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Background: Cushing disease (CD) may lead to accelerated cardiovascular remodeling and increased mortality. There are suspected differences in the mechanism of cardiovascular dysfunction between males and females with CD. The purpose of this study was to assess the effect of patient sex on the hemodynamic profile assessed via impedance cardiography and echocardiography in patients newly diagnosed with CD. Material and methods: The 54 patients newly diagnosed with CD (mean age 41 years; 77.8% of females) who were included in this prospective clinical study underwent impedance cardiography to assess specific parameters (including systemic vascular resistance index [SVRI], total arterial compliance index [TACI], Heather index [HI], stroke index [SI], cardiac index [CI], velocity index [VI], and acceleration index [ACI]) and transthoracic echocardiography to assess heart chamber diameters and left ventricular systolic and diastolic function. Results: Males with CD exhibited higher afterload, with higher SVRI (3,169.3 ± 731.8 vs. 2,339.3 ± 640.8 dyn*s*cm-5*m² in males and females, respectively; p=0.002), lower TACI (0.80 ± 0.30 vs. 1.09 ± 0.30 mL/mmHg*m²; p=0.008), and lower hemodynamic parameters of left ventricular function, with lower HI (9.46 ± 2.86 vs. 14.1 ± 5.06 Ohm/s²; p=0.0007), lower VI (35.1 ± 11.9 vs. 44.9 ± 13.1 1*1000-1*s-1; p=0.009), lower SI (36.5 ± 11.7 vs. 43.6 ± 9.57mL/m²; p=0.04), lower CI (2.36 ± 0.46 vs. 3.17 ± 0.76 mL*m-2*min-1; p=0.0009), and lower ACI (50.4 ± 19.8 vs. 73.6 ± 25.0 1/100/s²; p=0.006). There were no significant differences between the sexes in left ventricular systolic or diastolic function assessed by echocardiography. Conclusion: In comparison with females with CD, males with CD have a less favorable hemodynamic profile, with higher afterload and worse left ventricular function. Sex differences in cardiovascular system function should be taken into consideration in designing personalized diagnostic and therapeutic management of patients with CD. [ABSTRACT FROM AUTHOR]

Background: Although subclinical hypothyroidism (SCH) is related to abnormalities in left ventricular diastolic function, the use of levothyroxine as a regular treatment remains debatable. This meta-analysis aimed to determine whether thyroid hormone replacement therapy affects cardiac diastolic function in patients with SCH as measured by echocardiography. Methods: This meta-analysis included a search of the EMBASE, PubMed, Web of Science, and Cochrane Library databases from their inception to May 18, 2023, for studies analyzing cardiac morphology and functional changes in patients with SCH before and after thyroid hormone replacement. The outcome measures were cardiac morphology and diastolic and overall cardiac function, as assessed using ultrasound parameters (including ventricular wall thickness, chamber size, mitral wave flow, tissue Doppler, and speckle tracking). The quality of the studies was assessed using the Newcastle-Ottawa Scale. The standard mean differences (MDs) and 95% confidence intervals (CI) were calculated using fixed- or randomeffects models. Results: Seventeen studies met the inclusion criteria. A total of 568 patients participated and completed the follow-up. All studies specifically stated that serum thyrotropin levels returned to normal by the end of the study period. Compared with baseline levels, no significant morphological changes were observed in the heart. In terms of diastolic function, we discovered that the ratios of E-velocity to A-velocity (E/A) had greatly improved after thyroid hormone replacement therapy, whereas the ratios of the mitral inflow E wave to the tissue Doppler e' wave (E/e') had not. Global longitudinal strain (GLS) increased significantly after treatment with levothyroxine. Conclusion: In adult patients with SCH, thyroid hormone supplementation can partially but not completely improve parameters of diastolic function during the observation period. This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement, an updated guideline for reporting systematic reviews (11) and was registered with INPLASY (INPLASY202320083). [ABSTRACT FROM AUTHOR]

Purpose: Endothelial cell dysfunction is a major cause of early atherosclerosis. Although the role of extracellular vesicles in stabilizing atherosclerotic plaques is well established, the effect of circulating exosomes on plaque formation is still unknown. Here, we explored the effect of exosomes on atherosclerosis based on the function that exosomes can act on intercellular communication. Patients and methods: We extracted serum exosomes from the blood of CHD patients (CHD-Exo) and healthy individuals (Con-Exo). The obtained exosomes were co-cultured with human umbilical vein endothelial cells (HUVECs) in vitro. In addition, we determined that circ_0001785 functions as a competing endogenous RNA (ceRNAs) in coronary artery disease by dual luciferase reporter gene analysis. The protective effect of circ_0001785 against endothelial cell injury was also verified using over-expression lentiviral transfection functional assays. In vivo experiments, we injected over-expressed circ_0001785 lentivirus into the tail vein of mice to observe its therapeutic effect on a mouse model of atherosclerosis. Results: The vitro co-cultured results showed that the amount of plasma-derived exosomes have an increase in patients with coronary artery disease, and the inflammation and apoptosis of endothelial cells were exacerbated. Over-expression of circ_0001785 reduced endothelial cell injury through the ceRNA network pathway of miR-513a-5p/TGFBR3. Quantitative reverse transcription-polymerase chain reaction identified that the expressed amount of circ_0001785 was reduced in the circulating peripheral blood of CHD patients and increased within human and mouse atherosclerotic plaque tissue. The results of in vivo experiments showed that circ_0001785 reduced aortic endothelial cell injury and the formation of intraplaque neo-vascularization, and enhanced left ventricular diastolic function, thereby delaying the development of atherosclerosis in mice. Conclusion: Our results demonstrated a new biomarker, exosome-derived circ_0001785, for atherogenesis, which can reduce endothelial cell injury and thus delay atherogenesis through the miR-513a-5p/TGFBR3 ceRNA network mechanism, providing an exosome-based intervention strategy for atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Left ventricular (LV) circumferential and longitudinal strain provide important insight into LV mechanics and function, each contributing to volumetric changes throughout the cardiac cycle. We sought to explore this strain-volume relationship in more detail, by mathematically integrating circumferential and longitudinal strain and strain rate to predict LV volume and volumetric rates of change. Methods: Cardiac magnetic resonance (CMR) imaging from 229 participants from the Alberta HEART Study (46 healthy controls, 77 individuals at risk for developing heart failure [HF], 70 patients with diagnosed HF with preserved ejection fraction [HFpEF], and 36 patients with diagnosed HF with reduced ejection fraction [HFrEF]) were evaluated. LV volume was assessed by the method of disks and strain/strain rate were assessed by CMR feature tracking. Results: Integrating endocardial circumferential and longitudinal strain provided a close approximation of LV ejection fraction (EFStrain), when compared to gold-standard volumetric assessment (EFVolume: r = 0.94, P < 0.0001). Likewise, integrating circumferential and longitudinal strain rate provided a close approximation of peak ejection and peak filling rates (PERStrain and PFRStrain, respectively) compared to their gold-standard volume-time equivalents (PERVolume, r = 0.73, P < 0.0001 and PFRVolume, r = 0.78, P < 0.0001, respectively). Moreover, each integrated strain measure differentiated patients across the HF continuum (all P < 0.01), with the HFrEF group having worse EFStrain, PERStrain, and PFRStrain compared to all other groups, and HFpEF having less favorable EFStrain and PFRStrain compared to both at-risk and control groups. Conclusions: The data herein establish the theoretical framework for integrating discrete strain components into volumetric measurements across the cardiac cycle, and highlight the potential benefit of this approach for differentiating patients along the heart failure continuum. [ABSTRACT FROM AUTHOR]

Background: Coronary magnetic resonance angiography (coronary MRA) is increasingly being considered as a clinically viable method to investigate coronary artery disease (CAD). Accurate determination of the trigger delay to place the acquisition window within the quiescent part of the cardiac cycle is critical for coronary MRA in order to reduce cardiac motion. This is currently reliant on operator-led decision making, which can negatively affect consistency of scan acquisition. Recently developed deep learning (DL) derived software may overcome these issues by automation of cardiac rest period detection. Methods: Thirty individuals (female, n = 10) were investigated using a 0.9 mm isotropic image-navigator (iNAV)-based motion-corrected coronary MRA sequence. Each individual was scanned three times utilising different strategies for determination of the optimal trigger delay: (1) the DL software, (2) an experienced operator decision, and (3) a previously utilised formula for determining the trigger delay. Methodologies were compared using custom-made analysis software to assess visible coronary vessel length and coronary vessel sharpness for the entire vessel length and the first 4 cm of each vessel. Results: There was no difference in image quality between any of the methodologies for determination of the optimal trigger delay, as assessed by visible coronary vessel length, coronary vessel sharpness for each entire vessel and vessel sharpness for the first 4 cm of the left mainstem, left anterior descending or right coronary arteries. However, vessel length of the left circumflex was slightly greater using the formula method. The time taken to calculate the trigger delay was significantly lower for the DL-method as compared to the operator-led approach (106 ± 38.0 s vs 168 ± 39.2 s, p < 0.01, 95% CI of difference 25.5–98.1 s). Conclusions: Deep learning-derived automated software can effectively and efficiently determine the optimal trigger delay for acquisition of coronary MRA and thus may simplify workflow and improve reproducibility. [ABSTRACT FROM AUTHOR]

BACKGROUND Previous studies have found associations of red blood cell (RBC) traits (hemoglobin and RBC count) with blood pressure; whether these associations are causal is unknown. METHODS We performed cross-sectional analyses in the Lifelines Cohort Study (n = 167,785). Additionally, we performed bidirectional 2 sample Mendelian randomization (MR) analyses to explore the causal effect of the 2 traits on systolic (SBP) and diastolic blood pressure (DBP), using genetic instrumental variables regarding hemoglobin and RBC identified in UK Biobank (n = 350,475) and International Consortium of Blood Pressure studies for SBP and DBP (n = 757,601). RESULTS In cross-sectional analyses, we observed positive associations with hypertension and blood pressure for both hemoglobin (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.16–1.20 for hypertension; B = 0.11, 95% CI: 0.11–0.12 for SBP; B = 0.11, 95% CI: 0.10–0.11 for DBP, all per SD) and RBC (OR = 1.14, 95% CI: 1.12–1.16 for hypertension; B = 0.11, 95% CI: 0.10–0.12 for SBP; B = 0.08, 95% CI: 0.08–0.09 for DBP, all per SD). MR analyses suggested that higher hemoglobin and RBC cause higher DBP (inverse-variance weighted B = 0.11, 95% CI: 0.07–0.16 for hemoglobin; B = 0.07, 95% CI: 0.04–0.10 for RBC, all per SD). Reverse MR analyses (all per SD) suggested causal effects of DBP on both hemoglobin (B = 0.06, 95% CI: 0.03–0.09) and RBC (B = 0.08, 95% CI: 0.04–0.11). No significant effects on SBP were found. CONCLUSIONS Our results suggest bidirectional causal relationships of hemoglobin and RBC with DBP, but not with SBP. [ABSTRACT FROM AUTHOR]

Rationale: Right ventricular (RV) dysfunction is common among patients hospitalized with coronavirus disease (COVID-19); however, its epidemiology may depend on the echocardiographic parameters used to define it. Objectives: To evaluate the prevalence of abnormalities in three common echocardiographic parameters of RV function among patients with COVID-19 admitted to the intensive care unit (ICU), as well as the effect of RV dilatation on differential parameter abnormality and the association of RV dysfunction with 60-day mortality. Methods: We conducted a retrospective cohort study of ICU patients with COVID-19 between March 4, 2020, and March 4, 2021, who received a transthoracic echocardiogram within 48 hours before to at most 7 days after ICU admission. RV dysfunction and dilatation, respectively, were defined by guideline thresholds for tricuspid annular plane systolic excursion (TAPSE), RV fractional area change, RV free wall longitudinal strain (RVFWS), and RV basal dimension or RV end-diastolic area. Association of RV dysfunction with 60-day mortality was assessed through logistic regression adjusting for age, prior history of congestive heart failure, invasive ventilation at the time of transthoracic echocardiogram, and Acute Physiology and Chronic Health Evaluation II score. Results: A total of 116 patients were included, of whom 69% had RV dysfunction by one or more parameters, and 36.3% of these had RV dilatation. The three most common patterns of RV dysfunction were the presence of three abnormalities, the combination of abnormal RVFWS and TAPSE, and isolated TAPSE abnormality. Patients with RV dilatation had worse RV fractional area change (24% vs. 36%; P = 0.001), worse RVFWS (16.3% vs. 19.1%; P = 0.005), higher RV systolic pressure (45mmHg vs. 31mmHg; P = 0.001) but similar TAPSE (13mm vs. 13mm; P=0.30) compared with those with normal RV size. After multivariable adjustment, 60-day mortality was significantly associated with RV dysfunction (odds ratio, 2.91; 95% confidence interval, 1.01-9.44), as was the presence of at least two parameter abnormalities. Conclusions: ICU patients with COVID-19 had significant heterogeneity in RV function abnormalities present with different patterns associated with RV dilatation. RV dysfunction by any parameter was associated with increased mortality. Therefore, a multiparameter evaluation may be critical in recognizing RV dysfunction in COVID-19. [ABSTRACT FROM AUTHOR]

There is a scarcity of follow-up data on post-COVID syndrome and its physical, psychological, and quality of life attributes, particularly from South Asian populations. This study was conducted to assess the prevalence, associations, and impact of the post-COVID syndrome among patients treated at a dedicated COVID-19 treatment unit. A prospective cohort study was conducted to follow-up patients with moderate to severe disease or mild disease with co-morbidities at 2 and 6 weeks, 3 and 6 months and 1 year from discharge. Clinical notes, an interviewer-administered questionnaire and six-item cognitive impairment, Montreal Cognitive Assessment, Fatigue (11-item Chalder) and EQ5D5L questionnaires were used for data collection. All patients had follow-up echocardiograms and symptomatic patients had biochemical and haematological investigations, chest x-rays, high-resolution computed tomography of chest and lung function tests. Among 153 patients {mean age 57.2 ± 16.3 years (83 (54.2% males)}, 92 (60.1%) got the severe disease. At least a single post-COVID symptom was reported by 119 (77.3%), 92 (60.1%), 54 (35.3%) and 25 (16.3%) at 6 weeks, 3 months, 6 months and 1 year respectively. Post-COVID symptoms were significantly associated with disease severity (p = 0.004). Fatigue was found in 139 (90.3%), 97 (63.4%) and 66 (43.1%) patients at 2, 6 and 12 weeks respectively. Dyspnoea {OR 1.136 (CI 95% 0.525–2.455)}, arthralgia {OR 1.83(CI 95% 0.96–3.503)} and unsteadiness {OR 1.34 (CI 95% 0.607–2.957)}were strongly associated with age above 60 years. Both genders were equally affected. In multivariable logistic regression, fatigue and anxiety/depression were associated with poor quality of life (QoL) (p = 0.014, p ≤ 0.001) in 6 weeks. In cardiac assessments, diastolic dysfunction (DD) was detected in 110 (72%) patients at 2 weeks and this number reduced to 64 (41.8%) at 12 weeks. The decline in diastolic dysfunction in elderly patients was significantly higher compared to young patients (p = 0.012). Most post-COVID symptoms, QoL and cognition improve during the first few months. The severity of the disease and older age are associated with post-COVID symptoms. Transient DD may contribute to cardiac symptoms of post-COVID syndrome, especially in elderly patients. [ABSTRACT FROM AUTHOR]

Background: Echocardiography has become an integral part of the management of critically ill patients. It helps to diagnose and treat various conditions. COVID-19 patients can develop cardiac dysfunction. We planned to study the echocardiographic parameters in COVID-19 patients. Methods: We conducted a prospective observational multicenter study after institutional ethical committee approval. COVID-19 pneumonia patients admitted to the intensive care unit (ICU) were enrolled. The echocardiographic evaluation was done within 24–48 hours of admission. Assessment of the left and right heart with systolic and left ventricular diastolic function evaluation was done. The primary outcome was ICU mortality. The secondary outcomes were the length of ICU stay and duration of mechanical ventilation. Results: Among 573 patients mean age was 57.17 (14.67) with 68.60% being males. On day 1 of ICU, invasive mechanical ventilation was used in 257 (45%) patients. One hundred and forty-eight (25.83%) patients were on vasopressors when echocardiography was performed. Severe left ventricle (LV) systolic dysfunction was seen in 8.7% of patients and had higher odds of mortality [2.48(1.058–5.807), p = 0.037] followed by E and e′ with odds ratio of [0.984(0.971–0.998), p = 0.021] and 0.897 (0.805–0.998), p = 0.046], respectively. E/e′ indicative of filling pressure of the LV was not found to be significant. Troponin I, E/A, and RV dilatation were similar among survivors and non-survivors. Conclusion: Echocardiographic evaluation in COVID-19 patients showed severe LV systolic dysfunction was associated with ICU mortality. E/e′ was not found to be significant but lower e′ was associated with higher mortality. Trial registration IEC 131/2020, CTRI/2020/06/025858 date 13th June 2020 [ABSTRACT FROM AUTHOR]

Objectives: In acute pulmonary embolism (PE), the right ventricle (RV) may dilate compromising left ventricular (LV) size, thereby increasing RV/LV ratio. End‐diastolic RV/LV ratio is often used in PE risk stratification, though the cause of death is RV systolic failure. We aimed to confirm our pre‐clinical observations of higher RV/LV ratio in systole compared to diastole in human patients with PE. Methods: We blinded and independently analyzed echocardiograms from 606 patients with PE, evaluated by a Pulmonary Embolism Response Team. We measured RV/LV ratios in end‐systole and end‐diastole and fractional area change (FAC). Our primary outcome was a composite of 7‐day clinical deterioration, treatment escalation or death. Secondary outcomes were 7‐day and 30‐day all‐cause mortality. Results: RV/LV ratio was higher in systole compared to diastole (median 1.010 [.812–1.256] vs..975 [.843–1.149], p <.0001). RV/LV in systole and diastole were correlated (slope = 1.30 [95% CI 1.25–1.35], p <.0001 vs. slope = 1). RV/LV ratios in both systole and diastole were associated with the primary composite outcome but not with all‐cause mortality. Conclusion: The RV/LV ratio is higher when measured in systole versus in diastole in patients with acute PE. The two approaches had similar associations with clinical outcomes, that is, it appears reasonable to measure RV/LV ratio in diastole. [ABSTRACT FROM AUTHOR]

Aims Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction, microvascular dysfunction, and myocardial fibrosis with recent evidence implicating the immune system in orchestrating cardiac remodelling. Methods and results Here, we show the mouse model of deoxycorticosterone acetate (DOCA)-salt hypertension induces key elements of HFpEF, including diastolic dysfunction, exercise intolerance, and pulmonary congestion in the setting of preserved ejection fraction. A modified single-cell sequencing approach, cellular indexing of transcriptomes and epitopes by sequencing, of cardiac immune cells reveals an altered abundance and transcriptional signature in multiple cell types, most notably cardiac macrophages. The DOCA-salt model results in differential expression of several known and novel genes in cardiac macrophages, including up-regulation of Trem2, which has been recently implicated in obesity and atherosclerosis. The role of Trem2 in hypertensive heart failure, however, is unknown. We found that mice with genetic deletion of Trem2 exhibit increased cardiac hypertrophy, diastolic dysfunction, renal injury, and decreased cardiac capillary density after DOCA-salt treatment compared to wild-type controls. Moreover, Trem2-deficient macrophages have impaired expression of pro-angiogenic gene programmes and increased expression of pro-inflammatory cytokines. Furthermore, we found that plasma levels of soluble TREM2 are elevated in DOCA-salt treated mice and humans with heart failure. Conclusions Together, our data provide an atlas of immunological alterations that can lead to improved diagnostic and therapeutic strategies for HFpEF. We provide our dataset in an easy to explore and freely accessible web application making it a useful resource for the community. Finally, our results suggest a novel cardioprotective role for Trem2 in hypertensive heart failure. [ABSTRACT FROM AUTHOR]

Platelets play crucial roles in the development and progression of coronary artery disease (CAD). The triggering receptor expressed in myeloid cells-like transcript-1 (TLT-1) is stored in platelet α granules, and activated platelets release a soluble fragment (sTLT-1). We set out to better characterize the constituent amino acids of sTLT-1 and to evaluate sTLT-1 for use as a biomarker in patients with stable CAD. We evaluated sTLT-1 release using immunoprecipitation and mass spectrometry and employed statistical methods to retrospectively correlate sTLT-1 concentrations, utilizing ELISA in plasma samples from 1510 patients with documented stable CAD. We identified TLT-1 residues to 133 in platelet releasates. ADAM17 cuts TLT-1, suggesting that S136 is the C-terminal amino acid in sTLT-1. Our results revealed that for CAD patients, sTLT-1 levels did not differ significantly according to primary outcomes of death or major cardiac event; however, patients with left ventricular (LV) dysfunction had significantly lower plasma sTLT-1 levels as compared to those with normal LV function (981.62 ± 1141 pg/mL vs. 1247.48 ± 1589 pg/mL; p = 0.003). When patients were stratified based on sTLT-1 peak frequency distribution (544 pg/mL), a significant association with congestive heart failure was identified (OR = 2.94; 1.040–8.282; p = 0.042), which could be explained by LV dysfunction. [ABSTRACT FROM AUTHOR]

Objective: It's a well‐known scientific statement that the heart and kidney functions are frequently tied together and the impairment of one directly alters the other. However, there exist knowledge gaps about this intricate pathophysiologic link and the exact unifying mechanism is not established. Herein, we aimed to investigate the presence of cardiorenal interaction at subclinical level while the conventional cardiac and renal clinical parameters are not disrupted yet in patients with hypertension. Methods: We chose a novel renal Doppler ultrasonographic parameter—augmented velocity index (Avi)—and an echocardiographic measure—ventriculoarterial coupling—which is complex to analyze but increasingly used after its acceptance about being a key determinant of cardiovascular efficiency. We recruited 137 patients without a previous history of antihypertensive medication use (47.4% women; median age, 49 years). Renal Avi, renal resistive index (RI), arterial elastance (Ea), ventricular elastance (Ees) and Ea/Ees (ventriculoarterial coupling) parameters were all examined. Results: Renal Avi, Ea, and Ea/Ees values were higher in females. Correlation analysis revealed that renal Avi was correlated with many hemodynamic variables including Ea and Ea/Ees. On multiple linear regression analysis, Ea and Ea/Ees remained as significant independent predictors of renal Avi but not of renal RI after adjustments for co‐variables (β = 0.488, P <.001 for Ea; β = 0.380, P <.001 for Ea/Ees). Conclusions: In comparison to renal RI, we suggest that renal Avi is a more reliable and promising index that can even measure subclinical changes in the cardiorenal circulation which needs to be elucidated. [ABSTRACT FROM AUTHOR]

Aims Patients with heart failure with preserved ejection fraction (HFpEF) are characterized by impaired diastolic function. Left ventricular (LV) strain–volume loops (SVL) represent the relation between strain and volume during the cardiac cycle and provide insight into systolic and diastolic function characteristics. In this study, we examined the association of SVL parameters and adverse events in HFpEF. Methods and results In 235 patients diagnosed with HFpEF, LV-SVL were constructed based on echocardiography images. The endpoint was a composite of all-cause mortality and Heart Failure (HF)-related hospitalization, which was extracted from electronic medical records. Cox-regression analysis was used to assess the association of SVL parameters and the composite endpoint, while adjusting for age, sex, and NYHA class. HFpEF patients (72.3% female) were 75.8 ± 6.9 years old, had a BMI of 29.9 ± 5.4 kg/m2, and a left ventricular ejection fraction of 60.3 ± 7.0%. Across 2.9 years (1.8–4.1) of follow-up, 73 Patients (31%) experienced an event. Early diastolic slope was significantly associated with adverse events [second quartile vs. first quartile: adjusted hazards ratio (HR) 0.42 (95%CI 0.20–0.88)] after adjusting for age, sex, and NYHA class. The association between LV peak strain and adverse events disappeared upon correction for potential confounders [adjusted HR 1.02 (95% CI 0.96–1.08)]. Conclusion Early diastolic slope, representing the relationship between changes in LV volume and strain during early diastole, but not other SVL-parameters, was associated with adverse events in patients with HFpEF during 2.9 years of follow-up. [ABSTRACT FROM AUTHOR]

Right heart failure is the leading cause of death in pulmonary hypertension (PH), and echocardiography is a commonly used tool for evaluating the risk hierarchy of PH. However, few studies have explored the dynamic changes in the structural and functional changes of the right heart during the process of PH. Previous studies have found that pulmonary circulation coupling right ventricular adaptation depends on the degree of pressure overload and other factors. In this study, we performed a time-dependent evaluation of right heart functional changes using transthoracic echocardiography in a SU5416 plus hypoxia (SuHx)-induced PH rat model. Rats were examined in 1-, 2-, 4-, and 6-week using right-heart catheterization, cardiac echocardiography, and harvested heart tissue. Our study found that echocardiographic measures of the right ventricle (RV) gradually worsened with the increase of right ventricular systolic pressure, and right heart hypofunction occurred at an earlier stage than pulmonary artery thickening during the development of PH. Furthermore, sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2), a marker of myocardial damage, was highly expressed in week 2 of SuHx-induced PH and had higher levels of expression of γ-H2AX at all timepoints, as well as higher levels of DDR-related proteins p-ATM and p53/p-p53 and p21 in week 4 and week 6. Our study demonstrates that the structure and function of the RV begin to deteriorate with DNA damage and cellular senescence during the early stages of PH development. [ABSTRACT FROM AUTHOR]

Vegetarians have less hypertension, diabetes mellitus and obesity, hence possibly lower risk of congestive heart failure (HF). We studied associations between vegetarian diets and echocardiographic markers of stage B HF. In a cross-sectional study, dietary pattern was ascertained by a validated FFQ. Echocardiograms were interpreted using standardised criteria. Participants were free-living subjects in Southern California who were older Adventist Health Study-2 cohort members. After exclusions, 133 subjects aged >60 years were enrolled. Their mean age was 72·7 (sd 8·7) years, 48·1 % were female, 32 % were African American and 71 % were vegetarian. Non-vegetarians had higher body weight (80·3 (sd 15·17) kg v. 71·3 (sd 16·2), P < 0·005), body surface area (1·92 (sd 0·24) m2 v. 1·81 (sd 0·22) m2, P = 0·01) and prevalence of hypertension (63 % v. 47 %, P = 0·10). Adjusting for age, sex, race and physical activity, it is found that vegetarians had greater echocardiographic mitral annular e' velocity (a measure of left ventricular (LV) relaxation) 7·44 v. 6·48 (non-vegetarian) cm/s (P = 0·011) and a yet greater contrast when vegans (7·66 cm/s, P = 0·011) were the group of interest. The ratio mid-to-late-diastolic mitral flow velocity (E/A) was also higher in vegans compared with non-vegetarians (1·02 and 0·84, respectively, P = 0·008). Mediation analyses suggested these associations may be partly related to higher blood pressures and BMI in the non-vegetarians. We conclude that vegetarians, especially vegans, appear to have better LV relaxation and fewer diastolic abnormalities than others. As dietary exposure is modifiable, one may speculate pending further investigation about the potential for reduction of stage B HF and later mortality. [ABSTRACT FROM AUTHOR]

Background: The manifestations, severity, and mortality of COVID-19 are considered to be associated with the changes in various hematological parameters and in immunity. Associations of immunoglobulin G antibodies against severe acute respiratory syndrome-linked coronavirus (IgG-SARS)-positive status with cardiac function and hematological and biochemical parameters in apparently health subjects are poorly understood. Methods: The present cross-sectional study included 307 healthy volunteers (24–69 years of age; 44.8 ± 8.6 years; 80.4% men) and was initiated in 2019 before the COVID-19 pandemic. COVID-19 episodes were confirmed by detection of IgG-SARS against SARS-CoV-2 S1 RBD to reveal 70 IgG-SARS-positive and 237 negative participants. Numerous ultrasound characteristics were assessed by echocardiography, and 15 hematological and biochemical parameters were assayed in the blood. Descriptive and comparative analysis was based on the IgG-SARS status of the participants. Results: The left ventricular mass index, mitral ratio of peak early to late diastolic filling velocity or flow velocity across the mitral valve, and deceleration time of early mitral inflow were decreased (p < 0.05) in IgG-SARS-positive participants versus those in IgG-SARS-negative participants according to multivariate logistic regression analysis. Erythrocyte sedimentation rate and platelet count were slightly increased, and blood hemoglobin was decreased in IgG-SARS-positive participants compared with those in IgG-SARS-negative participants. Conclusions: LV filling, inflammation, blood coagulation, and hemoglobin appear to be influenced by COVID-19 infection in healthy participants. Our observations contribute to the definition of vulnerabilities in the apparently healthy subjects with long COVID-19. These vulnerabilities may be more severe in patients with certain chronic diseases. [ABSTRACT FROM AUTHOR]

Iron deficiency (ID) is common during gestation and in early infancy and can alter developmental trajectories with lasting consequences on cardiovascular health. While the effects of ID and anemia on the mature heart are well documented, comparatively little is known about their effects and mechanisms on offspring cardiac development and function in the neonatal period. Female Sprague-Dawley rats were fed an iron-restricted or iron-replete diet before and during pregnancy. Cardiac function was assessed in a cohort of offspring on postnatal days (PD) 4, 14, and 28 by echocardiography; a separate cohort was euthanized for tissue collection and hearts underwent quantitative shotgun proteomic analysis. ID reduced body weight and increased relative heart weights at all time points assessed, despite recovering from anemia by PD28. Echocardiographic studies revealed unique functional impairments in ID male and female offspring, characterized by greater systolic dysfunction in the former and greater diastolic dysfunction in the latter. Proteomic analysis revealed down-regulation of structural components by ID, as well as enriched cellular responses to stress; in general, these effects were more pronounced in males. ID causes functional changes in the neonatal heart, which may reflect an inadequate or maladaptive compensation to anemia. This identifies systolic and diastolic dysfunction as comorbidities to perinatal ID anemia which may have important implications for both the short- and long-term cardiac health of newborn babies. Furthermore, therapies which improve cardiac output may mitigate the effects of ID on organ development. [ABSTRACT FROM AUTHOR]

Summary: Although studies have shown that continuous positive airway pressure (CPAP) therapy to treat obstructive sleep apnea improves left ventricular diastolic function, modifiers of improvement are unknown. We explored race and pre‐treatment 24‐h non‐dipping blood pressure status as modifiers of improved diastolic function. Participants (N = 220) with obstructive sleep apnea (apnea–hypopnea index ≥15 events/h) and hypertension were recruited to a cohort study that examined effects of 3‐month CPAP therapy on 24‐h blood pressure. Those who completed echocardiogram at baseline and follow‐up were included in this analysis. Diastolic function parameters (E, A, e′, E/A, E/e′) were assessed. Race was categorised to African American versus others. Participants were categorised as nocturnal dippers (night‐time blood pressure decrease by ≥10%) versus non‐dippers. We compared changes in parameters of diastolic function by race and nocturnal dipping status. A total of 92 participants were included. They were men (86%), African American (67.4%), and current smoker (29.5%). Mean apnea–hypopnea index was 32.9 events/h. Mean CPAP usage was 3.15 h/day. After 3 months of CPAP treatment, there were significant improvements in measures of diastolic function: a median (interquartile range [IQR]) increase in E velocity by 4.00 (−5.75 to 13.75) cm/s, an increase in e′ by 2.00 (0–4.00) cm/s, and a decrease in the E/e′ ratio by 1.74 (−4.27 to 0.00) at follow‐up (p < 0.05). These changes did not differ by race or nocturnal dipping status. Improvements in diastolic function after CPAP therapy did not differ by race or nocturnal dipping status. Further studies are needed to understand predictors of CPAP effects on diastolic function. [ABSTRACT FROM AUTHOR]

Epidemiological studies have established that exposure to tungsten increases the risk of developing cardiovascular diseases. However, no studies have investigated how tungsten affects cardiac function or the development of cardiovascular disease. Inhalation of tungsten particulates is relevant in occupational settings, and inhalation of particulate matter has a known causative role in driving cardiovascular disease. This study examined if acute inhalation to tungsten particulates affects cardiac function and leads to heart tissue alterations. Female BALB/c mice were exposed to Filtered Air or 1.5 ± 0.23 mg/m3 tungsten particles, using a whole-body inhalation chamber, 4 times over the course of two weeks. Inhalation exposure resulted in mild pulmonary inflammation characterized by an increased percentage and number of macrophages and metabolomic changes in the lungs. Cardiac output was significantly decreased in the tungsten-exposed group. Additionally, A′, an indicator of the amount of work required by the atria to fill the heart was elevated. Cardiac gene expression analysis revealed, tungsten exposure increased expression of pro-inflammatory cytokines, markers of remodeling and fibrosis, and oxidative stress genes. These data strongly suggest exposure to tungsten results in cardiac injury characterized by early signs of diastolic dysfunction. Functional findings are in parallel, demonstrating cardiac oxidative stress, inflammation, and early fibrotic changes. Tungsten accumulation data would suggest these cardiac changes are driven by systemic consequences of pulmonary damage. • Inhalation of tungsten particulates results in mild inflammation and metabolomic changes in the lungs. • Inhalation of tungsten results in early signs of cardiac injury (decreased cardiac output and increased atrial workload). • Tungsten increases expression of pro-inflammatory, cardiac remodeling, and oxidative stress genes in the heart. • Tungsten accumulation data would suggest these cardiac changes are driven by systemic consequences of pulmonary damage. [ABSTRACT FROM AUTHOR]

Hutchinson–Gilford Progeria Syndrome results in rapid aging and severe cardiovascular sequelae that accelerate near end-of-life. We found a progressive disease process in proximal elastic arteries that was less evident in distal muscular arteries. Changes in aortic structure and function were then associated with changes in transcriptomics assessed via both bulk and single cell RNA sequencing, which suggested a novel sequence of progressive aortic disease: adverse extracellular matrix remodeling followed by mechanical stress-induced smooth muscle cell death, leading a subset of remnant smooth muscle cells to an osteochondrogenic phenotype that results in an accumulation of proteoglycans that thickens the aortic wall and increases pulse wave velocity, with late calcification exacerbating these effects. Increased central artery pulse wave velocity is known to drive left ventricular diastolic dysfunction, the primary diagnosis in progeria children. It appears that mechanical stresses above ~ 80 kPa initiate this progressive aortic disease process, explaining why elastic lamellar structures that are organized early in development under low wall stresses appear to be nearly normal whereas other medial constituents worsen progressively in adulthood. Mitigating early mechanical stress-driven smooth muscle cell loss/phenotypic modulation promises to have important cardiovascular implications in progeria patients. [ABSTRACT FROM AUTHOR]

Background: The arrhythmogenic cardiomyopathy (ACM) phenotype, with life-threatening ventricular arrhythmias and heart failure, varies according to genetic aetiology. We aimed to characterise the phenotype associated with the variant c.1211dup (p.Val406Serfs*4) in the plakophilin‑2 gene (PKP2) and compare it with previously reported Dutch PKP2 founder variants. Methods: Clinical data were collected retrospectively from medical records of 106 PKP2 c.1211dup heterozygous carriers. Using data from the Netherlands ACM Registry, c.1211dup was compared with 3 other truncating PKP2 variants (c.235C > T (p.Arg79*), c.397C > T (p.Gln133*) and c.2489+1G > A (p.?)). Results: Of the 106 carriers, 47 (44%) were diagnosed with ACM, at a mean age of 41 years. By the end of follow-up, 29 (27%) had experienced sustained ventricular arrhythmias and 12 (11%) had developed heart failure, with male carriers showing significantly higher risks than females on these endpoints (p < 0.05). Based on available cardiac magnetic resonance imaging and echocardiographic data, 46% of the carriers showed either right ventricular dilatation and/or dysfunction, whereas a substantial minority (37%) had some form of left ventricular involvement. Both geographical distribution of carriers and haplotype analysis suggested PKP2 c.1211dup to be a founder variant originating from the South-Western coast of the Netherlands. Finally, a Cox proportional hazards model suggested significant differences in ventricular arrhythmia–free survival between 4 PKP2 founder variants, including c.1211dup. Conclusions: The PKP2 c.1211dup variant is a Dutch founder variant associated with a typical right-dominant ACM phenotype, but also left ventricular involvement, and a possibly more severe phenotype than other Dutch PKP2 founder variants. [ABSTRACT FROM AUTHOR]

Aim: Diabetic cardiomyopathy is a subset of heart disease that is directly associated with diabetes, and left ventricular diastolic dysfunction is the earliest sign. We aimed to investigate the association between sex differences and left ventricular diastolic function in patients with type 2 diabetes.Methods: This was a cross-sectional study included patients with type 2 diabetes who visit the National Metabolic Management Center (MMC) at the First People's Hospital of Yunnan from 2018 to 2021. Patients with hypertension, history of heart disease or ejection fraction < 50% were excluded from the study. Logistic regression was used to analyze their associations.Results: A total of 1778 patients were included in the study. The study included 1205 (70%) males and 573 (30%) females. Compared with males, females had higher total cholesterol and LDL cholesterol levels but lower diastolic pressure, body mass index (BMI), visceral fat area, HbA1c, blood urea nitrogen (BUN), serum creatinine and triglyceride. Females had a relatively higher ejection fraction than males (68.17 ± 6.055 vs 67.5 ± 6.096, P < 0.05). More female patients than male patients in the age group of 45– 60 years old had left ventricular diastolic dysfunction (female vs male, 54.5% vs 46.9%, P < 0.05). We also found that females were independently associated with left ventricular diastolic dysfunction, after adjusting for important clinical factors.Conclusion: Left ventricular diastolic function might be worse in female patients with type 2 diabetes. Further study is needed to verify the underlying mechanism. [ABSTRACT FROM AUTHOR]

The anti-fibrotic drug pirfenidone (PFD) is currently in clinical testing for the treatment of heart failure with preserved ejection fraction; however, its effects on human cardiac cells have not been fully investigated. Therefore, we aimed to characterize the impact of PFD on human cardiac fibroblasts (CF) in 2D culture as well as in 3D-engineered connective tissues (ECT). We analyzed proliferation by automated cell counting and changes in signaling by immunoblotting. We generated ECT with different geometries to modify the cellular phenotype and investigated the effects of PFD on cell number and viability as well as on cell cycle activity. We further studied its effect on ECT compaction, contraction, stiffening, and strain resistance by ECT imaging, pole deflection analysis, and ultimate tensile testing. Our data demonstrate that PFD inhibits human CF proliferation in a concentration-dependent manner with an IC50 of 0.43 mg/ml and its anti-mitogenic effect was further corroborated by an inhibition of MEK1/2, ERK1/2, and riboprotein S6 (rpS6) phosphorylation. In ECT, a lower cell cycle activity was found in PFD-treated ECT and fewer cells resided in these ECT after 5 days of culture compared to the control. Moreover, ECT compaction as well as ECT contraction was impaired. Consequently, biomechanical analyses demonstrated that PFD reduced the stiffness of ECT. Taken together, our data demonstrate that the anti-fibrotic action of PFD on human CF is based on its anti-mitogenic effect in 2D cultures and ECT. [ABSTRACT FROM AUTHOR]

Background: In patients undergoing incident hemodialysis, increased fibroblast growth factor-23 (FGF-23) levels are associated with the development of cardiovascular disease (CVD), but the influence of residual kidney function (RFK) on this association is unclear. This study aimed to investigate the association between FGF-23 levels, RKF, and CVD in patients undergoing prevalent hemodialysis. Methods: This cross-sectional and longitudinal observational study included 296 patients undergoing maintenance hemodialysis for at least three months who were followed up for a median of 44 months. RKF was defined as 24-h urine output >200 mL, left ventricular (LV) diastolic dysfunction as E/E' >15 on echocardiographic parameters. CVD was defined as hospitalization or emergency room visits due to cardiovascular causes, such as angina, myocardial infarction, or congestive heart failure. Results: The median intact FGF-23 (iFGF-23) level was 423.8 pg/mL (interquartile range, 171-1,443). Patients with an FGF-23 level > 423.8 pg/mL significantly had a lower proportion of RKF (39.2% vs. 60.1%, P < 0.001) and a higher proportion of LV diastolic dysfunction (54. 1% vs. 29.1%, P < 0.001) than those with an iFGF-23 level ≤ 423.8 pg/mL. The odds ratio (OR) for LV diastolic dysfunction was significantly higher in patients with RFK (OR per one-unit increase in the natural log-transformed iFGF-23 levels, 1.80; 95% confidence interval [CI]: 1.11-2.93) than in patients without RKF (OR per one-unit increase in the natural log-transformed iFGF-23 levels: 1.42; 95% CI: 1.01-1.99) in multivariate analysis (p < 0.001). During the follow-up period, 55 patients experienced CVD. The hazard ratio (HR) for CVD development was also significantly higher in patients with RKF (HR per one-unit increase in the natural log-transformed iFGF- 23 levels, 2.64; 95% CI: 1.29-5.40) than those without RKF (HR per one-unit increase in the natural log-transformed iFGF-23 levels: 1.44; 95% CI: 1.04-1.99) in multivariate analysis (p = 0.05). Conclusions: Increased iFGF-23 levels were associated with LV diastolic dysfunction and CVD development in patients undergoing prevalent hemodialysis; however, the loss of RKF attenuated the magnitude of these associations. Therefore, in these patients, RKF strongly influenced the detrimental role of iFGF-23 in the development of CVD. [ABSTRACT FROM AUTHOR]

Introduction: Cardiovascular mortality is significantly higher in patients with primary hyperparathyroidism (PHPT) compared to the general population. The role of the renin-angiotensin-aldosterone system (RAAS) as a mediator of cardiovascular pathology in PHPT is unclear, as is the question whether successful parathyroidectomy (PTX) mitigates hypertension (HT), and left-ventricular (LV) dysfunction. Methods: In 45 consecutive, hypercalcemic PHPT patients (91% female, 20 normotensive, mean age 54.6 ± 14.6), laboratory examinations, and 24 h ambulatory blood pressure monitoring (ABPM) were performed before, one and six months after successful PTX, while transthoracic echocardiography (TTE) pre- and six months post-PTX. Results: Both in patients with normotension (NT) and HT, lower calcemia and parathyroid hormone (PTH) as well as higher phosphatemia were observed on follow-up, while B-type natriuretic peptide, aldosterone, plasma renin activity, and aldosterone-to-renin ratios were comparable. Six months post-PTX, only in patients with HT, median 24-hour SBP/DBP decreased by 12/6 mmHg, daytime SBP by 10, and nighttime DBP by 5 mmHg. Improvement in BP was observed in approximately 78% of patients with HT. Six months post-PTX, TTE revealed: 1) decrease in median LV mass index (by 2 g/m2) and end-diastolic dimension (by 3 mm) among patients with HT; 2) normalization of global longitudinal strain in 22% of patients (comparable between those with NT and HT); 3) a mean 12.7% reduction in left-atrium volume index among patients with HT, which underlay normalization of indeterminate diastolic function in 3 out of 6 patients with HT, who exhibited it at baseline (dysfunction persisted in 2). Conclusions: PTX was shown to significantly reduce BP, LV hypertrophy and diastolic dysfunction parameters in PHPT patients with HT, and improve systolic function in all PHPT patients. [ABSTRACT FROM AUTHOR]

Background: Infants with single‐ventricle (SV) physiology undergo the 3‐stage Fontan surgery. Norwood patients, who have completed the first stage, face the highest interstage mortality. The Berlin Heart EXCOR (BH), a pediatric pulsatile ventricular assist device, has shown promise in supporting these patients. However, clinical questions regarding device configurations prevent optimal support. Methods: We developed a combined idealized mechanics‐lumped parameter model of a Norwood patient and simulated two additional patient‐specific cases: pulmonary hypertension (PH) and post‐operative treatment with milrinone. We quantified the effects of BH support across different device volumes, rates, and inflow connections on patient hemodynamics and BH performance. Results: Increasing device volume and rate increased cardiac output, but with unsubstantial changes in specific arterial oxygen content. We identified distinct SV–BH interactions that may impact patient myocardial health and contribute to poor clinical outcomes. Our results suggested BH settings for patients with PH and for patients treated post‐operatively with milrinone. Conclusions: We present a computational model to characterize and quantify patient hemodynamics and BH support for infants with Norwood physiology. Our results emphasized that oxygen delivery does not increase with BH rate or volume, which may not meet patient needs and contribute to suboptimal clinical outcomes. Our findings demonstrated that an atrial BH may provide optimal cardiac loading for patients with diastolic dysfunction. Meanwhile, a ventricular BH decreased active stress in the myocardium and countered the effects of milrinone. Patients with PH showed greater sensitivity to device volume. In this work, we demonstrate the adaptability of our model to analyze BH support across varied clinical situations. [ABSTRACT FROM AUTHOR]

We investigated the acute cardiac consequences of a long-duration (>5 h) adventure race in adolescent athletes from evaluations of left ventricular (LV) strains and myocardial work. Twenty trained male adolescents (i.e. 8 ± 4 h·week−1 of endurance sports) aged 14–17 years participated in a competitive long-duration adventure race. Blood samples were collected before, immediately and 24 h after the race to determine the time course of troponin I (cTnI) considered a myocardial damage biomarker. Resting echocardiography was conducted before and after the race to assess myocardial regional strains, LV twisting mechanics and myocardial work using speckle tracking echocardiography. The mean completion time of the race was 05:38 ± 00:20 h, with a mean heart rate (HR) of 83 ± 5% of maximal HR. cTnI concentration significantly increased in 16/20 participants after the race (pre: 0.001 ± 0.002 vs. post: 0.244 ± 0.203 ng·dL−1, p <.001) and returned to baseline within 24 h. Stroke volume, ejection fraction and global longitudinal strains remained unchanged after the race, while LV twist and global myocardial work significantly decreased (8.6 ± 3.3 vs. 6.3 ± 3.3 deg and 2080 ± 250 vs. 1781 ± 334 mmHg%, p <.05). Diastolic function, indexes of myocardial relaxation and LV untwisting rate (−91.0 ± 19.0 vs. −56.4 ± 29.1 deg·s−1, p <.001) were affected after the race. We demonstrated that in trained adolescents, a high-intensity endurance exercise of several hours induced an increase of the cTnI concentration associated with an alteration of myocardial function. Highlights This is the first study to explore the acute cardiac consequences of a very-long duration and high-intensity race in trained adolescents The cardiac evaluations before and immediately after the race were conducted using up-to-date advances in echocardiography, including not only regional left ventricular strains, rotations and twists, but also global myocardial work to consider changes in loading conditions that occur after such exercises. We observed exercise-induced cardiac fatigue in the adolescents, characterized by a drop in myocardial work, associated with an increase of cardiac troponin I in 16/20 participants. The cardiac alterations were principally observed at the apical level of the heart: the apical strains and rotations were decreased and delayed. Consequently, left ventricular twist and twisting rates were also delayed, which probably affected the diastolic function after the race. [ABSTRACT FROM AUTHOR]

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The shape of the left ventricle (LV) of a cardiac magnetic resonance image (CMRI) helps physicians to diagnose different cardiac abnormalities. The similarity of pixel intensity and shape of LV with neighbor tissues, the imprecision of boundaries, and the presence of noise are the challenges to accurate segmentation of LV. This paper contributes to the successful implementation of an automatic edge contouring method to segment LV area from CMRI and detect whether the ventricle belongs to abnormalities. This method proposes the regression-based artificial neural network to predict the possible initial position of the deformable edge-based active contour model for precise segmentation of the LV. Using the segmented shapes of the LV from a series of CMRI slices, LV volumes are estimated to find the end-diastole and end-systole volumes. From the volumetric features of normal LV as a reference, the proposed work decides the patient's abnormalities with their corresponding CMRI images. The proposed method has been applied to a renowned database and found an overall prediction accuracy of 85.7%, as well as the accuracy for abnormality detection, which is 92.9%. The result is convincing for clinical applications to replace the manual efforts in LV-related abnormalities detection from CMRI images. [ABSTRACT FROM AUTHOR]

Background: The use of simultaneous veno-arterial extracorporeal membrane oxygenation (ECMO) with or without an Intra-Aortic Balloon Pump (IABP) is a widely used tool for mechanical hemodynamic support. Endothelial function, especially in relation to different cannulation techniques, is rarely investigated in the setting of extracorporeal life support (ECLS). In this study, we analyzed endothelial function in relation to hemodynamic and laboratory parameters for central and peripheral ECMO, with or without concomitant IABP support in a large animal model to gain a better understanding of the underlying basic mechanisms. Methods: In this large animal model, healthy female pigs with preserved ejection fraction were divided into the following groups related to cannulation strategy for ECMO and simultaneous IBAP support: control (no ECMO, no IABP), peripheral ECMO (pECMO), central ECMO (cECMO), pECMO and IABP or cECMO and IABP. During the experimental setting, the blood flow in the ascending aorta, left coronary artery and arteria carotis was measured. Afterwards, endothelial function was investigated after harvesting the right coronary artery, arteria carotis and renal artery. In addition, laboratory markers, such as creatine kinase (CK), creatine kinase muscle–brain (CK-MB), troponin, creatinine and endothelin were analyzed. Results: The blood flow in the ascending aorta and the left coronary artery was significantly lower in all discussed experimental settings compared to the control group. Of note, the cECMO cannulation strategy generated favorable hemodynamic circumstances with higher blood flow in the coronary arteries than pECMO regardless of flow circumstances in the ascending aorta. The concomitant usage of IABP did not result in an improvement of the coronary blood flow, but partially showed a negative impact on the endothelial function of coronary arteries in comparison to the control. These findings correlate to higher CK/CK-MB levels in the setting of cECMO + IABP and pECMO + IABP. Conclusions: The usage of mechanical circulatory support with concomitant ECMO and IABP in a large animal model might have an influence on the endothelial function of coronary arteries while not improving the coronary artery perfusion in healthy hearts with preserved ejection. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) as a chemotherapeutic agent can cause mitochondrial dysfunction and heart failure. COX5A has been described as an important regulator of mitochondrial energy metabolism. We investigate the roles of COX5A in DOX-induced cardiomyopathy and explore the underlying mechanisms. C57BL/6J mice and H9c2 cardiomyoblasts were treated with DOX, and the COX5A expression was assessed. An adeno-associated virus serum type 9 (AAV9) and lenti-virus system were used to upregulate COX5A expression. Echocardiographic parameters, morphological and histological analyses, transmission electron microscope and immunofluorescence assays were used to assess cardiac and mitochondrial function. In a human study, we found that cardiac COX5A expression was dramatically decreased in patients with end-stage dilated cardiomyopathy (DCM) compared to the control group. COX5A was significantly downregulated following DOX stimulation in the heart of mice and H9c2 cells. Reduced cardiac function, decreased myocardium glucose uptake, mitochondrial morphology disturbance, reduced activity of mitochondrial cytochrome c oxidase (COX) and lowered ATP content were detected after DOX stimulation in mice, which could be significantly improved by overexpression of COX5A. Overexpression of COX5A effectively protected against DOX-induced oxidative stress, mitochondrial dysfunction and cardiomyocyte apoptosis in vivo and in vitro. Mechanistically, the phosphorylation of Akt (Thr308) and Akt (Ser473) were also decreased following DOX treatment, which could be reserved by the upregulation of COX5A. Furthermore, PI3K inhibitors abrogated the protection effects of COX5A against DOX-induced cardiotoxicity in H9c2 cells. Thus, we identified that PI3K/Akt signaling was responsible for the COX5A-mediated protective role in DOX-induced cardiomyopathy. These results demonstrated the protective effect of COX5A in mitochondrial dysfunction, oxidative stress, and cardiomyocyte apoptosis, providing a potential therapeutic target in DOX-induced cardiomyopathy. [ABSTRACT FROM AUTHOR]

Volume status, congestion, endothelial activation, and injury all play roles in glomerular filtration rate (GFR) decline. In this study, we aimed to determine whether the plasma endothelial and overhydration markers could serve as independent predictors for dialysis initiation in patients with chronic kidney disease (CKD) 3b-5 (GFR < 45 mL/min/1.72 m2) and preserved ejection fraction. A prospective, observational study in a single academic center was conducted from March 2019 to March 2022. Plasma levels of angiopoietin (Ang)-2, Vascular Endothelial Growth Factor-C (VEGF-C), Vascular Cell Adhesion Molecule-1 (VCAM-1), Copeptin (CPP), beta-trace protein (BTP), brain natriuretic peptide (BNP), and cardiac troponin I (cTnI) were all measured. Lung ultrasound (US) B-lines, bioimpedance, and echocardiography with global longitudinal strain (GLS) were recorded. The study outcome was the initiation of chronic dialysis (renal replacement therapy) during 24 months of follow-up. A total of 105 consecutive patients with a mean eGFR of 21.3 mL/min/1.73 m were recruited and finally analyzed. A positive correlation between Ang-2 and VCAM-1 and BTP was observed. Ang-2 correlated positively with BNP, cTnI, sCr, E/e′, and the extracellular water (ECW)/intracellular water (ICW) ratio (ECW/ICW). After 24 months, a deterioration in renal function was observed in 47 patients (58%). In multivariate regression analysis, both VCAM-1 and Ang-2 showed independent influences on risk of renal replacement therapy initiation. In a Kaplan-Meier analysis, 72% of patients with Ang-2 concentrations below the median (3.15 ng/mL) survived without dialysis for two years. Such an impact was not observed for GFR, VCAM, CCP, VEGF-C, or BTP. Endothelial activation, quantified by plasma levels of Ang-2, may play a key role in GFR decline and the need for dialysis initiation in patients with CKD 3b, 4, and 5. [ABSTRACT FROM AUTHOR]

Disagreement exists regarding the long-term prognosis and recovery of left ventricular (LV) function in patients with fulminant myocarditis (FM). This study reported the outcome and LV ejection fraction (EF) changes in FM treated with Chinese protocol, and assessed whether global longitudinal strain (GLS) by two-dimensional speckle tracking echocardiography (2-D STE) could provide additional information. This retrospective study included 46 FM adult patients who applied timely circulatory support and immunomodulatory therapy with adequate doses of both glucocorticoids and immunoglobulins as core approaches and survived after acute phase. They all presented with acute onset of cardiac symptoms < 2 weeks. LV end-diastolic dimensions, LVEF and GLS at discharge and 2-year were obtained and compared. We then performed linear regression and ROC analysis to determine independent factors to predict normalization of GLS at 2-year. At 2 years, the survival was 100% in our cohort. And the GLS improved modestly (15.40 ± 3.89% vs 17.24 ± 2.89%, P = 0.002). At two years, a proportion of patients whose LV function remained abnormal, being 22% evaluated by EF (< 55%) and higher to 37% by GLS (< 17%). Moreover, GLS at discharge but not at presentation correlated with GLS at 2-year (r = 0.402, P = 0.007). The FM adult treated with Chinese protocol have good survival and modest improvement of LV function during 2-year. [ABSTRACT FROM AUTHOR]

The mineralocorticoid receptor is a steroid hormone receptor that contributes to cardiac tissue inflammation, fibrosis, and cardiac dysfunction and plays an important role in the pathophysiology of heart failure. Mineralocorticoid receptor antagonists (MRA) are an important component of guideline‐directed medical therapy for heart failure to improve clinical outcomes. Clinical trial evidence in heart failure with reduced ejection fraction (HFrEF) informed a strong guideline recommendation for use of MRA in symptomatic patients, barring contraindications. In heart failure with mildly reduced ejection fraction (HFmrEF) and in heart failure with preserved ejection fraction (HFpEF), data are less robust, and this drug class received a weaker recommendation in the heart failure treatment guidelines. Thus, careful selection of patients with HFmrEF/HFpEF who are most likely to benefit from MRA is paramount to better optimize use of these medications. The purpose of this narrative review is to outline the rationale for the use of MRA in heart failure, summarize the clinical trial evidence for MRA in HFmrEF/HFpEF, discuss clinical considerations for their use, and describe investigations of nonsteroidal MRA in HFmrEF/HFpEF. [ABSTRACT FROM AUTHOR]

This suggests that the FGF23-mediated activation of the local RAAS may be a novel therapeutic target for preventing or treating cardiac hypertrophy and fibrosis in patients with CKD or other conditions associated with FGF23 dysregulation. Gulati et al. [[14]] explored the relationship between chronic obstructive pulmonary disease (COPD) exacerbations and circulating FGF23 levels across a cohort of 70 stable COPD patients. In individuals with elevated FGF23 levels, such as those with chronic kidney disease (CKD), FGF23 may contribute to systemic inflammation by activating immune cells and inducing the production of pro-inflammatory cytokines [[5], [7]]. Fibroblast growth factors (FGFs) and their cognate receptors (FGFRs) are important biological molecules with a wide array of pleiotropic functions. [Extracted from the article]

Moreover, they focus on the effects of insulin resistance and chronic hyperglycemia in determining micro- and macrovascular complications (cardiovascular disease, heart failure, hypertension, chronic kidney disease, and atherosclerosis). The Special Issue "Metabolic Regulation in the Development of Cardiovascular Disease and Heart Failure" focused on how metabolic diseases could cause a predisposition to cardiovascular diseases and, in particular, heart failure due to systolic or diastolic dysfunction or a combination thereof. In patients with chronic HF, a significant negative correlation was observed between PACAP and NT-proBNP levels, whereas the correlation was positive in patients with acute HF. The original article of Szabó et al. [[7]] evaluated the role of pituitary adenylate cyclase-activating polypeptide (PACAP) and its specific PAC1 receptor in the plasma and myocardial tissue of patients with heart failure (HF). [Extracted from the article]

Background: The existing algorithm for defining exercise‐induced diastolic dysfunction incorporates resting e' velocity as a surrogate of myocardial relaxation. The additive prognostic value of incorporating post‐exercise e' velocity in definition of exercise‐induced diastolic dysfunction is poorly studied. Aim: To define the additive prognostic value of post‐exercise e' septal velocity in the assessment of exercise‐induced diastolic dysfunction compared to the traditional approach. Methods: This retrospective study included 1409 patients undergoing exercise treadmill echocardiography with available full set of diastolic variables. Doppler measures of diastolic function included resting septal e' velocity, post‐exercise septal e' velocity, post‐exercise E/e' ratio, and post‐exercise tricuspid regurgitant jet velocity. Approaches incorporating resting septal e' velocity and post‐exercise septal e' velocity were compared in defining exercise‐induced diastolic dysfunction, and for association with adverse cardiovascular outcomes. Results: The mean age of study subjects was 56.3 ± 16.5 years and 791 (56%) patients were women. A total of 524 patients had disagreement between resting and post exercise septal e' velocities, and these values showed only weak agreement (kappa statistics:.28, P =.02). All categories of the traditional exercise‐induced DD approach incorporating resting septal e' velocity witnessed reclassification when exercise septal e' velocity was used. When both approaches were compared, increased event rates were only evident when both approaches agreed on exercise‐induced diastolic dysfunction (HR: 1.92, P <.001, 95% CI: 1.37–2.69). This association persisted after multivariable adjustment and propensity score matching for covariates. Conclusion: Incorporation of post‐exercise e' velocity into the set of variables defining exercise‐induced diastolic dysfunction can improve the prognostic utility of diastolic function assessment. [ABSTRACT FROM AUTHOR]

Uremic cardiomyopathy (UC), the peculiar cardiac remodeling secondary to the systemic effects of renal dysfunction, is characterized by left ventricular (LV) diffuse fibrosis with hypertrophy (LVH) and stiffness and the development of heart failure and increased rates of cardiovascular mortality. Several imaging modalities can be used to obtain a non-invasive assessment of UC by different imaging biomarkers, which is the focus of the present review. Echocardiography has been largely employed in recent decades, especially for the determination of LVH by 2-dimensional imaging and diastolic dysfunction by pulsed-wave and tissue Doppler, where it retains a robust prognostic value; more recent techniques include parametric assessment of cardiac deformation by speckle tracking echocardiography and the use of 3D-imaging. Cardiac magnetic resonance (CMR) imaging allows a more accurate assessment of cardiac dimensions, including the right heart, and deformation by feature-tracking imaging; however, the most evident added value of CMR remains tissue characterization. T1 mapping demonstrated diffuse fibrosis in CKD patients, increasing with the worsening of renal disease and evident even in early stages of the disease, with few, but emerging, prognostic data. Some studies using T2 mapping highlighted the presence of subtle, diffuse myocardial edema. Finally, computed tomography, though rarely used to specifically assess UC, might provide incidental findings carrying prognostic relevance, including information on cardiac and vascular calcification. In summary, non-invasive cardiovascular imaging provides a wealth of imaging biomarkers for the characterization and risk-stratification of UC; integrating results from different imaging techniques can aid a better understanding of the physiopathology of UC and improve the clinical management of patients with CKD. [ABSTRACT FROM AUTHOR]

Introduction and Aims : Dilated cardiomyopathy (DCM) is an important cause of heart failure (HF) among children. Research on pediatric DCM remains surprisingly scarce. The primary objective of the study was to evaluate the clinical profile and outcomes of pediatric DCM and the secondary objective was to study the predictors of outcome. Methods and Results : We enrolled all patients with cardiomyopathy who presented to us between 1990 and 2020 and were younger than 18 years. During the 30-year study period, we identified 233 cases of pediatric cardiomyopathy. One hundred and nineteen (51%) cases had DCM. This retrospective cohort was analyzed to study their outcome and the possible predictors of outcome. Nearly, 8% presented in the neonatal period, and 37% in infancy. The most common mode of presentation was dyspnea on exertion (71%). Ninety-three patients presented in heart failure (78%). The median left ventricular dimension z-score in diastole was 4.3 (range 2.5--9.06). The median left ventricle (LV) ejection fraction was 31%. Seventy-two percent of this cohort were on angiotensin-converting-enzyme inhibitors, 40% on aldosterone antagonists, and 47% on beta-blockers. One-third had syndromic, metabolic, genetic, or any secondary cause identified. Twenty-seven patients satisfied the three-tiered clinical classification for the diagnosis of probable acute myocarditis. Over a mean follow-up of 3.29 years, 27% were lost to follow-up. Among the remaining patients who were on follow-up (n = 86), 39 (45%) died, 31 (36%) recovered, and 16 (18%) had persistent LV dysfunction. Heart Failure was the most common cause of death. Eight patients in this cohort (4.2%) had thromboembolic phenomena. Nine had sustained ventricular arrhythmias and six had atrial/junctional arrhythmias. Among the various risk factors studied, only infantile onset had a significant relationship with death or ventricular arrhythmias (P value-- 0.05). The 5-year survival rate of DCM patients was 59%. Conclusion : A reasonably good percentage of our population showed recovery of the left ventricular function (36%). Only infantile onset had a significant relationship with death or ventricular arrhythmias. The outcome in our DCM cohort is similar to other population cohorts. [ABSTRACT FROM AUTHOR]

To measure the left atrial (LA) function in patients with hypertrophic cardiomyopathy (HCM; with [OHCM] and without obstruction [NOHCM]) and hypertension-related left ventricular hypertrophy (H-LVH) using cardiovascular magnetic resonance imaging feature tracking (CMR-FT). Patients who met the criteria for HCM (n= 68), H-LVH (n= 46), and 30 healthy controls participated. Left atrial strain was analysed using CMR-FT in cine images with two and four chambers. The strain rate and LA strain measurements showed that patients with HCM, and H-LVH had impaired conduit and reservoir functions (versus controls). These capacities were more severely impaired in OHCM than those seen in NOHCM and H-LVH. The LA volume parameters (LAVIpac, LAVImin and LAVImax) from the OHCM group were higher than both the NOHCM and H-LVH groups (all p< 0.05). There were differences between the OHCM and H-LVH groups in terms of the parameters for LA reservoir function (εs), booster pump function (SRa), and conduit function (SRe, LA passive EF, εe; p< 0.05). The strongest correlations included the associations between LA total EF and εs, εe and LA passive EF, and SRe and LA passive EF. CMR-FT can reliably identify LA dysfunction and deformation in the early stages of HCM and H-LVH. • CMR-FT can be employed to evaluate left atrial dysfunction and deformation • Early differential diagnosis of hypertension and hypertrophic cardiomyopathy • Myocardial strain is a sensitive indicator of early impairment of cardiac function • The left atrial strain parameter may be able to identify lesions earlier [ABSTRACT FROM AUTHOR]

Background: Monochorionic diamniotic (MCDA) twin pregnancies are considered high-risk for several reasons, especially the risk of twin-to-twin transfusion syndrome (TTTS). Renal artery Doppler (RAD) is reported as a useful tool for predicting oligohydramnios in singleton pregnancies. We aimed to compare the RAD indices between MCDA twins with and without TTTS. Materials and Methods: In this case--control study, all pregnant women aged 18--38 years, with gestational age ≥ 18 weeks, who were referred to two Prenatal Clinics, Alzahra and Beheshti Educational Hospitals, affiliated to Isfahan University of Medical Sciences, Isfahan, Iran, October 2020--March 2022 were enrolled; the women with MCDA twin pregnancies complicated by TTTS (case group, n = 12) and without TTTS (control group, n = 24). For each twin, biometric analysis, fetal weight, and Doppler study of fetal arteries, including RAD, middle cerebral artery (MCA), umbilical artery, and ductus venosus were performed. Peak systolic velocity, Pulsatility index (PI), resistance index (RI), and systole/diastole (S/D) were measured for all arteries. Results: The donors of the case group had a lower mean MCA S/D (4.48 ± 1.89) than the control group (6.48 ± 1.97) (P = 0.01) and higher mean umbilical parameters, including PI, RI, and S/D (P < 0.05). The recipients of the case group had a lower mean renal PI than the control (P = 0.008) and lower mean MCA PI, RI, and S/D (P < 0.05). The donor group had a higher mean umbilical RI and S/D than the recipient twin, while the mean fetal weight of the recipient group was higher (P < 0.05). Conclusion: Comparing the RAD parameters between the twins with and without TTTS in the present study did not identify significant results, which rejected the primary hypothesis. Among all RAD parameters, the only significant difference observed in the present study was the lower RAD PI in RT, which cannot suggest this measurement as a valuable tool for the prediction of TTTS in MCDA twins. Therefore, the results of the present study failed to show the additional value of RAD, compared with the conventional Doppler examination of fetal arteries. Further studies are required to prove this conclusion. [ABSTRACT FROM AUTHOR]

Objectives: To identify the inflow (filling time fraction [FTF] and E/A ratio) characteristics of fetuses with anemia, and to evaluate the performance of the inflow markers in predicting the affected fetuses. Methods: Fetuses at risk of hemoglobin (Hb) Bart's disease at 17–22 weeks were prospectively recruited to undergo echocardiography before diagnostic cordocentesis. Cardiac Doppler images were digitally stored for off‐line blinded measurements of FTF and E/A ratio. Results: A total of 428 fetuses at risk of Hb Bart's disease were analyzed, including 88 affected fetuses (20.6%). The mean gestational age at the time of diagnosis was 19.43 ± 1.5 weeks. The FTFs in both sides were significantly lower in the affected fetuses, whereas the E/A ratios of both sides were significantly higher in the affected group. According to the receiver operating characteristic curves, the performance of the FTF of the right side in predicting affected fetuses was slightly better than that of the left side (area under curve: 0.707 versus 0.680, P <.001). Likewise, the performance of the E/A ratio of the tricuspid valve was slightly better than that of the mitral valve. Also, FTF was superior to E/A ratio in predicting the affected fetuses. Conclusions: New insights leading to a better understanding of the fetal cardiac response to anemia are: 1) the FTFs in both sides were significantly decreased, suggesting some degree of diastolic ventricular dysfunction; 2) the E/A ratios of both sides were significantly increased, indicating volume load; and 3) The inflow parameters may be useful as a new predictor of fetal anemia, especially among pregnancies at risk. [ABSTRACT FROM AUTHOR]

Background: Recently, a novel left atrioventricular coupling index (LACI) has been introduced providing prognostic value to predict cardiovascular events beyond common risk factors in patients without cardiovascular disease. Since data on cardiovascular magnetic resonance (CMR)-derived LACI in patients following acute myocardial infarction (AMI) are scarce, we aimed to assess the diagnostic and prognostic implications of LACI in a large AMI patient cohort. Methods: In total, 1046 patients following AMI were included. After primary percutaneous coronary intervention CMR imaging and subsequent functional analyses were performed. LACI was defined by the ratio of the left atrial end-diastolic volume divided by the left ventricular (LV) end-diastolic volume. Major adverse cardiac events (MACE) including death, reinfarction or heart failure within 12 months after the index event were defined as primary clinical endpoint. Results: LACI was significantly higher in patients with MACE compared to those without MACE (p < 0.001). Youden Index identified an optimal LACI cut-off at 34.7% to classify patients at high-risk (p < 0.001 on log-rank testing). Greater LACI was associated with MACE on univariate regression modeling (HR 8.1, 95% CI 3.4–14.9, p < 0.001) and after adjusting for baseline confounders and LV ejection fraction (LVEF) on multivariate regression analyses (HR 3.1 95% CI 1.0–9, p = 0.049). Furthermore, LACI assessment enabled further risk stratification in high-risk patients with impaired LV systolic function (LVEF ≤ 35%; p < 0.001 on log-rank testing). Conclusion: Atrial-ventricular interaction using CMR-derived LACI is a superior measure of outcome beyond LVEF especially in high-risk patients following AMI. Trial registration ClinicalTrials.gov, NCT00712101 and NCT01612312 [ABSTRACT FROM AUTHOR]

Premature ventricular contractions (PVC) are frequently seen in children. We evaluated left ventricular diastolic function in PVC children with normal left ventricular systolic function to detect whether diastolic function disturbances affect physical performance. The study group consisted of 36 PVC children, and the control group comprised 33 healthy volunteers. Echocardiographic diastolic function parameters such as left atrial volume index (LAVI), left atrial strains (AC-R, AC-CT, AC-CD), E wave, E deceleration time (Edt), E/E' ratio, and isovolumic relaxation time (IVRT) were measured. In the cardiopulmonary exercise test (CPET), oxygen uptake (VO2 max) was registered. Evaluation of diastolic function parameters revealed statically significant differences between the patients and controls regarding Edt (176.58 ± 54.8 ms vs. 136.94 ± 27.8 ms, p < 0.01), E/E' (12.6 ± 3.0 vs. 6.7 ± 1.0, p < 0.01), and IVRT (96.6 ± 19.09 ms. vs. 72.86 ± 13.67 ms, p < 0.01). Left atrial function was impaired in the study group compared to controls: LAVI (25.3 ± 8.2 ml/m2 vs. 19.2 ± 7.5 ml/m2, p < 0.01), AC-CT (34.8 ± 8.6% vs. 44.8 ± 11.8%, p < 0.01), and AC-R-(6.0 ± 4.9% vs. −11.5 ± 3.5%, p < 0.01), respectively. VO2 max in the study group reached 33.1 ± 6.2 ml/min/kg. A statistically significant, moderate, negative correlation between VO2 max and E/E' (r = −0.33, p = 0.02) was found. Left ventricular diastolic function is impaired and deteriorates with the arrhythmia burden increase in PVC children. Ventricular arrhythmia in young individuals may be related to the filling pressure elevation and drive to exercise capacity deterioration. [ABSTRACT FROM AUTHOR]

Background: Inflammation has been associated with progression and complications of chronic heart failure (HF) but no effective therapy has yet been identified to treat this dysregulated immunologic state. The selective cytopheretic device (SCD) provides extracorporeal autologous cell processing to lessen the burden of inflammatory activity of circulating leukocytes of the innate immunologic system. Aim: The objective of this study was to evaluate the effects of the SCD as an extracorporeal immunomodulatory device on the immune dysregulated state of HF. HF. Methods and results: SCD treatment in a canine model of systolic HF or HF with reduced ejection fraction (HFrEF) diminished leukocyte inflammatory activity and enhanced cardiac performance as measured by left ventricular (LV) ejection fraction and stroke volume (SV) up to 4 weeks after treatment initiation. Translation of these observations in first in human, proof of concept clinical study was evaluated in a patient with severe HFrEFHFrEF ineligible for cardiac transplantation or LV LV assist device (LVAD) due to renal insufficiency and right ventricular dysfunction. Six hour SCD treatments over 6 consecutive days resulted in selective removal of inflammatory neutrophils and monocytes and reduction in key plasma cytokines, including tumor necrosis factor-alpha (TNF-α),), interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1. These immunologic changes were associated with significant improvements in cardiac power output, right ventricular stroke work index, cardiac index and LVSV index.... Stabilization of renal function with progressive volume removal permitted successful LVAD implantation. Conclusion: This translational research study demonstrates a promising immunomodulatory approach to improve cardiac performance in HFrEFHFrEF and supports the important role of inflammation in the progression of HFHF. [ABSTRACT FROM AUTHOR]

NIMA (never in mitosis, gene A)-related kinase-6 (NEK6), a cell cycle regulatory gene, was found to regulate cardiac hypertrophy. However, its role in diabetes-induced cardiomyopathy has not been fully elucidated. This research was designed to illustrate the effect of NEK6 involved in diabetic cardiomyopathy. Here we used a streptozotocin (STZ)-induced mice diabetic cardiomyopathy model and NEK6 knockout mice to explore the role and mechanism of NEK6 in diabetic-induced cardiomyopathy. NEK6 knockout mice and wild-type littermates were subjected to STZ injection (50 mg/kg/day for 5 days) to induce a diabetic cardiomyopathy model. As a result, 4 months after final STZ injection, DCM mice revealed cardiac hypertrophy, fibrosis, and systolic and diastolic dysfunction. NEK6 deficiency causes deteriorated cardiac hypertrophy, fibrosis, and cardiac dysfunction. Furthermore, we observed inflammation and oxidative stress in the hearts of NEK6 deficiency mice under diabetic cardiomyopathy pathology. Adenovirus was used to upregulate NEK6 in neonatal rat cardiomyocytes, and it was found that NEK6 ameliorated high glucose-induced inflammation and oxidative stress. Our findings revealed that NEK6 increased the phosphorylation of heat shock protein 72 (HSP72) and increased the protein level of PGC-1α and NRF2. Co-IP assay experiment confirmed that NEK6 interacted with HSP72. When HSP72 was silenced, the anti-inflammation and anti-oxidative stress effects of NEK6 were blurred. In summary, NEK6 may protect diabetic-induced cardiomyopathy by interacting with HSP72 and promoting the HSP72/PGC-1α/NRF2 signaling. Key messages: NEK6 knockout deteriorated cardiac dysfunction, cardiac hypertrophy, fibrosis as well as inflammation response, and oxidative stress. NEK6 overexpression attenuated high glucose induced inflammation and oxidative stress. The underlying mechanisms of the protective role of NEK6 in the development of diabetic cardiomyopathy seem to involve the regulation of HSP72-NRF2- PGC-1α pathway. NEK6 may become a new therapeutic target for diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

BACKGROUND: The prognostic utility of follow-up transthoracic echocardiography (FUTTE) in patients with hypertrophic cardiomyopathy (HCM) is unclear, specifically in terms of whether changes in echocardiographic parameters in routine FU-TTE parameters are associated with cardiovascular outcomes. METHODS: From 2010 to 2017, 162 patients with HCM were retrospectively enrolled in this study. Using echocardiography, HCM was diagnosed based on morphological criteria. Patients with other diseases that cause cardiac hypertrophy were excluded. TTE parameters at baseline and FU were analyzed. FU-TTE was designated as the last recorded value in patients who did not develop any cardiovascular event or the latest exam before event development. Clinical outcomes were acute heart failure, cardiac death, arrhythmia, ischemic stroke, and cardiogenic syncope. RESULTS: Median interval between the baseline TTE and FU-TTE was 3.3 years. Median clinical FU duration was 4.7 years. Septal trans-mitral velocity/mitral annular tissue Doppler velocity (E/e'), tricuspid regurgitation velocity, left ventricular ejection fraction (LVEF), and left atrial volume index (LAVI) at baseline were recorded. LVEF, LAVI, and E/e' values were associated with poor outcomes. However, no delta values predicted HCMrelated cardiovascular outcomes. Logistic regression models incorporating changes in TTE parameters had no significant findings. Baseline LAVI was the best predictor of a poor prognosis. In survival analysis, an already enlarged or increased size LAVI was associated with poorer clinical outcomes. CONCLUSIONS: Changes in echocardiographic parameters extracted from TTE did not assist in predicting clinical outcomes. Cross-sectionally evaluated TTE parameters were superior to changes in TTE parameters between baseline and FU at predicting cardiovascular events. [ABSTRACT FROM AUTHOR]