Significant Disagreement Between Conventional Parameters and 3D Echocardiography-Derived Ejection Fraction in the Detection of Right Ventricular Systolic Dysfunction and Its Association With Outcomes.

AIMS: Conventional echocardiographic parameters such as tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and free-wall longitudinal strain (FWLS) offer limited insights into the complexity of right ventricular (RV) systolic function, while 3D echocardiography-derived RV ejection fraction (RVEF) enables a comprehensive assessment. We investigated the discordance between TAPSE, FAC, FWLS, and RVEF in RV systolic function grading and associated outcomes. METHODS: We analyzed two- and three-dimensional echocardiography data from 2 centers including 750 patients followed up for all-cause mortality. Right ventricular dysfunction was defined as RVEF <45%, with guideline-recommended thresholds (TAPSE <17 mm, FAC <35%, FWLS >-20%) considered. RESULTS: Among patients with normal RVEF, significant proportions exhibited impaired TAPSE (21%), FAC (33%), or FWLS (8%). Conversely, numerous patients with reduced RVEF had normal TAPSE (46%), FAC (26%), or FWLS (41%). Using receiver-operating characteristic analysis, FWLS exhibited the highest area under the curve of discrimination for RV dysfunction (RVEF <45%) with 59% sensitivity and 92% specificity. Over a median 3.7-year follow-up, 15% of patients died. Univariable Cox regression identified TAPSE, FAC, FWLS, and RVEF as significant mortality predictors. Combining impaired conventional parameters showed that outcomes are the worst if at least 2 parameters are impaired and gradually better if only one or none of them are impaired (log-rank P < .005). CONCLUSION: Guideline-recommended cutoff values of conventional echocardiographic parameters of RV systolic function are only modestly associated with RVEF-based assessment. Impaired values of FWLS showed the closest association with the RVEF cutoff. Our results emphasize a multiparametric approach in the assessment of RV function, especially if 3D echocardiography is not available.

NASH triggers cardiometabolic HFpEF in aging mice.

Both heart failure with preserved ejection fraction (HFpEF) and non-alcoholic fatty liver disease (NAFLD) develop due to metabolic dysregulation, has similar risk factors (e.g., insulin resistance, systemic inflammation) and are unresolved clinical challenges. Therefore, the potential link between the two disease is important to study. We aimed to evaluate whether NASH is an independent factor of cardiac dysfunction and to investigate the age dependent effects of NASH on cardiac function. C57Bl/6 J middle aged (10 months old) and aged mice (24 months old) were fed either control or choline deficient (CDAA) diet for 8 weeks. Before termination, echocardiography was performed. Upon termination, organ samples were isolated for histological and molecular analysis. CDAA diet led to the development of NASH in both age groups, without inducing weight gain, allowing to study the direct effect of NASH on cardiac function. Mice with NASH developed hepatomegaly, fibrosis, and inflammation. Aged animals had increased heart weight. Conventional echocardiography revealed normal systolic function in all cohorts, while increased left ventricular volumes in aged mice. Two-dimensional speckle tracking echocardiography showed subtle systolic and diastolic deterioration in aged mice with NASH. Histologic analyses of cardiac samples showed increased cross-sectional area, pronounced fibrosis and Col1a1 gene expression, and elevated intracardiac CD68+ macrophage count with increased Il1b expression. Conventional echocardiography failed to reveal subtle change in myocardial function; however, 2D speckle tracking echocardiography was able to identify diastolic deterioration. NASH had greater impact on aged animals resulting in cardiac hypertrophy, fibrosis, and inflammation.

Right ventricular pressure-strain relationship-derived myocardial work reflects contractility: Validation with invasive pressure-volume analysis.

Three-dimensional (3D) echocardiography-derived right ventricular (RV) ejection fraction (EF) and global longitudinal strain (GLS) are valuable RV functional markers; nevertheless, they are substantially load-dependent. Global myocardial work index (GMWI) is a novel parameter calculated by the area of the RV pressure-strain loop. By adjusting myocardial deformation to instantaneous pressure, it may reflect contractility. To test this hypothesis, we enrolled 60 patients who underwent RV pressure-conductance catheterization to determine load-independent markers of RV contractility and ventriculo-arterial coupling. Detailed 3D echocardiography was also performed, and we calculated RV EF, RV GLS, and using the RV pressure trace curve, RV GWMI. While neither RV EF nor GLS correlated with Ees, GMWI strongly correlated with Ees. In contrast, RV EF and GLS showed a relationship with Ees/Ea. By dividing the population based on their Reveal Lite 2 risk classification, different characteristics were seen among the subgroups. RV GMWI may emerge as a useful clinical tool for risk stratification and follow-up in patients with RV dysfunction.

Deep Learning-Derived Myocardial Strain.

BACKGROUND: Echocardiographic strain measurements require extensive operator experience and have significant intervendor variability. Creating an automated, open-source, vendor-agnostic method to retrospectively measure global longitudinal strain (GLS) from standard echocardiography B-mode images would greatly improve post hoc research applications and may streamline patient analyses. OBJECTIVES: This study was seeking to develop an automated deep learning strain (DLS) analysis pipeline and validate its performance across multiple applications and populations. METHODS: Interobserver/-vendor variation of traditional GLS, and simulated effects of variation in contour on speckle-tracking measurements were assessed. The DLS pipeline was designed to take semantic segmentation results from EchoNet-Dynamic and derive longitudinal strain by calculating change in the length of the left ventricular endocardial contour. DLS was evaluated for agreement with GLS on a large external dataset and applied across a range of conditions that result in cardiac hypertrophy. RESULTS: In patients scanned by 2 sonographers using 2 vendors, GLS had an intraclass correlation of 0.29 (95% CI: -0.01 to 0.53, P = 0.03) between vendor measurements and 0.63 (95% CI: 0.48-0.74, P < 0.001) between sonographers. With minor changes in initial input contour, step-wise pixel shifts resulted in a mean absolute error of 3.48% and proportional strain difference of 13.52% by a 6-pixel shift. In external validation, DLS maintained moderate agreement with 2-dimensional GLS (intraclass correlation coefficient [ICC]: 0.56, P = 0.002) with a bias of -3.31% (limits of agreement: -11.65% to 5.02%). The DLS method showed differences (P < 0.0001) between populations with cardiac hypertrophy and had moderate agreement in a patient population of advanced cardiac amyloidosis: ICC was 0.64 (95% CI: 0.53-0.72), P < 0.001, with a bias of 0.57%, limits of agreement of -4.87% to 6.01% vs 2-dimensional GLS. CONCLUSIONS: The open-source DLS provides lower variation than human measurements and similar quantitative results. The method is rapid, consistent, vendor-agnostic, publicly released, and applicable across a wide range of imaging qualities.

Myocardial work of the systemic right ventricle and its association with outcomes.

We aimed to evaluate clinical and prognostic significance of myocardial work parameters of the systemic right ventricle (SRV). Thirty-eight patients with the SRV underwent echocardiographic assessment of the SRV systolic function including 3D-echocardiography derived ejection fraction, 2D longitudinal strain and myocardial work analysis. The study endpoint was the combination of all-cause mortality and heart transplantation. Global constructive work (GCW) and global work index (GWI) demonstrated moderate correlation with the 3DE-derived SRV ejection fraction (EF) (Rho 0.64, p < 0.0001 and Rho 0.63, p < 0.0001, respectively). GCW showed the strongest correlation with the BNP level (Rho - 0.77, p < 0.0001), closely followed by GWI, 4-chamber longitudinal strain and 3DE EF (all Rho - 0.73, p < 0.0001). GCW and GWI were significantly lower in patients with moderate or severe tricuspid regurgitation compared with less than moderate regurgitation (1226 ± 439 vs 1509 ± 264 mmHg%, p = 0.02, and 984 ± 348 vs 1259 ± 278 mmHg%, p = 0.01, respectively). During a follow-up of 3.5 (2.8-3.9) years, seven patients (18%) died and one received transplantation (3%). They had significantly lower GCW and GWI compared with patients who did not reach the study endpoint (908 ± 255 vs 1433 ± %, p < 0.001 and 721 ± 210 vs 1173 ± 315 mmHg%, p < 0.001, respectively). In Cox regression analysis, GCW, GWI, 3DE SRV volumes and EF were the best-fit models based on the Akaike Information Criterion, outperforming longitudinal strain parameters. GWI and GCW, novel echocardiographic parameters of myocardial work, provided reliable quantification of the SRV systolic function. GWI, GCW and 3DE-derived SRV parameters were closely associated with all-cause mortality and heart transplantation in patients with the SRV.

Right Ventricular Structure and Function in Adolescent Athletes: A 3D Echocardiographic Study.

The aim of this study was to characterize the right ventricular (RV) contraction pattern and its associations with exercise capacity in a large cohort of adolescent athletes using resting three-dimensional echocardiography (3DE). We enrolled 215 adolescent athletes (16±1 years, 169 males, 12±6 hours of training/week) and compared them to 38 age and sex-matched healthy, sedentary adolescents. We measured the 3DE-derived biventricular ejection fractions (EF). We also determined the relative contributions of longitudinal EF (LEF/RVEF) and radial EF (REF/RVEF) to the RVEF. Same-day cardiopulmonary exercise testing was performed to calculate VO2/kg. Both LV and RVEFs were significantly lower (athletes vs. controls; LVEF: 57±4 vs 61±3, RVEF: 55±5 vs 60±5%, p<0.001). Interestingly, while the relative contribution of radial shortening to the global RV EF was also reduced (REF/RVEF: 0.40±0.10 vs 0.49±0.06, p<0.001), the contribution of the longitudinal contraction was significantly higher in athletes (LEF/RVEF: 0.45±0.08 vs 0.40±0.07, p<0.01). The supernormal longitudinal shortening correlated weakly with a higher VO2/kg (r=0.138, P=0.044). Similarly to the adult athlete's heart, the cardiac adaptation of adolescent athletes comprises higher biventricular volumes and lower resting functional measures with supernormal RV longitudinal shortening. Characteristic exercise-induced structural and functional cardiac changes are already present in adolescence.

Three-dimensional echocardiographic evaluation of longitudinal and non-longitudinal components of right ventricular contraction: results from the World Alliance of Societies of Echocardiography study.

AIMS: Right ventricular (RV) functional assessment is mainly limited to its longitudinal contraction. Dedicated three-dimensional echocardiography (3DE) software enabled the separate assessment of the non-longitudinal components of RV ejection fraction (EF). The aims of this study were (i) to establish normal values for RV 3D-derived longitudinal, radial, and anteroposterior EF (LEF, REF, and AEF, respectively) and their relative contributions to global RVEF, (ii) to calculate 3D RV strain normal values, and (iii) to determine sex-, age-, and race-related differences in these parameters in a large group of normal subjects (WASE study). METHODS AND RESULTS: 3DE RV wide-angle datasets from 1043 prospectively enrolled healthy adult subjects were analysed to generate a 3D mesh model of the RV cavity (TomTec). Dedicated software (ReVISION) was used to analyse RV motion along the three main anatomical planes. The EF values corresponding to each plane were identified as LEF, REF, and AEF. Relative contributions were determined by dividing each EF component by the global RVEF. RV strain analysis included longitudinal, circumferential, and global area strains (GLS, GCS, and GAS, respectively). Results were categorized by sex, age (18-40, 41-65, and >65 years), and race. Absolute REF, AEF, LEF, and global RVEF were higher in women than in men (P < 0.001). With aging, both sexes exhibited a decline in all components of longitudinal shortening (P < 0.001), which was partially compensated in elderly women by an increase in radial contraction. Black subjects showed lower RVEF and GAS values compared with white and Asian subjects of the same sex (P < 0.001), and black men showed significantly higher RV radial but lower longitudinal contributions to global RVEF compared with Asian and white men. CONCLUSION: 3DE evaluation of the non-longitudinal components of RV contraction provides additional information regarding RV physiology, including sex-, age-, and race-related differences in RV contraction patterns that may prove useful in disease states involving the right ventricle.

PCSK9, A Promising Novel Target for Age-Related Cardiovascular Dysfunction.

Cardiovascular diseases (CVDs) are the leading cause of death among elderly people. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important regulator of cholesterol metabolism. Herein, we investigated the role of PCSK9 in age-related CVD. Both in humans and rats, blood PCSK9 level correlated positively with increasing age and the development of cardiovascular dysfunction. Age-related fatty degeneration of liver tissue positively correlated with serum PCSK9 levels in the rat model, while development of age-related nonalcoholic fatty liver disease correlated with cardiovascular functional impairment. Network analysis identified PCSK9 as an important factor in age-associated lipid alterations and it correlated positively with intima-media thickness, a clinical parameter of CVD risk. PCSK9 inhibition with alirocumab effectively reduced the CVD progression in aging rats, suggesting that PCSK9 plays an important role in cardiovascular aging.

Highlights of right ventricular characteristics of left ventricular noncompaction using 3D echocardiography.

Highlights of right ventricular characteristics of left ventricular noncompaction using 3D echocardiography. The aspects of right ventricular volumes and function investigated with 3D echocardiography in a large cohort of left ventricular noncompaction morphology (LVNC) population remains unclear. The objective of our research was to study the left (LV) and right (RV) ventricular parameters using 3D echocardiography and analyze the clinical features of a LVNC population with preserved LV ejection fraction (EF > 50 %) in comparison with healthy controls (HC). We selected 41 LVNC subjects with preserved LV function (EF: 52.91 ± 3 %, male n = 26) and without any comorbidities and compared them with an age and sex-matched HC. Three dimensional endocardial contours were evaluated to determine the following LV and RV parameters: end-diastolic (EDV) and end-systolic (ESV) volumes, stroke volume, EF, LV global longitudinal and circumferential strain and RV septal and free wall longitudinal strain. Regarding the clinical characteristics, the family involvement had a notable proportion, accounting for 51%. The EF and strain values of the LVNC population were significantly decreased in both RV and LV compared to HC. Although the LV volumes of the LVNC group were significantly elevated, the RV volumetric parameters did not differ significantly compared to controls. We found significant correlations between LV and RV volumetric and functional parameters and linear regression models showed that LV EDV and LV ESV determined the RV volumetric values. While the alteration and relationship of the RV parameters may represent the potential of biventricular involvement, clinical characteristics of the LVNC group underlines the necessity of monitoring this population, even with preserved EF.

Clinical and functional relevance of right ventricular contraction patterns in pulmonary hypertension.

BACKGROUND: The right ventricle has a complex contraction pattern of uncertain clinical relevance. We aimed to assess the relationship between right ventricular (RV) contraction pattern and RV-pulmonary arterial (PA) coupling defined by the gold-standard pressure-volume loop-derived ratio of end-systolic/arterial elastance (Ees/Ea). METHODS: Prospectively enrolled patients with suspected or confirmed pulmonary hypertension underwent three-dimensional echocardiography, standard right heart catheterization, and RV conductance catheterization. RV-PA uncoupling was categorized as severe (Ees/Ea < 0.8), moderate (Ees/Ea 0.8-1.29), and none/mild (Ees/Ea ≥ 1.3). Clinical severity was determined from hemodynamics using a truncated version of the 2022 European Society of Cardiology/European Respiratory Society risk stratification scheme. RESULTS: Fifty-three patients were included, 23 with no/mild, 24 with moderate, and 6 with severe uncoupling. Longitudinal shortening was decreased in patients with moderate vs no/mild uncoupling (p <0.001) and intermediate vs low hemodynamic risk (p < 0.001), discriminating low risk from intermediate/high risk with an optimal threshold of 18% (sensitivity 80%, specificity 87%). Anteroposterior shortening was impaired in patients with severe vs moderate uncoupling (p = 0.033), low vs intermediate risk (p = 0.018), and high vs intermediate risk (p = 0.010), discriminating high risk from intermediate/low risk with an optimal threshold of 15% (sensitivity 100%, specificity 83%). Left ventricular (LV) end-diastolic volume was decreased in patients with severe uncoupling (p = 0.035 vs no/mild uncoupling). CONCLUSIONS: Early RV-PA uncoupling is associated with reduced longitudinal function, whereas advanced RV-PA uncoupling is associated with reduced anteroposterior movement and LV preload, all in a risk-related fashion. CLINICALTRIALS: GOV: NCT04663217.

Deep Learning-Based Prediction of Right Ventricular Ejection Fraction Using 2D Echocardiograms.

BACKGROUND: Evidence has shown the independent prognostic value of right ventricular (RV) function, even in patients with left-sided heart disease. The most widely used imaging technique to measure RV function is echocardiography; however, conventional 2-dimensional (2D) echocardiographic assessment is unable to leverage the same clinical information that 3-dimensional (3D) echocardiography-derived right ventricular ejection fraction (RVEF) can provide. OBJECTIVES: The authors aimed to implement a deep learning (DL)-based tool to estimate RVEF from 2D echocardiographic videos. In addition, they benchmarked the tool's performance against human expert reading and evaluated the prognostic power of the predicted RVEF values. METHODS: The authors retrospectively identified 831 patients with RVEF measured by 3D echocardiography. All 2D apical 4-chamber view echocardiographic videos of these patients were retrieved (n = 3,583), and each subject was assigned to either the training or the internal validation set (80:20 ratio). Using the videos, several spatiotemporal convolutional neural networks were trained to predict RVEF. The 3 best-performing networks were combined into an ensemble model, which was further evaluated in an external data set containing 1,493 videos of 365 patients with a median follow-up time of 1.9 years. RESULTS: The ensemble model predicted RVEF with a mean absolute error of 4.57 percentage points in the internal and 5.54 percentage points in the external validation set. In the latter, the model identified RV dysfunction (defined as RVEF <45%) with an accuracy of 78.4%, which was comparable to an expert reader's visual assessment (77.0%; P = 0.678). The DL-predicted RVEF values were associated with major adverse cardiac events independent of age, sex, and left ventricular systolic function (HR: 0.924 [95% CI: 0.862-0.990]; P = 0.025). CONCLUSIONS: Using 2D echocardiographic videos alone, the proposed DL-based tool can accurately assess RV function, with similar diagnostic and prognostic power as 3D imaging.

Get to the heart of pediatric kidney transplant recipients: Evaluation of left- and right ventricular mechanics by three-dimensional echocardiography.

Background: Kidney transplantation (KTX) markedly improves prognosis in pediatric patients with end-stage kidney failure. Still, these patients have an increased risk of developing cardiovascular disease due to multiple risk factors. Three-dimensional (3D) echocardiography allows detailed assessment of the heart and may unveil distinct functional and morphological changes in this patient population that would be undetectable by conventional methods. Accordingly, our aim was to examine left- (LV) and right ventricular (RV) morphology and mechanics in pediatric KTX patients using 3D echocardiography. Materials and methods: Pediatric KTX recipients (n = 74) with median age 20 (14-26) years at study enrollment (43% female), were compared to 74 age and gender-matched controls. Detailed patient history was obtained. After conventional echocardiographic protocol, 3D loops were acquired and measured using commercially available software and the ReVISION Method. We measured LV and RV end-diastolic volumes indexed to body surface area (EDVi), ejection fraction (EF), and 3D LV and RV global longitudinal (GLS) and circumferential strains (GCS). Results: Both LVEDVi (67 ± 17 vs. 61 ± 9 ml/m2; p < 0.01) and RVEDVi (68 ± 18 vs. 61 ± 11 ml/m2; p < 0.01) were significantly higher in KTX patients. LVEF was comparable between the two groups (60 ± 6 vs. 61 ± 4%; p = NS), however, LVGLS was significantly lower (-20.5 ± 3.0 vs. -22.0 ± 1.7%; p < 0.001), while LVGCS did not differ (-29.7 ± 4.3 vs. -28.6 ± 10.0%; p = NS). RVEF (59 ± 6 vs. 61 ± 4%; p < 0.05) and RVGLS (-22.8 ± 3.7 vs. -24.1 ± 3.3%; p < 0.05) were significantly lower, however, RVGCS was comparable between the two groups (-23.7 ± 4.5 vs. -24.8 ± 4.4%; p = NS). In patients requiring dialysis prior to KTX (n = 64, 86%) RVGCS showed correlation with the length of dialysis (r = 0.32, p < 0.05). Conclusion: Pediatric KTX patients demonstrate changes in both LV and RV morphology and mechanics. Moreover, the length of dialysis correlated with the contraction pattern of the right ventricle.

There is more than just longitudinal strain: Prognostic significance of biventricular circumferential mechanics.

Introduction: Despite the significant contribution of circumferential shortening to the global ventricular function, data are scarce concerning its prognostic value on long-term mortality. Accordingly, our study aimed to assess both left (LV) and right ventricular (RV) global longitudinal (GLS) and global circumferential strain (GCS) using three-dimensional echocardiography (3DE) to determine their prognostic importance. Methods: Three hundred fifty-seven patients with a wide variety of left-sided cardiac diseases were retrospectively identified (64 ± 15 years, 70% males) who underwent clinically indicated 3DE. LV and RV GLS, and GCS were quantified. To determine the prognostic power of the different patterns of biventricular mechanics, we divided the patient population into four groups. Group 1 consisted of patients with both LV GLS and RV GCS above the respective median values; Group 2 was defined as patients with LV GLS below the median while RV GCS above the median, whereas in Group 3, patients had LV GLS values above the median, while RV GCS was below median. Group 4 was defined as patients with both LV GLS and RV GCS below the median. Patients were followed up for a median of 41 months. The primary endpoint was all-cause mortality. Results: Fifty-five patients (15%) met the primary endpoint. Impaired values of both LV GCS (HR, 1.056 [95% CI, 1.027-1.085], p < 0.001) and RV GCS (1.115 [1.068-1.164], p < 0.001) were associated with increased risk of death by univariable Cox regression. Patients with both LV GLS and RV GCS below the median (Group 4) had a more than 5-fold increased risk of death compared with those in Group 1 (5.089 [2.399-10.793], p < 0.001) and more than 3.5-fold compared with those in Group 2 (3.565 [1.256-10.122], p = 0.017). Interestingly, there was no significant difference in mortality between Group 3 (with LV GLS above the median) and Group 4, but being categorized into Group 3 versus Group 1 still held a more than 3-fold risk (3.099 [1.284-7.484], p = 0.012). Discussion: The impaired values of both LV and RV GCS are associated with long-term all-cause mortality, emphasizing the importance of assessing biventricular circumferential mechanics. Reduced RV GCS is associated with significantly increased risk of mortality even if LV GLS is preserved.

Association of Right Ventricular Functional Parameters With Adverse Cardiopulmonary Outcomes: A Meta-analysis.

AIMS: We aimed to confirm that three-dimensional echocardiography-derived right ventricular ejection fraction (RVEF) is better associated with adverse cardiopulmonary outcomes than the conventional echocardiographic parameters. METHODS: We performed a meta-analysis of studies reporting the impact of unit change of RVEF, tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and free-wall longitudinal strain (FWLS) on clinical outcomes (all-cause mortality and/or adverse cardiopulmonary outcomes). Hazard ratios (HRs) were rescaled by the within-study SDs to represent standardized changes. Within each study, we calculated the ratio of HRs related to a 1 SD reduction in RVEF versus TAPSE, or FAC, or FWLS, to quantify the association of RVEF with adverse outcomes relative to the other metrics. These ratios of HRs were pooled using random-effects models. RESULTS: Ten independent studies were identified as suitable, including data on 1,928 patients with various cardiopulmonary conditions. Overall, a 1 SD reduction in RVEF was robustly associated with adverse outcomes (HR = 2.64 [95% CI, 2.18-3.20], P < .001; heterogeneity: I2 = 65%, P = .002). In studies reporting HRs for RVEF and TAPSE, or RVEF and FAC, or RVEF and FWLS in the same cohort, head-to-head comparison revealed that RVEF showed significantly stronger association with adverse outcomes per SD reduction versus the other 3 parameters (vs TAPSE, HR = 1.54 [95% CI, 1.04-2.28], P = .031; vs FAC, HR = 1.45 [95% CI, 1.15-1.81], P = .001; vs FWLS, HR = 1.44 [95% CI, 1.07-1.95], P = .018). CONCLUSION: Reduction in three-dimensional echocardiography-derived RVEF shows stronger association with adverse clinical outcomes than conventional right ventricular functional indices; therefore, it might further refine the risk stratification of patients with cardiopulmonary diseases.

IL-1ß neutralization prevents diastolic dysfunction development, but lacks hepatoprotective effect in an aged mouse model of NASH.

Interleukin-1ß (IL-1ß) is a key mediator of non-alcoholic steatohepatitis (NASH), a chronic liver disease, and of systemic inflammation-driven aging. IL-1ß contributes to cardio-metabolic decline, and may promote hepatic oncogenic transformation. Therefore, IL-1ß is a potential therapeutic target in these pathologies. We aimed to investigate the hepatic and cardiac effects of an IL-1ß targeting monoclonal antibody in an aged mouse model of NASH. 24 months old male C57Bl/6J mice were fed with control or choline deficient (CDAA) diet and were treated with isotype control or anti-IL-1ß Mab for 8 weeks. Cardiac functions were assessed by conventional-and 2D speckle tracking echocardiography. Liver samples were analyzed by immunohistochemistry and qRT-PCR. Echocardiography revealed improved cardiac diastolic function in anti-IL-1ß treated mice with NASH. Marked hepatic fibrosis developed in CDAA-fed group, but IL-1ß inhibition affected fibrosis only at transcriptomic level. Hepatic inflammation was not affected by the IL-1ß inhibitor. PCNA staining revealed intensive hepatocyte proliferation in CDAA-fed animals, which was not influenced by neutralization of IL-1ß. IL-1ß inhibition increased hepatic expression of Pd-1 and Ctla4, while Pd-l1 expression increased in NASH. In conclusion, IL-1ß inhibition improved cardiac diastolic function, but did not ameliorate features of NASH; moreover, even promoted hepatic immune checkpoint expression, with concomitant NASH-related hepatocellular proliferation.

Long-term prognostic value of left atrial longitudinal strain in an elderly community-based cohort.

Despite the well-known importance of left atrial (LA) mechanics in diastolic function, data are scarce regarding the prognostic power of LA longitudinal strain and its potential added value in the risk stratification of an elderly population. Accordingly, our aim was to determine the long-term prognostic importance of 2D speckle-tracking echocardiography-derived peak atrial longitudinal strain (PALS) in a community-based screening sample. Three hundred and fourteen volunteers were retrospectively identified from a population-based screening program (mean age 62 ± 11 years; 58% female) with a median follow-up of 9.5 years. All subjects who participated in the screening program underwent 2D echocardiography to measure left ventricular (LV) ejection fraction (EF), global longitudinal strain (GLS), and PALS, as well as low-dose cardiac CT to determine the Agatston score. The primary endpoint was all-cause mortality. Thirty-nine subjects (12.4%) met the primary endpoint. Subjects with adverse outcomes had significantly lower LV GLS (dead vs. alive; - 19.2 ± 4.3 vs. - 20.6 ± 3.5%, p < 0.05) and PALS (32.3 ± 12.0 vs. 41.8 ± 14.2%, p < 0.001), whereas LV EF did not show a difference between the two groups (51.1 ± 7.0 vs. 52.1 ± 6.2, %, p = NS). By multivariable Cox regression analysis, PALS was found to be a significant predictor of adverse outcomes independent of LV GLS, and Agatston and Framingham scores. In subjects with PALS values below the standard cut-off of 39%, the risk of all-cause mortality was almost 2.5 times higher (hazard ratio: 2.499 [95% confidence interval: 1.334-4.682], p < 0.05). Beyond the assessment of LV EF and LV GLS, PALS offers incremental value in cardiovascular risk stratification in a community-based elderly cohort. PALS was found to be a significant and independent predictor of long-term mortality among other classical cardiovascular risk estimators.

Cardiopulmonary examinations of athletes returning to high-intensity sport activity following SARS-CoV-2 infection.

After SARS-CoV-2 infection, strict recommendations for return-to-sport were published. However, data are insufficient about the long-term effects on athletic performance. After suffering SARS-CoV-2 infection, and returning to maximal-intensity trainings, control examinations were performed with vita-maxima cardiopulmonary exercise testing (CPET). From various sports, 165 asymptomatic elite athletes (male: 122, age: 20y (IQR: 17-24y), training:16 h/w (IQR: 12-20 h/w), follow-up:93.5 days (IQR: 66.8-130.0 days) were examined. During CPET examinations, athletes achieved 94.7 ± 4.3% of maximal heart rate, 50.9 ± 6.0 mL/kg/min maximal oxygen uptake (V̇O2max), and 143.7 ± 30.4L/min maximal ventilation. Exercise induced arrhythmias (n = 7), significant horizontal/descending ST-depression (n = 3), ischemic heart disease (n = 1), hypertension (n = 7), slightly elevated pulmonary pressure (n = 2), and training-related hs-Troponin-T increase (n = 1) were revealed. Self-controlled CPET comparisons were performed in 62 athletes: due to intensive re-building training, exercise time, V̇O2max and ventilation increased compared to pre-COVID-19 results. However, exercise capacity decreased in 6 athletes. Further 18 athletes with ongoing minor long post-COVID symptoms, pathological ECG (ischemic ST-T changes, and arrhythmias) or laboratory findings (hsTroponin-T elevation) were controlled. Previous SARS-CoV-2-related myocarditis (n = 1), ischaemic heart disease (n = 1), anomalous coronary artery origin (n = 1), significant ventricular (n = 2) or atrial (n = 1) arrhythmias were diagnosed. Three months after SARS-CoV-2 infection, most of the athletes had satisfactory fitness levels. Some cases with SARS-CoV-2 related or not related pathologies requiring further examinations, treatment, or follow-up were revealed.

Baseline clinical characteristics of heart failure patients with reduced ejection fraction enrolled in the BUDAPEST-CRT Upgrade trial.

AIMS: The BUDAPEST-CRT Upgrade study is the first prospective, randomized, multicentre clinical trial investigating the outcomes after cardiac resynchronization therapy (CRT) upgrade in heart failure (HF) patients with intermittent or permanent right ventricular (RV) pacing with wide paced QRS. This report describes the baseline clinical characteristics of the enrolled patients and compares them to cohorts from previous milestone CRT studies. METHODS AND RESULTS: This international multicentre randomized controlled trial investigates 360 patients having a pacemaker (PM) or implantable cardioverter defibrillator (ICD) device for at least 6 months prior to enrolment, reduced left ventricular ejection fraction (LVEF ≤35%), HF symptoms (New York Heart Association [NYHA] functional class II-IVa), wide paced QRS (>150 ms), and ≥20% of RV pacing burden without having a native left bundle branch block. At enrolment, the mean age of the patients was 73 ± 8 years; 89% were male, 97% were in NYHA class II/III functional class, and 56% had atrial fibrillation. Enrolled patients predominantly had conventional PM devices, with a mean RV pacing burden of 86%. Thus, this is a patient cohort with advanced HF, low baseline LVEF (25 ± 7%), high N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (2231 pg/ml [25th-75th percentile 1254-4309 pg/ml]), and frequent HF hospitalizations during the preceding 12 months (50%). CONCLUSION: When compared with prior CRT trial cohorts, the BUDAPEST-CRT Upgrade study includes older patients with a strong male predominance and a high burden of atrial fibrillation and other comorbidities. Moreover, this cohort represents an advanced HF population with low LVEF, high NT-proBNP, and frequent previous HF events. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02270840.

Cardiorespiratory fitness status of elite handball referees in Hungary.

In various team sports, such as handball, referees work on the court by continuously moving with the players. Therefore, their physical fitness also has an impact on their reaction time, which could affect their professional decisions. The cardiorespiratory fitness status of healthy Hungarian elite handball referees was examined via body composition analysis and vita maxima cardiopulmonary exercise testing with lactate measurements. One hundred referees were examined (age: 29.0 ± 7.9 years; male: 64.0%; training: 4.3 ± 2.0 hours/week; ratio of former elite handball players: 39.0%; 51.0% first and 49.0% second division referees of the Hungarian National Handball Leagues). A resting heart rate (HR) of 79.0 ± 12.6 BPM was measured. On the basis of the body composition analysis the fat-free mass index proved to be 19.9 ± 2.6 kg/m2. The referees achieved a maximal oxygen uptake (V̇O2max) of 44.6 ± 6.1 ml/kg/min, with a maximal HR of 187.2 ± 11.1 BPM (which was 98.1 ± 4.6% of their calculated maximal HR) and a peak lactate of 9.2 ± 3.2 mmol/l at 557.1 ± 168.3 sec on our continuous speed, increasing slope treadmill protocol. Second division referees were younger, on a weekly average they trained more, achieved higher treadmill exercise time (respectively, 463.8 ± 131.9 vs 658.4 ± 143.9 sec, p < 0.001) and anaerobic threshold time (respectively, 265.8 ± 100.9 vs 348.2 ± 117.1 sec, p < 0.001), while the two different divisional referees had similar V̇O2max values. Regarding our physical fitness measurements, huge individual differences were observed between the referees (exercise time range: 259.0-939.0 sec, V̇O2max range: 25.3-62.4 ml/kg/min). Since it can affect their performance as referees, individual training planning, regular physical fitness measurements, and strict selection methods are suggested.