The load dependence of global longitudinal strain (GLS) means that changes in systolic blood pressure (BP) between visits may confound the diagnosis of cancer-treatment-related cardiac dysfunction (CTRCD). We sought to determine whether the estimation of myocardial work, which incorporates SBP, could overcome this limitation. In this case–control study, 44 asymptomatic patients at risk of CTRCD underwent echocardiography at baseline and after oncologic treatment. CTRCD was defined on the basis of the change in the ejection fraction. Those with CTRCD were divided into subsets with and without a follow-up SBP increment >20 mmHg (CTRCD+BP+ and CTRCD+BP−), and matched with patients without CTRCD (CTRCD−BP+ and CTRCD−BP−). The work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were assessed in addition to the GLS. The largest increases in the GWI and GCW at follow-up were found in CTRCD−BP+ patients. The CTRCD+BP− patients demonstrated significantly larger decreases in GWI and GCW than their CTRCD+BP+ and CTRCD−BP− peers. ROC analysis for the discrimination of LV functional changes in response to increased afterload in the absence of cardiotoxicity revealed higher AUCs for GCW (AUC = 0.97) and GWI (AUC = 0.93) than GLS (AUC = 0.73), GWW (AUC = 0.51), or GWE (AUC = 0.63, all p-values < 0.001). GCW (OR: 1.021; 95% CI: 1.001–1.042; p < 0.04) was the only feature independently associated with CTRCD−BP+. Myocardial work is superior to GLS in the serial assessments in patients receiving cardiotoxic chemotherapy. The impairment of GLS in the presence of an increase in GWI and GCW indicates the impact of elevated afterload on LV performance in the absence of actual myocardial impairment.

Blood concentration of galectin-3 (Gal-3) - a biomarker of fibrosis useful in diagnostics and prognostication in heart failure (HF) - is known to be elevated in patients with renal impairment, a condition which often accompanies cardiac insufficiency. To investigate the effect of moderately reduced renal function (estimated glomerular filtration rate (eGFR) 30-60 mL/min/1.73 m2) on the diagnostic and prognostic utility of circulating Gal-3 in patients with HF with preserved ejection fraction (HFpEF). Clinical, biochemical and echocardiographic variables were collected at baseline in 154 patients with HFpEF: 101 with normal and 53 with moderately reduced renal function, who were followed up for 48 (24-60) months for HF hospitalization and cardiovascular (CV) death (composite endpoint). Patients with moderately impaired renal function were characterized by higher age, Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score, Gal-3, B-type natriuretic peptide (BNP) and New York Heart Association (NYHA) class, lower hemoglobin, and more advanced left ventricular diastolic dysfunction. Older age, female sex and deeper impairment of renal performance were determinants of higher Gal-3 blood concentrations. Lower exercise capacity (lower peak VO2) was associated with higher Gal-3 level and more pronounced renal impairment. Multivariable regression analysis demonstrated the significance of renal dysfunction as a determinant of lower exercise capacity and revealed a significant interaction between Gal-3 and eGFR with respect to peak VO2. The addition of Gal-3 to the prognostic models based on clinical data improved their predictive power for the study endpoint. The Kaplan-Meier analysis revealed that the presence of moderately reduced renal function with eGFR 30-60 mL/min/1.73 m2 did not enhance the increased risk of adverse outcome associated with Gal-3 above the median. In patients with HFpEF, the coexistence of moderate renal dysfunction does not deteriorate the prognostic usefulness of circulating Gal-3. However, renal impairment modifies the association between Gal-3 and exercise capacity, which supports the need to adjust for kidney function when interpreting the contribution of Gal-3 to exercise intolerance in this population.

Gametogenesis is a fundamental biological process that ensures both genetic recombination and the continuity of successive generations. Interspecific hybrids can reproduce through modified mechanisms, such as hybridogenesis, by transmitting clonal, unrecombined genomes of only one of the parental species via their gametes. Pelophylax grafi (RP) is a natural hybrid frog composed of mixed genomes (subgenomes) of two related species, Pelophylax perezi (P) and Pelophylax ridibundus (R), and coexists in populations with P. perezi. This study tested the involvement of programmed genome elimination in gamete production of P. grafi, providing new insight into reproductive mechanisms of hybrid vertebrates. Using comparative genomic hybridization (CGH) and fluorescent in situ hybridization (FISH), we examined the genomic constitution of germline cells in tadpoles and adult male and female P. grafi. Controlled crosses between P. perezi and P. grafi produced F1 hybrid tadpoles, whose genotypes confirmed that P. grafi parents transmitted the R subgenome through their gametes. In the early germline cells (gonocytes) of these tadpoles, P chromosomes were selectively eliminated via micronuclei formation during interphase. The occasional presence of the R genome and mixed R/P genome micronuclei suggests variability and imperfect fidelity in the elimination process. In adult hybrids, the majority of diplotene oocytes, spermatogonial stem cells (SSC) and spermatocytes carried R subgenomes. We demonstrated that programmed genome rearrangement in Pelophylax hybrids is an evolutionarily conserved mechanism underlying this unique reproductive strategy.

Gametogenesis is a fundamental biological process that ensures both genetic recombination and the continuity of successive generations. Interspecific hybrids can reproduce through modified mechanisms, such as hybridogenesis, by transmitting clonal, unrecombined genomes of only one of the parental species via their gametes. Pelophylax grafi (PR) is a natural hybrid frog composed of mixed genomes (subgenomes) of two related species, Pelophylax perezi (P) and Pelophylax ridibundus (R), and coexists in populations with P. perezi. This study tested the involvement of programmed genome elimination in gamete production of P. grafi, providing new insight into reproductive mechanisms of hybrid vertebrates. Using comparative genomic hybridization (CGH) and fluorescent in situ hybridization (FISH), we examined the genomic constitution of germline cells in tadpoles and adult male and female P. grafi. Controlled crosses between P. perezi and P. grafi produced F1 hybrid tadpoles, whose genotypes confirmed that P. grafi parents transmitted the R subgenome through their gametes. In the early germline cells (gonocytes) of these tadpoles, P chromosomes were selectively eliminated via micronuclei formation during interphase. The occasional presence of the R genome and mixed R/P genome micronuclei, suggests variability and imperfect fidelity in the elimination process. In adult hybrids, the majority of diplotene oocytes, spermatogonial stem cells (SSC) and spermatocytes carried R subgenomes. We demonstrated that programmed genome rearrangement in Pelophylax hybrids is an evolutionarily conserved mechanism underlying this unique reproductive strategy.

Background/Objectives: Currently, the most popular techniques for orthotopic heart transplantation (OHTx) are bicaval and total OHTx. Although bicaval OHTx has shown advantages over the biatrial approach, comparisons between bicaval and total OHTx reain limited. To compare the functional and morphological characteristics of the left atrium (LA) in patients after bicaval and total OHTx. Methods: Sixty-six patients (age 51.2 ± 10.5 years) after total OHTx (33 patients) and bicaval OHTx (33 patients) were included in this case–control study. Recipients were matched for sex, age, and time from transplantation and absence of severe graft rejection based on routine endomyocardial biopsies (EMB) performed during follow-up. Echocardiography included standard measurements along with a speckle-tracking assessment of LA strain. Results: Compared with the bicaval OHTx, the total OHTx group showed higher atrial mitral inflow velocity, resulting in a lower E/A ratio, lower LA volume index, and higher LA emptying fraction. Both the reservoir and contraction components of LA function, as assessed by LA deformation, were found to show more favorable profiles in the total OHTx group than in the bicaval group (26.5 ± 6.9 vs. 17.4 ± 4.7, p < 0.001 and 14.8 ± 5.8 vs. 6.0 ± 4.5, p < 0.001, respectively). Multivariable analysis identified surgical technique, left ventricular global longitudinal strain, and the presence of diabetes in the recipient as independent determinants of LA strain. Conclusions: Total OHTx is associated with better LA morphology and function than bicaval OHTx. This may provide better conditions for LA-LV coupling in transplanted hearts and contribute to a more stable electrophysiological environment in atrial tissue.

Background. Left ventricular (LV) systolic impairment, particularly in the longitudinal direction, is considered an early and sensitive marker of hypertensive heart disease and increased cardiovascular risk. The evidence indicates that aortic stiffness and central hemodynamic factors are important determinants of LV performance, mediating the interaction between the heart and vascular load. Despite the existence of cross-sectional analyses linking central blood pressure (BP) parameters with LV mechanics, no longitudinal data are available which include serial measurements in the course of antihypertensive treatment. Objectives. To investigate the associations between changes in LV longitudinal and circumferential function with alterations in arterial hemodynamics and ventricular-arterial coupling (VAC) in patients with uncomplicated hypertension during a 12-month follow-up. Materials and methods. In this retrospective study, 216 patients (age 64.3 +/- 7.6 years) underwent echocardiography including left ventricular longitudinal (GLS) and circumferential strain (GCS) analysis, brachial BP measurements, VAC (combining echocardiography and brachial BP), and arterial hemodynamics using radial tonometry at baseline and after 12 months of antihypertensive therapy. Patients were grouped into 2 subsets: with improvement in GLS (n = 103) and with deterioration in GLS (n = 113). Results. No significant differences were observed in the majority of cardiovascular, demographic or clinical characteristics between the groups. The subset with improvement in GLS demonstrated more favorable changes over follow-up in pulse wave velocity (p = 0.03), central augmentation pressure (p = 0.01) and ventricular-arterial coupling (p = 0.04) compared to patients showing deterioration in GLS. In the multi variable analysis, independent determinants of changes in GLS were: GLS at baseline (-0.48; p < 0.001), changes from baseline to follow-up in central augmentation pressure (-0.29; p = 0.002) and ventricular arterial coupling (-0.25; p = 0.004). Independent determinants of analogous changes in GCS were: GCS at baseline (-0.46; p < 0.001) and changes in central augmentation pressure (-0.22; p = 0.02). Conclusions. Left ventricular longitudinal and circumferential functional remodeling over time in hypertensive patients is associated with arterial hemodynamics and ventricular-arterial coupling.