Dialysate calcium concentration (d[Ca]) might have a cardiovascular impact in patients on haemodialysis (HD) since a higher d[Ca] determines better hemodynamic tolerability. We have assessed the influence of d[Ca] on global longitudinal strain (GLS) by two-dimensional echocardiography using speckle-tracking imaging before and in the last hour of HD. This is an observational crossover study using d[Ca] 1.75 mmol/L and 1.25 mmol/L. Ultrafiltration was the same between interventions; patients aged 44 ± 13 years (N = 19). The 1.75 mmol/L d[Ca] was associated with lighter drop of blood pressure. Post HD serum total calcium was higher with d[Ca] 1.75 than with 1.25 mmol/L (11.5 ± 0.8 vs. 9.1 ± 0.5 mg/dL, respectively, p < 0.01). In almost all segments strain values were significantly worse in the peak HD with 1.75 mmol/L d[Ca] than with 1.25 mmol/L d[Ca]. GLS decreased from -19.8 ± 3.7% at baseline to -17.3 ± 2.9% and -16.1 ± 2.6% with 1.25 d[Ca] and 1.75 d[Ca] mmol/L, respectively (p < 0.05 for both d[Ca] vs. baseline and 1.25 d[Ca] vs. 1.75 d[Ca] mmol/L). Factors associated with a worse GLS included transferrin, C-reactive protein, weight lost, and post dialysis serum total calcium. We concluded that d[Ca] of 1.75 mmol/L was associated with higher post dialysis serum calcium, which contributed to a worse ventricular performance. Whether this finding would lead to myocardial stunning needs further investigation.

We investigated factors associated with right ventricular (RV) function and size in hypertrophic cardiomyopathy (HCM) patients. Two hundred fifty-three consecutive HCM patients and 20 healthy volunteers underwent cardiac magnetic resonance examination. In addition to measuring RV function (ejection fraction-RVEF) and size (end-diastolic volume-RVEDV), each image was inspected for the presence of RV and left ventricular (LV) hypertrophy, and the maximal wall thickness of the left and right ventricles was recorded. HCM patients had higher RVEF and lower RVEDV than healthy volunteers and similar RV mass. The mean RV wall thickness was higher in HCM patients than in controls. LV late gadolinium enhancement (LGE) was present in 89.7% of patients, and RV LGE was present in 3.1% of patients (p < 0.0001). Univariate and multivariable analyses revealed that LVEF, peak LV outflow tract gradient, LV LGE, maximal LV wall thickness, and tricuspid regurgitation (TR) volume by magnetic resonance imaging were positive predictors of RVEF. In addition to TR volume, the only independent predictor of RVEF < 45% was LVEF (odds ratio = 0.80, 95% confidence interval 0.67-0.95). Multivariable analysis revealed that LVEDV and TR volume were positive predictors of RVEDV, whereas negative predictors were RVEF, maximal RV wall thickness, LV LGE, and age. Neither estimated systolic pulmonary artery pressure nor TR grade by echocardiography proved to be predictors of RVEF. There were no differences in either the maximal RV wall thickness or the maximal left ventricular (LV) wall thickness in patients stratified according to NYHA functional class (p = 0.93 and p = 0.15, respectively). There were no differences in mean RV wall thickness in patients categorised based on the number of clinical risk factors for sudden cardiac death (SCD), i.e., non-sustained ventricular tachycardia, family history of SCD, or unexplained syncope (p = 0.79). On the other hand, there was a weak positive association between RV hypertrophy and the estimated probability of SCD at 5 years (rho = 0.16, p = 0.01). RV systolic dysfunction measured as decreased RVEF was uncommon in HCM and was associated with poor LV systolic function. LV also had a significant impact on RV size.

A leftward motion of the ventricular septum prior to ejection, known as the septal flash (SF), is frequently observed in patients with left bundle-branch block (LBBB). We investigated whether the abnormal motion of the ventricular septum affects right ventricle (RV) contractile performance in LBBB patients with preserved left ventricular ejection fraction (LVEF). Forty-four patients with complete LBBB were selected using standard 12-lead electrocardiograms (ECGs), with 30 healthy individuals serving as controls. According to the presence of SF, patients with LBBB were allocated to two subgroups: those with SF (LBBB-SF, n = 24) and those without SF (LBBB-NSF, n = 20). RV longitudinal strain (LS) decreased in LBBB patients with preserved LVEF compared to control subjects (p = 0.002). And RV LS decreased significantly in LBBB-SF patients compared to NSF-LBBB patients (p = 0.04). RV LS correlated negatively with involved septal myocardial segments of SF (r = -0.36, p = 0.02), but did not correlate with the magnitude of SF. RV contractile performance deceased in LBBB patients with preserved LVEF. SF, particularly the extent of this phenomenon, may further affect RV contractile performance.

Heart failure (HF) and cardiac arrhythmias share overlapping pathological mechanisms that act cooperatively to accelerate disease pathogenesis. Cardiac fibrosis is associated with both pathological conditions. Our previous work identified a link between phytosterol accumulation and cardiac injury in a mouse model of phytosterolemia, a rare disorder characterized by elevated circulating phytosterols and increased cardiovascular disease risk. Here, we uncover a previously unknown pathological link between phytosterols and cardiac arrhythmias in the same animal model. Phytosterolemia resulted in inflammatory pathway induction, premature ventricular contractions (PVC) and ventricular tachycardia (VT). Blockade of phytosterol absorption either by therapeutic inhibition or by genetic inactivation of NPC1L1 prevented the induction of inflammation and arrhythmogenesis. Inhibition of phytosterol absorption reduced inflammation and cardiac fibrosis, improved cardiac function, reduced the incidence of arrhythmias and increased survival in a mouse model of phytosterolemia. Collectively, this work identified a pathological mechanism whereby elevated phytosterols result in inflammation and cardiac fibrosis leading to impaired cardiac function, arrhythmias and sudden death. These comorbidities provide insight into the underlying pathophysiological mechanism for phytosterolemia-associated risk of sudden cardiac death.

This study evaluated the effects of mitral regurgitation (MR) on cardiac structure and function in left ventricular noncompaction (LVNC) patients. The clinical and cardiovascular magnetic resonance (CMR) data for 182 patients with noncompaction or hypertrabeculation from three institutes were retrospectively included. We analyzed the difference in left ventricular geometry, cardiac function between LVNC patients with and without MR. The results showed that patients with MR had a worse New York Heart Association (NYHA) class and a higher incidence of arrhythmia (P < 0.05). MR occurred in 48.2% of LVNC patients. Compared to LVNC patients without MR, the two-dimensional sphericity index, maximum/minimum end-diastolic ratio and longitudinal shortening in LVNC patients with MR were lower (P < 0.05), and the peak longitudinal strain (PLS) of the global and segmental myocardium were obviously reduced (P < 0.05). No significant difference was found in strain in LVNC patients with different degree of MR; end diastolic volume, end systolic volume, and global PLS were statistically associated with MR and NYHA class (P < 0.05), but the non-compacted to compacted myocardium ratio had no significant correlation with them. In conclusion, the presence of MR is common in LVNC patients. LVNC patients with MR feature more severe morphological and functional changes. Hypertrabeculation is not an important factor affecting structure and function at the heart failure stage.

Extracellular volume (ECV) has been validated as a surrogate measure of interstitial fibrosis, that is increased in both hypertension-induced left ventricular hypertrophy (H-LVH) and hypertrophic cardiomyopathy (HCM). We aimed to explore the correlation between ECV and left ventricular cardiac function. Eighty-one patients with HCM, 44 with H-LVH and 35 controls were prospectively enrolled. Even among patients with normal diastolic function, patients in HCM group had increased- ECV. In terms of diastolic dysfunction (DD), a similar increase in ECV was associated with a larger percentage of patients with severe or moderate-to-severe DD in HCM group. In addition, there was a compensatory increase in the left ventricular ejection fraction (LVEF) in HCM, but no hyperdynamic LVEF was observed in H-LVH. ECV was negatively correlated with LVEF in the late gadolinium enhancement (+) (LGE+) subgroups in the H-LVH group, while no significant linear correlation was observed in HCM group. The increased ECV in HCM patients with normal diastolic function warrants further exploration of the prognostic value of ECV assessments in the early stages of HCM. The associations between ECV and left ventricular functional parameters differed and taking both LGE and ECV into account might be reasonable way to differentiate between the two disorders.

Calcium regulation plays a central role in cardiac function. Several variants in the calcium channel Cav1.2 have been implicated in arrhythmic syndromes. We screened patients with Brugada syndrome, short QT syndrome, early repolarisation syndrome, and idiopathic ventricular fibrillation to determine the frequency and pathogenicity of Cav1.2 variants. Cav1.2 related genes, CACNA1C, CACNB2 and CACNA2D1, were screened in 65 probands. Missense variants were introduced in the Cav1.2 alpha subunit plasmid by mutagenesis to assess their pathogenicity using patch clamp approaches. Six missense variants were identified in CACNA1C in five individuals. Five of them, A1648T, A1689T, G1795R, R1973Q, C1992F, showed no major alterations of the channel function. The sixth C-terminal variant, Cavα1c-T1787M, present mostly in the African population, was identified in two patients with resuscitated cardiac arrest. The first patient originated from Cameroon and the second was an inhabitant of La Reunion Island with idiopathic ventricular fibrillation originating from Purkinje tissues. Patch-clamp analysis revealed that Cavα1c-T1787M reduces the calcium and barium currents by increasing the auto-inhibition mediated by the C-terminal part and increases the voltage-dependent inhibition. We identified a loss-of-function variant, Cavα1c-T1787M, present in 0.8% of the African population, as a new risk factor for ventricular arrhythmia.

Patients with type 2 diabetes treated with Sodium glucose transporter 2 (SGLT2) inhibitors show reduced mortality and hospitalization for heart failure (HF). SGLT2 inhibitors are considered to activate multiple cardioprotective pathways; however, underlying mechanisms are not fully described. This study aimed to elucidate the underlying mechanisms of the beneficial effects of SGLT2 inhibitors on the failing heart. We generated a left ventricular (LV) pressure overload model in C57BL/6NCrSlc mice by transverse aortic constriction (TAC) and examined the effects of empagliflozin (EMPA) in this model. We conducted metabolome and transcriptome analyses and histological and physiological examinations. EMPA administration ameliorated pressure overload-induced systolic dysfunction. Metabolomic studies showed that EMPA increased citrulline levels in cardiac tissue and reduced levels of arginine, indicating enhanced metabolism from arginine to citrulline and nitric oxide (NO). Transcriptome suggested possible involvement of the insulin/AKT pathway that could activate NO production through phosphorylation of endothelial NO synthase (eNOS). Histological examination of the mice showed capillary rarefaction and endothelial apoptosis after TAC, both of which were significantly improved by EMPA treatment. This improvement was associated with enhanced expression phospho-eNOS and NO production in cardiac endothelial cells. NOS inhibition attenuated these cardioprotective effects of EMPA. The in vitro studies showed that catecholamine-induced endothelial apoptosis was inhibited by NO, arginine, or AKT activator. EMPA activates the AKT/eNOS/NO pathway, which helps to suppress endothelial apoptosis, maintain capillarization and improve systolic dysfunction during LV pressure overload.

Clinical presentation of left ventricular non-compaction cardiomyopathy (LVNC) can be heterogeneous from asymptomatic expression to congestive heart failure. Deformation indices assessed by cardiovascular magnetic resonance (CMR) can determine subclinical alterations of myocardial function and have been reported to be more sensitive to functional changes than ejection fraction. The objective of the present study was to investigate the determinants of myocardial deformation indices in patients with LVNC. Twenty patients with LVNC (44.7 ± 14.0 years) and twenty age- and gender-matched controls (49.1 ± 12.4 years) underwent functional CMR imaging using an ECG-triggered steady state-free-precession sequence (SSFP). Deformation indices derived with a feature tracking algorithm were calculated including end-systolic global longitudinal strain (GLS), circumferential strain (GCS), longitudinal and circumferential strain rate (SRll and SRcc). Twist and rotation were determined using an in-house developed post-processing pipeline. Global deformation indices (GLS, GCS, SRll and SRcc) were significantly lower in patients with LVNC compared to healthy controls (all, p < 0.01), especially for midventricular and apical regions. Apical rotation and twist were impaired for LVNC (p = 0.007 and p = 0.012), but basal rotation was preserved. Deformation indices of strain, strain rate and twist correlated well with parameters of the non-compacted myocardium, but not with the total myocardial mass or the thinning of the compacted myocardium, e.g. r = 0.595 between GLS and the non-compacted mass (p < 0.001). In conclusion, CMR deformation indices are reduced in patients with LVNC especially in affected midventricular and apical slices. The impairment of all strain and twist parameters correlates well with the extent of non-compacted myocardium.

Little is still known about the effect of dietary patterns on left ventricular hypertrophy (LVH). Here, we derived dietary patterns by principal component analysis (PCA) and evaluated their association with LV structure, function, and remodelling. Our cross-sectional study included 438 members (aged 25-65 years; 59.1% women) of the Kardiovize Brno 2030 with no history of cardiovascular disease. Two dietary patterns were derived using PCA, namely prudent and western. Primary outcomes were echocardiographic parameters and LV geometric patterns, such as concentric LV remodelling (cLVR), concentric LVH (cLVH), and eccentric LVH (eLVH). Interestingly, participants with high adherence to the prudent dietary pattern had decreased odds of cLVH after adjustment for socio-demographic, clinical and behavioral covariates (OR = 0.24, 95% CI = 0.08-0.88; p = 0.031). By contrast, several echocardiographic parameters increased with increasing adherence to the western dietary pattern, which resulted in higher odds of cLVH among participants with high adherence (OR = 5.38, 95% CI = 1.17-23.58; p = 0.035). Although our findings may have an immediate relevance for public-health strategies, further large-size prospective studies should be encouraged to better understand the observed association and their causality.

Abnormal conduction and improper electrical impulse propagation are common in heart after myocardial infarction (MI). The scar tissue is non-conductive therefore the electrical communication between adjacent cardiomyocytes is disrupted. In the current study, we synthesized and characterized a conductive biodegradable scaffold by incorporating graphene oxide gold nanosheets (GO-Au) into a clinically approved natural polymer chitosan (CS). Inclusion of GO-Au nanosheets in CS scaffold displayed two fold increase in electrical conductivity. The scaffold exhibited excellent porous architecture with desired swelling and controlled degradation properties. It also supported cell attachment and growth with no signs of discrete cytotoxicity. In a rat model of MI, in vivo as well as in isolated heart, the scaffold after 5 weeks of implantation showed a significant improvement in QRS interval which was associated with enhanced conduction velocity and contractility in the infarct zone by increasing connexin 43 levels. These results corroborate that implantation of novel conductive polymeric scaffold in the infarcted heart improved the cardiac contractility and restored ventricular function. Therefore, our approach may be useful in planning future strategies to construct clinically relevant conductive polymer patches for cardiac patients with conduction defects.

Children with chronic kidney disease suffer from excessive cardiovascular mortality and early alterations of the cardiovascular system. Tissue doppler imaging is a validated echocardiographic tool to assess early systolic and diastolic cardiac dysfunction. We hypothesized that tissue Doppler velocities would reveal reduced cardiac function in children with chronic kidney disease compared to healthy children. A standardized echocardiographic exam was performed in 128 patients of the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) Study aged 6-17 years with an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2. Tissue Doppler measurements included early (E') and late (A') diastolic and systolic (S') velocity at the mitral and septal annulus of the left ventricle. Measured values were normalized to z-scores using published reference data. Predictors of E'/A', E/E', S' and left ventricular mass index (LVMI) were assessed by multiple linear regression analyses. Tissue Doppler E' was reduced and tissue Doppler A' increased, resulting in a reduced tissue Doppler E'/A' ratio (z-score -0.14, p < 0.0001) indicating reduced diastolic function compared to healthy children. Reduced tissue Doppler E'/A' Z-Scores were independently associated with lower eGFR (p = 0.002) and increased systolic blood pressure (p = 0.02). While E/E' Z-Scores were increased (Z-score 0.57, p < 0.0001), patients treated with pharmacological RAS blockade but not with other antihypertensive treatments had significantly lower E/E' and higher E'/A' Z-Scores. Systolic tissue Doppler velocities were significantly decreased (Z-score -0.24, p = 0.001) and inversely correlated with E/E' Z-Scores (r = -0.41, p < 0.0001). LVMI was not associated with systolic or diastolic tissue Doppler velocities. Concentric left ventricular hypertrophy showed a tendency to lower S' in multivariate analysis (p = 0.13) but no association to diastolic function. Concentric left ventricular geometry was significantly associated with lower midwall fractional shortening. In summary, systolic and diastolic function assessed by tissue Doppler is impaired. eGFR, systolic blood pressure and the type of antihypertensive medications are significant predictors of diastolic function in children with CKD. Left ventricular morphology is largely independent of tissue Doppler velocities. Tissue Doppler velocities provide sensitive information about early left ventricular dysfunction in this population.

Left ventricular (LV) trabeculation has been studied in certain forms of cardiomyopathy. However, the changes of LV endocardial trabeculation during the remodeling process leading to heart failure (HF) are unclear. Seventy-four patients with systolic heart failure (SHF), 65 with heart failure with preserved ejection fraction (HFpEF) and 61 without HF were prospectively enrolled. All subjects received magnetic resonance imaging (MRI) study including cine, T1 and late gadolinium enhancement (LGE) images. Trabecular-papillary muscle (TPM) mass, fractal dimension (FD) and extracellular volume (ECV) were derived. The results showed that TPM mass index was higher in patients with SHF than that in patients with HFpEF and non-HF. The TPM mass-LV mass ratio (TPMm/LVM) was higher in SHF group than that in HFpEF and non-HF. FD was not different among groups. The presence of LGE was inversely associated with TPM mass index and TPMm/LVM while the ECV were positively associated with TPMm/LVM. The FD was positively associated with LV chamber size. In conclusion, TPM increases in patients with SHF and are probably related to myocardial cell hypertrophy and fibrotic repair during remodeling. The FD increases with the dilatation of LV chamber but remain unchanged with the deterioration of LV function.

Cardiovascular magnetic resonance imaging is the gold standard for cardiac function assessment. Quantification of clinical results (CR) requires precise segmentation. Clinicians statistically compare CRs to ensure reproducibility. Convolutional Neural Network developers compare their results via metrics. Aim: Introducing software capable of automatic multilevel comparison. A multilevel analysis covering segmentations and CRs builds on a generic software backend. Metrics and CRs are calculated with geometric accuracy. Segmentations and CRs are connected to track errors and their effects. An interactive GUI makes the software accessible to different users. The software's multilevel comparison was tested on a use case based on cardiac function assessment. The software shows good reader agreement in CRs and segmentation metrics (Dice > 90%). Decomposing differences by cardiac position revealed excellent agreement in midventricular slices: > 90% but poorer segmentations in apical (> 71%) and basal slices (> 74%). Further decomposition by contour type locates the largest millilitre differences in the basal right cavity (> 3 ml). Visual inspection shows these differences being caused by different basal slice choices. The software illuminated reader differences on several levels. Producing spreadsheets and figures concerning metric values and CR differences was automated. A multilevel reader comparison is feasible and extendable to other cardiac structures in the future.

Biventricular pacing is an important modality to improve left ventricular (LV) synchronization and long-term function. However, the biological effects of this treatment are far from being elucidated and existing animal models are limited and demanding. Recently, we introduced an implanted device for double-site epicardial pacing in rats and echocardiographically demonstrated favorable effects of LV and biventricular (LV-based) pacing modes typically observed in humans. Here, this new animal model was further characterized. Electrodes were implanted either on the right atria (RA) and right ventricle (RV) or on the RV and LV. Following recovery, rats were either used for invasive hemodynamic measurements (pressure-volume analysis) or exposed to sustained RV vs. biventricular tachypacing for 3 days. RV pacing compromised, while LV-based pacing modes markedly enhanced cardiac performance. Changes in LV performance were associated with prominent compensatory changes in arterial resistance. Sustained RV tachypacing increased the electrocardiogram QTc interval by 7.9 ± 3.1 ms (n = 6, p < 0.05), dispersed refractoriness between the right and left pacing sites and induced important molecular changes mainly in the early-activated septal tissue. These effects were not observed during biventricular tachypacing (n = 6). Our results demonstrate that the rat is an attractive new model to study the biological consequences of LV dyssynchrony and resynchronization.

Cardiac Magnetic Resonance (CMR) is the gold standard for left ventricular (LV) function assessment in small rodents and, though echocardiography (ECHO) has been proposed as an alternative method, LV volumes may be underestimated when marked eccentric remodeling is present. In the present study we described a novel echocardiographic method and we tested the agreement with CMR for LV volumes and ejection fraction calculation in mice with experimental myocardial infarction. Sham-operated and infarcted mice, subjected to Coronary Artery Ligation, underwent ECHO and CMR. Volumes and ejection fraction were calculated by ECHO using a standard Simpson's modified method (ECHO pLAX) or a method from sequential parasternal short axis (ECHO pSAX) acquired mechanically by translating the probe every 1 mm along the left ventricle. The mean differences ±1.96 standard deviation near to zero suggested close agreement between ECHO pSAX and CMR; contrarily ECHO pLAX agreement with CMR was lower. In addition, ECHO was three times shorter and cheaper (Relative cost difference: pLAX: -66% and pSAX -57%) than CMR. In conclusion, ECHO pSAX is a new, fast, cheap and accurate method for LV function assessment in mice.

The effects of left ventricular (LV) cavity size on cardiac function and overload have not yet been fully elucidated. We performed a covariance structure analysis and drew theoretical path models to clarify the effects of hemodynamic parameters on the stroke volume index (SVI) as a marker of cardiac function and on the plasma B-type natriuretic peptide (BNP) level as a marker of cardiac overload. We simultaneously measured various hemodynamic parameters and the BNP levels during cardiac catheterization in 1,715 inpatients of our institution. The current path models tested the validity of the Frank-Starling law in patients with heart failure using the SVI, the LV end-systolic volume index (LVESVI) and the LV end-diastolic volume index (LVEDVI). Using the BNP levels, the path models clearly demonstrated that LVESVI substantially augmented cardiac overload, whereas LVEDVI palliated this parameter. These volume indices exerted opposite effects on cardiac function and overload. These results advance the understanding of the relationships between LV cavity size and both cardiac function and overload and indicate the increasing importance of LV diastolic volume in heart failure and the utility of LVESVI as an important marker of cardiac remodeling for further relevant studies.

Recently, associations between the biomarker galectin-3 and numerous pathological processes involved in heart failure (HF) and right ventricular (RV) function have been observed. We aimed to assess the long-term prognostic ability of galectin-3 and RV function parameters for all-cause mortality in HF patients treated with cardiac resynchronization therapy (CRT). We prospectively studied 63 symptomatic HF patients with a left ventricular (LV) ejection fraction (EF) ≤ 35%. The median serum galectin-3 concentration was 13.4 ng/mL (IQR 11.05, 17.15). A detailed assessment of LV and RV geometry and function was performed with echocardiography. CRT defibrillator implantation was achieved in all patients without major complications. The follow-up lasted 5 years. In the multivariable Cox regression model, independent predictors for all-cause mortality were log baseline galectin-3 and baseline RV function expressed as tricuspid annular plane systolic excursion with HR 2.96 (p = 0.037) and HR 0.88 (p = 0.023), respectively. Analysis of subgroups defined by galectin-3 concentration and CRT response showed that patients with high baseline galectin-3 concentrations and a lack of response to CRT had a significantly lower probability of survival. In our patient cohort, the baseline galectin-3 concentration and RV function were independent predictors of long-term all-cause mortality in HFrEF patients following CRT implantation.

Contractile dysfunction is underdiagnosed in early stages of diabetic cardiomyopathy. We evaluated the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers of subclinical cardiac abnormalities in type 2 diabetes. Forty-eight men with well-controlled type 2 diabetes and 12 healthy age-matched volunteers were enrolled in the study. Left ventricular (LV) parameters were measured by magnetic resonance imaging. A panel of lncRNAs was quantified in serum by RT-qPCR. No differences in expression levels of lncRNAs were observed between type 2 diabetes patients and healthy volunteers. In patients with type 2 diabetes, long intergenic non-coding RNA predicting cardiac remodeling (LIPCAR) was inversely associated with diastolic function, measured as E/A peak flow (P < 0.050 for all linear models). LIPCAR was positively associated with grade I diastolic dysfunction (P < 0.050 for all logistic models). Myocardial infarction-associated transcript (MIAT) and smooth muscle and endothelial cell-enriched migration/differentiation-associated long noncoding RNA (SENCR) were directly associated with LV mass to LV end-diastolic volume ratio, a marker of cardiac remodelling (P < 0.050 for all linear models). These findings were validated in a sample of 30 patients with well-controlled type 2 diabetes. LncRNAs are independent predictors of diastolic function and remodelling in patients with type 2 diabetes.

Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have the ability of differentiating into functional cardiomyocytes (CMs) for cell replacement therapy, tissue engineering, drug discovery and toxicity screening. From a scale-free, co-expression network analysis of transcriptomic data that distinguished gene expression profiles of undifferentiated hESC, hESC-, fetal- and adult-ventricular(V) CM, two candidate chromatin remodeling proteins, SMYD1 and SMARCD1 were found to be differentially expressed. Using lentiviral transduction, SMYD1 and SMARCD1 were over-expressed and suppressed, respectively, in single hESC-VCMs as well as the 3D constructs Cardiac Micro Tissues (CMT) and Tissue Strips (CTS) to mirror the endogenous patterns, followed by dissection of their roles in controlling cardiac gene expression, contractility, Ca2+-handling, electrophysiological functions and in vitro maturation. Interestingly, compared to independent single transductions, simultaneous SMYD1 overexpression and SMARCD1 suppression in hESC-VCMs synergistically interacted to increase the contractile forces of CMTs and CTSs with up-regulated transcripts for cardiac contractile, Ca2+-handing, and ion channel proteins. Certain effects that were not detected at the single-cell level could be unleashed under 3D environments. The two chromatin remodelers SMYD1 and SMARCD1 play distinct roles in cardiac development and maturation, consistent with the notion that epigenetic priming requires triggering signals such as 3D environmental cues for pro-maturation effects.