To evaluate the left ventricular (LV) longitudinal function changes in rabbits after acute occlusion of the left anterior descending artery (LAD) by two-dimensional speckle tracking imaging (2D–STI).Forty-eight New Zealand white rabbits underwent echocardiography examination. EchoPAC was used to measure LV peak systolic longitudinal strain (LS) of the endocardium, middle myocardium, and epicardium, peak longitudinal strain rate (LSr), segmental and global longitudinal rotation (LR) degrees. Ligated the LAD and repeated all measurements after 10 min.P < 0.05). In apical four-chamber view, there was significant difference in the degrees of rotation of the LV lateral wall in preoperative and postoperative rabbits (P < 0.05). In apical three-chamber view, the rotation degrees of the posterior wall and the LR were significantly lower in the postoperative than in the preoperative (P < 0.001). In apical two-chamber view, the rotation degrees of the inferior wall and the LR were significantly lower in the postoperative (P < 0.05).Peak LS and LSr were significantly different between the preoperative and postoperative rabbits among most LV walls  contains supplementary material, which is available to authorized users. Acute myocardial ischemia (AMI) is commonly associated with heart disease and frequently manifests in the clinic as pericardial discomfort, or chest pain. Diagnosis of AMI is an important factor in the determination of patient prognosis; however, in cases of AMI without myocardial infarction, echocardiogram examination cannot reveal the abnormal segmental wall activity. Coronary angiography is the most commonly used and accurate technique for atherosclerosis diagnosis, but it is invasive and expensive.Two-dimensional speckle tracking imaging (2D–STI) is a relatively new method of angle-independent quantification of left ventricular (LV) strain, strain rate and LV twist –4. The tA normal myocardium consists of endocardium, middle myocardium, and epicardium fibers. Current 2D–STI researches on the myocardial function has primarily focus on the global systolic and/or diastolic function, the torsion and torsion velocity changes between the apex and the base of the heart –12. Few Therefore, the first aim of our research was the measure LV peak systolic longitudinal strain (LS) of the endocardium, middle myocardium, and epicardium, peak longitudinal strain rate (LSr). Second, we phrased a specific hypothesis which is there have global LR in the LV of rabbits. In this study, we sought to investigate whether LR occurs and evaluated early longitudinal function changes in the LV of rabbits after AMI.This study conformed to the Guide for the Care and Use of Laboratory Animals and was approved by the Ethics Committee of Changzhou No.2 People’s Hospital Institutional Animal Care and Use Committee. The methods carried out in the experiment were in accordance with the approved guidelines. The ARRIVE guidelines , weighing 1.5–2.0 kg, were provided by the Experimental Animal Center of NanJing Medical University, China. All rabbits were lived in an alone cage, that the dimensions were 80 cm for length, 60 cm for width and 60 cm for height. Every day we feed them 3–4 times, and washed the cages 2 times . All of the rabbits were healthy, and all of them had not examined or treated by veterinarians before or during the research procedures. All rabbits were anesthetized with pentobarbital , and ECG leads were connected to each subject. Thoracotomy was performed to expose the heart, and a suture was used to occlude the left anterior descending coronary artery (LAD) for 10 min, following the procedure we just used the Lidocaine to reduce the pain. We used Lidocaine just before thoracotomy and begin to closed thorax. We had taken the subcutaneous injection method. In general, every rabbit used a piece of Lidocaine (5 ml: 0.1 g). Afterwards, the thorax was closed and the rabbits were monitored by ECG to confirm ST segment changes and the establishment of the acute myocardial infarction model.Conventional echocardiography was performed on forty-eight New Zealand white rabbits using the GE Vivid7 Dimension ultrasound machine. Preoperative and postoperative LV end-systolic volume (LVESV), end-diastolic volume (LVEDV), stroke volume (SV) and LV ejection fraction (LVEF) were recorded in the rabbits, and standard high frame rate apical four, three and two-chamber views of three consecutive cardiac cycles were stored for off-line analysis.We analyzed the apical four, three and two-chamber preoperative and postoperative views using 2D–STI software to obtain the strain, strain rate index and LR . LR was defined by the global rotation of the LV cross-section. We sketched the endocardial contours, and the software automatically created regions of interest containing the endocardium, middle myocardium, and epicardium, then adjusted the regions of interest to match the endocardial-myocardial and epicardial-myocardial borders. In the apical four-chamber, three-chamber, two-chamber views, the LV walls were subdivided into six: septum, lateral, anteroseptum, posterior, anterior, inferior walls. Segmental LR and global LR of the LV were assessed from the same echocardiograms using 2D–STI . Normal data distribution was assessed using Kolmogorov-Smirnov’s test. If the data distribution was normal, the data was compared using a paired The values of postoperative LVEF were significantly lower than the values observed in preoperative rabbits. There were no significant differences between the preoperative and postoperative LVEDV, LVESV and SV Table .Table 1TIn the preoperative and postoperative rabbits, the pattern of peak systolic LS of the three different myocardial layers was: endocardium > middle myocardium > epicardium. The peak systolic global LS was significantly different between the preoperative and postoperative rabbits. The values of the postoperative were lower than preoperative. The segmental peak systolic LS of the three different myocardial layers had significant difference between the preoperative and postoperative rabbits exclude the epicardial and middle myocardial layers of the septal wall. The values of the postoperative were lower than preoperative. Tables , Fig. 2TThe global peak LSr in the systolic, early and late diastolic period had significant difference between the preoperative and postoperative rabbits. The values of the postoperative were lower than preoperative. The segmental peak LSr in the systolic, early and late diastolic period had significant difference between the preoperative and postoperative rabbits exclude the systolic and early diastolic of the septal. The values of the postoperative were lower than preoperative. Tables , Fig. 3Tp < 0.001). In the apical two-chamber view, the degrees of rotation about the inferior wall was significantly lower in the postoperative than in the preoperative rabbits, and the LR was also significantly lower in the postoperative rabbits .  the peak systolic LS of different myocardial layers, peak LSr in the postoperative rabbits were lower than in the preoperative. (2) There was LR in the cardiac of the postoperative rabbits.AMI is a common heart disease. In recent years, the incidence of AMI and its associated mortality have increased annually. Cell death occurs after approximately 20 min of severe ischemia, and progresses in a wave front from the subendocardium into the subepicardium of the ischemic bed-at-risk. In ischemia, the lack of oxygen is caused by a reduction in coronary flow and towards cell death and necrosis and or infarction . In ordeHowever, early diagnosis of AMI is difficult. While coronary angiography can accurately evaluate the degree of stenosis of coronary artery, the technique is prohibitively invasive and expensive. 2D–STI is a new technique that is useful for the effective diagnosis of myocardial ischemia, myocardial infarction. In acute myocardial infarction, 2D–STI can easily and accurately determine the infarcted area –21. HoweQian FU et al.  evaluateAn advantage of rabbits as experimental subjects for myocardial ischemia is that rabbits do not require artificial ventilation during the LAD ligation experiments. According to previous studies, rabbits have minimal coronary collateral circulation. Blood flow to the coronary artery of the rabbit is mainly via the left anterior descending coronary artery, LV branch and the right coronary artery. The LAD perfuses the LV and a small portion of right ventricle wall, and the LV branch supplies a wider portion of the LV, but the right coronary artery only perfuses the right ventricular free wall . LAD ligIn our studies, we experimented with several methods of producing an accurate model of AMI in the rabbit. We observed that ligate the root of the LV branch might lead to sudden death. Ligating the distal end of the LV branch did not produce a good model of AMI, and caused papillary muscle and apical myocardial infarction instead. Therefore, we choose to model of AMI by ligating LAD. This study presented an innovative evaluation of the changes in LV function by detecting the three different myocardial layers and LR in the early stages of AMI in rabbits using the 2D–STI technique. We examined LV function and LR in preoperative rabbits as a self-control to minimize the variability between the groups.The study reported in this article investigated a rabbit model of AMI induced following LAD ligation. We used this model to calculate and compare the LV function. The values of postoperative LVEF were significantly lower than the values observed in preoperative rabbits, and there were no significant differences in the LVEDV, LVESV and SV between the preoperative and postoperative rabbits. These values indicated that the ligation of LAD in rabbits had a significant influence on LV systolic function.The pattern of peak systolic LS of the three different myocardial layers was: endocardium > middle myocardium > epicardium. At rest, most left ventricular wall thickening occurs as a result of endocardial thickening; the middle myocardium layer contributes only modestly to thickening; and the contribution of the epicardium is negligible . Accordip < 0.05), and the LR in the apical three and two-champer views were also significantly lower . We concluded that the LR changes between the preoperative and postoperative rabbits were related to the anatomy of rabbit coronary.This study used the LR of the LV to reflect changes in systolic function following AMI in rabbits. Previous studies have reported LR in the LV of dilated cardiomyopathy patients and other heart failure patients; however, before our study it was unknown whether LR was associated with AMI in rabbits. We observed that the degrees of rotation of the LV lateral, posterior and inferior walls were significantly lower in the postoperative rabbits (The LAD of the left coronary artery perfuses the interventricular septum, and when it is occluded, the LR of interventricular septum had no significant differernce between preoperative and postoperative rabbits, but the value is decreased. For the reason, we considered it was related to the collateral circulation, when the LAD was occluded, the collateral circulation maybe rebuilded. Why, then, were the LR of the inferior and posterior walls reduced? Due to the “muscle band”, the inferior and posterior walls are downstream of the interventricular septum, and, therefore, they may be influenced by the upstream muscle. Our results demonstrated that LR may be related to the condition of the surrounding muscle. The origin of the LR is unclear. Gallagher KP et al.  performeIn this study, LV function was impaired in the early phase after acute occlusion of LAD coronary artery. The LS of different myocardial layers could reflect the LV function very conveniently. The LR of LV could be an important indicator of cardiac function in the early phases of AMI. In the clinical practice, the early detection of the cardiac dysfunction after AMI can make these patients have early treatment, and can also evaluate the efficacy of different treatment.


Using simultaneously acquired PET/CMR data from patients early after AMI, this study quantitatively compares these three imaging markers and investigates links to blood markers of myocardial injury and systemic inflammatory activity.Characterization of tissue integrity and inflammatory processes after acute myocardial infarction (AMI) using non-invasive imaging is predictive of patient outcome. Quantitative cardiovascular magnetic resonance (CMR) techniques such as native T1 data were acquired using a modified Look-Locker inversion recovery (MOLLI) sequence, ECV maps were calculated using individually sampled hematocrit. 18F-FDG PET was executed after 1 day of dietary preparation, 12 h of fasting, and administration of heparin. ECV, 18F-FDG and native T1 data were compared mutually as well as to peak counts of peripheral blood markers  and infarct size.A total of 25 patients without microvascular obstruction were retrospectively recruited. All imaging was simultaneously performed 5 ± 1 days after revascularization following AMI on an integrated 3T PET/MRI scanner. Native and post-contrast T18F-FDG PET and native T1 signal increases were observed in combination with no inter-patient correlation of maximum absolute values at the infarct center, suggesting well-colocalized but physiologically diverse processes begetting the respective image signals. Comparison of maximum image signals to markers of myocardial damage and systemic inflammation yielded highly significant correlations of ECV to peak creatine kinase-MB and overall infarct size as well as between native T1 and peak monocyte counts.High intra-patient correlations of relative ECV, 1 values at the infarct core early after AMI can be linked to the systemic inflammatory response independent of infarct size. Absolute ECV at the infarct core is related to both infarct size and blood markers of myocardial damage.Absolute native TThe online version of this article (10.1186/s12968-018-0454-y) contains supplementary material, which is available to authorized users. Both mapping techniques have usually been evaluated as more sensitive or accurate versions of late gadolinium enhancement (LGE) or T2-weighted imaging for the determination of infarct size or AAR in the context of AMI [1 mapping, which for the first time allow non-invasive CMR of the local severity of myocardial injury and edematous processes as opposed to only measuring their extent.The development of quantitative cardiovascular magnetic resonance (CMR) imaging techniques as a means for myocardial tissue characterization has seen a number of advances in recent years. Due to their relative robustness , especiaications , 3 and bications –6. For aications , 8 and ttions [1 , 10 and tions [1  mapping.tions [1 , 13, stut of AMI , 14. Thi18F-fluorodeoxyglucose (18F-FDG) is used in combination with metabolic preparation to target cardiac infiltration by inflammatory cells [18F-FDG imaging signal when applied in a clinical setting [The assessment of post-AMI inflammatory processes have recently also come into the focus of positron emission tomography (PET) imaging, where ry cells , 16. How setting . In this setting , 18.18F-FDG uptake, native T1 and ECV in the context of a complex tissue state consisting of diverse processes including inflammation, edema and cellular tissue damage after revascularized AMI. In addition, blood markers of myocardial damage and blood counts of inflammatory cells have been obtained following the acute event. Consequently, quantitative regional results from the three imaging methods under investigation are compared among themselves as well as with peripheral blood parameters. It is investigated to what degree the three imaging methods indicate independent features of the post-ischemic healing process, and to what degree these features are co-localized.The study at hand employs PET/CMR to quantitatively investigate the relationship of the three imaging markers Proceeding in this fashion, it is the goal of this manuscript to highlight the potential in making full use of available quantitative information from cardiac multimodality imaging for a better understanding of image signals and their relation to pathophysiology.n = 25) represent a large subgroup of a cohort from a previously published study [18F-FDG uptake and LGE and their relationship to functional outcome. All patients underwent examination on a clinical 3T PET/MRI scanner  5 ± 1 days after myocardial infarction and subsequent, successful revascularization  grade ≥ 2, average: 2.9). The study was approved by the local ethics committee, performed in agreement with the Declaration of Helsinki, and all participants gave written and informed consent. Criteria for retrospective enrollment were membership in the final study cohort reported in [1 data. Additionally, patients showing signs of microvascular obstruction (MVO) in LGE images were excluded from quantitative analysis, as the necessary contrast agent equilibration for ECV mapping is not attainable. Also, segmentation of MVO border zones was deemed not practicable in these cases due to the differences in spatial resolution between PET and CMR images, and quantitative values would not have been comparable to results from transmural segmentation. A detailed description of the criteria for retrospective enrollment similar to the corresponding statements in [Patients that were retrospectively enrolled for this investigation  to further suppress physiological myocardial FDG uptake [18F-FDG. Correction of emission data was performed for randoms, scatter, dead time and attenuation. Attenuation correction was accomplished using 2-point Dixon sequence as previously described [18F-FDG image signals were expressed as standardized uptake values based on lean body mass (SUV LBM) or - for comparison to blood markers - also as tissue-to-background ratio (TBR) normalized to blood signal taken from an LV-centric region of interest.G uptake . A list-escribed . Parts oescribed . For rec1 maps were acquired using a MOLLI prototype sequence in three short axis slices per patient. Acquisition (3(3)3(3)6) scheme [1 image series as it was acquired in shallow breathing. After registration, ECV maps were calculated from the resulting T1 maps using individually measured hematocrit. LGE images covering the complete left-ventricular (LV) myocardium were acquired directly following post contrast T1 maps after a cumulative dose of 0.2 mmol/kg Gd-DTPA .As part of a comprehensive resting-state CMR exam, native and post-contrast T) scheme ), retros) scheme . If nece18F-FDG PET images with ECV and native T1 maps. Manual alignment was performed between ungated PET data and individually motion-corrected CMR data if necessary. Manual segmentation on the basis of ECV maps was performed for the most infarct-centric of the three acquired slices, which was determined on the basis of LGE images covering the whole left ventricle. Basal and mid-ventricular slices were segmented into 32 sectors , equally spaced along a centerline between endo and-epicardial borders without additional morphological reference. This segmentation was applied to the registered ECV, native T1 and 18F-FDG PET images of that slice. For each patient, segmentation of the chosen slice therefore resulted in 32 transmural sector values  for each of the three image signals under investigation as shown in Fig. 18F-FDG uptake respectively refers to the average from the so-defined remote sectors, and the maximum value refers to the average of the two highest sector values. Additional measures of infarct size in % of LV volume were obtained by manual delineation of enhancement regions in the LGE images as described previously [For PET/CMR image registration, the MunichHeart software  was usedeviously .Fig. 1ViDaily blood sampling was performed for up to 6 days after revascularization. Peak levels of blood parameters creatine kinase (CK), creatine kinase-MB (CK-MB), troponin T as well as peak leukocyte and monocyte counts were taken from this sampling period as previously reported .p-values are given as Pearson correlation coefficients with a 5% significance level.Data processing and statistical analysis were executed in Matlab R2017a . Between-subject correlations represent a correlation of per-subject means, within-subject correlations were calculated using multiple regression . R- and n = 25) are shown in Table 1 maps (n = 3) or breathing artifacts in the PET attenuation map (n = 1).The physiological characteristics of the final patient cohort n = 5 are shoR = 0.60, 0.43, 0.51). The lower panel of Fig. R = 0.91, 0.87, 0.88) than the globally pooled comparison.The total number of sectors after exclusions was 662 for each imaging method, consisting of 32  or 16  sectors per patient for each of the 25 subjects. The upper panel of Fig. 1/FDG and 1.9 sectors between nT1/ECV.The underlying inter-patient variability of absolute values at the high end was most clearly discernible for the comparison of FDG/ECV. Consequentially, if only the average of the two maximum sector values from each patient were compared, no significant correlations were observed for FDG/ECV, FDG/native T1 nor ECV/native T1 Fig. . Table 318F-FDG uptake and native T1 are shown in Fig. p = 0.002). Conversely, no significant correlation between infarct size and either maximum 18F-FDG uptake or maximum native T1 was observed.Results for comparing infarct sizes with corresponding maximum values of ECV, 18F-FDG uptake  and a significant correlation with peak CK-MB (p = 0.006) were observed, despite no correlation to peak troponin or monocytes. The comparison to peak CK-MB revealed a tight relationship at the low end and a larger variability at the high end of values , and none was found for 18F-FDG TBR normalized to LV blood  to peak monocyte counts and a significant correlation with troponin (p = 0.024). The corresponding comparisons to peak leukocyte counts are not shown, yielding a significant trend (p = 0.033) with native T1.Maximum ECV Fig. , 18F-FDGute Fig.  and TBR). 1 Fig.  were comues Fig. . For abs18F-FDG uptake, extracellular volume and native T1 in patients early after revascularized myocardial infarction using simultaneously acquired PET/CMR data. Quantitative results have been derived for a single, infarct-centric slice position that was co-localized between all three methods, which can be seen as a biopsy-like imaging approach. An effort was made to link the so-obtained image signals to underlying pathophysiological processes using independent measures of infarct size and peripheral blood markers of cardiac damage and inflammatory cell populations. The study did not investigate correlations between image signals and functional recovery post AMI as these have already been given separately for ECV [18F-FDG [1 [The study at hand has compared absolute measures of  for ECV , 18F-FDG[18F-FDG  and natiF-FDG [1  in quant18F-FDG uptake and native T1 appeared as representing mutually distinct combinations of features with respect to infarct-related pathophysiology, while the respective underlying processes seemed to be largely co-localized.The first step was the comparison of inter-patient and intra-patient (i.e. intra-slice) signals as shown in Fig. 1 mapping have been shown to be sensitive to a number of different disease processes [For myocardial ECV, estimates derived from pre- and post-contrast Trocesses  and histrocesses . With rerocesses  but furtrocesses , the samrocesses . This ob18F-FDG uptake at the infarct center with peak monocyte or leukocyte counts or global infarct size. This was irrespective of whether maximum 18F-FDG was evaluated in absolute terms as SUV LBM or normalized to LV blood activity as a TBR. A similar finding [18F-FDG is taken up by inflammatory cell populations [18F-FDG uptake as a purely inflammatory signal [18F-FDG image signals are generally regarded as a mixture of background/blood pool, post-ischemic and inflammatory constituents in this context.With respect to FDG, data from this study suggest no correlation of maximum  finding  has beenulations , the inty signal . Therefo1 may reflect a variety of pathologic tissue alterations, but is generally accepted to indicate the edematous increase of free water content early after AMI [1 observed in this study is therefore attributed to an edematous reaction, which, however, did not show a correlation with infarct size as ECV did. With respect to native T1, the most interesting finding from this study is a highly significant correlation with peak monocyte counts and a weaker but still significant association to peak leukocyte counts, of which monocytes are a subset specific to inflammatory activity. As for ECV, this association of biopsy-like imaging results with peripheral blood markers is remarkable, even more so considering that native T1 was not found to be related to infarct size. Therefore, the data at hand provides evidence for the fact that myocardial edema and the systemic inflammatory reaction post AMI are quantitatively associated.Native myocardial Tfter AMI . The exp18F-FDG uptake and native T1 suggest their association with a more patient- than infarct-specific reaction to the ischemic insult. This notion is strongly supported by the observed association of native T1 with peak monocyte counts.Summarizing the comparison of imaging results with peripheral blood parameters, the data at hand suggest ECV as a marker of cellular damage early after reperfused AMI, with maximum values related to infarct size and therefore reflecting most likely a mechanistic property of the respective infarct. Conversely, the missing correlation to infarct size for maximum An important translational limitation to results from this study is that patients exhibiting MVO post AMI were not amenable to the presented analysis. While there exist propositions on the segmentation of MVO border zones for e.g. ECV mapping , the dif1 mapping has been shown to be more sensitive to variations in heart rate than other, more recently proposed schemes [1  do not suggest this as a major confounder to the presented findings.The acquisition scheme (3(3)3(3)6) used in this study for MOLLI T schemes . Howeverp-values < 0.01.Additionally, the practice of using peak values of peripheral blood markers as a surrogate for their summed activity may have introduced additional variability into the reported results. While the described practice is known to be relatively accurate for CK/CK-MB , the inf18F-FDG uptake, native T1 and ECV early after revascularized AMI. A biopsy-like imaging approach has revealed links between CMR-derived ECV estimates and blood markers of muscular damage as well as an association of the edematous response indicated by absolute native T1 estimates with the systemic inflammatory activity indicated by peripheral monocyte counts.Simultaneously acquired PET/CMR data from this study have shown a close spatial concordance of relative signal increase in combination with a divergence of absolute signal magnitudes between Additional file 1:Comparison of 18F-FDG uptake TBR  with peripheral blood markers CK, CK-MB, troponin and monocyte counts. (PNG 568 kb)


In about 30% of the cases evaluated by AS, we found AVA ≤ 1.0cm2, indicative of severe AS, with a mean gradient < 40 mmHg,suggestive of moderate AS.4 Thisdissociation makes it difficult to establish an adequate and definitive diagnosis to thepatient with AS, fundamental point in the therapeutic decision making. If, on the onehand, patients with moderate AS do not benefit from valve intervention, those withsevere AS require surgical aortic valve replacement or a transcatheter aorticbioprosthesis implant, especially if they are symptomatic.1-3Severe aortic stenosis (AS) is defined as a significant reduction of the aortic valvearea . These patients present apathophysiology similar to that of diastolic heart failure, with hypertrophy and leftventricular compliance reduction, leading to a "low-flow" state, defined by an ejectedvolume (stroke volume) of < 35 ml/m2 (stroke volume = Diastolic Volume -Systolic Volume / Body Surface).5-7In 2007, Hachicha et al.,5, corroborated by some subsequent studies,8-11 was the demonstration of a better survival ofsymptomatic patients with paradoxical AS after valve intervention when compared toclinical treatment. However, patients with paradoxical AS, despite being benefited byvalve intervention, present higher surgical mortality when compared with patients withclassic AS (mean gradient > 40mmHg).1-3,8,9,11Another important contribution of Hachicha et alIn this paper, we propose an algorithm to facilitate the diagnostic confirmation ofparadoxical AS. In three steps, we perform the Recognition of Paradoxical AS,Measurement Error Evaluation and Pathophysiological Confirmation :1-3 For this reason, patientswith AVA ≤ 1.0 cm2, jet velocity < 4 m/s or meangradient < 40 mmHg and ejection fraction > 50% should be classified ashaving paradoxical AS or low-flow, low-gradient AS with preserved ejectionfraction.1. Recognition of Paradoxical AS: this step is the first and most important.The delay in the diagnosis of paradoxical AS causes delayed intervention,leading to an increase in mortality. The classification of "moderate tosevere" or even "moderately-severe" valvulopathy is not described in any ofthe current guidelines and impairs clinical reasoning.7 3Dechocardiogram is a promising test for more accurate evaluation of VSVE andAVA by planimetry, however, specific studies for the population withparadoxical AS are necessary for its routine indication. Two points areextremely important for the clinical cardiologist. First, in patients withsmall corporeal surface, a reduced AVA may correspond to moderate AS. Inthis way we must always index AVA by the corporeal surface (iAVA), beingthat an iAVA ≤ 0.6 cm2/m2 suggests importantAS. In obese patients (BMI ≥ 30 kg/m2) we must assume alower cut-off value (< 0.5 cm2/m2) so as not tooverestimate the anatomical severity.12 The second data that should be evaluated issystolic blood pressure in gradient measurement moment, which should be lessthan 140 mmHg.1 Higherpressures contribute to underestimating the mean gradient and generate anincrease in the valvulo-arterial impedance, a measure that estimates theventricular afterload added to arterial and valvular overload ventricle, andit is also associated with mortality.13 In summary, the clinical cardiologist shouldremember to index the AVA and make sure that the systolic blood pressure was< 140 mmHg at the time of gradient measurement, while theechocardiographer should be attentive to errors in gradient measurement andmeasure the AVA by the planimetry.2. Evaluation of Measurement Errors: In this stage, we must identify eventualmeasurement errors that justify an underestimated gradient or AVA. Theechocardiographer should be aware of the correct alignment of the Dopplercontinuous wave for velocity and gradient measurement, avoidingunderestimating these measurements. Another orientation is to avoid AVAmeasurement by continuity equation and using whenever possible measurementby planimetry. AVA measurement by continuity equation may underestimate AVA,since such measurement takes into account left ventricular outflow tractarea calculation (VSVE) . The VSVE dimension is usuallymeasured with a 2D echocardiogram, assuming that the VSVE is circular.However, such a structure can often be elliptical, causing measurementerrors.14 However, females maypresent the same anatomic severity as men, but with lower values ofcalcification, being advised to apply differentiated cutoff values forfemale patients (> 1200 AU).15 Pathophysiology of low flow should be confirmed bystroke volume calculation, as previously described. In order to justify lowgradient in a patient with severe AS, he must necessarily present a smallcavity with stroke volume < 35 ml/m2.1-3,5-73. Pathophysiology Confirmation: Finally, we must confirm the pathophysiologyof AS and low-flow, low-gradient. In developed countries, the main etiologyof AS is degenerative, also known as calcific. Valvular calcificationcorrelates with anatomic severity and values greater than 1650 AU, verifiedby computed tomography, suggest anatomically severe AS.Thus, through this 3 steps algorithm, we help in the recognition of paradoxical ASanatomical severity, facilitating the clinician to identify the ideal moment forintervention in this difficult diagnosis entity.


Advanced heart failure treated with a left ventricular assist device is associated with a higher risk of right heart failure. Many advanced heart failures patients are treated with an ICD, a relative contraindication to MRI, prior to assist device placement. Given this limitation, left and right ventricular function for patients with an ICD is calculated using radionuclide angiography utilizing planar multigated acquisition (MUGA) and first pass radionuclide angiography (FPRNA), respectively. Given the availability of MRI protocols that can accommodate patients with ICDs, we have correlated the findings of ventricular functional analysis using radionuclide angiography to cardiac MRI, the reference standard for ventricle function calculation, to directly correlate calculated ejection fractions between these modalities, and to also assess agreement between available echocardiographic and hemodynamic parameters of right ventricular function.A retrospective review from January 2012 through May 2014 was performed to identify advanced heart failure patients who underwent both cardiac MRI and radionuclide angiography for ventricular functional analysis. Nine heart failure patients  were identified. The average time between the cardiac MRI and radionuclide angiography exams was 38.9 days (range: 1 - 119 days). All patients undergoing cardiac MRI were scanned using an institutionally approved protocol for ICD with no device-related complications identified. A retrospective chart review of each patient for cardiomyopathy diagnosis, clinical follow-up, and echocardiogram and right heart catheterization performed during evaluation was also performed.R = 0.5). The increased discrepancies for RV analysis were statistically significant using an unpaired t-test . Echocardiogram parameters of RV function, including TAPSE and FAC, were for available for all 9 patients and agreement with cardiac MRI demonstrated a kappa statistic for TAPSE of 0.39 (95% CI of 0.06 – 0.72) and for FAC of 0.64 (95% of 0.21 – 1.00).The 9 patients demonstrated a mean left ventricular ejection fraction (LVEF) using cardiac MRI of 20.7% (12 – 40%). Mean LVEF using MUGA was 22.6% (12 – 49%). The mean right ventricular ejection fraction (RVEF) utilizing cardiac MRI was 28.3% (16 – 43%), and the mean RVEF calculated by FPRNA was 32.6% (9 – 56%). The mean discrepancy for LVEF between cardiac MRI and MUGA was 4.1% (0 – 9%), and correlation of calculated LVEF using cardiac MRI and MUGA demonstrated an R of 0.9. The mean discrepancy for RVEF between cardiac MRI and FPRNA was 12.0% (range: 2 – 24%) with a moderate correlation (Heart failure patients are increasingly requiring left ventricular assist device placement; however, definitive evaluation of biventricular function is required due to the increased mortality rate associated with right heart failure after assist device placement. Our results suggest that FPRNA only has a moderate correlation with reference standard RVEFs calculated using cardiac MRI, which was similar to calculated agreements between cardiac MRI and echocardiographic parameters of right ventricular function. Given the need for identification of patients at risk for right heart failure, further studies are warranted to determine a more accurate estimate of RVEF for heart failure patients during pre-operative ventricular assist device planning. Advanced left heart failure therapy is focused on hospitalization and heart transplantation given the poor outcomes of medical therapy alone in these patients , 2. HoweGiven the prevalence of advanced heart failure, potential LVAD recipients in the US is estimated to be 150,000 to 250,000 patients , 9. FurtWhile echocardiography is a widely available and non-invasive method of ventricular functional analysis with RV function assessed by both tricuspid annular plane systolic excursion (TAPSE) and fractional area of change (FAC), monitoring RV function and size with ultrasound parameters is not currently advocated for definitive RV evaluation . RadionuDespite the advantages of cardiac MRI, ventricular function using radionuclide angiography continues to be favored with the multi-gated acquisition technique (MUGA) used to calculate LVEF, and the first-pass radionuclide angiography (FPRNA) technique used to calculate the RVEF. Multiple factors contribute to the continued preferred status of radionuclide angiography in societal guidelines; particularly, the limited availability of cardiac MRI, and that is contraindicated in patients with implantable cardiac devices (ICDs) –33.In a continued effort for accurate assessment of both left and right ventricular function for patients prior to LVAD placement, a workflow was implemented at our institution for patients with conventional ICDs allowing for scanning with a 1.5 T MRI utilizing a published evidence-supported protocol –40. Our An IRB-approved, retrospective review from January 2012 through May 2014 was performed at a single US academic medical center. The review identified all adult advanced heart failure patients treated with an ICD who were being evaluated for either LVAD placement or heart transplantation. All patients were included who underwent left and right ventricular function evaluation with both cardiac MRI and radionuclide angiography within 120 days. A comparison of the calculated left and right ventricular ejection functions was performed comparing cardiac MRI with radionuclide angiography. The electronic medical record for each patient who met inclusion criteria was reviewed for the clinical course, specifically whether the patient went on to receive a LVAD. Medical record review also included performance of any echocardiogram or right heart catheterization performed during the evaluation period. While these exams do not provide a calculated ejection fraction, that right ventricular functional parameters from these exams have been shown to be predictive of post-operative right ventricular failure after LVAD placement .Cardiac MRI exams included in the study required the performance of a complete short-axis series of the ventricles using cine EKG-gated sequences. Radionuclide angiography examinations included in the study required performance of both a MUGA and FPRNA exam for respective LVEF and RVEF evaluation. Right ventricular functional parameters from available echocardiograms included tricuspid annular plane systolic excursion (TAPSE) and fractional area of change (FAC), and from available right heart catheterization (RHC) parameters included central venous pressure (CVP), mean pulmonary artery pressure (MPAP), and right ventricular stroke work index (RVSWI) utilizing thermodilution.Nine patients including 8 (89%) men and 1 (11%) woman with a mean age of the patients was 57.0 years  underwent ventricular ejection fraction evaluation with both cardiac MRI and radionuclide angiography for pre-operative heart failure evaluation for planning of LVAD placement or heart transplantation. Four patients were diagnosed with ischemic cardiomyopathy, and 5 patients were diagnosed with nonischemic cardiomyopathy. The average time interval between the cardiac MRI and radionuclide angiography (MUGA and FPRNA) was 38.9 days (range: 1 - 119 days). The average dose of intravenously administered technetium-99 m labeled RBCs for radionuclide angiography was 23.0 mCi (range 20.1 – 25.0 mCi).All patient had a transthoracic echocardiogram performed during their evaluation with the average time between echocardiogram and cardiac MRI of 41 days (range: 1 – 125 days). Additionally, 7 of the 9 patients underwent RHC with an average time between RHC and cardiac MRI of 47 days (range 1-125 days).All patients evaluated had previously undergone ICD placement prior to cardiac MRI examination, which was performed using an institutionally approved ICD safe protocol. There were no device-related complications from cardiac MRI in our study population.All patients were screened by a multi-specialty team prior to performance of the MRI. Screening required a cardiology evaluation consisting of electrophysiology laboratory interrogation of the ICD. The approved selection criteria required all cardiac leads in place for more than 6 weeks; stable pace, sense, and impedance parameters, normal battery function, and a stable non-paced heart rhythm with a heart rate greater than 50 beats per minute. If any of parameters were unable to be achieved, the patient was unable to undergo an MRI.Prior to the MRI examination, the ICD was programmed to a sensing-only mode without cardiac pacing within the EP laboratory by electrophysiology-specialized cardiologists. Ventricular tachycardia and ventricular fibrillation detection, a feature in implantable defibrillators, was also turned off if applicable. The patient was monitored during the entire exam, and after the MRI was performed the patient was immediately returned to the electrophysiology laboratory where the ICD was reprogrammed to its original settings. Performance of the Cardiac MRI was done under the supervision of a dedicated advanced cardiac imaging radiologist and an MRI physicist who were both present for the entirety of each examination.Each cardiac MRI was performed using a 1.5 T Siemens Magnetom Aera  with a multiphase array body coil. Specific absorption rate was limited to 1.5 W/kg for a maximum of 30 min. Gradient recalled echo (GRE) images were obtained for all bright blood and cine gated images to minimize susceptibility artifact related to the ICD battery pack. All images were obtained during breath hold. GRE cine gated images of the LV long-axis were performed in the 2, 3, and 4 chamber orientations for ventricular assessment. For complete ventricular analysis, GRE cine gated short axis series including complete coverage both ventricles were performed. The short axis series consisted of a stack of 8 mm thick images with a 10% distance factor between images. No gadolinium-based contrast agents were administered during the examination.Cardiac MRI interpretation and offline post-processing analysis  of ventricular ejection fractions was performed by consensus between two fellowship trained cardiovascular radiologists. Ventricular ejection fraction calculations were performed by manual contouring of the endocardial border of both ventricles during both end-diastole and end-systole utilizing all relevant sequences of the short axis series. Offline post-processing analysis also calculated end diastolic, end systolic, and stroke volumes of both ventricles. The results of the original studies were collected retrospectively, and were not reinterpreted.Ventricular ejection fraction determined by radionuclide angiography was performed using an intravenous injection of Technetium-99 m-tagged red blood cells (RBC). Radiopharmaceutical tagging was performed using an in vitro labelling technique to ensure a high percentage of RBC tagging, and to prevent the injection of free Technetium-99 m. The RBCs for tagging were acquired from a 1 - 3 mL intravenous blood sample from the patient, which was subsequently tagged with radiopharmaceutical by a commercial tagging kit  prior to reinjection. After tagged RBC reinjection, the FPRNA examination was performed by obtaining dynamic nuclear angiography images in the RAO 30° projection at a rate of 50 msec/frame for a total acquisition of 440 frames. Additional, gated planar images in the RAO 30° projection were subsequently obtained for 300 s. After the FPRNA examination was performed, the MUGA portion of the radionuclide angiography examination was performed for LVEF evaluation. The MUGA images were acquired with gated images performed in the LAO 45° projection for 10 min.RVEF was calculated by performance of computer contouring of the right ventricle in the RAO 30° position throughout the cardiac cycle and computer detection of the end diastole (ED) and end systole (ES) frames. Right ventricular contouring was performed by identification of the tagged RBC within the RV cavity and contouring of the endocardial border of the RV while excluding the right atrium and main pulmonary artery Fig. . LVEF waAll patients underwent a comprehensive 2D transthoracic echocardiographic examination performed during rest from the left parasternal, apical and subcostal windows using the GE ultrasound . RV assessment included TAPSE, which was measured by M-mode to assess RV longitudinal function by tracing movement of the tricuspid valve annulus from end diastole to end systole. RV area was measured by planimetry of the RV cavity in the apical view along the RV free wall to the apex and back to the tricuspid annulus for both systole and diastole to obtain the end-systolic area (ESA) and end-diastolic areas (EDA) respectively. Fractional area change (FAC) was calculated as [(EDA-ESA)/EDA] × 100.RHC was performed through the right internal jugular or femoral approach in 7 subjects at rest using the Swan-Ganz pulmonary artery catheter in the supine position. Direct measurements of RAP, pulmonary artery systolic pressure, PA diastolic pressure (PADP), mean PA pressure (MPAP), cardiac output (CO) by thermodilution, cardiac index (CI) and pulmonary artery wedge pressure (PAWP) were obtained and real-time tracings were displayed on a monitor. Right ventricular stroke work index (RVSWI) was calculated as (CI/HR) x MPAP × 0.0144.Statistical analysis ventricular ejection fractions of the nine patients who met inclusion criteria included calculation of discrepancies and correlation coefficient between the ejection fractions provided by cardiac MRI and radionuclide angiography, which provided LVEF by MUGA and RVEF by FPRNA. Discrepancy values were evaluated for statistical significance using an unpaired t-test.The mean RVEF using cardiac MRI was 28.3% . The mean RVEF calculated using FPRNA was 32.6% . The mean LVEF calculated using cardiac MRI was 20.7% , and mean LVEF calculated using MUGA was 22.6% .t = 3.19, p = 0.006) . The mean LVEF discrepancy between cardiac MRI and MUGA was 4.1% . The difference in discrepancies between the two modalities for RV and LV analysis was statistically significant using an unpaired t-test  for left ventricular support. One of the patients who underwent LVAD implantation was successfully bridged to transplant while the other two are still awaiting transplant. One patient identified for LVAD placement did not receive their LVAD secondary to complications from ischemic bowel disease that resulted in the patient expiring prior to LVAD placement. One patient identified for LVAD placement was deemed unsuitable for transplant due to lack of social support and inability to comply with smoking cessation program. Three patients improved clinically on optimal medical therapy and optimized medical management was pursued. One patient was discovered to have arrhythmogenic right ventricular dysplasia (ARVD) based on the MRI findings and improved on optimal medical therapy Table .Table 1DPatients with advanced heart failure being evaluated for LVAD placement require reliable and reproducible evaluation of right ventricular size and function given the high risk of mortality associated with RVF after LVAD placement. Despite evidence that cardiac MRI provides the most accurate assessment of left and right ventricular size and function, it has not been readily available for heart failure patients given that many of these patients have previously undergone placement of ICD. Despite the recent approval of the first conditional ICD by the FDA, current societal guidelines regard all current, conventional ICDs as a relative contraindication to MRI , 45 leadIn our study, we compare the benefits of right ventricular evaluation cardiac MRI for “gold standard” calculation of RVEF with the additional functional and volumetric parameters provided by this modality against ejection fraction calculated by radionuclide angiography. While LVEF calculation using MUGA demonstrated an expected strong correlation (R of 0.9) with cardiac MRI, our research demonstrated only a moderate correlation (R of 0.5) between RVEF using FPRNA compared to cardiac MRI. Additionally, the discrepancy between RVEF calculated by cardiac MRI and radionuclide angiography was larger than LVEF values from cardiac MRI and MUGA.Previous studies have shown that non-invasive echocardiographic assessments of such as FAC and TAPSE show a strong correlation to RVEF calculated with radionuclide angiography , and whiSince the calculation of ventricular ejection fraction using cardiac MRI has been accepted as the most accurate assessment of ventricular function, our results suggest that the use of an RVEF calculated by FPRNA may not be the optimum method for patient risk stratification prior to LVAD implantation given the high risk of mortality in patients who progress to RVF. Conversely, our results validate that LVEF calculation determined by radionuclide angiography is acceptable for calculation of left ventricular EF given the strong correlation (R of 0.9) when compared to cardiac MRI. However, the inability of MUGA to provide additional functional parameters; e.g., left ventricular end-diastolic and end-systolic volumes, stroke volume, etc., should foster continued research for evaluation of left ventricular functional and volumetric assessment in patients with ICDs.Given the evidence supporting heart failure severity with increasing RV chamber size and the increased mortality with the development of RVF after LVAD implantation, we suggest that further investigation of cardiac MRI for RVEF assessment is warranted given the high discrepancy and a moderate correlation of RVEFs acquired by gold-standard cardiac MRI and the more widely utilized FPRNA. Also, given the utility of RHC for detecting of RV failure, further studies to categorize the severity of RHF into a mild, moderate, and severe classification system of these parameters may provide further utility for pre-operative assessment of RV function.While cardiac MRI is still limited by both the availability and the complexities of ICD safe MRI protocols, our data suggests that further investigation for surrogate measurements is warranted. Given echocardiographic and hemodynamic examinations both provide multiparametric right ventricular function analysis, our study suggest further study of these parameter may provide a equivocal or improved RV functional assessment compared to first-pass radionuclide angiography techniques when compared to ‘gold standard’ MRI derived values. Also, further study of RV volumetric assessments utilizing echocardiogram and/or cardiac MRI may also be useful given that studies demonstrated that multiple echocardiographic parameters, including smaller RV chamber size or abnormal RV short-axis to long-axis ratio, have been a significant predictor of post-operative RVF after LVAD placement .Although this study showed statistically significant discrepancy between RVEFs calculated using cardiac MRI compared to FPRNA, our findings are limited since it was a retrospective study with a small sample population due to the inclusion criteria applied to the study, which required a careful and strict screening to ensure safe performance of MRI with ICD. Given the small patient population we attempted to strengthen our finding by comparing additional available parameters of RV functional assessment including echocardiography and RHC. Furthermore, continued research into cardiac MRI derived right ventricle metrics, such as echocardiographic stroke volume index or end diastolic volume index, may provide further insight into proper risk stratification of patients being evaluated for the either a left-sided or biventricular assist device thus minimizing the morbidity and mortality associated with post-LVAD implantation RVF.Advanced heart failure patients are increasingly being treated with left ventricular assist device placement; however, definitive evaluation of both left and right ventricular function is required due to the increased mortality rate associated with right heart failure after LVAD placement. Our results suggest that FPRNA only has a moderate correlation with RVEF calculated using cardiac MRI. Furthermore, echocardiographic parameters of RV function including TAPSE and FAC demonstrated a fair and moderate agreement, respectively, compared to cardiac MRI suggesting a possible substitute for FPRNA. With the increasing need for identification of patients at risk for right heart failure, further studies are warranted to find a more accurate estimate of RVEF. Since this study and prior studies comparing radionuclide or echocardiographic RV function analysis to cardiac MRI-derived RVEFs produced at best a moderate agreement/correlation, investigation in how these methodologies attempt to reduce the complicated anatomy of RV into a planar measurement would be helpful. Furthermore, refinement of these planar measurements and improved quality control regarding attention to anatomic boundaries may increase agreement with MRI allowing for a more readily available non-invasive assessment of RV function.The expected increase in availability of MRI-conditional ICDs suggests that evaluation of advanced heart failure patients with cardiac MRI also should be further investigated as a definitive assessment for both left and right ventricular function prior to left ventricular assist device placement, and that cardiac MRI data may serve as the most accurate standard for RV volume and functional analysis for determination of the optimal pre-operative planning technique for patients undergoing LVAD implantation for bridge to transplant or destination therapy, or for other advanced devices such as a BiVAD or TAH.


Mitral valve prolapse is a benign condition. Mitral regurgitation is onlycomplicated in patients with severe mitral valve prolapse. Women with mitralvalve prolapse in the absence of other cardiovascular disorders toleratepregnancy well and do not develop remarkable cardiac complications.Nevertheless, serious complications of mitral valve prolapse, includingarrhythmia, infective endocarditis and cerebral ischemic events, can be presentin pregnancy. Debates remain with regard to the use of prophylactic antibioticsand β-blockers in the pregnant women with mitral valve prolapse. Theprognosis of the pregnant patients might be closely related to the pathologicaland (or) functional changes of the mitral valve. Non-myxomatous mitral valveprolapse poses no or little obstetric risks in terms of pregnancy, labor andneonatal complications; whereas myxomatous mitral valve prolapse is a majoretiology of valvular heart disease in women of childbearing age. In the pregnantpatients with mitral valve prolapse progressing into major complications,surgical interventions are considered. Medicinal treatment of such patients withβ-blockers should be a concern for the fetal safety. MVP ischaracterized by elongated chordae tendineae and redundant valve leaflets, whichprolapse into the left atrial cavity as the ventricle contacts. The prolapse may ormay not result in mitral regurgitation (MR). It is uncommon that the patients are complicated withsevere sequelae, the most frequent of which are severe MR that usually warrants asurgical correction. MVP may bedue to a primary connective tissue disease involving the mitral valve leaflets, thesubvalvular apparatus, or the mitral annulus, or secondary to mitral valve apparatusabnomalities. Primary or idiopathic MVP is usually associated with myxomatous,redundant valve leaflets and progressive annular dilation. In contrast, patientswith secondary MVP have thin leaflets, which prolapse slightly into the left atriumduring systole as a result of mismatch of the anatomical relationship between themitral valve apparatus and left ventricle. Hence, secondary MVP may be seen insecundum atrial septal defects, infective endocarditis, rheumatic mitral stenosisand calcified mitral annulus.The reason of the mucopolysaccharide accumulation predilection in the mitral valveremains uncertain. MVP was also regarded as an autosomal dominant cardiacabnormality with age and sex dependent expression. Nevertheless, it is believed that MVP is a resultof progressive myxomatous valve changes and it may bring about chordal rupture insome patients. The progressionof MVP into severe MR usually occur after the age of 50 years; whereas younger patients may havegood exercise tolerance, and would not show any circulatory deterioration.Mitral valve prolapse (MVP) is defined as a prolapse of one or both mitral valveleaflets at least 2 mm beyond the long axis annular plane with or without mitralthickening. The incidenceof cardiac disease in the pregnant women was estimated to be 0.5%, of which mitralvalve disease was more common than aortic (94.5% vs. 5.5%), and MVP was more common(39.2%) than MR (19.9%), mitral stenosis (16.9%), or combined valvular disorders was a major etiology of valvular heart disease in women ofchildbearing age. Gelson et al. reported that MVP is the most common cardiac disorder in thepregnant population, accounting for 12-17% of women of childbearing age. Women withMVP in the absence of other cardiovascular disorders may tolerate pregnancy well anddo not develop remarkable cardiac complications. Although rare, more seriouscomplications of MVP, such as arrhythmia, infective endocarditis and cerebralischemic events, have been reported during pregnancy. Debates still remain in the management of MVP inthe pregnant patients. This article aimed to delve deeper into this topic.Cardiac problems in pregnancy have been a contemporary important topic ofconcern. Disappearance of auscultatory findings, midsystolic click andlate systolic murmur of MR may pose a special problem in diagnosis of MVP duringpregnancy. Perhapsthese changes leave many cases of MVP undetected leading to false reduction in theincidence of MVP during pregnancy. Patients with MVP may have MR and benign ventricularectopics. Anatomic findings of MVP include 1) mitral annular dilation, 2) redundantand thickened leaflets, 3) myxomatous transformation of valve substance due tocollagen dissolution or disruption and severe acid mucopolysaccharide accumulation,and 4) absence of inflammatory changes. However, these patients may not show any deteriorationthroughout pregnancy. MVP withdiffusely thickened, redundant leaflets (myxomatous change) are more prone todeformity, degeneration and infection compared to those with only MVP withoutthickened leaflets (non-myxomatous changes). Recognizing and diagnosing MVP will explain episodes ofdyspnea, palpitation and chest pain during pregnancy. Most obstetric patients withMVP are in the low risk group, i.e., the non-myxomatous form, and should be expectedto have excellent obstetric outcomes.The routine use of echocardiography has greatly facilitated the identification of MVPin young adults. Symptoms are variable, but the most frequent complaints aredizziness, palpitation and faintness. Besides, obviousballoon-like changes, leaflet thickening and elongation, annular dilation, leftatrial and left ventricular enlargement, and diminution, elongation, or rupture ofchordae tendineae could be seen on two-dimensional echocardiography. On M-modeechocardiography, posterior displacement of mitral valve coaptation line (CDsegment) is > 2 mm during late systolic phase, and > 3 mm during pansystolicphase. Meanwhile, one or two leaflets may show hammock-like changes. In patients with prolapse of theanterior mitral leaflet, the mitral regurgitant flow could be seen along theposterior wall of the left atrium  in addition to the rigid prosthetic semicircular ring (Gregori-Brailering) for correction of mitral annulus dilation, in the replace of the widelyaccepted valve replacement. It is quitepossible that the majorities remain undiagnosed during pregnancy and undergoregional anesthesia without any untoward hemodynamic side effects. Current American Heart Associationguidelines stipulate that the presence of a murmur or echocardiographicallydemonstrated MR in patients with MVP constitutes a moderate risk of endocarditiswith invasive procedures.Regional anesthesia is usually avoided because of the sympathetic denervationresulting in increased venous capacity and decreased peripheral resistance. Thisleads to a reduction of ventricular volume, which may increase the degree ofprolapse. However, the safe use of epidural anesthesia in a patient with MVP hasbeen reportedWomen with MVP in the absence of other cardiovascular problems may tolerate pregnancywell. In the pregnant patients with MVP progressing into major complications,surgical interventions should be considered. Medicinal treatment in such patientswith β-blockers should be a concern for the fetal safety. In the patientswith severe MR and left ventricular fuctional impairment or New York HeartAssociation function class III or IV, delivery should be with the aid of carefullytitrated epidural anesthesia and invasive hemodynamic monitoring.


Cardiac magnetic resonance (CMR) T1 mapping and tissue-tracking strain analysis are useful quantitative techniques that can characterize myocardial tissue and mechanical alterations, respectively, in patients with early diabetic cardiomyopathy. The purpose of this study was to assess the left ventricular myocardial T1 value, extracellular volume fraction (ECV), and systolic strain in asymptomatic patients with type 2 diabetes mellitus (T2DM) and their underlying relationships with clinical parameters.We recruited 50 T2DM patients  and 32 sex-, age-and BMI-matched healthy volunteers to undergo contrast-enhanced CMR examinations. The myocardial native T1, post-contrast T1 and ECV values of the left ventricle were measured from T1 and ECV maps acquired using the modified Look-Locker inversion recovery technique. The left ventricular global systolic strain and the strain rates were evaluated using routine cine images and tissue-tracking analysis software. The baseline clinical and biochemical indices were collected before the CMR examination.p < 0.001; native T1: 1026.9 ± 30.0 ms vs. 1011.8 ± 26.0 ms, p = 0.022). However, the left ventricular global systolic strain, strain rate, volume, myocardial mass, ejection fraction, and left atrial volume were similar between the diabetic patients and the healthy controls. In the diabetic patients, the native T1 values were independently correlated with the hemoglobin A1c levels . The ECVs were independently associated with the hemoglobin A1c levels , angiotensin-converting enzyme inhibitor (ACEI) treatment  and HCT values .The myocardial ECV and native T1 values were significantly higher in the diabetic patients than in the controls. (ECV: 27.4 ± 2.5% vs. 24.6 ± 2.2%, Type 2 diabetes mellitus patients with normal myocardial systolic strain exhibit increased native T1 values and ECVs indicative of myocardial extracellular interstitial expansion, which might be related to poor glycemic control. The amelioration of myocardial interstitial matrix expansion might be associated with ACEI treatment. A valid assessment of the association of glucose control and ACEI treatment with myocardial fibrosis requires notably larger trials. Over the last decade, cardiovascular disease has been the leading cause of morbidity and mortality for diabetic patients , 2. DiabLate gadolinium enhancement imaging with cardiovascular magnetic resonance (CMR) can accurately detect regional myocardial infarction or fibrosis . HoweverPrevious research using speckle tracking echocardiography (STE) has revealed myocardial systolic strain dysfunction in diabetic patients –21. HoweConsequently, we used multiple advanced CMR technologies, including T1 mapping and tissue-tracking analysis, to compare the myocardial tissue characterization and strain alterations between patients with type 2 diabetes mellitus (T2DM) and healthy volunteers and to assess the contribution of related factors to early diabetic cardiomyopathy.2 for women or 81 g/m2 for men according to the definition proposed by Olivotto et al. /L, where L was the shortest dimension from the back wall to the line across hinge points of the mitral valve between the above two chambers) [Commercial post-processing software (cvihambers) . All of Extracellular volume fraction mapping was automatically calculated using a prototype inline processing function from Siemens, based on native and post-contrast T1 mapping at the same slice and the subject-specific HCT value. The native and post-contrast T1 and ECV values were measured by manually delineating regions of interest in the mid-layer myocardium of the left ventricular basal, middle and apical segments. The 16 regions of interest for each volunteer were drawn based on the American Heart Association 16-segment model  42, Circle, Calgary, AB, Canada). A consecutive stack of short-axis cine images and 2- and 4-chamber long-axis images were imported into this software. The left ventricular endocardial and epicardial contours of the end diastole were manually delineated on the short-axis and two long-axis cine images. The trabeculae and papillary muscles were included in the left ventricular cavity. The left ventricular global longitudinal (GLS), circumferential (GCS) and radial strain (GRS) and the early systolic strain rate were calculated by automatically tracking the contours in each cardiac cycle  were selected for entry into the multiple stepwise regression model. A p value < 0.05 (two-tailed) was considered significant.Statistical analyses of all data were performed using SPSS software . The normality of all continuous data was checked using the Kolmogorov–Smirnov test. Normally and non-normally distributed data and categorical variables are expressed as the means ± standard deviations and the medians (interquartile range) and frequencies (percentages), respectively. The independent-sample Student’s t test was used to compare two groups of normally distributed variables, and the Chi square test was used to compare categorical variables. The analysis of covariance (ANCOVA) was used to compare HCT-adjusted ECV values between two groups. Correlational analyses were performed with Pearson’s correlation for normally distributed variables and Spearman’s correlation for non-normally distributed data. Multiple linear regression analyses were used to identify the determinants of the myocardial T1 values and ECVs in patients with T2DM. All candidate variables (2) and 32 controls . The median diabetic duration and mean HbA1C in the patients were 10 years (IQR: 6–13) and 8.9 ± 2.3%, respectively. No differences were observed with respect to sex, age, blood pressure or BMI between the patients and the controls. Of the 50 diabetic patients, 19 had well-controlled hypertension, 14 had retinopathy, 10 had neuropathy and 6 had peripheral vascular disease.Table 2; p = 0.336), LVESV index , LVEF , LVM index  and LAV index  between the patients and the controls.Table p = 0.022) and ECV  were significantly higher in the diabetic patients than in the healthy controls. The ANCOVA indicated that the HCT-adjusted ECV value was also significantly higher in the diabetic patients (27.1 ± 0.30%) than in the healthy controls (25.0 ± 0.38%) . However, no difference in the post-contrast T1 values  was observed between the patients and the controls , circumferential  and longitudinal strain  between the diabetic patients and the controls. Similarly, there were no significant differences in the left ventricular global systolic radial , circumferential  and longitudinal strain rate  between the two groups    Fig. . However6) Table .Fig. 4a p = 0.002), angiotensin-converting enzyme inhibitor (ACEI) treatment  and HCT values  , ACEI treatment  and HCT values  (model R2 = 0.412)  values in the intra-observer analysis were 0.967, 0.980, 0.984, 0.965, 0.974, and 0.899 for native T1, post-contrast T1, ECV, GRS, GCS, and GLS, respectively. The ICC values in the interobserver analysis were 0.972, 0.971, 0.975, 0.973, 0.963, and 0.893 for native T1, post-contrast T1, ECV, GRS, GCS, and GLS, respectively.The present study demonstrated that patients with T2DM exhibited significantly increased mean native T1 values and ECVs of the LV myocardium compared with the normal control group, although no significant differences in the LV structural and functional parameters were observed between the two groups. Moreover, the increased myocardial native T1 values and ECVs were significantly associated with poor glycemic control (HbA1c), and ACEI treatment was related to a lower myocardial ECV.Cardiac magnetic resonance T1 mapping to quantify diffuse myocardial fibrosis has been validated in many previous histological studies –36. ThesIn the present study, the MR tissue-tracking-derived strain analysis demonstrated that the LV global systolic longitudinal, circumferential and radial strain and the strain rates were similar between diabetic patients and healthy individuals. Significant alterations in the LV and LA volumes and the LV mass were not observed. Therefore, native T1 and ECV, as early parameters, may be more sensitive than the myocardial systolic strain for the detection of early diabetic cardiomyopathy given the increased native T1 values and ECVs of the diabetic patients in our study. However, we did not observe decreased myocardial systolic strain as reported in some previous studies , 21, 42.myocardium/Δ R1blood, where R1 = 1/T1 [In our study, the existence of a significant correlation between the HbA1c level and native T1 or ECV suggests that myocardial interstitial expansion might be ascribed to poor glycemic control. An in vivo animal study demonstrated that hyperglycemia directly led to cardiomyocyte apoptosis by activating reactive oxygen species (ROS) production . ROS gen1 = 1/T1 . HoweverThe present study has several limitations. First, our sample size was small. Second, although previous histological studies demonstrated that the myocardial ECV exhibited significant correlation with the myocardial collagen volume fraction , confirmIn conclusion, our study demonstrates that an increased native myocardial T1 value and ECV can be detected before myocardial systolic strain abnormalities have developed in patients with T2DM. The HbA1c level is a determinant of increased native T1 and ECV indicative of myocardial interstitial expansion, and the amelioration of myocardial interstitial matrix expansion might be associated with ACEI treatment. The increased myocardial ECV was associated with a lower HCT value in diabetic patients. In future research, the effect of the degree of glycemic control and medication on myocardial interstitial expansion warrants a detailed longitudinal, large-scale study. Myocardial T1 mapping might have the potential to quantify the severity of early diabetic myocardial abnormalities and monitor the progress of medication treatment.