P<0.01) had good Pfirrmann grade performances in the NP with IVD degeneration. LFJ T2* values were significantly different between grades I and IV , as were T1ρ values between grades II and III  and grades III and IV . Correlations were moderately negative for T1ρ values between LFJ cartilage and NP , and between LFJ cartilage and PAF . T1ρ values of LFJ cartilage was weakly correlated with T2 (r = 0.007) and T2* (r = −0.158) values. Overall, we show that axial T1ρ effectively assesses early LFJ cartilage degeneration. Using T1ρ analysis, we propose a link between LFJ degeneration and IVD NP or PAF changes.Recent advancements in magnetic resonance imaging have allowed for the early detection of biochemical changes in intervertebral discs and articular cartilage. Here, we assessed the feasibility of axial T2, T2* and T1ρ mapping of the lumbar facet joints (LFJs) to determine correlations between cartilage and intervertebral discs (IVDs) in early lumbar vertebral degeneration. We recruited 22 volunteers and examined 202 LFJs and 101 IVDs with morphological  and axial biochemical  sequences using a 3.0T MRI scanner. IVDs were graded using the Pfirrmann system. Mapping values of LFJs were recorded according to the degeneration grades of IVDs at the same level. The feasibility of T2, T2* and T1ρ in IVDs and LFJs were analyzed by comparing these mapping values across subjects with different rates of degeneration using Kruskal-Wallis tests. A Pearson’s correlation analysis was used to compare T2, T2* and T1ρ values of discs and LFJs. We found excellent reproducibility in the T2, T2* and T1ρ values for the nucleus pulposus (NP), anterior and posterior annulus fibrosus (PAF), and LFJ cartilage (intraclass correlation coefficients 0.806–0.955). T2, T2* and T1ρ mapping (all  Low back pain (LBP) is a common disease that limits the activities of daily living, and is thus a major economic burden on health care systems. It is widely accepted that intervertebral lumbar discs (IVDs) and lumbar facet joints (LFJs) are the main sources of LBP, 2.Degeneration changes in the IVD are characterized by a loss of hydrated proteoglycan-rich matrix of the nucleus pulposus (NP) and collagen, both of which affect the mechanics of the IVD. In faceWith the improvements in MRI over the past two decades, new quantitative functional techniques-T2, T2* and T1ρ mapping, diffusion-weighted imaging, and delayed gadolinium-enhanced MRI have been used to reveal early biochemical changes in IVDs and in articular cartilage–11. In IT1ρ mapping, however, uses a “spin lock” pulse to change the relaxation rates of water associated with large macromolecules, such as PGs and GAGs. Decreased GAG content may lead to an increased mobile proton density in bulk water and an increased in T1ρ relaxation times. Therefore, T1ρ mapping could be a reliable method for quantitatively assessing PG content in IVDs and cartilage without the need for a contrast agent, 19–21.To the best of our knowledge, only a few articles have explored the relevance of biochemical parameters, such as T2 values for assessing LFJs and IVDs, 22. TheThe study was approved by our institution’s research ethics committee of Xiangya Hospital, Central South University (NO. 201301008), and all volunteers involved in this study signed informed consent and agreed to the use of their imaging information for this analysis.This was a prospective study. A total of 22 volunteers, each with 5 lumbar IVDs and 10 LFJs, were recruited from September 2015 to March 2016. The inclusion criteria were healthy volunteers or other adults with nonspecific acute LBP, which was defined as pain lasting < 2 h per day over a period of < 3 months in subjects aged 20 to 45 years. The exclusion criteria were chronic LBP > 3 months, LBP caused by injury, LBP with a visual analog scale  score ≥ 4 points, disc herniation or spinal stenosis, lumbar spondylolisthesis, tuberculosis, tumor or any other spinal diseases that would affect the stability of the lumbar spine and the loading state of the FJ. Subjects with a body mass index (BMI) > 25 or having other conditions that might generate unreadable data were also excluded from our study. All volunteers were examined by MRI in the morning  to maintain the intervertebral discs in a relatively stable physiological situation.All MR examinations were performed by a 3.0 T MR unit  and a dedicated eight-channel spine coil. Morphological  and biochemical  sequences were performed, covering the IVDs L1/2 to L5/S1.T2 and T2* mapping were carried out in the axial plane using a 2D multi-echo spin-echo (MESE) sequence and 2D multi-echo fast spoiled gradient-echo (ME-FSGRE) sequence, respectively . Five axT1ρ mapping was performed in the axial plane by 3D spoiled gradient-echo (SPGR) sequence . The spiTwo experienced readers independently assessed the morphology of the IVDs from L1/2 to L5/S1 according to the Pfirrmann grading system on sagittal T2 FSE images. The Pfirrmann grading system is primarily based on changes in signal intensity from the NP, the distinction between the NP and the annulus fibrosus, and disc height–25. The r were used to indicate very strong correlation (r = 0.80 to 1.00), strong correlation (r = 0.60 to 0.79), moderate correlation (r = 0.40 to 0.59), weak correlation (r = 0.20 to 0.39) or no correlation (r<0.20). All statistical evaluations were performed using PASW Statistics software . A P< 0.05 was considered statistically significant.Mean values were used for statistical analyses. The intraclass correlation coefficients (ICC) with 95% confidence intervals (95% CIs) were used to evaluate the reproducibility of T2, T2* and T1ρ relaxation times, and an ICC>0.75 was considered excellent agreement. The Kruskal-Wallis and Nemenyi tests were used to compare the differences in the T2, T2* and T1ρ values of discs and LFJs among the different Pfirrmann grades. A Pearson correlation analysis was performed to compare T2, T2* and T1ρ values of the disc and LFJs. The absolute value of correlation coefficients A total of 22 volunteers were recruited . In all, 202 LFJs and 101 IVDs from L1/2 to L5/S1 were assessed. The morphological IVD Pfirrmann grades on sagittal T2WI are shown in P<0.001), especially in the T1ρ values between grades II (166.93±15.87 ms) and III (108.98±10.31 ms) (P = 0.000). There were no significant differences in the T2, T2* and T1ρ values for the AAF . Although there were differences in the T2, T2* and T1ρ values for the PAF  and the T2, T2*, and T1ρ mapping of the IVD and LFJ are shown in  the PAF , we founPL = 0.961, PR = 0.855, rL = 0.081,rR = 0.033, rL = −0.169,rR = 0.046, rL = −0.004,rR = 0.047, The T2, T2* and T1ρ values for the LFJ cartilage tended to change with an increase in Pfirrmann grade Figs . The corPL = 0.032, PR = 0.026, rL = 0.148,rR = 0.215, rL = 0.021, rR = 0.087) nor the PAF T2* value  was correlated with that of the LFJ  and IV  , and grades III and IV  . A moderately negative correlation was found between the LFJ and the NP  and T2* values (r = −0.158)  .Quantitative MRI has attracted increasing attention over the past two decades as a way to evaluate articular cartilage and IVD, 26–29. Previous studies have reported the ranges of T2, T2* and T1ρ values for healthy and osteoarthritis (OA) cartilage in knees–34. We pThe changes in the molecular biochemical components in degenerated IVDs can be accurately evaluated by T2, T2* and T1ρ mapping. T2 mapping might be more sensitive to tissue hydration; however, T2* mapping might be more sensitive to collagen integrity, and T1ρ mapping can show slow-motion interactions between macromolecules and bulk water in the extracellular matrix, 26, 28.In this study, we noted different sensibilities for the T2, T2* and T1ρ values of the FJ in detecting degeneration of the LFJ with increasing Pfirrmann grades of the IVD. T2* and T1ρ values could detect LFJ changes with increasing Pfirrmann grades of IVD, but no significant results were found for T2 values. Stelzeneder D et al. reported comparable results regarding FJ T2 values in segments with normal and abnormal Pfirrmann scores. CompareAnother meaningful finding in this study was that the degenerative changes of the LFJ may correlate with IVD degeneration, as measured through T1ρ values, especially the NP and the PAF. We did not find any meaningful correlations for T2 and T2* values for the LFJ. A previous study found that FJs were weakly correlated with T2 values for the PAF according to axial T2 mapping. HoweverThe major limitation of our study was that there was no histological assessment of disc degeneration or LFJ cartilage. We should also point out that the T2, T2* and T1ρ values of the LFJ cartilage do not remove the effect of joint fluid, and this may be a result of relatively poor resolution of the mapping. However, there appears to have been a limited effect of joint fluid on our results.Our study uniquely assessed the feasibility of detecting IVD and LFJ degeneration using three quantitative biochemical methods on axial scanning. Our results demonstrated that T1ρ values are more sensitive than T2 and T2* values for assessing the early degenerative changes in the LFJ cartilage, and showed that LFJ degeneration may be correlated with changes in the NP and PAF of the IVD.S1 Text(DOCX)Click here for additional data file.S1 Fig(DOCX)Click here for additional data file.


Chronic total occlusion percutaneous coronary intervention (CTO-PCI) can improve angina and left ventricular ejection fraction (LVEF). These benefits were not assessed in populations with heart failure with reduced ejection fraction (HFrEF). We studied the effect of CTO-PCI on left ventricular function and clinical parameters in patients with HFrEF.Using cardiovascular magnetic resonance (CMR), we studied 29 patients with HFrEF and evidence of viability and/or ischemia in the territory supplied by a CTO who were successfully treated with CTO-PCI. In patients with multi-vessel disease, non-CTO PCI was also performed. Imaging parameters, clinical status, and brain natriuretic peptide (BNP) levels were evaluated before and 6 months after CTO-PCI.p = 0.029) and an increase in LVEF  were observed. There were no differences in LVEF improvement between patients who underwent non-CTO PCI (n = 11) and those without this intervention (n = 18); (p = 0.73). The number of segments showing perfusion defects was significantly reduced . Angina (p = 0.002) and NYHA functional class (p = 0.004) improved, and BNP levels decreased (p = 0.004) after CTO-PCI.A decrease in left ventricular end-systolic volume (160 ± 54 ml vs. 143 ± 58 ml; In this group of patients with HFrEF showing CMR evidence of viability and/or ischemia within the territory supplied by the CTO, an improvement in ejection fraction, left ventricular end-systolic volume and ischemia burden was observed after CTO-PCI. Clinical and laboratory parameters also improved.NCT02570087. Registered 6 October 2015.ClinicalTrials.gov  A chronic total occlusion (CTO) is defined as a coronary obstruction with thrombolysis in myocardial infarction (TIMI) grade 0 flow that persists for at least 3 months . This tyn = 256). A CTO was defined as an occlusion of at least 3 months of duration based on a previous angiogram showing the occluded vessel or clinical data on previous coronary ischemic events potentially related to a coronary occlusion. Patients who did not meet any of the exclusion criteria, detailed below, underwent cardiovascular magnetic resonance (CMR) study . The main reasons for exclusion were a lack of ischemia and myocardial viability in at least two contiguous CTO dependent myocardial segments by CMR , the presence of a pacemaker or an implantable cardioverter defibrillator  and surgical or percutaneous revascularization during the candidacy evaluation with no chance to perform basal assessments . The final study population included the 32 patients with successful CTO-PCI (82 % success rate).We prospectively collected data from consecutive patients referred to our institution for invasive coronary angiography from January 2011 to June 2013, selecting those with at least one CTO and LVEF ≤40 % measured by echocardiography, gated-SPECT or contrast ventriculography , or hospital admission within the previous 90 days due to decompensated heart failure, myocardial infarction or unstable angina. Additional criteria were iodine contrast or gadolinium allergy, aspirin or clopidogrel allergy, asthma, NYHA IV, chronic kidney disease with serum creatinine levels ≥2.5 mg/dl or glomerular filtration rate ≤30 ml/min/1.73 mTechnical criteria for exclusion were CTO distal vessel not visible through collateral circulation, CTO distal vessel diameter <2 mm or absence of acceptable vascular access.All CMR studies  were performed using a General Electric Signa HDxt 1.5-T scanner equipped with an 8-channel coil and cardiac-dedicated software. Perfusion studies were conducted using a gradient-echo turbo-field sequence prescribed in the left ventricular short-axis orientation, at the basal, mid-ventricular and apical levels after 4 min of intravenous administration of adenosine (Atepodin®) at a dose of 140 mcg/kg/min and simultaneous administration of 0.1 mmol/kg of gadobutrol  at 5 ml/s rate. Functional and volumetric assessment of the left ventricle (LV) was conducted by conventional Steady State Free Precession (SSFP) cine sequence, prescribed in sequential short-axis slices, and encompassing the entire LV as well as the 2-, 3-, and 4-chamber views. Typical temporal and in-plane spatial resolution of these images was 40 ms and 1.4 × 1.4 mm, respectively. Rest perfusion images were obtained at least 10 min after the stress perfusion study using the same sequence, location, and contrast injection protocol. At 10 min post-administration of the gadolinium dose for the rest perfusion study, late gadolinium-enhancement (LGE) images were obtained using a segmented inversion-recovery spoiled gradient echo sequence in the same location and identical spatial resolution as the cine images.th segment)  and end-diastolic (LVEDV) volumes, the endocardial and epicardial borders were manually traced at end-systole and end-diastole in the cine short-axis images using a dedicated software package . In addition, infarct size was quantified by planimetry of enhanced areas on the stack of short-axis images. Regional wall motion analysis was performed by visual grading of the cine images according to the 17-segment model proposed by the American Heart Association  as follont) Fig. . The preAny segment graded ≤2 was considered viable . Image aUnilateral or bilateral femoral puncture was the vascular access of choice. Antegrade approach was the choice in all cases, with retrograde approach being used in some re-attempts. With the intention being complete anatomical revascularization, non-CTO PCI was performed when myocardial viability was detected. In the presence of multivessel disease and appropriate distal beds for surgical revascularization, CTO-PCI was the first scheduled interventional procedure enabling patient referral to surgical revascularization in case of failure. If the patient was not a candidate for surgical revascularization, any non-occlusive stenosis was treated first, leaving CTO-PCI as the last procedure. The average time between PCI procedures was 4 weeks. Drug-eluting stents were implanted when feasible. Successful CTO-PCI was defined as the restoration of TIMI grade 3 flow with residual stenosis of less than 30 % and no immediate angiographic complications.Clinical follow-up visits were scheduled at 30 days, 3 months and 6 months after CTO-PCI. Angina status and NYHA functional class for dyspnea were assessed before and 6 months after successful CTO-PCI. Plasma levels of BNP were also obtained before the procedure and at follow-up using ADVIA Centaur® BNP chemiluminescence immunoassay and autoanalyzer . All patients included in the study had been on guidelines recommended medication for HFrEF for at least 3 months before CTO-PCI procedure. Furthermore, during the 6-month study period there were no changes in prescribed medical treatment for angina or heart failure according to data collected at each follow-up visit, and no cardiac resynchronization therapy devices were implanted.p < 0.05 was considered significant. Statistical analysis was performed using SPSS version 13.0 .In the descriptive analysis, categorical variables are presented as n and percentage. Continuous variables are presented as mean ± SD when normally distributed, and median (interquartile range [IQR]) otherwise. Group differences were evaluated using chi-square or Fisher exact test for categorical variables. Student t test and Mann-Whitney rank sum test were used for continuous variables. Comparisons between pre- and post-PCI clinical parameters, BNP levels, and CMR studies were performed by paired t-tests, Wilcoxon signed rank or McNemar test, as appropriate. CMR regional contractility and perfusion defect analysis were repeated, taking into account only those segments within the myocardium subtended by a CTO considered for PCI. Additionally, the difference in LVEF between baseline and 6-month follow-up CMR studies was analyzed in a mixed-effects multivariate model adjusted for baseline characteristics and non-CTO PCI procedure. A two-tailed In total, 32 patients with successful CTO-PCI were included in the study. Baseline demographic and clinical characteristics of this population are shown in Table Baseline angiographic characteristics of the 32 patients with successful CTO-PCI are shown in Table Myocardial viability in at least two contiguous CTO dependent myocardial segments was present in all the included patients. Only five patients (16 %) had ischemia in two or more myocardial segments subtended by a CTO (mean number of ischemic segments subtended by a CTO in the study population was 0.6 ± 1.4 per patient [range 0–6]).p = 0.029), along with a 6.4-point improvement in LVEF  (Table p = 0.25) and necrotic mass  were seen after successful CTO-PCI. There was no difference in LVEF improvement between the 11 patients (38 %) who underwent associated non-CTO PCI and the 18 patients (62 %) without this intervention . The improvement in LVEF after successful CTO-PCI persisted in a mixed-effects multivariate model adjusted for baseline ACEF score and non-CTO PCI (p < 0.001). The degree of LVEF improvement was not significantly modified by baseline parameters such as LVEF , history of hypertension , hypercholesterolemia  or diabetes , or treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers , beta blockers  or aldosterone receptor antagonists .At 6-month follow-up, CMR studies were performed in 29 patients (two patients refused the repeat CMR and 1 patient suffered sudden cardiac death before follow-up CMR). A significant decrease in LVESV was found  and the number of segments with severe hypokinesia, akinesia, or dyskinesia was significantly reduced . The same changes were seen when the analysis was restricted to recanalized CTO-dependent myocardial segments (Table p = 0.043). In the global analysis including 16 segments per patient, a trend toward a reduction in the number of ischemic segments was maintained .A total of 464 segments were available for perfusion analysis and 493 for regional contractility. The number of segments with normal wall motion or mild/moderate hypokinesia improved after successful CTO-PCI  and in BNP levels   (Fig. At 6 months after successful CTO-PCI a significant reduction, compared to baseline, was observed in the proportion of patients with angina (34.4 % vs. 3.1 %; In this study we show that in a small group of patients with CTO and HFrEF, selected for the presence of viability and/or ischemia in myocardial segments subtended by the occluded vessel by means of CMR study, a significant improvement in LVESV, regional contractility, LVEF and myocardial ischemia was observed after successful CTO-PCI.From a clinical point of view, an improvement in angina and NYHA functional class, along with a decrease in BNP levels was seen after CTO recanalization.To our knowledge, this is the first study to date evaluating the benefits of CTO-PCI in patients with HFrEF. The proportion of patients with history of previous myocardial infarction and the high prevalence of classic cardiovascular risk factors in this cohort are consistent with previous published data , 23. ImpCMR is a powerful tool over other modalities to assess viability in patients with reduced LVEF being considered for CTO-PCI and to determine improvement in LVEF after successful CTO-PCI in this population. The CMR findings in our study partially correlate with those reported by Baks et al. and Kirschbaum et al. , 10 BothOne third of our patients with successful CTO-PCI also underwent PCI of non-occlusive coronary stenosis. No differences in the degree of LVEF improvement were seen when this group was compared with patients who did not undergo non-CTO PCI, suggesting that changes in LV function parameters after successful CTO-PCI were derived from CTO recanalization. Baseline patient characteristics such as LVEF, targeted therapies for HFrEF and the presence of cardiovascular risk factors did not have a significant impact on the degree of LVEF improvement after CTO-PCI.Improvement in myocardial ischemia assessed by CMR adenosine stress perfusion imaging after successful CTO-PCI has been previously demonstrated in small series. Pujadas et al.  showed aInterestingly, changes in CMR parameters after successful CTO-PCI were associated with an improvement in NYHA functional class for dyspnea in our study, along with a significant reduction in BNP levels. These clinical outcomes had not been previously evaluated in the CTO-PCI field. Along with LVEF and NYHA functional class, BNP levels are a prognostic marker in the population with HFrEF and they can be a useful clinical tool to stratify the risk of adverse events in this population , 25. ImpFinally, the absence of procedural complications or any increase in the amount of myocardial necrosis in the present study may suggest that the CTO-PCI procedure is safe in selected patients with HFrEF.This study has several limitations worthy of mention. The first and main limitation is that this was a non-randomized study without a predefined control group; therefore, changes in LV function and volumes or in clinical parameters cannot directly be attributed to the CTO-PCI procedure, but may be related to conservative therapy. The second major limitation is the small sample size. Third, given the strict patient selection, the study may not be representative of the whole population with CTO and HFrEF. Finally, we did not perform a second angiography at 6 months after PCI in any of the patients. The major strength of this study is that it is the first report of CMR assessment of LV function after CTO-PCI to focus specifically on the important population of patients with HFrEF. The results derived from this study should be interpreted cautiously and prospective randomized controlled trials are warranted to validate these findings with more reliable clinical evidence.In this group of patients with HFrEF showing CMR evidence of viability and/or ischemia within the territory supplied by the CTO, an improvement in ejection fraction, left ventricular end-systolic volume and ischemia burden was observed after CTO-PCI. Clinical and laboratory parameters also improved.


Many studies showed electrocardiogram (ECG) parameters are useful for predicting fatal ventricular arrhythmias (VAs). However, the studies have several shortcomings. Firstly, all studies lack of effective way to present behavior of various ECG parameters prior to the occurrence of the VAs. Secondly, they also lack of discussion on how to consider the parameters as abnormal. Thirdly, the reports do not include approaches to increase the detection accuracy for the abnormal patterns. The purpose of this study is to address the aforementioned issues. It identifies ten ECG parameters from various sources and then presents a review based on the identified parameters. From the review, it has been found that the increased risk of VAs can be represented by presence and certain abnormal range of the parameters. The variation of parameters range could be influenced by either gender or age. This study also has discovered the facts that averaging, outliers elimination and morphology detection algorithms can contribute to the detection accuracy. Malignant spontaneous ventricular arrhythmias (VAs), namely ventricular tachycardia (VT) and ventricular fibrillation (VF) can cause sudden cardiac arrest. Patients who are susceptible to VT/VF always have a risk of sudden cardiac death . TherefoResearchers has discovered that ECG signals comprise non-invasive parameters that could reflect underlying VT/VF –5. The EIn order to track development of the ECG parameters as promising predictors, a comprehensive review is necessary. A few reports, such in , 4 seem Second, the reports are also not clearly in defining how to consider the patterns as abnormal. For example, researchers in  only prei) as predictors when there are difficulties in measuring the QTi correctly. The discussed problems so far leave three important questions unanswered:i.How to effectively present the patterns of the ECG parameters prior to occurrence of the VAs?ii.How to identify abnormal patterns for the parameters?iii.How to improve detection accuracy of the ECG parameters?Third, these reports have not included approaches to increase detection accuracy of the parameters. The detection accuracy is important because the abnormal patterns may undetected if the parameters fail to be accurately identified. A report that is presented in  stated cThese problems are selected to be solved since the solutions are beneficial in two aspects. Firstly, they could speed up the process of reviewing the parameters. It is because the brief information of the parameters will be firstly presented in a table before further discussion. The solutions simplify relevant information for the ECG parameters and thus researchers can have a clear idea of the parameters. Secondly, they provide a way to improve quality of researches. The researches that have unsatisfied prediction result can apply the solutions in the review to produce better outcome.i.This paper groups the patterns for the increased risk of the arrhythmias based on behavior changes of these ECG parameters before the arrhythmias. Some parameters are absent in normal condition of cardiac patients, and only present before the VAs onset. There are also parameters that indicate the future VAs if prolong or decrease until certain ranges. The behavior changes could be increase, decrease or presence. The groups of the parameters will be further discussed in details in Sect. ii.i [This paper describes abnormal behaviors of the parameters according to their normal ranges. As aforementioned, the parameters, which have value either higher or lower than certain range, have been considered as increased risk for the arrhythmic events. For instance, patients with TpTe greater than 100 ms have increased risk of the VT/VF –9. Gendei .iii.The parameters are mostly derived from two ECG components, namely QRS duration and T-wave. This paper has identified several suggested methods from literatures to increase correct detection rate of the parameters used in the VAs prediction.To address above the problems, this article covers results of works as follows:This paper consists of six sections. It begins with an Introduction section, followed by four sections that describe ECG parameters that can predict the life-threatening VT/VF, and ends with a Conclusion section. The first section explains selection of the potential ECG parameters. The next two sections are inline with the identified three problems. And, the fourth section provides a discussion on the selected ten ECG parameters that have predictive value for occurrence of VAs.i/QT dispersion, signal-averaged ECG, and HRV [There are many ECG parameters that have been reviewed before, such as early repolarization, QT and HRV , 4. HoweAs illustrated in Fig. Table c/QTvi/QTvi/QTd, HRV, HRT, iCEB, QT dynamicity and TpTe are parameters that can be easily measured if relevant ECG components are detected. In some cases, the parameters might have different predictive result in patients with different diseases. Therefore, the parameters are tested for various diseases. The details are further discussed in the following paragraphs.As it can be seen from the Table, the parameters are derived from different ECG signal components, such as QRS complex, which can be used for deriving fQRS, ER and VLP. In addition, based on methods to identify parameters, the parameters are categorized into morphology based and measurable. QTc/QTvi/QTvi/QTd, HRV, HRT, iCEB, QT dynamicity and TpTe are parameters that can be easily measured if relevant ECG components are detected. In some cases, the parameters might have different predictive result in patients with different diseases. Therefore, the parameters are tested for various diseases. The details are further discussed in the following paragraphs.As shown in Table i) and T wave; the rest are derived from QT interval and ST segment. The former components are easier to be acquired since they only involve detection of one component of the signal, i.e. QRS complex, R wave or T wave. Thus, most of the parameters, such as fQRS, HRV and TpTe are derived from these components. Whereas, the latter components require detection of both QRS complex and T wave to derive the parameters, where failure detection in either one component can cause the derivation unsuccessful.Figure Figure The ECG parameters are useful in predicting the VAs for patients with certain diseases. As shown in Fig. c), QT interval variability (QTvi), QT interval dispersion (QTd), fQRS, early repolarization (ER), ventricular late potentials (VLP), HRV, HRT, index of cardio electro physiological balance (iCEB), QT dynamicity, TWA as well as TpTe. The parameters have various behavior changes prior to VA onset.Section c) [vi [d [Table c)  /QTvi [2c) [vi  /QTd [8,) [vi [d , turbule) [vi [d , QT dyna) [vi [d , 27, as ) [vi [d , 25 migh) [vi [d , 29 and ) [vi [d , 25. The) [vi [d , 31 is tc/QTvi/QTd, TO of HRT, TWA and TpTe. Whereas, the parameters that have lower values than normal heart condition are HRV and TS of HRT. The parameters, such as fQRS, VLP and ER, in which their presence indicate the increased risk of VAs can also be identified using predefined thresholds. The details of the parameters are discussed further in the following subsections. Secondly, the researchers compare the parameters in two groups, namely healthy people and patients prone to the arrhythmias [The increase or decrease of the parameters can be identified according to certain ranges. In reviewed literatures, researchers utilized two methods to define abnormal ranges. Firstly, the researchers match the parameters with predefined threshold values that indicate the abnormal ranges. The parameters that have abnormal prolongation prior to the arrhythmias are iCEB, QT dynamicity, QThythmias . Using eIn order to know whether the parameters are beneficial in clinical practice to guide decision making, a cutoff for predicted probability is needed. An optimal cutoff is defined by decision context. Once the cutoff is selected, clinical usefulness measures can be defined . The meaIn addition, Ac is a ratio of total correct assessments to all assessments, where Ac = (TN + TP)/(TN + TP + FN + FP). Next, Se is related to an ability to correctly identify patients with VT/VF risk, where Se = TP/(TP + FN). Sp is related to an ability to correctly identify either normal people or patients with VT/VF risk, where Sp = TN/(TN + FP). And, +P is a probability where a patient with positive test is actually at risk of VT/VF, where +P = TP/(TP + FP). These four measures represent a perfect test if 100% is obtained. Using the aforementioned clinical usefulness measures, the ten potential ECG parameters are discussed together with their behavior changes preceding VAs onset in the following subsections.The VLP is a high-frequency and very-low-intensity signal that is localized at the end of QRS duration, and on the beginning part of ST segment , as showThe presence of the VLPs can be identified using predefined thresholds. According to studies , 35, theThe VLP that is detected from signal-averaged electrocardiogram (SAECG) system could be a useful VT/VF predictor for BS and STEMI patients. The VLP has been obtained from 24 h ECG monitoring produced a P value of 0.003 in a recent BS study . This inThe fQRS is additional spikes within QRS duration without bundle branch block , which cIn a recent study , researcThe fQRS is a significant predictor for patients with ARVCM , HOCM 1 and IDCMSimilar to both VLP and fQRS, the ER can also be detected at QRS duration. ER is a notching or slurring morphology of the terminal QRS in at least two contiguous inferior or lateral leads , 38, 39,The notched ER and slurred ER patterns can be determined using an algorithm as shown in Kentta et al. study . The algThe ER is associated with increased risk of fatal VT/VF in patients with CAD  and VF hThe TpTe is defined as time interval between T wave peak amplitude and the end of T wave [44. TpTe can be a useful predictor for patients with diseases, such as Chagas disease , BrugadaThe definition of abnormal prolongation for TpTe is value larger than 100 ms –9. The pi is measured from the start of Q wave to the end of T wave [c is QTi corrected for heart rate [d is difference between maximum and minimum of QTi [vi is a ratio comparing repolarization variability to HRV [i related parameters are as shown in Eqs. The QTf T wave . QTc is art rate , 46. QTdm of QTi . And, QTy to HRV . Equatioi is measured from one R wave to the next R wave before the QTic, QTd and QTvi are values greater than 460 ms, 65 ms and −0.47 respectively [i usually ranged from 0.36 to 0.44 s. From these ranges, adult males have shorter range than adult females, and people from age 1 to 15 are in between them, as shown in Table i with value greater than 0.47 s is considered as dangerous for any gender or age.The abnormal ranges for QTectively , 48. Accectively , the norvi on ICD has predictive value for patients with structural heart disease, an observed result or more extreme is obtained in more than 96% of experiments [i has no predictive value for patients with no recurrence of VAs and AMI, an observed result or more extreme result is achieved in less than 1.1 and 0.1% of experiments respectively [Measuring of the QT related parameters can detect patients who are at increased risk of developing VT/VF and with diseases such as structural heart disease , AMI 2424 and VAeriments . Assuminectively , 24.The TWA is a repeating ABAB pattern in the morphology and amplitude of T wave or ST segment , as illuThe TWA can be either an independent predictor  using Eqμ and σ are mean and standard deviation of spectral noise, P0.5 is alternans power at 0.5 cycles/beats and (P0.5 − μ) is alternans voltage. The TWA is considered as significant if K score is more than three [an three .The HRT is a short-term fluctuation in sinus cycle length that follows spontaneous ventricular premature complex, in which consists of brief heart rate acceleration, followed by more gradual heart rate deceleration . The acc−2 and RR−1 are two intervals immediately preceding ventricular pre- mature complexes (VPC); and RR1 and RR2 are two RR intervals immediately after compensatory pause.The another parameter derived from HRT is TS, which represents the deceleration of heart rate. The TS can be measured based on the maximum positive regression slope assessed over any five consecutive sinus rhythm RR interval within the first 15 sinus rhythm RR intervals after ventricular premature contraction . Therefoi [Both HRT and TWA have different thresholds to identify abnormal behavior. The abnormal TO of HRT in patients have value 0% and above. On the other hand, the abnormal TS of HRT is value less than 2.5 ms per RRi , 54. Andi , 25.The combined TWA and HRT on 12-leads ECG and implantable cardioverter defibrillators (ICD) indicates VT/VF risk in patients with AMI , 25. AccThe HRV has both time domain and frequency domain variables that have predictive power for the arrhythmic events. Examples of the time domain variables are standard deviation of all RR/normal-to-normal (NN) intervals (SDNN) and mean of RR/NN interval (RRm) , which ci and LF are found significantly decreased in females, i.e. P < 0.05.The abnormal HRV can be recognized by comparing both normal range of HRV in healthy people and abnormal range in patients prone to the arrhythmias. In average, normal range of HRV for females is low than males . StatistIn this review, the HRV is the only one predictor that is used in short term VT/VF prediction. Ebrahimzadeh et al.  shows tiThe iCEB is a hypothesized that equivalent to cardiac wavelength, which is a product of effective refractory period and conduction velocity (ERP × CV). It reflects balance and imbalance of depolarization (QRS duration) and repolarization (QTi) of the cardiac electrophysiology, as shown in Fig. The iCEB increased prior to TdP VT/VF (LQTS) and decreased before non-TdP VT/VF (BS). Assuming the iCEB has no predictive value for both LQTS and BS, an observed result or more extreme result is achieved in less than 0.01% of experiments .i and RRi [i/RRi, as expressed in Eq.  or interpolation (replacing the outliers) can be performed . The defThe third method is application of morphology based algorithms, in which as discussed in Sect. There are also some additional recommended settings in the reviewed literatures for the parameters. For instance, suggested frequency band for LF and HF in HRV are 0.04–0.15 and 0.15–0.4 Hz respectively , 55. Whec/QTvi/QTvi/QTd, fQRS, ER, VLP, HRV, HRT, TWA as well as TpTe. These parameters are popular in recent studies and thus investigation regarding to the parameters is necessary.As showed in Sect. The aforementioned parameters have achieved significant prediction results in most of the studies; however, some literatures reported that predictive value of the parameters in patients with certain heart diseases are insignificant. From Table vi [Furthermore, most of the reviewed literatures may only reflect the occurrence of VT/VF after a few months or years (long-term) –9, but nvi . The convi , 60 may Section The ranges can only be fit after the parameters have been detected and measured. The detection can be missed and the measurement can be inaccurate if lack of appropriate detection or measurement methods. The methods are collected from literatures as in Sect. In conclusion, this study reviewed ten ECG parameters for prediction of VT/VF from 25 articles, as shown in Table


Cardiac growth after heart transplantation (HTx) in children has been reported to be normal in the long-term follow-up. The aim of our study was to evaluate ventricular volumes, mass and function in a cohort of pediatric HTx patients using cardiac magnetic resonance (CMR).Seventy-five pediatric HTx patients  were assessed by CMR 11.2 ± 5.4 years after HTx . Right (RV) and left ventricular (LV) volumes and LV mass were derived from short-axis cine images. The results were compared with a healthy reference population of 79 patients  from the German Competence Network for Congenital Heart Defects. LV strain measurements were performed using CMR feature tracking (FT) software  and were compared with a group of 46 healthy controls .Both LV and RV enddiastolic and -systolic volumes were significantly smaller in the HTx group compared to healthy controls while LV mass was significantly higher in HTx patients. RV and LV ejection fraction were both reduced in HTx patients. While LV longitudinal (LS) and radial strain (RS) were significantly reduced, LV circumferential strain (CS) was preserved in the HTx group. LV-CS and LV-RS correlated with LV enddiastolic volume . LV mass was inversely related to diastolic LV function assessed by early diastolic strain rate .Compared to healthy references, children and adolescents after HTx show impaired cardiac growth, increased myocardial mass and reduced global systolic pump function. Smaller LV dimensions are associated with impaired systolic strain while higher LV myocardial mass is related to diastolic function.


Background. This study was undertaken to determine relative contributions of phosphorylation and oxidation to the increased activity of calcium/calmodulin-stimulated protein kinase II (CaMKII) in juveniles with cardiac myocyte dysfunction due to increased pressure overload. Methods. Juvenile rats underwent abdominal aortic constriction to induce heart failure. Four weeks after surgery, rats were then randomly divided into two groups: one group given valsartan  and the other group given placebo (HF + PBO). Simultaneously, the sham-operated rats were randomly given valsartan  or placebo (Sham + PBO). After 4 weeks of treatment, Western blot analysis was employed to quantify CaMKII and relative calcium handling proteins (RyR2 and PLN) in all groups. Results. The deteriorated cardiac function was reversed by valsartan treatment. In ventricular muscle cells of group HF + PBO, Thr287 phosphorylation of CaMKII and S2808 phosphorylation of RyR2 and PLN were increased and S16 phosphorylation of PLN was decreased compared to the other groups, while Met281 oxidation was not significantly elevated. In addition, these changes in the expression of calcium handling proteins were ameliorated by valsartan administration. Conclusions. The phosphorylation of Thr286 is associated with the early activation of CaMKII rather than the oxidation of Met281. With the increasing incidence of cardiovascular disease, the study of its pathogenesis and treatment has become a focus of medical research. Heart failure (HF) is a pathophysiological process involving systolic and/or diastolic cardiac dysfunction in which the heart cannot meet the metabolic needs of the body. Pediatric heart failure is primarily caused by congenital heart disease, myocarditis, cardiomyopathy, or severe respiratory disease , 2. Alth2+/calmodulin-dependent protein kinase II (CaMKII) plays a key role in the development of HF [α, β, γ, and δ) with differential distribution and function within particular tissues and cell types. CaMKIIδ is the isoform primarily expressed in the heart, while a small amount of CaMKIIγ can also be detected in cardiac tissue. Within cardiac myocytes CaMKIIδc is mainly localized in the cytoplasm, whereas CaMKIIδB and CaMKIIγ are present in the nucleus [In myocardial cells, dysfunction of proteins associated with calcium homeostasis is thought to play a major causative role in cardiac dysfunction, electrophysiological instability, and arrhythmia . Researcnt of HF . CaMKII nt of HF . There a nucleus , 8.δc transgenic rats demonstrate increased incidence of arrhythmia. This suggests that CaMKII regulates cardiac electrical activity, possibly by inducing sarcoplasmic reticulum (SR) calcium leakage through phosphorylated RyRs [δ-mediated increase in SR calcium leak through RyRs accompanies heart function decompensation, while the inhibition of CaMKIIδ improved many symptoms associated with heart failure such as expansion of the heart chamber, pulmonary edema, myocardial fibrosis, and apoptosis [In cardiovascular disease, the overexpression of CaMKII leads to hyperphosphorylation of LTCC, ryanodine receptors (RyRs), and SERCA/PLN, which in turn contribute to cardiac excitation contraction coupling (ECC) and heart dysfunction . CaMKIIδted RyRs . Animal poptosis .In addition to phosphorylation-mediated activation sites, CaMKII may have other activation sites mediated by reactive oxygen species (ROS) . In turnHere, we investigate the mechanisms of CaMKII-mediated calcium regulation in myocardial cells. We also explore the effects of valsartan on heart failure and on the phosphorylation and oxidative activation of CaMKII in juvenile rats with cardiac dysfunction. Our findings inform future research on novel therapeutic approaches for the treatment of heart failure in pediatric patients.Experiments were performed using male juvenile Sprague-Dawley (SD) rats aged from 21 to 28 days, with a body weight from 60 to 80 g. Animals were housed individually with free access to food and water and were maintained on a 12 : 12 h light-dark cycle with independent ventilation, temperature, and humidity controls. All animal studies were performed in accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health, and all efforts were made to minimize suffering. The Ethics Committee of the Children's Hospital of Chongqing Medical University (permit number: SYXK2007-0016) approved all experiments. All animals (SPF grade) were purchased from the Animal Experiment Center of Chongqing Medical University.Naive rats were anesthetized with an intraperitoneal injection of 10% chloral hydrate (0.3 ml/100 g). Heart failure was induced by abdominal aortic constriction (AAC) according to a previously described method , 15 and Four weeks after the ACC procedure, valsartan  solution was prepared fresh before intragastric administration by dissolving the drug in distilled water with carboxymethyl cellulose (CMC), resulting in a final CMC concentration of 0.5%. Every day for 4 weeks, valsartan  or Rats were anesthetized with 10% chloral hydrate and echocardiography was performed by ultrasound  with a 12.5 MHz linear array ultrasound transducer. The left ventricle (LV) was assessed in both parasternal long-axis and short-axis views at a frame rate of 120 Hz. End-systole and end-diastole were defined as the phases in which the LV had the smallest and largest area, respectively. LV internal dimension systole (LVIDs), LV internal diastolic diameter (LVIDd), LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), LV ejection fraction (LVEF), and LV fractional shortening (LVFS) were measured from the LV M-mode tracing with a sweep speed of 50 mm/s at the mid-papillary muscle level.μm thickness were cut and mounted on silanized slides. Mounted sections were dried in an oven overnight at 60°C. Morphometric analysis of heart tissues from all experimental groups utilized hematoxylin and eosin (H&E) [Freshly isolated rat hearts from all experimental groups were fixed in 4% paraformaldehyde for at least 24 hr. Heart tissues were then processed routinely for dehydration with 70–100% graded alcohol and embedded in blocks of paraffin wax. Serial sections of 4 in (H&E)  stainingin (H&E) . Cross-sμg per lane) from the homogenate of isolated ventricular myocytes was separated by 10% SDS-PAGE  and transferred to a PDVF membrane. The PVDF membrane was blocked with T-TBS containing 5% BSA  at room temperature for 1 hour and then incubated with rabbit anti-phospho-CaMKII , rabbit anti-oxidized-CaMKII , rabbit anti-CaMKII , mouse anti-PLN , rabbit anti-phospho-PLN , rabbit anti-phospho-RyR2 , mouse anti-RyR2 , and mouse anti-GAPDH  antibodies overnight at 4°C. The membranes were then washed with Tris-buffered saline-Tween (0.05%) solution and incubated with HRP-conjugated secondary antibody  for 1 hour. The membranes were developed using a super ECL assay kit  and a G-BOX imaging system .Whole protein was extracted from cardiac tissue  and quantified using a BCA assay . Total protein .All statistical analyses were performed with SPSS software (version 19.0). For normal distribution, comparisons of LV diameter, LV volume, heart function, left ventricular mass index (LVMI), and levels of phosphorylated CaMKII, oxidized CaMKII, CaMKII, phosphorylated RyR2, RyR2, phosphorylated PLN, and PLN among all the experimental groups were performed using one-way ANOVA, and the LSD method was applied to estimate pairwise comparisons. For nonnormal distribution, intergroup comparisons of cross-sectional area of myocardial fibers and collagen deposition were assessed with the use of the Kruskal-Wallis P ≤ 0.001); no significant changes were observed in the ACC-surgery rats treated with valsartan relative to the sham-operated, vehicle-treated control animals (P > 0.05). However, heart functions between Sham + PBO and Sham + Val are significantly different. LVIDs were increased (P = 0.044) with decreasing LVEF and LVFS  in the Sham + Val group compared to the Sham + PBO group.To investigate the protective effects of valsartan, we evaluated cardiac function using a Doppler echocardiogram. As shown in P = 0.006).As shown in P ≤ 0.001)  . The expression of oxidized CaMKII, which represents reactive oxygen species- (ROS-) mediated CaMKII activation, did not differ among the four groups (P > 0.05)    (Figures We performed Western blot analysis to determine whether valsartan affected the levels of phosphorylated CaMKII and oxidized CaMKII following AAC. As shown in Figures  Figures . We also Figures . The lev Figures  and PLN  Figures  were ele Figures  was decrWe found that AAC surgery, which resembles a cardiac dysfunction condition, significantly reduced the LV ejection fraction in juvenile rats. This is consistent with findings reported by others , 21. Our2+/CaM or the activation of phosphorylation and/or the oxidation sites of CaMKII. However, even if the concentration of Ca2+/CaM is very low in the basal state, there is still some small proportion of CaMKII proteins that are activated by autophosphorylation of Thr286/287 [In the basal state, CaMKII is inactivated by the connection of the modulate region and the catalytic domain of CaMKII. In heart failure, increased CaMKII activity is initially through linking to Car286/287 –25. ROS-r286/287 –29. An er286/287 . Anotherr286/287 .Our study showed that the cardioprotective effect of valsartan is mediated by direct interruption of CaMKII signaling. Compared with sham-operated rats, phosphorylation of the Thr287 site of CaMKII was significantly increased in pups with overload pressure-induced cardiac dysfunction. However, there was no significant increase in the oxidation of Met281, suggesting that in early-stage heart dysfunction CaMKII is activated through phosphorylation rather than oxidation. Whether this is because of a low level of oxidative stress in rats with early-stage heart failure needs further research.2+ entering into cardiomyocytes triggers a large amount of Ca2+ released through RyR2 from the sarcoplasmic reticulum. During the diastolic period, most of the released Ca2+ was retaken by RyR2 from the cytoplasm. Dysfunctional RyR2 response to abnormal Ca2+ leak can deteriorate arrhythmia. The phosphorylation of PLN decreases in cardiac dysfunction in juveniles when compared with controls. Dephosphorylation of PLN induces active monomeric PLN, which can serve as an inhibitor of SERCA2a, causing low affinity of SERCA2a to Ca2+ and accelerating the progress of HF. In our study, valsartan also shows a protective role in maintaining calcium homeostasis through restoring the protein level of RyR2 and PLN.In addition, expression of RyR2 was remarkably increased in vehicle-treated AAC rats, contrasting that in vehicle sham rats. During the myocardial contractile period, a small amount of CaIn conclusion, valsartan shows a protective effect on the heart failure in juvenile rats maybe through the pathway of calcium handling in cardiomyocytes, especially by attenuating phosphorylation of CaMKII.


Whether type 2 diabetes mellitus (DM) in the absence of hypertension (HTA) and coronary artery disease (CAD) affects left ventricular (LV) phenotype and function among asymptomatic DM patients that can be easily discovered in everyday practice, what is the clinical risk profile for diabetic cardiomyopathy and how HTA and CAD modulate LV structure and function above diabetic cardiomyopathy, are still incompletely answered questions.In 210 DM patients  and 80 healthy individuals, comprehensive echocardiography including speckle tracking strain and strain rate analysis, was done.long) and early diastolic longitudinal strain rate (SRlong E) were impaired in group I compared to control, even when EF was preserved. Peak circumferential strain (Scirc) was impaired only when DM was associated with HTA or CAD. In multivariate analysis DM was significantly and independently from HTA, CAD, age, gender and body mass index associated with: increased LV mass, concentric LV remodeling, lower EF, FS, MAPSE, Slong, SRlongE and distorted diastolic parameters. DM duration, glycosylated hemoglobin, microalbuminuria and retinopathy, were not independent predictors of LV geometry and function.Compared to control DM patients without HTA and CAD had increased LV mass, more frequently concentric remodeling, impaired LV relaxation and lower LV ejection fraction (EF), fraction of shortening (FS) and mitral annular plane excursion (MAPSE). Addition of HTA further impaired EF, FS and MAPSE and aggravated diastolic dysfunction, whereas concomitant CAD further impaired FS and MAPSE. Peak global longitudinal strain (SDM per se has strong and independent influence on LV phenotype and function that can be detected by conventional and speckle tracking echocardiography in everyday clinical practice, even in asymptomatic patients. We could not confirm that these changes were independently related to duration of DM, quality of metabolic control and presence of microvascular complications. Concomitant HTA or CAD furthermore distorted LV systolic and diastolic function. A strong correlation between cardiovascular diseases and diabetes mellitus type 2 (DM) has been persistently shown –3. AdultThe primary aim of this study was to investigate the impact of DM without HTA or CAD on LV phenotype, its systolic and diastolic function, using conventional and speckle tracking echocardiographic techniques among asymptomatic patients. The second aims were to compare these results with the influence of DM coupled with HTA or CAD and to define clinical risk profile for diabetic cardiomyopathy.lone DM), group II (DM patients with HTA and no CAD) and group III . The inclusion criteria for group I were: asymptomatic DM patient without HTA and CAD  and with negative stress echocardiography. The inclusion criteria for group II (DM+HTA) were: DM patients with HTA and no CAD  and with negative stress echo. The antihypertensive therapy was optimized for patients in group II and they had well controlled blood pressure (i.e. BP < 140/90 mmHg) at least 7 days before echocardiographic examination. The inclusion criteria for group III (DM+CAD) were: DM patient without HTA and with CAD  and with positive stress echo (i.e. documented inducible ischemia). For patients in group III medical therapy was optimized and they were without anginal pain at least 7 days before echocardiographic examination. Initially 492 consecutive DM patients were examined. Patients with unstable angina pectoris, pervious myocardial infarction, uncontrolled HTA, congenital heart diseases, primary hypertrophic and dilated cardiomyopathy, significant heart valve disease, left bundle branch block, atrial fibrillation, severe form of ventricular arrhythmias (Lown class IV and V), anemia, malignancy, severe obstructive pulmonary disease, disorders of thyroid function, myocarditis and deformities of the chest that technically limit echocardiographic examination were excluded. The final study population included 210 DM patients . For the control group, 80 individuals similar in age and gender as DM patients and with normal echo studies, without DM, cardiology or other major health problems were pooled from the clinic database, and called to participate in the study. This prospective, single centre study was conducted in the outpatient cardiology clinic “Corona”, Uzice, from the beginning of January 2012 to the end of May 2014. This study was approved by the Ethics committee, School of medicine, Belgrade University and was a part of the PhD thesis of BL. Written informed consent was obtained from all patients who participated in the study.In order to evaluate the influence of DM on LV phenotype and function and to compare it with the additional influence of HTA or CAD, three study groups were defined: group I , blood pressure, ECG and laboratory analysis including measurements of blood glucose level, serum lipid levels, and concentration of glycosylated hemoglobin (HbA1c), presence of microalbuminuria and examination of eye fundus in order to detect diabetic retinopathy.Echocardiographic examination was done using a commercially available ultrasound machine (ESAOTE My LAB 30 CV) and 3 MHz multifrequency transducer using second harmonic technology. Echocardiography included conventional resting 2D examination and quantification of LV mechanics using 2D speckle tracking strain and strain rate analysis. The studies were stored in digital format with coded patient’s identity. Analysis of echocardiographic studies were done off- line by experienced echocardiographer (BL) blinded to patient’s identity.Following parameters were measured for the evaluation of LV geometry and function according to ASE recommendation : LV end Pulmonary venous inflow was obtained by pulsed wave Doppler in apical 4-chamber view . A two oM-mode images were obtained at the LV septal, lateral, anterior, and posterior borders of the mitral ring in the apical 2C- and 4C views, and an average mitral annular plane systolic excursion (MAPSE) value was calculated .Flow propagation velocity  of the mitral inflow was measured in the apical 4-chamber view, using color flow imaging with a narrow color sector. The M-mode scan line was placed through the center of the LV inflow blood column from the mitral valve to the apex. Then the color flow baseline was shifted to lower the Nyquist limit so that the central highest velocity jet became blue. Vp was measured as the slope of the first aliasing velocity during early filling, measured from the mitral valve plane to 4 cm distally into the LV cavity .Tei index was measured as previously described [interval a). The sample volume was then located in the LV outflow tract, just below the aortic valve  for the measurement of LV ejection time . The interval a includes the isovolumic contraction time (IVCT), the ejection time (ET) and the isovolumic relaxation time (IVRT), and the Tei index was calculated as (a-b)/b, also expressed by the formula IVCT+IVRT/ET.escribed . The samEarly diastolic mitral annular velocity was measured for septal and lateral mitral annulus by tissue Doppler and averaged for Eprim and then E/Eprim ratio was calculated.long; %), and early diastolic longitudinal strain rate  were measured for each of the 16 segments and then averaged. From short axis view at the level of papillary muscle peak circumferential strain  were measured for six segments and then averaged. Longitudinal and circumferential strains are shown in absolute values.Quantification of LV mechanic was done according to the recommendation using 2D speckle tracking echocardiography . A standT test, analysis of variance (ANOVA) and Pearson Chi square test were used for group comparisons. Linear regression and binary logistic analysis was used to assess correlation between dependent variable and independent predictors. To assess the reproducibility of myocardial strain and strain rate measurements intra-class correlation coefficients (ICC) was done. All p values less than 0.05 were considered significant. All data were analyzed using SPSS 20.0 (IBM corp.) statistical software.Data are presented as count (percent) or mean ± standard deviation, depending on data type. The study included a total of 210 patients with DM and 80 healthy volunteers. Baseline characteristics of the study groups are shown in Table Comparison of conventional echocardiographic parameters between groups is presented in Table p < 0.05) and peak longitudinal strain rate in early diastole (p < 0.05), whereas peak circumferential strain was impaired only when DM was associated with HTA or CAD. Among patients with DM, presence of CAD was associated with further decrement of peak longitudinal and peak circumferential strains.Left ventricular mechanic evaluated by longitudinal and circumferential strain and longitudinal strain rate are presented in Table In order to investigate whether DM without CAD or HTA has impact on LV function even when LV ejection fraction is preserved, comparison between healthy control and subgroup of patients from group I with EF ≥ 55% was done. DM patients with no HTA or CAD and with preserved ejection fraction (i.e. EF ≥ 55%) had increased LV mass, LV mass index, LA volume and LA volume index, lower EF, lower longitudinal systolic LV function , higher myocardial performance index and impaired parameters of diastolic LV function compared to control Table .Table 4Cp < 0.001), LV mass index , LA volume , LA volume index , LV ejection fraction , LV fraction of shortening , MAPSE , E/A ratio , E deceleration time , Isovolumic relaxation time , Eprim , Vp , myocardial performance index , Slong  and SRlongE .In order to evaluate impact of age, gender, BMI, DM, HTA and CAD on LV phenotype , parameters of systolic and diastolic LV function linear regression and binary logistic analysis was done Table . The preIn order to analyze whether duration of DM, quality of metabolic control (HbA1c) and presence of microvascular complications  are associated with LV phenotype and LV function among DM patients, regression analysis was done. None of the parameter of DM duration and severity was significant and independent predictor of analyzed parameters of LV phenotype and LV function (results are not shown).long (ICC 0.91), Scirc (ICC 0.78) and SRlongE (ICC 0.87).The echocardiographic studies were analyzed by experienced ultrasonographer (BL) The intraobserver variability was very good for SThe present study evaluated influence of type 2 DM on LV phenotype  and LV function using conventional and speckle tracking echocardiography. The results pointed to several interesting things. First, DM was associated with greater LV mass, LV concentric remodeling, bigger left atria, impaired LV systolic function and impaired LV relaxation independently of age, gender, BMI, HTA and CAD. Addition of HTA further impaired LV ejection fraction, fraction of shortening and MAPSE and aggravated diastolic dysfunction. Concomitant CAD lowered furthermore LV fraction of shortening and MAPSE. Second, DM patients without CAD and HTA, had impaired longitudinal systolic and longitudinal diastolic function , independently from other cofounding variables, whereas circumferential systolic function was impaired only when DM was associated with HTA or CAD. Third, even asymptomatic DM patients without HTA and CAD and with preserved EF (ie EF ≥55%) had increased LV mass coupled with both systolic and diastolic impairment compared to control. Forth, LV changes were not independently related to DM duration, quality of metabolic control and presence of microvascular complications.Discovery of diabetic cardiomyopathy or subtle changes in LV morphology and function in asymptomatic diabetic patients without other risk factors is challenging in everyday clinical practice. Two major hallmarks, diastolic dysfunction and cardiac hypertrophy in the absence of CAD and HTA are suggested as cornerstones for diagnosis of diabetic cardiomyopathy among patients with type 2 DM , at leaslone DM (i.e. without HTA and CAD) had LV hypertrophy (i.e. LV mass index above reference points), LV mass and LV mass index were increased compared to matched control. Increased LV mass is negative prognostic marker, an independent risk factor for sudden death and ventricular arrhythmias and might contribute to increased cardiovascular risk among DM patients.The impact of DM on LV mass has been extensively investigated. Santra et al. in 135 normotensive individuals, half with DM and half healthy, reported higher LV mass in DM patients compared to controls . In the Left atrial size is often referred to as HbA1c of diastolic dysfunction and LV filling pressure. Our results support the observation of Atas et al. who found among normotensive DM patients without symptomatic cardiovascular disease higher volume, impaired compliance and contractility of the left atrium, even when LV geometry and LV systolic function were within normal limits .lone DM. Although EF in the majority of these patients was above 55%, the mean value of EF for the group was significantly lower compared to matched control. Data regarding this issue in literature are diverse. In retrospective SOLVD study (Studies of Left Ventricular Dysfunction) that included 2821 participants with asymptomatic LV dysfunction, significant interplay between DM and ischemic cardiomyopathy as risks for progression from asymptomatic LV dysfunction to symptomatic heart failure was reported [In our study, ejection fraction and fractional shortening were significantly lower in DM groups compared to control, including patients with reported . DM was reported . Howeverreported .lone DM compared to controls and decreased further with CAD and HTA. While EF is more related to radial LV function, MAPSE represents the global change of the LV in the long-axis direction. Hu et al., reported that reduced MAPSE is a consequence of longitudinal function impairment primarily caused by ischemia, fibrosis or increased wall stress, the latter two frequently present in diabetic cardiomyopathy [MAPSE in our study was significantly lower in patients with myopathy .lone DM. The explanation for these findings might be the interaction between longitudinal and circumferential myofibers suggested by Cioffi et al. [In our study peak global longitudinal strain and early diastolic longitudinal strain rate were impaired in DM patients without HTA and CAD, compared to control. In normotensive DM patients with normal coronary artery and preserved EF, Zoroufian et al. also found decreased longitudinal strain and higher LV dyssynchrony based on segmental longitudinal strain . Eranndei et al. . In shorlone DM is coupled with impaired LV relaxation that becomes even more impaired in DM patients with HTA. In our study E/Eprim ratio was significantly higher in all DM patients, indicating increased LV filling pressure among DM subjects. Compared to control S/D ratio was significantly lower only in DM patients with CAD or HTA, suggesting that decreased LA compliance and increased LA pressure occur predominately when DM is coupled with other cardiovascular comorbidities. Vp, that correlates well with the time constant of LV relaxation, was significantly lower in our DM patients compared to controls. Although diastolic parameters of impaired relaxation are influenced by age and some of them by BMI, in our study DM was independently from age, BMI, HTA and CAD associated with impaired LV relaxation.Diastolic dysfunction is an important component of diabetic cardiomyopathy –40 and wDiabetic cardiomyopathy among in type 2 DM is frequently described as a typical heart failure with preserved EF with diastolic dysfunction playing the major role , 12. OurMyocardial performance index, a parameter of both systolic and diastolic function, was significantly higher in all our DM groups compared to control. MPI became higher in DM patients with HTA compared to lone DM. Pattoneri et al. found MPI significantly higher in DM patients compared to control and suggested that this index can be used to assess subclinical damage of systolic and diastolic LV function .In our study none of investigated clinical parameters, including duration of DM, level of glycosylated hemoglobin, presence of microalbuminuria and retinopathy, was independent predictor of LV geometry, systolic and diastolic function. Although some data in literature are pointing to potential relation between microalbuminuria and glycosylated hemoglobin with diastolic dysfunction and subclinical impairment of longitudinal LV systolic function among normotensive DM patients, further studies are needed to define clinical profile for the development of diabetic cardiomyopathy , 42.In conclusion, DM per se, in the absence of HTA and CAD, is an independent determinator of LV phenotype and function, especially LV mass, concentric LV remodeling, impaired LV relaxation and impaired longitudinal systolic function, that can be appreciated by conventional and speckle tracking echocardiography.


IE) training has been shown to reduce resting arterial blood pressure (ABP) in hypertensive, prehypertensive, and normotensive populations. However, the acute hemodynamic response of the heart to such exercise remains unclear. We therefore performed a comprehensive assessment of cardiac structure, function, and mechanics at rest and immediately post a single IE session in 26 male (age 44.8 ± 8.4 years) prehypertensive participants. Conventional echocardiography recorded standard and tissue Doppler measures of left ventricular (LV) structure and function. Speckle tracking echocardiography was used to measure LV global longitudinal, circumferential, and radial strain and strain rate. From this data, apical and basal rotation and rotational velocities, LV twist, systolic twist velocity, untwist velocity, and torsion were determined. IE led to a significant post exercise reduction in systolic  and diastolic  blood pressure, with no significant change in heart rate . There were significant reductions in LV end systolic diameter , LV posterior wall thickness , relative wall thickness  estimated filling pressure  and proportion of participants with LV concentric remodeling , and significant increases in LV ejection fraction , fractional shortening , cardiac output , and stroke volume . In this setting, there were significant increases in global longitudinal strain  and strain rate , basal rotation , basal systolic rotational velocity , basal diastolic rotational velocity , LV twist , systolic twist velocity , and untwist velocity . These results suggest that IE improves LV function and mechanics acutely. This may in turn be partly responsible for the observed reductions in ABP following IE training programs and may have important implications for clinical populations.Isometric exercise ( Systemic arterial hypertension remains a significant global public health problem, which is estimated to affect ≈1 billion individuals worldwide World,  and is aInternational guidelines recommend nonpharmacological intervention, including regular physical activity, salt restriction, and weight loss for the primary and secondary prevention of hypertension  classified as prehypertensive (defined as a blood pressure of 120–139 mmHg systolic and/or 80–90 mmHg diastolic) with no history of cardiac or metabolic disease, nonsmokers currently taking no medication, and with a normal clinical cardiovascular examination and 12‐lead electrocardiogram. We aimed to study a population with pre‐HTN, who were otherwise healthy for three main reasons; first, the homogenous population reduces the impact of other comorbidities on cardiac responses, second, pre‐HTN precedes the development of hypertension, and third, cardiac mechanical responses in this group may provide important mechanistic information for blood pressure reduction, which may prove important for future IE training interventions in hypertensive populations.All procedures for this investigation conformed to the Declaration of Helsinki principles and Canterbury Christ Church Universities Faculty of Social and Applied Sciences Research Ethics Committee approved the study (Ref: 12/SAS/122). Signed, informed written consent was obtained from all participants. We studied 26 physically inactive Caucasian males   to ensure participants remained within safe exercising limits defined by American College of Sports Medicine.Prior research has demonstrated that when constant electromyography (EMG) was used to determine exercise intensity, a steady state heart rate was achieved at 10, 15, 20, 25, and 30% EMG , which consisted of four 2‐min isometric wall squats interspersed with 2‐min recovery. On the third visit, each participant repeated the single IE training session at their prescribed training angle and physiological data were recorded pre and immediately post the IE session.Transthoracic echocardiography was performed using a commercially available, portable ultrasound system  with a 1.5–3.6 MHz phased array transducer (M4S‐RS Matrix cardiac ultrasound probe), pre and immediately post the single IE training session. The same sonographer acquired all images, with the participant examined in the left lateral decubitus position. Cardiac structural and functional measurements were recorded as recommended by current guidelines  and the LV apex (circular LV cavity with no papillary muscle visible), as described previously  . A paired sample t‐test was used to compare baseline and post‐IE measurements after confirmation of normal distribution. A chi‐squared test was used to compare categorical data. A All 26 participants recruited completed the IE training session, which comprised of four 2‐min isometric wall squats at each participant's prescribed knee joint angle, interspersed with 2‐min recovery. Echocardiographic images suitable for complete analysis were obtained on all subjects at rest and immediately post exercise.−1, P < 0.001), predominantly mediated via a significant increase in stroke volume  post exercise, since there was no significant change in heart rate . In addition, IE was associated with a significant reduction in systolic , diastolic , and mean ABP  in recovery.There was a significant increase in cardiac output (4.3 ± 0.7 vs. 6.1 ± 1 L·minP = 0.002), LV posterior wall thickness  and relative wall thickness  following the IE training session, with no change in LV end diastolic diameter, interventricular septal thickness or LV length. There was a significant increase in the proportion of participants with normal LV geometry following IE .Baseline and post IE echocardiographic structural, functional, and tissue Doppler parameters are detailed in Table P < 0.001) and fractional shortening  following IE. There were no significant changes in global diastolic function; however, there were significant increases in LV tissue Doppler S'  and E' , with the latter resulting in a significant decrease in estimated filling pressure post IE .There was a significant increase in LV ejection fraction  and strain rate  significantly increased post IE with no difference in global longitudinal diastolic strain rate . There was a significant increase in both basal and apical circumferential strain  and strain rate  and significant increase in apical radial strain . There was a significant increase in basal rotation , basal systolic rotational velocity , and basal diastolic rotational velocity ; however, there was no significant change in apical rotation, apical systolic rotational velocity, and apical diastolic rotational velocity. The increase in basal mechanics translated into a significant increase in LV twist , systolic twist velocity , untwist velocity , and LV length‐corrected torsion . Figure Myocardial mechanics pre and post IE are displayed in Table To the best of our knowledge, this study is the first to investigate the acute effects of isometric wall squat exercise on cardiac structure, function, and LV mechanics in men with pre‐HTN. A single IE training session was associated with a significantly reduced LV end systolic internal diameter, LV posterior wall thickness, relative wall thickness, and proportion of patients characterized with concentric LV remodeling. These favorable LV remodeling responses to acute IE are similar to those reported in patients with hypertension following a program of aerobic exercise training or prescribed diuretics  and post exercise reductions in ABP, following a single bout of bilateral isometric hand‐grip exercise .


Hemodynamic data  were evaluated retrospectively for the short‐term right ventricular compensatory mechanisms and limits  10 animals showed stable arterial blood pressures, whereas 12 pigs exhibited a significant drop of 16.4 ± 9.9 mmHg. Cardiac output and heart rate were comparable in both groups. In contrast, right ventricular contractility and coronary flow only rose in the stable group. The unchanging values in the decrease group correlated with an increasing ST‐segment depression and a loss of ventricular synchronism and resulted in a larger septum bulging to the right ventricle. Simultaneously, a reduced left‐ventricular end‐diastolic volume and a missing improvement in contractility in the posterior septal and inferior free wall of the left ventricle have been observed. Our findings suggest that right ventricular compensation during acute pulmonary hypertension is strongly dependent on the individual capability to increase coronary flow. The cause for inter‐individual variability could be the dimension and reactivity of the coronary system.The extent of right ventricular compensation compared to the left ventricle is restricted and varies among individuals, which makes it difficult to define. While establishing a model of acute pulmonary hypertension in pigs we observed two different kinds of compensation in our animals. Looking deeper into the hemodynamic data we tried to delineate why some animals could compensate and others could not. Pulmonary hypertension (mean pressure 45 mmHg) was induced gradually by infusion of a stable thromboxane A Pulmonary hypertension (PHT) in a perioperative and intensive care setting is accompanied by a significantly increased risk for postoperative complications and a high mortality rate  greater than 25 mmHg at rest  release that leads to coronary vasodilatation and maintains coronary blood flow (CBF) . The protocols were designed according to the 2 analogue U46619 though the central venous catheter. For this study, 13 pigs had to be excluded due to missing data concerning the exact PHT interstages.For this study, data from 22 female breeding pigs (German Landrace) with a mean weight of 30.2 ± 1.45 kg (mean ± standard deviation) were evaluated retrospectively. In these pigs, PHT was induced in stages using a continuous infusion of thromboxane A®; Draeger, Luebeck, Germany). Ringer's solution was infused (10 ml/kg/h), and active heating was used as needed to maintain normothermia (38.5°C). Cardiac rhythm, oxygen saturation and invasive femoral arterial pressure were continuously monitored during experimental procedures .After an acclimation period of 5 days and overnight fasting, the animals received an intramuscular premedication of azaperone (4 mg/kg) and intravenous propofol (3 mg/kg) for general anesthesia. Oral intubation followed, and anesthesia was maintained with a continuous infusion of thiopental (15 mg/kg/h). No muscle relaxants were given. Volume‐controlled mechanical ventilation was performed with 21% oxygen with a tidal volume of 10 ml/kg, a positive end‐expiratory pressure of 7 mbar and a breathing rate of 20–24 per minute . A pressure sensor was placed at a distance of approximately 5 cm from the apex.To be able to provoke a short‐term LV preload reduction, a balloon occlusion catheter was placed in the inferior vena cava via the right femoral vein.After median sternotomy and opening of the pericardium, ultrasound transit‐time flow probes were placed proximally around the right coronary artery (RCA)  and the main pulmonary artery . An RV conductance catheter was inserted via a small puncture site at the RV apex, and a pressure sensor was introduced via an RV wound in the RV outflow tract with the tip of the sensor located 3–4 cm distally from the pulmonary valve .After successful positioning of the catheters, a break of approximately 2 h was taken so that the hemodynamic parameters could recover from manipulation, and stable baseline parameters could be established.2 analogue U46619  was continuously administered as an infusion with increasing dosage (0.2 to 0.8 μg/kg/min).To induce PHT within 45 min in 5 mmHg stages between a mPAP of 20 mmHg and 45 mmHg, stable thromboxane AMean arterial pressure (mAP), mean pulmonary artery pressure (mPAP), and heart rate (HR) were recorded continuously. Cardiac output (CO) was calculated from pulmonary arterial flow measurements.Conductance catheters were used to collect continuous, real‐time recordings of the intraventricular pressures and volumes (such as the Ved). A calibration of the volume measurement was carried out by injecting 5 ml of 10% intravenous saline solution at each measurement point. The exact calculation has been described in previous studies  and high (40–45 mmHg) levels of mPAP  to perform strain analysis in defined segments of the LV, and therefore, evaluate systolic and diastolic contractility. SrR were calculated at low and high levels of mPAP using speckle tracking analysis  from the short axis midpapillary view. The results are displayed as the differences with standard deviations (SD).In addition, the integral of the transseptal pressure gradient (∫RVP‐LVP) .P < 0.05 was considered significant.A The results are displayed in graphs after grouping mPAP values into groups of 5 mmHg starting with a group center of 20 mmHg Fig. A. All fin = 10). In all other cases, they were allocated to the decrease group (DG) (n = 12).Based on the mAP trend during the stepwise mPAP increase, animals were divided into two groups for further analysis. With an mAP decrease less than 5 mmHg, they were classified as “stable” group (SG)  of the different groups at the different cardiac segments were compared using repeated analyses of variance (ANOVA). Differences in the individual groups were further analyzed using post hoc tests.P < 0.001) . An mPAP‐dependent mAP reduction in up to 16.4 ± 9.9 mmHg was observed in the other 12 animals, which were allocated to the DG (n = 12).Ten animals showed a steady, or even marginal, rise in mAP of 2.9 ± 3.0 mmHg at maximum mPAP conditions. They were subsequently allocated to the SG (P < 0.001).In contrast, HR and CO changed concordantly in both groups. There was a significant increase in HR Fig. B and a sP = 0.031). The RV end‐diastolic volume (RV‐Ved) initially rose in both groups, and no significant differences in preload were observed  Fig. B. The loved Fig. A.τ (Tau) denotes the time constant for isovolumetric relaxation) increased with mPAP augmentation from 27.3 ± 9.9 ms (DG) and 25.9 ± 2.6 ms (SG) to 48.4 ± 13.6 ms (DG) and 50.6 ± 13.7 ms (SG), which are almost two times longer      Fig. A. Furthe01) Fig. B but notP < 0.001)  Fig. E and dia01) Fig. D–E.group*mPAP = 0.007)  Fig. C.2) and the coronary oxygen extraction between the groups did not differ significantly. Consumption and extraction both slightly rose with the increase in mPAP   Fig. B. As a pThe LV contractility increased as well, but the differences between groups were not significant Fig. A.n = 8; DG: n = 9), basal segmental radial strain rates (SrRs) (mPAP 20–25 mmHg) were subtracted from SrRs during PHT (mPAP 40–45 mmHg). The generated differences are illustrated in Figure To evaluate the echocardiographic LV data of 17 animals  with approximately constant mAP values and the DG (n = 12) with significantly reduced mAP values at higher mPAP levels (≥37.5 mmHg). In our comparison, the SG showed beside the stable mAP values, a larger increase in RCA flow, a gain of RV contractility, less pronounced ST depressions, a reduced loss of inter‐ventricular asynchrony and longer LV relaxation times. Overall adaptation was considerably better in the SG.Infusion of the thromboxane AAt the onset of significant group differences, SG and DG separate in RV contractility and RCA flow both in systole and in diastole (at mPAP ≥32.5 mmHg). Interestingly, mAP differences appear later (at mPAP ≥37.5 mmHg). Therefore, the mAP increase cannot be the decisive factor for the observed CBF gain in our experiments. The wall tension could also not have caused the observed CBF gain because elevated RV wall tensions during PHT would deteriorate instead of elevate CBF  has not yet been determined. A stable flow down to CBPs of 30 mmHg in pigs has been described   , which is similar to the differences in mAP. Finally (mPAP ≥42.5 mmHg) LV preload exhibited significantly different values in the groups, which indicates a distinct right heart failure with venous congestion in the DG.2 demand (Zong et al. It is characteristic for the RV that HR, afterload and contractility dictate the OBecause both ventricles share the septal wall, they affect each other directly. Therefore, when assessing RV function, it is necessary to consider ventricular interdependence as well. Therefore, mainly ventricular asynchrony leads to great changes in physiological characteristics.There is an increase in RV‐Tau during PHT, whereas LV‐Tau lessens simultaneously Fig. C–D, thatAppropriately, falling CO, that is known to be sign of RV decompensation, occurs with increasing mPAP values Fig. C Forres.RVP‐LVP provides reliable information concerning RV function because it demonstrates duration and quantity of the reversed transseptal pressure gradient. It is important to note that the findings depend on the RV volume state (Handoko et al. In addition, calculating ∫How far the loss of ventricular synchronism provokes right heart failure or if RV failure in fact causes the delay has not been entirely clarified.Furthermore reliable examination of interventricular interaction can be done regarding echocardiography and septal strain analysis.Pulmonary hypertension has been demonstrated to provoke only septal a reduced radial and circumferential strain (Chua et al. Analysis of the whole LV echocardiographic data particularly underlines the significant differences in contractility changes between the groups in the posterior septal wall and the inferior posterior LV free wall Fig. . The pro2 analogue U46619 infusion itself might have had a small systemic effect, but as the two groups did not differ significantly in the dosage of U46619 needed and the CO, the drug could not explain the observed major differences in mAP. Moreover an influence of U46619 on the inotropy of the heart cannot be ruled out completely, but given the divergent effects on the different wall regions (Fig. We focused on the examination of acute PHT so that our statements are limited to this specific event because the time course plays an important role in the pathogenesis of the disease. Moreover, studying one animal species can lead to problems with transferability in cases of existing interspecies variability. Furthermore, the experimental setup itself could have influenced the results. For example, general anesthesia influences the cardiovascular system in different ways. It has been demonstrated that it can possibly modify coronary muscle tone (Vatner and Braunwald ons Fig.  it is veIn summary, our data suggest that the increasing CBF is essential for patient adaptation to acute PHT. The decisive factor for adaptation to rising pulmonary pressure could be the differences in coronary supply territories.Indeed, our findings may suggest that further research, especially with regard to reasons and possible signs for early detection of CBF rise, is needed.The authors declare that they have no conflicts of interest regarding the publication of this paper.


Impaired arterial strain is associated with increased stiffness in the great arteries. In patients with repaired coarctation of the aorta (CoA), we sought to assess ventriculo-vascular characteristics using cardiac magnetic resonance (CMR) derived aortic area strain (AS) in conjunction with left atrial (LA) and left ventricular (LV) longitudinal and circumferential strain (LS and CS).2) were measured, and AS (%) was calculated as 100 X (Area max - Area min)/ Area min). LA and LV LS were measured from horizontal long axis steady state free precession cine (4-chamber image) and LVCS from mid-ventricular short axis cine using CMR-feature tracking . LA and LV end-diastolic volumes (EDV), ejection fraction (EF) and LV mass were also measured (Medis) in all subjects. Measurements were compared between the 3 groups.Seventy five subjects, including 50 patients with repaired CoA divided into hypertensive (n=25), and normotensive groups (n=25), and 25 healthy subjects (controls) were studied. Hypertension was defined per National High Blood Pressure Education Program Working Group guidelines as systolic blood pressure (SBP) ≥95th percentile. For aorta acquisitions, through-plane, free-breathing, phase-contrast CMR protocol was used and AS measured at 3 levels: ascending aorta, proximal descending aorta and descending aorta at diaphragm. Maximal and minimal luminal areas (mmThe mean age of CoA patients were 19.7 ±6.7 years (range 8.5-43 years) and controls were 23 ±15 years (range 7.1-51 years). All strains  were significantly lower in CoA subgroups compared to controls (Figure Ascending AS in CoA correlated with LV mass, EF and LVLS. In hypertensive CoA subjects, ascending AS was significantly reduced compared to normotensive CoA and healthy controls of similar age and body surface area. These observations may be indicative of differences in vascular remodeling influenced by ongoing hypertension.Childrens Hospital and Medical Center Foundation, Omaha, USA.


Left bundle branch block (LBBB) is common following trans-catheter aortic valve replacement (TAVR) and has been linked to increased mortality, although whether this is related to less favourable cardiac reverse remodeling is unclear. The aim of the study was to investigate the impact of TAVR induced LBBB on cardiac reverse remodeling.48 patients undergoing TAVR for severe aortic stenosis were evaluated. 24 patients with new LBBB (LBBB-T) following TAVR were matched with 24 patients with a narrow post-procedure QRS (nQRS). Patients underwent cardiovascular magnetic resonance (CMR) prior to and 6 m post-TAVR. Measured cardiac reverse remodeling parameters included left ventricular (LV) size, ejection fraction (LVEF) and global longitudinal strain (GLS). Inter- and intra-ventricular dyssynchrony were determined using time to peak radial strain derived from CMR Feature Tracking.P < 0.001) leading to inter- and intra-ventricular dyssynchrony . Change in indexed LV end-systolic volume (LVESVi), LVEF and GLS was significantly different between the two groups . There was a significant correlation between change in QRS and change in LVEF  and between change in QRS and change in GLS . Post-procedure QRS duration was an independent predictor of change in LVEF and GLS at 6 months.In the LBBB-T group there was an increase in QRS duration from 96 ± 14 to 151 ± 12 ms (TAVR-induced LBBB is associated with less favourable cardiac reverse remodeling at medium term follow up. In view of this, every effort should be made to prevent TAVR-induced LBBB, especially as TAVR is now being extended to a younger, lower risk population. The aortic valve lies close to the electrical conduction system of the heart and is prone to damage at the time of aortic valve intervention, often manifesting as new left-bundle branch block (LBBB). New LBBB is infrequent following surgical aortic valve replacement , but mucWe hypothesised that LBBB-T 1) negatively impacts on cardiac reverse remodeling at 6 m follow up and 2) is associated with inter- and intra-ventricular dyssynchrony compared with a matched ‘control’ population with a narrow QRS (nQRS) post-TAVR.We evaluated 88 patients undergoing either Boston Lotus  or Medtronic CoreValve  TAVR for severe symptomatic aortic stenosis at a single tertiary centre from April 2009 to April 2015. Exclusion criterion included pre-existing QRS prolongation (>120 ms) or contra-indication to CMR scanning. Decision for TAVR was taken by a multi-disciplinary heart team in accordance with international guidance [24 patients with LBBB-T were identified. These were matched with 24 patients with a nQRS post-procedure for sex, valve type, and baseline CMR variables known to impact on reverse remodeling following TAVR including LV ejection fraction (LVEF), indexed LV mass and indexed LV end diastolic volume (LVEDVi)  Fig. 1)1).Fig. 15, V6) [12-lead electrocardiogram recordings acquired immediately prior to TAVR and at the time of post-procedure hospital discharge were reviewed by a single author blinded to clinical and procedural data. Heart rhythm, PR interval and QRS duration were recorded. LBBB-T was defined as post-procedural v1-negative QRS complex with a duration of >120 ms and a notched or slurred R wave in at least one of the lateral leads  .Details of the CMR pulse sequence acquisition protocol have been published previously . Briefly42 . Endocardial and epicardial contours were manually contoured at end-diastole and end-systole with papillary muscles and trabeculations excluded to allow the calculation of ventricular volumes (summation of discs methodology) and mass ). Values were indexed to body surface area. Post-procedural myocardial infarct was determined by direct comparison of pre- and 6 m CMR LGE acquisitions. Fibrosis mass was quantified using a threshold of 5 standard deviations technique [CMR analysis was performed by a single experienced operator blinded to clinical data using cmrechnique . Left atechnique . Aortic t Test  and the Mann-Whitney or Wilcoxen signed rank test . Linear regression analysis (Enter model) was performed to establish univariate and multivariate predictors of change in LVEF and GLS post-procedure. Univariate predictors with P < 0.05 were included in the multivariate analysis. P < 0.05 was considered statistically significant. Using CMR, in order to detect a 3% difference in LVEF with a 90% power and an α error of 0.05 a sample size of at least 12 patients in each arm was required [Statistical analysis was performed using SPSS version 22 . Categorical data were presented as numbers (percentages) and compared using the Pearson Chi squared test. Continuous variables were expressed as mean ± SD and were tested for normality using the Shapiro-Wilks test. Data were compared using Students required .n = 12), those with post-procedure right bundle branch block (n = 2) and those with CMR LGE evidence of post-procedural myocardial infarction (n = 1) were excluded from analysis. In addition, 3 patients died within the 6 m follow up period and 5 patients declined follow up  had atrial fibrillation at baseline. There were no new cases of post-procedural atrial fibrillation. For those in sinus rhythm, mean PR interval remained similar pre and post procedure in both the nQRS group  and the LBBB-T group . In the nQRS group there was no change in QRS duration . In the LBBB-T group, QRS duration increased from 96 ± 14 to 151 ± 12 ms (p < 0.001).Mean heart rate at baseline was 67 ± 11 and at 6 m was 68 ± 13 bpm. 7 patients (15%)  . Pre and post-procedure values for all CMR characteristics can be seen in Table 2, p = 0.367) as was change in LVEDVi . Neither group experienced any change in right ventricular longitudinal function . Post-procedure aortic regurgitant fraction was similar between groups . There was a significant correlation between change in QRS and change in LVEF  and between change in QRS and change in GLS . The relationship between post-procedure QRS duration and change in LVESVi, LVEF and GLS can be seen in Fig. Change in LVEF and GLS was significantly different between the two groups . In the nQRS group, TAVR was not associated with an improvement in dyssynchrony . There was evidence of significant inter- and intra-ventricular dyssynchrony in the LBBB-T group at 6 m compared with the nQRS population . There was a significant correlation between post-procedure QRS duration and inter- and intra-ventricular dyssynchrony . A typical LV contraction pattern in nQRS and LBBB-T can be seen in Fig. As a group as a whole baseline inter- and intra-ventricular dyssynchrony was 68 ± 62 and 54 ± 83 ms respectively. Those that subsequently developed LBBB demonstrated more interventricular dyssynchrony at baseline but had similar baseline intraventricular dyssynchrony  and post-procedure QRS  were independent predictors of change in LVEF at 6 m on multiple regression analysis. Baseline LVEF , baseline GLS  and post-procedure QRS  were independent predictors of a change in GLS at 6 m. Infarct pattern LGE at baseline did not impact on post-procedural change in LVEF or change in GLS on univariate analysis.Baseline variables which may affect cardiac reverse remodeling following TAVR  were analysed to determine univariable predictors of change in LVEF and GLS Table . BaselinThis is the first study using CMR to investigate the impact of TAVR-induced LBBB on cardiac reverse remodeling in a matched population. The main findings of this study are 1) Those with a narrow QRS post-TAVR have better LVEF and GLS compared to those with LBBB-T 6 m post-procedure, 2) Patients with LBBB-T exhibited significant inter- and intra-ventricular dyssynchrony compared with those with narrow QRS and 3) Post-procedure QRS duration remained a significant independent predictor of change in LVEF and GLS following TAVR on multivariable analysis.TAVR-induced LBBB is common, occurring in 16–65% patients depending on valve type . AlthougOur study adds further insight into the impact of LBBB-T on cardiac reverse remodeling. The accuracy and reproducibility of CMR means that important differences can be determined using studies 87% smaller than echocardiographically based studies, with only 11 patients per group required to detect a 3% difference in LVEF . Our stuThe novel use of CMR feature tracking allows us to report values for intra- and inter-ventricular dyssynchrony. In LBBB, the normally functioning right bundle conducts the electrical impulse to the right ventricle prompting early right ventricular contraction followed by activation of the interventricular septum and finally lateral wall contraction resulting in inter- and intra-ventricular dyssynchrony. This dyssynchrony leads to the classical abnormal septal motion pattern of contraction seen in LBBB which is felt to impair LV filling and ejection in its own right Fig. . This dyIt is well established that TAVR leads to conduction abnormalities . Trauma The impact of TAVR-induced LBBB on mortality is a subject of debate, however, it has been shown in many studies to be a predictor of mortality –5, 29 anAlthough patients were recruited in a prospective manner, they were matched retrospectively and hence the study is prone to the selection bias of this type of study. Patients with LBBB-T were matched according to those factors known to influence cardiac reverse remodeling  but otheNew LBBB following TAVR is associated with less favourable cardiac reverse remodeling, including effects on LVEF, global longitudinal strain and inter- and intra-ventricular dyssynchrony. In view of this, every effort should be made to minimise the risk of TAVR-induced LBBB especially as TAVR is now being extended to a younger, lower risk population.