anesthetised, open-chest dogs (n = 32): 1- controls , 2- ischemic preconditioning , 3- cardiac decentralization (CD) and 4- CD+PC; all dogs underwent 60-min coronary occlusion and 180-min reperfusion. Coronary blood flow and reactive hyperemic responses were assessed using a blood volume flow probe. Infarct size (tetrazolium staining) was related to anatomic area at risk and coronary collateral blood flow (microspheres) in the anatomic area at risk. Post-ischemic reactive hyperemia and repayment-to-debt ratio responses were significantly reduced for all experimental groups; however, arterial perfusion pressure was not affected. Infarct size was reduced in CD dogs  compared to 25.2±5.5% in CTR dogs and was less in PC dogs as expected ; after acute CD, PC protection was conserved . In conclusion, our findings provide strong evidence that myocardial protection against ischemic injury can be preserved independent of extrinsic cardiac nerve inputs. Intrathoracic ganglia on the heart and their interconnections coordinate with central neurons in the spinal cord, brain stem and supraspinal central neuronal regions and modulate autonomic control of heart function. in situ experimental preparations where extracardiac nerves have been sectioned. While many studies use the term ‘cardiac denervation’ to describe their experimental preparation after surgical ablation of extracardiac inputs use of ‘cardiac decentralization’ may be a more accurate descriptor of the animal model as mid and bottom levels of the neuronal hierarchy appear to be intact. In large animal studies, disruption of the extracardiac nervous system exerts either protective et al reported increased myocardial stunning and patchy necrosis in cardiac denervated animals and suggested that the absence of cardiac nerves impaired recovery of cardiac function. in situ canine preparation examined the effect of cardiac decentralization on post-ischemic coronary vascular reserve and development of acute ischemic injury. We hypothesized that a loss of central command inputs (i.e. sympathetic and parasympathetic control) to the local neuronal hierarchy would diminish coronary vascular reserve and worsen myocyte necrosis.Within the left ventricle sympathetic and parasympathetic nerves are localized near cardiac myocytes to permit rapid crosstalk Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health ; Laval University is compliant with these guidelines (A5012-01). The experimental protocol was approved by the Laval University Animal Ethics Committee.Adult mongrel dogs of either sex (20–25 Kg) were used for these studies. Dogs were treated in compliance with the Dogs were pre-medicated with acepromazine maleate ; anesthesia was induced with sodium pentobarbital (30 mg/Kg IV) and maintained with hourly administrations of 5 mg/Kg IV. After endotracheal intubation, dogs were ventilated with oxygen-enriched room air; respiratory rate and tidal volume were adjusted to maintain blood gases within physiological values. Butorphenol (0.2 mg/Kg IM) was administered for analgesia. Normothermia (38±1°C) was maintained with a water-jacketed Micro-Temp heating blanket ; temperature was continuously monitored with a thermal probe in the trachea and saline was given IV (250 mL/h) to replace fluid loss.In the supine position, vascular introducer sheaths  were placed in the left and right femoral arteries; a triple-lumen central venous catheter  was placed in the right femoral vein for administration of drugs and fluids. In the left lateral position the heart was exposed by thoracotomy. Extracardiac nerves were carefully dissected and excised; the stellate ganglia, ansae subclaviae and vagus nerves were targeted bilaterally. The heart was suspended in a pericardial cradle. The left anterior descending artery (LAD) was dissected distal to the first diagonal branch to allow positioning of a vascular clamp (for determination of coronary reactive hyperemia (RH) responses and coronary occlusion (CO)) and a blood volume flow probe . Polyethylene catheters (7 Fr) were inserted into the internal thoracic artery  and left atrium (injection of microspheres). A 5 Fr micro-tipped pressure transducer  was placed in the LV cavity through the apex to measure LV pressure and its first derivative; a 7 Fr Pigtail catheter was advanced to the aortic root via the left femoral artery to measure arterial pressures. After all catheters were positioned dogs were given heparin sodium  and allowed to stabilize for 30-min prior to data collection.Left atrial and ascending aorta catheters were connected to Statham P23Db strain gauge manometers; zero was set at mid-chest level. The Millar micromanometer transducer was cross-calibrated with systolic aortic and diastolic left atrial pressures. Coronary blood flow was measured using a volume flow meter . All data were continuously recorded and stored on computer hard drive for later analysis using AxoScope acquisition software. These parameters include heart rate, LV and aortic systolic/diastolic pressures, phasic and mean coronary blood flow. Rate-pressure product (RPP) was used as an indicator of myocardial oxygen demand and has been reported to correlate with myocardial oxygen consumption The experimental design is depicted schematically in RH responses within the ischemic stress zone (i.e. LAD vascular bed) were obtained to assess the maximal vasodilator capacity of this vascular bed under stable conditions prior to PC and at the end of the ischemia-reperfusion protocol; a 20-sec acute, regional CO was used as this degree of ischemia produces maximal dilatation All dogs were given lidocaine  at 55-min CO to suppress ventricular arrhythmias. Hearts that developed ventricular fibrillation or sustained ventricular tachycardia were cardioverted (1 J/Kg) using internal paddles.Transmural myocardial blood flow was measured at 30-min CO using neutron activated microspheres  as previously described At the end of each study, the LAD was re-ligated at the original site of occlusion; the area at risk (AAR) was outlined by perfusion of the coronary ostium with Monastral blue dye. Under deep pentobarbital anesthesia, cardiac arrest was induced by intra-atrial injection of saturated potassium chloride. A 1.5% solution of warmed (37°C) 2,3,5-triphenyltetrazolium chloride was infused into the ischemic region via a cannula in the LAD  over 30-min. The heart was rapidly excised, rinsed in saline and fixed in 10% buffered formaldehyde. The LV was cut from apex to base and the outline of each slice, the necrotic area (AN) and the AAR were traced onto acetates. The LV area, AAR and AN were determined using a digitizing tablet (Summagraphics II Plus) interfaced with a personal computer and analyzed with Sigma Scan software . Results are expressed as the AAR and the AN indexed to AAR (%). Tissue samples from the mid-region of the LV within the AAR and from the non-ischemic LV were further subdivided into endocardial and epicardial pieces for blood flow  analyses; blood and tissue samples were dried for 48 h at 50°C and sent to a core processing facility ; Differences in cardiac hemodynamics and regional blood flow were determined by ANOVA and multiple comparisons were performed using the Student-Newman-Keuls multiple range test. A probability (p) level of ≤0.05 was considered statistically significant; normality and variance assumptions were fulfilled. The influence of ventricular tachycardia/fibrillation on survival after the combined ischemia-reperfusion insult was determined using the Fisher Exact test and Chi-square analysis; all statistical analyses were carried out using SAS software . Sample size determination for these studies was based on the provision of a 90% power to detect, at a p≤0.05 significance level, a minimum 20 percent reduction/augmentation (expected standard deviation of ±8%) in infarct size.base) and peak (Qpeak) flow, flow debt and repayment volumes were determined as previously described; RH responses were measured from strip chart recordings, baseline  were randomly allocated to the study groups and all completed the experimental protocol. Incidence of ventricular tachycardia/fibrillation during ischemia/reperfusion  was not statistically different. Arterial blood gas and hematocrit values (data not shown) were all within physiological levels.Cardiac hemodynamic data are summarized in base was significantly reduced in all groups and Qpeak decreased almost 50 percent less for each group; as such, 60-min CO resulted in an overall loss of coronary flow reserve (cf. Qpeak/Qbase) regardless of cardiac nerve status. While no change in CVCbase was detected at REP180, CVCpeak was significantly less in all experimental groups. Coronary blood flow repayment-to-debt ratio decreased markedly following ischemia-reperfusion in CTR and CD dogs even though arterial perfusion pressures remained stable (cf. Changes in coronary RH responses (used to assess coronary flow reserve) produced by ischemia-reperfusion injury are reported in able cf. ; no chanThe AAR (% LV area) was similar for all experimental groups  as shown in Although direct comparisons of infarct size by ANOVA demonstrate reduced tissue injury by PC (or CD) this statistical method does not take into consideration the important influence of coronary collateral blood flow (independent covariant) within the AAR on development of tissue necrosis. In CTR dogs an inverse relationship between coronary collateral blood flow and infarct size was obtained . Results of the present study show that a 60-min period of ischemia substantially reduces coronary vascular reserve; a similar impairment of this parameter was observed after acute ablation of all extracardiac neuronal inputs . These effects were independent of pretreatment by cardiac conditioning. Myocardial necrosis was significantly reduced in CD dogs; a similar level of tissue protection was afforded by conditioning pretreatment independent of CD.Coronary flow reserve can evaluate coronary microvessel function and provides well-established risk and prognostic variables. et al in dogs subject to total coronary occlusion. in situ in animals with intact cardiac nerves or in isolated buffer-perfused hearts have been reported in the literature to reduce myocardial injury and infarct size. et al also documented significant infarct size reduction by PC pretreatment after acute cardiac denervation . In CD animals not subject to PC pretreatment infarct size was significantly smaller. While these findings are in agreement with those previously reported Sympathetic dysinnervation secondary to myocardial infarction has been reported in animal and human studies. A priori consideration was not given to either surgical or anesthetic preconditioning since all animals were treated similarly. Additional risk factors that influence myocardial infarct size such as duration and depth  of ischemia and anatomic risk zone size were measured in the present studies and were uniform for all study groups. There are some limitations in our study. We used an open-chest, isoflurane-anesthetized canine experimental preparation. In conclusion, cardioprotection against ischemic injury is conserved by preconditioning even when the target tissues are disconnected from central command. These findings suggest that preconditioning and the intrinsic cardiac nervous system could share common pathways to delay development of myocyte necrosis. Results of the present studies could have implications for understanding physiopathology of ischemia-induced heart failure. Further studies are needed to determine whether neuromodulation of the intrinsic cardiac nervous system would be beneficial against ischemia-reperfusion.


T1-relaxation times and infarct sizes. Furthermore, the rapid acquisition of functional cine-data allowed for the first time in mice measurement of left-ventricular peak filling and ejection rates under intravenous infusion of dobutamine. The results demonstrate that a threefold accelerated data acquisition is generally feasible without compromising the accuracy of the results. This strategy may eventually pave the way for routine, multiparametric phenotyping of mouse hearts in vivo within one imaging session of tolerable duration. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc.MRI has become an important tool to noninvasively assess global and regional cardiac function, infarct size, or myocardial blood flow in surgically or genetically modified mouse models of human heart disease. Constraints on scan time due to sensitivity to general anesthesia in hemodynamically compromised mice frequently limit the number of parameters available in one imaging session. Parallel imaging techniques to reduce acquisition times require coil arrays, which are technically challenging to design at ultrahigh magnetic field strengths. This work validates the use of an eight-channel volume phased-array coil for cardiac MRI in mice at 9.4 T. Two- and three-dimensional sequences were combined with parallel imaging techniques and used to quantify global cardiac function,  Genetically and surgically modified mice are widely used as models for human cardiac disease. MRI has become a routine tool in many research laboratories to noninvasively assess ventricular volumes and mass in order to characterize global cardiac function in these animal models. Analogous to the human heart, MRI can also be used in murine hearts to assess regional and transmural wall motion ,2, straiWe have designed and characterized an eight-channel volume receive array integrated into a linear driven volume transmit birdcage resonator . FollowiFor our experiments we used a volumetric coil array consisting of eight elements  arranged inside a linearly driven volume coil  (see Ref. Imaging experiments were carried out on a 9.4 T (400 MHz) MR system  comprising a horizontal magnet (bore size 210 mm), a VNMRS Direct Drive™ console and two actively shielded gradient systems .C57BL/6 mice were obtained from a commercial breeder  at least 1 week prior to the first imaging time point to allow naturalization to new surroundings. The mice were kept under controlled conditions for temperature, humidity and light, with chow and water available ad libitum. Anesthesia was induced in an anesthetic chamber using 4% isoflurane in 100% oxygen. Animals were then positioned prone on dedicated mouse cradles and maintained at 1.5–2% isoflurane at 2 L/min oxygen flow throughout the MRI experiments. Temperature was maintained at ∼37°C using a warm air blanket placed on the front or back of the animal. Cardiac and respiratory signals were continuously monitored using an in-house developed electrocardiogram (ECG) and respiratory gating device .All investigations conformed to Home Office Guidance on the Operation of the Animals (Scientific Procedures) Act, 1986 and to institutional guidelines.2, matrix size 256 × 256, echo time/pulse repetition time = 1.7/4.6 msec, 15° sinc excitation pulse, number of averages [i.e. number of transients (NT)] = 1 (coil array)/NT = 2 (birdcage coil). The sequence in both cases was ECG-triggered and respiratory gated with steady-state maintenance during respiration  over a period of ∼3 months during which body weight (BW) ranged from 17.1–28.5 g . These scans were performed to study the effect of increasing coil loading on the coil (array) performance. Each TP consisted of two imaging days, with cardiac functional imaging using the eight-channel array on day 1 and the quadrature birdcage coil on day 2, respectively. After positioning the mice in the magnet with the heart in the centre, and scouting for long- and short-axis orientation of the heart using a cardiac triggered and respiratory gated, segmented gradient-echo sequence, shimming and pulse calibration were performed automatically prior to each experiment. Eight contiguous cine slices (slice thickness slth = 1 mm) were then acquired in short-axis orientation covering the entire heart. The imaging parameters were: field of view 25.6 mm).6 mm2, mpiration —and wereidl-software  as described previously  were generated in postprocessing from the phased-array data, followed by TGRAPPA and sum-of-square reconstruction, resulting in four datasets per mouse. All raw data were isotropically zerofilled by a factor of two and filtered  and functional parameters were determined by a single operator (LAS), blinded to animal ID and acquisition/reconstruction scheme, as described before  on the fourth frame (corresponding to early systole) of a midventricular short-axis slice using a bootstrap method  as described above with a matrix size of 128 × 128, applied over two cardiac cycles. Following a baseline scan, dobutamine was infused intravenously via the tail vein at a rate of 27.8 μL/(g·h). Cine MRI commenced ∼7 min after start of infusion, which is the maximal time to achieve steady state in this strain (V/dt)min/max·EDV−1.Stress-cine MRI was performed in three female mice (28.2 ± 1.9 g) using a threefold accelerated TGRAPPA sequence  as described previously  = 120–150 msec—depending on cardiac cycle length), acceleration factors R = 1, 2, 3, and 4 was applied in short-axis orientation. Twenty to thirty images on the inversion curve were used to map T1. Undersampled datasets were subjected to GRAPPA reconstruction using 24 autocalibration (ACS) lines acquired without inversion pulse. The inversion times, which depended on the heart rate, were logged during the experiment and the mean inversion time for each image on the inversion curve was calculated.eviously ,14. In bT1-weighting and steady-state maintenance was applied in three male mice (29.3 ± 2.1 g) 1 day post myocardial infarction as reported previously  ∼700 msec, NT = 1, flip-angle = 15°, inversion time individually adjusted in multiples of cardiac cycle lengths (400–420 ms)]. After an intraperitoneal bolus injection of 0.5 μmol/g Omniscan® , the mice were placed in the scanner. Following scouting, shimming and pulse calibration, an ACS dataset  was acquired. High-resolution infarct imaging started 18 ± 9 min post injection with undersampling factors R = 1–4 (applied in random order) in the first phase-encoding direction. The undersampled data were subjected to GRAPPA reconstruction . Agreement in TP1 = −0.5 ± 0.1 g; ΔBWTP2 = 0.1 ± 0.3 g; ΔBWTP3 = 0.6 ± 0.3 g—day 1 − day 2; mean ± SD), which were significant for TP1 and TP3 (P < 0.01 each). Hence, the loading was equivalent for both coils for each time point. Midventricular end-diastolic (top row) and end-systolic frames (bottom row) in short-axis orientation are shown in R = 2,  R = 3 and  performance. Only small changes in body weight between day 1 and day 2 were noted for all imaging time points ( – SNRn)/SNRn × 100%; n is the number of contributing coils) of 30% and 15% was observed for the region of interest (ROI) in the anterior LV wall when combing the signal of two or three anterior located coil elements . The two lateral elements increase the SNR in the posterior wall by 11%  and by 9% , whereas the SNR in the anterior wall is only improved by 7% and 4%. The posterior coil elements add another ∼5% to the posterior ROI and ∼4% to the anterior ROI. Similar findings were obtained for the other two time points (data not shown).To determine the relative contribution of each coil element to improving SNR, the mean SNR as measured in the anterior and the posterior wall is plotted as a function of the number of contributing coil elements  in g-factor, calculated for the GRAPPA reconstruction according to  and 12% (TP3) .The mean SNR based on location of compartment, coil/acquisition scheme was compared longitudinally under a range of loading conditions. rding to , in the R = 3 datasets; intervariability assessed in three randomly selected datasets: 4.5 ± 3.2 %). Bland-Altman plots for LV mass, EDV, ESV and EF obtained from the birdcage coil compared with threefold accelerated data are shown in R = 3 datasets. There was a small negative bias for EF (−3.8%).Cardiac functional parameters and LV mass measurements obtained by a single blinded observer for TP3 are summarized in R = 3 under baseline conditions and under intravenous dobutamine infusion (V/dt)min/max·EDV−1] are evident. More specifically, an increase in heart rate of 11 ± 2% was observed under dobutamine infusion. The maximum rate of volume change (dV/dt)max·EDV−1 as a measure of relaxation increased from 20.3 × 103 ± 5.3 × 103 s−1 to 22.8 × 103 ± 4.1 × 103 s−1, whereas the minimum rate of volume change (dV/dt)min·EDV−1 as a measure of contraction decreased from −(14.5 ± 1.7) × 103 s−1 to −(17.4 ± 1.7) × 103 s−1 . Interestingly, determining the contractility parameters in the same way from a single midventricular slice only showed no difference for (dV/dt)max·EDV−1, while (dV/dt)min·EDV−1 was significantly different to the values determined for the whole heart (P < 0.05).In a test application for accelerated cine imaging, time–volume curves were obtained from the whole ventricle during the experiment using TGRAPPA, infusion . The incT1-mapping and T1-weighted imaging could also be accelerated, parallel imaging was combined with the respective method in two dimension (2D) or 3D. Representative T1-parameter maps for acceleration factors R = 1–4 are shown in T1 maps were masked in the range 0–3 sec to remove outliers from the fitting procedure. No significant difference in the parameter maps can be seen up to R = 3, while the increased noise levels and g-factors in the fourfold undersampled inversion recovery data impact on the fit accuracy  are listed in T1 values for each tissue type.To determine whether accuracy . QuantitR = 1–3. The required scan times  were: R = 1: 1189 ± 85 sec; R = 2: 626 ± 44 sec; R = 3: 401 ± 47 sec; and R = 4: 317 ± 40 sec, respectively. P < 0.01 and P = 0.027, respectively), while the left ventricular volumes remained constant (P = 0.73).Midventricular sections out of a 3D slab following intraperitoneal injection of Gd are shown in The aim of this article was to establish and validate a phased-array setup for cardiac MRI in mice at ultrahigh magnetic fields . We used an eight-channel array designed to fit mice with a body weight range of approximately 20–35 g, and compared the phased array to a quadrature driven birdcage coil with a matching inner diameter that has been optimized and is routinely used in various laboratories for cardiac mouse MR. While the coil setup has been characterized in detail previously , the appIn agreement with our previous work , we obseT1-mapping and contrast-enhanced infarct MRI.The most important advantage of the array over the birdcage coil is the parallel imaging capability, which provides a significant reduction of scan time. Three different techniques were investigated in this context, i.e., cardiac functional imaging, R = 1) and with threefold acceleration (data not shown). There was no difference in parameter variability between high- and low-SNR datasets, importantly despite the decrease in SNR with increasing acceleration factors. In particular, the overall intraobserver variability and interobserver variability for both volume and array coil data were in the same range as previously published values min·EDV−1) between single slice and whole LV volume analysis. While the physiological relevance of this finding is questionable in this particular example , it may well play a role in surgically or genetically modified hearts, where the exact location and orientation of the midventricular slice may impact on the calculated minimum and maximum rates of volume change. Whole heart coverage eliminates this problem.One application facilitated by the combination of parallel imaging with cine MRI is pharmacological stress testing, e.g., by dobutamine infusion, and the assessment of LV volumes and maximum rates of volume change using whole ventricular coverage. LV volumes of the entire ventricle following intraperitoneal bolus injection of dobutamine have been quantified before , contracT1 has been quantified in mouse hearts before  down to ∼50 sec (R = 3) for a single slice. Only three heartbeats (<500 msec) were required to acquire the ACS data, required for the GRAPPA reconstruction. Mapping the myocardial blood flow (i.e. perfusion) by means of arterial spin-labeling (ASL) techniques requires two T1-parameter maps, acquired with slice-selective and with global inversion pulse, respectively. Hence, parallel imaging will reduce the scan time requirements for ASL-based perfusion imaging in mouse hearts below 5 to 10 min, depending on the method used (s before ,6,8,14, ter maps  and repr1 values , reducinR. However, a decrease in SNR cannot be responsible for this result alone as the LV volumes were still accurately obtained for R = 3 (R = 2 compared with R = 1 is mainly driven by mouse 1 (T1 module, and by fully utilizing the reconstruction proposed by Blaimer et al (Contrast enhanced infarct size assessment in combination with parallel imaging was performed to investigate the benefits for 3D applications. The short-axis orientation of the imaging slab is dominated by the axial component. Therefore, the datasets were only undersampled in the first phase-encoding direction, as the coil elements are located radially. We found a statistically significant trend toward smaller infarct sizes with increasing or R = 3 . Hence,  mouse 1 , and tha mouse 1 . A thoroer et al , which eT1 relaxation times and infarct sizes, with parallel imaging techniques. A threefold acceleration was generally feasible without impairment of accuracy of the various parameters. These achievements allowed us to measure for the first time left-ventricular peak filling and ejection rates under intravenous infusion of dobutamine. Our method offers substantial reductions in scan time, without compromising the accuracy of the results. This strategy may pave the way for routine multi-parametric cardiac phenotyping, including stress tests and contrast-enhanced techniques, within a single imaging session of tolerable duration.In conclusion, we have validated the use of an eight-channel volume phased-array coil for cardiac MRI in mice at 9.4 T. We have combined 2D and 3D sequences to quantify global cardiac function,


Despite heart failure having been identified in subjects in sub-Saharan Africa over the last 60 years, there is still a dearth of data, especially echocardiographic data on heart failure. We therefore set out to analyse the clinical and echocardiographic features of all consecutive subjects presenting with heart failure in a tertiary institution in Nigeria.Three hundred and forty subjects with heart failure, according to the guidelines of the European Society of Cardiology, were studied. Each patient had two-dimensional guided transthoracic echocardiography.The mean age of the patients was 50.60 ± 15.29 years, and 50.9% of the study population were males while 49.1% were females. The commonest cause of heart failure identified was hypertension in 61.5% of the patients; 75.5% had systolic heart failure, whereas 23.5% had heart failure with preserved ejection fraction.Untreated hypertension has been identified as the leading cause of heart failure in Abuja, Nigeria, which is similar to that in many other parts of sub-Saharan Africa. Coronary artery disease is a rare cause of heart failure in this population group. With recent improvements in the control of infectious diseases and malnutrition on the one hand, and the migration to urban areas with a complete change in lifestyle on the other, cardiovascular diseases such as hypertension and cerebrovascular accident have emerged as major causes of morbidity and mortality in mostAfrican countries, including Nigeria.12We therefore set out to analyse the clinical and echocardiographic features of all consecutive subjects presenting with heart failure at the University of Abuja Teaching Hospital from April 2006 to August 2008, in order to ascertain the pattern of heart failure in Abuja, Nigeria.The study was carried out at the University of Abuja Teaching Hospital, Nigeria, which is the largest tertiary health centre in the federal capital territory (FCT) of Nigeria. It receives referrals from hospitals in the FCT and neighbouring states, including Kogi, Niger, Nasarawa and Kaduna.In this prospective, observational study, 340 eligible subjects were recruited consecutively. Subjects were eligible if they were 15 years and older, and with a confirmed diagnosis of heart failure. Heart failure was defined according to the recommendations of the European Society of Cardiology.14Baseline clinical and demographic characteristics of subjects were obtained using a structured questionnaire. Information obtained was gender, history of hypertension, diabetes mellitus and rheumatic fever in the past, and cigarette smoking and alcohol consumption. Subjects were weighed without shoes and in light clothing on a standard beam balance, while height was measured to the nearest centimetre using an anthropometric plane with subjects without shoes or headgear.2 and blood pressure measurements were obtained according to standard guidelines with a mercury sphygmomanometer . Systolic and diastolic blood pressures were measured at Korotkoff sounds I and V respectively. Blood pressure was measured three times on the right arm after a fiveminute rest with patients in a sitting position, and the average of the three measurements was obtained. Subjects with blood pressure of 140/90 mmHg and above, or on anti-hypertensive treatment were classified as hypertensive.Body mass index was calculated using the formula weight/heightM-mode and two-dimensional Doppler echocardiography with colour flow and tissue Doppler imaging were performed on all the subjects by two experienced cardiologists  according to the recommendations of the American Society of Echocardiography.16Heart failure was classified2) or Doppler echocardiography techniques.18A diagnosis of rheumatic mitral stenosis was based on the presence of thickened and/or calcified mitral leaflets and subvalvular apparatus, ‘hockey-stick’ appearance of anterior mitral valve leaflet in diastole, immobility of the posterior mitral leaflet, and narrowed ‘fish-mouth’ orifice of the mitral valve in the short axis, measurable with planimetry , and almost invariably occurring with rheumatic mitral valve disease.18Rheumatic aortic stenosis was defined by the presence of thickened or calcified and immobile aortic valve cusps, with commissural fusion causing a narrowed orifice  with global systolic and diastolic dysfunctions in subjects with no known cause of heart failure.20t-test. P-values < 0.05 were considered statistically significant.Data were analysed using the Statistical Package for Social Services (SPSS) version 10.0. Baseline variables were expressed as mean ± SD. Comparison of echocardiographic parameters between subjects with systolic heart failure and those with heart failure with preserved ejection fraction was performed by the Student’s p = 0.000). The mean end-systolic diameter for subjects with systolic heart failure was 4.85 ± 1.03 cm compared to 2.83 ± 0.70 cm for subjects with heart failure with preserved ejection fraction (p = 0.000). Finally, 103 (30.3%) of the subject population had impaired left ventricular filling function, seven (2.1%) had pseudo-normal filling function and 135 (39.7%) had restrictive filling pattern.This study identified untreated hypertension as the commonest cause of heart failure, degenerative valvular disease as an emerging cause of heart failure, and coronary artery disease as a rare cause of heart failure among Nigerian Africans. Untreated hypertension accounted for 62.6% of the cases studied, similar to the findings in Zaria, Nigeria.The finding of hypertension as the leading cause of heart failure in this study further supports the fact that hypertension tends to run a more severe course with more target-organ damage in blacks compared to Caucasians. In the INTERHEART study,Hypertension, idiopathic dilated cardiomyopathy and rheumatic heart disease were found to be the three leading causes of heart failure in this study, similar to findings in other parts of sub-Saharan Africa.Degenerative valvular disease was found to be an emerging cause of heart failure in this study, being responsible for heart failure in 4.1% of cases. This interesting finding may point to the fact that a higher number of geriatric people are seeking medical care in our environment, and this may be attributable to better awareness and education on the part of the population. We also think that better nutrition and medical facilities, compared to previously, may be causing an increase in our geriatric population.One of the cases of heart failure was secondary to the use of cytotoxic medication, which is in keeping with previous findings. 6There was no identified case of coronary artery disease in this study (using a history of chest pain and 12-lead electrocardiography as diagnosis). This confirms the observation that coronary artery disease is not common in black Africa.et al.In 85 (25%) of the subjects, some factors were identified to have precipitated a deterioration in clinical condition, leading to in-patient care. These included severely elevated blood pressure in 50.6%, arrhythmias  in 25.9%, chest infection in 14.1% and anaemia in 9.4% of cases. In Kenya, Oyoo and Ogola3 identified inadequate therapy, arrhythmia, chest infection, anaemia and also infective endocarditis as factors associated with patient deterioration and hospital admission, while Falase The average age of subjects in this study was 50.60 ± 15.29 years, which is similar to findings by other workers in sub-Saharan Africa.et al.33A minority (23.5%) of the study population had heart failure with preserved ejection fraction. In Cameroun, Kingue Untreated hypertension has been identified as the leading cause of heart failure in Abuja, Nigeria, while coronary artery disease is a rare cause of heart failure in this population. Also, degenerative valvular disease was found to be gradually emerging as a significant cause of heart failure in this environment.


There is increasing recognition that pulmonary artery stiffness is an important determinant of right ventricular (RV) afterload in pulmonary arterial hypertension (PAH). We used intravascular ultrasound (IVUS) to evaluate the mechanical properties of the elastic pulmonary arteries (PA) in subjects with PAH, and assessed the effects of PAH-specific therapy on indices of arterial stiffness.Using IVUS and simultaneous right heart catheterisation, 20 pulmonary segments in 8 PAH subjects and 12 pulmonary segments in 8 controls were studied to determine their compliance, distensibility, elastic modulus and stiffness index β. PAH subjects underwent repeat IVUS examinations after 6-months of bosentan therapy.–2 mm2/mmHg vs 4.49±0.43×10–2 mm2/mmHg, p<0.0001), distensibility , elastic modulus , and stiffness index β . Strong inverse exponential associations existed between mean pulmonary artery pressure and compliance , and also between mean PAP and distensibility . Bosentan therapy, for 6-months, was not associated with any significant changes in all indices of PA stiffness.At baseline, PAH subjects demonstrated greater stiffness in all measured indices compared to controls: compliance (1.50±0.11×10Increased stiffness occurs in the proximal elastic PA in patients with PAH and contributes to the pathogenesis RV failure. Bosentan therapy may not be effective at improving PA stiffness. Pulmonary arterial hypertension (PAH) is a group of conditions characterised by similar pathophysiological changes in the pulmonary vascular bed, resulting in pre-capillary pulmonary hypertension, increased right ventricular (RV) afterload and ultimately RV failure.In clinical practice, RV afterload is often described in terms of PVR but this is only a measure of steady pulmonary pressure-flow relationship and neglects the pulsatile nature of blood flow in any circulation.The proximal elastic pulmonary arteries (PA) function as conduit vessels to buffer the pulsatile arterial load and distribute blood flow to the peripheral circulation. Post-mortem histological studies have demonstrated morphological changes in the elastic PA in subjects with PAH.Intravascular ultrasound (IVUS) allows real-time imaging of the morphology and function of the pulmonary vasculature when performed with simultaneous hemodynamic monitoring. It can provide direct assessment of local changes in arterial stiffness as opposed to global changes affecting the entire circulation. To date, only few studies have characterised the mechanical properties of the proximal elastic PA in patients with PAH using the IVUS technique. in vivo effects on proximal PA stiffness and remodeling have not been studied in humans. Therefore, we sought to use IVUS to determine the local elastic properties of the proximal PA in patients with PAH, and evaluate the effects of 6-months therapy with bosentan on arterial stiffness.Current PAH-specific therapies target the dysfunctional pathways implicated in disease pathogenesis and have predominantly vasodilator effects on the pulmonary vasculature. Bosentan, a dual endothelin receptor antagonist, has been shown to reverse arterial remodeling in animal models of PAH, but its The research was conducted according to the principles expressed in the Declaration of Helsinki. The study was approved by the local ethics committee and all subjects provided informed consent.The study subjects consisted of a healthy control group (n = 8) and a PAH group (n = 8). PAH subjects were assessed as part of a 6-month study that investigated the effect of bosentan therapy on pulmonary endothelial function,Right heart catheterisation was performed via the right femoral vein approach. Right atrial, right ventricular and pulmonary artery pressures were all measured at end-expiration. With continuous hemodynamic monitoring, IVUS imaging of PA were performed using a 40 MHz catheter , which had an axial resolution of 200 um. IVUS images were displayed by an image console  at a frame rate of 30/secs.The IVUS catheter was advanced distally into a selected lobar PA, followed by a pullback manoeuvre at a rate of 0.5 mm/sec. If feasible and anatomically accessible, we attempted to image multiple pulmonary lobes in each subject. Twenty-one pulmonary lobes were imaged in PAH subjects; and 13 pulmonary lobes in control subjects. Image quality was inadequate for analysis in one lobe of a PAH subject and also in one lobe of a control subject. Thus, a total of 20 pulmonary lobes from 8 PAH subjects were included in the final analysis . For the controls, a total of 12 pulmonary lobes from 8 subjects were included .Selective pulmonary angiography was performed to determine the anatomical position of each imaged PA segment. On follow-up studies, the same PA segments were imaged according to baseline angiography. IVUS images were recorded and digitalised for off-line analysis. The accuracy of IVUS-derived measurements of PA diameter, luminal area and wall thickness has previously been validated against in vitro anatomical measurements.s) and end-diastolic luminal area (Ad), respectively. Vessel diameters in end-systole (Ds) and end diastole (Dd) were derived from the equation; D = 2×√(A/π).IVUS image analysis was performed by two study investigators blinded to the clinical status and hemodynamics of subjects, using a commercially available imaging software . The baseline study was cued to the most distal, least-branching segment of the PA with good image quality . The follow-up IVUS was then cued to a point of equivalent PA diameter. Analyses of IVUS images were averaged over 3 consecutive cardiac cycles. The luminal margin PA were traced at end-systole (defined as T wave onset on ECG) and end-diastole (defined as QRS onset on ECG) to determine the end-systolic luminal area (As–Ad)/pulse pressure); distensibility was defined as the relative percentage area change for a given pressure change (distensibility = (As–Ad)×100/pulse pressure×Ad ), elastic modulus as the pressure change required for a theoretical 100% increase in vessel diameter (elastic modulus = pulse pressure×Dd/[Ds–Dd]), and stiffness index β was calculated by the formula (Stiffness Index β = ln(SPAP/DPAP)/[(Ds–Dd)/Dd]).Using the IVUS-derived measurements and pulmonary hemodynamic acquired at the same procedure (simultaneously), indices of arterial stiffness were used to characterise the elastic properties of PA. Compliance was defined as the absolute area change for a given pressure change .Data are expressed as mean±SD unless otherwise stated. Independent sample t-tests were used to compare baseline differences between the control and PAH groups; and paired t-tests were used to compare the effects of bosentan within the PAH group. The association between mean pulmonary artery pressure and stiffness indices were explored using regression analysis, and different curve fitting models were tested and compared with F and RThe age and gender of PAH subjects and control subjects were well matched . In the PAH group , baseline hemodynamic revealed severe pulmonary hypertension with a mean pulmonary artery pressure (PAP) of 48±3 mmHg, pulmonary capillary wedge pressure (PCWP) of 10±3; and all subjects were in NYHA functional class III. Control group had normal pulmonary hemodynamic with mean PAP of 16±2 mmHg and PCWP of 9±3 mmHg.At baseline, the mean luminal diameters of PAs were similar in PAH and control subjects . PAH subjects demonstrated increased % wall thickness compared to controls , as previously reported.-2 mm2/mmHg vs 4.49±0.43×10–2 mm2/mmHg; mean±SEM, p<0.0001), reduced distensibility , higher elastic modulus , and higher stiffness index β   .Of the 20 pulmonary lobes interrogated with IVUS in the PAH group at baseline, only 14 lobes were able to be accessed anatomically and studied at follow-up. If the results were analyzed by consideration of only the 14 lobes that were measured before and after bosentan, we still found a significant difference in all stiffness indices between controls and PAH subjects at baseline.Following 6-months of bosentan therapy, no significant differences in all indices of PA stiffness were found in the PAH group . Similar2 = 0.82, p<0.0001). Similarly, there was a strong inverse exponential relationship between mean PAP and distensibility   .The present study demonstrates that arterial stiffness is significantly increased in the proximal elastic PA in patients with PAH, and this increase in stiffness occurs in the setting of wall thickening and vessel remodeling. This is also the first human study to evaluate the effects of bosentan on local PA stiffness. We did not observe any significant beneficial effects of bosentan on arterial stiffness following 6-months of therapy.PAH is regarded traditionally as a disease of the distal small muscular arteries (<500 um in diameter).in vivo imaging with IVUS, allowed comprehensive assessment of regional arterial properties and demonstrated that all indices of arterial stiffness are abnormal in the proximal elastic PA in PAH subjects.In health, the proximal elastic PA are conduit vessels and function as high capacitance tubes to deliver blood to the peripheral microcirculation. Arterial compliance is most easily and commonly determined by the ratio of the stroke volume to pulse pressure, which describes the compliance of the entire pulmonary circulation. Although useful, this measurement fails to describe regional or local changes in arterial structure and function. Our study, using per se. Since the proximal elastic PA constitute a significant proportion of the total compliance of the pulmonary circulation, our findings indicate that proximal PA stiffening in PAH is an important contributor to the total RV afterload. Our study is in agreement with recent magnetic resonance imaging (MRI) work in humans that has also shown increased proximal PA stiffness in PAHThe increase in % wall thickness, compared to healthy controls, suggests that these vessels have undergone significant remodeling, and this process of remodeling explains, in part, the increase in arterial stiffness. Stiffness index β has been used as an index of arterial stiffness that is less pressure dependent compared to other commonly used stiffness indices, as the logarithmic transformation adjusts for the non-linear relationship between arterial elasticity and luminal distending pressure.The compliance and distensibility data in our subjects demonstrated strong inverse exponential associations with PA pressure. Similar associations were also found by Sanz et alThe findings of our present study and those of Lankhaar et al may also explain the apparent lack of effect of bosentan on measures of arterial stiffness after 6-months of therapy. Although bosentan may reduce PVR significantly via its vasodilator effect on the distal microvasculature, PAH patients with advanced disease are operating at the flat part of the RC curve, and a significant reduction in compliance would be an unexpected finding even if a large reduction in resistance were to occur. In other words, patients with advanced disease and a higher starting PVR may, with therapy, reduce their PVR with little change in compliance. In contrast, patients with early disease and a lower starting PVR may experience a proportional improvement in both PVR and compliance.The findings of the present study must be interpreted in the context of the following limitations. The main limitation is the small number of subjects in our present study. Although we did not observe any significant differences in PA stiffness following 6 months of bosentan therapy, our study may have lacked sufficient power to detect such a difference. However, a post-hoc analysis indicates that our study was powered to detect a relative change of 40% in PA compliance over time. We were unable to study the same number of pulmonary lobes in all subjects, mainly due to technical difficulties in assessing all arterial territories and the radiation exposure associated with prolonged fluoroscopy times. In this study, the quality of the IVUS image was inadequate for interpretation (>90° of the PA cross section was unclear) in approximately 10% of the PAs studied. Nonetheless, the majority of IVUS images were suitable for analysis and measurements were reproducible. Although IVUS is an invasive imaging modality, right heart catheterisation remains a necessary component of the diagnostic evaluation of subjects with suspected PAH, and IVUS can potentially be performed in the same setting.in vivo assessment with IVUS, that the proximal elastic PA in patients with PAH undergo remodeling accompanied by a marked increase in arterial stiffness. Thus, pathophysiological changes of the proximal elastic PA play an important contributing role to the overall RV afterload and the development of RV failure in PAH. Despite the known vasodilator effects of bosentan on the distal microvasculature, no change in proximal arterial stiffness was observed following 6-months of therapy. Current PAH-specific therapy may not exert significant beneficial effect on arterial stiffness in subjects with advanced disease, owing to the physiological phenomenon that changes arterial stiffness occur early in PAH. This study further supports the notion that evaluating changes in PA stiffness may have a role in the early detection of pulmonary vascular disease.We have demonstrated, using


Speckle tracking echocardiography is increasingly being used to assess cardiac function in neonates. The objective was to compare speckle tracking strain indices between asphyxiated infants and healthy controls and to ascertain correlations between strain and 2D Doppler derived indices and cardiac troponin .Clinical and echocardiographic data from severely asphyxiated infants undergoing therapeutic hypothermia was evaluated retrospectively. This was compared with prospective data from healthy infants. Correlations between variables were assessed using Pearson’s coefficient of correlation.2 = 0.86, p< 0.001) and negatively with serum troponin levels . GLS was less impaired in infants on inotropes compared to those not on inotropic support, -12.55% (1.9) vs -10.2% (1.3), p= 0.018. Infants who died had a lower global strain value compared to survivors, – 9.7% (1.6) vs – 12.8% (2.6), p = 0.02.Twenty four infants with severe perinatal asphyxia were admitted during the study period of which 3 were not cooled and were excluded. The gestational age and birth weights of cases and controls were comparable. The mean left ventricular global longitudinal strain (GLS) from apical 4 chamber view was noted to be significantly impaired in the asphyxiated infants . Cardiac output was significantly lower in the asphyxiated infants (97 ± 26 vs 230 ± 60 ml/kg/min). In asphyxiated infants, GLS correlated positively with cardiac output (r2D Speckle derived strain was impaired in asphyxiated infants. Significant correlations between GLS and cardiac output and troponin were noted. Speckle tracking echocardiography (STE) is a relatively new technique for assessing neonatal cardiac function though it has been used in adult studies previously . Strain,Approximately 1–2 newborns per 1000 live births could be affected by severe perinatal asphyxia  which caSerum cardiac troponin (cTnT) has also been studied as a marker of myocardial injury in neonates . A valueUnit electronic database was accessed to identify infants with severe perinatal asphyxia administered therapeutic hypothermia during the period from January 2010 till August 2012. Demographic details and clinical data were retrieved and the archived echocardiographic images were analysed using AFI software (GE Echopac™). Echocardiographic monitoring of infants with clinical haemodynamic compromise is practised in the Unit since 2009 and has been approved as a quality improvement activity by the institutional ethics committee. One echocardiogram was done by echo-technologists from paediatric cardiology department; all others were done by investigator (AS). The information from the asphyxiated neonates was analysed retrospectively. Normative data collection from healthy term neonates was done prospectively and was approved as a separate study by the institutional ethics committee. At the institution, a daily list of deliveries is generated. The healthy controls in the postnatal ward were approached for participation in the study. The usual practice is for these infants to be discharged with mothers after 2 days  or 4–5 days for caesarean section deliveries. Data was analysed using software SPSS v18 and is presented as mean ± standard deviation and percentages for parametric and non-parametric data. Correlations between variables were assessed by Pearson’s coefficient of correlation while data between the cases and controls was compared using two tailed Unpaired Student-t test. Significance was set at p< 0.05. The intraobserver repeatability was analysed by calculating the intraclass correlation coefficients. This is an estimate of the reliability of the measurement and varies from 0 (no reliability) to 1 . The intraobserver variability was assessed by performing off-line analysis on the same patients one week apart. The observer was blinded to the categorization of the infant.Therapeutic hypothermia is the standard of care for asphyxiated infants in Australia and New Zealand. The infants are cooled when all 3 of the following criteria are met:a) Gestational age > 35 weeks and birth weight > 2000 gb) At least 2 of the following• Apgar score ≤ 5 at 10 minutes and/or• Mechanical ventilation or need for resuscitation at 10 minutes and/or• Cord pH < 7.0 or arterial/venous blood gas pH < 7.0 or base deficit ≥ 12 on sample obtained within 1 hour of birthc) Moderate or severe hypoxic ischaemic encephalopathy (Sarnat’s & Sarnat’s staging).The aim is to maintain the core body temperature between 33–34°C for the first 72 hours and achieve rewarming over a period of 12 hours. None of the infants in this study received sedation or were paralysed.Echopac system. Gain settings were optimized to obtain as clear differentiation as possible between the ventricular cavity and the wall. Endocardial tracing over a single frame was manually drawn for the LV. This was followed by automatic tracking of endocardial borders throughout the cardiac cycle. The LV was divided into six segments: basal septal, middle septal, apical septal, apical lateral, middle lateral and basal lateral  and 10 Hz probe. Real time 2D data on the first postnatal day was collected from an apical 4 chamber view in all the subjects and stored digitally for offline analysis on the 2/4] × heart rate)/body weight. The angle of insonation was kept to < 15°. The cross sectional area was uniformly measured at the valve hinges. Diastolic performance was evaluated from Doppler interrogation of transmitral flow. Specifically, the peak velocity of early passive wave (E wave) and late active wave (A wave) were measured to calculate the E/A ratio [LVO was measured from the apical 5 chamber view. Ventricular output was calculated in ml/kg/min by the formula . The likely aetiology in 17/21 cases was meconium aspiration syndrome. Two infants were born in the setting of antepartum haemorrhage while one had a tight cord around the neck. Exact cause of asphyxia in one was not known. Table 2 = 0.5, p < 0.001, Figure The mean LV GLS was noted to be significantly impaired in the asphyxiated infants . Table Speckle tracking echocardiography is a relatively recent addition to neonatal non-invasive cardiac diagnostics and this study presents data on its application in asphyxiated infants. LV GLS was noted to be significantly impaired in asphyxiated infants. No significant segmental gradient was noted. Global strain was associated with a low cardiac output state and elevated cTnT.Myocardial deformation is affected by complex interactions between inherent cardiac contractile force and extrinsic loading (both pre and after) conditions. Hence, both could determine the pattern and the magnitude of deformation. Impairment in deformation could affect both shortening and lengthening. In acute ischemic conditions, the affected myocardial tissue does not demonstrate shortening or lengthening activity and it reflects in reduced systolic SR or strain. The deformation data related to ischemia and infarction is predominantly from adult literature and used DTI strain analysis. Our study used STE to assess asphyxiated infants. These infants were already severely haemodynamically compromised which reflected in abnormal conventional parameters of fractional shortening, stroke volume and LVO. While the numbers in each group were small, infants on inotropes had greater global deformation compared to those who were not on inotropes. There is limited data on the effect of inotropes on myocardial deformation which has been studied using DTI. In porcine myocardium, the peak systolic strain rate increased with incremental dobutamine challenge ,11. UsinCzernik and colleagues used STE to assess evolution in cardiac performance during various phases of therapeutic hypothermia in 8 asphyxiated neonates . AssessmMyocardial deformation is an angle independent measurement if the speckle tracking technique is based on 2D gray ultrasound image acquisitions. Conventional Doppler derived indices (such as LVO), on the other hand, typically depend on the angle of insonation. Given that a third of the patients were on inotropes, it might under estimate the severity of the haemodynamic compromise. We noted a significant correlation between LV GLS and LVO in both groups and between GLS and cTNT in the asphyxiated infants. The latter remains the best marker of acute heart injury with high predictive values . The DTI2D strain analysis has been shown to be useful in neonatal settings as well. El-Khuffash et al recently demonstrated feasibility and reliability of STE in premature infants with a haemodynamically significant ductus arteriosus . EchocarAs with all new echocardiographic methods, feasibility and variability are key areas for investigators. Feasibility of STE has been previously demonstrated in neonates and adults ,16,17. IWhile the small number of subjects as a limitation is accepted, this study is preliminary work describing STE in critically sick neonates. We only depicted the apical 4- chamber approach which enables assessment of the interaction of inferolateral and anteroseptal segments simultaneously; radial and circumferential measurements could give additional information. Since therapeutic hypothermia is standard of care in the region, we did not have a population of asphyxiated infants who were not cooled for comparison with the study population. Lack of serial measurements as a limitation is accepted.Myocardium of asphyxiated infants showed impaired global and segmental deformation as well as rate of deformation during systole compared to healthy term neonates. Deformation indices correlated with 2D Doppler derived indices of cardiac output in both groups. While the conventional parameters remain the cornerstone of echocardiographic assessments, speckle tracking is an upcoming research tool which has shown promise in various neonatal clinical situations. We believe these measurements could potentially be useful in the management of haemodynamically unstable infants, especially those needing inotropic support; however, additional research is required.SR: Strain rate; AFI: Automated functional imaging; DTI: Doppler tissue Imaging; cTnT: cardiac troponin; LVO: Left ventricular output; GLS: Global longitudinal strain.The authors declare that they have no competing interests.AS- Contribution to study design and conception, data acquisition and analysis, drafting the manuscript. Is the corresponding author. FW-Critical revision and drafting manuscript, with data interpretation. SM-Design and conception with critical review on the topic. All authors read and approved the final manuscript.


In patients with acute myocardial infarction (AMI) the myocardial salvage index (MSI) quantified by Cardiovascular Magnetic Resonance (CMR) is defined as the volumetric difference of myocardial edema, reflecting the perfusion bed, and the infarcted tissue.While after a coronary occlusion time of more than 8 hours, relevant myocardial salvage is highly unlikely, previous data however showed myocardial edema surrounding the infarcted tissue after prolonged occlusion times. We therefore speculated that peri-infarct edema can be consistently observed in very late reperfused MI, indicating that edema in late reperfused MI does not necessarily reflect myocardial salvage.In 7 tertiary hospitals, 80 patients who underwent PCI between 8 to 24 hours after presentation with AMI were included in the study. The time to reperfusion (TTR) was correlated with infarct size (IS), extent of myocardial edema and MSI. Standard CMR protocols were used to characterize the extent of myocardial edema, infarction, microvscular obstruction (MO) and the apparent myocardial salvage index. A stratified analysis was conducted considering subjects divided in four quartiles of TTR.The mean TTR was 706±238 minutes. The edematous area was consistently larger than the infarct (mean difference 9.8± 8.3%) and the apparent myocardial salvage index was 31.1±20.1%. There was a strong correlation between the area of infarction and the extent of myocardial edema . TTR was not correlated with the infarct area (p=0.45), the extent of myocardial edema (p=0.17), MO (p=0.65) or the myocardial salvage index (p=0.19).In patients with late reperfused myocardial infarction, myocardial edema surrounding the infarcted tissue is a consistent finding. Its extent is not correlated with the time to reperfusion. These data indicate that in late reperfused myocardial infarction: a) Peri-infarct edema is a consistent finding and thus has to be taken into account when assessing myocardial salvage and b) Relevant myocardial salvage appears very unlikely. These findings have significant implications for the quantification of myocardial salvage by CMR and for studies on the "time window" for myocardial revascularization.None


Myocardial salvage is an important surrogate endpoint assessing the success of coronary reperfusion in acute myocardial infarction. Single photon emission computed tomography (SPECT), the established modality for assessment of myocardial salvage, is logistically demanding and associated with a considerable radiation exposure. The combination of T2 and late-enhancement imaging in cardiac magnetic resonance (CMR) can assess myocardial salvage in one examination, but up to now data comparing both modalities is very limited.We analyzed 180 patients who were treated by primary revascularization in acute myocardial infarction and underwent both SPECT and CMR for assessment of myocardial salvage. The first SPECT scan was performed with tracer injection before revascularization and image acquisition within 8 hours after revascularization, the second SPECT scan and the CMR scan were performed 3 to 7 days after the event. In CMR T2 weighted turbospin echo sequences and inversion recovery gradient echo sequences 15 minutes after application of dimeglumingadopentetat were performed. Area at risk and infarct size was quantified automatically using thresholds of 2 resp. 3 standard deviations above healthy myocardium.With SPECT, mean area at risk was 29.4 ± 18.7% of left ventricle (LV) and infarct size was 14.7 ± 16.9% LV, resulting in a mean salvage are of 14.9 ± 15.1% LV. With MRI, mean area at risk was 28.0 ± 14.5% LV and infarct size was 16.0 ± 13.5% LV, resulting in a mean salvage are of 11.9 ± 12.3%. Results of both modalities correlated well for area at risk (r=0.80), scar size (r=0.87) and salvage area .Assessment of the salvage area by CMR using T2 and late enhancement imaging correlates well with the established modality of SPECT. The use of CMR for myocardial salvage assessment can significantly simplify the procedure and may make the method usable beyond the realm of highly specialized centers.This trial was supported in part by the research grant from “Förderverein des Deutschen Herzzentrums”, Munich, Germany.


Implantable defibrillators are lifesavers and have improved mortality rates in patients at risk of sudden death, both in primary and secondary prevention.  However, they are unable to modify the myocardial substrate, which remains susceptible to life-threatening ventricular arrhythmias. Electrical storm is a clinical entity characterized the recurrence of hemodynamically unstable ventricular tachycardia and/or ventricular fibrillation, twice or more in 24 hours, requiring electrical cardioversion or defibrillation. With the arrival of the implantable cardioverter-defibrillator, this definition was broadened, and electrical storm is now defined as the occurrence of three or more distinct episodes of ventricular tachycardia or ventricular fibrillation in 24 hours, requiring the intervention of the defibrillator  (anti-tachycardia pacing or shock). Clinical presentation can be very dramatic, with multiple defibrillator shocks and hemodynamic instability. Managing its acute presentation is a challenge, and mortality is high both in the acute phase and in the long term. In large clinical trials involving patients implanted with a defibrillator both for primary and secondary prevention, electrical storm appears to be a harbinger of cardiac death, with notably high mortality soon after the event. In most cases, the storm can be interrupted by medical therapy, though transcatheter radiofrequency ablation of ventricular arrhythmias may be an effective treatment for refractory cases.This narrative literature review outlines the main clinical characteristics of electrical storm and emphasises critical points in approaching and managing this peculiar clinical entity. Finally focus is given to studies that consider transcatheter ablation therapy in cases refractory to medical treatment. The term electrical storm (ES) was introduced in the 1990s to describe a state of electrical instability of the heart characterized by a series of malignant ventricular arrhythmias in a short period of time . The rapES was formerly defined as the recurrence of hemodynamically unstable ventricular tachycardia and/or ventricular fibrillation, twice or more in 24 hours, requiring electrical cardioversion or defibrillation -6. With Between 1996 and 2006, several studies were carried out in order to investigate the incidence and prognosis of ES in ICD recipients . HoweverThe time from ICD implantation to the onset of electrical storm also differs in the various case-records. Indeed, the time-lapse seems to be particularly affected by the population considered, the myocardial substrate, the medical therapy undertaken and the indications for device implantation.  In one of the earliest studies , the aveThe number of VT that occurs during an episode of electrical storm varies substantially among the different studies. Verma reported an average of 5±5 shocks , while GMany papers report that in the majority of patients, an evident trigger i.e. a contingent cause that prompts the storm, cannot be identified . CrednerLike triggers, the risk factors for ES are also difficult to identify. Severely compromised ventricular function, chronic renal insufficiency and ventricular tachycardia as the onset arrhythmia all seem to correlate significantly with the development of storms .  In theAlthough these data on the causes and risk factors are not conclusive, it emerges that ES is the result of multiple interactions between a predisposing electrophysiological substrate and alterations in the autonomous nervous system and cellular milieu . The proThe immediate clinical consequence of ES is hospitalization, which takes place in 80% of patients, particularly those who have received a shock from the device (100% if >3 shocks are received) . MoreoveWith regard to mortality, it is not surprising that studies conducted on large numbers of patients for a sufficiently long period of follow-up have documented an increase.  In the AVID study , patientVerma  also obsSuch mechanisms remain plausible, though unconfirmed. What is clear, however, is that, while immediate mortality linked to ES in ICD patients is not high, the first few months after the episode seem to be critical on account of the increased mortality that is related not so much to the potential arrhythmic instability as to the progression of cardiac dysfunction . This fiElectrical storm constitutes a critical clinical situation both on account of the difficulty in approaching and managing hemodynamically unstable ventricular arrhythmias and because it is associated with significant pain and anxiety, which further increase the sympathetic tone and facilitate further arrhythmias .A patient with ES has to be hospitalized and monitored in an intensive care unit. The most urgent evaluation concerns the hemodynamic stability of the arrhythmias and, if they degenerate into acute heart failure, prompt assessment of the complications linked to this .When a trigger can be identified, its correction may reverse the electrical instability of the myocardium.  For this reason, thorough clinical and laboratory evaluation is of fundamental importance in order to search for possible pro-arrhythmic triggers, such as hydro-electrolytic imbalance or the intensification of myocardial ischemia . If any In the absence of contraindications (such as QT lengthening or polymorphic ventricular tachycardia), amiodarone is generally the antiarrhythmic drug of choice and has been validated in numerous clinical trials ,5. If thFor what concerns the prevention of ES, interesting results have been yielded by some drugs such as azamilide, a class III antiarrhythmic which blocks the calcium channels and prolongs the refractory period .Nevertheless, the principal factor in the prevention of electrical instability is correct ICD programming . Given tIn cases that are refractory to drug therapy, transcatheter radiofrequency ablation of the arrhythmogenic myocardial substrate can be carried out during ES.  This was first described in a few case reports -29 and sWillems et al.  were theStrickbeger  reportedSra  was the Silva  reportedMarrouche  reportedBansch  reports In 10 patients with sustained ventricular arrhythmia, Brugada  reportedCarbucicchio  reports Electrical storm is a very challenging clinical event that can be considered under two perspectives: the arrhythmic event can constitute the clinical manifestation of worsening heart failure or it might compromise myocardial function, thereby giving rise to the high long-term mortality seen in these patients.Treatment in the acute phase is off-label and often requires the simultaneous intravenous administration of several antiarrhythmic drugs.Recent studies have proposed transcatheter ablation in cases of electrical storm that are refractory to drug therapy. In several case-records, this approach proved to be safe and effective in interrupting the rapid sequence of life-threatening ventricular arrhythmias, nevertheless it does not seem to change the long-term prognosis of these patients, who continue to bear an increased burden of mortality.


Left atrial (LA) function plays an important role in the maintenance of cardiac output, however, in patients with constrictive pericarditis (CP), whether pericardial restriction and adhesion can lead to LA dysfunction, and the characteristics of LA function remain unclear. The aim of the study is to compare the left atrial (LA) function of patients with CP to that of healthy study participants using speckle tracking echocardiography (STE) and conventional echocardiography.P <0.001). LA function was correlated with the early diastolic velocity of the lateral mitral annulus (P <0.05).Thirty patients with CP and 30 healthy volunteers (controls) were enrolled in the study. The underlying cause of CP was viral pericarditis in 24 (80%) patients and unknown in 6 (20%) patients. The LA maximum volume (Vmax), LA minimal volume (Vmin), and LA volume before atrial contraction (Vpre-a) were measured using biplane modified Simpson’s method. The LA expansion index (LA reservoir function) was determined as follows: ([LAVmax - LAVmin]/LAVmin) ×100. The passive emptying index (LA conduit function) was calculated as follows: ([LAVmax - LAVpre-a]/LAVmax) ×100, and the active emptying index (booster pump function) was calculated as follows: ([LAVpre-a - LAVmin]/LAVpre-a) ×100. All the patients underwent two-dimensional STE. The LA global systolic strain (S), systolic strain rate (SrS), early diastolic strain rate (SrE) and late diastolic strain rate (SrA) were measured. The LA expansion index, passive emptying index, the active emptying index and the LA global S, SrS, SrE, SrA were found to be significantly lower in patients with CP than in the control participants (Although left ventricular systolic function was preserved in patients with CP, the LA reservoir, conduit, and booster functions were impaired. Pericardial restriction and impairment of the LA myocardium may play an important role in the reduction of LA function in patients with CP. Chronic constrictive pericarditis (CP) is caused by reduction in the elasticity of the pericardium, which leads to impaired diastolic filling of the heart. The diastolic pressure of the heart, especially the end-diastolic pressure, is elevated because of the constricted pericardium; an enlarged left atrium in patients with chronic constrictive pericarditis is a common finding in clinical practice. Although left atrial (LA) abnormalities are associated with abnormal diastolic function of the left ventricle, the characteristics and pathophysiology of the left atrium in patients with CP is poorly understood.Measurement of LA volumes, myocardial wall motion, and transmitral flow using conventional two-dimensional 2-D) and Doppler echocardiography can provide important information for the evaluation of LA function. However, these approaches are limited with regard to the evaluation of myocardial performance and have other technical limitations that are common to all Doppler-based techniques . Two-dim-D and DoThirty patients (21 men and 9 women) with CP from the First Affiliated Hospital of China Medical University were enrolled in this study between October 2007 and May 2011. The patients with CP included those with heart failure who were diagnosed with CP according to the echocardiographic criteria and evidence of thickened pericardium  or surgically confirmed during pericardiectomy. Respiratory variation in Doppler transmitral early diastolic flow velocity (> 25%) was seen in 25 (83%) patients. There were 14 (47%) patients who underwent computed tomography during preoperative assessment. Five of these patients were found to have pericardial calcifications. All of the patients with CP had sinus rhythm, and none of them had other types of heart disease. The underlying cause of CP was viral pericarditis in 24 (80%) and unknown in 6 (20%) patients. Thirty healthy volunteers (21 men and 9 women), who were matched in age and gender with the study patients were enrolled as controls. Clinical and echocardiographic data were prospectively collected in electronic patient dossier Written informed consent was obtained from all participants, and the study was approved by the China Medical University Ethics Committee.While the participants were in the left lateral recumbent position, images were acquired using a Vivid 7 Dimension ultrasound system . equipped with a 2-4 MHz phased array probe. All images and measurements were acquired from standard views according to the guidelines of the American Society of Echocardiography, and were digitally stored for offline analysis .The left ventricular (LV) ejection fraction was measured using the biplane modified Simpson’s method and was used as a standard index of global LV systolic function. The ratio between the peak early (E) and late (A) diastolic velocity across the mitral valve was used as a standard index of LV diastolic function. LV longitudinal function was determined by measuring peak systolic velocity , peak early diastolic velocity , and late diastolic velocity  at the level of the mitral septal annulus and lateral annulus on the apical four-chamber view .The LA anteroposterior dimension was obtained from the parasternal long-axis view. The following indices were calculated using the biplane modified Simpson’s method as follows: (1) maximum LA volume (Vmax), measured at the point of the mitral valve opening; (2) preatrial contraction LA volume (Vpre-a), measured at the onset of the P-wave on the simultaneously recorded electrocardiogram; and (3) minimum LA volume (Vmin), measured at the point of mitral valve closure. LA reservoir function was assessed from the filling volume, which was calculated as the Vmax -Vmin; the expansion index, calculated as [LAVmax - LAVmin]/LAVmin) ×100. The LA conduct function was assessed from the the passive atrial stroke volume, which was calculated as LAVmax – LAVpre-a; the passive emptying index, calculated as ([LAVmax – LAVpre-a]/LAVmax) ×100; and the LA conduit volume, calculated as the LV stroke volume – LA filling volume. The LA pump function was assessed from the active atrial stroke volume, which was calculated as LAVpre-a - LAVmin; and the active emptying index, calculated as [LAVpre-a - LAVmin]/LAVpre-a) ×100 –10.Dynamic 2-D ultrasound images of 3 cardiac cycles from apical 4-chamber views were acquired using conventional ultrasound, with a frame rate of 57-72 fps. To measure strain and strain rate, the images were analyzed using customized software within the EchoPAC work station . The endocardial boundary of the left atrium was delineated manually, and then the software automatically drew the epicardial boundary. The widths of the regions of interest were adjusted manually to match the actual endocardial and epicardial boundaries. Similar to STE-derived LV analysis, an automatically generated region of interest was divided into 6 segments. LA longitudinal systolic strain and strain rate were calculated from the mean value of the peak systolic strain and strain rate of all LA segments obtained on the four-chamber view during LV systole. The LA longitudinal early diastolic strain rate was calculated from the mean value of the peak early diastolic strain rate of all LA segments obtained on the four-chamber view during LV early diastole. The LA longitudinal late diastolic strain rate was calculated from the mean value of the peak late diastolic strain rate of all LA segments obtained on the four-chamber view during LV late diastole.Calibrated IBS evaluates myocardial ultrasound reflectivity, providing an estimate of myocardial structural alterations and fibrotic content –13. The t-test, and Pearson correlation analysis was performed. P < 0.05 was considered statistically significant.Statistical analysis was performed using SPSS 17.0 software, and all the measurements are shown as mean ± SD. Data from the patient and control cohorts were compared using an unpaired A total of 60 patients were analyzed as 2 groups: patients with CP (n = 30) and healthy volunteers (n = 30). The characteristics of the study participants are shown in There was no statistical difference in the LV ejection fraction (LVEF) of the 2 study groups; the LV end-diastolic diameter, LV end-systolic diameter, LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV) and stroke volume (SV) were significantly decreased in the patients with CP. The E/A ratio was significantly increased in patients with CP. The E/Ea-sep ratio was significantly decreased in patients with CP, and there was no significant difference in the E/Ea-lat ratios  and negatively correlated with the global SrS . Moreover, the structural alteration in the LA lateral wall region evaluated by calibrated IBS was positively correlated with the global SrE . The E/Ea-sep was not correlated with the STE values. The correlation between SrA and Ea-lat was significant (r = -0.399 P = 0.032), whereas the SrA not significantly correlated with the Ea-sep. The mitral E/A was not correlated with the STE values, and there was also no significant correlation between the LVEF and STE values.In patients with CP, the E/Ea-lat ratio was positively correlated with the global SrE  as a reservoir during LV systole and isovolumic relaxation; (2) a conduit for blood transiting from the pulmonary veins to the left ventricle during early diastole; (3) an active contractile chamber that establishes final LV end-diastolic volume in late diastole; and (4) a suction source that refills itself in early systole ,15. In nSome investigators have demonstrated that LA function is an important predictor of cardiovascular events, and is independently associated with the risks for stroke and death ,20. The Previous studies have suggested that a Frank-Starling mechanism also exists in the human left atrium –28. In dDuring left ventricular contraction, LA reservoir function is determined by LA myocardial contraction and relaxation and displacement of the mitral annulus . In thisLA conduit function is mainly determined from the rate of LV relaxation . In thisr = 0.478, P=0.013) and negatively correlated with the global SrS . In addition, the correlation between SrA and Ea-lat was significant (r = -0.399 P =0.032) was found in patients with CP, suggesting that LA myocardial function is potentially affected by the pericardium, because the Ea-lat is potentially affected by pericardial calcifications or adhesions [Recently, E/Ea has been proposed as a tool for assessing LV filling pressures. Several investigators have shown that in patients with either impaired or pseudonormal relaxation or with sinus tachycardia, E/Ea is positive correlated with pulmonary artery or pulmonary capillary wedge pressure (PCWP) ,34. Howedhesions .r = 0.405, P=0.024) in patients with CP, suggested the myocardial fibrotic changes may play an important role in the reduction of LA function.Several studies have demonstrated that IBS correlated with the collagen content of the myocardium ,37. TherA major limitation of this study was the lack of invasive hemodynamic data, primarily because invasive data was not clinically indicated . SeveralIn this study, the LA systolic and diastolic function of patients with CP were found to be reduced, the pericardial restriction and LA myocardial impairment resulting from fibrotic changes and inflammation of the pericardium may play an important role in the reduction of LA function.