Whether T1-mapping cardiovascular magnetic resonance (CMR) can accurately quantify the area-at-risk (AAR) as delineated by T2 mapping and assess myocardial salvage at 3T in reperfused ST-segment elevation myocardial infarction (STEMI) patients is not known and was investigated in this study.18 STEMI patients underwent CMR at 3T (Siemens Bio-graph mMR) at a median of 5 (4–6) days post primary percutaneous coronary intervention using native T1 (MOLLI) and T2 mapping . Matching short-axis T1 and T2 maps covering the entire left ventricle (LV) were assessed by two independent observers using manual, Otsu and 2 standard deviation thresholds. Inter- and intra-observer variability, correlation and agreement between the T1 and T2 mapping techniques on a per-slice and per patient basis were assessed.P = 0.25) or myocardial salvage index  between the T1 and T2 mapping techniques. On a per-slice analysis, there was an excellent correlation between T1 mapping and T2 mapping in the quantification of the AAR with an R2 of 0.95 (P < 0.001), with no bias (mean ± 2SD: bias 0.0 ± 9.6 %). On a per-patient analysis, the correlation and agreement remained excellent with no bias .A total of 125 matching T1 and T2 mapping short-axis slices were available for analysis from 18 patients. The acquisition times were identical for the T1 maps and T2 maps. 18 slices were excluded due to suboptimal image quality. Both mapping sequences were equally prone to susceptibility artifacts in the lateral wall and were equally likely to be affected by microvascular obstruction requiring manual correction. The Otsu thresholding technique performed best in terms of inter- and intra-observer variability for both T1 and T2 mapping CMR. The mean myocardial infarct size was 18.8 ± 9.4 % of the LV. There was no difference in either the mean AAR (32.3 ± 11.5 % of the LV versus 31.6 ± 11.2 % of the LV, T1 mapping CMR at 3T performed as well as T2 mapping in quantifying the AAR and assessing myocardial salvage in reperfused STEMI patients, thereby providing an alternative CMR measure of the the AAR. Despite timely myocardial reperfusion by primary percutaneous coronary intervention (PPCI), patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) still experience significant morbidity and mortality –3. New cIn this regard, T2-weighted (short tau inversion recovery) cardiovascular magnetic resonance (CMR) of myocardial edema in the first few days following PPCI has emerged as a promising technique for retrospectively quantifying the AAR in reperfused STEMI patients , 7. Thisnative T1-mapping CMR (referred to as T1-mapping or T1 map throughout the manuscript for simplicity) has been found to be superior to T2-weighted CMR in detecting myocardial edema in the context of acute myocarditis [Recently, carditis  and acutcarditis . T1-mappcarditis . Langhancarditis  found thcarditis  have rec2, presence of ferromagnetic implants). All eligible patients provided informed written consent and the local ethics committee (London - Harrow) approved all study-related procedures. The patients recruited in this study formed part of a cohort of patients included in a recently conducted hybrid simultaneous Positron Emission Tomography/MR study [18 PPCI-treated STEMI patients were recruited over a 7-month period from one UK center. The main exclusion criteria were previous MI and standard contraindications to CMR  days post-PPCI using a 3T MR scanner . The MR imaging protocol included cine imaging for function, followed by T1 maps and T2 maps for AAR and Late Gadolinium Enhancement (LGE) for MI size. T1 maps and T2 maps  were acquired as previously described . For T1 The T1 and T2 maps were acquired to match the short-axis cines to cover the entire left ventricle. Gadolinium contrast  was administered at a dose of 0.1 mmol/kg. LGE was performed using segmented two-dimensional inversion-recovery turbo fast low-angle shot LGE sequences  10–15 min after single bolus contrast agent injection and short-axis slices of the entire left ventricle were acquired to match the T1 maps and T2 maps . MI size was quantified following manual delineation of the endocardium and epicardium of short axis slices and using 5 standard deviations (SD) threshold above the mean remote myocardium . Transmu2) was used to assess inter-method correlation. A linear regression analysis was performed to obtain the regression slope and its 95 % confidence interval to compare against the reference line with a slope of 1 which would represent AAR by T1 and T2 to be identical. Bland-Altman analysis was performed to assess agreement and bias detection between methods and presented as average difference ± 2SD. Inter-observer and intra-observer variability was assessed using intra-class correlation coefficient (ICC) and mean difference between interobserver and intraobserver measurements of T1 and T2 AAR ± SD. Receiver Operating Characteristic (ROC) analysis was performed to provide cut-off values for T1 and T2 for detecting acute myocardial necrosis defined by an LGE score of 1. ROC curves were compared for statistical difference using the method described by Delong et al. [Statistical analysis was performed using SPSS  and MedCalc . Continuous data was expressed as mean ± SD or median (interquartile range). Categorical data was reported as frequencies and percentages. Both per-slice and per-patient comparison was performed. Paired student t-tests and Wilcoxon Rank sum test were performed to compare mean or median between paired groups. Pearson’s correlation coefficient expressed as its square . 18 pairs of images were excluded due to suboptimal image quality . Both T1 and T2 CMR were equally prone to susceptibility artifacts in the lateral wall. As we did not have any patients with a circumflex territory infarction, these artifacts were remote from the AAR and the slices  were kept for analysis and manual correction was required. 27 slices had normal T1 and T2 values and 80 slices had abnormal T1 and T2 values (using 2SD from the remote myocardium as a reference). Both T1 and T2 maps were equally likely to be affected by MVO requiring manual correction to include the core as part of the AAR and occurred in 13/18 patients, 45/107 slices of the T2 maps, and 42/107 of the T1 maps.In total, 125 pairs of T1 maps and T2 maps of the LV short axis from base to apex were acquired. The acquisition times for T1 maps and T2 maps per patient were similar  for T2 mapping were 31.8 ± 11.7 %, 31.6 ± 11.2 % and 38.7 ± 15 % and for T1 mapping were 32.0 ± 11.5 %, 32.3 ± 11.5 % and 38.4 ± 13.6 % respectively. The ICC for intra-observer and inter-observer variability of the 3 analytical techniques were excellent, both for T1 and T2 mapping and was highest for the Otsu technique. The 2SD technique had the largest differences both for intra-observer and inter-observer measurements for both mapping techniques. These findings are summarized in Table 2 of 0.95 and a regression slope 0.97 (95 % CI 0.93 – 1.01). There was no bias on Bland Altman analysis (mean ± 2SD: bias 0.0 ± 9.6 %) as illustrated in Fig. 2 0.95, regression slope 0.95 (95 % CI 0.84 – 1.07), bias 0.7 ± 5.1 %; Fig. P = 0.25).On a per-slice analysis, there was an excellent correlation between the T1 mapping and T2 mapping with an RP = 0.25)  between the 2 mapping techniques.The mean MI size by LGE was 18.8 ± 9.4 % of the LV, (range 2.0 - 34.0 %). Myocardial salvage (AAR subtract the MI size) was 12.8 ± 10.0 % of LV (range 0 – 42.0 %) by T2 mapping. The myocardial salvage index  was 0.40 ± 0.26 (range 0 – 0.89). There were no difference in either myocardial salvage .The T1 and T2 values in the AAR was significantly higher than those in the remote myocardium .This is the first study to compare the diagnostic performance of T1 mapping against T2 mapping at 3T to detect acute myocardial necrosis and the results are in keeping with the previous study by Dall’Armellina et al.  in whichLanghans et al.  recent lWe found that the Otsu thresholding method performed best with excellent inter-observer and intra-observer variability for both mapping techniques. The algorithm automatically divides a signal intensity histogram into two classes requires minimal user input compared to manual delineation, SD thresholding and full width half maximum techniques. It automatically calculates an optimal threshold  and has Currently, it would appear that T1 and T2 mapping could be used interchangeably to assess the AAR in reperfused STEMI patients. In studies investigating post-contrast T1 and extracellular volume fraction in acute myocardial infarction patient, there is the possibility of shortening the scanning time by omitting T2 maps as the T1 maps would be available for AAR quantification. However, T1 mapping may not be suitable in acute myocardial infarction patients who also have a chronic infarct in the remote myocardium. T1 mapping CMR has recently been shown to identify chronic infarct with high diagnostic accuracy  in a canCertain cardioprotective therapies such as ischemic postconditioning  and remoAlthough, we only included a small number of patients, we did include a range of ischemic times and performed detailed slice-per-slice comparisons, including inter and intra-observer performance. Unfortunately we did not recruit any patients with a circumflex territory myocardial infarction as it would have been interesting to assess the effect of off-resonance artifacts in the lateral wall in those patients with lateral wall MI on both mapping techniques. Our study was performed at 3T and whether T1 mapping performs as well as T2 mapping in quantifying the AAR at 1.5 T in the clinical setting remains to be determined.We have shown for the first time that T1 mapping CMR at 3T can accurately quantify the AAR delineated by T2 mapping in reperfused STEMI patients. However, further work is needed to replicate these findings at 1.5 T, assess the dynamic change of T1 over time compared to T2, and determine whether the AAR delineated by T1 mapping is affected by cardioprotective therapies in a similar manner to T2 mapping.


Cardiac magnetic resonance imaging (CMR) is frequently used to assess myocardial involvement to confirm diagnosis of myocarditis. CMR techniques employ T2- weighted, early and late gadolinium enhancement (LGE), with two positive sequences widely considered diagnostic for myocardial inflammation. However, these techniques are qualitative and subjective, thus prone to interpretation error. Feature tracking (FT) allows quantitative segmental myocardial strain analysis using traditional cine CMR images. Our hypothesis was that left ventricular (LV) segmental strain would be a more sensitive indicator for myocardial involvement in patients with clinical myocarditis. Regional strain was compared to presence of LGE as a measure of myocardial involvement.Patients with clinical diagnosis of myocarditis and structurally normal hearts who underwent CMR at our institution from 2004-2014 were studied retrospectively. Consecutive healthy young adults with normal cardiac anatomy, function and absent LGE were selected as controls. FT was performed on CMR cine images; longitudinal strain analysis was performed in four chamber (4C) and two chamber (2C) images, circumferential strain was calculated at basal, midventricular (mid), and apical levels. Global and segmental strain data was compared to troponin leak and presence of LGE. Sensitivity, specificity, and criterion values of strain were determined by comparison to controls. Descriptive statistics, t-tests, logistic regression analysis, and receiver operator characteristic curves were utilized.Twenty-nine myocarditis patients and nineteen controls were analyzed by FT. All myocarditis patients demonstrated abnormal myocardial strain in at least one longitudinal or circumferential distribution including patients in whom LGE was negative. Twenty of the 29 myocarditis patients with normal ejection fraction were included in the final analysis. Myocarditis patients had significantly diminished longitudinal 4C, longitudinal 2C, global circumferential, circumferential basal, mid, and apical strain when compared with normal controls Table . MultivaFT derived longitudinal and circumferential strain is more sensitive and specific in identifying myocardial involvement. FT can be a useful adjunct to traditional CMR techniques as an objective measure of myocardial involvement especially in patients with myocarditis and normal LV function. Feature tracking may prove advantageous in cases of clinical myocarditis where traditional CMR techniques are inconclusive.N/A.


Patients with diabetes mellitus (DM) of longer duration have an increased incidence of heart failure, independent of hypertension and coronary disease, as shown in large population based studies. Mechanisms of diabetic cardiomyopathy are multifactorial and not fully elucidated. Cardiovascular magnetic resonance (CMR) and magnetic resonance spectrocopy (MRS) provide a non-invasive assessment of the functional, structural and metabolic status of the heart. Here we assessed whether subclinical functional, structural and metabolic alterations can be detected using MRI in a patient cohort of early-onset, stable and uncomplicated type 2 DM.The aim of this study was to assess the earliest manifestations of diabetic cardiomyopathy using multiparametric CMR and MRS in a cohort of uncomplicated type 2 DM patients with a short duration of disease.13 patients  with early-onset (median 3 [IQR: 1-4] years) type 2 DM and 10 healthy volunteers  were enrolled. Patients were either drug naive for diabetic therapy or on treatment with metformin monotherapy, HBA1c ≥ 6.7 and ≤ 8%, with no history of coronary artery disease or uncontrolled hypertension. Myocardial lipid content and PCr/ATP ratios were quantified using 1H- and 31P MRS, respectively. CMR included cine, tagging and native T1 mapping was performed at 3.0 T. LV diastology was characterised using echocardiography.Diabetic patients were well-matched with controls Figure . MyocardAbnormal myocardial energy metabolism, cardiac steatosis and reduced LV strain are present in uncomplicated type 2 DM patients with a short duration of disease and precede the development of structural or other functional changes. CMR is a sensitive, non-invasive tool for assessment of myocardial pathophysiology, and may be helpful in the comprehensive phenotyping and staging of myocardial involvement in DM.'The National Institute for Health Research Oxford Biomedical Research Council and Hoffmann-La Roche supported this work.


We report a case of transient biventricular dysfunction post therapeutic pericardiocentesis, with classic features of stress cardiomyopathy (SCM). In our patient, the clinical and echocardiographic features were more in keeping with Takotsubo-type SCM than pericardial decompression syndrome (PDS). Our case is instructive in challenging our understanding of the aetiology of LV dysfunction complicating pericardiocentesis, and in highlighting the importance of careful clinical evaluation  in suspecting acute LV dysfunction after initial clinical improvement with pericardial aspiration.The online version of this article (doi:10.1186/s12947-015-0026-3) contains supplementary material, which is available to authorized users. We report a case of reversible biventricular dysfunction following successful pericardiocentesis with classic features of stress or “Takotsubo” cardiomyopathy (SCM). Reports of SCM after pericardiocentesis are rare , as distA 62-year-old male presented with progressive dyspnoea for 10 days. He had a background of stage IV metastatic non-small lung carcinoma treated for 6 months with non-cardiotoxic chemotherapy (carboplatin and gemcitabine), and recently commenced on target therapy (Erlotinib). Clinical examination revealed signs consistent with cardiac tamponade, including significant pulsus paradoxus, tachycardia (heart rate 101), tachypnea (respiratory rate 25), elevated jugular venous pressure and muffled heart sounds. He was normotensive at 130/90mmHg. The patient was extremely anxious and spontaneously expressed concern about his imminent death.His electrocardiogram (ECG) Fig.  demonstrOvernight (9 h post procedure) the patient developed chest discomfort, dyspnea, tachycardia (HR 110) and tachypnoea RR 24). TTE the next morning showed no re-accumulation of pericardial fluid, but detected new severe impairment in function of both ventricles, with akinesis of the apex and peri-apical region  coronary artery were clinically unlikely. The former was excluded by the absence of new pericardial bleed post procedure. Laceration of the LAD was also clinically unlikely given relatively small rise in cardiac enzymes and absence of large infarct, the presence of concurrent RV dysfunction, spontaneous recovery of ventricular function in a short period of time; additionally CT scan showed no evidence of haematoma or injury to the LAD.Accordingly, we reviewed the literature describing SCM and PDS. Whereas SCM has been rarely reported after pericardiocentesis, much has been published on PDS. The incidence of PDS or new left or right systolic dysfunction has been reported to range from 5 % to 36 % of patients post pericardiocentesis , especiaA number of mechanisms have been proposed to explain the pathogenesis of LV systolic dysfunction in PDS. Acute withdrawal of exaggerated sympathetic drive during relief of tamponade may trigger paradoxical haemodynamic instability . MechaniThe classic echocardiographic feature in SCM is transient LV apical ballooning, although other segmental patterns have been described , 13. A sMore recent case reports have made reference to LV apical ballooning related to PDS as similar to SCM , 15–17, SCM has relatively characteristic clinical presentation, with rise of cardiac enzymes , and oftGenerally SCM has a benign course, with recovery of LV function and good prognosis , whilst Current literature has not specifically addressed risk factors for the development of ventricular dysfunction after pericardiocentesis. In our patient, the malignant nature of the effusion, the presence of tamponade and larger size of pericardial effusion , may havOur patient’s apical systolic dysfunction post pericardiocentesis was associated with chest discomfort, transient loss of R waves and rise in cardiac enzymes are typical of classic SCM. The clinical sequence of HR and RR improving immediately post decompression and then increasing again hours after the procedure, was a useful clinical marker of myocardial dysfunction, prompting investigation which identified new ventricular impairment. It is likely that the frequency of transient LV dysfunction is underestimated in these patients.We report a case of transient biventricular dysfunction post pericardiocentesis, with classic features of SCM. LV dysfunction post pericardiocentesis and in PDS is more prevalent than previously thought, and some previous reports of PDS may also be potentially considered as SCM complicating pericardiocentesis. In addition to judicious and gradual decompression to avoid ventricular dysfunction or PDS, patients undergoing therapeutic pericardiocentesis should have careful haemodynamic monitoring, as changes in parameters such as heart rate and respiratory rate can raise suspicion of acute LV impairment.Written informed consent was unable to be obtained from the patient for publication of this Case report and any accompanying images, as he has passed away. His next of kin are not contactable after their subsequent return to their home country of China. Professor L. Kritharides, Head of Department, approves the publication of this report, with all patient identifiers kept confidential and material presented solely for educational purposes arising from the clinical encounter.


Compensatory renal hypertrophy following unilateral nephrectomy (UNX) occurs in the remaining kidney. However, the long-term cardiac adaptive process to UNX remains poorly defined in humans. Our goal was to characterize myocardial structure and function in living kidney donors (LKDs), approximately 12 years after UNX.Cardiac function and structure in 15 Italian LKDs, at least 5 years after UNX (median time from donation = 8.4 years) was investigated and compared to those of age and sex matched U.S. citizens healthy controls (n = 15). Standard and speckle tracking echocardiography (STE) was performed in both LKDs and controls. Plasma angiotensin II, aldosterone, atrial natriuretic peptide (ANP), N terminus pro B-type natriuretic peptide (NT-proBNP), cyclic guanylyl monophosphate (cGMP), and amino-terminal peptide of procollagen III (PIIINP) were also collected. Median follow-up was 11.9 years. In LKDs, LV geometry and function by STE were similar to controls, wall thickness and volumes were within normal limits also by CMR. In LKDs, CMR was negative for myocardial fibrosis, but apical rotation and LV torsion obtained by STE were impaired as compared to controls . Serum creatinine and PIIINP levels were increased  μg/L, respectively), while urinary cGMP was reduced [270 (250–355) vs 581 (437–698) pmol/mL] in LKDs. No LKD developed cardiovascular or renal events during follow-up.Long-term kidney donors have no apparent structural myocardial abnormalities as assessed by contrast enhanced CMR. However, myocardial deformation of the apical segments, as well as apical rotation, and LV torsion are reduced. The concomitant increase in circulating PIIINP level is suggestive of fibrosis. Further studies, focused on US and EU patients are warranted to evaluate whether these early functional modifications will progress to a more compromised cardiac function and structure at a later time. Assessm®) with inversion recovery prepared fast gradient echo sequences ) than for longitudinal dSR-E .LV wall thickness, LV volumes and EF, evaluated by CMR, were normal in all LKDs, and consistent with echocardiographic measures. Delayed enhancement, as assessed by CMR with gadolinium, was present in the one patient with grade I hypertension. In this single case, delayed enhancement was localized to the basal segment of the infero-lateral wall, and to the middle segment of the lateral wall .The analyses outlined above have been repeated stratifying groups by SBP  irrespective of control or donor status. According to this stratification criterion, age and radial diastolic strain rate at early diastole were the only values to be different between Group I and Group II , and determined cardiac function and structure by combining state of the art in-depth imaging modalities, including ECG-gated CMR and echo strain analysis, with levels of established and emerging humoral markers. We further compared these findings to those obtained in age and gender matched healthy control subjects, free of known cardiovascular risk factors. The findings of the current investigation suggest that in LKDs there is evidence of mild, pre-clinical myocardial dysfunction, affecting LV deformation both in systole and in diastole, localized at the apex, and associated with abnormal torsion/detorsion of the LV. However, after ~ 8 years post UNX, these early anomalies were not accompanied by signs of myocardial fibrosis/remodeling, as determined by contrast enhanced CMR. Nevertheless, an elevated level of PIIINP was observed that suggests development of fibrosis possible related to extra-cardiac fibrosis or occult cardiac fibrosis.Cardiovascular disease is a leading cause of morbidity and mortality for individuals with low GFR in the general population , and is In spite of this evidence, several studies showed that kidney donors do not incur shortened survival: Fehrman-Ekholm et al. found thWe studied the possible long-term cardiac adaptation to UNX in a small sample of highly selected long standing Italian LKDs, using thorough imaging investigation with state of the art contrast-enhanced CMR and echocardiography in a cross-sectional study design. Here, similar to what has been reported in these previous studies, during a median follow-up period of almost 12 years, none of our patients died, or developed CV events or ESRD. Only one patient presented stage I hypertension at the time of evaluation, which was controlled with diet and exercise, without clinically evident signs of progression. LV geometry and function of LKDs, as assessed by standard echocardiography and CMR, were normal and comparable to healthy controls. Importantly, CMR provides comprehensive assessment of myocardial anatomy and function, with unmatched levels of accuracy and reproducibility. The use of gadolinium contrast agent has further enhanced the accuracy and precision of this approach to analyze myocardial tissue composition, especially myocardial fibrosis content. In order to detect any myocardial pathologic process, we purposely enrolled patients who donated several years before evaluation. After an average time of 8.4 years post UNX, subtle myocardial fibrosis was detected only in the donor with stage I hypertension, but in none of the other donors. The lack of cardiac fibrotic deposition was also consistent with the normal LV volumes and performance (both systolic and diastolic) observed with standard echocardiography, and with the event free follow-up.It is perhaps more difficult to explain the significant reduction in myocardial deformation as assessed by speckle myocardial imaging, as well as the abnormal LV twisting parameters we observed in LKDs. First, global reduction in myocardial deformation does not involve radially oriented myofibers, and this is consistent with the normal LV ejection fraction observed in donors. Second, although longitudinal sS and dSR-E are lower in LKDs compared to our controls, the values are well inside the accepted range of normality . This isIn order to definitely ascertain fibrogenesis status in our group of LKDs, we also measured serum level of PIIINP, an extension peptide of type III procollagen that is cleaved during conversion of type III procollagen to collagen. This peptide is then eliminated by the liver (mainly) and by the kidney (secondarily). PIIINP is increased in a number of conditions where increased fibrogenesis, or turnover of connective tissue occurs, and is therefore employed to monitor ventricular remodeling in hypertension, congestive heart failure, and non-ischemic cardiomyopathies . In our The main limitation of the present work is the small sample size. Virtually all studies of long-term outcomes in donors are retrospective , many with large losses to follow-up. Our study is cross-sectional, and although it enrolled a small number of subjects, study population was highly homogeneous, has been studied with the most recent cardiovascular imaging techniques, and no subject was lost to follow-up. Moreover, the observed statistically significant differences between donors and controls suggest adequate power of the study, and low risk of type II error. Of note, we have compared different populations of patients , and although there was no difference in demographic or biometric characteristics, more subtle differences, related to genetic background, culture, and social habits, cannot be excluded: for example, according to the world health organization (WHO) data, italians have on average higher life expectancy as compared to US citizens ; consistUnderstandably, living donors are very carefully screened, and so are inherently healthier at baseline than the general population . ConsequTo our knowledge this is the first investigation to have enrolled and extensively assessed myocardial structure and LV function, using the most accurate and sensitive imaging techniques available today (i.e. CMR and thorough echocardiographic examination), in a homogeneous group of clinically healthy LKDs who donated, on average, 8 years before enrollment. Our findings suggest that LKDs, even several years after UNX, do not develop myocardial fibrosis or abnormalities in LV geometry or function. Risk of cardiovascular or renal events is not increased in a time span reaching 12 years, with normal level of a widely accepted surrogate marker, NT-proBNP. In spite of these reassuring observations, our donors exhibited a mild reduction in systolic as well as diastolic myocardial deformation parameters along the longitudinally oriented myocardial fibers, particularly evident at the apical level, and specifically affecting rotation and torsion of the LV. These alterations have been associated with an increased risk of worsening cardiac function in patients with Non-Compaction cardiomyopathy . Signs oS1 TableClinical, laboratory and echocardiographic measurements in recruited subjects (patients and controls), grouped by systolic blood pressure values. Descriptions are with mean ± standard deviation (SD), median (inter-quartile range) or count (percent).(DOC)Click here for additional data file.


Biomarkers such as natriuretic peptides (NPs) have evolving clinical utility beyond the scope of heart failure. The role of NPs in the management of valvular heart disease is a growing area of investigation. NPs have much potential in the assessment of asymptomatic patients with hemodynamically significant valvular lesions who have traditionally been excluded from consideration of surgical intervention. NPs also have a role in the risk stratification of these patients as well as in routine surveillance and monitoring. Together with echocardiographic data and functional status, NPs are being incorporated into the management of valvular heart disease. In this review we examine the evidence for the role of natriuretic peptides in assessment of VHD. Valvular heart disease (VHD) is comprised primarily of stenotic and regurgitant lesions of heart valves. VHD is among the most common causes of heart failure and sudden cardiac death , 2. It iEchocardiography is the most commonly used imaging modality to assess the severity of VHD and left ventricular (LV) function; however it is operator dependent and has several limitations. For this reason, there is a growing need for other objective measures to help identify patients with VHD. Various biomarkers have been examined for diagnosis and assessment of VHD severity and preoperative risk stratification. The list of such biomarkers is long and includes but is not limited to brain natriuretic peptide (BNP), NT-BNP , N-terminal-pro-BNP (NT-pro-BNP), cardiotrophin-1, and tumor necrosis factor receptors 1 and 2. For a biomarker to be used in assessment and management of VHDs, it must reflect LV wall stress and predict echocardiographic and clinical progression of the disease. Among the various biomarkers, natriuretic peptides have shown promising results in several studies, and BNP in particular has emerged as an important potential biomarker for the diagnosis, management, and assessment of valvular heart diseases. In this review we examine the evidence for the role of natriuretic peptides in assessment of VHD.Atrial natriuretic peptide (ANP) and B-type natriuretic peptide are the two major hormones which are produced by cardiac myocytes in response to increased stress in the form of either pressure or volume overload. ANP is generally stored in the atrial muscles and released in response to stretch, whereas BNP is released by muscle tissue of the ventricles. BNP is a prohormone which is cleaved to produce its inactive form known as NT-pro-BNP , 4. TheyNPs are shown to be correlated with the severity of aortic stenosis (AS) measured either by transvalvular gradient or valvular area –17. Gerb2) and preserved LV function  on univariate analysis after 2 years of MitraClip therapy [Moreover, there is paucity of data evaluating role of BNP or NT-pro-BNP in patients undergoing transcatheter mitral valve repair or replacement (TMVR). In subanalysis of MitraSWISS registry, Toggweiler and colleagues have reported significantly lower survival rates among patients who have NT-pro-BNP ≥ 5000 ng/L at baseline [HR 6.18  is most commonly caused by rheumatic fever; however, its incidence has declined considerably over the past several decades . The carsurotomy . SurgicaSharma et al. in 2011 performed a study to compare atrial (ANP) and brain natriuretic peptides in the assessment of mitral stenosis and its severity . They diA Turkish study examined NT-pro-BNP to determine if and how closely the biomarker correlated with clinical symptoms and echocardiographic evidence of MS. They found that significantly higher levels of NT-pro-BNP had a close correlation with echocardiographic data and functional capacity of patients . The finAs mentioned previously, percutaneous balloon valvuloplasty is the surgical intervention that is typically used to manage patients with MS and meet the indication for intervention. BNP and NT-pro-BNP levels have been repeatedly shown to decline after successful intervention –47. ThisNPs are a helpful tool to aid in the evaluation of asymptomatic patients with hemodynamically significant valvulopathy as well as in the surveillance of known valvular disease to monitor disease progression. There are however limitations that should be noted when using BNP and NT-pro-BNP clinically. NPs have been traditionally used in the inpatient setting to support the clinical diagnosis of decompensated heart failure . The mecJust as there are clinical conditions which drive BNP levels up further, there are also conditions which cause BNP to be lower than expected. One commonly known reason for this is obesity and while the exact mechanism is unclear, there is some speculation as to why. One explanation suggests that adipocytes express higher levels of clearance receptors leading to lower plasma concentrations . Other cAnother potential limitation to the clinical application and value of BNP is its variation between individuals. Certainly the aforementioned conditions causing fluctuations in BNP can account for some variation between patients; however it is important to determine a patient's own baseline BNP or NT-pro-BNP level to more accurately identify significant changes . These bIn addition to variation between individuals there can be considerable variation within an individual, particularly in a patient with chronic heart failure. Although there is conflicting data, patients generally require a change in NT-pro-BNP and BNP of 25% and 40%, respectively, to represent a clinically significant change in volume status , 54. ThiThe measurement of biomarkers such as BNP and NT-pro-BNP is readily accessible diagnostic aids and provide valuable information in risk stratification and postprocedure outcomes in patients with VHD. These biomarkers are particularly helpful in the early identification of patients with hemodynamically significant valvulopathy in the absence of clinical symptoms. Further, the emergence of BNP as an independent prognostic biomarker for the evaluation of valvular heart disease highlights the need for further research regarding early surgical intervention in specific patient populations, particular those with asymptomatic but severe lesions.


Reproducibility data of the extent and patterns of late gadoliniumenhancement (LGE) in hypertrophic cardiomyopathy (HCM) is limited.To explore the reproducibility of regional wall thickness (WT), LGE extent,and LGE patterns in patients with HCM assessed with cardiac magneticresonance (CMR).The extent of LGE was assessed by the number of segments with LGE, and by thetotal LV mass with LGE (% LGE); and the pattern of LGE-CMR was defined foreach segment.A total of 42 patients (672 segments) with HCM constituted the studypopulation. The mean WT measurements showed a mean difference betweenobservers of -0.62 ± 1.0 mm (6.1%), with limits of agreement of 1.36mm; -2.60 mm and intraclass correlation coefficient (ICC) of 0.95 (95% CI0.93-0.96). Maximum WT measurements showed a mean difference betweenobservers of -0.19 ± 0.8 mm (0.9%), with limits of agreement of 1.32mm; -1.70 mm, and an ICC of 0.95 (95% CI 0.91-0.98). The % LGE showed a meandifference between observers of -1.17 ± 1.2 % (21%), with limits ofagreement of 1.16%; -3.49%, and an ICC of 0.94 (95% CI 0.88-0.97). The meandifference between observers regarding the number of segments with LGE was-0.40 ± 0.45 segments (11%), with limits of agreement of 0.50segments; -1.31 segments, and an ICC of 0.97 (95% CI 0.94-0.99).The number of segments with LGE might be more reproducible than the percentof the LV mass with LGE. Notwithstanding, current risk stratification algorithms failto identify a significant number of patients at risk of SCD deemed at low risk,possibly due to a large heterogeneity in the phenotypic expression and the myriad ofgenes involved in this disease.3 Maximum wall thickness (WT) and percent of leftventricle (LV) with LGE (% LGE) are, respectively, established and emerging riskfactors for SCD. Indeed, the % LGE has emerged as a variable with a continuousrelationship with the risk of SCD. Nevertheless, reproducibility data of % LGE inHCM is limited, and there is a lack of data in this population regardingreproducibility patterns of LGE and regional WT. Given the wide range of prevalenceof LGE in HCM reported in the literature (ranging from 40 to 80%), these data arepivotal for the internal validation aimed at improving risk stratificationstrategies, and also to establish threshold levels above which longitudinal changesmight be significant.7In a recent large cohort of patients with HCM who underwent LGE-CMR, the extent offibrosis was independently associated to an increase in SCD and to the developmentof end-stage HCM.The objective of this observational study is to explore the reproducibility ofregional wall thickness (WT), % LGE, and LGE patterns in patients with HCM. Tothat end, we retrospectively searched our CMR database from September 2013 toSeptember 2014 and selected patients with confirmed or suspected HCM referred toour institution for LGE-CMR evaluation. Patients with moderate to severevalvular heart disease were excluded, as well as patients with known ischemiccardiomyopathy and those who had underwent septal myectomy or percutaneousseptal alcohol ablation.All CMR exams were performed using the same system . A five-element cardiac phased-array coil was usedfor signal reception and cardiac synchronization was performed using a vectorelectrocardiogram. Cine-CMR images were acquired in 8-10 contiguous short-axisslices from the level of the mitral valve annulus through the LV apex using acommercially available steady-state free precession pulse sequence. Technicalparameters were as follows: TR/TE (ms): 3.5/1.8; flip angle: 60°; sectionthickness: 8 mm; matrix: 144 x 157; field of view: 320 mm; voxel size: 2.2 x 2.0mm; and number of phases: 30. For detection of the presence, extent and locationof fibrosis, a breath-hold, T1-weighted, contrast-enhanced inversion-recoverysegmented gradient echo sequence (TR/TE (ms): 4.8/2.3; flip angle: 25°; sectionthickness: 10 mm; matrix: 184 x 154; field of view: 320 mm; voxel size: 1.75 x1.95 mm) was used. These LGE-CMR images were acquired 10 minutes afterintravenous administration of 0.2 mmol/kg of a commercially available gadoliniumchelate of diethylenetriamine pentaacetic acid bismethoxyethylamide, using identical long- andshort-axis planes to the cine images, except for the most apical short-axisslice, which was excluded because it can be affected by partial-volumeeffects.All CMR studies were analyzed offline, independently, in a dedicated workstation by two similarly experienced observers  blinded to theclinical history and patient's demographics. LV end-diastolic volume (EDV) andend-systolic chamber volume (ESV) were calculated using the Simpson method andLVEF was calculated as [EDV-ESV]/EDVx100. Basal image position was defined asthe basal-most image encompassing at least 75% of the circumferentialmyocardium. Myocardial mass was obtained on the basis of end-diastolicendocardial and epicardial contours, and calculated as the product of myocardialvolume and specific density of myocardial tissue (1.05 g/mL).11 The extent of LGE was defined using the AHA 17-segmentLV model, excluding the apex (AHA-segment 17) from the analysis. The extent ofLGE was assessed both visually by the number of segments with LGE, andquantitatively by the total LV mass with LGE (% LGE). For this purpose, the LVendocardial and epicardial borders on LGE images were manually planimetered todefine the myocardium, excluding papillary muscles and the intertrabecular bloodpool .Continuous variables are presented as means ± standard deviations ormedian (interquartile range), as indicated. The interobserver and intraobserver agreements wereassessed using intraclass correlation coefficients,  with 95% confidenceintervals, and Bland-Altman plots for continuous variables, and Cohen's kappacoefficient for categorical variables.A total of 42 patients with HCM who completed LGE-CMR investigation between September2013 and September 2014 constituted the study population. The mean age was 51.2± 17.7 years, and 28 (67 %) were male. Data regarding LV diastolic andsystolic volumes, LV ejection fraction, and left atrium area are depicted in Six hundred and seventy two LV segments were independently evaluated by twoobservers, with a mean regional WT of 9.9 ± 5.4 mm measured by observer 1 andof 10.5 ± 5.2 mm measured by observer 2 .Detailed analyses of regional WT are depicted in The mean difference between observers and limits of agreement were as follows: 1) ForWT , the mea15 In particular,recent reports have found that the extent of fibrosis identified by LGE-CMR inpatients with HCM is independently associated to an increase in SCD and to thedevelopment of end-stage HCM.3CMR has been established as the reference standard to evaluate (LV) morphology andfunction, offering advantages regarding spatial resolution and volumetric imaging,and without limitations common to other techniques such as restricted acousticwindow or radiation. Furthermore, numerous studies have validated late gadoliniumenhancement CMR (LGE-CMR) to identify the presence, extent, and distribution ofmyocardial fibrosis in patients with HCM.7 Such variabilitymight be attributed not only to the aforementioned genetic heterogeneity that havebeen suggested to include more than 1400 mutations in at least 13 genes, butpossibly to a previously deemed negligible interobserver variability.16The main finding of the present study was that LGE-CMR measurements had acceptablereproducibility, with average differences close to zero, narrow limits of agreement,and a very high intraclass correlation coefficient between observers. As expected,excellent agreement was observed regarding the maximum WT. Furthermore, there wasgood agreement regarding the presence of LGE on both per patient and per segmentbasis, with the identification of LGE in more than 70% of cases and in more than 20%of the segments evaluated. These results are in line with previously reported datashowing a wide range of LGE in patients with HCM, between 40 and 80%. It should bestressed, however, that the percent of the total LV mass with LGE is related topatient population, CRM system and acquisition parameters, and the employedquantification technique.Indeed, it is noteworthy that in our study, relative differences reached 11% and 21%for the number of segments with LGE and for the % LGE respectively, suggesting thatreporting the number of segments with LGE might be more accurate than the percent ofthe LV mass with LGE. Such relative differences and the acknowledgement of thelimits of agreement are of outmost importance not only due to the fact that LGE-CMRis increasingly uprising as a means to improve risk stratification in patients atrisk of SCD, but also since the temporal change of such measurements mightpotentially become a surrogate imaging endpoint in longitudinal HCM studies.19 Furthermore, a transmural pattern has beenreported in up to 50 % of HCM patients.17 In our study, the presence of LGE was assessed visually,since it has been shown that such analysis is highly correlated to that obtainedfrom using a threshold of equal or more than six standard deviations above the meansignal intensity of normal myocardium, and is generally used as the referencestandard.10Of note, we identified significant differences between observers regarding the mainLGE pattern identified in every segment. This is not very surprising consideringthat almost every pattern, distribution and location of LGE has been reported inHCM.11 reported theinterobserver variability of a number of semi-automated LGE quantificationtechniques in 15 patients with HCM. Furthermore, Harrigan et al. explored thereproducibility of different semiautomated gray-scale thresholding techniques forquantifying LGE in a relatively large cohort of patients with HCM. Nonetheless,neither LGE patterns nor the number of segments were assessed in theirstudy.8 The number ofsegments with LGE has gained clinical relevance, since it has been reported as avariable associated to an increased incidence of adverse events in differentscenarios.22To the best of our knowledge, this is the first study that has specifically addressedthe reproducibility of LGE-CMR patterns in patients with HCM. Mikami etal.In turn, we evaluated in 42 patients with HCM the reproducibility not only of LGEextension (using two approaches), but also of other parameters related to riskstratification including regional WT and LGE patterns both on a per patient and persegment basis. Our results might therefore aid investigators to perform precisepower calculations for longitudinal studies.A number of limitations should be acknowledged. We included a relatively smallpopulation of patients with HCM considering the large genetic and phenotypicheterogeneity of this disease. Furthermore, the significant differences foundbetween observers regarding LGE patterns, aside from confirming the considerableheterogeneity in the phenotypic expression of the disease, might be partly relatedto the fact that only the most predominant pattern was registered per segment.Nevertheless, to the best of our knowledge, this is the largest study thatspecifically evaluated the reproducibility of LGE-CMR in HCM patients. We did notaddress the intraobserver variability since interobserver differences are usuallylarger and more clinically relevant for longitudinal studies.In this study, the assessment of the regional mean and maximum wall thickness usingLGE-CMR in patients with HCM showed excellent reproducibility, whereas the extensionof myocardial fibrosis was acceptably reproducible, and significant differencesbetween observers were identified regarding LGE patterns. Importantly, relativedifferences reached 11% and 21% for the number of segments with LGE and for thepercent LGE respectively, suggesting that reporting the number of segments with LGEmight be more reproducible than the percent of the LV mass with LGE.


Myocardial redox imbalance is a hallmark of this syndrome, since excessive reactive oxygen and nitrogen species can behave as signaling molecules in the pathogenesis of hypertrophy and heart failure, leading to dysregulation of cellular calcium handling, of the contractile machinery, of myocardial energetics and metabolism, and of extracellular matrix deposition. Recently, following new interesting advances in understanding myocardial ROS and RNS signaling pathways, new promising therapeutical approaches with antioxidant properties are being developed, keeping in mind that scavenging ROS and RNS The prevalence of heart failure (HF) is still increasing worldwide, with enormous human, social, and economic costs –6, despiThe etiology of heart dysfunction is heterogeneous, although individuals with HF have rather common symptoms as fatigue, shortness of breath, and fluid retention. Half of HF patients present with contractile failure and a dilated heart (systolic HF), while other patients have normal systolic function with a preserved ejection fraction (EF) and a nondilated, but often hypertrophied, heart. This latter is also named HF with preserved ejection fraction (HFpEF) .Central to the pathogenesis of systolic HF is decreased left ventricular (LV) contractile function, due to an initial ischaemic insult  or to nonischaemic insult . These insults induce an inexorable series of compensatory responses in the body, including the retention of salt and water by the kidneys, the release of neurohormones, and the activation of intracellular signaling cascades in the heart and vasculature that modify cellular and organ morphology and function. Such responses initially offset reduced cardiac performance but then become part of the disease process, increasing organ failure and worsening clinical prognosis –7.β-adrenergic and angiotensin receptor blockade and angiotensin converting enzyme (ACE) inhibition and on hemodynamic control with nitrates and diuretics, with the net effect of producing vasodilation and lowering blood pressure, therefore unloading the heart i has been recently shown to lower mitochondrial Ca2+ uptake, increasing ROS production i and oxidative stress [+]i would then stimulate NCX and intracellular Na+ would be exchanged with extracellular Ca2+ with consequent Ca2+ overload and electrical and mechanical dysfunction, in a scenario in which SERCA2a is inhibited and the RyR2 is activated by ROS [+]i can be identified as an interesting therapeutic target for HF treatment [Na with ranolazine has been proven beneficial in experimental HF [Enhanced myocytes [Naoduction . The samortation . In turninase II , 143 tha channel , 145, the stress . High [Nd by ROS , 147. Hereatment . Indeed,ental HF , 148–1512O2. Pharmacological or genetic manipulation of such enzymes could then prove beneficial in cardiac dysfunction [Other promising therapeutic targets are monoaminoxidases: MAO A and MAO B have been recently proposed to play a role in experimental hypertrophy and failure via increased generation of Hfunction , 153   is a mitResveratrol is a widely used antioxidant dietary supplement with promising experimental results on pressure overload cardiac hypertrophy, but beneficial effects on clinical hypertrophy have not yet been reported , 158.2N2O3) demonstrated significant improvements in load-independent LV contractility, associated with reductions in preload volume and diastolic pressure [2+ sensitivity and force generation [Currently, in HF treatment the room for inotropic therapies such as dopamine, dobutamine, and milrinone is very limited by the mortality associated with long-term treatment with these drugs –117. Nitpressure , 162. Thpressure  with no pressure , but ratpressure , 166 andpressure  and on mneration . Recentlneration , 169–171ROS and RNS at physiological concentrations are beneficial molecules and play a role in the regulation of cellular signaling pathways . ROS/RNS


We have demonstrated for years, the efficacy of urea to treat euvolemic (SIADH) or hypervolemic hyponatremia. We briefly describe the indications of urea use in symptomatic and paucisymptomatic hyponatremic patients. Urea is a non-toxic, cheap product, and protects against osmotic demyelinating syndrome (ODS) in experimental studies. Prospective studies showing the benefit to treat mild chronic hyponatremia due to SIADH and comparing water restriction, urea, high ceiling diuretics, and antivasopressin antagonist antagonist should be done.Oral urea has been used in the past to treat various diseases like gastric ulcers, liver metastases, sickle cell disease, heart failure, brain oedema, glaucoma, Meniere disease,  It represents about half of our daily osmotic load eliminated in the urine. It is synthesized in the liver (“urea cycle”) and corresponds to the catabolism of amino-acids in excess of our needs (coming from food) and which are not used by the organism (mainly protein synthesis) [Urea is the main nitrogen-containing substance in the urine of man. It is highly soluble in water and practically non-toxic  in the past, and, for years ,3, liverIt has been mainly used to treat brain oedema ,10,11, gUrea has been used orally or intravenously over time as an osmotic diuretic drug and as an agent to reduce intracranial and intraocular pressure .As opposed to mannitol, urea enters intracellular spaces rapidly (in less than one hour) throughout the body, decreasing the immediate risk of sudden cardiac decompensation due to rapid intravascular volume expansion and does not induce a transient decrease in serum sodium (SNa) as observed with mannitol (translocation hyponatremia) .However, because urea penetrates into the central nervous system (CNS) only about one-tenth as quickly as into muscle, a significant intravascular to CNS urea gradient occurs (during 4 to 10 h) . DecreasHigh doses of urea can be given on a long-term basis without renal toxicity, which is not the case for mannitol.In individuals with previously normal baseline renal function, the mean total dose of mannitol that precipitated acute renal failure was 626 ± 270 g over two to five days  (which retc.) treated with 1 L isotonic saline over 12 h and urea (0.5 g/kg) administered by gastric tube over 5–10 min. In these patients, mean SNa increased by 7 mmol/L in eight hours. All the patients made a rapid neurological recovery [2O during a few hours  [We are using urea, mainly orally (by gastric tube if needed). Oral urea is less expensive than the intravenous route . Figure recovery . At the recovery . Hypertoination)  and will2O/day, an additional osmotic charge of 500 mOsM provided by the administration of 30 g of urea will result in a diuresis of 1500 mL for a fixed urine osmolality of 800 mOsm/kg/H2O. If water intake is limited from 1500 to 2000 mL/day, 30 g of urea, either in one or in two divided doses (2 × 15 g), is generally sufficient to maintain a normonatremia. One can calculate, with the aid of the measured urine osmolality, the daily dose of urea required to obtain the additional volume of urine necessary to maintain normonatremia, e.g., 30 g urea (500 mOsm) allows the excretion of 1 L free water if urine osmolality is fixed at 500 mOsm/kg/H2O. Oral crystalline urea is dissolved in 100 mL water and is taken after meals to avoid gastric intolerance. The poor palatal taste of the preparation could be avoided by addition of fruit syrup. For patients who do not tolerate oral urea (~15% of patients) we usually prescribed an effervescent solution, used in the past to treat gastric ulcer [3 2 g, citric acid 1.5 g and sucrose 200 mg to be dissolved in 50 mL to 100 mL water). Urea can been used for years without toxicity and is an alternative to vasopressin V2 antagonist ([It is well known that urea induces water loss by increasing the daily osmotic charge eliminated in the urine. During the initial phase of the treatment with urea, normalization of the serum sodium is due to the “antinatriuretic” and osmotic property of urea . During agonist (,28, see agonist (,32,33. Dagonist (. For theagonist (,34,35,36agonist (,37.These data show that urea is a simple and inexpensive therapy to treat euvolemic hyponatremia.


The differential diagnosis of hypertrophic phenotype remains challenging in clinical practice, in particular between hypertrophy cardiomyopathy (HCM) and increased left ventricular wall thickness (LVWT) due to systemic hypertension. Diffuse myocardial fibrosis is the characteristic feature in HCM, whereas hypertensive response is underpinned by addition of myofibrils in otherwise normal myocardial tissue. Late gadolinium enhancement (LGE) imaging provided important new way of differentiation between these two entities by separating those cases with evidence of regional fibrosis. Whereas approximately 60% of patients with HCM reveal visually discernable LGE, T1 mapping is highly discriminative, irrespective of the presence of LGE.Sixty patients with diagnosis of unequivocally hypertrophic cardiomyopathy and fifty patients with hypertensive cardiomyopathy underwent routine cardiac MRI protocol including assessment of function and scar (3-Tesla). T1 values were measured conservatively within septal myocardium in midventricular short-axis slice prior to administration of 0.2 mmol/kg of gadobutrol.HCM group showed higher LV mass and maximum LVWT than the hypertensive group . There was LGE in 20% of hypertensive  and in 84% of hypertrophic cardiomyopathy  (p < 0.001). Patients with HCM showed significantly higher T1 values compared to hypertensive patients . Native T1 values were concordant to LVWT and LV mass . T1native held superior diagnostic accuracy compared to conventional functional parameters and the presence of LGE to discriminate between hypertrophic or hypertensive cardiomyopathy  comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital National Health Service Foundation Trust. Dr. Rocio Hinojar was supported by the Fundacion Alfonso Martin Escudero.


In order to understand the physiology of the neonatal heart, one must have an understanding of both the fetal circulation and the cardiac function of the adult heart. Transitional changes occur in the neonatal period, where the function of one ventricle has important effects on the function of the contralateral ventricle . In the Giovanni Biglino and Adelaide De Vecchi have organized a research topic entitled “Ventricular mechanics in congenital heart disease” in order to increase the current knowledge on the physiology of the neonatal and infant heart, particularly in relationship to the coupling of the ventricular function with the systemic and pulmonary resistance. This research topic will concentrate on myocardial function in complex congenital heart defects, including conditions with a morphologic right ventricle sustaining the systemic circulation and hearts with functionally a single ventricle.Biglino et al.). This research topic will be of particular interest to those who involved in the treatment of complex congenital heart defects.The ventricular interactions in the presence of congenital heart defects have been primarily investigated for the past few decades using ultrasound and radioisotopes . This reResearch articles stimulated by this research topic will improve the understanding of the ventricular function in congenital heart defects and will facilitate the decision-making process related to the timing and type of intervention.An improved knowledge of the degree of myocardial dysfunction as a result of ventricular pressure and/or volume overload due to the presence of cardiac malformations should result in improved comprehensive management strategies for each type of congenital heart defect.The author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Objective. This study was performed to determine the level of procalcitonin, Brain Natriuretic Peptide (BNP), and uric acid in children with cardiomyopathy in comparison with controls and the association with echocardiographic findings. Methods. The levels of BNP, procalcitonin, and serum uric acid were measured and the amounts of biomarkers compared with echocardiographic findings. Results. In this study mean age of participants was the same (p=0.321). The majority of echocardiographic indices in left and right heart have different means in case and controls (p<0.05). Means of BNP, procalcitonin, and uric acid were 213.814 ± 309.601, 9.326 ± 3.881, and 6.846 ± 1.814 for case group and 2.76 ± 1.013, 1.851 ± 1.466, and 3.317 ± 0.924 for control (p<0.001), respectively. In the patients group there was relationship of Ross classification with BNP  and with age . For uric acid and procalcitonin no significant relationships were observed. Conclusions. procalcitonin, uric acid, and BNP had significant relationship with many echocardiographic findings in participants. For patients, procalcitonin did not show correlation. The severity of illness based on the Ross classification showed significant correlation with BNP level and age in patients. Cardiomyopathies, diseases of the heart muscles, primarily affect the left ventricle in which there is the main pumping chamber of the heart. Dilated cardiomyopathy (DCM) is recognized by left ventricular dilation that is concerned with systolic dysfunction. Diastolic dysfunction and impaired right ventricular function can occur. Left or right ventricular failure or both can be risk factors for affected individuals by DCMP. It may lead to ventricular arrhythmia, atrioventricular block, syncope, and sudden death . The yeat-test and one-way ANOVA were used and otherwise same nonparametric tests were applied. For the relationship between variables Pearson correlation was used. In all tests the value of 0.05 was considered for significant differences or correlations.This study was performed in two training hospitals located in Sistan and Baluchestan Province, Zahedan, Iran, from February 2014 to January 2015 among all patients with dilated cardiomyopathy. Patients' age ranged from 1 to 18 years. The study complies with the current ethical considerations. Informed consent was obtained from each patient's parents of the minors included in the study, and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution's Human Research Committee. Exclusion criteria were hemoglobin less than 10 g/dL, endocrine, metabolic, and valvular disorders, dysrhythmia, and heart block. After considering exclusion criteria 37 patients were included in the study as case group and compared with 37 healthy children who matched in age and gender with case group. The control group was selected according to the normal status in clinical examination and echocardiography. Taking history, physical examination, CXRay, ECG, and echocardiography by MyLab 60 with transducer 3, 8  were performed for all the participants. In this study, children weights for those over 2 years old were measured using RASA Mark made in Iran by an error of 100 g, while those for children under 2 years old were measured by MIKA Mark recumbent weighing scale made in Japan by an error rate of 10 g. In addition, under-2-year-old children's height was measured in the recumbent position by using a flat wooden calibration table, while that of the children above 2 years old was measured in the standing position with a scale ruler. Heart failure stratification was performed by modified Ross classification. The participant patients were normal in respect of Na, K, Ca, BUN, and creatinine. Three mL of blood was drawn from the patients while fasting at 8 am. Samples were centrifuged at 5°C with around 3000 g for 10 minutes. The separated serum was kept in −80°C refrigerator. The levels of BNP and procalcitonin were measured by ELISA kits. Serum uric acid level was measured by autoanalyser (NMCI). Echocardiography findings were measured by MyLab 60 made in Italy. Since the sample size is larger than 50, we use the Kolmogorov-Smirnov test for variables in the study. The null hypothesis for the test of normality stated that the actual distribution of the variable is equal to the expected distribution; that is, the variable is normally distributed. Since the probability associated with the test of normality for all variables except weight, left ventricular end-diastolic volume, fractional shortening, left peak E velocity, and right isovolumic contraction time is less than or equal to the level of significance (0.05), we reject the null hypothesis and conclude that these variables are normally distributed. Data analysis was performed by SPSS 20.0 software and, in the case of normality, independent t-test results show nonsignificant difference (p = 0.321). The means of weight are 35.133 ± 18.471 and 28.7 03 ± 10.553 kg in control and case groups, respectively (p = 0.078). The means of height are 128.721 ± 29.231 and 127.405 ± 18.712 cm in control and case groups, respectively (p = 0.574). t-test to compare means of echocardiographic findings of left and right heart in case and control groups. Means of left ventricular end-diastolic volume for case and control groups are 66.108 ± 22.129 and 39.279 ± 14.782 with significant different  and same trends for means of left peak E velocity with 85.974 ± 17.759 and 101.558 ± 19.648, respectively. The majority of echocardiographic indices in left , peak A velocity , ejection time , and interventricular septal dimension in diastole . Level of uric acid of patients has significant correlation with BNP  peak A  and IVSDD . BNP values have significant correlation with Et-p  and IVSDD . r = 2.28, p = 0.02), At-L , and Et-R . Weight of participants has significant mostly negative correlation with At-L , Et-R , Pep/et-R , LVPWD , and IVSS . Height like weight has negative or positive significant correlation with some of echocardiographic parameters or biomarkers, namely, EF , At-L , and dt-R . Procalcitonin has strong and significant correlation with the most echocardiographic parameters except At-R, dt-R, At-L, EF, and ivds. At the end of study, from 10 patients in group one, 2 patients died due to disease progression. All nine participants in the second group survived until the end of follow-up. In group 3 one patient died and one had heart transplantation (from 10 patients). And finally, for the fourth group, from eight patients, two received heart transplantation, one was with three-chamber pacemaker (died), and two individuals withdrew from the study.In this study 74 children were recruited in equal case and control of 37 subjects. The participants' age ranged from 1 to 18 years with mean of 10.56 7 ± 5.5 and 12.135 ± 4.626 years for control and case, respectively, in which  in left  and righ in left  heart haThis study demonstrated that LVEDV (left ventricular end-diastolic volume), LVEDD (left ventricular end-diastolic dimension), LVESD (left ventricular end-systolic dimension), MPI , ICT (isovolumic contraction time), IRT (isovolumic relaxation time), E (peak E velocity), PEP/ET (preejection period/ejection time), ET (ejection time), IVSDD , LVPWDD , IVSDS , and LVPWDS  in left heart and MPI, IRT, DT (deceleration time), E, A (peak A velocity), PEP/ET, PEP, and ET in right heart were significantly different between two groups. We found that in patients with DCM the majority of echocardiographic parameters are increased in case group compared to control group. It also resulted that BNP and procalcitonin were increased significantly according to Ross classification but uric acid decreased nonsignificantly in the case group. Also some echocardiographic parameters were correlated with BNP and uric acid and also it was seen that BNP is a better marker compared with others due to association with severity and progression or regression of disease.Increased BNP may approve the presence of DCM due to diastolic dysfunction and probably systolic dysfunction but without differentiation power between systolic and diastolic types. Accordingly, BNP has been approved by FDA for diagnosis of heart failure. Similarly we found association between BNP and MPI that shows systolic and diastolic dysfunction . JefferiSponholz et al. in a systematic review reported that, after uncomplicated cardiac surgery, procalcitonin levels increase to the peak level within 24 hours and return to normal levels within one week after operation. The degree of procalcitonin elevation depends on the intraoperative course and the type of the surgical procedure. Higher procalcitonin levels were observed in patients with a complicated postoperative course, with infection or sepsis syndromes compared to patients with an uncomplicated course. Procalcitonin is a useful test in differentiating acute graft rejection of heart and lung transplantation from bacterial and fungal, but not from viral, infections . In our The present research was performed on patients with DCM and showed that procalcitonin, uric acid, and Brain Natriuretic Peptide had significant relationship with the majority of echocardiographic parameters when we considered both case and control groups. Procalcitonin did not show any correlation with echocardiographic parameters in patients. The severity of illness based on the Ross classification showed significant and positive correlation with BNP level and age in patients.


Two-dimensional speckle tracking provides valuable information for regional wall motion abnormalities. The purpose of this study was to determine the diagnostic value of left ventricular longitudinal strain and torsion to diagnose coronary artery disease during dobutamine stress echocardiography.We studied 100 patients  with known or suspected coronary artery disease, excluding those with prior history of transmural infraction. All of them underwent dobutamine stress echo and coronary angiography within one month. Wall-motion score index, left ventricular global longitudinal strain and torsion were measured at rest and peak stress. Additionally, the respective differences between rest and stress were also calculated. Optimal cut-offs were derived from receiver operating characteristic curves for strain and torsion values.Mean left ventricular ejection fraction was 55 ± 5.4 %. Coronary angiography revealed significant lesions in 67 patients. Values regarding sensitivity, and specificity for wall motion score index difference were 78 % and 88 % respectively (area under curve 0.84). Global longitudinal strain difference (median 0.5 %) illustrated 81 % sensitivity and 72 % specificity for disease detection . The respective values for torsion difference (median 4.7°) were 81 % and 82 % . Combination of wall motion score index difference and torsion difference for disease detection showed 91 % sensitivity and 79 % specificity (area under curve 0.85).The implementation of speckle tracking during dobutamine stress echo could serve as an adjunct method for coronary artery disease assessment, providing quantitative diagnostic information. Timely and prompt detection of coronary artery disease (CAD) is of paramount importance for patient management in daily clinical practice. Dobutamine stress echocardiography (DSE) is a non-invasive method with established diagnostic accuracy. Still, it remains subjective, mainly because of its dependence from operator experience on image acquisition and interpretation , 2.Speckle tracking echocardiography is a novel method for the assessment of global and regional left ventricular myocardial function. It provides valuable insights to myocardial deformation by quantifying strain and torsion with the inherent advantage of being angle-independent , 4. FromSpeckle tracking derivatives are less susceptible to translational motion and tethering, which lead to erroneous qualitative evaluation of stress echo images. So far few studies have been published exploring the implementation and clinical utility of speckle tracking imaging during DSE –13. The 114 consecutive patients with known or suspected coronary artery disease who were referred to our tertiary center for evaluation of myocardial ischemia or coronary angiography. Fourteen patients were rejected due to poor acoustic window, unsuitable for speckle tracking echo. Eventually 100 patients were included in the study. All of them underwent DSE and coronary angiography within one month. Patients with depressed left ventricular function (EF < 45 % at rest), significant valvular heart disease, left bundle branch block on ECG, pacemaker and history of coronary artery bypass surgery were also excluded. The study protocol was approved by the ethics committee of the Hippokration Hospital of Athens and all patients gave written informed consent.We studied All studies were performed with an iE33 ultrasound machine , equipped with the 2.5 MHz S5-1 transducer. Images were obtained with patients being positioned in the left lateral decubitus position, in the parasternal short axis  and apical 4-, 3- and 2-chamber views at rest and peak dobutamine infusion. Two-dimensional grayscale images were obtained at a frame rate of 70–80 Hz in order to be optimal for speckle tracking, during three cardiac cycles and were then digitally stored for off-line analysis. Quantitative measurements of longitudinal strain and torsion were made using the QLAB 9.0 software package.Dobutamine stress echo was performed using a standard protocol . An intrThe stress protocol was terminated if : (1) the age-adjusted target heart rate was achieved; (2) four or more contiguous segments showed signs of ischemia; (3) the patient reported intense chest pain; (4) the electrocardiogram showed VT, ventricular bigeminy or trigeminy, or multiform premature ventricular complexes; (5) if any other grade > 2 adverse event appeared.Wall motion was assessed by an expert observer. The 17-segment model of the left ventricle was used . MyocardLongitudinal strain and torsion measurements with the implementation of 2D speckle tracking were performed as previously described . End-sysTo assess left ventricle rotation, six tracking points were placed on the myocardium, avoiding the pericardium on an end-diastolic frame in each parasternal short-axis image as determined automatically by the software algorithm. Counterclockwise rotation, as viewed from the apex, was expressed as a positive value; clockwise rotation was expressed as a negative value. Analysis was performed to evaluate the peak apical rotation during the ejection phase, the basal rotation at a time isochronous with that of peak apical rotation during the ejection phase and the net instantaneous torsion of the left ventricle, which was calculated as peak apical minus the basal rotation at a time isochronous with peak apical rotation.Anterior and posterior circulation was evaluated separately as proposed by Geleijnse et al. . For antAll patients underwent coronary angiography within one month according to the Judkins technique. All images were evaluated by an experienced operator, and significant coronary artery disease was defined as >70 % luminar diameter stenosis.p-value < 0.05, was regarded as statistically significant. For global intra- and interobserver variability, 10 patients were selected at random, and measurements were repeated by the same observer on the same echocardiographic images 2 weeks apart and by another independent observer. The inter-observer variability was assessed using a two-way mixed, absolute agreement, single measures intra-class correlation.Data analysis was performed using the SPSS 20.0 statistical package for Windows . Continuous variables were presented as mean ± SD, whereas categorical variables were expressed as percentages. The chi-square test was used to compare categorical variables. Independent t-tests were used for comparison of matched segments in patients with and without CAD. Receiver operating characteristics curves (ROC) for each of the strain and torsion parameters was calculated and the optimal stain and torsion cutoff values for predicting CAD were then determined. In all cases, a Patient demographic data and hemodynamics are illustrated in detail in Tables We analyzed 3400 segments both in rest and stress. A total of 425 of the analyzed myocardial segments were rejected due to poor tracking. More specific, in rest the feasibility rates were 90 % , whereas in peak stress the feasibility rates were 85 % . In addition, we sought to determine inter and intra-observer variability at rest and peak stress. The correlation coefficient for the same observer at rest was 0.95 for 2D strain and 0.91 for torsion, while between the 2 observers were 0.91 and 0.89 respectively. At peak stress, the respective values for a single observer were 0.87 for GLS and 0.82 for torsion, while between two observes were 0.83 and 0.80.p < 0.005). Similarly, torsionΔ values were significantly reduced in ischemic patients as compared to normal persons  , exhibited 78 % sensitivity, 88 % specificity . Speckle tracking echo measurements are shown in Table p < 0.05). The combined assessment of GLSΔ and WMSIΔ revealed 87 % sensitivity and 73 % specificity (AUC 0.80), not statistically significant different than either indice alone. On the other hand the combined assessment of TorsionΔ and WMSIΔ revealed 91 % sensitivity and 79 % specificity (AUC 0.85), higher than either indice separately . Comparison of AUC is depicted in detail in Table The combination of GLSΔ and ΤorsionΔ for the detection of CAD showed 97 % sensitivity and 52 % specificity (AUC 0.77). The diagnostic value of the combined GLSΔ and ΤorsionΔ assessment was more sensitive as compared to wall-motion assessment alone (p < 0.001). Again, for posterior circulation strain values were changed in similar fashion . Area under the curve for LAD detection was 0.87, reporting 94.7 % sensitivity and 62.5 % specificity . For posterior circulation AUC was 0.78 . Changes in torsion values between rest and stress were able to predict LAD disease with 56 % sensitivity and 78 % specificity , while for posterior circulation the reported values were 81 and 60 % respectively   were excluded. Finally, there are certain limitations inherent to the technique of STE, which could reduce the signal-to-noise ratio especially during higher heart rates. Another limitation is that we did not use contrast agents to improve wall motion interpretation. Although this might have increased the diagnostic capability of WMSI, it would also have made speckle tracking imaging impossible.Given that deformation parameters and specifically global longitudinal strain can detect ischemia in an early stage, it could potentially provide better risk stratification for our patients. Furthermore, LV torsion was more sensitive in detecting posterior circulation disease, perhaps due to the fact that the apical rotation is less pronounced than basal rotation. This finding could be translated into clinical efficacy, since the ability of DSE to diagnose posterior circulation disease is somehow obscured by imaging difficulties of this specific region of interest. In addition, novel software algorithms allow for easier, faster and reproducible measurements, transforming speckle tracking into a robust clinical tool in the near future.In the present study we showed that the measurement of LV torsion and 2D-strain is feasible during DSE. Therefore, both of them might be used as a quantitative tool in combination with wall motion abnormalities for the detection of CAD. In addition, 2D-strain can give quantitative information for segmental ischemia, which comes in accordance with the angiographic findings.


Acute respiratory failure (ARF) is a leading indication for performing critical care ultrasonography (CCUS) which, in these patients, combines critical care echocardiography (CCE) and chest ultrasonography. CCE is ideally suited to guide the diagnostic work-up in patients presenting with ARF since it allows the assessment of left ventricular filling pressure and pulmonary artery pressure, and the identification of a potential underlying cardiopathy. In addition, CCE precisely depicts the consequences of pulmonary vascular lesions on right ventricular function and helps in adjusting the ventilator settings in patients sustaining moderate-to-severe acute respiratory distress syndrome. Similarly, CCE helps in identifying patients at high risk of ventilator weaning failure, depicts the mechanisms of weaning pulmonary edema in those patients who fail a spontaneous breathing trial, and guides tailored therapeutic strategy. In all these clinical settings, CCE provides unparalleled information on both the efficacy and tolerance of therapeutic changes. Chest ultrasonography provides further insights into pleural and lung abnormalities associated with ARF, irrespective of its origin. It also allows the assessment of the effects of treatment on lung aeration or pleural effusions. The major limitation of lung ultrasonography is that it is currently based on a qualitative approach in the absence of standardized quantification parameters. CCE combined with chest ultrasonography rapidly provides highly relevant information in patients sustaining ARF. A pragmatic strategy based on the serial use of CCUS for the management of patients presenting with ARF of various origins is detailed in the present manuscript. Acute respiratory failure (ARF) is a leading indication for performing critical care ultrasonography (CCUS), which combines critical care general ultrasonography  and critical care echocardiography (CCE) . CCUS isCardiogenic pulmonary edema (CPE) is a frequent cause of ARF. Although congestive heart failure remains commonly encountered in this clinical setting, CPE is increasingly attributed to heart failure with a preserved ejection fraction (EF) . Since CLV filling pressures closely depend on cardiac diastolic properties and volume status. CCE assessment of LV filling pressures mainly relies on the combined use of pulse-wave Doppler interrogation of mitral inflow  and tissue Doppler measurement of LV lengthening velocity during early diastole (E’ wave) which reflects myocardial relaxation . DopplerIn patients with CPE secondary to a decompensated congestive heart failure, CCE allows a comprehensive assessment of the causative cardiomyopathy. In the absence of LV systolic dysfunction and underlying cardiomyopathy, an acute volume overload should first be ruled out . Severe mitral regurgitation (MR) may be challenging to identify using TTE color Doppler mapping in the presence of eccentric jets. In this case, TEE more accurately depicts the regurgitant jet which has a clockwise or anticlockwise direction within the left atrium (LA) and may preferably enter left or right pulmonary veins, resulting in unilateral or asymmetrical pulmonary edema . This fr2 ; and (iii) LV diastolic dysfunction or its surrogates such as LV hypertrophy, LA enlargement, atrial fibrillation, or elevated plasma natriuretic peptides levels [Heart failure with normal LVEF—and no acute volume overload—is increasingly encountered in patients presenting with CPE . Predisps levels . LV diass levels . The sevs levels .Lung ultrasonography relies on the identification of findings  and artifacts  which can be combined , 19 Tab The presence of B-lines (and the loss of A-lines) is highly suggestive of interstitial pulmonary edema Table . ImportaCCE should be performed as a first-line diagnostic test in patients presenting with suspected CPE. First, it allows semi-quantitative assessment of LV filling pressures to differentiate CPE from acute respiratory distress syndrome (ARDS) . Second,Spontaneous breathing trial (SBT) has been compared to an exercise . Interru2O pressure-support with zero positive end-expiratory pressure (PEEP) trial [CCE accurately depicts an SBT-induced increase in LV filling pressures, irrespective of systolic function . PatientP) trial , 46, theP) trial . Whethern = 14) when compared to those who succeeded. This suggested a greater loss of lung aeration in patients who failed SBT [n = 29) and remained higher 4 h after extubation. A LUS ≥17 measured at the end of the SBT was associated with a likelihood ratio of post-extubation respiratory distress of 11.8 [During SBT, the inability to maintain lung aeration is consistent with weaning failure. The development or increased number of B-lines reflects this loss of lung aeration. Soummer et al  used a siled SBT . Interes of 11.8 . FinallyCCE should be used as a screening tool to objectively identify patients at high risk of weaning failure –43. In tARDS is an injury of both the alveoli and the pulmonary circulation, leading to acute pulmonary hypertension. With its ability to evaluate lung aeration, pulmonary artery pressure, and right ventricular (RV) function, CCUS is ideally suited to guide the management of ARDS patients. Specifically, it provides valuable information on the effects of PEEP on lung aeration and RV function. In patients with suspected ARDS, the first step is to rule out a cardiac failure or a fluid overload as the origin of ARF . CCE is 2/FiO2 ratio <150 mmHg, driving pressure ≥18 cmH2O, and PaCO2 ≥ 48 mmHg. When all these factors are present, the risk of ACP exceeds 60 %, whereas when no factor is present the risk is lower than 10 % [Circulatory failure involves more than half of ARDS patients , 53. Amohan 10 % .2/FiO2 ratio [CCUS is usually part of the initial assessment of most ICU patients. Specifically, the initial CCE evaluation of patients with ARDS is best performed within 24 h of ICU admission or tracheal intubation to achieve three objectives. First, it allows intensivists to rule out any cardiogenic mechanism at the origin of ARF (see above). Second, it provides a comprehensive assessment of hemodynamics and potentially a better understanding of the mechanism of a potential associated circulatory failure, especially in case of sepsis . In someO2 ratio . At the O2 ratio . In thes2 on the one hand and to maintain a PaO2/FiO2 ratio in a “safe” range on the other hand. In such a situation, the prone position is valuable in the absence of any contraindication since it has been proven to increase oxygenation and compliance of the respiratory system, and to decrease PaCO2 without increasing the PEEP level [2 extracorporeal removal could improve RV function and prognosis in ARDS patients remains to be elucidated [Most of the adaptation of the respiratory management has been described in the so-called “RV protective approach” . BrieflyEP level . InteresEP level  was not EP level , and proEP level . As expeEP level . Whetherucidated .p < 0.0001). They also observed that an ultrasound reaeration score ≥18 predicted a gain of aeration of more than 600 mL. Conversely, an ultrasound lung reaeration score <14 indicated an aeration gain between 75 and 450 mL. The reaeration score and observed increase in PaO2 were significantly correlated  [Systematic ultrasonographic examination of pleural spaces allows the ruling out of the presence of large pleural effusions which may participate in chest X-ray opacities, thus contributing to establishing the diagnosis of ARDS . In ARDS < 0.05) . As prev < 0.05) , alveola < 0.05) .Patients sustaining pulmonary embolism (PE)-related RV failure commonly present with a circulatory failure, rather than with isolated ARF. In this clinical setting, CCE may expedite diagnosis at the bedside in depicting ACP in conjunction with an embolus-in-transit within right cardiac cavities or with a thrombus entrapped into the proximal pulmonary arteries . VasculaA-line pattern associated with lung sliding and normal lung surface, especially when associated with a non-compressible deep vein, is highly suggestive of central PE. In a population of 352 patients with suspected PE (194 patients with confirmed diagnosis), the presence in the dorsal and basal areas of at least two triangular or rounded pleural-based lesions or one typical lesion associated with pleural effusion had a 74 % sensitivity and a 95 % specificity for the diagnosis of distal PE .CCE allows hemodynamic assessment of patients sustaining severe pneumonia associated with septic shock. Chest ultrasonographic findings associated with infectious pneumonia are lung consolidation and pleural effusion. The presence of lung consolidation has a 93 % sensitivity to identify community-acquired pneumonia in non-severely immunosuppressed patients . An air Thoracic ultrasonography may provide further information in patients with ARF of other etiologies ) Table . Lung slCCUS combining CCE and chest ultrasonography rapidly provides valuable information in patients presenting with ARF. A pragmatic and systematic applied protocol may first evaluate how aerated is the lung and whether there is pulmonary edema. CCE helps the physician in identifying the cause of poor lung aeration or lung edema, and in assessing LV filling pressure and ventricular function. In various clinical settings, including difficult ventilator weaning, CCUS is valuable in guiding the diagnostic work-up and therapeutic management of patients with ARF, whether they are mechanically ventilated or not.ACP, acute cor pulmonale; ARDS, acute respiratory distress syndrome; ARF, acute respiratory failure; CCE, critical care echocardiography; CCUS, critical care ultrasonography; COPD, chronic obstructive pulmonary disease; CPE, cardiogenic pulmonary edema; EF, ejection fraction; ICU, intensive care unit; LA, left atrium; LUS, lung ultrasound score; LV, left ventricular; MR, mitral regurgitation; PAOP, pulmonary artery occlusion pressure; PE, pulmonary embolism; PEEP, positive end-expiratory pressure; RV, right ventricular; SBT, spontaneous breathing trial; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography