Late cardiotoxicity is a known complication of anthracycline therapy. CMR is the gold standard for assessment of cardiac function, with demonstrated utility in the detection of subtle abnormalities of myocardial structure and motion. Using conventional and novel CMR techniques, we re-examined a cohort of late cancer survivors, previously studied with echocardiography in childhood. We compared them concurrently to healthy controls, aiming to characterise myocardial abnormalities in the context of longitudinal functional data.30 patients exposed to anthracyclines in childhood and 19 age and sex-matched controls underwent conventional functional CMR, T1 mapping, Tissue Phase Mapping (TPM) and detailed echocardiography. Myocardial T1 maps were obtained using a Modified Look-Locker Inversion Recovery (MOLLI) sequence. Native T1 maps were obtained in controls, and patients were given 0.15mmol/kg gadolinium for extracellular volume (ECV) quantification. Respiratory self-gated TPM was performed, using a rotating golden-angle spiral acquisition with retrospective cardiac gating. Both were acquired in the left ventricular (LV) mid-short axis.2 for either leukaemia or Wilms tumour.The patients' mean age was 31 ±5 years and they were studied a median of of 25 (range 16-32) years following a median cumulative anthracycline dose of 220 (range 90-370) mg/m2 0.26, p <0.01) and positively with mid-term FS .Mid-term fractional shortening (FS), 8 years following therapy had a mean value 33.1 ±5.1%. Current CMR-derived LVEF was normal, although reduced compared to controls  and correlated negatively with cumulative anthracycline dose .Native myocardial T1 was not significantly different, comparing patients and controls . Mean ECV was 0.26 ±0.04 and was higher in patients receiving cumulative doses of >300mg/mTPM-derived LV radial, longitudinal and tangential systolic velocities, and longitudinal E/A ratio were not significantly reduced compared to controls.2. Previous studies have shown significantly increased ECV, a median of 8 years post therapy. Our finding, associated with detailed myocardial motion analysis, provides further insight into the mechanisms of long-term remodeling in this specific cohort.This is the first detailed assessment of myocardial function using novel CMR techniques in survivors, 25 years following childhood anthracycline therapy. Mild, asymptomatic, dose-related reduction in LVEF is seen, with no associated change in native T1 values. Increased ECV is seen only at cumulative doses >300mg/mDr Quyam was funded by a start-up grant from CHILDREN with CANCER UKRegistered charity no. 298405.


Tricuspid annular plane systolic excursion (TAPSE) is an easily measureable,fast and reproducible echocardiographic parameter which gives relevant information about biventricular cardiac function.To explore the utility of tricuspid annular plane systolic excursion (TAPSE) for biventricular function assessment in critically ill ICU patients at admission.Prospective observational study.A 12-bed medical-surgical critical care unit.Hundred and one patients admitted to the ICU for sepsis, septic shock, acute cardio respiratory failure or other organ supportivecare. A trained cardiologist conducted transthoracic echocardiography within 48 hours of admission to ICU. Echocardiographic parameters of both right and left heart along with demographic, prognosis, hemodynamic, ventilator, and laboratory parameters wererecorded.TAPSE, right ventricle (RV) fractional area change (FAC), the left ventricular ejection fraction (LVEF), were measured using Doppler echocardiography. Mean age and TAPSE of patients was 41.54 ± 16.07 years and 23.09 ± 5.534 mm respectively. Positive correlation of TAPSE was observed with pulsed doppler peak velocity at annulus (right) , RVFAC , pulsed doppler peak velocity at annulus (left) , LVEF. Also observed was a negative correlation was with tissue doppler myocardial performance index (left) . On logistic regression analysis TAPSE showed a significant impact on both RVFAC  = 11.329; 95% C.I = 1.832-70.079) and LVEF  = 14.154; 95% C.I = 1.127-177.825).TAPSE is reflective of biventricular function at baseline in critically ill ICU patients. Its potential as a hemodynamic monitoring tool needs further exploration in critical illness.


The natural history of acute myocarditis (AM) remains highly variable and predictors of outcome are largely unknown. The objectives were to determine the potential value of various cardiovascular magnetic resonance (CMR) parameters for the prediction of adverse long-term outcome in patients presenting with suspected AM.In a single-centre longitudinal prospective study, 203 routine consecutive patients with an initial CMR-based diagnosis of AM  were followed over a mean period of 18.9 ± 8.2 months. Various CMR parameters were evaluated as potential predictors of outcome. The primary endpoint was defined as the occurrence of at least one of the combined Major Adverse Clinical Events (MACE) .N = 143,70 %) presented with chest pain, mild to moderate troponin elevation and ST-segment or T wave abnormalities. Various CMR parameters were evaluated on initial CMR performed 3 ± 2 days after acute clinical presentation . Out of the 203 patients, 22 experienced at least one major cardiovascular event (10.8 %) during follow-up for a total of 31 major cardiovascular events. Among all CMR parameters, the only independent CMR predictor of adverse clinical outcome by multivariate analysis was an initial alteration of LVEF (p = 0.04).The vast majority of patients (In routine consecutive patients without severe hemodynamic compromise and a CMR-based diagnosis of AM, various CMR parameters such as the presence and extent of myocardial edema and the extent of late gadolinium-enhanced LV myocardial lesions were not predictive of outcome. The only independent CMR predictor of adverse clinical outcome was an initial alteration of LVEF. Acute myocarditis (AM), which is most frequently caused by a viral infection , 2, is cEndomyocardial biopsy (EMB) remains the gold standard for the diagnosis of AM but is recommended for the most severe patients, namely those with acute dilated cardiomyopathy and hemodynamic compromise, life-threatening arrhythmias, or those requiring circulatory support, thus excluding the vast majority of patients presenting with AM in routine practice . EMB is Between October 2008 and December 2011, we conducted a single-centre longitudinal prospective non-randomized study in consecutive patients presenting with a first episode of suspected AM at our Institutions (CMR Laboratory in a tertiary Cardiovascular Centre). To participate at the screening phase, patients were eligible if they had a clinical presentation suggesting the diagnosis of AM. Patients who had hat least 3 of the following criteria: 1) chest pain, 2) recent history (<1 month) of acute viral infection, 3) abnormal ST segment or T waves on ECG, 4) troponin elevation, were eligible to undergo CMR at the time of acute clinical presentation. Patients presenting with ST segment elevation >1 mm in at least 2 contiguous derivations were scheduled for prompt coronary angiography. They were eligible for the CMR study if the coronary angiogram did not show any significant (>50 % diameter stenosis) coronary disease. Patients were then eligible to participate in the study if initial CMR showed nonischemic suggestive patterns of AM as defined below and if the patient had no contraindication to CMR.Exclusion criteria were: 1) severe noncardiac disease compromising life expectancy during the period of the study 2) pre-existing other cardiac disease, 3) relevant coronary artery disease (coronary stenosis ≥50 %) proven by angiography, 4) severe hemodynamic compromise that precluded the CMR study. All patients gave informed written consent and the study was approved by the Local Ethic Committee of our Institutions.The patients eligible for participation in the study were scheduled to undergo CMR at our Institutions between day 0 and day 7 after initial presentation with a detailed CMR protocol as described below. When the diagnosis of AM was made on CMR, medical treatment included ASA (3 g per day), β-blockers and ACE inhibitors for at least 6 weeks. Supporting therapy was provided when appropriate in case of acute or subacute heart failure. Patients with diagnosis of AM were then included after informed consent and scheduled for a follow up assessment between 12 and 18 months after the initial event. The follow up consisted of a clinical visit for patients who were initially hospitalized in our Institutions or a direct contact with the patient and the referring cardiologist for patients who were initially referred to our CMR suite from other hospitals. For all patients, a clinical questionnaire with a detailed description of clinical study endpoints was thoroughly filled out by two senior cardiologists  in charge of the follow up assessment. The LV function was assessed by CMR when available or by echocardiography between 6 months and one year after initial presentation.Patients were followed over time and the primary clinical end-point was the occurrence of at least one of the combined Major Adverse Clinical Events (MACE) defined by: cardiac death (or aborted sudden cardiac death), cardiac transplantation, sustained documented ventricular tachycardia (documented by Holter ECG or ECG in symptomatic patients), the need for hospitalization for heart failure (NYHA class IV and III), recurrence of acute myocarditis, and the need for hospitalization for cardiac causes. Clinical event adjudication was based on the follow up clinical visit or contact, with a consensus reached by the 2 senior cardiologists in charge of follow up . The secondary end-points were the LV ejection fraction (EF) on last echocardiography  or on CMR , and the persistence of clinical symptoms as defined by a clinical score as follows: 1 point for chest pain, palpitations, arrhythmia, asthenia; 1 point for each NYHA functional class; 1 point for the need of a referral to the cardiologist; and 3 points for hospitalization.In eligible patients, CMR was promptly performed between day 0 and day 7 after acute clinical presentation in a dedicated Cardiovascular MR laboratory on a Siemens Magnetom Espree® 1,5 T scanner  with 32-channel anterior and spinal coils for reception. Long-axis  and short-axis cine MR images encompassing the left ventricle from base to apex were obtained with a retrospectively gated fast imaging Steady State Free Precession (SSFP) sequence. Myocardial edema and inflammation was investigated in matched long axis 2-, 3-, and 4—chamber, and in short-axis views through T2-weigthed triple inversion-recovery turbo spins echo sequence with inversion pulses for fat and blood suppression. Then, a bolus of gadolinium contrast  was injected at a rate of 4 ml/s with an injector . Focal early gadolinium enhancement (EGE) was visually assessed on SSFP cine-MR images in the long axis 2-, 3-, 4-chamber views and short-axis locations, acquired between 2 and 5 min. after Gadolinium injection. Late gadolinium enhanced (LGE)-CMR was acquired 10 min. after contrast administration in matched long axis 2-, 3-, 4- chamber and short-axis views through the use of spoiled 2D fast gradient echo inversion-recovery sequence with a TI set to null normal myocardial signal (TI scout sequence). The diagnosis of AM was made based on the following criteria: 1) spontaneous intramyocardial and/or supepicardial hypersignal on T2-weighted spin echo images indicative of myocardial edema, 2) intramyocardial and/or supepicardial LGE on CMR images, 3), absence of microvascular obstruction and acute myocardial infarction (MI) on CMR images. The criteria 2 and 3 were mandatory for the diagnosis of AM and participation to the study.When the diagnosis of AM was made, medical treatment included ASA (3 g per day), β-blockers and ACE inhibitors for at least 6 weeks. Supporting therapy was provided when appropriate in case of acute or subacute heart failure.CMR images were analyzed by two blinded experienced observers and in case of discordance by a third observer for consensus. Myocardial segmentation was assessed using the 17-segment model according to the consensus of the North American Society of Myocardial Imaging. Endocardial and epicardial borders were manually traced on end-diastolic and end-systolic short-axis cine images from base to apex. LV volumes and ejection fraction were derived by summation of epicardial and endocardial contours . Myocardial edema was assessed as a hypersignal that was present before contrast injection on black-blood T2-weighted images. The extent of myocardial edema on T2-weighted images, of early gadolinium enhancement (EGE) on cine images and of late gadolinium enhancement (LGE) was assessed through the use of a semi-quantitative analysis. Each of the 17 LV myocardial segments was divided into 3 layers . The presence of myocardial lesions was determined in each of the 3 layers for each myocardial segment. Finally, myocardial lesions on CMR data were delineated by planimetry using an automated threshold greater than 4SD above mean myocardial signal intensity and expressed as percentage of LV myocardial surface area. Myocardial damage on LGE-CMR was localized in details in the sub-epicardium, midwall or transmural and its shape was characterized as nodular or linear.t-test for continuous data. Differences between groups were considered statistically significant if the 95 % CI around the difference of the means did not contain zero. In a prespecified analysis, baseline predictors for MACE were identified using Cox multivariate analysis including variables showing a p value <0.20 in association with MACE by univariate analysis. In the multivariate analysis, colinearity was considered if Pearson’s correlation coefficient was > 0.6 or the standard error of a covariate was > 5.0. If colinearity was identified, the multivariate analysis was repeated after removal of the responsible covariate.Statistical analysis was performed using STATA 10.1 . Baseline descriptive statistics are presented as frequency and percentage for categorical variables and mean ± SD or median (interquartile range) for continuous variables. The normality of data was assessed using the Skewness and Kurtosis normality test. The differences between the groups were assessed with the chi-square test or Fisher exact test for categorical data and Student N = 143, 70 %) presented with a clinical scenario including chest pain, mild to moderate troponin elevation and ST-segment or T wave abnormalities on ECG. Out of these 143 acute coronary syndrome-like patients, 99 (69 %) had prompt normal coronary angiography because of ST segment elevation in at least 2 contiguous derivations. In the 44 remaining patients (31 %), coronary angiography was not performed because of the lack of ST segment elevation and a very low risk profile . The remaining 60 patients had a presentation that included for the majority of them a clear recent history of acute viral infection with fever (38/60), and the characteristics of chest pain were highly suggestive of non ischemic origin . Ten patients presented with mild or moderate heart failure, 12 with arrhythmias. All patients were relatively young and had no cardiovascular risk factors. They all had typical patterns of acute non ischemic lesions on LGE-CMR  and for those reasons were not referred to cath. The other symptoms at initial presentation are listed in Table Overall, 240 patients were screened to participate. Six of them had contra-indications to MRI  and only one refused to participate. Thus, 233 patients were considered for the study. Out of them, 28 patients were excluded because of the presence of relevant coronary artery disease in 8, severe hemodynamic compromise in 3 (cardiogenic shock), myocardial involvement in inflammatory systemic diseases in 5 , other concomitant cardiac diseases in 9 , and pericardial diseases in 3. Finally, 205 patients were enrolled in the study and followed over time. Two patients were lost to follow-up and the final study population consisted of 203 patients. The baseline characteristics of patients are detailed in Table 2. Out of the 203 patients, 39 (19 %) presented at least one asynergic myocardial segment on cine CMR. Hyper-T2 myocardial signal on fat suppressed black-blood spin echo T2-weighted CMR was present in 100 patients (62.5 %) with a mean extent of 10.9 ± 5.7 % of LV myocardial mass. Myocardial lesions on LGE were mostly limited in the posterolateral LV wall (60 %), often nodular (74 %), and located in the sub-epicardial layers (82 %) with a mean myocardial extent by planimetry of 11.4 ± 7.0 % of LV myocardial mass.The initial CMR findings are listed in Table The clinical follow-up was assessed after a mean period of 18.9 ± 8.2 months. Out of the 203 patients, 22 experienced at least one major cardiovascular event (10.8 %) during follow-up. A total of 31 major cardiovascular events occurred during the study period and their characteristics are detailed in Table p = 0.04; and mean myocardial extent of EGE 5.1 ± 6.0 % of LV myocardial mass vs. 2.2 ± 4.1 %, respectively, p = 0.0056) (Table p = 0.16) . No relationship was found between the extension, patterns (nodular/linear), localisation and wall distribution of LGE lesions and the occurrence of MACE . Also, an initial alteration of LVEF was associated to the presence of clinical symptoms at follow-up . Initial alteration of LVEF at diagnosis was found to be significantly associated to an abnormal EF at follow-up . A larger LV end-diastolic volume at initial presentation was associated to altered LVEF at follow-up . No relationship was found between the extension, patterns (nodular/linear), localisation and wall distribution of LGE lesions and subsequent alterations of LV functional parameters. Similarly, no association was found between the extent of EGE or T2 lesions and LVEF (P = NS).There was an inverse association between the extent of T2 lesions and the persistence or occurrence of clinical symptoms during follow-up  with electrocardiographic and/or biological data, and CMR that showed nodular or linear intra-myocardial lesions highly suggestive of acute nonischemic tissue damage. The criteria for the diagnosis of AM on CMR were slightly different from the established Lake-Louise criteria where AM is present when 2 out of 3 parameters  are met . In our Although not significant, there was a clear trend between the presence and extent of myocardial edema on initial T2-weighted CMR and a lower rate of subsequent MACE, as well as less persistent clinical symptoms during follow-up. Recently, McLellan et al. reported concordant results in patients with acute onset cardiomyopathy, showing that the amount of myocardial inflammation identified by an elevated global relative enhancement (GRE) could predict recovery of LV function . HoweverOverall, the current study confirms and highlights the favorable outcome of patients presenting with initially non severe AM and no hemodynamic compromise. For this reason, the combined clinical primary end point was broad and no patient experienced a hard event . Recently, Schumm et al. reported that patients presenting with suspected clinical myocarditis and normal CMR scans had favorable outcomes .In our sudy population, the lower extent of EGE as compared to LGE might appear to be in contradiction to the sole physiology of gadolinium kinetics within the myocardium. As stated in the White JACC paper, T2 sequences for depiction of regional edema may have a limited sensitivity in less severe inflammation . It is lFinally, an ischemic etiology was ruled out in a significant proportion of patients based upon clinical parameter assumption and CMR characteristics. This is a limitation of the study since no specific examination was performed to formally rule out coronary disease. The study did not provide comparisons between biomarkers and myocardial lesions on CMR in relation to the clinical outcome. Also, the empirical medical regimen based on betablockers and ACE inhibitors might have had some influence on patient outcomes and this impact is largely unknown.In routine consecutive patients without severe hemodynamic compromise and a CMR-based diagnosis of acute myocarditis, various CMR parameters such as the presence and extent of myocardial edema and the extent of late gadolinium-enhanced LV myocardial lesions were not predictive of outcome. The only independent CMR predictor of adverse clinical outcome at follow-up was an initial alteration of LVEF.


The present paper aims to review the main pathophysiological links between red blood cell disorders and cardiovascular diseases, provides a brief description of the latest studies in this area, and considers implications for clinical practice and therapy. Anemia is associated with a special risk in proatherosclerotic conditions and heart disease and became a new therapeutic target. Guidelines must be updated for the management of patients with red blood cell disorders and cardiovascular diseases, and targets for hemoglobin level should be established. Risk scores in several cardiovascular diseases should include red blood cell count and RDW. Complete blood count and hemorheological parameters represent useful, inexpensive, widely available tools for the management and prognosis of patients with coronary heart disease, heart failure, hypertension, arrhythmias, and stroke. Hypoxia and iron accumulation cause the most important cardiovascular effects of sickle cell disease and thalassemia. Patients with congenital chronic hemolytic anemia undergoing splenectomy should be monitored, considering thromboembolic and cardiovascular risk. There are several criteria enabling the diagnosis of anemia. Hemoglobin below 13 g/dL and 12 g/dL in men and women, respectively, according to the criteria of the World Health Organization defines anemia.Anemia, a condition frequently associated with chronic diseases, is an independent risk factor for cardiovascular complications  and a 1 The present paper aims to review the main pathophysiological links between red blood cell disorders and cardiovascular diseases, provides a brief description of the latest studies in this area, and considers implications for clinical practice and therapy. The present review will enable updating of the guidelines for the management of patients with both red cell disorders and cardiovascular pathology.Multimorbidity is common in patients with cardiovascular diseases . Prognos Cardiovascular compensatory consequences of anemia include tachycardia, increased cardiac output, a hyperdynamic state due to reduced blood viscosity, and vasodilation enabling tissue perfusion. Arterial dilatation involves also the recruitment of new vessels and formation of collaterals and arteriovenous shunts [Anemia causes hypoxia due to decreased hemoglobin level, and there are several nonhemodynamic  and hemodynamic compensatory mechanisms . The clis shunts , hypoxics shunts . Anemia s shunts . Increass shunts , 11. Tiss shunts .Anemia increases morbidity and mortality in cardiovascular diseases, due to compensatory consequences of hypoxia, such as a hyperdynamic state with increased cardiac output, left ventricular hypertrophy and progressive cardiac enlargement, and, probably, a proatherogenic role. chronic heart failure and is associated with an increased all-cause and cardiovascular mortality, reduced exercise capacity due to reduced oxygen carrying and storage capacity, impaired quality of life, a higher risk for hospitalization [Congestive heart failure is uncommon in patients with anemia without heart disease and may occur only in cases of severe anemia with hemoglobin of 5 g/dL or less . Anemia lization , 13, femlization . The inclization  and due lization , 17.Anemia in patients with heart failure is often normochromic and normocytic, with a low reticulocyte count , 18. VitAnemia impairs prognosis in heart failure patients due to a reduced oxygen supply, ventricular remodeling, the neurohumoral profile, the proinflammatory state, and several comorbidities, including renal failure and cardiac cachexia. Probably, anemia is both a mediator and a marker of a poor outcome in heart failure .μg/L [Therapy includes iron, folic acid, blood transfusions, and erythropoiesis-stimulating agents (ESA). ESA may be considered as adjunctive therapy in patients with heart failure, improving, besides hemoglobin level, also left ventricular ejection fraction and functional class and reducing diuretic doses and left ventricular remodeling –32. EPO μg/L . Markers acute heart failure and is associated with poor outcome [Iron deficiency, defined as depleted body iron stores (low serum hepcidin) and unmet cellular iron requirements (high-serum soluble transferrin receptor), is common in outcome .The simultaneous presence of anemia, heart failure, and chronic kidney diseases forms a pathological triangle called cardiorenal anemia syndrome . The preThe main mechanisms of anemia in patients with heart failure are renal dysfunction, increased sympathetic and renin-angiotensin-aldosterone activity, hemodilution, absolute or functional iron deficiency, impaired erythropoietin production and activity, activation of the inflammatory cascade, angiotensin converting enzyme inhibition and angiotensin receptor blockade, and vitamin B12 and folic acid deficiency . Therapy ischemic heart disease and a frequent finding in patients with acute coronary syndrome [Anemia is a known risk factor forsyndrome –44. Multsyndrome . Severalsyndrome , 43, 46,syndrome , 48. A rsyndrome . A few ssyndrome . Thrombosyndrome .The anemia of inflammation can reduce hemoglobin within 1-2 days, due to hemolysis of red blood cells and a suppression of the response to erythropoiesis mediated by tumor necrosis factor and acute changes in iron metabolism , 51, 52.The prevalence of anemia increases during hospitalization. Both the admission hemoglobin level and the subsequent fall in hemoglobin level >1.8 g/dL were associated with an increased risk of all-cause mortality or cardiogenic shock in patients with acute coronary syndrome . The mai erythrocyte membrane fluidity and cardiovascular events during long term follow-up [Sargento et al. evaluated the prognostic value of biohemorheological profile in transmural infarction survivors, revealing a close relationship between leukocyte count, protein C activity, andollow-up . Membranollow-up , 56. red cell distribution width (RDW), reflecting mean corpuscular volume heterogeneity, is an early parameter of iron deficiency, sideroblastic, vitamin B12, and folic acid deficiencies [Theciencies . In paticiencies . The menciencies . RDW wasciencies , 59. hemoglobin level and adverse cardiovascular outcomes in women with chest pain, in the absence of myocardial infarction or congestive heart failure, reporting a higher risk of death from any causes, a higher risk of adverse outcomes, and shorter survival time free of adverse outcome, but no correlation between hemoglobin level and presence or severity of coronary atherosclerosis [Freudenberger and Carson investigated the relationship betweenclerosis . hematocrit was less than 25% [It has been suggested to correct anemia in patients with coronary artery disease, if hemoglobin levels have fallen to 9-10 g/dL in symptomatic angina . In sevethan 25% . Other athan 25% , 64. Thethan 25% . Well dethan 25% .Components of the complete blood count, such as hematocrit, white blood cell count, and their subtypes, are associated with coronary heart disease and can improve our ability to predict coronary heart disease risk . SeveralAn imbalance between oxygen demand and supply, bleeding episodes due to invasive procedures and anticoagulation, inflammation, hemodilution, and kidney failure are the main mechanisms linking anemia and coronary heart disease . Red bloNormocytic anemia is common among hypertensive patients. Lower hemoglobin concentrations were found in patients with uncontrolled than among those with well controlled hypertension, indicating a higher cardiovascular risk in uncontrolled hypertension . PatientAnemia is associated with higher cardiovascular risk, higher blood pressure values, and lower dipping status in hypertensive patients, and hemoglobin should be monitored in hypertensive patients.Several electrocardiographic changes were described in patients with anemia, including ST segment depression, T wave inversion, QT interval prolongation, and reduced amplitude of the QRS complex –72. A loBindra et al. reported both supraventricular  and ventricular arrhythmias  in patients with coronary heart disease and anemia . PatientProlonged QT intervals and arrhythmia risk are linked to anemia, macrocytosis, anisocytosis, serum ferritin, and hemoglobin, and hypoxemia supports these links.Stroke is the leading cause of adult disability and the third cause of mortality and has a high prevalence, considering the growth and aging of the population. Complete blood count abnormalities represent a useful tool for stroke patients' prognosis . A low hAnemia enables cerebral ischemia, blood flow turbulence, migration of a thrombus, and embolism and reduces penumbra oxygen reserves. Besides that, anemia was associated with increased mortality after ischemic and hemorrhagic stroke. beta-thalassemia, which explains the appearance of premature ventricular contractions, ventricular tachycardia, and late ventricular potentials [Thalassemia is the most common hereditary disease, a genetic blood disorder due to reduced synthesis of beta or alpha globin chains , 85. Regtentials , 89. Irotentials . Bradicatentials . Tachycatentials . The abstentials . Impairmtentials , 86. ECGtentials , 91. Wittentials . The cartentials . Thalasstentials . A protetentials , 95.The survival of patients with thalassemia major has improved lately, as a result of regular transfusions and chelation therapy and new imaging methods, which allow better management of iron overload . There aThe main cardiovascular effects of thalassemia are due to hypoxia and iron accumulation. Iron overload explains most cardiovascular problems in thalassemic patients, such as left ventricular systolic and diastolic dysfunction, reentry ventricular arrhythmias, atrial mechanical depression, myocardial fibrosis, vascular inflammation with early vascular aging, and hypercoagulability.Sickle cell anemia is caused by hemoglobin S, which changes the shape of the red blood cells from discs to sickles, reduces their deformability, and enhances stickiness, leading to obstructive adhesion of sickle cells . ReperfuMeloni et al. compared biventricular dimensions and function using cardiovascular magnetic resonance in pediatric, chronically transfused patients with sickle cell disease and thalassemia major and normal cardiac iron levels, reporting significantly greater biventricular dilation and left ventricular hypertrophy and lower left ventricular ejection fraction in the first group .Tantawy et al. investigated 50 young patients with sickle cell disease, revealing hypercoagulability, significantly higher aortic stiffness, and pulmonary artery pressure compared to healthy controls . The hypThe main cardiovascular effects of sickle cell disease are due to the rigid erythrocytes with hemoglobin S, impairing blood flow, enabling vasoocclusive crises, and explaining the appearance of myocardial infarction, stroke, microcirculation damage, and degeneration of the excitoconductor system. Sickle cell anemia is also associated with other cardiovascular complications, such as cardiac autonomic neuropathy, arrhythmias, tricuspid regurgitation, and increased arterial stiffness. Besides disordered hemoglobin structure and function, a prothrombotic state due to changes in the hemostatic system, such as thrombin activation, decreased levels of anticoagulants, impaired fibrinolysis, and platelet activation are also involved in the pathogenesis of sickle cell disease .Hereditary spherocytosis is the most common inherited hemolytic anemia , charactSplenectomy is recommended in patients with moderate and severe forms, considering that it results in near complete resolution of hemolysis . PersonsAnticoagulation prophylaxis and lipid lowering drugs should be considered after splenectomy in patients with chronic hemolytic disorders, besides postsplenectomy sepsis prophylaxis, especially if there is an additional high thromboembolic risk due to surgery or immobilisation .The presence of anemia is associated with a special risk for patients with any form of proatherosclerotic condition and heart disease. Anemia became a new therapeutic target in patients with cardiovascular pathology, improving oxygen supply. Guidelines must be updated for the management of patients with anemia and cardiovascular diseases, and targets for hemoglobin level should be established, in order to improve prognosis. Early primary care diagnosis, monitoring, and management of patients with anemia and cardiovascular morbidity and evaluation of iron, vitamin B12, folic acid, and nutritional status may be worthwhile. On the other hand, the unfavorable effects of therapy should also be considered, including blood pressure elevation, the prothrombotic effect, and increased viscosity. Risk scores in several cardiovascular diseases should include red blood cell count and RDW.Complete blood count abnormalities and hemorheological parameters represent useful, inexpensive, widely available tools for the management and prognosis of patients with coronary heart disease, heart failure, hypertension, arrhythmias, and stroke.The main cardiovascular effects of sickle cell disease and thalassemia are due to hypoxia and iron accumulation, respectively. Thromboembolic risk and lipid profile should be monitored after splenectomy in patients with congenital chronic hemolytic anemia.


The transmural extent of myocardial infarction (MI) as assessed by late gadolinium enhancement (LGE) CMR predicts functional recovery. In acute MI (AMI), myocardial edema and effects of reperfusion therapy reduce the predictive accuracy of LGE. LGE assesses tissue dichotomously as "viable" or "non-viable", but does not consider the severity of tissue damage within the hyperenhanced infarct zone. Extracellular volume (ECV) estimation, using native and post-contrast T1 mapping CMR, allows for quantitative assessment of severity of myocardial damage. We aimed to assess if CMR-derived measurement of infarct ECV offers additional predictive value over LGE extent for contractile recovery in reperfused AMI.35 patients presenting with first ST-segment elevation AMI treated by primary percutaneous coronary intervention underwent acute (day 2) and convalescent (3 months) CMR at 3.0 Tesla. Cine imaging, tissue tagging, modified Look-Locker inversion T1 mapping  natively and 15 minutes post gadolinium-contrast administration and LGE imaging at 20 minutes were performed. The ability of acute infarct ECV and acute transmural extent of LGE to predict convalescent wall motion, ejection fraction (EF) and strain were compared. A per-patient analysis was performed using a region of interest corresponding to the core of the infarct, excluding any microvascular obstruction (MO). Segmental analysis was also performed and evaluated using a multilevel linear mixed-effects model to account for non-independence of segmental data.Per-patient, ECV and transmural extent of LGE correlated with convalescent wall motion score  and convalescent EF . Per-segment, acute ECV and LGE transmural extent were associated with convalescent wall motion score .


ODC) activity and intracellular polyamines associated with cyclic adenosine monophosphate (cAMP) increases. The aim of the study was to establish the role of these in the human heart in living patients. For this, polyamines (by high performance liquid chromatography) and the activity of ODC and N1‐acetylpolyamine oxidases (APAO) were determined in the right atrial appendage of 17 patients undergoing extracorporeal circulation to correlate with clinical parameters. There existed enzymatic activity associated with the homeostasis of polyamines. Left atria size was positively associated with ODC  and negatively with APAO‐N1‐acetylspermine , suggesting that increased levels of polyamines are associated with left atrial hemodynamic overload. Left ventricular ejection fraction (LVEF) and heart rate were positively associated with spermidine  and negatively with N1‐acetylspermidine . LVEF was negatively correlated with cAMP levels  and with cAMP/ODC , cAMP/spermidine  and cAMP/spermine  ratios. Abnormal LVEF patients showed decreased ODC activity and spermidine, and increased N1‐acetylspermidine, and cAMP. Spermine decreased in congestive heart failure patients. The trace amine isoamylamine negatively correlated with septal wall thickness  and was increased in cardiac heart failure. The results indicated that modifications in polyamine homeostasis might be associated with cardiac function and remodelling. Increased cAMP might have a deleterious effect on function. Further studies should confirm these findings and the involvement of polyamines in different stages of heart failure.Polyamines contribute to several physiological and pathological processes, including cardiac hypertrophy in experimental animals. This involves an increase in ornithine decarboxylase ( The polyamines putrescine, spermidine and spermine are aliphatic molecules ubiquitously distributed in tissues that are associated with cell replication, growth and differentiation In experimental animals, polyamines have also been related to several cardiac pathological conditions and diseases, such as hypertrophy and myocardial damage in response to numerous hormonal and trophic stimuli in vivo and ex vivo studies in experimental animals, and on rodent and human cultured cardiomyocytes. The lack of human studies regarding polyamine metabolism, trace amines, and cardiac function has led to the analysis of the correlation between biochemical parameters related to the synthesis and interconversion of intracellular polyamines and intracellular cAMP, determined in human heart tissue samples, with clinical and echocardiographic parameters in patients with heart failure.The finding of the involvement of polyamines in heart physiology and pathology is based on The study was carried out in 17 patients, 12 men (age 65–79 years old) and 5 women (age 52–82 years old). Their clinical characteristics are shown in Table 2, 1.8; MgCl2, 1.05; NaH2PO4, 0.42; NaHCO3, 11.9 and glucose, 5.5), saturated with a 95% O2 and 5% CO2 mixture, and brought to the laboratory. The elapsed time was less than 40 min., otherwise the samples were discarded. When the sample size allowed, it was cut into several pieces  to be able to perform as many of the proposed biochemical assays as possible on the same right atrial appendage from a patient. The viability of the method of preservation was studied in two patients, cutting one piece to be frozen as soon as possible, in liquid nitrogen, and another one after 40 min. in cold Tyrode's solution. There were no differences between both methods, regarding polyamines and cAMP determinations, leading to preserve the samples in Tyrode solution given its simplicity.A piece of right atrial appendage, 714.19 ± 50.02 mg in weight, was obtained at the time of atrial cannulation  immediately placed at 4°C in Tyrode's solution .The resting heart rate , systolic and diastolic blood pressure (mmHg), and the presence of diseases and medications of the patients were noted. Using 2D echocardiography the septal wall thickness (as reference for LV hypertrophy) and the left atrial diameter, in transversal projection, and LVEF were measured. The LVEF, septal wall thickness and left atria size were also categorized following the 2015 Guidelines of Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults For the clinical stages of heart failure the New York Heart Association (NYHA) criteria were followed.To measure cAMP levels, frozen samples were homogenized using a Polytron in 1 ml of ice‐cold 10 mM Tris‐HCl pH 7.2 buffer containing 4 mM ethylenediaminetetraacetic acid (EDTA). Homogenates were boiled for 10 min. and then centrifuged at 18,000 × g for 15 min. at 4°C. Cyclic AMP in the supernatant was measured by means of a commercial radioimmunoassay kit from GE Healthcare , following the manufacturer's instructions. Cyclic AMP levels were expressed as pmol/mg/protein. The protein content was determined according to the Bradford procedure.14CO2 released from L‐[1‐14C] ornithine, substrate of the reaction, was trapped in a filter paper and measured by liquid scintillation. The specific ODC activity was expressed as pmol of 14CO2 evolved per hour per mg of protein (pmol/hr/mg protein).Ornithine decarboxylase activity was determined as previously described For this purpose, 100–200 mg of atrial appendage were homogenized using a Polytron in 1 ml ice‐could buffer [HEPES (2‐[4‐(2‐hydroxyethyl)piperazin‐1‐yl]ethanesulfonic acid) 10 mM, sucrose 0.25 M and EDTA 1 mM, pH 7.2] four times for 10 sec. The homogenate was centrifuged for 10 min. at 550 × g, at 4°C. Then, 400 μl of the supernatant were taken and preserved at −80°C.1‐acetylpolyamine oxidases (APAO) activity was determined by a previously described method 1‐acetylspermine or N1‐acetylspermidine was used as substrate of the reaction. Similarly, polyamine oxidase activity was assayed using spermine as substrate instead. One unit of enzyme activity was defined as 1 nmol H2O2 formed per min. The data were expressed as mIU/mg of protein.NPolyamine levels and trace amines were determined using a precolumn derivatization method as previously described ® reverse transcriptase  following the manufacturer's instructions. For each sample, a negative control was prepared without transcriptase.Total RNA was isolated from the samples of the right atrial appendage using the guanidine isothiocyanate method as previously described 1‐acetyltransferase (SSAT) and 5′‐CAATACAGGACTC TTTCGAG‐3′ and 5′‐TTATGGTCGGAACTAACGACG‐3′ for 18S rRNA, used as an internal control for relative RT‐PCR.Target cDNAs were amplified by PCR using Taq DNA polymerase  and pairs of specific primers for each gene product, 5′‐TACTTCCCATCGGACTC TGG‐3′ and 5′‐CATGAGTTGCC ACATTGACC‐3′ for ODC; 5′‐TT TGGAGAGCACCCCTTTTA‐3′ and 5′‐TCCAAC CCTCTTCACTGGAC‐3′ for spermidine/spermine N® 10.1 for Windows .Two reactions from each cDNA obtained were performed in a thermocycler  with an initial 4 min. denaturation step at 95°C followed by 35 cycles of 95°C for 15 sec., 55°C for 30 sec. and 72°C for 30 sec. in the case of ODC and SSAT and twenty cycles for 18S rRNA. Amplified products were separated by electrophoresis, visualized using UV after ethidium bromide staining, and photographed using a Vilber Lourmat Photodocumentation system. The size of the specific bands matched the predicted length of the amplicons. Intensity of the bands was quantified using the program PhotoCaptMw14C] ornithine was purchased from ICN Biomedicals . Putrescine (tetramethylenediamine), spermidine , spermine , N1‐acetylputrescine (N1‐Acetylputrescine hydrochloride), N1‐acetylspermidine (N1‐Acetylspermidine dihydrochloride), N1‐acetylspermine (N1‐Acetylspermine trihydrochloride), isoamylamine (isopentylamine: 1‐Amino‐3‐methylbutane) and 2‐hydroxydiaminopropane were from Sigma‐Aldrich . [3H]AMP radioassay kit was from GE Healthcare .L‐[I‐t‐test for unpaired data. The number of patients was at least three in each case, otherwise the results were not taken into account. The Pearson's correlation coefficient (r) was used to determine the linear relationship between two variables. Multiple regression analysis was performed to explore the relationship between the dependent variables  and other variables that could be used as predictors. Values of P ≤ 0.05 were considered as significant.The data were expressed as the means ± S.E.M. of the respective units of measure. The statistical significance between groups was calculated by means of Student's versus 65.08 ± 2.21 years, respectively, P = 0.046), and for putrescine and N1‐acetylspermidine determined in the right atrial appendage, which were lower for female. These were 0.83 ± 0.12 (n = 11) versus 0.37 ± 0.11 (n = 5) nmol/mg protein (P = 0.017) for putrescine and 34.04 ± 5.95 (n = 10) versus 11.29 ± 2.82 (n = 4) nmol/mg protein (P = 0.004) for N1‐acetylspermidine respectively for male versus female.The clinical data of the patients are shown in the Table P = 0.027), supporting the factorability of the correlation matrix.Ornithine decarboxylase activity and endogenous polyamines, determined in the right atrial appendage, were subjected to principal component analysis. The correlation matrix showed the presence of many coefficients of 0.3 and above. The Kaiser–Meyer–Olkin value was 0.64, exceeding the recommended value of 0.6 r = 0.211)  and spermine  . There existed a positive correlation between the determinations of N1‐acetylspermidine and putrescine   .The linear regression analysis of the biochemical determination showed that ODC activity of the right atrial appendage positively and significantly correlated with the determinations of the polyamines spermidine , and APAO‐N1‐acetylspermidine correlated negatively with spermine .Ornithine decarboxylase and APAO‐Nr = −0.885, P = 0.004, n = 8) , and without statistical significance with spermine   Fig. D and sper = 0.661, P = 0.027, n = 11)  Left atrial size significantly correlated with ODC (P < 0.001). They also had a significant increase in the heart rate by comparison to the patients with normal septal thickness, 82 ± 3.06 versus 72 ± 2.08 bpm (P = 0.022).Septal wall thickness ranged from 9 to 14 mm, 3 (23.5%) patients having a normal range, 9 (47.1%) mildly abnormal and 5 (29.4%) moderately abnormal   when the variable was categorized . Correlations with other variables were not observed.Septal wall thickness was negatively correlated with isoamylamine (16) Fig. C, and thThe multivariable regression analysis did not find independent variables as predictors of left atria size or septal wall thickness.Of the 17 patients, 12 were diagnosed of congestive heart failure. These patients showed a significant increase in the left atrial size with respect to those without it Fig. A. Congesr = 0.690, P = 0.003, n = 16) was positively and significantly correlated with the LVEF , and negative for N1‐acetylspermidine  .The functional implication of polyamines on heart function was studied by the analysis of the linear correlation of the different variables with the LVEF. Spermidine  and almost a significant decrease in the ODC/cAMP ratio  with respect to a normal LVEF.Patients that did not have preserved ejection fraction showed a significant decrease in ODC activity in atrial appendage  was positively and significantly correlated with the heart rate of patients  .Spermidine  and almost for heart rate  , cAMP/spermidine  and cAMP/spermine  ratios.Left ventricular ejection fraction negatively and significantly correlated with cAMP (10) Fig. C. As wel1‐acetylspermine explained 75.8% of the variance in heart rate (P = 0.008). These independent variables also made a statistical significant unique contribution to heart rate. The equation of the model was: Yheart rate = 91.03 (constant) + spermidine × 19.83+ spermine × −9.06+ N1‐acetylspermine × −0.32.The multivariable regression analysis did not find independent variables as predictors of LVEF. However, spermidine, spermine and Nn = 6) in comparison with untreated patients of 60 ± 1.32% (n = 8), P = 0.024. No significant differences were observed in the remaining variables analysed, except on age 62.5 ± 2.59 (n = 6) for treated patients by comparison with untreated of 70.50 ± 2.31% (n = 8), P = 0.04.Patients treated with atenolol showed a decrease in the LVEF 52.67 ± 2.78%  1‐acetylputrescine (via N‐acetyltransferase) They fitted, using factorial analysis, into two components, reflecting an interrelationship, with biological meaning, in a subset of the total variables studied. There is a first component for spermine, spermidine, ODC and N1‐acetylspermidine activity ratio. These changes might be related to a causal effect and/or as a response to the left atrial dilation.In the patients studied, ODC activity and intracellular polyamines were associated with trophic and functional parameters Fig. . In thisLeft atrial size is clinically related to a sustained overload; in fact the patients with cardiac heart failure have increased left atrial size. This may be a consequence of diastolic (because of ventricular hypertrophy) and/or systolic dysfunction. With regard to diastolic dysfunction, a correlation with septal wall thickness should be expected, but this was not the case, ruling out such a possibility in these patients.1‐acetylspermidine activity, increased polyamine levels or changes in the expression of ODC and SSAT. This suggests that, at least, in mild to moderately abnormal septal wall thickness the association of polyamines with cardiac deleterious effect reported in experimental animals were not observed. We cannot rule out an anabolic effect of polyamines in cardiac hypertrophy in the case of severely abnormal thickness, because none of the patients fulfilled this criterion.Activation of polyamine metabolism, by induction of ODC, has been proposed as an adaptive mechanism of heart through cardiac hypertrophy 1‐acetylspermidine, was negatively associated with LVEF and resting heart rate. The resting heart rate could be predicted in 3/4 of patients via the values of spermidine, spermine and N1‐acetylspermidine determined in the right atrial appendage.Left atrial overload might be a compensatory signal for increasing the synthesis/catabolism ratio of polyamines preventing systolic dysfunction in these patients. In this sense, intracellular levels of spermidine were positively correlated with LVEF and resting heart rate. Consistent with this finding, the catabolism of spermidine, taking into account the increase in NIn patients with an abnormal LVEF ODC activity and its ratio with cAMP were significantly decreased by comparison with those having preserved function. When they had congestive heart failure a significant decrease in the intracellular levels of spermine in the right atrial appendage was observed. Overall, intracellular polyamines seem to be important for cardiac function. Similarly, the up‐regulation of polyamines synthesis contributes to preconditioning‐induced cardioprotection and attenuation of contractile dysfunction in the murine heart via APAO, may also lead to the formation of ROS The cellular effects of polyamines are complex. Thus, polyamines function as reactive oxygen species (ROS) scavengers and anti‐inflammatory molecules In the right atrial appendage of the patients studied, cAMP was negatively associated with ODC activity, spermidine and spermine levels. Cyclic adenosine monophosphate and the cAMP/ODC, cAMP/spermidine and cAMP/spermine ratios are negatively associated with LVEF. However, cAMP levels were not related to left atrial size and ventricular septal thickness. This underlines the possibility of contractile dysfunction when cAMP increases, and that higher ODC activity and intracellular spermidine and spermine levels could improve it. An inverse association between intracellular polyamines and cAMP was also reported in primary beating heart cells of chick embryos 1‐adrenoceptor stimulation. Heart failure, initially compensated for by sympathetic activation of β‐adrenoceptors, turned into a diminished inotropic reserve of the heart, because of an altered expression of the β1/β2‐adrenoceptors ratio, its coupling to G‐proteins and phosphodiesterases It is interesting that some patients included in the study were treated with atenolol, a cardioselective β‐blocker, which should prevent the increase in intracellular cAMP, but this was not the case. This indicates that in these patients, cAMP levels might be independent of βBesides polyamines, isoamylamine, a primary amine produced by leucine decarboxylation, was present in the right atrial appendage. This is characterized as agonists of trace amine‐associated receptors According to these results, ODC activity is associated with left atrial hemodynamic overload and polyamines with an improvement in ventricular inotropism, which might be a compensatory mechanism to preserve cardiac contractility. These associations do not necessary imply a causal relationship with cardiac pathology, or that the biochemical changes observed in the polyamine pathway in the right atrial appendage occur in the left ventricles or whether they play a role in the physiopathology of cardiac diseases. Although they can also be released from cells and produce biological effects in cardiomyocytes In addition, the pharmacological treatment of cardiac hypertrophy, as well as cancer chemotherapies, based on the inhibition of ODC and a decrease in intracellular polyamines, must be carefully considered in terms of cardiac function.The authors confirm that there are no conflicts of interest.


Background. Congenital heart diseases often involve chronic pressure overload of the right ventricle (RV) which is a major cause of RV dysfunction. Pulmonary artery (PA) banding has been used to produce animal models of RV dysfunction. We have devised a new and easier method of constricting the PA and compared it directly with the partial ligation method. Methods. Eight-week-old male Sprague-Dawley rats (240–260 g) were divided into three groups: sham operation, partial pulmonary artery ligation (PAL) procedure, and pulmonary artery half-closed clip (PAC) procedure. RV function and remodeling were determined by echocardiography and histomorphometry. Results. Surgical mortality was significantly lower in the PAC group while echocardiography revealed significantly more signs of RV dysfunction. At the 8th week after surgery RV fibrosis rate was significantly higher in the PAC group. Conclusions. This procedure of pulmonary artery banding in rats is easier and more efficient than partial ligation. The exact prevalence of pediatric heart failure is largely unknown but it is increasing. Recent advances in diagnostic methods, new surgical techniques, and improved perioperative management have contributed to an increased survival for patients with complex congenital heart disease who today often survive into adulthood .Even after successful repair, however, right ventricle (RV) pressure overload remains in some patients and eventually impairs RV function and influences long-term mortality and morbidity –4.Although compensated hypertrophy develops initially, ultimately RV failure will occur. The mechanisms underlying the progression from compensated to decompensated RV hypertrophy have not been well defined .Clinically, the relationship between progressive fibrosis and RV function must be addressed , 7. But The partial pulmonary artery ligation procedure has been widely used to produce right heart failure caused by pressure overload, but this procedure might have important drawbacks including a high surgical mortality caused by bleeding, sudden cardiac arrest, or pulmonary thrombus.Pressure overload may also be induced using half-closed paper clips easily applied with a stopper. We could adjust the closing size by moving the stopper. The objective of this study was to establish rats model of RV failure using the pulmonary artery half-closed clip procedure comparing with partial ligation procedure.All experimental procedures and protocols used in this investigation were reviewed and approved by the institutional animal care and use committee and were in accordance with the National Institutes of Health “guide for the care and use of laboratory animals” .2 by using a volume controlled respirator . A left thoracotomy was performed at the fourth intercostal space, and the main pulmonary artery (mPA) was carefully exposed (A rat model of the pulmonary artery banding (PAB) was established to create chronic RV pressure overload. Eight-week-old male Sprague-Dawley rats (240–260 g) were anesthetized with intraperitoneal pentobarbital (50 mg/kg body weight) and xylazine (5 mg/kg) and ventilated with 100% O exposed .A 7-0 prolene suture was tied tightly around an 18-gauge needle alongside the mPA. After subsequent rapid removal of the needle, a fixed constricted opening was created in the lumen equal to the diameter of the needle , 8, 9.A small clip (LT100 ETHICON) was half-closed around the mPA using a clip applier (LX107 ETHICON) with a stopper . The bloThereafter, the thorax was closed in layers, and the ventilator setting was changed (90 cycles/min) for half an hour to reduce the respiratory load.−1) for half an hour to reduce the respiratory load.A left thoracotomy was performed at the fourth intercostal space, and the mPA was carefully exposed. The thorax was closed in layers, and the ventilator setting was changed (90 cycles min−1 body weight) but were breathing spontaneously and were positioned on their left side.Echocardiograms were recorded on the preoperative day and on the 4th week and 8th week after the procedure. The rats were anaesthetized for echos  and Doppler imaging were performed with a 6.5 MHz transducer .The RV morphology was assessed as RV free wall thickness (RVWT) and RV end-diastolic diameter (RVDd) and RV outflow tract dimension (RVOTD). RVWT was measured by M-mode either in the 2-dimensional parasternal short-axis view below the tricuspid valve or in the parasternal long-axis view, depending on the quality of RV free wall visualization. RVDd was measured as the maximal distance from the RV free wall to the septum from the apical four-chamber view.RVOTD and aortic dimension (AoD) were measured at the aortic valve level in the short-axis view. The ratio of RVOTD to AoD (RVOTD/AoD) was calculated as representative of RV dilatation. The position of the transducer was aligned to visualize the RV apex.The maximal RV cavity size preceding the frame with the onset of systolic closure of tricuspid valve leaflets was used to measure RVDd. To assess RV function, the tricuspid annular plane systolic excursion (TAPSE) of the lateral portion of the tricuspid annular plane was measured by the base-to-apex shortening during systole. This was recorded in the M-mode format under two-dimensional echocardiographic guidance from the apical four-chamber view.Furthermore, PA velocity (PAv) was recorded at the aortic valve level in the short-axis view. This was used as an echocardiographic indicator of RV pressure overload , 11.The left ventricle (LV) M-mode echocardiograms were recorded to evaluate LV function, as previously described. LV end-diastolic dimension (LVDd), LV end-systolic dimension (LVDs), interventricular septal wall thickness (IVST), and LV posterior wall thickness (LVPW) were measured at the papillary muscles level, and LV fractional shortening (LVFS) was calculated as follows: n = 8) were killed 8 weeks after surgery. In the PAC group, 4 rats were killed 4 weeks after surgery and all the remaining rats (n = 6) were killed 8 weeks after surgery. In the sham group, 6 rats were killed 4 or 8 weeks after surgery. The hearts were quickly removed, and the ventricles were dissected free of atrial tissue and large blood vessels. The right ventricle was carefully separated from the left ventricle and interventricular septum (IVS). The fresh ventricular tissues were immediately blotted dry and weighted separately to determine the degree of RV hypertrophy based on 2 parameters: RV wall weight/body weight (RV/BW) and RV wall weight/LV and IVS wall weight (RV/LV + IVS).In the PAL group, the remaining 4 rats were killed 4 weeks after surgery and all the remaining rats  with a light microscope (OLYMPUS SZX12). The number of pixels of the blue-stained collagen area was calculated with Adobe Photoshop CS5 soft and then divided by the total number of pixels in the RV wall per slide, analyzed, and averaged.t-test or analysis of variance for parametric values was used to compare group means. Probability of 0.05 or less was considered to be statistically significant.All data were expressed as mean ± SEM and range. Student's unpaired p < 0.01). For the PAL procedure, 5 major hemorrhages occurred during trimming the mPA compared to only one major hemorrhage for the PAC procedure.Surgical procedure time was defined as the interval from starting to incise the skin to skin closure. The surgical procedure time was 27.6 ± 1.4 min for PAL and 17.3 ± 2.1 min for PAC  or PAC (n = 28) or sham (n = 12) in the surgical risk study. During the perisurgical period, which was the time from the beginning of surgery to 6 hours after surgery, 1 rat in the PAC group out of 28 died due to bleeding (3.6%).Sixty-eight rats underwent PAL . Of those 7 rats, 1 died from an intubation accident, 2 died from bleeding, 2 died from pneumothorax, and 2 died from sudden cardiac arrest. All of the animals in the sham group survived regardless of the surgical procedure. After the perisurgical period, there were 3 and 12 deaths in the PAL and PAC groups, respectively. The most common reasons for post-PAB death in both groups were pleural and/or pericardial effusion  occurring between weeks 4 and 8 after surgery. Some of the rats died of unknown causes although we assumed these were due to either cardiac arrhythmia or heart failure as autopsy of these rats showed no blood in the thoracic cavity.The signs of RV failure associated with TAPSE were more severe in the PAC group than in the PAL group. The signs of moderate or severe tricuspid regurgitation (TR) or pleural effusion or IVC dilation were detected in the PAC group 5 weeks after the PAC procedure, but we could seldom detect these signs in the PAL group throughout the observation period (PAC versus PAL: moderate or more TR 21/27 (77.8%) versus 3/21 (14.3%), pleural effusion 18/27 (66.7%) versus 2/21 (10.0%), and IVC dilation 20/27 (74.1%) versus 0/21 (0%)).Furthermore, the standard deviation in the PAC group was greater than the PAL group. In other words, the data of the PAL group varied more widely than that of the PAC group. More stable data might be obtained with the PAC procedure.μm versus 21.3 ± 3.47 μm versus 22.8 ± 2.38 μm, 8th week: sham versus PAL versus PAC: 14.3 ± 1.40 μm versus 34.7 ± 7.22 μm versus 35.1 ± 8.19 μm)  weight ratios in the PAC and PAL groups to be similar and significantly higher than in the sham group . Whole h8.19 μm) .Masson's trichrome staining showed fibrosis in the RV free walls of the sham, PAL, and PAC groups . At the Definition of heart failure was challenging because there were neither objective cutoff values of cardiac or ventricular dysfunction nor changes in pressure, dimension, or volume that could be reliably used to identify patients with heart failure. According to The European Society of Cardiology task force for the diagnosis and treatment of heart failure, both symptoms at rest or during exertion and objective evidence of cardiac dysfunction at rest should be present to diagnose heart failure .In animal models, however, heart failure symptoms like fatigue or breathlessness are difficult to detect and quantify. Then evaluation of the models depends on objective findings such as reduced cardiac output, increased filling pressure, and progressive fibrosis , 7, 13. Most attention is given to LV function, whereas RV function and disease have seldom been focused on. It is an established fact that there is a relationship between LV and RV function. Impairment of the RV might influence LV function , 16. RV To the best of our knowledge this is the first reported evaluation of a newly devised means of stressing the right ventricle—the half-closed clip procedure—and its comparison with the pulmonary artery banding procedure. Using this new technique we could produce a right heart failure model in significantly less time and with much faster recovery and fewer surgical deaths than the PAL procedure. Most importantly, this novel procedure more fully developed subsequent myocardial damage and postsurgery cardiac dysfunction than did the PAL procedure. Furthermore, if we adjust the position of the stopper, we can produce different PAB models using this procedure.A recent study in rats who underwent banding of the mPA by the existing partial ligation procedure showed that pressure overload alone was insufficient to explain right heart failure; the rats showed no effect on cardiac output or fibrosis . Using tp = 0.051).Hardziyenka and colleagues reported LV atrophy in pulmonary hypertension . HoweverThis study demonstrated that the application of a tantalum half-closed clip around the pulmonary artery induced right ventricle dysfunction in a reproducible manner. This model should prove valuable in the investigation and treatment of right heart failure caused by pressure overload.


No significant differences were found between baseline characteristics of HCM and control groups . HCM patients had significantly higher Bas-Rotation, AP-Rotation, LV Twist, LVEF, LADs, IVST, LAVi, E/Em and LVMI than controls  and significantly lower LVDd and E/A (both p < 0.001). Bas-Rotation, AP-Rotation, LV-Twist, LADs, IVST, LAVi, E/Em and LVMI were significantly higher in HCM patients with fibrosis than in those without fibrosis (p < 0.001), but no significant differences in other echocardiographic parameters were found between those with and without fibrosis. Age, Bas-Rotation, AP-Rotation, LV twist, LADs, IVST, LAVi, E/A, E/Em, and LVMI were significant effect factors for fibrosis. AUROC analysis showed that LV twist had high discriminatory power to detect extent of myocardial fibrosis . Left ventricular twist mechanics are associated with the extent of myocardial fibrosis. LV-twist assessment by STE may be clinically useful.We aimed to investigate whether left ventricular (LV) twist analysis can detect the extent of myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM). This prospective case–control study recruited 81 consecutive patients with HCM examined between January 2012 and April 2013. Data of 76 patients were analyzed after excluding 5 patients whose echocardiographic images were of poor quality. Healthy volunteers (n = 46) served as controls. Both groups underwent comprehensive echocardiographic examination  and magnetic resonance imaging. Between-group differences were analyzed by independent The online version of this article (doi:10.1007/s10554-014-0509-6) contains supplementary material, which is available to authorized users. Myocardial fibrosis is a pathological entity associated with extracellular matrix remodeling, which may lead to increased myocardial stiffness and left ventricular systolic and diastolic dysfunction , 2. LateSpeckle tracking echocardiography (STE), which is based on tracking and measurement of tissue displacement, has the potential to accurately and reliably assess myocardial mechanics, providing a relatively simple, noninvasive approach to the study of LV rotation and twist –9. LV twThis prospective case–control study recruited a total of 81 consecutive patients with HCM who were examined in our department between January 2012 and April 2013. The diagnosis of HCM was made by echocardiography based on the criteria of the World Health Organization/International Society and Federation of Cardiology. All patients had also undergone MRI examination. Patients’ medical records were thoroughly reviewed to ensure that there was no history of hypertension, and no patient presented with hypertension during the study period. Patients were excluded if they had poor resolution of echocardiographic images; obstructive HCM ; left ventricular ejection fraction (LVEF) <50 % as assessed by echocardiography; cardiac muscle disease secondary to any known systemic condition; atrial fibrillation, implantation of a pacemaker or defibrillator; significant valvular heart disease; or known coronary artery disease (lesions >50 % on angiogram). Finally, after five patients were excluded because their echocardiographic images were of poor quality and not suitable for the present study, the data from 76 patients were retained for subsequent analysis.Patients were classified as having asymmetric septal hypertrophy if wall thickness in the basal or mid anterior/inferior septum was >1.3 cm and septal/lateral wall thickness ratio was >1.3. Patients were classified as having a septal bulge if the proximal anterior/inferior septum was >1.3 cm and the mid or apical anterior/inferior septum was <1.3 cm. Apical hypertrophy was diagnosed if the ratio of maximal segmental wall thickness of the apex and the rest of the ventricle was >1.5. All patients were in sinus rhythm.All drugs were discontinued at least 24 h before echocardiography and MRI evaluation, as previously recommended . PatientFor the purpose of analysis, the HCM group (n = 76) was further divided (after imaging and echocardiographic examinations described below) into a fibrosis group and a non-fibrosis group.In addition, a group of 46 healthy volunteers who underwent advanced LV-twist analysis by echocardiography served as controls. These subjects had no documented history of cardiovascular disease, including hypertension or HCM. These subjects did not undergo MRI evaluation.This study was reviewed and approved by the hospital’s Institutional Review Board. All included patients and control subjects provided signed informed consent.Magnetic resonance imaging examination was performed within 2 weeks of echocardiographic examination. MRI was performed using a 1.5-T Sonata scanner . Electro cardio-gating breath-holding sequential scanning was carried out with the patient in the dorsal position. Axial and sagittal single-shot turbo spin echo imaging was carried out on the basis of conventional axial, sagittal and coronal phases. Cine-imaging was carried out for left ventricular two-chamber and four-chamber longitudinal planes as well as LV outflow tract planes and LV shot-axis view for 6–8 layers, and the scanning sequence was retrospective ECG gating true fast imaging, as described previously . The lefEchocardiography was carried out using the Phillips iE33 Color Doppler Ultrasound System with probe frequency 3.5 MHz . The Qlab multiparameter analysis workstation (Phillips) was equipped with STE analysis software. The second-harmonic B-mode images of apical  and short-axis  views were obtained. The frame rate was more than 50 frames/s. The LV endocardial border was manually traced at the end-systolic frame and the speckle tracking region of interest was automatically selected. The width of the region of interest was adjusted as necessary to accommodate the total thickness of the LV wall . The comThe peak values of basal rotation were defined as the maximum negative values of the curves from the short-axis view at the mitral valve level. The peak values of apical rotation were defined as the maximum positive values of the curves from the short-axis view at the apical level . Every vStandard two-dimensional measurements were obtained using standard methods. LVEF was calculated using the two-dimensional Simpson’s biplane method. LV mass was assessed with the two-dimensional area-length method and the left ventricular mass was normalized to body surface area, as previously described . Left vep < 0.05 indicated statistical significance.Continuous variables were presented as mean and standard deviation, with independent t test used to compare differences between groups. Categorical variables were presented as counts and percentages, with Fisher’s exact tests used to compare differences between groups. Logistic regression was performed to detect which factor provides the strongest influence among myocardial fibrosis groups. Factors that were significant in univariate logistic regression were included in multivariate logistic regression, with stepwise model selection used to select the best factor to detect myocardial fibrosis. The receiver operating characteristic (ROC) curve was used to examine the factor performance in fibrosis and non-fibrosis groups. The cut-off value of factors that may distinguish myocardial fibrosis or not were selected using Youden index, which was defined as sensitivity + specificity − 1. Area under ROC curve with null hypothesis: AUC = 0.5 was performed using the Wilcoxon rank sum test. All statistical analyses were performed with SPSS software version 17 , and two-tailed 2, mean BMI was 23. 9 kg/m2, mean SBP was 122.5 mmHg andmean DBP was 80.4 mmHg. In the HCM group, 26.3 % had a history of HCM and 13.2 % had unexplained syncope.Patients’ baseline characteristics in HCM and control groups are presented in Table p > 0.05). The means of SBP and DBP were significantly higher in the HCM group than in the control group . The HCM group had more patients with a history of HCM and unexplained syncope than the control group  . LVDd and E/A were significantly lower in the HCM group than in the control group (both p < 0.001) (Table Comparisons of echocardiography parameters between HCM and control groups are presented in Table p < 0.001). Means of age and E/A were significantly lower in the fibrosis group compared with non-fibrosis group . No significant differences were found between non-fibrosis vs. fibrosis groups in heart rate, BSA, BMI, SBP, DBP and LVEF (p > 0.05). Representative examples are shown in Fig. The distribution of characteristics in HCM patients with and without fibrosis is presented in Table In addition, LV-twist showed a significant, positive and linear correlation with IVST, LVPWT, RWT, LAVi and E/Em in HCM patients with fibrosis. The greater the increase in LV-twist, the greater were IVST, LVPWT, RWT, LAVi and E/Em. No significant linear correlations were found between LV-twist and E/A, untwisting velocity .p < 0.001, Fig. p < 0.001; E/Em: AUC 0.99, 95 % CI 0.99–1.0, p < 0.001) . When ROC curve analysis was used to examine the LV-Twist performance in HCM patients with and without myocardial fibrosis, the AUC showed high discriminatory power for LV-twist to distinguish between myocardial fibrosis or no fibrosis  Fig. ; with an01) Fig. .Fig. 3TResults of the present study demonstrate that patients with HCM, even in the presence of preserved EF, show impaired regional myocardial deformation with increased LV twist. LV twist is significantly associated with myocardial fibrosis segments, suggesting that LV twist may provide useful information on the presence and extent of myocardial fibrosis and cardiac events in HCM patients with normal LVEF. Differences in diagnostic parameters between HCM patients and controls.Our results showed that the apical horizontal rotation angle, base rotation angle and left ventricular torsion angle in HCM patients were significantly higher than those in healthy controls. This might be explained by the fact that cardiac hypertrophy in HCM patients may increase the moment of epicardial fibers, resulting in dominant counterclockwise rotation of the epicardial fibers. Miyazaki et al.  studied In another study, apical rotation, basal rotation and torsion or LV twist were increased in patients with HCM compared to results of these CMRI parameters in normal volunteers . In thatA review by Sengupta et al.  suggesteIn the present study, left ventricular myocardial fibrosis was detected in 49 HCM patients (65.5 %), and LV twist and apical rotation were significantly higher in the fibrosis subgroup than in the non-fibrosis subgroup. This may be the result of subendocardial ischaemia with dysfunction of subendocardial fibres causing rotation of the apex in a clockwise direction . MicrovaWe also found differences between groups in the left ventricular torsion angle, which was significantly larger in the fibrosis group than in the non-fibrosis group. This may be ascribed to subendocardial myocardial hypoperfusion due to myocardial fibrosis, affecting endomyocardial function and reducing negative torsional deformation. In addition, the apical horizontal rotation angle was markedly larger than that in the non-fibrosis group, but the base rotation angle was comparable between the two groups. Thus, the overall left ventricular rotation angle in the fibrosis group increased significantly compared to that in the non-fibrosis patients. Popovic et al.  applied In the present study, the E/Em and left atrial volume index in the fibrosis group were significantly higher than those in the non-fibrosis group. This may be ascribed to the myocardial interstitial fibrosis and the subsequent increase in ventricular wall stiffness and ventricular wall tension. In addition, the reduction in myocardial relaxation capability and compliance may have resulted in restricted ventricular filling in the early diastolic phase, with an increase in left atrial pressure and subsequent elevation in left atrial volume and E/Em. Additionally, the anteroposterior diameter in the left atrial systolic phase was comparable between the fibrosis group and non-fibrosis group, but marked difference was observed in left atrial volume index. This implies that the frequently used left atrial anteroposterior diameter may not accurately reflect the actual size of the left atrium.Results of the present study revealed no differences in LVEF between the two subgroups. However, we observed that patients with fibrosis demonstrated larger left atrial volumes, LAVi and diastolic dysfunction as measured by E/A-ratio and tissue Doppler-derived methods  as early signs for LV pathology and LV diastolic dysfunction. These data agree with results of previous studies showing early onset of markers of diastolic dysfunction in HCM patients , 29. As In the present study, the left ventricular torsion angle was closely related to the number of myocardial fibrotic segments, suggesting that LV twist analysis has good sensitivity and specificity in reflecting the severity of myocardial fibrosis in HCM patients. The area under the ROC curve was 0.814 using LV twist to detect myocardial fibrosis (95 % CI 0.625–0.890), which indicates that LV twist can sensitively and specifically reflect the degree of myocardial fibrosis in HCM patients. Our results are consistent with those of Saito et al. , who demThe present study has several limitations. First, the number of patients in the study was small, which results in relatively weak statistical power. Secondly, LV twist measured by 2D speckle tracking was not actually global twist because LV twist was measured from only three short-axis views . Since the distribution of LV twist and hypertrophy in the left ventricular is not uniform in HCM, it is possible that LV twist did not completely reflect the extent of LV myocardial fibrosis. The further development of three-dimensional (3D) speckle tracking might resolve this issue, as suggested by other authors . ThirdlyIn conclusion, LV twist and rotation in patients with HCM can be accurately measured using STE and results may be relevant to making clinical decisions. LV twist evaluation may provide useful information on myocardial fibrosis and cardiac events in HCM patients with normal chamber function. This clinically promising parameter may be useful for risk stratification in patients with HCM.Supplementary material 1 (DOC 30 kb)Below is the link to the electronic supplementary material.


Qualitatively, FLAIR MR imaging is sensitive to the detection of hippocampal sclerosis (HS). Quantitative analysis of T2 maps provides a useful objective measure and increased sensitivity over visual inspection of T2-weighted scans. We aimed to determine whether quantification of normalised FLAIR is as sensitive as T2 mapping in detection of HS.Dual echo T2 and FLAIR MR images were retrospectively analysed in 27 patients with histologically confirmed HS and increased T2 signal in ipsilateral hippocampus and 14 healthy controls. Regions of interest were manually segmented in all hippocampi aiming to avoid inclusion of CSF. Hippocampal T2 values and measures of normalised FLAIR Signal Intensity (nFSI) were compared in healthy and sclerotic hippocampi.HS was identified on T2 values with 100% sensitivity and 100% specificity. HS was identified on nFSI measures with 60% sensitivity and 93% specificity.T2 mapping is superior to nFSI for identification of HS. •T2 mapping has significantly outperforms normalised FLAIR in differentiating sclerotic from healthy hippocampi.•Due to high sensitivity and specificity T2 mapping carries high potential to point out potential bilateral pathology.•The difference of ability to detect the pathology by the two techniques is likely to hold for advanced FLAIR sequences.•T2 mapping should be the technique of choice to differentiate hippocampal sclerosis in clinical setting. FLAIR MQuantification of hippocampal T2 signal is useful as an objective measure of hippocampal pathology  that is Hippocampal T2 mapping has been used to good effect for many years, and can be estimated using a dual echo sequence . It woulWe aimed to check if normalised FLAIR technique is as sensitive and specific as clinically validated T2 mapping technique in the task of the detection of HS.22.1We analysed MRI data from three cohorts of subjects, comprising patients with histologically confirmed right (13) HS, left (14) HS and elevated T2 values measured in vivo with a dual echo method , and 14 The patients were scanned for clinical purposes using the established clinical protocol that included T2 FLAIR and dual T2 images. The Research Ethics Committee did not require individual patient consent as the study was classified as a service evaluation. The HS was diagnosed preoperatively on MRI of all patients and confirmed histologically. Healthy controls gave written, informed consent.2.2The images utilised for the analysis were acquired on a GE Excite 3T MRI scanner with an 8-channel head coil.T2 Fluid Attenuated Inversion Recovery (FLAIR): Fast Spin Echo (FSE), TE 140 ms, TR 11,000 ms, TI 2250, NEX = 1, FOV 24 × 24 cm, 32 slices, 256 × 256 matrix size, voxel size 0.94 × 0.94 × 5 mm, and scan duration 2 min 57 s.Dual-echo T2 mapping: Fast Relaxation Fast Spin Echo (FRFSE), TR 2000 ms, TE 30 and 80 ms, FOV 24 × 24 cm, 32 slices, 256 × 256 matrix size; voxel size 0.94 × 0.94 × 5 mm, and scan duration 3 min 1 s.Both scans were oriented in the oblique coronal plane in the same axis as the brain stem, orthogonal to the hippocampus, so as to minimise partial volume effects .2.3Pixel-by-pixel T2 maps were calculated from the FRFSE images by using the expression T2 = (TE2 − TE1) / [ln(S1 / S2)], where S1 and S2 are the signal intensity in the early- and late-echo images, with echo times TE1 = 30 ms and TE2 = 80 ms, respectively .2 and as large as could be accommodated within the outline of the hippocampus while avoiding CSF and partial volume effect with CSF. The T2 map and T2 FLAIR images were arranged on the screen next to each other in the process of segmentation  was placed manually within the hippocampus both on FLAIR and T2 map images, in 4–5 consecutive 5 mm thick coronal slices from posterior to anterior. The ROI was at least 18 mmentation , to ensuThe average signal intensities were measured across each coronal slice of each hippocampal ROI of both T2 FLAIR and T2 images. The data from each individual slice were averaged to yield a single measure for each hippocampus.The hippocampal ROI measures obtained from the T2 FLAIR were normalised using the average T2 FLAIR signal intensity across white matter in pons and anterior frontal lobes as described previously for nFSI analysis . The nFS3The upper limit of normal of nFSI, defined as mean + 2SDs, was 1683 normalised units. The nFSI of one control has reached 1750 n.u. exceeding the normal limit. 11/27 sclerotic hippocampi had nFSI values below the normal limit with one very close to the borderline (1680 n.u.).T2 values: 100% sensitivity and 100% specificity;nFSI values: 60% sensitivity and 93% specificity,The healthy hippocampi were differentiated from sclerotic hippocampi proved histologically based on:where specificity and sensitivity were calculated based on the thresholds shown in As expected, in some patients the hippocampus contralateral to HS had abnormal T2 values in 6/27 (22%) cases , reflect4We compared the sensitivity and specificity of normalised FLAIR and T2 mapping techniques in the task of the detection of HS based on the cohort of patients with histologically confirmed HS and elevated T2 signal in the ipsilateral hippocampus.The results demonstrate a higher rate of differentiation between healthy and sclerotic hippocampi when using dual-echo T2 mapping technique compared to nFSI.We applied the same method of analysis for images of both sequences in order to concentrate on comparison of the imaging techniques rather than the specificities of the analysis. The only difference — the step of normalisation of the T2 FLAIR image — was unavoidable as the FLAIR image is not quantitative.The accurate segmentation of hippocampal ROI is crucial for this study. Despite the recent significant advances in automated segmentation of hippocampi  the manuTherefore, our choice of the analysis algorithm was predefined by the method of manual segmentation and the technique which has been successfully used in clinical practice .The two cases with additional pathology  were the only left HS cases showing weak evidence for bilateral HS according to the T2 mapping results  whereas T2 FLAIR is based on one measurement. This is an inherent difference of the modalities, which leads to the T2 mapping technique to have twice the amount of data as the FLAIR and thus likely also a higher SNR. The performance of the nFSI method would improve with twice the sampling. However, the doubled sampling would increase the duration of the T2 FLAIR scan making it less practical clinically and more prone to the motion artefact.It remains to be determined whether nFSI may detect abnormalities in the small minority of cases with sclerotic hippocampi in which T2 mapping is within the normal range.5T2 mapping remains the technique of choice for differentiation of the patients with HS from healthy subjects when applying the criterion of T2 signal intensity.3 isotropic.There is a high degree of confidence that this conclusion will persist even with advances with neuroimaging equipment and introduction of diagnostic T2 images with resolution at the level of 1 mm