However, individual increases in native T1 time and ECV correlated with increased galectin-3 serum levels . The progression of skin involvement assessed using the Rodnan skin score and a decrease in the diffusing capacity of the lungs were associated with increased GDF-15 values . Conclusions: During the 5-year follow-up, there was no new onset of heart disease observed in patients with SSc. However, in some patients, CMR detected progression of sub-clinical myocardial fibrosis that significantly correlated with elevated galectin-3 levels. GDF-15 values were found to be associated with disease severity progression.Introduction and objectives: Cardiac involvement in systemic sclerosis (SSc) patients affects mortality. Cardiac magnetic resonance (CMR) is capable of detecting structural changes, including diffuse myocardial fibrosis that may develop over time. Our aim was to evaluate myocardial structure and function changes using CMR in patients with SSc without known cardiac disease during a 5-year follow-up and find possible correlations with selected biomarkers. Methods: A total of 25 patients underwent baseline and follow-up CMR examinations according to a pre-specified protocol. Standard biochemistry, five biomarkers , and disease-specific functional parameters enabling the classification of disease severity were also measured. Results: After five years, no patient suffered from manifest heart disease. Mean extracellular volume (ECV) and T1 mapping values did not change significantly ( Systemic sclerosis (SSc) is an immune-mediated rheumatic disease characterized by excessive extracellular matrix deposition, widespread fibrosis of the skin and visceral organs, microvascular injury, and immune system activation . SSc canMyocardial involvement can be demonstrated as a combination of myocardial ischemia and patchy fibrotic deposits, equally distributed throughout the left and right ventricular myocardium, with or without inflammation . MyocardCardiac magnetic resonance imaging (CMR) appears to be a reliable technique for anatomical and functional assessment of the heart, helping clinicians detect and analyze different mechanisms of cardiac involvement, including inflammatory, microvascular, and fibrotic processes . In the Several biomarkers have been studied concerning myocardial involvement. Values of high sensitivity cardiac troponins and N-terminal pro-brain natriuretic peptides (NT-proBNP) are known to be elevated in SSc patients ,11 and hThe published data suggest that the development of myocardial fibrosis is a slow and silent process that can evolve outside the detection limits of standard biochemistry or ECHO ,15,16. TThis prospective study included 25 out of 33 patients with progressive systemic sclerosis who underwent a baseline study examination in 2015 . In shorThe study was approved by the Ethics Committee at the University Hospital in Pilsen. All participants signed informed consent for the study. Each subject underwent all study procedures in one day .Follow-up CMRs were performed using the same MRI scanner used for the baseline examinations. The 3.0 T device  was equipped with a 32-element surface coil for the thorax or a body coil. All sequences were performed during mild breath-holding with ECG synchronization (retrospective ECG gating technique). All measurements were done by an experienced radiologist who performed image analyses at baseline; however, the radiologist was blinded to any previous or current results. The protocol consisted of the following steps: (1) routine TrueFISP (True Fast Imaging with Steady-state Precession) sequence for morphological orientation and left ventricular function assessment in standard long-axis orientations (four-chamber and two-chamber); (2) pre-contrast (native) T1 maps; (3) dynamic (first-pass) perfusion; (4) TrueFISP sequence covering the whole left ventricle in short axis for functional analysis; (5) T1-weighted phase-sensitive inversion recovery (PSIR) sequence for detection of late gadolinium enhancement (LGE) and (6) post-contrast T1-maps. Native and post-contrast T1 maps were performed in three short-axis levels  of the left ventricle. The sequence based on modified look-locker inversion recovery (MOLLI) with single shot TrueFISP was part of the commercially available package MyoMaps . T1 maps sequences were performed in the same levels using a single shot inversion recovery TrueFISP (fast imaging with steady-state free precession) with following parameters: TR 280.56 ms, TE 1.12 ms, echo spacing 2.7 ms, flip angle 35°, SL 8 mm, FOV 360 mm, matrix size 256 × 66%, voxel size 1.4 mm × 1.4 mm × 8 mm, iPAT 2. The native T1 maps were performed using a MOLLI type 5(3)3 sequence. Post-contrast T1 maps used MOLLI type 4(1)3(1) sequence and were performed with a minimal 15 min delay after the contrast agent  was administered intravenously at 0.05 mmol/kg body weight . The T2 Two independent radiologists, blinded to baseline images, performed all measurements in random order. Interobserver and intraobserver agreement of T1 value measurements were excellent using an intraclass correlation coefficient (0.94 for interobserver and 0.96 for intraobserver). T1 values analysis was performed using a region of interest (ROI) that was manually drawn in the intramyocardial part of the interventricular septum and the final T1 value was calculated as a mean of values from all three layers . ROIs were carefully performed and the borders of the myocardium were not included. Regions of LGE were avoided to prevent influencing the final T1 value. The value of the extracellular volume (ECV%) fraction using native and post-contrast myocardial T1 values and hematocrit was calculated according to the following formula: [ECV (%) = (1 − hematocrit) × (1/post-contrast T1 of myocardium − 1/native T1 of myocardium)/1/post-contrast T1 of blood − 1/native T1 of blood) .All patients underwent a follow-up echocardiographic examination according to the baseline ECHO protocol , with th® ST2 Assay kit . Routine biochemical parameters including renal functions were also measured in all subjects and did not change over time.N-terminal pro-brain natriuretic peptide (NT-proBNP) was determined using original analytical kits from Roche  on a Cobas 8000 analyzer. High-sensitivity cardiac troponin I (hsTnI) was measured using the Architect i2000 platform with the STAT High Sensitive Troponin-I assay . Growth/Differentiation Factor-15  and galectin-3  concentrations were determined using ELISA kits on a Nexgen ELISA four reader . Suppression of tumorigenicity2 (sST2) was measured using a Critical Diagnostics PresageThe severity of skin fibrosis was quantified using the modified Rodnan skin score (mRSS). The skin thickness at each of the 17 anatomical sites was classified from 0 to 3; the maximum score was 51. The carbon monoxide diffusing capacity of the lungs (DLCO) was measured using the single-breath method and a body plethysmograph Platinum elite™ .For statistical analysis, SAS software version 9.4  was used. Changes in levels of biomarkers from baseline to the end of the follow-up were evaluated using the paired Wilcoxon test. Differences in biomarkers between groups were tested using the Mann–Whitney U test. The strength of relationships between examined biomarkers was measured using the Pearson correlation. Statistical significance was set at the level of α = 0.05.Our study population consisted of 25 SSc patients aged 55.5 years at baseline (range 26–71); 88% were women. The median duration of the disease was 10.0 years (range 2–40). The majority of patients (84%) suffered from the diffuse form. The median follow-up was 5.2 years (range 4.9–5.3). The proportion of patients using corticosteroids was 64% both at baseline and after 5 years of follow-up, and the use of disease-modifying anti-rheumatic drugs was 52% at baseline and 56% after 5 years of follow-up, which remained similar over time. As expected, the parameters reflecting pulmonary (DLCO) or skin progression (mRSS) of the disease worsened over the five years of follow-up . Howeverp = 0.95) nor extracellular volume (p = 0.073) changed significantly over time. In addition to the parameters listed in Regarding CMR, neither mean values of native T1 relaxation time (p = 0.0078) and GDF15 . Mean levels of hsTnI, NT-proBNP, and galectin-3 remained similar (p = 0.0050) and extracellular volumes , while GDF-15 positively correlated with higher mRSS  and negatively with lower values of DLco . Changes in hsTnI, NT-proBNP, or sST2 were not significantly related to changes in any of the monitored CMR parameters or clinical examinations. Of the tested biomarkers, we observed a significant increase in sST2  or sartan, the serum levels of galectin-3 decreased (Δ −1.31 ± 2.07 ng/mL), while in non-users, the values increased , and a greater decrease in TnI values in the RAAS blocker users compared to non-users . No significant effect of RAAS blockade on CMR or other biochemical parameters was observed.Furthermore, there was a smaller increase in sST2 in the RAAS blocker users compared to non-users  mean values of native T1 time and ECV detected by CMR in patients with systemic sclerosis did not change significantly during the 5-year follow up, but there are patients with CMR signs of progression or regression of the sub-clinical myocardial deterioration. These changes were significantly correlated with the dynamics of galectin-3. (2) The GDF-15 values were significantly correlated with the change of clinical scores of pulmonary or skin progression of the disease, thus potentially serving as a biomarker of the disease activity. (3) RAAS inhibitors did not show an effect on CMR parameters in patients without clinical signs of myocardial dysfunction but, when compared to RAAS non-users, were associated with either a decrease or a smaller increase of galectin-3, sST2, and hsTnI.Concerning the CMR results in our group of patients, the baseline values of native T1 and ECV were already increased compared to healthy controls, thus confirming the presence of sub-clinical myocardial involvement . Other sConcerning the dynamics of selected biomarkers, galectin-3 values well reflected the changes in native T1 relaxation time and ECV. This biomarker is a multifunctional protein implicated in various biological processes, including fibrosis, angiogenesis, cell differentiation and apoptosis, and immune activation, all of which are associated with the development of systemic sclerosis . GalectiWe observed worsening of skin thickness and a decrease in pulmonary diffusing capacity over time in our patients. Contrary to previous studies ,21,22, oAnother marker of fibrosis, the sST2, serves as a decoy receptor for interleukin-33 and negatively regulates anti-fibrotic pathways in the myocardium. It can induce fibrosis of pulmonary, hepatic, skin, renal, and pancreatic tissue . Our stuRecent papers demonstrated that RAAS pathways interact with the transformation of growth factor-beta to enhance or retard fibrotic processes in multiple organs. Inhibition of the classic RAAS pathway is a promising approach . In the The study has specific limitations: (1) It is a single-center study with only a small number of patients and a relatively short follow-up. Due to the rare incidence of SSc and the slow disease progression, long-term follow-up of patients is very difficult for logistic reasons. (2) We did not evaluate the prognostic impact of our results; therefore, postulations of clinical recommendations regarding the frequency of CMRs or collection of biomarkers cannot be determined. (3) We did not perform any global peak systolic strain (GLPS) measurements during the follow-up ECHO examination due to logistic reasons and time constraints. (4) The selection of biomarkers was based on their availability in our institution and limited by financial constraints. (5) For disease severity assessment, we chose the most relevant and the most frequently disease-affected organs to follow and detect progression of the disease: skin (mRSS) and lungs (DLco). Although routine biochemistry values, capable of detecting renal or hepatic deterioration, remained consistent over time, no other findings from imaging or specialized SSc examinations were included in the study. Nevertheless, the majority of patients had a diffuse form of SSc, which was largely inclined to cause skin and pulmonary changes.Cardiac magnetic resonance was able to detect subtle diffuse myocardial fibrosis in asymptomatic SSc patients during the follow-up. Deterioration of CMR parameters associated with fibrosis development correlated with an increase in serum galectin-3 levels. Skin impairment and a decrease in diffuse lung capacity were related to an increase in GDF-15. In an observation analysis, concomitant treatment with RAAS inhibitors best correlated with galectin-3 levels but also positively affected hsTnI and sST2 levels, suggesting that RAAS medication is involved in the modulation of the fibrotic process. Whether galectin-3 is a suitable candidate biomarker for detecting myocardial damage in SSc patients requires further investigations.


During the last decade, studies have raised awareness of the crucial role that the right ventricle plays in various clinical settings, including diseases primarily linked to the left ventricle. The assessment of right ventricular performance with conventional echocardiography is challenging. Novel echocardiographic techniques improve the functional assessment of the right ventricle and they show good correlation with the gold standard represented by cardiac magnetic resonance. This review summarizes the traditional and innovative echocardiographic techniques used in the functional assessment of the right ventricle, focusing on the role of right ventricular dysfunction in heart failure with reduced ejection fraction and providing a perspective on recent evidence from literature. Heart failure (HF) remains a rising public health concern, with an estimated prevalence of almost 38 million individuals worldwide ,2. The tMost of the previous research demonstrated the high prognostic value of left ventricular (LV) dysfunction , while tIn the era of multi-modality imaging, cardiac magnetic resonance (CMR) imaging remains the gold standard for RV quantification, despite the technical innovations in the field of echocardiography ,11,12,13However, the high cost and low availability of CMR hamper its unrestricted use on all patients with HF. By comparison, echocardiography is a bedside, widely available tool, and novel echocardiographic techniques such as myocardial strain imaging and three-dimensional (3D) echocardiography allow an accurate RV quantification that has been validated against (CMR) ,19.The aim of this review is to summarize the role of both conventional and novel echocardiographic parameters of RV function in patients with HF and reduced EF (HFrEF), while focusing on recent research.The echocardiographic assessment of the RV faces several challenges: (1) the complex RV geometry; (2) its position behind the sternum; (3) the cumbersome endocardial tracing due to prominent trabeculations; and (4) its dependence on hemodynamic load and the RV–LV interdependence. In fact, some authors suggest that up to 20–40% of RV stroke volume results from the contraction of the LV . The RV There is no ideal echocardiographic parameter for RV quantification , hence aMost of these parameters  assess only the longitudinal RV function, while others (such as FAC) account for both the longitudinal and radial components of the RV contraction. However, most of the RV functional parameters neglect the contribution of the outflow tract contraction, potentially leading to an underestimation or overestimation of the global RV systolic performance . This liTAPSE is a highly reproducible, easy obtainable parameter  of RV loLoad-dependency means that TAPSE will change with different loading conditions without actual changes in myocardial contractility. TAPSE decreases with increased pulmonary vascular resistance , but it ≤ 14 mm predict unfavorable outcomes in patients with HF, irrespective of its ischemic or non-ischemic etiology [Ghio et al. showed that TAPSE ≤ 14 mm is an independent predictor of death or emergency cardiac transplantation in patients with congestive HF . Similaretiology .The systolic velocity of the tricuspid lateral annulus is measured in the apical four-chamber view by placing the tissue Doppler marker on the lateral tricuspid annulus ,30. SimiStudies found that decreased TDI systolic velocity of the tricuspid annulus is an independent predictor of either cardiac death ,40 or caThe RV myocardial performance index, also known as the right Tei index, is a measure of both systolic and diastolic RV function. It is a unitless parameter, calculated by dividing the total isovolumic time (isovolumic contraction plus isovolumic relaxation) by the ejection time (ET) . SystoliThe prognostic value of the pulsed-Doppler-derived RV MPI was assessed in a cohort of HFrEF patients, who were prospectively followed for 5 years for a combined endpoint of cardiac death and readmissions for HF. The authors found that an RV MPI > 0.38 was an independent predictor of adverse outcomes . In a stFAC is a 2D measure of RV systolic function obtained from the RV-focused apical four chamber view by manually tracing the endocardial border of the RV in end-diastole and end-systole. It is calculated as: (end-diastolic area − end-systolic area)/end-diastolic area × 100% . The RV-Zornoff et al. found that RV FAC is an independent predictor of total mortality, cardiovascular mortality, and development of HF in patients with LV systolic dysfunction following a myocardial infarction (MI), with each 5% decrease in FAC being associated with a 16% increase in odds of cardiovascular mortality . SimilarA small retrospective study found that RV FAC < 26.7% is predictive of death or LV assist device implantation in patients with DCM, providing better prognostic value than TAPSE and S’ wave velocity . SimilarMyocardial acceleration during isovolumic contraction is usually obtained using TDI at the lateral tricuspid annulus in the apical four-chamber view. It is calculated as the peak myocardial velocity during isovolumic contraction divided by the time needed to reach this velocity . While iSpeckle-tracking echocardiography is a non-invasive, innovative technique that analyzes the segmental myocardial deformation along different planes through the displacement of speckles . OriginaSTE assesses the deformation of myocardial speckles in two dimensions along the myocardial wall direction, thus being less confounded by the motion of the heart  and relaMartin et al. analyzed which of the RV strain parameters was a better predictor of hospitalizations for HF in patients with left heart disease. They showed that the RV global longitudinal strain independently predicts readmissions, providing additional prognostic information to that obtained by TAPSE . SimilarCarluccio et al. proved the superiority of RV strain over TAPSE, by following 200 patients with HFrEF but preserved TAPSE (>16 mm) for a composite endpoint of death and HF rehospitalization. The authors found that the RVFW longitudinal strain was an independent predictor of adverse outcome, with a cutoff value for endpoint prediction of −15.3% . In a reSeveral studies discovered independent prognostic roles for both global RV strain and RVFW strain in HFrEF. Cameli et al. found that in patients with advanced systolic HF referred for cardiac transplantation, both global and free-wall RV strain are independent predictors of an adverse outcomes , with stronger predictive power than other conventional parameters, including parameters of LV function . Another3D echocardiography overcomes the geometric assumptions used in 2D echocardiography. As such, it is particularly useful for the evaluation of the RV, which—due to its complex anatomy—cannot be comprehensively assessed with 2D measurements only. 3D echocardiography integrates both the longitudinal and radial components of RV contraction  and, unlIn a population-based cohort study that enrolled 1004 elderly people, Nochioka et al. used 2D and 3D echocardiography to analyze the prevalence and prognostic role of RV dysfunction in HF. Among patients with no HF at baseline, 3D RVEF proved to be an independent predictor of death or incident HF: each 5% decrease in 3D RVEF was associated with a 20% increase in the hazard of death or hospitalization for HF, independent of LVEF .Magunia et al. found that 3D RVEF is an independent predictor of post-operative RV failure in LVAD recipients , which iA recent retrospective study of Surkova et al. evaluated the relative importance of different combinations of reduced and preserved 3D LVEF and 3D RVEF in predicting mortality in patients with different cardiac diseases. Reduced 3D RVEF, but not LVEF, was a strong and independent predictor of both all-cause mortality and cardiovascular mortality . Moreove3D STE is a novel imaging technique that evaluates myocardial deformation using 3D full-volume data sets. It is currently limited to research and not available for routine use, but it appears to be a promising tool for the assessment of the complex RV myocardial motion . A studyThe interaction between the RV and the pulmonary circulation unit is reflected in the RV–pulmonary artery coupling (RVPAC), which is usually assessed with right heart catheterization. This parameter reflects the adaptation of the RV to afterload, and it is calculated from invasive pressure–volume loops as the ratio of RV end-systolic elastance to pulmonary artery elastance . SeveralAs innovative echocardiographic techniques become part of the comprehensive assessment of RV performance, some researchers used 2D RV longitudinal strain or 3D RVEF for the non-invasive estimation of RVPAC, which was calculated as either RV strain/PASP ratio ,90 or asFractional shortening of the RVOT (RVOT-FS) is an index of RV performance that is obtained using M-mode echocardiography in the parasternal short axis window at the level of the aortic root. It is calculated as the percentage change in RVOT diameter at end-systole compared to end-diastole . SeveralThe above-mentioned studies evaluating the prognostic role of RV dysfunction in HF are summarized in Artificial intelligence (AI) techniques, such as machine learning (ML) and deep learning, can improve the diagnostic accuracy of echocardiography, by providing fully automated image analysis and thus potentially reducing human error . So far,The RV plays a crucial role in various clinical settings. RV dysfunction is a strong independent predictor of mortality and adverse outcomes not only in diseases of the right heart or pulmonary vascular bed but also in diseases primarily involving the LV. In the particular setting of DCM, RV FAC appears to be a better outcome predictor than other conventional RV parameters, while RVFW strain has a higher prognostic value than global RV strain. There is no perfect single parameter that comprehensively evaluates RV performance. Integrating novel techniques in the RV echocardiographic assessment allows a better evaluation and an enhanced risk stratification for patients with HF, thus improving therapeutic strategies and potentially leading to an improved outcome.


Hypertrophic cardiomyopathy (HCM) is a common disease that can be acquired due to chronic hypertension or via autosomal dominant inheritance. Several patterns of HCM have been described, of which a rare variant is apical hypertrophic cardiomyopathy (AHCM). Atrial thrombus is a well-recognized complication of HCM especially in the setting of atrial fibrillation (AF). However, left ventricular thrombus (LVT) formation is not nearly as prevalent as atrial thrombus. Here is a case of a 57-year-old Hispanic female with AHCM who presented with significant unintentional weight loss and unexplained anemia and was subsequently found to have a large left intraventricular mass suspicious for a tumor vs. ventricular thrombus. The diagnosis was complicated due to the large size of the mass and presenting symptoms suspicious of malignancy.  The development of a left ventricular thrombus (LVT) is a well-known complication in various cardiac conditions with the highest rate observed in acute anterior myocardial infarction and severe left ventricular (LV) systolic dysfunction. In a study of 949 eligible patients, the prevalence of LVT seen by transthoracic echocardiography (TTE) was 8.85% with the highest prevalence of 39.29% (33/84) observed in patients with dilated cardiomyopathy, followed by myocardial infarction with a prevalence of 29.76% (25/84) . AHCM isMalignancy is also an important consideration in the differential diagnosis of LV masses, especially when presenting with symptoms including fevers, night sweats, cachexia, and weight loss. Primary cardiac tumors are rare compared to secondary tumors. In general, cardiac metastases are considered to be rare; however, when sought for, the incidence seems to be not as low as expected, ranging from 2.3% to 18.3% [The patient is a 57-year-old Hispanic female with hypertension, type 2 diabetes mellitus, hyperlipidemia, AHCM, and grade 3 diastolic dysfunction with preserved ejection fraction at 60% who presented to the emergency department (ED) complaining of bilateral lower extremity edema and lightheadedness since a day. Her history was significant for 76-pound weight loss over the past year. Her vitals were normal on presentation. Her significant laboratory findings were hemoglobin 9.8 g/dL, brain natriuretic peptide 1119 pg/mL, albumin 2.9 g/dL, blood urea nitrogen (BUN) 26 mg/dL, and creatinine 1.14 mg/dL. The patient was in acute heart failure exacerbation and was started on IV diuretics. A TTE was ordered to evaluate the degree of heart failure, which revealed an incidental large partially mobile echo density extending from the mid-lateral wall to the apex and covering approximately one-third of the LV cavity measuring 4.8 cm x 3.4 cm as shown in Figures The patient underwent further diagnostic imaging with a transesophageal echocardiogram (TEE) and CT of the chest, abdomen, and pelvis. TEE revealed a very large partially mobile mass in the LV that was either a tumor/mass or a thrombus as shown in Video Hypertrophic cardiomyopathy has many known morphological variants including asymmetrical or diffuse that may be obstructing or non-obstructing. Additionally, a rare variant known as AHCM is found in about 3%-11% of the North American population . AHCM maLeft ventricular thrombus is a potentially fatal complication that is implicated in LV dysfunction and seen after acute myocardial infarction, however, with advancements in percutaneous coronary interventions and medical goal-directed therapies, the incidence of LVT has significantly decreased. It has now become apparent that LVT may be implicated in other disease processes, such as heart failure, HCM, and AHCM. When evaluating an LV mass, transesophageal echocardiography has been broadly accepted as the primary screening modality. Other imaging modalities such as cardiac CT and cardiac MRI can provide additional information when echocardiography cannot delineate the extent of cardiac wall involvement .In one study of patients identified by echocardiograms as having LVT, 68.5% had heart failure as a precipitating factor with 38% being de novo heart failure diagnosis with inadequate guideline-directed medical therapy with 86% having EF less than or equal to 40%, 8% having EF between 41% and 49%, and 5% having EF greater than or equal to 50% . The secAlthough potential causes of LVT are well understood, namely pathologies that reduce ventricular contractility, cause local myocyte injury and hypercoagulable states, the pharmacological interventions are far less understood. In the GISSI-3 trial, patients who underwent treatment for MI with beta-blockers did not show a significant reduction in the incidence of LVT formation as compared with those who did not receive treatment . CurrentRegardless of etiology, current treatment strategies for LVT include oral anticoagulation  or warfarin. Current recommendations from the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) state that warfarin is a reasonable therapy of choice for patients with ST-elevation MI as well as asymptomatic LVT, however, as per the American College of Cardiology/American Heart Association (ACC/AHA) guidelines there is no definite duration for treatment . WhereasAlthough the current treatment for LVT is not completely agreed upon, anticoagulation for three to six months after identification of an LVT is reasonable. After the treatment period is finished, repeat imaging should be considered to determine if the thrombus had resolved. If no thrombus is identified anticoagulation should be stopped. If a new thrombus appears on echocardiography, continued anticoagulation should be administered. The difficult decision lies regarding whether an LV mass is still identified on repeat imaging. Differentiating between residual thrombus and a new thrombus may be difficult to determine from echocardiography findings, therefore, it would be reasonable to assess the mass with cardiac MRI (CMRI) as that would help differentiate acute vs. old thrombus. In that acute thrombus would show high signal intensity on T1 and T2 weighted imaging while older thrombus shows low signal and may show evidence of calcification . From thIdentification of LV mass requires a broad differential from thrombus formation to malignant and benign cancers. Understanding risk factors, precipitating events and imaging findings help aid in differentiating the diagnosis. Once an LVT is identified, guidelines recommend anticoagulation using warfarin, with a reasonable goal of three to six months. Further anticoagulation should be based on clinical presentation while balancing the risks and benefits. We present a case of a de novo LVT identified on imaging that was completely resolved after three months of anticoagulation with warfarin without thromboembolic complications.


Background: Maternal gestational weight gain (GWG) may be associated with cardiovascular diseases in the offspring from childhood to adulthood. We aimed to investigate the association between maternal GWG and the left ventricle (LV) geometry and function in the offspring, and explore the influence of the intrauterine environment on early childhood cardiac change.Methods: Data of 981 mother-offspring pairs from the Shanghai Birth Cohort was used. Maternal pre-pregnancy weight and height, weight in the first trimester (≤ 12 weeks), and before delivery were measured. The echocardiography, blood pressure, and anthropometry assessment were evaluated in the offspring at 4 years of age.Results: Interventricular septal thickness during diastole had a significantly positive correlation with total GWG . In the second and third trimesters, LV mass index , interventricular septal thickness in systole , and in diastole  were positively associated with GWG. The risks of eccentric  and concentric hypertrophy  increased with the elevation of maternal GWG.Conclusions: This study suggested that the excessive maternal GWG was associated with the thickening of the interventricular septum in the offspring, especially during the second and third trimesters. Excessive GWG in the second and third trimesters was a risk factor for LV eccentric and concentric hypertrophy in the offspring. Left ventricle (LV) geometry and function are important factors that influence cardiac remodeling, and are also determinants of cardiovascular events in adulthood , 2. LV gThe LV geometry and functional changes are often evaluated in adults and adolescents. Morphologic changes in the LV could progress due to cumulative exposures from an early age, which could impair LV function ultimately in later life . HoweverApart from early influences during childhood, the LV geometry and function could also be affected by various maternal factors, such as obesity, gestational hypertension, and diabetes –9. GestaBased on the Shanghai Birth Cohort (SBC), we aimed to investigate the association of maternal GWG with offspring LV geometry and function at 4 years of age to explore the influence of the intrauterine environment on early childhood cardiac geometry and function.The SBC is an ongoing prospective cohort study conducted in six collaborating hospitals in Shanghai, China. Volunteer couples were recruited during preconception care or in early pregnancy from 2013 to 2016, and the mother-fetus pairs were followed from preconception or early pregnancy to the end of the gestation. A detailed description of the cohort has been provided elsewhere (2), normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥ 30.0 kg/m2) , reproductive characteristics , lifestyle factors , and history of gestational hypertension or diabetes were collected through structured questionnaires and extraction of the inpatient history of the pregnant women from medical records. Pre-pregnancy weight and height, weight in the first trimester (≤ 12 weeks), and weight before delivery were measured at each clinical visit. Maternal pre-pregnancy body mass index (BMI), total GWG, GWG in the first (≤ 12 weeks) or second and third trimesters (>12 weeks) were calculated. Based on the World Health Organization (WHO) criteria, the pre-pregnancy BMI was categorized as underweight (< 18.5 kg/m0 kg/m2) .The height and weight of the offspring were measured according to the standard protocol. BMI was calculated in the 4-year-old children. Blood pressure (BP) and heart rate (HR) of the 4-year-old children were assessed by one trained staff while they were supine using the OMRAN HBP-1300 automatic BP device  on the left arm at heart level and with the appropriate cuff size for arm circumference. Three measurements were taken at 5-min intervals. The mean of the measurements was used in all analyses.Transthoracic echocardiography examinations were performed for the children according to the American and European guidelines  by train2.7  was calculated by the sum of the thickness of the LV posterior wall in diastole (LVPWd) and interventricular septal thickness in diastole (IVSd), then divided by the internal LV diameter in diastole (LVDd) . LV mass2.7 .Pulse wave Doppler was used to measure the mitral early diastolic flow velocity (E), late diastolic flow velocity (A) to calculate the E/A ratio. The Doppler time intervals, including the ejection time (ET), isovolumic contraction time (ICT), and isovolumic relaxation time (IRT), were obtained at the mitral inflow and LV outflow tracts to calculate the Tei index, with the formula: Tei index = (ICT + IRT)/ET. These indices were used to assess the diastolic function of the LV.For 2D speckle-tracking analysis, 2D images of 3–5 cardiac cycles were collected and analyzed with the commercial Qlab version 10.5 software ] at a frame rate of ≥ 60/s. Peak longitudinal strain was measured in the apical four, two, and three-chamber and global peak longitudinal strain (GLS) was calculated using the strain value of each segment in LV.2.7, RWT = 0.27 in girls and LVMI = 33.76 g/m2.7, RWT = 0.27 in boys represented the sex-specific 95th percentiles in the cohort. Four groups were constructed for LV geometry patterns: (1) LVMI <33.24 g/m2.7 for girls and <33.76 g/m2.7 for boys, and RWT < 0.27 was classified as normal left ventricular geometry; (2) normal LVMI with increased RWT (>0.27) was classified as concentric remodeling; (3) increased LVMI , and normal RWT (<0.27) was defined as eccentric hypertrophy; and (4) increase in both variables was identified as concentric hypertrophy.The LV geometry patterns were defined using the LVMI and RWT according to Ganau and colleagues' descriptions . There wAll the examinations were performed by a single experienced operator. Both the sonographers and the observers were blinded to the participants' details.Linear regression models were used to investigate the associations between maternal GWG and offspring LV geometry and function changes. Five sets of models were constructed: the basic model was adjusted for none of the maternal factors or offspring factors. Model 1 was adjusted for maternal factors, including age at delivery, race, educational level, alcoholic drink intake history, exposure to passive smoke, pre-pregnancy BMI, gestational diabetes mellitus (GDM), and gestational hypertension or pre-eclampsia. Model 2 was adjusted additionally for gestational age, sex of offspring, delivery mode, and parity. Model 3 was adjusted additionally for BMI at 4 years of age. Model 4 was adjusted additionally for BP at 4 years of age. The GWG was divided into three groups according to the gestational trimesters as the total, first trimester, and second and third trimesters.To further eliminate the effect of pre-pregnancy BMI on the LV geometry and function change in offspring, the study population was stratified into three groups  according to the WHO criteria . Linear To test the risk of LV geometry pattern changes caused by an increase in GWG, including eccentric hypertrophy, concentric hypertrophy, and remodeling, multiple logistic regression analysis was performed in different groups, and odds ratio (OR) was calculated.Statistical analysis was carried out using the SPSS 19.0 software program . All tests were two-sided with a significance level of 0.05.The baseline characteristics of the study participants are presented in In the basic model , almost The gestational time was divided into the total, first trimester (≤ 12 weeks), and second and third trimesters (>12 weeks). In the basic model, LVMI , LVDd , IVSd , and IVSs  had a positive association with the second and third trimester GWG. GWG in the first trimester had no significant correlation with any structural and functional indices. After adjusting for maternal and offspring factors, LVMI , IVSs , and IVSd  continued to be positively associated with GWG in all models during the second and third trimesters. The RWT and the LV function indices had no significant correlation with GWG in any trimester.GWG was strongly related to pre-pregnancy BMI . Taking The risk of four types of LV geometry change patterns in offspring with maternal GWG in different trimesters is presented in In this prospective cohort study, we found that greater GWG was associated with LV morphologic changes in the offspring as early as 4 years of age, especially the thickening of IVS. Greater GWG during the second and third trimesters was an independent risk factor for LV eccentric and concentric hypertrophy in the offspring.Cardiac structural changes usually occur before global functional alteration, which is often evaluated during adulthood and adolescence. However, morphologic changes in the LV could progress due to accumulated exposures during childhood, which could impair the LV function ultimately in later life . In our LV wall thickening is the manifestation of myocardial hypertrophy . The thiWe focused on the LV geometry and functional patterns in a birth cohort comprising randomly selected children. These LV structural changes, including thickening of the IVS, may be physiologic during early childhood since the pathological changes usually occur in adolescents , 36 and Greater GWG was associated with many adverse maternal and offspring outcomes from birth to adulthood. Greater maternal pre-pregnancy weight and GWG were associated with higher systolic blood pressure , adverseThere are several possible explanations for the mechanisms responsible for a greater GWG increasing the risk of LVH. Greater maternal GWG is an abnormal metabolic state, which modifies the intrauterine environment, thereby influencing placental function and fetal programming of the cardiovascular system, which, in turn, affects fetal heart development. A mother with excessive weight gain or obesity has a suboptimal uterine nutritional climate, which may disrupt the inflammatory and hormone metabolic homeostasis of the mother, including insulin resistance, increased level of leptin, lipid, and pro-inflammatory cytokines. These metabolic disorders may change the placental hemodynamics causing placental vascular insufficiency, increased lipogenesis, infarction, hypoxia, and inflammatory activation . These mEarly screening of LV geometry and function by echocardiography at 4 years of age without the administration of any sedative agents was feasible. Thus, this age may be a suitable time for early screening. Furthermore, early screening of LV structural changes should be recommended in the offspring of mothers who had excessive weight gain during pregnancy, and emphasize the need for additional monitoring and weight management during the second and third trimesters.To our knowledge, this study was the largest prospective birth cohort study that assessed LV geometry and function using detailed echocardiography during early childhood in China. Furthermore, previous research on the association between maternal and offspring factors associated with LV geometry usually focused on maternal obesity  and wereOur study has several limitations. First, cardiac magnetic resonance imaging is the gold standard to evaluate LV geometry. However, this procedure requires the administration of sedatives in young children. Therefore, in our study, we opted for echocardiography as a more suitable modality for children aged 4 years. Second, data on maternal weight during the second trimester were not available in the medical records, which may need a more detailed investigation in future studies. Third, there was an unequal representation of the populations enrolled in our study regarding the different degrees of GWG and pre-pregnancy BMI, which may have influenced the results of the subgroup analysis.Excessive GWG, especially during the second and third trimesters, was associated with increased thickening of the IVS. Thus, excessive GWG during the second and third trimesters is a risk factor for LV eccentric and concentric hypertrophy at 4 years of age in the offspring. Our results provide evidence supporting the early screening of LV geometry and function during early childhood, and emphasize the need for additional monitoring and weight management of pregnant mothers during the second and third trimesters.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the research ethics boards of Shanghai Xinhua Hospital . Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.JW, BD, and YW drafted and revised the manuscript. JW, BD, YW, ZL, YW, SC, and KS contributed to the conception and design of the work. JW, BD, YW, ZL, and YY contributed to the acquisition of data. JW, BD, YW, QC, XZ, and ZL contributed to the analysis or interpretation of the data. YW, SC, and KS critically revised the manuscript. All authors gave their final approval and agreed to be accountable for all aspects of this work ensuring its integrity and accuracy.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


One way to prevent cement from ending up in landfills after its shelf life is to regain its activity and reuse it as a binder. As has been discovered, milling by planetary ball mill is not effective. Grinding by collision is considered a more efficient way to refine brittle material and, in the case of cement, to regain its activity. There has been considerable research regarding the partial replacement of cement using disintegrated cement in mortar or concrete in the past few decades. This article determines and compares the creep and shrinkage properties of cement mortar specimens made from old disintegrated, old non-disintegrated, and new non-disintegrated Portland cement. The tests show that the creep strains for old disintegrated and old non-disintegrated cement mortars are close, within a 2% margin of each other. However, the creep strains for new non-disintegrated cement mortar are 30% lower. Shrinkage for old disintegrated and non-disintegrated cement mortar is 20% lower than for new non-disintegrated cement mortar. The research shows that disintegration is a viable procedure to make old cement suitable for structural application from a long-term property standpoint. Additionally, it increases cement mortar compressive strength by 49% if the cement is disintegrated together with sand. In 2020, it was expected that global cement production would reach 5.9 billion tons, and with that would come more than 4.8 billion tons of CO2 [There has been a significant amount of research and industrial development in the material processing field to achieve the construction components’ longevity, reduce resource consumption and pollution caused by new material production, and reduce waste management costs . These as of CO2 ,4.One way to refine and make used or old materials into fine powders is to use mills. Traditionally ball and planetary ball mills are used. However, these mills have weaknesses; for example, there is extensive wear of grinding parts of the mills, as the materials are exposed to intense heat, etc. Grinding by collision is considered a more effective way to refine brittle materials and an alternative for the mills that produce mineral supplements for construction mixtures. This method is referred to as disintegrator technology, where the material is milled by highly effective high-speed and high-intensity impact in contrast to low-speed impact abrasion . MillingCreep and shrinkage are considered to be the main long-term properties that affect such human-made materials as concrete. Most of the creep and shrinkage develops in the first decade after construction. Afterward, developed strains are not expected to impact the structural performance significantly ,9,10,11.Many factors affect the nature of creep in concrete. The main factors are mixture proportions, curing age, environmental temperature, relative humidity, and applied stress level .Shrinkage is a decrease in volume of cementitious material that occurs without external loads. Shrinkage and also drying shrinkage are factors that influence long-term strains. It has been assumed that in normal-strength concrete, the entire shrinkage strain is from drying shrinkage, and any contribution from autogenous shrinkage can be disregarded . It has Various testing codes and recommendations that are available for creep and shrinkage tests, such as RILEM TC 107, ASTM C512/C512M-10, and ASTM C157/C157M, state the conditions that have to be fulfilled for creep and shrinkage tests ,21,22. AThis research aims to continue research in the field of disintegration product application carried out by Bumanis G., Dvorak K., and others ,24,25,26For testing purposes, three cement composite mixes based on Aalborg white Portland cement were prepared. One group of specimens was new cement with sand that had not been subjected to grinding/activation with the disintegrator. Another was old cement with sand that had not been subjected to disintegration, and the last one was old cement with sand that had been subjected to disintegration. The old Aalborg cement had been stored in the laboratory for ten years. After those ten years, it had hydrated on the surface due to packaging and relative humidity changes in the room. The state of the new and old cement is shown in A disintegrated sand and cement mix was prepared in a DESI-16C disintegrator. Before the dry material was loaded into the disintegrator, the cement was sifted out through a sieve with 2 mm holes. Afterward, the cement and sand were mixed so that by the time they went through the disintegrator, they mixed even better, promoting finer milling of the cement grain. The linear impact speed in the disintegrator was 100 m/s. The disintegration process is shown in The mix differences between the disintegrated old cement with sand and non-disintegrated old cement with sand are visible in After the disintegration process, the dry samples of each mix were XRD tested and mixes of disintegrated and non-disintegrated compounds were made.The X-ray diffraction analyses were performed with the help of Rigaku Ultima + X-ray diffractometry equipment, which uses copper cathode radiation. The scanning speed of the sample was 4 degrees/min. The voltage was 40 kV, current −5 mA, 2θ scanning angle range from 5–60°. Data processing software (Software) Jade MDI 9 and electronic ICDD databases  were used to identify and qualitatively analyse the test substance, thus comparing the obtained data with the database file.The mix proportions are shown in The mixes were poured into cylindrical moulds with dimensions Ø 46 × 250 mm according to RILEM TC 107. For testing purposes, more than thirty cylindrical moulds were prepared and filled. Specimens were unmoulded 24 h after they were poured.When the cylinders were unmoulded, they were Ø 46 × 250 mm as the moulds were. At 1 day after unmoulding, specimens were cut and ground according to RILEM TC 107 recommendation requirements for long-term testing in compression; this is a diameter to height ratio of 1/4 . For thiWhen specimens reached 7 days of age, they were prepared for creep and shrinkage tests, and their compressive strength was determined. The compressive strength was determined using a compression machine with an accuracy of ± 0.01 MPa and loading rate of 0.7 MPa/s. The specimens meant for long-term tests had six aluminium plates (10 × 15 mm) glued on. The plates were glued so that deformation gauges had a proper grip on the specimens and could obtain correct readings. Prepared creep and shrinkage specimens are shown in Simultaneously with long-term specimen moulding, cases for semi-adiabatic calorimetry tests were also poured. This test was undertaken to verify that disintegration does activate cement that has been stored beyond its shelf life. In each container, 0.33 L of each mix was poured. The mix container holder was lined with insulation, and mix containers were placed inside. Afterward, the insulation material was also positioned above the containers. Temperature probes were placed in each of the mortar containers, and the hydration temperature was measured. Temperature readings were taken every 60 s, and the tests lasted for 40 h. The test setup is shown in The prepared cylindrical specimens were tested in creep lever test stands, shown in Specimens in compression were loaded with 20% of the compressive strength value. All creep specimens were loaded in the linear strain state in the specimen-specific stress state .Simultaneously with creep testing, shrinkage measurements were also carried out. The shrinkage specimens were placed alongside the creep specimens, but they were not subjected to load. The shrinkage strain readings were registered at the same time as the creep readings.The creep and shrinkage tests were carried out in a controlled environment with a temperature of 21 ± 1 °C and relative humidity of 20 ± 3%.After the disintegration process for each mix, a PSA test was done to determine the particle size of the compositions.As is apparent in X-ray diffractograms of old disintegrated, old non-disintegrated, and new non-disintegrated cement and quartz sand mixtures . After disintegration the intensity of alite increased. This could be explained by an increase in the specific surface area and activity of the cement mineral as a result of the disintegration process.As the XRD was performed for solid raw compositions, relatively high intensity peaks of crystalline SiOPSA and XRD tests for the tested sample dry mixes were undertaken within 12 h after cement composite mix disintegration.At the beginning of testing, a semi-adiabatic calorimetry test was undertaken. As a result, The curves show that the disintegration effect on hydration temperature development was not significant, and it seems that the activation effect was not noticeable. In contrast to the new cement, the old one had a 25% lower hydration temperature, which means that the old cement was 25% less active. The disintegrated mix had less than a 1% difference in hydration temperature from a non-disintegrated mix. That leads to thinking that one disintegration cycle did not significantly activate the old cement. Before the creep and shrinkage tests, compressive strength values were determined. The compressive strength test was carried out for specimens at the age of 7 days. Specimens were loaded at a rate of 0.6 ± 0.2 MPa/s. The results of compressive strength tests are compiled in As is apparent from the compressive strength values in Compressive strength results on day 7  correspoAccording to these strength values, the creep specimens were loaded with 20% compressive strength for testing purposes. The long-term tests were carried out for 62 days.As is visible, the shrinkage strains were significantly smaller than the total strains from loaded specimens. The total strain readings contain shrinkage as well. This way, the results are more reliable if creep specimens were not wrapped in water evaporation restraining materials or coated with some other solution that could interact and change the compression’s raw material properties. As the shrinkage specimens were kept in the same environment, it is a matter of taking out of the full strain shrinkage strain, and the raw creep strains are obtained, as shown in Additionally, it becomes apparent that shrinkage specimens did not achieve their inner humidity balance with the relative humidity in the laboratory. The strains kept on rising throughout the testing time.From Specific creep is calculated by dividing strains with applied stress:The actual creep properties of the three tested mortars show when the stress influence is taken out from the strains. In The currently conducted research on creep and shrinkage of concrete materials concerns the use of re-activated old cement to produce concrete mortars. The results show the possibility of using disintegration as a process to improve raw material properties and regain properties of old materials to be used as raw materials once again. Additionally, the use of concrete aggregates from construction and demolition waste to produce new cement mortars correlates with this claim. Previous research has determined that the disintegration of sand does increase material activity and improves mortar compressive strength. Additionally, it has been noticed that partial replacement with recycled aggregate and the addition of shrinkage-reducing admixtures have a positive effect on the mechanical properties and change the tendency of creep kinetics . In addiAn interesting future development of the research carried out in this article would be the use and property assessment of recycled concrete aggregates and old disintegrated cement in building materials or elements of transport infrastructure. Combining these two methods would bring measurable economic and environmental benefits.Disintegration does not show activity regeneration in old cement. There is a less than 1% difference in the hydration temperatures of non-disintegrated old and disintegrated old cement mortars and these are 25.4% lower than that of non-disintegrated new cement mortar. This further confirms that one cycle of collision milling does not affect the chemical composition of old cement.Disintegrated old cement mortar shows a 31% higher compressive strength than non-disintegrated new cement mortar whereas non-disintegrated old cement mortar shows an 18% lower compressive strength than non-disintegrated new cement mortar.Shrinkage strain readings show 21.8% and 17.5% larger strains to non-disintegrated new cement mortar and old non-disintegrated cement mortar than disintegrated old cement mortar. It means that shrinkage can be reduced by having finer base material and therefore better packing in the mould. The hydration temperature in this case does not have a significant role.New non-disintegrated cement mortar shows a vastly lower amount of creep strain than disintegrated old and non-disintegrated cement mortar; 26% and 26.1% less, correspondingly. However, when the stress impact to strains is taken out, or, in other words, specific creep is calculated, the most significant reduction in specific creep value is to that of old disintegrated cement mortar, with 7% and 51% increases in specific creep in new non-disintegrated and old non-disintegrated cement mortars, respectively. This means that disintegration makes old cement mortar 51% less willing to creep than non-disintegrated cement mortar and 7% less willing to creep than new cement mortar.Together with XRD analysis, it is safe to conclude from our study that proper storage of cement does not significantly reduce its properties over a short period. The disintegration effect on material properties is more related to obtaining finer material with a higher specific surface area after milling than it had before disintegration. Applying disintegration to old cement does not regain its chemical activity but it does make cement significantly finer and therefore ensures better packing of the compound into moulds, which decreases porosity and other heterogeneities of elements.The main purpose of the research is to determine the disintegration influence of recovering cement properties. It also aims to evaluate the differences in long-term properties between old cement, new cement, and old cement that has been disintegrated:


Background and Objectives: Two-dimensional speckle tracking echocardiography (2D-STE) is viewed as an outstanding technique, competent of uncovering earlier subclinical myocardial anomalies compared to conventional echocardiography. A few endeavors adopted 2D-STE as a tool to estimate right ventricular (RV) function in subjects with end-stage kidney disease (ESKD). There is no published prospective study on an adult ESKD cohort exploring the consequences of commencing elective hemodialysis (HD) on RV behavior. Materials and Methods: We investigated the RV systolic function using traditional  and 2D-STE  parameters following the initiation of HD. We enrolled 79 consecutive patients with ESKD and assessed them in four steps—at baseline, before HD, and at 3, 6, and 12 months. Results: RVFWLS, FAC, and TAPSE values had a significant increase at 3, 6, and 12 months from baseline (p < 0.001) and a significant increase at 6 months from 3 months (p < 0.001). However, differences between 12 months and 6 months were not significant (p > 0.05) according to Dunn–Bonferroni post hoc tests. Seventeen deaths were recorded before the completion of the study. RVFWLS, FAC, and TAPSE values significantly decreased at 3 and 6 months in all 17 deceased patients, in clear opposition with the values survivors had. All the studied parameters had a significant prediction power on mortality (p < 0.001) having an outstanding performance: baseline-RVFWLS (AUC: 1.000 (95% C.I.: 1.000–1.000)), baseline-FAC (AUC: 0.974 (95% C.I.: 0.942–1.000)), and baseline-TAPSE (AUC: 0.962 (95% C.I.: 0.920–1.000). Conclusions: Our study is the first to investigate RV function by 2D-STE and correlate it with traditional methods in patients with ESKD before and after the initiation of HD. RV function was significantly ameliorated at 3, 6, and 12 months compared to the pre-HD values. FAC and RVFWLS gain an outstanding prognostic role on mortality in this population. Cardiovascular disease (CVD) continues to be the most important cause of major ad-verse cardiovascular events (MACE) and death in end-stage kidney disease (ESKD) patients, as reported by the international registries . The patA distinct and distressing moment in the life of an ESKD patient is the initiation of hemodialysis (HD) sessions . The patConventional echocardiography may not be capable enough to expose precocious cardiac abnormalities in CKD patients , but twoA few investigations also adopted 2D-STE as a tool to appraise the right ventricular (RV) functionality in subjects with ESKD . To our Our research enrolled 79 consecutive patients with ESKD starting HD and assessed in 4 steps—at baseline, before HD, and at 3, 6, and 12 months. The current investigation was conducted between December 2019 to December 2020 at the “Dr. C. I. Parhon” Hospital, Department of Nephrology, Iași, Romania.The participants were clinically stable, in sinus rhythm, without any acute diseases, and with a proper acoustic window for echocardiography and strain analysis.The exclusion criteria were: unwillingness to participate in the study, indication for acute HD, severe pulmonary hypertension and other severe valvular diseases, arrhythmias , disabling stroke, active malignancy, and LV dysfunction or any other comorbidities which may limit the lifespan of the subject to less than 12 months.Of 79 patients, only 62 of them finished the study at 12 months, with 17 deaths recorded from CV causes.This investigation was a prospective cohort study. The local Ethical Commission approved the design of the research. Patients who met the eligibility criteria were recorded after studying principles and signing the informed consent. There was no interference to correct the subjects’ routines regarding their medication or water drinking constraints for the duration of the study. Patients started HD with central venous catheters and transitioned to arteriovenous fistula access within 90 days. HD sessions were programmed as three and a half hours.All the recruited subjects received periodical clinical and echocardiography evaluation at 3, 6, and 12 months. Our main goal was to determine if HD could have favorable aftermath on the function and mechanics of the RV, including subclinical impairment assessed by 2D-STE. In addition, any evaluated parameter was assessed for any potential prognostic role.All echocardiographic evaluations were achieved with commercial ultrasound systems , and strain analysis was performed with customized computer software .We obtained the apical 4-chamber view focused on the RV  to calculate distinct indicators of RV size and function, and then the offline analysis of the recorded images was done using computer. Additional dedicated images optimizing the free wall right ventricle strain were acquired at high frame rates (>70 frames/s). All images were stored digitally, and analysis was performed offline.Only cine loops with good quality images acquired at high frame rates were utilized.A first echocardiographic evaluation was made within 24 h before the first HD session, and all the indices were also investigated at 3, 6, and 12 months. A professional ultrasonographer gathered all the data using the standard protocol. In order to ensure an unbiased outcome, two other experienced ultrasonographers  analyzed and interpreted the offline images independently.Although all patients received a comprehensive evaluation of the size and function of all cardiac chambers, in this study, we reported only those concerning the RV systolic function and mechanics.Firstly, we focused on the traditional evaluation of the systolic function using M-mode measurements for tricuspid annular plane systolic excursion (TAPSE) and two-dimensional standard echocardiography for fractional area change (FAC) using an RV-focused apical four-chamber view. TAPSE represents an estimation of RV longitudinal function, having satisfactory correspondence with other parameters measuring RV overall systolic function, with a value of less than 17mm being deeply evocative for RV systolic dysfunction. TAPSE is defined by the distance of systolic excursion of the RV annular segment along its longitudinal plane from a standard apical 4-chamber window . FAC, deThe strain appraisal was made on an offline groundwork. We manually traced the RV endocardium at the end of the ventricular diastole by selecting 3 or 6 points of interest ; the software automatically drew the desired contour on adjacent images. Region of interest (ROI) was estimated, manually tailored to fit the thickness of the RV free wall as well as of the interventricular septum. Subsequently, the specific deformation curves were displayed, with automatic calculation of the global RV strain and the free wall (RVFWLS). FAC was defined as (end-diastolic area − end-systolic area)/end-diastolic area × 100. RVFWLS was defined as the mean longitudinal peak systolic strain of three segments of the RV free wall, according to the established guidelines . Our stuWe averaged the two measurements offered by our ultrasonographers for each echocardiographic evaluation considering the interobserver variability for RV strain.All the data from the study were analyzed using IBM SPSS Statistics 25. Quantitative variables were tested for normal distribution using the Shapiro–Wilk test and were written as averages with standard deviations or medians with interquartile ranges. Qualitative variables were written as counts or percentages. Quantitative independent variables were tested using the Mann–Whitney U test, according to their distribution, while quantitative paired variables were tested using Friedman’s tests with Dunn–Bonferroni post hoc tests. Qualitative variables were tested using Fisher’s Exact tests. ROC curves were used for establishing cutoff values in the prediction of mortality.This investigation was performed on 79 consecutive hypertensive subjects with ESRD, including 44 men and 35 women who started hemodialysis and followed for 12 months, with 62 patients completing the study and 17 death were recorded at the end of it.Data from The average value of hemoglobin was 9.75 ± 1.77 g/dL with a median of 9.7 g/dL, with 36.7% of the patients having anemia. The average value of uric acid was 7.46 ± 1.92 mg/dL with a median of 7.25 mg/dL, with 40% of the patients having hyperuricemia. The average value of the volumetric ejection fraction was 54.35 ± 9.74% with a median value of 55%, with 6.3% of the patients having a value of less than 40% EF%. Of the analyzed patients, 21.5% died before the 12 months check-up.p = 0.004), had a significantly lower EF% , were significantly more associated with diabetes , and were more associated with NYHA Class III heart failure . Other parameters were not significantly different in comparison with mortality (p > 0.05).Among the analyzed parameters, we observed that patients that died were significantly older  and 3, 6, and 12 months are depicted in p < 0.05). The differences between the parameters measured at different times were significant according to Friedman’s tests (p < 0.001), with RVFWLS, FAC, and TAPSE values having a significant increase at 3/6/12 months from baseline (p < 0.001) and a significant increase at 6 months vs. 3 months (p < 0.001). The differences between 12 months and 6 months, however, were not significant (p > 0.05), according to Dunn–Bonferroni post hoc tests.Data from p < 0.05). The differences observed of the evolution values in comparison to mortality were statistically significant according to Mann–Whitney U tests (p < 0.001), showing that the RVFWLS, FAC, and TASPE values had a higher increase at 3 months from baseline, 6 months vs. 3 months, and 6 months from baseline in survivor patients than in deceased patients (where these parameters had a decrease over time).Data from p < 0.001), having outstanding performance.Data from -A baseline value lower than 18.5 for RVFWLS has a sensitivity of 94.1% and specificity of 100% for mortality prediction;-a baseline value lower than 25.62 for FAC has a sensitivity of 88.2% and specificity of 90.1% for mortality prediction;-a baseline value lower than 18 for TAPSE has a sensitivity of 88.2% and specificity of 85.5% for mortality prediction.Using the ROC curve, cutoff values were established for each parameter:This paper aimed to investigate whether the initiation of HD improves the RV function as judged by conventional methods (TAPSE or FAC) and by modern RV strain assessment using 2D-STE. Moreover, we focused on identifying the RV systolic function parameters that can hold a predictive value for one-year mortality.Our research brings new evidence in a context of deep uncertainties reported by the international guidelines regarding the cardiovascular risks and benefits of dialysis initiation. There is a general conception that the first few months on dialysis are prone to high cardiovascular risks, though it is unclear whether the adverse events are triggered by dialysis initiation ,12. HearHigh uncertainties derive from a few studies with extremely heterogeneous results that evaluated longitudinal changes in subclinical HF after initiation of dialysis: the CRIC study reported a decline in LVEF , the CASAs a consequence of these important inconsistencies, Kidney Disease: Improving Global Outcomes (KDIGO) guidelines encourage further clinical trials in which patients are followed beyond dialysis initiation . TherefoRV function appears to play a central role in post-HD cardiovascular deterioration. A regression analysis  showed tOur research has three main strengths. Chiefly, it is the first clinical study to assess long-term RV function after HD initiation. Secondly, it proposes a novel, modern alternative to evaluate RV function by RV strain assessment using 2D-STE. Thirdly, our results emphasize that a low RV strain has an important predictive power for mortality, irrespective of HD, suggesting that the high health risks associated with HD initiation may not be directly linked through a cause–effect mechanism.p < 0.001) and, very interestingly, a statistically compelling increment was also observed at 6 months for all parameters mentioned . At the end of the study, RVFWLS, FAC, and TAPSE did not suffer any other variations compared to the 6 month evaluation (p > 0.05).In our prospective approach, there was a significant increase in RVFWLS, FAC, and TAPSE values at 3/6/12 months from baseline . We found that TAPSE, FAC, and RVFWLS have an outstanding prognostic role concerning one-year mortality in this frail population.


Growing interest has been accumulated in the definition of worsening effects of diabetes in the cardiovascular system. This is associated with epidemiological data regarding the high incidence of heart failure (HF) in diabetic patients. To investigate the detrimental effects both of hyperglycemia and insulin resistance, a lot of preclinical models were developed. However, the evidence of pathogenic and histological alterations of the so-called diabetic cardiomyopathy (DCM) is still poorly understood in humans. Here, we provide a stringent literature analysis to investigate unique data regarding human DCM. This approach established that lipotoxic-related events might play a central role in the initiation and progression of human DCM. The major limitation in the acquisition of human data is due to the fact of heart specimen availability. Postmortem analysis revealed the end stage of the disease; thus, we need to gain knowledge on the pathogenic events from the early stages until cardiac fibrosis underlying the end-stage HF. Cardiovascular disease (CVD) is the leading cause of mortality in patients with type 2 diabetes (T2D), . NotablyDCM shows symptoms and signs comparable to a dilated cardiomyopathy caused by toxic agents or viral myocarditis . Indeed,The aging could cause the cardiac remodeling by decreasing LV dimensions and increasing fractional shortening. T2D could diminish but it does not reverse this LV remodeling pattern . FurtherThe T2D patients as compared to patients without diabetes have higher LV mass, wall thickness, arterial stiffness, and reduced LVEF . These aThe initial stage of LV diastolic dysfunction in T2D patients could be evidenced by cardiac catheterization . Indeed,Intriguingly, in T2D patients we could have the reduction of LV ejection time, with increased pre-ejection period and ratio of the pre-ejection period to LV ejection time . TherefoMany hypotheses have been formulated about the mechanisms underlying the etiology of DCM, as insulin resistance and hyperglycemia, with oxidative stress, inflammatory components, inappropriate modulation of immune properties, alteration of subcellular components, endothelial and coronary microcirculation abnormalities with apoptosis, fibrosis, inflammation, and lipid accumulation , 31. Theγ, and lower levels of SERCA2a [In this stage, we do not have significant changes in myocardial structure and systolic function by echocardiographic evaluations , 33 in t SERCA2a . However SERCA2a . Intrigu SERCA2a . Further SERCA2a . Remarka SERCA2a . Paralle SERCA2a . Therefo SERCA2a . Finally SERCA2a , 47. The SERCA2a , 49 and  SERCA2a , and theIn patients with advanced stage of diabetic cardiomyopathy, the echocardiography could evidence several modifications of diastolic function  and systolic function (later in the process), which are the result of increased cardiac fibrosis . Thus, tβ1–SMAD signaling pathway increases myocardial collagen and fibronectin content and interstitial fibrosis in concert with impaired insulin signaling [α signaling) and fibrosis [Changes of the metabolism with abnormal neurohumoral activation, and development of myocardial fibrosis could promote the coronary microcirculation, then leading to diastolic function and systolic dysfunction in the late stage of the human DCM , 52, 53.ignaling –58. Morefibrosis –58. Indefibrosis –58. Howefibrosis –58.Much advance is now gained in the pathogenesis of human DCM. However, we need to establish the precise chain of events from the early accumulation of lipotoxicity within the myocardium until the stage of advanced HF. A novel study model proposed in the transplanted heart has been proposed by our group. Long-term studies should be carried in this model, and the search for liquid biopsy biomarkers can be integrated into the light of precision medicine of human DCM.


Heart failure (HF) is one of the most common causes of hospitalization in the geriatric age group, above 65 years. It is associated with high morbidity, mortality, and bad prognosis. Subclinical hypothyroidism (SCH) is a common condition present in this age group that significantly affects the cardiovascular system. Thus, this review attempts to elaborate on the association between subclinical hypothyroidism and heart failure in terms of their prevalence, pathogenesis, prognosis, and possible management in a geriatric age group. Among the various published literature on this topic on PubMed, PubMed Central, and Google Scholar, 36 relevant studies were selected to correlate this association. We found that both SCH and HF can be present concurrently in this age group. Especially in the geriatric population with thyroid-stimulating hormone (TSH) higher than ten mIu/L, there is an increased incidence of heart failure and a worse prognosis with preexisting heart failure. However, randomized controlled trials will be needed to explore further whether treatment is warranted or not in this age group. Heart failure (HF) occurs when the ventricle cannot eject blood or fill blood. It is a common condition in the geriatric population and a prevalent cause for hospitalization in the geriatric population aged 65 and above . Heart fThyroid hormone has a significant impact on hemodynamic changes in the body. It has a substantial role in the heart's functioning and cardiovascular system-specifically, its vascular resistance, heart rate, and cardiac contraction actions . SubclinIt has been accounted that subclinical hypothyroidism is associated with atherosclerosis, heart failure advancement, and morbidity with cardiovascular diseases . ImpaireDespite the high prevalence of subclinical hypothyroidism, its treatment is reserved for patients at risk for overt hypothyroidism (TSH>10 miU/L), presence of antithyroid antibodies (TPOAb), infertile women, women of childbearing age, symptomatic and pregnant patients. There is very little evidence regarding the benefits and the risks of treatment in the geriatric age group . In caseA population-based study, healthy aging, and body composition study address the correlation of subclinical hypothyroidism with heart failure and its recurrence. This study consists of 2730 people of 70-79 years old with follow-up for four years to figure an association between TSH and cardiovascular impact. Comprised of 12.4% of the subclinical hypothyroid population, the outcome shows increased incidence and risk of recurrent heart failure about 3.26 times higher in the group with TSH>= 10. Whether subclinical hypothyroidism can cause or worsen existing heart failure is not clear [A better understanding of why there is an increasing prevalence of subclinical hypothyroidism in aged people with heart failure and its effect upon heart failure prognosis is still unclear. Therefore, this literature review intends to clarify the correlation between these diseases in the geriatric population. It could also help resolve issues about the geriatric population's treatment with subclinical hypothyroidism in general and in the geriatric population with preexisting heart failure.We reviewed scientific literature available on various databases PubMed, Cochrane, PubMed Central, Google Scholar with keywords and medical subject heading (MeSH) keywords. The search strategy for this literature review was done through keywords, as shown in Tables In the last 20 years, those articles published in the English language, including observational studies, controlled trials, clinical trials, meta-analysis, and review articles, were selected to get a clearer picture. Articles with animal studies, editorials were excluded from this study. After removing duplicates from the different databases and screening with relevance to our topic and criteria, a total of 55 articles are selected. Reviewing these articles, relevant 35 articles were chosen, and their findings were added to our paper.DiscussionEffects of Subclinical Hypothyroidism in Heart TSH levels between 4.5 miU/L and 10 miU/L when T4 level is normal is defined as subclinical hypothyroidism ,12. PatiHeart Failure and Its Prevalence With Subclinical Hypothyroidism in Geriatric PopulationThe geriatric population encompasses most heart failure patients and that too with the worst prognosis . There iVarious studies show that subclinical hypothyroidism is indeed associated with the development of heart failure and its worse outcome among heart failure patients. Another study Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a prospective cohort study was done among 70-82-year-old, 5316 total number with preexisting cardiac risk or disease for 3.2 years. This study revealed an increased incidence of heart failure present among those subclinical hypothyroid patients with TSH above ten compared to their euthyroid counterparts. It mentioned an increased hospitalization rate with HR of 4.99  in patients with heart failure among patients with SCH ,19. A meThyroid hormone replacement for subclinical hypothyroidism (TRUST) trial for subclinical hypothyroidism study reveals no significant change in the incidence of heart failure in a geriatric population (mean of 65 years) with SCH when started on thyroid hormone supplementation to the placebo group . More thHow Can Subclinical Hypothyroidism Lead to Heart Failure?Cardiac function, contraction, and relaxation can be affected by thyroid hormone imbalance and can lead to HF . Few stuGupta et al. revealed a strong correlation between TSH and inflammation in patients with SCH. It suggests a role of the inflammatory markers like ESR, CRP, and interleukin-6. Therefore, inflammation can play a role in the heart's altered diastolic function with SCH . PatientPrognosis of HF With SCH Different studies performed epidemiologically have suggested lower thyroid hormone levels associated with increased risk of heart failure and bad prognosis . A heartWhat Are the Challenges of Treatment of Subclinical Hypothyroidism in the Geriatric Population?American thyroid association recommends thyroid supplementation if TSH is more than 10, even dating back to 2005 . It is cTreatment is challenging, with some studies showing mortality increased with arrhythmia induced by treatment with levothyroxine in the geriatric population, especially those over 70. According to the European thyroid association, for this age group with TSH below 10 miU/l, treatment is not recommended with its risk of increasing cardiac ischemia and arrhythmia, especially in patients with heart disease . In the The Rationale for Treatment of SCH in HF Geriatric Population PatientsThere is no clear understanding when it comes to treating patients with HF and SCH. As already known, thyroid replacement has a good effect on lipid profile, especially cholesterol and LDL, and maintaining blood pressure and carotid atherosclerosis . HayashiThyroid hormone replacement in subclinical hypothyroidism improves the heart's diastolic and systolic function. The Cardiovascular health study by Rodondi et al. included 3044 people above 65 years of age who underwent one yr follow-up. Those with TSH over 10 had peak E velocity  higher than others. Peak E velocity is a measurement that determines the heart's diastolic function while performing echocardiography. This measurement positively correlates with the incidence of heart failure. Simultaneously, the risk of heart failure was not raised in another elder group with TSH below 10. Therefore, it showed that the incidence of heart failure was significantly higher in the subthyroid geriatric population  in comparison to their euthyroid counterparts. This can be due to delayed relaxation of the left ventricle due to thyroid dysfunction. Cardiac function was noted over five years through echocardiography in about 70 percent of the group. Echo showed left ventricle mass to be increased in comparison to euthyroid. It is one of the changes that can be regressed with thyroxine therapy, and therefore levothyroxine supplementation reduces the risk of heart failure, preventing heart failure ,18,30. RFew studies suggest levothyroxine supplementation be beneficial, particularly for heart failure patients in terms of the heart's functioning; given the prevalence of hypothyroidism in heart failure patients, supplementation is promising . SCH treAs a person ages, TSH increases and some study says it can lead to a long life. Nothing has been said about heart disease risk and mortality, especially in the preexisting heart failure population. RCT with older people is not enough to decide whether thyroxine supplementation in this age group is beneficial or instead reverting to euthyroidism can cause more harm . CardiovDo We Need to Treat SCH in Geriatric Population Patients? TSH increases as age increases and can be a beneficial factor in longevity. Anything below 10 miU/L in most cases does not need medication unless thyroid antibodies, comorbidities are present, or pregnant women. Still, when it comes to TSH> 10 in the geriatric population, it can be considered for treatment after taking other factors into account like their comorbidities. There can be more harm than good, like fractures with their overtreatment risk . A studyA study with SCH women in the Netherlands showed the correlation between SCH and high risk for mi and aortic calcification. However, consensus regarding the long-term effect on the benefit of thyroid replacement in cardiac function improvement in SCH geriatric population patients lacks randomized controlled trials to form proper guidelines . Even inReference is still 4-5 miU/L, with age TSH increases, leading to more estimation of the geriatric population with SCH than prevalent in a geriatric population. There is a lack of large RCT that have shown promising effects from thyroxine replacement; the rationale is difficult. Treatment just based on anticipation of potential cardiovascular benefits does not seem realistic. Therefore, observation seems to be the best choice for this age group, unlike in young individuals .The disparity can explain the overall disparity in different kinds of literature, trials, and the different result variation in the mean age of individuals, disparity of gender prevalence, comorbidities present, different follow-up duration, the difference with TSH levels present in SCH, and reversal of subclinical thyroid status to euthyroid during the study period in a geriatric population.LimitationsOur study had many limitations. Firstly, our study was based on information collected through different databases, including different articles and not with direct patient contact. Secondly, it cannot be generalized to the younger group, and there is a lot of difference in the management of heart failure and subclinical thyroidism between these groups. Despite our limitations, our study shows that the geriatric population with TSH more than 10 has increased HF incidence, the prevalence of HF, and even those with preexisting HF have a poor prognosis. Therefore, it raises the question of whether the treatment of SCH in the geriatric population can improve HF outcomes.  We addressed the relationship between subclinical hypothyroidism and heart failure in the geriatric population. We elaborated on the thyroid hormone's action on the cardiovascular system, emphasizing how subclinical hypothyroidism can lead to heart failure. Besides, we tried to rationalize thyroxine supplementation in elderly with heart failure among those with TSH greater than 10 miU/L. Though subclinical hypothyroidism can lead to diastolic dysfunction, it is still associated with many cardiovascular effects. When it comes to thyroxine supplementation in the elderly, this is debatable with a narrow therapeutic index of the treatment. Therefore, management regarding this condition is unclear. In the case of the elderly wait and watch approach is accepted generally. Even if thyroxine were to be given, it is started in the lowest dose possible with frequent follow-up, and close observation is recommended. Randomized controlled trials, placebo-controlled with a large number of the geriatric population, should be conducted to determine the clinical outcome for treating the geriatric population with subclinical hypothyroidism with heart failure. To solve the query of whether heart failure prevention or progression is possible with the treatment of SCH, it is must to conduct these trials.