However, current BOLD CMR methods  are limited by poor spatial coverage and image artifacts . To address these limitations, we developed a fast, free breathing 3D T2 mapping technique at 3T that utilizes near 100% imaging efficiency. This quantitative BOLD approach, which can be performed within 5 minutes, permits full LV coverage during adenosine stress. In this study, we tested our approach in a canine model and validated our findings with simultaneously acquired 3 with 14 partitions, adiabatic T2 prep pulses  every other heart beat. Total acquisition time for whole LV coverage was 5 mins. For validation, dynamic 13N-ammonia PET scans were acquired along with MR data. PET images were analyzed using qPET . Epi and endo-cardial contours were used to segment the myocardium and mean myocardial T2 (T2avg) values were measured from basal, mid and apical slices at rest and adenosine stress. The corresponding slices were matched to 13N-ammonia PET images and mean myocardial perfusion (Qavg) values were measured. Myocardial BOLD reserve (T2avg (stress):T2avg(rest)) and perfusion reserve (T2avg (stress):T2avg(rest)) were computed on a slice basis and regressed.Mongrel dogs (n=3) were studied with a state of the art PET-MR system . After scouting and whole-heart shimming, fast 3D free-breathing T2 mapping sequence were prescribed at rest and under adenosine stress (140 mg/min/kg) with the following scan parameters: TR/TE =3.4/1.7 ms, flip angle = 15°, imaging resolution = 2 x 2 x 6 mm2=0.67, p<0.05).A representative set of BOLD and PET images acquired from a canine under rest and adenosine stress are collected in Fig. The proposed fast 3D free breathing T2 mapping at 3T permits whole LV assessment of BOLD changes between rest and adenosine stress. The BOLD responses were very closely correlated with PET perfusion, suggesting that the proposed BOLD CMR method is a viable approach for imaging myocardial perfusion. Further studies are required to examine its utility in the setting of ischemic heart disease.This work was supported in part by National Heart, Lung, and Blood Institute HL091989.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, And Blood Institute or the National Institutes of Health.


The management of iron overload has been transformed by the use of T2* as a surrogate marker of cardiac iron loading. The presence of iron however not only changes T2*, but also T2 and T1. Recent advances make T1 mapping a possible complementary technique to T2*. Preliminary data are encouraging, but the relative advantages and disadvantages and optimal mathematical model for the relationship between T1 and T2* remain unknown.This was a single centre prospective study of 250 patients (age 37 ± 13 years) referred with potential iron overload for T2* assessment, with 50 healthy volunteers (age 44 ± 11 years) as a reference comparison group. Each participant underwent short axis septal T2* (standard Siemens sequence using 8 different TE) at 1.5T and in addition myocardial T1 mapping (ShMOLLI sequence).27% of patients required more than one T2* acquisition to obtain optimal images for analysis compared with 12% for T1 mapping. ShMOLLI images were uninterpretable in 2 patients due to the presence of an MRI conditional pacemaker, and the positioning of a PORT-A-CATH implantable venous access system. It is known that some patients were unable to complete T2* sequences (21 heart beat scan), but these were not captured by the inclusion criteria of the study.2=0.71, p<0.001, figure 2=0.83, p<0.001, figure 2=0.07, figure There was an exponential relationship between T1 and T2* across all patients and healthy volunteers ; 14ms (705ms) and 10ms (636ms). If T1 is accurate for iron, then using the lower limit of normal for T1 (895ms) would suggest that the normal limit for T2* would be 29ms. However, of the 50 healthy volunteers, 8 (16%) had T2*s lower than this, possibly due to relatively lower precision of T2* measurements.In potential cardiac iron overload, not all patients manage good image quality on the first breath-hold with either technique. Measured myocardial T1 and T2* are best modelled using an exponential curve fit but only correlate below a T2* of 20ms. T1 data suggests that the lower limit of normal T2* should be 29ms and thus far more patients have myocardial iron than is currently recognised - but such a high cutpoint for T2* would generate a poor specificity.AAG is supported by a research grant from the Rosetrees Trust.


Background. Tension pneumothorax can infrequently cause ventricular arrhythmias and increase the threshold of defibrillation. It should be suspected whenever there is difficulty in defibrillation for a ventricular arrhythmia. Purpose. To report a case of traumatic tension pneumothorax leading to ventricular tachycardia and causing defibrillator failure. Case. A 65-year-old African-American female was brought in to our emergency department complaining of dyspnea after being forced down by cops. She had history of mitral valve replacement for severe mitral regurgitation and biventricular implantable cardioverter defibrillator inserted for nonischemic cardiomyopathy. Shortly after arrival, she developed sustained ventricular tachycardia, causing repetitive unsuccessful ICD shocks. She was intubated and ventricular tachycardia resolved with amiodarone. Chest radiograph revealed large left sided tension pneumothorax which was promptly drained. The patient was treated for congestive heart failure; she was extubated on the third day of admission, and the chest tube was removed. Conclusion. Prompt recognition of tension pneumothorax is essential, by maintaining a high index of suspicion in patients with an increased defibrillation threshold causing ineffective defibrillations. Tension pneumothorax, although usually associated with pulseless electrical activity, can infrequently cause serious ventricular arrhythmias. Moreover, it has been reported to increase the threshold of internal and external defibrillation of such arrhythmias. Pneumothorax should be suspected whenever there is failure or difficulty in internal or external defibrillation of ventricular arrhythmias. We report a case of ventricular tachycardia following the development of traumatic tension pneumothorax and review the pertinent literature.2 59 mmHg, PaO2 91 mmHg, HCO3− 14 mmol/L, and O2 sat 90%. Other laboratory studies were pertinent for serum creatinine 1.54 mg/dL, potassium 5.9 mmol/L, digoxin 0.9 ng/mL, glucose 381, lactic acid 6.2 mmol/L, BNP 1400 pg/mL, and troponin I 0.51 ng/mL. The patient was treated for congestive heart failure; she was extubated on the third day of admission, and the chest tube was removed. ICD was found to be functioning properly upon interrogation, with ventricular tachycardia zone set at 171 BPM (cycle length of 350 ms) and ventricular fibrillation zone at 250 BPM. Ventricular tachycardia at a rate of 182 BPM (cycle length of 330 ms) was detected by the ICD with two unsuccessful attempts at antitachycardia pacing which resulted in acceleration of the ventricular tachycardia to 211 BPM (cycle length of 285 ms), followed by 4 defibrillations.A 65-year-old African-American female was brought in to our emergency department by ambulance complaining of dyspnea after being forced down by cops during the arrest of her son. She had history of mitral valve replacement for severe mitral regurgitation. She also had a left-sided biventricular implantable cardioverter defibrillator (ICD) inserted for symptomatic severe nonischemic cardiomyopathy with left bundle branch block, which replaced a right-sided dual chamber pacemaker previously implanted for intermittent complete heart block. Shortly after arrival, she developed a brief episode of pulseless electrical activity followed by sustained ventricular tachycardia , which gVarious arrhythmias have been reported in patients sustaining chest trauma and blunt cardiac injury, ranging from benign premature supraventricular and ventricular beats to more serious paroxysmal supraventricular and ventricular tachycardias, atrial fibrillation and flutter, and fatal ventricular fibrillation . Blunt cTension pneumothorax occurs when air gathers rapidly between the lung and the chest wall, causing collapse of the lung on the affected side and compression of the mediastinum. It has long been recognized as a reversible cause of pulseless electrical activity , which hIatrogenic pneumothorax, requiring chest tube placement, following pacemaker insertion, has been reported in 190 out of 28,860 patients (0.66%) in a large population-based study . TensionThe mechanism of the hemodynamic compromise associated with tension pneumothorax leading to pulseless electrical activity appears to depend on the extent of intrapleural pressure  and has The increased threshold to defibrillation following pneumothorax has been postulated to result from the increased impedance to current flow through the chest imposed by air, especially in a left-sided pneumothorax, which can act as an insulator and consequently raise the DFT ; whetherOur patient had an ICD placed for primary prevention. She was forcefully pushed down to the ground, which resulted in left-sided pneumothorax, likely because of the existence of the ICD on the same side, causing increased DFT and ineffective ICD shocks. Direct cardiac effect of the trauma is less likely but cannot be excluded. Even though she was hypoxic and acidotic, these were unlikely to affect her DFT .Pneumothorax has long been recognized as a reversible cause of serious ventricular arrhythmia  and incr


In acute myocardial infarction (MI), late Gadolinium enhancement (LGE) has been proposed to include the infarcted myocardium and area at risk. However, little information is available on the optimal timing after contrast injection to differentiate these 2 areas. Our aim was to determine in acute and chronic MI whether imaging time after contrast injection influences the LGE size that better predicts infarct size and functional recovery.Subjects were evaluated by cardiovascular magnetic resonance (CMR) the first week (n = 60) and 3 months (n = 47) after a percutaneously revascularized STEMI. Inversion-recovery single-shot (ss-IR) imaging was acquired at multiple time points following contrast administration and compared to segmented inversion-recovery (seg-IR) sequences. Inversion time was properly adjusted and images were blinded, randomized and measured for LGE volumes.In acute MI, LGE volume decreased over several minutes (p = 0.005) with the greatest volume occurring at 3 minutes and the smallest at 25 minutes post-contrast injection; however, LGE volume remained constant over time in chronic MI (p = 0.886). Depending on the imaging time, in acute phase, a change in the transmurality index was also observed. A transmural infarction (>75%) at 25 minutes better predicted the absence of improvement in the wall motion score index (WMSI), a higher increase in left ventricular volumes and a lower ejection fraction compared to 10 minutes.A change was observed in LGE volume in the minutes following contrast administration in acute but not in chronic MI. Infarct transmurality 25 minutes post-contrast injection better predicted infarct size and functional recovery at follow-up. Cardiovascular magnetic resonance (CMR) utilizing the late Gadolinium enhancement (LGE) technique is a highly accurate method for characterizing reversible and irreversible myocardial injury to obtain information on myocardial viability in both acute and chronic myocardial infarction ,2. StudiHowever, early studies in animal models conducted at different minutes after the administration of contrast in reperfused acute MI showed that the area of LGE could potentially overestimate the true extent of infarction –7. MoreoRather than conclude that Gadolinium overestimates acute infarct size, it is more challenging to understand the kinetics of Gadolinium contrast enhancement and its wash-out to determine why Gadolinium can show both the penumbra of the area at risk and the core of the LGE that represents the infarct .The aims of this study were to serially investigate differences in LGE and MVO sizes over time after contrast injection in acute and chronic infarcts and also to determine the timing post-contrast that better predicts myocardial functional recovery, left ventricular volumes and ejection fraction.Between January 2006 and July 2008, 72 patients admitted to the coronary care unit following an ST-segment elevation acute myocardial infarction (STEMI) successfully reperfused through percutaneous coronary intervention (PCI) were prospectively enrolled. Patients were included if they fulfilled the criteria of documented acute STEMI with  chest paAll CMR studies were performed with a 1.5 T clinical scanner  using a phased-array cardiac receiver coil. Retrospectively electrocardiogram-gated breath-hold short-axis cine views were performed to quantify volumes and ejection fraction . Additional 2-chamber, 3-chamber and 4-chamber views were also obtained. LGE images were acquired at identical slice positions to the cine images after the administration of 0.2 mmol/kg of body weight Gadolinium-DTPA (Gd-DTPA) . A single-shot inversion recovery (ss-IR) steady-state free precession sequence  was acquQuantitative analyses of left ventricular (LV) mass, end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) were performed by manually tracing the epicardial and endocardial borders as previously described . Volume Early MVO were considered if they were present 1 minute after contrast administration [late MVO when seen 10 min later [acute and chronic CMRs) were blinded, randomized and measured for LGE volumes; 990 stacks of images were analyzed. Dynamic changes in LGE were evaluated with the use of different parameters: LGE volume, relative LGE volume, LGE transmurality and LGE lateral extension.For objective quantification of LGE and MVO, a reference region of interest (ROI) was placed in remote myocardium. The signal intensity threshold indicating LGE was imposed 2 standard deviations (SD) above the mean intensity of the reference ROI on each of the contrast-enhanced CMR tomograms and summed, as previously described ,14. Micrstration  and latein later , on singin later ,18. The LGE transmurality was expressed as the mean percentage of transmurality of the LGE in all affected slices at each time point. Transmurality in each slice was calculated by dividing the LGE mass by the total mass of the affected myocardium in each segment ,20.LGE lateral extension was determined by calculation of the infarct endocardial surface area (Infarct-ESA), as previously described .acute and chronic CMRs were analyzed using different standard deviations  over remote signal intensity to establish the effect of different thresholds on LGE volume.Further, single-shot stacks of images in the Signal intensity was obtained in the hyperenhanced area, the remote myocardium and background noise for calculation of the signal-to-noise and contrast-to-noise ratios .In a subset of 56 stacks of single-shot images including a mix of acute and chronic CMRs, interobserver and intraobserver reproducibility was performed.Finally, the LGE volume obtained with seg-IR sequences was measured and compared with the volume obtained by the ss-IR at the same slice position and same time point in order to compare both sequences.t-test if they presented a normal distribution or ANOVA with Bonferroni correction for multiple comparisons, and Mann–Whitney U test if they did not present a normal distribution. For categorical variables, general characteristics of the sample were assessed by percentages (chi-square test). Interobserver and intraobserver variabilities were calculated using the intraclass correlation coefficient. Agreement between ss-IR and seg-IR sequences was examined using the intraclass correlation coefficient and Bland–Altman analysis.Continuous demographic variables were expressed as mean ± standard deviation. The Kolmogorov-Smirnov test was used to evaluate the normality distribution of variables. Inter-group differences for continuous parameters were assessed by Student's A two-tailed P value < 0.05 was considered statistically significant. SPSS 19.0 software version  was used for the analysis.Acute CMR, mean: 2.6 ± 1.5 days; range: 1–6) and approximately 4 months  after admission.The clinical and angiographic characteristics of patients are shown in Table acute compared to the chronic CMRs    Fig. . Thus, nely Fig. .Fig. 2ReIn the analysis of infarct size, an intraclass correlation coefficient of 0.94 was found : 0.88-0.96; p < 0.0001) for interobserver and 0.98  for intraobserver variabilities.acute CMR. A decrease of 4.91 ± 9.08 grams, 22.20% relative reduction between the 3rd and 25th minutes, p = 0.001 was observed (Table chronic CMR with no significant differences after contrast administration (p = 0.886)  and relative LGE volume (p = 0.005) over several minutes after contrast administration was observed. The largest increase in LGE volume was between the 1st and 3rd minutes, and LGE volume subsequently decreased in ed Table . Represe6) Table . There wEarly MVO was seen in 35 patients (58%) and late MVO in 16 (27%), all of whom also had early MVO. MVO was not present in the chronic CMR studies. A significant decrease was observed in MVO volume (p = 0.005) with the greatest volume 1 minute after contrast administration and the smallest after 25 minutes (Table early or late MVO. Patients with late MVO presented slower wash-in of Gd-DTPA with a maximum LGE volume at 7 minutes post-contrast injection compared with the 3 minutes observed in patients with early MVO (early MVO: p = 0.022 and late MVO: p = 0.046)  Fig. .acute CMR, a drop in LGE transmurality was observed over time with an increase for the first 3 minutes and with a subsequent decrease (following the same pattern as LGE volume over time) (p = 0.05). However, the infarct-ESA remained stable over time, thereby suggesting that the change in LGE size was due to a decrease in its transmurality rather than in its lateral extension (p = 0.981)  Fig. .Fig. 4Dyacute CMR studies, each image obtained by the seg-IR sequence was compared with its homologous ss-IR at the same slice position and same time point. Mean LGE size by ss-IR (3.57 ± 1.96 g) did not differ statistically from the seg-IR (3.48 ± 1.91 g), p = 0.72. Intraclass correlation coefficients between ss-IR and seg-IR were 0.92 . Bland-Altman analysis showed a bias of 0.09 grams of LGE size .In acute (p = 0.019) and chronic settings (p = 0.039)  and no manual planimetry correction. A reduction in mean LGE size was observed when the SD was increased in both A dynamic change on the transmural index and the number of patients at a certain degree of transmurality Table  was obseThese dynamic changes were also observed in the myocardial segmental recovery of function. Thus, in patients with a transmural index > 75% 10 min post-contrast, 3.25 ± 2.76 segments improved their function and the wall motion score index improved 4.00 ± 4.78 in the chronic CMR. However, in patients with a transmural index > 75% 25 min post-contrast, only 2.00 ± 1.97 segments recovered its function and the wall motion score index improved only 2.00 ± 3.50  , ESV (p < 0.001) and a higher decrease of EF (p < 0.001) at follow-up compared to those patients to whom the transmural index > 75% was determined 10 minutes post-contrast. Table , Fig. 6.We report the first detailed time course study, examining LGE in the setting of an acute and chronic MI in the same cohort of patients treated with primary PCI for STEMI. More importantly, we found that the timing and delay of viability imaging acquisition, following contrast administration, is vitally important in predicting global and segmental left ventricular recovery. This dynamic distribution of LGE is consistent with previous experimental and clinical studies ,10.The main findings in our study are that 1) the distribution of Gadolinium within the infarcted area constitutes a dynamic process, with a maximum volume 3 minutes after contrast administration and subsequent decreases over time; 2) these changes are present in the acute setting but not in chronic MI; 3) changes in LGE size is due to a decrease in the transmural extension (within the area at risk) rather than the lateral borders; 4) dynamics of Gadolinium also occur if MVO is present, in this case, a slower rate of wash-out is observed.Different mechanisms have been proposed to account for the Gd-DTPA enhancement patterns seen in reperfused infarcted tissue and the peri-infarct zone. First, there is an increase in the extracellular volume due to interstitial edema and/or loss of cell membrane integrity, which would increase the volume of distribution of Gd-DTPA. These findings were confirmed by Arheden et al., who found that the distribution volume was higher in the infarcted myocardium and intermediate in the peri-infarct zone compared to remote myocardium, and increased significantly with prolongation of the ischemic period . Also, KAnother hypothesis is that injured myocardium may also have abnormal Gadolinium wash-in and wash-out kinetics due to various factors . Slow wash-in, in reperfused infarcted regions, would lead to early low tissue contrast concentrations, whereas slow wash-out would eventually lead to higher contrast concentrations compared with normal tissue ,7. In thThe fact that Gadolinium accumulates in the peri-infarct zone of reversibly injured myocardium tissue could explain our findings. This hypothesis is supported by the fact that these dynamic changes are only seen in the acute setting, where edema and necrotic myocytes are present, and not in chronic infarcts with a dense collagenous matrix. Moreover, as we have demonstrated, the reduction of the infarct size is due to a decrease in the transmural extension rather than at the lateral borders after a coronary occlusion. Reimer and Jennings  and otheClassical studies have shown that the transmural extent of infarction as defined by CMR predicts improvement in contractile function in acute and chronic MI ,2. HowevAlthough our and other studies ,10,5 supNevertheless, when the LGE is performed 20 minutes after the contrast injection the transmural extent of LGE correlated inversely with wall thickening and the ejection fraction both in the acute phase and at follow-up . These rlate MVO, dynamic changes of LGE were delayed compared to patients with smaller areas of MVO. Moreover, we demonstrate a rapid decline in the presence and volume of MVO in the minutes following contrast administration. This fact is of paramount importance as these rapid changes can potentially bias studies evaluating interventional trials aimed in reducing MVO. Nevertheless, due to the reduced number of patients in each group we could not find statistically significant differences and this finding should be further investigated.MVO in LGE imaging has been reported to occur in 28% to 58% of patients after STEMI . Klein eThe segmented technique has been used as the gold standard for the detection of myocardial infarction and accurate assessment of viability . Howeveracute CMR. Nevertheless, this hypothesis cannot be supported for many reasons: 1) the parameters used in the single-shot sequence  support the T1 contrast compared with the T2 contrast. 2) The area of infarction is not overestimated on the ss-IR sequence when compared with the seg-IR at the same slice position.A mixed T1 and T2 contrast is known for single-shot sequences . As a reThe methodology used to measure LGE sequences is one of the most important points to consider in order to accurately quantify the size of MI. Kim et al. validated that LGE closely tracks the area of irreversible myocardial injury using an intensity thresholding of 2 SD above the mean of the normal myocardial intensity . AlthougCurrently, the contrast kinetics following 25 minutes are unknown. However, due to the stability of infarct mass 20 to 25 minutes after the administration of the contrast and the specificity of the transmurality index at 25 minutes to predict the functional recovery at follow-up, we do not expect that longer periods of time would imply significant differences in our results.Although our study suggests that the volume of LGE 3 minutes after contrast injection should correlate the AAR (early contrast enhancement) and the infarct size 25 minutes after (late contrast enhancement), we did not perform T2-weighted images to compare our findings. However, using the same patient population we have previously demonstrated a good correlation within the Infarct-ESA and the BARI score to assess the AAR .There is a change in LGE size over time in acute human reperfused STEMI not seen in the chronic phase, with a maximum size 3 minutes after the contrast administration and a decrease thereafter. This reduction occurs within the area at risk  rather than in the lateral boundaries.It is important to wait at least 25 minutes to ensure a more accurate determination of infarct size in acute but not in chronic infarcts, in order to better predict left ventricular recovery at follow-up.We consider that these findings have important implications and should be considered in clinical trials that consider infarct size and infarct transmurality as end-points or to predict global or regional recovery.


Cardiac complications are the main cause of death in thalassemia major (TM) patients. Cardiovascular Magnetic Resonance (CMR) plays a key role in their management, assessing myocardial iron overload (MIO), biventricular function, atrial dimensions, and myocardial fibrosis. We evaluated the predictive value of CMR parameters for heart failure and arrhythmias.We followed prospectively 487 TM patients free of a cardiac complications at the first CMR. All prognostic variables associated with the outcome at the univariate Cox model were placed in the multivariate model and were ruled out if they did not significantly improve the adjustment.At baseline the mean age was 29.5 ± 9.0 years and 222 patients were males. The mean follow-up time was 58 ± 18 months. After the first CMR only the 37.8% of the patients did not change the chelation regimen or the frequency/dosage. We recorded 19 episodes of heart failure. Male sex, heart iron, ventricular dysfunction, ventricular dilation, atrial dilation, and myocardial fibrosis were significant univariate prognosticators. In the multivariate analysis the independent predictive factors were an homogeneous pattern of MIO (compared to no MIO) , myocardial fibrosis  and ventricular dysfunction . Figure We detected few cardiac events thanks to a MR-guided, patient-specific adjustment of the chelation therapy. Severe and homogeneous MIO, myocardial fibrosis and ventricular dysfunction identify patients at high risk of heart failure. Heart T2* doesn't have any power in predicting arrhythmias while male sex and atrial dilation are independent prognosticators.The MIOT project receives "no-profit support" from industrial sponsorships (Chiesi and Apopharma). This study was also supported by: "Ministero della Salute, fondi ex art. 12 D.Lgs. 502/92 e s.m.i., ricerca sanitaria finalizzata anno 2006" e "Fondazione L. Giambrone".


Left ventricular noncompaction (LVNC) is classified by the American Heart Association as a primary genetic cardiomyopathy and is attributed to defects in cardiac embryogenesis resulting in the intrauterine arrest of the compaction of the loose meshwork that makes up the fetal myocardium. From echocardiographic data, the prevalence of LVNC has been estimated at 0.05% of the general population. With the increasing use of cardiac magnetic resonance imaging (CMR), there has been a surge in the reports of patients with LVNC. Interestingly, many patients that have been diagnosed with non-ischemic dilated cardiomyopathy (NIDCM) have also been noted to have prominent left ventricular trabeculations. We sought to evaluate the difference in clinical outcomes in patients with NIDCM compared to those with LVNC as diagnosed by established CMR criteria.A retrospective analysis was performed on 71 patients diagnosed with NIDCM at a single tertiary care center who had undergone a CMR between January 1, 2012 and August 30, 2014. The diagnosis of cardiomyopathy was established based on clinical suspicion and a dilated left ventricle (LV) when indexed to body surface area. Baseline characteristics and clinical outcomes were obtained. Volumetric quantification was performed to obtain chamber volumes and ejection fractions (EF). The ratio of compacted:non-compacted myocardium was measured at end-diastole in both the 4- and 2-chamber orientations. The data was analyzed using analysis of variance (ANOVA) and Pearson's chi squared testing with SPSS Statistics for Windows.Of 71 patients, 25% were found to meet the criteria of LVNC based on established CMR criteria. The mean age of individuals diagnosed with LVNC was 50.9 years as compared to 50.4 years (p=0.907). The incidence of prior stroke, diabetes mellitus, hypertension, end-stage renal disease, and cancer treated with chemotherapy or radiation did not differ between the two groups. The mean LVEF in both groups was 36% (p=0.992). There was no statistical difference in the mean number of heart failure admissions when comparing patients with LVNC and NIDCM . Both groups exhibited similar occurrences of ventricular (p=0.473) and atrial arrhythmias (p=0.204). For all patients, the most commonly trabeculated areas were the anterior and lateral walls, while the least was the septum. The apical segments were noted to have the most prominent trabeculations.This represents the largest study comparing the clinical outcomes of those patients with MRI defined LVNC to those with NIDCM. Our results demonstrate LVNC may not be prognostically different than NIDCM, suggesting that LVNC may be a morphological variant of NIDCM or perhaps that the current CMR criteria for LVNC need to be revised. Larger studies are necessary to better evaluate and understand LVNC.None.


Adverse cardiac remodeling is a key component of the failing heart. Increased diastolic wall stress plays a pivotal role in the development and progression of adverse cardiac remodeling. The forces generated by the left ventricular (LV) myocardium initiate blood flow, while the moving blood itself also exerts a force on the ventricular wall and heart valves. Abnormal hemodynamic forces may contribute to increased diastolic wall stress. We calculated LV hemodynamic forces from the moving blood, and hypothesized that these forces are mostly directed along the "mitral valve (MV) to apex axis" in the healthy LV, while the distribution is altered in myopathic LVs.3. The LV was segmented from the morphological images using Segment (http://www.segment.heiberg.se). The LV pressure gradients were computed from the 4D flow data using the Navier-Stokes equations. By integrating the pressure gradients over the LV volume at every time frame, the LV hemodynamic force was calculated . The ratio between the LV hemodynamic forces acting in the LV SAx and LAx directions was used to calculate the "SAx-max/LAx-max force-ratio" for the early (E-wave) and the late (A-wave) diastolic filling (figure Ten dilated cardiomyopathy (DCM) patients  with mild to moderate ventricular dysfunction and ten healthy subjects  underwent a cardiac CMR examination at 1.5T (Philips Achieva), where morphological short- (SAx) and long-axis (LAx) images and 4D flow data was acquired. 4D flow MRI was acquired with retrospective cardiac gating; acquired temporal resolution 50.4ms and spatial resolution 3x3x3mmThere was no significant difference in age  or heart rate  between the groups, while LV ejection fraction , LV end-diastolic volume  and LV sphericity index  was significantly different. The "SAx-max/LAx-max"ratio (figure 4D flow CMR data allow quantification of hemodynamic forces acting on the LV myocardium. The present data show that the distribution of hemodynamic forces is altered in LVs of DCM patients compared to LVs of healthy subjects.This study was funded by the Swedish Heart-Lung foundation, the Swedish Research Council and the European Research Council.


Despite the usefulness of N-terminal propeptide of type III procollagen (PIIINP) in detecting enhanced collagen turnover in patients with congestive heart failure, the value added by PIIINP to the use of clinical variables and echocardiography in relation to directly measured left ventricular (LV) end-diastolic pressure (EDP) and the outcome of acute coronary syndrome (ACS) has not been clearly defined.post hoc p<0.05). The presence of coronary artery disease, the left atrial volume index (LAVI), the ratio of transmitral early and late diastolic flow velocities, a′, and the eas index were significantly correlated with LVEDP. According to multiple stepwise analysis, PIIINP, LAVI and the eas index were the three independent predictors of the level of LVEDP . During follow-up , 32 participants suffered from cardiac events, PIIINP and LAVI were significant predictors of cardiac mortality and hospitalization  2.589, p = 0.002; LAVI, HR 1.040, p = 0.027).This study involved 168 adult patients with ACS, who underwent echocardiography, measurement of serum PIIINP levels, and cardiac catheterization. Pulsed wave tissue Doppler imaging (PWTDI), which revealed mean peak systolic (s′), early (e′), and late diastolic (a′) velocities, was carried out and the eas index of LV function was evaluated: e′/(a′×s′). The patients were divided into three study groups based on the degree of LVEDP – normal (<16 mmHg), intermediate (16–30 mmHg), and high (>30 mmHg) LVEDP. All patients were followed-up to determine cardiac-related death and revascularization. Patients with high LVEDP had significantly more PIIINP than those with intermediate or normal LVEDP (all PIIINP is a highly effective means to evaluate LVEDP in patients with ACS. The PIIINP is also correlated with cardiac mortality and revascularization, providing an additional means of evaluating and managing patients with ACS. Acute coronary syndromes (ACS) refer to a continuum from unstable angina to non-ST-elevation and ST-elevation myocardial infarction (MI). The prognosis of patients with ACS typically depends on the occurrence and extent of myocardial necrosis Myocardial histological changes, including extracellular collagen deposition, strongly influence LV systolic and diastolic properties. In patients with ischemic heart disease, hormonal and immune activations are considered to affect the progression of LV dysfunction and heart failure This study determines whether PIIINP concentration may be associated with ventricular compliance dysfunction in patients with ACS. We hypothesize that patient with a higher PIIINP level exhibit a higher LVEDP, which can be directly measured by catheterization, and a poorer prognosis.The prospective investigation enrolled adult patients who had suffered their first ACS and were admitted to our hospital between 2010 and 2011 and scheduled to undergo percutaneous coronary intervention. Coronary wall atheromatous plaque with luminal reduction of greater than 50% will limit compensatory vasodilatation and thereby impede the flow coronary artery. Accordingly, coronary artery disease (CAD) is regarded as present when an obstruction of the vessel lumen exceeds 50%, as described elsewhere Serum samples for the measurement PIIINP concentrations were obtained before coronary catheterization. The concentration of PIIINP antigens in serum was evaluated by an equilibrium-type radioimmunoassay . Interassay and intra-assay variations for the PIIINP analyses were less than 7 %.Each subject underwent transthoracic M-mode, 2D and Doppler echocardiography using commercially available echocardiography units  before cardiac catheterization was performed. The left atrium volume index (LAVI), the LV end-diastolic volume index (LVEDVI), the LV end-systolic volume index (LVESVI), and LVEF were evaluated in apical two - and four -chamber views using modified Simpson’s rule. Transmitral early (E) and late (A) diastolic flow velocities, the isovolumic relaxation time (IVRT), and the myocardial performance index (MPI) were also measured.A TDI of the mitral annulus was obtained at six sites with the apical four -chamber, two-chamber and long-axis views. The PWTDI, which incorporates the mean peak systolic (s′), early (e′), and late diastolic (a′) velocities at six mitral annular sites was evaluated. PWTDI was also calculated to generate a combined index (eas index) of LV performance: e′/(a′×s′). A value that combined transmitral flow velocity and annular velocity (E/e′) was estimated to quantify the LV filling pressure Follow-up information was obtained from clinical records, death certificates, and correspondence. The PIIINP and LVEDP values blinded for the physician who followed-up these patients. The clinical end-points of follow-up were cardiac death and re-hospitalization for ACS.t-test , or Mann-Whitney U test , and chi-squire test  were tested for the difference of clinical characteristics. For the comparison of continuous variables among multiple groups, one-way analysis of variance (ANOVA) and LSD post hoc test was used.Continuous variables are expressed as mean ± SD, and categorical variables are expressed as absolute numbers (percentages). Unpaired p <0.1) in the preceding, unadjusted analysis of covariates of the 168 patients. Unadjusted Cox proportional hazards were used to evaluate the significance of various variables as predictors of cardiac death or re-hospitalization. Variables that were predictive of outcome (p<0.1) were then input into multivariate Cox proportional hazards regression models (backward selection) to identify independent predictors of outcomes. The outputs of the Cox regression analysis are presented as hazard ratios (HR) with a 95% confidence interval (CI). Cumulative curves for cardiac events were obtained using the Kaplan-Meier method. PIIINP concentrations were adjusted for age, baseline LVEF, gender, hypertension, and body mass index p ≤ 0.05 was considered to indicate statistical significance. SPSS software  was utilized to analyze data.Multivariate association between LVEDP and the other parameters was determined by stepwise multiple linear regressions with variables that reached significance  were analyzed. Fifty-one patients had normal LVEDP (<16 mmHg): 60 had intermediate LVEDP (between 16 and 30 mmHg), and 57 had high LVEDP (> 30 mmHg). The three groups resembled each other in age, male gender, heart rate, mean blood pressure, Killip class III or IV, hyperlipidemia, diabetes mellitus, and hypertension. Notably, group C contained a significantly higher percentage of patients with CAD than did in group A and B. The patients took the following medications; 145, antiplatelet agents; 83, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers; 133, beta-adrenoreceptor blockers; 76, statin. Ninety-three patients received coronary revascularization on initial management for ACS.Comparing the patients with high LVEDP (Group C) with those in group A or group B revealed that they significantly differed in LA volume index, E/A ratio, a′, and eas index.Patients with ACS in all three groups exhibit the same degree of LVEDVI, LVESVI, LV mass index, LVEF and MPI. Moreover, these patients in the three groups exhibited comparable E, A, IVRT, s′, e′, a′ and E/e′ ratio values across the three groups.µg/L) exhibited a higher concentration of PIIINP than both group A (4.60 ± 0.75 µg/L) and group B (5.05 ± 0.68 µg/L), and group B exhibited a higher concentration thereof than group A .As present in p <0.001), LAVI  and eas index  were independently related to the other covariates on LVEDP.When LVEDP was the outcome variable, and the presence of CAD, LAVI, E/A ratio, a′, eas index and PIIINP level were covariates. PIIINP concentration (standardized coefficients (r) = 0.373, p = 0.002; LAVI, HR 1.040, 95% CI, 1.005–1.076, p = 0.027). p = 0.007; log-rank test).The mortality and morbidity rates of the patients over 24 months were 19 %. All of the variables that predicted the combined outcome of death and hospitalization based on unadjusted Cox regression analysis (p<0.1) were input a backward multivariate Cox regression analysis. PIIINP and LAVI emerged as independent predictors of outcome for patients with ACS (PIIINP, HR 2.589, 95% CI, 1.404–4.773, This investigation studies the association of LVEDP with clinical manifestations in patients with ACS, and reveals that PIIINP concentration is an independent predictor of LVEDP. The PIIINP concentration also correlates closely with cardiac mortality and hospitalization for revascularization.The pathophysiology that underlies high LVEDP is strongly related to stiffness of the LV chamber During ventricular diastole, the LA is directly exposed to LV pressure through the open mitral valve. LA size is therefore largely governed by the factors that affect diastolic LV filling The transmitral flow pattern and TDI remain the most effective means of routinely measuring systolic and diastolic function and predicting prognosis in patients with heart failure PIIINP is regarded as a circulating collagen biomarker of extracellular matrix remodeling in the heart because elevated PIIINP concentration reflects increased collagen turnover, involving synthesis and deposition, as well as alternating degradation and elimination Numerous studies have claimed that increased PIIINP is related to a restrictive mitral filling pattern and diastolic dysfunction Despite its contributions, this investigation has some limitations. The number of participating patients was still relatively small and a larger patient population should be analyzed to verify the analytic results herein. Additionally, patients with ACS in this cohort study may not be homogeneous comparing with previous studies including the percentage of revascularization as well as administration of beta blockers The evaluation of cardiac fibrosis using PIIINP level may contribute significantly to efforts to evaluate and manage patients with unstable angina, non-ST-elevation or ST-elevation MI. The PIIINP level can be used to distinguish patients with normal LVEDP from those with intermediate or high LVEDP, supporting the importance of LVEDP in the pathophysiological mechanism of cardiac fibrosis in these patients. The PIIINP level also predicts clinical outcome.


The rapid development of interventional procedures for the treatment of arrhythmias in humans, especially the use of catheter ablation techniques, has renewed interest in cardiac anatomy. Although the substrates of atrial fibrillation (AF), its initiation and maintenance, remain to be fully elucidated, catheter ablation in the left atrium (LA) has become a common therapeutic option for patients with this arrhythmia. Using ablation catheters, various isolation lines and focal targets are created, the majority of which are based on gross anatomical, electroanatomical, and myoarchitectual patterns of the left atrial wall. Our aim was therefore to review the gross morphological and architectural features of the LA and their relations to extracardiac structures. The latter have also become relevant because extracardiac complications of AF ablation can occur, due to injuries to the phrenic and vagal plexus nerves, adjacent coronary arteries, or the esophageal wall causing devastating consequences. There continues to be a lack of understanding of the pathogenesis of AF. Current evidence suggests that the pathogenesis of AF is multifactorial, because this arrhythmia may not only accompany a variety of pathological conditions, but also occur in a heart with no known structural abnormality, a condition known as “lone AF” . Recent From a gross anatomical viewpoint, the LA has four components : (1) a vAn anatomic septum in a heart is like a wall that separates adjacent chambers so that its removal would enable us to enter from one chamber to the other without exiting the heart. Thus, the true IAS wall is confined to the flap valve of the oval fossa. The flap valve is hinged from the muscular rim of IAS that, deriving from the septum secundum, is seen from the right atrial aspect of the interatrial wall . At its The major part of the endocardial LA including the septal wall and interatrial groove component is relatively smooth. The left aspect of the interatrial groove, apart from a small crescent-like edge , is almoThe walls of LA are nonuniform in thickness  and in gDetailed dissections of the subendocardial and subepicardial myofibers along the entire thickness of the LA walls have shown a complex architecture of overlapping bands of aligned myocardial bundles , 13 Fig. The terAlthough there are some individual variations, our epicardial dissections of the LA have shown a distinctive pattern of arrangement of the myocardial fibers . On the The epicardial fibers of the superior wall are composed of longitudinal or oblique fibers, (named by Papez as the “septopulmonary bundle” in 1920)  Figures that ariOn the subendocardial aspect of LA, most specimens showed a common pattern of general architecture. The dominant fibers in the anterior wall were those originating from a bundle described by Papez as the septoatrial bundle . The fibAtrial fibrillation is the most common sustained cardiac arrhythmia and is characterized by uncoordinated contraction of the atrium. It is still unclear whether the initiation and maintenance of human AF depends on automatic focal or reentrant mechanisms. Recent reports have shown the contribution of different atrial regions on the fibrillatory process and to the maintenance of AF, emphasizing the role of structural discontinuities and heterogeneous fiber orientation favoring anatomic reentry or anchoring rotors , 16. TheAlthough different mechanisms of AF exist, it is well established that the myocardial sleeves of the PVs, especially the superior veins, are crucial sources of triggers that initiate AF . CardiacNormal PVs anatomy consists of two right-sided and two left-sided PVs with separate ostia Figures  and 3. HThe presence of atrial myocardial tissue extending over the wall of the PVs has been confirmed both macroscopically and histologically by many investigators –31. In mSeveral studies have been designed to investigate and to compare the pathology of the PVs in patients with and without AF , 31. AltThe left lateral ridge (LLR) between the orifices of the left PVs and the mouth of the LAA is the most relevant structural prominence of the endocardial LA  Figures, and 8. Within the LLR, the oblique vein of Marshall runs, together with abundant autonomic nerve bundles  and a smLinear ablation connecting the inferior margin of the ostium of the left inferior PV and the mitral annulus, particularly when complete linear block is achieved, appears to increase the success rate of catheter ablation in patients with persistent or long-standing/permanent atrial fibrillation and prevent macroreentry around the mitral annulus or the left PVs . AlthougAdditional linear ablation lesions are created to improve the outcomes of PV isolation during AF ablation. In their study Cho et al.  using muThe LAA appears to be responsible for triggering AF in 27% of patients presenting for repeat procedures of catheter ablation . The LAAIn autopsy specimens and imaging studies, the LAA ostium is usually elliptical or round and in elliptical-shaped variant and its long axis is obliquely orientated relative to the mitral annulus , 53. TheIn some specimens (28%), muscular trabeculations can be found extending inferiorly from the appendage to the vestibule of the mitral valve . These eDue to the close proximity of the esophagus to the posterior wall of the LA, ablation procedures involving this region of the LA may cause esophageal damage and result in the formation of an atrial esophageal fistula  Figure . In an aThermal injury may involve the periesophageal vagal nerves, resulting in acute pyloric spasm and gastric hypomotility . The vagThe phrenic nerves lie along the lateral mediastinum and run from the thoracic inlet to the diaphragm . PhrenicThe intrinsic cardiac nervous system (ICNS) is a crucial regulator of heart rate, atrial and ventricular refractoriness, contractility, and coronary blood flow. Morphologically, the ICNS forms a neural ganglionated plexus that may be subdivided into epicardial and myocardial subplexuses. Several studies indicate that the ICNS is a complex of distinct subplexuses and that the cardiac ganglia are mainly distributed on (1) the superior surface of the right atrium, (2) the superior surface of the left atrium, (3) the posterior surface of the right atrium, (4) the posterior medial surface of the left atrium , and (5) the inferior and lateral aspect of the posterior left atrium and left PVs , 64. PosCatheter ablation has been shown to be an increasingly important therapeutic option for patients with paroxysmal, persistent, and chronic AF. Ablation techniques have evolved from rather limited initial approaches to quite extensive atrial interventions. The LA has a distinctive atrial appendage and an atrial body that comprises component parts that blend into one another. The patterns of general myocardial arrangement in the left atrial wall and the presence of interatrial muscle bundles may provide some anatomic background to atrial and interatrial conduction. Understanding the structure of the component parts and their relationship to one another and to other cardiac structures is relevant to interventional procedures inside and outside of the LA.


Myocardial infarction (MI) causes contractile dysfunction in the affected tissue, which can be assessed by using DENSE (Displacement ENcoding with Stimulated Echoes) to quantify myocardial strain,2. The a50 male patients (age 56 ± 10 years) underwent CMR on a 1.5T Siemens Avanto within 7 days of MI, and 47 returned for a follow-up scan after 6 months. The protocol included cine, DENSE (2D) and late gadolinium enhancement (LGE) imaging. Cine images were used to assess cardiac function by calculating LV ejection fraction (LVEF) and end-systolic volume (LVESV). DENSE and LGE were compared using a single mid-ventricular short-axis slice, which was analysed both as a whole slice and after division into 6 AHA segments. The percentage of each segment which contained LGE was calculated using a threshold of mean+5SD of remote myocardium intensity. DENSE images were analysed to obtain a value for peak circumferential strain (Ecc). Segments in the baseline scans were grouped according to the extent of LGE , and the change in peak Ecc between baseline and follow-up was evaluated using a one-way ANOVA with Tukey's post-hoc test. Individual patients were compared directly, and the correlations between change in strain and (i) change in LGE (segments) and (ii) change in cardiac function (slices) were assessed.Diagnostic images were obtained for 50 patients at baseline, and for 43 patients at follow-up. The results of the group comparisons and the individual patient comparisons are illustrated in Figure Strain recovery was disclosed by DENSE in infarcted tissue at 6 months post-MI. An increase in peak Ecc at follow-up is associated with a reduction in LGE, and improvement in LVEF and LVESV. Further work is required to take infarction in adjacent segments and slices into account, as this may provide a more precise insight into the relationship between myocardial strain, LGE and cardiac function.N/A.


Due to the imaging findings, an infiltrative cardiomyopathy, such as cardiac amyloidosis, was suspected. However, amyloid accumulation was excluded by endomyocardial biopsy, which revealed the presence of diffuse myocardial fibrosis in an advanced hypertensive heart disease.Left ventricular (LV) hypertrophy can be related to a multitude of cardiac disorders, such as hypertrophic cardiomyopathy (HCM), cardiac amyloidosis, and hypertensive heart disease. Although the presence of LV hypertrophy is generally associated with poorer cardiac outcomes, the early differentiation between these pathologies is crucial due to the presence of specific treatment options. The diagnostic process with LV hypertrophy requires the integration of clinical evaluation, electrocardiography (ECG), echocardiography, biochemical markers, and if required CMR and endomyocardial biopsy in order to reach the correct diagnosis. Here, we present a case of a patient with severe LV hypertrophy (septal wall thickness of 23 mm, LV mass of 264 g, and LV mass index of 147 g/m Increased left ventricular (LV) wall thickness, referred to as LV hypertrophy, is a powerful predictor of cardiovascular morbidity and mortality . LV hypeAmyloidosis is characterized by the extracellular deposition of amyloid, as a result of misfolding of a precursor protein, the most common of which are light chains, transthyretin, and serum amyloid A . CardiacIn clinical routine, the diagnostic workup of patients with LV hypertrophy is important due to specific therapeutic strategies aiming at the different disease etiologies. Here, we present a case where the presence of cardiac amyloidosis was suspected based on cardiac imaging findings. However, endomyocardial biopsy revealed an unexpected diagnosis.A 56-year-old male patient was referred to our department due to exertional dyspnea and gradual decrease of his exercise tolerance within the last 6 months. The patient had no history of cardiac diseases and no history of arterial hypertension, hyperlipidemia, and diabetes mellitus. Physical examination revealed normal heart sounds, no murmurs, and mild peripheral edema with clear lung fields. Blood pressure was elevated at 180/90 mmHg with normal pulse of 58 bpm. An ECG suggested a sinus rhythm without signs of myocardial ischemia or low QRS voltage but negative T-waves in V4–V6. Echocardiography, on the other hand, revealed the presence of severe LV hypertrophy Figures  with sep2), small pericardial effusion, and impaired longitudinal wall motion with an ejection fraction of 54%  was subsequently performed. CMR confirmed the presence of severe LV hypertrophy  comparable to the initial findings.The morphological findings and clinical features of LV hypertrophy may be similar to disorders, such as HCM, amyloidosis, and hypertensive heart disease, so misdiagnosis can frequently occur. Our case demonstrates the presence of severe LV hypertrophy, small pericardial effusion, and late gadolinium enhancement by CMR, so infiltrative disease, such as cardiac amyloidosis, was suspected. However, myocardial biopsy revealed the presence of hypertensive heart disease, which could be effectively treated using a combination of antihypertensive drug therapies.Clinical presentation of patients with LV hypertrophy may differ between absence of clinical signs upon presentation and life-threatening arrhythmias or symptomatic congestive heart failure. Although the 12-lead ECG may be helpful for the identification of HCM , such paTo date, several imaging methods are available for the diagnostic workup of patients with myocardial hypertrophy. Echocardiography represents the first-line imaging modality for the evaluation of LV hypertrophy, allowing the assessment of LV wall thickness, end-diastolic and end-systolic volumes, and LV mass. In addition, the assessment of diastolic function, myocardial strain, and strain rate by echocardiography can add incremental value for the differentiation between cardiac amyloidosis and other myocardial disorders causing LV hypertrophy , 13. DesCMR, on the other hand, exhibits higher spatial resolution than echocardiography, and its versatility allows for the assessment of ventricular thickness and mass, myocardial function (ejection fraction), perfusion, and if required myocardial deformation and viability  by LGE within a single examination and without radiation exposure for the patients .A number of previous studies investigated the ability of CMR to differentiate patients with LV hypertrophy due to HCM, amyloidosis, and hypertensive heart disease. Thus, Sipola et al.  suggesten = 4) and midwall (n = 2) nonischemic LGE in 6 of 11 patients with hypertensive heart disease, predominantly in septal and inferior regions [The presence of LGE with hypertensive heart disease, on the other hand, is rated differently in the current literature. Thus, LGE was seen in 14 of 43 patients with HCM but in none of 39 patients with hypertensive heart disease . In the  regions . Convers regions –23. In oWith hypertensive heart disease, on the other hand, left ventricular hypertrophy results from chronic pressure overload due to systemic hypertension. In the absence of antihypertensive treatment, diastolic dysfunction occurs, which may lead to heart failure symptoms. During later stages of the disease, subendocardial interstitial fibrosis is increasing, compromising myocardial contractility and ultimately causing systolic LV dysfunction , 25. DesFinally, from a technical point of view, T1 mapping may have further helped in differentiating between amyloidosis, hypertrophic cardiomyopathy, and hypertensive heart disease in our case but was unfortunately not yet implemented with our scanner at the time of the study , 26.In conclusion, the diagnostic process with LV hypertrophy requires the integration of clinical evaluation, electrocardiography, echocardiography, and if required CMR, biochemical and serological markers, and endomyocardial biopsy. Although the latest improvements with noninvasive diagnostic techniques have reduced the need for biopsy, in our case, endomyocardial biopsy excluded cardiac amyloidosis, as suspected by CMR, and revealed the presence of hypertensive heart disease.


Single-phase cardiac MRI acquires data only during a brief period of the cardiac cycle. To avoid motion artifacts, the operator must select a trigger delay that corresponds to a period of minimal cardiac motion, typically at end-systole or mid-diastole. This can be done by inspecting a prior cine scan for quiescent periods. However, because these cardiac phases can vary in temporal position and duration as a function of heart rate, another option should be available if the heart rate at the time of the single-phase scan differs from that during the cine scan. The goal of this work was to analytically determine the optimal trigger delays for cardiac MRI.An electromechanical analysis of Wiggers diagram was used to determine the trigger delays (time after R-wave) at which systolic and diastolic quiescence begin Figure .sys should occur at 5/6 (83%) of LVET. From Figure sys = IVC + 0.83*LVET, where LVET = QS2 - QonsetRpeak - IVC. Using the substitutions IVC = 40 ms [onsetRpeak = 40 ms [sys = 423 - 1.826*HR (where HR is heart rate in beats per minute).End-systolic quiescence occurs during isovolumic relaxation, but due to the averaging effect of the data acquisition window, reduced heart motion appears slightly earlier. Also, because 20% of the stroke volume is ejected during the last 1/3 of the LV ejection time (LVET) [dias begins 50 ms prior to the end of rapid filling (Trapid). From Figure dias = QS2 - QonsetRpeak + IVR + Trapid - 50. Using the above substitutions with IVR = 80 ms [rapid = 313 - 0.957*HR [dias= 894 - 3.157*HR. These models were compared with ECG-gated short-axis cine scans from 87 adult patients that were retrospectively studied to identify the systolic and diastolic trigger delays at which minimal heart motion began. To assess the efficacy of the equations in a clinical population, only patients with significant akinesis or dyskinesis were excluded. Tdias was recorded only for patients exhibiting discernible periods of diastasis.End-diastolic quiescence occurs during diastasis, but for MRI scans, sufficiently reduced motion can begin 50 ms earlier [ = 80 ms  and TrapFigure Although previous studies have presented general quantitative relationships between various heart phases and heart rate, this work derives recommended trigger delays specifically for use with single-phase cardiac MRI. The models demonstrate good agreement with clinical results and can be valuable for automatically selecting optimal trigger delays when the heart rate varies during an exam or when no reference images are available.N/A


VNS) is an already FDA‐approved therapy for drug‐resistant epilepsy and depression, and has been shown to normalize autonomic function and improve objective measures of heart function and subjective measures of heart failure symptoms. However, it remains unclear whether VNS may induce negative effects in patients with potentially healthy hearts where VNS can be used for epileptic patients. Hence, this study aims to investigate the effects of VNS on the hearts of healthy rats with normal autonomic balance. Sprague–Dawley rats were implanted with stimulators and randomized to either Sham or VNS groups. Rats in VNS group received 10 weeks of chronic intermittent VNS via stimulation of the right cervical vagus nerve. Echocardiography was performed at Baseline (prior to VNS), Week 2, and Week 9. After 10 weeks, high‐resolution optical mapping was performed in ex vivo perfused hearts to evaluate the electrophysiological remodeling that occurs in the heart as a result of the VNS therapy. Chronic VNS modified the electrophysiological properties of healthy rat hearts by reducing the action potential duration at 50% (APD50) and 80% (APD80) repolarization. Chronic VNS also affected the restitution properties of the heart at the APD50 level and increased myocardial conduction velocity (CV). VNS did not induce any significant changes to ventricular ejection fraction (EF) and spatial dispersion of APD, thus indicating that VNS did not negatively affect cardiac function. VNS also reduced the susceptibility to ventricular arrhythmias (ventricular fibrillation [VF] and ventricular tachycardia [VT]) during ex vivo programmed electrical stimulation. In summary, chronic application of cyclic VNS induces changes to the electrophysiological properties of healthy rat hearts. The observed decrease in APD and increase in CV suggest that the beneficial effects of VNS do not require the presence of existing autonomic imbalance.Cardiovascular disease degrades the regulatory function of the autonomic nervous system. Cyclic vagus nerve stimulation ( Vagus nerve stimulation (VNS) is an approved clinical therapy for drug‐refractory epilepsy and depression, and more than 130,000 VNS therapy systems have been implanted since 1995 Shuchman . In the The autonomic nervous system consists of two distinct branches: the parasympathetic and sympathetic nervous systems. The balance between the two systems plays a significant role in regulating cardiovascular functions and specifically, the coordination of the electromechanical function of the heart, leading to optimized cardiac output under a variety of environmental and metabolic stressors. Heart diseases such as chronic heart failure (HF) and hypertension (HTN) are associated with autonomic dysregulation characterized by a sustained increase in sympathetic drive and withdrawal of parasympathetic activity  and atrioventricular (AV) nodes, it was initially believed by many that vagal fibers only sparsely innervate the ventricles Coote . HoweverAs a result of this finding, it is important to gain a better understanding and fully characterize how stimulating the vagus nerve may affect the normal heart when the autonomic nervous system is in balance. In addition, as applies to any novel therapy, testing in normal, healthy controls is essential to understanding the mechanisms of action of VNS. Most importantly, it makes it feasible to evaluate any potential negative effects the therapy may have without the interferences of other confounding factors. Moreover, VNS is FDA‐approved to treat epileptic patients; however, the electrophysiological side effects of VNS on their potentially healthy hearts are not well characterized. Hence, the main objective of this novel study is to investigate the effects of chronic, intermittent VNS on the electrophysiological properties of healthy rat hearts.All animal experiments were approved by the University of Minnesota Animal Care and Use Committee and were conducted in accordance with both the Institutional and National Institute of Health Guidelines for the Care and Use of Laboratory Animals.n = 9, 250–300 g, Charles River Laboratories, Wilmington, MA) were randomized into two groups: Sham (n = 6) and VNS (n = 3). Sham group animals were implanted with nonfunctional vagus nerve stimulators, and VNS group animals were implanted with functional vagus nerve stimulators . All animals were maintained and monitored for a total of 10 weeks. Rats were placed in a quiet, temperature‐ and humidity‐controlled room with a 12:12 h light–dark cycle. Food and water were available ad libitum.Male Sprague–Dawley rats  and Sham (n = 2) rats prior to VNS implantation surgery (Baseline), two weeks after surgery (Week 2), and one week prior to killing (Week 9). Anesthesia was induced with 2% isoflurane gas in 100% oxygen, and transthoracic echocardiography  was performed. Echocardiographic M‐mode images of the left ventricle (LV) were obtained using a parasternal short‐axis view at the middle of papillary muscle level. Left ventricular end diastolic (LVEDV) and systolic (LVESV) volumes were measured and used to calculate the percentage of LV ejection fraction (EF), an index of LV function, for each animal using the following equation: EF = ((LVEDV − LVESV)/LVEDV) × 100%.Echocardiography was performed in both VNS (n = 3) and Sham (n = 4) rats were killed and hearts were quickly extracted through a thoracotomy. Immediately upon removal, the hearts were immersed in cold cardioplegic solution . The aorta was then quickly cannulated and perfused (retrograde) with warm (37 ± 1°C) oxygenated Tyrode's solution . The hearts were immersed in a chamber and superfused with the same Tyrode's solution.At the end of 10 weeks, VNS  was added to the perfusate. Two 532 nm diode continuous green lasers  were used to illuminate both the right ventricles (RV) and LV surfaces of the heart. Fluorescence signals from more than 80% of total ventricular surface were captured with two 12‐bit charge‐coupled device (CCD) cameras , that ran synchronously at 600 frames per second with 64 × 64 pixel resolutions. Blebbistatin (10–15 μmol/L) was added to the Tyrode's solution to stop heart contractions and reduce motion artifacts  were applied to the base of the RV at progressively decreasing basic cycle length (BCL) from 200 msec in steps of 20 msec until BCL reached 80 msec or until ventricular tachycardia (VT) or fibrillation (VF) was initiated , and two‐dimensional (2D) APD maps were constructed to reveal the spatial distribution of APDs on the epicardial surface of the heart. Mean APD was obtained at different BCLs by averaging APDs from all pixels.Optical action potential duration was measured at both 50% and 80% repolarization (APDmax) for the spatial regions of 5 × 5 pixels were fitted with the plane, and gradients of activation times gx and gy were calculated for each plane along the x and y axes, respectively. The magnitude of the local CV was calculated for each pixel as (gx2+gy2)−1/2.Local conduction velocity (CV) was calculated as described previously . Statistical comparison of echocardiographic assessment among Baseline, Week 2, and Week 9 were performed using a paired Student's t‐test. Comparison of CV was performed using a paired t‐test. Values of P < 0.05 were considered to be statistically significant.All data are presented as means ± SE. Statistical comparisons of APD, To determine both the in vivo acute and chronic effects of VNS on cardiac performance in the healthy animals, LV function was assessed using echocardiography at both Weeks 2 and 9 after VNS implantation. As presented in Figure 80 and APD50 maps, respectively, obtained at a BCL of 200 msec and 100 msec for both Sham and VNS‐treated rats. The lower panels show corresponding traces of action potentials from a representative single pixel. Figure Ex vivo optical mapping was used to probe action potential conduction and restitution dynamics in order to determine how long‐term intermittent VNS modulates the basic electrophysiological properties of the healthy myocardium. Changes in APD were measured during periodic pacing at gradually decremented BCLs. Figure 50 and APD80) were significantly lower than those of Sham rats. For instance, at BCL 200 msec, the APD80 and APD50 values for Sham rats were 70.69 ± 0.34 msec and 45.39 ± 0.84 msec, respectively. After VNS treatment, the APD80 and APD50 values of VNS rats were both significantly (P < 0.05) reduced to 60.12 ± 2.16 msec and 29.81 ± 1.59 msec, respectively. This APD shortening effect disappeared at lower BCLs (between 100 msec and 80 msec). At BCL 100 msec, the APD80 values for Sham and VNS rats were 63.98 ± 1.82 msec and 61.87 ± 0.22 msec (P = NS), respectively. Furthermore, the APD50 values for Sham and VNS rats were 42.89 ± 1.42 msec and 37.22 ± 0.28 msec (P = NS).The change in APD of all VNS and Sham rats is shown in Figure 80 and APD50) did not monotonically decrease as BCL decreased, in contrast to APDs of Sham rats  showed that the APD of VNS rats .To determine whether VNS affected the spatial dispersion of APD, we calculated the heterogeneity index P < 0.05). Specifically, by 23% for BCL 200 msec (from 0.676 ± 0.024 m/sec to 0.830 ± 0.039 m/sec) and by 31% for BCL 100 msec (from 0.604 ± 0.026 m/sec to 0.792 ± 0.045 m/sec).To investigate the effect of VNS on action potential propagation in the ventricular myocardium surfaces, we constructed activation time maps for both Sham and VNS groups at various BCLs. Representative examples of 2D activation time maps at BCL 100 msec is shown in Figure The anti‐arrhythmic effects of VNS on healthy hearts were assessed by measuring the inducibility of the hearts to cardiac arrhythmias during ex vivo programmed electrical stimulation. As shown in Figure μ); (3) VNS significantly affected the restitution properties of the heart at the APD50, but not at the APD80, levels; (4) VNS had anti‐arrhythmic effects that has been previously only reported for diseased hearts  10 weeks of intermittent VNS produced beneficial electrophysiological changes to the heart, including reduction of APD at larger BCLs and an increase of CV at all BCLs; (2) VNS did not induce any detrimental effects to the heart: neither affecting the LV function of the heart verified via echocardiography nor increasing the spatial dispersion of APD  channels  and sodium–calcium exchanger (NCX1) protein expressions in a chronic HF rat model  induces electrophysiological changes to a normal, healthy rat heart; thus, rendering the hearts less vulnerable to inducible arrhythmias. These results also suggest that VNS does not require the existence of autonomic imbalance to generate its positive effects.While we were able to demonstrate the effects of VNS on the electrophysiological properties of the healthy myocardium, no histochemical results from the ventricles were performed in parallel to confirm and/or investigate mechanisms. Another limitation is that an animal group with age‐matched controls, that is, that did not have an implanted stimulator and electrode, was not included in this study. However, since the objective of our study was to directly investigate the effects of VNS, we removed the confounding factor of surgical procedure effects on electrophysiology by implanting nonfunctional stimulators in our Sham group. Hence, not including such a control group will not affect the interpretation of our results. The conclusions of our study are also limited by the small sample size of rats used.Drs. Imad Libbus and Bruce H. KenKnight are employees of Cyberonics Inc.


Aortic stenosis is characterized by impaired myocardial perfusion reserve due to coronary microvascular dysfunction. T1 mapping is sensitive to myocardial water content of both intra- and extracellular in origin, but the effect of intravascular compartment changes on T1 has never been assessed previously. We aimed to assess the effect of adenosine-induced vasodilatation on native (pre-contrast) T1 values in patients with severe aortic stenosis (AS) before and after aortic valve replacement (AVR).42 subjects (26 patients with severe AS without obstructive coronary artery disease and 16 controls) underwent cardiovascular magnetic resonance at 3T for native T1-mapping (ShMOLLI), first-pass perfusion  at rest and during adenosine stress, and late gadolinium enhancement (LGE).AS patients had increased resting myocardial T1 , reduced MPRI , and increased left ventricular mass index (LVMI) and LGE volume compared to controls (Table Our findings suggest that intravascular compartment is a significant contributor to myocardial T1 relaxation time. Vasodilator stress T1 mapping may be a potential technique to assess coronary reserve without the need for contrast administration. Performing T1 mapping soon after vasodilator stress may affect ECV measurements given that hyperemia alone substantially alters T1 values.N/A.


Right ventricular (RV) structure and function serve as important indicators of a wide spectrum of heart diseases such as congenital heart disease, pulmonary hypertension, hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy/disease (ARVC/D) –3. Over The study is certainly very interesting in the sense that the right ventricle in normal subjects does not always appear normal when visualised by CMR. Especially, regional wall motion abnormalities are predominantly seen in the apico-lateral segments. However, the study warrants the following three comments. First, also acknowledged by the authors, the study was based on a small patient population. As a result, the description of normal variations in RV morphology as observed by CMR are not necessarily absolute and should only be regarded as hypothesis-generating for studying larger patient samples. Second, according to the authors, there is supposedly no in-depth knowledge on RV motion in healthy subjects. This is an obvious understatement as already in 2004 Pennell’s group  showed that CMR demonstrated good inter-study reproducibility for RV function parameters in 20 healthy subjects, in 20 patients with heart failure, and in 20 patients with hypertrophy, suggesting that CMR is reliable for serial RV assessment . In 2008To summarise, despite the above-mentioned critical comments, the study by Quick et al.  is a val


The ATP12A gene encodes a catalytic subunit of an ATPase that can function as a Na+/K+ pump. We, therefore, investigated the association between LV function and common genetic variants in ATP12A.Left ventricular (LV) function depends on the activity of transmembrane electrolyte transporters. Failing human myocardium has lower NaATP12A. In our analysis we focused on rs10507337 because it is located within a transcription factor binding site.A random sample of 1166 participants  was recruited in Belgium, Poland, Italy and Russia. We measured transmitral early and late diastolic velocities (E and A) by pulsed wave Doppler, and mitral annular velocities (e’ and a’) by tissue Doppler. Using principal component analysis, we summarized 7 Doppler indexes – namely, E, A, e’ and a’ velocities, and their ratios  – into a single diastolic score. We genotyped 5 tag SNPs  in P = 0.003), e’ (P = 5.8×10−5), e’/a’ (P = 0.003) and diastolic score (P = 0.0001) compared to TT homozygotes. Our findings were confirmed in the haplotype analysis and in the family-based analyses in 74 informative offspring.In the population-based analyses while adjusting for covariables and accounting for family clusters and country, rs10507337 C allele carriers had significantly higher E/A  contains supplementary material, which is available to authorized users. Left ventricular (LV) diastolic dysfunction refers to a condition in which abnormalities in LV function are present during diastole and is characterized by impaired relaxation and/or filling of the heart. LV diastolic dysfunction is associated with common risk factors such as hypertension and it can progress to symptomatic heart failure . The pre+) is increased in failing cardiomyoctes as compared to normal myocardium. The possible cause for this observation might be related to changes in Na+/K+ ATPase expression and/or function [+/K+-ATPase [ATP12A belongs to the family of P-type cation transport ATPases that can function as Na+/K+ ATPase in human cells [ATP12A might influence myocardial Na+ handling and consequently myocardial function. We recently genotyped top SNPs that might be associated with cardiovascular phenotypes and that have been identified in a recent genome-wide association study [ATP12A were genotyped. Therefore, in the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO) and the European Project On Genes in Hypertension (EPOGH) we investigated whether echocardiographic variables reflecting LV diastolic function are associated with common genetic variants in ATP12A.Cardiomyocyte contraction and relaxation depend on the balance of electrolytes  across the cellular membranes ,12. The function ,12. Amon+-ATPase ,16, ATP1an cells . Taking on study . Among tFrom August 1985 until December 2005, we randomly recruited a family-based population sample (the FLEMENGHO cohort) from a geographically defined area in northern Belgium as described in previous publications . EPOGH rn = 217), atrial fibrillation (n = 1) or because LV diastolic Doppler indexes could not be reliably measured (n = 5). Thus, 1166 subjects were analyzed including 777 FLEMENGHO participants  and 389 EPOGH participants from Krakow, Poland (n = 143), Mirano, Italy (n = 109) and Novosibirsk, Russia (n = 137).In the FLEMENGHO study, from May 2005 until January 2010, we invited 1055 former participants from a previously identified random population for a follow-up examination at the field centre, including echocardiography. Of those, 828 renewed their written consent. In the EPOGH study, from January 2007 until September 2009, we invited 631 former participants for an examination including echocardiography. Of those, 561 gave their consent in writing. We excluded 223 subjects from analysis, because DNA was missing or of bad quality  interfaced with a 2.5- 3.5 MHz phased-array probe, according to a standardized protocol as published elsewhere . With thUsing TDI, the observer recorded low-velocity, high-intensity myocardial velocity at a high frame rate (>190 FPS), while adjusting the imaging angle to ensure parallel alignment of the ultrasound beam with the myocardial segment of interest. From the apical window, a 5 mm Doppler sample was placed at the septal, lateral, inferior and posterior sites of the mitral annulus to obtain the pulsed wave TDI velocities.All echocardiographic recordings included at least 5 cardiac cycles and were digitally stored for off-line analysis. One experienced observer (TK) analyzed the digitally stored images from all centers, using the EchoPac software, version 4.0.4 , selecting and averaging 3 cardiac cycles obtained at the end-expiration. The observer was blinded to the genetic results. LV internal diameter and interventricular septal and posterior wall thickness were measured at end-diastole from the 2 dimensionally guided M-mode tracing according to the guidelines. When optimal orientation of M-mode ultrasound beam could not be obtained (in approximately 5% of echocardiographic recordings), the reader performed linear measurements on correctly oriented two-dimensional images. End-diastolic left ventricular dimensions were used to calculate LV mass by an anatomically validated formula. LV mass was indexed to body surface area (BSA). LV end-systolic and end-diastolic volumes were measured off-line using the standard biplane Simpson’s method.We assessed LV diastolic function using recordings of conventional blood flow and tissue Doppler velocities. Pulsed-wave Doppler signals of transmitral blood flow were used to measure peak early (E) and late (A) diastolic velocities. From the pulsed wave TDI recordings, we measured the early (e’) and late (a’) peak diastolic velocities of the mitral annulus displacement, and the e’/a’ ratio at the 4 acquisition sites. We calculated the E/e’ ratio by dividing transmitral E peak by e’ averaged from the 4 acquisition sites. As reported previously , the intWe administered a standardized questionnaire to collect detailed information on subjects’ medical history, smoking and drinking habits, and intake of medications. The conventional blood pressure was the average of five consecutive auscultatory readings obtained with the subject in the seated position. Hypertension was defined as a blood pressure of at least 140 mm Hg systolic or 90 mm Hg diastolic or as use of antihypertensive drugs. Body mass index was weight in kilograms divided by the square of height in meters.ATP12A SNPs we used 15 K Illumina Infinium custom chip , designed for the HYPERGENES project [ATP12A gene lies within chromosome 13q12.1-q12.3 (http://www.ncbi.nlm.nih.gov/gene/479) and spans approximately 32 kb. It contains 23 exons and 22 introns [We extracted DNA from white blood cells. For genotyping of  project  to cover introns . The sel2 test, respectively. We tested minimum allele frequency, proportion of missing genotypes and Hardy-Weinberg equilibrium using JMP Genomics, version 6.1 . We reconstructed haplotypes using the PROC HAPLOTYPE procedure implemented in the genetics module of the SAS software.For database management and statistical analysis, we used SAS software, version 9.3 . We compared means and proportions by the z test and by the χP value for variables to enter and stay in the regression models at 0.10.The diastolic Doppler velocities are measured using similar technique (Doppler) and are highly intra-correlated. Therefore, some redundancy in the cumulative variance of the Doppler velocities exists. This redundancy can be decreased by a mathematical procedure, the principal component analysis. This thechnique enables summarization of intra-correlated variables into an artificial score that carries information from all the contributing variables. Individual values of the artificial score are calculated by summarization of optimally weighted values of the contributing measured indexes. We, therefore, summarized transmitral E and A blood flow velocities, averaged TDI e’ and a’ mitral annulus velocities and their ratios  into a single composite diastolic score. Normality of diastolic score distribution was evaluated by Shapiro-Wilk’s statistic and skewness by computation of the coefficient of skewness. The association between the composite diastolic score and velocities was described using factors loadings. We performed stepwise linear regression to identify correlates of the composite diastolic score with sex, age, height, weight, body mass index, heart rate, systolic and diastolic blood pressures, left ventricular mass index, and ejection fraction. We set the P-values corrected for multiple testing using the Bonferroni method.First, we performed the association analyses of dependent variables (LV phenotypes) with the genotypes or haplotypes of interest by use of a mixed model in each examination center. Covariables with known relevance for LV structure and function  were incet al. [http://www.sph.umich.edu/csg/abecasis/QTDT). In this model the between-family component is sensitive to population structure whereas the within-family component is significant in the presence of transmission disequilibrium.We performed the transmission disequilibrium test for quantitative traits (QTDT). We evaluated the within- and between-family components of phenotypic variance using the orthogonal model as implemented by Abecasis et al.  in the QTable ATP12A SNPs. In our analyses we focused on rs10507337 because it is located within a transcription factor binding site and, therefore, it might influence the ATP12A gene expression. The r2 reflecting linkage disequilibrium between rs10507337 and rs12872010 was 0.83. On the other hand, we observed no correlation between rs10507337 and three other ATP12A SNPs, rs963984, rs9553395 and rs2071490, with the r2 values ranged from 0.008 to 0.245, respectively. The genotype frequencies of rs10507337 complied with Hardy-Weinberg equilibrium (P = 0.97). Center specific and cumulative rs10507337 genotype distributions are listed in Table Additional file ATP12A  had higher values of the composite score. In stepwise multiple regression, the composite diastolic score significantly and independently decreased with age, body mass index, heart rate, diastolic blood pressure and left ventricular mass index , transmitral E/A (P = 0.003), TDI e’/a’ (P = 0.003) and composite diastolic score (P = 0.0001). The heterogeneity tests (P = 0.04) suggested that there was borderline but significant heterogeneity among the centers for peaks E and e’ , e’/a’ ratio and composite diastolic score (Table P > 0.40). Haplotype analysis further confirmed that in all subjects combined, composite diastolic score  higher in carriers of rs12872010 T allele compared to non-carriers  included 749 founders and 417 offspring from 357 families. In our family-based analyses we used 74 informative offspring belonging to 35 families . The number of offspring per informative family amounted to one in 10 families, two in 17 families, three in 4 families, and more than three in 4 families. We adjusted the QTDT analyses as described in the previous section. For LV diastolic function indexes in relation to rs10507337 genotypes, the orthogonal model did not demonstrate population stratification (P ≥ 0.08). Transmitral E/A, TDI e’ , TDI e’/a’ and composite diastolic score significantly increased with transmission of at least one C allele to offspring  for E/A, 1.19 cm/s  for e’, 0.26  for e’/a’ and 0.62  for composite score , we found also the significant associations between this haplotype and LV diastolic function indexes. The family-based analyses included only 74 informative offspring but nevertheless confirmed that transmission of at least one C allele to offspring was associated with higher transmitral and tissue Doppler velocities during early diastole and composite diastolic score. On the contrary, we did not observe any association of the genetic variants in ATP12A and other LV phenotypes including LV mass index and ejection fraction.The main finding of the present study was that LV diastolic function as assessed by conventional and tissue Doppler indexes was associated with genetic variation in the The gold standard for assessing diastolic function remains the pressure-volume relationship, but this requires an invasive approach. Doppler measurements of mitral inflow and the TDI technique open up the possibility of evaluating non-invasively diastolic function . In our ATP12A gene. So far, only a whole DNA array survey in spontaneously hypertensive rats identified the ATP12A gene among probable candidate genes for hypertension [et al. [ATP12A expression might contribute to development of hypertension in spontaneously hypertensive rats. There is a high level of structural similarity (up to 86%) in the ATP12A gene between humans and rodents [ATP12A gene product is a catalytic alpha (ATP12Aα) subunit of an ATP dependent transmembrane electrolyte pump family (X+-K+-ATPases) [http://www.genecards.org/cgi-bin/carddisp.pl?gene=ATP12A). Functional X+-K+-ATPases are heterodimers, composed of alpha and beta subunits. Alpha subunits of ATPases have catalytic and ion-binding properties [+-K+-pump [+-K+-ATPases [To our knowledge, no previous study reported the association of cardiovascular phenotypes with the rtension . Kinoshi [et al.  demonstr rodents . The ATPATPases) ,19 whichoperties . Previou-K+-pump ,23. More-ATPases .+ concentration due to changes of Na+-K+-ATPase expression and activity, might lead to important changes of Ca2+ extrusion, a process central for myocardial contractility and relaxation [et al. [+-K+-ATPase concentration and, a consequence, had elevated intracellular Na+ levels [+-K+-ATPase activity and leads to elevated intracellular Na+ concentration [Small perturbations in Nalaxation ,12. Schw [et al. ,26 demon+ levels . Moreoventration .+-K+-ATPase in electrolyte homeostasis makes ATP12A a possible candidate gene that might modify cardiac function. In our study, we investigated the genetic variation which is located in a transcription factor binding site of the ATP12A promoter area. Several transcription factors can bind this promoter region including CTCF (CCCTC-binding factor) and NF-kB that both act in NF-kB cascade [+-K+-ATPase.Involvement of Na cascade . Of noti cascade . TherefoATP12A promoter area had significantly higher transmitral and tissue Doppler velocities during early diastole and, therefore, demonstrated an enhanced early myocardial relaxation compared to overall population mean. Overall, these findings might be indicative of the functional importance of the described genetic variation in ATP12A. However, we do not know whether rs10507337 C allele is associated with increased or decreased expression of the ATP12A gene. The precise mechanisms underlying the association of LV diastolic function with ATP12A remain to be elucidated.In our study we observed that subjects with minor C allele in the Our echocardiographic estimation of diastolic function included measurement of diastolic blood flow  and mitral annular movement , and calculation of several ratios . Since each of these Doppler indexes represents a somewhat distinct feature of diastolic function, none of them is sufficient to stand alone . On the The present study must be interpreted within the context of its limitations and strengths. All participants were white Europeans. Thus, the association cannot be generalized to other ethnic or racial groups. Transmitral and TDI diastolic velocities are quantitative echocardiographic traits that arise from complex interaction between multiple genes, hemodynamic, and environmental factors and are prone to measurement error. For the present study, one experienced observer in each center performed all echocardiographic examinations. Digitally stored images were post-processed centrally by one observer with high reproducibility . There wATP12A promoter. We observed that carriers of rs10507337 C allele or CCTTC haplotype had better pattern of myocardial relaxation as compared to non-carriers. Further studies are necessary to clarify the functional significance of this genetic variation.Left ventricular diastolic function as assessed by conventional and tissue Doppler indexes was associated with genetic variation in the