Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients.The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function.Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2–12 mo) after the treatment of hypercortisolism.P < .001 for all) and increased end-diastolic LV segmental thickness (P < .001). Treatment of hypercortisolism was associated with an improvement in ventricular and atrial systolic performance, as reflected by a 15% increase in the LV ejection fraction (P = .029), a 45% increase in the LA ejection fraction (P < .001), and an 11% increase in the RV ejection fraction (P = NS). After treatment, the LV mass index and end-diastolic LV mass to volume ratio decreased by 17% (P < .001) and 10% (P = .002), respectively. None of the patients had late gadolinium myocardial enhancement.Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism. Cardiovascular complications are a major cause of morbidity and mortality in patients with Cushing's syndrome –3. Patie–4–10–To date, descriptions of cardiac structure and function in patients with Cushing's syndrome have been limited to two-dimensional (2D) echocardiography and restricted to the left ventricle (LV). A few studies have shown LV hypertrophy, concentric remodeling, and reduced systolic and diastolic performance –19. LV d–In contrast, cardiac magnetic resonance imaging (CMR) provides a highly accurate and comprehensive assessment of cardiac geometry and function. CMR provides regional myocardial wall thickness, myocardial mass, and atrial and ventricular volumes based on precise delineation of myocardial borders without the need for geometric assumptions , 22. In Patients were recruited in the Endocrinology Department of a tertiary referral center from September 2009 to March 2013. Patients aged 15–60 years were eligible if they had active endogenous Cushing's syndrome (newly diagnosed or uncontrolled after first surgery). Cushing's syndrome was diagnosed according to the usual clinical and biological criteria, including elevated urinary free cortisol (UFC) excretion, loss of the circadian plasma cortisol pattern, and lack of cortisol suppression during the overnight 1-mg dexamethasone suppression test . All procedures conformed to the Declaration of Helsinki.1) were measured with standard procedures. In patients not known to have diabetes mellitus, glucose metabolism was assessed by a standard oral glucose tolerance test (OGTT). In the OGTT, the plasma glucose concentration was measured 2 hours after an oral intake of 75 g of glucose. Diabetes mellitus and impaired glucose tolerance were diagnosed according to the usual diagnostic criteria  was determined with an automatic validated BP recorder . The reported clinical BP is the mean value obtained in the 3 days preceding CMR. Plasma fasting glucose, triglycerides, total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, potassium and glycated hemoglobin  was performed when successful treatment was achieved, with clinical and biological remission of hypercortisolism. Patients were considered in remission after treatment if they presented either with secondary adrenal insufficiency, with low morning serum cortisol concentrations and low UFC excretion rates or with eucortisolism, with normal UFC excretion rates (<65 μg per 24 hours or < 179 nmol per 24 h), normal overnight suppression of serum cortisol after the administration of 1 mg dexamethasone and normal sleeping midnight serum cortisol concentration (<2 μg/dL or 55 nmoL/L for both) . The per1c were determined with standard analytical methods. UFC excretion was measured with a specific RIA using polyclonal antibodies as previously reported  MRI scanner using a dedicated torso 8-element phased array coil and electrocardiographic gating. All acquisitions were done with breath holding. Cine images were acquired using a steady-state free precession sequence and covered the heart in axial views (10–12 slice levels) and in cardiac short-axis views covering the entire right and left ventricles (10–12 slice levels) with the following parameters: echo time, 1.5 msec; repetition time, 3.5 msec; slice thickness, 8 mm; spacing, 10 mm; acquisition matrix, 224 × 192; spatial resolution, 0.78 mm; and number of phases, 40. Late gadolinium enhancement of the myocardium was studied with a T1-weighted 2D inversion recovery sequence on long- and short-axis end-diastolic views of the LV, 10–15 minutes after iv infusion of 0.2 mmol/kg of a gadolinated contrast agent  with the following parameters: echo time, 1.5 msec; repetition time, 5.3 msec; slice thickness, 8 mm; spacing, 10 mm; acquisition matrix, 224 × 160; spatial resolution, 0.86 mm; and inversion time, 250 msec. These investigations were repeated in the same conditions during the patients' usual follow-up visits after effective treatment of Cushing's syndrome.End-diastolic and end-systolic LV and right ventricular (RV) myocardial contours were generated on short-axis images by using semiautomated software  by an experienced reader and were all validated by consensus after adjustment if necessary by an expert reader for all subjects. Endocardial contours were used to estimate ventricular end-diastolic and end-systolic volumes by the disk summation method. Similarly, end-diastolic LV myocardial contours were used to measure LV myocardial volume and, subsequently, LV mass (grams) as LV myocardial volume × myocardial density (1.06 g/mL). Left atrial end-diastolic and end-systolic endocardial contours were traced manually on axial cine images with the same method and used to measure left atrial (LA) volumes. LV and RV stroke volumes (milliliters) were then calculated as end-diastolic volume minus end-systolic volume, and ejection fractions were calculated (in percentages) as stroke volume/end-diastolic volume. Segmental wall thickness (millimeters) was measured as the mean segmental thickness on each American Heart Association segment  using ep1c, UFC, morning plasma cortisol) and the LV, RV, and LA ejection fractions, the LV mass index and mean wall thickness were analyzed with the Spearman rank correlation, as were associations with treatment-induced changes in these parameters. To evaluate the influence of selected predictive variables on treatment-induced changes in the LV, RV, and LA ejection fractions, the LV mass index and mean wall thickness, we used multiple linear regression models with adjustment for age, gender, BMI, and systolic BP, testing each independent variable individually. Significance was assumed at P < .05. Stata 11SE (StataCorp) and SAS 9.1 software (SAS Institute) were used for statistical analyses.The LV and RV ejection fractions were used as the main measures of ventricular systolic performance. Continuous variables are expressed as the median and interquartile range. Differences between the controls and patients with active Cushing's syndrome were analyzed with the Mann-Whitney test. Treatment-induced changes in the patients are expressed as baseline-adjusted changes from baseline . The effects of Cushing's syndrome treatment were assessed with a Wilcoxon's rank-signed test. Univariate associations between clinical variables  and biological variables  had New York Heart Association (NYHA) II-III dyspnea. The other patients had no symptoms of heart failure (NYHA I). Six patients were obese (BMI > 30 kg/m2), six were overweight (25 < BMI < 30 kg/m2), and six had a normal BMI (<25 kg/m2). Nine patients had arterial hypertension , seven of whom were on antihypertensive treatment. Five patients were diabetic , of whom three required oral antidiabetic drugs. The OGTT revealed impaired glucose tolerance in another four patients. Five patients had hypertriglyceridemia and one had hypercholesterolemia. Three patients were on statin therapy and three patients required potassium supplementation.Eighteen patients with active Cushing's syndrome (16 women and two men) with a median age of 35 years (range 15–59 y) were included. Fourteen patients had newly diagnosed Cushing's syndrome. Four patients had previously been treated by pituitary surgery and had developed recurrent hypercortisolism before entering the study. Fifteen patients had Cushing's disease, one had ectopic ACTH secretion, and two had cortisol-secreting adrenal adenomas. The patients' baseline clinical and hormonal characteristics are summarized in As expected, sex, age, and BMI were similar in the patients and controls. Systolic and diastolic BPs were higher in the patients than in the controls .The second evaluation was performed a median of 6 months (range 2–12 mo) after correction of the glucocorticoid excess. Ten patients underwent transphenoidal surgery, four received steroidogenesis inhibitors, and one received both transphenoidal surgery and medical treatment. The patient with ectopic ACTH secretion was prepared with medical therapy before curative thoracic surgery. Both patients with cortisol-secreting adrenal adenomas were cured by unilateral adrenalectomy. Clinical and biological remission of hypercortisolism was obtained in all the patients . Fourtee1c levels also fell after treatment. Diabetes mellitus and impaired glucose tolerance reversed in all treated patients. Triglyceride, total cholesterol, and LDL cholesterol levels did not change, whereas HDL cholesterol levels fell after treatment. Statins could be discontinued in one patient.Data for 17 patients were included in the analyses of the response to treatment. Patient 18 was excluded from further investigations because of pregnancy. In addition, data for the subgroup of 13 patients with surgical remission and secondary corticotroph deficiency also were analyzed separately. The impact of correction of the glucocorticoid excess on clinical and biological parameters is summarized in P < .001) and tended to have a smaller LV stroke volume index (P = .08) (P < .001), and also a trend toward higher LV mass (P = .012), lower RV stroke volumes (P = .033), and lower RV ejection fractions (P < .001) (P = .042). Consequently, LA ejection fractions (P < .001). In a univariate analysis, the patients' baseline CMR LV and RV function estimates did not correlate with their clinical or biological variables. The LA ejection fraction was associated only with elevated fasting glucose , and the LV mass index was associated only with systolic BP . No delayed myocardial enhancement was observed.LV, RV, and LA parameters in the patients and controls are compared in P = .08) . In addi LV mass . Only on LV mass . At base LV mass . Differe < .001) . Maximalractions  were marP = .042) and LV EF (P = .029) (P < .001). Segmental myocardial wall thickness decreased by 37%, 34%, and 35% at the basal, mid-LV, and apical levels , respectively. LV mass/end-diastolic volume decreased by 10% (P < .001), pointing to a more eccentric LV geometry, because the decrease in LV mass was associated with a trend toward an increase in end-diastolic volume (P = .033) and 11% (P = .16), respectively, reflecting the improvement in RV systolic function (P = .004) and, consequently, the LA ejection fraction increased by 45% (P < .001) (P = .13) when the four nonsurgically treated patients were excluded from the analysis. The effects of Cushing's syndrome treatment on ventricular function and structure, as assessed by CMR in patient 16, are illustrated in Changes in LV, RV, and LA parameters after the treatment of Cushing's syndrome are presented in  = .029) . Treatmec volume . Treatmefunction . Maximal < .001) . The resP = .042). The treatment-induced decrease in the LV mass index correlated only with the decrease in blood glucose . In a multivariate analysis with adjustment for age, gender, BMI, and systolic BP, the only individual variable significantly associated with the increase in the LV ejection fraction was the decrease in mean wall thickness . Independent correlates of the decrease in the LV mass index included decreased fasting glucose , decreased BMI , and decreased mean wall thickness . None of the patients had late gadolinium enhancement of the myocardium on follow-up CMR.In a univariate analysis, treatment-induced changes in the LV, RV, and LA ejection fraction did not correlate with changes in any of the clinical or biological parameters, except for an association between increased RV ejection fractions and decreased systolic BP  and controls, ruling out marked preload differences . PreviouIn addition to biventricular systolic dysfunction, patients with Cushing's syndrome had a markedly lower LA ejection fraction than controls, pointing to diastolic LV dysfunction. This parameter showed a marked improvement after treatment. Diastolic LV dysfunction has previously been reported in terms of abnormal transmitral flow velocity patterns on Doppler US –16, 19 a–This study further demonstrates that cortisol excess is associated with increased regional LV wall thickness. However, no significant increase in total LV mass was found, probably owing to the small number of patients we were able to study, this being a rare disease. The LV mass to end-diastolic volume ratio remained close to young healthy control values and lower than values associated with an adverse prognosis in the asymptomatic general population . However17–The pathophysiology of cardiac hypertrophy and decreased systolic function in Cushing's syndrome remains unclear. The myocardium seems to be exempt from the generalized muscular atrophy seen in Cushing's syndrome, resulting from increased protein catabolism . ArteriaDecreased systolic performance in Cushing's syndrome points to ultrastructural abnormalities in heart muscle, altering its contractility. Recently increased myocardial fibrosis, indirectly assessed by calibrated integrated backscatter, has been described in patients with Cushing's syndrome. Fibrosis was associated with systolic and diastolic dysfunction and regressed after treatment of hypercortisolism . In the The heterogeneity of the treatments used to control Cushing's syndrome is a potential limitation of this study. However, the results of reevaluation analysis did not chance substantially after exclusion of patients controlled only by medical therapy. Furthermore, we cannot rule out a potential impact of hydrocortisone replacement on the cardiac structure and function in patients with surgical remission and secondary corticotroph insufficiency.In conclusion, this CMR study shows that patients with Cushing's syndrome frequently have significant subclinical biventricular and LA systolic dysfunction and increased LV mass, in the absence of dense myocardial fibrosis. Successful treatment of the cortisol excess improves systolic ventricular and atrial performance and leads to regression of the LV mass and myocardial thickness, in parallel with an improvement in glucose metabolism and BMI. Structural and functional abnormalities of the myocardium occur early in Cushing's syndrome and should be actively investigated to guide strategies designed to prevent overt heart failure. Although endogenous Cushing's syndrome is a rare disease, our findings may also have implications for patients receiving long-term treatment with exogenous corticosteroids, a common clinical situation.


Fatty acid-binding protein 4 (FABP4) is expressed in both adipocytes and macrophages. Recent studies have shown secretion of FABP4 from adipocytes and association of elevated serum FABP4 level with obesity, insulin resistance, hypertension, and atherosclerosis. However, little is known about role of FABP4 in cardiac function.From the database of the Tanno-Sobetsu Study, data for 190 subjects  who were not treated with any medication and underwent echocardiography in 2011 or 2012 were retrieved for analyses of relationships between serum FABP4 concentration, metabolic markers and parameters of echocardiography.Serum FABP4 level was positively correlated with age, body mass index (BMI), blood pressure (BP), LDL cholesterol, HOMA-R and mean left ventricular (LV) wall thickness  and was negatively correlated with HDL cholesterol, estimated glomerular filtration rate (eGFR) and peak myocardial velocity during early diastole , an index of LV diastolic function. However, no significant correlation was found between FABP4 level and LV end-diastolic dimension, LV ejection fraction or LV mass index. There were significant correlations of e’ with age, BMI, BP, eGFR, brain natriuretic peptide (BNP), FABP4, metabolic markers and LVWT. Multivariate regression analysis adjusted by HOMA-R, BMI, eGFR, BNP or LVWT in addition to age, gender and BP revealed that serum FABP4 concentration was independently correlated with e’.Elevation of circulating FABP4 may contribute to LV diastolic dysfunction in a general population. Fatty acid-binding proteins (FABPs) are a group of intracellular lipid chaperones that coordinate lipid responses in cells ,2. FABPsAdipose tissue is now known to secrete a variety of bioactive molecules called adipokines, such as tumor necrosis factor-α (TNFα), leptin and adiponectin, which are implicated in a wide range of biological phenomena. Interestingly, recent studies have shown that FABP4 is secreted from adipocytes ,9, thougObesity is a risk factor for several kinds of cardiac insults, such as left ventricular (LV) hypertrophy, LV diastolic dysfunction and heart failure with preserved or reduced ejection fraction. It has been suggested that several adipokines provide a direct pathophysiological link between enlarged adipose tissue and obesity-associated cardiac dysfunction . HoweverThe Tanno-Sobetsu Study is a study with a population-based cohort design recruiting residents of two rural towns, Tanno and Sobetsu, in Hokkaido and includes annual health examination, pathophysiological assessment of metabolic syndrome and cardiovascular disease, and follow-up survey. A total of 357 female subjects (mean age: 66 ± 13 years) in 2011 and 277 male subjects (mean age: 66 ± 13 years) in 2012 received annual examinations in Sobetsu Town. Female and male participants in 2011 and 2012, respectively, were invited to receive echocardiographic examinations. Subjects who were being treated with any regular medications for diseases were excluded. Other exclusion criteria were atrial fibrillation and conductional abnormalities such as left bundle branch block on electrocardiogram or severe valvular disease and left ventricular hypertrophy  on echocardiogram. A total of 190 subjects who underwent echocardiography  contributed to the present analyses. This study conformed to the principles outlined in the Declaration of Helsinki and was performed with the approval of the Ethical Committee of Sapporo Medical University. Written informed consent was received from all of the subjects.Medical check-ups were performed between 06:00 h and 09:00 h after an overnight fast. After measuring anthropometric parameters, blood pressure was measured twice consecutively on the upper arm using an automated sphygmomanometer  with subjects in a seated resting position, and average blood pressure was used for analysis. Body mass index (BMI) was calculated as body weight (in kilograms) divided by the square of body height (in meters). Peripheral venous blood samples were obtained from study subjects after physical examination for complete blood count and biochemical analyses of the serum. The serum samples were analyzed immediately or stored at −80°C until biochemical analyses.2) = 194 × Cr(‐ 1.094) × age(‐ 0.287) × 0.739 . HOMA-R, an indicator of insulin resistance, was calculated by the previously reported formula: insulin(μU/ml) × glucose(mg/dl)/405.Serum concentration of FABP4 was measured using a commercially available enzyme-linked immunosorbent assay kit for FABP4 . The accuracy, precision and reproducibility of the kit have been described previously . The int2). Left atrial (LA) dimension (mm) was measured by M-mode echocardiography, and LA volume was measured using biplane Simpson’s method and normalized for body surface area  [After medical check-ups and collection of urine and blood samples, echocardiographic examinations were performed by three well-experienced echocardiographers who were blinded to clinical data, using Vivid 9  equipped with a 2.5-MHz frequency transducer. Two-dimensional and color tissue Doppler imaging modes were used to obtain images from standard echocardiographic views, including parasternal long-axis and apical four-, three-, and two chamber views at a left lateral decubitus position. Standard parameters in two-dimensional measurements, including LV end-diastolic and end-systolic dimensions (mm) and septal and posterior wall thicknesses at end-diastole (mm), were determined. Mean LV wall thickness (mm) was calculated by the average of septal and posterior wall thicknesses at end-diastole. LV ejection fraction (%) was calculated using biplane modified Simpson’s method. LV mass was calculated according to the recommendations of the American Society of Echocardiography  and norm, ml/m2) . Each pat test. One-way analysis of variance and Tukey-Kramer post hoc test were used for detecting significant differences in data between multiple groups. The correlation between two variables was evaluated using Pearson’s correlation coefficient. Multivariate regression analysis was performed to identify independent determinants of e’ using the variables with a significant and non-confounding correlation in simple regression analysis as independent predictors, showing the t-ratio calculated as the ratio of regression coefficient and standard error of regression coefficient and the percentage of variance in the object variables that they explained (R2). A p value of less than 0.05 was considered statistically significant. Holm-Bonferroni sequential correction was also performed in multivariate regression analysis. All data were analyzed by using JMP 9 for Macintosh .Numeric variables are expressed as means ± SD for normal distributions or medians (interquartile ranges) for skewed variables. The distribution of each parameter was tested for its normality using the Shapiro-Wilk W test, and non-normally distributed parameters were logarithmically transformed for comparison and regression analyses. Comparison between two groups was done with an unpaired Basal characteristics of the study subjects are shown in Table In analyses of data from all study subjects, serum FABP4 level was positively correlated with age, BMI, systolic and diastolic blood pressures, total cholesterol, LDL cholesterol, triglycerides, insulin, HOMA-R, Cr and hsCRP and was negatively correlated with eGFR Table . SimilarRegarding echocardiographic parameters, FABP4 concentration was positively correlated with LA dimension, LA volume index and mean LV wall thickness , though correlation with FABP4 was not significant for LV end-diastolic dimension or LV mass index. FABP4 level was positively correlated with E/e’ and negatively correlated with e’ Figure , whereas2 = 0.563).Multivariate regression analysis was performed to identify independent determinants of e’ using systolic blood pressure, the most strongly correlated factor among anthropometric and biochemical parameters , in addition to age and gender (Model 1) and showed that serum FABP4 concentration was independently correlated with e’  was significantly higher than that in a group with high levels of FABP4 (FABP4-High) Figure . FurtherThe salient finding in the present study was that FABP4 was independently and negatively correlated with e’, which reflects LV relaxation and is known as one of the most sensitive indexes of LV diastolic function in a healthy population . LV dias2+ level in a dose-dependent manner [Previous studies using animal models indicated that FABP4 plays a significant role in several aspects of metabolic syndrome, including insulin resistance, type 2 diabetes and atherosclerosis, through its action at the interface of metabolic and inflammatory pathways in adipocytes and macrophages ,2,4-6. Et manner  and impat manner . Therefot manner ,23. ImpaInflammation is an important factor in the pathogenesis and progression of heart failure. It has been shown that increased inflammatory cytokines produced by mononuclear cells including macrophages and/or damaged myocardium impaired myocardial function by inducing apoptosis, necrosis and hypertrophic response in cardiomyocytes . In the Up-regulation of FABP4 expression and other adipokines in heart failure has been demonstrated in recent studies -28, indiCirculating FABP4 level was associated with increased LV mass in overweight and obese women  and in pSimilar to our results, a very recent study by Baessler et al.  demonstrA genetic variant at the FABP4 locus associated with decreased FABP4 expression in adipose tissue has been reported to reduce the risk of cardiovascular disease in a population study . We and Since FABP4 is a low-molecular-weight protein and freely filtered at the glomerulus, a decrease in glomerular function was shown to result in an elevation of FABP4 concentration . In the The present study has some limitations. Since it has been reported that several drugs, including statin, angiotensin II receptor blocker and peroxisome proliferator-activated receptor γ agonist, affect FABP4 concentrations -42, we eThe present study is the first study to show an independent association of serum FABP4 level with LV diastolic dysfunction in a general population. The increase in serum FABP4 concentration might precede development of the early phase of cardiac dysfunction. Whether FABP4 can serve as a biomarker for early diagnosis of high-risk individuals with heart disease and a potential therapeutic target for cardiac dysfunction warrants further investigation.


Despite the advancement in medicine, management of heart failure (HF), which usually presents as a disease syndrome, has been a challenge to healthcare providers. This is reflected by the relatively higher rate of readmissions along with increased mortality and morbidity associated with HF. In this review article, we first provide a general overview of types of HF pathogenesis and diagnostic features of HF including the crucial role of exercise in determining the severity of heart failure, the efficacy of therapeutic strategies and the morbidity/mortality of HF. We then discuss the quality control measures to prevent the growing readmission rates for HF. We also attempt to elucidate published and ongoing clinical trials for HF in an effort to evaluate the standard and novel therapeutic approaches, including stem cell and gene therapies, to reduce the morbidity and mortality. Finally, we discuss the appropriate utilization/documentation and medical coding based on the severity of the HF alone and with minor and major co-morbidities. We consider that this review provides an extensive overview of the HF in terms of disease pathophysiology, management and documentation for the general readers, as well as for the clinicians/physicians/hospitalists. Heart failure (HF) is a clinical syndrome caused by structural and functional defects in myocardium resulting in impairment of ventricular filling or the ejection of blood. The most common cause for HF is reduced left ventricular myocardial function; however, dysfunction of the pericardium, myocardium, endocardium, heart valves or great vessels alone or in combination is also associated with HF. Some of the major pathogenic mechanisms leading to HF are increased hemodynamic overload, ischemia-related dysfunction, ventricular remodeling, excessive neuro-humoral stimulation, abnormal myocyte calcium cycling, excessive or inadequate proliferation of the extracellular matrix, accelerated apoptosis and genetic mutations .2 and low systemic vascular resistance. The common causes of high output failure are severe anemia, vascular shunting, hyperthyroidism and vitamin B1 deficiency. This occurs as a result of ineffective blood volume and pressure, which stimulate the sympathetic nervous system and renin-angiotensin-aldosterone system (RAAS), causing the release of antidiuretic hormone (ADH), which all together ultimately lead to ventricular enlargement, negative ventricular remodeling and HF. Low output failure is much more common than high-output failure and is characterized by insufficient forward cardiac output, particularly during times of increased metabolic demand. Left ventricular dysfunction due to large MI, right ventricular dysfunction due to an acute pulmonary embolus and biventricular dysfunction are important causes of low output failure. More recently, exercise intolerance in HFpEF is proposed to be due to a decrease in oxygen delivery to or impaired oxygen utilization by the exercising skeletal muscles. Oxygen utilization is being calculated as the arterial–venous oxygen content difference (A-VO2 Diff), rather than reduced cardiac output (CO) [2 without affecting endothelial function [Heart failure can be classified as predominantly left ventricular, right ventricular or biventricular based on the location of the deficit. Depending on the time of onset, HF is classified as acute or chronic. Clinically, it is typically classified into two major types based on the functional status of heart: heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). In patients with HFpEF who are mostly females and older adults, EF is usually more than 50%; the volume of the left-ventricular (LV) cavity is typically normal, but the LV wall is thickened and stiff; hence, the ratio of LV mass/end-diastolic volume is high . HFpEF iput (CO) . Considefunction ,8.Class I:HF does not cause limitations to physical activity; ordinary physical activity does not cause symptoms.Class II:HF causes slight limitations to physical activity; the patients are comfortable at rest, but ordinary physical activity results in HF symptoms.Class III:HF causes marked limitations of physical activity; the patients are comfortable at rest, but less than ordinary activity causes symptoms of HF.Class IV:HF patients are unable to carry on any physical activity without HF symptoms or have symptoms when at rest.The New York Heart Association (NYHA) functional classification defines four functional classes as:Stage A:High risk of heart failure, but no structural heart disease or symptoms of heart failure;Stage B:Structural heart disease, but no symptoms of heart failure;Stage C:Structural heart disease and symptoms of heart failure;Stage D:Refractory heart failure requiring specialized interventions.The American College of Cardiology/American Heart Association (ACC/AHA) staging system is defined by the following four stages:2 supply or mismatch with the O2 supply vs. demand in HF patients. Therapeutic strategies to improve muscle microvascular and oxidative function via exercise training, anti-inflammatory and antioxidant agents have been proposed to be essential to provide better exercise tolerance and quality of life [The clinical presentation of HF comprises symptoms of shortness of breath (SOB)/dyspnea ; orthopnea/SOB on lying own (sensitivity of 22%–50% and a specificity of 74%–77%); paroxysmal nocturnal dyspnea ; fatigue/weakness/lethargy ; edema, abdominal distention and right hypochondrial pain  ,12. Rece of life .HF has primarily been recognized as a disease of the elderly population (>60 years) and is reported to affect about 2%–3% of people in the United States. Of these include 10% of males and 8% of females. Unfortunately, these numbers are on a gradual increase due to the on-going prevalence of HF with increasing age. In the USA itself, about more than three million physician visits per year have been accounted for patients with HF as the primary health issue. In 2013, the total number of HF patients were 5.1 million, and direct costs were equal to $32 billion; and this cost is being projected to increase by about three-fold by 2030 . As of 2N-oxide (TMAO) is reported to be elevated in HF patients and has recently been correlated to higher long-term mortality risk independent of other HF risk factors [The underlying pathogenesis of HF also involves silent inflammatory and immune-regulatory responses, the activation of which still has not been completely understood. It has been proposed that in HF, excessive neuroendocrine activation leads to the activation of neuro-hormones and pro-inflammatory cytokines following an initial cardiac insult. Many of these pro-inflammatory and anti-inflammatory cytokines and their receptors, released endotoxins, adhesion molecules, nitric oxide and reactive oxygen species have been associated with various pathological aspects of HF ,21. The  factors . For thi factors .The evaluation for HF is performed using various parameters: physical examination to determine the presence of clinical symptoms and signs, blood tests, including complete blood count, urinalysis, complete metabolic profile for levels of serum electrolytes , blood urea nitrogen, serum creatinine, glucose, fasting lipid profile, liver function tests and thyroid-stimulating hormone.N-terminal proBNP (NT-proBNP) with 99% sensitivity and 85% specificity, the measurement which has been recommended both in outpatient and in the hospital settings [N-terminal fragment, NT-proBNP, and the 32-peptide, biologically-active hormone BNP. NT-proBNP and BNP have clinical significance both as diagnostic and prognostic markers in the management of HF. During the diagnosis of HF, in patients presenting with acute dyspnea, BNP levels of less than 100 pg/mL have a 90% negative predictive value (NPV), and values of more than 500 pg/mL have an 81% positive predictive value (PPV) [Other HF-specific laboratory tests  include brain natriuretic peptide (BNP) with 70% sensitivity and 99% specificity and settings . BNP is ue (PPV) . The BNPue (PPV) . A recenue (PPV) . Accordiue (PPV) . NT-proBue (PPV) .Biomarkers not only provide valuable information about the pathophysiology of the disease, but also shed light on the severity of ongoing disease. As far as biomarkers for HF are concerned, the National Academy of Clinical Biochemistry has set forth comparable goals in a consensus document stating that a biomarker in HF ideally enables clinicians to: (i) identify possible underlying  causes of HF; (ii) confirm the presence or absence of the HF syndrome; and (iii) estimate the severity of HF and the risk of disease progression.Multiple biomarkers have been classified depending on their putative functional impact on cardiac myocytes and the resulting pathophysiological changes in patients with HF and include (a) myocyte stretch biomarkers; (b) myocyte necrosis biomarkers; (c) systemic inflammation biomarkers; (d) oxidative stress biomarkers; (e) extracellular matrix turnover biomarkers; (f) neuro-hormone biomarkers; and (g) biomarkers of extra-cardiac processes, such as renal function. The specific biomarkers are shown in Other diagnostic tests for HF include chest X-ray, transthoracic echocardiography (TTE), computerized tomography (CT) scans and magnetic resonance imaging (MRI). Chest X-rays are useful in evaluating heart size, pulmonary congestion and to detect alternative cardio-pulmonary diseases that may cause or contribute to the patient’s symptoms. A ‘two-dimensional echocardiogram with Doppler’ is recommended for initial evaluation of patients presenting with HF. TTE is useful to assess ventricular function, size, wall thickness, wall motion and valve function. TTE also helps to determine the ejection fraction of the heart and thus helps in selecting the appropriate therapy. Furthermore, TTE helps to assess the mitral valve inflow pattern, the pulmonary venous inflow pattern, mitral annular velocity to precisely evaluate LV filling and the left atrial pressure of the dysfunctional heart. Other parameters include tricuspid valve regurgitant gradient coupled with the measurement of inferior vena caval diameter and its response during respiration, which provide estimates of systolic pulmonary artery pressure and central venous pressure . Many of2/VO2 max capacity (VO2 max is the maximum intake of oxygen despite an increase in exercise intensity) has been considered as the primary predictor of mortality and morbidity [In HF patients, exercise intolerance characterized by the reduction in peak VOorbidity ,36. In aorbidity ,38,39,40Serum urea >15 mmol/LSystolic blood pressure <115 mmHgSerum creatinine >2.72 mg/dL (or 240 μmol/L)N-terminal pro-brain natriuretic peptide (NT-pro-BNP) >986 pg/mLLeft ventricular ejection fraction <45%Some of the other predictors of relative poor outcome in chronic heart failure ,10,41 arHigh NYHA functional classReduced left ventricular ejection fractionThird heart soundIncreased pulmonary artery capillary wedge pressureReduced cardiac indexDiabetes mellitusReduced sodium concentrationRaised plasma catecholamine and natriuretic peptide concentrationsThe major goals of treatment in heart failure are (1) to improve prognosis and reduce mortality and (2) to alleviate symptoms and reduce morbidity by reversing or slowing the cardiac and peripheral dysfunction. For in-hospital patients, in addition to the above goals, other goals of therapy are (1) to reduce the length of stay and subsequent readmission (2) to prevent organ system damage and (3) to appropriately manage the co-morbidities that may contribute to poor prognosis .The 2013 American College of Cardiology/American Heart Association (ACC/AHA) updated guidelines , 2010 He‘In-patient’ management of HF: It is advised to admit the patient in the telemetry bed or in ICU and the treatment is based on the following points.2 < 60% or SaO2 < 90%.Monitor oxygen, whether PaOProvide noninvasive positive pressure ventilation (NIPPV) in the few cases with respiratory distress for respiratory support to avoid subsequent intubation.Diuretics  (to reduce the edema by the reduction of blood volume and venous pressure) and salt restriction (to reduce fluid retention) in patients with current or previous heart failure symptoms and reduced left ventricular ejection fraction (LVEF) for symptomatic relief.Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for neuro-hormonal modification, vasodilatation and improvement in LVEF .Beta-adrenergic blockers for neuro-hormonal modification, improvement in symptoms and LVEF, survival benefit, arrhythmia prevention and control of ventricular rate.Aldosterone antagonists, as an adjunct to other drugs for additive diuresis, heart failure symptom control, improved heart rate variability, decreased ventricular arrhythmias, reduction in cardiac workload, improved LVEF and an increase in survival.Digoxin, which can lead to a small increase in cardiac output, improvement in heart failure symptoms and a decreased rate of heart failure hospitalizations.Anticoagulants, if applicable, to decrease the risk of thromboembolism.Inotropic agents to restore organ perfusion and reduce congestion in patients with heart failure with reduced ejection fraction, so as to increase in cardiac output and reduce neuro-humoral activation.Some other agents have been described under clinical trial .Use the following pharmacological agents depending on the precipitating factors and symptoms/signs for congestion:In the case of refractory HF, ultrafiltration therapy is used for fluid reduction for patients that are not responsive to medical therapy . In patiExacerbating factors have been addressed and are under controlVolume status has been optimizedDiuretic therapy has been successfully transitioned to oral medication, with discontinuation of IV vasodilator and inotropic therapy if required for at least 24 hOral therapy for chronic heart failure (HF), including angiotensin convertase enzyme inhibitors (ACEIs) and beta blockers (for patients with reduced LVEF), has been established with stable clinical statusPatient and family education completed, including clear discharge instructionsLeft ventricular ejection fraction (LVEF) documented: echocardiography is the gold standardSmoking cessation (if applicable) counseling initiatedFollow-up clinic visit scheduled within three days of discharge, usually for 7–10 daysThe patients of ADHF are ready for discharge when they meet the following criteria ,10:ExacOral medication regimen for heart failure has been established for 24 hNo intravenous vasodilator or inotropic agent for at least 24 hAmbulation before discharge to evaluate the beneficial effect of therapy and restoration of functional capacityPlans for post-discharge management to prevent readmission Appropriate referral to a specialist for disease management of precipitant cause(s) if applicableFor patients with advanced HF or recurrent admissions for HF, before discharge, the following are preferred ,10:OralMedication reconciliation, written plans for dietary sodium restriction and recommended activity levelFollow-up by phone or clinic visit soon after discharge to reassess volume statusMedication and dietary adherenceAlcohol moderation and cessation of smokingMonitoring of body weight, electrolytes and renal functionConsideration of referral for formal disease managementThe discharge plan for the hospitalized patients should address the following issues ,10:MediComprehensive education and counseling individualized to the patient’s disease and socio-economic and educational levelEducation/promotion of self-care, including self-adjustment of diuretic therapy in appropriate patients with the help of a family member/caregiverEarly attention to signs and symptoms of fluid overloadEmphasis on behavioral strategies to increase adherenceOptimization of medical therapyVigilant follow-up after hospital discharge or after periods of instabilityIncreased access to providers or healthcare/social servicesAssistance with social and financial concerns(1)Medication noncompliance (21%–66%)(2)Smoking (60%)(3)Sodium- and fluid-restricted diet noncompliance (30%–44%)(4)Failure of documentation of discharge information and patient education (41%)(5)Co-morbidities (21%–34%) Readmission is defined as a subsequent hospital admission within 30 days following an original admission (or index stay). The overall 30-day readmission rate nation-wide (USA) is about 23%–26% . Among M(1)Medical predictors: severity of orthopnea, renal dysfunction, hemodynamic instability, high levels of Pro-BNP, hyponatremia and presence of co-morbidities.(2)Demographic predictors: male gender, advanced age, previous admission within six months, low median income, lack of psychosocial support, medication compliance and compliance to follow-up visits.In light of the repeated readmission of HF patients, the Affordable Care Act (ACA) of 2010 required HHS  to establish a readmission reduction program. This program, effective 1 October 2012, was designed to provide incentives for hospitals to implement strategies to reduce the number of costly and unnecessary hospital readmissions, especially for diseases of Medicare diagnosis-related groups. Under this program, ACA implemented a financial penalty of up to three percent of their Medicare payments to hospitals for excessive readmissions for hospitals . A few sMultidisciplinary HF clinics/centers Visiting nurse services and nurse specialist Physician-directed heart failure transitional care program Home tele-monitoring or structured phone calls Follow-up one-week post discharge Transition care intervention home program These strategies have been further refined through the incorporation of the findings from the completed and ongoing clinical trials  and fluid restriction <2 L/day is considered when the fluid retention persists and when severe hyponatremia (serum Na <130 mEq/L) is present.2 delivery, while simultaneously correcting mitochondrial and contractile efficiency. The localized muscle training has been shown to improve convective and diffusive O2 transport in HF and, hence, is useful for patients with minimal lung reserve capacity; several variables, such as exercise type, duration, frequency, intensity, etc., need to be taken into consideration to best benefit from such training [healthy lifestyle changes ; especially, recent studies have advocated the importance of exercise training to HF patients via improvement in the skeletal muscle Otraining ,65,66.efforts to improve patients’ compliance with medical regimens and interventions, such as phone calls, reminders and home nurse, to help patients remember to take the medications.understand the alarming signs and symptoms, such shortness of breath, excessive fatigue, swelling of feet/ankle, etc. .weight monitoring (weight daily and record: (i) get up in the morning; (ii) empty bladder; (iii) step on the scale and record) ,11.Patient education:Arranging follow-up care: This includes assistance in scheduling the first follow-up appointment post-hospitalization along with re-enforcement of the importance of other follow-up visits. It also includes documentation of the date, time and location of the follow-up visit on the discharge plan, as well as sending reminders for subsequent appointments. One recent study has shown that it is possible to predict the readmission based on the response of the patients on the automated follow-up questionnaire .Home tele-monitoring: This is a unique approach where the transmission of clinical parameters and symptoms of patients with HF at home to their healthcare provider, such as weight, blood pressure, heart rate, oxygen saturation, along with patients queries and questions regarding medications and symptoms and signs is conducted, thereby titrating the therapy based on the symptoms and signs. A few studies have shown that home tele-monitoring reduces mortality and hospitalizations, while in other studies, home tele-monitoring was found to be equivalent to telephone calls by a nurse .Transition home program: This helps patients to have a safe transition to home or to another healthcare setting, such as a skilled nursing facility, and includes thorough patient and caregiver education, enhanced individualized assessment of post-discharge needs, patient-centered communication with caregivers and a standardized process for further management of HF along with follow-up visits with healthcare professionals ,60,68.Nurse assurance program: This program facilitates home service to follow-up on the patients with HF .Specialized referral or health centers: This is designed to provide personalized care to HF patients with thorough assessment for heart transplantation needs. The referral to an HF program is shown to result in a decrease in the frequency of hospitalization of ≈50% ,68.The schematic diagram summarizing the causes and pathogenesis of HF along with an in-depth description of the management strategies based on the different phases of the HF in order to meet the recommended goals of the HF management is shown in There have been numerous clinical trials all around the world as early as the 1990s CONSENSUS clinical trial, which determined the efficacy of diuretics for symptomatic HF. Soon, other clinical trials were designed to identify the best possible therapeutic agent to improve the clinical outcome of HF via pharmacological, non-pharmacological and novel treatment strategies. Current medical management for heart failure only alleviates symptoms, delays deterioration and prolongs life modestly. As the science has progressed by leaps and bounds, the idea of rejuvenation of the failing myocardium has begun to seem feasible when the accumulating evidence from preclinical studies demonstrated that rejuvenating the myocardium at the molecular and cellular level can be achieved by gene therapy and stem cell transplantation .Stem cells are the population of cells that have self-renewal properties and the potential to generate daughter cells capable of differentiating into specific cell lineages . Stem ceThe stem cell applications should be preferably undertaken in cases of acute injury. For example, the background pathophysiology is significantly different between chronic ischemic heart failure and acute myocardial infarction. This scenario is especially beneficial in acute myocardial infarction where the injured heart tissue secretes the inflammatory cytokines, which may even help in the homing of the infused stem cells to the injured tissue by the mechanism of chemotaxis. Thus, it will be easier for the stem cells to impact their beneficial effect, thus enhancing grafting and minimizing the degenerative remodeling, if the therapy is provided immediately after the myocardial injury. In hearts associated with acute myocardial infarction, the tissue is freshly injured and has not undergone remodeling which is often the case in chronic ischemic HF. Once cardiac remodeling has already taken place, the stem cells may not have a homing signal to graft into the infarcted site at the heart. Repeated injections of modified stem cells may also be an important aspect that has not been explored in the clinical application of stem cells. For patients of chronic ischemic heart disease, elective procedures to inject stem cells via epicardial or endocardial catheter have shown benefits. It has been seen that direct intramyocardial injections allow a greater myocardial retention of applied stem cells compared to that of intracoronary or systemic administration of stem cells .Besides stem cell therapy, gene therapy equally holds promise in the field of HF. The success of gene therapy depends on the specific genes, types of vector and routes of application. For the successful application of gene therapy, the vectors should satisfy the criteria of efficient myocardium-specific transduction (specificity), high frequency of transduction (frequency) and long-term transgene expression (duration). The clinical outcomes of gene therapy have been limited due to obstacles like the development of neutralizing antibodies, cellular immunity against the viral vectors, immunity against the genetically-modified implanted cells and the low level of gene expression or transduction . For exa2+ handling and myocardial contractility, such as adenylyl-cyclase 6 (AC6) and sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), where SERCA2a is shown to be an inhibitor of ventricular remodeling [2+ ions back to sarcoplasmic reticulum, reducing the cytoplasmic concentration of Ca2+ and allowing myofilament relaxation. Another important mention about cardiac gene therapy is Beta 2 adrenergic receptor therapy [The molecular targets of cardiac gene therapy can be well defined based on the participation of the gene in a specific function . The angmodeling . Indepen therapy . In anim therapy . In summ therapy .In addition to having the knowledge of the pathophysiology of the HF and its management with the help of established and novel therapies, it is important for a physician to understand how to document the therapy so as to satisfy the reimbursement requirements. The utilization process ensures the appropriateness of the incurred healthcare costs by reviewing inpatient and outpatient services and comparing them against medical necessity guidelines. Usually the “clinical documentation improvement” (CDI) team facilitates the appropriate coding of the disease according to the guidelines and documents the codes in the International Classification of Diseases, Clinical Modification Version 10 (ICD-10-CM) mode. ICD-10 contains codes for human diseases, signs and symptoms, abnormal findings, social scenarios, external causes of injury or diseases and ‘diagnostic and procedure codes’ associated with inpatient, outpatient and physician office utilization in the United States . Some ofThe Centers for Medicare and Medicaid Services (CMS) implemented the National Correct Coding Initiative (NCCI) to promote correct coding methodologies and to control improper coding leading to inappropriate payment for the hospitalized patients. HF is classified under the Diagnosis-Related Group (DRG), which is a statistical system of classifying possible diagnoses into more than 20 major body systems and subdividing them into roughly 500 groups for the purpose of Medicare reimbursement. Factors used to determine the DRG payment amount include the involved diagnosis, as well as the hospital resources necessary to treat the condition. Based on the absence or presence of co-morbidity, DRGs are further sub-classified as ‘DRG with no complication/comorbidity’ (labeled as Non-CC); ‘DRGs with complication/comorbidity’ (CC) and ‘DRGs with major complication/comorbidity’ . The DRG codes for HF are categorized based on the severity, associated co-morbid conditions and reflect the level of utilization of hospital resources along with the payment reimbursement . The folIn summary, healthcare professionals should work with team members of the case-management department so as to provide precise documentation of the procedures needed for accurate prediction of the patient’s condition and diagnosis along with comorbid conditions, so as to receive the maximum reimbursement of payments.Heart failure indeed is a complex disease and so far has been a major cause of morbidity and mortality in developing and developed countries. A standardized medical therapy has been successful in the early stages of HF. Advanced stages of HF require frequent hospitalization due to the presence of severe HF and or associated co-morbid conditions, which require strict implementation of an appropriately individualized multidisciplinary approach and quality measures to reduce re-admissions. While pharmacological management has a limited role in advanced cases of HF, novel therapeutic agents, such as regenerative and gene therapy, are in the developmental stages and need further refinement before their approval for the treatment of HF. Despite the appropriate measures, hospitalization in HF as a DRG has been a great challenge, especially since the adoption of the financial penalty program for excessive readmissions related to HF. In addition to the appropriate management of cases, healthcare professionals also need to provide precise and complete medical codes for procedures and diagnosis to help hospitals to receive the maximum reimbursement for the services provided to such patients.


Heart failure is usually associated with left ventricle remodelling, wall thickening, and worsening of the systolic function. Ventricular tachycardia is a common and a negative prognostic factor in patients with endocardial scarring following myocardial infarction and aneurysm formation. The authors present a case of a 51-year-old man with ischemic heart disease, who suffered myocardial infarction four years ago. The patient was admitted to the hospital with sustained ventricular tachycardia despite maximal pharmacotherapy and also underwent unsuccessful percutaneous radiofrequency ablation in the right ventricle. Transthoracic echocardiography revealed left ventricle dysfunction with ejection fraction of 25%, aneurysm of the apex of the left ventricle with thrombus formation inside the aneurysm. Surgical therapy consisted of the cryoablation applied at the transitional zone of the scar and viable tissue and the resection of the aneurysm. The patient remained free of any ventricular tachycardia four months later. Heart failure in patients with ischemic heart disease is associated with increased mortality. The progression of heart failure is associated with left ventricle remodelling, with increased left ventricle end-diastolic and end-systolic volumes, wall thickening, and worsening of the systolic function. Left ventricular dilatation is a predictor of increased mortality in heart failure .Several surgical procedures have been developed to counteract the ventricular remodelling process. Surgical ventricular restoration (SVR) involves resection of scar, septal exclusion, cavity reduction by endoventricular patch, and complete coronary grafting.Ventricular tachycardia (VT) is a common and a negative prognostic factor in patients with postinfarction ventricular dilatation and aneurysm. This is of particular importance in patients with endocardial scarring following myocardial infarction.The treatment of postinfarction VTs with antiarrhythmic drug therapy and implantable automatic defibrillators also includes different surgical procedures such as endocardial resection of the scar or endocardial cryoablation.In this paper we present successful surgical treatment of sustained VT in patient with postinfarction left ventricle aneurysm complicated with thrombus formation.The authors present a case of a 51-year-old man with ischemic heart disease who suffered acute transmural myocardial infarction  in his history, with delayed percutaneous angioplasty and stent implantation into the left anterior descending branch. Four years later, the patient (NYHA III) was admitted to the hospital with sustained ventricular tachycardia. He underwent percutaneous radiofrequency ablation in the right ventricle and implantation of the ICD . In the next period the patient suffered repeat sustained monomorphic VT resistant to maximal pharmacotherapy with amiodarone , prajmaline , or ajmaline .Transthoracic echocardiography revealed left ventricle dysfunction with ejection fraction of 25%, aneurysm of the apex of the left ventricle with thrombus formation inside the aneurysm .β-blocker  was given in the postoperative period. In the period of four-month followup no recurrent ventricular tachycardia was detected. According to the ICD no VT was detected in the follow-up period, and only paroxysmal supraventricular tachycardia was detected. Transthoracic echocardiography showed improvement in the ejection fraction of the left ventricle (45%) and no signs of thrombus.The surgery procedure was carried out via median sternotomy. Cardiopulmonary bypass was established via cannulation of the ascending aorta and right atrium. The aorta was cross-clamped, and myocardial protection was achieved with intermittent cold antegrade blood cardioplegia. The left ventricle was incised parallel to the interventricular septum and the left anterior descending artery. The interventricular clots were removed. Continuous encircling linear cryolesions  were applied at the transitional zone of the scar and viable tissue . The lefThe review of the clinical information was approved by the Clinical Ethics Committee of the University Hospital in Hradec Kralove.The association between VT and postinfarction left ventricular aneurysm has been noted since the 1930s. Considering the fact that ventricular arrhythmia is responsible for more than 50% of death in remodelled ventricles after myocardial infarction, surgical treatment was attempted [Monomorphic ventricular tachycardia could be induced in the presence of arrhythmogenic substrate such as a left ventricular aneurysm or recent myocardial infarction. In these patients surgical revascularization alone will most likely fail to prevent the incidence of postoperative ventricular arrhythmia, especially in the presence of poor left ventricular function.Left ventricular aneurysmectomy to treat drug-resistant VT was described in 1959 by Couch . GuiraudAmong applied several surgical procedures, two major approaches have become prevalent. These are ablation or resection of arrhythmogenic foci performed after precise either intraoperatively or percutaneously mapping or more extensive surgical ablation procedures without mapping (including cryoablation or thermoexclusion by laser).Generally, map-guided procedures have been used for surgical treatment of VT. Ostermeyer et al. demonstrated good long-term results of electrophysiologically guided resection for VT with survival rate of 75% and 45% at 1 year and 5 years, respectively [The results yielded from other studies reported favourable outcomes of nonguided methods . In the Sartipy et al. from The Karolinska group in Stockholm presented 53 patients who underwent the Dor procedure with nonelectrophysiologically guided subtotal endocardectomy and cryoablation for VT at the transition zone of the scar and viable tissue. Early mortality was 3.8%. Overall survival was 94%, 80%, and 59% at 1 year, 3 years, and 5 years, respectively. Freedom from spontaneous VT after a mean follow-up period of 3.7 ± 2.0 years was 90%. Postoperative VT suppression was similar in patients with preoperative spontaneous or inducible VT [Wellens et al. have published their experience with endoaneurysmorrhaphy and cryoablation without intraoperative mapping in a population of 31 patients with hospital mortality rate of 6.5%. Postoperative electrophysiologic study revealed freedom from VT induction in 25 patients and inducible VT in five patients .These studies show that there is a subset of patients who remarkably benefits from the combined approach for treatment of postinfarction VT including aneurysmectomy of postinfarction left ventricular aneurysm and extended blind cryoablation without perioperative mapping. It is a simple surgical technique, reproducible in most of the cardiac centres where a cryosource is available. It offers excellent arrhythmia control and satisfactory clinical outcomes.Cryoablation without mapping and anerurysmectomy offers good arrhythmia control and long-term clinical outcome in patients presenting with VT arising from post-myocardial infarction aneurysm.


Quantitative T2'-mapping detects regional changes of the relation of oxygenated and deoxygenated hemoglobin (Hb) by using their different magnetic properties in gradient echo imaging and might therefore be a surrogate marker of increased oxygen extraction fraction (OEF) in cerebral hypoperfusion. Since elevations of cerebral blood volume (CBV) with consecutive accumulation of Hb might also increase the fraction of deoxygenated Hb and, through this, decrease the T2’-values in these patients we evaluated the relationship between T2’-values and CBV in patients with unilateral high-grade large-artery stenosis.Data from 16 patients  with unilateral symptomatic or asymptomatic high-grade internal carotid artery (ICA) or middle cerebral artery (MCA) stenosis/occlusion were analyzed. MRI included perfusion-weighted imaging and high-resolution T2’-mapping. Representative relative (r)CBV-values were analyzed in areas of decreased T2’ with different degrees of perfusion delay and compared to corresponding contralateral areas.No significant elevations in cerebral rCBV were detected within areas with significantly decreased T2’-values. In contrast, rCBV was significantly decreased (p<0.05) in regions with severe perfusion delay and decreased T2’. Furthermore, no significant correlation between T2’- and rCBV-values was found.rCBV is not significantly increased in areas of decreased T2’ and in areas of restricted perfusion in patients with unilateral high-grade stenosis. Therefore, T2’ should only be influenced by changes of oxygen metabolism, regarding our patient collective especially by an increase of the OEF. T2’-mapping is suitable to detect altered oxygen consumption in chronic cerebrovascular disease. Cerebral perfusion abnormalities are suspected to play a key role in the pathophysiology of carotid occlusive disease  and are Since an increased cerebral oxygen extraction fraction (OEF) has been shown to be an indicator of exhausted autoregulatory reserve and an independent risk factor for stroke in several longitudinal positron emission tomography (PET) studies on patients with unilateral high-grade carotid stenosis/occlusion, , 5 MRI tQuantitative T2’-mapping has been used to describe changes in cerebral oxygen metabolism by using the different magnetic properties of oxygenated and deoxygenated hemoglobin (Hb). , 7 In co2 supply at constant O2 demand, or can result from an increased O2 consumption and constant supply in case of neuronal activation. Further, an increased cerebral blood volume (CBV) might lead to an accumulation of deoxygenated Hb. The latter should be considered especially in patients with hemodynamically relevant stenosis, because cerebral autoregulation might try to compensate decreased cerebral blood flow (CBF) by an increase of CBV. [T2’ has been shown to be decreased in perfusion-restricted brain regions in chronic cerebral hypoperfusion  as well  of CBV. In a previous study on patients with high grade occlusive carotid disease,  we foundWe performed a retrospective analysis of a prospectively acquired dataset  of which parts have previously been published by our group.  All patiImaging data including T2’-maps and CBV-maps, MTT- and TTP-maps of 16 patients  were analyzed. The patient characteristics, inclusion and exclusion criteria and perfusion deficits have been described in detail elsewhere.  Patients2, isotropic in-plane resolution 1.25 mm, turbo factor (number of spin echoes per excitation): 11, delay between subsequent echoes: 17.1 ms. For quantitative T2-mapping, five TSE data sets were acquired with identical parameters but different TE values . The total duration for all five TSE data sets was 11 minutes and 50 seconds.Data acquisition and postprocessing have been described in detail in several recent studies. , 10, 12 2, isotropic in-plane resolution 1.25 mm, duration 6 minutes 24 seconds. As quantitative T2*-mapping is considerably prone to artifacts induced by intrascan subject motion, the acquisition was repeated with half the spatial resolution in phase encoding direction (duration: 3 minutes 12 seconds). The k-space data of the full and the half resolution data sets were subsequently combined in a special manner for suppression of motion artefacts, as described earlier. [For high-resolution and motion-corrected  T2*-mappearlier. 2, matrix size 64×64, isotropic in-plane resolution 2 mm, slice thickness 4 mm, number of slices 16, duration 75 seconds). For verification of intracranial stenosis and exclusion of significant (>50%) contralateral intracranial ICA or MCA stenosis, a 3-dimensional time-of-flight angiography was performed.Perfusion-weighted imaging was based on a GE echo-planar imaging (EPI) sequence . Maps of T2 and T2* were derived by mono-exponential fitting of the respective data sets across the different TE values. Maps of T2′ were calculated as 1/T2′ = 1/T2*−1/T2.Raw images (turbo spin echo and perfusion-weighted) were linearly coregistered to the first raw T2*-weighted image by means of the FMRIB Linear Registration Tool , relative mean transit time (rMTT) and relative CBV (rCBV). The shape of the arterial input function was determined by manually choosing 5 to 10 pixels over the distal MCA trunk in the unaffected hemisphere. –16 For cFor the acquisition of quantitative T2- and T2*- maps, five spin echo and eight gradient echo data sets, respectively, were aquired at different echo times with a relatively high in-plane resolution that enabled a precise alignment for coregistration and for the calculation of T2’-maps. Due to the relatively long acquisition time however, this could only be achieved at the expense of an increased vulnerability to artifacts potentially induced by patients’ intrascan movement. Apart from our previously described motion correction algorithm,  this washttp://rsb.info.nih.gov/ij/index.html). Moreover, we calculated R2’ (1/T2’)-values since R2’ is assumed to be proportional to rCBV and OEF [As time-to-peak (TTP) and mean transit time (MTT) are known to show substantial intersubject variation we used a semiquantitative method for the definition of perfusion abnormalities. Perfusion-disturbed areas on TTP- and MTT-maps were defined as regions with a perfusion delay in comparison to the upper limit of normoperfusion in the unaffected hemisphere, which we defined as the mean TTP and mean MTT plus two standard deviations. Mean TTP and MTT were assessed by placing a standardized circular region-of-interest  in the MCA territory of the healthy hemisphere. First, the images were then thresholded according to the mean value plus two standard deviations which led to a delineation of the entire perfusion-restricted areas on TTP- and MTT-maps (perfusion delay > 0 sec). Furthermore, we gradually increased this threshold to receive areas with different perfusion thresholds  and perfusion delay ranges  and for each patient . The lat and OEF  and mighth, 75th percentile) throughout the results section unless stated otherwise.As both T2’- and rCBV-values were not normally distributed we only performed non-parametric statistical testing: the Wilcoxon-signed rank test was used for comparison of T2’, R2’ and rCBV within perfusion-restricted and contralateral areas, the Spearman’s rank correlation for the assessment of a parameter correlation and the Mann-Whitney test was used for group comparisons. Significance level was set to p<0.05. Statistical analysis was performed with SPSS 22 . Due to the skewed distribution data are given as median  and of a MTT-delay ≥6 s and ≥8 s, where rCBV was decreased . In these areas (except for an MTT-delay ≥6 s), T2’ was also significantly  decreased . AlthougWhen correlating median T2’-values with hemispheric ratios of rCBV we found a not significant positive correlation for areas with TTP-delay  and a weak not significant negative correlation for areas with MTT-delay . Also the correlation of T2’ and rCBV hemispheric ratios did not reveal any significant relationship, neither for areas with TTP hypoperfusion  nor for areas with MTT-delay . Similar results were obtained when analyzing the correlation between R2’-values and R2’ hemispheric ratios with rCBV ratios . When coConsidering all ROIs in the analysis there were few ROIs in which we found a significantly reduced T2’ (respectively increased R2’) with simultaneously elevated rCBV (hemispheric ratio>1) Figs . The coiOur study underlines the validity of T2’ to detect changes of cerebral oxygen metabolism in patients with chronic hypoperfusion.It is known that T2’ is decreased in areas of hypoperfusion in patients with unilateral high- grade ICA or MCA stenosis.  T2’ is c2 supply (CBF) at constant demand, which is expected to occur in case of an exhausted autoregulatory capacity. Decreased T2’ would then result primarily from the increased deoxygenated Hb concentration as a result of a preserved O2 consumption at decreased supply. 2. Elevations of rCBV with an accumulation of Hb as a consequence of autoregulatory vasodilation. In this case, the increasing accumulation of deoxygenated Hb in areas of increased CBV would considerably contribute to the decrease of T2’ in areas of prolonged MTT, and T2’ could not be used to reliably estimate the OEF.We therefore tested possible changes of CBV in our previously published collective  of patieWe found that in areas of slight to moderate MTT-delay , hemispheric ratios of rCBV indeed tend to increase up to 9%, but rCBV-values did not differ significantly between the perfusion-disturbed and the contralateral corresponding areas  and in the entire TTP-delayed area (>0 s delay), hemispheric ratios of rCBV decreased up to 6% and rCBV-values also tended to decrease with a significant decrease in areas with MTT-delay ≥6 and ≥8 seconds compared to the contralateral hemisphere . As T2’ These findings are in line with the literature. , 25, 26 Our study has to deal with several limitations that should be addressed. CBV was measured by the means of dynamic susceptibility contrast (DSC) imaging. It has to be stated that those values are only representative relative values due to different influencing technical factors.  When comFurther, we did not differentiate between different compounds contributing to total CBV. Although arterial CBV should not have a relevant influence on T2’ as we assume a constant arterial blood oxygen saturation, for a more precise assessment of the relationship between T2’ and CBV venous and arterial proportions of CBV should be estimated separately. In addition, our sample size was small and we included symptomatic and asymptomatic patients that might differ in terms of risk profiles as well as hemodynamic and metabolic parameters. Apart from changes of oxygen metabolism, T2’- and R2’-values could be influenced by iron deposition in hypoperfused tissue, both due to pathologic changes of iron metabolism and blood-brain barrier damage. Although we found no evidence for this in our data, being able to rule out these possible conditions would make our results more reliable. Last, our single-center results require an external confirmation by others and a validation with the golden standard for the imaging of cerebral oxygen metabolism, PET.The findings of this study support the hypothesis that T2’ can be used to assess the grade of metabolic impairment in patients with unilateral high grade carotid stenosis. It could be shown that the decrease of T2’, presumably reflecting an increase of OEF, in the territory of a unilateral high-grade stenotic large-artery is largely independent from changes of CBV as measurable by MRI. Although giving only representative relative values for CBV, MRI with T2’ and DSC-perfusion can therefore be used reliably to assess changes of oxygen metabolism in patients with chronic cerebral hypoperfusion.S1 File(XLS)Click here for additional data file.S2 File(XLS)Click here for additional data file.S1 TablePWI: perfusion-weighted imaging; TTP: time-to-peak; MTT: mean transit time.(DOCX)Click here for additional data file.S2 TableDue to the rather small differences in rCBV-values between the hemispheres, these data are presented with two decimals. In patient 5 and patient 14 no MTT-delay was detected. q: quantitative; rCBV: relative cerebral blood volume; TTP: time-to-peak; MTT: mean transit time. *Baseline absolute values of qT2’ for the entire TTP-and MTT-delayed areas have already been presented in a previous publication .(DOCX)Click here for additional data file.


This study aimed to assess myocardial performance index (MPI) and arterial elasticity indices in asymptomatic patients with beta-thalassemia major without known heart disease and to determine relationship between these indices and parameters indicating iron load of body.The study included 55 asymptomatic beta-thalassemia patients (median age: 20 years (10 - 48 years)) without known history of heart disease and 40 age- and sex-matched healthy controls. MPI and arterial elasticity indices were determined by using standard two-dimensional and Doppler echocardiography. Data were analyzed by SPSS for Windows version 20.0 .Left ventricular mass index (83.917 (50.62 - 144) and 68.37 (41.9 - 113.3)) and MPI (0.464 (0.33 - 0.68) and 0.431 (0.31 - 0.51)) were significantly higher in patients with beta-thalassemia when compared to control group (P < 0.001 and P = 0.006). Aortic elasticity indices were significantly higher while aortic strain and distensibility values were significantly lower in patients with beta-thalassemia compared to controls . Positive correlations were detected between aortic stiffness index and platelet  and ferritin values . Presence of thalassemia  and higher platelet value  were significant determinants for increased aortic stiffness in linear regression analysis.Arterial elasticity indices and MPI are impaired in patients with beta-thalassemia major and these parameters may be used to predict cardiovascular complications in asymptomatic patients with beta-thalassemia major. Thalassemia is a group of heterogeneous diseases with autosomal recessive inheritance, which is characterized by hypochromic, microcytic anemia resulting from disrupted synthesis of hemoglobin chains. Degree of cardiovascular involvement is one of the major factors determining prognosis in beta-thalassemia syndromes. Parenchymal injury secondary to myocardial iron deposition and immune-inflammatory processes are known to be primary reasons for cardiovascular disorders in patients with thalassemia . It is kEchocardiography is a reliable, feasible and non-invasive modality for early detection and serial assessment of alterations in cardiac morphology and functions in patients at risk for myocardial iron deposition. Myocardial performance index (MPI) and arterial elasticity indices are helpful for early diagnosis of cardiovascular complications . In prevIn this case-control study, 55 patients (median age: 20 years (10 - 48 years)) suffering from B-thalassemia major were recruited from the Thalassemia Clinic of Mugla Sitki Kocman University Education and Research Hospital. Patients with heart failure, systemic hypertension, diabetes mellitus, thyroid dysfunction, or parathyroid dysfunction were excluded. They had normal echocardiography and were on sinus rhythm. Forty age- and sex-matched healthy individuals, with no clinical, electrocardiographic, or echocardiographic evidence of cardiovascular disease were enrolled as controls. The Local Ethics Committee approved the study, and all subjects gave informed consent.All patients underwent a thorough clinical, electrocardiographic, and echocardiographic examination 48 h prior to blood transfusion, and blood samples were collected for hematologic measurements on the same day. The control group also underwent a full echocardiographic study and blood measurements. Body weight and height were measured, and body surface area was calculated accordingly.BP levels were measured from the brachial artery at the level of the heart with a sphygmomanometer after resting for at least 5 min in the supine position. Three measurements, at least 2 min apart, were carried out, and the average of the closest two readings was recorded. A pressure drop rate of approximately 2 mm Hg/s was applied, and Korotkoff phases I and V were used for systolic and diastolic BP levels, respectively. All BP measurements were made by a cardiologist blinded to the study protocol. Pulse pressure (PP) was calculated as systolic minus diastolic BP.Standard two-dimensional and Doppler echocardiography was performed using a commercially available echocardiographic machine  with a 2.0 - 3.5 MHz transducer. Measurements were made during normal breathing at end expiration. Left ventricular (LV) end-systolic (LVSd) and end-diastolic diameters (LVDd), end-diastolic interventricular septal thickness (IVSd) and end-diastolic LV posterior wall thickness (PWd) were measured at end-diastole according to established standards of the American Society of Echocardiography [Pulsed Doppler ultrasound scanning recordings of the mitral inflow velocities were obtained from the apical four-chamber view by placing the sample volume between the tips of the mitral leaflets. Peak early (E) and late (A) diastolic velocities, deceleration time, and the ratio of early to late peak velocities (E/A), were analyzed. Pulse wave tissue Doppler was performed with a 2-mm sample volume placed at the lateral corner of the mitral annulus from the apical four-chamber view. Filters were set to exclude high-frequency signals and gain minimized. Doppler ultrasound scanning intervals were measured from mitral annular velocity intervals. Left ventricular MPI was determined by using this equation: MPI = (IRT + ICT)/ET, where IRT is isovolumic relaxation time, ICT is isovolumic contraction time, and ET is ejection time .2dyn-110-3) = (2 × aortic strain)/PP; aortic stiffness index = (ln (systolic pressure/diastolic pressure))/aortic strain; and elastic modulus E(p) = PP/strain [Thoracic aortic diameters (cm) were measured 3 cm above the aortic valve by two-dimensional guided M-mode transthoracic echocardiography of the aortic root at left parasternal long-axis view . Aortic P/strain . Stiffnet-test was used to compare mean values of quantitative variables with normal distribution while Mann-Whitney U test was used to compare quantitative variables with skewed distribution. In correlation analyses, Pearson test was used for parametric variables while Spearmen test was used for non-parametric variables. Linear regression analysis was performed to assess relationship between variables found to be correlated. Statistical significance was interpreted by using P value in data obtained. P value < 0.05 was considered as statistically significant.Data were analyzed by using SPSS for Windows version 20.0 . Kolmogorov-Smirnov test was used to assess distribution of continuous variables where homogeneity was tested. Numeric variables with normal distribution were expressed as mean ± standard deviation while those with skewed distribution were expressed as median (min-max). Log transformation was applied to numeric variables with skewed distribution. After log transformation, it was seen that parameters including age, E/A ratio, RDW, lymphocyte values, aortic strain, distensibility, stiffness and elastic modulus exhibited normal distribution pattern. Student’s In our study, it was shown that echocardiographic elasticity parameters such as MPI, aortic strain, aortic distensibility, aortic stiffness index and elastic modulus differed significantly in thalassemia patients without known cardiac dysfunction or symptom who had normal routine echocardiographic parameters such as EF when compared to controls.Cardiovascular diseases are most important causes of mortality in beta-thalassemia syndromes. Parenchymal injury secondary to myocardial iron deposition is the most important pathological mechanism in the development of cardiovascular diseases . Iron deIt is known that early ventricular myocardial dysfunction can occur even in patients with beta-thalassemia receiving effective chelation therapy. MPI is obtained from ratio of isovolumetric contraction and relaxation times to ejection time, which can assess both systolic and diastolic functions, and appears as a marker used for early identification of myocardial functions in many instances. In a study on diabetic patients without marked cardiac failure or coronary artery disease, authors concluded that MPI can be a sensitive marker for diagnosis of LV dysfunction in patient with diabetes mellitus .Elevated MPI is associated with cardiac disorders such as heart failure. MPI is a readily available parameter that does not prolong echocardiographic evaluation time and is independent from ventricular geometry. It can be used by all clinicians due to low inter-observer variability . In our in vitro studies, it was shown that there was an increase in soluble adhesion molecules, decrease in endothelial cell mitosis, apoptosis and abnormality vascular endothelial cells when cells from healthy individuals were incubated by thalassemic serum [It is known that vascular pathologies as well as myocardial parenchymal injury facilitate cardiovascular complications in patients with thalassemia. It is also known that vascular complications such as early arterial aging and atherosclerosis are more commonly observed in patients with thalassemia . In in vic serum .Role of iron deposition in the development of atherogenesis-related disorders is not fully understood although its pathological role in myocardial injury is well known. It is known that there is an association between increased lipid peroxidation products and atherogenic vascular complications in patients with thalassemia major . In a stHowever, physiopathology of vasculopathy in patients with thalassemia cannot be explained by iron-related oxidative injury alone, as arterial stiffness or similar disorders does not always accompany to hemochromatosis. Hemolytic process resulting in release of free hemoglobin observed in the course of patient with thalassemia contributes to vasculopathy by impairing nitric oxide bioavailability and activity. However, high levels of inflammatory markers such as interleukin-6 and soluble vascular adhesion molecules have been linked to impaired endothelial function in patients with thalassemia . ActivatThe term, arterial stiffness, is used to define viscoelastic features of vessel wall such as mechanical strain or elasticity. Arterial stiffness, used as one of the important mechanical parameters of cardiovascular system, is created by dynamic and complex interaction between cellular and structural elements within vessel wall . In geneThere is remarkable evidence indicating that increased stiffness in large arteries is major determinant of adverse cardiovascular results . Aortic In recent years, arterial elasticity parameters which can be assessed by relatively simple, non-invasive methods are used to assess vascular involvement in patient with beta-thalassemia. Increased aortic stiffness or decreased distensibility is used as a marker for diffuse atherosclerotic involvement in vascular system . MoreoveIn our study, correlation and regression analyses between aortic stiffness and strain and clinical and hematological parameters showed that there was a positive correlation between aortic stiffness and platelet and ferritin values. In addition, it was shown that beta-thalassemia and platelet values played role as independent risk factor for aortic stiffness.In conclusion, it is known that early cardiac dysfunction can develop in patients with beta-thalassemia, even in those receiving effective chelation therapies. MPI and arterial elasticity indices can help clinician for early detection of cardiovascular disorders in patients with thalassemia even in the presence of normal echocardiography findings such as ejection fraction. Particularly, the indices should be used to predict and monitor cardiovascular complications in asymptomatic patients with beta-thalassemia.One limitation is to use BP values obtained from brachial artery in the assessment of aortic elasticity, although the fact that BP was measured by using same technique in both thalassemia and control groups did not affect the results. In addition, another limitation is failure to use T2-weighted MRI as marker of body iron load.


Failed hip prostheses can cause elevated circulating cobalt and chromium levels, with rare reports of fatal systemic organ deposition, including cobalt cardiomyopathy. Although blood cobalt and chromium levels are easily measured, organ deposition is difficult to detect without invasive biopsy. The T2* magnetic resonance (MR) method is used to quantify tissue iron deposition, and plays an important role in the management of iron-loading conditions. Cobalt and chromium, like iron, also affect magnetism and are proposed MR contrast agents.We describe a case of a 44-year-old male with a failed hip implant and very elevated blood cobalt and chromium levels. Despite normal cardiac MR findings, liver T2* and R2 values were abnormal, triggering tissue biopsy. Liver tissue analysis, including X-ray fluorescence, demonstrated heavy elemental cobalt and chromium deposition in macrophages, and no detectable iron.Our case demonstrates T2* and R2 quantification of liver metal deposition in a patient with a failed hip implant. Further work is needed to investigate the role of T2* and R2 MR in the detection of metal deposition from metal on metal hip prostheses. Hip replacement surgery is highly successful and 300,000 procedures are performed per year in the US alone. Sometimes they fail early. Recently a new mechanism and consequence of failure has been identified: the release of metal debris. This is common in patients with metal-on-metal (MoM) hip implants, but may occur in other implant types when ceramic/plastic components fracture.The metal alloys used in hip implants are safe when the bulk material is considered. However, wear and corrosion of these alloys may result in the generation of metal nanoparticles and metal ions with the most clinically relevant metal elements being cobalt (Co) and chromium (Cr) in both physical forms. Metal ion release can cause local soft tissue reactions and systemic toxicity, with reports of fatal cobalt cardiomyopathy, thyroid, and neuro-ocular toxicity , 2. AlthSerial measurement of serum metal ion levels in symptomatic patients with MoM hips is currently recommended by the medical device regulatory bodies (including the FDA and MHRA), and guides management including revision , 7. A thMagnetic resonance (MR) imaging using the T2* or R2 technique is the current gold-standard method for detection and quantification of iron deposition in patients with iron overload, and has histological validation , 9. In sA 44-year-old man presented to our institution with hip pain, a peri-prosthetic mass and scar pigmentation. He had initially undergone primary total hip arthroplasty 35 months previously, with a ceramic on ceramic bearing for osteoarthritis. 16 months following implantation, this was revised to a metal on polyethylene bearing implant, following a ceramic acetabular liner fracture. On presentation to our institution, laboratory investigations revealed extreme blood Co and Cr levels (587.9 mcgg/L and 20.4 mcgg/L respectively), with normal inflammatory markers. Urgent re-revision surgery to a new ceramic on ceramic bearing hip implant was performed. At surgery we found a catastrophically worn metal head  and substantial soft tissue metallosis. His blood ion levels reduced after re-revision surgery but were sufficient to cause concern regarding potential cobalt cardiotoxicity, and he was therefore referred for cardiac assessment using cardiovascular MR (CMR). Due to the nature of the referral with concerns of metal loading, tissue characterization sequences of the liver were also acquired.Blood Co and Cr levels were very high and fell with revision, Table . All rou°, field of view read/ phase: 400 mm/75 %). In addition, a T2  measurement (FerriScan®) was performed through the middle of the liver in the transverse plane [CMR was performed using a 1.5 Tesla Magnetic Resonance scanner . Cardiac volumes and function were calculated from short-axis steady state free precession (SSFP) cine images. Pre-contrast myocardial and liver T2* maps were acquired using a single breath-hold ECG-gated multi-echo technique to generate eight (heart) and twelve (liver) images  of this, we performed micro-X-ray Fluorescence (μXRF) and micro X-ray Absorption Spectroscopy (μXAS) on beamline I18 at Diamond Light Source  [We present the first description of the use of T2* and R2 MR to non-invasively detect and map liver Co and Cr. Our patient had extremely elevated blood metal levels from a failed hip prosthesis with wear of the Co-Cr head and the highest values seen by their attending surgeons at a large specialist retrieval unit in London. Liver biopsy followed by μXRF and μXAS confirmed Co-Cr debris in liver macrophages, with no other ferromagnetic material deposits found. Serial assessment suggested clearance from the liver was far slower than from the blood.More than one million people globally have MoM hip prostheses and are “at-risk” of Co-Cr release. This causes a high failure rate due to local soft tissue reactions causing pain and pseudotumors. The failure rate of these hips can be up to 40 % by 7 years , and impThis case illustrates that systemic deposition of Co and Cr in the liver can occur in subjects with extreme blood levels of metal secondary to failed hip implants, even without blood markers of hepatic abnormality. The absence of liver enzyme disturbance suggests that this patient tolerated the Co and Cr, at least in the short term. The relationship of liver deposition/sequestration to other organ toxicity  is unknown. In iron loading states the deposition of iron occurs primarily in the liver followed by deposition in other organs including the heart. A similar pattern may be seen in patients with increased levels of blood Co and Cr. The relative proportions of Co and Cr suggest progressive particle processing during the transport from the hip to the liver, although this mechanism remains unknown.T2* and R2 MR are currently routinely used to detect and quantify iron tissue deposition in the heart and liver, and have significantly changed disease outcomes. Iron deposition with T2* MR of the pancreas, pituitary and kidneys is also potentially quantifiable. These techniques could also be repurposed for non-invasive screening of Co-Cr deposition in at-risk patients. To date, only non-specific qualitative abnormalities have been reported on CMR scans in patients with biopsy proven Co cardiomyopathy , 21; theOver one million patients with MoM hip prostheses are at risk of cobalt/ chromium toxicity with potentially devastating complications. The T2* method plays an integral part in the management of patients with iron overload, and this technique may also detect CoCr deposition in the liver as demonstrated by our case. Further work is needed to assess the utility of T2* and R2 MR as a screening tool in at-risk patients with MoM hip prostheses.Written informed consent was obtained from the patient for publication of this case report and any accompanying images.


Measuring the area-at-risk (AAR) allows the assessment of myocardial salvage in reperfused STEMI patients. T2-weighted CMR has been used to quantify the AAR but is hampered by low signal-to-noise ratio and image artifacts. T1 and T2 mapping CMR may improve upon this. We compared T1 and T2 mapping for quantifying the AAR at 3T.CMR imaging at 3T  was performed in 18 STEMI patients within 10 days of PPCI using T2-mapping and T1-mapping by MOLLI . Matched short-axis T1 and T2 maps covering the entire left ventricle were analyzed by 2 experienced investigators using 3 analytical methods : manual segmentation, Otsu, and the 2 standard deviation (2SD) thresholding . Analysis of the T1 and T2 maps using the manual and Otsu techniques yielded similar results for the AAR, whereas the AAR quantified by the 2SD technique was about 7% larger. There was excellent inter-observer variability for T1 and T2 mapping using all 3 analytical techniques (Intraclass Correlation Coefficient>0.98:P<0.001). The Otsu-derived AAR (expressed as a % of the left ventricle [LV] volume) quantified by T1 and T2 mapping were similar . There was excellent correlation , the Rosetrees Trust, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre.